recent journal articles: allergy


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Recent Articles in Journal of Allergy and Clinical Immunology

Hancox RJ, Welch D, Poulton R, Taylor DR, McLachlan CR, Greene JM, Sears MR
Cigarette smoking and allergic sensitization: A 32-year population-based cohort study.
J Allergy Clin Immunol. 2007 Nov 30;
BACKGROUND: Cigarette smoke has immunosuppressant effects, but its effect on allergic sensitization is unclear. OBJECTIVE: To investigate associations between parental and personal smoking and skin prick tests (SPTs) for atopy in a population-based birth cohort of 1037 participants followed to adulthood. METHODS: Parental history of atopic disease, parental smoking, and personal smoking were obtained at multiple assessments between birth and age 32 years. Atopy was assessed by SPTs for 11 common inhaled allergens at ages 13 and 32 years. RESULTS: Children of atopic parents were less likely to have positive SPTs at age 13 years if either parent smoked (odds ratio, 0.55; P = .009). This association was not significant after adjusting for breast-feeding history, number of siblings, and childhood socioeconomic status. Subjects with atopic parents were also less likely to develop positive results to SPTs between ages 13 and 32 years if they smoked themselves (odds ratio, 0.18; P < .001). This reduction in risk remained significant after adjusting for multiple potential confounding factors. Neither parental nor personal smoking was significantly associated with allergic sensitization among subjects whose parents did not have a history of atopic disease. Few of those with positive SPT results at age 13 years had negative tests at age 32 years, and there was no evidence that this was influenced by smoking. CONCLUSION: Personal and parental smoking is associated with a reduced risk of allergic sensitization in people with a family history of atopy. [Abstract]

Justicia JL, Mullol J
Higher evidence for specific immunotherapy than reported in the ARIA update.
J Allergy Clin Immunol. 2007 Nov 30; [Abstract]

Passalacqua G, Durham SR
Reply.
J Allergy Clin Immunol. 2007 Nov 30; [Abstract]

Fantuzzi G
Adiponectin and inflammation: Consensus and controversy.
J Allergy Clin Immunol. 2007 Nov 30;
Circulating levels of adiponectin decrease with increasing visceral obesity and are lower in patients with type 2 diabetes, the metabolic syndrome, and cardiovascular disease compared with controls matched by body mass index. Several reports demonstrated anti-inflammatory effects of adiponectin. Because increased adipose tissue is associated with low-grade chronic inflammation and proinflammatory factors inhibit adiponectin production, the current hypothesis states that chronic inflammation associated with visceral obesity inhibits production of adiponectin, perpetuating inflammation. The negative correlation between adiponectin and markers of inflammation in the aforementioned conditions supports this hypothesis. In contrast with disorders typically associated with excess adiposity and positive energy balance, adiponectin levels are elevated-rather than decreased-in classic chronic inflammatory/autoimmune diseases that are unrelated to increased adipose tissue, such as rheumatoid arthritis, SLE, inflammatory bowel disease, type 1 diabetes, and cystic fibrosis. In these patients, adiponectin levels positively-rather than negatively-correlate with inflammatory markers. Furthermore, proinflammatory effects of adiponectin have been reported in tissues such as joint synovium and colonic epithelium. Thus, adiponectin is regulated in the opposite direction and may exert differential functions in classic versus obesity-associated inflammatory conditions. This article discusses this apparent paradox and presents possible alternative and/or complementary explanations. [Abstract]

Scordamaglia F, Balsamo M, Scordamaglia A, Moretta A, Mingari MC, Canonica GW, Moretta L, Vitale M
Perturbations of natural killer cell regulatory functions in respiratory allergic diseases.
J Allergy Clin Immunol. 2007 Nov 30;
BACKGROUND: Allergic diseases are characterized by abnormal responses to allergens favored by an inappropriate regulation of the T(H)1-T(H)2 polarization. Natural killer (NK) cells give rise to a complex NK/dendritic cell (DC) cross-talk that would help T(H)1 responses. OBJECTIVE: By analyzing peripheral blood NK cells from 12 patients with either allergic rhinitis or rhinitis and intermittent asthma, we evaluated whether these cells were impaired in their ability to interact with DCs. METHODS: Different circulating NK cell subsets were analyzed by flow cytofluorimetry. Mixed NK/DC cultures were performed to assess the reciprocal functional interactions. NK cells were analyzed for their ability to induce DC maturation and cytokine production, and to kill immature DCs. In addition, DCs were assessed for their ability to induce cytokine production by NK cells. RESULTS: We first analyzed the CD56(++)CD16(+/-) cells, a subset of circulating NK cells that is able to respond to DCs by proliferating and producing IFN-gamma. Our analysis revealed that this NK cell subpopulation was significantly reduced in most patients. This was reflected by reduced NK cell-mediated IFN-gamma production in response to DCs. Also, the capability of promoting DC maturation and/or killing immature DCs, a function sustained by CD56(+)CD16(+) NK cells, was reduced in most patients. CONCLUSIONS: We suggest that allergic diseases are accompanied by a partial impairment of the NK cell capability of promoting and maintaining appropriate T(H)1 responses. [Abstract]

Lanz MJ, Prendes S, Peyrou N, Toledo G, Ferrer CM
Nasal nitric oxide as a noninvasive marker in the antibiotic treatment of acute bacterial sinusitis.
J Allergy Clin Immunol. 2007 Nov 30; [Abstract]

Smith H, Wade J, Frew A
How readable are the American Academy of Allergy, Asthma & Immunology "Tips to remember" leaflets?
J Allergy Clin Immunol. 2007 Nov 30; [Abstract]

Basagańa M, Bartolomé B, Pastor C, Torres F, Alonso R, Vivanco F, Cisteró-Bahíma A
Allergy to human seminal fluid: Cross-reactivity with dog dander.
J Allergy Clin Immunol. 2007 Nov 30;
BACKGROUND: Human seminal plasma (HSP) allergy is uncommon, with symptoms ranging from vulvovaginal pruritus to life-threatening anaphylaxis. Although several seminal plasma allergens have been reported and their molecular masses have been estimated to range between 12 and 75 kd, the prostate-specific antigen (PSA) has recently been identified as a causative allergen. Given that in a large number of cases symptoms appeared during or after the first intercourse, a cross-reactivity phenomenon might be implicated. OBJECTIVE: We sought to assess the presence of IgE cross-reactivity among proteins from dog epithelium and HSP and to attempt to identify the allergens involved. METHODS: Forty-one patients with dog epithelium allergy were selected. One of them experienced anaphylaxis in contact with her husband's seminal plasma. Skin prick tests, serum specific IgE measurements, SDS-PAGE immunoblotting, and inhibition tests were performed to study the pattern of IgE-binding proteins and the potential cross-reactivity between HSP and dog epithelium. Mass spectrometry was carried out to identify the protein involved in allergy reactions. RESULTS: Twenty-four percent of the sera from patients with dog epithelium allergy recognized an IgE-binding band of 28 kd in HSP immunoblotting. Mass spectrometry identified this band as the PSA. SDS-PAGE immunoblotting-inhibition showed a complete IgE-binding inhibition when sera from these patients were preincubated with dog dander extract. CONCLUSIONS: IgE cross-reactivity among proteins from dog dander and human PSA is demonstrated. [Abstract]

Matsumoto K, Tamari M, Saito H
Involvement of eosinophils in the onset of asthma.
J Allergy Clin Immunol. 2007 Nov 30; [Abstract]

Canino G, Vila D, Normand SL, Acosta-Pérez E, Ramírez R, García P, Rand C
Reducing asthma health disparities in poor Puerto Rican children: The effectiveness of a culturally tailored family intervention.
J Allergy Clin Immunol. 2007 Nov 30;
BACKGROUND: Island and mainland Puerto Rican children have the highest rates of asthma and asthma morbidity of any ethnic group in the United States. OBJECTIVE: We evaluated the effectiveness of a culturally adapted family asthma management intervention called CALMA (an acronym of the Spanish for "Take Control, Empower Yourself and Achieve Management of Asthma") in reducing asthma morbidity in poor Puerto Rican children with asthma. METHODS: Low-income children with persistent asthma were selected from a national health plan insurance claims database by using a computerized algorithm. After baseline, families were randomly assigned to either the intervention or a control group. RESULTS: No significant differences between control and intervention group were found for the primary outcome of symptom-free days. However, children in the CALMA intervention group had 6.5% more symptom-free nights, were 3 times more likely to have their asthma under control, and were less likely to visit the emergency department and be hospitalized as compared to the control group. Caregivers receiving CALMA were significantly less likely to feel helpless, frustrated, or upset because of their child's asthma and more likely to feel confident to manage their child's asthma. CONCLUSION: A home-based asthma intervention program tailored to the cultural needs of low income Puerto Rican families is a promising intervention for reducing asthma morbidity. [Abstract]


Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007.
J Allergy Clin Immunol. 2007 Nov;120(5 Suppl):S94-138.
Highlights of the National Asthma Education and Prevention Program's Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Full Report 2007 are presented in this EPR-3 summary report. The updated guidelines emphasize the importance of asthma control. Asthma control is the degree to which the manifestations of asthma are minimized by therapeutic intervention and the goals of therapy are met. Because asthma is highly variable, the level of control must be monitored on a periodic basis to determine whether therapy should be maintained or adjusted (stepped up if necessary, stepped down if possible). On the other hand, asthma severity is the intrinsic intensity of the disease process, most easily and directly measured in a patient not receiving long-term control therapy. For managing asthma, the recommendation is to assess severity to initiate therapy and assess control to adjust therapy. Recommendations for managing asthma include an expanded section on childhood asthma with addition of an age group 5 to 11 years old (earlier guidelines combined this group with adults). The guidelines provide new recommendations on patient education in settings beyond the physician's office, and new advice for controlling environmental factors that can cause asthma symptoms.The concepts of current impairment (frequency and intensity of symptoms, low lung function, and limitations of daily activities) and future risk (likelihood of exacerbations, progressive loss of lung function, or adverse side effects from medications) support a new approach to assessing and monitoring the patient's level of asthma control through use of multiple measures. The guidelines stress that some patients can still be at high risk for frequent exacerbations even if they have few day-to-day effects of asthma.Moreover, EPR-3 confirms the importance of teaching patients skills to self-monitor and manage asthma and to use a written asthma action plan, which should include instructions for daily treatment and ways to recognize and handle worsening asthma. New recommendations encourage expanding educational opportunities to reach patients in a variety of settings, such as pharmacies, schools, community centers, and patients' homes. A new section addresses the need for clinician education programs to improve communication with patients and to use system-wide approaches to integrate the guidelines into health care practice.The guidelines describe new evidence for using multiple approaches to limit exposure to allergens and other substances that can worsen asthma; research shows that single steps are rarely sufficient. EPR-3 also expands the section on common conditions that can affect asthma and notes that management of these conditions may help to improve asthma control.Expert Panel Report 3 continues the use of a stepwise approach to control asthma. When assessing the level of asthma control to determine the need for adjusting therapy, EPR-3 reconfirms the importance of assessing patient adherence to medication, inhaler technique, and environmental control measures before making a step up in therapy.The stepwise approach expands from 4 steps to 6 steps of care. Medications have been repositioned within these 6 steps. Recommendations on medications are updated to reflect the latest evidence on effectiveness and safety. EPR-3 reaffirms that patients with persistent asthma need both long-term control medications to control asthma and prevent exacerbations and quick-relief medication for symptoms, as needed. EPR-3 also reaffirms that inhaled corticosteroids are the most effective long-term control medication across all age groups. New recommendations on treatment options such as leukotriene receptor antagonists and cromolyn for long-term control; long-acting beta-agonists as adjunct therapy with inhaled corticosteroids; omalizumab for severe asthma; and albuterol, levalbuterol, and corticosteroids for acute exacerbations are included. [Abstract]

Huebner M, Kim DY, Ewart S, Karmaus W, Sadeghnejad A, Arshad SH
Patterns of GATA3 and IL13 gene polymorphisms associated with childhood rhinitis and atopy in a birth cohort.
J Allergy Clin Immunol. 2007 Nov 21;
BACKGROUND: GATA3 activates transcription of the T(H)2 cytokines, including IL13, an important step in the allergic inflammatory pathway. OBJECTIVE: We sought to identify associations of single nucleotide polymorphisms of the genes GATA3 and IL13 and their interactions with rhinitis and allergic sensitization during childhood. METHODS: We performed genetic association studies in a cohort of children (n = 923) who have been evaluated for the development of rhinitis and allergic sensitization by means of skin prick tests (SPTs) at age 10 years. Pyrosequencing was used to genotype 7 polymorphisms from GATA3 and 5 from IL13. A novel model-selection procedure combining logistic regression models and classification was used to study the contributions of the polymorphisms and their interactions. RESULTS: Combinations of polymorphisms and their interactions increase the risk for rhinitis and allergic sensitization at age 10 years. A model with rs1058240, rs379568, and rs4143094 (GATA3) and rs1800925 (IL13) and their interactions was selected to predict rhinitis and positive SPT responses. rs1058240 was associated with rhinitis and allergic rhinitis (P < .05), and the gene-gene interaction rs1058240:rs1800925 was associated with rhinitis (P = .043). The odds ratios for 4 genotype combinations were significant for rhinitis or SPTs (P < .044). CONCLUSION: Gene-gene interaction between GATA3 and IL13 polymorphisms can influence the risk of childhood rhinitis. Our study suggests that set associations of polymorphisms are important in studying genetic associations for complex phenotypes, such as rhinitis and atopy. [Abstract]

Leb VM, Jahn-Schmid B, Schmetterer KG, Kueng HJ, Haiderer D, Neunkirchner A, Fischer GF, Nissler K, Hartl A, Thalhamer J, Bohle B, Seed B, Pickl WF
Molecular and functional analysis of the antigen receptor of Art v 1-specific helper T lymphocytes.
J Allergy Clin Immunol. 2007 Nov 21;
BACKGROUND: Ninety-five percent of patients with mugwort allergy are sensitized to Art v 1, the sole major allergen in mugwort (Artemisia vulgaris) pollen. Sixty-nine percent of patients recognizing the single immunodominant T-cell epitope Art v 1(25-36) have an HLA-DRB1*01 phenotype. OBJECTIVE: We studied cloning and functional expression of a human alphabeta T-cell receptor (TCR) specific for Art v 1(25-36). METHODS: TCR chains were RT-PCR amplified from an Art v 1(25-36)-specific T-cell clone, retrovirally transferred, and functionally tested in Jurkat T cells or alternatively in peripheral blood T lymphocytes of nonallergic individuals. RESULTS: The alpha-chain of the TCR is composed of TRAV17 and TRAJ45 segments, and the beta-chain uses TRBV18, TRBD1, and TRBJ2-7. Analyses of 23 other Art v 1-specific T-cell clones did not reveal preferential usage of the TRAV17, TRBV18, or other TCR gene families. Efficient TCR transfer into Jurkat T cells was shown by binding of TCR Vbeta18-specific mAb and DRB1*0101/Art v 1 tetramers. Transgenic Jurkat T cells specifically recognized syngeneic EBV B cells pulsed with Art v 1(25-36) peptide and artificial antigen-presenting cells expressing invariant chain::Art v 1 fusion proteins. Moreover, transfer of the TCR into peripheral blood lymphocytes generated T cells that were Art v 1 reactive. Activation of transgenic T cells by artificial antigen-presenting cells was strictly dependent on costimulation. CONCLUSION: For the first time, a detailed molecular and functional analysis of a human allergen-specific TCR is presented. [Abstract]

Lagranderie M, Abolhassani M, Vanoirbeek J, Lefort J, Nahori MA, Lapa E Silva JR, Huerre M, Vargaftig B, Marchal G
Mycobacterium bovis BCG killed by extended freeze-drying reduces airway hyperresponsiveness in 2 animal models.
J Allergy Clin Immunol. 2007 Nov 21;
BACKGROUND: Live BCG administered intranasally to mice inhibits the development of ovalbumin (OVA)-induced eosinophilia and airway hyperresponsiveness (AHR). It is unacceptable to treat human subjects intranasally with live BCG. OBJECTIVE: We investigated whether BCG killed by extended freeze-drying (EFD) and subcutaneously injected has a protective effect in murine and guinea pig models of allergic airway inflammation. METHODS: Mice were OVA sensitized (days 0 and 7), treated subcutaneously (day 14) with EFD and live or heat-killed BCG, and then OVA challenged (day 42). OVA-sensitized mice (days 0 and 7) were challenged (day 14) and EFD treated (day 18) before OVA rechallenge (day 46) to demonstrate the capacity of EFD to reverse the established lung inflammation. Guinea pigs were OVA sensitized (days 0 and 14), treated intradermally (day 35) with EFD, and OVA challenged (days 90-105). RESULTS: In mice and guinea pigs EFD treatment reduced AHR. Among 3 BCG preparations, only EFD efficiently reduced AHR, eosinophilia, and the recruitment of dendritic cells to the lungs after OVA challenge. The protective effect of EFD is associated with production of the immunoregulatory cytokine IL-10. Moreover, EFD treatment did not induce toxic effects or delayed-type hypersensitivity to mycobacterial antigens; that is, it did not interfere with the diagnosis of tuberculosis. CONCLUSION: EFD administered subcutaneously inhibits the development of allergic airway inflammation and prevents AHR without inducing delayed-type hypersensitivity and side effects associated with live or heat-killed BCG. [Abstract]

Kanazawa H, Tochino Y, Asai K
Angiopoietin-2 as a contributing factor of exercise-induced bronchoconstriction in asthmatic patients receiving inhaled corticosteroid therapy.
J Allergy Clin Immunol. 2007 Nov 21;
BACKGROUND: Airway microcirculation has the potential to contribute to the pathogenesis of exercise-induced bronchoconstriction (EIB) in asthma. Recently, angiopoietin-1 has been found to stabilize microvessels and make them leak resistant, whereas angiopoietin-2 is an antagonist of angiopoietin-1 and enhances microvascular permeability. OBJECTIVE: We sought to examine the roles of angiopoietin-2 in EIB in asthmatic patients with inhaled corticosteroid therapy. METHODS: Levels of angiopoietin-1 and angiopoietin-2 in induced sputum were examined in 32 asthmatic patients who were receiving inhaled corticosteroid therapy for more than 6 months at the entry of this study and 14 healthy control subjects. All asthmatic patients performed an exercise test. RESULTS: The degree of eosinophilic airway inflammation did not differ significantly between asthmatic patients and healthy control subjects. Angiopoietin-1 levels were also similar in the 2 groups (asthmatic patients: median, 6.0 ng/mL [range, 2.0-10.7 ng/mL]; healthy control subjects: median, 4.2 ng/mL [range, 1.5-10.7 ng/mL]). In contrast, angiopoietin-2 levels were significantly higher in asthmatic patients than in healthy control subjects (asthmatic patients: median, 0.74 ng/mL [range, 0.3-1.2 ng/mL]; healthy control subjects: median, 0.26 ng/mL [range, 0.05-0.47 ng/mL]; P < .001). There was no significant correlation between angiopoietin-1 levels and the severity of EIB in asthmatic patients. However, angiopoietin-2 levels were significantly correlated with the severity of EIB and airway microvascular permeability index. CONCLUSION: Angiopoietin-2 levels were increased in the airways of asthmatic patients with inhaled corticosteroid therapy, and its levels were associated with the severity of EIB. [Abstract]

Flinterman AE, Akkerdaas JH, den Hartog Jager CF, Rigby NM, Fernandez-Rivas M, Hoekstra MO, Bruijnzeel-Koomen CA, Knulst AC, van Ree R, Pasmans SG
Lipid transfer protein-linked hazelnut allergy in children from a non-Mediterranean birch-endemic area.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Hazelnut allergy in birch pollen-exposed areas is usually due to cross-reactivity (Cor a 1 and 2) and is usually mild in nature (oral allergy). In areas without birches, severe reactions are more prevalent and linked to sensitization to the lipid transfer protein (LTP) Cor a 8. OBJECTIVE: We sought to investigate whether sensitization to LTP plays a role in more severe (objective) hazelnut-induced symptoms in children from a birch-endemic area. METHODS: Sensitization to Cor a 8, Cor a 2, Cor a 1, and Bet v 1 was determined by means of RASTs and immunoblotting in hazelnut-sensitized children with (n = 8) and without (n = 18) objective reactions during double-blind, placebo-controlled food challenges. Additionally, samples from 191 hazelnut-sensitized nonchallenged children were analyzed. RESULTS: Children with objective reactions during double-blind, placebo-controlled food challenge had higher IgE titers to hazelnut (P < .001) and recognized more allergens on immunoblotting (P = .001) than those without such reactions. All children with objective symptoms were sensitized to Cor a 8 (0.51-23.3 IU/mL) compared with only 1 child without objective reactions (0.90 IU/mL). In a multivariate analysis only IgE against Cor a 8 remained as an independent risk factor (undefined odds ratio; P < .0001). In the group of nonchallenged children (n = 191), the prevalence of LTP sensitization was greater than 30%. Unexpectedly, sensitization to Cor a 1 was observed in children not sensitized to Bet v 1. CONCLUSION: Sensitization to hazelnut LTP is a risk factor for objective symptoms in children from a birch-endemic area. [Abstract]

Allam JP, Peng WM, Appel T, Wenghoefer M, Niederhagen B, Bieber T, Bergé S, Novak N
Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Despite high bacterial colonization, acute infections are rare in the oral mucosa, implicating tolerogenic predominance. Bacterial antigens like LPSs are recognized by innate immunity receptors such as Toll-like receptor 4 (TLR4), associated with LPS receptor (CD14). OBJECTIVES: Toll-like receptor 4 agonist monosphoryl lipid A has been successfully used as adjuvant in subcutaneous immunotherapy, suggesting reinforcement of allergen-specific tolerance. Recently sublingual immunotherapy (SLIT) has been shown to be an effective alternative to subcutaneous immunotherapy. We observed CD14 expression on human oral Langerhans cells (oLCs), representing a major target of SLIT. However, not much is known about TLR4 expression and its effect on oLCs. METHODS: Cell suspensions were obtained by trypsinization of human oral mucosa and analyzed by flow cytometry, RT-PCR, cytometric bead arrays, ELISA, and mixed lymphocyte reactions. RESULTS: We could show that oLCs express TLR4, and its ligation by monosphoryl lipid A upregulated expression of coinhibitory molecules B7-H1 and B7-H3 while surface expression of costimulatory molecule CD86 was concomitantly decreased. Furthermore, TLR4 ligation on oLCs increased their release of the anti-inflammatory cytokine IL-10 and decreased their stimulatory capacity toward T cells. Moreover, TLR4-ligation on oLCs induced IL-10, TGF-beta1, Forkhead box protein 3, IFN-gamma, and IL-2 production in T cells. CONCLUSION: In view of these data, TLR4-ligation on oLCs might not only play a role in pathogen recognition for efficient immunity but also contribute to the tolerogenic state predominating in the oral cavity. [Abstract]

Yokoi H, Choi OH, Hubbard W, Lee HS, Canning BJ, Lee HH, Ryu SD, von Gunten S, Bickel CA, Hudson SA, Macglashan DW, Bochner BS
Inhibition of FcvarepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. METHODS: Human mast cells were generated from CD34(+) precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by FcvarepsilonRI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca(++) flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcvarepsilonRI-dependent histamine and prostaglandin D(2) release, Ca(++) flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta-hexosaminidase release and Ca(++) flux triggered through FcvarepsilonRI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. CONCLUSION: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells. [Abstract]

Saffar AS, Dragon S, Ezzati P, Shan L, Gounni AS
Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Glucocorticoids have been shown to inhibit human neutrophil apoptosis, with implications that this might help accentuate neutrophilic inflammation. OBJECTIVE: The aim of this study was to investigate the molecular mechanisms involved in glucocorticoid-mediated inhibition of primary human neutrophil apoptosis. METHODS: Primary human neutrophils were isolated from peripheral blood of healthy volunteers and cultured in vitro with dexamethasone. RESULTS: Here we confirm that dexamethasone, a classical glucocorticoid, significantly inhibited apoptosis of primary human neutrophils. This inhibition was not dependent on transrepression of proapoptotic molecules but was associated with induction of antiapoptotic Mcl-1. Remarkably, glucocorticoid-mediated enhancement of Mcl-1 and survival were significantly suppressed by pharmacologic inhibition of p38 mitogen-activated protein kinase or phosphatidylinositol 3-kinase. Inhibition of the above kinases also blocked glucocorticoid-induced maintenance of mitochondrial transmembrane potential and suppression of caspases. CONCLUSION: Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase are protein kinases that regulate the prosurvival effect of glucocorticoids on human neutrophils. [Abstract]

Schroeder JT, Chichester KL, Bieneman AP
Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE-dependent activation is mediated by autocrine TNF-alpha.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Functional significance for the alphagamma(2) variant of the high-affinity IgE receptor (FcvarepsilonRI) reportedly expressed on human dendritic cell subtypes remains poorly understood. Studies show that immature plasmacytoid dendritic cells (pDCs) secrete large quantities of TNF-alpha and IL-6 when directly stimulated with anti-IgE antibody. This mode of activation, however, reduces Toll-like receptor 9 (TLR9) expression in pDCs and their ability to mount an IFN-alpha response when subsequently activated with oligodeoxynucleotide containing CpG. OBJECTIVE: To investigate the mechanisms underlying this IgE-dependent suppression of TLR9 and innate immune responsiveness in pDCs by focusing on autocrine cytokine responses. METHODS: pDCs were isolated from blood by using blood dendritic cell antigen 4 selection. Cytokine responses to anti-IgE antibody-dependent and/or CpG-dependent stimulation were measured by using ELISA. TLR9 expression was determined by using quantitative RT-PCR and Western blotting. RESULTS: The time required for downregulating TLR9 expression in pDCs after anti-IgE stimulation correlated with the induction and duration of TNF-alpha secreted by these cells. Pretreatment of pDCs with recombinant TNF-alpha (but not IL-6 or IL-10) markedly suppressed TLR9 expression. Functional response to CpG (ie, IFN-alpha induction) was also inhibited with TNF-alpha pretreatment (inhibitory concentration(50) = approximately 200 pg/mL). Finally, an antibody that neutralizes TNF-alpha activity completely restored TLR9 expression during anti-IgE stimulation and significantly improved IFN-alpha secretion on subsequent activation with CpG. CONCLUSION: Autocrine TNF-alpha secretion resulting from IgE/FcvarepsilonRI-dependent activation plays a critical role in suppressing TLR9-dependent responses in pDCs that normally promote T(H)1 activity. [Abstract]

Brightling C, Berry M, Amrani Y
Targeting TNF-alpha: A novel therapeutic approach for asthma.
J Allergy Clin Immunol. 2007 Nov 22;
Approximately 5% to 10% of patients with asthma have severe disease that is refractory or poorly responsive to inhaled corticosteroid therapy. These patients represent an important unmet clinical need because they experience considerable morbidity and mortality and consume a disproportionately large amount of health care resources. TNF-alpha is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. Evidence is emerging to suggest that it might play an important role in severe refractory disease. The development of novel TNF-alpha antagonists has allowed us to test the role of this cytokine in vivo. Preliminary studies have demonstrated an improvement in asthma quality of life, lung function, and airway hyperresponsiveness and a reduction in exacerbation frequency in patients treated with anti-TNF-alpha therapy. However, there is marked heterogeneity in response, suggesting that benefit is likely to be reserved to a small subgroup. Importantly, where efficacy is reported, this also needs to be considered in the context of concerns about the safety of anti-TNF-alpha therapies. Therefore the challenge for clinicians is to evaluate the risk/benefit ratio of these therapies in individual patients with asthma. [Abstract]

Bittner C, Grassau B, Frenzel K, Baur X
Identification of wheat gliadins as an allergen family related to baker's asthma.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Flour is still one of the most common causes of occupational asthma worldwide. Thus far, little is known about the relevant allergens causing baker's asthma. Therefore the reliability of current diagnostic procedures is insufficient. Only few of the suspected causative wheat allergens have been hitherto characterized on the molecular level. OBJECTIVE: The aim was to identify and characterize unknown wheat allergens related to baker's asthma to improve the reliability of diagnostic procedures. METHODS: A wheat pJuFo cDNA phage display library was created and screened for IgE binding to wheat proteins with pooled sera from patients with baker's asthma. After identifying an alphabeta-gliadin, the frequency of sensitization was investigated by means of ELISA screening of 153 bakers' sera with the recombinant alphabeta-gliadin. Furthermore, the allergenicity of native total gliadin (alphabeta, gamma, omega) was analyzed by means of ImmunoCAP. RESULTS: One cDNA clone was identified as an alphabeta-gliadin. Serum IgE antibodies to the recombinant allergen were found in 12% of bakers with occupational asthma. Of the asthmatic bakers, 33% showed sensitization to native total gliadin; 4% of them had negative results on routine IgE testing with wheat extract. CONCLUSIONS: Gliadins represent a newly discovered family of inhalable allergens in baker's asthma. This finding demonstrates that water-insoluble proteins might also represent causative allergens. [Abstract]

Maneechotesuwan K, Supawita S, Kasetsinsombat K, Wongkajornsilp A, Barnes PJ
Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Indoleamine-2, 3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays a key role in the regulation of T-lymphocyte function. IDO inhibits eosinophilic inflammation in a murine asthma model, but little is known about its role in asthmatic patients or the effects of corticosteroids on this key regulatory enzyme. OBJECTIVE: We studied IDO activity and the effect of inhaled corticosteroids (ICSs) in patients with asthma and how this correlated with eosinophilic inflammation. METHODS: After a 1-week run-in period on no therapy, 34 asthmatic patients were treated with only short-acting beta(2)-agonists as required or an ICS or an ICS in combination with a long-acting beta(2)-agonist, which were required for asthma control, and the treatment was continued for a further 4 weeks. Each patient underwent sputum induction at the end of the run-in and treatment periods. Sputum supernatant specimens were analyzed for IDO activity and kynurenine concentrations by using HPLC. RESULTS: All patients with mild intermittent and mild-to-moderate persistent asthma had low baseline IDO activity in induced sputum compared with that seen in age-matched nonasthmatic subjects. The IDO activity was markedly enhanced by either ICS (P = .03) or ICS/long-acting beta(2)-agonist (P < .0001) treatment, and this increase negatively correlated with sputum eosinophils but was positively associated with an increase in IL-10-positive macrophages. CONCLUSION: ICSs might exert their anti-inflammatory activity in asthmatic airways, at least in part, through the upregulation of IDO activity associated with increased IL-10 secretion from macrophages. [Abstract]

Ueda T, Niimi A, Matsumoto H, Takemura M, Yamaguchi M, Matsuoka H, Jinnai M, Chin K, Minakuchi M, Cheng L, Shirakawa T, Mishima M
TGFB1 promoter polymorphism C-509T and pathophysiology of asthma.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: TGF-beta1 can modulate airway inflammation and exaggerate airway remodeling. A polymorphism of a promoter region of TGFB1, C-509T, might be associated with the development of asthma, but its pathophysiologic relevance remains poorly understood. OBJECTIVE: We investigated relations of the C-509T polymorphism to airflow obstruction, sputum eosinophilia, and airway wall thickening, as assessed by means of computed tomography, in 85 patients with stable asthma. METHODS: The CC, CT, and TT genotypes were examined by means of PCR and restriction enzyme fragment length polymorphism. At a selected bronchus, 3 indices of airway wall thickness were measured with an automatic method. RESULTS: The CC, CT, and TT genotypes were found in 22, 46, and 17 patients, respectively. Serum TGF-beta1 levels were significantly associated with the polymorphism and were increased in the CT/TT genotypes. FEV(1) and sputum eosinophil percentages were also significantly associated with the polymorphism and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to airway wall thickness. CONCLUSION: In addition to increased serum TGF-beta1 levels, the T allele of the C-509T polymorphism is related to increased airflow obstruction but attenuated eosinophilic inflammation. The former relation is not attributed to thickening of the central airway walls. The latter relation might reflect the anti-inflammatory effect of TGF-beta1. The C-509T polymorphism has a complex role in asthma pathophysiology, presumably because of the diverse functions of TGF-beta1 and its various interactions with cells and humoral factors in vivo. [Abstract]

Schmechel D, Green BJ, Blachere FM, Janotka E, Beezhold DH
Analytical bias of cross-reactive polyclonal antibodies for environmental immunoassays of Alternaria alternata.
J Allergy Clin Immunol. 2007 Nov 22;
BACKGROUND: Alternaria alternata is recognized as an important aeroallergen indoors and outdoors, and exposure to the fungus has been identified as a risk factor for asthma. Two recent publications concluded that 95% to 99% of American homes contained detectable amounts of Alternaria antigens when analyzed with a polyclonal antibody (pAb)-based ELISA. OBJECTIVES: We investigated the cross-reactivity of the commercially available pAbs that were used in those studies. METHODS: Reactivity to 24 fungal species commonly found in indoor environments was analyzed by inhibition ELISA by using solid-phase A alternata antigen. The pAbs were also tested by immunoblotting and halogen immunoassay for a subgroup of fungi. RESULTS: Spores of 7 fungi including species of Alternaria, Ulocladium, Stemphylium, Epicoccum, Drechslera, and Exserohilum strongly inhibited the binding of the pAbs when tested by ELISA. Six other fungi reacted in the ELISA at a lower level, and 11 fungal species including several Penicillium, Aspergillus, Fusarium, and Cladosporium species failed to show inhibition. The immunoblots and the halogen immunoassay staining confirmed the cross-reactivity patterns of the ELISA. CONCLUSION: The pAbs against A alternata were found to cross-react broadly with related and nonrelated fungi. The prevalence data previously reported for A alternata should be considered to be fungal-reactive rather than A alternata-specific. [Abstract]

Levesque MC, Hauswirth DW, Mervin-Blake S, Fernandez CA, Patch KB, Alexander KM, Allgood S, McNair PD, Allen AS, Sundy JS
Determinants of exhaled nitric oxide levels in healthy, nonsmoking African American adults.
J Allergy Clin Immunol. 2007 Nov 23;
BACKGROUND: Asthma is a significant cause of morbidity and mortality for African Americans. Fraction of exhaled nitric oxide (FeNO) levels are increased in patients with asthma, and airway levels of nitric oxide metabolites regulate airway inflammation and airway diameter. More needs to be known about the factors that regulate FeNO. There is a need for FeNO reference values for African Americans. OBJECTIVE: We sought to establish reference values and identify factors associated with FeNO levels in healthy African American adults. METHODS: FeNO levels were measured in 895 healthy, nonsmoking African Americans between the ages of 18 and 40 years. FeNO measurements were repeated in 84 subjects. Factors potentially associated with FeNO were measured, including blood pressure, height, weight, and serum total IgE, eosinophil cationic protein, C-reactive protein, and nitrate levels. Data on respiratory symptoms, including upper respiratory tract infection (URI) symptoms, were collected. Univariate and multivariate analyses of the relationship between these variables and FeNO levels were performed. RESULTS: In healthy, nonsmoking African Americans FeNO levels were stable during repeated measurements (intraclass correlation coefficient, 0.81). Sex (P < .0001), serum total IgE levels (P < .0001), and current URI symptoms (P = .0002) contributed significantly to FeNO variability but together accounted for less than 50% of the variation in FeNO levels. CONCLUSION: The high correlation between repeated measurements of FeNO and the low correlation coefficients of known factors associated with FeNO suggest that other factors might contribute substantially to variability of FeNO levels in African Americans. [Abstract]

Woszczek G, Chen LY, Nagineni S, Kern S, Barb J, Munson PJ, Logun C, Danner RL, Shelhamer JH
Leukotriene D(4) induces gene expression in human monocytes through cysteinyl leukotriene type I receptor.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: Cysteinyl leukotrienes (CysLTs) are important mediators of innate immune responsiveness and chronic inflammatory diseases. CysLTs acting through CysLT receptors can influence the migration and activity of cells, such as eosinophils, monocytes, and dendritic cells. OBJECTIVE: We sought to determine the gene expression signature of human monocytes in response to CysLTs and to elucidate the signaling pathways involved in monocyte activation. METHODS: Gene expression was analyzed by using oligonucleotide microarrays. Responsiveness to CysLTs was assessed by using real-time PCR, calcium flux, kinase activation, and chemotaxis assays. RESULTS: CysLT type 1 receptor (CysLTR(1)) transcript 1 is predominantly expressed in human monocytes, and CysLTs signal through CysLTR(1) in these cells. Several immediate-early genes, including early growth response 2 and 3, FBJ murine osteosarcoma viral oncogene homolog B, activating transcription factor 3, and nuclear receptor subfamily 4 were significantly induced by leukotriene (LT) D(4). This effect was mediated by CysLTR(1) coupled to the G protein alpha inhibitory subunit, activation of phospholipase C, and inositol-1,4,5-triphosphate and store-operated calcium channels. LTD(4) induced p38 mitogen-activated protein kinase phosphorylation, a pathway also involved in the regulation of immediate-early gene expression in monocytes. LTD(4) stimulated monocyte chemotactic activity that was fully blocked by a selective CysLTR(1) inhibitor, MK571, and pertussis toxin, suggesting that CysLTR(1) coupled to the G protein alpha inhibitory subunit is a dominant functional pathway in human monocytes. CONCLUSION: Our data show that CysLTs acting through CysLTR(1) can significantly influence the activation and migration of human monocytes and that these effects can be fully inhibited by CysLTR(1) antagonists. CLINICAL IMPLICATIONS: Antileukotriene therapies are likely to significantly block the proinflammatory functions of human monocytes. [Abstract]

Casale TB, Romero FA, Spierings EL
Intranasal noninhaled carbon dioxide for the symptomatic treatment of seasonal allergic rhinitis.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: Noninhaled intranasal carbon dioxide (CO(2)) has been shown to be effective in the abortive treatment of migraine headache. Migraine headache is associated with trigeminal neuronal activation and release of calcitonin gene-related peptide, events also implicated in allergic rhinitis. Intranasal CO(2) might inhibit trigeminal neuronal activation and suppress the release of calcitonin gene-related peptide. OBJECTIVE: We studied whether noninhaled intranasal CO(2) would be effective in the treatment of seasonal allergic rhinitis. METHODS: We conducted a single-center, randomized, double-blind, placebo-controlled, parallel-group study. Treatment consisted of either CO(2) (verum) or air (placebo) at a 2:1 ratio administered in each nostril for 60 seconds per nostril at a flow rate of 10 mL/s. The primary efficacy end point was the change from baseline in total nasal symptom score (TNSS), the sum of congestion, rhinorrhea, itching, and sneezing scored on a 0- to 5-point scale, at 30 minutes. RESULTS: Eighty-nine subjects received treatment, 60 with CO(2) and 29 with placebo, and all subjects completed the study. CO(2) resulted in a statistically significant improvement in TNSS at 30 minutes over placebo (absolute changes of 5.0 for CO(2) and 2.2 for placebo, P = .00019). Improvement from baseline in TNSS (CO(2) vs placebo) was statistically significant at 10 minutes and remained so for 24 hours. CONCLUSION: Two 60-second intranasal CO(2) treatments resulted in rapid (10 minutes) and sustained (24 hours) relief of seasonal allergic rhinitis symptoms. CLINICAL IMPLICATIONS: Noninhaled intranasal CO(2) has potential as a safe and effective treatment for seasonal allergic rhinitis. [Abstract]

Salamon P, Shoham NG, Puxeddu I, Paitan Y, Levi-Schaffer F, Mekori YA
Human mast cells release oncostatin M on contact with activated T cells: Possible biologic relevance.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: We have recently demonstrated that mast cells can be activated by heterotypic adhesion to activated T cells. OBJECTIVE: We sought to perform gene expression profiling on human mast cells activated by either IgE cross-linking or by T cells and to characterize one of the cytokines, oncostatin M (OSM). METHODS: Gene expression profiling was done by means of microarray analysis, OSM expression was validated by means of RT-PCR, and the product was measured by means of ELISA in both the LAD 2 human mast cell line and in cord blood-derived human mast cells. Immunocytochemistry was used to localize OSM in human mast cells, and its biologic activity was verified by its effect on the proliferation of human lung fibroblasts. RESULTS: OSM was expressed and released specifically on T cell-induced mast cell activation but not on IgE cross-linking. OSM was localized to the cytoplasm, and its expression was inhibited by dexamethasone and mitogen-activated protein kinase inhibitors. OSM was also found to be biologically active in inducing lung fibroblast proliferation that was partially but significantly inhibited by anti-OSM mAb. In vivo mast cells were found to express OSM in both biopsy specimens and bronchoalveolar lavage fluid from patients with sarcoidosis. CONCLUSION: The production of OSM by human mast cells might represent one link between T cell-induced mast cell activation and the development of a spectrum of structural changes in T cell-mediated inflammatory processes in which mast cells have been found to be involved. CLINICAL IMPLICATIONS: Mast cells might serve as a target for treating T cell-mediated fibrotic processes. [Abstract]

Wang M, Karlsson C, Olsson C, Adlerberth I, Wold AE, Strachan DP, Martricardi PM, Aberg N, Perkin MR, Tripodi S, Coates AR, Hesselmar B, Saalman R, Molin G, Ahrné S
Reduced diversity in the early fecal microbiota of infants with atopic eczema.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: It might be that early intestinal colonization by bacteria in westernized infants fails to give rise to sufficient immune stimulation to support maturation of regulatory immune mechanisms. OBJECTIVE: The purpose of the present study was to characterize the very early infantile microbiota by using a culture-independent approach and to relate the colonization pattern to development of atopic eczema in the first 18 months of life. METHODS: Fecal samples were collected from 35 infants at 1 week of age. Twenty infants were healthy, and 15 infants were given diagnoses of atopic eczema at the age of 18 months. The fecal microbiota of the infants was compared by means of terminal restriction fragment length polymorphism (T-RFLP) and temporal temperature gradient gel electrophoresis (TTGE) analysis of amplified 16S rRNA genes. RESULTS: By means of T-RFLP analysis, the median number of peaks, Shannon-Wiener index, and Simpson index of diversity were significantly less for infants with atopic eczema than for infants remaining healthy in the whole group and for the Swedish infants when AluI was used for digestion. The same was found when TTGE patterns were compared. In addition, TTGE analysis showed significantly less bands and lower diversity indices for the British atopic infants compared with those of the control subjects. CONCLUSION: There is a reduced diversity in the early fecal microbiota of infants with atopic eczema during the first 18 months of life. CLINICAL IMPLICATIONS: This finding, if confirmed in larger patients and control populations, might inspire future strategies for primary prevention of IgE-mediated atopic eczema. [Abstract]

Kelly A, Bowen H, Jee YK, Mahfiche N, Soh C, Lee T, Hawrylowicz C, Lavender P
The glucocorticoid receptor beta isoform can mediate transcriptional repression by recruiting histone deacetylases.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: The glucocorticoid receptor (GR) is able to participate in regulation of transcription by a variety of mechanisms, one of which involves DNA binding and recruitment of regulatory cofactors. The best-studied forms of the receptor are the 777-amino-acid alpha and the 742-amino-acid beta variants. The beta isoform, which does not bind cortisol in human subjects, has been proposed to be a dominant-negative inhibitor of the transcriptional activation-competent GRalpha isoform. OBJECTIVE: GRalpha has roles in both transcriptional activation and repression. We wished to determine the influence of GRbeta on genes that are normally transcriptionally repressed by glucocorticoids. We studied IL5 and IL13, which both contribute to the asthmatic phenotype. METHODS: We used transient transfection systems and coimmunoprecipitation experiments to determine whether GRbeta has repressive activity on the promoters of the human IL5 and IL13 genes. RESULTS: GRbeta is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes. CONCLUSION: GRalpha and GRbeta act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GRbeta does not act as a dominant-negative inhibitor of GRalpha. CLINICAL IMPLICATIONS: Our data suggest that if GRbeta contributes toward glucocorticoid resistance by acting as a dominant-negative inhibitor of GRalpha function, then its influence does not lie at genes such as IL5 and IL13. GRbeta might have a more important role at genes that are normally activated by glucocorticoids. [Abstract]

Real FG, Svanes C, Omenaas ER, Antň JM, Plana E, Jarvis D, Janson C, Neukirch F, Zemp E, Dratva J, Wjst M, Svanes K, Leynaert B, Sunyer J
Lung function, respiratory symptoms, and the menopausal transition.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: There is limited information on potential changes in respiratory health when women enter the menopausal transition. OBJECTIVE: We sought to investigate whether the menopausal transition is related to lung function and asthma and whether body mass index (BMI) modifies associations. METHODS: Four thousand two hundred fifty-nine women from 21 centers (ECRHS II, 2002) responded to a questionnaire concerning women's health. Women aged 45 to 56 years not using exogenous sex hormones (n = 1274) were included in the present analysis. Lung function measurements (n = 1120) and serum markers of hormonal status (follicle-stimulating hormone, luteinizing hormone, and estradiol; n = 710) were available. Logistic and linear regression analyses were adjusted for BMI, age, years of education, smoking status, center, and height. RESULTS: Women not menstruating for the last 6 months (n = 432, 34%) had significantly lower FEV(1) values (-120 mL [95% CI, -177 to -63]), lower forced vital capacity values (-115 mL [95% CI, -181 to -50]), and more respiratory symptoms (odds ratio [OR], 1.82 [95% CI, 1.27-2.61]) than those menstruating regularly. Results were similar when restricting analyses to those who never smoked. Associations were significantly stronger in women with BMIs of less than 23 kg/m(2) (respiratory symptoms: OR, 4.07 [95% CI, 1.88-8.80]; FEV(1) adjusted difference: -166 [95% CI, -263 to -70]) than in women with BMIs of 23 to 28 kg/m(2) (respiratory symptoms: OR, 1.10 [95% CI, 0.61-1.97], P(interaction): .04; FEV(1) adjusted difference, -54 [95% CI, -151 to 43], P(interaction) = .06). CONCLUSIONS: Menopause is associated with lower lung function and more respiratory symptoms, especially among lean women. CLINICAL IMPLICATIONS: Clinicians should be aware of increased asthma risk and lower lung function in women reaching menopause. These problems appeared to be less pronounced among women with a BMI of approximately 25 kg/m(2). [Abstract]

Julius P, Lommatzsch M, Kuepper M, Bratke K, Faehndrich S, Luttmann W, Virchow JC
Safety of segmental allergen challenge in human allergic asthma.
J Allergy Clin Immunol. 2007 Oct 26;
BACKGROUND: Segmental allergen challenge is widely used to study mechanisms of human allergic asthma. Despite the relatively large dissemination, limited information is available about the safety of this method. OBJECTIVE: Observational, retrospective study to report the adverse events of segmental allergen challenge in a large group of volunteers with asthma. METHODS: In total, 78 cases from several studies performed between 1994 and 2007 were pooled for this analysis. Volunteers underwent allergen challenge using either a fixed dose of allergen (7 cases) or an individually standardized allergen dose defined by an inhaled allergen test before the challenge (71 cases). A subgroup of 13 volunteers underwent repeated challenges, with more than 6 months between the challenges. RESULTS: With a fixed dose instilled during bronchoscopy, 43% of the participants developed wheezing and coughing, requiring 2-6 puffs of a ss(2)-agonist after segmental allergen challenge. In volunteers with individually standardized doses, a ss(2)-agonist was required in only 19% of the cases. No severe adverse events occurred in all cases studied. Volunteers who underwent repeated challenges did not develop more adverse events than those who underwent 1 challenge. CONCLUSIONS: Segmental allergen challenge is a safe tool to study the mechanisms of human allergic asthma, even when repeated challenges are performed in the same patient. It is associated with only a few, tolerable adverse events, especially when the dose of allergen is standardized individually. CLINICAL IMPLICATIONS: This retrospective analysis confirms that segmental allergen challenge is a safe tool in human asthma research. [Abstract]

Pégorier S, Arouche N, Dombret MC, Aubier M, Pretolani M
Augmented epithelial endothelin-1 expression in refractory asthma.
J Allergy Clin Immunol. 2007 Dec;120(6):1301-7.
BACKGROUND: Airway remodeling in patients with severe steroid-refractory asthma might result from a reduced ability of steroid therapy to limit the transcription of remodeling factors by the bronchial epithelium. OBJECTIVE: We sought to compare the levels of transcripts encoding remodeling factors in bronchial epithelium of healthy volunteers and of asthmatic patients with either steroid-sensitive or steroid-refractory disease and to correlate these levels with hallmarks of airway remodeling. METHODS: By means of real-time quantitative PCR, we assessed the levels of 14 transcripts encoding remodeling factors, matrix metalolproteinases, and extracellular matrix proteins in laser-capture microdissected bronchial epithelium of healthy volunteers, patients with mild steroid-untreated asthma, and patients with steroid-sensitive and steroid-refractory asthma (n = 8-10 in each group). Histologic features of airway remodeling and endothelin-1 (EDN1) immunolocalization were determined by using frozen specimens. RESULTS: Patients with steroid-refractory asthma had greater levels of EDN1 transcripts (4.1-fold increase, P = .026) and protein (P = .0009) in their bronchial epithelium compared with patients with steroid-sensitive asthma. EDN1 mRNA levels and protein expression in asthmatic patients were negatively correlated with prebronchodilator and postbronchodilator FEV(1) value (r(2) >/= 0.193, P </= .03), and they were positively related to airway smooth muscle areas (r(2) = 0.253, P = .01 and r(2) = 0.281, P = .005 for EDN1 mRNA and protein expression, respectively). CONCLUSION: Increased EDN1 synthesis by the bronchial epithelium characterizes severe refractory asthma and correlates with airway remodeling and airflow obstruction. CLINICAL IMPLICATIONS: Targeting EDN1 might represent a novel therapeutic strategy for severe steroid-refractory asthma. [Abstract]

Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV
American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis.
J Allergy Clin Immunol. 2007 Dec;120(6):1373-7.
The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology Executive Committees formed the Omalizumab Joint Task Force with the purpose of reviewing the Genentech Xolair (omalizumab) clinical trials and postmarketing surveillance data on anaphylaxis and anaphylactoid reactions. Using the definition of anaphylaxis proposed at a 2005 multidisciplinary symposia, the Omalizumab Joint Task Force concluded that 35 patients had 41 episodes of anaphylaxis associated with Xolair (omalizumab) administration between June 1, 2003, and December 31, 2005. With 39,510 patients receiving Xolair (omalizumab) during the same period of time, this would correspond to an anaphylaxis-reporting rate of 0.09% of patients. Of those 36 events for which the time of reaction was known, 22 (61%) reactions occurred in the first 2 hours after one of the first 3 doses. Five (14%) of the events after the fourth or later doses occurred within 30 minutes. Considering the timing of these 36 events, an observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions. The OJTF report provides recommendations for physicians who prescribe Xolair (omalizumab) on (1) the suggested wait periods after administration and (2) patient education regarding anaphylaxis. [Abstract]


Recent Articles in Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology

Flicker S, Steinberger P, Eibensteiner PB, Lebecque S, Kraft D, Valenta R
Molecular characterization of a human immunoglobulin G4 antibody specific for the major birch pollen allergen, Bet v 1.
Clin Exp Allergy. 2007 Dec 7; .
Background Allergen-specific IgG4 antibodies induced by specific immunotherapy are thought to represent a protective immune response. Objective Our aim was the molecular characterization of a human IgG4 antibody (BAB5) specific for the major birch pollen allergen Bet v 1 that was derived from an immunotherapy-treated patient. Methods The cDNA coding for BAB5 was obtained by reverse transcriptase-PCR from the BAB5-producing cell line, compared with the germ line sequences and was expressed as a soluble antibody fragment in Escherichia coli. The epitope specificity and cross-reactivity of BAB5 were investigated with recombinant and synthetic Bet v 1 fragments and Bet v 1 homologous allergens from pollen. The ability of BAB5 to block allergic patients IgE was determined by competition experiments and sandwich ELISA. Results BAB5 is an affinity-matured Bet v 1-specific IgG4 antibody that reacts exclusively with Bet v 1 but not with Bet v 1-related allergens. Unlike an earlier-described monoclonal IgG1-blocking antibody, BAB1, which had been isolated from the same patient, BAB5 did not block allergic patients' IgE reactivity to Bet v 1. Conclusion Our study demonstrates that not all allergen-specific IgG antibodies inhibit IgE recognition of allergens and can contribute to the success of immunotherapy. The epitope specificity and affinity of IgG antibodies but not their isotype are decisive for their protective activity. [Abstract]

Pereira-Santos MC, Baptista AP, Melo A, Alves RR, Soares RS, Pedro E, Pereira-Barbosa M, Victorino RM, Sousa AE
Expansion of circulating Foxp3(+)CD25(bright) CD4(+) T cells during specific venom immunotherapy.
Clin Exp Allergy. 2007 Dec 7;
Background Venom immunotherapy (VIT) induces long-lasting immune tolerance to hymenoptera venom antigens, but the underlying mechanisms are not yet clarified. Regulatory T cells are thought to play an important role in allergic diseases and tolerance induction during specific immunotherapy. Aim Characterize longitudinally the impact of VIT on the pool of circulating regulatory T cells. Methods Fourteen hymenoptera venom-allergic patients with severe reactions (grades III-IV) were studied before, 6 and 12 months after starting ultra-rush VIT. Freshly isolated peripheral blood mononuclear cells were surface stained with a panel of markers of T cell differentiation and intracellularly for CTLA-4 and Foxp3 and analysed by flow cytometry. foxp3 mRNA was quantified by real-time PCR. VIT responses were assessed by measuring specific IgG4 and IgE levels. Eleven individuals with no history of insect venom allergy were studied as controls. Results VIT induces a significant progressive increase in both the proportion and the absolute numbers of regulatory T cells defined as CD25(bright) and/or Foxp3(+) CD4(+) T cells. These changes are not related to alterations in the expression of activation markers or imbalances in the naďve/memory T cell compartments. foxp3 mRNA levels also increased significantly during VIT. Of note, the increase in circulating regulatory T cell counts significantly correlates with the venom-specific IgG4/IgE ratio shift. Conclusion VIT is associated with a progressive expansion of circulating regulatory T cells, supporting a role for these cells in tolerance induction. [Abstract]

Takeuchi H, Zaman K, Takahashi J, Yunus M, Chowdhury HR, Arifeen SE, Baqui A, Wakai S, Iwata T
High titre of anti-Ascaris immunoglobulin E associated with bronchial asthma symptoms in 5-year-old rural Bangladeshi children.
Clin Exp Allergy. 2007 Dec 7;
Background Increasing interest has arisen whether helminthic infections protect against asthma and allergy. The prevalence of wheezing among Bangladeshi children is higher in rural areas where helminthic infectious burden is greater, which is contrary to the general assumption. Objective We therefore examined the association between Ascaris infection, serum level of anti-Ascaris IgE, which should be investigated differently from the infection, and wheezing in 5-year-old children from rural Bangladesh. Methods A total of 219 children who reported wheezing during the previous 12 months and 122 randomly selected age-matched individuals who had never experienced wheezing were tested for serum levels of total and specific Ascaris, Dermatophagoides pteronyssinus, alternaria and cockroach IgEs, and for intestinal helminth infection as well. Results Anti-Ascaris IgE levels were significantly and independently associated with current wheezing during the previous 12 months [odds ratio (OR) per log(e) increment is 1.31 (95% confidence interval (CI) 1.08-1.60), P=0.007], a history of at least four episodes of wheezing [OR per log(e) increment is 1.52 (95% CI 1.18-1.96), P=0.001], wheezing with sleep disturbances [OR per log(e) increment is 1.35 (95% CI 1.10-1.64), P=0.011] and wheezing with speech disturbances [OR per log(e) increment is 1.57 (95% CI 1.19-2.08), P=0.001]. These were adjusted for gender, pneumonia history, parental asthma, Trichuris infection, use of dry leaves as fuel and other specific IgE levels. The prevalence of Ascaris infection by the presence of wheezing was not significantly different (76% vs. 72%, respectively). Conclusion We conclude that a high titre of anti-Ascaris IgE is associated with an increased risk of asthma symptoms among 5-year-old rural Bangladeshi children with a high helminthic infectious load. [Abstract]

Liu X, Feng J, Xu ZR, Wang YZ, Liu JX
Oral allergy syndrome and anaphylactic reactions in BALB/c mice caused by soybean glycinin and beta-conglycinin.
Clin Exp Allergy. 2007 Dec 7;
Background Soybean protein is used in a number of food products but is also a common cause of food allergy. Soybean glycinin and beta-conglycinin represent up to one-third of protein in the soybean. Many reports have indicated that glycinin and beta-conglycinin have been characterized as major soybean allergens involved in food hypersensitivity. Objective To investigate oral allergy syndrome and anaphylactic reactions in BALB/c mice caused by soybean glycinin and beta-conglycinin with an intragastric feeding protocol without using an adjuvant. Methods BALB/c mice were sensitized by gavages with glycinin and beta-conglycinin, and allergen-specific IgE and IgG1 responses were studied by a passive cutaneous anaphylaxis assay. Serum histamine release and blood pressure were measured according to other methods. Epithelium and mast cell dye used the method of light microscopy. Results Sensitization with soybean allergens induced high levels of antigen-specific IgE and IgG1 and increased serum histamine in BALB/c mice. Percentiles of intact mast cell of small intestine in mice sensitized with glycinin and beta-conglyinin significantly decreased for 28 days. Degranulation of mast cells and damage of the epithelium in the small intestine of mice sensitized with globulins were observed. The level of blood pressure in sensitized mice reached a minimum at 3 h. Conclusion Soybean-specific IgE and IgG1 antibodies increased, with high levels of histamine release, severe degranulation of mast cells and damage of the epithelium of small intestine in mice sensitized with glycinin and beta-conglyinin. [Abstract]

Nagakura T, Ogino S, Okubo K, Sato N, Takahashi M, Ishikawa T
Omalizumab is more effective than suplatast tosilate in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis.
Clin Exp Allergy. 2007 Dec 7;
Background Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a major problem in Japan. Omalizumab, a humanized monoclonal anti-IgE antibody, improves symptoms associated with SAR, but a comparative study with an anti-allergy drug has not yet been conducted. Objective To compare the efficacy and safety of omalizumab with suplatast tosilate, a selective T-helper type 2 (Th2) cytokine inhibitor, in patients with Japanese cedar pollen-induced SAR. Methods A randomized, double-blind, double-dummy study was conducted in 308 Japanese patients with a history of moderate-to-severe SAR who showed a CAP-RAST value (>/=2+) specifically to Japanese cedar pollens. Patients were treated for 12 weeks with omalizumab plus placebo of suplatast tosilate or suplatast tosilate plus placebo of omalizumab. Results The mean daily nasal symptom medication scores (sum of the daily nasal symptom severity score and daily nasal rescue medication score) were significantly lower in the omalizumab group than in the suplatast tosilate group during three evaluation periods (P<0.001). The omalizumab group also had significantly lower mean daily nasal severity scores, each of the mean daily nasal and ocular symptom severity scores (sneezing, runny nose, stuffy nose, itchy nose, itchy eyes, watery eyes, and red eyes). Omalizumab reduced rescue medication requirements, and the proportion of days with any rescue medication use in the omalizumab group was significantly lower. Serum-free IgE levels markedly decreased in the omalizumab group and it was associated with clinical efficacy. The adverse reaction profiles were similar between the two groups. The overall incidence of injection site reactions was higher in the omalizumab group than in the suplatast tosilate group, but all these events were of mild degree. No anti-omalizumab antibodies were detected. Conclusion Omalizumab showed significantly greater improvements than suplatast tosilate in the treatment of SAR induced by Japanese cedar pollens. [Abstract]

Saarelainen S, Rytkönen-Nissinen M, Rouvinen J, Taivainen A, Auriola S, Kauppinen A, Kinnunen T, Virtanen T
Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity.
Clin Exp Allergy. 2007 Dec 7;
Background Although knowledge of the IgE cross-reactivity between allergens is important for understanding the mechanisms of allergy, the regulation of the allergic immune response and the development of efficient modes of allergen immunotherapy, the cross-reactivity of animal allergens is poorly known. Objective The aim of this study was to characterize IgE cross-reactivities between lipocalin proteins, including five animal-derived lipocalin allergens and one human endogenous lipocalin, tear lipocalin (TL). Methods The recombinant proteins were validated by chromatography and mass spectrometry. The IgE-binding capacity of the allergens was confirmed by IgE. immunoblotting and IgE immunoblot inhibition. IgE ELISA was performed with sera from 42 atopic patients and 21 control subjects. The IgE cross-reactivities between the lipocalin proteins were determined by ELISA inhibition. Results ELISA inhibition revealed IgE cross-reactivities between Can f 1 and human TL, between Can f 1 and Can f 2, and between Equ c 1 and Mus m 1. Low levels of IgE to human TL were found in the sera of seven dog-allergic patients of whom six were IgE-positive for Can f 1. Conclusion Several lipocalins exhibited IgE cross-reactivity, probably due to the sequential identity of the proteins and also due to similarities in their three-dimensional structures. The clinical significance of the findings needs to be elucidated. Low-level IgE cross-reactivity can play a role in regulating immune response to lipocalin allergens. [Abstract]

Wigginton SJ, Furtado PB, Armour KL, Clark MR, Robins A, Emara M, Ghaemmaghami AM, Sewell HF, Shakib F
An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of FcepsilonRI with FcgammaRIIb.
Clin Exp Allergy. 2007 Dec 7;
Background IgE binds to mast cells and basophils via its high-affinity receptor, FcepsilonRI, and cross-linking of FcepsilonRI-bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross-linking of FcepsilonRI with FcgammaRIIb, an ITIM-containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti-idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to FcepsilonRI-bound IgE, via its Fab regions, and the negative regulatory receptor, FcgammaRIIb, via its Fc region. Objective To assess the ability of human 2G10 to inhibit anti-IgE and allergen-driven basophil degranulation through cross-linking of FcepsilonRI-bound IgE with FcgammaRIIb. Methods 2G10 was assessed for its ability to bind to FcgammaRIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti-IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL-4 expression intracellularly, using flow cytometery. Results Human 2G10 was able to bind to FcgammaRIIb on transfected cells and on purified basophils, and induce a dose-dependent inhibition of both anti-IgE and Der p 1-driven degranulation of basophils. Conclusion The inhibition of basophil degranulation by the human IgG1 anti-idiotype 2G10 highlights the therapeutic potential of IgE-reactive IgG antibodies in restoring basophil integrity through recruitment of the inhibitory receptor FcgammaRIIb. [Abstract]

Horiguchi S, Tanaka Y, Uchida T, Chazono H, Ookawa T, Sakurai D, Okamoto Y
Seasonal changes in antigen-specific T-helper clone sizes in patients with Japanese cedar pollinosis: a 2-year study.
Clin Exp Allergy. 2007 Dec 7;
Background Allergic rhinitis (AR) is a typical type I allergic disease that occurs through the induction of allergen-specific effector T cells. Once established, new effector T cells derive mostly from memory T cells that are capable of surviving for extended periods, although the mechanisms by which these memory functions are maintained have not yet been clarified. In particular, the exact life-span of memory T cells is still not well understood. Objective Pollinosis patients seemed to be suitable subjects to investigate because such patients are exposed to antigens strongly for only a limited period once a year. We compared the seasonal changes in memory T-helper type 2 (Th2) between pollinosis and perennial allergic subjects. Methods The clone sizes of the Japanese cedar pollen-specific memory Th cells were measured by an ELISPOT assay using specific peptides from the patients with cedar pollinosis, and the seasonal changes were noted. This study was performed for 2 years. The cedar-specific IgE levels in the peripheral blood were also studied. Mite allergy patients were also enrolled in the study. Results The Japanese cedar-specific IL-4-producing Th2 cells were detected in all patients examined, although the number of cells was low. These Th memory cells increased during the pollen season and decreased during the off-season. However, more than 60% of the cedar-specific memory Th2 cells survived up to 8 months after the pollen season. The cedar-specific IgE levels exhibited changes similar to the cedar-specific Th cells. On the other hand, there was no drifting of Th memory clone size with the mite allergics, and the IgE levels also did not change. Conclusions While pollen-specific Th cells decreased after pollen exposure, their memory functions continued. Memory clone size maintenance therefore requires repetitive antigen irritation. [Abstract]

Granell R, Heron J, Lewis S, Smith GD, Sterne JA, Henderson J
The association between mother and child MTHFR C677T polymorphisms, dietary folate intake and childhood atopy in a population-based, longitudinal birth cohort.
Clin Exp Allergy. 2007 Dec 7;
Background A recent study suggested a link between folate metabolism and atopy, based on a positive association between a common polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and allergic sensitization in Danish adults. Objective We investigated the associations between MTHFR C677T and allergy or atopy in a large, population-based birth cohort of children and their mothers, the Avon Longitudinal Study of Parents and Children (ALSPAC). We also looked for evidence of a pre-natal effect of maternal folate metabolism on subsequent atopic disease in the offspring. Methods Mothers were recruited in pregnancy and the children followed from birth. Atopy in the child was assessed at 7-8 years of age by skin prick tests to common allergens. Asthma was defined as a physician diagnosis and current symptoms at 71/2 years of age. Asthma and allergy status of the mothers were obtained from self-completion questionnaires. Results Data on MTHFR C677T genotype and allergy were available for 5364 children and on allergy and/or asthma for 7356 mothers. In children, the prevalence of atopy was 20.0% and asthma 10.0% whereas in mothers, the prevalence of self-reported allergy was 42.7% and asthma 11.5%. Atopy in the child was associated with male gender (P<0.001), less tobacco smoke exposure and higher maternal education. MTHFR C677T genotype was not associated with social factors or dietary folate intake. We found no evidence of associations between the MTHFR C677T variant allele and atopy, allergy or asthma in mothers or children. There was no evidence to support an effect of maternal MTHFR C677T genotype on atopy in the offspring. Conclusion The results of this study do not support the hypothesis that impaired folate metabolism is associated with allergy in adults or children in this population. [Abstract]

Zosky GR, Larcombe AN, White OJ, Burchell JT, Janosi TZ, Hantos Z, Holt PG, Sly PD, Turner DJ
Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation.
Clin Exp Allergy. 2007 Dec 7;
Background Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. Objective To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. Methods BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. Results An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. Conclusions The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma. [Abstract]

Ko HM, Kang NI, Kim YS, Lee YM, Jin ZW, Jung YJ, Im SY, Kim JH, Shin YH, Cho BH, Lee HK
Glutamine preferentially inhibits T-helper type 2 cell-mediated airway inflammation and late airway hyperresponsiveness through the inhibition of cytosolic phospholipase A(2) activity in a murine asthma model.
Clin Exp Allergy. 2007 Dec 7;
Background The non-essential amino acid, l-glutamine (Gln), is abundant in the human body. Gln exhibits beneficial effects on endotoxic shock through the inhibition of cytosolic phospholipase A(2) (cPLA(2)) activity. cPLA(2) has been reported to be implicated in the pathogenesis of asthma, but the effects of Gln on asthma have not yet been defined. Objective To investigate the effects of Gln on allergic bronchial inflammation and airway hyperresponsiveness (AHR), and to determine the possible action mechanisms of Gln in a murine model of asthma. Methods cPLA(2) phosphorylation was assessed by immunoprecipitation and Western blotting. Smears of bronchoalveolar lavage cells were stained with Diff-Quik solution for differential cell counting. Airway levels of the proteins [T-helper type-1 (Th1) and Th2 cytokines, and mucin] were measured by ELISA. mRNA expression of cytokines was assessed by real-time RT-PCR. AHR was assessed as a change in airway resistance (RL). Histological studies were performed to assess the levels of mucin and pulmonary inflammation. Results Systemic Gln administration inhibited cPLA(2) phosphorylation and its enzymatic activity in the lungs. Additionally, Gln effectively suppressed the key features of Th2-dependent asthmatic features, such as airway eosinophilia, mucus formation, and airway type 2 cytokine production, as well as late AHR. Conclusion Gln was found to be effective in the suppression of Th2-dependent phenotypes and late AHR, and this effect of Gln appeared to be at least partially attributable to its ability to suppress cLPA(2) activity in the airway. Our results suggest that clinical use of Gln for patients with asthma may be beneficial. [Abstract]

Sullivan Dillie KT, Tisler CJ, Dasilva DF, Pappas TE, Roberg KA, Carlson-Dakes KT, Evans MD, Rosenthal LA, Gangnon RE, Gern JE, Lemanske RF
The influence of processing factors and non-atopy-related maternal and neonate characteristics on yield and cytokine responses of cord blood mononuclear cells.
Clin Exp Allergy. 2007 Dec 7;
Rationale Several studies have evaluated the associations between cord blood cellular responses and atopic diseases in children, but the results of these studies are inconsistent. Variations in blood processing factors and maternal and infant characteristics are typically not accounted for and may contribute to these inconsistencies. Methods Cord blood samples were obtained from 287 subjects participating in the Childhood Origins of ASThma project, a prospective study of children at high risk for the development of asthma/allergies. Mononuclear cells were stimulated with phytohaemagglutinin (PHA), phorbal myristate acetate/ionomycin or a suspension of killed staphylococcus, and IFN-gamma, IL-10 and IL-13 were quantitated by ELISA. Cell yields and cytokine production were related to processing factors and maternal and infant characteristics. Results The strongest relationships between independent variables and cell yield or cytokine responses occurred with the season of birth. The highest median cell yields were seen in fall, and the lowest in summer (difference of 47%, P=0.0027). Furthermore, PHA-induced IL-5 and IL-13 responses were approximately 50% higher in spring and summer than in fall or winter (P<0.0001). Clots in the cord blood samples were associated with a reduced median cell yield (42% reduction, P<0.0001), and an increased PHA-induced IL-10 secretion (27% increase, P=0.004). Conclusions These data suggest that season of collection, and to a lesser extent clotting in samples, affect cord blood mononuclear cell yield and cytokine responses. Careful documentation and analysis of processing and environmental variables are important in understanding biological relationships with cytokine responses, and also lead to greater comparability among studies using these techniques. [Abstract]

Joachim RA, Noga O, Sagach V, Hanf G, Fliege H, Kocalevent RD, Peters EM, Klapp BF
Correlation between immune and neuronal parameters and stress perception in allergic asthmatics.
Clin Exp Allergy. 2007 Dec 7;
Background Asthma is a chronic disease defined by airway inflammation, increased airway hyperresponsiveness and episodes of airway obstruction. Although there are abundant clinical and experimental data showing that stress may worsen asthma, the mechanisms linking stress to asthma are not well understood. By inducing a pro-inflammatory cytokine milieu, stress might enhance airway inflammation in bronchial asthma. We therefore investigated the correlation of stress perception and the cytokine profile of circulating lymphocytes in humans. Methods Allergic asthmatic patients and healthy controls were evaluated for perceived level of stress, demographic and lung function data. Whole blood cells were obtained and stimulated by mitogen to assess intracellular IL-4, IFN-gamma and TNF-alpha by flow cytometry. Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were measured in serum. Results Asthmatic patients showed significantly higher percentages of TNF-alpha-producing T cells than healthy controls. Only in asthmatic patients was stress perception correlated with percentages of TNF-alpha-producing T cells and serum BDNF levels, while forced expiratory volume in 1 s (% predicted) was negatively correlated to BDNF. Conclusion The results of our study support the hypothesis that stress deteriorates bronchial asthma by inducing a pro-inflammatory cytokine profile in allergic asthmatics. Stress management might provide a supplement therapy of allergic asthma. [Abstract]

Hogan SP, Rothenberg ME
Dietary allergenic proteins and intestinal immunity: a shift from oral tolerance to sensitization.
Clin Exp Allergy. 2007 Dec 7; [Abstract]

Vally H
Allergic and asthmatic reactions to alcoholic drinks: a significant problem in the community.
Clin Exp Allergy. 2007 Nov 21; [Abstract]

Brown JM, Wilson TM, Metcalfe DD
The mast cell and allergic diseases: role in pathogenesis and implications for therapy.
Clin Exp Allergy. 2007 Nov 21;
Mast cells have long been recognized for their role in the genesis of allergic inflammation; and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and mucosal membranes, which interface with the external environment; as well as being found within vascularized tissues next to nerves, blood vessels and glandular structures. Mast cells have the capability of reacting both within minutes and over hours to specific stimuli, with local and systemic effects. Mast cells express the high affinity IgE receptor (FcepsilonRI) and upon aggregation of FcepsilonRI by allergen-specific IgE, mast cells release and generate biologically active preformed and newly synthesized mediators which are involved in many aspects of allergic inflammation. While mast cells have been well documented to be essential for acute allergic reactions, more recently the importance of mast cells in reacting through pattern recognition receptors in innate immune responses has become recognized. Moreover, as our molecular understanding of the mast cell has evolved, novel targets for modulation have been identified with promising therapeutic potential. [Abstract]

Kim JH, Lee SY, Kim HB, Jin HS, Yu JH, Kim BJ, Kim BS, Kang MJ, Jang SO, Hong SJ
TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma.
Clin Exp Allergy. 2007 Nov 21;
Background Thromboxane A2 receptor (TBXA2R) gene polymorphism has been associated with atopy and asthma, but few studies have reported the effect of this gene polymorphism on asthma-related phenotype or responsiveness to leukotriene receptor antagonist (LTRA) in asthmatic children. This study investigated associations between asthma-related phenotypes and TBXA2R polymorphism, and also analysed whether the TBXA2R polymorphism has an effect on the efficacy of the LTRA, montelukast, in asthmatic children with exercise-induced bronchoconstriction (EIB). Methods Asthmatic children (n=695) and control children (n=159) were evaluated for asthma-related phenotypes including total IgE, pulmonary function test, and bronchial hyperresponsiveness to methacholine or exercise. Genotypes were detected by PCR-RFLP. In the montelukast study, exercise challenge was performed before and after an 8-week montelukast treatment. Results The TBXA2R polymorphism was not associated with asthma susceptibility and the clinical parameters of asthma. However, asthmatic children with combinations of the TBXA2R+795T>C and +924T>C risk alleles had significantly higher total IgE levels (P=0.01), total eosinophil counts (P<0.01) and lower forced expiratory volume in 1 s (FEV(1)) (P=0.02) and forced expiratory rates at 25-75% of vital capacity (P=0.02) than those carrying the common alleles. When compared with individuals with the common alleles, patients with the TBXA2R+924T>C TT homozygote and TBXA2R+795T>C hetero- or homozygote (CT or CC) had a 3.67-fold poor response to 8-week montelukast treatment with respect to maximum percent fall in FEV(1) after exercise (odds ratio, 3.67; 95% confidence interval, 1.15-11.15). Conclusions A combined effect of TBXA2R+795T>C and +924T>C risk alleles may be linked to IgE production, eosinophilic inflammation, and severity of asthma. In addition, the TBXA2R+795T>C genotype may be a predictive marker of a clinical response to the LTRA in Korean asthmatic children with EIB. [Abstract]

Hill DJ, Hosking CS, de Benedictis FM, Oranje AP, Diepgen TL, Bauchau V
Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study.
Clin Exp Allergy. 2007 Nov 19;
Background Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE-FS) that are commonly associated with IgE food allergy. Objectives To explore the relationship between high levels of IgE-FS and AE in a large cohort of young children with eczema participating in a multi-centre, international study. Methods Two thousand one hundred and eighty-four subjects (mean age 17.6 months, range 11.8-25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP-FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP-FEIA levels exceeded previously reported age-specific cut-off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high-risk IgE-FS (HR-IgE-FS). Results Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR-IgE-FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR-IgE-FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset-age <3 months had HR-IgE-FS. Conclusion Early-onset severe eczema in infancy was associated with HR-IgE-FS. Clinical implications Food allergies should be routinely assessed in infants with moderate or severe eczema. Capsule summary In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE-FS. [Abstract]

Miyake Y, Arakawa M, Tanaka K, Sasaki S, Ohya Y
Tuberculin reactivity and allergic disorders in schoolchildren, Okinawa, Japan.
Clin Exp Allergy. 2007 Nov 19;
Background Bacillus Calmette-Guérin (BCG) vaccination triggers a T-helper type 1 response. Whether BCG vaccination and positive tuberculin reactivity are preventive against allergic disorders remains controversial. Objective The current cross-sectional study investigated the relationship of BCG vaccination and tuberculin reactivity with the prevalence of allergic disorders using data from the Ryukyus Child Health Study (RYUCHS). Methods Subjects were 5717 schoolchildren aged 8-11 years in Okinawa, Japan. The RYUCHS collected information on symptoms of allergic disorders and potential confounding factors. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Data on BCG vaccination and tuberculin tests were obtained from school records. Allowance was made for grade, sex, sibship size, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Results No measurable relationship was found between BCG vaccination in infants and the prevalence of allergic disorders. Among 5567 BCG-vaccinated children, positive tuberculin reactivity (induration >/=10 mm) in the first grade was independently associated with a decreased prevalence of wheeze, asthma, and atopic eczema: the multivariate odds ratios for wheeze, asthma, and atopic eczema were 0.80 (95% confidence interval [CI], 0.67-0.94), 0.78 (95% CI, 0.64-0.95), and 0.77 (95% CI, 0.62-0.95), respectively. The inverse associations were more pronounced in children with a negative parental allergic history than in those with a positive parental allergic history. There was no significant relationship between tuberculin reactivity and allergic rhinoconjunctivitis. Conclusions The findings suggest that positive tuberculin reactivity may be inversely associated with the prevalence of wheeze, asthma, and atopic eczema, but not allergic rhinoconjunctivitis, especially among Japanese children without a parental allergic history. [Abstract]

Rebelo Gomes E, Fonseca J, Araujo L, Demoly P
Drug allergy claims in children: from self-reporting to confirmed diagnosis.
Clin Exp Allergy. 2007 Nov 19;
Background Poorly documented self-reported drug allergy (DAll) is a frequent problem in daily clinical practice and has a considerable impact on prescription choices. The diagnostic work-up of drug hypersensitivity (DHs) allows a better classification of the reactions and provides patients with more reliable information and recommendations for future treatments. Objective To assess the prevalence of self-reported adverse drug reactions (ADRs) and DAll in a paediatric population and to investigate children reporting suspected DAll in order to achieve a firm diagnosis. Design The first phase was based on a cross-sectional survey assessing the life occurrence of ADRs and self-reported DAll carried out at the outpatient clinic of a paediatric hospital. The second phase was based on the diagnostic work-up in children with parent-reported DAll, including detailed anamnesis and in vitro and in vivo investigations (skin and provocation tests). Participants One thousand four hundred and twenty-six parents responded to the initial survey. Sixty of the 67 patients with reported DAll were evaluated at the allergy clinic. Results The prevalences of self-reported ADRs and DAll were 10.2% and 6.0%, respectively. Most of the suspected allergic reactions were non-immediate cutaneous events attributable to beta-lactam antibiotics and occurred in very young children. Thirty-nine of the 60 patients consulting for evaluation had a plausible clinical history and were recommended further investigation. DHs was diagnosed in three children only, based on positive responses in skin (n=1) and oral provocation (n=2) tests. Conclusion ADRs are frequently reported in children, and many children are classified as having a DAll. After complete evaluation, only a few of these reactions can be attributed to DHs and DAll. Most of the patients (94% in this study) could actually tolerate the initially suspected drug. [Abstract]

Tanabe T, Fujimoto K, Yasuo M, Tsushima K, Yoshida K, Ise H, Yamaya M
Modulation of mucus production by interleukin-13 receptor alpha(2) in the human airway epithelium.
Clin Exp Allergy. 2007 Nov 19;
Background IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor alpha2 (IL-13Ralpha(2)) has been suggested to act as a 'decoy receptor' in the airway epithelium by inhibiting the IL-13 signal. However, the regulatory mechanisms for mucus production by IL-13Ralpha(2) remain unclear. Objective The aim of this study was to examine the role of IL-13Ralpha(2) in goblet cell hyperplasia and mucus overproduction by IL-13. Methods Bronchi were obtained from patients who underwent a lung resection due to lung cancer or benign lung tumours. Normal human bronchial epithelial cells (NHBECs) were isolated and cultured using an air-liquid interface (ALI) method. Results The number of periodic acid-Schiff's (PAS)-positive cells, goblet cells and MUC5AC-positive cells increased after adding IL-13 into NHBECs. The concentrations of MUC5AC protein in the supernatant and the mRNA expression of MUC5AC significantly increased after adding IL-13, and returned to control levels at 21 days. The mRNA expression of IL-13Ralpha(2) significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13Ralpha(2) in the supernatants significantly increased at 14 and 21 days. Anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2) reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL-13Ralpha(2) antibody increased the number of these cells and MUC5AC mRNA. The concentration of MUC5AC protein in the supernatant induced by IL-13 was reduced by anti- IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13Ralpha(2). Conclusion The soluble form of IL-13Ralpha(2) may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13Ralpha(1) in NHBECs. [Abstract]

Wopfner N, Bauer R, Thalhamer J, Ferreira F, Chapman M
Immunologic analysis of monoclonal and immunoglobulin E antibody epitopes on natural and recombinant Amb a 1.
Clin Exp Allergy. 2007 Nov 19;
Background Amb a 1 is the major allergen from ragweed pollen and more than 90% of ragweed-allergic patients react with this protein. Although Amb a 1 was cloned and sequenced in 1991, little is known of the specificity of anti-Amb a 1 antibodies or of the immunologic properties of the recombinant allergen. Objective To compare binding of monoclonal antibodies (mAb) and IgE antibodies to purified natural Amb a 1 (nAmb a 1) and recombinant Amb a 1 (rAmb a 1). Methods Binding of a panel of anti-Amb a 1 mAb and IgE antibodies to nAmb a 1 or rAmb a 1 was compared by immunoblotting. Chimeric ELISA was used to measure specific IgE to these allergens using 89 ragweed-allergic sera from Austria, Italy, Canada and the United States. Results The 8 mAb bound to a 38 kDa Amb a 1 band in ragweed pollen extract and a subset of 5 mAb also bound to the 26 kDa chain of nAmb a 1. A two-site ELISA was developed using a mAb pair, which was approximately 10-fold more sensitive to rAmb a 1. There was a significant correlation between IgE antibody binding to nAmb a 1 and rAmb a 1 (n=89, r=0.79, P<0.001). A subset of approximately 40% of patients showed greater reactivity to nAmb a 1 than to rAmb a 1. Conclusions The data suggest that there is less reactivity of human IgE to rAmb a 1 compared with nAmb a 1. The development of more sensitive, quantitative ELISA for Amb a 1 will require the production of new mAb especially directed against nAmb a 1. [Abstract]

Bossé Y, Thompson C, McMahon S, Dubois CM, Stankova J, Rola-Pleszczynski M
Leukotriene D(4)-induced, epithelial cell-derived transforming growth factor beta1 in human bronchial smooth muscle cell proliferation.
Clin Exp Allergy. 2007 Nov 19;
Background Cysteinyl-leukotrienes (cys-LTs) orchestrate many pathognomonic features of asthma in animal models of allergic airway inflammation, including bronchial smooth muscle cell (BSMC) hyperplasia. However, because cys-LTs alone do not induce mitogenesis in monocultures of human BSMC, the effect observed in vivo seemingly involves indirect mechanisms, which are still undefined. Objective This study aims to investigate the regulatory role of leukotriene (LT)D(4) on TGF-beta1 expression in airway epithelial cells and the consequence of this interplay on BSMC proliferation. Methods HEK293 cells stably transfected with cys-LT receptor 1 (CysLT1) (293LT1) were stimulated with LTD(4) and TGF-beta1 mRNA and protein expression was measured using Northern blot and ELISA, respectively. Conditioned medium (CM) harvested from LTD(4)-treated cells was then assayed for its proliferative effect on primary human BSMC. TGF-beta1 mRNA expression was also determined in tumoural type II pneumocytes A549 and in normal human bronchial epithelial cells (NHBE) following LTD(4) stimulation. Results The results demonstrated that LTD(4)-induced TGF-beta1 mRNA production in a time- and concentration-dependent manner in 293LT1. TGF-beta1 secretion was also up-regulated and CM from LTD(4)-treated 293LT1 was shown to increase BSMC proliferation in a TGF-beta1-dependent manner. The increased expression of TGF-beta1 mRNA by LTD(4) also occured in A549 and NHBE cells via a CysLT1-dependent mechanism. Conclusion In conclusion, elevated expression of cys-LTs in asthmatic airways might contribute to BSMC hyperplasia and concomitant clinical features of asthma such as airway hyperresponsiveness via a paracrine loop involving TGF-beta1 production by airway epithelial cells. [Abstract]

Pesonen M, Ranki A, Siimes MA, Kallio MJ
Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20-year follow-up study.
Clin Exp Allergy. 2007 Nov 19;
Background Previous studies suggest an association between an altered lipoprotein profile and atopy. The association has been hypothesized to be due to alterations in the dietary fat intake, a factor possibly contributing to the increase of allergic diseases in industrialized countries. Objective We aimed at assessing whether there is an association between the serum lipid levels in infancy and subsequent development of allergic symptoms in childhood and adolescence. Methods A cohort of 200 unselected newborns was prospectively followed up from birth to age 20 years (from 1981 to 2002) with repeated measurements of total cholesterol from birth and throughout the first year of life. The subjects were re-examined at the ages of 5, 11 and 20 years, with assessment of the occurrence of allergic symptoms, skin prick testing (SPT) and measurement of total IgE and of the total, high- and low-density lipoprotein cholesterol. Results Children and adolescents with allergic symptoms, SPT positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the non-atopic subjects. The difference was not detectable in cord blood, but became significant from age 2 months onward. Conclusion The inverse association between the cholesterol level in infancy and subsequent manifestations of atopy seems not to be due to atopy-related dietary alterations, because it was already present in early infancy, when virtually all the infants were on a similar diet, i.e. on exclusive breastfeeding. [Abstract]

Roessler A, Friedrich U, Vogelsang H, Bauer A, Kaatz M, Hipler UC, Schmidt I, Jahreis G
The immune system in healthy adults and patients with atopic dermatitis seems to be affected differently by a probiotic intervention.
Clin Exp Allergy. 2007 Nov 19;
Background Probiotic bacteria are proposed to alleviate atopic dermatitis (AD) in infants. There are few indications about the effect of probiotics on AD in adults. Objective The purpose of this study was to elucidate the influence of a probiotic drink containing a combination of the probiotics Lactobacillus paracasei Lpc-37, Lactobacillus acidophilus 74-2 and Bifidobacterium animalis subsp. lactis DGCC 420 (B. lactis 420) in healthy volunteers and in patients with AD on clinical and immunological parameters and their detection in feces. Methods A double-blind, placebo-controlled, randomized cross-over study was conducted in 15 healthy adults and 15 patients with AD. The probiotic product or placebo was given over 8 weeks. A 2-week washout period was interconnected before the intervention was crossed. At the end of each period, blood and stool samples were collected. In patients, the severity of AD was evaluated using the Scoring of Atopic Dermatitis (SCORAD). Results L. paracasei and B. lactis were recovered in high numbers in feces after supplementation, whereas L. acidophilus marginally increased. In patients, the SCORAD tended to decrease by 15.5% (P=0.081). Major lymphocyte subsets were not affected by the probiotic intervention. However, CD57(+) increased significantly (P=0.034) in healthy subjects after probiotic intake and was not changed in patients, whereas CD4(+)CD54(+) decreased significantly (P=0.031) in patients with AD and remained uninfluenced in healthy subjects. The expression of CD4(+)CD25(+) T cells was similar in healthy subjects and AD patients. The phagocytic activity of monocytes and granulocytes was significantly increased in healthy subjects after probiotic intervention (P=0.014). Conclusion L. paracasei Lpc-37 and B. lactis 420 are able to colonize the intestine transiently. This study reveals that the probiotics differently modulate peripheral immune parameters in healthy subjects and patients with AD. [Abstract]

Agrawal DK, Cheng G, Kim MJ, Kiniwa M
Interaction of suplatast tosilate (IPD) with chloride channels in human blood eosinophils: a potential mechanism underlying its anti-allergic and anti-asthmatic effects.
Clin Exp Allergy. 2007 Nov 19;
Introduction Alterations in chloride ion channels have been implicated in the induction of changes in cell shape and volume. Because blood and tissue eosinophilia are hallmarks of bronchial asthma, in this study we examined the role of chloride channels in the underlying effects of suplatast tosilate (IPD), an anti-allergic drug, in human blood eosinophils. Methods Eosinophils were isolated and purified from the blood of allergic asthmatic donors. Chloride ion currents were recorded using the whole-cell patch-clamp technique in freshly isolated eosinophils. The current-voltage relationship of whole-cell currents in human blood eosinophils was calculated and recorded. The effect of chloride channel blockers was examined on superoxide release, eosinophil chemotaxis as measured by the Boyden chamber, and eosinophil adhesion to endothelial cells. Radioligand binding studies with [(3)H]IPD and competition curves with chloride channel blockers were performed. Results IPD increased both inward and outward chloride currents in human blood eosinophils. IPD in 1 ng/mL did not have significant effect on chloride current. However, at 5 ng/mL IPD activated both outward and inward currents in human blood eosinophils. Chloride channel blockers inhibited IPD-induced respiratory burst in eosinophils, eosinophil chemotaxis, and eosinophil adhesion to endothelial cells. All these effects of IPD on chloride current and the resultant functional responses in human blood eosinophils were not due to its basic salt, p-toluenesulphonic acid monohydrate. Human blood eosinophils contained specific binding sites for [(3)H]IPD with K(D) and B(max) values of 187.7+/-105.8 nm and 58.7+/-18.7 fmol/10(6) cells, respectively. Both NPPB and DIDS competed, in a dose-dependent manner, for the specific binding of [(3)H]IPD in human blood eosinophils. Conclusion These data suggest that the anti-allergic and anti-asthmatic effects of IPD could be due to its interaction with chloride channels in human blood eosinophils. [Abstract]

Porsbjerg C, Brannan JD, Anderson SD, Backer V
Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients.
Clin Exp Allergy. 2007 Nov 19;
Background Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect airway inflammation more closely compared with AHR measured by stimuli that act directly on BSM. Methods Fifty-three adult non-smoking asthmatics (28 females, 18-56 years) who were not taking inhaled steroids were challenged with mannitol (up to 635 mg) and methacholine (up to 8 mumol). Induced sputum eosinophils, exhaled nitric oxide (eNO), peak flow variation and clinical severity of asthma according to the Global Initiative for Asthma guidelines were measured in addition to the health-related quality-of-life score using the Juniper asthma quality-of-life questionnaire. Findings Both AHR to mannitol as well as to methacholine was associated with elevated markers of airway inflammation: in 83% of asthma patients with AHR to mannitol, and in 88% of asthma patients with AHR to methacholine, the eNO level was >20 p.p.b. Sputum% eosinophils >1% was measured in 70% of asthma patients with AHR to mannitol and in 77% of asthma patients with AHR to methacholine. In asthma patients without AHR, 15% had an eNO level >20 p.p.b., but none had sputum% eosinophils >1%. AHR to mannitol was more closely associated with the percentage of sputum eosinophils (PD(15) to mannitol vs. sputum% eosinophils: r: -0.52, P<0.05), compared with AHR to methacholine (PD(20) to methacholine vs. sputum% eosinophils: r: -0.28, NS). Furthermore, there was a stronger correlation between AHR to mannitol and the level of eNO [PD(15) to mannitol vs. eNO (p.p.b.): r: -0.63, P<0.001], compared with AHR to methacholine [PD(20) to methacholine vs. eNO (p.p.b.): r: -0.43, P<0.05]. Interpretation In asthma patients not being treated with steroids, AHR to mannitol and to methacholine indicated the presence of airway inflammation. AHR to mannitol reflected the degree of airway inflammation more closely when compared with methacholine. [Abstract]

Kobayashi M, Kume H, Oguma T, Makino Y, Ito Y, Shimokata K
Mast cell tryptase causes homologous desensitization of beta-adrenoceptors by Ca(2+) sensitization in tracheal smooth muscle.
Clin Exp Allergy. 2007 Nov 19;
Background Recent studies have revealed that in asthma, mast cells infiltrate to the smooth muscle layer and release tryptase, an enzymatic activator of protease-activated receptor 2 (PAR2). This phenomenon, mast cell myositis, is proposed as a new feature of asthma. However, little is known about the involvement of mast cell myositis in the pathophysiology of asthma. Objective This study was designed to determine whether mast cell degranulation has any functional impact on beta-adrenoceptors via PAR2 in airway smooth muscle. Moreover, we focused on Ca(2+) signalling as a mechanism underlying alteration of smooth muscle tone and responsiveness. Methods Isometric tension and F(340)/F(380), an indicator of the concentration of intracellular Ca(2+) ([Ca(2+)](i)), were simultaneously measured using fura-2-loaded tissues isolated from guinea-pig tracheal smooth muscle. Results Tryptase (1-100 nm) caused tension with elevated F(340)/F(380), and after exposure to tryptase for 15 min the inhibitory effect of isoprenaline (ISO) against methacholine was attenuated without elevating F(340)/F(380) in a concentration-dependent manner. Tryptase (<1 nm) had a modest effect on tension, but prolonged treatment (</=120 min) with 0.1 nm tryptase also reduced the effects of ISO in a time-dependent manner. When tissues were incubated with tryptase in the presence of Y-27632, a Rho-kinase inhibitor, reduced responsiveness to ISO by tryptase was reversed without affecting F(340)/F(380). In contrast, pre-treatment with SKF96365, a non-selective inhibitor of Ca(2+) channels, did not antagonize the effect of tryptase. Moreover, pre-treatment with SLIGKV-NH(2), a non-enzymatic activator of PAR2, resulted in a loss of beta-adrenergic efficacy, similar to tryptase. The effect of cAMP-related agents bypassing beta-adrenoceptors was not attenuated after exposure to tryptase. Conclusion In mast cell myositis, tryptase released from mast cells acts on airway smooth muscle, leading to homologous beta-adrenergic desensitization mediated by [Ca(2+)](i)-independent mechanisms via PAR2 activation. [Abstract]


Corrigendum.
Clin Exp Allergy. 2007 Dec;37(12): [Abstract]


British society for allergy and clinical immunology annual conference - july 2007 - abstracts.
Clin Exp Allergy. 2007 Dec;37(12): [Abstract]

Lin J, Renault N, Haas H, Schramm G, Vieths S, Vogel L, Falcone FH, Alcocer MJ
A novel tool for the detection of allergic sensitization combining protein microarrays with human basophils.
Clin Exp Allergy. 2007 Dec;37(12):
Background Protein microarray (PM) is a powerful alternative to costly or labour-intensive diagnostic for the large-scale detection of allergen-specific IgE. In this study, we established a proof-of-concept that coupling the diversity of protein array with the biological output of basophilic cells is a feasible proposition. Method Human basophils purified from the peripheral blood of healthy donors were stripped, re-sensitized with the serum or IgE preparation to be tested, and incubated with manually spotted protein array chips (FAST slides). The basophilic cell lines KU-812 and RBL-703/21 likewise sensitized were compared with peripheral blood basophils by the same approach. Purified basophils or other basophilic cells were incubated with FAST slides for various periods of time, washed, and cell binding was visualized by light microscopy. Basophil activation, indicating the effective cross-linking of IgE by allergens, was monitored via up-regulation of basophil activation surface marker (CD 63). Results Purified stripped peripheral basophils, re-sensitized with the serum of a grass pollen-allergic patient, displayed strong binding to anti-IgE antibody and grass pollen extract with relatively low unspecific binding. Similar results were obtained with RBL-703/21, which may be a good replacement for peripheral basophils to avoid the costly, cumbersome and time-consuming basophil purification. Conclusion Our data suggest that coupling the diversity of a PM approach with the potential functionality and biological activity of a cell-based test is feasible and may result in a new system to detect allergic sensitization. [Abstract]

Kuehni CE, Strippoli MP, Low N, Brooke AM, Silverman M
Wheeze and asthma prevalence and related health-service use in white and south Asian pre-schoolchildren in the United Kingdom.
Clin Exp Allergy. 2007 Dec;37(12):
Background Epidemiological data for south Asian children in the United Kingdom are contradictory, showing a lower prevalence of wheeze, but a higher rate of medical consultations and admissions for asthma compared with white children. These studies have not distinguished different asthma phenotypes or controlled for varying environmental exposures. Objective To compare the prevalence of wheeze and related health-service use in south Asian and white pre-schoolchildren in the United Kingdom, taking into account wheeze phenotype (viral and multiple wheeze) and environmental exposures. Methods A postal questionnaire was completed by parents of a population-based sample of 4366 white and 1714 south Asian children aged 1-4 years in Leicestershire, UK. Children were classified as having viral wheeze or multiple trigger wheeze. Results The prevalence of current wheeze was 35.6% in white and 25.5% in south Asian 1-year-olds (P<0.001), and 21.9% and 20.9%, respectively, in children aged 2-4 years. Odds ratios (ORs) (95% confidence interval) for multiple wheeze and for viral wheeze, comparing south Asian with white children, were 2.21 (1.19-4.09) and 1.43 (0.77-2.65) in 2-4-year-olds after controlling for socio-economic conditions, environmental exposures and family history. In 1-year-olds, the respective ORs for multiple and viral wheeze were 0.66 (0.47-0.92) and 0.81 (0.64-1.03). Reported GP consultation rates for wheeze and hospital admissions were greater in south Asian children aged 2-4 years, even after adjustment for severity, but the use of inhaled corticosteroids was lower. Conclusions South Asian 2-4-year-olds are more likely than white children to have multiple wheeze (a condition with many features of chronic atopic asthma), after taking into account ethnic differences in exposure to some environmental agents. Undertreatment with inhaled corticosteroids might partly explain their greater use of health services. [Abstract]

Kay AB, Holgate ST
Editorial announcement.
Clin Exp Allergy. 2007 Dec;37(12): [Abstract]

Larramendi CH, Ferrer A, Huertas AJ, García-Abujeta JL, Andreu C, Tella R, Cerdŕ MT, Bartra J, Lavín JR, Pagán JA, López-Matas MA, Fernández-Caldas E, Carnés J
Sensitization to tomato peel and pulp extracts in the Mediterranean Coast of Spain: prevalence and co-sensitization with aeroallergens.
Clin Exp Allergy. 2007 Nov 13;
Background Tomatoes (Lycopersicon esculentum) are consumed world-wide. The prevalence of sensitization to tomatoes remains unknown. Objective To determine the prevalence of skin test reactivity to tomato and to describe the characteristics of tomato-sensitized subjects. Methods Individuals attending for the first time during the period of the study to six Allergy centres, located along the Mediterranean coast of Spain, reporting respiratory and/or cutaneous symptoms, were included. All patients were skin prick tested with a battery of inhalant allergens and with peel and pulp of Canary tomato extracts. Results The study included 1734 individuals (757 males, 977 females; 31.9+/-17.8 years old). The prevalence of sensitization to tomato was 6.52% (113 patients; 65 males, 48 females; 29.5+/-13 years old). The peel extract was positive in 110 patients and the pulp extract in 47 patients; three patients were positive exclusively to pulp. Only 1.8% of individuals reported symptoms with tomato; 44% of them had skin test negative to both extracts. Among tomato-sensitized subjects, 16% reported symptoms with tomato, 97% were sensitized to inhalant aeroallergens, including 84% to pollens (mainly Artemisia vulgaris and Platanus hybrida), with differences between Northern and Southern centres. Conclusions The prevalence found of skin test sensitivity to tomato is high. Peel extracts detected most of the sensitized subjects. Most of the sensitized subjects were asymptomatic and some patients reported symptoms without skin test sensitivity. Positive subjects were very frequently sensitized to pollens, suggesting allergen cross-reactivity. Regional differences may exist, possibly related to the pattern of sensitization to cross-reacting pollens. [Abstract]

Cardoso CR, Teixeira G, Provinciatto PR, Godoi DF, Ferreira BR, Milanezi CM, Ferraz DB, Rossi MA, Cunha FQ, Silva JS
Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation.
Clin Exp Allergy. 2007 Nov 13;
Background Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. Objective To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. Methods C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. Results Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gammadelta(+) and CD4(+)CD25(+)Foxp3(+) cells in Peyer's patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. Conclusion A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response. [Abstract]


Recent Articles in Allergy

Serrano C, Guilarte M, Tella R, Dalmau G, Bartra J, Gaig P, Cerdŕ M, Cardona V, Valero A
Oestrogen-dependent hereditary angio-oedema with normal C1 inhibitor: description of six new cases and review of pathogenic mechanisms and treatment.
Allergy. 2007 Dec 7; .
Background: Hereditary angio-oedema (HAE) is a rare condition in which there is a deficiency in the quantity or activity of C1 inhibitor (C1INH). Recently, an additional type of HAE with no alterations in the levels or the function of C1INH has been reported. It is defined as HAE with normal C1INH, and named type III HAE or oestrogen-dependent HAE. The aim of this study is to describe the clinical and laboratory findings of six new cases of type III HAE and to review the literature about this disease. Methods: A short description of six women with recurrent angio-oedema is provided. The characteristics of the patients are compared with the previously reported case series in a literature-based review. Results: The mean age of the patients at onset was 22 years (range 16-30). All of them had angio-oedema attacks during oestrogen-based contraceptive treatment and four reported episodes during pregnancy. Four patients reported a positive past family history. Two of them had experienced episodes of laryngeal oedema. None of the patients responded to corticoids or antihistamines during the attacks. Levels and functional activity of C1INH were within the normal range in all cases. Conclusions: Clinical and laboratory findings mirror the observations of previous reports of oestrogen-dependent angio-oedema with normal C1INH. This is the first published series of type III HAE in Spain. [Abstract]

Zhou LF, Zhang MS, Hu AH, Zhu Z, Yin KS
Selective blockade of NF-kappaB by novel mutated IkappaBalpha suppresses CD3/CD28-induced activation of memory CD4(+) T cells in asthma.
Allergy. 2007 Dec 7;
Background: Nuclear factor kappaB (NF-kappaB) overactivation plays a crucial role in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation and decreased apoptosis of CD4(+) T cells. We have shown that targeted NF-kappaB suppression in dendritic cells by adenoviral gene transfer of a novel mutated inhibitor of NF-kappaB (IkappaBalpha) (AdIkappaBalphaM) contributes to T-cell tolerance, but the immunosuppressive action of AdIkappaBalphaM on memory (CD45RO(+)) CD4(+) T cells remains enigmatic. Methods: CD45RO(+) T cells from Dermatophagoides farinaei-sensitized asthmatic patients, untransfected or transfected with AdIkappaBalphaM or AdLacZ (beta-galactosidase) for 24 h, were stimulated with anti-CD3 (1.0 mug/ml) plus anti-CD28 (0.5 mug/ml) monoclonal antibody for an additional 24 h. IkappaBalphaM transgene expression and NF-kappaB activation were detected by polymerase chain reaction (PCR), reverse transcriptase-PCR (RT-PCR), Western blot analysis, and electrophoretic mobility shift assay. Phenotype and apoptosis were measured by flow cytometry, annexin V binding, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling analyses. Cytokine production and cell proliferation were determined using enzyme-linked immunosorbent assay and [(3)H] thymidine incorporation. Results: A unique 801-bp IkappaBalphaM cDNA and a dose-dependent increase in IkappaBalphaM transgene expression were observed in AdIkappaBalphaM-transfected CD45RO(+) T cells. Significantly, AdIkappaBalphaM inhibited CD3/CD28-mediated NF-kappaB activation in CD45RO(+) T cells, leading to evident apoptosis, reduction of eotaxin, RANTES, Th1 [interferon (IFN)-gamma and interleukin (IL)-2], and Th2 (IL-4, IL-5, and IL-13 despite a slight decrease in IL-10) cytokines and secondary proliferative response. AdIkappaBalphaM also upregulated cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and downregulated CD69 besides no change in CD28. Conclusion: IkappaBalphaM might be beneficial to augment memory CD4(+) T-cell tolerance through modulating B7-CD28/CTLA-4 co-stimulatory pathways and NF-kappaB-dependent cytokine profiles in allergic inflammatory diseases including asthma. [Abstract]

Bousquet PJ, Chatzi L, Jarvis D, Burney P
Assessing skin prick tests reliability in ECRHS-I.
Allergy. 2007 Dec 7;
Introduction: Atopy, the clinical definition of an immunoglobulin E (IgE) high-responder, can be documented either by the detection of IgE antibodies in serum or by a positive skin prick test. Epidemiological studies use different reaction sizes to define a skin test reaction as positive or negative. The aim of the study was to identify the best cut-off level for skin prick tests. Method: Using the data collected during the European Community Respiratory Health Survey (ECHRS I) the association of serum allergen-specific IgE and skin prick tests [Dermatophagoides pteronyssinus (Der p), cat, timothy grass and Cladosporium] were assessed. Results: The proportion of the 11 355 subjects (49.9% men), with positive skin tests ranged from 10.4% (cut-off >5 mm) to 20.9% (cut-off >0 mm) for Der p, 3.5-10.2% for cat, 9.3-16.6% for timothy grass and 0.2 and 2.3% for Cladosporium. For identifying subjects with detectable specific IgE (>0.35 kU/l) the most appropriate cut-off appeared to be over 0 mm for Der p, cat and timothy grass (Youden Index over 0.81). However, the relationship between serum IgE and skin prick test for Cladosporium was weak (Youden index under 0.56). Conclusion: In epidemiological studies, a single method may be chosen to assess allergenic sensitivity. A cut-off level of over 0 mm for skin prick tests was best at identifying those with allergen-specific IgE. [Abstract]

Gaga M, Ong YE, Benyahia F, Aizen M, Barkans J, Kay AB
Skin reactivity and local cell recruitment in human atopic and nonatopic subjects by CCL2/MCP-1 and CCL3/MIP-1alpha.
Allergy. 2007 Dec 6;
Background: Monocyte chemotactic protein (MCP-1/CCL2), the ligand for CCR2 and CCR5, and macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3), the ligand for CCR1 and CCR5, are potent chemo-attractants in vitro and produce lesions in experimental animals, which resemble immediate and delayed-type hypersensitivity (DTH) reactions. CCL3 induces mononuclear cell and granulocyte infiltration in human atopic and nonatopic skin. Whether CCL2 (MCP-1) has comparable activity in man is uncertain as is the capacity of both the chemokines to elicit immediate- and DTH-like reactions in humans. Methods: Inflammatory cells were counted by immunohistochemistry in 24 and 48-h skin biopsies from atopics and nonatopics after intradermal injection of CCL2 and CCL3. Immediate (15 min) wheals-and-flares and delayed (24 and 48 h) indurations were also recorded. Results: Both chemokines induced immediate- (15 min) and delayed (24 and 48 h) reactions, which were associated with significant infiltrations of CD68+ macrophages, CD3+, CD4+ (but not CD8+) T cells, neutrophils, and eosinophils in biopsies from injection sites. CCL2, but not CCL3, also induced infiltration of basophils. Neither chemokine produced significant changes in the numbers of tryptase+ cutaneous mast cells. There were no differences in the pattern of skin reactivity or the numbers of infiltrating leukocytes in response to CCL2 and CCL3 between atopic and nonatopic subjects. In general, maximal infiltration of inflammatory cells was observed at the 24-h, rather than the 48-h, time point. Conclusions: CCL2 and CCL3 induce both immediate and delayed skin reactions in atopics and nonatopics, and evoke a similar profile of local T cell/macrophage and granulocyte recruitment which, in general, confirm previous in vitro findings and in vivo experimental animal data. [Abstract]

Bochenek G, Nizankowska E, Gielicz A, Szczeklik A
Mast cell activation after adenosine inhalation challenge in patients with bronchial asthma.
Allergy. 2008 Jan;63(1): [Abstract]

Benucci M, Manfredi M, Demoly P, Campi P
Injection site reactions to TNF-alpha blocking agents with positive skin tests.
Allergy. 2008 Jan;63(1): [Abstract]

Camargos P, Ibiapina C, Lasmar L, Cruz AA
Author's reply on: 'Obtaining concomitant control of allergic rhinitis and asthma with a nasally inhaled steroid'.
Allergy. 2008 Jan;63(1): [Abstract]

Chaudhuri R, McSharry C, McCoard A, Livingston E, Hothersall E, Spears M, Lafferty J, Thomson NC
Role of symptoms and lung function in determining asthma control in smokers with asthma.
Allergy. 2008 Jan;63(1):
BACKGROUND: Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known. AIM OF THE STUDY: The aim of this study was to compare asthma control in smokers vs never-smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV(1)) value. METHODS: This was a cross-sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with >or=15% reversibility in FEV(1) after salbutamol. All subjects completed the ACQ, recording FEV(1) and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler). RESULTS: Compared with the never-smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1-2.3) vs 2.8 (1.7-3.4); (P < 0.0001)] and in each of the six individual symptom question scores (P < 0.001), but no difference in FEV(1) levels (P = 0.908). CONCLUSION: Asthma control is significantly worse in asthmatics who smoke compared with never-smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV(1). [Abstract]

Accordini S, Corsico A, Cerveri I, Gislason D, Gulsvik A, Janson C, Jarvis D, Marcon A, Pin I, Vermeire P, Almar E, Bugiani M, Cazzoletti L, Duran-Tauleria E, Jőgi R, Marinoni A, Martínez-Moratalla J, Leynaert B, de Marco R
The socio-economic burden of asthma is substantial in Europe.
Allergy. 2008 Jan;63(1):
BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females. [Abstract]

Fraj J, Valero A, Vives R, Pérez I, Borja J, Izquierdo I, Picado C
Safety of triflusal (antiplatelet drug) in patients with aspirin-exacerbated respiratory diseases.
Allergy. 2008 Jan;63(1):
BACKGROUND AND AIMS: Aspirin, a cyclo-oxygenase (COX)-1 and COX-2 inhibitor, is the antiplatelet drug of choice to prevent serious vascular events. Adverse reactions to aspirin are frequent particularly among patients with asthma, chronic rhinosinusitis and nasal polyps. COX-1 inhibitors but not COX-2 inhibitors precipitate asthma attacks. Triflusal is a preferential COX-2 inhibitor antiplatelet agent that is as effective as aspirin in the prevention of serious vascular events. The aim of the study was to assess the tolerability of triflusal in patients with aspirin-exacerbated respiratory disease (AERD). METHODS: We studied 26 asthma patients [11 males, aged 52 (23-75) years] who had suffered asthma episodes triggered by one or more (23% of patients) nonsteroidal anti-inflammatory drugs. Aspirin sensitivity was confirmed by either intranasal or oral aspirin challenge. All subjects underwent a single-blind, placebo-controlled oral challenge with three doses of triflusal separated by 1 week (first cumulative dose = 225 mg; second cumulative dose = 450 mg; third cumulative dose = 900 mg). Cutaneous, respiratory, general symptoms and lung function were monitored for 4 h in the laboratory and for 24 h at home. RESULTS: No clinical reactions to triflusal were observed. There were no significant changes in lung function measurements. CONCLUSION: Our study appears to demonstrate that triflusal is a suitable alternative to aspirin as antiplatelet agent to prevent AERD. [Abstract]

LaForce C, Alexander M, Deckelmann R, Fabbri LM, Aisanov Z, Cameron R, Owen R, Higgins M
Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study.
Allergy. 2008 Jan;63(1):
BACKGROUND: Indacaterol is a novel, once-daily beta(2)-agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation. OBJECTIVE: A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol. METHODS: A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 microg via multi-dose dry-powder inhaler (MDDPI; Certihaler), indacaterol 400 microg via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored. RESULTS: All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV(1)) from 22 to 24 h postdose (P <or= 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment-placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 microg via MDDPI and 400 microg via SDDPI, respectively. All doses increased mean FEV(1) (P < 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild-to-moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders. CONCLUSION: Once-daily dosing with indacaterol provided sustained 24-h bronchodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 microg appears the optimum dose, offering the best efficacy/safety balance. [Abstract]

Jacobson JS, Mellins RB, Garfinkel R, Rundle AG, Perzanowski MS, Chew GL, Andrews HF, Goldstein IF
Asthma, body mass, gender, and Hispanic national origin among 517 preschool children in New York City.
Allergy. 2008 Jan;63(1):
BACKGROUND: Striking differences in asthma prevalence have been reported among Hispanic adults and children living in different cities of the USA. Prevalence is highest among those of Puerto Rican and lowest among those of Mexican origin. We hypothesized that body size would mediate this association. METHODS: Parents of children in New York City Head Start programs completed a questionnaire including demographic factors, health history, a detailed history of respiratory conditions, lifestyle, and home environment. Children's height and weight were measured in home visits. Logistic regression was used to model the association of asthma with body mass index percentile (<85th percentile, gender/age specific vs>or=85th percentile, gender/age specific), national origin, and other factors. RESULTS: Of 517 children at mean age of 4.0 +/- 0.6 years, 34% met the study criteria for asthma, and 43% were above the 85th percentile. Asthma was strongly associated with non-Mexican national origin, male gender, allergy symptoms, and maternal asthma, and marginally with body size. The odds of asthma among boys of non-Mexican origin was 5.9 times that among boys of Mexican origin [95% confidence interval (CI): 2.9-12.2]; the comparable odds ratio (OR) among girls was 1.8 (95% CI: 0.9-3.6). Body mass was associated with asthma among girls [OR = 2.0 (95% CI: 1.1-3.7)], but not boys [OR = 1.4 (95% CI: 0.8-2.6)]. CONCLUSIONS: The association of asthma with both body mass and national origin was gender-specific among the children in our study. Ours is one of the first studies to report on pediatric asthma in different Hispanic populations in the same city, by gender. [Abstract]

Schoefer Y, Schäfer T, Meisinger C, Wichmann HE, Heinrich J
Predictivity of allergic sensitization (RAST) for the onset of allergic diseases in adults.
Allergy. 2008 Jan;63(1):
BACKGROUND: Specific IgE antibodies are often detected without any clinical manifestation of allergies. We aimed to analyse the predictivity of allergic sensitization for incident symptoms of allergic diseases in adults during a 10-year follow-up. METHODS: In 1994/95 specific IgE antibodies against five common inhalant allergens (grass pollen, birch pollen, house dust mite, cat dander and Cladosporium) were diagnosed by radioallergosorbent test in 4178 adults aged 25-74 years. A subset of 2656 participants could be re-evaluated in 2004/05. Information on socio-economic factors and medical history, including data on atopic diseases, was assessed by a combination of a personal interview and a self-administered questionnaire. Logistic regression models were applied to study associations between allergic sensitization and incident allergic diseases. RESULTS: Allergic sensitization was an important predictor for incident hay fever (OR 7.95, CI 95% 4.64-13.62) and asthma (OR 1.82, CI 95% 1.29-2.57). Specific IgE antibodies were mainly related to outdoor allergens (grass and birch pollen) for hay fever and indoor allergens (mite and cat dander) for asthma, while for atopic dermatitis no specific IgE antibodies were identified as major predictors. CONCLUSIONS: Allergic sensitization not only covers clinically apparent allergies, but indicates a prognostic factor for later allergies, even in adulthood. [Abstract]

Lin YL, Shieh CC, Wang JY
The functional insufficiency of human CD4+CD25 high T-regulatory cells in allergic asthma is subjected to TNF-alpha modulation.
Allergy. 2008 Jan;63(1):
BACKGROUND: Natural CD4(+)CD25(high)Foxp3(+) regulatory T (nTreg) cells are important in maintaining immunologic tolerance, but their role in the pathogenesis of allergic asthma is unclear. We studied the function of nTreg cells in allergic asthmatic children and assessed the factors which may relate to the functional insufficiency of nTreg cells. METHODS: The percentage of CD4(+)CD25(high) Treg cells, the expression of Foxp3, and the cell-induced suppressive activity of nTreg cells isolated from nonatopic controls, allergic asthmatics, and allergen-specific immunotherapy (AIT)-treated asthmatic patients were studied. RESULTS: Although the percentage of nTreg in peripheral blood mononuclear cells was increased, the expression of Foxp3 and its cell-induced suppressive activity were significantly lower in Dermatophagoides pteronyssinus (Der p)-sensitive asthmatic children when compared to nonatopic controls. In contrast, the expression of Foxp3 and the functional activity of nTreg cells were reversed in allergic asthmatics who received AIT. The addition of recombinant tumor necrosis factor (TNF)-alpha directly downregulated Foxp3 expression and abrogated the cell-induced suppressive function of Treg cells. The anti-TNF-alpha reagent, etanercept, restored the functional activity and Foxp3 expression of CD4(+)CD25(high) Treg derived from allergic asthmatics. CONCLUSIONS: The functional insufficiency of nTreg cells in patients with allergic asthma may be related to the enhanced production of TNF-alpha and its effect on the Foxp3 expression. These results may explain, in part, the effectiveness of anti-TNF-alpha therapy in the treatment of allergic asthma. [Abstract]

Brozek JL, Baena-Cagnani CE, Bonini S, Canonica GW, Rasi G, van Wijk RG, Zuberbier T, Guyatt G, Bousquet J, Schünemann HJ
Methodology for development of the Allergic Rhinitis and its Impact on Asthma guideline 2008 update.
Allergy. 2008 Jan;63(1):
BACKGROUND: We describe the methodology for the 2008 update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The methodology differs from the 2001 edition in several respects. The most prominent change is the application of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to compiling evidence, assessing the quality of evidence and grading of recommendations. METHODS AND RESULTS: Representatives of the GRADE working group joined the ARIA guideline panel to achieve these tasks. While most recommendations result from existing systematic reviews, systematic reviews were not always available and the panel compiled the best available evidence in evidence profiles without conducting actual reviews. The panel conducted two meetings and used the GRADE criteria to assess the quality of evidence (four categories of high, moderate, low and very low) and the strength of recommendation (strong and weak) based on weighing up the desirable and undesirable effects of management strategies, considering values and preferences influencing recommendations, and resource implications. The guideline panel has chosen the words 'we recommend'--for strong recommendations and 'we suggest'--for weak recommendations. Both categories indicate the best course of action for a given patient population, but their implementation, requires different considerations as we describe subsequently in this article. CONCLUSIONS: The 2008 update of the ARIA guidelines has become more evidence-based. Future iterations of the guidelines will further be improved by following the described processes even closer, such as ensuring availability of updated high quality systematic reviews for each question. [Abstract]

Simons FE, Frew AJ, Ansotegui IJ, Bochner BS, Golden DB, Finkelman FD, Leung DY, Lotvall J, Marone G, Metcalfe DD, Müller U, Rosenwasser LJ, Sampson HA, Schwartz LB, van Hage M, Walls AF
Practical allergy (PRACTALL) report: risk assessment in anaphylaxis.
Allergy. 2008 Jan;63(1):
Effector mechanisms in anaphylaxis were reviewed. Current approaches to confirmation of the clinical diagnosis were discussed. Improved methods for distinguishing between allergen sensitization (which is common in the general population) and clinical risk of anaphylaxis (which is uncommon) were deliberated. Innovative techniques that will improve risk assessment in anaphylaxis in the future were described. [Abstract]

Bacharier LB, Boner A, Carlsen KH, Eigenmann PA, Frischer T, Götz M, Helms PJ, Hunt J, Liu A, Papadopoulos N, Platts-Mills T, Pohunek P, Simons FE, Valovirta E, Wahn U, Wildhaber J
Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report.
Allergy. 2008 Jan;63(1):
Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative, which is endorsed by both academies. [Abstract]

Bousquet J, Bieber T, Fokkens W, Humbert M, Kowalski ML, Niggemann B, Simon HU, Schünemann H
Consensus statements, evidence-based medicine and guidelines in allergic diseases.
Allergy. 2008 Jan;63(1): [Abstract]

Hens G, Vanaudenaerde BM, Bullens DM, Piessens M, Decramer M, Dupont LJ, Ceuppens JL, Hellings PW
Sinonasal pathology in nonallergic asthma and COPD: 'united airway disease' beyond the scope of allergy.
Allergy. 2007 Dec 5;
Background: In contrast to the epidemiological and clinical association between allergic rhinitis and asthma, upper airway inflammation is less characterized in patients with nonatopic asthma and virtually unexplored in chronic obstructive pulmonary disease (COPD). Here, sinonasal pathology is studied in patients with allergic asthma, nonallergic asthma and COPD. Methods: Ninety patients with stable bronchial disease were included in the study, of which 35 were diagnosed with allergic asthma, 24 with nonallergic asthma and 31 with COPD. Concurrently, 61 control subjects without pulmonary disease were included and matched for age and smoking habits respectively with the asthma and the COPD group. Sinonasal symptoms were evaluated on a visual analogue scale and rhinosinusitis-related impairment of quality of life was assessed with the sino-nasal outcome test-22 (SNOT-22) questionnaire. Nasal mucosal abnormalities were quantified with nasal endoscopy and nasal secretions collected for measuring inflammatory mediators. Results: Allergic asthmatics, nonallergic asthmatics and COPD patients reported more nasal symptoms than their respective control subjects, had a higher SNOT-22 score and presented more mucosal abnormalities in the nose. Nasal secretions of both allergic and nonallergic asthmatics contained higher levels of eotaxin, G-CSF, IFN-gamma and MCP-1 than controls. Allergic asthmatics had higher nasal IP-10 levels as well. COPD-patients had higher nasal levels of eotaxin, G-CSF and IFN-gamma than controls. Conclusion: Patients with allergic and nonallergic asthma and COPD show increased nasal symptoms and more nasal inflammation. Hence, our data confirm the 'united airways' concept to be beyond the scope of allergic asthma. [Abstract]

Sohn SW, Lee HS, Park HW, Chang YS, Kim YK, Cho SH, Kim YY, Min KU
Evaluation of cytokine mRNA in induced sputum from patients with allergic rhinitis: relationship to airway hyperresponsiveness.
Allergy. 2007 Dec 5;
Background: Although airway hyperresponsiveness (AHR) is a characteristic feature of asthma, it is also frequently present in allergic rhinitis (AR). However, the pathogenesis of AHR is unclear and the roles of cytokines in the airway have not been well established in AR. We sought to compare cytokine mRNA levels in the sputum of AR patients with or without AHR and those of asthma patients, and to evaluate whether differences in cytokine levels are associated with the development of an abnormal airway response and the absence of respiratory symptoms in AR patients with AHR. Methods: Airway cells were obtained by sputum induction from 18 AR patients with AHR, 58 AR patients without AHR, and 27 asthma patients. Airway cell cytokine levels, interleukin (IL) -4, IL-5, IL-13, vascular endothelial growth factor (VEGF), and interferon-gamma (IFN-gamma), were studied at the mRNA level by RT-PCR. Results: Vascular endothelial growth factor and IL-5 mRNA levels were significantly higher in AR patients with AHR than in AR patients without AHR, but these were lower than those of asthmatic patients. Eosinophils were significantly higher in AR patients with AHR and in asthmatic patients than in AR patients without AHR. Interleukin-4, IL-13, and IFN-gamma levels were not elevated in AR patients with or without AHR vs asthma patients. Conclusions: These findings suggest that VEGF and IL-5 can be important determinants of the development of AHR in AR patients and that lower levels of other cytokines may be associated with the absence of asthmatic symptoms in AR patients with AHR. [Abstract]

Lei Z, Liu G, Huang Q, Lv M, Zu R, Zhang GM, Feng ZH, Huang B
SCF and IL-31 rather than IL-17 and BAFF are potential indicators in patients with allergic asthma.
Allergy. 2007 Dec 5;
Background: Although the prevalence of allergic asthma increased quickly in the past decade, the diagnostic criteria have not been well established. The aim of the present study was to explore whether stem cell factor (SCF), B cell-activating factor (BAFF), and cytokines interleukin (IL)-17 and IL-31 are usable parameters for the diagnosis of allergic asthmatics. Methods: Blood samples were collected from patients with allergic asthma, control patients, and healthy control subjects. The serum concentrations of SCF, BAFF, IL-17, and IL-31 were measured by enzyme-linked immunosorbent assay. The corresponding mRNA levels in peripheral blood mononuclear cells (PBMCs) were determined by real-time reverse-transcription polymerase chain reaction. Results: A good correlation existed between protein levels of SCF and IL-31 and their mRNA levels (SCF: r = 0.6162; IL-31: r = 0.5463). The serum concentrations of SCF and IL-31 in allergic asthmatic patients, but not control patients, were significantly higher than those in normal control subjects (SCF: median 1.83 vs 0.85 ng/ml, P < 0.01; IL-31: 50.15 vs 10.01 pg/ml, P < 0.001). Consistently, the levels of SCF and IL-31 mRNAs in allergic asthmatic patients' PBMCs were also significantly higher than those in normal control subjects (P = 0.002 and P < 0.001, respectively). Conclusions: These findings suggest that allergic asthma is characterized by an elevation of cytokines SCF and IL-31 and the measurement of their expression at either protein level in serum or mRNA level in PBMCs will be a valuable parameter for the diagnosis of allergic asthma. [Abstract]

Venter C, Pereira B, Voigt K, Grundy J, Clayton CB, Higgins B, Arshad SH, Dean T
Prevalence and cumulative incidence of food hypersensitivity in the first 3 years of life.
Allergy. 2007 Dec 5;
Background: Prevalence and incidence of food hypersensitivity (FHS) and its trends in early childhood are unclear. Methods: A birth cohort born on the Isle of Wight (UK) between 2001 and 2002 was followed-up prospectively. Children were clinically examined and skin prick tested at set times and invited for food challenges when indicated. Results: Nine hundred and sixty-nine children were recruited and 92.9%, 88.5% and 91.9% of them respectively were assessed at 1, 2 and 3 years of age. Prevalence of sensitization to foods was 2.2%, 3.8% and 4.5% respectively at these ages. Cumulatively, 5.3% [95% confidence interval (CI): 3.9-7.1] children were sensitized to a food. Using open food challenge and a good clinical history, the cumulative incidence of FHS was 6.0% (58/969, 95% CI: 4.6-7.7). Based on double-blinded, placebo-controlled, food challenge (DBPCFC) and a good clinical history, the cumulative incidence was 5.0% (48/969, 95% CI: 3.7-6.5). There is no evidence to suggest that the incidence of FHS has increased, comparing these results with previous studies. Overall, 33.7% of parents reported a food-related problem and of these, 16.1% were diagnosed with FHS by open challenge and history and 12.9% by DBPCFC and history. Main foods implicated were milk, egg and peanut. Conclusions: By the age of 3 years, 5-6% of children suffer from FHS based on food challenges and a good clinical history. There were large discrepancies between reported and diagnosed FHS. Comparing our data with a study performed in the USA more than 20 years ago, there were no significant differences in the cumulative incidence of FHS. [Abstract]

Carracedo-Martinez E, Sanchez C, Taracido M, Saez M, Jato V, Figueiras A
Effect of short-term exposure to air pollution and pollen on medical emergency calls: a case-crossover study in Spain.
Allergy. 2007 Dec 5;
Background: A symmetric case-crossover design was used to analyse the short-term relationship between air pollution, pollen and emergency calls to medical services. Methods: This study covered patients who made medical emergency calls in the City of Vigo (Spain) during the period 1996-1999. Morbidity data were obtained from the records of the 061 Medical Emergency Control Center, in its capacity as the body officially coordinating all medical emergencies by telephone. Air pollution data were furnished by the Vigo Municipal Air Pollution Surveillance Grid. Pollen levels were provided by the staff of the Spanish Aerobiology Network in Vigo. Results: A rise of 10mug/m(3) in ambient particulate levels led to the risk of medical emergency calls requesting attention increasing by: (i) 1.97% [95% confidence interval (95% CI): 1.83-2.11%] for circulatory causes on the same day; (ii) 1.95% (95% CI: 1.76-2.14%) for respiratory causes at 2 days and (iii) 1.34% (95% CI: 1.23-1.45%) for combined circulatory and respiratory causes on the same day. A number of pollens displayed a statistically significant relationship with emergency calls. No interaction was in evidence between pollens and air pollutants. Conclusions: While elevations in particulate air pollution increase medical emergency calls because of cardiac or respiratory causes or both combined, elevations in pollen levels increase medical emergency calls because of respiratory causes. [Abstract]

Canonica GW, Bousquet J, Mullol J, Scadding GK, Virchow JC
A survey of the burden of allergic rhinitis in Europe.
Allergy. 2007;62 Suppl 85
BACKGROUND: The perceptions of patients and physicians regarding the symptoms and impact of allergic rhinitis (AR) were assessed in a prospective, cross-sectional, international survey. This paper presents the combined survey results from five European countries (Germany, France, Italy, Spain and the UK). METHODS: Data were recorded by 1,482 patients and matched with records from 415 primary care physicians and specialists. Diagnostic tests to confirm AR had been performed on 1,279 (86.3%) patients. Both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation in addition to those symptoms frequently, but not currently, present. Health-related quality of life (HRQoL) was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: A large proportion of patients had moderate-severe disease (67.2%; n = 996), persistent disease (42.5%; n = 630) and comorbidities such as asthma (31.5%; n = 467). Overall, patients rated their disease as more severe than did physicians (P < 0.001). At the time of the consultation, one-third of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. According to the physicians' assessment, good control of nasal and ocular symptoms was achieved in 45.4% (n = 673) and 51.3% (n = 760) of patients, respectively, and poor symptom control in 18.0% (n = 267) and 12.1% (n = 179). Overall, 43.3% (n = 641) of those surveyed were using two or more medicines for their AR. Health-related quality of life was correlated with disease severity and with the number of days without symptoms in the previous 4 weeks. Allergic rhinitis had a significantly greater impact in patients with more persistent disease than in those with intermittent disease (2.3 +/- 1.3 vs 1.9 +/- 1.2; P < 0.001). Nonetheless, 81.8% (n = 601) of patients with intermittent disease reported some impairment of their daily life as a result of their AR. CONCLUSIONS: Allergic rhinitis remains a significant health problem because of the high burden of symptoms and its impact on general well being and HRQoL among patients consulting for this condition. Overall, there was a poor correlation between patients and physicians in the reporting of disease severity. [Abstract]

Schatz M
A survey of the burden of allergic rhinitis in the USA.
Allergy. 2007;62 Suppl 85
BACKGROUND: A prospective, cross-sectional, international survey was conducted among patients and physicians to identify symptom perception and the impact of allergic rhinitis (AR) on health-related quality of life (HRQoL). This paper presents the results from the USA. METHODS: Data were recorded by 447 patients and matched with data collected on these patients by primary care physicians or specialists. Tests to confirm a diagnosis of AR had been performed on 345 (77.2%) patients. Because of the intermittent nature of the disease, both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation, in addition to symptoms frequently, but not currently, present. Health-related quality of life was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: According to the physicians' assessment, a large proportion of patients had moderate or severe disease (62.6%; n = 280), persistent disease (47.0%; n = 213) and comorbidities such as asthma (28.4%; n = 127). Comparison of the physicians' and patients' assessment of disease severity found that patients rated their disease as more severe than physicians across all three types of AR (P < 0.001). At the time of the consultation, 44.0% (n = 197) of patients were suffering from nasal and ocular symptoms, and 23.7% (n = 106) of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. More than 50% of the patients surveyed (56.4%; n = 252) were using two or more medications for their AR. Health-related quality of life correlated negatively with the number of symptom-free days in the previous 4 weeks. Allergic rhinitis had a significantly greater impact on patients with more persistent disease compared with those with intermittent disease (2.3 +/- 1.3 vs 1.4 +/- 1.1; P < 0.001); nevertheless, approximately two-thirds of patients with intermittent disease reported some impairment of their professional or daily life as a result of AR. CONCLUSIONS: The results of this survey highlight the unmet needs of the many patients in the USA who present during routine care with moderate or severe and/or persistent disease and an associated high symptom burden and impaired HRQoL. [Abstract]

Higgins V, Kay S, Small M
Physician and patient survey of allergic rhinitis: methodology.
Allergy. 2007;62 Suppl 85
Methodology for Disease Specific Programme (DSP) surveys designed by Adelphi Group Products is used each year to survey patients and physicians on their perceptions of treatment effectiveness, symptoms and impact of diseases. These point-in-time surveys, conducted in the USA and Europe (France, Germany, Italy, Spain and UK), provide useful information on the real-world management and treatment of diseases. This paper describes the methodology for the DSP survey in allergic rhinitis, detailing the preparation of materials, recruitment of physicians, data collection and data management. [Abstract]

Scadding GK, Bousquet J
Introduction: allergic rhinitis.
Allergy. 2007;62 Suppl 85 [Abstract]


Late breaking poster abstract sessions.
Allergy. 2007;62 Suppl 83 [Abstract]


Late breaking abstract sessions.
Allergy. 2007;62 Suppl 83 [Abstract]


Poster sessions.
Allergy. 2007;62 Suppl 83 [Abstract]


Poster discussion sessions.
Allergy. 2007;62 Suppl 83 [Abstract]


Oral sessions.
Allergy. 2007;62 Suppl 83 [Abstract]


Prelims.
Allergy. 2007;62 Suppl 83 [Abstract]

Magnan A, Meunier JP, Saugnac C, Gasteau J, Neukirch F
Frequency and impact of allergic rhinitis in asthma patients in everyday general medical practice: a French observational cross-sectional study.
Allergy. 2007 Nov 20;
Background: Allergic rhinitis (AR) and asthma are inflammatory conditions of the airways that often occur concomitantly. This observational, cross-sectional, national study was undertaken to describe the frequency and severity of AR in asthmatic patients. The impact of AR on the quality of life and the therapeutic management of patients in everyday general medical practice were also assessed. Methods: From April to October 2005, 1906 French general practitioners (GP) participated in the study. Each physician had to fill out a questionnaire (including the Juniper Asthma Control Questionnaire and a Rhinitis Questionnaire) for up to 10 consecutive adult asthmatic patients. The first three patients with a confirmed diagnosis of AR (Allergic Rhinitis and its Impact on Asthma classification) were asked to complete the Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Results: A total of 14 703 patient questionnaires and 4335 auto-questionnaires were analysed. Patients presented with intermittent (45%), mild (25%), moderate (25%) and severe (4%) persistent asthma. The frequency of AR in asthmatic patients was 55.2% (CI: 95%, 54.4-56.0%). Allergic rhinitis was mild for 54% and moderate/severe for 46% of patients. The frequency and severity of AR increased with the severity of asthma (P < 0.001). Moreover, AR was associated with worse asthma control whatever be the severity of asthma (P < 0.001). The global RQLQ scores of AR patients worsened with the severity of asthma (P < 0.001). Prescription of anti-asthma treatments significantly increased with the severity of AR. The majority of AR patients (81%) were treated for rhinitis. Conclusions: This survey suggested that AR was associated with more severe asthma, more difficulty to control asthma and substantial impairment of quality of life. The high frequency of AR in asthma patients requires that these conditions should be recognized and managed by GP. [Abstract]

Shaw J, Roberts G, Grimshaw K, White S, Hourihane J
Lupin allergy in peanut-allergic children and teenagers.
Allergy. 2007 Nov 19;
Background: Lupin has now been introduced into food production in the UK. There is a concern that, on account of cross-reactivity, peanut-allergic children are at high risk for lupin allergy. Aims: To investigate the prevalence of lupin sensitization and allergy in children with peanut allergy compared with atopic controls. Methods: Children (<18 years) were recruited. Peanut-allergic subjects either had a convincing history of peanut allergy with diagnostic peanut skin prick test (SPT) or specific-immunoglobulin E (IgE) results or a positive food challenge. Control subjects were atopic but not peanut-allergic. All subjects had SPT to peanut and lupin. Sensitized subjects were offered a randomized, double-blind, placebo-controlled lupin challenge. Lupin allergy was defined as objective immediate hypersensitivity reaction at food challenge. Results: Forty-seven peanut-allergic children and 46 atopic controls were recruited. Sixteen peanut-allergic children were sensitized to lupin [34%, 95% confidence interval (CI): 21-49%]. Nine were challenged to lupin. Two reacted (itchy mouth and urticaria; itchy mouth and 20% drop in peak expiratory flow rate) giving a minimum prevalence of lupin allergy in peanut-allergic children of 4.0% (95% CI: 1-15%). Atopic controls were significantly (P = 0.001) less likely to be sensitized to lupin (4%, 95% CI: 1-15%) and had smaller wheals and serum-specific IgE results. None of the atopic controls reacted on lupin challenge, giving a rate of allergy in the atopic controls of 0% (95% CI: 0-8%). Conclusions: A small but significant number of children with peanut allergy are allergic to lupin. Sensitization to lupin is much rarer in nonpeanut-allergic atopic subjects. [Abstract]


Recent Articles in Annals of Allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology

Mann RM
Response to "Allergist report: America faces an allergy/asthma crisis".
Ann Allergy Asthma Immunol. 2007 Nov;99(5):470; author repely 470-1. [Abstract]

Keat K, Harnett P, Fulcher DA
Carboplatin desensitization.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):468-9. [Abstract]

Williams AN, Kelso JM
Radiocontrast-induced anaphylaxis despite pretreatment and use of iso-osmolar contrast.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):467-8. [Abstract]

Fenton ME, Cockcroft DW, Wright JL, Churg A
Hypersensitivity pneumonitis as a cause of airway-centered interstitial fibrosis.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):465-6.
BACKGROUND: Airway-centered interstitial fibrosis (ACIF) has been postulated to be related to environmental exposures. OBJECTIVE: To describe a patient with ACIF associated with hypersensitivity pneumonitis. METHODS: We evaluated a patient with a 2-year history of progressive dyspnea and exercise intolerance. We performed computed tomography, pulmonary function tests, and skin prick tests. RESULTS: The patient's computed tomogram suggested hypersensitivity pneumonitis. Pulmonary function testing demonstrated a restrictive pattern. Results of skin prick tests to chicken, goose, canary, and budgie were negative. However, serum precipitins were positive to serum from pigeon, goose, duck, and chicken feathers. The patient was diagnosed as having ACIF. CONCLUSION: We believe that ACIF may represent a final common pathway for lung injury due to environmental exposure. [Abstract]

Paris K, Sorensen RU
Assessment and clinical interpretation of polysaccharide antibody responses.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):462-4.
This second article in the miniseries Practical Aspects of Ambulatory Diagnosis and Management of Immunodeficiency Disorders' extends the discussion on evaluation of individuals with suspected humoral immunodeficiency by reviewing the logistics and interpretation of the patient's ability to produce antibodies to polysaccharide antigens, specifically pneumococcal surface polysaccharides. The response to these polysaccharides is important in the evaluation of patients with documented immune abnormalities and those individuals who have normal total immunoglobulin levels. Although profound immune deficiencies, such as X-linked agammaglobulinemia and severe combined immunodeficiency, are always associated with a defect in specific antibody production, some immune disorders may have variable responses, whereas others with persistent IgG or IgG subclass deficiencies may have normal or clearly abnormal antipolysaccharide antibodies. Measurement of the response to pneumococcal polysaccharides is preferred because of the availability of a pure polysaccharide vaccine for antigen challenge and standardized techniques to measure specific antibody responses. [Abstract]

de Blay F, Barnig C, Kanny G, Purohit A, Leynadier F, Tunon de Lara JM, Chabane H, Guérin L
Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a double-blind, placebo-controlled study.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):453-61.
BACKGROUND: Sublingual immunotherapy (SLIT) is accepted as a safe and effective route for the treatment of grass pollen allergy, but clarification of its clinical and biological efficacy requires more study. OBJECTIVE: To evaluate the efficacy, safety, and compliance of SLIT with a standardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma. METHODS: This multicenter, randomized, double-blind study included 127 patients (aged 12-41 years; mean age, 24.9 years) with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma. They received either SLIT with a high-dose, standardized, 3-grass pollen extract or placebo for 10 months before and during the grass pollen season. The efficacy evaluation compared weekly clinical scores (defined as the sum of the symptom score and rescue medication score) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season. We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels. RESULTS: There was a trend in favor of the study group in the mean adjusted clinical score. The groups were not comparable on inclusion (P = .02): the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level. Additional exploration according to subgroups with and without asthma found that among the patients without asthma, the SLIT group had a significantly better clinical score (P = .045). Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group. CONCLUSION: SLIT with a standardized, high-dose, 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season. [Abstract]

Huang CF, Wang CC, Wu TC, Chu CH, Peng HJ
Effect of sublingual administration with a native or denatured protein allergen and adjuvant CpG oligodeoxynucleotides or cholera toxin on systemic T(H)2 immune responses and mucosal immunity in mice.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):443-52.
BACKGROUND: Sublingual immunotherapy has been recently used for allergic diseases, but its mechanisms are still unclear. OBJECTIVE: To examine the effect of sublingual administration of a native or denatured allergen alone or plus adjuvant on systemic T(H)2 responses and mucosal immunity in mice. METHODS: Naive or sensitized BALB/c mice were sublingually vaccinated biweekly for 3 weeks with ovalbumin (OVA) or urea-denatured OVA (CM-OVA) only or plus adjuvant CpG oligodeoxynucleotides (CpG) or cholera toxin (CT). Two weeks later, their specific serum IgG, IgG1, IgG2a, IgE, and saliva secretory IgA (SIgA) antibody responses and the cytokine profiles of spleen and cervical lymph node cells were investigated. RESULTS: Specific SIgA antibody responses were induced by vaccination with CM-OVA plus CpG or CT. Whereas vaccination with CM-OVA and CpG enhanced T(H)1 responses but inhibited IgE production, vaccination with CT and CM-OVA or OVA increased cervical lymph node cell production of interleukin (IL) 4, IL-5, and IL-6 and serum IgG1 antibody responses. In previously sensitized mice, sublingual vaccination with OVA or CM-OVA plus CT or CpG stimulated mucosal SIgA antibody responses, but did not enhance ongoing IgE antibody responses. CONCLUSIONS: Sublingual vaccination with OVA or CM-OVA plus adjuvant CT or CpG all can induce systemic and mucosal immunity, but CM-OVA plus CpG had the best prophylactic and therapeutic effects on IgE antibody production. It is likely that sublingual vaccines may have a role for the prophylaxis and immunotherapy of allergic reactions. [Abstract]

Lee WI, Huang JL, Kuo ML, Lin SJ, Chen LC, Chen MT, Jaing TH
Analysis of genetic defects in patients with the common variable immunodeficiency phenotype in a single Taiwanese tertiary care hospital.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):433-42.
BACKGROUND: Seven known genetic defects, including Bruton tyrosine kinase (Btk), CD4OL, and signaling lymphocyte activation molecule-associated protein (SAP) (all X-linked) and inducible costimulator molecule (ICOS), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B-cell-activating factor of the tumor necrosis family receptor (BAFFR), and CD19 (all autosomal recessive), were found in patients with the phenotype of common variable immunodeficiency (CVID). OBJECTIVE: To investigate these 7 candidate protein expressions and candidate gene sequences for comprehensive analysis of known genetic defects in patients with CVID. METHODS: These 7 candidate protein expressions were evaluated by flow cytometry or Western blot, and candidate genes were evaluated by direct sequencing. RESULTS: Of 9 CVID patients from a single Taiwanese tertiary care hospital, we identified 2 cousins with decreased Btk expression who had a mutated (Asp521Val) kinase domain of Btk (1694A>T in exon 15) and 1 patient with decreased CD40L expression who had a mutated (Thr254Met) extracellular domain of CD40L (782T>C in exon 5). CONCLUSION: This comprehensive approach revealed that, in Taiwan, in some patients mild forms of X-linked agammaglobulinemia and hyper-IgM syndrome caused the CVID phenotype. No mutations of SAP, ICOS, TACI, BAFFR, and CD19 were identified in this study, although selection bias among the small study population and genetic variation may exist. [Abstract]

Oren E, Banerji A, Clark S, Camargo CA
Food-induced anaphylaxis and repeated epinephrine treatments.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):429-32.
BACKGROUND: Research on the use of more than 1 dose of epinephrine in the treatment of food-induced anaphylaxis is limited. OBJECTIVE: To perform a medical record review to examine the frequency of repeated epinephrine treatments in patients presenting with food-induced anaphylaxis to the emergency department (ED). METHODS: We reviewed 39 medical records of patients who presented with food-induced allergic reactions to the Massachusetts General Hospital ED during a 1-year period. The analysis focused on the timing of the onset of symptoms and on the number of epinephrine treatments given before and during the ED visit. RESULTS: Of the 39 patients, 34 had an acute food-induced allergic reaction. Nineteen had anaphylaxis. Twelve patients with anaphylaxis (63%; 95% confidence interval, 38%-84%) received at least 1 dose of epinephrine, and 3 (16%; 95% confidence interval, 3%-40%) were given 2 doses. Although statistical analysis was not possible, repeated epinephrine treatment occurred in patients with anaphylaxis to peanut or tree nut and hypotension. There was no apparent association between time from ingestion of the causative agent to epinephrine treatment(s). CONCLUSIONS: Of patients presenting to the ED with food-induced anaphylaxis, approximately 16% were treated with 2 doses of epinephrine. This study supports the recommendation that patients at risk for food-induced anaphylaxis carry 2 doses of epinephrine. Further study is needed to confirm these results and to expand them to patients who do not present to the ED because that group may have a lower frequency of epinephrine use. [Abstract]

Shaker MS
An economic evaluation of prophylactic self-injectable epinephrine to prevent fatalities in children with mild venom anaphylaxis.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):424-8.
BACKGROUND: Mild (cutaneous) venom anaphylaxis is the most common presentation of systemic venom hypersensitivity during childhood. Guidelines recommend prophylactic self-injectable epinephrine for children with mild venom anaphylaxis. However, progressive venom-associated reactions are uncommon in this population. OBJECTIVE: To characterize the cost-effectiveness of prophylactic self-injectable epinephrine in mild childhood venom anaphylaxis from a societal perspective. METHODS: Cohort simulations were used, and the base case was represented by a 6-year-old child with a history of mild venom-associated anaphylaxis. Long-term survival was modeled using age-adjusted mortality from the 2002 U.S. life tables together with the risk of venom-associated mortality. Model assumptions included market costs of self-injectable epinephrine; the prevalence of venom allergy; US census estimates; venom-associated fatality estimates by the Joint Council of Allergy, Asthma, and Immunology (at least 40 deaths per year); and venom-associated mortality statistics from January 1, 1999, to December 31, 2003, provided by the Centers for Disease Control and Prevention. RESULTS: The incremental cost of prophylactic self-injectable epinephrine for mild childhood venom anaphylaxis was $469,459 per year of life saved ($6,882,470 per death prevented). In sensitivity analyses, the strategy was only cost-effective when the annual venom-associated fatality rate exceeded 2 per 100,000 persons at risk. CONCLUSION: Use of prophylactic self-injectable epinephrine to prevent fatalities in children with mild venom anaphylaxis is not cost-effective if the annual venom-associated fatality rate is less than 2 per 100,000 persons at risk. [Abstract]

Sullivan AF, Schatz M, Wenzel SE, Vanderweil SG, Camargo CA
A profile of U.S. asthma centers, 2006.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):419-23.
BACKGROUND: Asthma is a significant public health problem that results in 1.8 million annual emergency department (ED) visits. Many ED visits may be prevented with specialized asthma care. OBJECTIVE: To describe US asthma centers with a long-term goal of exploring their potential role in improving outcomes for ED patients with acute asthma. METHODS: We conducted initial online surveys in 2004. One survey identified asthma centers and their directors through reports by emergency medicine researchers and fellowship directors (allergy/immunology, pulmonary, and critical care) at US hospitals. A second survey asked asthma center directors to describe their asthma center. Follow-up surveys were conducted 2 years later in 2006. RESULTS: Eighty-seven (49%) of the 177 hospitals surveyed have asthma clinics. Although spirometry was available on the day of the visit at all asthma centers surveyed in 2006, only 21% (95% confidence interval, 11 %-34%) of sites reported that at least 90% of visits per week included a spirometry test. Only one quarter (26%; 95% confidence interval, 15%-40%) of asthma centers reported that at least 90% of patients undergo a skin or blood test for environmental allergens during 1 of their visits. Half of center directors (53%) were unsure of the approximate number of annual ED visits for acute asthma at their hospital. No significant measured changes were noted in asthma centers between 2004 and 2006. CONCLUSIONS: Asthma centers are heterogenous, with different services available. Although challenges remain, collaboration between EDs and asthma centers may contribute to improved asthma outcomes and merits further study. [Abstract]

Suttithawil W, Ploysongsang Y, Nunthapisud P, Fuangtong R
Acute primary Chlamydophila pneumoniae bronchitis and bronchial hyperresponsiveness in young nonasthmatic Thai military recruits.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):413-8.
BACKGROUND: A correlation between chronic Chlamydophila pneumoniae infection and chronic airway diseases has been suggested by several studies, but direct evidence to support the link between acute Cpneumoniae infection and new-onset asthma is insufficient. OBJECTIVES: To determine the association between C. pneumoniae infection and subsequent bronchial hyperresponsiveness (BHR) and hence asthma. METHODS: We studied 110 Thai military conscripts during an epidemic of Cpneumoniae infection in Thailand, from November 1, 1998, through February 28, 1999. The diagnosis was based on a standardized microimmunofluorescence technique. Spirometry and methacholine challenge tests (MCTs) were conducted. This cohort study excluded all conscripts with preexisting positive MCTs. RESULTS: Ninety-three percent of the conscripts presented with an acute cough of a mean duration of 15.2 days. The pattern of serologic response revealed that 83% had acute primary infections and 10% had acute reinfections. Mean forced expiratory volume in 1 second was 99.5%, with an improvement of 1.8% after bronchodilator administration. Only 3.6% revealed small airways disease (forced expiratory flow between 25% and 75% of <65%) on spirometry. Methacholine challenge tests failed to demonstrate BHR in all conscripts, and none had developed a new-onset wheeze (physician-diagnosed asthma) at up to 2 years of follow-up. CONCLUSIONS: This study demonstrates that cough in patients with acute primary Cpneumoniae infection is not associated with BHR among previously healthy adults. The pathogenetic mechanism by which organisms cause coughing and wheezing in acute bronchitis seems to be different among causative respiratory pathogens. [Abstract]

Jang AS, Lee JH, Park SW, Park JS, Kim DJ, Park CS
Risk factors related to fixed airway obstruction in patients with asthma after antiasthma treatment.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):408-12.
BACKGROUND: There are many unanswered questions about the role of airway remodeling in asthma. OBJECTIVE: To evaluate the physiologic factors related to airway remodeling after antiasthma drug treatment for 1 year. METHODS: We gave 582 patients with asthma long-term control medication for 1 year according to the severity of their asthma. Airway remodeling was defined using forced expiratory volume in 1 second/forced vital capacity and a predicted forced expiratory volume in 1 second of less than 75% after antiasthma treatment. RESULTS: Of the 582 patients, 49 (8.4%) had airway remodeling. Severe asthma resulted in more airway remodeling than mild-to-moderate asthma. Asthmatic patients with airway remodeling were significantly older and had a longer duration of asthma. Asthmatic patients with airway remodeling had more emphysema on high-resolution computed tomography, a higher rate of near-fatal asthma attacks, a lower percentage of sputum eosinophils, a lower atopy frequency, a greater response to short-acting bronchodilators, and a lower body mass index (BMI) than those without airway remodeling. Age, asthma duration, and BMI were important discriminators of airway remodeling. CONCLUSION: Nonatopy, asthma duration, emphysema on high-resolution computed tomography, sputum eosinophils, age, and BMI before antiasthma treatment are important factors related to airway remodeling in patients with asthma. [Abstract]

Pelikan Z
The role of nasal allergy in chronic secretory otitis media.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):401-7.
BACKGROUND: Chronic secretory otitis media (SOM) has multifactorial causes, and nasal allergy is suspected as one of these causative factors. OBJECTIVES: To investigate the possible role of nasal allergy in SOM in adults and to determine the diagnostic value of nasal challenges with allergens (nasal provocation tests) combined with tympanometry for the diagnosis of this disorder. METHODS: In 69 young adults with chronic or recurrent SOM, 173 nasal challenges with allergens were performed by anterior rhinomanometry combined with tympanometry (pure-tone air conduction tympanometry). In 42 control subjects with only allergic rhinitis and no history of middle ear disease, 42 nasal challenges with allergens were repeated and combined with tympanometry. The study design was a placebo-controlled comparison. RESULTS: Of the 69 patients, 54 developed 129 positive nasal responses of various types (P < .01), 117 of which were accompanied by significant changes in middle ear pressure (P < .01). No significant tympanometric changes (P > .10) were recorded during the 42 positive nasal responses in control subjects. CONCLUSIONS: These results may confirm the occurrence of chronic SOM in some adult patients and the possible involvement of nasal allergy in chronic SOM. The nasal challenges with allergen performed by rhinomanometry, combined with tympanometry, seem to be a valuable supplementary tool for the diagnosis of this disorder. [Abstract]

Liccardi G, Senna G, Rotiroti G, D'Amato G, Passalacqua G
Intimate behavior and allergy: a narrative review.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):394-400.
OBJECTIVE: To determine how sex and intimate contacts can represent a risk factor for allergic reactions, because they may favor direct contact with sensitizing substances. DATA SOURCES: We collected in this review the available literature on this subject. The MEDLINE database was searched by a combination of keywords: sex OR sexual intercourse OR kiss OR seminal plasma OR condom AND allergy OR allergic reaction. STUDY SELECTION: The studies retrieved were independently evaluated by the authors and included in this review based on their clinical pertinence (i.e., dealing with clinical presentation, diagnosis, or treatment). RESULTS: Sex and intimate behavior seem to be increasingly described as triggers of allergic reactions, although the pertaining literature is represented mostly by case reports. Kissing has been described as a risk factor for food- and drug-induced severe reactions. Seminal plasma allergy has been repeatedly described and investigated. In this case, practical diagnostic algorithms have been proposed, and desensitization protocols are available. Similarly, there are numerous case reports of allergic reaction due to latex condoms, for which the diagnostic procedure is standardized. CONCLUSIONS: The available literature on intimate behavior, and sex in general, as a trigger of allergic reactions is not abundant. This is probably because of the particular nature of the problem, which concerns intimacy. Nevertheless, reliable diagnostic procedures are available in some specific cases. The possible link between sex and allergy should become part of the personal culture of allergists to extend and improve the diagnosis of unusual or unexplained conditions. [Abstract]

Kaliner MA
A novel and effective approach to treating rhinitis with nasal antihistamines.
Ann Allergy Asthma Immunol. 2007 Nov;99(5):383-90; quiz 391-2, 418.
OBJECTIVES: To review existing treatments for rhinitis and summarize data available on the use of a nasal antihistamine (azelastine) in treating allergic and nonallergic vasomotor rhinitis. Data Sources: Relevant articles and references published between 1995 and 2007 regarding the treatment of allergic and vasomotor rhinitis were identified from PubMed, review articles, meta-analyses, and practice guidelines. Study Selection: All key relevant articles were reviewed and the most relevant selected for inclusion in this review. RESULTS: The efficacy and safety of azelastine nasal spray in treating allergic rhinitis and vasomotor rhinitis have been determined in a number of U.S. multicenter, randomized, double-blind, placebo-controlled trials. In all trials, azelastine was associated with a rapid onset of action and a sustained improvement over time in rhinitis, congestion, and other symptoms. In patients with allergic rhinitis, the combination of azelastine and nasal corticosteroids increased treatment efficacy by more than 40% compared with either product alone. CONCLUSIONS: Intranasal antihistamine therapy represents an effective mode of drug delivery in patients with allergic and nonallergic vasomotor rhinitis and is an important option for rhinitis therapy, particularly if rapid symptom relief is required or if congestion is a major symptom. Use of azelastine plus nasal corticosteroids is effective in both allergic rhinitis and vasomotor rhinitis, suggesting that this combination represents an effective treatment strategy for all patients with either allergic or nonallergic vasomotor rhinitis. [Abstract]

Weber RW
Carex (genus in family Cyperaceae).
Ann Allergy Asthma Immunol. 2007 Nov;99(5):A4. [Abstract]

Yamada Y, Yoshihara S, Arisaka O
Successful treatment of pediatric hypereosinophilic syndrome with suplatast tosilate.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):380-1. [Abstract]

Yu TC, Shyur SD, Huang LH, Wen DC, Li JS
Paternal mosaicism and hereditary angioedema in a Taiwanese family.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):375-9.
BACKGROUND: Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 INH). Most patients with HAE have an absolute deficiency of C1 INH (type I HAE), whereas the rest (approximately 15%) synthesize a dysfunctional C1 INH protein (type II HAE). Mosaicism is rare in HAE. OBJECTIVE: To describe the clinical manifestations, laboratory findings, and molecular genetic studies in a Taiwanese family with type I HAE with paternal mosaicism. METHODS: A family that included a 34-year-old man (index patient) and his 25-year-old brother who both had recurrent peripheral angioedema was evaluated. A younger sister had died of an unexplained cause at 18 years of age. We analyzed blood levels of C3, C4, and C1 INH and sequenced the SERPING] (C1NH) gene that codes for C1 INH in 5 family members, including the parents and 3 brothers. RESULTS: The 4 men in the family had a novel mutation c.3_73del, p.N1fsX34 in exon 3 of the C1INH gene, resulting in C1 INH deficiency. Although the father carried this mutant gene, he had normal serum levels of C1 INH. Based on quantitative analysis of allele dosage by DNA fragment analysis (GeneScan), the father was determined to have genetic mosaicism. CONCLUSION: Parental mosaicism is a possible explanation for normal C1 INH plasma concentrations in both parents despite clinically apparent HAE in the children. [Abstract]

Yamaguchi M, Niimi A, Minakuchi M, Matsumoto H, Shimizu K, Chin K, Mishima M
Corticosteroid-induced myopathy mimicking therapy-resistant asthma.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):371-4.
BACKGROUND: Therapy-resistant asthma is an important clinical problem. However, before considering asthma truly therapy resistant, it is essential to exclude diagnoses that may masquerade as therapy-resistant asthma, such as vocal cord dysfunction and recurrent aspiration, as well as factors related to loss of asthma control, including poor compliance, exposure to allergens, and sinusitis. Corticosteroid-induced myopathy may be an unrecognized but potentially important consideration in both settings. OBJECTIVES: To describe a patient with corticosteroid-induced myopathy complicating recurrent exacerbations of asthma, which presented with persistently reduced airflow that mimicked therapy-resistant asthma. METHODS: A 20-year-old Japanese woman with severe intractable asthma who had a history of near-fatal attacks was admitted with recurrent asthma exacerbations that required long-term systemic corticosteroids. RESULTS: Wheezing episodes decreased but airflow limitation persisted, which was due to not only uncontrolled asthma but also corticosteroid-induced myopathy. Myopathy prevented the adequate use of inhalers, which in turn complicated the tapering of corticosteroids, leading to a vicious cycle. Careful and gradual reduction of corticosteroid dose, while continuing systemic administration of nonsteroidal antiasthma medications, resulted in a resolution of clinical and electromyographic signs of myopathy and pulmonary function abnormalities. CONCLUSIONS: Corticosteroid-induced myopathy can masquerade as therapy-resistant asthma and can cause poor asthma control. [Abstract]

Arora R, Newton TC, Nelson MR
Subcutaneous immunoglobulin therapy in an 11-year-old patient with common variable immunodeficiency and von Willebrand disease.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):367-70.
BACKGROUND: Subcutaneous immunoglobulin (SCIG) is an option for replacement therapy in patients with humoral immune deficiencies. OBJECTIVE: To describe a patient with common variable immunodeficiency (CVID) and von Willebrand disease who tolerated immunoglobulin replacement via the subcutaneous route. METHODS: An 11-year-old boy receiving monthly intravenous immunoglobulin (IVIG) since 5 years of age presented to an academic medical center after moving to the area. The patient also had a history of von Willebrand disease. He had started receiving IVIG because of recurrent infections and an absent IgG subclass 3. Further immunologic assessment revealed a normal B-cell count, decreased IgM level, and an abnormal response to bacteriophage phiX174. Given these findings and the lack of another cause, the patient was diagnosed as having CVID. Because of difficult intravenous access, a port was placed for IVIG administration in 1999. The initial port was removed because of infectious complications, and a second port was found to be distally displaced in the right atrium, requiring removal. RESULTS: Continued difficulties with intravenous access and the potential complications with maintaining a long-term indwelling catheter prompted consideration of alternative methods for immunoglobulin administration. After removal of the port, the patient was prescribed weekly SCIG infusions. He tolerated the infusions well without bleeding complications related to the von Willebrand disease and was able to transition to home infusions. CONCLUSIONS: SCIG was well tolerated by a pediatric patient with CVID and von Willebrand disease without any significant bleeding complications. [Abstract]

Oppenheimer J, Aaronson D
Impact of recent black box warnings in the allergy world.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):364-6. [Abstract]

Milgrom H, Kittner B, Lanier R, Hampel FC
Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in children 2 to 5 years old.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):358-63.
BACKGROUND: The safety of fexofenadine has been examined extensively in adults and school-age children. However, the safety of fexofenadine in children younger than 6 years has not been reported to date. OBJECTIVE: To compare the safety and tolerability of twice-daily fexofenadine hydrochloride, 30 mg, and placebo in preschool children aged 2 to 5 years with allergic rhinitis. METHODS: This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study, conducted between February 29, 2000, and June 14, 2001. Participants were randomized to either fexofenadine hydrochloride, 30 mg, or placebo twice daily for a 2-week period. To facilitate dosing, capsule content was mixed with applesauce (approximately 10 mL). Safety assessments depended on date of entry into the study because of an amendment to the protocol. Before the amendment, assessments included physical examination, vital signs reporting (oral temperature, heart rate, and respiratory rate), and adverse event (AE) reporting. After the amendment, safety assessments included laboratory testing (blood chemistry and hematology profiles), physical examination, 12-lead electrocardiography, and vital signs (oral temperature, blood pressure, heart rate, and respiratory rate) and AE reporting. RESULTS: Treatment-emergent AEs were observed in 116 of 231 participants receiving placebo and 111 of 222 receiving fexofenadine. These AEs were possibly related to study medication in 19 (8.2%) and 21 (9.5%) of the participants receiving placebo and fexofenadine, respectively, and most frequently involved the digestive system. No clinically relevant differences in laboratory measures, vital signs, and physical examinations were observed. CONCLUSIONS: The findings show that fexofenadine hydrochloride, 30 mg, is well tolerated and has a good safety profile in children aged 2 to 5 years with allergic rhinitis. [Abstract]

Goldberg A, Confino-Cohen R
Effectiveness of maintenance bee venom immunotherapy administered at 6-month intervals.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):352-7.
BACKGROUND: Extension of the intervals at which maintenance venom immunotherapy (MVIT) is administered has been attempted for many years. However, published evidence on its effect, especially in intervals of longer than 3 months, is sparse. OBJECTIVE: To examine whether the administration of a bee venom (BV) maintenance dose at 6-month intervals is safe and efficacious. METHODS: The 3-month intervals at which venom-allergic patients were receiving their MVIT were gradually extended to 6 months. Systemic reactions (SRs) to immunotherapy injections or to field stings were regularly recorded. Patients who were allergic to BV alone or also to other venoms were deliberately sting challenged by a honeybee after reaching the 6-month interval. RESULTS: The 3-month intervals were extended in 47 patients. A single patient (2%) developed an SR after receiving the injection at an interval of 4 months. Two field stings in 2 patients resulted in a mild SR in 1 patient. Of 14 sting-challenged patients, 3 (21%) developed an SR after the challenge. The 3 SRs occurred only among the 8 patients (38%) who were allergic to BV alone. The 3 patients with the SR to the challenge continued to receive the regular maintenance dose at monthly intervals 3 to 5 more times. Repeated sting challenges were then well tolerated in all 3 patients. CONCLUSION: The administration of MVIT at 6-month intervals does not provide suitable protection in BV-allergic patients, and they should continue MVIT at the accepted 1- to 3-month intervals. [Abstract]

Whalley B, Jacobs PA, Hyland ME
Correlation of psychological and physical symptoms with chronically elevated cytokine levels associated with a common immune dysregulation.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):348-51.
BACKGROUND: Chronically elevated levels of proinflammatory cytokines are associated with inflammatory diseases and psychological symptoms of depression and tiredness. OBJECTIVE: To test the prediction that, in a healthy population without medically diagnosed diseases, psychological symptoms (depression and tiredness) associated with proinflammatory cytokines correlate with physical symptoms associated with inflammatory disease. METHODS: A total of 1,143 women between 45 and 65 years old completed a health complaint checklist containing 11 target symptoms (5 related to allergy, 4 to gastrointestinal symptoms, and 2 to pain), 7 control symptoms or health complaints, and 2 psychological symptoms (depression and tiredness). They also completed a menopausal quality-of-life questionnaire; to compensate for response bias, we removed variance attributable to quality of life. RESULTS: The partial correlations show that tiredness (but not depression) correlated with 9 of the 11 target symptoms (P < .001) but with 0 of the 7 control symptoms or complaints. Symptoms of both the specific and the systemic components of inflammatory disease are correlated in a healthy population. CONCLUSION: Immune dysregulation may explain the existence and covariation of psychological and physical symptoms in the healthy population, including people with medically unexplained symptoms. [Abstract]

Shirasaki H, Seki N, Fujita M, Kikuchi M, Kanaizumi E, Watanabe K, Himi T
Agonist- and T(H)2 cytokine-induced up-regulation of cysteinyl leukotriene receptor messenger RNA in human monocytes.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):340-7.
BACKGROUND: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases, and their actions are mediated via specific receptors named CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R). Little information is known about the role of T(H)2 cytokines in the regulation of both CysLT1R and CysLT2R expression. OBJECTIVE: To investigate the possible modulation of both CysLT1R and CysLT2R messenger RNA (mRNA) expression, we have developed a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay based on the TaqMan fluorescence method to quantify CysLT1R and CysLT2R mRNA in human monocytes. METHODS: Human monocytes were stimulated with leukotriene D4 or interleukin (IL) 4 or IL-13, and the levels of CysLT1R and CysLT2R mRNA were measured by the quantitative RT-PCR. RESULTS: CysLT1R and CysLT2R mRNA was increased after stimulation with leukotriene D4. CysLT1R mRNA was augmented 150-fold after treatment with IL-4; however, no significant increase was observed in CysLT2R mRNA level. IL-13 could induce a biphasic augmentation of CysLT1R mRNA level. In contrast to IL-4, IL-13 enhanced CysLT2R mRNA level, with a maximal effect at 2 hours of incubation. CONCLUSIONS: CysLT1R and CysLT2R expression can be regulated by CysLT itself and T(H)2 cytokines at the transcriptional level. [Abstract]

Sutherland TJ, Taylor DR, Sears MR, Cowan JO, McLachlan CR, Filsell S, Williamson A, Greene JM, Poulton R, Hancox RJ
Association between exhaled nitric oxide and systemic inflammatory markers.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):334-9.
BACKGROUND: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation. OBJECTIVE: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers. METHODS: The Dunedin Multidisciplinary Health and Development Study is a birth cohort of approximately 1,000 individuals born between April 1, 1972, and March 31, 1973. At the age of 32 years, study members were assessed for diagnosis of asthma, atopy by skin prick testing, smoking, body mass index, exhaled nitric oxide, high-sensitivity serum CRP, and plasma fibrinogen level. RESULTS: There was no significant association between exhaled nitric oxide and CRP (P = .99). There was a trend to an inverse association between exhaled nitric oxide and fibrinogen (P = .049), but this was not significant after adjusting for smoking and use of corticosteroids or after further adjustment for body mass index and atopy (P = .71). CONCLUSION: In this population-based sample of young adults, there was no association between airway inflammation, as measured by exhaled nitric oxide, and systemic inflammation, as measured by either CRP or fibrinogen. [Abstract]

Cruz NV, Wilson BG, Fiocchi A, Bahna SL
Survey of physicians' approach to food allergy, Part 1: Prevalence and manifestations.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):325-33.
INTRODUCTION: Food allergy (FA) prevalence is increasing and is being popularly claimed by the general population. OBJECTIVE: To evaluate attitudinal differences between allergists and nonallergists with regard to prevalence, manifestations, offending food component, and time of onset of FA reactions. METHODS: A 2-page questionnaire was mailed to 3,000 members of the American College of Allergy, Asthma and Immunology and 4,000 nonallergists (1,000 each of internists, pediatricians, family practitioners, and otolaryngologists). RESULTS: Responses were received from 584 allergists and 77 nonallergists. The overall estimated prevalence of FA was significantly higher for nonallergists than allergists (12.1% vs 4.6%) and in each age group. The most common gastrointestinal manifestation of FA was oropharyngeal itching according to allergists (67.2%) vs diarrhea according to nonallergists (42.5%). More nonallergists than allergists reported neurobehavioral manifestations, musculoskeletal symptoms, and upper airway symptoms as common in FA. On the other hand, more allergists than nonallergists considered atopic dermatitis, acute urticaria or angioedema, and anaphylaxis to be common. Nonallergists considered carbohydrates, fat, and additives as causing allergy much more than allergists did (34.4% vs 6.9%; P < .001). With regard to time of onset of FA, nonallergists had higher estimates than allergists for both late (25.5.% vs 13.0%; P < .001) and delayed (22.1% vs 4.5%; P < .001) reactions. CONCLUSION: Significant differences in attitudes toward FA were revealed between allergists and nonallergists, which highlights the need to enhance education in this area. [Abstract]

Bender BG
Depression symptoms and substance abuse in adolescents with asthma.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):319-24.
BACKGROUND: Depression and risk behaviors occur often in adolescents in the United States, but their frequency in youth with asthma is not well documented. OBJECTIVE: To establish rates of and associations between depression and substance use in youth with asthma. METHODS: The Centers for Disease Control and Prevention conducted the 2005 Youth Risk Behavior Survey with 13,917 students in grades 9 to 12 from 159 high schools in 40 states, producing a nationally representative distribution of students by grade, sex, and race/ethnicity. The Youth Risk Behavior Survey documents self-reported suicide intent and health risk behaviors, including use of tobacco, marijuana, alcohol, and cocaine. RESULTS: In 720 adolescents reporting current asthma (5.2% of the total sample), depression symptoms, cigarette smoking, and cocaine use occurred more frequently than in youth without asthma. Substance use increased with depression; of youth with asthma reporting suicidal ideation, 40% had smoked cigarettes, 67% had smoked marijuana, 37% had engaged in binge drinking, and 12% had used cocaine in the past 30 days. Overall odds ratios for substance abuse in the group with asthma were not altered when controlling for age, sex, and race, although odds ratios for specific risk behaviors in those with asthma varied slightly within age, sex, and race groups. CONCLUSIONS: National rates of depression and associated risk behaviors in youth with asthma have not been previously reported, indicate a need to screen adolescents with asthma for depression, and suggest that risk behaviors in this population may signal heightened need for intervention. [Abstract]

Lupoli TA, Lockey RF
Temporomandibular dysfunction: an often overlooked cause of chronic headaches.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):314-8.
OBJECTIVE: To review and discuss the role of temporomandibular dysfunction (TMD) as a cause of chronic headaches and facial pain. DATA SOURCES AND STUDY SELECTION: A literature review was performed using the PubMed database for English-language articles published between January 1, 1981, and August 31, 2006, using the following keywords: temporomandibular dysfunction, temporomandibular disorder, temporomandibular joint, and chronic headache. Additional information was obtained from a review of current medical texts. RESULTS: Allergists and immunologists are frequently called on to evaluate patients with chronic headaches and facial pain. TMD is known to cause recurrent facial discomfort and headaches. Many individuals with the disorder present with headache or facial discomfort as their only chief complaint. They mistakenly think it is a "sinus" headache. Nearly 10 million Americans are affected by the disorder, and early studies estimate that TMD pain is the cause of chronic headaches in 14% to 26% of individuals with recurrent headaches. CoNCLUSIONS: TMD is a likely underdiagnosed cause of chronic headache and facial discomfort. As such, many patients with the disorder are routinely mislabeled as experiencing chronic sinusitis and are unnecessarily subjected to multiple courses of broad-spectrum antibiotics and other unnecessary therapy. TMD can be readily diagnosed by a careful history and physical examination. Patients typically respond well to conservative therapy, which includes behavioral modification and nonsteroidal anti-inflammatory drugs. The disorder should be suspected in individuals with a long-standing history of chronic daily headaches and facial pain without objective evidence of sinus, neurologic, or intracranial abnormalities. [Abstract]

Evora PR, Simon MR
Role of nitric oxide production in anaphylaxis and its relevance for the treatment of anaphylactic hypotension with methylene blue.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):306-13.
OBJECTIVE: To review the role of nitric oxide production in anaphylaxis. DATA SOURCES: We performed MEDLINE searches of the literature. In addition, some references known to the authors but not listed in MEDLINE, such as abstracts and a CD-ROM, were included. Finally, additional clinical details of the cases were provided by one of the authors. STUDY SELECTION: Primary reports were preferentially selected for inclusion. However, some secondary publications are also cited. RESULTS: Histamine along with other mediators, such as leukotrienes, tumor necrosis factor, and platelet-activating factor, induce the production of nitric oxide. Nitric oxide can inhibit the release and effects of catecholamines. Sympathetic amines may inhibit production of nitric oxide. Studies in animals have demonstrated the generation of nitric oxide during anaphylaxis. Inhibition of nitric oxide synthase improves survival in an animal model of anaphylaxis. Nitric oxide causes vasodilation indirectly by increasing the activation of guanylyl cyclase, which then causes smooth muscle relaxation by increasing the concentration of smooth muscle cyclic guanosine monophosphate. Methylene blue is an inhibitor of guanylyl cyclase, which increases systemic vascular resistance and reverses shock in animal studies. The previously reported successful treatment with methylene blue of 11 patients with anaphylactic hypotension is reviewed. CONCLUSION: Nitric oxide plays a significant role in the pathophysiology of anaphylaxis. Treatment with methylene blue should be considered in patients with anaphylactic hypotension that has not responded to other interventions. [Abstract]

Randhawa I, Klaustermeyer WB
Oral corticosteroid-dependent asthma: a 30-year review.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):291-302; quiz 302-3, 370.
OBJECTIVE: To identify novel aspects of the pathogenesis, therapeutic options, and prophylaxis measures of corticosteroid-dependent asthma. DATA SOURCES: PubMed searches were undertaken of studies published between 1966 and 2006 on the pathogenesis of and corticosteroid-sparing therapies for corticosteroid-dependent asthma. Identified review articles were surveyed for additional and earlier citations. Recent American Academy of Asthma, Allergy, and Immunology meeting abstracts were also searched to identify other recently published and unpublished studies. STUDY SELECTION: Inclusion of studies in the review was decided by simple agreement of both reviewers, who independently read the "Methods" and "Discussion" sections of articles identified using the search strategy. Quality assessment was performed by the 2 reviewers. RESULTS: High-dose inhaled corticosteroids are the first-line option for corticosteroid-dependent asthmatic patients with clear efficacy. Omalizumab is effective in reducing oral corticosteroid requirements in allergic asthma. Methotrexate, gold, and cyclosporine have corticosteroid-sparing effects clinically that must be weighed against a serious adverse effect profile. Nebulized diuretics and lidocaine, with a low adverse effect profile, offer promising results but require further study. Clarithromycin and telithromycin seem to have an independent mechanism of inflammatory modulation, but their effect on corticosteroid-dependent asthma remains to be seen. Etanercept offers only early clinical evidence of a role in corticosteroid-dependent asthma. CONCLUSIONS: With no clear consensus on corticosteroid-sparing treatment in corticosteroid-dependent asthmatic patients, systemic glucocorticoids remain the foremost therapy, with adverse effects that require monitoring and prophylaxis. [Abstract]

Weber RW
On the cover. Rabbitbrush.
Ann Allergy Asthma Immunol. 2007 Oct;99(4):A4. [Abstract]

Loria RC
Allergy shots or automobiles: which is more dangerous?
Ann Allergy Asthma Immunol. 2007 Sep;99(3):290. [Abstract]

Leifer KN, Leifer C
Allergy shots or automobiles: which is more dangerous?
Ann Allergy Asthma Immunol. 2007 Jun;98(6):604. [Abstract]


Recent Articles in International Archives of Allergy and Immunology

Elfman L, Brannstrom J, Smedje G
Detection of Horse Allergen around a Stable.
Int Arch Allergy Immunol. 2007 Nov 15;145(4):269-276.
Background: Integrating horse stables with built-up areas may lead to conflicts. Dispersion of horse allergen may become a health risk for allergic people. The aim was to measure the dispersion of horse allergen around a stable, considering wind speed and direction and vegetation. The disturbance of staff at a workplace nearby a stable was investigated. Methods: Air sampling was performed around a stable (32 horses) at distances of 50-500 m in all directions. Sampling was done with a pump and an IOM sampler. Samples were collected at 50 points during all seasons. Horse allergen levels were determined using ELISA. Disturbance by horses was studied with a questionnaire handed to the employees in an office near the stable. Results: The median horse allergen level at the stable entrance was 316 U/m(3), in the horse fields 40 U/m(3) and in the whole source area 16 U/m(3), which declined to <2 U/m(3) at about 50 m from the source area. Downwind of the prevailing winds low levels of horse allergen (2-4 U/m(3)) could sometimes be detected at up to 500 m. The staff, including those allergic to horses, managed to tolerate horses close to the workplace. Conclusions: At low winds horse allergen spread in ambient air about 50 m from the stable and horse fields. At higher winds low allergen levels were sometimes found in open areas up to 500 m from the source area. These levels were similar to those found in the office after moving away from the stable area. The employees did not report more symptoms of allergy or asthma while working close to the stable compared to after the move. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Ito W, Tanimoto M, Ono K, Mizuno S, Yoshida A, Koga H, Fuchimoto Y, Kondo N, Tanimoto Y, Kiura K, Matsumoto K, Kataoka M, Nakamura T, Gelfand EW, Kanehiro A
Growth Factors Temporally Associate with Airway Responsiveness and Inflammation in Allergen-Exposed Mice.
Int Arch Allergy Immunol. 2007 Nov 14;145(4):324-339.
Background: To clarify whether growth factors play critical roles in the development of airway hyperresponsiveness (AHR) and airway inflammation in the early stages of asthma, the relationship between growth factors and AHR and airway inflammation were analyzed in a mouse model of asthma. Methods: Following ovalbumin (OVA) sensitization and challenge, airway function, inflammation, cytokine and growth factor levels were monitored. Results: AHR to inhaled methacholine increased at 6 h, peaked at 48 h, and remained elevated for 14 days. IL-4 and IL-5 levels in bronchoalveolar lavage (BAL) fluid were increased at 6 h, peaked at 24 h, but returned to baseline quickly. IL-13 levels increased up to 14 days, peaking at 48 h. Increases in BAL fluid transforming growth factor-beta(1) and platelet-derived growth factor were observed at 12 h, and remained elevated at 14 days. Nerve growth factor levels were increased at 24-28 days. BAL fluid hepatocyte growth factor (HGF) was detected at 12 h, peaked at 24 h, and returned to baseline by 72 h. c-Met/HGF receptor was detected in the airways at 6 h, before HGF in the BAL, and continued to be observed 96 h after the last OVA challenge. Conclusions: These data identify a temporal association between growth factor production and Th2 cytokine production and the kinetics of AHR. Growth factors may play important roles in the development of allergic airway inflammation and AHR even in the early stages of asthma, before remodeling is initiated. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Asero R, Mistrello G, Roncarolo D, Amato S
Respiratory and Skin Allergy to Galleria mellonella (Bee Moth).
Int Arch Allergy Immunol. 2007 Nov 13;145(4):340-342.
This case report describes a patient with bee moth-induced rhinoconjunctivitis, asthma and contact urticaria. Immunoblot analysis showed IgE reactivity to two distinct bee moth proteins at 23 and 70 kDa, respectively. ELISA inhibition studies excluded cross-reactivity to the other popular live bait, fly larva. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Tan GH, Su JM, Wang CC, Huang FY, Wang H, Huang YH, Lin YY
A Recombinant DNA Plasmid Encoding the Human Interleukin-5 Breaks Immunological Tolerance and Inhibits Airway Inflammation in a Murine Model of Asthma.
Int Arch Allergy Immunol. 2007 Nov 13;145(4):313-323.
Background: Eosinophils play a pivotal role in the generation of asthma inflammation. Interleukin (IL)-5 is the major activator of eosinophils. We hypothesize that modulating IL-5 activity could be an effective strategy for asthma therapy. In this study, we tested whether the plasmid encoding human IL-5 as a xenogeneic DNA vaccine could induce the production of autoantibodies, and be used for asthma treatment. Methods: A eukaryotic plasmid encoding the human IL-5 was constructed, and used as a DNA vaccine. A mouse model of asthma was established to observe its antiasthma activities. Eosinophils in tissue, blood and the bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness (AHR) was determined by whole body plethysmography. Antibody characters and cytokines were detected with immunological methods. Results: Immunization with a plasmid encoding the human IL-5 as DNA vaccine reduced airway inflammation, reversed Th2 cytokines, and decreased AHR in mice. In addition, this immunization induced the production of polyclonal antibodies that were cross-reactive with native murine IL-5, and IgG1 and IgG2a were the major subclasses. Adoptive transfer of the purified antibodies from the sera of mice immunized with the plasmid encoding the human IL-5 resulted in similar antiasthma effects. Conclusions: Our results suggest that active vaccination against IL-5 may be a rational therapeutic approach for the treatment of asthma and potentially other eosinophilic disorders. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Wegienka G, Havstad S, Shue L, Zoratti E, Ownby DR, Johnson CC
Birth Order and Cord Immunoglobulin E: Results Using a High-Sensitivity Immunoglobulin E Protocol.
Int Arch Allergy Immunol. 2007 Nov 13;145(4):305-312.
Background: Studies have shown an inverse association between birth order and allergic disease risk; some but not all have shown an inverse association between cord blood immunoglobulin E (IgE) and birth order. We further examined the relationship between birth order and cord blood IgE in a racially diverse birth cohort. Methods: Women were interviewed about their pregnancy history, and their babies' cord blood was collected to measure total IgE using a high-sensitivity protocol (lower detection limit 0.01 IU/ml). We analyzed cord IgE as both a continuous and categorical measure. Results: Of the 733 children, 171 (23%) were first born, 92 (13%) were first born with the mother having prior pregnancies but no live births, and 470 (64%) were born second or later. By birth order, the geometric means +/- standard deviations were: first born 0.26 +/- 4.2 IU/ml, first born after prior pregnancies 0.35 +/- 3.9 IU/ml, second born 0.30 +/- 4.8 IU/ml, third born 0.28 +/- 5.1 IU/ml, and fourth born or greater 0.28 +/- 4.5 IU/ml (trend p = 0.51). Other factors considered (maternal allergic disease history, age, race, exposure to smoking and cats/dogs during pregnancy, fetal gender, season of delivery) neither modified nor confounded these relationships. Conclusions: Unlike some previous reports, there was no association between total cord IgE level and birth order. Mechanisms other than cord IgE should be studied in the quest to understand the role of birth order in allergic disease risk. Categorization of a continuous measure of IgE may incorrectly create statistically significant results. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Fernández-Caldas E, Gallego M, Carnés J, Iraola V
Enzymatic Activity of Dermatophagoides pteronyssinus Extracts after Acidic Treatment.
Int Arch Allergy Immunol. 2007 Nov 13;145(4):298-304.
Background: Mite extracts contain potent enzymes. These enzymes, especially Der p 1, may affect the bronchial homeostasis and the amplification of the allergic response. The objectives of this study were to determine how depigmentation affects the enzymatic activity of allergen extracts of Dermatophagoides pteronyssinus and to verify if these depigmented extracts retain their in vitro allergenic properties. Methods: Four native extracts were manufactured from 4 different batches of raw material of D. pteronyssinus. Once extracted, native extracts were reconstituted and modified by adding increasing quantities of 2 M HCl to the solution and dialyzed against double-distilled water. The enzymatic activity of these 8 extracts (4 native and 4 depigmented) was evaluated using in vitro methods. The allergenic potency was evaluated by human specific IgE and IgG ELISA inhibition experiments. The major allergen content (Der p 1 and Der p 2) was measured with monoclonal antibodies. Results: Protease, phosphatase, lipase and glycosidase activity was detected in native extracts. After depigmentation, all the enzymatic activities showed a significant decrease. SDS-PAGE reveals the same protein profile in both types of extracts. The results of ELISA inhibition confirmed that depigmented extracts preserved their antigenic and allergenic capacity. Der p 2 levels increased in depigmented extracts, while the detection capacity of Der p 1 decreased. Conclusions: The depigmentation process significantly reduced the enzymatic activity of these mite extracts, while preserving their allergenicity and antigenicity. No significant differences were observed in the antigenic profile of native and depigmented extracts. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Fukumoto A, Nonaka M, Ogihara N, Pawankar R
Induction of TARC Production by Lipopolysaccharide and Interleukin-4 in Nasal Fibroblasts.
Int Arch Allergy Immunol. 2007 Nov 13;145(4):291-297.
Background: Th2 cell infiltration is a characteristic feature of allergic chronic sinusitis. However, the mechanisms that cause the predominance of Th2 cells in this disease have yet to be clarified. The airway is often exposed to not only Th2 cytokines but also bacterial products such as lipopolysaccharides (LPS). A CC chemokine, TARC, is a potent chemoattractant for Th2 cells. The objectives of this study were twofold. First, we examined whether nasal polyp fibroblasts were able to produce TARC when costimulated with LPS and IL-4. Second, we investigated whether there was any heterogeneity in TARC production among fibroblasts derived from different airway sites. Methods: Fibroblast lines were established from human biopsy tissue. The amount of TARC in the supernatants was measured by ELISA. The expression of TARC mRNA was quantitated by real-time PCR. Results: Combined stimulation with LPS and IL-4 significantly induced TARC production by nasal polyp fibroblasts in a dose- and time-dependent manner. This induction occurred in normal nasal fibroblasts, but not in normal lung fibroblasts. Conclusions: Via TARC production, nasal fibroblasts may play an important role in the recruitment of Th2 cells into the sinus mucosa as well as nasal polyps. The heterogeneity in TARC production may reflect functional differences between upper and lower airway fibroblasts. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Duffort O, Quintana J, Ipsen H, Barber D, Polo F
Antigenic Similarity among Group 1 Allergens from Grasses and Quantitation ELISA Using Monoclonal Antibodies to Phl p 1.
Int Arch Allergy Immunol. 2007 Nov 13;145(4):283-290.
Background: Group 1 allergens elicit a specific IgE response in about 90% of grass pollen-allergic patients. The aim of this work was to study the antigenic similarity among group 1 allergens from different grasses and to develop a monoclonal antibody (MAb)-based quantitation ELISA. Methods: Twenty specific MAbs were produced from BALB/c mice immunized with natural Phl p 1. These MAbs were tested for specificity with thirteen different grass pollen extracts from the Poaceae family and in cross-inhibition experiments for the binding of Phl p 1. Purified group 1 allergens from Poeae grasses (Dactylis glomerata, Lolium perenne, Festuca pratensis and Poa pratensis) were tested for parallelism in quantitation ELISA. Results: Eighteen to nineteen anti-Phl p 1 MAbs recognized the homologous allergen in pollen extracts from grasses of the Poeae tribe. In contrast, only four MAbs recognized group 1 from Cynodon dactylon and Phragmites communis. Four groups of MAbs with different epitope specificity were identified. A grass group 1 quantitation ELISA was developed using a mix of three MAbs on the solid phase and a polyclonal rabbit antibody as the second antibody. The group 1 content could be measured in different batches of Phleum pratense as well as in pollen extracts from Poeae grasses, since they showed parallel dose-response curves. Conclusions: MAbs produced in this work enabled us to show the high antigenic similarity between group 1 allergens from temperate grasses. The results prove the usefulness of the ELISA method developed for standardization of grass allergen products. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Tanizaki H, Kambe N, Nakamura Y, Tanaka A, Matsuda H, Miyachi Y
Oral Administration of Bepotastine Besilate Suppressed Scratching Behavior of Atopic Dermatitis Model NC/Nga Mice.
Int Arch Allergy Immunol. 2007 Nov 13;145(4):277-282.
Background: Pruritus is the most severe problem in atopic dermatitis. Even though its mechanism is still not fully understood, antihistamines have been prescribed for atopic dermatitis. Objective: To evaluate the effect of antihistamine on atopic dermatitis, we analyzed the scratching behavior in atopic dermatitis model NC/Nga mice. Methods: BALB/c mice, in which scratching behavior was induced by intradermal injection of compound 48/80 (100 mug/100 mul/mouse), and NC/Nga mice, housed in a conventional environment and having developed spontaneous eczematous regions, were monitored with a SCLABA system after oral administration of bepotastine besilate. The number of eosinophils in the ear skin and the serum leukotriene B(4) (LTB(4)) levels were also evaluated. Results: Bepotastine at doses of 3 and 10 mg/kg effectively inhibited the compound 48/80-induced scratching behavior of BALB/c mice 1 h after oral administration, comparable with the blood T(max), which was reached within 0.8-1.6 h in humans. Bepotastine also significantly inhibited the scratching behavior of NC/Nga mice 1 h after oral administration. Even though 10 mg/kg bepotastine could not influence the number of tissue eosinophils, it effectively suppressed the serum LTB(4) levels, just comparable with the suppression of scratch behavior of NC/Nga mice. Conclusion: Bepotastin effectively suppressed the scratch behavior of atopic dermatitis model mice, which may not simply be explained by the suppression of histamine but also by the suppression of other mediators like LTB(4). Bepotastine could be useful in the treatment of pruritus, especially early after oral administration. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Bargagli E, Rottoli P
Omalizumab Treatment Associated with Churg-Strauss Vasculitis.
Int Arch Allergy Immunol. 2007 Oct 5;145(3):268. [Abstract]

Giovannetti A, Pierdominici M, Esposito A, Cagliuso M, Stifano G, Giammarioli AM, Maselli A, Malorni W, Salsano F, Aiuti F
Progressive Derangement of the T Cell Compartment in a Case of Evans Syndrome.
Int Arch Allergy Immunol. 2007 Oct 5;145(3):258-267.
Background: Evans syndrome (ES) is a rare disorder characterized by combined autoimmune thrombocytopenia and autoimmune hemolytic anemia. Several studies have documented a number of B cell defects, whereas only limited information is currently available about the T cell subset. Methods: A wide panel of immunological analyses aiming specifically at a quantitative and qualitative evaluation of the T cell compartment was performed in an unusual case of ES. The peripheral distribution of the T cell subsets, the diversity of the T cell receptor (TCR) repertoires, the cytokine profile and the T cell apoptosis have been longitudinally evaluated. Results: On first investigation, flow-cytometric immunophenotyping showed a remarkable alteration of T cell homeostasis with deeply reduced CD4+ naive T cells and recent thymic emigrants. This was seen in association with increased levels of T cell activation and apoptosis. Consistently with these data the cytokine profile was characterized by high interferon-gamma and low interleukin-2 levels. Staining for CD4 and CD25 molecules showed decreased percentages of circulating regulatory T cells according to the autoimmune nature of ES. Finally, restricted TCR repertoires were demonstrated by a skewed TCR beta chain variable (TCRBV) gene usage as well as oligoclonal third complementarity- determining region (CDR3) profiles. A deterioration of the above-mentioned parameters and a worsening of the clinical condition were observed during the follow-up requiring more intensive treatments. Conclusion: The demonstration of multiple T cell defects, in addition to providing pathogenetic information, is likely to alter both acute treatment and outcome of ES. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Nonaka Y, Izumo T, Izumi F, Maekawa T, Shibata H, Nakano A, Kishi A, Akatani K, Kiso Y
Antiallergic Effects of Lactobacillus pentosus Strain S-PT84 Mediated by Modulation of Th1/Th2 Immunobalance and Induction of IL-10 Production.
Int Arch Allergy Immunol. 2007 Oct 4;145(3):249-257.
Background: Many types of fermented food are consumed in Japan. Although some are produced by plant-origin lactic-acid bacteria (LAB) fermentation, the physiological functions of such bacteria remain unclear. We therefore isolated LAB of plant origin from Kyoto pickles and determined the immunological activity of heat-killed preparations of plant-origin LAB. Methods: The Lactobacillus pentosus strain S-PT84 was selected from among 16 LAB of plant origin as the strongest interleukin (IL)-12-inducing strain. IL-12- and IL-10-inducing activities were determined with macrophages from BALB/c mice. The in vivo immunomodulating effect of S-PT84was determined with BALB/c mice fed S-PT84. The antiallergic activity of S-PT84 was examined in ovalbumin (OVA)/alum-administered BALB/c mice. Results: The L. pentosus strain S-PT84 induced production of both IL-12 and IL-10 in vitro. S-PT84 enhanced splenic natural-killer activity and modulated the T helper (Th) type 1/type 2 balance toward a Th1-dominant state. In the OVA-induced allergy model, orally administered S-PT84 lowered serum IgE levels and suppressed active cutaneous anaphylaxis reaction and splenic IL-4 production. IL-10 production from splenocytes of OVA-immunized mice was upregulated by feeding S-PT84. Conclusions: Despite heat-killing, S-PT84 exhibited antiallergic effects by modulating the Th1/Th2 balance and inducing regulatory T cells. The L. pentosus strain S-PT84, which is of plant origin and isolated from a traditional Japanese food, is expected to be useful for treatment of many immune diseases including allergies, tumors, infectious diseases and auto-immune diseases. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Moin M, Aghamohammadi A, Gharavi MH, Ardestani A, Faghihimehr A, Kouhi A, Mazloumi M
Risk Factors Leading to Hospital Admission in Iranian Asthmatic Children.
Int Arch Allergy Immunol. 2007 Oct 4;145(3):244-248.
Background: Asthma is one of the most common chronic diseases in the world, leading to an increased rate of hospitalization. We performed this study to better understand the factors leading to admission among asthmatic children. Methods: We performed a study among asthmatic children in a referral hospital for asthma and allergy in Tehran. Sixty-three cases were selected from asthmatic children admitted to the emergency room (ER) who still had an indication for ward or intensive care unit admission after primary treatment. Our control group was the asthmatic children discharged after primary treatment and patients who were referred to the asthma and allergy clinic (63 patients). Data were obtained by structured questionnaires filled out during clinical interviews. Results: There was a significant difference in mean age (5 years for cases vs. 6 years for controls; p = 0.049), personal and familial allergic history (69.8 and 57.1% for cases vs. 34.9 and 36.5% for controls; p < 0.01 and p = 0.02, respectively), history of recent respiratory infections (79.4% for cases vs. 49.2% for controls; p < 0.01), hospitalization history due to asthma (57.1% for cases vs. 23.8% for controls; p < 0.01) and regular use of inhaled corticosteroid (66.7% for cases vs. 33.3% for controls; p < 0.01). Conclusions: Our findings confirm most previous observations, suggesting that recent respiratory infections, hospitalization, personal or familial allergy, disease severity and lower ages are important factors leading to hospitalization. We also found that regular clinical follow-up, regular use of inhaled corticosteroids, higher IgE levels and O(2) saturation may lower the probability of hospitalization during asthmatic attacks. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Carson Iv WF, Guernsey LA, Singh A, Vella AT, Schramm CM, Thrall RS
Accumulation of Regulatory T Cells in Local Draining Lymph Nodes of the Lung Correlates with Spontaneous Resolution of Chronic Asthma in a Murine Model.
Int Arch Allergy Immunol. 2007 Oct 4;145(3):231-243.
Background: Mice sensitized to ovalbumin develop allergic airway disease (AAD) with short-term aerosol challenge; however, airway inflammation resolves with long-term aerosol challenge, referred to as local inhalational tolerance (LIT). Methods: We sought to determine if resolution of airway inflammation correlated with increases in lymphocyte subsets in local lung compartments, including putative regulatory T cells. Results: At the AAD stage, total numbers of T and B lymphocytes in bronchoalveolar lavage (BAL) were significantly increased above controls; however, at LIT, T and B lymphocytes were significantly reduced compared to AAD. In the lung tissue, the only alteration was a significant increase in CD4+ CD25+ T cells at AAD. In the hilar lymph node (HLN), CD4+ and CD4+ CD25+ T cells were significantly increased at AAD and LIT. In addition, CD8+ T cells were significantly elevated in the HLN at LIT, and CD19+ B cells were significantly increased at AAD. Adoptive transfer of HLN lymphocytes to lymphopenic mice confirmed that AAD lymphocytes could induce airway inflammation in response to aerosol challenge, whereas LIT lymphocytes were unable to do so. Depletion of CD4+ CD25+ T cells in vivo resulted in exacerbation of inflammation at AAD and LIT. CD4+ CD25+ T cells in the HLN also displayed suppressive activity in vitro. Additionally, T cells expressing Foxp3 were increased in the BAL and HLN during LIT. Conclusions: These results indicate that lymphocytes with regulatory functions are increased and sustained in local lung compartments at LIT and that their appearance correlates with the resolution of lung inflammation. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Mistrello G, Harfi H, Roncarolo D, Kwaasi A, Zanoni D, Falagiani P, Panzani R
Date Palm Pollen Allergoid: Characterization of Its Chemical-Physical and Immunological Properties.
Int Arch Allergy Immunol. 2007 Oct 3;145(3):224-230.
Background: Date palm (DP) pollen can cause allergic symptoms in people living in different countries. Specific immunotherapy with allergenic extracts by subcutaneous route is effective to cure allergic people. However, the risk of side effects has led to explore safer therapeutic modalities. The aim of our work was to evaluate IgE cross-reactivity between DP and autochthonous palm (European fan palm, EFP) pollen extracts, to chemically modify DP extract with potassium cyanate in order to obtain an allergoid, and to characterize it. Methods: By radioallergosorbent test inhibition, immunoblotting (IB) and skin prick test, in vitro and in vivo allergenic activities of native and modified DP extracts were compared. By SDS-PAGE and IB, we compared the protein profile and IgE-binding capacity of both native and modified DP, as well as of EFP extracts. By IB inhibition, IgE cross-reactivity of native DP and EFP extracts was evaluated. By ELISA, the capacity of modified DP-induced IgG to react with native DP extract was determined. Results: Radioallergosorbent test inhibition, IB and skin prick test results demonstrated that modified DP was significantly less allergenic than native DP extract. The SDS-PAGE profile showed that potassium cyanate treatment of DP extract did not alter the molecular weight of its components. In addition, no difference was observed between native DP and EFP extracts. Subsequent IB inhibition data evidenced the existence of a strong IgE cross-reactivity between native DP and EFP extracts. ELISA results indicated that the administration of modified DP in mice was able to induce specific IgG also recognizing native DP extract. Conclusions: Modified DP extract (allergoid) seems to be a good candidate for immunotherapy of patients affected by specific allergy. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Eyerich K, Huss-Marp J, Darsow U, Wollenberg A, Forster S, Ring J, Behrendt H, Traidl-Hoffmann C
Pollen Grains Induce a Rapid and Biphasic Eczematous Immune Response in Atopic Eczema Patients.
Int Arch Allergy Immunol. 2007 Oct 3;145(3):213-223.
Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6-96 h after allergen application and investigated immunohistochemically. Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-gamma in the late phase. The NPT was continuously dominated by IFN-gamma. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Carnés J, Boquete M, Carballada FJ, Iraola V, Gallego MT, Fernández-Caldas E
Enzymatic Activity in Body and Fecal Extracts of the Storage Mite Chortoglyphus arcuatus.
Int Arch Allergy Immunol. 2007 Oct 3;145(3):207-212.
Background:Chortoglyphus arcuatus has been described in many countries. Many allergens are potent enzymes, which may promote a Th2 immune response. The aim of this study was to evaluate the enzymatic activity of body and fecal extracts of C. arcuatus. Material and Methods: Feces and bodies of full-grown C. arcuatus cultures were separated by sieving, extracted in PBS, dialyzed and lyophilized. The antigenic profile of both extracts was determined by SDS-PAGE. Immunoblot experiments were conducted using a pool of sera from allergic individuals residing in Galicia, a region of Spain, where this species is abundant. The enzymatic activity of the extracts was evaluated by the zymogram technique. Serine and cysteine protease activity was measured using in vitro methods. The API Zym(R) system was used to determine the enzymatic properties of the extracts. Results: The antigenic profile showed that the body extract contained more and better defined bands than the fecal extract. Allergens were detected in both extracts in a molecular weight range between 14 and 100 kDa. Gelatinolytic gels confirmed that fecal extracts contain more hydrolytic enzymatic activity than body extracts. Serine protease activity in fecal extracts was higher than in body extracts (5.98 vs. 2.701 IU of trypsin/mg of freeze-dried material). No cysteine protease activity was detected. Conclusion:C. arcuatus extracts contain several allergens and proteins with high enzymatic activity, especially in the feces. Some of these allergens may be enzymes. Fecal extracts have more enzymatic activity than body extracts. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Kahlert H, Suck R, Weber B, Nandy A, Wald M, Keller W, Cromwell O, Fiebig H
Characterization of a Hypoallergenic Recombinant Bet v 1 Variant as a Candidate for Allergen-Specific Immunotherapy.
Int Arch Allergy Immunol. 2007 Oct 2;145(3):193-206.
Background: Recombinant allergens and especially their hypoallergenic variants are promising candidates for a more effective and safer specific immunotherapy. Methods: Physicochemical and immunological characteristics of a folding variant of recombinant Bet v 1 (rBet v 1-FV) were investigated in comparison to natural Bet v 1 (nBet v 1) and the correctly folded recombinant Bet v 1 (rBet v 1-WT) by SDS-PAGE, size exclusion chromatography, multi-angle light scattering, circular dichroism, immunoblotting and enzyme allergosorbent test inhibition assay for detection of IgE reactivity and ELISA with Bet v 1-specific monoclonal antibodies. The functional IgE reactivity of the different Bet v 1 proteins was investigated using basophil activation in terms of CD203c expression and histamine release. T cell reactivity was investigated using T cell lines raised from birch pollen-allergic subjects against nBet v 1. Immunogenicity was investigated in mice. Results: Physicochemical characterization revealed purity, homogeneity and monomeric properties of rBet v 1-FV. Unlike nBet v 1 and rBet v 1-WT, rBet v 1-FV showed almost no IgE binding in immunoblots. The reduction of allergenicity was further proved by IgE-binding inhibition assays, basophil activation and histamine release. T cell reactivity was completely conserved, as demonstrated by proliferation of Bet v 1-specific T cell lines with multiple epitope specificities. rBet v 1-FV showed strong immunogenicity in mice. Conclusions: Due to its reduced IgE reactivity and decreased capacity to activate basophils, but retained T cell reactivity and strong immunogenicity, rBet v 1-FV proved to be a very promising candidate for specific immunotherapy in birch pollen-allergic subjects. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Gilmartin L, Tarleton CA, Schuyler M, Wilson BS, Oliver JM
A Comparison of Inflammatory Mediators Released by Basophils of Asthmatic and Control Subjects in Response to High-Affinity IgE Receptor Aggregation.
Int Arch Allergy Immunol. 2007 Oct 2;145(3):182-192.
Background: In human blood basophils, cross-linking the high-affinity IgE receptor FcepsilonRI with multivalent antigen activates a signaling pathway leading to secretion of inflammatory mediators and cytokine production. Basophils are known to play an important role in the pathogenesis of asthma but there has been no comprehensive examination of the effectors these cells produce. Here a study of the transcription and release of a selection of chemokines and cytokines from basophils was undertaken. Methods: A Cartesian antibody array provided an effective method of assaying for multiple cytokines and chemokines simultaneously. Results were verified by RT-PCR and ELISA assays. This allowed the comparison of freshly prepared peripheral blood basophil responses to cross-linking of the high-affinity IgE receptor, with and without preincubation with IL-3. Results: Evidence that human blood basophils produce the chemokines MIP-5, eotaxin and GM-CSF was provided by antibody array and RT-PCR analyses. Preincubation with IL-3 enhanced the expression and release of IL-13, IL-8 and mRNA transcripts encoding MIP-5 and GATA2 in basophils from both asthmatic and control subjects. Leptin mRNA transcription, storage and release in basophils are described for the first time. Conclusions: Surveying cytokine and chemokines stored and released by peripheral blood basophils shows that asthmatic and control subjects share similar profiles even when their degranulation responses are distinct. Evidence is provided for the production of leptin, GM-CSF, eotaxin and MIP-5 by peripheral blood basophils. IL-3 preincubation enhances the production and release of IL-8 upon IgE receptor cross-linking. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Nakano S, Yoshinuma T, Yamada T
Reactivity of Shrimp Allergy-Related IgE Antibodies to Krill Tropomyosin.
Int Arch Allergy Immunol. 2007 Oct 2;145(3):175-181.
Background: Krill, which morphologically resembles small shrimp, represents small ocean crustaceans and has been used for human consumption in Japan and some other countries. The major allergen in crustaceans has been reported to be tropomyosin, but the allergenicity of krill tropomyosin remains uncertain. Methods: Amino acid sequences of tropomyosin in two species of krill (Euphausia superba and E. pacifica) were deduced. Recombinant krill tropomyosins were produced in Escherichiacoli using a pCold IV vector system, and the cross-reactivity of shrimp allergy-related IgE to the recombinant tropomyosins and several animal protein extracts was assessed by immunoblotting. Results: The deduced amino acid sequences of the E. superba and E. pacifica tropomyosins (designated as Eup s 1 and Eup p 1, respectively) were 284 residues and showed significant homology to those of shrimp, lobster and crab tropomyosins. Shrimp allergy-related IgE reacted to approximately 38-kDa protein bands in krill (E. superba), shrimp, lobster and crab protein extracts but did not react to protein extracts from either mollusks or vertebrates. Furthermore, the IgE recognized rEup s 1 and rEup p 1 as 38-kDa protein bands, and absorption of the IgE with rEup s 1 removed IgE reactivity to recombinant tropomyosins and protein extracts from krill and shrimp. Conclusions: Krill tropomyosins included highly homologous sequences to previously reported IgE-binding epitopes in Pen a 1 (tropomyosin of Penaeus aztecus). The cross-reactivity in shrimp allergy-related IgE binding among krill, shrimp, lobster and crab tropomyosins was revealed. These observations suggest the potential allergenicity of krill tropomyosin. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Morishima H, Kajiwara K, Akiyama K, Yanagihara Y
Ligation of Toll-Like Receptor 3 Differentially Regulates M2 and M3 Muscarinic Receptor Expression and Function in Human Airway Smooth Muscle Cells.
Int Arch Allergy Immunol. 2007 Sep 11;145(2):163-174.
Background: Viral infection causes asthma exacerbations and airway hyperreactivity. Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) of viral or synthetic origin in a fashion different from protein kinase R (PKR). The aim of this study was to examine the expression and function of TLR3 in human airway smooth muscle (ASM) cells. Methods: Expression of TLR3 and muscarinic receptor (MR), histamine receptor (HR), and cysteinyl leukotriene receptor (CysLTR) subtypes was analyzed by quantitative real-time PCR, flow cytometry, or Western blotting. It was assessed whether ASM cells respond to polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of dsRNA, with alterations in M2R, M3R, H1R, and CysLT1R expression. The function of these subtypes was evaluated by cholinergic regulation of forskolin-stimulated cyclic AMP accumulation or by mobilization of intracellular calcium upon stimulation. Results: ASM cells expressed TLR3 and PKR, and intracellular TLR3 expression was demonstrated. Poly I:C caused decreased M2R and increased M3R expression, without affecting H1R and CysLT1R expression. Poly I:C-treated cells showed decreased cholinergic inhibition of forskolin-stimulated cyclic AMP accumulation and enhanced calcium flux in response to acetylcholine, but not to histamine and LTD(4). These modulating effects of poly I:C were reversed by chloroquine, but not by 2-aminopurine. Conclusions: The data indicate that poly I:C internalized by ASM cells differentially regulates M2R and M3R expression and function by interacting with TLR3 rather than with PKR, suggesting that these changes may contribute to airway hyperreactivity. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Van Overtvelt L, Lombardi V, Razafindratsita A, Saint-Lu N, Horiot S, Moussu H, Mascarell L, Moingeon P
IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma Model.
Int Arch Allergy Immunol. 2007 Sep 11;145(2):152-162.
Background: IL-10-inducing adjuvants could enhance the efficacy of allergy vaccines in establishing allergen-specific tolerance.The aim of this study wasto identify such adjuvants using in vitro cultures of human and murine cells and to evaluate them in a therapeutic murine model of sublingual immunotherapy (SLIT). Methods: Adjuvants stimulating IL-10 gene expression by human or murine immune cells were tested sublingually in BALB/c mice sensitized to ovalbumin (OVA), assessing the reduction in airway hyperresponsiveness (AHR) by whole-body plethysmography. The induction of regulatory T cells (T(reg)) was evaluated using phenotypic and functional assays. T-cell proliferation in cervical lymph nodes (LNs) was assessed following intravenous transfer of CFSE-labelled OVA-specific T cells and FACS analysis. Results: A combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3/Dex) as well as Lactobacillus plantarum were found to induce IL-10 production by human and murine dendritic cells (DCs). The former inhibits LPS-induced DC maturation, whereas L. plantarum induces DC maturation. Following stimulation with VitD3/Dex-pretreated DCs, CD4+ naďve T cells exhibit a T(reg) profile.In contrast, a Th1/T(reg) pattern of differentiation is observed in the presence of DCs treated with L. plantarum. Both adjuvants significantly enhance SLIT efficacy in mice, in association with either induction of Foxp3+ T(reg) cells (for VitD3/Dex) or proliferation of OVA-specific T cells in cervical LNs (for L. plantarum). Conclusions: Both VitD3/Dex and L. plantarum polarize naďve T cells towards IL-10-expressing T cells, through distinct mechanisms. As adjuvants, they both enhance SLIT efficacy in a murine asthma model. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Wakabayashi H, Nariai C, Takemura F, Nakao W, Fujiwara D
Dietary Supplementation with Lactic Acid Bacteria Attenuates the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice in a Strain-Dependent Manner.
Int Arch Allergy Immunol. 2007 Sep 11;145(2):141-151.
Background: Dietary supplementation with lactic acid bacteria (LAB) is a potential approach to the prevention and manipulation of allergic diseases such as atopic dermatitis (AD). However, the influence of different bacterial strains and their immunomodulating capacities is still largely unknown. Methods: AD-like skin lesions were induced by sensitization to and repeated challenges with picrylchloride in the Th2-skewed NC/Nga mouse strain. The effects of LAB supplementation were assessed over time by monitoring clinical scores and plasma IgE levels. In some cases, mast cell infiltration, cutaneous hypersensitivity responses and cytokine mRNA expression in auricles were also examined. Additionally, cytokine production in vitro and cytokine mRNA accumulation in major lymphoid tissues were measured, comparing Lactobacillus paracasei KW3110 with L. rhamnosus GG (LGG). Results: Supplementation with KW3110 significantly reduced the development of AD-like skin lesions, accompanied by less mast cell infiltration and lower plasma IgE levels. KW3110 also suppressed immediate hypersensitivity reactions and IL-4 mRNA expression in the auricles. These preventive effects sustained when supplementation was terminated; moreover, inhibitory effects were also observed even when supplementation was initiated after the onset of symptoms. In accordance with its effects on IL-12 and IL-4 production in vitro, KW3110 prevented the emergence of clinical symptoms more effectively than LGG in vivo. Conclusions: Supplementation with KW3110 significantly attenuated the onset and exacerbation of AD-like symptoms in NC/Nga mice. The effects were more prominent than those obtained with LGG, suggesting the importance of differences between LAB strains and their immunomodulating capacity. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Shefler I, Zavaro O, Raz T, Baram D, Sagi-Eisenberg R
Inhibition of Basic Secretagogue-Induced Signaling in Mast Cells by Cell Permeable Galphai-Derived Peptides.
Int Arch Allergy Immunol. 2007 Sep 10;145(2):131-140.
Background: Basic secretagogues of connective tissue mast cells act as receptor mimetic agents that trigger mast cells by activating G proteins. This leads to simultaneous propagation of two signaling pathways: one that culminates in exocytosis, while the other involves protein tyrosine phosphorylation and leads to release of arachidonic acid metabolites. We have previously shown that introduction of a peptide that comprises the C-terminal end of Galphai(3) into permeabilized mast cells inhibits basic secretagogue-induced exocytosis [Aridor et al., Science 1993;262:1569-1572]. We investigated whether cell-permeable peptides, composed of the C-terminus of Galphai(3) fused with importation sequences, affect mast cell function. Methods: Following preincubation with the fused peptides, rat peritoneal mast cells were activated by compound 48/80 and analyzed for histamine and prostaglandin D(2) release and protein tyrosine phosphorylations. Results: We demonstrate that out of three importation sequences tested only Galphai(3) peptide fused with the Kaposi fibroblast growth factor importation sequence (ALL1) inhibited release of histamine. ALL1 as well as a cell-permeable peptide that corresponds to Galphai(2) also blocked compound 48/80-stimulated protein tyrosine phosphorylation, though the latter did not block histamine release. ALL1 effect was G protein-specific, as it was incapable of blocking protein tyrosine phosphorylation stimulated by pervanadate. Conclusion: ALL1, a transducible Galphai(3)-corresponding peptide, blocks the two signaling pathways in mast cells: histamine release and protein tyrosine phosphorylation. Cell permeable peptides that block these two signaling cascades may constitute a novel approach for preventing the onset of the allergic reaction. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Buters JT, Kasche A, Weichenmeier I, Schober W, Klaus S, Traidl-Hoffmann C, Menzel A, Huss-Marp J, Kramer U, Behrendt H
Year-to-Year Variation in Release of Bet v 1 Allergen from Birch Pollen: Evidence for Geographical Differences between West and South Germany.
Int Arch Allergy Immunol. 2007 Sep 10;145(2):122-130.
Background: The release of the aeroallergen Bet v 1 from pollen is a major determinant in the etiology of allergic airway disease due to birch pollen. Objective: We determined the release of the major birch pollen allergen Bet v 1 from pollen of birch trees growing in 2 different geographic regions in Germany for 2 consecutive years. Methods: Catkins were collected during pollination in 2002 and 2003 from 82 healthy trees in South (Munich) and West Germany (North Rhine-Westphalia). The release of Bet v 1 from pollen samples was determined by a Bet v 1-specific ELISA. Results: Pollen from South Germany released about 3 times more Bet v 1 than those from West Germany in both 2002 and 2003 (p = 0.034 and p = 0.007, respectively). This was independent of the number of pollen during the pollen flight season. In 2003, the release of Bet v 1 from pollen was more than 5 times higher than in 2002 in both regions (South Germany 6.1 times, p < 0.001; West Germany 5.4 times, p = 0.003). Conclusions: Despite large individual differences, there seem to be regional and year-to-year variations in Bet v 1 release from birch pollen. Therefore, the combination of pollen count and release of Bet v 1 from this pollen must be assessed to estimate Bet v 1 exposure reliably. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Heijink IH, Kauffman HF, Vellenga E, Veltman-Starkenburg CA, Postma DS, de Monchy JG
Effect of Ciclesonide Treatment on Allergen-Induced Changes in T Cell Regulation in Asthma.
Int Arch Allergy Immunol. 2007 Sep 10;145(2):111-121.
Background: The allergen-induced release of CCL17/thymus and activation-regulated chemokine (TARC) may be crucial in asthmatic airway inflammation by recruitment of Th2 cells. In addition, it might lead to aberrant Th2 cell activity through impairment of beta(2)-adrenergic receptor (beta(2)-AR) control. We questioned how chemokine patterns change upon allergen challenge and whether treatment with the inhaled steroid ciclesonide can reduce chemokine release and subsequently prevent allergen-induced changes in Th2 cell regulation and migration. Methods: Asthma patients were double-blindly treated with placebo or 80 mug ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of beta(2)-agonist fenoterol over T cell migration and alpha-CD3/alpha-CD28-induced cytokine production. Results: Treatment with 80 mug ciclesonide significantly diminished the late asthmatic response. The late asthmatic response was associated with increased sputum levels of CCL17 and CCL4 (but none of the other chemokines measured) and loss of beta(2)-AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered beta(2)-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and alpha-CD3/alpha-CD28-induced cytokine production. Conclusion: Our data support the hypothesis that CCL17 is involved in allergen-induced dysregulation of Th2 cell migration and cytokine production. Ciclesonide treatment inhibits T cell migration and cytokine production upon allergen inhalation, which is regulated independently from reducing CCL17 release, but may contribute to beneficial effects of ciclesonide on Th2-mediated airway inflammation. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Oberhuber C, Ma Y, Wopfner N, Gadermaier G, Dedic A, Niggemann B, Maderegger B, Gruber P, Ferreira F, Scheiner O, Hoffmann-Sommergruber K
Prevalence of IgE-Binding to Art v 1, Art v 4 and Amb a 1 in Mugwort-Allergic Patients.
Int Arch Allergy Immunol. 2008 Sep 7;145(2):94-101.
Background: Mugwort (Artemisia vulgaris) represents an important source of weed pollen allergens. The objectives of the present study were (i) to analyze the IgE binding profiles in a group of mugwort-allergic patients, (ii) to identify individual marker allergens crucial for the diagnosis of mugwort allergy and (iii) to identify potential crossreactive allergens present in ragweed (Ambrosia artemisiifolia) pollen extract. Methods: Sera from 100 pediatric mugwort-allergic patients were analyzed for their IgE binding pattern to natural mugwort and ragweed pollen proteins, purified natural and recombinant Art v 1, recombinant Art v 4 and recombinant Amb a 1 using immunoblots and ELISA. Results: 91% of the patients' sera tested displayed IgE binding to one or more mugwort pollen allergens in ELISA and 88% were positive in immunoblot. Purified natural Art v 1 was recognized by 79%, the recombinant protein by 39% of the patients tested and purified recombinant Art v 4 by 34% of the patients' sera. 67% of the sera displayed crossreactive IgE to one or more ragweed pollen allergens. Recombinant Amb a 1 was noted in only 14% of the mugwort-allergic sera. Conclusions: Allergen-specific in vitro diagnosis was performed in 100 pediatric mugwort-allergic serum samples. Using two allergens (Art v 1 and Art v 4), 91% of the patients could be identified as mugwort pollen-sensitized patients by IgE in vitro tests. Crossreactivity to ragweed pollen allergens was demonstrated by in vitro experiments, suggesting a new important and potent allergen source expanding across Europe. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Guo P, Piao X, Cao Y, Ou D, Li D
Recombinant Soybean Protein beta-Conglycinin alpha'-Subunit Expression and Induced Hypersensitivity Reaction in Rats.
Int Arch Allergy Immunol. 2007 Sep 7;145(2):102-110.
Background: The major storage protein in soybean seed is beta-conglycinin and this protein has been identified as being responsible for food-allergic reactions in several species. However, the mechanism through which beta-conglycinin induces an allergic reaction has not yet been elucidated. In addition, assessing the antigenic activity of beta-conglycinin by studying the activity of a subunit has rarely been conducted. Therefore, the objective of the present study was to characterize the antigenic specificity of the beta-conglycinin alpha'-subunit. Methods: We established an Escherichia coli expression system to obtain beta-conglycinin alpha'-subunit. The fusion proteins were then used in a rat model to induce a hypersensitive reaction. Immunoblotting, IgE and IgG1 level, histamine release, and passive cutaneous anaphylaxis reactions and intestinal histology were tested to assess the allergenic activity of the beta-conglycinin alpha'-subunit. Results: Pure beta-conglycinin alpha'-subunit was obtained by expression in E. coli. The recombinant proteins were shown to have the same biological activity as the natural beta-conglycinin alpha'-subunit using immunoblotting analysis. Both the IgE and IgG1 level in serum and the histamine concentration in the intestine were increased while passive cutaneous anaphylactic reactions were induced in Brown Norway rats by intragastric gavage with the alpha'-subunit. Histamine release of mast cells was also elevated in vitro. Conclusions: Our results indicate that the beta-conglycinin alpha'-subunit possesses an intrinsic immune-stimulating capacity and that it can induce an allergic reaction. Moreover, this study showed that beta-conglycinin alpha'-subunit-induced anaphylaxis is IgE mediated, and mast cell degranulation and histamine release are associated with anaphylactic symptoms. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Zeller S, Glaser AG, Vilhelmsson M, Rhyner C, Crameri R
Immunoglobulin-E-Mediated Reactivity to Self Antigens: A Controversial Issue.
Int Arch Allergy Immunol. 2007 Sep 7;145(2):87-93.
Immunoglobulin E (IgE) reactivity to self antigens is well established in vitro by ELISA, inhibition ELISA, Western blot analyses and T cell proliferation experiments. In vivo, IgE-binding self antigens are able to elicit strong type I reactions in sensitized individuals and, in the case of human manganese superoxide dismutase, to elicit eczematous reactions on healthy skin areas of patients suffering from atopic eczema. The reactions against self antigens sharing structural homology with environmental allergens can be plausibly explained by molecular mimicry between common B cell epitopes. For the second class of IgE-binding self antigens without sequence homology to known allergens, it is still unclear if the structures are able to induce a B cell switch to IgE production, or if the reactivity is due to sequence similarity shared with not yet detected environmental allergens. However, in all cases, cross-reactivity is never complete, indicating either a lower affinity of IgE antibodies to self allergens than to the homologous environmental allergens or the presence of additional B cell epitopes on the surface of the environmental allergens, or both. Increasing evidence shows that self allergens could play a decisive role in the exacerbation of long-lasting atopic diseases. However, the only observation supporting a clinical role of IgE-mediated autoreactivity is confined to the fact that IgE levels against self antigens correlate with disease severity. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]


Proceedings of the 19th Workshop on Eosinophils in Allergy and Related Diseases. June 24, 2006. Tokyo, Japan.
Int Arch Allergy Immunol. 2007;143 Suppl 11-109. [Abstract]

Simon-Nobbe B, Denk U, Poll V, Rid R, Breitenbach M
The Spectrum of Fungal Allergy.
Int Arch Allergy Immunol. 2007 Aug 20;145(1):58-86.
Fungi can be found throughout the world. They may live as saprophytes, parasites or symbionts of animals and plants in indoor as well as outdoor environment. For decades, fungi belonging to the ascomycota as well as to the basidiomycota have been known to cause a broad panel of human disorders. In contrast to pollen, fungal spores and/or mycelial cells may not only cause type I allergy, the most prevalent disease caused by molds, but also a large number of other illnesses, including allergic bronchopulmonary mycoses, allergic sinusitis, hypersensitivity pneumonitis and atopic dermatitis; and, again in contrast to pollen-derived allergies, fungal allergies are frequently linked with allergic asthma. Sensitization to molds has been reported in up to 80% of asthmatic patients. Although research on fungal allergies dates back to the 19th century, major improvements in the diagnosis and therapy of mold allergy have been hampered by the fact that fungal extracts are highly variable in their protein composition due to strain variabilities, batch-to-batch variations, and by the fact that extracts may be prepared from spores and/or mycelial cells. Nonetheless, about 150 individual fungal allergens from approximately 80 mold genera have been identified in the last 20 years. First clinical studies with recombinant mold allergens have demonstrated their potency in clinical diagnosis. This review aims to give an overview of the biology of molds and diseases caused by molds in humans, as well as a detailed summary of the latest results on recombinant fungal allergens. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Pagani M, Bonadonna P, Senna GE, Antico A
Standardization of Skin Tests for Diagnosis and Prevention of Hypersensitivity Reactions to Oxaliplatin.
Int Arch Allergy Immunol. 2007 Aug 17;145(1):54-57.
Background: Platinum salts can cause allergic sensitization. Recently, hypersensitivity reactions to oxaliplatin, the most recent platinum coordination complex introduced into clinical practice, have been reported. Objective: To validate and standardize skin tests to diagnose and possibly prevent hypersensitivity reactions to oxaliplatin. The secondary aims were to confirm IgE-mediated pathogenesis of the clinical manifestations and to evaluate skin tests to predict patients at risk of hypersensitivity reactions to oxaliplatin. Methods: We performed skin tests atincreasing concentrations of oxaliplatin on 15 patients never exposed to platinum salts, on 10 patients treated with oxaliplatin without any adverse reactions, and on 4 patients who had shown hypersensitivity reactions to the drug. Moreover we performed skin tests on 8 additional patients starting before the 5th dose and following a course of chemotherapy. Results: A positive skin reaction to the prick test at a concentration of 1 mg/ml was seen in 1 patient with hypersensitivity reactions. The intradermal test was positive in all the patients with hypersensitivity reactions at a concentration of 0.1 mg/ml. It was negative in the 15 nonexposed subjects, and in the 10 patients who had been exposed to oxaliplatin without hypersensitivity reactions. The skin test administered to patients before chemotherapy was positive in one case. Conclusion: A skin prick test at a concentration of 1 mg/ml and, in the case of a negative response, an intradermal test at the optimal concentration of 0.1 mg/ml should be used, starting from the 5th course of therapy, to diagnose and prevent hypersensitivity reactions to oxaliplatin. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Greco E, Bottini N, Canu G, Maccari AM, Saccucci P, Gloria-Bottini F, Fontana L
Skin Testing Correlates Negatively with High-Activity ACP1 *B/*C Genotype.
Int Arch Allergy Immunol. 2007 Aug 17;145(1):48-53.
Background: Previous studies have shown a negative association between ACP1 *B/*C genotype and total IgE level. ACP1 (acid phospatase locus 1) is a polymorphic phosphotyrosine phosphatase that interacts with IL4-RA and is involved in T cell receptor signaling. Methods: In the present paper, we have studied the relationship between *B/*C genotype which shows high ACP1 activity and skin testing in 300 adult subjects referred for allergic manifestations. ACP1 genotypes were determined by DNA analysis. Results: There is a significant negative correlation between the intensity of skin test reaction and *B/*C genotype (p = 0.01). The proportion of *B/*C genotype is lower in allergic subjects with intense skin reaction than in allergic subjects with moderate skin reaction and in healthy controls. Conclusions: This new observation confirms by a different approach the relationship between ACP1 polymorphism and allergic manifestations, suggesting that high ACP1 activity protects against these manifestations. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Szczepankiewicz A, Br?borowicz A, Skibi?ska M, Wi?ko?? M, Tomaszewska M, Hauser J
Association Analysis of Tyrosine Kinase FYN Gene Polymorphisms in Asthmatic Children.
Int Arch Allergy Immunol. 2007 Aug 17;145(1):43-47.
Background: FYN is nonreceptor tyrosine kinase that represents the earliest detectable signaling response after antigen-activated inflammatory cells. Studies in animal models of allergic asthma have shown that inhibitors of tyrosine kinases exert an anti-inflammatory effect. In the FYN gene, several polymorphisms have been described. There have, however, been no studies analyzing the impact of FYN gene polymorphisms on the course and severity of asthma. The aim of this study was to analyze the possible relationship between three polymorphisms (-93A/G, Intron10+37C/T and Ex12+894T/G) in the FYN gene and asthma. Methods: We analyzed 120 pediatric asthmatic patients aged from 6 to 18 years. The diagnosis of allergic asthma was based on clinical manifestation, lung function test and positive skin prick tests and/or an increased IgE level. The control group consisted of 187 healthy subjects. The polymorphisms were genotyped with use of the PCR-RFLP method. Results: We observed an association of the -93A/G polymorphism and the presence of asthma (p = 0.014 for genotypes and p = 0.019 for alleles) and in the subgroup of 55 patients with severe asthma (p = 0.042 for genotypes and p = 0.021 for alleles). We also found an association of the Ex12+894T/G polymorphism in the whole group analyzed (p = 0.067 for genotypes and p = 0.024 for alleles), but not in the subgroup with severe asthma. For the Intron10+37T/C polymorphism, we did not find a significant difference between the whole group of asthmatic patients and the control group nor between the subgroup with severe asthma and the control group. In the linkage disequilibrium analysis, we observed a modest linkage between -93A/G and Intron10+37T/C polymorphisms (lod = 18.7, D' = 0.62, 95% CI: 0.51-0.71, r(2) = 0.29); however, it was not strong enough to generate any haplotypes. Conclusions: The results may suggest a relationship between the FYN polymorphisms and allergic asthma. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]

Arlian LG, Morgan MS, Peterson KT
House Dust and Storage Mite Extracts Influence Skin Keratinocyte and Fibroblast Function.
Int Arch Allergy Immunol. 2007 Aug 17;145(1):33-42.
Background: The bodies of allergy-causing dust and storage mites likely contain many bioreactive molecules, including some that are allergenic. These molecules may penetrate the epidermis and dermis of the skin. However, little is known about the effects that most of the molecules from mites have on the function of cells in the skin, the overall inflammatory and immune reactions and the manifestation of allergic disease.The purpose of this research was to determine the response of cultured skin cells (keratinocytes and fibroblasts) to extracts of house dust and storage mites. Methods: Normal human epidermal keratinocytes and dermal fibroblasts were cultured with varying doses of extracts of the storage mites Acarus siro, Chortoglyphus arcuatus or Lepidoglyphus destructor or of the house dust mites Dermatophagoides farinae, D. pteronyssinus or Euroglyphus maynei in the absence or presence of lipopolysaccharide. Culture supernatants were collected 24 h later and assayed for the presence of various chemokines and cytokines. Results: Keratinocytes constitutively secreted interleukin (IL)-1 receptor antagonist/IL-1F3, growth-related oncogene alpha and transforming growth factor alpha, and these secretions were modulated by extracts of 1 or more of the mites tested. Mite extracts also modulated the production of IL-6, IL-8, monocyte chemoattractant protein 1, macrophage colony-stimulating factor and vascular endothelial growth factor from fibroblasts. Conclusions: The effects that mite extracts exerted on both keratinocytes and fibroblasts varied among the house dust mite species, among the storage mite species and between the house dust and storage mites. This study showed that extracts of mites contain substances that modulate the production of proinflammatory cytokines and chemokines secreted by normal human epidermal keratinocytes and dermal fibroblasts, and therefore may influence the course of pathophysiology in the skin in atopic dermatitis. Copyright (c) 2007 S. Karger AG, Basel. [Abstract]


Recent Articles in Pediatric Allergy and Immunology: Official Publication of the European Society of Pediatric Allergy and Immunology

Felisati G, Ramadan H
Rhinosinusitis in children: the role of surgery.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18 .
Indications and nature of surgery for chronic rhinosinusitis (CRS) have yet to be elucidated in children. After review of the literature and based on their experience, the authors suggest guidelines for the treatment of CRS in children. They suggest grouping children with rhinosinusitis into two groups: those with complicated acute rhinosinusitis and those with CRS. For the first group, the authors suggest an early surgical intervention because of the potential serious consequences and sometimes irreversible damage. For the second group, most agree that maximal medical management should be the first line of treatment with antibiotics, nasal lavage and as a last resort surgery. It is important to realize that surgery should be considered in these cases if medical treatment fails. Once surgery is recommended, the kind of surgery then becomes an issue between adenoidectomy, endoscopic sinus surgery or a combination of the two depending on the age and other conditions. [Abstract]

Fiocchi A, Sarratud T, Bouygue GR, Ghiglioni D, Bernardo L, Terracciano L
Topical treatment of rhinosinusitis.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
We reviewed current clinical evidence for the use of topical treatments in pediatric rhinosinusitis. Repeated Entrez PubMed searches were done using the template algorithm [rhinosinusitis AND (...)] with the settings: [Humans; English; All Child 0-18; Clinical trial; Last 10 yr] for the following comparators: steroid, irrigation, saline, antihistamine, decongestant, antibiotic, antimycotic, fungicide. The authors' clinical experience in the pediatric allergy unit of a university hospital was also drawn upon. Pediatric studies were retrieved but only one satisfied current evidence-based medicine standards for reporting clinical trials. Studies could not be systematized because of methodological, analytical, and interpretation biases. While saline irrigation, nasal decongestants, steroids, antibiotics, antihistamines and fungicides are all in widespread pediatric use, comparing studies from the literature for evidence of efficacy implied subjective appraisal, except in the case of topical steroids. Evidence for the efficacy of topical treatment for pediatric rhinosinusitis is narrative albeit this modality cannot be excluded from individualized patient protocols on the basis of the clinical literature alone. With the exception of topical steroids, no weighable evidence of effectiveness supports the premise that topical treatments actually serve the purpose for which they are widely prescribed in pediatrics. [Abstract]

Gelardi M, Fiorella ML, Leo G, Incorvaia C
Cytology in the diagnosis of rhinosinusitis.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Nasal cytology is a diagnostic tool currently used in rhinology, with the aim of assessing cell changes in the nasal epithelium exposed to irritant or inflammatory agents. Its rationale is based on the knowledge that nasal mucosa of healthy individuals is constituted by four cytotypes (ciliata, mucipara, striata, and basalis) and does not show other cells except, rarely, neutrophils and, very rarely, bacteria. In this view, the detection of a given cell type different from these is a sign of possible pathology. The advantage and the diffusion of nasal cytology were increased by a number of factors such as the easiness of performance, the non-invasiveness allowing repetition (which is often needed in the efficacy monitoring of medical or surgical treatment of nasal diseases), and the low cost. This makes nasal cytology particularly feasible for application in children. The cytological feature characterizing infectious inflammation is the presence of abundant bacteria, which may be found in extracellular tissue and also inside neutrophils as a result of phagocytosis. In such clinical condition it is important to monitor the disease with cytological controls to verify the significant decrease, or the disappearance of inflammatory cells, which indicates the resolution of the pathology. [Abstract]

Passalacqua G, Canonica GW, Baiardini I
Rhinitis, rhinosinusitis and quality of life in children.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Quality of life (QoL) or, rather, health-related QoL, is currently regarded as a crucial aspect of the general well-being of patients and, in consequence, of the effects of a disease and its treatment. This is particularly true for respiratory allergy (asthma and rhinitis), which are chronic diseases and also for sinusitis (rhinosinusitis). A number of questionnaires (instruments), either generic or specific, have been developed and validated to assess the QoL in adults and children, for asthma and rhinitis, whereas there are few specific instruments for chronic rhinosinusitis. The literature provides strong evidence of the effects of allergic rhinitis, asthma and their treatments on QoL in paediatric patients, as well as in adults, whereas the number of experimental data on rhinosinusitis is limited, especially in children. Clinical trials evidenced some controversial points, mainly the weak correlation existing between QoL and traditional objective parameters. It has become clear that the QoL questionnaires measure the aspects of the disease that partially differ from the routinely evaluated parameters and that QoL should integrate, not replace, the objective measurements. [Abstract]

Leo G, Piacentini E, Incorvaia C, Consonni D
Sinusitis and Eustachian tube dysfunction in children.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Because of its anatomic and functional connections, middle ear disorders frequently occur in sinusitis. Its prevalence, however, is likely to be underestimated. We evaluated the prevalence of Eustachian tube dysfunction in children with chronic sinusitis, in a large group of patients with chronic respiratory symptoms and its possible relationship with respiratory allergy. From a population of 1810 children with respiratory symptoms referred to our Pediatric Allergy Center, subjects with chronic sinusitis diagnosed by clinical criteria were selected. The children underwent testing of Eustachian tube function by tympanometry and of allergy by skin tests with common environmental allergens. Patients were divided into three groups according to age: group 1, <3 yr; group 2, between 3 and 6 yr, group 3, older than 6 yr. Overall 402 children (22.2%) had clinical diagnosis of chronic sinusitis according to the established criteria. Thirty-three patients were in group 1, 299 in group 2, and 70 in group 3. Altered middle ear pressure was found in 69.1% of patients, with a significantly higher rate of altered tympanograms in younger children (p = 0.001). A positive skin-prick test was found in 29.8% of children, with a significantly higher rate of positivity in older children (p = 0.015). The decrease in the rate of Eustachian tube dysfunction with age is likely to be associated with the anatomic development of the upper airways, while the presence of atopy does not seem to play a role in their occurrence. [Abstract]

Marchisio P, Ghisalberti E, Fusi M, Baggi E, Ragazzi M, Dusi E
Paranasal sinuses and middle ear infections: what do they have in common?
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Otitis media and sinusitis are among the most common pediatric diseases and they share common features. Although the anatomy, physiology and disease processes are not identical, knowledge of the pathophysiology of middle ear disorders often provides to the pediatrician a useful understanding of sinus diseases. The same risk factors identified for otitis media may play a pivotal role in the development of sinusitis. Moreover, as both paranasal sinuses and middle ear acquire respiratory pathogens from nasopharynx, acute sinusitis is usually caused by the same bacterial pathogens that cause acute otitis media, with a major role for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, while anaerobes may predominate in chronic disease. A responsibility of bacterial biofilms in chronic sinusitis, similarly to otitis media, has been recently suggested. Biofilms, three-dimensional aggregates of bacteria, are refractory to antibiotics and thus might explain why some patients improve while on antibiotics but relapse after completion of therapy. [Abstract]

Carraro S, Gottardi G, Bonetto G, Baraldi E
Exhaled nitric oxide in children with asthma and sinusitis.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Exhaled nitric oxide (FE(NO)) is a surrogate marker of eosinophilic airway inflammation. The measurement of this gas can be easily performed in children and the result is immediately available. Because of these characteristics, measurement of FE(NO) is slowly becoming part of the routine clinical evaluation of an asthmatic patient. FE(NO) measurement may have a role both in the diagnosis of asthma and as a guide in therapy algorithms. For example when FE(NO) levels are persistently normal and the asthmatic child is asymptomatic, the steroid therapy may be decreased or even stopped. In patients with acute or chronic rhinosinusitis the levels of nasal nitric oxide (nNO) are significantly decreased, while they rise up after a course of antibiotics. The measurement of nasal NO has been proposed as a functional test to evaluate sinus ventilation. Nasal NO is significantly reduced also in primary ciliary dyskinesia and can be used as a screening tool to identify patients affected by this condition. [Abstract]

Peroni DG, Piacentini GL, Ceravolo R, Boner AL
Difficult asthma: possible association with rhinosinusitis.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Difficult asthma is rare in childhood; when child's asthma is difficult to control, review of the diagnosis and evaluation of the different risk factors for exacerbations are recommended. The relationship between rhinosinusitis and bronchial asthma is provided by epidemiologic data. Doubts persist as to whether rhinosinusitis worsens asthma, or whether these are manifestations in different parts of the respiratory tract of the same underlying disease process. However, nasal sinus disease may contribute to less control in asthma, and patients with severe asthma appear to have the most prominent abnormalities on computed tomography scanning of the paranasal sinuses. From a pathogenetic point of view, many inflammatory mediators and the cellular infiltrate are often the same in the two entities, with a relevant role probably played by eosinophils. Antibiotic treatment of chronic sinus disease in asthmatic children may improve subjective asthmatic symptoms, lung function, and decrease bronchial hyperreactivity. Scientific evidence confirms that there may be an association between asthma and sinusitis even in childhood asthma: this could be relevant for diagnostic and therapeutic purposes. [Abstract]

Barbi E, Longo G
Chronic and recurrent cough, sinusitis and asthma. Much ado about nothing.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Respiratory infections are the main causes of chronic or recurrent cough in children. Children present 3.8-8 infective episodes per year with cough lasting, on average, 1-3 wk and 10% will still have cough after 4 wk. There is evidence of over-treatment of cough with antibiotics, anti-asthmatic drugs (in Italy) and symptomatic treatments, all with insufficient evidence of efficacy. The relation between sinusitis, asthma and isolated cough is possibly overemphasized. Cough is a symptom of sinusitis, but one can rarely expect isolated persistent or recurrent cough as the only symptom. The issue of chronic cough as the only sign of asthma has been extensively investigated. Recent literature established that the majority of children with isolated cough do not have asthma in terms of both absence of signs of typical asthma inflammation and response to steroid treatment. This unconfirmed hypothesis has unfortunately often resulted in a misunderstood use of inhaled steroids as 'symptomatic' treatment. Our aim should be to avoid unnecessary medicalization and lessen anxiety not by simply prescribing, but by spending time in evaluating patients and explaining to parents what are mostly physiological events, which should resolve spontaneously over time. [Abstract]

Leo G, Piacentini E, Incorvaia C, Consonni D, Frati F
Chronic rhinosinusitis and allergy.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
The role of allergic sensitization in chronic sinusitis in childhood is currently unclear, as contrasting results were reported in the studies thus far available. In fact, some surveys found prevalence of atopy up to 60% in subjects with chronic sinusitis, while other failed to confirm any association between the two conditions. The data we obtained in a cross-sectional study on a large population of children should help in better defining such issue. Among 2200 children referring for evaluation of chronic respiratory symptoms, subjects satisfying at least two of major criteria for the definition of chronic sinusitis were recruited, and underwent to allergen sensitization workup by skin prick test with common inhalant allergens and total IgE measurement. Patients were stratified according to age lower than 3 years (group 1), age between 3 and 6 years (group 2), and age above 6 years (group 3). In all, 351 children (217 boys, 134 girls, mean age 5.23 +/- 2.11 years, range 1.5-15 years) were available for evaluation and formed three groups (27 in group 1, 261 in group 2 and 63 in group 3). Prevalence of both sensitization to at least one inhalant allergen by skin test and of high total IgE was 29.9%, with significant difference for the former across age groups, with a value of 7.4% in group 1, 31.4% in group 2 and 33.3% in group 3 (p = 0.028), but after adjusting for age, sinusitis and aeroallergen sensitization were not significantly correlated. The difference across groups for high total IgE did not reach statistical significance, with respective prevalence of 22.7%, 30.1% and 32.1%. It is possible to conclude that the prevalence of sensitization to aeroallergens in children with chronic sinusitis is comparable with that of the general paediatric population, as assessed in the Italian arm of the ISAAC study and this does not account for routine investigation for allergy in children with chronic sinusitis. [Abstract]

Marseglia GL, Castellazzi AM, Licari A, Marseglia A, Leone M, Pagella F, Ciprandi G, Klersy C
Inflammation of paranasal sinuses: the clinical pattern is age-dependent.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18
Acute rhinosinusitis (ARS) represents a common disorder, associated with consistent morbidity as well as with a large prescription of antibiotics. ARS has a significant impact on clinical practice; it usually presents with respiratory complaints persisting longer than 10 days and showing no signs of improvement. Throughout the evaluation of 256 pediatric patients (152 males and 135 females, aged between 2 and 15 yr), with ARS confirmed by nasal endoscopy, we have been able to provide evidence that age has a significant influence on clinical patterns in children with ARS. [Abstract]

Leo G
Rhinosinusitis and associated disorders in children: an introduction.
Pediatr Allergy Immunol. 2007 Nov;18 Suppl 18 [Abstract]

Khan S, Kandula L, Orenstein SR
Educational clinical case series in pediatric allergy and immunology.
Pediatr Allergy Immunol. 2007 Nov;18(7):
Eosinophilic inflammation may occur in any part of the intestinal tract from the esophagus to the rectum. Despite 70 yr having passed since the first reference to a case of eosinophilic gastroenteritis, the epidemiology and natural history of eosinophilic gastrointestinal disorders are still poorly known. Insights into their etiology and pathogenesis have revealed an important role for allergens; interleukins 4, 5, and 13; the eotaxin family of chemokines; and eosinophil-derived proteins. Diagnosis is confirmed by typical histologic features in a patient with a suggestive clinical phenotype. Treatment involves eliminating triggering allergens, making dietary restrictions the first choice of therapy in a compliant patient; corticosteroids [topical in eosinophilic esophagitis (EE)], despite the potential for serious side effects, are used with success in refractory and non-compliant patients. In this study we discuss EE and gastroduodenitis against the backdrop of clinical case presentations. [Abstract]

Passalacqua G
Reply to the letter by Dr de Bot.
Pediatr Allergy Immunol. 2007 Nov;18(7): [Abstract]

de Bot CM, Moed H
Quantitative assessment of the compliance with once-daily sublingual immunotherapy in children.
Pediatr Allergy Immunol. 2007 Nov;18(7): [Abstract]

Alessandri C, Mari A
Efficacy of donkey's milk in treating cow's milk allergic children: Major concerns.
Pediatr Allergy Immunol. 2007 Nov;18(7): [Abstract]

Brooks K, Hasan H, Samineni S, Gangur V, Karmaus W
Placental p,p'-dichlorodiphenyldichloroethylene and cord blood immune markers.
Pediatr Allergy Immunol. 2007 Nov;18(7):
Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration. [Abstract]

Contin-Bordes C, Petersen A, Chahine I, Boralevi F, Chahine H, Taďeb A, Sarrat A, Moreau JF, Taupin JL
Comparison of ADVIA Centaur((R)) and Pharmacia UniCAP((R)) tests in the diagnosis of food allergy in children with atopic dermatitis.
Pediatr Allergy Immunol. 2007 Nov;18(7):
In a study comprising 63 children diagnosed with atopic dermatitis, the results of the ADVIA Centaur system was compared with the results obtained with the Pharmacia UniCAP100 system, which has been widely considered as a reference method for seric specific IgE (sIgE) measurements. The individual immunization against the most common food allergens [egg (f1), cow milk (f2), cod (f3), wheat (f4), peanut (f13) and soy bean (f14)] was determined by in vitro serum IgE testing and skin prick test (SPT). The comparison of the sIgE titers revealed a good concordance between the Centaur and the UniCAP tests for f1, f3, and f13 (94 %, 91 %, and 96 % respectively). However, the concordance was lower for f2, f4, and f14 (76 %, 77 %, and 77 % respectively) because of discrepancies between the two techniques. When compared with SPT and clinical diagnosis, on the 40 discordant cases found between the Centaur and the UniCAP, the Centaur showed concordance with the patients food reaction and SPT in 34/40 cases, and UniCAP in only 6/40 cases. Accordingly, the Centaur test displayed a statistically significantly better performance on specificity and concordance with SPT for f2, f4, and f14 (concordance/specificity = 70%/71%, 76%/75% and 90%/88% respectively), than the CAP test (49%/54%, 51%/52% and 67%/65% respectively). [Abstract]

El-Khouly F, Lewis SA, Pons L, Burks AW, Hourihane JO
IgG and IgE avidity characteristics of peanut allergic individuals.
Pediatr Allergy Immunol. 2007 Nov;18(7):
The role of antibody avidity in allergy is poorly understood and there is no existing literature describing antibody avidity in food allergy. The main aim of this study was to investigate IgE and IgG avidity to a total peanut protein extract (TPPE) and purified Ara h 2 in a group of well-characterized peanut allergic individuals. Forty peanut allergic patients underwent a double-blind placebo-controlled low-dose peanut challenge, during which the severity of the patients' peanut allergy was scored. Serum peanut-specific IgE (psIgE) and IgG (psIgG) concentrations were measured for 37 individuals and the avidities of the same antibodies to a TPPE and purified Ara h 2 were determined using a thiocyanate ELISA method. Both IgE and IgG avidity to Ara h 2 showed weak positive correlations with challenge score [r = 0.459 (p = 0.012) and r = 0.486 (p = 0.003), respectively]. IgE avidity to TPPE showed a weak positive correlation with skin prick test results (SPT), r = 0.467 (p = 0.004) and there was an inverse relationship between the ratio of total IgE:psIgE and challenge score r = -0.561 (p < 0.001). No significant relationship was found between the ratios of IgE avidity:IgG avidity and challenge score or SPT. This is the first description of IgE and IgG avidity in peanut allergy, and it appears that the avidities of IgE and IgG antibodies to purified Ara h 2 are weakly related to the severity of peanut allergy (as measured by a challenge score). [Abstract]

Vita D, Passalacqua G, Di Pasquale G, Caminiti L, Crisafulli G, Rulli I, Pajno GB
Ass's milk in children with atopic dermatitis and cow's milk allergy: Crossover comparison with goat's milk.
Pediatr Allergy Immunol. 2007 Nov;18(7):
Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single-blind, controlled, randomized crossover. Twenty-eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS-PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter-group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM. [Abstract]

Mauro C, Claudia A, Tullio F, Sandra L, Stefano MS, Valentina P, Daniela Z, Maria ZA
Correlation between skin prick test using commercial extract of cow's milk protein and fresh milk and food challenges.
Pediatr Allergy Immunol. 2007 Nov;18(7):
The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges. [Abstract]

Kurt E, Metintas S, Basyigit I, Bulut I, Coskun E, Dabak S, Deveci F, Fidan F, Kaynar H, Uzaslan EK, Onbasi K, Ozkurt S, Pasaoglu G, Sahan S, Sahin U, Oguzulgen K, Yildiz F, Mungan D, Yorgancioglu A, Gemicioglu B, Fuat Kalyoncu A
Prevalence and risk factors of allergies in Turkey: Results of a multicentric cross-sectional study in children.
Pediatr Allergy Immunol. 2007 Nov;18(7):
The Prevalence And Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate prevalence and risk factors of asthma and allergic diseases and also to find out which geographical variables and/or climatic conditions play a role determining the prevalence of allergic diseases in Turkish school children. Study was planned as cross-sectional questionnaire-based. About 25,843 questionnaires from 14 centers were appropriate for analysis. Parental history of allergy, having an atopic sibling and other atopic disease in index case was significant risk factors for all allergic diseases. Breast feeding decreased the risk of current asthma (OR: 0.92, CI: 0.86-0.99) and wheezing (OR: 0.93, CI: 0.87-0.99) but not allergic rhinitis and eczema. Respiratory infection in the past was an important risk factor for the occurrence of allergic diseases especially for asthma which was increased 4.53-fold. Children exposed to household smoke were significantly at higher risk of asthma, wheezing, and allergic rhinitis (OR: 1.20, CI: 1.08-1.33; OR: 1.21, CI: 1.09-1.34; and OR: 1.32, CI: 1.21-1.43, respectively). All allergic diseases were increased in those children living in areas which have altitude of below 1000 m and mean yearly atmospheric pressure above 1000 mb. The study has suggested that household and country-specific environmental factors are associated with asthma, wheezing, allergic rhinitis, and eczema risk during childhood in Turkey. [Abstract]

Zar HJ, Ehrlich RI, Workman L, Weinberg EG
The changing prevalence of asthma, allergic rhinitis and atopic eczema in African adolescents from 1995 to 2002.
Pediatr Allergy Immunol. 2007 Nov;18(7):
The prevalence of asthma and allergic disease in children has been increasing in developed countries, but there is little information on these trends in Africa. The aim of this study was to assess time trends in the symptoms of asthma, allergic rhinitis, and atopic eczema among South African adolescents. The study was carried out by comparing cross-sectional data from two International Study of Asthma and Allergies in Childhood (ISAAC phase I and phase III) questionnaire based surveys conducted 7 yr apart of self-reported symptoms in 13- to 14-yr-old adolescents. In both surveys, schools in the same geographical area in Cape Town, South Africa, were randomly selected. A school-based sample of 5178 (in 1995) and 5037 (in 2002) pupils participated. The 12-month prevalence of wheezing (16% vs. 20.3%), exercise-induced wheeze (21.5% vs. 32.5%), nocturnal cough (23.6% vs. 36.6%), sleep disturbance due to wheeze (9.6% vs. 16%), or severe wheeze (5.1% vs. 7.8%) increased significantly, as measured by the written questionnaire. A rise in asthma symptoms was confirmed by the video questionnaire responses, in which the 12-month prevalence of wheezing (6.5% vs.11.2%), exercise-induced wheeze (11.5% vs. 13.9%), nocturnal wheeze (3.9% vs. 5.3%), nocturnal cough (11.6% vs. 19.2%), or severe wheeze (5% vs. 7%) also increased significantly. There was a small increase in the percentage of children diagnosed with asthma from 1995 to 2002 (13.1% vs. 14.4%), this was not significant. The 12-month prevalence of symptoms of allergic rhinitis (30.4% vs. 38.5%), rhinoconjunctivitis (17.6% vs. 24.3%) and eczema (11.8% vs. 19.4%) also increased significantly. An increase in the prevalence of allergic symptoms occurred in girls and boys. Limitation of daily activity from nasal symptoms (22.3% vs. 37.8%) and sleep disturbance because of eczema (8.4% vs. 15.7%) increasingly affected quality of life on the quality of life. Symptoms of asthma, allergic rhinitis and atopic eczema in adolescents have increased over the past 7 yr in this geographical area. Allergic diseases are common in this group of adolescents and increasingly impair their quality of life. [Abstract]

Obihara CC, Bollen CW, Beyers N, Kimpen JL
Mycobacterial infection and atopy in childhood: A systematic review.
Pediatr Allergy Immunol. 2007 Nov;18(7):
The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta-analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966-2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross-sectionals, three case-controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta-analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross-sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51-0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross-sectional studies. In a meta-analysis, calculations showed a high level of heterogeneity (I(2)) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross-sectional observational studies indicates the need for population-based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial-based vaccines against atopic disease in the future. [Abstract]

Warner JO
Do we need more management guidelines?
Pediatr Allergy Immunol. 2007 Nov;18(7): [Abstract]

Roberts G
Anaphylaxis to foods.
Pediatr Allergy Immunol. 2007 Sep;18(6):
Three crucial areas of the management of anaphylaxis due to food allergy are discussed: making a diagnosis, deciding who needs a self-injectable adrenaline device and spotting the novel allergen. Managing children and teenagers with anaphylaxis is challenging due to the lack of available evidence that specific addresses these issue. The available evidence is presented and discussed. [Abstract]

Kopp MV, Stenglein S, Kamin W, Friedrichs F, von Berg A, Zielen S, Hamelmann E, Wahn U, Kuehr J
Omalizumab (Xolair) in children with seasonal allergic rhinitis: leukotriene release as a potential in vitro parameter to monitor therapeutic effects.
Pediatr Allergy Immunol. 2007 Sep;18(6):
To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3-17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy. [Abstract]

Ibańez MD, Kaiser F, Knecht R, Armentia A, Schöpfer H, Tholstrup B, Bufe A
Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in children.
Pediatr Allergy Immunol. 2007 Sep;18(6):
The aim of the study was to confirm the safety of an orodispersible grass allergen tablet 75,000 SQ-T (Grazax, ALK-Abelló A/S, Hřrsholm, Denmark) in children aged 5-12 yr. The study was randomized, double-blinded and placebo-controlled. Sixty children aged 5-12 yr suffering from grass pollen-induced rhinoconjunctivitis (with or without asthma) from five centres in two countries (three in Germany and two in Spain) participated in the study. They were randomized at the ratio of 3:1 as receiving either Grazax or placebo tablet given sublingually once daily for 28 days outside the grass pollen season. A total of 810 treatment-related adverse events were reported in the Grazax group. The majority of these were local reactions in the mouth or throat and were mostly mild (71%) to moderate (27%) in severity and resolved within days. Thirty-five (78%) subjects treated with Grazax and five (33%) treated with placebo reported at least one treatment-related adverse event. Oral pruritus, throat irritation, mouth oedema and ear pruritus appeared as the most frequently reported treatment-related adverse events. 62% (28 of 45) of the actively treated subjects reported oral pruritus, 36% (16 of 45) throat irritation, 31% (14 of 45) mouth oedema and 22% (10 of 45) ear pruritus. Two actively treated subjects withdrew from the study: one subject due to four adverse events (moderate eye pruritus, moderate pharyngolaryngeal pain, moderate non-cardiac chest pain and moderate dysphagia) and one subject due to a serious adverse event (asthmatic attack). The subjects recovered completely from the events. In conclusion, in the present study, Grazax was in general tolerated in a paediatric population and considered suitable for further clinical investigations in children. [Abstract]

Ozdemir C, Yazi D, Gocmen I, Yesil O, Aydogan M, Semic-Jusufagic A, Bahceciler NN, Barlan IB
Efficacy of long-term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite-allergic children with asthma.
Pediatr Allergy Immunol. 2007 Sep;18(6):
Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific-allergen immunotherapy, the efficacy of long-term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel-group, controlled study. Children with asthma aged 4-16 yr, sensitive to house dust mite (HDM) were followed up for a run-in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom-medication scores and lung function tests every 3 months, as well as skin-prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within-group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM-allergic children with asthma. [Abstract]

Vicente-Serrano J, Caballero ML, Rodríguez-Pérez R, Carretero P, Pérez R, Blanco JG, Juste S, Moneo I
Sensitization to serum albumins in children allergic to cow's milk and epithelia.
Pediatr Allergy Immunol. 2007 Sep;18(6):
Patients with persistent milk allergy and specific immunoglobulin E (IgE) to bovine serum albumin (BSA) have a greater risk of rhinoconjunctivitis and asthma because of animal dander. To prove the cross-reactivity between serum albumin (SA) of different mammals in milk, meat, and epithelia and determine if heat treatment of meats decrease the allergenicity of albumins. The study was performed using SDS-PAGE and IgE-immunoblotting using sera from eight patients sensitized to milk, BSA, and animal danders. Sera from non-allergic and only animal dander allergic subjects served as a control. With one exception, all patients' sera recognized SA in different meats (beef, lamb, deer, and pork), epithelia (dog, cat, and cow), and cow's milk. Some patients even were only sensitized to SA in meat and epithelia. Danders' allergic only recognized other proteins in epithelia but not SA. No patients reacted to SA from heated meat extracts. Serum albumin is an important allergen involved in milk, meat, and epithelia allergy. The first contact with SA was through cow's milk and patients developed sensitization to epithelia SA even without direct contact with animals. Patients with both BSA and cow's milk allergy must avoid raw meats and furry pets. [Abstract]

Bryan DL, Hart PH, Forsyth KD, Gibson RA
Immunomodulatory constituents of human milk change in response to infant bronchiolitis.
Pediatr Allergy Immunol. 2007 Sep;18(6):
Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p < or = 0.001). Further, the cells obtained from the mothers of infants hospitalized with bronchiolitis were found to produce a skewed cytokine profile ex vivo in response to stimulation by live RSV but not when cultured with a non-specific mitogen (concanavalin A). This study provides preliminary evidence for an immunological link between mothers and their breast-fed infants during severe respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants. [Abstract]

Chatzi L, Torrent M, Romieu I, Garcia-Esteban R, Ferrer C, Vioque J, Kogevinas M, Sunyer J
Diet, wheeze, and atopy in school children in Menorca, Spain.
Pediatr Allergy Immunol. 2007 Sep;18(6):
Epidemiological studies have shown inverse associations of asthma symptoms with fish, vegetable, and fruit intake. We evaluated the association between several dietary factors with wheeze and atopy among children in Menorca, a Spanish Mediterranean island. A cross-sectional analysis was performed on 460 children at age 6.5 yr. Parents completed a questionnaire on the child's respiratory and allergic symptoms, and a 96-item food frequency questionnaire. Children underwent skin prick tests with six common aeroallergens. The average daily intake was relatively high for fruits (177 g) and fish (54 g), and moderate for vegetables (59 g). A high consumption (>40 g/day) of fruity vegetables (tomatoes, eggplants, cucumber, green beans, zucchini) was found to have beneficial effect on current wheeze [odds ratio (OR), 0.38; 95% confidence interval (CI), 0.15-0.95, p < 0.05], and atopic wheeze with a significant decreasing trend when intake was increased (OR, 0.19; 95% CI, 0.04-0.95, p for trend = 0.04). No other fruits or vegetables were significantly associated with wheeze or atopy prevalence. An inverse association was found between a fish intake > or =60 g/day and atopy (OR, 0.43; 95% CI, 0.21-0.90, p < 0.05). The associations remained significant after adjustment for energy intake and maternal diet during pregnancy. Our results support a potential protective effect of fruity vegetables and fish intake during childhood on wheeze and atopy respectively. [Abstract]

Zöllner EW
Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids (Part 2)--the risk as determined by gold standard adrenal function tests: a systematic review.
Pediatr Allergy Immunol. 2007 Sep;18(6):
The evidence for hypothalamic-pituitary-adrenal axis (HPA) suppression by inhaled corticosteroids (ICS) was found to be conflicting. Reviewers have not distinguished between gold standard and basal adrenal function tests. The utility of the latter is limited by physiological and pathological variability as well as by methodological concerns. The risk of HPA suppression in asthmatic children and adolescents treated with ICS, as determined by gold standard adrenal function tests, needs to be established. A systematic review of the literature from January 1973 to July 2005 was performed. The Medline and Cochrane databases were searched, the reference lists of retrieved articles were inspected and pharmaceutical companies were approached. Randomized-controlled trials, cohort and case-control studies designed to detect HPA suppression caused by ICS, diagnosed by the insulin tolerance test (ITT) or the metyrapone test, performed on asthmatics of all ages not on oral steroids, were included and assessed for methodological quality. Of the 22 identified studies only four met the criteria for inclusion. All of these were published before 1988 and only one was methodologically sound. The cohort study showed that the baseline risk for HPA suppression is 0% while the absolute risk is 100% in asthmatic children treated with a beclomethasone dipropionate metered dose inhaler at a dose of 250-600 mug/m(2)/day for 6-42 months. As suggested by other observations these results could be generalized to other ICS. They may be of clinical significance especially if children are subjected to stress. Further research is needed to establish the cumulative dose for all ICS at which HPA suppression will be precipitated. Guidelines for future trials are suggested. [Abstract]

Machura E, Mazur B, Golemiec E, Pindel M, Halkiewicz F
Staphylococcus aureus skin colonization in atopic dermatitis children is associated with decreased IFN-gamma production by peripheral blood CD4(+) and CD8(+) T cells.
Pediatr Allergy Immunol. 2007 Jul 27;
Atopic dermatitis (AD) is a chronic inflammatory skin disorder, which is associated with an increased expression of Th2 cytokines with concomitant decrease in IFN-gamma production by circulating CD4(+) and CD8(+) T cells. The skin of patients with AD is often colonized by Staphylococcus aureus, which may reflect in changes in immunological parameters. The aim of the study was flow cytometric measurement of some peripheral blood lymphocyte subsets expressing naive/memory marker (RA/RO) and activation marker (CD25) as well as intracellular production of IFN-gamma by peripheral blood CD4(+) and CD8(+) T cells from varied severity AD children and determine the impact of S. aureus skin colonization on cytokines profiles. There was a significant increase in the percentage of CD4(+) and CD8(+) T cells producing IL-4 and IL-13 and decrease in the percentage of CD4(+) and CD8(+) T cells producing IFN-gamma upon in vitro stimulation with phorbol 12-myristate 13-acetate and ionomycin in children with AD compared to healthy ones. The absolute number of CD4(+) and CD8(+) T cells expressing memory marker CD45RO was elevated as compared with controls. The severity of AD was positively correlated with the percentage of lymphocyte subsets: CD45RO(+), CD4(+)CD45RO(+), and the percentage of CD3(+) and CD4(+) expressing CD25 as well as the number of S. aureus on the skin. In conclusion, both CD4(+) and CD8(+) memory T cells are involved in the immunopathogenesis of AD. S. aureus skin colonization is related with disease severity and changes in expression of CD45RO and CD25 on T cells. A decrease in the percentage of CD4(+) and CD8(+) T cells producing IFN-gamma in AD children may explain propensity for skin infection. [Abstract]

Lizaso MT, Tabar AI, García BE, Gómez B, Algorta J, Asturias JA, Martínez A
Double-blind, placebo-controlled Alternaria alternata immunotherapy: in vivo and in vitro parameters.
Pediatr Allergy Immunol. 2007 Jul 27;
Few studies have been published on the efficacy and safety of immunotherapy with fungal extracts, possibly because of difficulties arising from antigenic variability among different strains of fungus. The aim of the study was to analyze changes in the in vivo and in vitro parameters in response to immunotherapy with an Alternaria alternata extract. We studied 28 patients with rhinitis, bronchial asthma, or both caused by Alternaria. The patients were randomized to the active immunotherapy or placebo group, and a conventional schedule of immunotherapy was used. We recorded changes for a year in skin reactivity (skin prick test), conjunctival reactivity (conjunctival provocation test), and in vitro parameters (serum-specific IgE, IgG, IgG1 and IgG4 for A. alternata complete extract and for natural and recombinant Alt a 1). Twenty-three patients completed the study and all attained the maintenance dose. There were no changes in skin reactivity in the active treatment group, and reactivity increased at the end of the study period in the placebo group. Conjunctival sensitivity decreased only in the active treatment group when the maintenance dose was reached. Allergen-specific IgE decreased, and IgG, IgG1 and IgG4 increased in all periods of study in the active treatment group, with no changes in the placebo group. Allergen-specific immunotherapy with the A. alternata extract tested here led to a decrease in conjunctival reactivity and induced a significant immunologic response. [Abstract]


Recent Articles in Clinical Reviews in Allergy & Immunology

Yazawa N, Fujimoto M, Tamaki K
Recent Advances on Pathogenesis and Therapies in Systemic Sclerosis.
Clin Rev Allergy Immunol. 2007 Dec 7;
Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by extensive fibrotic changes in various organs, including skin and lung. Although the etiology of SSc remains unknown, three major abnormalities, abnormal humoral immunity, microvasculature, and fibroblast dysfunctions are considered to play important roles. Significant progress has been made in understanding the pathogenesis on SSc, and has been also providing clues to the treatment for this disease. This review summarizes recent advances on the pathogenesis and new therapeutic strategy for SSc. [Abstract]

Woodley DT, Remington J, Chen M
Autoimmunity to Type VII Collagen: Epidermolysis Bullosa Acquisita.
Clin Rev Allergy Immunol. 2007 Dec 4;
Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune, mechanobullous disease with clinical features reminiscent of genetic dystrophic epidermolysis bullosa (DEB). EBA patients have skin fragility, blisters, scars, and milia formation. DEB is due to a genetic defect in the gene-encoding type VII collagen, which makes anchoring fibrils, structures that attach the epidermis and its underlying basement membrane zone onto the papillary dermis. DEB patients have a decrease in normally functioning anchoring fibrils. EBA patients have the same problem, but their decrease in normally functioning anchoring fibrils is because of an abnormality in their immune system in which they produce anti-type VII collagen antibodies that attack their anchoring fibrils. These IgG anti-type VII collagen antibodies are "pathogenic" because when injected into a mouse, the mouse develops an EBA-like blistering disease. EBA has several distinct clinical presentations. It can present with features similar to DEB. It can also present with features reminiscent of bullous pemphigoid, cicatricial pemphigoid, Brunsting-Perry pemphigoid, or IgA bullous dermatosis. Treatment for EBA is unsatisfactory. Some therapeutic success has been reported with colchichine, dapsone, photopheresis, infliximab, and IVIG. [Abstract]

Borchers AT, Keen CL, Gershwin ME
Smoking Cessation: Significance and Implications for Children.
Clin Rev Allergy Immunol. 2007 Nov 13;
A number of people in the USA who are still current smokers remain a staggering figure. Although this number continues to decrease, there is still a considerable amount of second-hand smoke. More importantly and for the purpose of this review, the detrimental effects of passive smoke in children is significant. We will not review the specific health effects of passive smoke, but for pediatricians, in particular, it is important to place in perspective programs that are available to influence the parents of children to stop smoking. Indeed, approximately 25% of all children aged 3-11 live in a household with at least one smoker. Despite the increasing number of communities in the states that have instituted restrictions or complete bans on smoking in the workplace and in many public areas, the principal site of smoking remains the home. [Abstract]

Meijer JM, Pijpe J, Bootsma H, Vissink A, Kallenberg CG
The Future of Biologic Agents in the Treatment of Sjögren's Syndrome.
Clin Rev Allergy Immunol. 2007 Jun;32(3):292-7.
The gain in knowledge regarding the cellular mechanisms of T and B lymphocyte activity in the pathogenesis of Sjögren's syndrome (SS) and the current availability of various biological agents (anti-TNF-alpha, IFN- alpha, anti-CD20, and anti-CD22) have resulted in new strategies for therapeutic intervention. In SS, various phase I and II studies have been performed to evaluate these new strategies. Currently, B cell-directed therapies seem to be more promising than T cell-related therapies. However, large, randomized, placebo-controlled clinical trials are needed to confirm the promising results of these early studies. When performing these trials, special attention has to be paid to prevent the occasional occurrence of the severe side effects. [Abstract]

Mavragani CP, Moutsopoulos HM
Conventional Therapy of Sjogren's Syndrome.
Clin Rev Allergy Immunol. 2007 Jun;32(3):284-91.
Sjogren's syndrome (SS) is a chronic autoimmune disorder affecting mainly middle-aged women. It is characterized by lymphocytic infiltration and destruction of the exocrine glands (mainly the salivary and lacrimal glands), resulting in dry mouth and eyes. Symptoms of SS are chronic and sometimes devastating, compromising the quality of life at a major extent. Despite its autoimmune nature, evidence for the use of immunosuppressive agents, which are the mainstay of therapy of diseases of autoimmune origin, is limited. Keratoconjunctivitis sicca (KCS), the main ocular manifestation of SS, is managed with tear substitutes, as well as local and systemic stimulators of tear secretion and supportive surgical procedures. Management of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline are the cornerstone of current therapy in SS. Corticosteroids, cyclophoshamide, and nucleoside analogues are reserved for severe extraglandular manifestations of SS. The role of anti-B-cell therapy is a promising option for glandular and extraglandular manifestations of the disease, as well as for the management of SS-associated lymphoma. [Abstract]

Ramos-Casals M, Brito-Zerón P, Font J
Lessons From Diseases Mimicking Sjögren's Syndrome.
Clin Rev Allergy Immunol. 2007 Jun;32(3):275-83.
Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes because of functional impairment of the salivary and lacrimal glands. The histological hallmark is a focal lymphocytic infiltration of the exocrine glands, and the spectrum of the disease extends from an organ-specific autoimmune disease (autoimmune exocrinopathy) to a systemic process with diverse extraglandular manifestations. In the absence of an associated systemic autoimmune disease, patients with this condition are classified as having primary SS. The differential diagnosis includes processes that specifically involve the exocrine glands. On the one hand, some chronic viral infections may induce lymphocytic infiltration of the exocrine glands, in some cases indistinguishable from that observed in primary SS. On the other hand, some processes may mimic the clinical picture of SS through nonlymphocytic infiltration of the exocrine glands. This review focuses on these two groups of diseases that mimic SS (infections and infiltrating processes). [Abstract]

Voulgarelis M, Skopouli FN
Clinical, Immunologic, and Molecular Factors Predicting Lymphoma Development in Sjogren's Syndrome Patients.
Clin Rev Allergy Immunol. 2007 Jun;32(3):265-74.
Among autoimmune diseases, Sjogren's syndrome (SS) displays the highest incidence of non-Hodgkin lymphoma (NHL) development with the salivary extranodal marginal zone B cell lymphomas being the most common type. The majority of SS-associated NHLs are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Although the transition from a chronic inflammatory condition to malignant lymphoma is a multistep process yet poorly understood, there is increasing evidence that chronic antigenic stimulation by an exoantigen or autoantigens plays an essential role in the development of SS associated lymphoproliferation. Additional molecular oncogenic events such as microsatellite instability, loss of the B cell cycle control, and the forced overproduction of specific B cell biologic stimulators seem to contribute to the emergence and progression of the malignant overgrowth. Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely. [Abstract]

Katsifis GE, Moutsopoulos NM, Wahl SM
T Lymphocytes in Sjögren's Syndrome: Contributors to and Regulators of Pathophysiology.
Clin Rev Allergy Immunol. 2007 Jun;32(3):252-64.
Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. This multigenic and multifunctional disease can present as primary Sjögren's syndrome or secondary to an underlying connective tissue disease. Immune activation subsequent to activation or apoptosis of glandular epithelial cells in genetically predisposed individuals may expose autoantigens, which engage self-perpetuating T cell dependent autoimmune sequelae. The cellular and molecular context of this immune response may drive proinflammatory (Th1 and Th17) and restrain inhibitory (Treg) pathways. Inability to suppress the immune response results in persistent tissue damage and compromised function of salivary and lacrimal glands. Defining the contributions of participating T cells may unravel strategies for therapeutic intervention. [Abstract]

Routsias JG, Tzioufas AG
Sjögren's Syndrome-Study of Autoantigens and Autoantibodies.
Clin Rev Allergy Immunol. 2007 Jun;32(3):238-51.
The presence of autoantibodies is the hallmark of systemic autoimmune diseases. During the past 30 years, intense clinical and basic research have dissected the clinical value of autoantibodies in many autoimmune diseases and offered new insights into a better understanding of the molecular and functional properties of the targeted autoantigens. Unraveling the immunologic mechanisms underlying the autoimmune tissue injury, provided useful conclusions on the generation of autoantibodies and the perpetuation of the autoimmune response. Primary Sjögren's syndrome (pSS) is characterized by the presence of autoantibodies binding on a vast array of organ and non-organ specific autoantigens. The most common autoantibodies are those targeting the Ro/La RNP complex, and they serve as disease markers, as they are included in the European-American Diagnostic Criteria for pSS. Other autoantibodies are associated with particular disease manifestations, such as anti-centromere antibodies with Raynaud's phenomenon, anti-carbonic anhydrase II with distal renal tubular acidosis, anti-mitochondrial antibodies with liver pathology, and cryoglobulins with the evolution to non-Hodgkin's lymphoma. Finally, autoantibodies against autoantigens such as alpha- and beta-fodrin, islet cell autoantigen, poly(ADP)ribose polymerase (PARP), NuMA, Golgins, and NOR-90 are found in a subpopulation of SS patients without disease specificity, and their utility remains to be elucidated. In this review, the molecular and clinical characteristics (divided according to their clinical utility) of the autoantigens and autoantibodies associated with pSS are discussed. [Abstract]

Youinou P, Devauchelle V, Hutin P, Le Berre R, Saraux A, Pers JO
A Conspicuous Role For B Cells In Sjögren's Syndrome.
Clin Rev Allergy Immunol. 2007 Jun;32(3):231-7.
Although the relative contributions of T cells and B cells in Sjögren's syndrome (SS) are far from being settled, recent studies have suggested a crucial role for B cells in its pathophysiology. Early investigations have focused on the ability of B cells to produce autoantibodies, and new studies have enlarged the range of their functions. For example, beyond the paradigm that T lymphocytes maintain strict control over B cells, the latter cells are now acknowledged to solicit their own help from the former cells and release a flurry of cytokines. Further, some of these B cells act as antigen-presenting cells. Increased levels of the B cell activating factor (BAFF) found in SS may be responsible for high numbers of circulating Bm2/Bm2' cells and associated functional abnormalities of B cells, such as a BAFF-induced increased expression of CD19, which decreases the required strength generated by antigen binding for transmitting its signal. This review reports compelling evidence that B cells are involved in the pathophysiology of SS. As this brings novel prospects for the treatment of the disease, it is no surprise that B cell ablative treatment has proven to be relatively efficacious in SS. [Abstract]

Manoussakis MN, Kapsogeorgou EK
The Role of Epithelial Cells in the Pathogenesis of Sjögren's Syndrome.
Clin Rev Allergy Immunol. 2007 Jun;32(3):225-30.
Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy that is characterized by periductal mononuclear cell infiltrates in the affected exocrine glands. Epithelial cells are thought to play an important pathogenetic role, as suggested by the occurrence of infiltrating lesions in various epithelial tissues (described as autoimmune epithelitis) as well as the increased epithelial expression of several inflammatory proteins in the histopathologic lesions of patients. In the recent decade, the application of long-term cultured nonneoplastic salivary gland epithelial cell (SGEC) lines has permitted the more explicit analysis of the role of these cells in SS pathophysiology. In such studies, cultured SGEC have been demonstrated to express constitutively or inducibly various molecules that are implicated in innate and acquired immune responses, a fact that underscores the inherent capacity of these epithelial cells to induce and promote chronic inflammatory reactions. Furthermore, the parallel analysis of SGEC lines obtained from SS patients and disease controls has revealed the significantly increased constitutive expression of several molecules in cells derived from SS patients. This fact strongly suggests the operation of intrinsic activation mechanisms in the epithelia of patients and further supports the active participation of epithelia in SS pathogenesis. [Abstract]

Jonsson MV, Delaleu N, Jonsson R
Animal Models of Sjögren's Syndrome.
Clin Rev Allergy Immunol. 2007 Jun;32(3):215-24.
Sjögren's syndrome is an autoimmune, chronic inflammatory disease characterized by focal mononuclear cell infiltration of exocrine tissues, accompanied by loss of secretory function. The pathogenesis of autoimmune diseases is complex and, therefore, difficult to study in vitro. As of today, the role of initiating factors remains obscure, clinical symptoms develop late, and there are no tests for early diagnosis of SS. Hence, the disease is difficult to detect and treat. Animal models may provide insights into the identification of target antigens, narrowing the relevant pathological immune mechanisms, and to study the evolution of tissue pathology. This review summarizes current knowledge on murine strains, both spontaneous and induced models, used to study Sjögren's syndrome. Special attention is paid to the characteristics of different strains regarding their properties to mimic specific aspects or stages of the disease. [Abstract]

Triantafyllopoulou A, Moutsopoulos H
Persistent Viral Infection in Primary Sjogren's Syndrome: Review and Perspectives.
Clin Rev Allergy Immunol. 2007 Jun;32(3):210-4.
Exocrine gland pathology in primary Sjogren's syndrome is characterized by destruction of acinar epithelial cells and chronic lymphocytic infiltrates surrounding ductal epithelial cells. These cells seem to be activated, as it is inferred by their immunophenotype. The cause of this activation and the chronic inflammatory response that targets epithelial cells remain unknown. Here, we will review the evidence pointing to a persistent viral infection as a probable cause of primary Sjogren's syndrome and discuss potential directions for future research. [Abstract]

Moutsopoulos HM
Sjögren's Syndrome or Autoimmune Epithelitis?
Clin Rev Allergy Immunol. 2007 Jun;32(3):199-200. [Abstract]

Goodarzi H, Trowbridge J, Gallo RL
Innate Immunity: A Cutaneous Perspective.
Clin Rev Allergy Immunol. 2007 Nov 9;
The first responsibility for protection against microbial infection rests on the normal function of the innate immune system. This system establishes an antimicrobial barrier, recognizes attempts to breach this barrier, and responds rapidly to danger, all based on an innate defense system. Here, we review this system as it applies to mammalian skin, highlighting how a physical, cellular, and chemical barrier is formed to resist infection. When challenged, the diverse cellular components of the skin recognize the nature of the challenge and respond with an appropriate antimicrobial program including the release of antimicrobial peptides and, when necessary, recruitment and coordination with adaptive immune responses. Recent insights into these processes have advanced the understanding of disease pathogenesis and provided new therapeutic options for a variety of skin diseases. [Abstract]

Ramesh S
Food Allergy Overview in Children.
Clin Rev Allergy Immunol. 2007 Nov 8;
Food allergies have increased significantly in the past decade. An accurate history is crucial in approaching the management. At the outset, food intolerance must be distinguished from food allergies and, furthermore, these allergies should be classified into either an IgE, Non-IgE, or a mixed response. The clinical features vary from life-threatening anaphylaxis to milder IgE-mediated responses, atopic dermatitis, and gastrointestinal symptoms. The severity of the reaction and the potential risk for anaphylaxis on reexposure should be assessed. Milk, soy, egg, wheat, and peanut allergies are common in children, whereas peanut, tree nut, fish, shell fish allergies, and allergies to fruits and vegetables are common in adults. Structural proteins are important determinants of the severity of the reactions and may often predict the natural history and cross reactivity. Diagnostic work up must be guided by the clinical history. Skin testing and food-specific IgE done by standard methods are very useful, whereas oral challenges may be indicated in some situations. Majority of the patients outgrow their allergies to milk, soy, egg, and wheat, and some to peanut also, therefore, patients should be periodically reassessed. Novel diagnostic techniques which detect specific allergenic epitopes have been developed. Several newer therapies are promising. [Abstract]

Welliver RC
The Immune Response to Respiratory Syncytial Virus Infection: Friend or Foe?
Clin Rev Allergy Immunol. 2007 Nov 6;
The immune response to respiratory syncytial virus (RSV) infection has fascinated and frustrated investigators for decades. After adverse responses to early attempts at vaccination, it became popularly held that disease following infection was related to overly aggressive immune responses. However, recent data illustrate that severe forms of disease are related to inadequate, rather than hyperresponsive, adaptive immune reactions. Thus, recovery from primary (and perhaps later) RSV infection is dependent on the quality of innate immune responses. These findings should have enormous significance to the development of vaccines and antiviral compounds. [Abstract]

Williams PH, Cobb BL, Namjou B, Scofield RH, Sawalha AH, Harley JB
Horizons in Sjögren's Syndrome Genetics.
Clin Rev Allergy Immunol. 2007 Jun;32(3):201-9.
Sjögren's syndrome (SS) is a complex polygenic autoimmune disorder. A few major genetic effects have been identified. Historically, HLA and non-HLA genetic associations have been reported. Recently, the HLA region continued to reveal association findings. A new susceptibility region has been suggested by a study of a D6S349 microsatellite marker. Among non-HLA studies, recent association of immunoglobulin kappa chain allotype KM1 with anti-La autoantibodies in primary Sjögren's syndrome confirms findings in a study from two decades ago. Meanwhile, mouse models have been employed to study the genetic contribution to salivary lymphadenitis or dry eyes and mouth. Gene transfer exploration in mouse models shows promise. The authors review the HLA and non-HLA association studies and the mouse model work that has been reported. Newly developed genomic capacity will provide, in the future, a much closer approximation of the true picture of the genetic architecture of Sjögren's syndrome. [Abstract]

Nichols D, Chmiel J, Berger M
Chronic Inflammation in the Cystic Fibrosis Lung: Alterations in Inter- and Intracellular Signaling.
Clin Rev Allergy Immunol. 2007 Oct 25;
A vicious cycle of airway obstruction, infection, and inflammation continues to cause most of the morbidity and mortality in cystic fibrosis (CF). Mutations that result in decreased expression or function of the membrane Cl(-) channel, cystic fibrosis transmembrane regulator (CFTR), result in a decrease in the volume (and hence the depth) of liquid on the airway surface, impaired ciliary function, and dehydrated glandular secretions. In turn, these abnormalities contribute to a milieu, which promotes chronic infection with a limited but unique spectrum of microorganisms. Defects in CFTR also perturb regulation of several intracellular signaling pathways including signal transducers and activator of transcription, I-kappaB and nuclear factor-kappa B, and low molecular weight GTPases. Together, these abnormalities result in excessive production of NF-kappaB dependent cytokines such as interleukin (IL)-1, tumor necrosis factor (TNF), IL-6, and IL-8. There are decreased responses to interferon gamma and transforming growth factor beta leading to decreased production of iNOS and NO. Abnormalities of lipid mediators and decreased secretion of counter/regulatory cytokines have also been reported. Together, these effects combine to create a chronic inflammatory process, which damages and obstructs the airways, and eventually claims the life of the patient. [Abstract]

Yehudai D, Shoenfeld Y, Toubi E
Looking into the eyes of patients with antiphospholipid syndrome.
Clin Rev Allergy Immunol. 2007 Apr;32(2):192-7.
Diagnosis of antiphospholipid syndrome (APS) should be considered in all patients with recurrent systemic or ocular thrombosis in the absence of known risk factors. Because of the frequent ocular involvement in APS patients (as many as 80%), an ophthalmologic assessment should become a routine part of the clinical work-up of all patients in whom APS is highly suspected. The presence of isolated ocular thrombosis with persistently increased titers of antiphospholipid antibodies should be considered as definite APS. Ocular involvement in APS is frequently associated with other manifestations of the central nervous system (CNS), such as transient ischemic attack or cerebral vascular events. Diagnostic tools are needed to better establish a diagnosis of retinal vascular thrombosis. The treatment of isolated ocular APS should be based on the same principles as in all patients with systemic APS. Anticoagulation is aimed to prevent recurrent ocular or cerebral thromboses. [Abstract]

Liberato B, Levy RA
Antiphospholipid syndrome and cognition.
Clin Rev Allergy Immunol. 2007 Apr;32(2):188-91.
In addition to the well-defined neurologic events due to arterial and venous thrombotic vascular occlusions of antiphospholipid syndrome (APS), a broad spectrum of neuropsychiatric has been related to antiphospholipid (aPL). Experimental evidence of a pathogenic role of aPL in mice with impaired neurological function disclosed inflammatory reaction as a hallmark. The process that leads to neurological dysfunction seems to be both structurally destructive and functionally impairing. The most modern resources of neuroimmaging also suggest that, in addition to the micro-infarcts that occur in strategic areas, other metabolic impairments are related to progressive dementia and aPL presence. Although there is a lot of confusion among APS and lupus' cognitive involvement, there is a body of experimental and clinical evidence that aPL causes this kind of damage. [Abstract]

Reinstein E, Shoenfeld Y
Antiphospholipid syndrome and cancer.
Clin Rev Allergy Immunol. 2007 Apr;32(2):184-7.
Thrombosis is a frequent complication of cancer that is a substantial cause of morbidity and mortality. The association of antiphospholipid antibodies (aPL) and cancer has been under investigation for several years. Recent findings suggest an increased prevalence of certain cancers in aPL-positive patients; thus, an intensive search for an occult malignancy is prompted in these patients. In addition, several studies reported on elevated levels of aPL in various malignancies; it seems, however, that aPL levels do not reflect their pathogenicity; therefore, their pathological significance in these subset of patients is still elusive. Continuing research on the association between the antiphospholipid syndrome/aPL and malignancies is important, given the potential impact on the understanding and treatment of both antiphospholipid syndrome and cancer. [Abstract]

Amigo MC
The Heart and APS.
Clin Rev Allergy Immunol. 2007 Apr;32(2):178-83.
The heart is a target organ in antiphospholipid syndrome (APS). Endocardial disease, intracardiac thrombosis, myocardial involvement including coronary heart disease and microvascular thrombosis, as well as pulmonary hypertension have all been described in APS patients. Valvular involvement is the most common manifestation with a prevalence of 82% detected by transesophageal echocardiography. Symmetrical, nodular thickening of the mitral and/or aortic valves is characteristic. Anticoagulant/antiplatelet treatment is ineffective in terms of valvular lesion regression. Some patients require cardiac valve replacement. However, patients with APS have shown an increased perioperative morbidity and mortality. Intracardiac thrombosis, although a rare complication, can cause pulmonary and systemic emboli. Differential diagnosis with myxoma may be very difficult. [Abstract]

Jara LJ, Medina G, Vera-Lastra O
Systemic antiphospholipid syndrome and atherosclerosis.
Clin Rev Allergy Immunol. 2007 Apr;32(2):172-7.
Atherosclerosis (AT) is a metabolic, systemic inflammatory/immune disease characterized by lipoproteins metabolism alteration that leads to immune/inflammatory system activation with the consequent proliferation of smooth-muscle cells, narrowing arteries and atheroma formation. Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombophilic state and circulating antiphospholipid antibodies (aPL) including anti beta2-GPI. Experimental studies and human observations suggest that APS is associated with AT. In fact, innate and adaptive immune responses participate in the pathogenesis of both diseases. Anti-oxLDL, anti-aPL, anti beta2GPI, anti-HSP antibodies, among others, has been found in patients with APS and AT. Endothelial dysfunctions, oxidative stress, increase of cell adhesion molecules, active platelets, are common findings in both diseases. Macrophages, dendritic cells, T-cell activation, CD40-CD40 ligand interaction, are considered as pathogenic mechanism of AT and APS. Premature AT may be the first symptom of APS. Thrombophilia, aPL antibodies, and APS may be present in patients with premature AT. An association between AT and venous thrombosis (a clinical hallmark of APS) has been proposed in unselected patients with deep venous thrombosis of the legs without symptomatic AT. Asymptomatic AT, defined in terms of carotid intima media thickness and lumen diameter decrease, was observed in patients with APS. Premenopausal female patients with PAPS have a higher prevalence of cerebrovascular disease in comparison with male patients. Accelerated AT and hormones could be the explanation of these findings. High levels of aCLs, significantly predict the risk of future ischemic stroke in women but not in men. AT is one of the main features of systemic APS and offer opportunities for new treatment strategies. [Abstract]

Gorshtein A, Levy Y
Orthopedic involvement in antiphospholipid syndrome.
Clin Rev Allergy Immunol. 2007 Apr;32(2):167-71.
Antiphospholipid syndrome (APS) is a common autoimmune disease, manifested by vascular thrombosis and fetal loss in the presence of antiphospholipid antibodies. Orthopedic involvement is a relatively novel and under-recognized feature of APS. In this article we review the association of primary, secondary, and catastrophic APS with diverse orthopedic conditions, including osteonecrosis in adult and pediatric patients, bone marrow necrosis, nontraumatic fractures, and some other disorders. [Abstract]

Hodak E, David M
Primary anetoderma and antiphospholipid antibodies--review of the literature.
Clin Rev Allergy Immunol. 2007 Apr;32(2):162-6.
Primary anetoderma (PA) is a rare elastolytic disorder that develops in clinically normal skin or following a nonspecific inflammatory process. The old literature contains numerous reports of the association between PA and lupus eryhtematosus, although the relationship has not been clearly established. In recent years, there has been a growing body of literature linking PA with a wide range of immunologic abnormalities, the most common of which is the presence of antiphospholipid antibodies, with or without antiphospholipid syndrome. The present review summarizes the literature, from the early descriptions pointing toward an immunologic basis of PA and up to the present recognition that PA is a cutaneous sign for autoimmune disorders, in general, and the presence of antiphospholipid in particular. [Abstract]

Carp HJ, Shoenfeld Y
Anti-phospholipid antibodies and infertility.
Clin Rev Allergy Immunol. 2007 Apr;32(2):159-61.
Antiphospholipid syndrome (APS) or the presence of antiphospholipid antibodies (aPL), usually presents as pregnancy loss. However, aPL have also been reported to affect implantation, placentation, and early embryonic development. The binding of aPl to beta2GP1 may lead to breakdown of the phospholipid adhesion molecules between different elements of trophoblast. As aPL affect placental growth and function, aPl may prevent implantation presenting as infertility. Lupus anticoagulant and anticardiolipin antibody have been implicated in the prothrombotic effects of APS. Antibodies to other phospholipids such as anti-phosphatidylserine, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl Inositol etc. may be more relevant in infertility. Their role remains to be clarified. There is theoretical evidence from animal models and clinical infertility practice that aPL has a role in infertility. However, a large-scale meta-analysis has failed to confirm the association. To determine whether infertility or even pregnancy loss is associated with aPL, it is necessary to know that the embryo is chromosomally normal. Pregestational diagnosis has shown that up to 60% of embryos may be chromosomally aneuploid in failed in vitro fertilization (IVF); hence, may confound our understanding concerning the association between aPL and infertility, failed IVF or even pregnancy loss. [Abstract]

Asherson RA, Cervera R
Pulmonary hypertension, antiphospholipid antibodies, and syndromes.
Clin Rev Allergy Immunol. 2007 Apr;32(2):153-8.
Antiphospholipid antibodies have been associated with two types of pulmonary hypertension (PHT), the thromboembolic type, after deep venous thromboses in the lower limbs complicated by pulmonary embolism and the "primary" plexogenic type. The PHT may occur in the absence of any other manifestations of the antiphospholipid syndrome (APS), and cases have been recorded with very high levels of antiphospholipid antibodies. It may also accompany systemic lupus erythematosus (SLE) and may manifest with or without other features of the APS. It may also form part of the clinical presentation of a "primary" APS. Its prevalence is of the order of 1.8-3.5% of the manifestations of the APS depending on the series. Primary "idiopathic" PHT has long been regarded as an "immunological" disorder. Its manifestations are essentially to the primary type seen with the connective tissue disorders such as SLE, APS, mixed connective tissue disease, calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia variety of systemic sclerosis and Sjögren's syndrome. The high prevalence of PHT in patients with human immunodeficiency virus infection who demonstrate low CD4 counts points to a close relationship between the T regulatory cells (Treg) and the development of PHT, and this hypothesis is discussed in this review. Genetic and chromosomal aspects of PHT are also discussed. [Abstract]

Shovman O, Gilburd B, Barzilai O, Langevitz P, Shoenfeld Y
Novel insights into associations of antibodies against cardiolipin and beta2-glycoprotein I with clinical features of antiphospholipid syndrome.
Clin Rev Allergy Immunol. 2007 Apr;32(2):145-52.
Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with the persistence of lupus anticoagulant or anticardiolipin (aCL) antibodies. Accumulating evidence indicates that phospholipid binding protein, beta2-glycoprotein I (beta2GPI) represents the major target antigen for antiphospholipid (aPL) antibodies and plays a role in the pathogenesis of APS. It is widely accepted that aPL antibodies detected by conventional solid phase assays in patients with APS are mainly directed against a complex of aCL and anti-beta2GPI, although antibodies against beta2GPI protein can now also be detected by specific ELISA using purified proteins in solid phase. Despite the fact that these antibodies are not listed in the new diagnostic criteria, a high specificity of anti-beta2GPI assay for the clinical features of APS was established. During the last decade, numerous studies have investigated the clinical link between aCL and/or anti-beta2GPI antibodies and diverse features of APS. This manuscript reviews the current studies published recently in this field and discusses the relationship between the existence of aCL and anti-beta2GPI antibodies and the main and unusual manifestations of APS. [Abstract]

Toubi E, Shoenfeld Y
Livedo reticularis as a criterion for antiphospholipid syndrome.
Clin Rev Allergy Immunol. 2007 Apr;32(2):138-44.
Many consensus meetings were organized in an attempt to improve the present criteria for antiphospholipid syndrome (APS) classification. In this regard, a high prevalence of antiphospholipid antibodies in systemic lupus erythematosus patients was reported in association with the presence of livedo reticularis (LR). In these studies, the association between LR, migraine, and the development of thrombosis (strokes, valvular dysfunctions) was evident. During the last decade, it was strongly suggested that many clinical symptoms (LR, valvular dysfunctions) or laboratory features (thrombocytopenia) should be considered as "minor criteria" for APS. The inclusion of these clinical symptoms in the criteria for APS classification could become of additive value especially when they exist together in one patient. This review summarizes the data that question or support this idea. [Abstract]

Tarr T, Lakos G, Bhattoa HP, Soltesz P, Shoenfeld Y, Szegedi G, Kiss E
Clinical thrombotic manifestations in SLE patients with and without antiphospholipid antibodies: a 5-year follow-up.
Clin Rev Allergy Immunol. 2007 Apr;32(2):131-7.
OBJECTIVE: To analyze the association of antiphospholipid antibodies (aPL) with the development of clinical thrombotic manifestations and to characterize the efficacy of anti-thrombotic therapies used.METHODS: 272 systemic lupus erythematosus (SLE) patients participated in the study. Patient files and a cumulative database were used to collect patients' medical histories. Anti-cardiolipin (aCL), anti-beta2-glycoprotein I (abeta2GPI) antibodies, and lupus anticoagulant (LAC) were measured according to international recommendations. New thrombotic events were registered during follow-up.RESULTS: The patients were prospectively studied for 5 years, of whom 107 were aPL negative (aPL- group). Criteria for antiphospholipid syndrome (APS) were fulfilled by 84 of 165 aPL-positive patients (APS+ group) indicating that SLE patients with aPL have around 50% risk to develop thrombotic complications. The aPL+ group (n = 81) consisted of aPL+ but APS- patients. LAC was the most common aPL (n = 27, 32.1%) in patients with APS. The cumulative presence of aPL further increased the prevalence of thrombotic events. During the follow-up period, aPL developed in 8 of 107 patients (7.5%) from the aPL- group, of whom 3 (2.8%) presented with thrombotic complications. Other types of aPL developed in 7 of 165 (4.2%) aPL+ patients within 5 years. New thrombotic events occurred in 3.7% of aPL+ (n = 3) and 8.3% (n = 7) of the APS group. During follow-up, 52 of 81 aPL+ patients received primary prophylaxis, and 1 (1.9%) had transient ischemic attack (TIA). In the non-treatment group, 2 (6.9%) had stroke. Seventy-nine of 84 of the APS patients received secondary prophylaxis, and myocardial infarction occurred in 2 patients (on cumarine therapy maintaining an international normalized ratio around 2.5-3.0), and 5 suffered a stroke/TIA (1 on aspirin and 4 on aspirin + cumarine).CONCLUSION: The findings emphasize the importance of determining both aCL and abeta2GPI antibodies and LAC in SLE patients and the need for adequate anticoagulant therapy. [Abstract]

Shoenfeld Y
APS--more systemic disease than SLE.
Clin Rev Allergy Immunol. 2007 Apr;32(2):129-30.
The antiphospholipid syndrome is a systemic autoimmune disease that can have serious consequences for patients. Importantly, there is a wide range of clinical presentations. In this issue we have attempted to provide an overview of these features and place it in the context of autoimmunity. [Abstract]

Boren E, Teuber SS, Naguwa SM, Gershwin ME
A critical review of local anesthetic sensitivity.
Clin Rev Allergy Immunol. 2007 Feb;32(1):119-28.
With their ability to block pain signals to the brain, local anesthetics (LAs) have made possible many surgical procedures and interventions once thought impossible. LAs are generally safe and well tolerated when used correctly by trained professionals. However, adverse reactions do occur, and may generate a referral to an Allergist for evaluation of LA allergy. LA structure, classification, and metabolism will be briefly reviewed. A critical analysis of the studies and case reports involving LA allergy found via PubMed search for "local anesthetic allergy" and "local anesthetic hypersensitivity" will be discussed. In addition, the clinical evaluation of a patient with concern for a LA allergy will be examined. [Abstract]

Blank M, Barzilai O, Shoenfeld Y
Molecular mimicry and auto-immunity.
Clin Rev Allergy Immunol. 2007 Feb;32(1):111-8.
The term "molecular mimicry" was coined by R. Damian in 1964, who was first to suggest that antigenic determinants of micro-organisms may resemble antigenic determinants of their host. Damian suggested that this similarity served as a defense mechanism of a microorganism from the host's immune system and prevented the development of immune response to the micro-organism, thereby protecting it from host defense. Years later, the term "molecular mimicry" was attributed a different meaning-namely, antigenic determinants of microorganisms might elicit an auto-immune response that harms the host. The concept of molecular mimicry is based on a structural similarity between a pathogen or metabolite and self-structures. The similarity could be expressed as shared amino acid sequences (linear or mimotope) or similar conformational structure between a pathogen and self-antigen. "Molecular mimicry" has become a very popular explanation for the frequent association of infection with auto-immune disease. [Abstract]

Kong JS, Teuber SS, Gershwin ME
Aspirin and nonsteroidal anti-inflammatory drug hypersensitivity.
Clin Rev Allergy Immunol. 2007 Feb;32(1):97-110.
Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably, the clinician will encounter patients with clear indications for aspirin therapy but a history of aspirin sensitivity. Although protocols have been established for aspirin challenge and desensitization, it is not always an efficacious or safe procedure. This article reviews the different classifications of ASA/NSAIDs hypersensitivities to better guide the clinician in dealing with this patient population. History of crossrelativities between multiple NSAIDs implies a non-IgE-mediated process. Similarly, a history of monosensitivity to one NSAID implies an IgE-mediated process, although specific antibodies are often elusive. Despite the name, AERD can potentially be exacerbated by all cyclooxygenase (COX) inhibitors based on dose-dependent inhibition of COX-1. Aspirin desensitization can be achieved to improve both upper and lower respiratory symptoms for most patient with AERD. Aspirin desensitization can usually be achieved for those in need of the antiplatelet effects of aspirin, with the exception of those with aspirin-induced urticaria and baseline chronic urticaria. However, desensitization should only be attempted in those with stable coronary artery disease because the process of desensitization carries the inherent risk of anaphylaxis/anaphylactoid reaction, which may further increase cardiac demand and bring about ischemic injury. Therefore, desensitization is reserved until coronary artery disease is stabilized. [Abstract]


Recent Articles in Contact Dermatitis

Isaksson M
Systemic contact allergy to corticosteroids revisited.
Contact Dermatitis. 2007 Dec;57(6):386-8. [Abstract]

Hickey JR, Dunnill GS, Sansom JE
Photoallergic reaction to systemic quinine sulphate.
Contact Dermatitis. 2007 Dec;57(6):384-6. [Abstract]

Robertshaw H, Leppard B
Contact dermatitis to triclosan in toothpaste.
Contact Dermatitis. 2007 Dec;57(6):383-4. [Abstract]

Watsky KL
Occupational allergic contact dermatitis to platinum, palladium, and gold.
Contact Dermatitis. 2007 Dec;57(6):382-3. [Abstract]

Goiriz R, Delgado-Jiménez Y, Sánchez-Pérez J, García-Diez A
Photoallergic contact dermatitis from lavender oil in topical ketoprofen.
Contact Dermatitis. 2007 Dec;57(6):381-2. [Abstract]

Geier J, Lessmann H, Uter W, Schnuch A
Are concomitant patch test reactions to epoxy resin and BIS-GMA indicative of cross-reactivity?
Contact Dermatitis. 2007 Dec;57(6):376-80.
Background: Despite rare simultaneous exposure, concomitant sensitisation to bisphenol A diglycidyl methacrylate (BIS-GMA) and epoxy resin frequently occurs. Immunological cross-reactivity has not been proven by animal experiments so far. Objective: Our objective was to examine cross-reactivity epidemiologically by analysing data of the Information Network of Departments of Dermatology (IVDK). Patients/methods: From 2001 to 2005, 3,777 patients were patch tested with epoxy resin and BIS-GMA in the IVDK. We retrospectively analysed concomitant reactions to these allergens and to BIS-GMA and selected methacrylates. Additionally, we compared clinical characteristics of patients reacting to both, epoxy resin and BIS-GMA, with those of patients reacting to epoxy resin or BIS-GMA only. Results: 185 patients reacted to epoxy resin, and 40 to BIS-GMA. Of the latter, 34 reacted to epoxy resin. There was no difference concerning exposure between the above-mentioned groups of patients. Concomitant reactions to BIS-GMA and methacrylates hardly ever occurred. Conclusions: Considering the fact that very few patients had been potentially exposed to BIS-GMA and that 85% of those reacting to BIS-GMA also reacted to epoxy resin, we conclude that our data are presumably indicative of immunological cross-reactivity. A verification of this hypothesis by animal experiments would be promising. [Abstract]

Isaksson M, Zimerson E, Svedman C
Occupational airborne allergic contact dermatitis from methacrylates in a dental nurse.
Contact Dermatitis. 2007 Dec;57(6):371-5.
Background: There are very few reports of airborne allergic contact dermatitis from methacrylates. Objectives: To report a dental nurse with facial eczema supposedly caused by airborne methacrylates present in the work environment. Methods: Patch testing with serial dilutions of several methacrylates and work provocations in environments containing methacrylates was performed. Results: Patch testing with serial dilutions of several methacrylates disclosed a high patch test reactivity. Repeated provocations when working with methacrylates resulted in facial eczema that resolved out of work. Attempts to collect the sensitizers using air pumps for the collection of vapors and filters for the collection of air-born aerosols failed. Conclusions: The clinical presentation was that of a facial dermatitis due to airborne exposure to methacrylates. It seems likely that 1 or several of these allergens caused the dermatitis. [Abstract]

Aalto-Korte K, Ackermann L, Henriks-Eckerman ML, Välimaa J, Reinikka-Railo H, Leppänen E, Jolanki R
1,2-Benzisothiazolin-3-one in disposable polyvinyl chloride gloves for medical use.
Contact Dermatitis. 2007 Dec;57(6):365-70.
Background: Benzisothiazolinone is used as a slimicide in the manufacture of disposable powder-free polyvinyl chloride (PVC) gloves. We recently reported 6 patients from dentistry and health care probably sensitized to benzisothiazolinone in PVC gloves. Objective: The study aimed to investigate how widely disposable PVC gloves for medical use on the Finnish market in 2006 contain benzisothiazolinone and to report new cases from 2 clinics in Helsinki. Methods: 31 brands of disposable PVC gloves were analysed for their benzisothiazolinone content. We looked through the patient material of Helsinki University Central Hospital to find benzisothiazolinone allergic patients. We also described 3 previously unpublished benzisothiazolinone allergic patients from Finnish Institute of Occupational Health. Results: 9 (30%) of the 31 glove brands contained 3-26 p.p.m. benzisothiazolinone. From the 2 clinics, we found 5 new benzisothiazolinone allergic patients who had used PVC gloves containing benzisothiazolinone. In addition, 3 patients had used disposable PVC gloves whose benzisothiazolinone content remained unknown. Conclusions: In Finland, benzisothiazolinone in powder-free PVC gloves has caused a small epidemic of allergic contact dermatitis in dental personnel and other health care workers. 1/3 of the disposable PVC gloves contained some benzisothiazolinone. A concentration of 20 p.p.m. benzisothiazolinone in a glove seems to be enough for sensitization. [Abstract]

Vocanson M, Valeyrie M, Rozičres A, Hennino A, Floc'h F, Gard A, Nicolas JF
Lack of evidence for allergenic properties of coumarin in a fragrance allergy mouse model.
Contact Dermatitis. 2007 Dec;57(6):361-4.
Background: There is controversy as to whether coumarin, an ingredient in cosmetics and fragrances, is a contact allergen involved in fragrance allergy. We recently showed that the purity of coumarin is a critical parameter for its allergenicity because coumarin preparations containing trace amounts of contaminants induced cell proliferation in the local lymph node (LN) assay whereas pure coumarin did not. Objective/Method: In the present study, we analyzed the sensitizing properties of coumarin (purity > 99.9) and of dihydrocoumarin (DHC), in a recently developed model of fragrance allergy in mice. Results: DHC was able to prime T cells in LNs draining the sensitization skin site and to induce a typical allergic contact dermatitis (ACD) reaction upon challenge, confirming that DHC is endowed with moderate sensitizing properties. In contrast, no T-cell activation and no ACD responses were obtained following sensitization and challenge with coumarin. Conclsuion: These results confirm that pure coumarin is endowed with very weak sensitizing capacities, if any, and suggest that the presence of contaminants in coumarin preparations may account for the previously reported allergenic properties of coumarin. [Abstract]

Santos R, Goossens A
An update on airborne contact dermatitis: 2001-2006.
Contact Dermatitis. 2007 Dec;57(6):353-60.
Reports on airborne dermatoses are mainly published in the context of occupational settings. Hence, in recent years, dermatologists and also occupational physicians have become increasingly aware of the airborne source of contact dermatitis, resulting mainly from exposure to irritants or allergens. However, their occurrence is still underestimated, because reports often omit the term 'airborne' in relation to dust or volatile allergens. For the present update, we screened the journals 'Contact Dermatitis' (July 2000 to December 2006); 'Dermatitis', formerly named 'American Journal of Contact Dermatitis'; 'La Lettre du Gerda' (January 2000 to December 2006); and also included relevant articles from other journals published during the same period. This resulted in an updated list of airborne dermatitis causes. [Abstract]


2(nd) National Conference of Contact and Occupational Dermatoses Forum of India & Photocon - 2008 Coimbatore.
Contact Dermatitis. 2007 Nov;57(5):352. [Abstract]

Cusano F, Mariano M
Fiberglass dermatitis microepidemic in a primary school.
Contact Dermatitis. 2007 Nov;57(5):351-2. [Abstract]

Ueno M, Adachi A, Horikawa T, Inoue N, Mori A, Sasaki K
Allergic contact dermatitis caused by poly(adipic acid-co-1,2-propylene glycol) and di-(n-octyl) tin-bis(2-ethylhexylmaleate) in vinyl chloride gloves.
Contact Dermatitis. 2007 Nov;57(5):349-51. [Abstract]

Lakshmi C, Srinivas CR, Chinnusamy C
Retention of allergic potential of parthenium following composting.
Contact Dermatitis. 2007 Nov;57(5):348-9. [Abstract]

Rudzki E, Rebandel P
Sensitivity to paraphenylenediamine in Warsaw (Poland).
Contact Dermatitis. 2007 Nov;57(5):347-8. [Abstract]

Isaksson M, Siemund I, Bruze M
Allergic contact dermatitis from ethylcyanoacrylate in an office worker with artificial nails led to months of sick leave.
Contact Dermatitis. 2007 Nov;57(5):346-7. [Abstract]

Pigatto PD, Brambilla L, Guzzi G, Spadari F
Burning lips syndrome.
Contact Dermatitis. 2007 Nov;57(5):344-6. [Abstract]

Feighery C, McCoy EP, Johnston PB, Armstrong DK
Delayed hypersensitivity to hyaluronidase (Hyalase) used during cataract surgery.
Contact Dermatitis. 2007 Nov;57(5):343. [Abstract]

Polat M, Ozta? P, Yalçin B, Artüz F, Lenk N, Alli N
Contact dermatitis as a result of Urginea maritima.
Contact Dermatitis. 2007 Nov;57(5):343-4. [Abstract]

Uter W, Becker D, Schnuch A, Gefeller O, Frosch PJ
The validity of rating patch test reactions based on digital images.
Contact Dermatitis. 2007 Nov;57(5):337-42.
BACKGROUND: The proper reading of patch test (PT) reactions, based on morphological criteria, is of utmost importance. Digital images are increasingly used for medical training. OBJECTIVES: To assess the diagnostic validity of readings of 20 digital images of various PT reaction grades by congress attendants. METHODS: 122 volunteers took a PT quiz offered during the 8th ESCD meeting, September 2006, Berlin. No information on the respective allergen was given, nor the gold standard grading determined by an European Environmental and Contact Dermatitis Research Group (EECDRG) expert panel was disclosed while the quiz was open. RESULTS: Overall, 63.5% of all ratings agreed 'exactly' with the gold standard, and 87.8% 'grossly', that is, with regard to the distinction between non-positive [doubtful or irritant (IR)] and positive (+, ++, and +++) reactions. Most images prompted a fair proportion of correct classifications. The distinction between doubtful and + and between +++, and strong bullous IR reactions proved partly difficult, probably because of blinding of the test substance. The least experienced in particular tended to misclassify IR reactions. CONCLUSIONS: The rating of digital images of PT reactions represents just 1 particular, isolated aspect of PT evaluation. Results were largely valid. Thus, the method could be used for continuing medical education, and for standardization in multicentre networks. [Abstract]

Keegel T, Saunders H, LaMontagne AD, Nixon R
Are material safety data sheets (MSDS) useful in the diagnosis and management of occupational contact dermatitis?
Contact Dermatitis. 2007 Nov;57(5):331-6.
OBJECTIVES: This study assesses both the success of medical practitioners in accessing hazardous substances' information from product manufacturers and the accuracy and clinical usefulness of Material Safety Data Sheets (MSDS) presented by workers with suspected occupational contact dermatitis (OCD). PATIENTS/METHODS: 100 consecutively presented MSDS were collected from 42 workers attending an occupational dermatology clinic. Product manufacturers were contacted to verify ingredients. MSDS were evaluated for compliance with the Australian criteria for listing of OCD relevant information (sensitizers present at a concentration > or =1%, irritants present at a concentration > or =20%), and for clinical usefulness. All sensitizers were checked for clinical relevance to the worker's dermatitis. RESULTS: Manufacturers supplied product constituents for 77/100 MSDS. 58 MSDS satisfied the Australian standard. 57/58 MSDS were deemed clinically useful. Irritants were listed for 19/23 MSDS and sensitizers were listed for 30/68 MSDS (P = 0.001). 3 MSDS contained sensitizers, which were clinically relevant to the presenting worker's dermatitis, 1 appropriately listed, 1 present at > or =1% but not listed, and 1 present at <1% in the product and therefore, not required to be listed. CONCLUSIONS: Sensitizers are frequently omitted from MSDS and clinicians are often unsuccessful in obtaining crucial information from manufacturers. MSDS are inadequate for the protection and diagnosis of workers with suspected OCD. [Abstract]

Aalto-Korte K, Alanko K, Kuuliala O, Jolanki R
Methacrylate and acrylate allergy in dental personnel.
Contact Dermatitis. 2007 Nov;57(5):324-30.
BACKGROUND: Methacrylates are important allergens in dentistry. OBJECTIVE: The study aimed to analyse patch test reactivity to 36 acrylic monomers in dental personnel in relation to exposure. METHODS: We reviewed the test files at the Finnish Institute of Occupational Health from 1994 to 2006 for allergic reactions to acrylic monomers in dental personnel and analysed the clinical records of the sensitized patients. RESULTS: 32 patients had allergic reactions to acrylic monomers: 15 dental nurses, 9 dentists, and 8 dental technicians. The dentists and dental nurses were most commonly exposed to 2-hydroxyethyl methacrylate (2-HEMA), triethyleneglycol dimethacrylate (TREGDMA), and 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]propane (bis-GMA). 8 dentists and 12 dental nurses were allergic to 2-HEMA. The remaining dentist was positive to bis-GMA and other epoxy acrylates. The remaining 3 dental nurses reacted to diethyleneglycol diacrylate (DEGDA) or triethyleneglycol diacrylate (TREGDA), but not to monofunctional and multifunctional methacrylates. Our dental technicians were mainly exposed and sensitized to methyl methacrylate (MMA) and ethyleneglycol dimethacrylate (EGDMA). 1 technician reacted only to 2-HEMA, and another to ethyl methacrylate (EMA) and ethyl acrylate (EA). CONCLUSIONS: 2-HEMA was the most important allergen in dentists and dental nurses, and MMA and EGDMA in dental technicians. Reactions to bis-GMA, DEGDA, TREGDA, EMA and EA were relevant in some patients. [Abstract]

Hohwy T, Andersen KE, Sřlvsten H, Sommerlund M
Allergic contact dermatitis to methyl aminolevulinate after photodynamic therapy in 9 patients.
Contact Dermatitis. 2007 Nov;57(5):321-3.
This report describes 9 patients who developed allergic contact dermatitis to methyl aminolevulinate used for photodynamic therapy (PDT). The risk of developing contact allergy to methyl aminolevulinate in PDT treated patients was calculated to 1% after an average of 7 treatments (range 2-21). [Abstract]

Verma G, Sharma NL, Shanker V, Mahajan VK, Tegta GR
Pesticide contact dermatitis in fruit and vegetable farmers of Himachal Pradesh (India).
Contact Dermatitis. 2007 Nov;57(5):316-20.
BACKGROUND: Not many studies on pesticide allergic contact dermatitis are available from Himachal Pradesh (India). OBJECTIVE: We studied the role of commonly used pesticides in causing allergic contact dermatitis in fruit and vegetable farmers in the region. METHODS: 30 fruit and vegetable farmer patients having dermatitis involving face, neck, hands, and feet and 20 controls comprising 2 groups of 10 subjects each: Group-1 had history of exposure to pesticides but no dermatitis and Group-2 having neither dermatitis nor history of exposure to pesticides, were patch tested with 10 most common pesticides used in the region. RESULTS AND CONCLUSION: These 30 patients (M : F 21 : 9) were between 22-81 years of age having dermatitis for 4 days to 20 years with relapses and remissions. 21 patients had seasonal exacerbation. 10 patients attributed exacerbation of dermatitis to exposure to pesticides. Positive patch test reactions from pesticides were observed in 8 patients only. Captan was the most common sensitizer (5 patients), 2 patients were sensitive to propargite. Chlorpyrifos, tree spray oil and thiuram gave positive reaction in 1 patient each. 3 controls from Group-1 showed positive reactions to multiple pesticides. Pesticide related contact dermatitis appears more common than expected. [Abstract]

Wang BJ, Shiao JS, Chen CJ, Lee YC, Guo YL
Tumour necrotizing factor-alpha promoter and GST-T1 genotype predict skin allergy to chromate in cement workers in Taiwan.
Contact Dermatitis. 2007 Nov;57(5):309-15.
BACKGROUND: Construction workers exposed to cement are known to suffer from occupational contact dermatitis because of chromate sensitization. It is not clear whether certain genotypes are associated with increased susceptibility of chromate sensitization in those workers regularly exposed to cement. OBJECTIVE: The objective of this study was to determine the genotypes predisposing workers to cement-induced contact dermatitis. METHODS: A total of 153 current cement workers who had regular contact with cement were telephone interviewed for skin problems in the past 12 months, work exposure, and personal protection. A dermatologist examined their skin and conducted patch test with common skin allergens. Blood samples were donated for genotypic determination by polymerase chain reaction-based assays for GST-T1, GST-M1 (null/non-null), tumour necrosis factor (TNF) alpha promoter-308G/A, and interleukin (IL) 4-590C/T. RESULT: High percentage of dermatitis was noted in the 153 workers examined, which was correlated with reported skin problems. By patch testing, construction workers had a high-prevalence rate (12%) of sensitivity to chromate. Sensitivity to chromate was significantly associated with TNF alpha promoter-308 heterozygous (GA) as compared with GG genotype (odds ratio 3.9, 95% confidence interval 1.1-13.2), as well as with GST-T1 null genotype (odds ratio 5.5, 95% confidence interval 1.4-36.2), but neither the GST-M1 nor the IL-4 genotypes. CONCLUSION: It is concluded that among workers frequently exposed to cement in Southern Taiwan, those with TNF alpha promoter-308 heterozygous (GA) genotype or GST-T1 null genotype had increased risk of chromate sensitization. [Abstract]

Larsen JM, Geisler C, Nielsen MW, Boding L, Von Essen M, Hansen AK, Skov L, Bonefeld CM
Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivity.
Contact Dermatitis. 2007 Nov;57(5):300-8.
BACKGROUND: The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. OBJECTIVES: To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. PATIENTS/METHODS: Mice were sensitized and/or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. RESULTS: The presented method can be applied to evaluate the effect of different contact allergens on various cell populations of the immune system. CONCLUSIONS: Our study support recent findings that several cell types seem to be involved in CHS. [Abstract]

Thyssen JP, Linneberg A, Menné T, Johansen JD
The epidemiology of contact allergy in the general population--prevalence and main findings.
Contact Dermatitis. 2007 Nov;57(5):287-99.
A substantial number of studies have investigated the prevalence of contact allergy in the general population and in unselected subgroups of the general population. The aim of this review was to determine a median prevalence and summarize the main findings from studies on contact allergy in the general population. Published research mainly originates from North America and Western Europe. The median prevalence of contact allergy to at least 1 allergen was 21.2% (range 12.5-40.6%), and the weighted average prevalence was 19.5%, based on data collected on all age groups and all countries between 1966 and 2007. The most prevalent contact allergens were nickel, thimerosal, and fragrance mix. The median nickel allergy prevalence was 8.6% (range 0.7-27.8%) and demonstrates that nickel was an important cause of contact allergy in the general population and that it was widespread in both men and women. Numerous studies demonstrated that pierced ears were a significant risk factor for nickel allergy. Nickel was a risk factor for hand eczema in women. Finally, heavy smoking was associated with contact allergy, mostly in women. Population-based epidemiological studies are considered a prerequisite in the surveillance of national and international contact allergy epidemics. [Abstract]

Pérez-Calderón R, Gonzalo-Garijo A, Bartolomé-Zavala B, Lamilla-Yerga A, Moreno-Gastón I
Occupational contact urticaria due to pennyroyal (Mentha pulegium).
Contact Dermatitis. 2007 Oct;57(4):285-6. [Abstract]

Martínez FV, Muńoz Pamplona MP, Urzaiz AG, García EC
Occupational airborne contact dermatitis from saffron bulbs.
Contact Dermatitis. 2007 Oct;57(4):284-5. [Abstract]

Livideanu C, Giordano-Labadie F, Paul C
Contact dermatitis to hydrolyzed wheat protein.
Contact Dermatitis. 2007 Oct;57(4):283-4. [Abstract]

Field S, Bourke B, Hazelwood E, Bourke JF
Simvastatin - occupational contact dermatitis.
Contact Dermatitis. 2007 Oct;57(4):282-3. [Abstract]

Foti C, Bonamonte D, Conserva A, Pepe ML, Angelini G
Allergic contact dermatitis to cod liver oil contained in a topical ointment.
Contact Dermatitis. 2007 Oct;57(4):281-2. [Abstract]

Helsing P, Austad J, Talberg HJ
Onycholysis induced by nail hardener.
Contact Dermatitis. 2007 Oct;57(4):280-1.
Nail hardeners appeared in the market during the 1960s. They were basically solutions of formaldehyde. The first adverse effects were published in 1966 (1). Reactions were onycholysis, chromonychia, subungual haemorrhage, and hyperkeratosis. Onycholysis may be non-inflammatory or inflammatory, and is accompanied by throbbing pain. Inflammatory reactions are followed by paronychia and occasional dermatitis on the digital pulpa. [Abstract]

Polat M, Oztas P, Yalcin B, Tamer E, Gur G, Alli N
Contact dermatitis due to Allivum sativum and Ranunculus illyricus: two cases.
Contact Dermatitis. 2007 Oct;57(4):279-80.
Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for medical care. As alternative herbal remedies are becoming more widely used there is an increase in phytocontact dermatitis. Here we document two patients who developed contact dermatitis due to Allivum sativum, and Ranunculus illyricus after applying to the skin in order to relieve the rheumatological joint pain. [Abstract]

Ferreira M, Teixeira M, Silva E, Selores M
Allergic contact dermatitis to Aloe vera.
Contact Dermatitis. 2007 Oct;57(4):278-9.
We present the case of a 72-year-old woman observed for dermatitis on the legs followed by apperance of erythema on the eyelids. She had a past history of peripheral venous insufficiency and had been using self home-made Aloe vera juice over the legs for relief from pain. Patch tests showed positive reactions to the leaf of Aloe, the macerated Aloe jelly, and nickel sulfate. Although most manufacturers process Aloe products avoiding its irritant extracts, and probably as a consequence reports of allergic reactions are rare, one must remember that the growing popularity on the use of Aloe products may stimulate its use 'as is' by the patients. Furthermore, it is important to specifically ask patients about the use of these products, because they consider it as innocuous and thus would not spontaneously provide such information. [Abstract]


Recent Articles in The Journal of Asthma: Official Journal of the Association for the Care of Asthma

Milenkovi? B, Stojsi? J, Mandari? D, Stevi? R
Mucous gland adenoma simulating bronchial asthma: case report and literature review.
J Asthma. 2007 Nov;44(9):789-93.
We report a case of mucous gland adenoma arising in the left main bronchus which was initially misdiagnosed as asthma and review the previous reported cases of this rare tumor published in the available literature. [Abstract]

Grineski S
Characterizing children's asthma hospitalizations on the Texas-Mexico border.
J Asthma. 2007 Nov;44(9):783-7.
The objective of this paper is to study patterns in children's asthma hospitalizations along the Texas-Mexico border. Data for analysis were obtained from the State of Texas and the US Bureau of the Census. Estimated hospitalization rates are compared for border and off-border sociodemographic groups. A logistic regression equation is also used to predict border residence using individual patient characteristics (i.e., race, ethnicity, payer, admission source, severity, length of stay, and cost). Border children are hospitalized at a 36% greater rate than off-border children; additional disparities were found between social groups, particularly for Native American border children. These disparities are disconcerting and require monitoring and reduction. [Abstract]

Adams SK, Murdock KK, McQuaid EL
Complementary and alternative medication (CAM) use and asthma outcomes in children: an urban perspective.
J Asthma. 2007 Nov;44(9):775-82.
Asthma is a disease of significant social magnitude that disproportionately affects children from minority and low-income backgrounds. Poor asthma management is one of the leading causes for high morbidity and mortality rates. In addition to conventional medications, many parents use complementary and alternative medication (CAM) to treat their child's asthma symptoms. This study explored the impact of CAM use on asthma control and risks for nonadherence to conventional medications in 66 parents of children with asthma. Positive parental beliefs about CAM were significantly associated with greater risks for nonadherence and poorer asthma control. Future research should assess the specific pathways that may account for these associations among CAM use and asthma outcomes. [Abstract]

Munzenberger PJ, Thomas R, Bahrainwala A
Retention by children of device technique for inhaled asthma drugs between visits.
J Asthma. 2007 Nov;44(9):769-73.
This study determined retention by children of drug delivery device technique between visits. Patients had asthma requiring the daily use of at least one medication delivery device. Seventy-two patients completed the study; 24 used only the metered dose inhaler (MDI) (group 1), while 48 used the MDI and 1 other device (group 2). Patients or caregivers were initially instructed on and demonstrated the correct use of their medication delivery device(s). At their next visit, they demonstrated their technique for each device. At follow-up, 36% correctly performed all components of the MDI. Group 1 (50%) was higher than group 2 (29%). The percent of correct MDI components for group 1 (84) was also higher than group 2 (78) but not significantly. For both groups and devices, breathing out before inhalation and breath holding was problematic. This study reinforces the need to demonstrate and observe the correct use of inhalation devices at each clinic visit. [Abstract]

Stelmach R, Robles-Ribeiro PG, Ribeiro M, Oliveira JC, Scalabrini A, Cukier A
Incorrect application technique of metered dose inhalers by internal medicine residents: impact of exposure to a practical situation.
J Asthma. 2007 Nov;44(9):765-8.
We evaluated residents regarding maintenance treatment of asthma and the technique for using metered dose inhalers. Methods. Residents were asked to prescribe a treatment for a patient with poorly controlled persistent asthma and to demonstrate the use of metered dose inhaler (MDI) medication. Results. 76% of 239 residents correctly identified the medication indicated for the case; only 30% of them adequately performed the inhalation technique (49% from HCFMUSP vs. 19% from other institutions; p < 0.001). Conclusions. The results demonstrate that, when seeing a typical patient with uncontrolled persistent asthma, most residents are able to correctly identify the drugs indicated for treatment but not adequately instruct the MDI technique use. [Abstract]

Krouse HJ, Krouse JH
Diurnal variability of lung function and its association with sleep among patients with asthma.
J Asthma. 2007 Nov;44(9):759-63.
This prospective exploratory story examined diurnal variations in pulmonary function and their association with sleep and quality of life (QOL) in 20 adult asthmatics. Peak expiratory flow (PEF) was assessed for 7 days, before bedtime and upon awakening. There was no association between PEF variability and QOL. Six of 13 polysomnographic measures were significantly correlated with overnight decline in PEF. Individuals with greatest decline took longer to fall asleep and enter Stage 1 sleep, spent less time asleep, and experienced poorer sleep efficiency. Diurnal variations in PEF reflect adverse sleep quality, yet impact on QOL is often unnoticed. [Abstract]

Yoo KH, Molis WE, Weaver AL, Jacobson RM, Juhn YJ
The impact of electronic medical records on timeliness of diagnosis of asthma.
J Asthma. 2007 Nov;44(9):753-8.
We assessed timeliness of diagnosis of asthma before and after the inception of electronic medical record (EMR). The proportions of children with a delay in diagnosis of asthma before and after the inception of EMR were 67.8% and 56.8%, respectively (p = 0.088). A significant proportion of children have delayed diagnosis of asthma, and availability of EMR plays a minimal role in reducing delays in diagnosis of asthma. However, considering the limited statistical power and a potential trend of EMR toward the positive impact on timely diagnosis of asthma, the study results need to be revisited in a larger study. [Abstract]

Lisspers K, Ställberg B, Hasselgren M, Johansson G, Svärdsudd K
Quality of life and measures of asthma control in primary health care.
J Asthma. 2007 Nov;44(9):747-51.
AIM: To study quality of life and asthma control in primary care. A total of 1,477 patients 15 to 45 years of age received questionnaires regarding asthma control (77% responded) and quality of life, Mini Asthma Quality of Life Questionnaire (MiniAQLQ), (74% responded). Patients using short-acting beta-agonists more than twice in the last week had clinically significant lower MiniAQLQ scores (5.17 versus 5.91). This finding was consistent for night awakenings during the previous week (4.42 versus 5.86), courses of oral corticosteroids (4.82 versus 5.69), and reported emergency consultations during the last 6 months (4.85 versus 5.71). Good asthma control is associated with better quality of life in asthma patients in primary care. [Abstract]

Butz AM, Walker J, Land CL, Vibbert C, Winkelstein M
Improving asthma communication in high-risk children.
J Asthma. 2007 Nov;44(9):739-45.
Few child asthma studies address the specific content and techniques needed to enhance child communication during asthma preventive care visits. This study examined the content of child and parent communications regarding their asthma management during a medical encounter with their primary care provider (PCP). The majority of parents and children required prompting to communicate symptom information to the PCP during the clinic visit. Some high-risk families may require an asthma advocate to ensure that the clinician receives an accurate report of child's asthma severity and asthma control to ensure prescribing of optimal asthma therapy. [Abstract]

Noonan CW, Ward TJ
Environmental tobacco smoke, woodstove heating and risk of asthma symptoms.
J Asthma. 2007 Nov;44(9):735-8.
The effect of common indoor combustion heating sources on childhood asthma is not well described. The objective was to determine if the use of woodstoves in the home or other factors such as environmental tobacco smoke exposure were associated with the frequency of asthma-related symptoms among children in a rural community. Having a person in the household who smoked was associated with a more than doubling in risk for wheezing and other asthma-related symptoms. The use of woodstoves or other types of heating in the homes of children was not associated with reported wheezing during the winter. [Abstract]

Pearlman DS, Rees W, Schaefer K, Huang H, Andrews WT
An evaluation of levalbuterol HFA in the prevention of exercise-induced bronchospasm.
J Asthma. 2007 Nov;44(9):729-33.
BACKGROUND: Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 mug (two actuations of 45 microg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. METHODS: This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were > or =18 years, had a > or =6-month history of EIB, > or = 70% baseline predicted forced expiratory volume in 1 second (FEV1), and a 20% to 50% decrease in FEV(1) after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV1 from baseline (postdose/pre-exercise). The percentage of protected (< or = 20% decrease in post-exercise FEV1) patients was also assessed. RESULTS: Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo (LS mean +/- SE; -4.8% +/- 2.8% versus -22.5% +/- 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV1 compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. CONCLUSION: Levalbuterol HFA MDI (90 microg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. CLINICAL IMPLICATIONS: Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB. [Abstract]

Bergren DR
Tobacco smoke is an adjuvant for maintained airway sensitization in guinea pigs.
J Asthma. 2007 Nov;44(9):723-8.
Tobacco smoke (TS) exposure exacerbates asthma and may induce airway hyperresponsiveness in asymptomatic individuals. We hypothesized that TS exposure is an adjuvant to airway responsiveness. Ovalbumin (OA) sensitized guinea pigs were TS or air exposed. At 30 exposure days OA airway responsiveness was demonstrable in OA-treated animals exposed to either TS or air. After 130 exposure days only TS-exposed guinea pigs demonstrated OA airway responsiveness. Capsaicin airway responsiveness developed in non-sensitized and OA-sensitized guinea pigs exposed to TS. Therefore TS-exposure acts as an adjuvant to antigenic and neurogenic airway responsiveness. Combined antigen and adjuvant avoidance may attenuate or reverse airway responsiveness. [Abstract]

Bollinger ME, Smith SW, LoCasale R, Blaisdell C
Transition to managed care impacts health care service utilization by children insured by Medicaid.
J Asthma. 2007 Nov;44(9):717-22.
Purpose. To evaluate the impact of transition to managed care from fee for service on asthma service utilization among Maryland Medicaid insured children. Methods. Healthcare claims from 1997-2000 for children with asthma insured by Maryland Medicaid were extracted and analyzed. Results. Between 1997-2000, inhaled corticosteroid use increased as a proportion of all asthma medications. Outpatient asthma visits increased from 4.2% to 5.9% of all outpatient claims as both asthma-related hospitalizations and emergency department visits decreased. Conclusions. Restructuring of Maryland Medicaid for children from fee for service to managed care was associated with improvement in asthma-related healthcare utilization claims. [Abstract]

Cowen MK, Wakefield DB, Cloutier MM
Classifying asthma severity: objective versus subjective measures.
J Asthma. 2007 Nov;44(9):711-5.
National guidelines recommend the use of clinical history and spirometry to determine asthma severity. We examined the usefulness of the six guideline-recommended clinical questions in determining asthma severity and then compared guideline-determined severity to clinician-reported and spirometry-determined severity in a cross-sectional study of 201 children with asthma who were not receiving controller therapy. Four guideline-recommended questions (daytime and nocturnal symptoms, school absenteeism, and exercise impairment) determined asthma severity. Concordance between clinician-reported and spirometry-determined asthma severity was poor (kappa = 0.02). Clinical history alone underestimated spirometry-determined disease severity in 27% of children while spirometry results alone underestimated clinician-determined severity in 40% of children. [Abstract]

Cicutto L, Ashby M
The importance of a community-based asthma helpline.
J Asthma. 2007 Nov;44(9):705-10.
BACKGROUND: Individuals with asthma must often make management decisions without the support of asthma care providers. A toll-free asthma helpline is one solution for an easily accessible, community-based service to support individuals with management dilemmas. The study evaluated a toll-free asthma helpline staffed by Certified Asthma Educators (CAEs). METHODS: Helpline CAEs assessed and responded to callers' needs. Data collection occurred during the initial helpline call and a follow-up call 12-16 weeks later. 1,400 of 1,828 (76.6%) eligible callers randomly selected for participation completed the study. RESULTS: Most callers (79%) had poorly controlled asthma during their initial call. CAEs often advised callers (> 75%) to return to their asthma provider for assistance as a result of uncontrolled asthma, medication concerns, a questionable diagnosis, or the need for an action plan. Most participants (71%) returned to their provider and received medication changes (72%). CONCLUSION: The helpline is an important service to individuals affected by asthma (typically uncontrolled) through educating and coaching callers to discuss questions and concerns with their asthma providers. [Abstract]

Milenkovi? BA, Stankovi? IJ, Ili? AM, Petrovi? VI
Peak expiratory flow-guided self-management treatment of asthma in Serbia.
J Asthma. 2007 Nov;44(9):699-704.
The aims of this study were to compare the efficacy of 1-year peak expiratory flow (PEF)-based self-management of asthma against conventional treatment and to analyze the long-term effectiveness of self-management. Eighty adult patients with persistent asthma (group B). After 1 year, significant improvement was noted in markers of asthma severity in group A but there were no changes in group B. After 6 years of the self-management program, asthma morbidity and emergency use of health services were reduced. These results show short-term and long-term effectiveness of a PEF-based self-management program in persistent asthma. [Abstract]

Singh BB, Khorsan R, Vinjamury SP, Der-Martirosian C, Kizhakkeveettil A, Anderson TM
Herbal treatments of asthma: a systematic review.
J Asthma. 2007 Nov;44(9):685-98.
BACKGROUND: Asthma is a condition, often chronic, characterized by respiratory symptoms, variable airflow limitation and/or airway hyper-reactivity with symptoms causally related to family history, environmental influences, exposure to viruses and allergens as examples. The high economic burden associated with asthma is associated primarily with health care costs, missed work or school days. This systematic review was conducted to determine the study quality of articles investigating ayurvedic/collateral herbs, the effectiveness/efficacy and safety profile, as reported in the studies. METHODS: Literature searches were conducted using PubMed, EMBASE, Mantis, Ovid, Annotated Bibliography of Indian Medicine, and Cochrane library to identify published trials on herbal medicines for asthma of which Ayruvedic herbals are a subset. Randomized Controlled Trials (RCTs) and Quasi-Experimental Designs (QEDs) were included in this systematic review. The classic Jadad Scale, Singh RCT Scale with additional domains than Jadad, Safety Scoring Scale for clinical trials and the Singh QED Scale based on expanded features of QEDs were used to assess study quality. Herbs included in Traditional Chinese Medicine were excluded from this review. Forty-two articles were retrieved and 37 studies were ultimately reviewed utilizing 3 independent evaluators/1 arbitrator. RESULTS: Articles reviewed indicated benefit from most of the herbs used either as a primary or adjunctive treatment for Asthma. Study quality was mixed and therefore caution in interpretation of findings of usefulness of these herbals must be suggested. Limited safety information was mixed and generally was related to GI symptoms, though one herbal investigated reported more serious side effects. CONCLUSIONS: Herbs may be useful in treatment of asthma. There is insufficient evidence to make recommendations for or against the use of these herbals. Established effectiveness must be balanced with study quality and safety profile for the herb. [Abstract]


Abstracts.
J Asthma. 2007 Oct;44(8):681-3. [Abstract]

Bernstein JA, Crandall MS, Floyd R
Respiratory sensitization of a food manufacturing worker to konjac glucomannan.
J Asthma. 2007 Oct;44(8):675-80. [Abstract]

Bateman ED, Clark TJ, Frith L, Bousquet J, Busse WW, Pedersen SE
Rate of response of individual asthma control measures varies and may overestimate asthma control: an analysis of the goal study.
J Asthma. 2007 Oct;44(8):667-73.
BACKGROUND: Using a composite measure based on clinical outcomes, the GOAL study showed that achievement of Total Control of asthma was time dependent with the proportion of controlled patients continuing to rise through the year-long study. Taking data from this study, we compared time taken to achieve Total Control with time taken to achieve total control of each individual clinical criterion on treatment with salmeterol/fluticasone propionate (SFC) or fluticasone propionate (FP) alone. METHODS: Time to achieving total control of individual outcomes (day-time symptoms, night-time awakenings, rescue medication use, PEF > or =80% predicted every day) were analyzed by Kaplan Meier plots and compared with achievement of composite Total Control. RESULTS: Night-time awakenings responded most rapidly and daytime symptoms took longest to respond. After 12 weeks, the proportion of patients who achieved control of any individual clinical criterion was higher than the proportion who achieved control when using the composite outcome (no night-time awakenings achieved by 73% with SFC and 65% with FP; PEF > or =80% predicted every day, 55% and 45% respectively; no rescue usage 46% and 35% respectively; and no daytime symptoms, 35% and 24% respectively, compared with Total Control, 23% and 14% respectively). In every measure except night-time awakenings, more rapid responses were seen for SFC compared with FP alone. CONCLUSIONS: Speed of response of individual asthma measures varies and evaluation of control using any single measure overestimates total asthma control. Treatment should be continued until composite control is reached, rather than control of individual outcomes. [Abstract]

Wichmann J, Wolvaardt JE, Maritz C, Voyi KV
Household conditions, eczema symptoms and rhinitis symptoms: relationship with wheeze and severe wheeze in adolescents living in the Polokwane area, South Africa.
J Asthma. 2007 Oct;44(8):659-66.
OBJECTIVE: Determine the prevalence and risk factors of wheeze and severe wheeze in 13-to 14-year-old children. METHODS: The study was conducted August 2004 to February 2005 in the Polokwane area, South Africa. RESULTS: The 12-month prevalence rate was 18.9% for wheeze and 9.2% for severe wheeze (n = 3,926). The presence of other allergic symptoms and industrial activities appear to increase the likelihood of wheeze, even more so for severe wheeze. Socioeconomic-related factors appear to have a protective effect on wheeze. CONCLUSIONS: Wheeze appears to be a substantial public health problem in the Polokwane area. [Abstract]

Strine TW, Balluz LS, Ford ES
The associations between smoking, physical inactivity, obesity, and asthma severity in the general US population.
J Asthma. 2007 Oct;44(8):651-8.
The purpose of this study was to examine the associations between smoking, physical inactivity, obesity, and asthma severity among US adults. The magnitude of these associations was very strong. For example, those who visited an emergency room in the past year were 60% more likely than those who did not to smoke; those who used an inhaler > or =15 times in the past month (versus those who did not use an inhaler) were 90% more likely to be physically inactive; and those who had asthma symptoms all the time in the past 30 days (versus those with no symptoms) were 80% more likely to be obese. [Abstract]

Siebers R, Hayes J, Crane J
Upper body clothing is a source of fungal beta-(1,3)-glucan exposure.
J Asthma. 2007 Oct;44(8):649-50.
Beta-(1,3)-glucan is pro-inflammatory and has been associated with airway inflammation and respiratory symptoms. This study assessed beta-(1,3)-glucan levels from upper body clothing (jerseys) of 55 subjects. Beta-(1,3)-glucan levels were estimated with a modified Limulusamoebocyte lysate kinetic assay. Beta-(1,3)-glucan levels ranged widely from 2,697 to 162,690 ng/g. Beta-(1,3)-glucan levels were significantly lower from cotton jerseys and from warm water washed jerseys. Thus, jerseys are potentially a significant exposure source of beta-(1,3)-glucan. [Abstract]

Naqvi M, Thyne S, Choudhry S, Tsai HJ, Navarro D, Castro RA, Nazario S, Rodriguez-Santana JR, Casal J, Torres A, Chapela R, Watson HG, Meade K, LeNoir M, Avila PC, Rodriguez-Cintron W, Burchard EG
Ethnic-specific differences in bronchodilator responsiveness among African Americans, Puerto Ricans, and Mexicans with asthma.
J Asthma. 2007 Oct;44(8):639-48.
Socioeconomic and environmental differences do not fully explain differences in asthma prevalence, morbidity, and mortality among Puerto Ricans, African Americans, and Mexican Americans. Differences in response to albuterol may be a factor. We compared bronchodilator responsiveness between these three populations. All groups demonstrated below expected responsiveness. Puerto Ricans of all ages and African American children with moderate-to-severe asthma demonstrated the lowest responsiveness overall. Among subjects with moderate-to-severe asthma, children were even less likely than adults to show the expected bronchodilator response. We conclude that ethnic-specific differences in bronchodilator drug responsiveness exist between Mexicans, Puerto Ricans, and African Americans with asthma. This may be of importance in asthma management. [Abstract]

Stern T, Garg A, Dawson N, McFadden ER
Validating a guidelines based asthma decision support system: step one.
J Asthma. 2007 Oct;44(8):635-8.
Purpose. To quantify the accuracy of a computerized decision support system in discerning severe asthma in a clinical setting. Design. A total of 69 consecutive asthmatics examined in an asthma clinic were classified as "severe" or "mild" by the computerized decision support system and expert asthma clinicians. The expert asthma clinicians were the reference standard. Results. The accuracy was 91%, the sensitivity 96%, the specificity 73%, the positive predictive value 93%, and the negative predictive value 85%. Conclusions. The asthma decision support system was able to discern "mild" from "severe" asthma in a similar fashion to expert asthma clinicians. [Abstract]

Ratner P, Darken P, Wingertzahn M, Shah T
Ciclesonide and beclomethasone dipropionate coadministration: effect on cortisol in perennial allergic rhinitis.
J Asthma. 2007 Oct;44(8):629-33.
Coexisting asthma and allergic rhinitis (AR) are often treated with both intranasal and inhaled corticosteroids. This study investigated whether intranasal ciclesonide 200 microg once daily has an additional effect on cortisol suppression when coadministered with inhaled hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP). Adult patients (n = 150) with perennial AR received HFA-BDP 320 microg twice daily and placebo once daily during a run-in period. Patients were then randomized to ciclesonide or placebo and HFA-BDP (43 days). A single 2-mg dose of dexamethasone was administered on the last treatment day. Plasma cortisol decreased by 67.8 microg x h/dL (p < 0.001) during the run-in period. When ciclesonide was added, the change in mean plasma cortisol was similar for ciclesonide and placebo (8.5 microg x h/dL and 1.0 microg x h/dL, respectively). Dexamethasone decreased mean plasma cortisol (p < 0.001), demonstrating that further cortisol suppression was possible. This study suggests that intranasal ciclesonide can be used with an inhaled corticosteroid without increased cortisol suppression. [Abstract]

Hardie GE, Brown JK, Gold WM
Adrenergic responsiveness: FEV1 and symptom differences in Whites and African Americans with mild asthma.
J Asthma. 2007 Oct;44(8):621-8.
Decision-making about inhaler use is, in part, determined by the ability of asthmatic patients to compare their symptoms over time and to recall the previous response to the bronchodilator during an episode of asthma. The perception of airway symptoms across varied ethnic and cultural groups are poorly understood. Study purpose was (1) to determine if African Americans and Whites with mild asthma could accurately perceive bronchodilation and (2) to identify the word descriptors they used to describe their breathing. Sixteen African American and 16 White patients (34.5 +/- 9.7 years old, mean+/-SD) with mild atopic asthma (FEV1 > or =70% predicted normal) were given increasing doses of an inhaled bronchodilator (Albuterol) after a methacholine challenge. Albuterol (180 microg) was given, by spacer, at 15 min intervals until the FEV1 increased < 5%. Borg, VAS, and Word Descriptors were collected at baseline and after each dose of Albuterol. Baseline FEV1 after Methacholine provocation was 1.94 +/- .39 L for African Americans and 2.13 +/- .70 L for Whites. After 180 microg and again after 360 microg Albuterol, FEV1 increased to 2.88 +/- 0.48 L for African Americans and 3.37 +/- 0.91 L for Whites. But after 540 microg Albuterol, FEV1 decreased significantly (16%) to 2.42 +/- 1.19 L for African Americans while increasing only slightly to 3.47 +/- 0.95 L for Whites. After this dose, 10/16 African Americans felt "tight at the base of throat" (p < 0.01); 7/16 felt "speech-voice-tight" (p < 0.03) suggesting persistent airway discomfort despite marked improvement in FEV1, Borg and VAS scores compared with baseline values. Word descriptors by African Americans' are a more reliable measure of airway symptoms compared to FEV1, Borg or VAS. [Abstract]

Huang TT
Self-care behavior of adult asthma patients.
J Asthma. 2007 Oct;44(8):613-9.
The purpose of this study was to identify factors potentially associated with asthma self-care behavior among adult asthma patients. A correlational descriptive study was conducted with a convenience sample of 220 adults identified as having moderate-to-severe asthma and receiving outpatient care at a medical center in northern Taiwan. Participants were interviewed by questionnaires. The study found that asthma self-care behaviors were predicted by 5 factors: (1) younger age, (2) not smoking history, (3) better social support, (4) better knowledge, and (5) better skills regarding asthma self-care, accounting for 51.5% of the total variance. The study also showed that the initial model could be modified to obtain a recursive model with good fit. Determinant factors identified by the analysis highlight the need to educate adult asthma patients about self-care to minimize mortality and promote their quality of life. [Abstract]

Trakultivakorn M, Sangsupawanich P, Vichyanond P
Time trends of the prevalence of asthma, rhinitis and eczema in Thai children-ISAAC (International Study of Asthma and Allergies in Childhood) Phase Three.
J Asthma. 2007 Oct;44(8):609-11.
Using the same questionnaire as in ISAAC Phase One study conducted in 1995, the ISAAC Phase Three was carried out in Bangkok and Chiang Mai, Thailand, in 2001, among children aged 6-7 and 13-14 years. There was an increase in the prevalence of the three diseases in the younger age group, i.e., current asthma, rhinitis, rhinoconjunctivitis, and flexural eczema. In the older age group, the prevalence of rhinitis and rhinoconjunctivitis increased. There was no change of prevalence of asthma in Bangkok, but prevalence decreased in Chiang Mai. Prevalence of eczema in older children increased in Bangkok, but remained the same in Chiang Mai. [Abstract]

Eden E, Holbrook JT, Brantly ML, Turino GM, Wise RA
Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial.
J Asthma. 2007 Oct;44(8):605-8.
In a study comparing low-dose theophylline to montelukast in poorly controlled asthmatics, 285 subjects consented to be screened for alpha-1 antitrypsin deficiency. Of the 284 for which complete data was available, 10.5% carried a deficiency gene and 2.4% were mildly deficient with an alpha-1 antitrypsin serum level of less than 20 mu M. In the non-African-American cohort, an abnormal phenotype occurred in 12% and 2.9% were mildly deficient. Baseline pulmonary function and asthma scores were not significantly different between those with normal and abnormal AAT phenotype. However those with the deficiency tended to show a greater bronchodilator response. [Abstract]

Tsai HJ, Tsai AC
The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan.
J Asthma. 2007 Oct;44(8):599-603.
This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms. [Abstract]

Self TH, Arnold LB, Czosnowski LM, Swanson JM, Swanson H
Inadequate skill of healthcare professionals in using asthma inhalation devices.
J Asthma. 2007 Oct;44(8):593-8.
Inadequate skill in the use of asthma inhalation devices by healthcare professionals has been well documented over the past 25 years. We performed a PubMed search of the English literature for studies regarding skill by physicians, medical students, pharmacists, nurses, and respiratory therapists in using asthma inhalation devices. This review summarizes 20 studies that were identified. Results of these studies consistently showed lack of skill in using metered-dose inhalers, spacers, and dry powder inhalers by a majority of healthcare professionals. National and international guidelines for asthma management include detailed patient education as an essential component of care, yet a large percentage of healthcare professionals are not competent in using inhalation devices. Practical solutions to this problem are needed to enhance the care of asthma patients. [Abstract]


Abstracts.
J Asthma. 2007 Sep;44(7):589-91. [Abstract]

Milian A, Nierenberg K, Fleming LE, Bean JA, Wanner A, Reich A, Backer LC, Jayroe D, Kirkpatrick B
Reported respiratory symptom intensity in asthmatics during exposure to aerosolized Florida red tide toxins.
J Asthma. 2007 Sep;44(7):583-7.
Florida red tides are naturally occurring blooms of the marine dinoflagellate, Karenia brevis. K. brevis produces natural toxins called brevetoxins. Brevetoxins become part of the marine aerosol as the fragile, unarmored cells are broken up by wave action. Inhalation of the aerosolized toxin results in upper and lower airway irritation. Symptoms of brevetoxin inhalation include: eye, nose, and throat irritation, coughing, wheezing, chest tightness, and shortness of breath. Asthmatics appear to be more sensitive to the effects of inhaled brevetoxin. This study examined data from 97 asthmatics exposed at the beach for 1 hour during K. brevis blooms, and on separate occasions when no bloom was present. In conjunction with extensive environmental monitoring, participants were evaluated utilizing questionnaires and pulmonary function testing before and after a 1-hour beach walk. A modified Likert scale was incorporated into the questionnaire to create respiratory symptom intensity scores for each individual pre- and post-beach walk. Exposure to Florida red tide significantly increased the reported intensity of respiratory symptoms; no significant changes were seen during an unexposed period. This is the first study to examine the intensity of reported respiratory symptoms in asthmatics after a 1-hour exposure to Florida red tide. [Abstract]

Scharloo M, Kaptein AA, Schlösser M, Pouwels H, Bel EH, Rabe KF, Wouters EF
Illness perceptions and quality of life in patients with chronic obstructive pulmonary disease.
J Asthma. 2007 Sep;44(7):575-81.
This study aimed at identifying cognitive and emotional representations relevant for improving health care communication and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD). One-hundred-seventy-one COPD outpatients completed questionnaires on illness perceptions and QoL. After controlling for the effects of age, pulmonary function, and dyspnea, patients with decreased attention to symptoms, with more positive beliefs about the effects and outcomes of their illness, and with less strong emotional reactions to the illness, had higher QoL scores. The results of this study are discussed in relation to the associations found in other illnesses. [Abstract]


Recent Articles in Allergy and Asthma Proceedings: the Official Journal of Regional and State Allergy Societies

Oh JH, Hur KY, Ye YM, Kim JE, Park K, Park HS
Correlation between specific IgA and eosinophil numbers in the lavage fluid of patients with perennial allergic rhinitis.
Allergy Asthma Proc. 2007 Dec 6;
The mechanisms of eosinophil activation in perennial allergic rhinitis (AR) are not fully understood but may be mediated by a series of inflammatory mediators, including locally produced specific antibodies. The aim of this study was to evaluate the role of locally produced allergen-specific antibodies in the nasal lavage fluid during the recruitment of inflammatory cells in AR. Thirteen patients with AR and a positive nasal provocation test (NPT) with Dermatophagoides pteronyssinus and 10 asymptomatic subjects, sensitized to D. pteronyssinus but who had a negative NPT were enrolled. Nasal lavage fluids were collected before and at 10, 30, and 60 minutes and 3, 6, and 24 hours after the NPT. Inflammatory cells were counted, and eosinophil cationic protein (ECP) and specific immunoglobulin E (IgE), IgG, and IgA antibodies were measured by enzymelinkedimmunosorbent assay. After NPT, six subjects showed early responses and seven subjects showed dual responses. The eosinophil count and ECP level in lavage fluid were significantly increased after NPT in patients with positive NPTs, and these values were significantly higher than in the negative group. The specific IgA level in lavage fluid was increased after NPT in the positive group, and significant differences were noted for both the early and the late positive responses. Significant correlations were found between specific IgA and ECP levels in lavage fluid during early and late responses. Eosinophil recruitment occurred during both early and late responses after allergen exposure in perennial AR. Locally producedallergen-specific IgA but not IgE or IgG may be involved in eosinophil activation in both early and late responses. [Abstract]

Martínez-Girón R, Ribas A, Astudillo-González A
Flagellated protozoa in cockroaches and sputum: the unhygienic connection?
Allergy Asthma Proc. 2007 Sep-Oct;28(5):608-9. [Abstract]

Gewurz A
Letters to the editor.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):607; author reply 607-8. [Abstract]

Kavosh E, Bielory L
Letters to the editor.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):606-7. [Abstract]

Culp JA, Palis RI, Castells MC, Lucas SR, Borish L
Perioperative anaphylaxis in a 44-year-old man.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):602-5.
This article presents a case report of perioperative anaphylaxis in a previously nonallergic 44-year-old man undergoing cervical spine surgery. After receiving general anesthesia with midazolam, propofol, lidocaine, fentanyl, rocuronium, and sevoflurane and cefazolin for prophylaxis, the patient developed hypotension, tachycardia, bronchospasm, and generalized erythema. A serum tryptase concentration was markedly elevated 2 hours after the anaphylactic episode. Initial prick and intradermal skin tests (excluding skin testing for unavailable benzylpenicilloyl polylysine) and IgE immunoassays for penicillin and cefazolin were negative. However, repeat prick skin testing for cefazolin 6 weeks after anaphylaxis was positive. Although anaphylaxis to cephalosporins is rare, it remains a potential cause of perioperative anaphylaxis. All cases of perioperative anaphylaxis require a workup to identify the offending agent and to avoid future reactions. Skin testing regimens for several commonly implicated drugs used for general anesthesia are available and are described. [Abstract]

Caron AB
Allergy to multiple local anesthetics.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):600-1.
Real allergy to local anesthetic (LA) is very rare. This study was performed to report a case of anaphylaxis to multiple "caine." A 25-years-old atopic nurse developed a very severe anaphylactic reaction on her third infiltration for low back pain with bupivacaine, lidocaine, and methylprednisolone: she developed a vagal reaction, followed during the next 30 minutes by a pruriginous skin rash, followed by a tongue edema and a severe bronchospasm. Adrenalin was injected with a poor response. She was intubated and transferred to the intensive care unit for a few days and, finally, she recuperated completely. Skin-prick tests were done on two occasions. In the first session, no reactions were observed with triamcinolone and methylprednisolone at 1 mg/cc, but a rapid extending maculopapular erythema developed with a final diameter of 50 mm with lidocaine 0.1% (group 2) and 25 mm with procaine 2% (group 1): control 0 mm, histamine, 3 mm. She also complained of itchiness in the neck and shoulder, which resolved in the next 90 minutes. In the second session, a test with bupivacaine 0.0005% (group 2) gave a papule with a diameter of >5 mm, and a test with mepivacaine 0.001% (group 2) was negative: control, histamine, 3 mm; no subsequent tests with mepivacaine were done because she developed a cough and throat pruritus, voice modification, and a sensation of throat narrowing, that resolved with treatment. We reported a case of anaphylaxis to multiple LA (groups 1 and 2), possibly via an IgE-mediated mechanism. [Abstract]

Patel D, Garadi R, Brubaker M, Conroy JP, Kaji Y, Crenshaw K, Whitling A, Wall GM
Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: olopatadine hydrochloride versus mometasone furoate monohydrate.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):592-9.
Rapid relief of symptoms should be one of the primary goals of treatment for allergic rhinitis (AR). The onset and duration of action of olopatadine hydrochloride nasal spray, 665 mcg (OLO; Patanese), for seasonal AR (SAR) was evaluated in this study. This study was performed to determine the onset and duration of action of OLO compared with placebo spray, with mometasone furoate monohydrate, 50 mcg (MM; Nasonex), as a reference standard. This was a single center, single-dose, randomized, double-blinded parallel-group environmental exposure chamber study. Patients were primed at two 2-hour priming visits. Eligible patients were randomized to OLO, placebo spray, or MM, 2 sprays/nostril. Allergy symptoms (sneezing, runny, itchy, and stuffy nose) were rated by patients at 16 time points during 12 hours after dosing and patient satisfaction was assessed at 4 and 12 hours postdose. Safety was assessed by a review of adverse events, cardiovascular and nasal examination parameters. Four hundred twenty-five adult patients were randomized. OLO was superior to placebo spray in reducing total nasal symptoms (TNSS) within 30 minutes after dosing and maintained superiority for at least 12 hours (p < 0.05). The onset of MM was not observed until 150 minutes postdose and was smaller in magnitude compared with OLO. OLO was superior to both placebo spray (p < 0.0001) and MM (p < 0.05) in patient satisfaction. Treatment was well-tolerated with no safety concerns. OLO is superior to placebo spray and MM in reducing allergy symptoms; OLO has a rapid onset of action and a duration of effect of at least 12 hours. [Abstract]

Hasala H, Janka-Junttila M, Moilanen E, Kankaanranta H
Levocetirizine and cytokine production and apoptosis of human eosinophils.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):582-91.
Antihistamines are a common therapy for allergic symptoms. Eosinophilic infiltration is considered a hallmark of allergic inflammation. Eosinophils are capable of mediating airway mucosal damage by producing various inflammatory mediators including cytokines, chemokines, basic granule proteins, lipid mediators, and growth factors. Reduced eosinophil apoptosis is thought to be an important feature in the formation of eosinophilia in allergic diseases such as allergic rhinitis, atopic eczema, and asthma. The aim of this study was to investigate the effects of levocetirizine on the production of inflammatory mediators by eosinophils and on eosinophil apoptosis. The production of cytokines and other inflammatory mediators by human eosinophils was measured by a cytokine antibody array. Apoptosis of isolated human eosinophils was assessed by measuring the relative DNA content of propidium iodide-stained cells. Of the 40 cytokines studied, levocetirizine (1 microM) was found to enhance the release of tissue inhibitor of metalloproteinases 1 and 4, matrix metalloproteinase 9, and heparin-binding epidermal growth factor and to attenuate the production of interleukins (IL)-1 beta and IL-7 and stem cell factor in lipopolysaccharide-stimulated human eosinophils. Levocetirizine did not alter constitutive eosinophil apoptosis or eosinophil survival induced by IL-5, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, or salbutamol. The results of this study suggest that levocetirizine modulates the profile of inflammatory mediators including cytokines, growth factors, proteinases, and antiproteinases produced by eosinophils, which may be of importance in allergic inflammation and airway remodeling. However, eosinophil longevity seems not to be modulated by levocetirizine. [Abstract]

Ciprandi G, Cirillo I, Tosca MA, Marseglia G, Fenoglio D
Sublingual immunotherapy-induced IL-10 production is associated with changed response to the decongestion test: preliminary results.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):574-7.
Sublingual immunotherapy (SLIT) has been shown to be capable of inducing a regulatory T-cell response as evidenced by IL-10 production. Decongestion testing consists of spraying an intranasal vasoconstrictor drug to evaluate the recovery of nasal airflow limitation. The aim of this study was to assess the association of SLIT-induced IL-10 production with nasal airflow recovery after decongestion testing. Nineteen patients with perennial allergic rhinitis (PAR) were studied: 9 patients successfully assumed SLIT for 3 years and 10 patients were considered as control. In vitro IL-10 production was evaluated after SLIT. Rhinomanometry and decongestion testing were performed in all subjects before and after 3 years. After 3 years, SLIT patients showed a significant decrease of nasal resistances (0.048) and reduced response to decongestion testing (p = 0.044 for absolute values and p = 0.0051 for delta). The comparison with nontreated allergic patients shows significant differences concerning both pretest values (p = 0.02) and delta percentages (p = 0.00466). In addition, the decrease of nasal airflow resistance values and the percentages of reversibility were significantly associated with IL-10 levels (p = 0.0016 and p = 0.00294, respectively). This preliminary study provides the first evidence of a changed response to decongestion testing after SLIT that is associated with IL-10 production in patients with PAR. [Abstract]

Ruiz-Hornillos FJ, De Barrio Fernández M, Molina PT, Marcén IS, Fernandez GD, Sotés MR, de Ocariz ML
Occupational asthma due to esparto hypersensitivity in a building worker.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):571-3.
Esparto is a gramineous plant that has multiple applications in today's industry. Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation have been reported, but only one case of asthma caused by Aspergillus fumigatus contaminating esparto has been communicated. We report a case of asthma induced by esparto inhalation in a 58-year-old man, who is a building industry worker, with subclinical sensitization to grass pollen. The relation between clinical symptoms and work activities was supported by peak expiratory flow (PEF) monitorization; PEF values decreased by 20% the days he handled esparto. Prick test with esparto was positive. Immunoblot analysis revealed several allergens in the esparto extract, some of them present in Lolium and A. fumigatus extracts. IgE immunoblot inhibition revealed a complete inhibition of lolium and A. fumigatus IgE reactive bands by esparto proteins. The patient then avoided the exposure to esparto at work and has remained asymptomatic for the last 2 years. In conclusion, this is a case of occupational asthma caused by esparto dust mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from this gramineous plant, which cross-reacted with esparto allergens, were responsible for the disease. [Abstract]

Diéguez MC, Pulido Z, de la Hoz B, Blanco R, Cerecedo I, Fernández-Caldas E, Swanson M
Latex allergy in healthcare workers: an epidemiological study in a Spanish hospital.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):564-70.
To design an effective prevention program in health care workers who are allergic to latex it is necessary to know the current epidemiological situation. The objectives were to determine the main factors associated with latex allergy and to quantify levels of airborne latex particles in different areas of our hospital. A cross-sectional study was conducted using a questionnaire completed by health care workers. Those who answered the first questionnaire were given a second one to fill out and an allergological study (skin-prick test and latex-specific IgE antibodies) was performed. Latex aeroallergen particles were collected with a Quan-tec-air in different areas of the hospital. The first questionnaire was sent to 2551 health care workers. Eight hundred forty-one (33.14%) subjects returned the completed questionnaire and were given the second questionnaire. One hundred fifty-four completed second questionnaire. We identified 28 patients who were allergic to latex, and 126 patients who were not allergic to latex. In the allergic population there were more nurses aides. More allergic patients were found in the Surgery Department, Intensive Care Unit (ICU), and Vascular Radiology Unit (VRU). Allergic patients were more likely to use a higher number of latex gloves and during more hours than nonallergic workers. In the Surgery Department, ICU, VRU, and Laboratory Department more pairs of latex gloves were used and during more hours. The medium level of latex aeroallergens in 24 determinations in 14 areas of the hospital was 8.12 ng/m3 (SD, 13.32 ng/m3; range, 0.3-57.7 ng/m3). The higher levels were found in Laboratory (n = 2; mean (M) 23; SD, 25.95 ng/m3) and Surgery Departments (n = 11; M, 7.43; SD, 16.98 ng/m3; Kruskal Wallis test, p = 0.09). Latex allergy is an important health problem for health care workers, especially for those working in surgical areas or in those places where more latex gloves are used; in these areas higher levels of airborne latex particles are found. We should take into account these data to design an effective secondary prevention program. [Abstract]

Miri S, Pourpak Z, Zarinara A, Heidarzade M, Kazemnejad A, Kardar G, Firooz A, Moin A
Prevalence of type I allergy to natural rubber latex and type IV allergy to latex and rubber additives in operating room staff with glove-related symptoms.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):557-63.
There is lack of data on the prevalence of latex allergy in the health care setting in Iran. This study was performed to determine the prevalence of type I latex allergy and type IV allergy to latex and rubber additives among the operating room staff with glove-related symptoms in 13 general hospitals in Tehran. Skin-prick tests with commercial latex extract, patch tests with latex and 25 rubber additive series, and total and latex-specific IgE detection were performed on the operating room staff who reported latex glove-related symptoms. Five hundred twelve self-administered questionnaires (100%) were completed by all operating room staff and latex glove-related symptoms were reported by 59 (11.5%) employees. Among all symptomatic operating room staff tested, the prevalence of type I latex allergy was 30.5% and the prevalence rates of type IV allergy to latex and rubber additives were 16.7 and 14.6%, respectively. The most positive patch test result with rubber additives was related to tetramethylthiuram monosulfide (38.5%). The risk factors for type I latex allergy were female sex (p = 0.009) and positive patch test with rubber additives (p = 0.012). Subjects who had positive patch test with latex were significantly more likely to have positive patch test with rubber additives (p < 0.0001). Our results showed a high prevalence of type I latex allergy and type IV allergy to latex and rubber additives. Based on this study, we recommend eliminating powdered latex gloves from the operating rooms of the 13 studied general hospitals and support the substitution of powder-free latex gloves. [Abstract]

Ishizuka T, Hisada T, Aoki H, Yanagitani N, Kaira K, Utsugi M, Shimizu Y, Sunaga N, Dobashi K, Mori M
Gender and age risks for hoarseness and dysphonia with use of a dry powder fluticasone propionate inhaler in asthma.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):550-6.
Dry powder inhalers (DPIs) of fluticasone propionate (FP) are the most commonly prescribed inhaled glucocorticosteroid (ICS) devices in Japan because of their ease of use. FP has the strongest anti-inflammatory effects in vitro among ICS, and it has few systemic adverse effects because of its <1% oral bioavailability. However, local adverse effects, especially hoarseness or dysphonia (hoarseness/dysphonia), appear to be frequent. We investigated hoarseness/dysphonia in 313 patients with bronchial asthma who were using or had used the FP-DPI. Overall, 20.4% of FP-DPI users complained of hoarseness/dysphonia, with women and elderly patients complaining of it more frequently; 35.8% of female FP-DPI users > or =65 years of age complained of hoarseness/dysphonia. The prevalence of hoarseness/dysphonia was dose dependent in patients <65 years old but not in patients > or =65 years of age. Inspiratory flow rates adjusted by resistance of the DPIs were not related to the prevalence of hoarseness/dysphonia. In patients using ICS, especially in women and the elderly patients, who develop hoarseness/dysphonia, it is important to select the most suitable device so that patients can continue ICS therapy comfortably. [Abstract]

Mullaoglu S, Turktas H, Kokturk N, Tuncer C, Kalkanci A, Kustimur S
Esophageal candidiasis and Candida colonization in asthma patients on inhaled steroids.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):544-9.
The aim of this study was to evaluate the risk of esophageal candidiasis in asthma patients who are on inhaled steroids without any other risk factors for esophageal candidiasis by comparing the treatment group with the control group. Moreover, the oropharyngeal and esophageal Candida colonizations were evaluated in the subgroups of both control and treatment groups. Upper gastrointestinal system endoscopic evaluation was performed in 40 asthma patients who were on inhaled steroids for at least 1 month. The control group consisted of 40 steroid naďve patients without asthma. Oral and esophageal samples were obtained for performing quantitative culture. Candida growth in cultures without any clinical signs and symptoms was described as colonization. Candida growth accompanied by clinical signs and symptoms was described as infection. None of the patients in the control group had either esophageal or oropharyngeal candidiasis; however, one (2.5%) asthma patient had esophageal candidiasis and two (5%) asthma patients had oropharyngeal candidiasis. Esophageal and oropharyngeal Candida colonization was determined in 5 (22.7%) and 11 (50%) of the asthma patients and 7 (31%) and 9 (41%) of the control group, respectively. Although the mean numbers of Candida colonies were higher in the asthma group in both localizations, there were no statistically significant differences between the two groups regarding esophageal or oropharyngeal Candida colonization. The risk of esophageal candidiasis due to inhaled steroids is low and inhaled steroids may be used safely in terms of esophageal candidiasis. Future prospective studies are needed to draw more definitive conclusions. [Abstract]

Galli E, Gianni S, Auricchio G, Brunetti E, Mancino G, Rossi P
Atopic dermatitis and asthma.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):540-3.
Atopic dermatitis (AD), a chronic inflammatory skin disease, frequently associated with respiratory allergy, is one of the most common skin disorders observed in children. The prevalence of AD and other allergic diseases is increasing in industrialized countries, representing a major burden on health care cost. AD has been proposed as an "entry point" for subsequent allergic diseases, suggesting the possibility that effective management of AD could prevent the development of respiratory allergy or at least reduce the severity of asthma and allergic rhinitis. AD and asthma share a common genetic and pathogenic basis, and several longitudinal studies provided evidence for the atopic march from AD to allergic rhinitis and asthma. However, because only a few prospective studies starting at children's births and having a sufficiently long follow-up have been developed, little is known about the natural course of AD and the potential succession of atopic phenotypes in childhood. Finally, recent genetic and epidemiological data raised the question whether AD may either develop to asthma or be part of a syndrome consisting of both diseases. [Abstract]

Thomsen SF, Ulrik CS, Kyvik KO, Hjelmborg JB, Skadhauge LR, Steffensen I, Backer V
Importance of genetic factors in the etiology of atopic dermatitis: a twin study.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):535-9.
The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who were enrolled in The Danish Twin Registry, a total of 11,515 twin pairs were identified in a nationwide questionnaire survey. Subjects were classified as atopic dermatitis cases when responding affirmatively to the question, "Do you have, or have you ever had, eczema in the folds of your elbows or knees?" Latent factor models of genetic and environmental influences were fitted to the observed data using maximum likelihood methods. The overall lifetime prevalence of atopic dermatitis was 7.3%. A cotwin of an affected identical twin had a sevenfold increased risk of atopic dermatitis compared with a threefold increased risk among cotwins of an affected fraternal twin, relative to the general population. Genes accounted for 82% and nonshared environmental factors accounted for 18% of the individual susceptibility to develop atopic dermatitis. The same genes contributed to the susceptibility to atopic dermatitis both in male and female patients (p = 0.98). The estimates were adjusted for age. The susceptibility to develop atopic dermatitis is attributable to mainly genetic differences between people. However, differences in environmental exposures also are of importance. [Abstract]

Leonardi S, Rotolo N, Vitaliti G, Spicuzza L, La Rosa M
IgE values and T-lymphocyte subsets in children with atopic eczema/dermatitis syndrome.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):529-34.
High levels of IgE and IgE-mediated reactions represent a typical finding in patients with atopic eczema/dermatitis syndrome (AEDS). However, 10-30% of patients usually do not show any increase of total blood IgE levels and any detectable specific IgE sensitization. We performed this study to evaluate the difference of T-lymphocyte subsets in AEDS patients with high or normal IgE values. We enrolled 21 children with AEDS who were at least two years of age (8 boys and 13 girls, aged 2-13 years) and 20 children as control cases with the same age and sex. These patients were classified as IgE-associated AEDS or not IgE-associated AEDS syndrome according to their IgE levels. We used monoclonal antibodies against CD3 (T cells), CD4 (T-helper cells), CD8 (T-cytotoxic cells), CD 19 (B cells), CD56 and CD16 (natural killer cells), CD3/HLA-DR (activated T cells), CD45Ra in CD4 (naive lymphocytes), CD25 (interleukin-2 receptor), CD57 in CD3 (suppressor/cytotoxic), and CD5 in CD20 (Becton Dickinson, Mountain View, CA). The severity of atopic dermatitis (AD) was determined according to the Scoring Atopic Dermatitis (SCORAD) index. Moreover, we checked the levels of peripheral blood eosinophils and of total and specific IgE for a panel of inhalant and food allergens. We found that the CD8+ level was significantly lower and the CD4/CD8 ratio was significantly higher than in healthy cases. Moreover, patients with not IgE associated AEDS (aAD) showed CD4+ levels significantly higher than IgE aAD patients and healthy controls. We found no difference of the SCORAD index in the two groups but there was an inverse relationship between this index and CD4/CD8 ratio. We did not find any correlation between IgE levels and the SCORAD index between eosinophils and SCORAD index or between age and IgE values. A decrease of CD8+ circulating T cells and an increase of the CD4/CD8 ratio are peculiar findings in AEDS patients with either high or normal IgE values. [Abstract]

Caproni M, Antiga E, Torchia D, Volpi W, Barletta E, Gitti G, De Campora E, Fabbri P
FoxP3-expressing T regulatory cells in atopic dermatitis lesions.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):525-8.
Recently, studies were conducted to evaluate the impact of T regulatory (T regs) cells in the pathophysiology of atopic dermatitis (AD). The aim of this study was to investigate whether natural T regs are present in AD skin lesions. We performed skin biopsies in 12 adult patients affected by moderate-to-severe AD and 4 healthy volunteers. The specimens were stained immunohistochemically with anti-human CD25 and forkhead/winged helix transcription factor (FoxP3). Double immunostaining for CD25 and FoxP3 was performed also. CD25+ cells strongly infiltrated the perivascular and papillar dermis of all lesional specimens, and FoxP3+ cells were distributed in the perivascular and interstitial AD dermis, and some cells also infiltrated the dermoepidermal junction and the basal and suprabasal epidermal layers. All healthy skin specimens showed weak CD25 and FoxP3 stainings. Double immunostaining showed that CD25+ FoxP3+ cells were distributed in the perivascular, interstitial, and periadnexal dermis, and healthy skin specimens featured few CD25+ FoxP3+ cells scattered throughout the dermis. The past and present data show that an impaired function of natural T regs may not play a primary role in the pathophysiology of AD lesions. [Abstract]

Bahna SL, Khalili B
New concepts in the management of adverse drug reactions.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):517-24.
Our understanding of drug reactions and their management has changed markedly in recent years with the development of several new concepts. Epidermal cell death seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may result from Fas-Fas ligand-mediated apoptosis. Intravenous immunoglobulin (IVIG) contains anti-Fas antibodies that can abrogate apoptosis. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to healing. Furthermore, several studies have dispelled the myth of sulfonamide cross-reactivity. Immune-mediated reactions against antibacterial sulfonamides are directed against two unique side chains that non-antibacterial sulfonamides do not contain. Certain patients seem to have a genetic predisposition for "multiple drug sensitivities." Hence, they may react to several drugs that are not necessarily cross-reacting. Also, multiple studies have shown that IgE-mediated nonsteroidal anti-inflammatory drugs (NSAIDs) cross-reactivity is uncommon. Rather, it is cyclooxygenase (COX) 1 inhibition that results in pseudoallergic reactions to multiple NSAIDs. Several studies have indicated that selective COX-2 inhibitors can be safely administered in patients with aspirin-exacerbated respiratory disease and NSAID-induced cutaneous reactions, although their use has been curtailed by their cardiovascular side effects. Biological agents, such as infliximab, are being increasingly used for a variety of diseases and have caused adverse reactions in some patients. Studies differ as to whether concomitant immunosuppressive use with infliximab affects the development of drug-specific antibodies and infusion reactions. Successful desensitization protocols have been developed for reactions to some of these agents. [Abstract]

Kaiser HB
Compliance and noncompliance in asthma.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):514-6.
Compliance and noncompliance are big issues in asthma management. It has been well established that compliant patients experience less exacerbations than less compliant patients and that compliance rates often are <50%. The reasons for noncompliance are multiple and complex and not always clearly understood. Methods proposed to improve compliance include patient education, more partnership care, less frequent dosing, simple schedules, diaries, etc. Less dosing and simple schedules are most effective. It is difficult to improve compliance overall and despite extensive research and efforts, rates of compliance remain low. Noncompliance in asthma management is a fact of life and no single compliance-improving strategy probably will be as effective as a good physician-patient relationship. [Abstract]

Lieberman P
Objective measures of asthma control: sputum eosinophils, nitric oxide, and other inflammatory mediators.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):510-3.
This discussion concerns the tools we can use to measure the status of inflammation in asthma and therefore help us diagnose and manage this condition. Although measurement of pulmonary function is of course a necessity, it does not necessarily tell us the status of activity of the disease. For example, in a patient with fixed lung obstruction that can occur in asthma, the forced expiratory volume in 1 second (FEV(1)) may be markedly low in the absence of disease activity. In addition, the disease may be highly active in a patient with normal lung functions by virtue of the fact that they are receiving therapy with inhaled corticosteroids and bronchodilators. Finally, measurement of disease activity is useful in establishing a diagnosis of asthma in a patient who is asymptomatic with normal lung functions at the time of presentation. Therefore, tools to measure the status of inflammation would be extremely helpful. In this article two such tools are discussed: the measurement of eosinophilia and the assessment of exhaled nitric oxide. [Abstract]

Bellanti JA, Settipane RA
Atopic Dermatitis, Genetics, Immunology, and T regulatory cells.
Allergy Asthma Proc. 2007 Sep-Oct;28(5):507-9. [Abstract]


Minutes of the RSLAAIS.
Allergy Asthma Proc. 2007 Jul;28(4):505. [Abstract]

Rumbyrt J, Carlson B, Nathan R
How to get NPI right: one practice's NPI implementation plan.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):503-4. [Abstract]

Nguyen KD, Frieri M
Persistent dyspnea and leg edema.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):497-502.
This case illustrates a complexity of confounding and overlapping symptoms that can masquerade as another diagnosis. A 56-year-old African American man with persistent dyspnea and leg edema was hospitalized three times in a period of 6 months. The patient was treated for asthma, chronic obstructive pulmonary disease, and congestive heart failure. Hypertension and peptic ulcer disease were treated also. Complete clinical improvement was not observed. A careful review of his last admission and current admission clinical presentation and laboratory evaluation revealed a systemic manifestation and laboratory findings consistent with atypical systemic lupus erythematosus. [Abstract]

Greenberger PA, Yucha CB, Janson S, Huss K
Using rare diseases as models for biobehavioral research: allergic bronchopulmonary aspergillosis.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):489-96.
Biobehavioral science explores links between biological, psychosocial, and behavioral factors and health. Maintaining positive health outcomes over time and across a variety of populations and settings requires understanding interactions among biological, behavioral, and social risk factors as well as other variables that influence behavior. Some barriers to biobehavioral research are related to performing biobehavioral research along the natural history of an illness, limitations in existing methodologies to assess the biological impact of behavior, the unknowns relating to impact of behavior on biology, and lack of valid and reliable biobehavioral methods to assess outcomes. A rare disease, such as allergic bronchopulmonary aspergillosis (ABPA) can be used as a model of biobehavioral research. ABPA complicates asthma and cystic fibrosis. It is a hypersensitivity reaction to Aspergillus fumigatus in most cases. ABPA can be classified into five stages: acute, remission, exacerbation, steroid-dependent asthma, and fibrotic or end stage. Because of its rarity, there can be delays in diagnosis. Treatment has used oral corticosteroids and antifungal agents in addition to management of asthma or cystic fibrosis. The National Institute of Nursing Research held an invitational 2-day working group meeting on July 15-16, 2004 with biobehavioral, biological, and immunologic science experts to examine current knowledge of biobehavioral research and to provide recommendations for additional research. The focus was on biobehavioral methods of measurement and analysis with interdisciplinary/biobehavioral approaches. This article is an outcome of this meeting. [Abstract]

Forester JP, Johnson TL, Arora R, Quinn JM
Systemic reaction rates to field stings among imported fire ant-sensitive patients receiving >3 years of immunotherapy versus <3 years of immunotherapy.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):485-8.
As imported fire ants (IFAs) expand their range, hypersensitivity reactions to their stings are becoming a significant cause of morbidity and mortality in the United States. Currently, IFAs whole body extract (WBE) immunotherapy is the mainstay of treatment for IFA hypersensitivity but the optimal duration of treatment is unknown. A questionnaire was administered to patients diagnosed with IFA venom hypersensitivity based on history and the presence of IFA venom-specific IgE who had been offered immunotherapy. The patients were grouped into those who received > or =3 years of immunotherapy and those who received <3 years of immunotherapy. Forty of the 272 patients initially identified were successfully contacted (14%) with 6 patients being excluded. Of these patients, 19 reported having received <3 years of IFA immunotherapy (reduced course) and 15 stated they had been given >3 years of immunotherapy (complete course). Subsequent field stings were reported by 18 (95%) of the reduced course groups and 14 (93%) of the complete course group with 1 person from each group (6 and 7%, respectively) experiencing a systemic reaction. There were no significant differences between the two groups in the number of patients with subsequent field stings or systemic reactions after subsequent IFA stings. Less than 3 years of IFA immunotherapy may offer long-term protection against IFA hypersensitivity reactions although additional studies with more subjects and controls are necessary before definitive conclusions may be made. [Abstract]

Volkman KK, Inda MJ, Reichl PG, Zacharisen MC
Adverse reactions to orthodontic appliances in nickel-allergic patients.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):480-4.
Nickel allergy (NA) is common and causes more cases of allergic contact dermatitis (ACD) than all other metals combined. Many orthodontic appliances (ODAs) contain nickel but their clinical relevance in nickel-allergic patients is unclear. We aimed to characterize the relationship between NA and ODAs because the medical literature investigating this is controversial. A survey concerning adverse reactions to ODAs in patients with NA was distributed to members of the Wisconsin Society of Orthodontics. Forty-three surveys were analyzed. The surveyed group was experienced, representing a mean of 21.2 years in practice and averaging 242 appliances placed per year per orthodontist. Most new patients with orthodontia were 10-18 years old. Most wires used were nickel-titanium alloy. Although 76% of orthodontists inquired about NA at initial evaluation, 37% still placed nickel-containing ODAs in known nickel-allergic patients. Fifty percent placed a single intraoral appliance, observing for reactions. Three orthodontists applied ODAs to the skin similar to patch testing. Only 8 patients with reactions to ODAs were described in detail, 6 were female patients and 6 were aged 13-14 years. Intraoral and extraoral reactions were mild; diffuse urticaria was reported in one patient. Treatment included removing the appliances or changing to nonnickel alternatives with favorable outcomes. These cases, which included >33,000 patients, suggest a prevalence of 0.03%. Adverse reactions to ODAs in patients with NA have been observed but are uncommon. Using suitable alternatives, patients usually can be accommodated. [Abstract]

Melamed J, Beaucher WN
Delayed-type hypersensitivity (type IV) reactions in dental anesthesia.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):477-9.
The recommended methodology of evaluating patients who have presented with reactions to local anesthetics consists of epicutaneous skin testing and serial subcutaneous challenge. However, the role of type IV reactions in this group has been poorly documented. Epicutaneous routine testing and subcutaneous challenge to local anesthetic was performed, as well as patch testing and subcutaneous rechallenge of both at 24 and 48 hours with evaluation up to 72 hours was performed. Three patients presented with a history of localized edema after dental anesthesia. All had negative lidocaine and mepivacaine testing as well as negative lidocaine challenge on evaluation at 1 hour. The first patient, who had previously reacted to EMLA, reacted to both lidocaine and mepivacaine patch testing and challenge, with delayed swelling at 24 and 48 hours after challenge. This patient subsequently tolerated the ester anesthetic chloroprocaine. Two other patients had strong histories of contact dermatitis. Patch testing and challenge with lidocaine was negative, but strong reactions were found to benzocaine on patch testing. Patients undergoing local anesthetic testing should be screened historically for features and risk factors associated with type IV reactions. This should be considered in patients who react to multiple amide anesthetics, who have delayed swelling, or who have a history of severe contact dermatitis. We confirm previous data showing that patients reacting to benzocaine can tolerate lidocaine and that lidocaine-allergic individuals can tolerate ester anesthetics. [Abstract]

Kalogeromitros DC, Makris MP, Rouvas A, Theodossiadis PG, Spanoudaki N, Papaioannou D
Skin testing and adverse reactions in fluorescein: a prospective study.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):472-6.
Sodium fluorescein (SF) is widely used to assess chorioretinal disorders. Adverse reactions are well documented but the underlying mechanism is still uncertain. The aim of this study was the evaluation of skin testing to predict SF reaction, the identification of possible predisposing factors, and the objective record of the reported reactions. All patients with adequate indication for SF angiography (SFA) during an 18-month period were evaluated as follows: (a) detailed personal history of atopy, diabetes, previous SFA, and/or diagnostic procedures with radiocontrast media (RCM) and possible side effect; (b) skin testing with SF 10% diluted preparations; (c) SFA with 5 mL of SF, objective record of any reaction. Two hundred twenty-four patients (108 men and 116 women) with a mean age of 65.2 years (SD, 12.86; range, 16-92 years) underwent SFA. The overall rate of adverse reactions was 3.6% (8/224), which consists of 5 (2.2%) individuals with transient mild nausea; 2 (0.9%) subjects with face and upper trunk flushing that appeared in one case after 60 minutes and in the other case 24 hours later and both resolved without treatment, and I subject with transient bilateral frontal headache and dizziness. None of the 224 patients had positive skin or intradermal testings. One hundred thirty-six of 224 (60.7%) patients stated no previous SFA and 74.1% had not performed RCM injection. None of the recorded variables correlated with increased risk of reaction. SFA is a safe procedure with minor adverse effects. Although in vivo testing can not identify reactors it may help to exclude an underlying IgE-mediated mechanism in susceptible individuals. [Abstract]

Garcia-Rubio I, Martinez-Cocera C, Zayas L
Eosinophil cationic protein in feces: reference values in healthy and atopic individuals and patients with digestive diseases.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):468-71.
Eosinophil cationic protein (ECP) is a good indicator of eosinophilic activity and turnover, serving as a marker of activity in allergic and gastrointestinal diseases characterized by predominantly eosinophilic tissue infiltration. Our aim was to compare ECP levels infeces from healthy individuals, atopic patients, and patients with digestive diseases and establish reference values for this clinical setting. Thirty-nine healthy adults, 28 atopic patients, and 14 patients with digestive diseases were enrolled. The atopic patients had been diagnosed with allergic rhinoconjunctivitis and/or asthma. ECP concentrations in the supernatants from processed feces adjusted for semidry weight (microg/g feces) were determined by fluorescent enzyme immunoassay. Between-group comparisons were performed of medians and interquartile ranges (IQR) by nonparametric tests. Median (IQR) ECP levels were 8.16 (4.11-17.61), 10.83 (5.18-18.49), and 13.02 (5.17-21.97) microg/g feces in controls, atopic patients, and digestive disease patients, respectively; mean (SD) levels were 14.53 (13.77), 13.93 (11.30), and 16.51 (14.79) microg/g of feces. No significant differences in the medians were observed between the atopic group and controls (p = 0.725), the atopic group and digestive disease patients (p = 0.513), or the controls versus the digestive disease patients (p = 0.694). We provide reference values for ECP levels in feces for normal and atopic adults. There is considerable variability in ECP levels in feces and the median levels are similar in healthy and atopic individuals and patients with digestive diseases. [Abstract]

Snijders D, Cattarozzi A, Panizzolo C, Zanardo V, Guariso G, Calabrese F, Faggian D, Monciotti C, Barbato A
Investigation of children with chronic nonspecific cough: any clinical benefit of bronchoscopy and bronchoalveolar lavage?
Allergy Asthma Proc. 2007 Jul-Aug;28(4):462-7.
Chronic cough can be a complicated and frustrating diagnostic dilemma. The aim of this study was to identify the possible causes of chronic nonspecific cough in seemingly healthy children using fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). Eighteen children responded to criteria of selection for chronic cough. The average age was 5.8 years (range, 1.7-10.7 years) and BAL findings were compared with those of 16 nonatopic controls. Children with chronic cough had an increased percentage of BAL neutrophils in comparison with the control group (p = 0.098). Using a BAL neutrophil percent cutoff of 17%, 6 children had high BAL neutrophils (HBNs; median, 77%; range, 27-96%) and 12 children had normal BAL neutrophils (NBNs; median, 3%; range, 0-13%). In the HBN group, FOB showed endoscopic abnormalities in four patients, BAL culture was positive in three patients, and chest x-ray (CXRs) showed minimal densities in four. The IL-8 levels showed a significant increase with respect to the NBN group (p = 0.005). The combination of endoscopic anomalies, BAL culture, BAL IL-8 levels, and minor CXR changes can support the diagnosis of subclincal infection in seemingly healthy children with chronic nonspecific cough and HBN. [Abstract]

Piippo-Savolainen E, Remes S, Korppi M
Does early exposure or sensitization to inhalant allergens predict asthma in wheezing infants? A 20-year follow-up.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):454-61.
Early sensitization to inhaled allergens predicts later asthma and allergy until school age, but studies on early exposure have given conflicting results. The purpose of this study was to evaluate the association between early wheezing, early exposure, or sensitization to pets and pollens and later asthma or allergy until adulthood. We have prospectively followed-up a cohort of 83 infants hospitalized for bronchiolitis in 1981-1982. Cat and dog ownership (early exposure) and inhalant allergen-specific IgE measurements (early sensitization) were registered at <3 years of age. Later, asthma and allergy were evaluated repeatedly between 3 and 20 years of age. Twenty-eight children were exposed to pets in early life, and 8 children were sensitized to pets and 10 children were sensitized to pollens. Birth season and early exposure or sensitization to pets were not significantly associated with later asthma and allergy. Wheezing was present at 3-6 years of age in 8 of 10 children sensitized to pollens (OR, 5.07; 95% CI, 1.48-17.31 versus nonsensitized), and asthma was present in 4 of 9 children at 8.5-10 years of age (OR, 9.53; 95% CI, 2.01-45.54). In multivariate analyses, early sensitization predicted asthma until 13.5-16 years of age. Seasonal rhinoconjunctivitis was not significantly associated with early exposure or sensitization to pets or pollens. In wheezing infants, early sensitization to seasonal pollens predicts subsequent wheezing and asthma until adolescence. No association was found between early exposure and sensitization to pets and later outcome. [Abstract]

Fasce L, Tosca MA, Baroffio M, Olcese R, Ciprandi G
Atopy in wheezing infants always starts with monosensitization.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):449-53.
Previously, evidence has been provided that sensitization is frequent in asthmatic children and polysensitization represents the natural history of allergy. The aim of this study was to investigate whether polysensitization may occur primarily in infants with wheezing. Thus, 98 infants (<1 year of age) were studied at the onset of wheezing symptoms. All children underwent three visits (each including skin-prick test): at baseline and after 2 and 5 years. At onset of wheezing, approximately 20% of infants were sensitized, whereas at 6 years the percentage was >60%. The most important finding was that there was no polysensitized infant at baseline, whereas most of the sensitized children were polysensitized at 6 years. Moreover, the number of sensitizations increased with age. House-dust mites were the most important cause of allergic symptoms. Wheezing may disappear mainly in nonallergic children. In conclusion, this study provided the first evidence that respiratory allergy always starts with monosensitization and confirms previous studies concerning the natural history of allergy characterized by the progression toward polysensitization. [Abstract]

Calabria CW, Dice JP, Hagan LL
Prevalence of positive skin test responses to 53 allergens in patients with rhinitis symptoms.
Allergy Asthma Proc. 2007 Jul-Aug;28(4):442-8.
Prior studies looking at allergic sensitization have focused on narrow age ranges or small numbers of allergens. This study is the first to examine the prevalence of positive skin test responses in a symptomatic military population with a wide age range of patients and large number of allergens. This study was a retrospective analysis of our skin test database. We included 1137 patients aged 4-79 years old who underwent our standard skin-prick testing panel of 53 aeroallergens and 2 controls using the Quintest device (Hollister-Stier, Spokane, WA). Results indicated that 81.6% of patients had at least one positive skin test. Rates of atopy were similar between male and female patients; 9.2% of patients were monosensitized. The average number of positive skin tests peaked in the 10- to 19-year age group at 13.1 and declined in older age groups. The prevalence of atopy peaked in the 30- to 39-year age group at 85.5% and decreased in older age groups. The most common allergens were grasses, mountain cedar, and dust mites. Sensitization rates for many underreported allergens, including mouse and rat, are presented. This study shows that 81.6% of patients in a symptomatic military population were atopic. These rates are high, even when compared with other allergic populations. Atopy peaked in young adulthood and declined in older age groups. Grasses, mountain cedar, and dust mites were the most common allergens. Although performed in a military population, these results should be applicable to many allergy practices. [Abstract]