[Effects of thymic stromal lymphopoietin (TSLP) genotypes on asthma phenotypes defined by the atopy cluster -influence of smoking habits-].

INTRODUCTION: We have previously reported that a distinct sensitization pattern was associated with thymic stromal lymphopoietin (TSLP) genotype. The aim of this study is to identify the characteristics of asthma phenotypes determined by a cluster analysis of IgE responsiveness and the relationship between these phenotypes and TSLP genotypes. PATIENTS AND METHODS: We studied 297 patients of adult asthma and 1571 non-asthmatic healthy adults from Ibaraki, a prefecture in central Japan and Kamishihoro, a cedar-free, birch-dominant town in northern Japan. Levels of total serum IgE and specific IgE antibodies towards 14 major inhaled allergens were measured. With the use of these measures, cluster analysis was applied to classify the phenotypes of adult asthma. We also examined the genetic effects of 2 TSLP functional single nucleotide polymorphism (SNPs) on the development of each asthma phenotype using multinomial logistic regression analysis. RESULTS: The cluster analysis identified four distinct clinical phenotypes of asthma, including "Dust mite dominant" (A, N=82), "Multiple pollen" (B, N=14), "Cedar dominant" (C, N=44), and "Low reactivity" (D, N=154). Asthma phenotype A consisted of younger patients with elevated IgE levels and decreased pulmonary function. Asthma phenotype B was characterized by sensitization by many pollen allergens. Asthma phenotype C was not formed in Kamishihoro. Asthma phenotype D was a group of older women who are less atopic. In current or past smokers, both TSLP SNPs (rs2289276 and rs3860933) were associated with the asthma phenotype D (odds ratio 2.11 [1.36-3.30] and 2.11 [1.34-3.33], respectively). CONCLUSION: In patients with adult asthma who are less atopic, the genetic polymorphisms of TSLP may have some important roles in the development of the disease in smokers.

Parenting and relationship characteristics in mothers with their children having atopic disease.

This study compared parental cognitions and relationship characteristics of mothers of children with atopic disease with those of mothers of children without atopic disease. These factors include child-rearing attitudes, parental locus of control, parental sense of competence, attachment security, and maternal sensitivity. Preplanned subanalyses were carried out according to specific disease, mothers' perception of disease severity, and presence of concurrent atopic diseases. The descriptive comparative study of 233 Korean mothers included 102 mothers of children aged six years or younger with atopic dermatitis, asthma, and/or allergic rhinitis. Data were collected from 2007 to 2008 from local clinics and day care centers. Parental cognitions and relationship characteristics did not differ significantly between groups of mothers, except that mothers of children with atopic dermatitis showed less affection. However, subanalyses showed that mothers who perceived their child's disease to be severe were less likely to encourage autonomy and had a lower sense of competence, more rejecting attitudes, and an external locus of control. Although we should be cautious in generalizing these results, special care plans are strongly recommended for mothers of children with severe atopic disease to provide support and education, help mothers develop an internal locus of control, and increase parental sense of competence.

Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts.

BACKGROUND: Although atopic sensitization is one of the strongest risk factors for asthma, its relationship with asthma is poorly understood. We hypothesize that 'atopy' encompasses multiple sub-phenotypes that relate to asthma in different ways. METHODS: In two population-based birth cohorts (Manchester and Isle of Wight - IoW), we used a machine learning approach to independently cluster children into different classes of atopic sensitization in an unsupervised manner, based on skin prick and sIgE tests taken throughout childhood and adolescence. We examined the qualitative cluster properties and their relationship to asthma and lung function. RESULTS: A five-class solution best described the data in both cohorts, with striking similarity between the classes across the two populations. Compared with nonsensitized class, children in the class with sensitivity to a wide variety of allergens (~1/3 of children atopic by conventional definition) were much more likely to have asthma (aOR [95% CI0; 20.1 [10.9-40.2] in Manchester and 11.9 [7.3-19.4] in IoW). The relationship between asthma and conventional atopy was much weaker (5.5 [3.4-8.8] in Manchester and 5.8 [4.1-8.3] in IoW). In both cohorts, children in this class had significantly poorer lung function (FEV1 /FVC lower by 4.4% in Manchester and 2.6% in IoW; P < 0.001), most reactive airways, highest eNO and most hospital admissions for asthma (P < 0.001). CONCLUSIONS: By adopting a machine learning approach to longitudinal data on allergic sensitization from two independent unselected birth cohorts, we identified latent classes with strikingly similar patterns of atopic response and association with clinical outcomes, suggesting the existence of multiple atopy phenotypes.

Atopic keratoconjunctivitis.

Atopic keratoconjunctivitis (AKC) is a chronic allergic inflammatory disease that is at the severe end of a spectrum of allergic conjunctival diseases. AKC can involve the cornea and conjunctiva bilaterally, and at times can lead to visual loss from corneal complications. The classification, histology, ocular examination findings and complications of AKC are described herein, as well as the roles and interactions of inflammatory cells involved. Finally, current treatment options for AKC is reviewed and presented as a stepwise, multidisciplinary approach that involves the allergist/immunologist's medical interventions of topical and systemic immunomodulating agents, as well as the surgical skills of the ophthalmologist.

Sensitive skin: an overview.

Sensitive skin is less tolerant to frequent and prolonged use of cosmetics and toiletries. It is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation. With the change in lifestyle and also with increased opportunity to use many new brands of cosmetics and toiletries, there has been an increase in females complaining of unique sensation in their facial skin. Sensitive skin presents as smarting, burning, stinging, itching, and/or tight sensation in their facial skin. The condition is found in more than 50% of women and 40% of men, creating a sizable demand for products designed to minimize skin sensitivity. Good numbers of invasive and non-invasive tests are designed to evaluate and predict the sensitive skin. Management includes guidelines for selecting suitable cosmetics and toiletries in sensitive skin individuals.

Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System.

Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma and venom hypersensitivity and has the potential of producing serious life-threatening anaphylaxis. Adverse reactions are generally classified into 2 categories: local reactions, which can manifest as redness, pruritus, and swelling at the injection site, and systemic reactions (SRs). SRs can range in severity from mild rhinitis to fatal cardiopulmonary arrest. Early administration of epinephrine, which is the treatment of choice to treat anaphylaxis, may prevent the progression of an SR to a more serious life-threatening problem. Although there is little debate about using epinephrine to treat a SCIT SR, there is a lack of consensus about when it should be first used. A uniform classification system for grading SCIT SRs will be helpful in assessing more accurately when epinephrine should be administered. The primary purpose of this article is to discuss the proposed grading system for SCIT SRs.

EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria.

This guideline, together with its sister guideline on the management of urticaria [Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64:1427-1443] is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life-time prevalence for any subtype of urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors, and pathomechanisms. In addition, it outlines evidence-based diagnostic approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

[Immediate allergy to iodinated contrast agents and prevention of reactions]. / Allergie immédiate aux produits de contraste iodés et prévention des réactions.

The incidence and morbimortality of immediate hypersensitivity reactions following iodinated contrast media (ICM) injection remain unknown. The diagnosis of an immediate hypersensitivity reaction relies on a triad associating the precise description of the initial clinical manifestations and their delay of onset, the results of the biological assessment performed after the reaction including histamine and tryptase serum level measurements, and the results of skin testing with the culprit agent. Analysis of these data allows identification of the pathophysiologic mechanism of the reaction and the allergen involved in case of allergic hypersensitivity. Skin tests should be performed according to strict criteria. Cross-reactivity with ICM has to be investigated in order to propose a nonreactive ICM for future procedures. Allergic hypersensitivity to a given ICM imposes its definitive avoidance but not the avoidance of all iodinated drugs. The allergenic sequence has not yet been identified but is not the iodine atom itself. Asthma and treatment with beta-blockers are not risk factors of immediate allergic reactions to ICM per se, but may increase their severity. The various published protocols of premedication do not prevent the occurrence of an allergic/anaphylactic reaction to an ICM. The avoidance of the culprit ICM is the only way to prevent further reactions.

Atopic features of cough variant asthma and classic asthma with wheezing.

BACKGROUND: Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. OBJECTIVE: To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. METHODS: Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. RESULTS: Patients with classic asthma had higher total IgE (P<0.0001), larger numbers of sensitized allergens (P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens (P=0.02) and had higher rates of sensitization to HDM (P=0.01) and dog dander (P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease (n=60) and the subgroup with moderate-to-severe disease (n=55), as reported previously. CONCLUSIONS: Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential.

[Prevalence of atopy and atopic diseases in children living in an orphanage in Lodz area--pilot study]. / Czestosc wystepowania atopii i chorób atopowych u dzieci z lódzkich domów dziecka--badanie pilotazowe.

UNLABELLED: Over the past three decades there has been an increase in the prevelance of allergic diseases, specially among children. THE AIM OF THE STUDY: was to estimate the prevalence of atopy and atopic diseases in children who are living in orphanages in Lodz. MATERIAL AND METHODS: 120 children 5-18 years old living in 2 orphanages were studied. Main outcome measures were history, physical examination, FEV1, skin prick-test results with 18 allergens; peripheral blood eosinophil count, level of total and specific IgE in children with positive skin-test results were secondary and point. RESULTS: Bronchial asthma was diagnosed in 5.83% (6 of 120) patients, seasonal allergic rhinitis was diagnosed in 2.5% (3 of 120) patients and atopic dermatitis was diagnosed in 1.67% (2 of 120) patients. The skin prick-tests were positive in 12.5% children. Mean number of respiratory tracts infection in early childhood was significantly lower in atopic children than in non-atopic children--3.3 +/- 2,3 vs 8.7 +/- 2.5 (p<0.001). Mean total serum IgE concentration value reached upper limit in 26.6% of non-atopic patients and in 32.4% non-atopic children peripheral blood eosinophil count was significantly increased suggesting possible presence of active helminth infection, what might protect against atopy. CONCLUSION: In children living in orphanages we observed the lower prevalence of atopy (12.5%) and atopic diseases than in general population (25.4-40.2%).

EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).

Defining childhood atopic phenotypes to investigate the association of atopic sensitization with allergic disease.

AIMS: Although atopic sensitization is common in childhood, its relationship to clinical allergic disease remains incompletely understood. We therefore sought to explore this relationship by defining sensitization based atopic phenotypes. METHODS: Children were recruited at birth (n = 1456) and reviewed at 1, 2, 4 and 10 years. Skin prick testing (SPT) to common allergens was done at 4 (n = 980) and 10 years (n = 1036) with lung function (n = 981), bronchial challenge (n = 784) and serum IgE (n = 953) testing at 10. Atopic phenotypes were defined, by sensitization pattern, for children with SPT at both 4 and 10 years (n = 823). RESULTS: Of phenotyped children, 68.0% were never atopic, 4.3% early childhood atopic (only atopic at age 4), 16.5% chronic childhood atopics (at 4 and 10 years) and 11.2% delayed childhood atopics (only at 10). Never atopics showed small but identifiable prevalence of allergic diseases such as asthma, eczema and rhinitis. Amongst allergen-sensitized subjects, aeroallergen predominated over food sensitization throughout childhood. Chronic childhood atopics showed highest prevalence of lifetime plus persistent wheeze, eczema and rhinitis, increased prevalence of aeroallergen sensitization, some evidence of persistent food sensitization, significantly greater cord IgE than never atopics (P = 0.006), plus higher total IgE (P < 0.001) and bronchial hyper-responsiveness (P < 0.001) at 10 years than other phenotypes. CONCLUSION: A proportion of childhood eczema, rhinitis and asthma is nonatopic. The commonest childhood pattern of atopy is chronic sensitization, associated with early, persisting and clinically significant allergic disease. The currently accepted childhood 'Allergic March' may oversimplify the natural history of childhood atopy and allergic disease.

Outcomes of allergy to insect stings in children, with and without venom immunotherapy.

BACKGROUND: Children are thought to "outgrow" the allergy to insect stings, but there are no reports documenting the natural history of this reaction. We studied the outcome of allergic reactions to insect stings in childhood 10 to 20 years afterward in patients who had not received venom immunotherapy and in those who had been treated. METHODS: Between 1978 and 1985, we diagnosed allergic reaction to insect stings in 1033 children, of whom 356 received venom immunotherapy. We conducted a survey of these patients by telephone and mail between January 1997 and January 2000, to determine the outcome of stings that occurred in the period from 1987 through 1999. RESULTS: Of the 1033 patients, 512 patients (50 percent) responded, with a mean follow-up period of 18 years, a mean duration of venom immunotherapy of 3.5 years in treated patients, and an incidence of stings of 43 percent. Systemic reactions occurred less frequently in patients who had received venom immunotherapy (2 of 64 patients, or 3 percent) than in untreated patients (19 of 111 patients, or 17 percent; P=0.007). Patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (7 of 22 patients, or 32 percent) than if they had received venom immunotherapy (2 of 43 patients, or 5 percent; P=0.007). In patients who had been treated and who had a history of mild (cutaneous) systemic reaction (i.e., one with only cutaneous manifestations), none of the 21 subjects who received stings had a systemic reaction. CONCLUSIONS: A clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults.

Mechanisms of intrinsic asthma.

PURPOSE OF REVIEW: The phenomenon of intrinsic or nonatopic asthma continues to raise questions about the possible role of IgE-mediated mechanisms in asthma pathogenesis. With the current availability of anti-IgE therapy for asthma, clarification of this issue has never been more timely and relevant. RECENT FINDINGS: This article summarizes recent studies for and against the proposition that IgE-mediated mechanisms play a critical role in asthma pathogenesis. These data comprise epidemiological studies and recent molecular studies, suggesting that IgE synthesis may take place in the bronchial mucosa of patients with nonatopic asthma, despite the fact that allergen-specific IgE is not detectable in the periphery by standard skin prick testing. SUMMARY: At present, available data do not allow a firm conclusion to be made as to whether or not IgE-mediated mechanisms play an obligatory role in asthma pathogenesis. Implications for the future therapy of nonatopic asthma in either case are discussed, as well as some suggestions for further research.

The pattern of sesame sensitivity among infants and children.

Recently, we found sesame to be a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. The purpose of this study was to describe the different patterns of sesame sensitivity. We have identified three subgroups among our patients (n = 32). Group I (n = 23, M/F; 14/9) consisted of cases with IgE-mediated sesame allergy. The mean age of the first allergic reaction was 11.7 months. Although the main clinical manifestation was urticaria/angiedema (n = 14, 60%), anaphylaxis was the presenting symptom in seven (30%) patients; all of them were younger than 1 year. Sixteen (70%) were found to be allergic to other foods, and other atopic diseases were identified in 18 (78%) patients. Three patients 'outgrew' their allergy within 1-2 years. Group II (n = 2) included cases in whom sesame allergy was ruled out based on a negative skin prick test (SPT) together with a negative open oral challenge. Group III (n = 7) consisted of patients that were found to be SPT positive for sesame as part of a screening for other food allergies. Although sesame products have become fashionable in westernized countries, early exposure may cause sesame to share eventually the same 'noteriety and fate' as peanut - a major cause of severe food allergic reactions.