Showing papers in "Allergy in 2010"

Is the prevalence of asthma declining? Systematic review of Epidemiological studies

Abstract: Asthma prevalence has increased very considerably in recent decades such that it is now one of the commonest chronic disorders in the world. Recent evidence from epidemiological studies, however, suggests that the prevalence of asthma may now be declining in many parts of the world, which, if true is important for health service planning and also because this offers the possibility of generating and testing new aetiological hypotheses. Our objective was to determine whether the prevalence of asthma is declining worldwide. We undertook a systematic search of EMBASE, Medline, Web of Science and Google Scholar, for high quality reports of cohort studies, repeat cross-sectional studies and analyses of routine healthcare datasets to examine international trends in asthma prevalence in children and adults for the period 1990-2008. There were 48 full reports of studies that satisfied our inclusion criteria. The large volume of data identified clearly indicate that there are, at present, no overall signs of a declining trend in asthma prevalence; on the contrary, asthma prevalence is in many parts of the world still increasing. The reductions in emergency healthcare utilization being reported in some economically developed countries most probably reflect improvements in quality of care. There remain major gaps in the literature on asthma trends in relation to Africa and parts of Asia. There is no overall global downward trend in the prevalence of asthma. Healthcare planners will for the foreseeable future, therefore, need to continue with high levels of anticipated expenditure in relation to provision of asthma care.

The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review.

Abstract: Food allergy affects 6% of children but there is no cure, and strict avoidance of index allergens along with immediate access to rescue medication is the current best management. With specialist care, morbidity from food allergy in children is generally low, and mortality is very rare. However, there is strong evidence that food allergy and food hypersensitivity has an impact on psychological distress and on the quality of life (QoL) of children and adolescents, as well as their families. Until recently, the measurement of QoL in allergic children has proved difficult because of the lack of investigative tools available. New instruments for assessing QoL in food allergic children have recently been developed and validated, which should provide further insights into the problems these children encounter and will enable us to measure the effects of interventions in patients. This review examines the published impact of food allergy on affected children, adolescents and their families. It considers influences such as gender, age, disease severity, co-existing allergies and external influences, and examines how these may impact on allergy-related QoL and psychological distress including anxiety and depression. Implications of the impact are considered alongside avenues for future research.

Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper

Abstract: BACKGROUND: First-generation H(1)-antihistamines obtained without prescription are the most frequent form of self-medication for allergic diseases, coughs and colds and insomnia even though they have potentially dangerous unwanted effects which are not recognized by the general public. AIMS: To increase consumer protection by bringing to the attention of regulatory authorities, physicians and the general public the potential dangers of the indiscriminate use first-generation H(1)-antihistamines purchased over-the counter in the absence of appropriate medical supervision. METHODS: A GA(2)LEN (Global Allergy and Asthma European Network) task force assessed the unwanted side-effects and potential dangers of first-generation H1-antihistamines by reviewing the literature (Medline and Embase) and performing a media audit of US coverage from 1996 to 2008 of accidents and fatal adverse events in which these drugs were implicated. RESULTS: First-generation H(1)-antihistamines, all of which are sedating, are generally regarded as safe by laypersons and healthcare professionals because of their long-standing use. However, they reduce rapid eye movement (REM)-sleep, impair learning and reduce work efficiency. They are implicated in civil aviation, motor vehicle and boating accidents, deaths as a result of accidental or intentional overdosing in infants and young children and suicide in teenagers and adults. Some exhibit cardiotoxicity in overdose. CONCLUSIONS: This review raises the issue of better consumer protection by recommending that older first-generation H(1)-antihistamines should no longer be available over-the-counter as prescription- free drugs for self-medication of allergic and other diseases now that newer second- generation nonsedating H(1)-antihistamines with superior risk/benefit ratios are widely available at competitive prices. Language: en

Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema

Abstract: Background Prior to the discovery of filaggrin (FLG) mutations, evidence for an impaired skin barrier in atopic dermatitis (AD) has been documented, and changes in ceramide profile, altered skin pH and increased trans-epidermal water loss (TEWL) in patients with AD have been reported. Until now, no studies have analysed stratum corneum (SC) lipids combined with skin barrier parameters in subjects of known FLG genotype. Methods A cohort of 49 German individuals genotyped for the most common FLG mutations (R501X, 2282del4) had SC samples taken for lipid analysis by high-performance thin layer chromatography. In addition, TEWL, erythema, skin hydration and pH were measured. In 27 of the 49 individuals, a 24-h irritation patch test with sodium lauryl sulphate was performed. For the analysis, both the AD group and the control group were stratified by FLG mutation status (FLGmut/FLGwt). Results In the FLGmut AD group, significantly lower levels of ceramide 4 and significantly higher levels of ceramide 7 were observed when compared to both healthy control groups. However, ceramide 7 levels also significantly differed between FLGwt AD and FLGwt controls, as did ceramide 1 levels. No significant differences were observed for ceramide 2, 3, 5 and 6. FLGmut individuals had significantly higher skin pH values than individuals not carrying FLG mutations. Patients with AD with FLG mutations had significantly higher erythema compared to patients with AD without FLG mutations. Conclusion Our results confirm previous observations of altered ceramide levels in AD, which however appear to show no clear relationship with FLG mutations.

General considerations on rapid desensitization for drug hypersensitivity: a consensus statement

Abstract: Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs.

Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids.

Abstract: Eosinophilic esophagitis (EE) is a disease of increasing prevalence and is diagnosed if esophageal histology demonstrates >15 epithelial eosinophils per high power field (hpf), especially in the context of acid blockade to exclude gastroesophageal reflux (GERD) (1–3). Patients may present with dysphagia, vomiting, abdominal pain, or poor growth and the most significant complication is esophageal stricture formation requiring repeated dilation (1, 4, 7). Subepithelial fibrosis has been described in adult and pediatric EE patients, especially those who complain of dysphagia (5–8). Our previous studies demonstrated that significant esophageal remodeling occurs in the lamina propria (LP) of the esophagus of pediatric EE patients with concurrent strictures as compared with normal controls or children with GERD (5). Subepithelial fibrosis is accompanied by increased numbers of TGFβ-positive eosinophils and increased expression of the TGFβ signaling transcription factor, phosphorylated Smad2/3 (pSmad2/3) (5, 6). In addition, EE is associated with an increased number of activated blood vessels expressing VCAM-1 in the subepithelial space (5). Whether LP remodeling changes are influenced by therapies such as topical esophageal corticosteroids has not been systematically assessed in EE patients. Currently, EE studies utilize epithelial eosinophil resolution as the major diagnostic criterion for therapeutic response. The previous studies of topical corticosteroids such as fluticasone and budesonide in pediatric EE have demonstrated a 50–80% overall resolution of epithelial inflammation and clinical symptoms (1, 9–11). However, a difference in the resolution of esophageal remodeling among patients who do and do not respond to corticosteroid therapy has not been reported. We therefore hypothesized that EE subjects who demonstrated resolution of epithelial eosinophilia following topical corticosteroid therapy would be more likely to have resolution of LP remodeling than those who did not demonstrate resolution of epithelial eosinophilic inflammation. In addition, as LP is not obtained in all esophageal biopsy samples, it is important to determine whether changes in the epithelium (obtained in all esophageal biopsies) correlates with changes in LP fibrosis and inflammation. As current EE therapy involves repeated esophagogastroduodenescopy (EGD) with biopsy, the relationship between esophageal remodeling and clinical features and disease course, even in young children, can be determined. In this study, we demonstrate that treatment with swallowed topical budesonide decreases the severity of esophageal remodeling (LP fibrosis and vascular activation) and mediators (TGFβ1 and pSmad2/3) in EE patients who demonstrate resolution of epithelial eosinophilia but not in those who do not have an epithelial response to corticosteroid therapy. In a pilot study, we demonstrate that a SNP in the TGFβ promoter may correlate with patients who respond to therapy.

Time trends in the prevalence of peanut allergy: three cohorts of children from the same geographical location in the UK.

Abstract: Background: This article investigated the prevalence of peanut allergy in three cohorts of children born in the same geographical location, Isle of Wight, UK and seeks to determine whether the prevalence of peanut allergy has changed between 1994 and 2004. Methods: Three cohorts of children (age 3-4 years) born on the Isle of Wight, were assessed for peanut allergy and the outcomes compared: Cohort A: Born in 1989; reviewed at 4 years of age (n = 2181). Cohort B: Born between 1994 and 1996; reviewed between 3 and 4 years of age (n = 1273). Cohort C: Born between 2001 and 2002; reviewed at 3 years of age (n = 891). Results: Peanut sensitization increased significantly from 1.3% in Cohort A to 3.3% (P = 0.003) in Cohort B before falling back to 2.0% in Cohort C (P = 0.145). Similarly, clinical peanut allergy increased significantly from 0.5% in Cohort A to 1.4% (P = 0.023) in Cohort B, with a subsequent fall to 1.2% in Cohort C (P = 0.850). Conclusions: Our data from three cohorts of 3- to 4-year-old children born in the same geographical area shows that peanut allergy prevalence has changed over time. Peanut sensitization and reported allergy in children born in 1994-1996 increased from 1989 but seems to have stabilized or slightly decreased since the late 1990s, although not significant.

Anti‐infliximab IgE and non‐IgE antibodies and induction of infusion‐related severe anaphylactic reactions

Abstract: Background: Infliximab is a chimeric monoclonal antibody against TNF-a useful in the treatment of many chronic inflammatory diseases. Severe anaphylaxis has been reported during therapy, although the exact mechanism has not been fully defined. The reactions have been related to the infliximab immunogenicity and development of specific antibodies. Aims of the study: Evaluation of the development of IgE and non-IgE antibodies to infliximab and their relationship with infusion reaction. Methods: Seventy-one patients (11 reactives, 11 therapeutically nonresponders, and 49 unreactive therapeutically responders) and 20 non–infliximab-exposed control subjects (ten rheumatoid arthritis, five spondyloarthropathies, five vasculitis) were evaluated for the presence of IgE (ImmunoCAP assay), IgM, and non– isotype-specific (ELISA assays) anti-infliximab antibodies. Sera were obtained at baseline and during the course of treatment, before each infliximab infusion. Results: Eleven out of 71 patients had a hypersensitivity reaction to infliximab. Non–isotype-specific anti-infliximab antibodies were detected in eight reactive and two nonresponder patients. Three patients with severe reactions displayed anti-infliximab IgE antibodies and positive skin testing. Detectable levels of antiinfliximab IgM antibodies were shown in three additional IgE- and skin testingnegative patients. IgE and IgM antibodies to infliximab were not detectable in the two nonresponder patients. Antibodies developed before the 2nd and the 3rd infusion, and their appearance was strictly related to the timing of the reaction. Conclusions: This report indicates that in some patients with infliximab-related severe reactions, IgE or IgM antibodies against infliximab were detectable. The majority of reactions could be predicted by the appearance of anti-infliximab antibodies.

GA2LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma

Abstract: This pocket guide is the result of a consensus reached during several GA(2) LEN and EAACI meetings. The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of immunotherapy in allergic rhinoconjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions of practitioners in Europe, including 'practising allergists', general practitioners and any other physicians with special interest in allergen-specific immunotherapy (SIT). It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1998 EAACI position paper, the 1998 WHO Position Paper on SIT and the 2001 Allergic Rhinitis and its Impact on Asthma (ARIA). It is also based on the ARIA update 2008 (prepared in collaboration with GA(2) LEN), the 'Sub-lingual Immunotherapy: WAO Position Paper 2009' (from the World Allergy Organisation) and the Methodology paper of ARIA. The recommendations cover patient selection, allergen extract to be used, route of administration of SIT (in particular, sublingual and subcutaneous immunotherapy), and necessary precautions to be followed in using SIT.

Projections of the effects of climate change on allergic asthma: the contribution of aerobiology

Abstract: Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.

Health-related quality of life of food allergic patients: Comparison with the general population and other diseases

Abstract: Background: To date no studies have compared generic health-related quality of life (HRQL) of food allergic patients from childhood to adulthood with that of the general population or patients with other chronic diseases. The aim of this study was to compare generic HRQL of food allergic patients with the general population and other diseases. Methods: Generic HRQL questionnaires (CHQ-CF87 and RAND-36) were completed by 79 children, 74 adolescents and 72 adults with food allergy. The generic HRQL scores were compared with scores from published studies on the general population and patients with asthma, irritable bowel syndrome (IBS), diabetes mellitus (DM) and rheumatoid arthritis (RA). Results: Food allergic children and adolescents reported fewer limitations in school work due to behavioural problems (P ≤ 0.013), but food allergic adolescents and adults reported more pain (P = 0.020), poorer overall health (P < 0.001), more limitations in social activities (P < 0.001) and less vitality (P = 0.002) than individuals from the general population. Food allergic patients reported poorer generic HRQL than patients with DM, but better generic HRQL than patients with RA, asthma and IBS. Conclusion: HRQL is impaired in food allergic adolescents and adults, compared to the general population, and it is intermediate in magnitude between DM and RA, asthma and IBS. Children show the least impact on generic HRQL from food allergy.

Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review

Abstract: The increase in prevalence and burden of atopic diseases, i.e. eczema, rhinitis, and asthma over the past decades was paralleled by a worldwide increase in attentiondeficit/hyperactivity disorder (ADHD) diagnoses. We systematically reviewed epidemiologic studies investigating the relationship between atopic diseases and ADHD. Electronic literature search in PubMed and PsycINFO (until 02/2010) supplemented by handsearch yielded 20 relevant studies totaling 170 175 individuals. Relevant data were abstracted independently by two reviewers. Six studies consistently reported a positive association between eczema and ADHD with one study suggesting effect modification by sleeping problems. Twelve studies consistently found a positive association between asthma and ADHD, which, however, appeared to be at least partly explained (confounded) by concurrent or previous eczema. Rhinitis and serum-IgE level were not related to ADHD symptomatology. We conclude that not atopic disease in general, but rather that eczema appears to be independently related to ADHD. Conclusions about temporality and whether the observed association constitutes a causal relationship are impossible, as most studies were cross-sectional (n = 14; 70%) or case–control studies without incident exposure measurement (n = 5; 25%). Another methodological concern is that the criteria to define atopic disease and ADHD were inadequate in most studies. A failure to adjust for confounders in the majority of studies was an additional limitation so that meta-analysis was not indicated. Future interdisciplinary high-quality prospective research is needed to better understand the mechanisms underlying the relationship between eczema and ADHD and to eventually establish targeted preventive and treatment strategies.

Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis.

Abstract: To cite this article: Burney P, Summers C, Chinn S, Hooper R, van Ree R, Lidholm J. Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy 2010; 65: 1182–1188. Abstract Background: Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of sensitization to food allergens using standardized methods. Methods: Sera from the ‘random sample’ of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix. Results: Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common sensitizations are not represented in current commercial mixes. The prevalence of sensitization to foods was not related to that of sensitization to aeroallergens but was related to the geometric mean total IgE for the country. Conclusions: Sensitization to foods is common but highly variable. The relative prevalence of sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food sensitization.

Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease

Abstract: Epigenetic mechanisms provide new insights into how environmental changes may mediate the increasing propensity for complex immune diseases such as allergic disease. There is now strong evidence that early environmental exposures play a key role in activating or silencing genes by altering DNA and histone methylation, histone acetylation and chromatin structure. These modifications determine the degree of DNA compaction and accessibility for gene transcription, altering gene expression, phenotype and disease susceptibility. While there is already evidence that a number of early environmental exposures are associated with an increased risk of allergic disease, several new studies indicate in utero microbial and dietary exposures can modify gene expression and allergic disease propensity through epigenetic modification. This review explores the evidence that immune development is under clear epigenetic regulation, including the pattern of T helper (Th)1 and Th2 cell differentiation, regulatory T cell differentiation, and more recently, Th17 development. It also considers the mechanisms of epigenetic regulation and early immune defects in allergy prone neonates. The inherent plasticity conferred by epigenetic mechanisms clearly also provides opportunities for environmental strategies that can re-programme gene expression for disease prevention. Identifying genes that are differentially silenced or activated in relation to subsequent disease will not only assist in identifying causal pathways, but may also help identify the contributing environmental factors.

The small airways and distal lung compartment in asthma and COPD: a time for reappraisal.

Abstract: The involvement of small airways in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been debated for a long time. However, a proper definition of small airway disease is still lacking, and neither a widely accepted biomarker nor a functional parameter to assess small airway abnormalities and to explore the effect of tested compounds on small airways is available. Aiming towards increased knowledge and consensus on this topic, this perspective paper intends to (i) strengthen awareness among the scientific community on the role of small airways in asthma and COPD; (ii) examine the pros and cons of some biological, functional and imaging parameters in the assessment of small airway abnormalities; and (iii) discuss the evidence for distal airway pharmacological targeting in asthma and COPD.

The purinergic receptor P2Y2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation

Abstract: To cite this article: Muller T, Robaye B, Vieira RP, Ferrari D, Grimm M, Jakob T, Martin SF, Di Virgilio F, Boeynaems J-M, Virchow JC, Idzko M. The purinergic receptor P2Y2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. Allergy 2010; 65: 1545–1553. Abstract Background: Extracellular ATP contributes to the pathogenesis of asthma via signalling at purinergic receptors. However, the precise purinergic receptors subtypes mediating the pro-asthmatic effects of ATP have not been identified, yet. Methods: In vivo studies were performed using the OVA-alum model. Functional expression of the P2Y2 purinergic receptor subtype on human monocyte-derived dendritic cells and eosinophils was investigated using real-time PCR, migration assays, and production of reactive oxygen species. Results: Compared to wild-type animals P2Y2−/− mice showed reduced allergic airway inflammation which can be explained by defective migration of blood myeloid DCs towards ATP in vitro and in vivo, whereas the influence of ATP on maturation and cytokine production was not changed. Additionally, ATP failed to induce migration of bone marrow–derived eosinophils from P2Y2R-deficient animals. The relevance of our findings for humans was confirmed in functional studies with human monocyte-derived DCs and eosinophils. Interestingly, stimulation of human DCs derived from allergic individuals with house dust mite allergen induced functional up-regulation of the P2Y2R subtype. Furthermore, eosinophils isolated from asthmatic individuals expressed higher levels of P2Y2R compared to healthy controls. This was of functional relevance as these eosinophils were more sensitive to ATP-induced migration and production of reactive oxygen metabolites. Conclusions: In summary, P2Y2R appears to be involved in asthmatic airway inflammation by mediating ATP-triggered migration of mDCs and eosinophils, as well as reactive oxygen species production. Together our data suggest that targeting P2Y2R might be a therapeutic option for the treatment of asthma.

After 6 years with Xolair; a 3‐year withdrawal follow‐up

Abstract: P>Background: This study reports the clinical and immunological state of patients 3 years after a 6-year period of Xolair treatment for severe allergic asthma. Methods: The patient's cat allergen sensitivity, measured as CD-sens, IgE and IgE- and IgG4 antibodies, was analysed and compared with asthma severity evaluated from FEV1 and a questionnaire. Results: Three years after treatment with Xolair was stopped, 12/18 patients reported improved or unchanged asthma compared with ongoing Xolair treatment. Most of the patients were in a stable clinical condition, 16/18 had not increased nightly asthma attacks and 14/18 little or no increase in medication. The CD-sens to cat was still significantly lower (P < 0.02) than untreated patients with allergic asthma and lower than expected from their serum IgE antibody levels. Conclusion: Most of the patients in this study had, still 3 years after closing of 6 years Xolair treatment, a surprisingly mild and stable asthma. Interestingly, the observed, considerable, downregulation of basophil allergen sensitivity, CD-sens, most likely representing mast cell allergen sensitivity, contributed to the clinical results. (Less)

Validation of a questionnaire (CARAT10) to assess rhinitis and asthma in patients with asthma

Abstract: To cite this article: Fonseca JA, Nogueira-Silva L, Morais-Almeida M, Azevedo L, Sa-Sousa A, Branco-Ferreira M, Fernandes L, Bousquet J. Validation of a questionnaire (CARAT10) to assess rhinitis and asthma in patients with asthma. Allergy 2010; 65: 1042–1048. Abstract Background and aim: The Control of Allergic Rhinitis and Asthma Test (CARAT) was developed to be used in the concurrent management of these diseases, as recommended by the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. However, it was necessary to statistically identify and remove redundant questions and to evaluate the new version’s factor structure, internal consistency and concurrent validity. Methods: In this cross-sectional study 193 adults with allergic rhinitis and asthma from 15 outpatient clinics in Portugal were included. The CARAT questionnaire was reduced using descriptive analysis, exploratory factor analysis and internal consistency. Spearman’s correlations were used to compare the CARAT scores with a medical evaluation and other measures of control, including the Asthma Control Questionnaire and symptoms’ visual analogue scales. The performance against physician rating of control was summarized using the area under the curve (AUC) from receiver operating characteristic analysis. In addition, CARAT was compared with the physician’s decision to reduce, maintain or increase treatment. Results: The reduced version has 10 questions and 2 factors (CARAT10). The Cronbach’s alpha was 0.85. All correlation coefficients of CARAT10 and factors with the different measures of control met the a priori predictions, ranging from 0.58 to 0.79. The AUC was 0.82. For the physician’s decision groups of reduce, maintain or increase treatment, the mean (IC95%) scores of CARAT10 were 24 (21.4;26.6), 21 (19.4;21.9) and 15 (13.6;16.5), respectively. Conclusion: CARAT10 has high internal consistency and good concurrent validity, making it useful to compare groups in clinical studies.

Consumption of vegetables, fruit, and antioxidants during pregnancy and wheeze and eczema in infants

Abstract: To cite this article: Miyake Y, Sasaki S, Tanaka K, Hirota Y. Consumption of vegetables, fruit, and antioxidants during pregnancy and wheeze and eczema in infants. Allergy 2010; 65: 758–765. Abstract Background: Two previous cohort studies showed inverse relationships between maternal vitamin E and zinc intake during pregnancy and the risk of wheeze and/or asthma in the offspring. We investigated the association between maternal intake of vegetables, fruit, and selected antioxidants during pregnancy and the risk of wheeze and eczema in the offspring aged 16–24 months. Methods: Subjects were 763 Japanese mother–child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Data on symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood. Results: Higher maternal intake of green and yellow vegetables, citrus fruit, and β-carotene during pregnancy was significantly associated with a reduced risk of eczema, but not wheeze, in the offspring {adjusted odds ratios (ORs) between extreme quartiles [95% confidence intervals (CIs)] = 0.41 (0.24–0.71), 0.53 (0.30–0.93), and 0.52 (0.30–0.89), respectively}. Maternal vitamin E consumption during pregnancy was significantly inversely related to the risk of infantile wheeze, but not eczema [adjusted OR (95% CI) = 0.54 (0.32–0.90)]. No statistically significant exposure–response associations were observed between maternal intake of total vegetables, vegetables other than green and yellow vegetables, total fruit, apples, α-carotene, vitamin C, or zinc and the risk of wheeze or eczema in the children. Conclusions: Higher maternal consumption of green and yellow vegetables, citrus fruit, and β-carotene during pregnancy may be protective against the development of eczema in the offspring. Higher maternal vitamin E intake during pregnancy may reduce the risk of infantile wheeze.

Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review

Abstract: To cite this article: Choo KJL, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; 65: 1205–1211. Abstract Background: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. Objectives: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion. Results: None of the 2496 reports identified satisfied the inclusion criteria. Conclusions: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.

IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8‐year‐olds

Abstract: Background: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. Methods: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. Results: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97% vs 70%, P = 0.016), particularly respiratory symptoms (50% vs 9%, P = 0.002). Conclusions: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.

Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria.

Abstract: To cite this article: Takahagi S, Mihara S, Iwamoto K, Morioke S, Okabe T, Kameyoshi Y, Hide M. Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria. Allergy 2010; 65: 649–656. Abstract Background: The evaluation of disease severity and activity of chronic urticaria (CU) is essential for the adequate treatment of patients. However, there is no reliable biomarker for such evaluations. Recently, markers of blood coagulation and fibrinolysis have been revealed to be elevated in severe cases of CU. In this article, we studied the coagulation/fibrinolysis and inflammation markers and their relationship to disease activity in patients with CU. Methods: Plasma fibrin degradation products (FDP), d-dimer and serum C-reactive protein (CRP) were measured with the assessment of disease severity and skin reaction to autologous serum in 82 patients with CU and 37 patients with acute urticaria, idiopathic angioedema (AE) or inducible types of urticaria (IU). Results: The levels of FDP in patients with CU were significantly higher than those in patients with IU, but no other differences in FDP, d-dimer and CRP were observed among patients with different types of urticaria. These markers of patients with CU were well correlated with each other and significantly associated with disease severity of CU, but not with skin reactions to autologous serum. In 37 patients with CU, levels of all these parameters reduced as their disease condition improved, while they increased when the disease became aggravated. Regarding FDP, this relationship was observed even if FDP concentrations were within normal range throughout the study. Conclusions: The measurement of plasma FDP, d-dimer and serum CRP may be useful for the assessment of disease activity of CU.

TSLP Polymorphisms are Associated with Asthma in a Sex-Specific Fashion

Abstract: Background Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion.

Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes.

Abstract: We assessed 195 subjects with histories of adverse reactions to aminopenicillins, using 1) skin tests with penicilloyl polylysine (PPL), minor determinant mixture (MDM), benzylpenicillin (PG), amoxicillin, and ampicillin (read after 20 min and 48 h); 2) patch tests with PG, amoxicillin, and ampicillin; and 3) RAST for penicilloyls G and V. Oral challenges with ampicillin, amoxicillin, and penicillin V were administered to 34/60 patients reporting maculopapular reactions. Immediate hypersensitivity (IH), in most cases for both penicillin and aminopenicillins, was diagnosed (based on skin tests, RAST, or both) in 35 subjects who had suffered anaphylactic shock, or urticaria, angioedema, or both urticaria and angioedema. Thirty-three of the 60 subjects reporting maculopapular reactions presented delayed intradermal and patch-test positivity, indicating delayed hypersensitivity (DH), for ampicillin and amoxicillin, and three were also positive for PG. Diagnoses were confirmed with oral challenges in 18/33. The remaining 27/60 were negative in all allergologic tests, with oral-challenge confirmation in 16. Our findings highlight the importance of the amino group in DH to aminopenicillins. Moreover, the mean time interval between the last reaction and our tests was significantly (P < 0.01) longer in DH subjects (54.96 months) than in those with IH (18.62 months), suggesting that the time of testing is less important in cases of DH.

Pathophysiology and therapy of pruritus in allergic and atopic diseases

Abstract: Pruritus (itch) is a major characteristic and one of the most debilitating symptoms in allergic and atopic diseases and the diagnostic hallmark of atopic dermatitis. Pruritus is regularly defined as an unpleasant sensation provoking the desire to scratch. Although we achieved rather good knowledge about certain inducers of itch such as neuropeptides, amines, mu-opioids, cytokines and proteases, for example, less is known about the pathophysiological specifities among the different diseases, and the therapeutic consequences which may derive thereoff. This review dissects the role of mediators, receptors and itch inhibitors on peripheral nerve endings, dorsal root ganglia, the spinal cord and the CNS leading to the amplification or - vice versa - suppression of pruritus. As the treatment of pruritus in allergic and atopic skin disease is still not satisfactory, knowing these pathways and mechanisms may lead to novel therapeutic approaches against this frequently encountered skin symptom.

Gaps in anaphylaxis management at the level of physicians, patients, and the community: a systematic review of the literature

Abstract: Diagnosis and management of anaphylaxis can be a challenge because reactions are often unexpected and progress quickly The focus of anaphylaxis management has mostly been on the acute episode, with little attention given to the long-term management of patients at risk This is compounded by conflicting information in current guidelines and a general lack of agreement among clinicians about which management strategies are the most appropriate We systematically reviewed the literature to identify and summarize studies that investigated gaps in anaphylaxis management Our search included MEDLINE, EMBASE, CINAHL, and Evidence-Based Medicine Reviews Studies were included if they addressed an outcome describing gaps in anaphylaxis knowledge, education, anaphylaxis management, and quality of life (QOL) Populations of interest were health care professionals involved in the care of patients at risk for anaphylaxis, and patients of any age, their parents, caregivers, and teachers in primary care, hospital or community settings Of 5014 citations that were identified, the final 59 studies (selected from 75 full-text articles) met the inclusion criteria Two hundred and two gaps were identified and classified according to major themes: gaps in knowledge and anaphylaxis management (physicians and patients); gaps in follow-up care (physicians); and QOL of patients and caregivers Findings from this systematic review revealed gaps in anaphylaxis management at the level of physicians, patients, and the community Findings will be used to provide a basis for developing interventional strategies to help address these deficiencies

Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal epithelial cells in vitro.

Abstract: To cite this article: Sachse F, Becker K, von Eiff C, Metze D, Rudack C. Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal epithelial cells in vitro. Allergy 2010; 65: 1430–1437. Abstract Background: Staphylococcus aureus has been associated with chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis but its role is still controversially discussed. Here, we demonstrate S. aureus detection in the mucosa of CRSwNP. In addition, intracellular residency of S. aureus in nasal polyp epithelial cells (NPECs) and its capability to induce TH-2 cytokines were analyzed in vitro. Methods: Staphylococcus aureus detection in CRSwNP (n = 25), CRS without polyps (CRSsNP, n = 5), and turbinate mucosa (TM, n = 10) was performed by peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) and microbial cultivation from tissue biopsies. Intracellular residency was examined by intracellular persistence assay and electron microscopy. IL-6 and IL-13 responses to S. aureus infection and supernatants were quantified by ELISA. Results: Peptide nucleic acid-fluorescence in situ hybridization positive bacterial cells were significantly increased in the epithelium of CRSwNP (17/25) compared to CRSsNP (0/5) and TM (1/10). Good concordance of PNA-FISH results and S. aureus cultivation was found applying Cohen’s κ for CRSwNP (κ = 0.841) and TM (κ = 1.0). Intracellular persistence assay with S. aureus strain Newman and its corresponding small-colony variant mutant strain III33 demonstrated intracellular survival and replication of S. aureus within NPECs. Both S. aureus strains significantly induced IL-6 but not IL-13 in infected NPECs and in NPECs challenged with corresponding staphylococcal supernatants. Conclusion: Invasion of the epithelium by S. aureus was a phenomenon seen predominantly in CRSwNP. Regardless of an intra- or extracellular localization in the epithelium, S. aureus is capable to induce IL-6 synthesis in vitro and thus may contribute to the TH-2 cytokine pattern in CRSwNP.

Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study

Abstract: To cite this article: Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, Antepara I, Jauregui I, Valiente R, the Bilastine International Working Group. Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study. Allergy 2010; 65: 516–528. Abstract Background: Bilastine is a novel nonsedative H1-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). The aim of this study was to compare the clinical efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg and placebo in CU patients with moderate-to-severe symptoms. Methods: Overall 525 male and female subjects aged 18–70 years were randomized to receive bilastine 20 mg, levocetirizine 5 mg or placebo, once daily for 28 days, in double-blind manner, in 46 centres across Europe and Argentina. Patients rated symptoms of pruritus, number of wheals, and maximum size of wheals (on predefined scales) as reflective (over past 12 h) symptoms twice daily, for assessment of change from baseline in the total symptoms scores (TSS) over 28 days as the primary efficacy measure. Changes in reflective and instantaneous symptoms scores, Dermatology Life Quality Index (DLQI), and CU-associated discomfort and sleep disturbance were assessed as secondary outcomes. Safety was assessed according to adverse events, laboratory tests and electrocardiograms. Results: Bilastine reduced patients’ mean reflective and instantaneous TSS from baseline to a significantly greater degree than placebo (P < 0.001); from day 2 onwards of treatment. The DLQI, general discomfort, and sleep disruption were also improved significantly in bilastine-treated patients as compared with placebo-treated patients (P < 0.001 for all parameters). Comparison with levocetirizine indicated both treatments to be equally efficacious as well as equally safe and well tolerated as compared with placebo. Conclusions: Bilastine 20 mg is a novel effective and safe treatment option for the management of CU.

IPF: new insight on pathogenesis and treatment.

Abstract: To cite this article: Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy 2010; 65: 537–553. Abstract Recent years have seen a robust influx of exciting new observations regarding the mechanisms that regulate the initiation and progression of pulmonary fibrosis but the pathogenesis remains poorly understood. The search for an alternative hypothesis to unremitting, chronic inflammation as the primary explanation for the pathophysiology of idiopathic pulmonary fibrosis (IPF) derives, in part, from the lack of therapeutic efficacy of high-dose immunosuppressive therapy in patients with IPF. The inflammatory hypothesis of IPF has since been challenged by the epithelial injury hypothesis, in which fibrosis is believed to result from epithelial injury, activation, and/or apoptosis with abnormal wound healing. This hypothesis suggests that recurrent unknown injury to distal pulmonary parenchyma causes repeated epithelial injury and apoptosis. The resultant loss of alveolar epithelium exposes the underlying basement membrane to oxidative damage and degradation. Emerging concepts suggest that IPF is the result of epithelial–mesenchymal interaction. The initiation of this fibrotic response may depend upon genetic factors and environmental triggers; the role of Th1 or Th2 cell-derived cytokines may also be important. This process appears to be unique to usual interstitial pneumonia/IPF. It is clear that IPF is a heterogeneous disease with variations in pathology, high-resolution computed tomography findings, and patterns of progression. Idiopathic pulmonary fibrosis is a complex disorder, and no unifying hypothesis has been identified at present that explains all the abnormalities.

The management of the allergic child at school: EAACI/GA2LEN Task Force on the allergic child at school.

Abstract: Allergy affects at least one-quarter of European schoolchildren, it reduces quality of life and may impair school performance; there is a risk of severe reactions and, in rare cases, death. Allergy is a multi-system disorder, and children often have several co-existing diseases, i.e. allergic rhinitis, asthma, eczema and food allergy. Severe food allergy reactions may occur for the first time at school, and overall 20% of food allergy reactions occur in schools. Up to two-thirds of schools have at least one child at risk of anaphylaxis but many are poorly prepared. A cooperative partnership between doctors, community and school nurses, school staff, parents and the child is necessary to ensure allergic children are protected. Schools and doctors should adopt a comprehensive approach to allergy training, ensuring that all staff can prevent, recognize and initiate treatment of allergic reactions.