Epidemiology of cow’s milk allergy: has it changed?

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The effects of an insertion in the 5 ' UTR of the AMCase on gene expression and pulmonary functions

Cataloged from PDF version of article.Background: Studies regarding the physiological role of acidic mammalian chitinase (AMCase) and the effects of its genetic variants on asthma have produced conflicting results. Objectives: We aimed to determine the genetic variants in the AMCase gene that could regulate the gene expression and thus influence disease severity. Methods: Genetic variants of the AMCase gene were determined by sequencing of asthmatics and healthy controls in up to -1 kb in the promoter region and exon 1 and 2. In an association study, a population of asthmatic (n = 504) and healthy Turkish children (n = 188) were genotyped for the observed SNPs. A replication study was performed in a North American adult population of patients with mild (n = 317) and severe (n = 145) asthma. The functional properties of the insertion were determined by promoter reporter assay, electromobility shift assay and transcription factor ELISA experiments. Results: Of the identified SNPs, only a ten base pair insertion (CAATCTAGGC) in the 5'UTR region of exon 2 was significantly associated with lower FEV(1) (beta = -14.63 SE = 6.241, P = 0.019) in Turkish children with asthma. However, in the adult population, the same insertion showed a trend toward higher FEV(1). The insertion was shown to have enhancer activity and the mutant probe possessing the insertion had higher binding affinity for the nuclear extracts. Conclusion: Our study shows that a ten base pair insertion in the 5'UTR region of AMCase gene may modify gene expression and thus may affect the severity of asthma. However, its effects appear to be different in different populations. (C) 2011 Elsevier Ltd. All rights reserved

IgE-mediated Anisakis allergy in children

Anisakids are nematodes responsible for different clinical patterns in humans. The well-known human-infecting Anisakis species include members of the Anisakis simplex (AS) complex. Humans usually contract anisakiasis through ingestion of raw or undercooked seafood containing Anisakis larvae. Once Anisakis has been ingested, patients may develop disease driven directly by Anisakis larvae and/or by allergic reaction due to this nematode. The capability of inducing allergic reactions depends on the expression of specific antigens by nematodes and host factors. This study aims to resume actual knowledge about AS and Anisakiasis with regard to epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment. Particular attention is paid to Anisakis allergens and their cross-reactivity on available diagnostic methods, and defining a diagnostic pathway for Anisakis allergy. Because only a few data are available in the literature about pediatric population, we focus on this group of patients specifically

Epithelial barrier hypothesis and the development of allergic and autoimmune diseases

The “epithelial barrier hypothesis” proposes that genetic predisposition to epithelial barrier damage, exposure to various epithelial barrier–damaging agents and chronic periepithelial inflammation are responsible for the development of allergic and autoimmune diseases. Particularly, the introduction of more than 200,000 new chemicals to our daily lives since the 1960s has played a major role in the pandemic increase of these diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defence against external factors. A leaky epithelial barrier initiates the translocation of the microbiome from the surface of affected tissues to interepithelial and even deeper subepithelial areas. In tissues with a defective epithelial barrier, colonization of opportunistic pathogens, decreased microbiota biodiversity, local inflammation, and impaired regeneration and remodelling takes place. A dysregulated immune response against commensals and opportunistic pathogens starts. Migration of inflammatory cells to other tissues and their contribution to tissue injury and inflammation in the affected tissues are key events in the development and exacerbation of many chronic inflammatory diseases. Understanding the underlying factors that affect the integrity of epithelial barriers is essential to find preventive measures or effective treatments to restore its function. The aim of this review is to assess the origins of allergic and autoimmune diseases within the framework of the epithelial barrier hypothesis

Influence of the gut microbiome on IgE and non-IgE-mediated food allergies

Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) -- MAY 26-30, 2018 -- Munich, GERMANYWOS: 000441690400204Background: The prevalence of food allergy (FA) in children has been increasing in last decade. Recent studies show changes in gut microbiome with FA. However, whether gut microbiome may differ between IgE and non‐IgE‐mediated FA is not defined. The aim of this study is to examine the intestinal microbiome composition in infants with IgE and non‐IgE‐mediated FA and healthy infants. Method: Infants younger than 1‐year‐old, breastfed and diagnosed with FA by a physician were included in the study. DNA was isolated from stool samples of infants with non‐IgE‐mediated FA (n = 25) and IgE‐mediated FA (n = 11) and healthy infants (n = 7). Whole genome shotgun sequencing was applied to identify the composition of microbial DNA (an average depth of 3.1 ± 0.8 million paired end reads and 0.9 ± 0.2 gigabase pairs). Results: There were compositional differences among 3 different groups. Shannon index was significantly higher in IgE‐mediated FA compared to non‐IgE‐mediated FA group (Kruskal‐Wallis test, P = 0.034). Even though β‐diversity was similar, the Sparse Partial Least Square Discriminant Analysis (sPLS‐DA) demonstrated that there were taxa‐level differences among three groups. In species level, Veillonella parvula was in a significantly higher density in healthy infants compared to IgE and non‐IgE‐mediated FA groups. Rahnella aquatilis and Lactobacillus salivarius were significantly lower and Treponema succinifaciens significantly higher in IgE‐mediated FA group compared to other groups. Additionally, Prevotella sp. oral taxon 299 was significantly lower in non‐IgE‐mediated FA group compared to others. Prevotella sp oral taxon 299 was related to mucus in stool whereas urticaria related species were Olsenall uli, Bactreoides thetaiotaomicron, Klebsiella variiocola, Rahnella aquatilis, Treponema succinfaciens, Ethanoligenens harbinenese. Conclusion: Analysis of microbiome differences in FA patients may aid in the understanding of the disease process. The present data suggest that there are compositional variations mostly in species‐ level among infants with FA and healthy ones. Our results suggest that the gut microbiome has a stronger relationship to IgE‐mediated than non‐IgE‐mediated FA. Further functional analysis of the microbiome may help better understand the changes seen in the gut microbiome in FAs and improve our knowledge in the disease etiopathology.European Academy of Allergy and Clinical Immunolog

Mega-dose vitamin C attenuated lung inflammation in mouse asthma model

Asthma is a Th2-dependent disease mediated by IgE and Th2 cytokines, and asthmatic patients suffer from oxidative stresses from abnormal airway inflammation. Vitamin C is a micro-nutrient functioning as an antioxidant. When administered at a mega-dose, vitamin C has been reported to shift immune responses toward Th1. Thus, we tried to determine whether vitamin C exerted beneficial effects in asthma animal model. Asthma was induced in mice by sensitizing and challenging with ovalbumin. At the time of challenge, 3~5 mg of vitamin C was administered and the effects were evaluated. Vitamin C did not modulate Th1/Th2 balance in asthma model. However, it decreased airway hyperreactivity to methacholine, decreased inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration. These results suggest that vitamin C administered at the time of antigen challenge exerted anti-inflammatory effects. Further studies based on chronic asthma model are needed to evaluate a long-term effect of vitamin C in asthma. In conclusion, even though vitamin C did not show any Th1/Th2 shifting effects in this experiment, it still exerted moderate anti-inflammatory effects. Considering other beneficial effects and inexpensiveness of vitamin C, mega-dose usage of vitamin C could be a potential supplementary modality for the management of asthma

New-Onset Atrial Fibrillation Predicts Long-Term Mortality After Coronary Artery Bypass Graft

ObjectivesWe sought to investigate the association between new-onset atrial fibrillation after coronary artery bypass graft (CABG) (post-operative atrial fibrillation [POAF]) and long-term mortality in patients with no history of atrial fibrillation.BackgroundPOAF predicts longer hospital stay and greater post-operative mortality.MethodsA total of 16,169 consecutive patients with no history of AF who underwent isolated CABG at our institution between January 1, 1996, and December 31, 2007, were included in the study. All-cause mortality data were obtained from Social Security Administration death records. A multivariable Cox proportional hazards regression model was constructed to determine the independent impact of new-onset POAF on long-term survival after adjusting for several covariates. The covariates included age, sex, race, pre-operative risk factors (ejection fraction, New York Heart Association functional class, history of myocardial infarction, index myocardial infarction, stroke, chronic obstructive pulmonary disease, peripheral arterial disease, smoking, diabetes, renal failure, hypertension, dyslipidemia, creatinine level, dialysis, redo surgery, elective versus emergent CABG, any valvular disorder) and post-operative adverse events (stroke, myocardial infarction, acute respiratory distress syndrome, and renal failure), and discharge cardiac medications known to affect survival in patients with coronary disease.ResultsNew-onset AF occurred in 2,985 (18.5%) patients undergoing CABG. POAF independently predicted long-term mortality (hazard ratio: 1.21; 95% confidence interval: 1.12 to 1.32) during a mean follow-up of 6 years (range 0 to 12.5 years). This association remained true after excluding from the analysis those patients who died in-hospital after surgery (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32). Patients with POAF discharged on warfarin experienced reduced mortality during follow-up.ConclusionsIn this large cohort of patients, POAF predicted long-term mortality. Warfarin anticoagulation may improve survival in POAF

Allergen immunotherapy for IgE-mediated food allergy : a systematic review and meta-analysis

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.Peer reviewe

Dimethylthiourea protects against chlorine induced changes in airway function in a murine model of irritant induced asthma

<p>Abstract</p> <p>Background</p> <p>Exposure to chlorine (Cl₂) causes airway injury, characterized by oxidative damage, an influx of inflammatory cells and airway hyperresponsiveness. We hypothesized that Cl₂-induced airway injury may be attenuated by antioxidant treatment, even after the initial injury.</p> <p>Methods</p> <p>Balb/C mice were exposed to Cl₂gas (100 ppm) for 5 mins, an exposure that was established to alter airway function with minimal histological disruption of the epithelium. Twenty-four hours after exposure to Cl₂, airway responsiveness to aerosolized methacholine (MCh) was measured. Bronchoalveolar lavage (BAL) was performed to determine inflammatory cell profiles, total protein, and glutathione levels. Dimethylthiourea (DMTU;100 mg/kg) was administered one hour before or one hour following Cl₂exposure.</p> <p>Results</p> <p>Mice exposed to Cl₂had airway hyperresponsiveness to MCh compared to control animals pre-treated and post-treated with DMTU. Total cell counts in BAL fluid were elevated by Cl₂exposure and were not affected by DMTU treatment. However, DMTU-treated mice had lower protein levels in the BAL than the Cl₂-only treated animals. 4-Hydroxynonenal analysis showed that DMTU given pre- or post-Cl₂prevented lipid peroxidation in the lung. Following Cl₂exposure glutathione (GSH) was elevated immediately following exposure both in BAL cells and in fluid and this change was prevented by DMTU. GSSG was depleted in Cl₂exposed mice at later time points. However, the GSH/GSSG ratio remained high in chlorine exposed mice, an effect attenuated by DMTU.</p> <p>Conclusion</p> <p>Our data show that the anti-oxidant DMTU is effective in attenuating Cl₂induced increase in airway responsiveness, inflammation and biomarkers of oxidative stress.</p