Higher Polygenetic Predisposition for Asthma in Cow's Milk Allergic Children

Cow's milk allergy (CMA) is an early-onset allergy of which the underlying genetic factors remain largely undiscovered. CMA has been found to co-occur with other allergies and immunological hypersensitivity disorders, suggesting a shared genetic etiology. We aimed to (1) investigate and (2) validate whether CMA children carry a higher genetic susceptibility for other immunological hypersensitivity disorders using polygenic risk score analysis (PRS) and prospective phenotypic data. Twenty-two CMA patients of the Dutch EuroPrevall birth cohort study and 307 reference subjects were genotyped using single nucleotide polymorphism (SNP) array. Differentially genetic susceptibility was estimated using PRS, based on multiple P-value thresholds for SNP inclusion of previously reported genome-wide association studies (GWAS) on asthma, autism spectrum disorder, atopic dermatitis, inflammatory bowel disease and rheumatoid arthritis. These associations were validated with prospective data outcomes during a six-year follow-up in 19 patients. We observed robust and significantly higher PRSs of asthma in CMA children compared to the reference set. Association analyses using the prospective data indicated significant higher PRSs in former CMA patients suffering from asthma and related traits. Our results suggest a shared genetic etiology between CMA and asthma and a considerable predictive sensitivity potential for subsequent onset of asthma which indicates a potential use for early clinical asthma intervention programs

Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze

Preschool rhinovirus-induced wheeze is associated with an increased risk of asthma. In adult asthma, exhaled volatile organic compounds (VOC) are associated with inflammatory activity. We therefore hypothesised that acute preschool wheeze is accompanied by a differential profile of exhaled VOC, which is maintained after resolution of symptoms in those children with rhinovirus-induced wheeze. We included 178 children (mean +/- SD age 22 +/- 9 months) from the EUROPA cohort comparing asymptomatic and wheezing children during respiratory symptoms and after recovery. Naso- and oropharyngeal swabs were tested for rhinovirus by quantitative PCR. Breath was collected via a spacer and analysed using an electronic nose. Between-group discrimination was assessed by constructing a 1000-fold cross-validated receiver operating characteristic curve. Analyses were stratified by rhinovirus presence/absence. Wheezing children demonstrated a different VOC profile when compared with asymptomatic children (p <0.001), regardless of the presence (area under the curve (AUC) 0.77, 95% CI 0.07) or absence (AUC 0.81, 95% CI 0.05) of rhinovirus. After symptomatic recovery, discriminative accuracy was maintained in children with rhinovirus-induced wheeze (AUC 0.84, 95% CI 0.06), whereas it dropped significantly in infants with non-rhinovirus-induced wheeze (AUC 0.67, 95% CI 0.06). Exhaled molecular profiles differ between preschool children with and without acute respiratory wheeze. This appears to be sustained in children with rhinovirus-induced wheeze after resolution of symptoms. Therefore, exhaled VOC may qualify as candidate biomarkers for early signs of asthm

The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy

ObjectivesPrudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy.MethodsThe guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak.ResultsSixty recommendations were provided for suspected allergy to β-lactam antibiotics (BLAs) and non–β-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team.ConclusionsAccumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non–β-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.Immunogenetics and cellular immunology of bacterial infectious disease

Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans

Background: Prebiotic galacto- and fructo-oligosaccharides (scGOS/lcFOS) resembling non-digestible oligosaccharides in human milk reduce the development of atopic disorders. However, the underlying mechanisms are still unclear. Galectins are soluble-type lectins recognizing beta-galactoside containing glycans. Galectin-9 has been shown to regulate mast cell degranulation and T-cell differentiation. In this study, the involvement of galectin-9 as a mechanism by which scGOS/lcFOS in combination with Bifidobacterium breve M-16V protects against acute allergic symptoms was investigated. Methods: Mice were sensitized orally to whey, while being fed with a diet containing scGOS/lcFOS and Bifidobacterium breve M-16V (GF/Bb) or a control diet. Galectin-9 expression was determined by immunohistochemistry in the intestine and measured in the serum by ELISA. T-cell differentiation was investigated in the mesenteric lymph nodes (MLN) as well as in galectin-9-exposed peripheral blood mononuclear cells (PBMC) cultures. Sera of the mice were evaluated for the capacity to suppress mast cell degranulation using a RBL-2H3 degranulation assay. In addition, in a double-blind, placebo-controlled multicenter trial, galectin- 9 levels were measured in the sera of 90 infants with atopic dermatitis who received hydrolyzed formulae with or without GF/Bb. Results: Galectin-9 expression by intestinal epithelial cells and serum galectin-9 levels were increased in mice and humans following dietary intervention with GF/Bb and correlated with reduced acute allergic skin reaction and mast cell degranulation. In addition, GF/Bb enhanced T(h)1-and T-reg-cell differentiation in MLN and in PBMC cultures exposed to galectin-9. Conclusions: Dietary supplementation with GF/Bb enhances serum galectin-9 levels, which associates with the prevention of allergic symptom

Prevalence estimates and risk factors for early childhood wheeze across europe: The europrevall birth cohort

Background Preschool wheeze is an important problem worldwide.No comparative population-based studies covering different countries have previously been undertaken.Objective T o assess the prevalence of early childhood wheeze across Europe and evaluate risk factors focusing on food allergy, breast feeding and smoke exposure.Methods I nfants from nine countries were recruited into the EuroPrevall birth cohort.At 12 and 24 months, data on wheeze, allergic signs/symptoms, feeding, smoke exposure, infections and day care attendance were collected using questionnaires.Poisson regression was used to assess risk factors for wheeze.Results 12 049 infants were recruited.Data from the second year of life were available in 8805 (73.1%).The prevalence of wheeze in the second year of life ranged from &lt;2% in Lodz (Poland) and Vilnius (Lithuania) to 13.1% (95% CI 10.7% to 15.5%) in Southampton (UK) and 17.2% (95% CI 15.0% 19.5%) in Reykjavik (Iceland).In multivariable analysis, frequent lower respiratory tract infections in the first and second years of life (incidence rate ratio (IRR) 1.9 (95% CI 1.3 to 2.6) and 2.5 (95% CI 1.9 to3.4), respectively), postnatal maternal smoking (IRR 1.6, 95% CI 1.1 to 2.4), day care attendance (IRR 1.6, 95% CI 1.1 to 2.5) and male gender (IRR 1.3, 95% CI 1.0 to 1.7) were associated with wheeze.The strength of their association with wheeze differed between countries.Food allergy and breast feeding were not independently associated with wheeze.Conclusion T he prevalence of early childhood wheeze varied considerably across Europe.Lower respiratory tract infections, day care attendance, postnatal smoke exposure and male gender are important risk factors.Further research is needed to identify additional modifiable risk factors that may differ between countrie. © 2018 BMJ Publishing Group. All rights reserved