Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Contribution of host factors and workplace exposure to the outcome of occupational asthma

The outcome of occupational asthma after diagnosis is often poor. The identification of factors associated with a worse outcome may help in the management of the disease, determining its prognosis and assessing the permanent impairment attributable to occupational exposure. The aim of this systematic review was to provide the available evidence from the medical literature to answer the question: "What is the contribution of host factors and workplace exposure to the risk of a bad outcome of occupational asthma?" A systematic literature search was conducted in March 2010. We retrieved 177 abstracts. Of these, 67 were assessed as potentially relevant. After full text evaluation, 35 articles that were actually relevant for the question were included in the analysis. The information obtained was sufficient to establish that older age, high-molecular-weight agents, impaired lung function and longer duration of exposure to the offending agent at the time of diagnosis had a negative role on the outcome of occupational asthma. Atopy and smoking at diagnosis did not seem to influence the outcome of occupational asthma. A limited number of studies considered sex and the pattern of asthmatic reaction on specific inhalation challenge and their findings were contradictory

Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics

Background: Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. Methods: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. Results: Inhaled f2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to \u3b22 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. Conclusions: This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2

Glutathione-S-transferase genes and asthma phenotypes: a Human Genome Epidemiology (HuGE) systematic review and meta-analysis including unpublished data

Background: oxidative stress is thought to be involved in the pathogenesis of asthma. Glutathione-S-transferase (GST) enzymes, which play an important role in antioxidant defences, may therefore influence asthma risk. Two common deletion polymorphisms of GSTM1 and GSTT1 genes and the GSTP1 Ile105Val polymorphism have been associated with asthma in children and adults, but results are inconsistent across studies.Methods: systematic review and meta-analysis of the effects of GST genes on asthma, wheezing and bronchial hyper-responsiveness (BHR), with inclusion of unpublished data from three studies, including the large Avon Longitudinal Study of Parents and Children (ALSPAC). Random effect or fixed effect models were used as appropriate, and sensitivity analyses were performed to assess the impact of study characteristics and quality on pooled results.Results: the meta-analyses of GSTM1 (n = 22 studies) and GSTT1 (n = 19) showed increased asthma risk associated with the null genotype, but there was extreme between-study heterogeneity and publication bias and the association disappeared when meta-analysis was restricted to the largest studies. Meta-analysis of GSTP1 Ile105Val (n = 17) and asthma suggested a possible protective effect of the Val allele, but heterogeneity was extreme. Few studies evaluated wheezing and BHR and most reported no associations, although weak evidence was found for positive associations of GSTM1 null and GSTP1 Val allele with wheezing and a negative association of GSTP1 Val allele with BHR.Conclusions: our findings do not support a substantial role of GST genes alone in the development of asthma. Future studies of large size should focus on interactions of GST genes with environmental oxidative exposures and with other genes involved in antioxidant pathways. Quality of study conduct and reporting needs to be improved to increase credibility of the evidence accumulating over tim