S. Hasan Arshad

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

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

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.

Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study.

Background Asthma is considered to be associated with elevated levels of exhaled nitric oxide (FeNO). The nature of this relationship and how it is influenced by atopy are still not resolved. Methods The Isle of Wight birth cohort (N=1456) was reassessed at 18 years of age. Participants able to attend the research centre were assessed by questionnaires, skin prick testing and FeNO in order to explore the interrelationship between asthma, atopy and FeNO. Results Atopy was significantly associated with higher levels of FeNO. However, the level of FeNO for non-atopic asthmatic participants was no different to the non-atopic no-asthma group. The highest levels of FeNO were seen in subjects with both atopy and asthma. In addition, FeNO was positively associated with increasing atopic burden as evidenced by increasing FeNO with increasing skin prick testing positivity, and with increasing severity of atopic asthma as evidenced by the number of attacks of wheezing. FeNO and current inhaled corticosteroid use were not significantly associated. Conclusions FeNO behaves as a biomarker of atopy and the “allergic asthma” phenotype rather than asthma itself. This may explain why FeNO-guided asthma treatment outcomes have proved to be of limited success where atopic status has not been considered and accounted for.

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

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.

Epidemiology of Food Allergy

Food allergy (FA) is perceived as a common problem, especially during childhood. Accurate assessment of incidence and prevalence of FA has been difficult to establish, however, due to lack of universally accepted diagnostic criteria. Although many foods are reported to cause IgE-mediated FA, most studies focus on 4 common food groups: cows milk, hens egg, peanut/tree nuts, and fish/shellfish. There may be variation in the prevalence of FA in regions of the world and a likely increase in prevalence has been observed in recent decades. This cannot be stated with confidence, however, without the use of consistent methodology and diagnostic criteria.

Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence.

BACKGROUND Filaggrin is an epidermal protein that has a role in skin barrier function. Filaggrin loss-of-function (FLG-LOF) mutations are a significant risk factor for eczema and atopy, but their association with food allergy (FA) is less clear. OBJECTIVE We explored the longitudinal relationship between 3 common FLG-LOF mutations and FA using the Isle of Wight birth cohort. METHODS FA diagnosis was based on recognized allergic reactions within 4 hours after exposure to known food allergens. Food allergen sensitization (FAS) was identified by using skin prick tests conducted between 1 and 18 years of age to a range of food allergens. Three FLG mutations were genotyped in 1150 (79%) of 1456 children. The temporal relationships between FA, FAS, and eczema in children with FLG mutations were explored by using path analysis with total, direct, and indirect effect models. RESULTS There was a significant total effect of FLG-LOF mutations on the risk of FA in later childhood at the ages of 10 (odds ratio, 31.46; 95% CI, 2.86 to >100) and 18 (odds ratio, 4.25; 95% CI, 1.55-11.61) years. Path analysis showed that there was no direct effect of FLG-LOF mutations on FA at any age; however, an indirect effect was found on FA at all ages through eczema and FAS in the earlier years. CONCLUSION FLG-LOF mutations are associated with FA in older children through eczema and FAS during early childhood. Our results highlight a biologically plausible pathway, which suggests that skin barrier function is important in the development and persistence of FA.

Does exposure to indoor allergens contribute to the development of asthma and allergy

Common indoor allergens include house dust mite, cockroach, animal dander, and certain molds. In genetically susceptible children, exposure to these indoor allergens during the critical postnatal period may lead to sensitization in early childhood. Consistent evidence indicates that children sensitized to common indoor allergens are at several-fold higher risk of asthma and allergy. Due to conflicting evidence from prospective studies, some doubt remains regarding a direct and dose–response relationship between exposure and development of asthma. However, in recent years, evidence has accumulated that exposure to indoor allergen causes asthma and allergy, but this effect may depend on dose and type of allergen as well as the underlying genetic susceptibility of the child.

IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood, a longitudinal study.

BackgroundTobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.MethodsIn the Isle of Wight birth cohort (UK, 1989–1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.ResultsMaternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).ConclusionThis is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.

Multifaceted allergen avoidance during infancy reduces asthma during childhood with the effect persisting until age 18 years

Background Asthma is a chronic disease that often starts in childhood. The key risk factors are a childs environment and their genetic characteristics. The aim of this study was to evaluate the efficacy of environmental modification in the first 12 months of life on the prevalence of asthma in high-risk individuals. Methods Children (n=120) considered at high risk of allergic disorders (either dual heredity or single heredity and a high cord total IgE), were enrolled in a single-blinded, randomised controlled trial. Infants in the intervention arm were either breast fed with the mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite allergen was reduced. The control group followed standard advice. Children were assessed at ages 1, 2, 4, 8 and 18 years for the presence of asthma and atopy. Results At 18 years of age, there was a significantly lower prevalence of asthma in the prevention group compared with the control group (OR: 0.23, 95% CI 0.08 to 0.70, p=0.01), primarily due to asthma that developed during childhood but persisted until age 18 years. Repeated-measure analysis showed that there was an overall reduction in asthma prevalence from 1 to 18 years (OR: 0.51, CI 0.32 to 0.81, p=0.04). Prevalence of atopy was not significantly different between the two groups at age 18. Conclusion Comprehensive allergen avoidance in the first year of life is effective in preventing asthma onset in individuals considered at high risk due to heredity. The effect occurs in the early years, but persists through to adulthood.

Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.