Traffic-related air pollution and incident asthma in a high-risk birth cohort

Abstract OBJECTIVES: The risk of incident asthma and bronchial hyper-reactivity associated with early life exposure to traffic-related air pollution has not been fully elucidated. We aimed to evaluate the hypothesis that the risk of new onset asthma is positively associated with early exposure to traffic-related air pollution in a well-characterised high-risk birth cohort. METHODS: Infants at high-risk for asthma were recruited for an intervention study. Birth year exposures to NO, NO(2), black carbon and PM(2.5) were estimated by land use regression. At 7 years of age, asthma was assessed by a paediatric allergist and bronchial hyper-reactivity was measured by methacholine challenge. Associations between exposures and outcomes were analysed by stepwise multiple logistic regression, adjusted for potential confounding variables. RESULTS: Exposure estimates were available for 184 children; 23 were diagnosed with asthma and 68 with bronchial hyper-reactivity. The IQR (4.1 μg/m(3)) of birth year PM(2.5) was associated with a significantly increased risk of asthma (OR 3.1, 95% CI 1.3 to 7.4) and with a trend to increased risk of bronchial hyper-reactivity. Similar findings were noted in association with NO and NO(2), while black carbon did not appear to confer increased risk. CONCLUSION: Modest elevations in exposure to some traffic-related air pollutants during the year of birth are associated with new onset asthma assessed at age 7. That significant associations were revealed in spite of a limited sample size emphasises the strengths of a high-risk birth cohort model, along with individual air pollution exposure estimates and well-characterised data on covariates and outcomes

Airway hyperresponsiveness to methacholine in 7-year-old children: sensitivity and specificity for pediatric allergist-diagnosed asthma

BACKGROUND: The operating characteristics of PC(20) values used as cut-offs to define airway hyperresponsiveness, as it informs the diagnosis of asthma in children, are poorly understood. We examine data from a unique cohort to inform this concern. OBJECTIVE: Determine the sensitivity and specificity of incremental PC(20) cut-offs for allergist-diagnosed asthma. METHODS: Airway reactivity at age 7 was assessed in children within a birth cohort at high risk for asthma; PC(20) for methacholine was determined by standard technique including interpolation. The diagnosis of asthma was considered by the pediatric allergist without knowledge of the methacholine challenge results. Sensitivity and specificity were calculated using a cross-tabulation of asthma diagnosis with incremental PC(20) cut-off values, from 1.0 to 8.0 mg/ml, and plotted as receiver operator characteristic (ROC) curves. The 'optimal' cut-off was defined as that PC(20) conferring maximal value for sensitivity plus specificity while the 'balanced' cut-off was defined as that PC(20) at which sensitivity and specificity were most equal. RESULTS: 70/348 children (20.1%) were diagnosed with asthma. The optimal and balanced PC(20) cut-offs, both for all children and for females alone, were respectively 3 mg/ml (sensitivity 80.0%, specificity 49.1%) and 2 mg/ml (sensitivity 63.1%, specificity 64.7%). For males alone, the 'optimal' and 'balanced' PC(20) cut-offs were both 2 mg/ml. CONCLUSION: For this cohort of 7-year olds at high risk for asthma, methacholine challenge testing using a cut-off value of PC(20) 3 mg/ml conferred the maximal sum of specificity plus sensitivity. For contexts in which higher sensitivity or specificity is desired, other cut-offs may be preferred

Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort.

There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB-IgE in predicting asthma and other IgE-mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE-mediated allergic diseases. CB-IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB-IgE. Fifty-five (19.3%) of infants had detectable CB-IgE (>/=0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB-IgE. CB-IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB-IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention

Combined exposure to dog and indoor pollution: incident asthma in a high-risk birth cohort

The impact of single exposures on asthma development is better understood than the effect of multiple exposures. The objective of the present study was to evaluate the effect of combined early exposure to dog allergen (Can-f1) plus indoor nitrogen dioxide (NO₂) or environmental tobacco smoke (ETS) on asthma and bronchial hyperreactivity (BHR) in a high-risk birth cohort. We also aimed to assess atopy's impact on the effects of these exposures. Peri-birth ETS exposure was measured using cord blood cotinine (CCot). During year 1, atopy, NO₂, Can-f1, and urinary cotinine (UCot) were measured. At 7 yrs of age, 380 children were assessed for asthma and BHR. Exposure effects were determined using stepwise multiple linear regression. Co-exposure to elevated Can-f1 and NO₂, or Can-f1 and ETS (CCot), increased risk for asthma, relative to having neither such exposure (OR 4.8 (95% CI 1.1-21.5) and 2.7 (1.1-7.1), respectively); similar risks resulted when substituting dog ownership for allergen. Atopy increased asthma and BHR risk associated with several exposures; notably, atopy with elevated UCot, relative to atopy without such exposure, increased risk of BHR (OR 3.1 (95% CI 1.1-8.6)). In a high-risk birth cohort, early co-exposure to Can-f1 and NO₂ or ETS increased the risk of incident asthma. Atopy increased the risk of asthma and BHR associated with ETS.link_to_OA_fulltex

Indoor allergen exposure, sensitization, and development of asthma in a high-risk birth cohort

Contradictory findings have been observed for the association of house dust mite (HDM), cat, and dog allergen exposure with sensitization and asthma. We sought to determine the relationship between exposures to these allergens, at various points during early childhood, and specific sensitization and asthma at age 7 in a high-risk birth cohort. As part of a multi-faceted Canadian intervention program for the primary prevention of asthma in high-risk infants, children were assessed by pediatric allergists at age 7 for asthma and underwent allergy skin prick testing. House dust samples were analyzed for HDM, cat, and dog allergen levels at several time points during years 1 and 7 of life. Multiple logistic regression analyses were carried out for the combined cohort and separately for the control and intervention groups. Exposure to a higher level of HDM allergen in year 1 or year 7 was associated with a higher risk of year 7 sensitization to HDM but not asthma. Exposure to higher levels of cat allergen in year 1 or year 7 did not affect the risk of year 7 sensitization to cat or asthma. Dog ownership, or exposure to higher levels of dog allergen in year 1 or year 7, did not affect the risk of year 7 sensitization to dog; however, year 7 dog allergen exposure (intervention group only) or ownership was associated with increased year 7 asthma risk. Our findings suggest that in high-risk children, there are allergen-specific associations of exposure with sensitization and with asthma; early life-elevated HDM exposure was associated with risk of sensitization but not asthma while the opposite was true for dog exposure.link_to_subscribed_fulltex

Association between endotoxin and mite allergen exposure with asthma and specific sensitization at age 7 in high-risk children

The role of endotoxin and house dust mite allergen (HDM) in allergen sensitization and asthma is unclear. The timeframe of exposure and asthma assessment appears critical. We aimed to determine, in children at 7 yr of age, the association between current exposure to endotoxin and HDM and risks of recurrent wheeze, paediatric allergist diagnosed asthma and allergen sensitization. Three hundred and eighty children who had an increased risk of asthma because of family background were assessed at age 7 yr by a questionnaire-standardized interview, allergen skin testing and clinical examination by a paediatric allergist. Dust samples were collected from their homes and analysed for levels of endotoxin and HDM (Der p 1 and Der f 1). Levels of endotoxin in dust samples were associated with protection from paediatric allergist diagnosed asthma with inhaled steroid use (OR 0.69, 95% CI 0.53-0.91) and specific sensitization to dog allergen (OR 0.68, 95% CI 0.51-0.90) at the age of 7 yr; both endotoxin and HDM were associated with decreased risk of sensitization to dog allergen. In high-risk children at age 7, endotoxin levels were associated with decreased sensitization to dog, as well as with decreased asthma