Jennifer Perret

The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies

The impact of early childhood traffic‐related air pollution (TRAP) exposure on development of asthma and allergies remains unclear. Birth cohort studies are the best available study design to answer this question, but the evidence from such studies has not been synthesized to date. We conducted a systematic review and meta‐analyses of published birth cohort studies to understand the association between early childhood TRAP exposure, and subsequent asthma, allergies and sensitization. Increased longitudinal childhood exposure to PM2.5 and black carbon was associated with increasing risk of subsequent asthma in childhood (PM2.5: OR 1.14, 95%CI 1.00 to 1.30 per 2 μg/m3 and black carbon: OR 1.20, 95%CI 1.05 to 1.38 per 1 × 10−5 m−1). Also, early childhood exposure to TRAP was associated with development of asthma across childhood up to 12 years of age. The magnitude of these associations increased with age, and the pattern was prominent for PM2.5. Increasing exposure to PM2.5 was associated with sensitization to both aero‐ and food allergens. There was some evidence that TRAP was associated with eczema and hay fever. In summary, exposure to TRAP was related to asthma and allergic diseases. However, the substantial variability across studies warrants long‐term birth cohort studies with regular repeated follow‐ups to confirm these findings.

The Interplay between the Effects of Lifetime Asthma, Smoking, and Atopy on Fixed Airflow Obstruction in Middle Age

RATIONALE The contribution by asthma to the development of fixed airflow obstruction (AO) and the nature of its effect combined with active smoking and atopy remain unclear. OBJECTIVES To investigate the prevalence and relative influence of lifetime asthma, active smoking, and atopy on fixed AO in middle age. METHODS The population-based Tasmanian Longitudinal Health Study cohort born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968 was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005. A sample enriched for asthma and chronic bronchitis underwent a further questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick testing, lung volumes, and diffusing capacity measurements. Prevalence estimates were reweighted for sampling fractions. Multiple linear and logistic regression were used to assess the relevant associations. MEASUREMENTS AND MAIN RESULTS Main effects and interactions between lifetime asthma, active smoking, and atopy as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0% (95% confidence interval [CI], 4.5-7.5%). Its association with early-onset current clinical asthma was equivalent to a 33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.5-9.3; P = 0.005), compared with a 24 pack-year history for late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03-6.5; P = 0.042). An interaction (multiplicative effect) was present between asthma and active smoking as it relates to the ratio of post-bronchodilator FEV(1)/FVC, but only among those with atopic sensitization. CONCLUSIONS Active smoking and current clinical asthma both contribute substantially to fixed AO in middle age, especially among those with atopy. The interaction between these factors provides another compelling reason for atopic individuals with current asthma who smoke to quit.

Distinguishing adult-onset asthma from COPD: a review and a new approach.

Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and risk factors. Short-acting beta-agonists provide effective symptom relief in airway diseases. Inhalers combining a long-acting beta-agonist and corticosteroid are now widely used for both asthma and COPD. Written action plans are a cornerstone of asthma management although evidence for self-management in COPD is less compelling. The current management of chronic asthma in adults is based on achieving and maintaining control through step-up and step-down approaches, but further trials of back-titration in COPD are required before a similar approach can be endorsed. Long-acting inhaled anticholinergic medications are particularly useful in COPD. Other distinctive features of management include pulmonary rehabilitation, home oxygen, and end of life care.

Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age

Background: Traffic‐related air pollution (TRAP) exposure is associated with allergic airway diseases and reduced lung function in children, but evidence concerning adults, especially in low‐pollution settings, is scarce and inconsistent. Objectives: We sought to determine whether exposure to TRAP in middle age is associated with allergic sensitization, current asthma, and reduced lung function in adults, and whether these associations are modified by variants in Glutathione S‐Transferase genes. Methods: The study sample comprised the proband 2002 laboratory study of the Tasmanian Longitudinal Health Study. Mean annual residential nitrogen dioxide (NO2) exposure was estimated for current residential addresses using a validated land‐use regression model. Associations between TRAP exposure and allergic sensitization, lung function, current wheeze, and asthma (n = 1405) were investigated using regression models. Results: Increased mean annual NO2 exposure was associated with increased risk of atopy (adjusted odds ratio [aOR], 1.14; 95% CI, 1.02‐1.28 per 1 interquartile range increase in NO2 [2.2 ppb]) and current wheeze (aOR, 1.14; 1.02‐1.28). Similarly, living less than 200 m from a major road was associated with current wheeze (aOR, 1.38; 95% CI, 1.06‐1.80) and atopy (aOR, 1.26; 95% CI, 0.99‐1.62), and was also associated with having significantly lower prebronchodilator and postbronchodilator FEV1 and prebronchodilator forced expiratory flow at 25% to 75% of forced vital capacity. We found evidence of interactions between living less than 200 m from a major road and GSTT1 polymorphism for atopy, asthma, and atopic asthma. Overall, carriers of the GSTT1 null genotype had an increased risk of asthma and allergic outcomes if exposed to TRAP. Conclusions: Even relatively low TRAP exposures confer an increased risk of adverse respiratory and allergic outcomes in genetically susceptible individuals.

Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a systematic review and meta-analysis of the literature

Age-of-asthma onset is often used to distinguish different adult asthma phenotypes; however, similarities and differences between early- and late-onset adult asthma have not been summarized to date. Of the 2921 records found, we identified 12 studies comparing early- and late-onset current asthma in adults. Age 12 was most commonly used to delineate the two age-of-onset phenotypes. Adults with early-onset current asthma were more likely to be atopic and had a higher frequency of asthma attacks, whereas adults with late-onset disease were more likely to be female, smokers and had greater levels of spirometrically defined fixed airflow obstruction. The prevalence of severe asthma was similar in both groups, and, in general, there were few phenotypic differences between severe asthmatics regardless of age of onset. Findings for several key characteristics, including lung function, were inconsistent between studies. Overall, there appears to be distinctive phenotypic differences with age of asthma onset. Although early-onset adult asthma is likely more attributable to atopy and potentially genetic factors, late-onset adult asthma appears to be more related to environmental risk factors, and so may be better targeted by preventive strategies. More detailed research is required to better characterize these phenotypes and to clarify potential clinical implications.

Childhood lung function predicts adult chronic obstructive pulmonary disease and asthma-chronic obstructive pulmonary disease overlap syndrome

Rationale: The burden of chronic obstructive pulmonary disease (COPD) is increasing, yet there are limited data on early life risk factors. Objectives: To investigate the role of childhood lung function in adult COPD phenotypes. Methods: Prebronchodilator spirometry was performed for a cohort of 7‐year‐old Tasmanian children (n = 8,583) in 1968 who were resurveyed at 45 years, and a selected subsample (n = 1,389) underwent prebronchodilator and post‐bronchodilator spirometry. For this analysis, COPD was spirometrically defined as a post‐bronchodilator FEV1/FVC less than the lower limit of normal. Asthma‐COPD overlap syndrome (ACOS) was defined as the coexistence of both COPD and current asthma. Associations between childhood lung function and asthma/COPD/ACOS were examined using multinomial regression. Measurements and Main Results: At 45 years, 959 participants had neither current asthma nor COPD (unaffected), 269 had current asthma alone, 59 had COPD alone, and 68 had ACOS. The reweighted prevalence of asthma alone was 13.5%, COPD alone 4.1%, and ACOS 2.9%. The lowest quartile of FEV1 at 7 years was associated with ACOS (odds ratio, 2.93; 95% confidence interval, 1.32‐6.52), but not COPD or asthma alone. The lowest quartile of FEV1/FVC ratio at 7 years was associated with ACOS (odds ratio, 16.3; 95% confidence interval, 4.7‐55.9) and COPD (odds ratio, 5.76; 95% confidence interval, 1.9‐17.4), but not asthma alone. Conclusions: Being in the lowest quartile for lung function at age 7 may have long‐term consequences for the development of COPD and ACOS by middle age. Screening of lung function in school age children may identify a high‐risk group that could be targeted for intervention. Further research is needed to understand possible modifiers of these associations and develop interventions for children with impaired lung function.

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life

BACKGROUND Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. METHODS We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. FINDINGS Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory. INTERPRETATION We identified six potential FEV1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. FUNDING National Health and Medical Research Council of Australia; European Unions Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline.

Ambient wood smoke, traffic pollution and adult asthma prevalence and severity.

The impact of ambient wood smoke and traffic‐related air pollution on adult asthma has not been well studied. This paper aims to investigate associations between exposure to ambient wood smoke, traffic‐related air pollution and current asthma/asthma severity in middle age, and whether any associations are modified by atopic status.

Clinical and functional differences between early-onset and late-onset adult asthma: a population-based Tasmanian Longitudinal Health Study

Background Differences between early-onset and late-onset adult asthma have not been comprehensively described using prospective data. Aims To characterise the differences between early-onset and late-onset asthma in a longitudinal cohort study. Methods The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort. Respiratory histories and spirometry were first performed in 1968 when participants were aged 7 (n=8583). The cohort was traced and resurveyed from 2002 to 2005 (n=5729 responses) and a sample, enriched for asthma and bronchitis participated in a clinical study when aged 44 (n=1389). Results Of the entire TAHS cohort, 7.7% (95% CI 6.6% to 9.0%) had early-onset and 7.8% (95% CI 6.4% to 9.4%) late-onset asthma. Atopy and family history were more common in early-onset asthma while female gender, current smoking and low socioeconomic status were more common in late-onset asthma. The impact on lung function of early-onset asthma was significantly greater than for late-onset asthma (mean difference prebronchodilator (BD) FEV1/FVC −2.8% predicted (−5.3 to −0.3); post-BD FEV1FVC −2.6% predicted (−5.0 to −0.1)). However, asthma severity and asthma score did not significantly differ between groups. An interaction between asthma and smoking was identified and found to be associated with greater fixed airflow obstruction in adults with late-onset asthma. This interaction was not evident in adults with early-onset disease. Conclusions Early-onset and late-onset adult asthma are equally prevalent in the middle-aged population. Major phenotypic differences occur with asthma age-of-onset; while both share similar clinical manifestations, the impact on adult lung function of early-onset asthma is greater than for late-onset asthma.

Mother's smoking and complex lung function of offspring in middle age: A cohort study from childhood

Existing evidence that supports maternal smoking to be a potential risk factor for chronic obstructive pulmonary disease (COPD) for adult offspring has barely been mentioned in major guideline documents, suggesting a need for more robust and consistent data. We aimed to examine whether such early life exposure can predispose to COPD in middle age, possibly through its interaction with personal smoking.