Melanie Claire Matheson

There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex.10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25–55 years. In logistic and linear multilevel mixed models we adjusted for participants’ characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry.Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34–4.32 mL per year), more consistent in females (p_trend0.025) than in males (p_trend0.14). Asthma (OR 0.85, 95% CI 0.79–0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82–0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (p_interaction0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors.Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.

Early identification of people at risk of developing COPD is crucial for implementing preventive strategies. We aimed to systematically review and assess the performance of all published models that predicted development of COPD. A search was conducted to identify studies that developed a prediction model for COPD development. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies was followed when extracting data and appraising the selected studies. Of the 4,481 records identified, 30 articles were selected for full-text review, and only four of these were eligible to be included in the review. The only consistent predictor across all four models was a measure of smoking. Sex and age were used in most models; however, other factors varied widely. Two of the models had good ability to discriminate between people who were correctly or incorrectly classified as at risk of developing COPD. Overall none of the models were particularly useful in accurately predicting future risk of COPD, nor were they good at ruling out future risk of COPD. Further studies are needed to develop new prediction models and robustly validate them in external cohorts.

Glutathione S-transferase (GST) genes are involved in oxidative stress management and may modify the impact of indoor air pollution. We aimed to assess the influence of GST genes on the relationship between indoor air pollution and allergy/lung function.

Current evidence concerning the impact of exposure to traffic-related air pollution (TRAP) on adult respiratory morbidity mainly comes from cross-sectional studies. We sought to establish more robust measures of this association and potential gene–environment interactions using longitudinal data from an established cohort study.Associations between measures of TRAP (nitrogen dioxide (NO₂) and distance to major roads) and wheeze, asthma prevalence and lung function were investigated in participants of the Tasmanian Longitudinal Health Study at 45- and 50-year follow-ups. Generalised estimating equations were used to quantify associations and the potential modifying effect of glutathioneS-transferase gene variants.Living GSTT1null andGSTP1 val/valorile/valgenotypes. Over the 5-year period, higher NO₂exposures were associated with increased current asthma prevalence. Higher NO₂exposure was associated with lower forced vital capacity for carriers of theGSTT1null genotype.TRAP exposures were associated with increased risk of asthma, wheeze and lower lung function in middle-aged adults. The interaction with theGSTT1genotype suggests that deficient antioxidant mechanisms may play a role in these adverse health effects.

The association between obesity and bronchial hyperresponsiveness (BHR) is incompletely characterised. Using the 2006 follow-up of the Tasmanian Longitudinal Health Study, we measured the association between obesity and BHR and whether it was mediated by small airway closure or modified by asthma and sex of the patient.A methacholine challenge measured BHR. Multivariable logistic regression measured associations between body mass index (BMI) and BHR, adjusting for sex, asthma, smoking, corticosteroid use, family history and lung function. Mediation by airway closure was also measured.Each increase in BMI of 1 kg·m⁻²was associated with a 5% increase in the odds of BHR (OR 1.05, 95% CI 1.01–1.09) and 43% of this association was mediated by airway closure. In a multivariable model, BMI (OR 1.06, 95% CI 1.00–1.16) was associated with BHR independent of female sex (OR 3.26, 95% CI 1.95–5.45), atopy (OR 2.30, 95% CI 1.34–3.94), current asthma (OR 5.74, 95% CI 2.79–11.82), remitted asthma (OR 2.35, 95% CI 1.27–4.35), low socioeconomic status (OR 2.11, 95% CI 1.03–4.31) and forced expiratory volume in 1 s/forced vital capacity (OR 0.86, 95% CI 0.82–0.91). Asthma modified the association with an increasing probability of BHR as BMI increased, only in those with no or remitted asthma.An important fraction of the BMI/BHR association was mediatedviaairway closure. Conflicting findings in previous studies could be explained by failure to consider this intermediate step.

Background: Individuals with different patterns of lung function growth and decline may have different risks for developing COPD. Objectives: To investigate trajectories of lung function from childhood to middle age and their associated childhood factors. Methods: Modelling pre-bronchodilator FEV1 measured at 7, 13, 18, 45, 50 and 55 years among 2438 subjects from the Tasmanian Longitudinal Health Study, using Group Based Trajectory Modelling, 6 distinct trajectories were identified (Fig. 1) and associated with childhood factors. Results: “Early low, accelerated decline”, “persistently low”, and “early low, normal growth, normal decline” trajectories had increased risk of COPD (FEV1/FVC<LLN) at age 55 years compared with the reference trajectory: OR 57 (95%CI 27-117); 9.8 (4.5-21); and 3.8 (1.9-7.3) respectively. Childhood asthma, bronchitis, pneumonia, hay fever and maternal smoking were associated with the “early low, accelerated decline” group. Childhood asthma and eczema were associated with the “persistently low” group while pneumonia was a risk factor for the “early low, normal growth, normal decline” group. Conclusion: Individuals in a general population may follow distinct lung function patterns of which three have increased risk of developing COPD. Early life risk factors may predict an individual’s lung function pattern and should be targeted for maximizing lung function growth and preventing accelerated decline.

Background: Early identification of people at risk of developing COPD is crucial for implementing preventive strategies. We aimed to systematically review and assess the performance of all published models that predicted development of COPD. Methods: A search was conducted to identify studies that developed a new prediction model for COPD development. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist was followed when extracting data and appraising the selected studies. Results: Of the 4481 records identified, 30 articles were selected for full-text review, and only four of these were eligible to be included in the review. The only consistent predictor across all four models was a measure of smoking. Sex and age were used in most models, however other factors varied widely. The overall predictive performance of the models was unable to be fully assessed due to limitations in the data presented. Two of the models had good ability to discriminate between people who were correctly or incorrectly classified as at risk of developing COPD (concordance statistic 0.830-0.845). Conclusions: Overall none of the models were particularly useful in accurately predicting future risk of COPD, nor were they good at ruling out future risk of COPD. Further studies are needed to develop new prediction models and robustly validate them in external cohorts.

Systemic inflammation is an integral part of chronic obstructive pulmonary disease (COPD), and air pollution is associated with cardiorespiratory mortality, yet the interrelationships are not fully defined. We examined associations between nitrogen dioxide (NO₂) exposure (as a marker of traffic-related air pollution) and pro-inflammatory cytokines, and investigated effect modification and mediation by post-bronchodilator airflow obstruction (post-BD-AO) and cardiovascular risk. Data from middle-aged participants in the Tasmanian Longitudinal Health Study (TAHS, n = 1389) were analyzed by multivariable logistic regression, using serum interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) as the outcome. Mean annual NO₂ exposure was estimated at residential addresses using a validated satellite-based land-use regression model. Post-BD-AO was defined by post-BD forced expiratory ratio (FEV₁/FVC) < lower limit of normal, and cardiovascular risk by a history of either cerebrovascular or ischaemic heart disease. We found a positive association with increasing serum IL-6 concentration (geometric mean 1.20 (95% CI: 1.1 to 1.3, p = 0.001) per quartile increase in NO₂). This was predominantly a direct relationship, with little evidence for either effect modification or mediation via post-BD-AO, or for the small subgroup who reported cardiovascular events. However, there was some evidence consistent with serum IL-6 being on the causal pathway between NO₂ and cardiovascular risk. These findings raise the possibility that the interplay between air pollution and systemic inflammation may differ between post-BD airflow obstruction and cardiovascular diseases.