Lifetime Risk Factors for Post Bronchodilator Lung Function Decline: A Population-Based Study from 1st to 6th Decade

Abstract

Background: Interactions between early life and adult insults on lung function decline are not well understood, with most studies investigating pre-bronchodilator (BD) FEV1 decline. We investigated relationships between adult risk factors and post-BD lung function decline and their potential effect modification by specific early life and genetic factors. Methods: Multivariable regression was used to examine associations between adult exposures (asthma, smoking, occupational exposure, traffic pollution, atopy and obesity) and decline in post-BD spirometry between ages 45 to 53 years in the Tasmanian Longitudinal Health Study (n=857). Effect modification of these relationships by childhood respiratory risk factors including low childhood lung function, and glutathione S-transferase (GST) gene polymorphisms was investigated. Findings: Accelerated FEV1 decline was associated with baseline asthma of early onset (excess rate: -7·0; -12·5, -1·6 mL/year) and smoking (-13·8; -18·7, -9·0 mL/year). In addition, it was associated with occupational exposure to vapours/gases/dusts/fumes (-11·8: -19·0, -4·2 mL/year) only in carriers of the GSTM1 null allele (p-interaction=0·04). Findings for changes in exposure status support those for baseline exposures. Accelerated FEV1/FVC decline was associated with these factors and living <200m from main roads. Associations of occupational exposures and personal smoking with FEV1 decline were accentuated for those with lower childhood lung function (p-interaction= 0·04 and 0·06, respectively). Maternal smoking accentuated the effect of personal smoking on FEV1 decline (p-interaction=0·08). Interpretation: While establishing adult risk factors that affect post-BD lung function decline, this study provides new evidence for accentuation of individual susceptibility to adult risk factors by low childhood lung function, GSTM1 genotype and maternal smoking. These findings suggest that susceptibility to adult risk factors may be programmed in early life. Strategies should target high-risk groups to minimize synergy between potential risk factors on accelerated lung function decline. Funding Statement: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia under NHMRC project grant scheme (299901, 1021275) and NHMRC European collaborative grant scheme (1101313) as part of ALEC (Ageing Lungs in European Cohorts funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633212); 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. Declaration of Interests: Authors have no conflicts of interest Ethics Approval Statement: The study was approved by the Human Ethics Review Committees of all relevant institutions. Written informed consent was obtained from all participants.