Lifetime Risk Factors for Pre- And Post-Bronchodilator Lung Function Decline A Population-based Study

Rationale: Interactions between early life and adult insults on lung function decline are not well understood, with most studies investigating prebronchodilator (pre-BD) FEV₁ decline. Objectives: To investigate relationships between adult risk factors and pre- and post-BD lung function decline and their potential effect modification by early life and genetic factors. Methods: Multiple regression was used to examine associations between adult exposures (asthma, smoking, occupational exposures, traffic pollution, and obesity) and decline in both pre- and post-BD spirometry (forced expiratory volume in 1 s [FEV₁], forced vital capacity [FVC], and FEV₁/FVC) between ages 45 and 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 GST (glutathione S-transferase) gene polymorphisms, was investigated. Results: Baseline asthma, smoking, occupational exposure to vapors/gases/dusts/fumes, and living close to traffic were associated with accelerated decline in both pre- and post-BD FEV₁. These factors were also associated with FEV₁/FVC decline. Occupational exposure to aromatic solvents was associated with pre-BD but not post-BD FEV₁ decline. Maternal smoking accentuated the effect of personal smoking on pre- and post-BD FEV₁ decline. Lower childhood lung function and having the GSTM1 null allele accentuated the effect of occupational exposure to vapors/gases/ dusts/fumes and personal smoking on post-BD FEV₁ decline. Incident obesity was associated with accelerated decline in FEV₁ and more pronounced in FVC. Conclusions: This study provides new evidence for accentuation of individual susceptibility to adult risk factors by low childhood lung function, GSTM1 genotype, and maternal smoking.