Determinants of impaired lung function and lung cancer prediction among never-smokers in the UK Biobank cohort

Background: Impaired lung health represents a significant burden on global health, including chronic obstructive pulmonary disease (COPD) and lung cancer. Given its global health impact, it is important to understand the determinants of impaired lung function and its relation to lung cancer risk independent of smoking. However, to date, no study has evaluated determinants of impaired lung function in a cohort exclusively of never-smokers, who also represent a growing proportion of all lung cancers. Methods: A total of 222,274 never-smokers with reproducible spirograms were identified in the UK Biobank population-based cohort and included in the analysis. Baseline volumetric measures of lung function, including forced expiratory volumein 1-s (FEV1) and forced vital capacity (FVC), were used to define lung function impairment. Determinants of impaired lung function were evaluated using Poisson regression with robust variance estimation. The added value of lung function in lung cancer prediction was evaluated using Fine and Gray regression accounting for the competing risk of all-cause mortality. Findings: Lung function impairment was associated with low birthweight, ambient air pollution (PM2.5 mu g/mm(3)), and overweight, after adjustment for other important risk factors. We observed modest improvement in discrimination by adding lung function to our lung cancer prediction model for never-smokers. The highest optimism-corrected AUC at 3 (0.700, 95% CI: 0.654-0.734) and 5 years (0.694, 95% CI: 0.658-0.736) included FEV1 (% of GLI predicted FEV1), while the highest AUC at 7 years was based on the inclusion of FEV1/FVC (0.722, 95% CI: 0.687-0.762). Interpretation: We identified several modifiable risk factors associated with increased risk of lung function impairment among lifetime never-smokers in UKB. We achieved moderate discrimination for lung cancer risk-prediction for never-smokers, and found modest improvement with the inclusion of lung function. Fund: This study was supported by a Canada Research Chair to RJH. (c) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).