Small airways obstruction and mortality in the UK Biobank

<bold>Background:</bold> Small airways obstruction (SAO) may be an indicator of early lung disease, associated with respiratory symptoms and progression to COPD. However, whether SAO can also predict mortality remains unknown. <bold>Methods:</bold> We analysed high-quality spirometry data from 252,877 UK Biobank participants. We defined SAO as the ratio of the forced expiratory volume in three seconds to the forced expiratory volume in six seconds less than the lower limit of normal (FEV3/FEV6<LLN) and isolated SAO if the forced expiratory volume in one second to FEV6 ratio was normal (FEV1/FEV6≥LLN). We used a multivariable Cox regression model to assess the association of SAO, and isolated SAO, with all-cause and cause-specific mortality. We investigated the role of sex and repeated the analyses on never-smokers. All models were adjusted for confounders: sex, smoking status, smoking pack-years, assessment centre, Townsend deprivation index and ethnicity. <bold>Results:</bold> A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. We identified 59,744 participants with SAO of which 40.2% had isolated SAO. We observed an increased mortality risk among participants with SAO for all-cause (HR 1.25, 95%CI 1.21-1.29), cardiovascular (HR 1.28, 95%CI 1.18-1.39), respiratory (HR 2.11, 95%CI 1.84-2.41), and neoplasm-related (HR 1.21, 95%CI 1.15-1.26) mortality. Isolated SAO was also associated with an increased mortality risk. We observed increased respiratory and cardiovascular mortality risk in never smokers with SAO. There were no differences by sex. <bold>Conclusion:</bold> People with SAO have an increased risk of all-cause and disease-specific mortality. However further research is needed to determine the role of SAO in influencing mortality outcomes.