Small Airways Obstruction and Mortality: Findings From the UK Biobank

Abstract

BackgroundSmall airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases and progression to chronic obstructive pulmonary disease over time. Whether SAO predicts mortality is largely unknown. Research QuestionIs spirometry-defined SAO associated with increased mortality? MethodsWe analysed data from 252,877 adult participants, aged 40-69 at baseline, in the UK Biobank who had provided good quality spirometry measurements. 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). We considered SAO to be isolated if present when 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 disease-specific mortality. We investigated sex differences in these associations and repeated the primary analysis excluding ever smokers. All models were adjusted for potential confounders such as sex, body mass index, smoking status, smoking pack-years, assessment centre, Townsend deprivation index and ethnicity. ResultsWe identified 59,744 participants with SAO of which 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (HR=1.31, 95%CI 1.26-1.36), cardiovascular (HR=1.39, 95%CI 1.29-1.51), respiratory (HR=2.20, 95%CI 1.92-2.51), and neoplasm (HR=1.23, 95%CI 1.17-1.29) mortality risk. These associations were not modified by sex. However, in never smokers, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR=1.14, 95%CI 1.07-1.20). InterpretationIndividuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease.