Lung function decline and incidence of chronic obstructive pulmonary disease in participants with spirometry-defined small airway dysfunction: a 15-year prospective cohort study in China

Small airway dysfunction (SAD) is common but little is known about the longitudinal prognosis of spirometry-defined SAD. Therefore, we aimed to evaluate the risk of lung function decline and incident chronic obstructive pulmonary disease (COPD) of spirometry-defined SAD. It was a population-based prospective cohort study conducted in Guangdong, China. Participants were enrolled in the years 2002, 2008, 2012, 2017, and 2019, and those who completed baseline demographic data, a standardized epidemiological questionnaire for COPD, and spirometry were included. Follow-up visits were conducted every three years after enrolment, with a maximum follow-up time of 15 years and a minimum follow-up time of 3 years. Spirometry-defined SAD was defined as having at least two out of three parameters (maximal mid-expiratory flow, forced expiratory flow 50%, and forced expiratory flow 75%) below 65% of the predicted value. Non-obstructive SAD and obstructive SAD were further differentiated based on the presence of airflow obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] < 0.70). Pre- and post-bronchodilator spirometry measurements were analyzed separately. Pre-bronchodilator spirometry dataset included 4680 participants (mean age 55.3 [10.8] years, 2194 [46.9%] males). Participants with pre-bronchodilator SAD had a significantly faster annual decline of FEV1 % of predicted value (0.31 ± 0.05 vs. 0.20 ± 0.03 %/year; difference: 0.12 [95% confidence interval: 0.01-0.23]; P = 0.023), FVC, and FVC % of predicted value compared to those without pre-bronchodilator SAD. The annual decline of lung function in participants with pre-bronchodilator non-obstructive SAD was not significantly different from that in pre-bronchodilator healthy controls, but they were more likely to progress to spirometry-defined COPD (adjusted hazard ratio: 2.92 [95% confidence interval: 2.28-3.76], P < 0.001). Post-bronchodilator spirometry dataset yielded similar results. Individuals with spirometry-defined SAD have a faster decline in lung function compared to those without SAD, and non-obstructive SAD is more likely to progress to spirometry-defined COPD. Chinese Clinical Trials Registration ChiCTR1900024643. Registered on 19 July 2019.