Prolonged expiratory time constant and risk of moderate-to-severe exacerbations in stable COPD

Spirometry provides limited insight into small airway dysfunction in COPD, and evaluation of physiologic parameters such as the expiratory time constant (Tc) may offer complementary information for risk assessment. This retrospective cohort study included 1479 patients with COPD from two tertiary hospitals who underwent baseline chest computed tomography and post-bronchodilator spirometry between 2014 and 2023, with at least five years of follow-up. The Tc was computed from volume-time curves via standardized image analysis. The primary outcome was moderate-to-severe exacerbation. Subgroup analyses were conducted based on symptom severity, airflow limitation, emphysema extent, and airway wall thickness. A prolonged Tc was independently associated with an increased risk of moderate-to-severe exacerbations (adjusted hazard ratio, 1.188; 95% confidence interval, 1.028–1.373). This association was particularly evident in dyspneic patients and was more pronounced among those without a prior history of frequent exacerbations. Consistent patterns of association were observed across subgroups characterized by increased airway wall thickness, preserved diffusing capacity, and lower emphysema burden, corresponding to airway-predominant features. A threshold of 1.14 s was identified, above which the risk of exacerbation was significantly elevated. The Tc may improve individualized risk stratification by identifying patients with COPD who are at increased risk of exacerbations, even in the absence of prior exacerbation history or before the development of advanced parenchymal destruction.