Why Sleep Matters in COPD: Cluster-Derived Sleep Phenotypes Reveal Distinct Physiological, Comorbidity and Survival...

Sleep disturbances are highly prevalent in chronic obstructive pulmonary disease (COPD) but are not incorporated into current phenotypic classifications. We examined whether multidimensional sleep data identify clinically relevant patterns in COPD and whether these patterns are associated with all-cause mortality.

In a clinical cohort of 205 patients with COPD, home-based sleep assessment was performed using the WatchPAT™ device. Fifteen complementary variables reflecting sleep duration and architecture, nocturnal oxygenation, sleep-disordered breathing, and daytime sleepiness were analysed using Partitioning Around Medoids clustering. The resulting phenotypes were characterised by pulmonary function, gas exchange, functional capacity, systemic biomarkers, and comorbidity burden. Longitudinal follow-up was available for 199 participants; survival was assessed using Kaplan-Meier analysis and Cox regression adjusted for age, sex, post-bronchodilator FEV₁ and positive airway pressure (PAP) treatment.

Five distinct sleep phenotypes were identified: preserved sleep physiology (good sleepers, 20.5%), curtailed sleep duration (short sleepers, 33%), altered sleep architecture with REM suppression (light sleepers, 18.5%), predominant nocturnal hypoxaemia (hypoxic sleepers, 20%), and severe sleep-disordered breathing (apnoeic sleepers, 8%). Despite similar airflow limitation and COPD symptom burden, phenotypes differed in gas exchange, functional capacity, systemic inflammation, and cardiometabolic comorbidities. During a median follow-up of 4.2 years, 56 participants (28.1%) died. Compared with good sleepers, hypoxic sleepers had a higher hazard of death after adjustment for age, sex, and FEV₁ (HR 2.80, 95% CI 1.05-7.44). Following adjustment for PAP treatment, a higher mortality hazard was also observed among untreated apnoeic sleepers (HR 6.16, 95% CI 1.56-24.38).

Multidimensional sleep phenotyping identified clinically distinct clusters of patients with COPD beyond conventional spirometric severity and apnoea-hypopnoea index (AHI)-defined sleep-disordered breathing. These findings support sleep as a clinically relevant dimension of COPD heterogeneity, and warrant prospective validation of sleep-related traits and their clinical outcomes.