Differences in all-cause mortality by sex in obstructive and restrictive lung diseases

Chronic pulmonary diseases are major contributors to death for males and females, yet the extent to which mortality risk within individual pulmonary diseases differs between the sexes remains understudied. We hypothesized that mortality risk differs between males and females with obstructive and restrictive lung diseases after accounting for demographic factors, comorbidities, smoking history, disease severity, and neighborhood-level resource availability. We conducted a retrospective cohort study of adults aged 18-95 years (median age 67 years) with obstructive lung disease (OLD) or restrictive lung disease (RLD) who had their first pulmonary medicine visit at the Cleveland Clinic Health System between 2013 and 2025. Patients were included if they had ≥2 encounters with an OLD or RLD diagnosis and ≥1 pulmonary function test. Multivariable Cox proportional hazards models were used to estimate sex-specific risk of all-cause mortality and by disease subtype after adjusting for demographic characteristics and other clinical risk factors as covariates. The cohort included 70,218 patients (OLD n=49,254, RLD n=20,964) with a median duration of follow-up of 2.6 years. In OLD, males had a 37% higher unadjusted risk of death (hazard ratio [HR] 1.37, 95% CI 1.32-1.43), which remained elevated after adjustment (HR 1.16, 95% CI 1.11-1.20). In RLD, males had a 69% higher unadjusted mortality risk (HR 1.69, 95% CI 1.59-1.80) with persistent excess risk after adjustment (HR 1.49, 95% CI 1.36-1.63). Survival differences persisted after accounting for comorbidities, Area Deprivation Index, smoking history, or differences in pulmonary function.Males with obstructive and restrictive lung disease experienced consistently higher all-cause mortality compared to females in this cohort. These findings highlight sex-associated differences in survival across subtypes of obstructive and restrictive lung disease and underscore the need for future work to clarify underlying mechanisms and further refine prognostic risk stratification across a wide spectrum of chronic pulmonary diseases.