Sex Differences in Long-Term Survival of Chronic Obstructive Pulmonary Disease Patients following Initiation of Home Noninvasive Ventilation after Acute Hospitalization due to Respiratory Failure

INTRODUCTION: Home noninvasive ventilation (HNIV) is an established therapy for chronic obstructive pulmonary disease (COPD) with chronic respiratory failure. However, outcomes following HNIV initiation after discharge from the hospital after acute COPD exacerbation remain poorly investigated, in particular sex-related factors.

METHODS: We conducted a single-center, retrospective cohort study on COPD patients admitted to our respiratory care unit (RCU) for acute exacerbation with respiratory failure who were discharged home with newly established HNIV between 2013 and 2019. The primary endpoint was all-cause mortality after discharge from RCU. Sex-stratified survival analysis was performed using Kaplan-Meier curves, Cox proportional hazards models, and interaction models incorporating sex and clinical covariates, including lung function test and blood gases assessed at discharge.

RESULTS: A total of 84 patients fulfilled all inclusion and exclusion criteria. The median age was 74 (IQR: 68-77) years, the male-to-female ratio was 1.4:1, and the median forced expiratory volume in 1 s (FEV 1) at discharge was 25 (19.3-35.6)% predicted. Median survival was 158 (47-301) weeks, and Kaplan-Meier analysis demonstrated a longer survival time in males than in females (217 [77-434] vs. 130 [26-226] weeks; p = 0.036). After adjustment for age, FEV 1% and other significant sex-dependent variables, female sex remained an independent predictor of increased mortality (HR [95% CI], 2.13 [1.01-4.49]; p = 0.046). Interaction analysis confirmed improved model fit with sex-by-covariate terms (χ2 = 12.85, p = 0.045; C-index = 0.71). Higher FEV 1% was protective overall (HR [95% CI], 0.94 [0.86-0.99]; p = 0.028), but this benefit was only present in men (interaction p = 0.016). In a subgroup of patients, diffusing capacity of the lung for carbon monoxide (DLCO) data were available. Compared to males, females had lower DLCO and higher pCO 2 levels at hospital discharge, which may explain the observed sex difference in survival.

CONCLUSION: In COPD patients released home with newly established HNIV after hospitalization for acute exacerbation with respiratory failure, even after adjustment for established clinical covariates, female sex was associated with worse survival. FEV 1% was also associated with survival; however, only in males and not in females, indicating sex-specific disease trajectories. These findings highlight the importance of incorporating sex-by-covariate interactions into prognostic models and the need for sex-tailored management strategies in advanced COPD.