Defining a Phenotype of Severe COPD Patients Who Develop Chronic Hypercapnia

Introduction: Chronic hypercapnia, defined by elevated blood CO levels, is a serious complication most prevalent in severe COPD. It negatively impacts quality of life, increases hospitalization rates, and elevates mortality risks. However, not all severe COPD patients develop chronic hypercapnia, and its underlying mechanisms remain unclear. Identifying clinical and pathophysiological predictors of hypercapnia is essential for tailored treatment strategies. This study investigates the relationship between hypercapnia and patient characteristics, lung function, and CT scan features to identify potential therapeutic targets.

Methods: This cross-sectional study included 1526 COPD patients from three cohorts: a standard care cohort and two research cohorts (NCT04023409; NCT03053973). Data collected included demographic and clinical information, blood gases, lung function (FEV, FVC, TLC, RV, DLCOc), and high-resolution CT scans (lung volumes, air trapping, emphysema scores, airway wall thickness (Pi10), and diaphragm indices).

Results: Hypercapnia prevalence increased with COPD severity. Hypercapnic patients were older, more likely to smoke, and had more comorbidities. They exhibited lower FEV and FVC, and higher RV/TLC ratios, with CT scans showing lower emphysema scores and greater Pi10. Multivariate analysis identified lower PaO, FEV% predicted, and emphysema scores, along with higher RV/TLC ratios and NT-proBNP levels, as independent predictors of PaCO, collectively explaining 46.3 % of the variance.

Conclusion: COPD patients with chronic hypercapnia are characterized by higher smoking rates, lower PaO levels, poorer lung function, less emphysema, and increased airway pathology. These findings underscore the multifactorial nature of hypercapnia in COPD, highlighting the need for personalized therapeutic strategies targeting these factors to improve outcomes.