The Independent Contribution of Estimated Dead Space Fraction to Other Common Variables for Survival Analysis in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Abstract Objective: Mortality due to chronic obstructive pulmonary disease (COPD) is increasing. However, dead space fractions at rest (VD/VTrest) and peak exercise (VD/VTpeak) and variables affecting health-related quality of life and survival have not been evaluated. This study aimed to investigate these issues. Methods: This retrospective observational cohort study was conducted from 2010-2020. Patients with COPD who smoked, met the GOLD criteria, had available demographic, complete lung function test (CLFT), medication, acute exacerbation of COPD (AECOPD), Charlson Comorbidity Index, and survival data were enrolled. VD/VTrest and VD/VTpeak were estimated (estVD/VTrest and estVD/VTpeak). Univariate and multivariable Cox proportional hazard regression analyses with stepwise variable selection were performed to estimate hazard ratios of all-cause mortality. Results: Overall, 14,910 patients with COPD were obtained from the hospital database, and 456 were analyzed after excluding those without CLFT or meeting the lung function criteria. Of the 456 subjects, 81% had GOLD stages 2 and 3, highly elevated dead space fractions, mild air-trapping and diffusion impairment. The hospitalized AECOPD rate was 0.60±2.84/person/year. Forty-eight subjects (10.5%) died, including 30 with advanced cancer. The incidence density of death was 6.03 per 100 person-years. The crude risk factors for mortality were elevated estVD/VTrest, estVD/VTpeak, ³2 hospitalizations for AECOPD, advanced age, body mass index (BMI) <18.5 kg/m2, and cancer. The protective factors were high peak expiratory flow%, adjusted diffusing capacity%, alveolar volume%, and BMI 24-26.9 kg/m2. In stepwise Cox regression analysis after excluding cancer, estVD/VTrest and BMI <18.5 kg/m2 were risk factors, whereas BMI 24-26.9 kg/m2 was protective. Conclusion: Cancer was the main cause of all-cause mortality in this study; however, estVD/VTrest and BMI were independent prognostic factors for COPD after excluding cancer. VD/VTrest can be estimated with the predictive formula; however, its clinical implications for survival prediction should be interpreted with caution until the formula has been validated.