Background: Abnormal carbon monoxide diffusing capacity (DLCO) is a marker of pulmonary vascular disease and predicts the presence of pulmonary arterial hypertension (PAH) and poor prognosis in diseases such as systemic sclerosis and idiopathic pulmonary fibrosis. Little is known of its prognostic utility in World Health Organization (WHO) Group I PAH. Methods: We performed a cohort study of 408 patients with WHO Group I PAH from 1982 to 2006, with data on demographics, comorbidities, medications, functional class, laboratory tests, exercise testing, and hemodynamics. DLCO was determined upon entry into the study. We divided the cohort into tertiles based on DLCO and compared differences between groups. We used a Cox proportional hazards analysis to determine the association of DLCO with mortality, after adjusting for age, connective tissue disease etiology, functional class, pulmonary function testing variables, serum creatinine, albumin, hemoglobin, lung parenchymal abnormalities on chest computed tomography, oxygen use, and hemodynamic variables. Results: The lowest tertile of DLCO was independently associated with an increased risk of death (univariate hazard ratio [HR] = 2.7, 95% confidence interval [CI] 1.9 to 3.9, p < 0.0001; multivariate HR = 2.4, 95% CI 1.1 to 5.0, p = 0.025). On receiving operator characteristic (ROC) curve analysis, the c-statistic for the multivariate model without DLCO was 0.75, whereas the c-statistic for the multivariate model with DLCO was 0.78 (p = 0.003 by likelihood ratio test). Importantly, a multivariate model with hemodynamic variables alone (c-statistic = 0.61) was quite inferior to the multivariate model, which included DLCO. Conclusion: DLCO is an independent predictor of death in patients with WHO Group I PAH.
Bibliographical noteFunding Information:
Supported by the American Heart Association, Actelion Pharmaceuticals and the Doris Duke Charitable Foundation.
Dr. Gomberg-Maitland has received research grant support from Actelion, Gilead, Lilly ICOS, Pfizer, and United Therapeutics. She has served as a consultant for Biomarin, Gilead, Medtronic, and Pfizer.
- carbon monoxide diffusing capacity (DLCO)
- pulmonary arterial hypertension