Original clinical science
Carbon monoxide diffusing capacity and mortality in pulmonary arterial hypertension

https://doi.org/10.1016/j.healun.2009.07.005Get rights and content

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.

Section snippets

Methods

We studied patients in the Pulmonary Hypertension Connection (PHC) registry, which was initiated in March 2004, as described elsewhere.19 All patients evaluated at a single practice over time at three different university hospitals (University of Illinois at Chicago, Rush University Medical Center, and University of Chicago) between 1982 and 2006 were entered into the registry. Patients were entered retrospectively from 1982 to February 2004 and prospectively from March 2004 through 2006.

Results

The mean age of patients upon entry into the study was 48 ± 14 years and 77% were female. The cohort was divided into tertiles: Tertile I—DLCO <43% (range 11% to 42.5%) of predicted; Tertile II—DLCO 43% to 64% of predicted; and Tertile III—DLCO >64% (range 65% to 120%) of predicted. Table 1 lists differences in demographic, clinical, laboratory, exercise testing, and hemodynamic data by tertile of DLCO.

Reduced DLCO was associated with increased age, CTD etiology, poor functional class, oxygen

Discussion

In our study, the lowest tertile of DLCO was independently associated with death. Advantages of our study include the large number of patients with PAH and the comprehensive clinical characterization of the study subjects. To our knowledge, ours is the first study to associate reduction in DLCO with mortality in patients with PAH. Our finding of an independent association between the lowest tertile of DLCO (<43% of predicted) and death is consistent with studies of idiopathic pulmonary fibrosis

Disclosure Statement

The authors thank Tobias Perrino for help with data collection and validation of clinical data. We also thank Virginia Steen, MD, for advice and critical review during the early stages of this manuscript.

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.

Dr Chandra, Dr Archer, Dr Thenappan, and Dr Rich have no conflicts of interest to disclose.

References (40)

Cited by (0)

Supported by the American Heart Association, Actelion Pharmaceuticals and the Doris Duke Charitable Foundation.

S.C. and S.J.S. contributed equally to this study.

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