Use of diffusing capacity of the lung for carbon monoxide may be a useful prognostic tool in patients with chronic pulmonary disease who develop pulmonary hypertension, results from a single-center retrospective cohort study found.
“Historically, COPD-PH was thought to develop as the severity of airflow obstruction, measured by Forced Expiratory Volume in one second (FEV1), and subsequent chronic hypoxemia progressed,” authors led by Aparna Balasubramanian, MD, wrote in a study published online in CHEST. “However, airflow obstruction has increasingly been noted to be insufficient in predicting clinical outcomes in the general COPD population.”
Dr. Balasubramanian of the Johns Hopkins University Division of Pulmonary and Critical Care, Baltimore, and colleagues went on to note that, while studies in COPD-PH have identified hemodynamic measures as better predictors of prognosis, these metrics require right-heart catheterization (RHC), an invasive procedure that carries its own risks. “An alternative noninvasive measure of interest is diffusing capacity of the lung for carbon monoxide (DLCO). DLCO is a measure of gas exchange reflective of the complex interactions occurring at the alveolar-capillary interface, including morphologic changes in the pulmonary vasculature,” they wrote. “Recent work by our group in a large COPD cohort has demonstrated that DLCO is an indicator of disease morbidity beyond that represented by airflow obstruction or by CT evidence of emphysema alone. This may be particularly relevant for those with COPD-PH.”
The study population consisted of 71 patients enrolled in the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and January 2018, all of whom had right-heart catheterization (RHC)–proven PH and pulmonary function testing (PFT) data within 1 year of diagnostic RHC. The researchers calculated transplant-free survival from index RHC and used Cox proportional hazard methods to determine transplant-free survival with age, pulmonary vascular resistance, FEV1, oxygen use, and N-terminal pro-brain natriuretic peptide included as covariates.
The average age of patients was 65 years, 66% were female, their average body mass index was 28.3 kg/m2, and the mean number of pack-years smoked was 44. On unadjusted analysis, the transplant-free survival was 87% at 1 year, 60% at 3 years, and 51% at 5 years. Survival was associated with reduced DLCO across the observed range of pulmonary artery pressures and pulmonary vascular resistance. The researchers found that severe DLCO impairment was associated with poorer survival (P less than .001), and when they adjusted for covariates, they found that mortality increased by 4% for every percent predicted decrease in DLCO (hazard ratio, 1.04).
“This study demonstrates that DLCO, a readily available, inexpensive, noninvasive measurement, is a strong independent predictor of mortality in COPD patients with PH,” the authors concluded. “The presented findings suggest that DLCO should be considered for inclusion in prognostic tools for COPD-PH.”
Dr. Balasubramanian and associates acknowledged certain limitations of the study, including its modest sample size and single-center design and the fact that the cohort underwent subspecialty referral and invasive testing, thereby limiting its generalizability to the larger COPD population. “The findings do, however, offer insight into clinical and physiologic characteristics at one extreme of the pulmonary vascular disease spectrum among COPD patients, and generate hypotheses regarding measures that warrant further exploration in the larger COPD population,” they wrote.
The study was supported by National Heart, Lung and Blood Institute. One of the study authors has served as a consultant to GlaxoSmithKline and Celgene and receives royalties from UpToDate for authorship. Another study author has served as a consultant for Arena, Actelion, Liquidia, and United Therapeutics, and has served on the Scientific Leadership Council of the Pulmonary Hypertension Association. He also serves on the Rare Disease Advisory Panel of the Patient Centered Outcomes Research Institute. The other study authors reported having no disclosures.
SOURCE: Balasubramanian A et al. CHEST. 2020 Mar 14. doi: 10.1016/j.chest.2020.02.047.