Single breath diffusion capacity for carbon monoxide shows greater decline over time in COPD patients compared with controls, but declines significantly more in women compared with men, according to data from 602 adults with a history of smoking.
In previous studies, diffusion capacity for carbon monoxide (DLco) has been associated with decreased exercise capacity and poor health status in patients with COPD, but its association as a measure of disease progression has not been well studied, wrote Ciro Casanova, MD, of Hospital Universitario La Candelaria, Spain, and colleagues.
In a study published in the journal CHEST®, the researchers identified 506 adult smokers with COPD and 96 adult smoker controls without COPD. Lung function based on single breath DLco was measured each year for 5 years. The study population was part of the COPH History Assessment in SpaiN (CHAIN), an ongoing observational study of adults with COPD. COPD was defined as a history of at least 10 pack-years of smoking and a post-bronchodilator FEV1/FVC greater than 0.7 after 400 micrograms of albuterol, the researchers said.
During the 5-year period, the average overall annual decline in DLco was 1.34% in COPD patients, compared with .04% in non-COPD controls (P = .004). Among COPD patients, age, body mass index, FEV1%, and active smoking were not associated with longitudinal change in DLco values, the researchers said.
Notably, women with COPD at baseline had lower baseline DLco values compared with men (11.37%) and a significantly steeper decline in DLco (.89%) compared with men (P = .039). “Being a woman was the only factor that related to the annual rate of change in DLco,” the researchers said.
In a subgroup analysis, the researchers identified 305 COPD patients and 69 non-COPD controls who had at least 3 DLco measurements over the 5-year study period. In this group, 16.4% patients with COPD and 4.3% smokers without COPD showed significant yearly declines in DLco of –4.139% and –4.440%, respectively. Among COPD patients, significantly more women than men showed significant DLco declines (26% vs. 14%, P = .005). No significant differences were observed in mortality or hospitalizations per patient-year for COPD patients with and without DLco decline, the researchers said.
The study findings were limited by several factors including the lack of annual measurements of DLco among some patients, potential variability in the instruments used to measure DLco, and the absence of computerized tomography data for the chest, the researchers noted. However, the results support the value of the test for COPD progression when conducted at 3- to 4-year intervals, given the slow pace of the decline, they said. More research is needed, but “women seem to have a different susceptibility to cigarette smoke in the alveolar or pulmonary vascular domains,” they added.
DLco remains a valuable marker
The study is important because the usual longitudinal decline of diffusion capacity, an important physiological parameter in patients with COPD, was unknown, Juan P. de Torres, MD, of Queen’s University, Kingston, Ont., said in an interview.
“The finding of a different longitudinal decline of DLco in women was a surprise,” said Dr. de Torres, who was a coauthor on the study. “We knew from previous works from our group that COPD has a different clinical and prognostic behavior in women with COPD, but this specific finding is novel and important,” he said.
“These results provide information about the testing frequency (3-4 years) needed to use DLco as a marker of COPD progression in clinical practice,” Dr. de Torres added.
“What is the driving cause of this sex difference is unknown. We speculate that different causes of low DLco in COPD such as degree of emphysema, interstitial lung abnormalities, and pulmonary hypertension, may have a different prevalence and progression in women with COPD,” he said.
Looking ahead, “Large studies including an adequate sample of women with COPD is urgently needed because they will be the main face of COPD in the near future,” said Dr. de Torres. “Sex difference in their physiological characteristics, the reason to explain those differences and how they behave longitudinally is also urgently needed,” he added.
The study was supported in part by AstraZeneca and by the COPD research program of the Spanish Respiratory Society. The researchers and Dr. de Torres had no financial conflicts to disclose.