Natural Course of the Diffusion Capacity for Carbon Monoxide in COPD: Importance of Sex

Background: The value of the single breath diffusion capacity for carbon monoxide (DLco) relates to outcomes in COPD patients. However, little is known about the natural course of DLco over time, the intersubject variability and the factors that may influence DLco progression. Research question: What is the natural course of DLco in COPD patients over time, and which other factors, including sex differences could influence this progression? Study design and methods: We phenotyped 602 smokers (33% women) of which 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function including DLco was monitored annually over five years. A random-coefficient model was used to evaluate DLco changes over time. Results: The mean (±SE) yearly decline in DLco% in COPD patients was 1.34 ± 0.015%/year. This was steeper compared with non-COPD controls (0.04 ± 0.032%/year, p=0.004). Sixteen percent of the COPD patients vs 4.3% of the controls, had a statistically significant DLco% slope annual decline (4.14%/year). At baseline, women with COPD had lower DLco values (11.37 ± 2.27%, p \u3c0.001) in spite of a higher FEV1% than men. Compared to men, women with COPD had a steeper DLco annual decline of 0.89 ± 0.42 %/year, (p= 0.039). Interpretation: Patients with COPD have an accelerated decline in DLco compared to smokers without the disease. However, the decline is slow and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline of DLco values in women compared to men, suggests a differential impact of sex in gas exchange function. Keywords: COPD; Gender; Lung Function Decline; Monoxide Carbone Diffusion Capacity