On the role of abnormal DL_COin ex-smokers without airflow limitation: Symptoms, exercise capacity and hyperpolarised helium-3 MRI

Background: The functional effects of abnormal diffusing capacity for carbon monoxide (DL_CO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood. Objective: We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DL _CO with a group of ex-smokers with normal spirometry and DL _CO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD. Methods: We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George's Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 (³He) MRI. The 6MWT distance (6MWD), SGRQ scores, ³He MRI apparent diffusion coefficients (ADC) and CT attenuation values below -950 HU (RA₉₅₀) were evaluated. Results: Of 38 ex-smokers without COPD, 19 subjects had abnormal DL_CO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA₉₅₀ (p=0.53) compared with 19 ex-smokers with normal DL _CO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA₉₅₀ (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DL_CO. There was a significant correlation for ³He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=-0.51, p=0.0002). Conclusions: In ex-smokers with normal spirometry and CT but abnormal DL _CO, there were signi ficantly worse symptoms, 6MWD and ³He ADC compared with ex-smokers with normal DL_CO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DL_CO and hyperpolarised ³He MRI in ex-smokers without COPD.