Small Airways and Pulmonary Diffusing Capacity Decline in an 8‐Year Longitudinal Population Study

Background and Objective There are few population‐based longitudinal studies on the relationship of the single breath nitrogen (SBN 2 ) test (which functionally explores the small airways) with pulmonary diffusing capacity for carbon monoxide (DLCO). This study aimed to evaluate whether the slope of phase 3 (N 2 ‐slope) from the SBN 2 test may predict DLCO and DLCO/alveolar volume (KCO) decline, and whether the N 2 ‐slope and DLCO are related to COPD incidence. Methods Participants from an observational longitudinal population study underwent a SBN 2 test at baseline, and DLCO and spirometry at both baseline and follow‐up, 8 years apart. Multivariable regressions adjusted for sex, age, height, and smoking status were run: (1) linear regression to assess the association between N 2 ‐slope and DLCO or KCO decline; (2) logistic regression to assess the association between patterns of baseline normal/abnormal N 2 ‐slope/DLCO and COPD incidence (both GOLD and ATS‐ERS criteria). Results Six hundred and eighty‐seven participants (54.6% males, mean age 37.0 years) showed a mean DLCO decline of −0.12 ± 0.76 mL/mmHg/min/year, a mean KCO decline of −0.03 ± 0.12 mL/mmHg/min/L/year, COPD incidence of 9.0% (GOLD) and 3.9% (ATS‐ERS). The N 2 ‐slope was significantly associated with DLCO and KCO decline (−0.137 mL/mmHg/min/year and −0.014 mL/mmHg/min/L/year, respectively, for a one‐unit change in N 2 ‐slope). Participants with abnormal N 2 ‐slope and DLCO had the highest risk of developing COPD as measured by GOLD and ATS‐ERS criteria (RR 4.42, 95% CI 1.20–16.26, and 6.68, 95% CI 1.48–30.23, respectively). Conclusion In this longitudinal population study, the N 2 ‐slope is a predictor of DLCO and KCO decline, and abnormal N 2 ‐slope combined with abnormal DLCO is related to COPD development.