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

There are few population-based longitudinal studies on the relationship of the single breath nitrogen (SBN₂) 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 (N₂-slope) from the SBN₂ test may predict DLCO and DLCO/alveolar volume (KCO) decline, and whether the N₂-slope and DLCO are related to COPD incidence.

Participants from an observational longitudinal population study underwent a SBN₂ 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 N₂-slope and DLCO or KCO decline; (2) logistic regression to assess the association between patterns of baseline normal/abnormal N₂-slope/DLCO and COPD incidence (both GOLD and ATS-ERS criteria).

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 N₂-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 N₂-slope). Participants with abnormal N₂-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).

In this longitudinal population study, the N₂-slope is a predictor of DLCO and KCO decline, and abnormal N₂-slope combined with abnormal DLCO is related to COPD development.