The association of isolated small airways obstruction (SAO) with gas transfer and static lung volume measurements.

<bold>Introduction:</bold> Isolated SAO is associated with increased risk of progression to COPD over time. <bold>Aim:</bold> To determine if isolated reductions in FEF_25-75 and FEV₃/FVC are associated with impaired gas transfer and static lung volume measurements. <bold>Methods:</bold> We performed a retrospective analysis of lung function data obtained from consecutive adult patients referred to Cambridge University Hospitals between 2016 and 2023. Patients underwent spirometry, single breath gas transfer, and body plethysmography on the same visit according to ATS/ERS standards. Isolated SAO was defined for FEF_25-75 and FEV₃/FVC if a result was less than the lower limit of normal (LLN) with FEV₁/FVC and FVC ≥LLN. Multivariable regression analysis was used to investigate the association of isolated SAO with measures of diffusing capacity (TLCO), gas trapping (RV/TLC) and hyperinflation (IC/TLC), after adjusting for age, sex, BMI and smoking. <bold>Results:</bold> 12780 patients had lung function of an acceptable quality, of which 4183 (33%) had a normal FEV₁/FVC and FVC (53% female, age 57±15 years). 115 (3%) patients for FEF_25-75 and 356 (9%) for FEV₃/FVC had isolated SAO. Isolated SAO was associated with having a higher RV/TLC (FEF_25-75 β: 2.86%, 95%CI 1.92-3.80, FEV₃/FVC β: 1.66%, 95%CI 1.11-2.22, p<0.001) and lower IC/TLC (FEF_25-75 β: -2.85% 95%CI -4.06 to -1.64, FEV₃/FVC β: -1.11%, 95%CI -1.83 to -0.41 p<0.001) than those with normal spirometry. Only isolated SAO for FEV₃/FVC was associated with a lower TLCO (β: -0.18 mmol/min/kpa, 95%CI -0.35 to -0.01, p=0.034). <bold>Conclusion:</bold> Isolated SAO is associated with a mild impairment in measures of gas trapping, hyperinflation, and diffusing capacity.