Impaired diffusing capacity and COPD incidence in adults with symptoms and normal spirometry

Background: Impaired diffusing capacity of the lung (DLCO) in the absence of post-bronchodilator (BD) airflow obstruction has been proposed as a marker of ‘Pre-COPD’. However, the relationship between impaired DLCO and subsequent lung function decline and COPD incidence has not been examined in-depth. Methods: We conducted an observational study of adults aged between 40 and 70 years who were evaluated at a multi-centre lung function laboratory in Australia between 2014 and 2024. Adults referred with respiratory symptoms or a clinical suspicion of obstructive airways disease with follow-up spirometry obtained ≥12 months after the initial assessment were included. The relationship between impaired DLCO and subsequent lung function decline and COPD incidence was assessed among those with normal spirometry at baseline. Results: A total of 266 patients with a mean age of 53.2 (SD 12.8) years were evaluated after a median follow-up of 2.3 [IQR 1.5 to 3.3] years. We found no evidence of an association between impaired DLCO (below the lower limit of normal) and annualised rate of decline in post-BD FEV₁ (MD -0.1 % predicted per-year, 95%CI -1.3 to 1.2), FVC (−0.4 % predicted, 95%CI -1.6 to 0.8) or FEV₁/FVC (−0.1 % per-year, 95%CI -0.1 to 0.1). The sensitivity of impaired DLCO for COPD incidence was 40 %, and specificity 82 %. Findings were similar in sub-samples limited to current and former smokers, and when impaired DLCO was defined as < 80 % predicted. Conclusion: Impaired DLCO was not an effective discriminator of lung function decline or COPD incidence in this real-world cohort.