C73-12 Functional Small Airway Disease as a Treatable Trait for Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study

Background Chronic obstructive pulmonary disease (COPD) requires new markers as treatable traits to effectively guide precise treatment, owing to the disease’s great heterogeneity of clinical presentation and progression. Previous studies evidenced that CT-defined functional small airway disease (fSAD) was associated with poorer prognosis in COPD. We hypothesized that fSAD could be a treatable trait in COPD and provide additional advantages for precise treatment. Methods The ECOPD Study was a three-year, prospective cohort study conducted in China from July 2019 to September 2024. Eligible participants in this study included those who had completed spirometry, questionnaires, and CT in the ECOPD Study at baseline. The follow-up spirometry and acute exacerbation assessments were arranged annually. We excluded COPD patients with classic treatable traits (including CAT score ≥10, mMRC score ≥2, postbronchodilator FEV1 <60 % predicted, and frequent exacerbations). The definition of PRMfSAD referred to the areas of non-emphysematous gas trapping, and CT-defined fSAD was considered when baseline PRMfSAD ≥15%. The study outcomes were lung function decline and exacerbations. Findings 1462 participants were eligible for this study, and 1373 (94%) completed at least one follow-up spirometry and were added to the final analyses. Among the three groups, the patients with fSAD significantly displayed a most rapid rate whose annual postbronchodilator FEV1 decline rate was 51 confidence intervals [CI]: 37-65 ml/year (vs. patients with fSAD; patients without fSAD: 31 [95%CI: 19-42] ml/year, adjusted P < 0.001; normal spirometry: 34 [95%CI: 27-41] ml/year, adjusted P < 0.001). No significant difference was found in the annual decline of postbronchodilator FEV1 between patients without fSAD and normal spirometry. Similar results were shown in acute exacerbations. Interpretation Our results indicate that fSAD is a potential treatable trait in COPD patients. Further non-inferiority clinical trials are needed to validate the effectiveness of deciding whether to take medication based on fSAD in COPD treatment. This abstract is funded by: none