Association of FeNO Decline Rate with Symptom Improvement in COPD: A Real-World Observational Study

Background: The association between relative changes in fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) with patient-reported symptoms improvements remains uncertain. Objective: To assess the association of the rate of FeNO decline with the achievement of the minimum clinically important difference (MCID) in COPD Assessment Test (CAT) score. Methods: We conducted a single-center, retrospective real-world study involving 111 adults with COPD. Patients were classified into two groups: those with symptom improvement (CAT decline ≥ 2 points) and those with no improvement (CAT decline < 2 points). Logistic regression evaluated associations between FeNO decline rate and CAT MCID, adjusting for clinically relevant covariates. Receiver operating characteristic (ROC) curve analysis estimated the discriminatory performances of it. Results: Of 111 patients, 53 (47.7%) achieved the CAT MCID. Multivariate logistic regression found that the rate of FeNO decline was independently associated with symptom improvement (adjusted OR 2.08, 95% CI 1.01– 4.29, P =0.047). Baseline CAT also showed association with symptom improvement (adjusted OR 1.06, 95% CI 1.00– 1.12, P =0.034). BMI showed a positive trend but without statistical significance (adjusted OR 1.13, 95% CI 1.00– 1.29, P =0.056). AUC of FeNO decline rate, baseline CAT, combined with BMI in discriminating CAT MCID were 0.713 (95% CI 0.617, 0.809). Conclusion: The rate of FeNO decline was significantly associated with clinically meaningful CAT improvement in this study, which indicated dynamic measures of type-2 inflammation can complement blood eosinophil counts to refine phenotyping and inform precision management in COPD. Keywords: COPD, the rate of FeNO declined, CAT MCID, type-2 inflammation, treatable traits, precision medicine