Clinical characteristics, symptom burden, and pulmonary function trajectories of spirometry- and MMEF-defined...

Bronchodilator responsiveness (BDR) is a common indicator in chronic obstructive pulmonary disease (COPD), but its clinical relevance remains controversial. Traditional spirometry may fail to detect small airway reversibility, which can be captured by maximum mid-expiratory flow (MMEF). The clinical significance of combined-BDR (integrating spirometric indices and MMEF) in guiding phenotype-based and individualized COPD management under current Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations remains unclear. This study aimed to investigate the clinical significance of combined-BDR in patients with COPD.

In this single-center prospective study, a total of 137 patients with stable COPD were enrolled [post-bronchodilator forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) <0.70, age ≥40 years, smoking ≥10 pack-years]. Combined-BDR was defined as ≥12% and ≥200 mL increase in FEV₁ or FVC and/or ≥30% increase in MMEF post-bronchodilator. Symptoms [COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and St. George's Respiratory Questionnaire for COPD (SGRQ-C)], lung function, and moderate-to-severe exacerbations were assessed at baseline and 12 months. Multivariable regression and linear mixed-effects models were used to evaluate the associations between combined-BDR and clinical outcomes.

Of 137 patients, 49 (35.8%) exhibited Combined-BDR, while 88 (64.2%) did not. Baseline demographic characteristics, including age, sex, body mass index (BMI), smoking status, and fractional exhaled nitric oxide (FeNO) levels, were comparable between the two groups. Patients with combined-BDR had significantly higher mMRC scores (P<0.01), CAT total scores (11.73±6.29 vs. 9.26±5.71, P=0.02), and lower baseline FEV₁ (1.32±0.45 vs. 1.78±0.72 L, P<0.001). Over 12 months, patients with combined-BDR demonstrated greater improvements in pre-bronchodilator FEV₁ [adjusted mean difference 0.12 L, 95% confidence interval (CI): 0.02-0.21, P=0.02] and FVC (adjusted mean difference 0.22 L, 95% CI: 0.04-0.39, P=0.02).

Combined-BDR identifies a distinct COPD phenotype characterized by a higher baseline symptom burden but greater functional improvement following inhaled therapy, highlighting its potential value for phenotype-guided and individualized disease management.