Improvements With Tiotropium Maintenance Therapy in COPD Patients Without Dyspnea.

Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations emphasize symptom-driven management, which may limit the use of maintenance bronchodilator therapy in patients without dyspnea. In this exploratory post hoc analysis of the tiotropium in early-stage chronic obstructive pulmonary disease (Tie-COPD) trial, we assessed tiotropium in 305 patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) and a modified Medical Research Council dyspnea score of 0 (157 tiotropium, 148 placebo). Over 2 years, tiotropium maintained a higher pre-bronchodilator forced expiratory volume in 1 s (FEV1) than placebo (adjusted between-group differences 143-183 mL; all p < 0.001). The lung function benefit was similar across subgroups defined by age, body mass index, symptom burden, blood eosinophil count, GOLD stage, and smoking (all p for interaction >0.05). The annual exacerbation rate was lower with tiotropium (adjusted incidence rate ratio 0.51, 95% confidence interval [CI] 0.32, 0.82; p = 0.005), as was the risk of a first clinically important deterioration (adjusted hazard ratio 0.55, 95% CI 0.43, 0.70; p < 0.001), whereas COPD assessment test and clinical COPD questionnaire scores did not differ. These hypothesis-generating findings indicate that tiotropium may provide benefits in lung function and exacerbations in COPD without dyspnea, suggesting that a strictly symptom-based treatment criterion warrants prospective reevaluation.