Improvements With Tiotropium Maintenance Therapy in COPD Patients Without Dyspnea

ABSTRACT 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.