Improvement in Resting Inspiratory Capacity and Hyperinflation with Tiotropium in COPD Patients with Increased Static Lung Volumes

Background: In patients with COPD, changes in inspiratory capacity (IC) have shown a higher correlation to patient-focused outcomes, such as dyspnea with exercise, than other standard spirometric measurements. Changes in IC reflect changes in hyperinflation. Tiotropium is a once-daily inhaled anticholinergic that has its effect through prolonged M3 muscarinic receptor antagonism and has demonstrated sustained improvements in spirometric and health outcomes. We sought to evaluate changes in resting IC and lung volumes after long-term administration of tiotropium.

Methods: To evaluate the effect of tiotropium, 18 micro g/d, on IC, a 4-week, randomized, double-blind, placebo-controlled study was conducted in 81 patients with stable COPD. At each of the visits (weeks 0, 2, and 4) FEV(1), FVC, IC, slow vital capacity (SVC), and thoracic gas volume (TGV) were measured prior to study drug (- 60 and - 15 min) and after study drug (30 min, 60 min, 120 min, and 180 min).

Results: Mean age was 64 years; 62% were men. Mean baseline FEV(1) was 1.12 L (43% predicted). The mean differences (tiotropium - placebo) in FEV(1) trough (morning before drug), peak, and area under the curve over 3 h values (adjusted for baseline and center differences) at week 4 were 0.16 L, 0.22 L, and 0.22 L, respectively (p < 0.01 for all); differences in IC for these variables were 0.22 L, 0.35 L, and 0.30 L (p < 0.01 for all). Differences in TGV were - 0.54 L, - 0.60 L, and - 0.70 L, respectively (p < 0.01 for all). The percentage improvement in area under the curve above baseline with tiotropium was similar among FEV(1) and lung volumes (FEV(1), 18%; FVC, 20%; SVC, 16%; IC, 16%; TGV, 14%).

Conclusions: Observed improvements in IC and reductions in TGV with once-daily tiotropium reflect improvements in hyperinflation that are maintained over 24 h.