Effect of tiotropium on spontaneous expiratory flow–volume curves during exercise in GOLD 1-2 COPD

This substudy of a large, randomized, controlled trial (NCT01072396) examined tiotropium (18 μg qd) effects on dynamic hyperinflation during constant work rate treadmill exercise. Areas-under-the-spontaneous expiratory flow-volume (SEFV)-curves were compared in 20 COPD patients and 16 age-matched untreated controls, using rectangular area ratio (RAR) between peak intrabreath and end-expiratory flow. Seven patients exhibited SEFV curve concavity with RAR ≤ 0.5 (RARlow) in ≥1 test without tiotropium; (mean ± SD FEV₁: 1.60 ± 0.59 L; 63.4 ± 14.0%predicted). In RAR(low) patients, tiotropium increased end-exercise inspiratory capacity (IC, 2.10 ± 0.05 vs. 1.89 ± 0.05 L, tiotropium vs. placebo; p = 0.045) and RAR (0.57 ± 0.02 vs. 0.53 ± 0.02; p < 0.001). Patients without SEFV curve concavity with RAR > 0.5 (n = 13; RAR(high), had higher screening FEV₁ (2.15 ± 0.47 L; 79.6 ± 10.1%predicted) versus RARlow patients and no difference in end-exercise IC and RAR between tiotropium and placebo (IC: 2.24 ± 0.03 vs. 2.17 ± 0.03 L; RAR: 0.63 ± 0.005 vs. 0.62 ± 0.005). RAR and%predicted IC at peak exercise were positively correlated in RAR(low) patients (R² = 0.43, p = 0.0002).