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Tiotropium and Simplified Detection of Dynamic Hyperinflation^*

^* From the Department of Pharmacy Services (Dr. Shinar), Lakewood Regional Medical Center, Lakewood, CA; and Geffen School of Medicine at UCLA (Dr. Gelb), Los Angeles, CA; and Faculty of Medicine (Drs. Gutierrez, Rodrigues, Chapman, and Zamel, and Ms. McClean), University of Toronto, Toronto, ON. Canada.

Correspondence to: Arthur F. Gelb, MD, FCCP, 3650 E South St, Suite 308, Lakewood, CA 90712; e-mail: afgelb{at}msn.com

Abstract

Study objective: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium.

Methods: IC and FEV₁ were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 ± 10 years [± SD]) before and after 30 days of treatment with tiotropium bromide, 18 µg. Patients were encouraged to maintain a constant tidal volume during MPH.

Results: At baseline, mean FEV₁ was 1.5 ± 0.1 L (± SE) [57 ± 1.6% of predicted], mean FVC was 2.6 ± 0.1L (77 ± 1.8% of predicted), and mean FEV₁/FVC was 56 ± 1%. After 180 µg of aerosolized albuterol sulfate, mean FEV₁ was 1.7 ± 0.1 L (63 ± 1.5% of predicted) [p < 0.001] and mean FEV₁/FVC was 58 ± 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 ± 0.04L (p < 0.0001); FEV₁ of 0.13 ± 0.03 L (5.6 ± 0.8% of predicted; p = 0.0002); FVC of 0.22 ± 0.05 L (6.5 ± 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of – 3.1 ± 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of – 2.9 ± 1.3% (p = 0.03); and no change in TLC (– 0.06 ± 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (– 0.35 ± 0.03 L; p < 0.001); FEV₁ (– 0.05 ± 0.04 L; p = 0.2); and FVC (– 0.22 ± 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 ± 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 ± 1.3% of predicted, p < 0.003).

Conclusion: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.

Key Words: COPD • dynamic hyperinflation • lung function • metronome-paced hyperventilation • tiotropium