Chest
Volume 124, Issue 5, November 2003, Pages 1743-1748
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Clinical Investigations
COPD
Improvement in Resting Inspiratory Capacity and Hyperinflation With Tiotropium in COPD Patients With Increased Static Lung Volumes*

https://doi.org/10.1378/chest.124.5.1743Get rights and content

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 μg/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) FEV1, 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 FEV1 was 1.12 L (43% predicted). The mean differences (tiotropium − placebo) in FEV1 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 FEV1 and lung volumes (FEV1, 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.

Section snippets

Study Design

This was a randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the efficacy of tiotropium in patients with COPD. The first clinic visit was for screening of patients. Qualified patients were asked to return within 2 weeks for the baseline visit. If they continued to meet inclusion/exclusion criteria, they were randomized to receive one capsule daily of tiotropium, 18 μg, or placebo through the HandiHaler device (Boehringer Ingelheim; Ridgefield, CT) for 28

Results

A total of 128 patients were screened and signed informed consent, and 81 patients were randomized and entered the study. Of the 81 randomized patients, 75 patients completed the study. Of the six patients withdrawn after randomization, one patient from each treatment group withdrew due to worsening COPD. The other withdrawals were due to protocol violations.

Discussion

COPD is a disease characterized by the presence of incompletely reversible airflow limitation.15 In moderate-to-severe COPD, this airflow limitation is usually associated with gas trapping and hyperinflation as assessed objectively through an increase in TGV. This hyperinflation is also reflected by a reduction in IC. These physiologic abnormalities translate to symptoms of dyspnea, exercise intolerance, and patient disability.516 To this end, it is now accepted that while spirometric

ACKNOWLEDGMENT

We thank our co-investigators, Dr. D. Mahler, Dr. E. Diamond, Dr. C. Cote, and Dr. D. Maple.

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    Drs. Celli and ZuWallack are consultants for Boehringer Ingelheim.

    This study was financed by Boehringer Ingelheim, Inc.

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