Long-term Treatment Benefits With Tiotropium in COPD Patients With and Without Short-term Bronchodilator Responses

doi:10.1378/chest.123.5.1441

Chest

Volume 123, Issue 5, May 2003, Pages 1441-1449

https://doi.org/10.1378/chest.123.5.1441 Get rights and content

Objectives:

To determine whether long-term symptomatic improvement occurs in COPD patients with maintenance bronchodilator therapy despite a nonsignificant short-term improvement in FEV₁ following bronchodilator inhalation obtained at a single time point.

Methods:

Data obtained during two identical 1-year, placebo-controlled trials of tiotropium, 18 μg once daily, were analyzed retrospectively to determine the associations of long-term improvements in lung function and patient health status with short-term improvements in FEV₁, as measured on the first day of treatment. Based on the presence or absence of a short-term improvement in FEV₁ of ≥ 12% and ≥ 200 mL, respectively, patients who had been treated with tiotropium were characterized as being responsive to tiotropium (TIO-R) or poorly responsive to tiotropium (TIO-PR).

Results:

Baseline characteristics were similar other than baseline FEV₁, which was higher in the TIO-R group than in both the TIO-PR and placebo groups (p < 0.05). Baseline FEV₁ was 1.08 L in the TIO-R group (n = 263), 0.95 L in the TIO-PR (n = 255), and 0.99 L in the placebo group (n = 328). The mean (± SD) morning predose FEV₁ at 1 year significantly (p < 0.001) improved in patients in both of the tiotropium treatment subgroups (TIO-R group, 212 ± 17 mL; TIO-PR group, 94 ± 17 mL) relative to those treated with placebo. Statistically significant improvements in both tiotropium-treated groups also were noted over 1 year for dyspnea (p < 0.001), as assessed by the transition dyspnea index (TDI) [TIO-R group, 1.36 ± 0.23 L; TIO-PR group, 0.86 ± 0.23 L] relative to the placebo group. Patient health status assessed by the St. George Respiratory Questionnaire (SGRQ) showed statistically significant improvements over placebo for the TIO-R and TIO-PR groups (−3.96 ± 0.99 and −3.05 ± 1.00 L, respectively; p < 0.005). There was a significant correlation of the first-dose short-term FEV₁ response to the end-of-trial trough response (r = 0.43), but there was only a weak correlation to TDI focal score (r = 0.17) or SGRQ total score (r= −0.12).

Conclusions:

Tiotropium was effective in the treatment of patients with COPD, irrespective of the presence or absence of a short-term response on the first day of treatment. The short-term bronchodilator response should not be used as a definitive criterion for prescribing long-term treatment with inhaled bronchodilators.

Section snippets

Study Design

A retrospective analysis was performed using two identical 1-year clinical trials¹¹ that had been designed to establish the efficacy and safety of tiotropium in patients with COPD. A total of 50 clinical centers participated in these double-blind, placebo-controlled, parallel-group comparison trials. All patients had a clinical diagnosis of COPD, as defined by the American Thoracic Society.¹ Patients were required to have an FEV₁ of ≤ 65% predicted and an FEV₁/FVC ratio of < 70%. The use of

Patient Demographics

A total of 921 patients were enrolled in the two combined studies (tiotropium groups, 550 patients; placebo group, 371 patients). Baseline demographics and lung function (Table 1), and the pulmonary medications used (Table 2) were similar among the groups except for baseline FEV₁, which was higher in the TIO-R group than in both the TIO-PR and placebo groups (p < 0.05). While these differences were statistically significant, they were only modest in magnitude. On average, patients were in their

Discussion

The assessment of the short-term response to inhaled short-acting bronchodilators has formed part of the culture of lung function testing in obstructive lung disease for some time as a putative means of distinguishing the diagnosis of asthma from that of COPD or other obstructive lung diseases and also as a guide to pharmacotherapy. The premise has been that the airflow obstruction in asthma patients is reversible, while that in COPD is irreversible. However, as additional data have become

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: Dr. Tashkin is a consultant for Boehringer Ingelheim, and Dr. Kesten is an employee of Boehringer Ingelheim.

: This research was supported by Boehringer Ingelheim Pharmaceuticals, Inc.

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Chest

Clinical InvestigationsCOPDLong-term Treatment Benefits With Tiotropium in COPD Patients With and Without Short-term Bronchodilator Responses

Objectives:

Methods:

Results:

Conclusions:

Section snippets

Study Design

Patient Demographics

Discussion

Respir Med

Chest

Chest

Life Sci

Chest

Chest

Chest

Chest

Chest

Chest

Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Standardization of spirometry: 1994 update

Am J Respir Crit Care Med

Guidelines for the evaluation of impairment/disability in patients with asthma

Am Rev Respir Dis

Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Acute bronchodilator trials in chronic obstructive pulmonary disease

Am Rev Respir Dis

Clinical Investigations
COPD
Long-term Treatment Benefits With Tiotropium in COPD Patients With and Without Short-term Bronchodilator Responses