Chest
Volume 129, Issue 3, March 2006, Pages 509-517
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Original Research: COPD
Effects of Tiotropium With and Without Formoterol on Airflow Obstruction and Resting Hyperinflation in Patients With COPD

https://doi.org/10.1378/chest.129.3.509Get rights and content

Background

The combination of short-acting β2-agonists and anticholinergics in the treatment of COPD has been well documented, but data on combination of long-acting agents are lacking.

Methods

A randomized, open-label, placebo-controlled, three-way crossover study was conducted comparing 2-week treatment periods of tiotropium alone to tiotropium plus formoterol once or twice daily following a 2-week pretreatment period with tiotropium. Lung function (FEV1, FVC, and resting inspiratory capacity [IC]) serially over 24 h was measured in 95 patients with stable COPD at baseline and after 2 weeks of each treatment.

Results

Mean baseline FEV1 was 1.05 L (38% of predicted). There was a circadian variation in FEV1, FVC, and IC at baseline that was maintained during all treatment periods. Average FEV1 (0 to 24 h) improved by 0.08 L with tiotropium, by 0.16 L with tiotropium plus formoterol once daily, and by 0.20 L with tiotropium plus formoterol twice daily (p < 0.01 for all comparisons). Compared with tiotropium alone, add-on formoterol in the morning produced improvement in FEV1, FVC, and IC for > 12 h. The second add-on dose of formoterol in the evening caused further improvement in FEV1 for 12 h, but in FVC and IC for < 12 h. Peak increase in FEV1 was 0.23 L (22% of baseline) with tiotropium and 0.39 L (37% of baseline) with tiotropium plus formoterol (p < 0.0001). Compared with tiotropium alone, add-on formoterol once and twice daily reduced the use of rescue salbutamol during the daytime (p < 0.01) and with add-on formoterol twice daily also during the nighttime (p < 0.05). The combination of tiotropium and formoterol was well tolerated.

Conclusion:

In the treatment of COPD, there is benefit from adding formoterol once or twice daily to tiotropium once daily in terms of improvement in airflow obstruction, resting hyperinflation, and the use of rescue salbutamol.

Section snippets

Patients

Patients were required to have a clinical diagnosis of COPD according to the American Thoracic Society (ATS) criteria,12 stable airways obstruction with FEV1 ≤ 60% of predicted,13 and an FEV1/FVC ratio < 70%. The patients had to be at least 40 years old, and all had to be current or previous smokers (≥ 10 pack-years).

Patients with any of the following were excluded: history of asthma, allergic rhinitis, atopy or an elevated blood eosinophil count, significant disease other than COPD, or a

Patients

A total of 100 patients were screened; 95 of them were eligible and entered the study. Of the 95 randomized patients, 91 completed the study and 4 discontinued prematurely. The reasons for withdrawal were as follows: exacerbation of COPD (one patient in the tiotropium pretreatment period and one patient in the tiotropium plus formoterol once-daily period), pneumonia (one patient in the tiotropium period), and not available for follow-up (one patient in the tiotropium plus formoterol twice-daily

Discussion

The 2003 update of the GOLD management protocol states that long-acting bronchodilators are more effective and convenient than short-acting bronchodilators. This report also emphasizes that combining bronchodilators may improve efficacy without increasing the risk of side effects compared to increasing the dose of a single bronchodilator.1

The present study investigates the additional effect of the LABA formoterol, inhaled once or twice daily, on airflow obstruction and resting hyperinflation

ACKNOWLEDGMENT

The authors thank Prof. H. Folgering, Nijmegen, the Netherlands for reviewing the quality of the lung function measurements.

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  • Cited by (0)

    Dr. Van Noord has received speaking honoraria from Boehringer Ingelheim. Mr. Mueller and Dr. Cornelissen are employees of Boehringer Ingelheim.

    The study was funded by Boehringer Ingelheim.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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