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Effects of Short-Acting Bronchodilators Added to Maintenance Tiotropium Therapy^*

^* From University Medical Center Groningen (Dr. Kerstjens), Groningen; Amphia Hospital (Dr. Bantje), Breda; Gelre Hospitals (Dr. Luursema), Zutphen; Hospital Group Twente (Dr. Sinninghe Damste), Almelo; Sint Lucas Hospital (Dr. de Jong), Winschoten; Boehringer Ingelheim bv (Ms. Lee, Ms. Wijker, and Dr. Cornelissen), Alkmaar, the Netherlands.

Correspondence to: Huib A. M. Kerstjens, MD, PhD, Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands; e-mail: h.a.m.kerstjens{at}int.umcg.nl

Abstract

Background: Combining bronchodilators has been shown to be beneficial in patients with COPD. The additive effects of short-acting bronchodilators added to maintenance tiotropium therapy, however, are unknown.

Methods: Following 3 weeks of tiotropium pretreatment, 60 patients with COPD (FEV₁ 40% of predicted) participated in a randomized, placebo-controlled study to assess add-on bronchodilator effects of ipratropium bromide (40 µg) or fenoterol (200 µg). Short-acting bronchodilators were added as a single dose 2 h and 8 h after tiotropium dosing. Serial lung function tests were performed over 9 h.

Results: The peak FEV₁ add-on response within 6 h with fenoterol was significantly greater than with placebo (137 mL) or ipratropium (84 mL); the response with ipratropium was slightly but significantly larger than with placebo (52 mL). One hour after the second dose of the test drugs, a similar order of treatment responses was found. The peak FVC add-on response was significant for fenoterol (249 mL) but not for ipratropium (42 mL).

Conclusions: In conclusion, both short-acting bronchodilator classes were effective when added to maintenance treatment with tiotropium. The addition of the ß₂-adrenergic fenoterol provided greater additional bronchodilatation than the short-acting anticholinergic ipratropium. This is consistent with the expected effects of combining bronchodilators with different pharmacologic mechanisms. This randomized controlled trial was registered at www.clinicaltrials.gov (NCT00274066 [ClinicalTrials.gov] ).

Key Words: COPD • fenoterol • ipratropium bromide • short-acting bronchodilators • tiotropium