Bronchodilator reversibility to low and high doses of terbutaline and ipratropium bromide in patients with chronic obstructive pulmonary disease.

D M Newnham, D P Dhillon, J H Winter, C M Jackson, R A Clark, B J Lipworth

Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee.

BACKGROUND--There is uncertainty regarding the use of monotherapy or combination therapy with beta 2 agonists and anticholinergic drugs in patients with chronic obstructive pulmonary disease (COPD). The measurement of forced expiratory volume in one second (FEV1) or relaxed vital capacity (RVC) in the assessment of reversibility in these patients has also caused considerable debate. METHODS--Twenty seven patients with COPD were evaluated on two occasions. Patients received the following treatments in sequence: (sequence 1) low dose terbutaline 500 micrograms, high dose terbutaline 5000 micrograms, low dose ipratropium 40 micrograms, high dose ipratropium 200 micrograms; (sequence 2) low dose ipratropium 40 micrograms, high dose ipratropium 200 micrograms, low dose terbutaline 500 micrograms, high dose terbutaline 5000 micrograms. RVC, FEV1 and FVC were measured at baseline and 30 minutes after successive treatments. RESULTS--Values for FEV1 at baseline on the first and second study days were not significantly different: 0.90 (0.87-0.93) 1 v 0.90 (0.87-0.93) 1. Likewise, baseline values for RVC and FVC were not different. The number of patients showing a greater than 330 ml overall improvement in RVC was 20 of 27 for sequence 1 and 22 of 27 for sequence 2; similar trends were observed for FEV1 and FVC. For all three parameters there was a significant difference between mean responses to low and high doses of terbutaline when the latter was given as the first drug in sequence 1. When ipratropium was given first in sequence 2 there was, however, no significant improvement with high dose terbutaline over and above the response to low dose terbutaline. The latter effect was more noticeable with RVC than with either FEV1 or FVC. The total bronchodilator response at the end of each sequence was similar whether ipratropium was given first or second. CONCLUSIONS--The measurement of RVC, FEV1, and FVC were equally effective at picking up those patients who had a significant overall bronchodilator response to combined therapy with inhaled beta 2 agonist and anticholinergic medication. There was no significant benefit of adding a higher dose of terbutaline when ipratropium bromide had been given previously, particularly when using RVC as the parameter of response.

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• Donohue, J. F. (2005). Combination Therapy for Chronic Obstructive Pulmonary Disease: Clinical Aspects. Proc Am Thorac Soc 2: 272-281 [Abstract] [Full Text]  
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