Regular nebulised terbutaline in chronic obstructive airways disease: dose‐response studies fail to detect tolerance.

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Abstract
1. To determine the effects of high dose terbutaline on the possible development of tolerance we have examined the influence on dose- response of regular nebulised terbutaline. 2. We studied 10 subjects with severe chronic obstructive airways disease (COAD), mean age 63 years mean (s.e. mean) PEFR 142 l min-1 (19), FEV1 0.77 1 (0.12) and FVC 1.93 (0.19). Cumulative dose-response curves were measured (PEFR, FEV1 and FVC) to six incremental doses of terbutaline (0.5-8 mg) before and 1, 4, 8 and 12 weeks after starting nebulised terbutaline 5 mg four times a day. 3. Maximal bronchodilatation (Emax) was calculated by polynomial regression. Responses were examined by analysis of variance. 4. Mean baseline PEFR increased by 32 l min-1 (P less than 0.05), FEV1 by 0.16 1 (NS) and FVC by 0.54 l (P less than 0.05) after 12 weeks. Initial mean Emax PEFR was maintained throughout the study. The percentage of mean Emax PEFR achieved by each cumulative dose of terbutaline either increased (0.5 mg, 1 mg and 2 mg, P less than 0.01) or was maintained (4 mg, 6 mg and 8 mg) throughout the study. 5. We conclude that in severe COAD regular nebulised terbutaline 5 mg four times a day produces a sustained improvement in baseline lung function without changes in dose-response which would suggest tolerance.