Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 73, Issue 5, Pages 717-726Publisher
WILEY
DOI: 10.1111/j.1365-2125.2011.04143.x
Keywords
asthma; bronchial challenge; bronchoconstriction
Categories
Funding
- Chief Scientist Office for Scotland [CZB/4/716]
- Asthma and Allergy Research Group, Dundee, UK
- Chief Scientist Office [CZB/4/716] Funding Source: researchfish
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AIMS beta-adrenoceptor blockers are avoided in asthma due to concerns of bronchoconstriction. We investigated the safety of acute exposure to propranolol in asthmatics, sequentially challenged with histamine to mimic an asthma exacerbation and evaluated the role of intravenous hydrocortisone in potentiating salbutamol reversibility. METHODS Persistent atopic asthmatics, requiring <= 1000 mg day(-1) budesonide, performed a randomized double-blind placebo-controlled crossover study. Following 10 mg or 20 mg of oral propranolol, patients received 400 mg intravenous hydrocortisone or placebo, followed by histamine challenge with nebulized salbutamol 5mg and ipratropium 500 mg recovery. RESULTS Thirteen patients completed per protocol. Hydrocortisone did not potentiate salbutamol recovery post propranolol and histamine challenge vs. placebo (mean difference in FEV1 0.04 ml, 95% CI -0.07, 0.15, P = 0.417). beta-adrenoceptor blocker induced bronchoconstriction was demonstrated by spirometry and impulse oscillometry. For the placebo visit, FEV1 fell 4.7% 2 hours post propranolol (95% CI 1.8, 7.5, P = 0.008) whilst total airway resistance (R5%) increased 31.3% (95% CI 15.6, 47.0, P = 0.04). On both visits FEV1% and R5% returned to baseline after salbutamol post histamine. CONCLUSION Nebulized salbutamol and ipratropium produced a full recovery after propranolol and histamine induced bronchoconstriction, independent of hydrocortisone use. Since the greatest risk of beta-adrenoceptor blockade is after first dose, our findings offer reassurance to those undertaking further evaluation of chronic beta-adrenoceptor blockade as a potential treatment for mild-to-moderate asthma.
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