Effects of hydrocortisone on acute β-adrenoceptor blocker and histamine induced bronchoconstriction

Abstract

Aims: β-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 µg 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 5 mg and ipratropium 500 µg recovery.

Results: Thirteen patients completed per protocol. Hydrocortisone did not potentiate salbutamol recovery post propranolol and histamine challenge vs. placebo (mean difference in FEV(1) 0.04 ml, 95% CI -0.07, 0.15, P= 0.417). β-adrenoceptor blocker induced bronchoconstriction was demonstrated by spirometry and impulse oscillometry. For the placebo visit, FEV(1) 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 FEV(1) % 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 β-adrenoceptor blockade is after first dose, our findings offer reassurance to those undertaking further evaluation of chronic β-adrenoceptor blockade as a potential treatment for mild-to-moderate asthma.

Trial registration: ClinicalTrials.gov NCT01070225.

© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Figures

Figure 1

Study visit diagram. Hist histamine, salb salbutamol, IP ipratropium

Figure 2

Consort diagram

Figure 3

Effect of β-adenoceptor blockade, bronchial challenge and sequential reversibility with salbutamol and ipratropium on separate study visits (hydrocortisone and placebo). FEV1% (A and D), R5% (B and E) and serum potassium (D and F)

Figure 3

Effect of β-adenoceptor blockade, bronchial challenge and sequential reversibility with salbutamol and ipratropium on separate study visits (hydrocortisone and placebo). FEV1% (A and D), R5% (B and E) and serum potassium (D and F)