Reversal of Acute β-Blocker Induced Bronchoconstriction
Condition: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      Current therapies for the management of asthma include inhalers. Types of these medications
      (beta agonists), improve asthma symptoms by stimulating areas (receptors) within the human
      airway resulting in dilation of the human airway. Whilst these drugs are highly effectively
      in the immediate setting their longterm use, constantly stimulation of receptors within the
      airway has been associated with increased asthma exacerbations and rare cases of death.

      Conversely medications that block receptors within the human airway (betablockers)have been
      avoided in asthma.

      The main reason for this is because of the possible acute airway narrowing that can occur
      after soon after administration. However chronic use of betablockers in asthma has recently
      been shown to be of benefit in reducing airway inflammation which is of great importance in
      improving asthma control and reducing symptoms.

      Despite this early evidence supporting chronic use of beta blockers in asthma, there is
      concern in 2 major regards:their potential to cause acute airway narrowing (irrespective of
      longterm benefit) and the possibility that they could block the reliever action of beta
      agonists.

      The objective of this study is to establish how best to reverse the short term effects of a
      single dose of beta blocker.

      This study is designed as a single centre study, with participants attending the department
      on approximately 3 separate visits (including a screening visit) at approximately 1 weekly
      intervals.
    

Detailed description: 
      Asthma was originally thought to be associated with an intrinsic defect of β2- adrenoceptor
      function tipping the balance towards parasympathetic bronchoconstriction. While β2-agonists
      are highly effective for the acute relief of bronchoconstriction, their chronic use is
      accompanied by an adaptive reduction in β2ADR numbers and associated desensitisation of
      response, resulting in increased exacerbations and rare cases of death. Conversely the
      chronic use of β blockers have been shown in murine models to reduce airway inflammation and
      mucous metaplasia. Recent work in humans has further demonstrated a potential benefit of β
      blockers in asthmatics by demonstrating a significant improvement in airway
      hyperresponsiveness to bronchial challenge1.

      Despite this early evidence supporting chronic use of β blockers in asthma, there is concern
      in 2 major regards: their potential to cause acute bronchoconstriction (irrespective of
      long-term benefit) and the possibility that they could block the reliever action of
      β-agonists.

      Sub-sensitivity of β-adrenoceptors occurs following treatment with long-acting β-agonists.
      Previous work in our department has shown that high dose steroids can re-establish the
      β-adrenoceptor function following such down-regulation2. It therefore seems plausible that a
      similar response may occur following β-blockade (reversing β-blockade and re-establishing
      β-agonist sensitivity).

      The investigators wish to gather evidence for the best methods to treat β-blocked patients in
      the short term. The investigators therefore wish to examine the effects of acute-β blockade
      with low dose propranolol on mild-to-moderate asthmatics. The investigators wish to simulate
      airway stress and rescue in acutely β-blocked patients. For safety purposes the investigators
      have chosen propranolol due to its short half-life of 3 to 5 hours. Importantly the ability
      to achieve airway reversibility and recovery following acute β-blockade will influence the
      long term viability of chronic β blockers use in the management of asthma.
    

Intervention name(s): Hydrocortisone/ Placebo and Propranolol
Intervention type(s): Drug
Intervention description(s): Hydrocortisone 400mcg Propranolol 10mg or 20 mg
Intervention MeSH terms: Hydrocortisone; Propranolol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment