Asthma Exacerbations Steroid

“Can Severe Asthma Exacerbations Be Prevented With More Inhaled Steroid?” presented by Prof. Tim Harrison

As part of our ongoing seminar series, the Centre of Research Excellence in Severe Asthma hosted Prof. Tim Harrison, for a webinar titled “Can Severe Asthma Exacerbations Be Prevented With More Inhaled Steroid?” on 21 March, 2018.

Presentation Summary:

Asthma attacks often happen following a worsening of asthma symptoms. A temporary increase in inhaled corticosteroid (ICS) dose has been recommended to reduce asthma attacks. However, no data was available from randomised controlled trials to support this recommendation.

Prof. Harrison provides an overview of his work studying the effect of increased ICS dose on asthma attacks. His initial trial in 2004 demonstrated that doubling ICS dose did not improve lung function or reduce symptoms. In a single centre trial quadrupling ICS dose, a slight benefit was observed in a subset of patients.

A multi-centre, randomised, open label trial of 4-fold increase in ICS dose was undertaken. Increased ICS dose reduced severe asthma attacks by ~20%. However, a study of a 5-fold increase in ICS dose in children published at the same time showed no benefit. Prof. Harrison discusses the differences between the 2 trials, which may explain the different outcomes.

Key Points:

• Asthma management guidelines have recommended temporary increases in inhaled corticosteroids (ICS) dose when asthma symptoms worsen
• However, no controlled trial studies had been performed to support this recommendation
• In an initial randomised controlled trial (RCT), doubling prednisolone ICS dose did not improve lung function or alter symptoms (Harrison et al. 2004 Lancet)
• Quadrupling ICS dose reduced the requirement for oral corticosteroids (OCS), in a subgroup of patients that initiated the study inhaler (Oborne et al. 2009 AJRCCM)
• The FAST multicentre study (fourfold asthma study) assessed the ability of temporary quadrupling of ICS dose to prevent unscheduled health care visits and the need for systemic corticosteroids (McKeever et al. 2018 NEJM)
• Patients were randomised to quadruple their ICS dose for 7-14 days, when asthma control began to deteriorate (versus no change in ICS dose)
• Increased ICS dose (4-fold) reduced severe exacerbations by ~20%
• Improvement occurred regardless of the baseline ICS dose
• In a concurrent paediatric study, a 5-fold increase in ICS dose failed to reduce exacerbations in children (Jackson et al. 2018 NEJM)
• Differences in outcome may be explained by a number of differences between the studies:
  • Different populations (adult vs. paediatrics)
  • Study design (open label vs. double blinded)
  • Inclusion criteria (“real-life” poor adherence vs. strict adherence criteria)
  • Primary outcomes (unscheduled healthcare visits / systemic corticosteroids vs. increased reliever use)
• A “real world” pragmatic study design was used to assess the effects of 4-fold increase in ICS dose in the adult population
• A double-blind, highly controlled study design was used to assess the effects of 5-fold increase in ICS dose in the paediatric population
• Consideration of the differences in study design must be weighed, when interpreting the study findings and applying the findings to clinical recommendations

About Prof. Tim Harrison:

Prof. Tim Harrison is Professor and Honorary Consultant in the Faculty of Medicine & Health Sciences at the University of Nottingham.

His research explores the benefit of increasing the dose of inhaled steroids to prevent the development of asthma exacerbations. His research team is currently exploring the mechanisms for therapy resistant asthma and looking at new therapeutic options for these patients.

Prof. Harrison’s travel and refreshments for the event were supported by AstraZeneca.

To view other webinars on Severe Asthma please click here