The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity

Abstract

@ERSpublicationsA paradigm shift in asthma management that addresses the paradoxes of SABA reliever therapy is required; consideration needs to be given to replacement of SABA reliever with ICS/fast-onset β-agonist reliever therapy across the range of asthma severity http://ow.ly/ccff30lNLPv Cite this article as: Beasley R, Bird G, Harper J, et al. The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity. Eur Respir J 2018; 52: 1800694 [https://doi.org/ 10.1183/13993003.00694-2018].Should short-acting β-agonist (SABA) reliever monotherapy be replaced by combination inhaled corticosteroid (ICS)/fast-onset β-agonist as reliever therapy in asthma patients at Global Initiative for Asthma step 1 [1]? This uncertainty is the latest chapter in the controversy relating to the risks and benefits of β-agonist therapy in asthma management [2]. This 70-year controversy began with the introduction of isoprenaline and the concerns that it caused severe refractory asthma and an increased risk of death [3][4][5].The dilemma of evaluating the relative efficacy and risk of β-agonists has persisted since then. Two asthma mortality epidemics in the 1960s and 1970s/1980s were primarily caused by use of high-dose preparations of the potent, yet poorly β 2 -selective agonists, isoprenaline [6] and fenoterol [7], respectively. The epidemics ended abruptly with regulatory restriction and withdrawal of these agents [2,8]. In response to evidence that regular scheduled use of SABAs could increase asthma severity and the risk of exacerbations, the recommendation for their use was changed to "as required for relief of symptoms". This therapeutic approach, together with the increasing use of ICSs, both as separate inhalers and combination ICS/long-acting β-agonist (LABA) inhalers, has been associated with a marked reduction in asthma mortality since the 1990s, although the global rates of asthma mortality have now plateaued [9]. There is clearly a need for alternative treatment strategies to achieve further reductions in global asthma mortality.One strategy is to reduce the potential risks associated with starting SABA reliever monotherapy in intermittent and mild persistent asthma. This strategy was the focus of a recent review in the European Respiratory Journal [1], which identified five paradoxes of this therapeutic approach. The review summarised evidence that SABA reliever monotherapy exposes patients to significant avoidable risk and leads to learned behaviours, which result in difficulties for both patients and doctors (table 1). SABA reliever therapy not only reduces the potential to achieve optimal control at step 1, but also when patients progress to higher treatment steps in the stepwise approach to pharmacological therapy. In this editorial,

Effective Asthma Management: Is It Time to Let the AIR out of SABA?

“…However, as the disease advances, patients lose the autonomy of the decision when to treat (with maintenance controller) and are told to avoid the medication that meets their goals for treatment (the reliever), leading to conflict in their minds [7]. A combination of reliever with anti-inflammatory would then meet both the goals of the clinician and the patient [18].…”

“…Practical issues with current guidelines for the treatment of asthma are experienced daily by both physician and patient and limit the effective treatment of this disease. Many of the real issues identified in current practice stem from the series of paradoxes that stem from guideline recommendations for asthma treatment [7,18]. These paradoxes include the following:…”

“…Further, we now know that regular SABA use increases hyper-responsiveness in the lung, leading to greater sensitivity to triggers [18]. The use of a combination ICS with reliever (either SABA or fast acting LABA) across all patients has a better safety profile and efficacy in reducing exacerbation risk than a SABA alone [7,8,18,19].…”

“…Previous consensus driven international strategies have recommended SABAs as first-line therapy to relieve immediate asthma symptoms ( Figure 1A) [26]. This is despite the fact that asthma is most often characterized as an inflammatory condition characterized by exacerbations and persistent airflow limitations [7,18]. SABAs will resolve the immediate bronchospasm of an allergic trigger but have no inherent anti-inflammatory pharmacological properties and no effect on the late phase reaction.…”

GINA 2019: a fundamental change in asthma management

“…Of particular concern to GINA was the paradoxical switch in messaging for patients and clinicians between Step 1, where symptom relief was the priority and SABA use was encouraged, and Step 2, where patients were told that they should reduce what was to them a familiar, effective, low cost treatment, and that to achieve this, they should take a daily treatment even when asymptomatic [19,20]. Patient reliance on SABA was further reinforced by its prominent use in the trusted environments of emergency department and hospital care.…”