Achieving zero asthma-related hospitalisations in the world´s first SABA-free Asthma Center in Argentina

To the Editor, The Global Initiative for Asthma (GINA) 2021 strategy report no longer recommends short-acting β2-agonists (SABAs) as the preferred reliever therapy without concomitant inhaled corticosteroid (ICS) therapy (1). SABAs lack inherent anti-inflammatory properties to treat underlying airway inflammation in asthma (2); conversely, they could increase inflammation and bronchial hyperresponsiveness (2). Despite published evidence on safety concerns associated with SABA use in asthma (3), SABAs are still widely prescribed by physicians and purchased by patients globally. Herein, we describe the rationale that led to the implementation of a SABA-free Asthma Center in Argentina in 2014 and call for the elimination of SABA use in asthma management. Although problems with SABA overreliance were identified early, incorporation of clinical findings into evidence-based guidelines was delayed. In an initial proof-of-concept study in 1991, 10 patients with asthma experienced acute respiratory arrest (status asthmaticus) characterized by extreme hypercapnia and acidosis, establishing asphyxia as the underlying mechanism of near death, and not cardiac arrhythmias (4). The authors had initially speculated that under-treatment instead of over-treatment was responsible for these findings, however, SABA overreliance emerged as a common feature in all patients (5). SABA overreliance was shown to be a risk factor for asthma exacerbations, hospitalizations and mortality in a dose-dependent manner in subsequent studies (3). Despite numerous publications supporting the deleterious effects of SABA, as stated by GINA for years, SABA monotherapy was not fully replaced by ICS-formoterol as the preferred reliever until 2019 (6). In fact, SABAs were used for rapid symptom relief for over 50 years despite an inconsistent evidence base. SABA use was originally based on a study comparing single-dose salbutamol with other nonselective β-agonists in 24 patients with asthma in 1969 (7). Historically, designs of randomized controlled trials in asthma could have masked the detrimental effects of SABA. Apart from asthma studies that used anti-inflammatory reliever therapy, all trials used SABA as a reliever therapy with higher patient adherence to maintenance therapy than observed in real-world clinical practice. In the double-blind, placebo-controlled TRUST trial, regular use of inhaled salbutamol 400 μg four times daily for a year had no impact on exacerbation rates (8). It is possible that high ICS doses (>800 μg beclomethasone or equivalent) in some patients in this study prevented the increase in exacerbation rates with regular SABA use. Regardless of their adherence to maintenance therapy in the real world, it is safe to assume that patients will use SABA if they have SABA canisters readily available, either as a reliever or as maintenance treatment when they run out of ICS inhalers instead of refilling prescriptions. Therefore, eliminating SABA monotherapy use in alignment with the latest GINA recommendations is important (1). First, do no harm. Although physician and patient education are crucial to achieving good asthma control and zero hospitalizations, education alone is unlikely to be sufficient as exemplified by the 10-year asthma programme in Finland (9). The Finnish programme, based on early intervention with reimbursed ICS and as-needed SABA, had the following promising features: