Beta₂-agonist and anti-inflammatory combination therapy for asthma rescue: a paradigm shift in asthma care

The Global Initiative for Asthma (GINA) report and national and international guidelines have shifted away from short-acting beta₂-agonist (SABA)-only bronchodilators as first-line asthma rescue therapy, recognizing that both bronchoconstriction and inflammation underlie the increase in symptoms preceding an exacerbation. Instead, the GINA Committee supports strategies to reduce inflammation, such as anti-inflammatory reliever (AIR) therapy (as-needed, low-dose inhaled corticosteroid [ICS]-formoterol or SABA-ICS for symptom relief) and single maintenance and reliever therapy (SMART) or maintenance and reliever therapy (MART; i.e., ICS-formoterol used as both maintenance and as-needed rescue therapy). This narrative review discusses the rationale behind the move toward AIR and SMART regimens, examining the inflammatory pathophysiology of exacerbations and how the ramp-up phase may represent a "window of opportunity" for prompt anti-inflammatory treatment to prevent exacerbations. Key clinical data from studies of AIR and SMART regimens, as well as the importance of as-needed SABA-ICS use in routine clinical practice, are also discussed. The review highlights the importance of ICS delivery during times of wheezing and/or symptoms to reduce the ongoing inflammatory cascade, thereby reducing the likelihood of initial symptoms developing into an exacerbation. In this way, patients can avoid the need for systemic corticosteroids, reducing the overall lifetime steroid load and the risk of lifetime dose-dependent complications such as bone thinning, diabetes, hypertension, and many other conditions.