Asthma attacks can lead to death, and new approaches to prevent asthma deaths, particularly in children and adolescents, are clearly needed, as highlighted by Abrams and colleagues.1Abrams EM Shaker M Greenhawt M Fernandes RM Sinha I Treatment of mild-to-moderate asthma in childhood and adolescence in 2021. Underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA) are risk factors for death in people with asthma. Contributing to these risk factors is poor adherence to ICS, and the fact that many health-care professionals simply ignore the dangers of SABAs. As no evidence is available to suggest that these situations are improving, we ask if the time has come to end use of the blue inhaler.Compelling evidence indicates that stopping use of SABA inhalers in people with asthma aged 12 years and older is the right approach. A meta-analysis of randomised controlled trials showed that severe asthma attacks are significantly reduced with combined ICS–formoterol reliever therapy versus SABA reliever therapy, with and without ICS–long-acting β2-agonist (LABA) maintenance therapy.2Rogliani P Ritondo BL Ora J Cazzola M Calzetta L SMART and as-needed therapies in mild-to-severe asthma: a network meta-analysis. However, evidence in younger children, the age group in whom the burden of asthma is greatest, is scarce, as highlighted by Abrams and colleagues.1Abrams EM Shaker M Greenhawt M Fernandes RM Sinha I Treatment of mild-to-moderate asthma in childhood and adolescence in 2021. To our knowledge, only one study to date has included children aged 4–11 years. In this study, ICS–formoterol maintenance and reliever therapy reduced the risk of severe asthma attacks compared with maintenance ICS–formoterol and SABA reliever therapy by two-thirds.3Bisgaard H Le Roux P Bjåmer D Dymek A Vermeulen JH Hultquist C Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. This risk reduction was greater than that observed in adults and adolescents in the same study,4O'Byrne PM Bisgaard H Godard PP et al.Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. suggesting potentially greater efficacy of ICS–formoterol maintenance and reliever therapy in a younger population.In New Zealand, during the debate about the safety of the SABA fenoterol in 1989, the Health Minister at the time, Helen Clark, withdrew fenoterol on the rational grounds that a safer SABA (salbutamol) was available. The continued prescription of a drug that offered no advantage, but had considerable safety concerns (fenoterol), could not be supported. This regulatory action was associated with a greater than 50% reduction in asthma mortality within 12 months.5Pearce N Beasley R Crane J Burgess C Jackson R End of the New Zealand asthma mortality epidemic. On the basis of this experience, we question whether the Global Initiative for Asthma recommendation,6Reddel HK FitzGerald JM Bateman ED et al.GINA 2019: a fundamental change in asthma management: treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. that ICS–formoterol is the preferred reliever over SABAs, should be upgraded? Although a case can be made for the continued availability of a SABA reliever with maintenance ICS or ICS–LABA therapy, there seems to be no justification in people aged 12 years and older for SABA alone to be prescribed. Regulatory bodies should mandate SABA alone as off-label in this age group, and replace it withICS–formoterol alone as reliever therapy, a regimen which results in a greater than 50% reduction in severe attack risk in people aged 12 years and older.7Beasley R Holliday M Reddel HK et al.Controlled trial of budesonide–formoterol as needed for mild asthma., 8O'Byrne PM FitzGerald JM Bateman ED et al.Inhaled combined budesonide–formoterol as needed in mild asthma. Further evidence is urgently needed in children younger than12 years, to determine whether the same strategy should also be mandated in this age group.

SRD reports grants from Cure Kids and the Health Research Council of New Zealand, outside of the submitted work. CAB reports grants from Cure Kids, the Health Research Council of New Zealand, the Australian National Health and Medical Research Council, and FluLab, outside of the submitted work. RB reports grants and personal fees from AstraZeneca and the Health Research Council of New Zealand, grants from Cure Kids and Genentech, and personal fees from Avillion and Cipla, outside of the submitted work. RB is Chair of the Asthma and Respiratory Foundation of New Zealand adolescent and adult asthma guidelines 2020. AB and LH declare no competing interests.

References1.Abrams EM Shaker M Greenhawt M Fernandes RM Sinha I

Treatment of mild-to-moderate asthma in childhood and adolescence in 2021.

Lancet Respir Med. 9: 443-4452.Rogliani P Ritondo BL Ora J Cazzola M Calzetta L

SMART and as-needed therapies in mild-to-severe asthma: a network meta-analysis.

Eur Respir J. 5620006253.Bisgaard H Le Roux P Bjåmer D Dymek A Vermeulen JH Hultquist C

Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma.

Chest. 130: 1733-17434.O'Byrne PM Bisgaard H Godard PP et al.

Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma.

Am J Respir Crit Care Med. 171: 129-1365.Pearce N Beasley R Crane J Burgess C Jackson R

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Lancet. 345: 41-446.Reddel HK FitzGerald JM Bateman ED et al.

GINA 2019: a fundamental change in asthma management: treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents.

Eur Respir J. 5319010467.Beasley R Holliday M Reddel HK et al.

Controlled trial of budesonide–formoterol as needed for mild asthma.

N Engl J Med. 380: 2020-20308.O'Byrne PM FitzGerald JM Bateman ED et al.

Inhaled combined budesonide–formoterol as needed in mild asthma.

N Engl J Med. 378: 1865-1876Article InfoPublication History

Published: April 28, 2021

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DOI: https://doi.org/10.1016/S2213-2600(21)00185-5

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© 2021 Elsevier Ltd. All rights reserved.

ScienceDirectAccess this article on ScienceDirect Linked ArticlesTreatment of mild-to-moderate asthma in childhood and adolescence in 2021

In asthma, there is an emerging and much-needed focus on children with mild-to-moderate and episodic symptoms. Although 50–75% of children and adolescents with asthma are classified as having mild disease, approximately 30–40% of all severe exacerbations occur in this group.1 The burden of illness of mild asthma is significant, but uncertainties remain as to how to manage it, especially in children.

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