Global Strategy For Asthma Management and Prevention (2022 Update). Comprehensive updated resource. The most recent update provides updated definitions for mild and severe asthma, as well as recommendations on the use of LAMAs, azithromycin, and absolute eosinophil cut-offs for determining candidacy for biologics.

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2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. This update to the 2007 guidelines focuses on the use of FeNO, allergen mitigation, use of continuous vs. prn ICS, LAMAs, immunotherapy, and bronchial thermoplasty.

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Holguin F, Cardet JC, Kung JF, et al. Management of severe asthma: A European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020; 55:1900588. This document provides useful recommendations for the management of severe asthma, with an emphasis on selection of patients suitable for biologic therapies. which is defined as asthma requiring high dose inhaled corticosteroids in combination with a second controller and/or systemic corticosteroids.

PMID: 31558662

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As needed use of ICS/LABA for mild asthma

The following 2 large, randomized studies among patients with mild asthma are noteworthy for finding ICS/LABA inhaler used only on a prn basis resulted in an exacerbation rate similar to use of bid ICS maintenance therapy but with substantially lower overall steroid exposure. However, daily asthma symptom scores were better among subjects receiving ICS maintenance therapy. 

O'Byrne PM, FitzGerald JM, Bateman ED et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. 2018; 378:1865-1876.

PMID: 29768149

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Bateman ED, Reddel HK, O'Byrne PM et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018; 378:1877-1887.

PMID: 29768147

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Combination therapies

Bateman ED, Boushey HA, Bousquet J, et al. GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma Control study. Am J Respir Crit Care Med. 2004;170:836-44. This 1-year, randomized study (n=3,421) of patients with uncontrolled asthma compared the addition of LABA vs escalating steroid in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone alone.

PMID: 15256389

Peters SP, Kunselman SJ, Icitovic N, et al. for the National Heart, Lung, and Blood Institute Asthma Clinical Research Network. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 2010; 363:1715-26. The TALC study showed that, in patients with asthma inadequately controlled by low-moderate dose inhaled corticosteroid therapy, the addition of long-acting anticholinergic therapy was superior to corticosteroid dose escalation and noninferior to adding long-acting beta-agonist therapy. However, the study was not powered to compare the effect on exacerbations.

PMID: 20979471

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Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012; 367:1198-207. 48 week randomized study of 912 patients with persistent asthma found that the addition of tiotropium (Respimat soft-mist inhaler rather than dry powder) demonstrated a statistically significant improvement in FEV1 (230ml) that was less than the minimal clinically important difference, but also a 21% reduction in severe exacerbations.


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Azithromycin to reduce asthma exacerbations

Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017; 12;390: 659-668. Randomized double-blind trial of 420 patients with uncontrolled persistent asthma on medium-to-high dose ICS plus a LABA.  Azithromycin 500 mg three times per week reduced moderate/severe exacerbations (1.07 per patient year vs 1.86 per patient year, p<0.0001) and improved asthma QOL.

PMID: 28687413

Biologic Therapies

McGregor MC, Krings JG, Nair P, et al. Role of biologics in asthma. Am J Respir Crit Care Med. 2019; 199:433-445. A review of the action, indications, expected benefits, and side effects of approved biologics for severe uncontrolled asthma.

PMID: 30525902

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Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma.  N Engl J Med. 2021;384:1800-1809. Tezepelumab is a human monoclonal antibody which blocks thymic stromal lymphopoietin. This RCT of 1,061 patients with severe, uncontrolled asthma found tezepelumab reduced the annual rate of asthma exacerbations (0.93 vs. 2.10 for placebo, p < 0.001). The benefit was significant, but of lower magnitude, with absolute eosinophil counts < 300/microL and multiple measures showed improved symptom burden.

PMID: 33979488

The role of nonadherence in refractory asthma

Gamble J, Stevenson M, McClean E, et al. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med 2009;180:817-22. In a patient population referred for specialist care in the setting of refractory asthma, 35% of patients filled fewer than half of their prescriptions for inhaled corticosteroids. Nonadherent patients had significantly lower asthma-specific quality of life. This study highlights an important and often overlooked factor in asthma refractoriness.

PMID: 19644048

Bronchial thermoplasty

Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. (AIR2 Trial) Am J Respir Crit Care Med 2010;181:116-24. The AIR2 trial was the first large scale randomized study of bronchial thermoplasty to include a sham control. 288 patients with asthma symptoms despite standard therapy were included. During the 12 month follow up, the treatment group had a lower number of adverse respiratory events, severe exacerbations, emergency department visits, and hospitalizations, as well as a greater number (81%) of subjects reporting improvement in AQLQ. Notably, 63% of control subjects also reported clinically significant (>0.5) improvement in AQLQ. During treatment, 8.4% of patients in the treatment group were hospitalized for respiratory symptoms compared to 2.0% in the sham group.

PMID: 19815809

Exercise-induced bronchoconstriction

Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med 2013; 187:1016-1027. This guideline offers a succinct, practical overview of EIB management, including the strength of evidence supporting various options for diagnosis and treatment.

PMID: 23634861

***See also Invasive Mechanical Ventilation and Occupational Medicine