1-Minute Summary: Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline

Expert Name
Prof. Fernando Holguin
Expert Affiliation
University of Colorado
Expert Google Scholar or Orcid Url
European Respiratory Journal

In 2014, the first guidelines for the treatment of severe asthma in children and adults were composed by the European Respiratory Society/American Thoracic Society (ERS/ATS) [1]. Since 2017, a multidisciplinary Task Force of asthma experts, co-chaired by Dr Fernando Holguin and Dr Andy Bush, has worked on an updated version. The Task Force made 6 recommendations that were not addressed in the previous guideline (See Table), with a particular focus on new treatment options for severe eosinophilic asthma, such as anti-IL-4Rα, anti-IL5, or IL-5Rα antibodies, biomarkers for anti-IgE therapy, and the use of long-acting muscarinic antagonists, and macrolides [2].

Targeting IL5

IL5 drives eosinophilic inflammation; consequently, targeting either IL5 (mepolizumab, reslizumab) or its receptor IL-5Rα (benralizumab) has demonstrated efficacy in reducing exacerbations and hospitalisation of patients with severe eosinophilic asthma in 12 randomised controlled trials [3,4,5,6,7].

IgE treatment indicators.

Based on the results from 3 randomised trials a blood eosinophil cut-off of ⩾260/µL was suggested to guide initiation of anti-IgE treatment. Additionally, a fractional exhaled nitric oxide fraction cut-off (FeNO ⩾19.5 ppb) identified adolescents or adults with the greatest likelihood of response to anti-IgE therapy [8,9,10].

Muscarinic antagonists.

In total, 5 randomised controlled trials recommended use of long-acting muscarinic antagonist (LAMA) tiotropium in children, adolescents and adults with severe asthma. Tiotropium was most effective at treating worsening asthma and in controlling symptoms and exacerbations [11,12,13]


Macrolide antibiotics were previously recommended under the condition that long-term use should be avoided. In 6 recent randomised controlled trials, chronic macrolide treatment showed overall reduction of asthma exacerbations. However, these effects are limited to participants with persistently symptomatic asthma, which may be more exacerbation-prone. Since antimicrobial resistance associated with prolonged antibiotic treatment is a pressing public health issue, this therapy did not meet the ERS/ATS criteria for recommendation for chronic use [14,15,16,17,18,19].

Monoclonal anti-IL-4Rα.

5 randomised controlled trials with different age groups showed that dupilumab, directed against the α subunit of IL-4 receptor, has a positive effect on exacerbations and lung function when used as an add-on therapy to medium-to-high dose inhaled corticosteroids and a long-acting β2 agonist [20,21,22].


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  2. Holguin F, et al. Management of severe asthma : a European Respiratory Society / American Thoracic Society guideline. 2020;(April 2019).
  3. Bel EH, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371: 1189–1197
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  7. Castro M, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011; 184: 1125–1132
  8. Ledford D, et al. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy. J Allergy Clin Immunol 2017; 140: 162–169
  9. Hanania NA, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med 2013; 187: 804–811.
  10. Busse W, et al. High eosinophil count: a potential biomarker for assessing successful omalizumab treatment effects. J Allergy Clin Immunol 2013; 132: 485–486.
  11. Kerstjens HA, et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J Allergy Clin Immunol 2011; 128: 308–314.
  12. Kerstjens HA, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012; 367: 1198–1207.
  13. Hamelmann E, et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J 2017; 49: 1601100.
  14. Brusselle GG, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 2013; 68: 322–329.
  15. Gibson PG, 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; 390: 659–668.
  16. Strunk RC, et al. Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. J Allergy Clin Immunol 2008; 122: 1138–1144.
  17. Hahn DL, et al. Azithromycin for bronchial asthma in adults: an effectiveness trial. JAm Board Fam Med 2012; 25: 442–459.
  18. Sutherland ER, et al. A trial of clarithromycin for the treatment of suboptimally controlled asthma. J Allergy Clin Immunol 2010; 126: 747–753.
  19. Simpson JL, et al. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med 2008; 177: 148–155.
  20. Wenzel S, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal. The Lancet 2016; 388, P31-44.
  21. Castro M, C et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 2018; 378: 2486–2496.
  22. Rabe KF, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med 2018; 378: 2475–2485.

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