This document provides clinical recommendations for the management of severe
asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of
asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-
interleukin (IL)-5 and anti-
IL-5 receptor α for severe uncontrolled adult eosinophilic
asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL-1 to guide anti-IL-5 initiation in adult patients with severe
asthma; 3) suggest considering specific eosinophil (≥260 μL-1) and exhaled
nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to
anti-IgE therapy; 4) suggest using inhaled
tiotropium for adolescents and adults with severe uncontrolled
asthma despite Global Initiative for
Asthma (GINA) step 4-5 or National
Asthma Education and Prevention Program (NAEPP) step 5
therapies; 5) suggest a trial of chronic
macrolide therapy to reduce
asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5
therapies, irrespective of
asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic
asthma and for those with severe
corticosteroid-dependent
asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.