Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline

Abstract

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.

Conflict of interest statement

Conflict of interest: F. Holguin has nothing to disclose. Conflict of interest: J.C. Cardet has nothing to disclose. Conflict of interest: K.F. Chung has received honoraria for participating in advisory board meetings of GlaxoSmithKline, AstraZeneca, Novartis, Merck, Boehringer Ingelheim, 4D Pharma, Pieris and Teva regarding treatments for asthma, cough and chronic obstructive pulmonary disease and has also been remunerated for speaking engagements. Conflict of interest: S. Diver has nothing to disclose. Conflict of interest: D.S. Ferreira reports fellowship MTF 2015-02 from the European Respiratory Society, during the conduct of the study. Conflict of interest: A. Fitzpatrick has nothing to disclose. Conflict of interest: M. Gaga reports grants and personal fees from AstraZeneca and Chiesi, grants from Novartis, Menarini and Elpen, personal fees from MSD and BMS, outside the submitted work. Conflict of interest: L. Kellermeyer has nothing to disclose. Conflict of interest: S. Khurana reports grants from GlaxoSmithKline and Sanofi, outside the submitted work. Conflict of interest: S. Knight has nothing to disclose. Conflict of interest: V.M. McDonald reports grants from GlaxoSmithKline, grants and personal fees for lectures from AstraZeneca, personal fees for educational steering committee work from Menarini, outside the submitted work. Conflict of interest: R.L. Morgan has nothing to disclose. Conflict of interest: V.E. Ortega has nothing to disclose. Conflict of interest: D. Rigau acts as a European Respiratory Society methodologist. Conflict of interest: P. Subbarao has nothing to disclose. Conflict of interest: T. Tonia acts as a European Respiratory Society methodologist. Conflict of interest: I.M. Adcock has nothing to disclose. Conflict of interest: E.R. Bleecker undertaken clinical trials through his employer, Wake Forest School of Medicine and University of Arizona, for AstraZeneca, MedImmune, Boehringer Ingelheim, Genentech, Johnson and Johnson (Janssen), Novartis, Regeneron and Sanofi Genzyme, and has also served as a paid consultant for AstraZeneca, MedImmune, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Regeneron and Sanofi Genzyme, outside the submitted work. Conflict of interest: C. Brightling reports grants and personal fees from GlaxoSmithKline, Novartis, Genentech/Roche, Chiesi, 4D Pharma, Glenmark, Boehringer Ingelheim, Mologic, Gossamer and AstraZeneca/MedImmune, personal fees from Sanofi/Regeneron and Teva, outside the submitted work. Conflict of interest: L-P. Boulet reports research grants for participation in multicentre studies from AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharma, Sanofi and Takeda; support for research projects submitted by the investigator from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck and Takeda; consulting and advisory board work for AstraZeneca, GlaxoSmithKline, Novartis and Methapharm; nonprofit grants for production of educational materials from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck Frosst and Novartis; conference fees from AstraZeneca, GlaxoSmithKline, Merck and Novartis; support for participation in conferences and meetings from Novartis and Takeda. Conflict of interest: M. Cabana reports personal fees for consultancy from Genentech and Novartis, outside the submitted work. Conflict of interest: M. Castro receives university grant funding from NIH, American Lung Association and PCORI; receives pharmaceutical grant funding from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Sanofi-Aventis; is a consultant for Aviragen, Boston Scientific, Genentech, Nuvaira, Neutronic, Therabron, Theravance, Vectura, 4D Pharma, VIDA, Mallinckrodt, Teva and Sanofi-Aventis; is a speaker for AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron, Sanofi and Teva; and receives royalties from Elsevier. Conflict of interest: P. Chanez has undertaken consultancy services for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF, served on advisory boards for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi and Sanofi, received lecture fees from GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK, and received industry-sponsored grants from AstraZeneca, ALK and Novartis. Conflict of interest: A. Custovic reports personal fees for consultancy from Novartis, Regeneron/Sanofi, Boehringer Ingelheim and Philips, personal fees for lectures from Thermo Fisher Scientific and Novartis, outside the submitted work. Conflict of interest: R. Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and Teva, consultation for Teva and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline; and is a co-founder of and current consultant for, and has shares in, Synairgen, a University of Southampton spin-out company. Conflict of interest: U. Frey reports personal fees for meeting attendance from GlaxoSmithKline Scientific Advisory Board, outside the submitted work. Conflict of interest: B. Frankemölle has nothing to disclose. Conflict of interest: P. Gibson reports grants and personal fees for educational activities from GlaxoSmithKline, grants and personal fees for lectures and educational activities from AstraZeneca, personal fees for educational steering committee work from Novartis and Sanofi, outside the submitted work. Conflict of interest: D. Hamerlijnck is independent European Federation of Allergy and Airways (EFA) patient advisor to Novartis on patient involvement; patient co-chair of the ERS Severe Heterogeneous Asthma Registry, Patient-centred CRC; member of the scientific advisory board of the Veelbelovende Zorg for ZIN and ZonMw; member of the scientific advisory board of the BENEFIT (ZonMw–KBC Dutch Belgian collaboration); member of the IMI PARADIGM patient advisory group for EPF; member of the scientific advisory board for ERA-NET NEURON Biomarkers; patient reviewer for the Dutch Patient Federation and several ZonMw scientific committees. Conflict of interest: N. Jarjour reports the following, outside the submitted work: a grant from National Institutes of Health; personal fees for consultation from AstraZeneca and Boehringer Ingelheim. Conflict of interest: S. Konno reports grants from AstraZeneca, Kyorin Pharmaceutical, Japan Allergy Foundation, Novartis and Ministry of Education, Culture, Sports, Science and Technology of Japan, during the conduct of the study. Conflict of interest: H. Shen has nothing to disclose. Conflict of interest: C. Vitari has nothing to disclose. Conflict of interest: A. Bush has nothing to disclose.

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