Medtronic. Dr. Nead has received personal fees from Medtronic. Dr. Bowling has received personal fees from Medtronic. Dr. Murgu has received personal fees from Medtronic, Boston Scientific, Pinnacle Biologics, Olympus, Cook, Auris Robotics, and Elsevier; and has stock ownership in Concordia, Boston Scientific, and Merck. Dr. Krimsky has received personal fees from Medtronic, Innovital Systems, Gala Therapeutic, SOC, and Peytant; has stock ownership with Innovital Systems and CSA Medical; and has patents pending with Medtronic and Merit. Dr. Murillo has received support from Medtronic. Dr. LeMense has received personal fees from Medtronic. Dr. Minnich has received personal fees from Medtronic. Dr. Bansal has received personal fees from Medtronic, Pinnacle Biologics, Sunovion, and Veran Medical. Dr. Ellis has received support from Medtronic. Dr. Mahajan has received personal fees from Medtronic. Dr. Gildea has received personal fees from Medtronic. Dr. Bechara has received support from Medtronic. Dr. Sztejman has received support from Medtronic. Dr. Flandes has received grants from BTG-PneumRx and Ambu; and personal fees from Medtronic, BTG-PneumRx, Olympus, Ambu, PulmonX, and Boston Scientific. Dr. Rickman has received personal fees from Medtronic, Veran Medical, BD, Olympus, and Abbvie. Dr. Benzaquen has received support from Medtronic. Dr. Hogarth has received personal fees from Medtronic, Auris Surgical Robotics, Boston Scientific, Grifols, Shire, and CSL; and has stock ownership with Auris Surgical Robotics. Dr. Linden has received support from Medtronic. Dr. Wahidi has received personal fees from Medtronic and Veran Medical. Dr. Mattingley has received personal fees from Medtronic and is current employee of Medtronic (employment began after completion of enrollment). Dr. Hood is an employee with stock ownership at Medtronic; and has stock ownership with Boston Scientific. Ms. Lin and Ms. Wolvers are employees with stock ownership at Medtronic. Dr. Khandar has received personal fees from Medtronic.

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.

Purpose: The goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma. Methods: This multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebocontrolled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab. In COSMEX, patients received mepolizumab 100 mg subcutaneously every 4 weeks as add-on therapy for up to 172 weeks. Primary endpoints were adverse event frequency and exacerbation rate per year; also assessed were forced

Background: The fractional exhaled nitric oxide (FE NO ) test is a point-of-care test that is used in the assessment of asthma.Objective: To provide evidence-based clinical guidance on whether FE NO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered.Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FE NO . The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidencebased answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations.Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FE NO -based care. In patients with asthma in whom treatment is being considered, we suggest that FE NO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice.Conclusions: Clinicians should consider this recommendation to measure FE NO in patients with asthma in whom treatment is being considered based on current best available evidence.

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including metaanalyses, 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:• suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes;• suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma;• 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;• 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;• 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;• 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.