With novel therapies in development, there is an opportunity to consider asthma remission as a treatment goal. In this Rostrum, we present a generalized framework for clinical and complete remission in asthma, on and off treatment, developed on the basis of medical literature and expert consensus. A modified Delphi survey approach was used to ascertain expert consensus on core components of asthma remission as a treatment target. Phase 1 identified other chronic inflammatory diseases with remission definitions. Phase 2 evaluated components of those definitions as well as published definitions of spontaneous asthma remission. Phase 3 evaluated a remission framework created using consensus findings. Clinical remission comprised 12 or more months with (1) absence of significant symptoms by validated instrument, (2) lung function optimization/stabilization, (3) patient/provider agreement regarding remission, and (4) no use of systemic corticosteroids. Complete remission was defined as clinical remission plus objective resolution of asthma-related inflammation and, if appropriate, negative bronchial hyperresponsiveness. Remission off treatment required no asthma treatment for 12 or more months. The proposed framework is a first step toward developing asthma remission as a treatment target and should be refined through future research, patient input, and clinical study. With novel therapies in development, there is an opportunity to consider asthma remission as a treatment goal. In this Rostrum, we present a generalized framework for clinical and complete remission in asthma, on and off treatment, developed on the basis of medical literature and expert consensus. A modified Delphi survey approach was used to ascertain expert consensus on core components of asthma remission as a treatment target. Phase 1 identified other chronic inflammatory diseases with remission definitions. Phase 2 evaluated components of those definitions as well as published definitions of spontaneous asthma remission. Phase 3 evaluated a remission framework created using consensus findings. Clinical remission comprised 12 or more months with (1) absence of significant symptoms by validated instrument, (2) lung function optimization/stabilization, (3) patient/provider agreement regarding remission, and (4) no use of systemic corticosteroids. Complete remission was defined as clinical remission plus objective resolution of asthma-related inflammation and, if appropriate, negative bronchial hyperresponsiveness. Remission off treatment required no asthma treatment for 12 or more months. The proposed framework is a first step toward developing asthma remission as a treatment target and should be refined through future research, patient input, and clinical study. Asthma is the most common long-term respiratory disease, affecting more than 300 million people worldwide with significant morbidity and mortality.1GBD 2015 Chronic Respiratory Disease CollaboratorsGlobal, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet Respir Med. 2017; 5: 691-706Abstract Full Text Full Text PDF PubMed Scopus (964) Google Scholar The estimated annual cost of asthma in the United States, taking into account direct medical costs, mortality, and loss of attendance at school and work, was estimated to be in excess of $80 billion.2Nurmagambetov T. Kuwahara R. Garbe P. The economic burden of asthma in the United States, 2008-2013.Ann Am Thorac Soc. 2018; 15: 348-356Crossref PubMed Scopus (263) Google Scholar The mainstay of asthma therapy, inhaled and oral glucocorticoids, has not changed for decades, and although they remain very effective medications, their nonspecific anti-inflammatory mechanism of action has not been shown to have a significant long-term impact on the course of the disease. Other chronic inflammatory diseases, such as rheumatoid arthritis, have seen a transformation in the available treatment options, moving from glucocorticoids to disease-modifying antirheumatic drugs and on to targeted biologic therapies, which can slow down or even halt the progression of disease. Alongside these advances, the treatment paradigm in these diseases has advanced to “treat to target” key pathophysiologic pathways with the goal of inducing sustained disease remission or, when remission is not achievable, sustained reduction in disease activity.3Smolen J.S. Breedveld F.C. Burmester G.R. Bykerk V. Dougados M. Emery P. et al.Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.Ann Rheum Dis. 2016; 75: 3-15Crossref PubMed Scopus (730) Google Scholar With several novel therapies currently being used and developed for asthma, it is a logical time to consider whether remission in asthma is now an achievable treatment target.4Nannini L.J. Treat to target approach for asthma.J Asthma. 2019; 23: 1-4Google Scholar Disease remission is broadly defined as a state or period with low to no disease activity and can be spontaneous or a result of therapy.5van den Toorn L.M. Overbeek S.E. Prins J.B. Hoogsteden H.C. de Jongste J.C. Asthma remission: does it exist?.Curr Opin Pulm Med. 2003; 9: 15-20Crossref PubMed Scopus (20) Google Scholar,6The Free Dictionary. remission. (n.d.) Mosby’s Medical Dictionary, 8th edition. 2009.https://medical-dictionary.thefreedictionary.com/remissionDate accessed: January 10, 2019Google Scholar Assessments of disease activity can include clinical signs and patient symptoms of the disease as well as markers of disease processes derived from laboratory testing and/or imaging. To date, remission of asthma has only been described as the spontaneous cessation of asthma disease activity (eg, due to the transition from childhood to adulthood) and not as a therapeutic target.7Holm M. Omenaas E. Gislason T. Svanes C. Jogi R. Norrman E. et al.Remission of asthma: a prospective longitudinal study from northern Europe (RHINE study).Eur Respir J. 2007; 30: 62-65Crossref PubMed Scopus (42) Google Scholar, 8Upham J.W. James A.L. Remission of asthma: the next therapeutic frontier?.Pharmacol Ther. 2011; 130: 38-45Crossref PubMed Scopus (15) Google Scholar, 9Westerhof G.A. Coumou H. de Nijs S.B. Weersink E.J. Bel E.H. Clinical predictors of remission and persistence of adult-onset asthma.J Allergy Clin Immunol. 2018; 141: 104-109.e3Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 10Wu T.-J. Wu C.-F. Lee Y.L. Hsiue T.-R. Guo Y.L. Asthma incidence, remission, relapse and persistence: a population-based study in southern Taiwan.Respir Res. 2014; 15: 135Crossref PubMed Scopus (16) Google Scholar A consensus definition of asthma remission could become a new asthma treatment goal and allow further exploration and comparison of the efficacy of novel treatment regimens.8Upham J.W. James A.L. Remission of asthma: the next therapeutic frontier?.Pharmacol Ther. 2011; 130: 38-45Crossref PubMed Scopus (15) Google Scholar A comprehensive and pragmatic definition of remission as a treatment target must add value beyond the existing treatment goal of asthma control, which is based on current symptom control and future risk of adverse outcomes.11Global Initiative for AsthmaGlobal strategy for asthma management and prevention.http://www.ginasthma.orgDate accessed: July 10, 2018Google Scholar,12Juniper E.F. O’Byrne P.M. Guyatt G.H. Ferrie P.J. King D.R. Development and validation of a questionnaire to measure asthma control.Eur Respir J. 1999; 14: 902-907Crossref PubMed Scopus (1626) Google Scholar Although there are clear criteria for optimal control of a patient’s symptoms in the past 4 weeks, we lack explicit goals for symptom control over longer time intervals and for minimization of future risk, which is complicated by the high number of risk factors for poor outcomes and the fact that some risk factors are not modifiable. Assessment of asthma disease should be based on both objective and subjective measures and should incorporate all important aspects of the disease, including symptom control, exacerbation frequency, pulmonary function, and laboratory markers of inflammation.11Global Initiative for AsthmaGlobal strategy for asthma management and prevention.http://www.ginasthma.orgDate accessed: July 10, 2018Google Scholar The ideal definition of asthma remission should address current asthma symptom burden, recent exacerbation incidence, and future exacerbation risk and include the absence of ongoing airway inflammation and prevention of accelerated lung function decline and airway remodeling. The definition should require a sufficient duration of assessment to address the inherent variability in asthma, including seasonality of disease activity, and should be suitable for assessment in clinical studies as well as implementation in routine clinical practice. The definition of remission should be relevant across the entire spectrum of asthma severity and take into account the presence or absence of background medication. The current project therefore aims to develop a framework for asthma remission that satisfies the above criteria, based on expert consensus collected via a multistage Delphi survey and relevant medical literature in other chronic inflammatory conditions and asthma. This framework is envisioned as an initial step of an iterative, multistep journey toward a commonly accepted definition of asthma remission. Rather than create a single specific definition of remission, the goal of the current project was to propose a generalized framework that can be further refined and evaluated by future studies, interventional trials, clinical practice, patient input, and expert opinion. A modified Delphi survey was conducted among a small group of US and European experts in the primary and specialty care of asthma (authors A.M.G., M.B., W.W.B., T.B.C., J.W.H.K., I.D.P., S.J.S., and P.G.W.). The goal of the survey was to derive a consensus framework for asthma remission as a treatment goal, using an approach similar to that used to derive remission frameworks for other chronic inflammatory diseases.13van Vollenhoven R. Voskuyl A. Bertsias G. Aranow C. Aringer M. Arnaud L. et al.A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS).Ann Rheum Dis. 2017; 76: 554-561Crossref PubMed Scopus (150) Google Scholar, 14Vuitton L. Peyrin-Biroulet L. Colombel J.F. Pariente B. Pineton de Chambrun G. Walsh A.J. et al.Defining endoscopic response and remission in ulcerative colitis clinical trials: an international consensus.Aliment Pharmacol Ther. 2017; 45: 801-813Crossref PubMed Scopus (48) Google Scholar, 15Dejaco C. Duftner C. Cimmino M.A. Dasgupta B. Salvarani C. Crowson C.S. et al.Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi-based expert consensus.Ann Rheum Dis. 2010; 70: 447-453Crossref PubMed Scopus (56) Google Scholar Phase 1 identified other chronic inflammatory diseases with established definitions of remission as a treatment target. Phase 2 identified the key components of these definitions on the basis of published definitions of remission in these reference diseases as well as recent studies of spontaneous remission in asthma. Phase 3 tested a framework for asthma remission and clarifying statements based on phase 2 findings. Consensus was defined a priori as no more than 1 respondent dissenting from majority agreement. A more detailed description of the survey process in each phase can be found in this article’s Methods section in the Online Repository at www.jacionline.org. The structured literature search identified 6 diseases with established definitions of remission as a treatment target: rheumatoid arthritis (RA), Crohn disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), polymyalgia rheumatica (PMR), and psoriasis. These 6 diseases were categorized into 2 groups on the basis of rigor of the definition: group 1 (RA, CD, UC, and SLE) had clear definitions endorsed by regulatory authorities and/or internationally recognized professional societies, whereas group 2 (PMR and psoriasis) had less well-developed definitions and/or less consensus. Details regarding these definitions are outlined in this article’s Results section in the Online Repository at www.jacionline.org. Although definitions beyond the 6 diseases above exist in the medical literature, none were identified in our structured search for more established definitions. In the first Delphi survey, most respondents (88%; see Table E1 in this article’s Online Repository at www.jacionline.org) agreed to include RA, UC, CD, and SLE, but not PMR or psoriasis, because they were deemed less developed and not as relevant to asthma. The results of the literature summary on definitions of remission in RA, UC, CD, and SLE are presented in Table I. Efforts to define remission focused as a first stage on “clinical remission” based on systematic evaluations of disease signs and symptoms and routine laboratory (or in UC, endoscopic) assessments. All definitions allowed patients to receive ongoing treatment and still qualify for remission; however, definitions for UC, CD, and SLE required the patient to not be receiving long-term corticosteroid therapy due to associated toxicity (for SLE, this was specific to >5 mg/d prednisone or equivalent). Relevant laboratory measures routinely available in clinical practice are included in clinical remission in RA, CD, and SLE. Clinical remission in RA, CD, and SLE did not require imaging, histology, or other nonroutine diagnostic procedures, whereas UC remission required endoscopy assessment. CRP, C-reactive Disease A current assessment of these factors was deemed sufficient to remission in RA, UC, and there were no SLE included a nonspecific that remission be due to the of the disease, although experts did not on the specific of remission such as and were proposed in RA, CD, and SLE, based on imaging, histology, and other nonroutine diagnostic however, consensus definitions were not available for these of remission. The clinical experts were the summary of remission definition components in Table and a survey to the most relevant for remission in asthma. All experts and the of agreement for each is in Table in Table in this article’s Online Repository at All respondents agreed with the from the literature of remission definitions in RA, UC, CD, and SLE, and consensus was for several statements regarding asthma remission. other a majority and for the framework tested in phase Although RA, UC, and had no duration for remission, most experts that asthma remission should have a required with a The published definitions of asthma remission that we evaluated described spontaneous cessation of asthma disease activity to asthma treatment a pragmatic treatment goal. the definitions were evaluated to components of remission as a treatment target. definitions used care disease and all definitions required no asthma symptoms by patients 6 months to 3 of clinical remission on symptoms and whereas definitions of complete remission included of current lung function and/or negative airway 1 definition The of spontaneous remission across studies based on the patient and definition not not a in The results described above were presented to the clinical experts for the phase Delphi on components of the definitions the survey tested specific criteria for in our framework of asthma remission as a treatment goal. of a from 1 of the experts were not Table the of agreement for each that consensus are presented in Table in this article’s Online Repository at All respondents agreed with the from the literature and consensus was for several These as well as on other were into the framework and clarifying statements tested in phase to and statements that did not consensus can be found in Table hyperresponsiveness. the basis of expert in phase survey a generalized framework for definitions of clinical and complete remission in asthma, on and off treatment Complete remission that the criteria for clinical remission be with criteria to markers of inflammation and bronchial hyperresponsiveness. This framework was to be in several to of consensus. A Delphi survey was conducted to this framework and several clarifying statements regarding assessment of asthma lung function, and of the phase 3 survey, clinical experts were with the phase 2 survey All experts in the phase 3 Delphi survey, and the of agreement for each is in Table in this article’s Online Repository at www.jacionline.org. All respondents agreed with the proposed generalized framework for asthma remission presented in with all experts agreed that Asthma and Asthma are of appropriate, validated to the sustained absence of significant asthma and that for sustained absence of significant asthma symptoms is less than or than or to (or measure in future validated Clinical experts the of asthma symptom components in the of asthma remission, as from for asthma control respondents patient of asthma control, symptoms at and as in a definition of remission. a Delphi we have a framework for asthma remission as a treatment target that is with established definitions of remission in other chronic inflammatory diseases and the existing medical literature spontaneous asthma remission. the basis of these we propose that definitions with the framework in 1 be tested and refined via direct patient and prospective and of clinical study asthma remission treatment target must be in routine clinical practice, for and be associated with disease proposed remission framework the outcomes of clinical and complete remission, on and off Complete remission is the optimal but not be achievable or in in which clinical remission can be a goal. the goal of remission off all asthma treatment not be achievable for in which remission on treatment including systemic corticosteroid can have The of novel targeted therapies for asthma an opportunity to the treatment goal of asthma therapy from disease control to disease remission. The of currently used in asthma is no longer used in other chronic inflammatory has clinical but asthma symptom control is only to the patient’s current state and is not as a treatment goal as disease remission. of spontaneous remission in with asthma that clinical and complete remission are achievable in of asthma remission as a treatment goal a more target for novel therapies and treatment and a paradigm in the management of the disease. is to be the of novel therapies to asthma remission or even asthma in Clinical have shown that therapies can asthma on systemic corticosteroid therapy, and patient symptoms and of P. M. of in Respir Med. 2019; PubMed Scopus Google Scholar but we their to the course of asthma through progression and disease. has the most established remission definition and of published data regarding disease remission as a treatment goal. The “treat to target” strategy has treatment, long-term clinical outcomes and patient of J.S. Breedveld F.C. Burmester G.R. Bykerk V. Dougados M. Emery P. et al.Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.Ann Rheum Dis. 2016; 75: 3-15Crossref PubMed Scopus (730) Google L.J. Treat to target approach for asthma.J Asthma. 2019; 23: 1-4Google Scholar Remission is now the therapeutic goal, treatment of et of for the of 2016; PubMed Scopus Google Scholar The past years have in treatment with disease-modifying antirheumatic drugs and therapies, and remission has been associated with long-term G. J. B. 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The current was based on from clinical experts and be as a expert consensus. it is to be a first step toward developing asthma remission as a treatment goal, which require further and with from professional societies, regulatory and the current of a small group of experts in asthma was the Delphi process that required of studies and definitions of remission in our reference disease and asthma. A similar approach was used to develop initial remission frameworks in PMR and L. Peyrin-Biroulet L. Colombel J.F. Pariente B. Pineton de Chambrun G. Walsh A.J. et al.Defining endoscopic response and remission in ulcerative colitis clinical trials: an international consensus.Aliment Pharmacol Ther. 2017; 45: 801-813Crossref PubMed Scopus (48) Google C. Duftner C. Cimmino M.A. Dasgupta B. Salvarani C. Crowson C.S. et al.Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi-based expert consensus.Ann Rheum Dis. 2010; 70: 447-453Crossref PubMed Scopus (56) Google Scholar With to the of the proposed use of the remission with specific definition could be because future of inflammation or airway allow for assessment of aspects of the disease. In our proposed time of 12 months does not the for to inflammation and clinical and patients deemed in remission on treatment should be of the of to and their disease. The explicit of in our framework to the of agreed in our survey in asthma does not the risk of and even asthma The of remission from a our process was on asthma and did not include asthma. that and require R. et of and childhood asthma.J Allergy Clin Immunol. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar because they are still lung development, and of lung and in the pulmonary function is to define remission as a treatment goal in asthma. asthma remission as a treatment goal, we to asthma treatment and outcomes for similar to has been in and other chronic inflammatory To significant value to patients and our proposed asthma remission framework must be tested and refined through patient and future studies, studies clinical This process require significant across the asthma Remission is an treatment goal, but it is