Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization Consultation on Severe Asthma

Bousquet, Jean MD, PhD
Mantzouranis, Eva MD, PhD
Cruz, Alvaro A. MD
Aït-Khaled, Nadia MD, PhD
Baena-Cagnani, Carlos E. MD
Bleecker, Eugene R. MD
Brightling, Chris E. MRCP, PhD
Burney, Peter MA, MD, FRCP, FFPH, FMedSci
Bush, Andrew MD, FRCP, FRCPCH
Busse, William W. MD
Casale, Thomas B. MD
Chan-Yeung, Moira MD
Chen, Rongchang MD
Chowdhury, Badrul MD, PhD
Chung, Kian Fan DSc, MD
Dahl, Ronald MD, DrMedSci
Drazen, Jeffrey M. MD
Fabbri, Leonardo M. MD
Holgate, Stephen T. MD, DSc
Kauffmann, Francine MD
Haahtela, Tari MD
Khaltaev, Nikolaï MD, PhD
Kiley, James P. PhD
Masjedi, Mohammad R. MD
Mohammad, Yousser MD
O'Byrne, Paul MB, FRCPI, FRCP(C), FRCPE, FRCP(Glas)
Partridge, Martyn R. MD
Rabe, Klaus F. MD, PhD
Togias, Alkis MD
van Weel, Christiaan MD, PhD
Wenzel, Sally MD
Zhong, Nanshan MD
Zuberbier, Torsten MD, PhD

^aUniversity Hospital, Hôpital Arnaud de Villeneuve, Montpellier, France
^bCESP Center for Research in Epidemiology and Population Health, INSERM U1018, Villejuif, France
^cParis Sud 11, UMRS 1018, Villejuif, France
^dWorld Health Organization, Geneva, Switzerland
^eProAR—FMB, Federal University of Bahia, Salvador, Brazil
^fThe Union, Paris, France
^gFaculty of Medicine, Catholic University, Cordoba, Argentina, and School of Specialization, Respiratory Medicine, University of Genoa, Italy
^hWake Forest University Health Sciences, Winston-Salem, NC
ⁱInstitute for Lung Health, Leicester, United Kingdom
^jNational Heart and Lung Institute, Imperial College, Respiratory Epidemiology and Public Health, London, United Kingdom
^kRoyal Brompton Hospital and National Heart and Lung Institute, Imperial College, London, United Kingdom
^lNational Heart and Lung Institute, Imperial College London and Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom
^mImperial College London, NHLI Division at Charing Cross Hospital, London, United Kingdom
ⁿDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis
^oCreighton University, Omaha, Neb
^pUniversity of British Columbia, Vancouver, British Columbia, Canada
^qGuangzhou Institute of Respiratory Diseases and State Key Laboratory of Respiratory Diseases, Guangzhou Medical College, Guangzhou, China
^rUS Food and Drug Administration, Silver Spring, Md
^sAarhus University Hospital, Aarhus, Denmark
^tBrigham and Women's Hospital, Boston, Mass
^uUniversity of Modena and Reggio Emilia, Modena, Italy
^vSouthampton General Hospital, Southampton, United Kingdom
^wSkin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland
^xGlobal Alliance against Chronic Respiratory Diseases, Geneva, Switzerland
^yNational Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, Bethesda, Md
^zNational Institute of Allergy and Infectious Diseases, Bethesda, Md
^aaChronic Respiratory Diseases Research Center (CRDRC), National Research Institute of TB and Lung Diseases (NRITLD), Tehran, Islamic Republic of Iran, Tehran, Iran
^bbTishreen University School of Medicine, Lattakia, Syria
^ccDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada
^ddLeiden University Medical Center, Leiden, The Netherlands
^eeRadboud University Nijmegen Medical Center, Nijmegen, The Netherlands
^ffUniversity of Pittsburgh, Pittsburgh, Pa
^ggAllergy-Centre-Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany

^∗Reprint requests: Jean Bousquet, MD, PhD, Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, 371, avenue Doyen Gaston Giraud, F-34295 Montpellier Cedex 5, France. E-mail: [email protected].

In collaboration with the Global Allergy and Asthma European Network (GA²LEN), supported by the Sixth EU Framework program for research (contract no. FOOD-CT-2004–506378) and the World Health Organization Collaborating Center on Asthma and Rhinitis, Montpellier.

Disclosure of potential conflict of interest: J. Bousquet has received honorarium for scientific and advisory boards, lectures, and press conferences from Stallergenes, Actelion, Almirall, AstraZeneca, Chiesi, Ask, Merck, MSD, Novartis, OM Pharma, Sanofi-Aventis, Schering-Plough, Teva, and Uriach. A. A. Cruz has given talks for Novartis and GlaxoSmithKline; has received research support from Chiesi, Mantecorp (Brazil), CNPq (Brazil), National Research Council, Brazilian Ministry of Health, FAPESB State of Brazil Agency for Research, Wellcome Trust (UK), Novartis, and GlaxoSmithKline; is a member of the Planning Group for the Global Alliance against Chronic Respiratory Diseases; and is a member of the Executive Committee for the Global Initiative for Asthma and Allergic Rhinitis and its Impact on Asthma. E. R. Bleecker is a consultant for Aerovance, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Pfizer and has received research support from the NIH/NHLBI. C. E. Brightling is a consultant for MedImmune, AstraZeneca, and Roche and has received research support from MedImmune, AstraZeneca, and GlaxoSmithKline. P. Burney has received research support from the Department of Health (UK). W. W. Busse is on the Advisory Board for Altair, Amgen, Centocor, GlaxoSmithKline, Merck, Pfizer, Wyeth, and Johnson & Johnson; is a consultant for AstraZeneca, Boehringer Ingelheim, Novartis, TEVA, and GlaxoSmithKline; is a speaker for Merck; and has received research support from NIH-NIAID, NIH-NHLBI, Novartis, AstraZeneca, GlaxoSmithKline, MedImmune, and Ception. T. B. Casale is executive vice president of the AAAAI and is on the board of directors for WAO. R. Chen is a consultant on asthma and COPD for AstraZeneca and GlaxoSmithKline and has served as an expert witness on the topic of management of asthma. K. F. Chung is a consultant for Gilead; is on the advisory board for Merck and GlaxoSmithKline; and has received research support from MRC UK, Asthma UK, and Wellcome Trust. R. Dahl is a speaker for MSD, AstraZeneca, ALK, and GlaxoSmithKline; is a speaker and is on the advisory board for TEVA, Boehringer Ingelheim, UCB, Airsonett, Novartis, and Pfizer; is chairman for the Danish Respiratory Society; and is president of Interasma. L. M. Fabbri is a consultant for Nycomed, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sigma Tau, AstraZeneca, Merck Sharp & Dohme, Novartis, Roche, and Pfizer; has received paid lecture fees from Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Nycomed, Roche, and Pfizer; and has received research support from Nycomed, Abbott, AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Schering-Plough, Chiesi, GlaxoSmithKline, Merck Sharp & Dohme, UCB, Pfizer, the Italian Ministry of Health, and the Italian Ministry for University and Research. S. T. Holgate is a consultant for MSD, Novartis, Synergen, Altair, Amgen, and Almiral and owns shares in Synergen. T. Haahtela has received honoraria from Astellas, AstraZeneca, Leiras, MSD, and Orion Pharma. P. O'Byrne is on the advisory board and has received speakers' honoraria from AstraZeneca and GlaxoSmithKline; is on the advisory board for Topigen, Wyeth, and Schering; and has received research support from AstraZeneca, GlaxoSmithKline, Merck, Wyeth, Schering, and Alexion. K. F. Rabe has received remuneration from Nycomed, Forest, AZ, BI, Chiesi, Pearl, MSD, and GlaxoSmithKline and has received research support from Chiesi, AS, BI, and Novartis. C. van Weel has received research support from Boehringer Ingelheim, GlaxoSmithKline, Novartis, the Dutch Asthma Foundation (NAF), and the Netherlands Medical Research Council (Zon/Mw). S. Wenzel is a consultant for Altair, Merck, GlaxoSmithKline, Amgen, and Pearl Therapeutics; is on the scientific advisory board for Amira; and has received research support from MedImmune, GlaxoSmithKline, Aerovance, and Amgen. T. Zuberbier is a consultant for Schering-Plough, Novartis, Leti, Stallergenes, Bayer Schering, Ansell, Kryolan, UCB, MSD, DST, Sanofi-Aventis, and Procter & Gamble; is on the editorial board of the Journal of Allergy, the scientific advisory board of the German Society for Allergy and Clinical Immunology, and the Expert Commission “Novel Food” of the German Federal Ministry of Consumer Protection; is chairman of the European Academy of Allergology and Clinical Immunology, Dermatology Section; is head of the European Center for Allergy Research Foundation; is a committee member of the WHO Initiative Allergic Rhinitis and its Impact on Asthma; is a member of the World Allergy Organization Communications Council; and is secretary general of the Global Allergy and Asthma European Network. E. Mantzouranis, N. Aït-Khaled, C. E. Baena-Cagnani, A. Bush, M. Chan-Yeung, B. Chowdhury, J. M. Drazen, F. Kauffmann, N. Khaltaev, J. P. Kiley, M. R. Masjedi, Y. Mohammad, M. R. Partridge, A. Togias, and N. Zhong have declared that they have no conflict of interest.

Draft reviewed by I. Agache (Romania), E. Aka-Danguy (Cote d'Ivoire), I. J. Ansotegui (United Kingdom), E. D. Bateman (South Africa), A. Belevskiy (Russia), A. Ben Kheder (Tunisia), K. Bennoor (Bangladesh), M. Bergna (Argentina), K. Bissel (France), L. Bjermer (Sweden), L. P. Boulet (Canada), A. Bourdin (France), P. J. Bousquet (France), P. A. M. Camargos (Brazil), G. W. Canonica (Italy), K. H. Carlsen (Norway), P. Chanez (France), N. Chavannes (The Netherlands), Y. Z. Chen (China), C.-Y. Chiang (Taiwan), R. Chiron (France), T. Chivato (Spain), J. Chorostowska (Poland), A. Chuchalin (Russia), D. J. Costa (France), P. De Boer (The Netherlands), L. Delgado (Portugal), A. T. Dinh-Xuan (France), D. Dokic (Macedonia), B. Dolen (United States), H. Douagui (Algeria), R. Dubakiene (Lithuania), Y. El-Gamal (Egypt), R. Gerth van Wijk (The Netherlands), M. Gjomarkaj (Italy), E. Hamelmann (Germany), L. Heaney (United Kingdom), P. H. Howarth (United Kingdom), M. Humbert (France), S. K. Jindal (India), G. Joos (Belgium), O. Kalayci (Turkey), M. A. Kaliner (United States), R. Kauppinen (Finland), M. Khadadah (Kuwait), Y. Y. Kim (Korea), N. B. Koffi (Cote d'Ivoire), V. Kolek (Czech Republic), M. Kowalski (Poland), P. Kuna (Poland), L. T. Le (Vietnam), W. B. Lee (Singapore), E. Lemarié (France), R. F. Lockey (United States), T. Maglakelidze (Georgia), B. Mahbouh (United Arab Emirates), C. Massé (France), N. Miculinic (Croatia), M. Morais-Almeida (Portugal), C. K. Naspitz (Brazil), H. E. Neffen (Argentina), E. Nizankowska-Mogilnicka (Poland), P. Noel (United States), K. Ohta (Japan), S. Ouedraogo (Burkina Fasso), N. Papadopoulos (Greece), G. Passalacqua (Italy), R. Pawankar (Japan), C. Picado (Spain), T. Popov (Bulgaria), D. Postma (The Netherlands), P. Potter (South Africa), H. Reddel (Australia), N. Rodriguez (Mexico), J. Rosado-Pinto (Portugal), L. J. Rosenwasser (United States), D. Ryan (United Kingdom), M. Salapatas (Greece), M. Sanchez-Borges (Venezuela), H. J. Schünemann (Canada), V. Siroux (France), J. C. Sisul Alvariza (Paraguay), R. Smith (United States), T. M. Sooronbaev (Kyrgyzstan), M. A. Tageldin (Egypt), V. Taggart (United States), N. C. Thomson (United Kingdom), A. Todo-Bom (Portugal), A. Valiulis (Lithuania), E. Valovirta (Finland), G. Viegi (Italy), M. Wickman (Sweden), A. Yanes (Argentina), A. Yorgancioglu (Turkey), O. Yusuf (Pakistan), M. Zamboni (Brazil), H. Zar (South Africa), M. Zitt (United States).

Received for publication May 24, 2010; revised July 12, 2010; accepted for publication July 12, 2010.

Journal of Allergy & Clinical Immunology 126(5):p 926-938, November 2010.

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5–6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as “Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children).” Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment.