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Global Strategy for Asthma Management and Prevention
The GINA reports are available on www.ginasthma.org.
3. Global Strategy for Asthma Management and Prevention 2010 (update)
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GINA EXECUTIVE COMMITTEE* GINA EXECUTIVE COMMITTEE*
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Eric D. Bateman, MD, Chair Mark FitzGerald, MD, Chair
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University Cape Town Lung Institute University of British Columbia
Cape Town, South Africa Vancouver, BC, Canada
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Louis-Philippe Boulet, MD Neil Barnes, MD
Hôpital Laval London Chest Hospital
Sainte-Foy , Quebec, Canada London, England, UK
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Alvaro A. Cru , MD Peter J. Barnes, MD
Federal University of Bahia National Heart and Lung Institute
School of Medicine London, England, UK
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Salvador, Brazil
Eric D. Bateman, MD
Mark FitzGerald, MD University Cape Town Lung Institute
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University of British Columbia Cape Town, South Africa
Vancouver, BC, Canada
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Allan Becker, MD
Tari Haahtela, MD University of Manitoba
Helsinki University Central Hospital Winnipeg, Manitoba, Canada
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Helsinki, Finland
Jeffrey M. Drazen, MD
Mark L. Levy, MD Harvard Medical School
University of Edinburgh
London England, UK
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Boston, Massachusetts, USA
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Robert F. Lemanske, Jr., M.D.
Paul O’Byrne, MD University of Wisconsin School of Medicine
McMaster University Madison, Wisconsin, USA
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Ontario, Canada
Paul O’Byrne, MD
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Ken Ohta, MD, PhD McMaster University
Teikyo University School of Medicine Ontario, Canada
Tokyo, Japan
Ken Ohta, MD, PhD
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Pierluigi Paggiaro, MD Teikyo University School of Medicine
University of Pisa Tokyo, Japan
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Pisa, Italy
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Soren Erik Pedersen, M.D.
Soren Erik Pedersen, M.D. Kolding Hospital Kolding Hospital
Kolding, Denmark Kolding, Denmark
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Manuel Soto-Quiro, MD Emilio Pizichini, MD
Hospital Nacional de Niños Universidade Federal de Santa Catarina
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San José, Costa Rica Florianópolis, SC, Brazil
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Gary W. Wong, MD Helen K. Reddel, MD
Chinese University of Hong Kong Woolcock Institute of Medical Research
Hong Kong ROC Camperdown, NSW, Australia
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Sean D. Sullivan, PhD
Professor of Pharmacy, Public Health
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University of Washington
Seattle, Washington, USA
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Sally E. Wenzel, M.D.
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University of Pittsburgh
Pittsburgh, Pennsylvania, USA
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*Disclosures for members of GINA Executive and Science Committees can be found at:
http://www.ginasthma.com/Committees.asp?l1=7&l2=2 i
4. PREFACE
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Asthma is a serious global health problem. People of all In spite of these dissemination efforts, international
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ages in countries throughout the world are affected by surveys provide direct evidence for suboptimal asthma
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this chronic airway disorder that, when uncontrolled, can control in many countries, despite the availability of
place severe limits on daily life and is sometimes fatal. effective therapies. It is clear that if recommendations
The prevalence of asthma is increasing in most countries, contained within this report are to improve care of people
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especially among children. Asthma is a significant burden, with asthma, every effort must be made to encourage
not only in terms of health care costs but also of lost health care leaders to assure availability of and access to
productivity and reduced participation in family life. medications, and develop means to implement effective
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asthma management programs including the use of
During the past two decades, we have witnessed many appropriate tools to measure success.
scientific advances that have improved our understanding
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of asthma and our ability to manage and control it In 2002, the GINA Report stated that “It is reasonable
effectively. However, the diversity of national health to expect that in most patients with asthma, control
care service systems and variations in the availability of the disease can, and should be achieved and
of asthma therapies require that recommendations for maintained.” To meet this challenge, in 2005, Executive
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asthma care be adapted to local conditions throughout Committee recommended preparation of a new report
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the global community. In addition, public health officials not only to incorporate updated scientific information
require information about the costs of asthma care, how but to implement an approach to asthma management
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to effectively manage this chronic disorder, and education based on asthma control, rather than asthma severity.
methods to develop asthma care services and programs Recommendations to assess, treat and maintain asthma
responsive to the particular needs and circumstances control are provided in this document. The methods used
within their countries. T
to prepare this document are described in the Introduction.
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In 1993, the National Heart, Lung, and Blood Institute It is a privilege for me to acknowledge the work of the
collaborated with the World Health Organization to many people who participated in this update project, as
convene a workshop that led to a Workshop Report: well as to acknowledge the superlative work of all who
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Global Strategy for Asthma Management and Prevention. have contributed to the success of the GINA program.
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This presented a comprehensive plan to manage asthma
with the goal of reducing chronic disability and premature The GINA program has been conducted through
deaths while allowing patients with asthma to lead unrestricted educational grants from AstraZeneca,
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productive and fulfilling lives. Boehringer Ingelheim, Chiesi Group, GlaxoSmithKline,
Meda Pharma, Merck, Sharp & Dohme, Mitsubishi Tanabe
At the same time, the Global Initiative for Asthma (GINA) Pharma, Novartis, Nycomed, PharmAxis and Schering-
I
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was implemented to develop a network of individuals, Plough. The generous contributions of these companies
organizations, and public health officials to disseminate assured that Committee members could meet together
information about the care of patients with asthma while to discuss issues and reach consensus in a constructive
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at the same time assuring a mechanism to incorporate and timely manner. The members of the GINA Committees
the results of scientific investigations into asthma are, however, solely responsible for the statements and
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care. Publications based on the GINA Report were conclusions presented in this publication.
prepared and have been translated into languages to
promote international collaboration and dissemination of GINA publications are available through the Internet
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information. To disseminate information about asthma (http://www.ginasthma.org).
care, a GINA Assembly was initiated, comprised of asthma
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care experts from many countries to conduct workshops
with local doctors and national opinion leaders and to
hold seminars at national and international meetings. In
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addition, GINA initiated an annual World Asthma Day (in
2001) which has gained increasing attention each year
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to raise awareness about the burden of asthma, and to
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initiate activities at the local/national level to educate Eric Bateman, MD
families and health care professionals about effective Chair, GINA Executive Committee
methods to manage and control asthma. University of CapeTown Lung Institute
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Cape Town, South Africa
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5. GLOBAL STRATEGY FOR ASTHMA MANAGEMENT AND PREVENTION
Table of Contents
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PREFACE ii Medical History 16
Symptoms 16
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METHODOLOGY AND SUMMARY OF NEW Cough variant asthma 16
RECOMMENDATION, 2010 UPDATE vi Exercise-Induced bronchospasm 17
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Physical Examination 17
INTRODUCTION x Tests for Diagnosis and Monitoring 17
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Measurements of lung function 17
CHAPTER 1. DEFINITION AND OVERVIEW 1 Spirometry 18
Peak expiratory flow 18
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KEY POINTS 2 Measurement of airway responsiveness 19
Non-Invasive markers of airway inflammation 19
DEFINITION 2 Measurements of allergic status 19
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THE BURDEN OF ASTHMA 3 DIAGNOSTIC CHALLENGES AND
Prevalence, Morbidity and Mortality 3 DIFFERENTIAL DIAGNOSIS 20
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Social and Economic Burden 3 Children 5 Years and Younger 20
Older Children and Adults 20
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FACTORS INFLUENCING THE DEVELOPMENT AND The Elderly 21
EXPRESSION OF ASTHMA 4 Occupational Asthma 21
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Host Factors 4 Distinguishing Asthma from COPD 21
Genetic 4
Obesity 5 CLASSIFICATION OF ASTHMA
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Sex 5 Etiology 21
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Environmental Factors 5 Phenotype 22
Allergens 5 Asthma Control 22
Infections 5 Asthma Severity 23
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Occupational sensitizers 6
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Tobacco smoke 6 REFERENCES 24
Outdoor/Indoor air pollution 7
Diet 7 CHAPTER 3. ASTHMA MEDICATIONS 28
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MECHANISMS OF ASTHMA 7 KEY POINTS 29
Airway Inflammation In Asthma 8
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Inflammatory cells 8 INTRODUCTION 29
Structural changes in airways 8
Pathophysiology 8 ASTHMA MEDICATIONS: ADULTS 29
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Airway hyperresponsiveness 8 Route of Administration 29
Special Mechanisms 9 Controller Medications 30
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Acute exacerbations 9 Inhaled glucocorticosteroids 30
Nocturnal Asthma 9 Leukotriene modifiers 31
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Irreversible airflow asthma 9 Long-acting inhaled β2-agonists 32
Difficult-to-treat asthma 9 Theophylline 32
Diet 9 Cromones: sodium cromoglycate and
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nedocromil sodium 33
REFERENCES 9 Long-acting oral β2-agonists 33
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Anti-IgE 33
CHAPTER 2. DIAGNOSIS AND CLASSIFICATION 15 Systemic glucocorticosteroids 33
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Oral anti-allergic compounds 34
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KEY POINTS 16 Other controller therapies 34
Allergen-specific immunotherapy 35
INTRODUCTION 16
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CLINICAL DIAGNOSIS 16
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6. Reliever Medications 35 PREVENTION OF ASTHMA SYMPTOMS AND
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Rapid-acting inhaled β2-agonists 35 EXACERBATIONS 58
Systemic glucocorticosteroids 35 Indoor Allergens 58
Anticholinergics 36 Domestic mites 58
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Theophylline 36 Furred animals 58
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Short-acting oral β2-agonists 36 Cockroaches 59
Fungi 59
ASTHMA TREATMENT: CHILDREN 37 Outdoor Allergens 59
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Route of Administration 37 Indoor Air Pollutants 59
Controller Medications 37 Outdoor Air Pollutants 59
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Inhaled glucocorticosteroids 37 Occupational Exposures 59
Leukotriene modifiers 40 Food and Drug Additives 60
Long-acting inhaled β2-agonists 40 Drugs 60
Theophylline 40 Influenza Vaccination 60
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Anti-IgE 41 Obesity 60
Cromones: sodium cromoglycate and Emotional Stress 60
nedocromil sodium 41 Other Factors That May Exacerbate Asthma 60
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Systemic glucocorticosteroids 42
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Reliever Medications 42 COMPONENT 3: ASSESS,TREAT AND MONITOR
Rapid-acting inhaled β2-agonists and short-acting ASTHMA 61
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oral β2-agonists 42
Anticholinergics 42 KEY POINTS 61
REFERENCES 42
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INTRODUCTION 61
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CHAPTER 4. ASTHMA MANAGEMENT AND ASSESSING ASTHMA CONTROL 61
PREVENTION 52
TREATMENT TO ACHIEVE CONTROL 61
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INTRODUCTION 53 Treatment Steps to Achieving Control 16
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Step 1: As-needed reliever medication 62
COMPONENT 1: DEVELOP PATIENT/ Step 2: Reliever medication plus a single
DOCTOR PARTNERSHIP 53 controller 64
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Step 3: Reliever medication plus one or two
KEY POINTS 53 controllers 64
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Step 4: Reliever medication plus two or more
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INTRODUCTION 53 controllers 65
Step 5: Reliever medication plus additional
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ASTHMA EDUCATION 54 controller options 65
At the Initial Consultation 55
Personal Asthma Action Plans 55 MONITORING TO MAINTAIN CONTROL 65
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Follow-up and Review 55 Duration and Adjustments to Treatment 65
Improving Adherence 56 Stepping Down Treatment When Asthma Is
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Self-Management in Children 56 Controlled 66
Stepping Up Treatment In Response to Loss
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THE EDUCATION OF OTHERS 56 of Control 66
Difficult-to-Treat-Asthma 67
COMPONENT 2: IDENTIFY AND REDUCE EXPOSURE
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TO RISK FACTORS 57 COMPONENT 4: MANAGE ASTHMA
EXACERBATIONS 69
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KEY POINTS 57
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KEY POINTS 69
INTRODUCTION 57
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INTRODUCTION 69
ASTHMA PREVENTION 57
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7. ASSESSING OF SEVERITY 70 GINA DISSEMINATION/IMPLEMENTATION
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RESOURCES 102
MANAGEMENT-COMMUNITY SETTINGS 70
Treatment 71 REFERENCES 102
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Bronchodilators 71
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Glucocorticosteroids 71
MANAGEMENT-ACUTE CARE SETTINGS 71
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Assessment 71
Treatment 73
Oxygen 73
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Rapid-acting inhaled β2-agonists 73
Epinephrine 73
Additional bronchodilators 73
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Systemic glucocorticosteroids 73
Inhaled glucocorticosteroids 74
Magnesium 74
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Helium oxygen therapy 74
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Leukotriene modifiers 74
Sedatives 74
Criteria for Discharge from the Emergency
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Department vs. Hospitalization 74
COMPONENT 5: SPECIAL CONSIDERATIONS 76 T
Pregnancy 76
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Obesity 76
Surgery 76
Rhinitis, Sinusitis, and Nasal Polyps 77
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Rhinitis 77
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Sinusitis 77
Nasal polyps 77
Occupational Asthma 77
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Respiratory Infections 77
Gastroesophageal Reflux 78
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Aspirin-Induced Asthma 78
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Anaphylaxis and Asthma 79
REFERENCES 79
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CHAPTER 5. IMPLEMENTATION OF ASTHMA
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GUIDELINES IN HEALTH SYSTEMS 98
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KEY POINTS 99
INTRODUCTION 99
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GUIDELINE IMPLEMENTATION STRATEGIES 99
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ECONOMIC VALUE OF INTERVENTIONS AND
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GUIDELINE IMPLEMENTATION IN ASTHMA 100
Utilization and Cost of Health Care Resources 101
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Determining the Economic Value of Interventions in
Asthma 101
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8. Methodology and Summary of New Recommendations
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Global Strategy for Asthma Management and Prevention:
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2010 Update1
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Background: When the Global Initiative for Asthma (GINA) her/his judgment, the full publication, and answer four specific written
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program was initiated in 1993, the primary goal was to produce questions from a short questionnaire, and to indicate if the scientific
recommendations for the management of asthma based on the data presented impacts on recommendations in the GINA report. If so,
best scientific information available. Its first report, NHLBI/ the member is asked to specifically identify modifications that should
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WHO Workshop Report: Global Strategy for Asthma be made.
Management and Prevention was issued in 1995 and revised
in 2002 and 2006. In 2002 and in 2006 revised documents were The entire GINA Science Committee meets twice yearly to discuss each
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prepared based on published research. publication that was considered by at least 1 member of the Committee
to potentially have an impact on the management of asthma. The full
The GINA Science Committee2 was established in 2002 to review Committee then reaches a consensus on whether to include it in the
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published research on asthma management and prevention, to report, either as a reference supporting current recommendations, or
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evaluate the impact of this research on recommendations in the GINA to change the report. In the absence of consensus, disagreements
documents related to management and prevention, and to post yearly are decided by an open vote of the full Committee. Recommendations
updates on the GINA website. Its members are recognized leaders in by the Committee for use of any medication are based on the best
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asthma research and clinical practice with the scientific credentials to evidence available from the literature and not on labeling directives
contribute to the task of the Committee, and are invited to serve for a from government regulators. The Committee does not make
limited period and in a voluntary capacity. The Committee is broadly T
recommendations for therapies that have not been approved by at least
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representative of adult and pediatric disciplines as well from diverse one regulatory agency.
geographic regions.
For the 2010 update, between July 1, 2009 and June 30, 2010, 402
Updates of the 2006 report have been issued in December of each articles met the search criteria. Of the 402, 23 papers were identified
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year with each update based on the impact of publications from July to have an impact on the GINA report. The changes prompted by these
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1 of the previous year through June 30 of the year the update was publications were posted on the website in December 2010. These
completed. Posted on the website along with the updated documents were either: A) modifying, that is, changing the text or introducing
is a list of all the publications reviewed by the Committee. a concept requiring a new recommendation to the report; or B)
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confirming, that is, adding to or replacing an existing reference.
Process: To produce the updated documents a Pub Med search is
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done using search fields established by the Committee: 1) asthma, Summary of Recommendations in the 2010 Update:
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All Fields, All ages, only items with abstracts, Clinical Trial,
Human, sorted by Authors; and 2) asthma AND systematic, A. Additions to the text:
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All fields, ALL ages, only items with abstracts, Human,
sorted by author. The first search includes publications for July Pg 5, left column, delete current information about obesity
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1-December 30 for review by the Committee during the ATS meeting. and insert: Asthma is more frequently observed in obese subjects
The second search includes publications for January 1 – June 30 for (Body Mass Index > 30 kg/m2) and is more difficult to control127-130.
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review by the Committee during the ERS meeting. (Publications that Obese people with asthma have lower lung function and more co-
appear after June 30 are considered in the first phase of the following morbidities compared with normal weight people with asthma131. The
year.) To ensure publications in peer review journals not captured by use of systemic glucocorticosteroids and a sedentary lifestyle may
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this search methodology are not missed, the respiratory community promote obesity in severe asthma patients, but in most instances,
are invited to submit papers to the Chair, GINA Science Committee obesity precedes the development of asthma.
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providing an abstract and the full paper are submitted in (or translated
into) English. How obesity promotes the development of asthma is still uncertain
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but it may result from the combined effects of various factors. It has
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All members of the Committee receive a summary of citations and been proposed that obesity could influence airway function due to
all abstracts. Each abstract is assigned to at least two Committee its effect on lung mechanics, development of a pro-inflammatory
members, although all members are offered the opportunity to provide state, in addition to genetic, developmental, hormonal or neurogenic
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an opinion on all abstracts. Members evaluate the abstract or, up to influences35, 132-133. In this regard, obese patients have a reduced
vi
1
The Global Strategy for Asthma Management and Prevention (updated 2010), the updated Pocket Guides and the complete list of references examined by the Committee are available on the GINA website www.
ginasthma.org.
2
Members (2009-20010): M. FitzGerald, Chair; P. Barnes, N. Barnes, E. Bateman, A. Becker, J. DeJongste, J. Drazen, R. Lemanske, P. O’Byrne, K. Ohta, S. Pedersen, E. Pizzichini, H. Reddel, S. Sullivan, S. Wenzel.
9. expiratory reserve volume, a pattern of breathing which may Respir Med 2009;103(12):1791-5. Reference 222. Ernst E.
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possibly alter airway smooth muscle plasticity and airway function34. Homeopathy: what does the “best” evidence tell us? Med J Aust
Furthermore, the release by adipocytes of various pro-inflammatory 2010;192(8):458-60.
cytokines and mediators such as interleukin-6, tumor necrosis factor
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(TNF)-β eotaxin, and leptin, combined with a lower level of anti- Page 36, right column, last paragraph, replace segment on
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inflammatory adipokines in obese subjects can favour a systemic Butyeko breathing: Several studies of breathing and/or relaxation
inflammatory state although it is unknown how this could influence techniques for asthma and/or dysfunctional breathing, including
airway function134-135. Reference 127. Beuther DA, Sutherland the Buteyko method and the Papworth method210, have shown
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ER. Overweight, obesity, and incident asthma: a meta-analysis of improvements in symptoms, short-acting β2-agonist use, quality of
prospective epidemiologic studies. Am J Respir Crit Care Med life and/or psychological measures, but not in physiological outcomes.
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2007;175(7):661-6. Reference 128. Ford ES. The epidemiology A study of two physiologically-contrasting breathing techniques, in
of obesity and asthma. J Allergy Clin Immunol 2005;115(5):897- which contact with health professionals and instructions about rescue
909. Reference 129. Saint-Pierre P, Bourdin A, Chanez P, Daures inhaler use were matched, showed similar improvements in reliever
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JP, Godard P. Are overweight asthmatics more difficult to control? and inhaled glucocorticosteroid use in both groups122. This suggests
Allergy 2006;61(1):79-84. Reference 130. Lavoie KL, Bacon that perceived improvement with breathing techniques may be largely
SL, Labrecque M, Cartier A, Ditto B. Higher BMI is associated with due to factors such as relaxation, voluntary reduction in use of rescue
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worse asthma control and quality of life but not asthma severity. medication, or engagement of the patient in their care. Breathing
Respir Med 2006;100(4):648-57. Reference 131. Pakhale S, techniques may thus provide a useful supplement to conventional
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Doucette S, Vandemheen K, Boulet LP, McIvor RA, Fitzgerald JM, et al. asthma management strategies, particularly in anxious patients or
A comparison of obese and nonobese people with asthma: exploring those habitually over-using rescue medication. The cost of some
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an asthma-obesity interaction. Chest. 2010;137(6): 1316-23. programs may be a potential limitation.
Reference 132. Schaub B, von ME. Obesity and asthma, what are
the links? Curr Opin Allergy Clin Immunol 2005;5(6):185-93. Pg 54, left column, paragraph 1 insert: “…community health
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Reference 133. Weiss ST, Shore S. Obesity and asthma: directions workers371…” Reference 371. Postma J, Karr C, Kieckhefer
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for research. Am J Respir Crit Care Med 2004;169(8):963- G. Community health workers and environmental interventions
8. Reference 134. Shore SA. Obesity and asthma: possible for children with asthma: a systematic review. J Asthma
mechanisms. J Allergy Clin Immunol. 2008;121(5): 2009;46(6):564-76.
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1087-93. Reference 135. Juge-Aubry CE, Henrichot E, Meier CA.
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Adipose tissue: a regulator of inflammation. Best Pract Res Clin Pg 54, left column, insert end of paragraph 2: “…but
Endocrinol Metab 2005;19(4):547-66. regional issues and the developmental stage of the children may affect
the outcomes of such programs373. Reference 373. Clark NM,
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Pg 17, right column, paragraph 3, insert: If precision is Shah S, Dodge JA, Thomas LJ, Andridge RR, Little RJ. An evaluation
needed, for example, in the conduct of a clinical trial, use of a more of asthma interventions for preteen students. J Sch Health
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rigorous definition (lower limit of normal -LLN) should be considered. 2010;80(2):80-7.
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Pg 32, modifications of segment on side effects of long-acting β2- Pg 55, right column, fourth paragraph replace current
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agonists. sentence: Patients should be asked to demonstrate their inhaler
device technique at every visit, with correction and re-checking if it
Pg 33, right column, line 12 insert: Withdrawal of is inadequate33,375. Reference 375. Bosnic-Anticevich SZ, Sinha
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glucocorticosteroids facilitated by anti-IgE therapy has led to H, So S, Reddel HK. Metered-dose inhaler technique: the effect of two
unmasking the presence of Churg Strauss syndrome in a small number educational interventions delivered in community pharmacy over time.
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of patients221. Clinicians successful in initiating steroid withdrawal J Asthma 2010;47(3):251-6.
using anti-IgE should be aware of this side effect. Reference
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222. Wechsler ME, Wong DA, Miller MK, Lawrence-Miyasaki L. Pg 56, right column, line 4 insert: Short questionnaires can
Churg-strauss syndrome in patients treated with omalizumab. Chest assist with identification of poor adherence376. Reference 376.
2009;136(2):507-18. Cohen JL, Mann DM, Wisnivesky JP, Home R, Leventhal H, Musumeci-
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Szabó TJ, Halm EA. Assessing the validity of self-reported medication
Pg 36, right column, insert: Evidence from the most rigorous adherence among inner-city asthmatic adults: the Medication
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studies available to date indicates that spinal manipulation is Adherence Report Scale for Asthma. Ann Allergy Asthma
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not an effective treatment for asthma121. Systematic reviews Immunol 2009;103(4):325-31.
indicate that homeopathic medicines have no effects beyond
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placebo222.. Reference 121. Ernst E. Spinal manipulation Pg 56, right column, end of paragraph 2 insert: School-
for asthma: a systematic review of randomised clinical trials. based asthma education improves knowledge of asthma, self-efficacy,
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10. and self-management behaviors377. Reference 377. Coffman JM, up therapy for children with uncontrolled asthma receiving inhaled
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Cabana MD, Yelin EH. Do school-based asthma education programs corticosteroids. N Engl J Med 2010;362(11):975-85.
improve self-management and health outcomes? Pediatrics
2009;124(2):729-42. Pg 73, left column, fourth paragraph insert: The most cost
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effective and efficient delivery is by meter dose inhaler and a spacer
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Pg 59, left column, last paragraph add: Asthma patients who device64, 211.
smoke, and are not treated with inhaled glucocorticosteroids, have
a greater decline in lung function than asthma patients who do not Pg 77, right column, last paragraph insert: … and are
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smoke378. Smoking cessation needs to be vigorously encouraged for commonly found in children with asthma exacerbation380. Reference
all patients with asthma who smoke. Reference 378. O’Byrne PM, 391. Leung TF, To MY, Yeung AC, Wong YS, Wong GW, Chan PK.
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Lamm CJ, Busse WW, Tan WC, Pedersen S; START Investigators Group. Multiplex molecular detection of respiratory pathogens in children with
The effects of inhaled budesonide on lung function in smokers and asthma exacerbation. Chest 2010;137(2):348-54.
nonsmokers with mild persistent asthma. Chest 2009;136(6):1514-
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20.
B. References that provided confirmation or update of previous
Pg 60, left column, paragraph 3 insert: There is some evidence recommendations.
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that exposure to acetaminophen increases the risk of asthma and Pg 6, right column, paragraph 2, insert reference 136.
wheezing in both children and adults but further studies are needed379. O’Byrne PM, Lamm CJ, Busse WW, Tan WC, Pedersen S; START
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Reference 379. Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters Investigators Group. The effects of inhaled budesonide on lung function
M, Aminzadeh K, Fitzgerald JM. Acetaminophen use and the risk of in smokers and nonsmokers with mild persistent asthma. Chest
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asthma in children and adults: a systematic review and metaanalysis. 2009;136(6):1514-20.
Chest 2009;136(5):1316-23.
Pg 11, left column, replace reference 54 with: Sly PD, Kusel
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M, Holt PG. Do early-life viral infections cause asthma? J Allergy
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Pg 65, right column, insert at end of paragraph 2: General Clin Immunol 2010;125(6):1202-5.
practitioners should be encouraged to assess asthma control at every
visit, not just when the patient presents because of their asthma380. Pg 32, right column, insert reference 221. Wechsler ME,
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Reference 380. Mintz M, Gilsenan AW, Bui CL, Ziemiecki R, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ,
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Stanford RH, Lincourt W, Ortega H. Assessment of asthma control in et al. National Heart, Lung and Blood Institute’s Asthma Clinical
primary care. Curr Med Res Opin 2009;25(10):2523-31. Research Network Effect of beta2-adrenergic receptor polymorphism
on response to longacting beta2 agonist in asthma (LARGE trial): a
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Pg 66, right column, paragraph on inhaled genotype-stratified, randomised, placebo-controlled, crossover trial.
glucocorticosteroids, insert: However, there is emerging Lancet 2009;374(9073):1754-64.
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evidence that quadrupling the dose of inhaled glucocorticosteroid might
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be effective when asthma control starts to deteriorate, if doubling the Pg 54, left column, line 6, insert reference 372. van der Meer
does not work381. Reference 381. Oborne J, Mortimer K, Hubbard V, Bakker MJ, van den Hout WB, Rabe KF, Sterk PJ, Kievit J, Assendelft
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RB, Tattersfield AE, Harrison TW. Quadrupling the dose of inhaled WJ, Sont JK; SMASHING (Self-Management in Asthma Supported by
corticosteroid to prevent asthma exacerbations: a randomized, double- Hospitals, ICT, Nurses and General Practitioners) Study Group. Internet-
blind, placebo-controlled, parallel-group clinical trial. Am J Respir based self-management plus education compared with usual care in
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Crit Care Med 2009;180(7):598-602. asthma: a randomized trial. Ann Intern Med 2009;151(2):110-20.
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Pg 67, left column, add new paragraph: For children (6 to Pg 55, left column, second paragraph, add reference
17 years) who have uncontrolled asthma despite the use of low-dose 374. Wilson SR, Strub P, Buist AS, Knowles SB, Lavori PW, Lapidus
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inhaled glucocorticosteroids, step-up therapy with long-acting β2- J, Vollmer WM; Better Outcomes of Asthma Treatment (BOAT) Study
agonist bronchodilator was significantly more likely to provide the best Group. Shared treatment decision making improves adherence and
response than either step-up therapy with inhaled glucocorticosteroids outcomes in poorly controlled asthma. Am J Respir Crit Care Med
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or leukotriene receptor antagonist. However, many children had a 2010;181(6):566-77.
best response to inhaled glucocorticosteroids or leukotriene receptor
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antagonist step-up therapy, highlighting the need to regularly monitor Pg 84, replace current reference 116 with: Fogel RB, Rosario
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and appropriately adjust each child’s asthma therapy382. Reference N, Aristizabal G, Loeys T, Noonan G, Gaile S, Smugar SS, Polos PG.
382: Lemanske RF Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer Effect of montelukast or salmeterol added to inhaled fluticasone
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SJ, Martinez FD, et al.; Childhood Asthma Research and Education on exercise-induced bronchoconstriction in children. Ann Allergy
(CARE) Network of the National Heart, Lung, and Blood Institute. Step- Asthma Immunol 2010;104(6):511-7.
viii
11. Pg 86, replace current reference 148 with: Rodrigo GJ, Neffen
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H, Colodenco FD, Castro-Rodriguez JA. Formoterol for acute asthma in
the emergency department: a systematic review with meta-analysis.
Ann Allergy Asthma Immunol 2010;104(3):247-52.
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Pg 88, delete reference 187.
C. Inserts related to special topics covered by the Committee
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1. Asthma Control: Figure 2-4, page 22 (and the identical Figure
4.3-1, page 62) has been modified. Segment A: Assessment of Current
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Clinical Control was inadvertently omitted in the 2009 update and has
been added. The text that describes the purpose of the Figure as a
clinical tool has been embedded.
OR
2. Statement on Anti-IgE for use in children. Pg 41, insert new
statement on anti-IgE with supporting references.
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3. Special Considerations: Obesity. Page 76, insert new
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statement about asthma and obesity with supporting
references.
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4. Special Considerations: Gastroesophageal Reflux. Pg 78, insert
new statement with supporting references to update T
segment on gastroesophageal reflux.
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D. GRADE Evidence Statements. The GINA Science identified two
issues for evaluation using GRADE evidence technology, one related
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to an expensive medication, anti-IgE, and one related to a inexpensive
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medication, magnesium sulfate. The methodology, the evidence
statements, and the consensus statements can be found on the GINA
website, www.ginasthma.org.
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Pg 33. Question: “In adults with asthma, does monoclonal anti-IgE,
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omalizumab, compared to placebo improve patient outcomes?” The
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consensus recommendation:
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For allergic patients, with an elevated IgE, not controlled on high
dose inhaled glucocortico-steroids and a long acting β2-agonist and
who continue to have exacerbations, a trial of omalizumab can be
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considered. This recommendation is based on a modest response rate
for the main endpoint exacerbations, and its high cost.
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Pg 74: Question: “In adults with acute exacerbations of
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asthma, does intravenous magnesium sulphate compared
to placebo improve patient important outcomes?” The
consensus recommendation:
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In patients with severe, acute asthma, who have received maximal
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inhaled bronchodilator therapy and systemic glucocorticosteroids and
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who have not responded adequately, a single dose of magnesium
sulphate (two grams IV) is recommended. This recommendation, in
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this population, is based on the poor case definition in studies, as well
as its efficacy, low cost and safety.
ix
12. INTRODUCTION
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Asthma is a serious public health problem throughout the world, affecting people of all ages. When uncontrolled, asthma
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can place severe limits on daily life, and is sometimes fatal.
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In 1993, the Global Initiative for Asthma (GINA) was formed. Its goals and objectives were described in a 1995 NHLBI/
WHO Workshop Report, Global Strategy for Asthma Management and Prevention. This Report (revised in 2002 and
PR
2006), and its companion documents, have been widely distributed and translated into many languages. A network
of individuals and organizations interested in asthma care has been created and several country-specific asthma
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management programs have been initiated. Yet much work is still required to reduce morbidity and mortality from this
chronic disease.
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In 2006, the Global Strategy for Asthma Management and Prevention was revised to emphasize asthma management
based on clinical control, rather than classification of the patient by severity. This important paradigm shift for asthma
care reflected the progress made in pharmacologic care of patients. Many asthma patients are receiving, or have
received, some asthma medications. The role of the health care professional is to establish each patient’s current level
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of treatment and control, then adjust treatment to gain and maintain control. Asthma patients should experience no
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or minimal symptoms (including at night), have no limitations on their activities (including physical exercise), have no
(or minimal) requirement for rescue medications, have near normal lung function, and experience only very infrequent
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exacerbations.
The recommendations for asthma care based on clinical control described in the 2006 report have been updated
T
annually. This 2010 update reflects a number of modifications, described in “Methodology and Summary of New
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Recommendations.” As with all previous GINA reports, levels of evidence (Table A) are assigned to management
recommendations where appropriate in Chapter 4, the Five Components of Asthma Management. Evidence levels are
indicated in boldface type enclosed in parentheses after the relevant statement—e.g., (Evidence A). The methodological
issues concerning the use of evidence from meta-analyses were carefully considered1. The GINA Science Committee
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used the GRADE approach2 to examine use of anti-IgE, omalizumab and intravenous magnesium sulphate;
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recommendations are presented on the website, www.ginasthma.org.
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FUTURE CHALLENGES
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In spite of laudable efforts to improve asthma care over the past decade, a majority of patients have not benefited
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from advances in asthma treatment and many lack even the rudiments of care. A challenge for the next several years
is to work with primary health care providers and public health officials in various countries to design, implement,
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and evaluate asthma care programs to meet local needs. The GINA Executive Committee recognizes that this is a
difficult task and, to aid in this work, has formed several groups of global experts, including: a Dissemination and
Implementation Committee; the GINA Assembly, a network of individuals who care for asthma patients in many different
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health care settings; and two regional programs, GINA Mesoamerica and GINA Mediterranean. These efforts aim to
enhance communication with asthma specialists, primary-care health professionals, other health care workers, and
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patient support organizations. The Executive Committee continues to examine barriers to implementation of the asthma
management recommendations, especially the challenges that arise in primary-care settings and in developing countries.
HT
While early diagnosis of asthma and implementation of appropriate therapy significantly reduce the socioeconomic
burdens of asthma and enhance patients’ quality of life, medications continue to be the major component of the cost
IG
of asthma treatment. For this reason, the pricing of asthma medications continues to be a topic for urgent need and
a growing area of research interest, as this has important implications for the overall costs of asthma management.
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Moreover, a large segment of the world’s population lives in areas with inadequate medical facilities and meager
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financial resources. The GINA Executive Committee recognizes that “fixed” international guidelines and “rigid” scientific
protocols will not work in many locations. Thus, the recommendations found in this Report must be adapted to fit local
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practices and the availability of health care resources.
x
13. As the GINA Committees expand their work, every effort will be made to interact with patient and physician groups
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at national, district, and local levels, and in multiple health care settings, to continuously examine new and innovative
approaches that will ensure the delivery of the best asthma care possible. GINA is a partner organization in a program
launched in March 2006 by the World Health Organization, the Global Alliance Against Chronic Respiratory Diseases
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(GARD). Through the work of the GINA Committees, and in cooperation with GARD, progress toward better care for all
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patients with asthma should be substantial in the next decade.
Table A. Description of Levels of Evidence
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Evidence Sources of Evidence Definition
Category
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A Randomized controlled Evidence is from endpoints of well designed RCTs that provide a consistent
trials (RCTs). Rich body pattern of findings in the population for which the recommendation is made.
of data. Category A requires substantial numbers of studies involving substantial numbers
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of participants.
B Randomized controlled Evidence is from endpoints of intervention studies that include only a limited
trials (RCTs). Limited number of patients, posthoc or subgroup analysis of RCTs, or meta-analysis of
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body of data. RCTs. In general, Category B pertains when few randomized trials exist, they are
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small in size, they were under-taken in a population that differs from the target
population of the recommendation, or the results are somewhat inconsistent.
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C Nonrandomized trials. Evidence is from outcomes of uncontrolled or non-randomized trials or from
Observational studies. observational studies.
D Panel consensus judg- This category is used only in cases where the provision of some guidance was
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ment. deemed valuable but the clinical literature addressing the subject was insufficient
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to justify placement in one of the other categories. The Panel Consensus is
based on clinical experience or knowledge that does not meet the above listed
criteria.
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REFERENCES
1. Jadad AR, Moher M, Browman GP, Booker L, Sigouis C, Fuentes M, et al. Systematic reviews and meta-analyses on
treatment of asthma: critical evaluation. BMJ 2000;320:537-40.
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2. Guyatt G, Vist G, Falck-Ytter Y, Kunz R, Magrini N, Schunemann H. An emerging consensus on grading
recommendations? Available from URL: http://www.evidence-basedmedicine.com.
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14. CO
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1
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AND
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CHAPTER
OVERVIEW
DEFINITION
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UCE
15. Wheezing appreciated on auscultation of the chest is the
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KEY POINTS: most common physical finding.
• Asthma is a chronic inflammatory disorder of the The main physiological feature of asthma is episodic airway
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airways in which many cells and cellular elements obstruction characterized by expiratory airflow limitation.
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play a role. The chronic inflammation is associated The dominant pathological feature is airway inflammation,
with airway hyperresponsiveness that leads to sometimes associated with airway structural changes.
recurrent episodes of wheezing, breathlessness,
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chest tightness, and coughing, particularly at night Asthma has significant genetic and environmental
or in the early morning. These episodes are usually components, but since its pathogenesis is not clear, much
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associated with widespread, but variable, airflow of its definition is descriptive. Based on the functional
obstruction within the lung that is often reversible consequences of airway inflammation, an operational
either spontaneously or with treatment. description of asthma is:
Asthma is a chronic inflammatory disorder of the airways
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• Clinical manifestations of asthma can be controlled in which many cells and cellular elements play a role.
with appropriate treatment. When asthma is The chronic inflammation is associated with airway
controlled, there should be no more than occasional hyperresponsiveness that leads to recurrent episodes of
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flare-ups and severe exacerbations should be rare. wheezing, breathlessness, chest tightness, and coughing,
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particularly at night or in the early morning. These
• Asthma is a problem worldwide, with an estimated episodes are usually associated with widespread, but
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300 million affected individuals. variable, airflow obstruction within the lung that is often
reversible either spontaneously or with treatment.
• Although from the perspective of both the patient and
society the cost to control asthma seems high, the
T
Because there is no clear definition of the asthma
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cost of not treating asthma correctly is even higher. phenotype, researchers studying the development of
this complex disease turn to characteristics that can
• A number of factors that influence a person’s risk of be measured objectively, such as atopy (manifested as
developing asthma have been identified. These can the presence of positive skin-prick tests or the clinical
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be divided into host factors (primarily genetic) and response to common environmental allergens), airway
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environmental factors. hyperresponsiveness (the tendency of airways to narrow
excessively in response to triggers that have little or
• The clinical spectrum of asthma is highly variable, no effect in normal individuals), and other measures of
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and different cellular patterns have been observed, allergic sensitization. Although the association between
but the presence of airway inflammation remains a asthma and atopy is well established, the precise links
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consistent feature. between these two conditions have not been clearly and
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comprehensively defined.
This chapter covers several topics related to asthma,
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including definition, burden of disease, factors that There is now good evidence that the clinical manifestations
influence the risk of developing asthma, and mechanisms. of asthma—symptoms, sleep disturbances, limitations
It is not intended to be a comprehensive treatment of of daily activity, impairment of lung function, and use of
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these topics, but rather a brief overview of the background rescue medications—can be controlled with appropriate
that informs the approach to diagnosis and management treatment. When asthma is controlled, there should be no
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detailed in subsequent chapters. Further details are found more than occasional recurrence of symptoms and severe
in the reviews and other references cited at the end of the exacerbations should be rare1.
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chapter.
DEFINITION
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Asthma is a disorder defined by its clinical, physiological,
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and pathological characteristics. The predominant feature
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of the clinical history is episodic shortness of breath,
particularly at night, often accompanied by cough.
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2 DEFINITION AND OVERVIEW
16. Social and Economic Burden
THE BURDEN OF ASTHMA
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Social and economic factors are integral to understanding
asthma and its care, whether viewed from the perspective
Prevalence, Morbidity, and Mortality of the individual sufferer, the health care professional,
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or entities that pay for health care. Absence from school
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Asthma is a problem worldwide, with an estimated 300 and days lost from work are reported as substantial social
million affected individuals2,3. Despite hundreds of reports and economic consequences of asthma in studies from
on the prevalence of asthma in widely differing populations, the Asia-Pacific region, India, Latin America, the United
PR
the lack of a precise and universally accepted definition of Kingdom, and the United States9-12.
asthma makes reliable comparison of reported prevalence
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from different parts of the world problematic. Nonetheless, The monetary costs of asthma, as estimated in a variety of
based on the application of standardi ed methods to health care systems including those of the United States13-15
measure the prevalence of asthma and wheezing illness in and the United Kingdom16 are substantial. In analyses of
OR
children3 and adults4, it appears that the global prevalence economic burden of asthma, attention needs to be paid
of asthma ranges from 1% to 18% of the population in to both direct medical costs (hospital admissions and cost
different countries (Figure 1-1)2,3. There is good evidence of medications) and indirect, non-medical costs (time lost
that international differences in asthma symptom from work, premature death)17. For example, asthma is a
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prevalence have been reduced, particularly in the 13-14 major cause of absence from work in many countries4-6,121,
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year age group, with decreases in prevalence in North including Australia, Sweden, the United Kingdom, and the
America and Western Europe and increases in prevalence United States16,18-20. Comparisons of the cost of asthma in
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in regions where prevalence was previously low. Although different regions lead to a clear set of conclusions:
there was little change in the overall prevalence of current
wheeze, the percentage of children reported to have had • The costs of asthma depend on the individual patient’s
T
asthma increased significantly, possibly reflecting greater level of control and the extent to which exacerbations
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awareness of this condition and/or changes in diagnostic are avoided.
practice. The increases in asthma symptom prevalence
in Africa, Latin America and parts of Asia indicate that • Emergency treatment is more expensive than planned
treatment.
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the global burden of asthma is continuing to rise, but
the global prevalence differences are lessening126. The
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World Health Organization has estimated that 15 million • Non-medical economic costs of asthma are substantial.
disability-adjusted life years (DALYs) are lost annually due Guideline-determined asthma care can be cost
to asthma, representing 1% of the total global disease effective.Families can suffer from the financial burden
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burden2. Annual worldwide deaths from asthma have of treating asthma.
been estimated at 250,000 and mortality does not appear
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to correlate well with prevalence (Figure 1-1)2,3. There Although from the perspective of both the patient and
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are insufficient data to determine the likely causes of the society the cost to control asthma seems high, the cost
described variations in prevalence within and between of not treating asthma correctly is even higher122. Proper
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populations. treatment of the disease poses a challenge for individuals,
health care professionals, health care organizations, and
governments. There is every reason to believe that the
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Figure 1-1. Asthma Prevalence and Mortality2, 3
substantial global burden of asthma can be dramatically
reduced through efforts by individuals, their health care
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providers, health care organizations, and local and national
governments to improve asthma control.
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Detailed reference information about the burden of asthma
can be found in the report Global Burden of Asthma*.
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Further studies of the social and economic burden of
asthma and the cost effectiveness of treatment are needed
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in both developed and developing countries.
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Permission for use of this figure obtained from J. Bousquet. DEFINITION AND OVERVIEW 3
*(http://www.ginasthma.org/ReportItem.asp?I1=2&I2=2&intld=94
