U CE OD PR RE OR R TE AL T NO O -D I AL ER AT M ED HT RIG PYCO Global Strategy for Asthma Management and Prevention The GINA reports are available on www.ginasthma.org.
Global Strategy for Asthma Management and Prevention 2010 (update) CEGINA EXECUTIVE COMMITTEE* GINA EXECUTIVE COMMITTEE* UEric D. Bateman, MD, Chair Mark FitzGerald, MD, Chair ODUniversity Cape Town Lung Institute University of British ColumbiaCape Town, South Africa Vancouver, BC, Canada PRLouis-Philippe Boulet, MD Neil Barnes, MDHôpital Laval London Chest HospitalSainte-Foy , Quebec, Canada London, England, UK REAlvaro A. Cru , MD Peter J. Barnes, MDFederal University of Bahia National Heart and Lung InstituteSchool of Medicine London, England, UK ORSalvador, Brazil Eric D. Bateman, MDMark FitzGerald, MD University Cape Town Lung Institute RUniversity of British Columbia Cape Town, South AfricaVancouver, BC, Canada TE Allan Becker, MDTari Haahtela, MD University of ManitobaHelsinki University Central Hospital Winnipeg, Manitoba, Canada ALHelsinki, Finland Jeffrey M. Drazen, MDMark L. Levy, MD Harvard Medical SchoolUniversity of EdinburghLondon England, UK T Boston, Massachusetts, USA NO Robert F. Lemanske, Jr., M.D.Paul O’Byrne, MD University of Wisconsin School of MedicineMcMaster University Madison, Wisconsin, USA OOntario, Canada Paul O’Byrne, MD -DKen Ohta, MD, PhD McMaster UniversityTeikyo University School of Medicine Ontario, CanadaTokyo, Japan Ken Ohta, MD, PhD ALPierluigi Paggiaro, MD Teikyo University School of MedicineUniversity of Pisa Tokyo, Japan IPisa, Italy ER Soren Erik Pedersen, M.D.Soren Erik Pedersen, M.D. Kolding Hospital Kolding HospitalKolding, Denmark Kolding, Denmark ATManuel Soto-Quiro, MD Emilio Pizichini, MDHospital Nacional de Niños Universidade Federal de Santa Catarina MSan José, Costa Rica Florianópolis, SC, Brazil EDGary W. Wong, MD Helen K. Reddel, MDChinese University of Hong Kong Woolcock Institute of Medical ResearchHong Kong ROC Camperdown, NSW, Australia HT Sean D. Sullivan, PhD Professor of Pharmacy, Public Health IG University of Washington Seattle, Washington, USA R Sally E. Wenzel, M.D. PY University of Pittsburgh Pittsburgh, Pennsylvania, USACO*Disclosures for members of GINA Executive and Science Committees can be found at:http://www.ginasthma.com/Committees.asp?l1=7&l2=2 i
PREFACE CEAsthma is a serious global health problem. People of all In spite of these dissemination efforts, international Uages in countries throughout the world are affected by surveys provide direct evidence for suboptimal asthma ODthis chronic airway disorder that, when uncontrolled, can control in many countries, despite the availability ofplace severe limits on daily life and is sometimes fatal. effective therapies. It is clear that if recommendationsThe prevalence of asthma is increasing in most countries, contained within this report are to improve care of people PRespecially among children. Asthma is a significant burden, with asthma, every effort must be made to encouragenot only in terms of health care costs but also of lost health care leaders to assure availability of and access toproductivity and reduced participation in family life. medications, and develop means to implement effective RE asthma management programs including the use ofDuring the past two decades, we have witnessed many appropriate tools to measure success.scientific advances that have improved our understanding ORof asthma and our ability to manage and control it In 2002, the GINA Report stated that “It is reasonableeffectively. However, the diversity of national health to expect that in most patients with asthma, controlcare service systems and variations in the availability of the disease can, and should be achieved andof asthma therapies require that recommendations for maintained.” To meet this challenge, in 2005, Executive Rasthma care be adapted to local conditions throughout Committee recommended preparation of a new report TEthe global community. In addition, public health officials not only to incorporate updated scientific informationrequire information about the costs of asthma care, how but to implement an approach to asthma management ALto 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 asthmaresponsive to the particular needs and circumstances control are provided in this document. The methods usedwithin their countries. T to prepare this document are described in the Introduction. NOIn 1993, the National Heart, Lung, and Blood Institute It is a privilege for me to acknowledge the work of thecollaborated with the World Health Organization to many people who participated in this update project, asconvene a workshop that led to a Workshop Report: well as to acknowledge the superlative work of all who OGlobal Strategy for Asthma Management and Prevention. have contributed to the success of the GINA program. -DThis presented a comprehensive plan to manage asthmawith the goal of reducing chronic disability and premature The GINA program has been conducted throughdeaths while allowing patients with asthma to lead unrestricted educational grants from AstraZeneca, ALproductive and fulfilling lives. Boehringer Ingelheim, Chiesi Group, GlaxoSmithKline, Meda Pharma, Merck, Sharp & Dohme, Mitsubishi TanabeAt the same time, the Global Initiative for Asthma (GINA) Pharma, Novartis, Nycomed, PharmAxis and Schering- I ERwas implemented to develop a network of individuals, Plough. The generous contributions of these companiesorganizations, and public health officials to disseminate assured that Committee members could meet togetherinformation about the care of patients with asthma while to discuss issues and reach consensus in a constructive ATat the same time assuring a mechanism to incorporate and timely manner. The members of the GINA Committeesthe results of scientific investigations into asthma are, however, solely responsible for the statements and Mcare. Publications based on the GINA Report were conclusions presented in this publication.prepared and have been translated into languages topromote international collaboration and dissemination of GINA publications are available through the Internet EDinformation. To disseminate information about asthma (http://www.ginasthma.org).care, a GINA Assembly was initiated, comprised of asthma HTcare experts from many countries to conduct workshopswith local doctors and national opinion leaders and tohold seminars at national and international meetings. In IGaddition, GINA initiated an annual World Asthma Day (in2001) which has gained increasing attention each year Rto raise awareness about the burden of asthma, and to PYinitiate activities at the local/national level to educate Eric Bateman, MDfamilies and health care professionals about effective Chair, GINA Executive Committeemethods to manage and control asthma. University of CapeTown Lung InstituteCO Cape Town, South Africaii
GLOBAL STRATEGY FOR ASTHMA MANAGEMENT AND PREVENTION Table of Contents CEPREFACE ii Medical History 16 Symptoms 16 UMETHODOLOGY AND SUMMARY OF NEW Cough variant asthma 16 RECOMMENDATION, 2010 UPDATE vi Exercise-Induced bronchospasm 17 OD Physical Examination 17INTRODUCTION x Tests for Diagnosis and Monitoring 17 PR Measurements of lung function 17CHAPTER 1. DEFINITION AND OVERVIEW 1 Spirometry 18 Peak expiratory flow 18 REKEY POINTS 2 Measurement of airway responsiveness 19 Non-Invasive markers of airway inflammation 19DEFINITION 2 Measurements of allergic status 19 ORTHE BURDEN OF ASTHMA 3 DIAGNOSTIC CHALLENGES AND Prevalence, Morbidity and Mortality 3 DIFFERENTIAL DIAGNOSIS 20 R Social and Economic Burden 3 Children 5 Years and Younger 20 Older Children and Adults 20 TEFACTORS INFLUENCING THE DEVELOPMENT AND The Elderly 21 EXPRESSION OF ASTHMA 4 Occupational Asthma 21 AL Host Factors 4 Distinguishing Asthma from COPD 21 Genetic 4 Obesity 5 CLASSIFICATION OF ASTHMA T 21 Sex 5 Etiology 21 NO Environmental Factors 5 Phenotype 22 Allergens 5 Asthma Control 22 Infections 5 Asthma Severity 23 O Occupational sensitizers 6 -D Tobacco smoke 6 REFERENCES 24 Outdoor/Indoor air pollution 7 Diet 7 CHAPTER 3. ASTHMA MEDICATIONS 28 ALMECHANISMS OF ASTHMA 7 KEY POINTS 29 Airway Inflammation In Asthma 8 I ER Inflammatory cells 8 INTRODUCTION 29 Structural changes in airways 8 Pathophysiology 8 ASTHMA MEDICATIONS: ADULTS 29 AT Airway hyperresponsiveness 8 Route of Administration 29 Special Mechanisms 9 Controller Medications 30 M Acute exacerbations 9 Inhaled glucocorticosteroids 30 Nocturnal Asthma 9 Leukotriene modifiers 31 ED Irreversible airflow asthma 9 Long-acting inhaled β2-agonists 32 Difficult-to-treat asthma 9 Theophylline 32 Diet 9 Cromones: sodium cromoglycate and HT nedocromil sodium 33REFERENCES 9 Long-acting oral β2-agonists 33 IG Anti-IgE 33CHAPTER 2. DIAGNOSIS AND CLASSIFICATION 15 Systemic glucocorticosteroids 33 R Oral anti-allergic compounds 34 PYKEY POINTS 16 Other controller therapies 34 Allergen-specific immunotherapy 35INTRODUCTION 16COCLINICAL DIAGNOSIS 16 iii
Reliever Medications 35 PREVENTION OF ASTHMA SYMPTOMS AND CE Rapid-acting inhaled β2-agonists 35 EXACERBATIONS 58 Systemic glucocorticosteroids 35 Indoor Allergens 58 Anticholinergics 36 Domestic mites 58 U Theophylline 36 Furred animals 58 OD Short-acting oral β2-agonists 36 Cockroaches 59 Fungi 59ASTHMA TREATMENT: CHILDREN 37 Outdoor Allergens 59 PR Route of Administration 37 Indoor Air Pollutants 59 Controller Medications 37 Outdoor Air Pollutants 59 RE 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 OR Anti-IgE 41 Obesity 60 Cromones: sodium cromoglycate and Emotional Stress 60 nedocromil sodium 41 Other Factors That May Exacerbate Asthma 60 R Systemic glucocorticosteroids 42 TE Reliever Medications 42 COMPONENT 3: ASSESS,TREAT AND MONITOR Rapid-acting inhaled β2-agonists and short-acting ASTHMA 61 AL oral β2-agonists 42 Anticholinergics 42 KEY POINTS 61REFERENCES 42 T INTRODUCTION 61 NOCHAPTER 4. ASTHMA MANAGEMENT AND ASSESSING ASTHMA CONTROL 61 PREVENTION 52 TREATMENT TO ACHIEVE CONTROL 61 OINTRODUCTION 53 Treatment Steps to Achieving Control 16 -D Step 1: As-needed reliever medication 62COMPONENT 1: DEVELOP PATIENT/ Step 2: Reliever medication plus a single DOCTOR PARTNERSHIP 53 controller 64 AL Step 3: Reliever medication plus one or two KEY POINTS 53 controllers 64 I Step 4: Reliever medication plus two or more ERINTRODUCTION 53 controllers 65 Step 5: Reliever medication plus additional ATASTHMA EDUCATION 54 controller options 65 At the Initial Consultation 55 Personal Asthma Action Plans 55 MONITORING TO MAINTAIN CONTROL 65 M Follow-up and Review 55 Duration and Adjustments to Treatment 65 Improving Adherence 56 Stepping Down Treatment When Asthma Is ED Self-Management in Children 56 Controlled 66 Stepping Up Treatment In Response to Loss HTTHE EDUCATION OF OTHERS 56 of Control 66 Difficult-to-Treat-Asthma 67COMPONENT 2: IDENTIFY AND REDUCE EXPOSURE IG TO RISK FACTORS 57 COMPONENT 4: MANAGE ASTHMA EXACERBATIONS 69 RKEY POINTS 57 PY KEY POINTS 69INTRODUCTION 57CO INTRODUCTION 69ASTHMA PREVENTION 57iv
ASSESSING OF SEVERITY 70 GINA DISSEMINATION/IMPLEMENTATION CE RESOURCES 102MANAGEMENT-COMMUNITY SETTINGS 70 Treatment 71 REFERENCES 102 U Bronchodilators 71 OD Glucocorticosteroids 71MANAGEMENT-ACUTE CARE SETTINGS 71 PR Assessment 71 Treatment 73 Oxygen 73 RE Rapid-acting inhaled β2-agonists 73 Epinephrine 73 Additional bronchodilators 73 OR Systemic glucocorticosteroids 73 Inhaled glucocorticosteroids 74 Magnesium 74 R Helium oxygen therapy 74 TE Leukotriene modifiers 74 Sedatives 74 Criteria for Discharge from the Emergency AL Department vs. Hospitalization 74COMPONENT 5: SPECIAL CONSIDERATIONS 76 T Pregnancy 76 NO Obesity 76 Surgery 76 Rhinitis, Sinusitis, and Nasal Polyps 77 O Rhinitis 77 -D Sinusitis 77 Nasal polyps 77 Occupational Asthma 77 AL Respiratory Infections 77 Gastroesophageal Reflux 78 I Aspirin-Induced Asthma 78 ER Anaphylaxis and Asthma 79REFERENCES 79 ATCHAPTER 5. IMPLEMENTATION OF ASTHMA M GUIDELINES IN HEALTH SYSTEMS 98 EDKEY POINTS 99INTRODUCTION 99 HTGUIDELINE IMPLEMENTATION STRATEGIES 99 IGECONOMIC VALUE OF INTERVENTIONS AND R GUIDELINE IMPLEMENTATION IN ASTHMA 100 Utilization and Cost of Health Care Resources 101 PY Determining the Economic Value of Interventions in Asthma 101CO v
Methodology and Summary of New Recommendations CEGlobal Strategy for Asthma Management and Prevention: U 2010 Update1 ODBackground: When the Global Initiative for Asthma (GINA) her/his judgment, the full publication, and answer four specific written PRprogram was initiated in 1993, the primary goal was to produce questions from a short questionnaire, and to indicate if the scientificrecommendations 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 REWHO Workshop Report: Global Strategy for Asthma be made.Management and Prevention was issued in 1995 and revisedin 2002 and 2006. In 2002 and in 2006 revised documents were The entire GINA Science Committee meets twice yearly to discuss each ORprepared 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 fullThe GINA Science Committee2 was established in 2002 to review Committee then reaches a consensus on whether to include it in the Rpublished research on asthma management and prevention, to report, either as a reference supporting current recommendations, or TEevaluate the impact of this research on recommendations in the GINA to change the report. In the absence of consensus, disagreementsdocuments related to management and prevention, and to post yearly are decided by an open vote of the full Committee. Recommendationsupdates on the GINA website. Its members are recognized leaders in by the Committee for use of any medication are based on the best ALasthma research and clinical practice with the scientific credentials to evidence available from the literature and not on labeling directivescontribute to the task of the Committee, and are invited to serve for a from government regulators. The Committee does not makelimited period and in a voluntary capacity. The Committee is broadly T recommendations for therapies that have not been approved by at least NOrepresentative 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, 402Updates of the 2006 report have been issued in December of each articles met the search criteria. Of the 402, 23 papers were identified Oyear with each update based on the impact of publications from July to have an impact on the GINA report. The changes prompted by these -D1 of the previous year through June 30 of the year the update was publications were posted on the website in December 2010. Thesecompleted. Posted on the website along with the updated documents were either: A) modifying, that is, changing the text or introducingis a list of all the publications reviewed by the Committee. a concept requiring a new recommendation to the report; or B) AL confirming, that is, adding to or replacing an existing reference.Process: To produce the updated documents a Pub Med search is Idone using search fields established by the Committee: 1) asthma, Summary of Recommendations in the 2010 Update: ERAll Fields, All ages, only items with abstracts, Clinical Trial,Human, sorted by Authors; and 2) asthma AND systematic, A. Additions to the text: ATAll 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 M1-December 30 for review by the Committee during the ATS meeting. and insert: Asthma is more frequently observed in obese subjectsThe second search includes publications for January 1 – June 30 for (Body Mass Index > 30 kg/m2) and is more difficult to control127-130. EDreview 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. Theyear.) To ensure publications in peer review journals not captured by use of systemic glucocorticosteroids and a sedentary lifestyle may HTthis 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. IGproviding an abstract and the full paper are submitted in (or translatedinto) English. How obesity promotes the development of asthma is still uncertain R but it may result from the combined effects of various factors. It has PYAll members of the Committee receive a summary of citations and been proposed that obesity could influence airway function due toall abstracts. Each abstract is assigned to at least two Committee its effect on lung mechanics, development of a pro-inflammatorymembers, although all members are offered the opportunity to provide state, in addition to genetic, developmental, hormonal or neurogenicCOan opinion on all abstracts. Members evaluate the abstract or, up to influences35, 132-133. In this regard, obese patients have a reducedvi 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.
expiratory reserve volume, a pattern of breathing which may Respir Med 2009;103(12):1791-5. Reference 222. Ernst E. CEpossibly alter airway smooth muscle plasticity and airway function34. Homeopathy: what does the “best” evidence tell us? Med J AustFurthermore, the release by adipocytes of various pro-inflammatory 2010;192(8):458-60.cytokines and mediators such as interleukin-6, tumor necrosis factor U(TNF)-β eotaxin, and leptin, combined with a lower level of anti- Page 36, right column, last paragraph, replace segment on ODinflammatory adipokines in obese subjects can favour a systemic Butyeko breathing: Several studies of breathing and/or relaxationinflammatory state although it is unknown how this could influence techniques for asthma and/or dysfunctional breathing, includingairway function134-135. Reference 127. Beuther DA, Sutherland the Buteyko method and the Papworth method210, have shown PRER. Overweight, obesity, and incident asthma: a meta-analysis of improvements in symptoms, short-acting β2-agonist use, quality ofprospective epidemiologic studies. Am J Respir Crit Care Med life and/or psychological measures, but not in physiological outcomes. RE2007;175(7):661-6. Reference 128. Ford ES. The epidemiology A study of two physiologically-contrasting breathing techniques, inof obesity and asthma. J Allergy Clin Immunol 2005;115(5):897- which contact with health professionals and instructions about rescue909. Reference 129. Saint-Pierre P, Bourdin A, Chanez P, Daures inhaler use were matched, showed similar improvements in reliever ORJP, Godard P. Are overweight asthmatics more difficult to control? and inhaled glucocorticosteroid use in both groups122. This suggestsAllergy 2006;61(1):79-84. Reference 130. Lavoie KL, Bacon that perceived improvement with breathing techniques may be largelySL, Labrecque M, Cartier A, Ditto B. Higher BMI is associated with due to factors such as relaxation, voluntary reduction in use of rescue Rworse asthma control and quality of life but not asthma severity. medication, or engagement of the patient in their care. BreathingRespir Med 2006;100(4):648-57. Reference 131. Pakhale S, techniques may thus provide a useful supplement to conventional TEDoucette S, Vandemheen K, Boulet LP, McIvor RA, Fitzgerald JM, et al. asthma management strategies, particularly in anxious patients orA comparison of obese and nonobese people with asthma: exploring those habitually over-using rescue medication. The cost of some ALan 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 arethe links? Curr Opin Allergy Clin Immunol 2005;5(6):185-93. Pg 54, left column, paragraph 1 insert: “…community health TReference 133. Weiss ST, Shore S. Obesity and asthma: directions workers371…” Reference 371. Postma J, Karr C, Kieckhefer NOfor research. Am J Respir Crit Care Med 2004;169(8):963- G. Community health workers and environmental interventions8. Reference 134. Shore SA. Obesity and asthma: possible for children with asthma: a systematic review. J Asthmamechanisms. J Allergy Clin Immunol. 2008;121(5): 2009;46(6):564-76. O1087-93. Reference 135. Juge-Aubry CE, Henrichot E, Meier CA. -DAdipose tissue: a regulator of inflammation. Best Pract Res Clin Pg 54, left column, insert end of paragraph 2: “…butEndocrinol 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, ALPg 17, right column, paragraph 3, insert: If precision is Shah S, Dodge JA, Thomas LJ, Andridge RR, Little RJ. An evaluationneeded, for example, in the conduct of a clinical trial, use of a more of asthma interventions for preteen students. J Sch Health Irigorous definition (lower limit of normal -LLN) should be considered. 2010;80(2):80-7. ERPg 32, modifications of segment on side effects of long-acting β2- Pg 55, right column, fourth paragraph replace current ATagonists. sentence: Patients should be asked to demonstrate their inhaler device technique at every visit, with correction and re-checking if itPg 33, right column, line 12 insert: Withdrawal of is inadequate33,375. Reference 375. Bosnic-Anticevich SZ, Sinha Mglucocorticosteroids facilitated by anti-IgE therapy has led to H, So S, Reddel HK. Metered-dose inhaler technique: the effect of twounmasking the presence of Churg Strauss syndrome in a small number educational interventions delivered in community pharmacy over time. EDof 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 HT222. Wechsler ME, Wong DA, Miller MK, Lawrence-Miyasaki L. Pg 56, right column, line 4 insert: Short questionnaires canChurg-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- IG Szabó TJ, Halm EA. Assessing the validity of self-reported medicationPg 36, right column, insert: Evidence from the most rigorous adherence among inner-city asthmatic adults: the Medication Rstudies available to date indicates that spinal manipulation is Adherence Report Scale for Asthma. Ann Allergy Asthma PYnot an effective treatment for asthma121. Systematic reviews Immunol 2009;103(4):325-31.indicate that homeopathic medicines have no effects beyondCOplacebo222.. 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, vii
and self-management behaviors377. Reference 377. Coffman JM, up therapy for children with uncontrolled asthma receiving inhaled CECabana 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? Pediatrics2009;124(2):729-42. Pg 73, left column, fourth paragraph insert: The most cost U effective and efficient delivery is by meter dose inhaler and a spacer ODPg 59, left column, last paragraph add: Asthma patients who device64, 211.smoke, and are not treated with inhaled glucocorticosteroids, havea greater decline in lung function than asthma patients who do not Pg 77, right column, last paragraph insert: … and are PRsmoke378. Smoking cessation needs to be vigorously encouraged for commonly found in children with asthma exacerbation380. Referenceall patients with asthma who smoke. Reference 378. O’Byrne PM, 391. Leung TF, To MY, Yeung AC, Wong YS, Wong GW, Chan PK. RELamm CJ, Busse WW, Tan WC, Pedersen S; START Investigators Group. Multiplex molecular detection of respiratory pathogens in children withThe 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- OR20. B. References that provided confirmation or update of previousPg 60, left column, paragraph 3 insert: There is some evidence recommendations. Rthat 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 TEReference 379. Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters Investigators Group. The effects of inhaled budesonide on lung functionM, Aminzadeh K, Fitzgerald JM. Acetaminophen use and the risk of in smokers and nonsmokers with mild persistent asthma. Chest ALasthma 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 T M, Holt PG. Do early-life viral infections cause asthma? J Allergy NOPg 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 everyvisit, not just when the patient presents because of their asthma380. Pg 32, right column, insert reference 221. Wechsler ME, OReference 380. Mintz M, Gilsenan AW, Bui CL, Ziemiecki R, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, -DStanford RH, Lincourt W, Ortega H. Assessment of asthma control in et al. National Heart, Lung and Blood Institute’s Asthma Clinicalprimary 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 ALPg 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. Ievidence that quadrupling the dose of inhaled glucocorticosteroid might ERbe effective when asthma control starts to deteriorate, if doubling the Pg 54, left column, line 6, insert reference 372. van der Meerdoes not work381. Reference 381. Oborne J, Mortimer K, Hubbard V, Bakker MJ, van den Hout WB, Rabe KF, Sterk PJ, Kievit J, Assendelft ATRB, Tattersfield AE, Harrison TW. Quadrupling the dose of inhaled WJ, Sont JK; SMASHING (Self-Management in Asthma Supported bycorticosteroid 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 MCrit Care Med 2009;180(7):598-602. asthma: a randomized trial. Ann Intern Med 2009;151(2):110-20. EDPg 67, left column, add new paragraph: For children (6 to Pg 55, left column, second paragraph, add reference17 years) who have uncontrolled asthma despite the use of low-dose 374. Wilson SR, Strub P, Buist AS, Knowles SB, Lavori PW, Lapidus HTinhaled glucocorticosteroids, step-up therapy with long-acting β2- J, Vollmer WM; Better Outcomes of Asthma Treatment (BOAT) Studyagonist bronchodilator was significantly more likely to provide the best Group. Shared treatment decision making improves adherence andresponse than either step-up therapy with inhaled glucocorticosteroids outcomes in poorly controlled asthma. Am J Respir Crit Care Med IGor leukotriene receptor antagonist. However, many children had a 2010;181(6):566-77.best response to inhaled glucocorticosteroids or leukotriene receptor Rantagonist step-up therapy, highlighting the need to regularly monitor Pg 84, replace current reference 116 with: Fogel RB, Rosario PYand 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 fluticasoneCOSJ, 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
Pg 86, replace current reference 148 with: Rodrigo GJ, Neffen CEH, Colodenco FD, Castro-Rodriguez JA. Formoterol for acute asthma inthe emergency department: a systematic review with meta-analysis.Ann Allergy Asthma Immunol 2010;104(3):247-52. U ODPg 88, delete reference 187.C. Inserts related to special topics covered by the Committee PR1. Asthma Control: Figure 2-4, page 22 (and the identical Figure4.3-1, page 62) has been modified. Segment A: Assessment of Current REClinical Control was inadvertently omitted in the 2009 update and hasbeen added. The text that describes the purpose of the Figure as aclinical tool has been embedded. OR2. Statement on Anti-IgE for use in children. Pg 41, insert newstatement on anti-IgE with supporting references. R3. Special Considerations: Obesity. Page 76, insert new TEstatement about asthma and obesity with supportingreferences. AL4. Special Considerations: Gastroesophageal Reflux. Pg 78, insertnew statement with supporting references to update Tsegment on gastroesophageal reflux. NOD. GRADE Evidence Statements. The GINA Science identified twoissues for evaluation using GRADE evidence technology, one related Oto an expensive medication, anti-IgE, and one related to a inexpensive -Dmedication, magnesium sulfate. The methodology, the evidencestatements, and the consensus statements can be found on the GINAwebsite, www.ginasthma.org. ALPg 33. Question: “In adults with asthma, does monoclonal anti-IgE, Iomalizumab, compared to placebo improve patient outcomes?” The ERconsensus recommendation: ATFor allergic patients, with an elevated IgE, not controlled on highdose inhaled glucocortico-steroids and a long acting β2-agonist andwho continue to have exacerbations, a trial of omalizumab can be Mconsidered. This recommendation is based on a modest response ratefor the main endpoint exacerbations, and its high cost. EDPg 74: Question: “In adults with acute exacerbations of HTasthma, does intravenous magnesium sulphate comparedto placebo improve patient important outcomes?” Theconsensus recommendation: IGIn patients with severe, acute asthma, who have received maximal Rinhaled bronchodilator therapy and systemic glucocorticosteroids and PYwho have not responded adequately, a single dose of magnesiumsulphate (two grams IV) is recommended. This recommendation, inCOthis population, is based on the poor case definition in studies, as wellas its efficacy, low cost and safety. ix
INTRODUCTION CEAsthma is a serious public health problem throughout the world, affecting people of all ages. When uncontrolled, asthma Ucan place severe limits on daily life, and is sometimes fatal. ODIn 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 PR2006), and its companion documents, have been widely distributed and translated into many languages. A networkof individuals and organizations interested in asthma care has been created and several country-specific asthma REmanagement programs have been initiated. Yet much work is still required to reduce morbidity and mortality from thischronic disease. ORIn 2006, the Global Strategy for Asthma Management and Prevention was revised to emphasize asthma managementbased on clinical control, rather than classification of the patient by severity. This important paradigm shift for asthmacare reflected the progress made in pharmacologic care of patients. Many asthma patients are receiving, or havereceived, some asthma medications. The role of the health care professional is to establish each patient’s current level Rof treatment and control, then adjust treatment to gain and maintain control. Asthma patients should experience no TEor 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 ALexacerbations.The recommendations for asthma care based on clinical control described in the 2006 report have been updated Tannually. This 2010 update reflects a number of modifications, described in “Methodology and Summary of New NORecommendations.” As with all previous GINA reports, levels of evidence (Table A) are assigned to managementrecommendations where appropriate in Chapter 4, the Five Components of Asthma Management. Evidence levels areindicated in boldface type enclosed in parentheses after the relevant statement—e.g., (Evidence A). The methodologicalissues concerning the use of evidence from meta-analyses were carefully considered1. The GINA Science Committee Oused the GRADE approach2 to examine use of anti-IgE, omalizumab and intravenous magnesium sulphate; -Drecommendations are presented on the website, www.ginasthma.org. ALFUTURE CHALLENGES IIn spite of laudable efforts to improve asthma care over the past decade, a majority of patients have not benefited ERfrom advances in asthma treatment and many lack even the rudiments of care. A challenge for the next several yearsis to work with primary health care providers and public health officials in various countries to design, implement, ATand evaluate asthma care programs to meet local needs. The GINA Executive Committee recognizes that this is adifficult task and, to aid in this work, has formed several groups of global experts, including: a Dissemination andImplementation Committee; the GINA Assembly, a network of individuals who care for asthma patients in many different Mhealth care settings; and two regional programs, GINA Mesoamerica and GINA Mediterranean. These efforts aim toenhance communication with asthma specialists, primary-care health professionals, other health care workers, and EDpatient support organizations. The Executive Committee continues to examine barriers to implementation of the asthmamanagement recommendations, especially the challenges that arise in primary-care settings and in developing countries. HTWhile early diagnosis of asthma and implementation of appropriate therapy significantly reduce the socioeconomicburdens of asthma and enhance patients’ quality of life, medications continue to be the major component of the cost IGof asthma treatment. For this reason, the pricing of asthma medications continues to be a topic for urgent need anda growing area of research interest, as this has important implications for the overall costs of asthma management. RMoreover, a large segment of the world’s population lives in areas with inadequate medical facilities and meager PYfinancial resources. The GINA Executive Committee recognizes that “fixed” international guidelines and “rigid” scientificprotocols will not work in many locations. Thus, the recommendations found in this Report must be adapted to fit localCOpractices and the availability of health care resources.x
As the GINA Committees expand their work, every effort will be made to interact with patient and physician groups CEat national, district, and local levels, and in multiple health care settings, to continuously examine new and innovativeapproaches that will ensure the delivery of the best asthma care possible. GINA is a partner organization in a programlaunched in March 2006 by the World Health Organization, the Global Alliance Against Chronic Respiratory Diseases U(GARD). Through the work of the GINA Committees, and in cooperation with GARD, progress toward better care for all ODpatients with asthma should be substantial in the next decade. Table A. Description of Levels of Evidence PR Evidence Sources of Evidence Definition Category RE 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 OR 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 R body of data. RCTs. In general, Category B pertains when few randomized trials exist, they are TE 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. AL 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 T ment. deemed valuable but the clinical literature addressing the subject was insufficient NO 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. O -DREFERENCES1. Jadad AR, Moher M, Browman GP, Booker L, Sigouis C, Fuentes M, et al. Systematic reviews and meta-analyses ontreatment of asthma: critical evaluation. BMJ 2000;320:537-40. AL2. Guyatt G, Vist G, Falck-Ytter Y, Kunz R, Magrini N, Schunemann H. An emerging consensus on gradingrecommendations? Available from URL: http://www.evidence-basedmedicine.com. I ER AT M ED HT R IG PYCO xi
CO PY RIG HT ED M AT ER IAL -D O NO T AL TE R 1 OR AND RE PR CHAPTER OVERVIEW DEFINITION OD UCE
Wheezing appreciated on auscultation of the chest is the CE KEY POINTS: most common physical finding. • Asthma is a chronic inflammatory disorder of the The main physiological feature of asthma is episodic airway U airways in which many cells and cellular elements obstruction characterized by expiratory airflow limitation. OD 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, PR 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 RE 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 OR • 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 R flare-ups and severe exacerbations should be rare. wheezing, breathlessness, chest tightness, and coughing, TE particularly at night or in the early morning. These • Asthma is a problem worldwide, with an estimated episodes are usually associated with widespread, but AL 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 NO 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 O be divided into host factors (primarily genetic) and response to common environmental allergens), airway -D 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 AL 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 I consistent feature. between these two conditions have not been clearly and ER comprehensively defined.This chapter covers several topics related to asthma, ATincluding definition, burden of disease, factors that There is now good evidence that the clinical manifestationsinfluence the risk of developing asthma, and mechanisms. of asthma—symptoms, sleep disturbances, limitationsIt is not intended to be a comprehensive treatment of of daily activity, impairment of lung function, and use of Mthese topics, but rather a brief overview of the background rescue medications—can be controlled with appropriatethat informs the approach to diagnosis and management treatment. When asthma is controlled, there should be no EDdetailed in subsequent chapters. Further details are found more than occasional recurrence of symptoms and severein the reviews and other references cited at the end of the exacerbations should be rare1. HTchapter.DEFINITION IGAsthma is a disorder defined by its clinical, physiological, Rand pathological characteristics. The predominant feature PYof the clinical history is episodic shortness of breath,particularly at night, often accompanied by cough.CO2 DEFINITION AND OVERVIEW
Social and Economic BurdenTHE BURDEN OF ASTHMA CE Social and economic factors are integral to understanding asthma and its care, whether viewed from the perspectivePrevalence, Morbidity, and Mortality of the individual sufferer, the health care professional, U or entities that pay for health care. Absence from school ODAsthma is a problem worldwide, with an estimated 300 and days lost from work are reported as substantial socialmillion affected individuals2,3. Despite hundreds of reports and economic consequences of asthma in studies fromon the prevalence of asthma in widely differing populations, the Asia-Pacific region, India, Latin America, the United PRthe lack of a precise and universally accepted definition of Kingdom, and the United States9-12.asthma makes reliable comparison of reported prevalence REfrom different parts of the world problematic. Nonetheless, The monetary costs of asthma, as estimated in a variety ofbased on the application of standardi ed methods to health care systems including those of the United States13-15measure the prevalence of asthma and wheezing illness in and the United Kingdom16 are substantial. In analyses of ORchildren3 and adults4, it appears that the global prevalence economic burden of asthma, attention needs to be paidof asthma ranges from 1% to 18% of the population in to both direct medical costs (hospital admissions and costdifferent countries (Figure 1-1)2,3. There is good evidence of medications) and indirect, non-medical costs (time lostthat international differences in asthma symptom from work, premature death)17. For example, asthma is a Rprevalence have been reduced, particularly in the 13-14 major cause of absence from work in many countries4-6,121, TEyear age group, with decreases in prevalence in North including Australia, Sweden, the United Kingdom, and theAmerica and Western Europe and increases in prevalence United States16,18-20. Comparisons of the cost of asthma in ALin 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 currentwheeze, the percentage of children reported to have had • The costs of asthma depend on the individual patient’s Tasthma increased significantly, possibly reflecting greater level of control and the extent to which exacerbations NOawareness of this condition and/or changes in diagnostic are avoided.practice. The increases in asthma symptom prevalencein Africa, Latin America and parts of Asia indicate that • Emergency treatment is more expensive than planned treatment. Othe global burden of asthma is continuing to rise, butthe global prevalence differences are lessening126. The -DWorld 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 costto asthma, representing 1% of the total global disease effective.Families can suffer from the financial burden ALburden2. Annual worldwide deaths from asthma have of treating asthma.been estimated at 250,000 and mortality does not appear Ito correlate well with prevalence (Figure 1-1)2,3. There Although from the perspective of both the patient and ERare insufficient data to determine the likely causes of the society the cost to control asthma seems high, the costdescribed variations in prevalence within and between of not treating asthma correctly is even higher122. Proper ATpopulations. 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 M Figure 1-1. Asthma Prevalence and Mortality2, 3 substantial global burden of asthma can be dramatically reduced through efforts by individuals, their health care ED providers, health care organizations, and local and national governments to improve asthma control. HT Detailed reference information about the burden of asthma can be found in the report Global Burden of Asthma*. IG Further studies of the social and economic burden of asthma and the cost effectiveness of treatment are needed R in both developed and developing countries. PYCO 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