GINA-2024-Strategy-Report-24_05_22_WMS.pdf

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TE U IB TR IS D R O PY O C T O N O -D L IA ER AT M D TE H IG R Global Strategy for PY O C Asthma Management and Prevention Updated 2024 ©2024 Global Initiative for Asthma  Global Strategy for Asthma Management and Prevention (2024 update) The reader acknowledges that this report is intended as an evidence-based asthma management strategy, for the use of health professionals and policy-makers. It is based, to the best of our knowledge, on current best evidence and medical knowledge and practice at the date of publication. When assessing and treating patients, health professionals are strongly advised to use their own professional judgment, and to take into account local and national regulations and guidelines. GINA cannot be held liable or responsible for inappropriate health care associated with the use of this document, including any use which is not in accordance with applicable local or national regulations or guidelines. Suggested citation: Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2024. Updated May 2024. Available from: www.ginasthma.org TE U IB TR IS D R O PY O C T O N O -D L IA ER AT M D TE H IG R PY O C 1 Table of contents Tables and figures................................................................................................................................................ 5 Preface................................................................................................................................................................. 8 Members of GINA committees (2023–24)........................................................................................................... 9 Abbreviations......................................................................................................................................................11 Introduction........................................................................................................................................................ 14 Methodology...................................................................................................................................................... 15 WHAT’S NEW IN GINA 2024?........................................................................................................................... 19 1. Definition, description, and diagnosis of asthma in adults, adolescents and children 6–11 years............... 23 Definition of asthma....................................................................................................................................... 23 Description of asthma.................................................................................................................................... 23 TE U Making the initial diagnosis............................................................................................................................ 24 IB TR Differential diagnosis...................................................................................................................................... 27 IS D Confirming the diagnosis of asthma in patients already taking ICS-containing treatment............................ 32 R O How to make the diagnosis of asthma in other contexts............................................................................... 32 PY 2. Assessment of asthma in adults, adolescents and children 6–11 years....................................................... 35 O C Overview........................................................................................................................................................ 36 T O N Assessing asthma symptom control.............................................................................................................. 38 O -D Assessing future risk of exacerbations, lung function decline and adverse effects...................................... 41 L IA Role of lung function in assessing asthma control........................................................................................ 42 ER Assessing asthma severity............................................................................................................................ 43 AT M How to distinguish between uncontrolled asthma and severe asthma......................................................... 46 D TE 3. Principles of asthma management in adults, adolescents and children 6–11 years..................................... 48 H IG The patient–healthcare provider partnership................................................................................................. 49 R PY Long-term goal of asthma management........................................................................................................ 50 O C Remission of asthma..................................................................................................................................... 50 Personalized control-based asthma management........................................................................................ 52 Non-pharmacological strategies.................................................................................................................... 57 Referral for expert advice.............................................................................................................................. 66 4. Medications and strategies for adults, adolescents and children 6–11 years............................................... 67 Categories of asthma medications................................................................................................................ 69 Why should ICS-containing medication be commenced from the time of diagnosis?................................... 72 Adults and adolescents: asthma treatment tracks......................................................................................... 74 Initial asthma treatment for adults and adolescents...................................................................................... 75 Asthma treatment steps in adults and adolescents....................................................................................... 77 Track 1 (preferred): treatment steps 1–4 for adults and adolescents using ICS-formoterol reliever............. 78 2  Track 2 (alternative): treatment steps 1–4 for adults and adolescents using SABA reliever......................... 86 Step 5 (Tracks 1 and 2) in adults and adolescents....................................................................................... 91 About asthma treatment for children 6–11 years........................................................................................... 94 Initial asthma treatment in children 6–11 years............................................................................................. 94 Asthma treatment steps for children 6–11 years........................................................................................... 96 Reviewing response and adjusting treatment – adults, adolescents and children 6–11 years................... 100 Allergen immunotherapy.............................................................................................................................. 104 Vaccinations................................................................................................................................................. 106 Other therapies............................................................................................................................................ 106 5. Guided asthma self-management education and skills training.................................................................. 108 Skills training for effective use of inhaler devices........................................................................................ 108 TE Shared decision-making for choice of inhaler device.................................................................................. 109 U IB Adherence with medication and with other advice....................................................................................... 111 TR Asthma information.......................................................................................................................................113 IS D Training in guided asthma self-management................................................................................................114 R O Regular review by a healthcare provider or trained healthcare worker........................................................116 PY O School-based programs for children.............................................................................................................116 C T 6. Managing asthma with multimorbidity and in specific populations...............................................................117 O N O Managing multimorbidity...............................................................................................................................117 -D Managing asthma during the COVID-19 pandemic..................................................................................... 121 L IA Managing asthma in specific populations or settings.................................................................................. 123 ER AT 7. Diagnosis and initial treatment in adults with features of asthma, COPD or both....................................... 131 M D Objectives.................................................................................................................................................... 132 TE Background to diagnosing asthma and/or COPD in adult patients............................................................. 132 H IG R Assessment and management of chronic respiratory symptoms................................................................ 133 PY 8. Difficult-to-treat and severe asthma in adults and adolescents................................................................... 139 O C Definitions: uncontrolled, difficult-to-treat, and severe asthma.................................................................... 140 Prevalence: how many people have severe asthma?................................................................................. 140 Importance: the impact of severe asthma................................................................................................... 141 Overview of decision tree for assessment and management of difficult-to-treat and severe asthma......... 141 Investigate and manage difficult-to-treat asthma in adults and adolescents............................................... 146 Investigate the severe asthma phenotype and consider non-biologic therapies......................................... 149 Consider Type 2-targeted biologic therapies............................................................................................... 152 Assess, manage and monitor ongoing severe asthma treatment............................................................... 156 9. Management of worsening asthma and exacerbations in adults, adolescents and children 6–11 years.... 158 Overview...................................................................................................................................................... 159 Diagnosis of exacerbations.......................................................................................................................... 160 3  Self-management of exacerbations with a written asthma action plan....................................................... 161 Primary care management of asthma exacerbations (adults, adolescents, children 6–11 years).............. 166 Emergency department management of exacerbations (adults, adolescents, children 6–11 years).......... 171 Discharge planning and follow-up................................................................................................................ 176 10. Diagnosis of asthma in children 5 years and younger............................................................................... 178 Asthma and wheezing in young children..................................................................................................... 178 Clinical diagnosis of asthma........................................................................................................................ 179 Tests to assist in diagnosis.......................................................................................................................... 182 Risk profiles................................................................................................................................................. 183 Differential diagnosis.................................................................................................................................... 183 11. Assessment and management of asthma in children 5 years and younger.............................................. 185 TE Goal of asthma management...................................................................................................................... 185 U IB Assessment of asthma................................................................................................................................ 186 TR Remission of childhood wheezing and asthma........................................................................................... 186 IS D Medications for symptom control and risk reduction................................................................................... 189 R O Asthma treatment steps for children aged 5 years and younger................................................................. 192 PY O Reviewing response and adjusting treatment.............................................................................................. 194 C T Choice of inhaler device.............................................................................................................................. 194 O N O Asthma self-management education for carers of young children.............................................................. 195 -D 12. Management of worsening asthma and exacerbations in children 5 years and younger......................... 196 L IA Diagnosis of exacerbations.......................................................................................................................... 196 ER AT Initial home management of asthma exacerbations.................................................................................... 197 M D Primary care or hospital management of acute asthma exacerbations in children 5 years or younger...... 198 TE Discharge and follow-up after an exacerbation........................................................................................... 203 H IG R 13. Primary prevention of asthma.................................................................................................................... 204 PY Factors associated with increased or decreased risk of asthma in children............................................... 204 O C Advice about primary prevention of asthma................................................................................................ 207 Prevention of occupational asthma in adults............................................................................................... 208 14. Implementing asthma management strategies into health systems.......................................................... 209 Introduction.................................................................................................................................................. 209 Adapting and implementing asthma clinical practice guidelines................................................................. 209 Glossary of asthma medication classes.......................................................................................................... 212 References....................................................................................................................................................... 217 4 Tables and figures DIAGNOSIS Box 1-1. Diagnostic flowchart for adults, adolescents and children 6–11 years in clinical practice.................. 25 Box 1-2. Criteria for initial diagnosis of asthma in adults, adolescents, and children 6–11 years..................... 26 Box 1-3. Differential diagnosis of asthma in adults, adolescents and children 6–11 years............................... 27 Box 1-4. Steps for confirming the diagnosis of asthma in a patient already taking ICS-containing treatment.. 30 Box 1-5. How to step-down ICS-containing treatment to help confirm the diagnosis of asthma...................... 32 ASSESSMENT Box 2-1. Summary of assessment of asthma in adults, adolescents, and children 6–11 years........................ 36 Box 2-2. GINA assessment of asthma control at clinical visits in adults, adolescents and children 6–11 years37 Box 2-3. Specific questions for assessment of asthma in children 6–11 years................................................. 40 TE U Box 2-4. Investigating poor symptom control and/or exacerbations despite treatment..................................... 47 IB TR ASTHMA MANAGEMENT IS D Box 3-1. Communication strategies for healthcare providers............................................................................ 49 R O Box 3-2. Long-term goal of asthma management............................................................................................. 50 PY Box 3-3. The asthma management cycle for personalized asthma care.......................................................... 53 O C Box 3-4. Population-level versus patient-level decisions about asthma treatment........................................... 54 T O N Box 3-5. Treating potentially modifiable risk factors to reduce exacerbations and minimize OCS use............ 55 O -D Box 3-6. Non-pharmacological interventions – summary (see following text for details).................................. 57 L IA Box 3-7. Effectiveness of avoidance measures for indoor allergens................................................................. 62 ER Box 3-8. Indications for considering referral for expert advice, where available............................................... 66 AT M ASTHMA MEDICATIONS D TE Box 4-1. Terminology for asthma medications................................................................................................... 70 H IG Box 4-2. Low, medium and high daily metered doses of inhaled corticosteroids (alone or with LABA)............ 71 R PY Adults and adolescents O C Box 4-3. Asthma treatment tracks for adults and adolescents.......................................................................... 74 Box 4-4. Initial asthma treatment for adults and adolescents with a diagnosis of asthma................................ 75 Box 4-5. Flowchart for selecting initial treatment in adults and adolescents with a diagnosis of asthma......... 76 Box 4-6. Personalized management for adults and adolescents to control symptoms and minimize future risk77 Box 4-7. Track 1 (preferred) treatment Steps 1–4 for adults and adolescents.................................................. 78 Box 4-8. Medications and doses for GINA Track 1: anti-inflammatory reliever (AIR) therapy.......................... 84 Box 4-9. Track 2 (alternative) treatment Steps 1–4 for adults and adolescents................................................ 86 Children 6–11 years Box 4-10. Initial asthma treatment for children aged 6–11 years with a diagnosis of asthma........................... 94 Box 4-11. Flowchart for selecting initial treatment in children aged 6–11 years with a diagnosis of asthma.... 95 Box 4-12. Personalized management for children 6–11 years to control symptoms and minimize future risk. 96 5  Stepping down Box 4-13. Options for stepping down treatment in adults and adolescents once asthma is well controlled... 102 ASTHMA SELF-MANAGEMENT EDUCATION AND SKILLS TRAINING Box 5-1. Shared decision-making between health professional and patient about choice of inhalers........... 109 Box 5-2. Choice and effective use of inhaler devices.......................................................................................110 Box 5-3. Poor adherence with prescribed maintenance treatment in asthma..................................................112 Box 5-4. Asthma information.............................................................................................................................113 PATIENTS WITH FEATURES OF ASTHMA AND COPD Box 7-1. Current definitions of asthma and COPD, and clinical description of asthma-COPD overlap.......... 133 Box 7-2. Syndromic approach to initial treatment in patients with asthma and/or COPD............................... 134 Box 7-3. Spirometric measures in asthma and COPD.................................................................................... 135 TE Box 7-4. Specialized investigations sometimes used in patients with features of asthma and COPD........... 137 U IB DIFFICULT-TO-TREAT AND SEVERE ASTHMA TR Box 8-1. What proportion of adults have difficult-to-treat or severe asthma?................................................. 140 IS D Box 8-2. Decision tree – investigate and manage difficult to treat asthma in adult and adolescent patients.. 142 R O Box 8-3. Decision tree – assess and treat severe asthma phenotypes.......................................................... 143 PY O Box 8-4. Decision tree – consider add-on biologic Type 2-targeted treatments.............................................. 144 C T Box 8-5. Decision tree – monitor and manage severe asthma treatment....................................................... 145 O N O ASTHMA EXACERBATIONS -D Box 9-1. Factors associated with increased risk of asthma-related death...................................................... 160 L IA Box 9-2. Self-management of worsening asthma in adults and adolescents with a written asthma action plan162 ER AT Box 9-3. Optimizing asthma treatment to minimize need for OCS.................................................................. 165 M D Box 9-4. Management of asthma exacerbations in primary care (adults, adolescents, children 6–11 years) 167 TE Box 9-5. Discharge management after acute care for asthma........................................................................ 170 H IG R Box 9-6. Management of asthma exacerbations in acute care facility (e.g., emergency department)........... 171 PY CHILDREN 5 YEARS AND YOUNGER O C Diagnosis Box 10-1. Probability of asthma diagnosis in children 5 years and younger................................................... 179 Box 10-2. Features suggesting a diagnosis of asthma in children 5 years and younger................................ 180 Box 10-3. Questions that can be used to elicit features suggestive of asthma............................................... 180 Box 10-4. Common differential diagnoses of asthma in children 5 years and younger.................................. 183 Box 10-5. Key indications for referral of a child 5 years or younger for expert advice.................................... 184 Assessment and management Box 11-1. GINA assessment of asthma control in children 5 years and younger........................................... 188 Box 11-2. Personalized management of asthma in children 5 years and younger......................................... 190 Box 11-3. Low daily doses of inhaled corticosteroids for children 5 years and younger................................. 191 Box 11-4. Choosing an inhaler device for children 5 years and younger........................................................ 191 6  Exacerbations Box 12-1. Management of acute asthma or wheezing in children 5 years and younger................................ 199 Box 12-2. Initial assessment of acute asthma exacerbations in children 5 years and younger...................... 200 Box 12-3. Indications for immediate transfer to hospital for children 5 years and younger............................. 200 Box 12-4. Emergency department management of asthma exacerbations in children 5 years and younger. 201 PRIMARY PREVENTION OF ASTHMA Box 13-1. Advice about primary prevention of asthma in children 5 years and younger................................ 207 IMPLEMENTATION Box 14-1. Approach to implementation of the Global Strategy for Asthma Management and Prevention...... 210 Box 14-2. Essential elements required to implement a health-related strategy.............................................. 210 Box 14-3. Examples of barriers to the implementation of evidence-based recommendations........................211 TE Box 14-4. Examples of high-impact implementation interventions in asthma management............................211 U IB TR IS D R O PY O C T O N O -D L IA ER AT M D TE H IG R PY O C 7 Preface Asthma is a serious global health problem affecting all age groups. Its prevalence is increasing in many countries, especially among children. Although some countries have seen a decline in hospitalizations and deaths from asthma, asthma still imposes an unacceptable burden on healthcare systems, and on society through loss of productivity in the workplace and, especially for pediatric asthma, disruption to the family. In 2023 the Global Initiative for Asthma celebrated 30 years of working to improve the lives of people with asthma by translating medical evidence into better asthma care worldwide. Established in 1993 by the National Heart, Lung, and Blood Institute and the World Health Organization, GINA works with healthcare professionals, researchers, patients and public health officials around the world to reduce asthma prevalence, morbidity and mortality. The Global Strategy for Asthma Management and Prevention (‘GINA Strategy Report’) was first published in 1995, and has been updated annually since 2002 by the GINA Science Committee. It contains guidance for primary care practitioners, specialists and allied health professionals, based on the latest high-quality evidence available. More resources and supporting material are provided online at www.ginasthma.org. GINA supports global efforts to achieve environmental sustainability in health care, while ensuring that our guidance TE reflects an optimal balance between clinical and environmental priorities, with a particular focus on patient safety. U GINA also supports efforts to ensure global availability of, and access to, effective quality-assured medications, to IB TR reduce the burden of asthma mortality and morbidity. Since 2001, GINA has organized the annual World Asthma Day, IS a focus for local and national activities to raise awareness of asthma and educate families and healthcare D professionals about effective asthma care. R O GINA is an independent organization funded solely through sale and licensing of its educational publications. Members PY of the GINA Board of Directors are drawn globally from leaders with an outstanding demonstrated commitment to O C asthma research, asthma clinical management, public health and patient advocacy. GINA Science Committee T O members are highly experienced asthma experts from around the world, who continually review and synthesize N scientific evidence to provide guidance on asthma prevention, diagnosis and management. The GINA Dissemination O -D Task Group is responsible for promoting GINA resources throughout the world. Members work with an international network of patient representatives and leaders in asthma care (GINA Advocates), to implement asthma education L IA programs and support evidence-based care. GINA support staff comprise the Executive Director and Project Manager. ER AT We acknowledge the superlative work of all who have contributed to the success of the GINA program. In particular, M we recognize the outstanding long-term dedication of founding Scientific Director Dr Suzanne Hurd and founding D Executive Director Dr Claude Lenfant in fostering GINA’s development until their retirement in 2015, and we were said TE to hear of Dr Lenfant’s passing last year. A tribute to Dr Lenfant is available on the GINA website H IG (https://ginasthma.org/in-memorium-a-tribute-to-claude-lenfant-10-12-1928-to-06-26-2023/). We acknowledge the R invaluable commitment and skills of our current Executive Director Rebecca Decker, and Program Director Kristi PY Rurey. We continue to recognize the contribution of Prof J Mark FitzGerald to GINA for over 25 years until his passing O C in 2022. We also thank all members of the Science Committee, who receive no honoraria or reimbursement for their many hours of work in reviewing evidence and attending meetings, and the GINA Dissemination Working Group and GINA Advocates. We hope you find this report to be a useful resource in the management of asthma and that it will help you work with each of your patients to provide the best personalized care, Helen K Reddel, MBBS PhD Chair, GINA Science Committee Arzu Yorgancıoğlu, MD Chair, GINA Board of Directors 8 Members of GINA committees (2023–24) GINA Scientific Committee Liesbeth Dui ts, MD MSc Phd University Medical Center Helen K. Reddel, MBBS PhD, Chair Rotterdam, The Netherlands Woolcock Institute of Medical Research, Macquarie University Louise Fleming, MBChB MD Sydney, Australia Royal Brompton Hospital London, United Kingdom Leonard B. Bacharier, MD anderbilt University Medical Center Hiromasa Inoue, MD Kagoshima University Nashville, TN, USA Kagoshima, Japan Eric D. Bateman, MD Alan Kaplan, MD from March University of University of Cape Town Lung Institute Toronto Cape Town, South Africa Toronto, ntario, Canada TE Family Physician Airways Group of Canada U Matteo Bonini MD, PhD Markham, ntario, Canada IB Department of Public Health and Infectious Diseases, TR Sapienza University of Rome, Italy Fanny Wai san Ko, MD IS The Chinese University of Hong Kong Hong Kong D National Heart and Lung Institute NHLI , Imperial R College London, UK O Refiloe Masekela MBBCh, PhD PY Department of Paediatrics and O Arnaud Bourdin, MD, PhD Child Health, University of Kwa ulu Natal C Department of Respiratory Diseases, University of Durban, South Africa T O Montpellier N Montpellier, France Paulo Pitrez, MD, PhD O -D Pulmonary Division, Hospital Santa Casa de Porto Alegre L Christopher Brightling, FMedSci, PhD IA Universidade Federal de Ci ncias da Sa de de ER Leicester NIHR Biomedical Research Centre, Porto Alegre UFCSPA University of Leicester AT Porto Alegre, Brazil Leicester, UK M D Sundeep Salvi MD, PhD TE Guy Brusselle, MD, PhD Pulmocare Research and Education PURE H IG Ghent University Hospital Foundation R Ghent, Belgium Pune, India PY O Aziz Sheikh, BSc, MBBS, MSc, MD C Roland Buhl, MD PhD Mainz University Hospital The University of Edinburgh Edinburgh, United Kingdom Mainz, Germany GINA oar o Dire tors Jeffrey M. Drazen, MD Brigham and Woman s Hospital Arzu organcioglu, MD Chair Boston, MA, USA Celal Bayar University Department of Pulmonology Francine Ducharme, MD Manisa, Turkey Departments of Pediatrics and of Social and Preventive Medicine, Keith Allan, CBiol, MRSB Sainte Justine University Health Centre, Patient Partner University Hospitals of Leicester University of Montreal Leicester, UK Montreal, uebec, Canada 9 Eric D. Bateman, MD GINA Program University of Cape Town Lung Institute Rebecca Decker, BS, MSJ Cape Town, South Africa Kristi Rurey, AS Guy Brusselle, MD, PhD Ghent University Hospital Ghent, Belgium Editorial assistance Charu Grover, PhD Muhwa Jeremiah Chakaya, MD Respiratory Society of Kenya Jenni Harman, BVSc, BA Department of Medicine, Therapeutics, Dermatology and Psychiatry, Kenyatta University Nairobi, Kenya Graphics assistance Alvaro A. Cruz, MD Kate Chisnall Federal University of Bahia Salvador, BA, Brazil Information design for TE Hiromasa Inoue, MD severe asthma decision tree U Kagoshima University IB Kagoshima, Japan Tomoko Ichikawa, MS TR IS Hugh Musick, MBA Jerry A. Krishnan, MD PhD D University of Illinois Hospital & Health Sciences Institute for Healthcare Delivery Design R System O PY Chicago, IL, USA University of Illinois, Chicago, USA O C Mark L. Levy, MD T O Locum GP N Disclosures for members of GINA committees can be London, UK O found at www.ginasthma.org -D Helen K. Reddel, MBBS PhD L IA Woolcock Institute of Medical Research, Macquarie ER University AT Sydney, Australia M D GINA Dissemination Group TE H IG Mark L. Levy, MD Chair R Locum GP PY London, UK O C Keith Allan, CBiol, MRSB Patient Partner University Hospitals of Leicester Leicester, UK Hiromasa Inoue, MD Kagoshima University Kagoshima, Japan Helen K. Reddel, MBBS PhD Woolcock Institute of Medical Research, Macquarie University Sydney, Australia Arzu organcioglu, MD Celal Bayar University Manisa, Turkey 10 Abbreviations ABPA Allergic bronchopulmonary aspergillosis ACE Angiotensin-converting enzyme ACQ Asthma Control Questionnaire ACT Asthma Control Test (see also cACT) AERD Aspirin-exacerbated respiratory disease AIR Anti-inflammatory reliever (see Box 4-1, p.70) ANCA Antineutrophil cytoplasmic antibody Anti-IL4Rα Anti-interleukin 4 receptor alpha (monoclonal antibody) Anti-IL5 Anti-interleukin 5 (monoclonal antibody) Anti-IL5Rα Anti-interleukin 5 receptor alpha (monoclonal antibody) TE U Anti-TSLP Anti-thymic stromal lymphopoietin (monoclonal antibody) IB TR APGAR Activities, Persistent, triGgers, Asthma medications, Response to therapy IS D ATS/ERS American Thoracic Society and European Respiratory Society R BDP Beclometasone dipropionate O PY O BD Bronchodilator C T BMI Body mass index O N BNP B-type natriuretic peptide O -D bpm Beats per minute L IA BTS British Thoracic Society ER AT cACT Childhood Asthma Control Test M CBC Complete blood count (also known as full blood count [FBC]) D TE CDC Centers for Disease Control and Prevention [USA] H IG CI Confidence interval R PY COPD Chronic obstructive pulmonary disease O C COVID-19 Coronavirus disease 2019 CRP C-reactive protein CRSwNP Chronic rhinosinusitis with nasal polyps CRSsNP Chronic rhinosinusitis without nasal polyps CT Computerized tomography CXR Chest X-ray DLCO Diffusing capacity in the lung for carbon monoxide DEXA Dual-energy X-ray absorptiometry DPI Dry-powder inhaler ED Emergency department EGPA Eosinophilic granulomatosis with polyangiitis 11 FeNO Fractional concentration of exhaled nitric oxide FEV1 Forced expiratory volume in 1 second (measured by spirometry) FVC Forced vital capacity (measured by spirometry) FEV1/FVC Ratio of forced expiratory volume in 1 second to forced vital capacity GERD Gastro-esophageal reflux disease (GORD in some countries) GOLD Global Initiative for Chronic Obstructive Pulmonary Disease GRADE Grading of Recommendations Assessment, Development and Evaluation (an approach to clinical practice guideline development) HDM House dust mite HEPA High-efficiency particulate air HFA Hydrofluoroalkane propellant HIV/AIDS Human immunodeficiency virus/acquired immunodeficiency syndrome TE U ICS Inhaled corticosteroid IB TR Ig Immunoglobulin IS D IL Interleukin R IM Intramuscular O PY ICU Intensive care unit O C IV Intravenous T O N LABA Long-acting beta2 agonist O -D LAMA Long-acting muscarinic antagonist (also called long-acting anticholinergic) L IA LMIC Low- and middle-income countries ER LTRA Leukotriene receptor antagonist (also called leukotriene modifier) AT M MART Maintenance-and-reliever therapy (with ICS-formoterol); in some countries called SMART (single- D TE inhaler maintenance-and-reliever therapy) H n.a Not applicable IG R PY NSAID Nonsteroidal anti-inflammatory drug O NO2 Nitrogen dioxide (air pollutant) C O2 Oxygen OCS Oral corticosteroids OSA Obstructive sleep apnea PaCO2 Arterial partial pressure of carbon dioxide PaO2 Arterial partial pressure of oxygen PEF Peak expiratory flow PM10 Particulate matter with a particle diameter of 10 micrometers or less (air pollution) pMDI Pressurized metered-dose inhaler QTc Corrected QT interval on electrocardiogram RCT Randomized controlled trial SABA Short-acting beta2 agonist 12 SC Subcutaneous SCIT Subcutaneous allergen immunotherapy sIgE Specific immunoglobulin E SLIT Sublingual immunotherapy S02 Sulfur dioxide (air pollutant) T2 Type 2 airway inflammation (an asthma phenotype) TSLP Thymic stromal lymphopoietin URTI Upper respiratory tract infection VCD Vocal cord dysfunction (included in inducible laryngeal obstruction) WHO World Health Organization WHO-PEN The World Health Organization Package of essential noncommunicable disease interventions for primary care TE U IB TR IS D R O PY O C T O N O -D L IA ER AT M D TE H IG R PY O C 13 Introduction Asthma is a serious global health problem, affecting approximately 300 million people around the world, and causing around 1,000 deaths per day. Most of these deaths occur in low- and middle-income countries, and most of them are preventable. Asthma interferes with people’s work, education and family life, especially when children have asthma. Asthma is becoming more prevalent in many economically developing countries, and the cost of asthma treatment for healthcare systems, communities and individuals is increasing. The Global Initiative for Asthma (GINA) was established to increase awareness about asthma among healthcare providers, public health authorities and communities, to improve management of asthma, and to help prevent asthma. Every year GINA publishes a strategy report, containing information and recommendations on asthma, based on the latest medical evidence. GINA’s aim is for these to be available and used throughout the world. GINA also promotes international collaboration on asthma research. GINA Committee members are listed on page 9. Goals of asthma management The population goal of asthma management is to prevent asthma deaths and minimize the burden of asthma on TE individuals, families, communities, health systems and the environment. U IB For individuals with asthma of all ages, the goal of asthma management is to achieve the patient’s best possible TR long-term outcomes: IS D Long-term asthma symptom control, which may include: R - Few/no asthma symptoms O PY O - No sleep disturbance due to asthma C T - Unimpaired physical activity O N Long-term asthma risk minimization, which may include: O -D - No exacerbations L IA - Improved or stable personal best lung function ER No requirement for maintenance OCS AT - No medication side-effects. M - D TE The patient’s goals for their asthma may be different from these medical goals; and patients with few or no asthma H symptoms can still have severe or fatal exacerbations, including from external triggers such as viral infections, allergen IG exposure (if sensitized) or pollution. R PY Challenges in global asthma management O C For healthcare providers, the challenges of managing asthma differ between regions and health systems. Despite laudable efforts to improve asthma care over the past 30 years, and the availability of effective medications, many patients globally have not benefited from advances in asthma treatment and often lack even the rudiments of care. Many of the world’s population live in areas with inadequate medical facilities and meager financial resources. GINA recognizes that the recommendations found in this report must be adapted to fit local practices and the availability of healthcare resources. To improve asthma care and patient outcomes, evidence-based recommendations must also be disseminated and implemented nationally and locally, and integrated into health systems and clinical practice. Implementation requires an evidence-based strategy involving professional groups and stakeholders and considering local cultural and socioeconomic conditions. GINA is a partner organization in the Global Alliance against Chronic Respiratory Diseases (GARD). Through the work of GINA, and in cooperation with GARD and the International Union Against Tuberculosis and Lung Diseases (IUATLD), substantial progress toward better care for all patients with asthma should be achieved in the next decade. At the most fundamental level, patients in many areas do not have access to any inhaled corticosteroid-containing medications, which are the cornerstone of care for asthma patients of all severity. More broadly, medications remain the major contributor to the overall costs of asthma management, so the access to and pricing of high-quality asthma medications continues to be an issue of urgent need and a growing area of research interest.1-3 The safest and most 14 effective approach to asthma treatment in adolescents and adults, which also avoids the consequences of starting treatment with short-acting beta2 agonist (SABA) alone, and requires only a single medication, depends on access to the combination of inhaled corticosteroid and formoterol (ICS–formoterol) across all asthma severity levels.4,5 Budesonide-formoterol is included in the World Health Organization (WHO) essential medicines list, so the fundamental change to anti-inflammatory treatment that was first included in the 2019 GINA Strategy Report6 may provide a feasible solution to reduce the risk of severe exacerbations in low- and middle-income countries.5 The urgent need to ensure access to affordable, quality-assured inhaled asthma medications as part of universal health coverage must now be prioritized by all relevant stakeholders, particularly manufacturers of relevant inhalers. GINA is collaborating with IUATLD and other organizations to work towards a World Health Assembly Resolution to improve equitable access to affordable care, including inhaled medicines, for children, adolescents and adults with asthma.3 There is increasing concern globally about climate change, and its impact on the health and security of populations, particularly in low- and middle-income countries. The propellants in pressurized metered-dose inhalers contribute significantly to the carbon footprint of health care, particularly from use of SABAs. The GINA Track 1 approach not only provides a large reduction in exacerbations, in risk of adverse effects of oral corticosteroids, and in urgent health care TE compared with SABA-only treatment, but also, if implemented with a dry powder inhaler (as in most of the clinical U trials), it provides a very large reduction in carbon footprint.7 GINA fully supports initiatives to encourage use of IB dry-powder inhalers, where they are available and clinically appropriate, and to replace harmful propellants with TR low-carbon alternatives. At the same time, it is essential to ensure continuity of supply of essential inhaled medicines IS D to people in low-resource areas, to avoid exacerbating the existing serious global inequities in health care for asthma.8 R O Methodology PY O C T GINA SCIENCE COMMITTEE O N O The GINA Science Committee was established in 2002 to review published research on asthma management and -D prevention, to evaluate the impact of this research on recommendations in GINA documents, and to provide yearly L IA updates to these documents. The members are recognized leaders in asthma research and clinical practice, with the ER scientific expertise to contribute to the task of the Committee. They are invited to serve for a limited period and in a AT voluntary capacity. The Committee is broadly representative of adult and pediatric disciplines, and members are drawn M from diverse geographic regions. The Science Committee normally meets in person three times yearly, in conjunction D TE with the American Thoracic Society (ATS) and European Respiratory Society (ERS) international conferences and at a H stand-alone meeting, to review asthma-related scientific literature. During COVID-19, meetings of the Science IG Committee were held online each month, and online meetings have continued every 1–2 months since then. R PY Statements of interest for Committee members (p.9) are found on the GINA website www.ginasthma.org. O C PROCESSES FOR UPDATES AND REVISIONS OF THE GINA STRATEGY REPORT Literature search Details are provided on the GINA website (www.ginasthma.org/about-us/methodology). In summary, two PubMed searches are performed each year, each covering the previous 18 months, using filters established by the Science Committee. The search terms include asthma, all ages, only items with abstracts, clinical trial or meta-analysis or systematic review, and human. The search is not limited to specific PICOT (Population, Intervention, Comparison, Outcomes, Time) questions. The ‘clinical trial’ publication type includes not only conventional randomized controlled trials, but also pragmatic, real-life and observational studies. The search for systematic reviews includes, but is not limited to, those conducted using GRADE methodology.9 An additional search is conducted for guidelines documents published by other international organizations. The respiratory community is also invited to submit any other fully published peer-reviewed publications that they believe have been missed, providing that the full paper is submitted in (or translated into) English; however, because of the comprehensive process for literature review, such ad hoc submissions have rarely resulted in substantial changes to the report. 15 Systematic reviews Unique among evidence-based recommendations in asthma, and rare among clinical practice guidelines in most other therapeutic areas, the GINA report is based on an ongoing twice-yearly cumulative update of the evidence base for its recommendations. GINA does not normally carry out or commission its own GRADE-based reviews, because of the current cost of such reviews, the large number of PICOT questions that would be necessary for a comprehensive practical report of this scope, and because it would limit the responsiveness of the GINA Strategy Report to emerging evidence and new developments in asthma management. However, the Science Committee reviews relevant published systematic reviews conducted with GRADE methodology as part of its normal process. GINA recommendations are constantly being reviewed and considered for update as new evidence (including GRADE- based systematic reviews on specific topics) is identified and indicates the need. With recognition of allergen immunotherapy as an area of the GINA report that needed substantial updating, a GINA working group conducted a systematic review of articles on subcutaneous immunotherapy or sublingual immunotherapy since publication of two recent systematic reviews.10,11 From the period 01/01/2018 to 10/28/2023, the working group screened the titles and abstracts of 350 articles for quality and relevance, and undertook full-text review of 73 publications. On the basis of this systematic review, the section of the GINA report on allergen immunotherapy TE (p.104) has been extensively updated. U IB Literature screening and review TR Each article identified by the literature search, after removal of duplicates and those already reviewed, is pre-screened IS D in Covidence for relevance and major quality issues by the Editorial Assistant and by at least two non-conflicted R members of the Science Committee. Each publication selected from screening is reviewed for quality and relevance O PY by at least two members of the Science Committee, neither of whom may be an author (or co-author) or declare a O conflict of interest in relation to the publication. Articles that have been accepted for publication and are online in C advance of print are eligible for full text review if the approved/corrected copy-edited proof is available. All members T O receive a copy of all abstracts and full text publications, and non-conflicted members have the opportunity to provide N comments during the pre-meeting review period. Members evaluate the abstract and the full text publication, and O -D answer written questions in a review template about whether the scientific data impact on GINA recommendations, L and if so, what specific changes should be made. In 2020, the Critical Appraisal Skills Programme (CASP) checklist12 IA was provided in the review template to assist in evaluation of systematic reviews. A list of all publications reviewed by ER the Committee is posted on the GINA website (www.ginasthma.org). AT M Discussion and decisions during Science Committee meetings D TE Each publication that is assessed by at least one reviewer to potentially impact on the GINA Strategy Report is H discussed in a Science Committee meeting (virtual or face-to-face). This process comprises three parts, as follows: IG R PY 1. Quality and relevance of original research and systematic review publications. First, the Committee considers O the relevance of the publication to the GINA Strategy Report, the quality of the study, the reliability of the findings, and C the interpretation of the results, based on the responses from reviewers and discussion by members of the Committee. For systematic reviews, GRADE assessments, if available, are considered. However, for any systematic review, GINA members also independently consider the clinical relevance of the question addressed by the review, and the scientific and clinical validity of the included populations and study design. For network meta-analyses, reviewers also consider the appropriateness of the comparisons (e.g., whether differences in background exacerbation risk and ICS dose were taken into account) and the generalizability of the findings. During this discussion, a member who is an author (or was involved in the study) may be requested to provide clarification or respond to questions about the study, but they may not otherwise take part in this discussion about the quality and relevance of the publication. 2. Decision about inclusion of the evidence. During this phase, the Committee decides whether the publication or its findings affect GINA recommendations or statements and should be included in the GINA Strategy Report. These decisions to modify the report or its references are made by consensus by Committee members present and, again, any member with a conflict of interest is excluded from these decisions. If the chair is an author on a publication being reviewed, an alternative chair is appointed to lead the discussion in part 1 and the decision in part 2 for that publication. 16 3. Discussion about related changes to the GINA Strategy Report. If the committee resolves to include the publication or its findings in the report, an author or conflicted member, if present, is permitted to take part in the subsequent discussions about and decisions on changes to the report, including the positioning of the study findings in the report and the way that they would be integrated with existing (or other new) components of the GINA management strategy. These discussions may take place immediately, or over the course of the year as new evidence emerges or as other changes to the report are agreed and implemented. The approach to managing conflicts of interest, as described above, also applies to members of the GINA Board who, ex-officio, attend GINA Science Committee meetings. As with all previous GINA Strategy Reports, levels of evidence are assigned to management recommendations where appropriate. Current criteria (Table A) are based on those originally developed by the National Heart Lung and Blood Institute. From 2019, GINA has included in ‘Level A’ strong observational evidence that provides a consistent pattern of findings in the population for which the recommendation is made, and has also described the values and preferences that were considered in making major new recommendations. The table was updated in 2021 to avoid ambiguity about the positioning of observational data and systematic reviews. Table A. Description of levels of evidence used in this report TE Evidence Sources U Definition IB level of evidence TR IS A Randomized controlled Evidence is from endpoints of well-designed RCTs, systematic D trials (RCTs), systematic reviews of relevant studies or observational studies that provide a R reviews, observational O consistent pattern of findings in the population for which the PY evidence. Rich body of recommendation is made. Category A requires substantial numbers of O data studies involving substantial numbers of participants. C T O B Randomized controlled Evidence is from endpoints of intervention studies that include only a N O trials and systematic limited number of patients, post hoc or subgroup analysis of RCTs or -D reviews. Limited body of systematic reviews of such RCTs. In general, Category B applies L data when few randomized trials exist, they are small in size, they were IA ER undertaken in a population that differs from the target population of AT the recommendation, or the results are somewhat inconsistent. M D C Nonrandomized trials or Evidence is from non-randomized trials or observational studies. TE observational studies H IG R D Panel consensus This category is used only in cases where the provision of some PY judgment guidance was deemed valuable but the clinical literature addressing O C the subject was insufficient 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. New therapies and indications The GINA Strategy Report is a global strategy document. Since regulatory approvals differ from country to country, and manufacturers do not necessarily make regulatory submissions in all countries, some GINA recommendations are likely to be off-label in some countries. This is a particular issue for pediatrics, where across different diseases, many treatment recommendations for preschool children and for children aged 6–11 years are off-label. For new therapies, GINA’s aim is to provide clinicians with evidence-based guidance about new therapies and their positioning in the overall asthma treatment strategy as soon as possible; otherwise, the gap between regulatory approval and the periodic update of many national guidelines is filled only by advertising or educational material produced by the manufacturer or distributor. For new therapies for which the GINA Science Committee considers there is sufficient good-quality evidence for safety and efficacy or effectiveness in relevant asthma populations, recommendations may be held until after approval for asthma by at least one major regulatory agency (e.g., European Medicines Agency or US Food and Drug Administration), since regulators often receive substantially more safety 17 and/or efficacy data on new medications than are available to GINA through peer-reviewed literature. However, decisions by GINA to make or not make a recommendation about any therapy, or about its use in any specific population, are based on the best available peer-reviewed evidence and not on labeling directives from regulators. For existing therapies with evidence for new regimens or in different populations, the Science Committee may, where relevant, make recommendations that are not necessarily covered by regulatory indications in any country at the time, provided the Committee is satisfied with the available evidence around safety and efficacy/effectiveness. Since the GINA Strategy Report is a global strategy, the report does not refer to recommendations as being ‘off-label’. However, readers are advised that, when assessing and treating patients, they should use their own professional judgment and should also consider local and national guidelines and eligibility criteria, as well as locally licensed drug doses. External review Prior to publication each year, the GINA Strategy Report undergoes extensive external review by patient advocates and by asthma care experts from primary and specialist care in multiple countries. There is also continuous external review throughout the year in the form of feedback from end-users and stakeholders through the contact form on the GINA website. TE U Literature reviewed for GINA 2024 update IB TR The GINA Strategy Report has been updated in 2024 following the routine twice-yearly review of the literature by the IS GINA Science Committee. The literature searches for ‘clinical trial’ publication types (see above), systematic reviews D and guidelines identified a total of 3423 publications, of which 2961 duplicates/animal studies/non-asthma/pilot studies R O and protocols were removed. A total of 462 publications underwent screening of title and abstract by at least two PY reviewers, and 68 were screened out for relevance and/or quality. A total of 64 publications underwent full-text review O by at least two members of the Science Committee, and 34 publications were subsequently discussed at meetings of C T the Science Committee. O N A list of key changes in GINA 2024 is shown on page 19, and a copy showing tracked changes is archived on the O -D GINA website at www.ginasthma.org/archived-reports. L IA ER AT M D TE H IG R PY O C 18 WHAT’S NEW IN GINA 2024? The GINA Strategy Report has been updated in 2024 following the routine twice-yearly cumulative review of the literature by the GINA Scientific Committee, and extensive discussion about issues relevant to clinical practice and research. A copy showing tracked changes from the GINA 2023 report is archived on the GINA website. KEY CHANGES Diagnosis of asthma: The diagnostic flowchart for clinical practice (Box 1-1, p.25) has been revised, recognizing that, globally, a large proportion of health professionals do not have access (or timely access) to spirometry in their clinical practice. Although peak expiratory flow (PEF) is less reliable than spirometry, it is better than relying on symptoms alone. The flowchart allows for selection of different initial lung function tests, depending on local resources. The criteria for identifying variable expiratory airflow limitation (Box 1-2, p.26) have also been clarified, and more details provided about bronchodilator withholding. GINA again reviewed, but has not adopted, the recommendation by the American Thoracic Society and European Respiratory Society Technical Standards Committee to change the criterion for bronchodilator responsiveness from TE an increase from baseline of ≥12% and 200 mL to an increase from baseline of >10% predicted. The Technical U IB Standards Committee based this recommendation on data for survival, and had explicitly avoided making any TR recommendation about the use of this criterion for diagnostic decisions in clinical practice. This topic will be IS considered by GINA again when data from additional populations, and for other asthma outcomes, have been D R published, to inform the implications of the proposed new criterion for diagnosis of asthma in clinical practice (p.29). O PY Cough variant asthma: more information has been added (p.24 and p.32) about this clinical phenotype of asthma, O which is common in some countries. Cough variant asthma may be difficult to distinguish from other causes of C chronic cough in clinical practice, as spirometry may be normal and variable airflow limitation may be identified only T O from bronchial provocation testing. Some patients may later also develop wheezing and bronchodilator N O responsiveness. The treatment of cough variant asthma is the same as for asthma in general; the cough may return -D if inhaled corticosteroids (ICSs) are stopped. L