National Heart, Lung, and Blood Institute

National Asthma Education and Prevention Program

Expert Panel Report 3: Guidelines for the Diagnosis and

National Heart, Lung, and Blood Institute

National Asthma Education and Prevention Program

Expert Panel Report 3: Guidelines for the Diagnosis and

Management of Asthma

Full Report 2007

August 28, 2007 Contents

C O N T E N T S

Acknowledgements and Financial Disclosures xi Acronyms and Abbreviations………………………………………………………………………………………. xix Preface ……………………………………………………………………………………………………………………xxii Section 1, Introduction ……………………………………………………………………………………………….1 Overall Methods Used To Develop This Report …………………………………………………………….2

Background……………………………………………………………………………………………………………..2 Systematic Evidence Review Overview………………………………………………………………………..3

Inclusion/Exclusion Criteria……………………………………………………………………………………..3 Search Strategies ………………………………………………………………………………………………….3 Literature Review Process………………………………………………………………………………………3 Preparation of Evidence Tables……………………………………………………………………………….6 Ranking the Evidence…………………………………………………………………………………………….7 Panel Discussion…………………………………………………………………………………………………..8 Report Preparation ………………………………………………………………………………………………..8

References………………………………………………………………………………………………………………9

Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma …………………………………………………………………………………………………….11

Key Points: Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma……………………………………………………………………………………………………11 Key Differences From 1997 and 2002 Expert Panel Reports …………………………………………12 Introduction ……………………………………………………………………………………………………………12 Definition of Asthma ………………………………………………………………………………………………..12 Pathophysiology and Pathogenesis of Asthma…………………………………………………………….14

Pathophysiologic Mechanisms in the Development of Airway Inflammation ………………….16 Inflammatory Cells……………………………………………………………………………………………16 Inflammatory Mediators …………………………………………………………………………………….18 Immunoglobulin E…………………………………………………………………………………………….19 Implications of Inflammation for Therapy ……………………………………………………………..19

Pathogenesis ……………………………………………………………………………………………………..20 Host Factors ……………………………………………………………………………………………………20 Environmental Factors………………………………………………………………………………………22

Natural History of Asthma ………………………………………………………………………………………..23 Natural History of Persistent Asthma ………………………………………………………………………24

Children………………………………………………………………………………………………………….24 Adults …………………………………………………………………………………………………………….25 Summary ………………………………………………………………………………………………………..27

Effect of Interventions on Natural History of Asthma………………………………………………….27 Implications of Current Information About Pathophysiology and Pathogenesis, and Natural History for Asthma Management ……………………………………………………………..28

References…………………………………………………………………………………………………………….28

i

…………………………………………………………………

Contents August 28, 2007

Section 3, The Four Components of Asthma Management ………………………………………….35 Introduction ……………………………………………………………………………………………………………35

Section 3, Component 1: Measures of Asthma Assessment and Monitoring………………..36 Introduction ……………………………………………………………………………………………………………36 Overview of Assessing and Monitoring Asthma Severity, Control, and Responsiveness in Managing Asthma………………………………………………………………………..36 Key Points: Overview of Measures of Asthma Assessment and Monitoring …………………….36 Key Differences From 1997 and 2002 Expert Panel Reports …………………………………………37 Diagnosis of Asthma ……………………………………………………………………………………………….40 Key Points: Diagnosis of Asthma ……………………………………………………………………………..40 Key Differences From 1997 and 2002 Expert Panel Reports …………………………………………41

Medical History……………………………………………………………………………………………………41 Physical Examination …………………………………………………………………………………………..42 Pulmonary Function Testing (Spirometry)………………………………………………………………..43 Differential Diagnosis of Asthma…………………………………………………………………………….45

Initial Assessment: Characterization of Asthma and Classification of Asthma Severity………47 Key Points: Initial Assessment of Asthma ………………………………………………………………….47 Key Differences From 1997 and 2002 Expert Panel Reports …………………………………………48

Identify Precipitating Factors …………………………………………………………………………………48 Identify Comorbid Conditions That May Aggravate Asthma ………………………………………..49 Assess the Patient’s Knowledge and Skills for Self-Management………………………………..49 Classify Asthma Severity ………………………………………………………………………………………49

Assessment of Impairment ………………………………………………………………………………..50 Assessment of Risk ………………………………………………………………………………………….51

Periodic Assessment and Monitoring of Asthma Control Essential for Asthma Management ………………………………………………………………………………………………………….52 Key Points: Periodic Assessment of Asthma Control……………………………………………………52 Key Differences From 1997 and 2002 Expert Panel Reports …………………………………………54

Goals of Therapy: Asthma Control…………………………………………………………………………55 Asthma Control………………………………………………………………………………………………..55

Measures for Periodic Assessment and Monitoring of Asthma Control …………………………56 Monitoring Signs and Symptoms of Asthma …………………………………………………………57 Monitoring Pulmonary Function ………………………………………………………………………….58

Spirometry …………………………………………………………………………………………………..58 Peak Flow Monitoring ……………………………………………………………………………………59 Peak Flow Versus Symptom-Based Monitoring Action Plan ………………………………..60

Monitoring Quality of Life …………………………………………………………………………………..61 Monitoring History of Asthma Exacerbations ………………………………………………………..63 Monitoring Pharmacotherapy for Adherence and Potential Side Effects ……………………63 Monitoring Patient–Provider Communication and Patient Satisfaction ………………………63 Monitoring Asthma Control With Minimally Invasive Markers and Pharmacogenetics……………………………………………………………………………………………64 Pharmacogenetics in Managing Asthma………………………………………………………………66

Methods for Periodic Assessment and Monitoring of Asthma Control …………………………..66 Clinician Assessment ……………………………………………………………………………………….67 Patient Self-Assessment……………………………………………………………………………………67 Population-Based Assessment …………………………………………………………………………..67

Referral to an Asthma Specialist for Consultation or Comanagement ……………………………..68 References …………………………………………………………………………………………………………82

ii

August 28, 2007 Contents

Section 3, Component 2: Education for a Partnership in Asthma Care ………………………..93 Key Points: Education for a Partnership in Asthma Care………………………………………………93 Key Points: Provider Education ………………………………………………………………………………..95 Key Differences From 1997 and 2002 Expert Panel Reports …………………………………………95 Introduction ……………………………………………………………………………………………………………96 Asthma Self-Management Education at Multiple Points of Care……………………………………..97

Clinic/Office-Based Education ……………………………………………………………………………….97 Adults—Teach Asthma Self-Management Skills To Promote Asthma Control ……………97

Written Asthma Action Plans, Clinician Review, and Self-Monitoring …………………….98 Patient–Provider Partnership ………………………………………………………………………….99 Health Professionals Who Teach Self-Management…………………………………………100 Education With Multiple Sessions ………………………………………………………………….101

Children—Teach Asthma Self-Management Skills To Promote Asthma Control ……….101 Emergency Department/Hospital-Based Education …………………………………………………102

Adults …………………………………………………………………………………………………………..102 Emergency Department Asthma Education …………………………………………………….103 Hospital-Based Asthma Education…………………………………………………………………104

Children………………………………………………………………………………………………………..105 Educational Interventions by Pharmacists ……………………………………………………………..106 Educational Interventions in School Settings ………………………………………………………….107 Community-Based Interventions…………………………………………………………………………..108

Asthma Education ………………………………………………………………………………………….108 Home-Based Interventions ………………………………………………………………………………….109

Home-Based Asthma Education for Caregivers…………………………………………………..109 Home-Based Allergen-Control Interventions……………………………………………………….109

Other Opportunities for Asthma Education …………………………………………………………….111 Education for Children Using Computer-Based Technology ………………………………….111 Education on Tobacco Avoidance for Women Who Are Pregnant and Members of Households With Infants and Young Children………………………………………………..112 Case Management for High-Risk Patients ………………………………………………………….113

Cost-Effectiveness …………………………………………………………………………………………….114 Tools for Asthma Self-Management …………………………………………………………………………115

Role of Written Asthma Action Plans for Patients Who Have Asthma …………………………115 Role of Peak Flow Monitoring………………………………………………………………………………120 Goals of Asthma Self-Management Education and Key Educational Messages …………..121

Establish and Maintain a Partnership ……………………………………………………………………….124 Teach Asthma Self-Management …………………………………………………………………………125 Jointly Develop Treatment Goals………………………………………………………………………….131 Assess and Encourage Adherence to Recommended Therapy …………………………………131 Tailor Education to the Needs of the Individual Patient …………………………………………….133

Knowledge and Beliefs ……………………………………………………………………………………133 Health Literacy ………………………………………………………………………………………………134 Cultural/Ethnic Considerations………………………………………………………………………….135

Maintain the Partnership……………………………………………………………………………………..135 Asthma Education Resources ……………………………………………………………………………..140

Provider Education………………………………………………………………………………………………..141 Methods of Improving Clinician Behaviors ……………………………………………………………..141

Implementing Guidelines—Recommended Practices …………………………………………..141 Communication Techniques …………………………………………………………………………….143

Methods of Improving System Supports ……………………………………………………………….. 144 Clinical Pathways …………………………………………………………………………………………..144 Clinical Decision Supports ……………………………………………………………………………….145

References…………………………………………………………………………………………………………..146

iii

Contents August 28, 2007

Section 3, Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma………………………………………………………………………………..165

Key Points: Control of Environmental Factors and Comorbid Conditions That Affect Asthma………………………………………………………………………………………………………………..165 Key Differences From 1997 Expert Panel Report ……………………………………………………….166 Introduction ………………………………………………………………………………………………………….167 Inhalant Allergens …………………………………………………………………………………………………167

Diagnosis—Determine Relevant Inhalant Sensitivity ……………………………………………….167 Management—Reduce Exposure…………………………………………………………………………169 Immunotherapy …………………………………………………………………………………………………172 Assessment of Devices That May Modify Indoor Air ………………………………………………..174

Occupational Exposures ………………………………………………………………………………………..175 Irritants………………………………………………………………………………………………………………..175

Environmental Tobacco Smoke ……………………………………………………………………………175 Indoor/Outdoor Air Pollution and Irritants……………………………………………………………….176

Formaldehyde and Volatile Organic Compounds…………………………………………………176 Gas Stoves and Appliances……………………………………………………………………………..176

Comorbid Conditions……………………………………………………………………………………………..177 Allergic Bronchopulmonary Aspergillosis ……………………………………………………………….177 Gastroesophageal Reflux Disease ……………………………………………………………………….178 Obesity …………………………………………………………………………………………………………….179 Obstructive Sleep Apnea …………………………………………………………………………………….179 Rhinitis/Sinusitis ………………………………………………………………………………………………..180 Stress, Depression, and Psychosocial Factors in Asthma ………………………………………..180

Other Factors ……………………………………………………………………………………………………….181 Medication Sensitivities ………………………………………………………………………………………181

Aspirin ………………………………………………………………………………………………………….181 Beta-Blockers ………………………………………………………………………………………………..182

Sulfite Sensitivity ……………………………………………………………………………………………….182 Infections………………………………………………………………………………………………………….182

Viral Respiratory Infections………………………………………………………………………………182 Bacterial Infections …………………………………………………………………………………………183 Influenza Infection ………………………………………………………………………………………….183

Female Hormones and Asthma ……………………………………………………………………………183 Diet………………………………………………………………………………………………………………….184

Primary Prevention of Allergic Sensitization and Asthma …………………………………………….184 References…………………………………………………………………………………………………………..190

Section 3, Component 4: Medications……………………………………………………………………..213 Key Points: Medications ………………………………………………………………………………………..213 Key Differences From 1997 and 2002 Expert Panel Reports ……………………………………….215 Introduction ………………………………………………………………………………………………………….215 Overview of the Medications …………………………………………………………………………………..216

Long-Term Control Medications …………………………………………………………………………..216 Inhaled Corticosteroids ……………………………………………………………………………………216

Mechanism ………………………………………………………………………………………………..216 Inhaled Corticosteroid Insensitivity…………………………………………………………………217 Efficacy of Inhaled Corticosteroids as Compared to Other Long-Term Control Medications as Monotherapy ………………………………………………………………………..217 Efficacy of Inhaled Corticosteroid and Adjunctive Therapy (Combination Therapy) ……………………………………………………………………………………………………217 Dose-Response and Delivery Device …………………………………………………………….218 Variability in Response and Adjustable Dose Therapy………………………………………219 Safety of Inhaled Corticosteroids …………………………………………………………………..220

iv

August 28, 2007 Contents

Key Points: Safety of Inhaled Corticosteroids……………………………………………………………220 Key Points: Inhaled Corticosteroids and Linear Growth in Children ………………………………222

Oral Systemic Corticosteroids ………………………………………………………………………….224 Cromolyn Sodium and Nedocromil ……………………………………………………………………224 Immunomodulators…………………………………………………………………………………………225

Omalizumab ………………………………………………………………………………………………225 Antibiotics ………………………………………………………………………………………………….226 Others ………………………………………………………………………………………………………226

Leukotriene Modifiers ……………………………………………………………………………………..227 Inhaled Long-Acting Beta2-Agonists ………………………………………………………………….229

Safety of Long-Acting Beta2-Agonists …………………………………………………………….231 Key Points: Safety of Inhaled Long-Acting Beta2-Agonists ………………………………………….231

Methylxanthines …………………………………………………………………………………………….234 Tiotropium Bromide ………………………………………………………………………………………..235

Quick-Relief Medications …………………………………………………………………………………….235 Anticholinergics ……………………………………………………………………………………………..235 Inhaled Short-Acting Beta2-Agonists………………………………………………………………….235

Safety of Inhaled Short-Acting Beta2-Agonists …………………………………………………236 Key Points: Safety of Inhaled Short-Acting Beta2-Agonists………………………………………….236

Systemic Corticosteroids …………………………………………………………………………………237 Route of Administration ……………………………………..