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

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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

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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

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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 ...................................................................................................238

Alternatives to CFC-Propelled MDIs ............................................................................238

Spacers and Valved Holding Chambers ......................................................................239

Complementary and Alternative Medicine ...........................................................................240

Key Points: Complementary and Alternative Medicine .......................................................240

Acupuncture ....................................................................................................................240

Chiropractic Therapy .......................................................................................................241

Homeopathy and Herbal Medicine...................................................................................241

Breathing Techniques......................................................................................................241

Relaxation Techniques ....................................................................................................242

Yoga................................................................................................................................242

References..........................................................................................................................252

Section 4, Managing Asthma Long Term: Overview ......................................................... 277

Key Points: Managing Asthma Long Term .........................................................................277

Key Differences From 1997 and 2002 Expert Panel Reports ..............................................278

Introduction .........................................................................................................................279

Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11

Years of Age.......................................................................................................................... 281

Diagnosis and Prognosis of Asthma in Children ..................................................................281

Diagnosis of Asthma........................................................................................................281

Prognosis of Asthma .......................................................................................................281

Prevention of Asthma Progression ..................................................................................282

Monitoring Asthma Progression.......................................................................................283

Treatment: Principles of Stepwise Therapy in Children ......................................................284

Achieving Control of Asthma ...........................................................................................285

Selecting Initial Therapy ..............................................................................................285

Adjusting Therapy........................................................................................................286

Maintaining Control of Asthma.........................................................................................288

Key Points: Inhaled Corticosteroids in Children ..............................................................289

Key Points: Managing Asthma in Children 0–4 Years of Age ............................................289

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Contents August 28, 2007 

Treatment: Pharmacologic Issues for Children 0–4 Years of Age.......................................290

FDA Approval..................................................................................................................291

Delivery Devices..............................................................................................................291

Treatment: Pharmacologic Steps for Children 0–4 Years of Age........................................291

Intermittent Asthma .........................................................................................................292

Step 1 Care, Children 0–4 Years of Age......................................................................292

Persistent Asthma ...........................................................................................................293

Step 2 Care, Children 0–4 Years of Age......................................................................293

Step 3 Care, Children 0–4 Years of Age......................................................................294

Step 4 Care, Children 0–4 Years of Age......................................................................295

Step 5 Care, Children 0–4 Years of Age......................................................................296

Step 6 Care, Children 0–4 Years of Age......................................................................296

Key Points: Managing Asthma in Children 5–11 Years of Age.......................................296

Treatment: Special Issues for Children 5–11 Years of Age ................................................297

Pharmacologic Issues .....................................................................................................297

School Issues ..................................................................................................................298

Sports and Exercise Issues .............................................................................................298

Treatment: Pharmacologic Steps for Children 5–11 Years of Age ......................................299

Intermittent Asthma .........................................................................................................299

Step 1 Care, Children 5–11 Years of Age ....................................................................299

Persistent Asthma ...........................................................................................................300

Step 2 Care, Children 5–11 Years of Age ....................................................................300

Step 3 Care, Children 5–11 Years of Age ....................................................................301

Step 4 Care, Children 5–11 Years of Age ....................................................................303

Step 5 Care, Children 5–11 Years of Age ....................................................................303

Step 6 Care, Children 5–11 Years of Age ....................................................................303

References..........................................................................................................................319

Section 4, Managing Asthma Long Term in Youths  12 Years of Age and Adults .........326

Key Points: Managing Asthma Long Term in Youths  12 Years of Age and Adults ...........326

Section 4, Stepwise Approach for Managing Asthma in Youths  12 Years of Age 

and Adults .............................................................................................................................328

Treatment: Principles of Stepwise Therapy in Youths  12 Years of Age and Adults..........328

Achieving Control of Asthma ...........................................................................................329

Selecting Initial Therapy for Patients Not Currently Taking Long-Term Control 

Medications .................................................................................................................329

Adjusting Therapy........................................................................................................329

Impairment Domain .................................................................................................330

Risk Domain ............................................................................................................330

Maintaining Control of Asthma.........................................................................................331

Treatment: Pharmacologic Steps .......................................................................................333

Intermittent Asthma .........................................................................................................333

Step 1 Care .................................................................................................................333

Persistent Asthma ...........................................................................................................334

Step 2 Care, Long-Term Control Medication................................................................335

Step 3 Care, Long-Term Control Medications..............................................................336

Step 4 Care, Long-Term Control Medications..............................................................338

Step 5 Care, Long-Term Control Medications..............................................................338

Step 6 Care, Long-Term Control Medications..............................................................339

Special Issues for Adolescents ........................................................................................339

Assessment Issues......................................................................................................339

Treatment Issues.........................................................................................................340

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August 28, 2007 Contents 

School Issues ..............................................................................................................340

Sports Issues...............................................................................................................340

Special Issues for Older Adults........................................................................................341

Assessment Issues......................................................................................................341

Treatment Issues.........................................................................................................341

References..........................................................................................................................353

Section 4, Managing Asthma Long Term—Special Situations .......................................... 362

Introduction .........................................................................................................................362

Exercise-Induced Bronchospasm........................................................................................362

Diagnosis ........................................................................................................................362

Management Strategies ..................................................................................................363

Surgery and Asthma ...........................................................................................................364

Pregnancy and Asthma .......................................................................................................364

Racial and Ethnic Disparity in Asthma.................................................................................365

References..........................................................................................................................367

Section 5, Managing Exacerbations of Asthma .................................................................. 372

Key Points: Managing Exacerbations of Asthma ................................................................372

Key Differences From 1997 and 2002 Expert Panel Reports ..............................................373

Introduction .........................................................................................................................373

General Considerations.......................................................................................................375

Treatment Goals .................................................................................................................377

Home Management of Asthma Exacerbations ....................................................................380

Pre-hospital Management of Asthma Exacerbations ...........................................................383

Emergency Department and Hospital Management of Asthma Exacerbations ....................384

Assessment.....................................................................................................................384

Treatment........................................................................................................................391

Repeat Assessment ........................................................................................................395

Hospitalization .................................................................................................................395

Impending Respiratory Failure.........................................................................................396

Patient Discharge ............................................................................................................398

References..........................................................................................................................405

For More Information............................................................................................................415

vii 
Contents August 28, 2007 

List of Boxes And Figures 

FIGURE 1–1. LITERATURE RETRIEVAL AND REVIEW PROCESS: BREAKDOWN 

BY COMMITTEE .................................................................................................................4

FIGURE 1–2. LITERATURE RETRIEVAL AND REVIEW PROCESS: OVERALL

SUMMARY ..........................................................................................................................6

BOX 2–1. CHARACTERISTICS OF CLINICAL ASTHMA.........................................................12

FIGURE 2–1. THE INTERPLAY AND INTERACTION BETWEEN AIRWAY 

INFLAMMATION AND THE CLINICAL SYMPTOMS AND PATHOPHYSIOLOGY 

OF ASTHMA .....................................................................................................................13

FIGURE 2–2. FACTORS LIMITING AIRFLOW IN ACUTE AND PERSISTENT ASTHMA........15

BOX 2–2. FEATURES OF AIRWAY REMODELING ................................................................16

FIGURE 2–3. AIRWAY INFLAMMATION.................................................................................17

FIGURE 2–4. HOST FACTORS AND ENVIRONMENTAL EXPOSURES ................................20

FIGURE 2–5. CYTOKINE BALANCE .......................................................................................21

BOX 3–1. KEY INDICATORS FOR CONSIDERING A DIAGNOSIS OF ASTHMA...................42

BOX 3–2. IMPORTANCE OF SPIROMETRY IN ASTHMA DIAGNOSIS ..................................43

BOX 3–3. DIFFERENTIAL DIAGNOSTIC POSSIBILITIES FOR ASTHMA ..............................46

BOX 3–4. INSTRUMENTS FOR ASSESSING ASTHMA-SPECIFIC AND GENERIC 

QUALITY OF LIFE ............................................................................................................62

FIGURE 3–1. SUGGESTED ITEMS FOR MEDICAL HISTORY* .............................................69

FIGURE 3–2. SAMPLE QUESTIONS* FOR THE DIAGNOSIS AND INITIAL

ASSESSMENT OF ASTHMA ............................................................................................70

FIGURE 3-3a. SAMPLE SPIROMETRY VOLUME TIME AND FLOW VOLUME

CURVES ...........................................................................................................................71

FIGURE 3–3b. REPORT OF SPIROMETRY FINDINGS PRE- AND

POSTBRONCHODILATOR ...............................................................................................71

FIGURE 3–4a. CLASSIFYING ASTHMA SEVERITY IN CHILDREN 0–4 YEARS OF

AGE ..................................................................................................................................72

FIGURE 3–4b. CLASSIFYING ASTHMA SEVERITY IN CHILDREN 5–11 YEARS OF

AGE ..................................................................................................................................73

FIGURE 3–4c. CLASSIFYING ASTHMA SEVERITY IN YOUTHS 12 YEARS OF AGE

AND ADULTS....................................................................................................................74

FIGURE 3–5a. ASSESSING ASTHMA CONTROL IN CHILDREN 0–4 YEARS OF AGE........75

FIGURE 3–5b. ASSESSING ASTHMA CONTROL IN CHILDREN 5–11 YEARS OF

AGE ..................................................................................................................................76

FIGURE 3–5c. ASSESSING ASTHMA CONTROL IN YOUTHS 12 YEARS OF AGE 

AND ADULTS....................................................................................................................77

FIGURE 3–6. SAMPLE QUESTIONS FOR ASSESSING AND MONITORING ASTHMA

CONTROL.........................................................................................................................78

FIGURE 3–7. COMPONENTS OF THE CLINICIAN’S FOLLOWUP ASSESSMENT: 

SAMPLE ROUTINE CLINICAL ASSESSMENT QUESTIONS*..........................................79

FIGURE 3–8. VALIDATED INSTRUMENTS FOR ASSESSMENT AND MONITORING

OF ASTHMA .....................................................................................................................80

FIGURE 3–9. SAMPLE* PATIENT SELF-ASSESSMENT SHEET FOR FOLLOWUP

VISITS...............................................................................................................................81

FIGURE 3–10a. ASTHMA ACTION PLAN .............................................................................117

FIGURE 3–10b. ASTHMA ACTION PLAN .............................................................................118

viii 
August 28, 2007 Contents 

FIGURE 3–10c. ASTHMA ACTION PLAN .............................................................................119

FIGURE 3–11. HOW TO USE YOUR PEAK FLOW METER..................................................122

FIGURE 3–12. KEY EDUCATIONAL MESSAGES: TEACH AND REINFORCE AT

EVERY OPPORTUNITY .................................................................................................124

FIGURE 3–13. DELIVERY OF ASTHMA EDUCATION BY CLINICIANS DURING

PATIENT CARE VISITS ..................................................................................................126

FIGURE 3–14. HOW TO USE YOUR METERED-DOSE INHALER.......................................128

FIGURE 3–15. HOW TO CONTROL THINGS THAT MAKE YOUR ASTHMA WORSE .........129

FIGURE 3–16a. SCHOOL ASTHMA ACTION PLAN .............................................................137

FIGURE 3–16b. SCHOOL ASTHMA ACTION PLAN .............................................................139

BOX 3–5. THE STRONG ASSOCIATION BETWEEN SENSITIZATION TO 

ALLERGENS AND ASTHMA: A SUMMARY OF THE EVIDENCE .................................168

BOX 3–6. RATIONALE FOR ALLERGY TESTING FOR PERENNIAL INDOOR

ALLERGENS...................................................................................................................169

FIGURE 3–17. ASSESSMENT QUESTIONS* FOR ENVIRONMENTAL AND OTHER

FACTORS THAT CAN MAKE ASTHMA WORSE ...........................................................186

FIGURE 3–18. COMPARISON OF SKIN TESTS WITH IN VITRO TESTS ............................187

FIGURE 3–19. PATIENT INTERVIEW QUESTIONS* FOR ASSESSING THE CLINICAL 

SIGNIFICANCE OF POSITIVE ALLERGY TESTS ..........................................................187

FIGURE 3–20. SUMMARY OF MEASURES TO CONTROL ENVIRONMENTAL

FACTORS THAT CAN MAKE ASTHMA WORSE ...........................................................188

FIGURE 3–21. EVALUATION AND MANAGEMENT OF WORK-AGGRAVATED

ASTHMA AND OCCUPATIONAL ASTHMA ....................................................................189

FIGURE 3–22. LONG-TERM CONTROL MEDICATIONS......................................................243

FIGURE 3–23. QUICK-RELIEF MEDICATIONS ....................................................................247

FIGURE 3–24. AEROSOL DELIVERY DEVICES ..................................................................249

BOX 4–1. SAMPLE PATIENT RECORD. MONITORING THE RISK DOMAIN IN 

CHILDREN: RISK OF ASTHMA PROGRESSION (INCREASED 

EXACERBATIONS OR NEED FOR DAILY MEDICATION, OR LOSS OF LUNG 

FUNCTION), AND POTENTIAL ADVERSE EFFECTS OF CORTICOSTEROID 

THERAPY .......................................................................................................................283

FIGURE 4–1a. STEPWISE APPROACH FOR MANAGING ASTHMA IN CHILDREN

0–4 YEARS OF AGE.......................................................................................................305

FIGURE 4–1b. STEPWISE APPROACH FOR MANAGING ASTHMA IN CHILDREN

5–11 YEARS OF AGE.....................................................................................................306

FIGURE 4–2a. CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN

CHILDREN 0–4 YEARS OF AGE....................................................................................307

FIGURE 4–2b. CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN

CHILDREN 5–11 YEARS OF AGE..................................................................................308

FIGURE 4–3a. ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY

IN CHILDREN 0–4 YEARS OF AGE ...............................................................................309

FIGURE 4–3b. ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY

IN CHILDREN 5–11 YEARS OF AGE .............................................................................310

FIGURE 4–4a. USUAL DOSAGES FOR LONG-TERM CONTROL MEDICATIONS

IN CHILDREN* ................................................................................................................311

FIGURE 4–4b. ESTIMATED COMPARATIVE DAILY DOSAGES FOR INHALED

CORTICOSTEROIDS IN CHILDREN ..............................................................................314

FIGURE 4–4c. USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS IN

CHILDREN* ....................................................................................................................317

ix 
Contents August 28, 2007 

FIGURE 4–5. STEPWISE APPROACH FOR MANAGING ASTHMA IN YOUTHS 

12 YEARS OF AGE AND ADULTS ...............................................................................343

FIGURE 4–6. CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN

YOUTHS 12 YEARS OF AGE AND ADULTS................................................................344

FIGURE 4–7. ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN

YOUTHS 12 YEARS OF AGE AND ADULTS................................................................345

FIGURE 4–8a. USUAL DOSAGES FOR LONG-TERM CONTROL MEDICATIONS FOR 

YOUTHS 12 YEARS OF AGE AND ADULTS................................................................346

FIGURE 4–8b. ESTIMATED COMPARATIVE DAILY DOSAGES FOR INHALED

CORTICOSTEROIDS FOR YOUTHS 12 YEARS OF AGE AND ADULTS ....................349

FIGURE 4–8c.USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS FOR 

YOUTHS 12 YEARS OF AGE AND ADULTS................................................................351

FIGURE 5–1. CLASSIFYING SEVERITY OF ASTHMA EXACERBATIONS IN THE 

URGENT OR EMERGENCY CARE SETTING ................................................................374

FIGURE 5–2a. RISK FACTORS FOR DEATH FROM ASTHMA ............................................376

FIGURE 5–2b. SPECIAL CONSIDERATIONS FOR INFANTS ..............................................377

FIGURE 5–3. FORMAL EVALUATION OF ASTHMA EXACERBATION SEVERITY IN

THE URGENT OR EMERGENCY CARE SETTING ........................................................379

FIGURE 5–4. MANAGEMENT OF ASTHMA EXACERBATIONS: HOME TREATMENT.......381

FIGURE 5–5. DOSAGES OF DRUGS FOR ASTHMA EXACERBATIONS ............................385

FIGURE 5–6. MANAGEMENT OF ASTHMA EXACERBATIONS: EMERGENCY

DEPARTMENT AND HOSPITAL-BASED CARE .............................................................387

FIGURE 5–7a. EMERGENCY DEPARTMENT—ASTHMA DISCHARGE PLAN ....................401

FIGURE 5–7b. EMERGENCY DEPARTMENT—ASTHMA DISCHARGE PLAN: 

HOW TO USE YOUR METERED-DOSE INHALER ........................................................402

FIGURE 5–8. CHECKLIST FOR HOSPITAL DISCHARGE OF PATIENTS WHO HAVE

ASTHMA .........................................................................................................................404

x 
August 28, 2007 Acknowledgements and Financial Disclosures 

ACKNOWLEDGMENTS AND FINANCIAL DISCLOSURES 

External Review and Comment Overview

In response to a recommendation by the National Asthma Education and Prevention Program 

(NAEPP) Coordinating Committee, an Expert Panel was convened by the National Heart, Lung, 

and Blood Institute (NHLBI) to update the asthma guidelines. 

Several measures were taken in the development of these asthma guidelines to enhance 

transparency of the evidence review process and to better manage any potential or perceived 

conflict of interest. In addition to using a methodologist to guide preparation of the Evidence 

Tables, several layers of external content review were also embedded into the guidelines 

development process. Expert Panel members and consultant reviewers completed financial 

disclosure forms that are summarized below. In addition to review by consultants, an early draft 

of the guidelines was circulated to a panel of guidelines end-users (the Guidelines 

Implementation Panel) appointed specifically for their review and feedback on ways to enhance 

guidelines utilization by primary care clinicians, health care delivery organizations, and 

third-party payors. Finally, a draft of the guidelines was posted on the NHLBI Web Site for 

review and comment by the NAEPP Coordinating Committee and to allow opportunity for public 

review and comment before the guidelines were finalized and released. 

NAEPP COORDINATING COMMITTEE

Agency for Healthcare Research and 

Quality 

Denise Dougherty, Ph.D. 

Allergy and Asthma Network 

Mothers of Asthmatics 

Nancy Sander 

American Academy of Allergy, Asthma, 

and Immunology 

Michael Schatz, M.D., M.S. 

American Academy of Family Physicians 

Kurtis S. Elward, M.D., M.P.H., F.A.A.F.P. 

American Academy of Pediatrics 

Gary S. Rachelefsky, M.D. 

American Academy of Physician Assistants 

Tera Crisalida, P.A.-C., M.P.A.S. 

American Association for Respiratory Care 

Thomas J. Kallstrom, R.R.T., F.A.A.R.C., 

AE-C 

American College of Allergy, Asthma, and 

Immunology 

William Storms, M.D. 

American College of Chest Physicians 

John Mitchell, M.D., F.A.C.P. 

American College of Emergency Physicians 

Richard M. Nowak, M.D., M.B.A., 

F.A.C.E.P. 

American Lung Association 

Noreen M. Clark, Ph.D. 

American Medical Association 

Paul V. Williams, M.D. 

American Nurses Association 

Karen Huss, D.N.Sc., R.N., A.P.R.N.B.C., 

F.A.A.N., F.A.A.A.A.I. 

American Pharmacists Association 

Dennis M. Williams, Pharm.D. 

American Public Health Association 

Pamela J. Luna, Dr.P.H., M.Ed. 

American School Health Association 

Lani S. M. Wheeler, M.D., F.A.A.P., 

F.A.S.H.A. 

xi 
Acknowledgements and Financial Disclosures 

American Society of Health-System 

Pharmacists 

Kathryn V. Blake, Pharm.D. 

American Thoracic Society 

Stephen C. Lazarus, M.D. 

Asthma and Allergy Foundation of America 

Mo Mayrides 

Council of State and Territorial 

Epidemiologists 

Sarah Lyon-Callo, M.A., M.S. 

National Association of School Nurses 

Donna Mazyck, R.N., M.S., N.C.S.N. 

National Black Nurses Association, Inc. 

Susan B. Clark, R.N., M.N. 

National Center for Chronic Disease 

Prevention, Centers for Disease Control 

and Prevention (CDC) 

Sarah Merkle, M.P.H. 

National Center for Environmental Health, 

CDC 

Paul M. Garbe, M.D. 

National Center for Health Statistics, CDC 

Lara Akinbami, M.D. 

National Institute for Occupational Safety 

and Health, CDC 

Margaret Filios, S.M., R.N. 

National Heart, Lung, and Blood Institute 

National Institutes of Health (NIH) 

Elizabeth Nabel, M.D. 

August 28, 2007 

National Heart, Lung, and Blood Institute 

NIH, Ad Hoc Committee on Minority 

Populations 

Ruth I. Quartey, Ph.D. 

National Institute of Allergy and Infectious 

Diseases (NIAID), NIH 

Peter J. Gergen, M.D., M.P.H. 

National Institute of Environmental Health 

Sciences, NIH 

Charles A. Wells, Ph.D. 

National Medical Association 

Michael Lenoir, M.D. 

National Respiratory Training Center 

Pamela Steele, M.S.N., C.P.N.P., AE-C 

Society for Academic Emergency Medicine 

Rita Cydulka, M.D., M.S. 

Society for Public Health Education 

Judith C. Taylor-Fishwick, M.Sc., AE-C 

U.S. Department of Education 

Dana Carr 

U.S. Environmental Protection Agency 

Indoor Environments Division 

David Rowson, M.S. 

U.S. Environmental Protection Agency 

Office of Research and Development 

Hillel S. Koren, Ph.D. 

U.S. Food and Drug Administration 

Robert J. Meyer, M.D. 

THIRD EXPERT PANEL ON THE DIAGNOSIS AND MANAGEMENT OF ASTHMA 

William W. Busse, M.D., Chair 

University of Wisconsin Medical School 

Madison, Wisconsin 

Homer A. Boushey, M.D.

University of California–San Francisco 

San Francisco, California 

Carlos A. Camargo, Jr., M.D., Dr.P.H. 

Massachusetts General Hospital 

Boston, Massachusetts

David Evans, Ph.D., A.E.-C, 

Columbia University

New York, New York

xii 
August 28, 2007 Acknowledgements and Financial Disclosures 

Michael B. Foggs, M.D. 

Advocate Health Centers 

Chicago, Illinois 

Susan L. Janson, D.N.Sc., R.N., A.N.P., 

F.A.A.N. 

University of California–San Francisco 

San Francisco, California 

H. William Kelly, Pharm.D. 

University of New Mexico Health Sciences 

Center 

Albuquerque, New Mexico 

Robert F. Lemanske, M.D. 

University of Wisconsin Hospital and Clinics 

Madison, Wisconsin 

Fernando D. Martinez, M.D. 

University of Arizona Medical Center 

Tucson, Arizona 

Robert J. Meyer, M.D. 

U.S. Food and Drug Administration 

Silver Spring, Maryland 

Harold S. Nelson, M.D. 

National Jewish Medical and Research 

Center 

Denver, Colorado 

Thomas A. E. Platts-Mills, M.D., Ph.D. 

University of Virginia School of Medicine 

Charlottesville, Virginia 

Michael Schatz, M.D., M.S. 

Kaiser-Permanente–San Diego 

San Diego, California 

Gail Shapiro, M.D.† 

University of Washington 

Seattle, Washington 

Stuart Stoloff, M.D. 

University of Nevada School of Medicine 

Carson City, Nevada 

Stanley J. Szefler, M.D. 

National Jewish Medical and Research 

Center 

Denver, Colorado 

Scott T. Weiss, M.D., M.S. 

Brigham and Women’s Hospital 

Boston, Massachusetts 

Barbara P. Yawn, M.D., M.Sc. 

Olmstead Medical Center 

Rochester, Minnesota 

†

Deceased 

Development of the resource document and the guidelines report was funded by the NHLBI, 

NIH. Expert Panel members completed financial disclosure forms, and the Expert Panel 

members disclosed relevant financial interests to each other prior to their discussions. Expert 

Panel members participated as volunteers and were compensated only for travel expenses 

related to the Expert Panel meetings. Financial disclosure information covering the 3-year 

period during which the guidelines were developed is provided for each Panel member below. 

Dr. Busse has served on the Speakers’ Bureaus of GlaxoSmithKline, Merck, Novartis, and 

Pfizer; and on the Advisory Boards of Altana, Centocor, Dynavax, Genentech/Novartis, 

GlaxoSmithKline, Isis, Merck, Pfizer, Schering, and Wyeth. He has received funding/grant 

support for research projects from Astellas, AstraZeneca, Centocor, Dynavax, GlaxoSmithKline, 

Novartis, and Wyeth. Dr. Busse also has research support from the NIH. 

Dr. Boushey has served as a consultant for Altana, Protein Design Lab, and Sumitomo. He has 

received honoraria from (Boehringer-Ingelheim, Genentech, Merck, Novartis, and 

Sanofi-Aventis, and funding/grant support for research projects from the NIH. 

xiii 
Acknowledgements and Financial Disclosures August 28, 2007 

Dr. Camargo has served on the Speakers’ Bureaus of AstraZeneca, GlaxoSmithKline, Merck, 

and Schering-Plough; and as a consultant for AstraZeneca, Critical Therapeutics, Dey 

Laboratories, GlaxoSmithKline, MedImmune, Merck, Norvartis, Praxair, Respironics, 

Schering-Plough, Sepracor, and TEVA. He has received funding/grant support for research 

projects from a variety of Government agencies and not-for-profit foundations, as well as 

AstraZeneca, Dey Laboratories, GlaxoSmithKline, MedImmune, Merck, Novartis, and 

Respironics. 

Dr. Evans has received funding/grant support for research projects from the NHLBI. 

Dr. Foggs has served on the Speakers’ Bureaus of GlaxoSmithKline, Merck, Pfizer, Sepracor, 

and UCB Pharma; on the Advisory Boards of Alcon, Altana, AstraZeneca, Critical Therapeutics, 

Genentech, GlaxoSmithKline, and IVAX; and as consultant for Merck and Sepracor. He has 

received funding/grant support for research projects from GlaxoSmithKline. 

Dr. Janson has served on the Advisory Board of Altana, and as a consultant for Merck. She has 

received funding/grant support for research projects from the NHLBI. 

Dr. Kelly has served on the Speakers’ Bureaus of AstraZeneca and GlaxoSmithKline; and on 

the Advisory Boards of AstraZeneca, MAP Pharmaceuticals, Merck, Novartis, and Sepracor. 

Dr. Lemanske has served on the Speakers’ Bureaus of GlaxoSmithKline and Merck, and as a 

consultant for AstraZeneca, Aventis, GlaxoSmithKline, Merck, and Novartis. He has received 

honoraria from Altana, and funding/grant support for research projects from the NHLBI and 

NIAID. 

Dr. Martinez has served on the Advisory Board of Merck and as a consultant for Genentech, 

GlaxaSmithKline, and Pfizer. He has received honoraria from Merck. 

Dr. Meyer has no relevant financial interests. 

Dr. Nelson has served on the Speakers’ Bureaus of AstraZeneca, GlaxoSmithKline, Pfizer, and 

Schering-Plough; and as a consultant for Abbott Laboratories, Air Pharma, Altana Pharma US, 

Astellas, AstraZeneca, Curalogic, Dey Laboratories, Dynavax Technologies, 

Genentech/Novartis, GlaxoSmithKline, Inflazyme Pharmaceuticals, MediciNova, Protein Design 

Laboratories, Sanofi-Aventis, Schering-Plough, and Wyeth Pharmaceuticals. He has received 

funding/grant support for research projects from Altana, Astellas, AstraZeneca, Behringer, 

Critical Therapeutics, Dey Laboratories, Epigenesis, Genentech, GlaxoSmithKline, Hoffman 

LaRoche, IVAX, Medicinova, Novartis, Sanofi-Aventis, Schering-Plough, Sepracor, TEVA, and 

Wyeth. 

Dr. Platts-Mills has served on the Advisory Committee of Indoor Biotechnologies. He has 

received funding/grant support for a research project from Pharmacia Diagnostics. 

Dr. Schatz has served on the Speakers’ Bureaus of AstraZeneca, Genentech, GlaxoSmithKline, 

and Merck; and as a consultant for GlaxoSmithKline on an unbranded asthma initiative. He has 

received honoraria from AstraZeneca, Genentech, GlaxoSmithKline and Merck. He has 

received funding/grant support for research projects from GlaxoSmithKline and Merck and 

Sanofi-Adventis. 

xiv 
August 28, 2007 Acknowledgements and Financial Disclosures 

Dr. Shapiro† served on the Speakers’ Bureaus of AstraZeneca, Genentech, GlaxoSmithKline, 

IVAX Laboratories, Key Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Schering Corporation, 

UCB Pharma, and 3M; and as a consultant for Altana, AstraZeneca, Dey Laboratories, 

Genentech/Novartis, GlaxoSmithKline, ICOS, IVAX Laboratories, Merck, Sanofi-Aventis, and 

Sepracor. She received funding/grant support for research projects from Abbott, AstraZeneca, 

Boehringer Ingelheim, Bristol-Myers-Squibb, Dey Laboratories, Fujisawa Pharmaceuticals, 

Genentech, GlaxoSmithKline, Immunex, Key, Lederle, Lilly Research, MedPointe 

Pharmaceuticals, Medtronic Emergency Response Systems, Merck, Novartis, Pfizer, 

Pharmaxis, Purdue Frederick, Sanofi-Aventis, Schering, Sepracor, 3M Pharmaceuticals, UCB 

Pharma, and Upjohn Laboratories. 

Dr. Stoloff has served on the Speakers’ Bureaus of Alcon, Altana, AstraZeneca, Genentech, 

GlaxoSmithKline, Novartis, Pfizer, Sanofi-Aventis, and Schering; and as a consultant for Alcon, 

Altana, AstraZeneca, Dey, Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer, 

Sanofi-Aventis, and Schering. 

Dr. Szefler has served on the Advisory Boards of Altana, AstraZeneca, Genentech, 

GlaxoSmithKline, Merck, Novartis, and Sanofi-Aventis; and as a consultant for Altana, 

AstraZeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sanofi-Aventis. He has 

received funding/grant support for a research project from Ross. 

Dr. Weiss has served on the Advisory Board of Genentech, and as a consultant for Genentech 

and GlaxoSmithKline. He has received funding/grant support for research projects from 

GlaxoSmithKline. 

Dr. Yawn has served on the Advisory Boards of Altana, AstraZeneca, Merck, Sanofi-Aventis, 

and Schering-Plough. She has received honoraria from Pfizer and Schering-Plough, and 

funding/grant support for research projects from the Agency for Healthcare Research and 

Quality, the CDC, the NHLBI, Merck, and Schering-Plough. 

†

Deceased 

xv 
Acknowledgements and Financial Disclosures August 28, 2007 

CONSULTANT REVIEWERS 

The Expert Panel acknowledges the following consultants for their review of an early draft of the 

report. Financial disclosure information covering a 12-month period prior to the review of the 

guidelines is provided below for each consultant. 

Andrea J. Apter, M.D., M.Sc.

University of Pennsylvania Medical Center 

Philadelphia, Pennsylvania 

Noreen M. Clark, Ph.D. 

University of Michigan School of Public 

Health 

Ann Arbor, Michigan 

Anne Fuhlbrigge, M.D., M.S.

Brigham and Women’s Hospital 

Boston, Massachusetts

Elliott Israel, M.D.

Brigham and Women’s Hospital 

Boston, Massachusetts

Meyer Kattan, M.D.

Mount Sinai Medical Center 

New York, New York

Jerry A. Krishnan. M.D., Ph.D.

The Johns Hopkins School of Medicine 

Baltimore, Maryland

James T. Li, M.D., Ph.D., F.A.A.A.A.I. 

Mayo Clinic

Rochester, Minnesota 

Dennis R. Ownby, M.D. 

Medical College of Georgia 

Augusta, Georgia 

Gary S. Rachelefshy, M.D. 

University of California–Los Angeles, 

School of Medicine 

Los Angeles, California 

Brian H. Rowe, M.D., M.Sc., C.C.F.P. 

(E.M.), F.C.C.P. 

University of Alberta Hospital 

Edmonton, Alberta, Canada 

E. Rand Sutherland, M.D., M.P.H. 

National Jewish Medical and Research 

Center 

Denver, Colorado 

Sandra R. Wilson, Ph.D.

Palo Alto Medical Foundation 

Palo Alto, California 

Robert A. Wood, M.D.

The Johns Hopkins School of Medicine 

Baltimore, Maryland

Robert Zeiger, M.D.

Kaiser Permanente Medical Center 

San Diego, California 

Dr. Apter owns stock in Johnson & Johnson. She has received funding/grant support for 

research projects from the NHLBI. 

Dr. Clark has no relevant financial interests. 

Dr. Fulhlbrigge has served on the Speakers’ Bureau of GlaxoSmithKline, the Advisory Boards of 

GlaxoSmithKline and Merck, the Data Systems Monitoring Board for a clinical trial sponsored by 

Sepracor, and as a consultant for GlaxoSmithKline. She has received honoraria from 

GlaxoSmithKline and Merck, and funding/grant support for a research project from Boehringer 

Ingelheim. 

xvi 
August 28, 2007 Acknowledgements and Financial Disclosures 

Dr. Israel has served on the Speakers’ Bureau of Genentech and Merck, and as a consultant for 

Asthmatx, Critical Therapeutics, Genentech, Merck, Novartis Pharmaceuticals, Protein Design 

Labs, Schering-Plough Company, and Wyeth. He has received funding/grant support for 

research projects from Asthmatx, Boehringer Ingelheim, Centocor, Genentech, 

GlaxoSmithKline, and Merck. 

Dr. Kattan has served on the Speakers’ Bureau of AstraZeneca. 

Dr. Krishnan has received funding/grant support for a research project from Hill-Rom, Inc. 

Dr. Li has received funding/grant support for research projects from the American Lung 

Association, GlaxoSmithKline, Pharming, and ZLB Behring. 

Dr. Ownby has none. 

Dr. Rachelefsky has served on the Speakers’ Bureaus of AstraZeneca, GlaxoSmithKline, IVAX, 

Medpointe, Merck, and Schering-Plough. He has received honoraria from AstraZeneca, 

GlaxoSmithKline, IVAX, Medpointe, Merck, and Schering-Plough. 

Dr. Rowe has served on the Advisory Boards of Abbott, AstraZeneca, Boehringer Ingelheim, 

and GlaxoSmithKline. He has received honoraria from Abbott, AstraZeneca, Boehringer 

Ingelheim, and GlaxoSmithKline. He has received funding/grant support for research projects 

from Abbott, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Trudell. 

Dr. Sutherland has served on the Speakers’ Bureau of Novartis/Genentech and the Advisory 

Board of Dey Laboratories. He has received honoraria from IVAX and funding/grant support for 

research projects from GlaxoSmithKline and the NIH. 

Dr. Wilson has served as a consultant for the Department of Urology, University of California, 

San Francisco (UCSF); Asthmatx, Inc.; and the Stanford-UCSF Evidence-Based Practice 

Center. She has received funding/grant support for research projects from the NHLBI and from 

a subcontract to Stanford University from Blue Shield Foundation. 

Dr. Wood has served on the Speakers’ Bureaus of Dey Laboratories, GlaxoSmithKline, and 

Merck; on the Advisory Board of Dey Laboratories; and as a consultant to Dey Laboratories. He 

has received honoraria from Dey Laboratories, GlaxoSmithKline, and Merck, and funding/grant 

support for a research project from Genentech. 

Dr. Zeiger has served on the Data Monitoring Board of Genentech, Advisory Board of 

GlaxoSmithKline, and as a consultant for Aerocrine, AstraZeneca, and Genentech. He has 

received honoraria from AstraZeneca and funding/grant support for a research project from 

Sanofi-Aventis. 

xvii 
Acknowledgements and Financial Disclosures August 28, 2007 

National Heart, Lung, and Blood Institute Staff 

Robinson (Rob) Fulwood, Ph.D., M.S.P.H. 

Chief, Enhanced Dissemination and 

Utilization Branch 

Division for the Application of Research 

Discoveries 

James P. Kiley, Ph.D. 

Director 

Division of Lung Diseases

Gregory J. Morosco, Ph.D., M.P.H. 

Associate Director for Prevention,

Education, and Control 

Director 

Division for the Application of Research 

Discoveries 

Diana K. Schmidt, M.P.H.

Coordinator 

National Asthma Education and Prevention 

Program 

Division for the Application of Research 

Discoveries 

Virginia S. Taggart, M.P.H.

Program Director 

Division of Lung Diseases

American Institutes for Research Staff 

Heather Banks, M.A., M.A.T. 

Senior Editor 

Patti Louthian 

Senior Desktop Publisher 

Karen L. Soeken, Ph.D. 

Methodologist 

Mary Tierney, M.D. 

Project Manager 

xviii 
August 28, 2007 Acronyms and Abbreviations 

ACRONYMS AND ABBREVIATIONS 

AAI acute asthma index 

A. artemisiifolia Ambrosia artemisiifolia 

ABG arterial blood gas 

ABPA allergic bronchopulmonary aspergillosis 

ACE angiotensin converting enzyme 

ACIP Advisory Committee on Immunization Practices (CDC) 

ACT Asthma Control Test 

AHRQ Agency for Healthcare Research and Quality 

ALT alanine aminotransferase (enzyme test of liver function) 

Amb a 1 Ambrosia artemisiifolia 

AQLQ asthma-related quality of life questionnaire 

ATAQ Asthma Therapy Assessment Questionnaire 

ATS American Thoracic Society 

BDP beclomethasone dipropionate 

Bla g1 Blattella germanica 1 (cockroach allergen) 

BMD bone mineral density 

BPT bronchial provocation test 

CAMP Childhood Asthma Management Program 

CBC complete blood count 

CC Coordinating Committee 

CDC Centers for Disease Control and Prevention 

CFC chlorofluorocarbon (inhaler propellant being phased out because it harms 

atmosphere) 

CI confidence interval 

COPD chronic obstructive pulmonary disease 

COX-2 cyclooxygenase (an enzyme) 

CPAP continuous positive airway pressure 

CT computer tomography 

Der f Dermatophagoides farinae (American house-dust mite) 

Der p Dermatophagoides pteronyssinus (European house-dust mite) 

DEXA dual energy x-ray absorptiometry

DHHS U.S. Department of Health and Human Services 

DPI dry powder inhaler 

EBC exhaled breath concentrate 

ECP eosinophilic cationic protein 

ED emergency department

EIB exercise-induced bronchospasm

EMS emergency medical services

eNO exhaled nitric oxide 

EPR Expert Panel Report

EPR 1991, EPR 1997 (EPR—2), EPR—Update 2002, 

EPR—3: Full Report 2007 (this 2007 guidelines update) 

ER emergency room 

ERS European Respiratory Society 

ETS environmental tobacco smoke 

xix 
Acronyms and Abbreviations August 28, 2007 

FC�RI high-affinity IgE receptor 

FDA U.S. Food and Drug Administration 

FEF forced expiratory flow 

FEF25–75 forced expiratory flow between 25 percent and 75 percent of the vital 

capacity 

FeNO fractional exhaled nitric oxide 

FEV1 forced expiratory volume in 1 second 

FEV6 forced expiratory volume in 6 seconds 

FiO2 fractional inspired oxygen 

FRC functional residual capacity 

FVC forced vital capacity 

GERD gastroesophageal reflux disease 

GINA Global Initiative for Asthma

GIP Guidelines Implementation Panel (at NHLBI) 

GM-CSF granulocyte-macrophage colony-stimulating factor

HEPA high-efficiency particulate air (a type of filter) 

HFA hydrofluoroalkane (inhaler propellant) 

HMO health maintenance organization 

HPA hypothalamic-pituitary-adrenal (usually used with “axis”) 

HRT hormone replacement therapy

ICS inhaled corticosteroid(s) 

ICU intensive care unit

IFN-� interferon-gamma 

IgE immunoglobulin E (and similar types, such as IgG)

IL-4, IL-12, etc. interleukin-4, interleukin-12 (and similar) 

IL-4R interleukin-4 receptor (and similar) 

INR international normalized ratio 

IVIG intravenous immunoglobulin 

IVMg intravenous magnesium sulfate 

LABA/LABAs long-acting beta2-agonist(s) 

LTRA leukotriene receptor antagonist

Mab or MAb monoclonal antibody

MDC macrophage-derived chemokines

MDI metered-dose inhaler 

MDI/DED metered-dose inhaler (MDI) with delivery enhancement device (DED) 

MeSH Medical Subject Headings (in MEDLINE) 

MIP macrophage inflammatory protein 

NAEPP National Asthma Education and Prevention Program

NCHS National Center for Health Statistics 

NHANES National Health and Nutrition Examination Survey

(with roman numeral) 

NHIS National Health Information Survey 

NHLBI National Heart, Lung, and Blood Institute 

NIH National Institutes of Health 

NK natural killer cells 

xx 
August 28, 2007 Acronyms and Abbreviations 

NO or NO2 nitric oxide 

NSAID nonsteroidal anti-inflammatory drug 

OR odds ratio 

OSA obstructive sleep apnea 

PCO2 partial pressure of carbon dioxide 

PCP primary care provider (or physician) 

PD20 20 percent of provocative dose 

PEF peak expiratory flow 

PEFR PEF rate 

PI pulmonary index 

PImax maximal pulmonary inspiration 

PICU pediatric intensive care unit 

PIV parainfluenza virus 

PM10 particulate matter 10 micrometers 

RANTES Regulated on Activation, Normal T Expressed and Secreted 

RCT randomized controlled trial 

RR relative risk 

RSV respiratory syncytial virus 

RV residual volume 

SABA/SABAs short-acting beta2-agonist(s) (inhaled) 

SaO2 oxygen saturation 

SMART Salmeterol Multicenter Asthma Research Trial 

START Inhaled Steroid Treatment as Regular Therapy in Early Asthma study 

TAA triamcinolone acetonide 

TAO troleandomycin (antibiotic) 

Th1, Th2 T cell helper 1, T cell helper 2 

TLC total lung capacity 

TNF-� tumor necrosis factor-alpha 

TRUST The Regular Use of Salbutamol Trial 

USDA U.S. Department of Agriculture 

VC vital capacity 

VCD vocal cord dysfunction 

VHC valved holding chamber 

VOC volatile organic compounds (e.g., benzene) 

xxi 
Preface August 28, 2007 

xxii 

PREFACE 

The Expert Panel Report 3 (EPR–3) Full Report 2007: Guidelines for the Diagnosis and 

Management of Asthma was developed by an expert panel commissioned by the 

National Asthma Education and Prevention Program (NAEPP) Coordinating Committee 

(CC), coordinated by the National Heart, Lung, and Blood Institute (NHLBI) of the 

National Institutes of Health. 

Using the 1997 EPR–2 guidelines and the 2002 update on selected topics as the 

framework, the expert panel organized the literature review and updated 

recommendations for managing asthma long term and for managing exacerbations 

around four essential components of asthma care, namely: assessment and monitoring, 

patient education, control of factors contributing to asthma severity, and pharmacologic 

treatment. Subtopics were developed for each of these four broad categories. 

The EPR–3 Full Report has been developed under the excellent leadership of Dr. 

William Busse, Panel Chair. The NHLBI is grateful for the tremendous dedication of time 

and outstanding work of all the members of the expert panel, and for the advice from an 

expert consultant group in developing this report. Sincere appreciation is also extended 

to the NAEPP CC and the Guidelines Implementation Panel as well as other stakeholder 

groups (professional societies, voluntary health, government, consumer/patient 

advocacy organizations, and industry) for their invaluable comments during the public 

review period that helped to enhance the scientific credibility and practical utility of this 

document. 

Ultimately, the broad change in clinical practice depends on the influence of local 

primary care physicians and other health professionals who not only provide state-ofthe-art care to their patients, but also communicate to their peers the importance of 

doing the same. The NHLBI and its partners will forge new initiatives based on these 

guidelines to stimulate adoption of the recommendations at all levels, but particularly 

with primary care clinicians at the community level. We ask for the assistance of every 

reader in reaching our ultimate goal: improving asthma care and the quality of life for 

every asthma patient with asthma. 

Gregory Morosco, Ph.D., M.P.H. James Kiley, Ph.D. 

Director Director 

Division for the Application of Research Division of Lung Diseases 

 Discoveries National Heart, Lung, and Blood 

National Heart, Lung, and Blood Institute Institute 
Section 1, Introduction 

1 

August 28, 2007 

SECTION 1, INTRODUCTION 

Asthma is a chronic inflammatory disease of the airways. In the United States, asthma affects 

more than 22 million persons. It is one of the most common chronic diseases of childhood, 

affecting more than 6 million children (current asthma prevalence, National Health Interview 

Survey (NHIS), National Center for Health Statistics, Centers for Disease Control and 

Prevention, 2005) (NHIS 2005). There have been important gains since the release of the first 

National Asthma Education and Prevention Program (NAEPP) clinical practice guidelines in 

1991. For example, the number of deaths due to asthma has declined, even in the face of an 

increasing prevalence of the disease (NHIS 2005); fewer patients who have asthma report 

limitations to activities; and an increasing proportion of people who have asthma receive formal 

patient education (Department of Health and Human Services, Healthy People 2010 midcourse 

review). Hospitalization rates have remained relatively stable over the last decade, with lower 

rates in some age groups but higher rates among young children 0–4 years of age. There is 

some indication that improved recognition of asthma among young children contributes to these 

rates. However, the burden of avoidable hospitalizations remains. Collectively, people who 

have asthma have more than 497,000 hospitalizations annually (NHIS 2005). Furthermore, 

ethnic and racial disparities in asthma burden persist, with significant impact on African 

American and Puerto Rican populations. The challenge remains to help all people who have 

asthma, particularly those at high risk, receive quality asthma care. 

Advances in science have led to an increased understanding of asthma and its mechanisms as 

well as improved treatment approaches. To help health care professionals bridge the gap 

between current knowledge and practice, the NAEPP of the National Heart, Lung, and Blood 

Institute (NHLBI) has previously convened three Expert Panels to prepare guidelines for the 

diagnosis and management of asthma. The NAEPP Coordinating Committee (CC), under the 

leadership of Claude Lenfant, M.D., Director of the NHLBI, convened the first Expert Panel in 

1989. The charge to that Panel was to develop a report that would provide a general approach 

to diagnosing and managing asthma based on current science. Published in 1991, the “Expert 

Panel Report: Guidelines for the Diagnosis and Management of Asthma” (EPR 1991) organized 

the recommendations for the treatment of asthma around four components of effective asthma 

management: 

 Use of objective measures of lung function to assess the severity of asthma and to monitor 

the course of therapy 

 Environmental control measures to avoid or eliminate factors that precipitate asthma 

symptoms or exacerbations 

 Patient education that fosters a partnership among the patient, his or her family, and 

clinicians 

 Comprehensive pharmacologic therapy for long-term management designed to reverse and 

prevent the airway inflammation characteristic of asthma as well as pharmacologic therapy 

to manage asthma exacerbations 

The NAEPP recognizes that the value of clinical practice guidelines lies in their presentation of 

the best and most current evidence available. Thus, the Expert Panels have been convened 

periodically to update the guidelines, and new NAEPP reports were prepared: The “Expert 

Panel Report 2: Guidelines for the Diagnosis and Management of Asthma” (EPR⎯2 1997) and 
Section 1, Introduction 

2 

August 28, 2007 

“Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma—Update on 

Selected Topics 2002” (EPR⎯Update 2002). The “Expert Panel Report 3: Guidelines for the 

Diagnosis and Management of Asthma—Full Report, 2007” (EPR—3: Full Report 2007) is the 

latest report from the NAEPP and updates the 1997 and 2002 reports. The EPR—3: Full 

Report 2007 is organized as follows: Section 1—Introduction/Methodology; Section 2—

Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma; 

Section 3—The Four Components of Asthma Management; Section 4—Managing Asthma Long 

Term; and Section 5—Managing Exacerbations of Asthma. Key points and key differences are 

presented at the beginning of each section and subsection in order to highlight major issues. 

This report presents recommendations for the diagnosis and management of asthma that will 

help clinicians and patients make appropriate decisions about asthma care. Of course, the 

clinician and patient need to develop individual treatment plans that are tailored to the specific 

needs and circumstances of the patient. The NAEPP, and all who participated in the 

development of this latest report, hope that the patient who has asthma will be the beneficiary of 

the recommendations in this document. This report is not an official regulatory document of any 

Government agency. It will be used as the source to develop clinical practice tools and 

educational materials for patients and the public. 

OVERALL METHODS USED TO DEVELOP THIS REPORT 

Background 

In June 2004, the Science Base Committee of the NAEPP recommended to the NAEPP CC that 

its clinical practice guidelines for the diagnosis and management of asthma be updated. In 

September, under the leadership of Dr. Barbara Alving, M.D. (Chair of the NAEPP CC, and 

Acting Director of the NHLBI), a panel of experts was selected to update the clinical practice 

guidelines by using a systematic review of the scientific evidence for the treatment of asthma 

and consideration of literature on implementing the guidelines. 

In October 2004, the Expert Panel assembled for its first meeting. Using EPR—2 1997 and 

EPR—Update 2002 as the framework, the Expert Panel organized the literature searches and 

subsequent report around the four essential components of asthma care, namely: 

(1) assessment and monitoring, (2) patient education, (3) control of factors contributing to 

asthma severity, and (4) pharmacologic treatment. Subtopics were developed for each of these 

four broad categories. 

The steps used to develop this report include: (1) completing a comprehensive search of the 

literature; (2) conducting an indepth review of relevant abstracts and articles; (3) preparing 

evidence tables to assess the weight of current evidence with respect to past recommendations 

and new and unresolved issues; (4) conducting thoughtful discussion and interpretation of 

findings; (5) ranking strength of evidence underlying the current recommendations that are 

made; (6) updating text, tables, figures, and references of the existing guidelines with new 

findings from the evidence review; (7) circulating a draft of the updated guidelines through 

several layers of external review, as well as posting it on the NHLBI Web site for review and 

comment by the public and the NAEPP CC, and (8) preparing a final-report based on 

consideration of comments raised in the review cycle. 
Section 1, Introduction 

3 

August 28, 2007 

Systematic Evidence Review Overview 

INCLUSION/EXCLUSION CRITERIA 

The literature review was conducted in three cycles over an 18-month period (September 2004 

to March 2006). Search strategies for the literature review initially were designed to cast a wide 

net but later were refined by using publication type limits and additional terms to produce results 

that more closely matched the framework of topics and subtopics selected by the Expert Panel. 

The searches included human studies with abstracts that were published in English in 

peer-reviewed medical journals in the MEDLINE database. Two timeframes were used for the 

searches, dependent on topic: January 1, 2001, through March 15, 2006, for pharmacotherapy 

(medications), peak flow monitoring, and written action plans, because these topics were 

recently reviewed in the EPR—Update 2002; and January 1, 1997, through March 15, 2006, for 

all other topics, because these topics were last reviewed in the EPR—2 1997. 

SEARCH STRATEGIES 

Panel members identified, with input from a librarian, key text words for each of the four 

components of care. A separate search strategy was developed for each of the four 

components and various key subtopics when deemed appropriate. The key text words and 

Medical Subject Headings (MeSH) terms that were used to develop each search string are 

found in an appendix posted on the NHLBI Web site. 

LITERATURE REVIEW PROCESS 

The systematic review covered a wide range of topics. Although the overarching framework for 

the review was based on the four essential components of asthma care, multiple subtopics were 

associated with each component. To organize a review of such an expanse, the Panel was 

divided into 10 committees, with about 4–7 reviewers in each (all reviewers were assigned to 

2 or more committees). Within each committee, teams of two (“topic teams”) were assigned as 

leads to cover specific topics. A system of independent review and vote by each of the two 

team reviewers was used at each step of the literature review process to identify studies to 

include in the guidelines update. The initial step in the literature review process was to screen 

titles from the searches for relevancy in updating content of the guidelines, followed by reviews 

of abstracts of the relevant titles to identify those studies meriting full-text review based on 

relevance to the guidelines and study quality. 

Figure 1–1 summarizes the literature retrieval and review process by committee. 

Figure 1–2 summarizes the overall literature retrieval and review process. The combined 

number of titles screened from cycles 1, 2, and 3 was 15,444. The number of abstracts and 

articles reviewed for all three cycles was 4,747. Of these, 2,863 were voted to the abstract 

Keep list following the abstract-review step. A database of these abstracts is posted on the 

NHLBI Web site. Of these abstracts, 2,122 were advanced for full-text review, which resulted in 

1,654 articles serving as a bibliography of references used to update the guidelines, available 

on the NHLBI Web site. Articles were selected from this bibliography for evidence tables and/or 

citation in the text. In addition, articles reporting new and particularly relevant findings and 

published after March 2006 were identified by Panel members during the writing period (March 

2006–December 2006) and by comments received from the public review in February 2007. 
Section 1, Introduction 

4 FIGURE 1–1. LITERATURE RETRIEVAL AND REVIEW PR OCESS: BR EAKDOWN COMMITTEE 

Committee Citations Abstracts Full Text 

Screened for relevance to asthma guidelines 

Reviewed by 2 independent reviewers; vote based on relevance to guidelines and quality of study 

Reviewed by primary reviewer with secondary review of articles rejected by primary reviewer 

Evidence Ta

Topics Covered Number Number Number 

Table 

Number Table Tit

Assessment and Monitoring 3,996 758 214 1 Predictors of Exacerb

2 Usefulness of Peak F

Measurement 

Patient and Provider Education 1,860 873 442 3 Asthma Self-Managem

Education for Adults 

4 Asthma Self-Managem

Education for Children 

5 Asthma Self-Managem

Education in Commun

6 Cost-Effectiveness of 

Self-Management Edu

7 Methods for Improving 

Behaviors: ImplemenGuidelines 

8 Methods for Improving 

Support 

Control of Factors Affecting 2,574 1,108 195 9 Allergen Avoidance Asthma 10 Immunotherapy 
August 28, 2007 FIGURE 1–1. LITERATURE RETRIEVAL AND REVIEW PR OCESS: BR EAKDOWN COMMITTEE (CONTINUED) 

Committee Citations Abstracts Full Text 

Screened for relevance to asthma guidelines 

Reviewed by 2 independent reviewers; vote based on relevance to guidelines and quality of study 

Reviewed by primary reviewer with secondary review of articles rejected by primary reviewer 

Evidence Ta

Topics Covered Number Number Number 

Table 

Number Table Tit

Pharmacologic Therapy: Inhaled 724 463 155 11 Combination Therapy Corticosteroids 12 Dosing Strategies Pharmacologic Therapy: Immunomodulators 

141 63 28 13 Anti-IgE 

Pharmacologic Therapy: Leukotriene Receptor Antagonists 

364 130 56 14 Monotherapy/Effectiv

Pharmacologic Therapy: Bronchodilators 

921 438 183 15 Safety of Long-Acting 

Agonists 

16 Levalbuterol 

Pharmacologic Therapy: Special Situations 

3,187 222 107 No tables 

Complementary and Alternative Medicine 

171 134 81 No tables 

Managing Exacerbations 1,407 616 261 17 Increasing the Dose o

Corticosteroids 

18 IV Aminophylline 19 Magnesium Sulfate 20 Heliox 
Section 1, Introduction 

6 

August 28, 2007 

FIGURE 1–2. LITERATURE RETR IEVAL AND REVIEW PROCESS: 

OVERALL SUMMARY 

PREPARATION OF EVIDENCE TABLES 

Evidence tables were prepared for selected topics. It was not feasible to generate evidence 

tables for every topic in the guidelines. Furthermore, many topics did not have a sufficient body 

of evidence or a sufficient number of high-quality studies to warrant the preparation of a table. 

The Panel decided to prepare evidence tables on those topics for which an evidence table 

would be particularly useful to assess the weight of the evidence—e.g., topics with numerous 

articles, conflicting evidence, or which addressed questions raised frequently by clinicians. 

Summary findings on topics without evidence tables, however, also are included in the updated 

guidelines text. 

Evidence tables were prepared with the assistance of a methodologist who served as a 

consultant to the Expert Panel. Within their respective committees, Expert Panel members 

selected the topics and articles for evidence tables. The evidence tables included all articles 

that received a “yes” vote from both the primary and secondary reviewer during the systematic 

literature review process. The methodologist abstracted the articles to the tables, using a 

template developed by the Expert Panel. The Expert Panel subsequently reviewed and 

Selection Process Title Screening Abstract Review Article Review 

PubMed search results in 

15,444 titles to be 

screened 

Exclusions:

10,697 titles 

Title screening results in 

4,747 titles selected for 

abstract review 

Preliminary abstract 

review results in 2,863 

abstracts selected based 

on overall relevance and 

quality 

Final abstract review 

results in 2,122 abstracts 

selected for full-text 

review 

Full-text review results in 

1,654 articles selected 

for bibliography used in 

updating guidelines 

Exclusions:

1,884 titles 

Exclusions:

741 Abstracts 

Exclusions:

468 Abstracts 
Section 1, Introduction 

7 

August 28, 2007 

approved the final evidence tables. A total of 20 tables, comprising 316 articles are included in 

the current update (see figure 1–1). Evidence tables are posted on the NHLBI Web site. 

RANKING THE EVIDENCE 

The Expert Panel agreed to specify the level of evidence used to justify the recommendations 

being made. Panel members only included ranking of evidence for recommendations they 

made based on the scientific literature in the current evidence review. They did not assign 

evidence rankings to recommendations pulled through from the EPR—2 1997 on topics that are 

still important to the diagnosis and management of asthma but for which there was little new 

published literature. These “pull through” recommendations are designated by EPR—2 1997 in 

parentheses following the first mention of the recommendation. For recommendations that have 

been either revised or further substantiated on the basis of the evidence review conducted for 

the EPR—3: Full Report 2007, the level of evidence is indicated in the text in parentheses 

following first mention of the recommendation. The system used to describe the level of 

evidence is as follows (Jadad et al. 2000): 

 Evidence Category A: Randomized controlled trials (RCTs), rich body of data. 

Evidence is from end points of well-designed RCTs that provide a consistent pattern of 

findings in the population for which the recommendation is made. Category A requires 

substantial numbers of studies involving substantial numbers of participants. 

 Evidence Category B: RCTs, limited body of data. Evidence is from end points of 

intervention studies that include only a limited number of patients, post hoc or subgroup 

analysis of RCTs, or meta-analysis of RCTs. In general, category B pertains when few 

randomized trials exist; they are small in size, they were undertaken in a population that 

differs from the target population of the recommendation, or the results are somewhat 

inconsistent. 

 Evidence Category C: Nonrandomized trials and observational studies. Evidence is 

from outcomes of uncontrolled or nonrandomized trials or from observational studies. 

 Evidence Category D: Panel consensus judgment. This category is used only in cases 

where the provision of some guidance was deemed valuable, but the clinical literature 

addressing 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 

criteria for categories A through C. 

In addition to specifying the level of evidence supporting a recommendation, the Expert Panel 

agreed to indicate the strength of the recommendation. When a certain clinical practice “is 

recommended,” this indicates a strong recommendation by the panel. When a certain clinical 

practice “should, or may, be considered,” this indicates that the recommendation is less strong. 

This distinction is an effort to address nuances of using evidence ranking systems. For 

example, a recommendation for which clinical RCT data are not available (e.g., conducting a 

medical history for symptoms suggestive of asthma) may still be strongly supported by the 

Panel. Furthermore, the range of evidence that qualifies a definition of “B” or “C” is wide, and 

the Expert Panel considered this range and the potential implications of a recommendation as 

they decided how strongly the recommendation should be presented. 
Section 1, Introduction 

8 

August 28, 2007 

PANEL DISCUSSION 

The first opportunity for discussion of findings occurred within the “topic teams.” Teams then 

presented a summary of their findings during a conference call to all members of their 

respective committee. A full discussion ensued on each topic, and the committee arrived at a 

consensus position. Teams then presented their findings and the committee position to the full 

Expert Panel at an in-person meeting, thereby engaging all Panel members in critical analysis of 

the evidence and interpretation of the data. 

A series of conference calls for each of the 10 committees as well as four in-person Expert 

Panel meetings (held in October 2004, April 2005, December 2005, and May 2006) were 

scheduled to facilitate discussion of findings and to dovetail with the three cycles of literature 

review that occurred over the 18-month period. Potential conflicts of interest were disclosed at 

the initial meeting. 

REPORT PREPARATION 

Development of the EPR—3: Full Report 2007 was an iterative process of interpreting the 

evidence, drafting summary statements, and reviewing comments from the various external 

reviews before completing the final report. In the summer and fall of 2005, the various topic 

teams, through conference calls and subsequent electronic mail, began drafting their assigned 

sections of the report. Members of the respective committees reviewed and revised team 

drafts, also by using conference calls and electronic mail. During the calls, votes were taken to 

ensure agreement with final conclusions and recommendations. 

During the December 2005 meeting, Panel members reviewed and discussed all committee 

drafts. 

During the May 2006 meeting, the Panel conducted a thorough review and discussion of the 

report and reached consensus on the recommendations. For controversial topics, votes were 

taken to ensure that each individual’s opinion was considered. In July, using conference calls 

and electronic mail, the Panel completed a draft of the EPR—3: Full Report 2007 for 

submission in July/August to a panel of expert consultants for their review and comments. In 

response to their comments, a revised draft of the EPR—3: Full Report 2007 was developed 

and circulated in November to the NAEPP Guidelines Implementation Panel (GIP) for their 

comment. This draft was also posted on the NHLBI Web site for public comment in February 

2007. The Expert Panel considered 721 comments from 140 reviewers. Edits were made to 

the documents, as appropriate, before the full EPR—3: Full Report 2007 was finalized and 

published. The EPR—3: Full Report 2007 will be used to develop clinical practice guidelines 

and practice-based tools as well as educational materials for patients and the public. 

In summary, the NAEPP “Expert Panel Report 3: Guidelines for the Diagnosis and 

Management of Asthma—Full Report 2007” represents the NAEPP’s ongoing effort to keep 

recommendations for clinical practice up to date and based upon a systematic review of the 

best available scientific evidence by a Panel of experts, as well as peer review and critique by 

the collective expertise of external research/science consultants, the NAEPP CC members, 

guidelines implementation specialists, and public comment. The relationship between 

guidelines and clinical research is a dynamic one, and the NAEPP recognizes that the task of 

keeping guidelines’ recommendations up to date is an increasing challenge. In 1991, many 

recommendations were based on expert opinion because there were only limited randomized 

clinical trials in adults, and almost none in children, that adequately tested clinical interventions 
Section 1, Introduction 

9 

August 28, 2007 

grounded in research findings about the disease process in asthma. The large gaps in the 

literature defined pressing clinical research questions that have now been vigorously addressed 

by the scientific community, as the size of the literature reviewed for the current report attests. 

The NAEPP is grateful to all of the Expert Panel members for meeting the challenge with 

tremendous dedication and to Dr. William Busse for his outstanding leadership. The NAEPP 

would particularly like to acknowledge the contributions of Dr. Gail Shapiro, who served on 

NAEPP Expert Panels from 1991 until her death in August 2006. Dr. Shapiro provided valuable 

continuity to the Panel’s deliberations while simultaneously offering a fresh perspective that was 

rooted in observations from her clinical practice and was supported and substantiated by her 

clinical research and indepth understanding of the literature. Dr. Shapiro had a passion for 

improving asthma care and an unwavering commitment to develop evidence-based 

recommendations that would also be practical. Dr. Shapiro inspired in others the essence of 

what NAEPP hopes to offer with this updated Expert Panel Report: a clear vision for clinicians 

and patients to work together to achieve asthma control. 

References 

EPR. Expert panel report: guidelines for the diagnosis and management of asthma

(EPR 1991). NIH Publication No. 91-3642. Bethesda, MD: U.S. Department of Health and 

Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; 

National Asthma Education and Prevention Program, 1991. 

EPR⎯2. Expert panel report 2: guidelines for the diagnosis and management of asthma

(EPR⎯2 1997). NIH Publication No. 97-4051. Bethesda, MD: U.S. Department of Health 

and Human Services; National Institutes of Health; National Heart, Lung, and Blood 

Institute; National Asthma Education and Prevention Program, 1997. 

EPR⎯Update 2002. Expert panel report: guidelines for the diagnosis and management 

of asthma. Update on selected topics 2002 (EPR⎯Update 2002). NIH Publication 

No. 02-5074. Bethesda, MD: U.S. Department of Health and Human Services; National 

Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education 

and Prevention Program, June 2003. 

Jadad AR, Moher M, Browman GP, Booker L, Sigouin C, Fuentes M, Stevens R. Systematic 

reviews and meta-analyses on treatment of asthma: critical evaluation. BMJ 

2000;320(7234):537–40. 

NHIS. National health interview survey (NHIS 2005). Hyattsville, MD: National Center for 

Health Statistics (NCHS), Centers for Disease Control and Prevention, 2005. Available at 

http://www.cdc.gov/nchs/about/major/nhis/reports_2005.htm. 
Section 1, Introduction 

10 

August 28, 2007 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

11 

August 28, 2007 

SECTION 2, DEFINITION, PATHOPHYSIOLOGY AND PATHOGENESIS OF 

ASTHMA, AND NATURAL HISTORY OF ASTHMA 

KEY POINTS: DEFINITION, PATHOPHYSIOLOGY AND 

PATHOGENESIS OF ASTHMA, AND NATURAL HISTORY OF 

ASTHMA 

 Asthma is a chronic inflammatory disorder of the airways. This feature of asthma has 

implications for the diagnosis, management, and potential prevention of the disease. 

 The immunohistopathologic features of asthma include inflammatory cell infiltration: 

— Neutrophils (especially in sudden-onset, fatal asthma exacerbations; occupational 

asthma, and patients who smoke) 

— Eosinophils 

— Lymphocytes 

— Mast cell activation 

— Epithelial cell injury 

 Airway inflammation contributes to airway hyperresponsiveness, airflow limitation, 

respiratory symptoms, and disease chronicity. 

 In some patients, persistent changes in airway structure occur, including sub-basement 

fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, and 

angiogenesis. 

 Gene-by-environment interactions are important to the expression of asthma. 

 Atopy, the genetic predisposition for the development of an immunoglobulin E 

(IgE)-mediated response to common aeroallergens, is the strongest identifiable 

predisposing factor for developing asthma. 

— Viral respiratory infections are one of the most important causes of asthma exacerbation 

and may also contribute to the development of asthma. 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

12 

August 28, 2007 

KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 The critical role of inflammation has been further substantiated, but evidence is emerging for 

considerable variability in the pattern of inflammation, thus indicating phenotypic differences 

that may influence treatment responses. 

 Gene-by-environmental interactions are important to the development and expression of 

asthma. Of the environmental factors, allergic reactions remain important. Evidence also 

suggests a key and expanding role for viral respiratory infections in these processes. 

 The onset of asthma for most patients begins early in life with the pattern of disease 

persistence determined by early, recognizable risk factors including atopic disease, 

recurrent wheezing, and a parental history of asthma. 

 Current asthma treatment with anti-inflammatory therapy does not appear to prevent 

progression of the underlying disease severity. 

Introduction 

Asthma is a common chronic disorder of the airways that involves a complex interaction of 

airflow obstruction, bronchial hyperresponsiveness and an underlying inflammation. This 

interaction can be highly variable among patients and within patients over time. This section 

presents a definition of asthma, a description of the processes on which that definition is 

based—the pathophysiology and pathogenesis of asthma, and the natural history of asthma. 

Definition of Asthma 

Asthma is a common chronic disorder of the airways that is 

complex and characterized by variable and recurring 

symptoms, airflow obstruction, bronchial 

hyperresponsiveness, and an underlying inflammation 

(box 2–1). The interaction of these features of asthma 

determines the clinical manifestations and severity of 

asthma (figure 2–1) and the response to treatment. 

The concepts underlying asthma pathogenesis have 

evolved dramatically in the past 25 years and are still 

undergoing evaluation as various phenotypes of this 

disease are defined and greater insight links clinical features of asthma with genetic patterns 

(Busse and Lemanske 2001; EPR⎯2 1997). Central to the various phenotypic patterns of 

asthma is the presence of underlying airway inflammation, which is variable and has distinct but 

overlapping patterns that reflect different aspects of the disease, such as intermittent versus 

persistent or acute versus chronic manifestations. Acute symptoms of asthma usually arise 

from bronchospasm and require and respond to bronchodilator therapy. Acute and chronic 

inflammation can affect not only the airway caliber and airflow but also underlying bronchial 

hyperresponsiveness, which enhances susceptibility to bronchospasm (Cohn et al. 2004). 

BOX 2–1. 

CHARACTERISTICS OF 

CLINICAL ASTHMA 

 Symptoms 

 Airway obstruction 

 Inflammation 

 Hyperresponsiveness 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

13 

August 28, 2007 

FIGURE 2–1. THE INTERPLAY AND INTERACTION BETWEEN 

AIRWAY INFLAMMATION AND THE CLINICAL SYMPTOMS AND 

PATHOPHYSIOLOGY OF ASTHMA 

Inflammation Inflammation

Airway Hyperresponsiveness Airway Obstruction

Clinical Symptoms

Treatment with anti-inflammatory drugs can, to a large extent, reverse some of these processes; 

however, the successful response to therapy often requires weeks to achieve and, in some 

situations, may be incomplete (Bateman et al. 2004; O'Byrne and Parameswaran 2006). For 

some patients, the development of chronic inflammation may be associated with permanent 

alterations in the airway structure—referred to as airway remodeling—that are not prevented by 

or fully responsive to currently available treatments (Holgate and Polosa 2006). Therefore, the 

paradigm of asthma has been expanded over the last 10 years from bronchospasm and airway 

inflammation to include airway remodeling in some persons (Busse and Lemanske 2001). 

The concept that asthma may be a continuum of these processes that can lead to moderate and 

severe persistent disease is of critical importance to understanding the pathogenesis, 

pathophysiology, and natural history of this disease (Martinez 2006). Although research since 

the first NAEPP guidelines in 1991 (EPR 1991) has confirmed the important role of inflammation 

in asthma, the specific processes related to the transmission of airway inflammation to specific 

pathophysiologic consequences of airway dysfunction and the clinical manifestations of asthma 

have yet to be fully defined. Similarly, much has been learned about the host–environment 

factors that determine airways’ susceptibility to these processes, but the relative contributions of 

either and the precise interactions between them that leads to the initiation or persistence of 

disease have yet to be fully established. Nonetheless, current science regarding the 

mechanisms of asthma and findings from clinical trials have led to therapeutic approaches that 

allow most people who have asthma to participate fully in activities they choose. As we learn 

more about the pathophysiology, phenotypes, and genetics of asthma, treatments will become 

available to ensure adequate asthma control for all persons and, ideally, to reverse and even 

prevent the asthma processes. 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

14 

August 28, 2007 

As a guide to describing asthma and identifying treatment directions, a working definition of 

asthma put forth in the previous Guidelines remains valid: Asthma is a chronic inflammatory 

disorder of the airways in which many cells and cellular elements play a role: in particular, mast 

cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible 

individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest 

tightness, and coughing, particularly at night or in the early morning. These episodes are 

usually associated with widespread but variable airflow obstruction that is often reversible either 

spontaneously or with treatment. The inflammation also causes an associated increase in the 

existing bronchial hyperresponsiveness to a variety of stimuli. Reversibility of airflow limitation 

may be incomplete in some patients with asthma (EPR 1991; EPR⎯2 1997). 

This working definition and its recognition of key features of asthma have been derived from 

studying how airway changes in asthma relate to the various factors associated with the 

development of airway inflammation (e.g., allergens, respiratory viruses, and some occupational 

exposures) and recognition of genetic regulation of these processes. From these descriptive 

approaches has evolved a more comprehensive understanding of asthma pathogenesis, the 

processes involved in the development of persistent airway inflammation, and the significant 

implications that these immunological events have for the development, diagnosis, treatment, 

and possible prevention of asthma. 

Pathophysiology and Pathogenesis of Asthma 

Airflow limitation in asthma is recurrent and caused by a variety of changes in the airway. 

These include: 

 Bronchoconstriction. In asthma, the dominant physiological event leading to clinical 

symptoms is airway narrowing and a subsequent interference with airflow. In acute 

exacerbations of asthma, bronchial smooth muscle contraction (bronchoconstriction) occurs 

quickly to narrow the airways in response to exposure to a variety of stimuli including 

allergens or irritants. Allergen-induced acute bronchoconstriction results from an 

IgE-dependent release of mediators from mast cells that includes histamine, tryptase, 

leukotrienes, and prostaglandins that directly contract airway smooth muscle (Busse and 

Lemanske 2001). Aspirin and other nonsteroidal anti-inflammatory drugs (see section 3, 

component 3) can also cause acute airflow obstruction in some patients, and evidence 

indicates that this non-IgE-dependent response also involves mediator release from airway 

cells (Stevenson and Szczeklik 2006). In addition, other stimuli (including exercise, cold air, 

and irritants) can cause acute airflow obstruction. The mechanisms regulating the airway 

response to these factors are less well defined, but the intensity of the response appears 

related to underlying airway inflammation. Stress may also play a role in precipitating 

asthma exacerbations. The mechanisms involved have yet to be established and may 

include enhanced generation of pro-inflammatory cytokines. 

 Airway edema. As the disease becomes more persistent and inflammation more 

progressive, other factors further limit airflow (figure 2–2). These include edema, 

inflammation, mucus hypersecretion and the formation of inspissated mucus plugs, as well 

as structural changes including hypertrophy and hyperplasia of the airway smooth muscle. 

These latter changes may not respond to usual treatment. 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

15 

August 28, 2007 

FIGURE 2–2. FACTORS LIMITI NG AIRFLOW IN ACUTE AND 

PERSISTENT ASTHMA 

Neutrophil

Mast cell

IL-3, IL-4,

IL-13, IL-9 

Eosinophil

IL-3, IL-5 

GM-CSF 

Dendritic cell

IgE

Inflammation

(myo) fibroblasts

Blood vessels

Environmental factors and 

Inflammatory products 

mucus

Smooth muscle

Airway microenvironment

Pro-inflammatory mediators 

Th2/Th1 

cytokines (e.g., 

IL-13, TNF-α)

Initiation

Amplification

Propagation

TNF-α

B lymphocyte T lymphocyte

Acute Inflammation Persistent inflammation and 

development of remodeling

Environmental factors

Airway Effects

Bronchospasm

Acute Inflammation

Persistent Inflammation

Remodeling

Key: GM-CSF, granulocyte-macrophage colony-stimulating factor; IgE, immunoglobulin E; IL-3, interleukin 3 (and 

similar); TNF-α, tumor necrosis factor-alpha 

Source: Adapted and reprinted from The Lancet, 368, Holgate ST, Polosa R. The mechanisms, diagnosis, and 

management of severe asthma in adults, 780–93. Copyright (2006), with permission from Elsevier. 

 Airway hyperresponsiveness. Airway hyperresponsiveness—an exaggerated 

bronchoconstrictor response to a wide variety of stimuli—is a major, but not necessarily 

unique, feature of asthma. The degree to which airway hyperresponsiveness can be 

defined by contractile responses to challenges with methacholine correlates with the clinical 

severity of asthma. The mechanisms influencing airway hyperresponsiveness are multiple 

and include inflammation, dysfunctional neuroregulation, and structural changes; 

inflammation appears to be a major factor in determining the degree of airway 

hyperresponsiveness. Treatment directed toward reducing inflammation can reduce airway 

hyperresponsiveness and improve asthma control. 

 Airway remodeling. In some persons who have asthma, airflow limitation may be only 

partially reversible. Permanent structural changes can occur in the airway (figure 2–2); 

these are associated with a progressive loss of lung function that is not prevented by or fully 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

16 

August 28, 2007 

reversible by current therapy. Airway remodeling involves 

an activation of many of the structural cells, with 

consequent permanent changes in the airway that increase 

airflow obstruction and airway responsiveness and render 

the patient less responsive to therapy (Holgate and Polosa 

2006). These structural changes can include thickening of 

the sub-basement membrane, subepithelial fibrosis, airway 

smooth muscle hypertrophy and hyperplasia, blood vessel 

proliferation and dilation, and mucous gland hyperplasia 

and hypersecretion (box 2–2). Regulation of the repair and 

remodeling process is not well established, but both the 

process of repair and its regulation are likely to be key 

events in explaining the persistent nature of the disease and 

limitations to a therapeutic response. 

PATHOPHYSIOLOGIC MECHANISMS IN THE 

DEVELOPMENT OF AIRWAY INFLAMMATION 

Inflammation has a central role in the pathophysiology of asthma. As noted in the definition of 

asthma, airway inflammation involves an interaction of many cell types and multiple mediators 

with the airways that eventually results in the characteristic pathophysiological features of the 

disease: bronchial inflammation and airflow limitation that result in recurrent episodes of cough, 

wheeze, and shortness of breath. The processes by which these interactive events occur and 

lead to clinical asthma are still under investigation. Moreover, although distinct phenotypes of 

asthma exist (e.g., intermittent, persistent, exercise-associated, aspirin-sensitive, or severe 

asthma), airway inflammation remains a consistent pattern. The pattern of airway inflammation 

in asthma, however, does not necessarily vary depending upon disease severity, persistence, 

and duration of disease. The cellular profile and the response of the structural cells in asthma 

are quite consistent. 

Inflammatory Cells 

Lymphocytes. An increased understanding of the development and regulation of airway 

inflammation in asthma followed the discovery and description of subpopulations of 

lymphocytes, T helper 1 cells and T helper 2 cells (Th1 and Th2), with distinct inflammatory 

mediator profiles and effects on airway function (figure 2–3). After the discovery of these 

distinct lymphocyte subpopulations in animal models of allergic inflammation, evidence emerged 

that, in human asthma, a shift, or predilection, toward the Th2-cytokine profile resulted in the 

eosinophilic inflammation characteristic of asthma (Cohn et al. 2004). In addition, generation of 

Th2 cytokines (e.g., interleukin-4 (IL-4), IL-5, and IL-13) could also explain the overproduction of 

IgE, presence of eosinophils, and development of airway hyperresponsiveness. There also may 

be a reduction in a subgroup of lymphocytes, regulatory T cells, which normally inhibit Th2 cells, 

as well as an increase in natural killer (NK) cells that release large amounts of Th1 and 

Th2 cytokines (Akbari et al. 2006; Larche et al. 2003). T lymphocytes, along with other airway 

resident cells, also can determine the development and degree of airway remodeling. Although 

it is an oversimplification of a complex process to describe asthma as a Th2 disease, 

recognizing the importance of n families of cytokines and chemokines has advanced our 

understanding of the development of airway inflammation (Barnes 2002; Zimmermann et al. 

2003). 

BOX 2–2. 

FEATURES OF 

AIRWAY 

REMODELING 

 Inflammation 

 Mucus hypersecretion 

 Subepithelial fibrosis 

 Airway smooth muscle 

hypertrophy 

 Angiogenesis 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

17 

August 28, 2007 

FIGURE 2–3. AIRWAY INFLAMMATION 

Inhaled antigen activates mast cells and Th2 cells in the airway. They in turn induce the production of mediators of 

inflammation (such as histamine and leukotrienes) and cytokines including interleukin-4 and interleukin-5. 

Interleukin-5 travels to the bone marrow and causes terminal differentiation of eosinophils. Circulating eosinophils 

enter the area of allergic inflammation and begin migrating to the lung by rolling, through interactions with selectins, 

and eventually adhering to endothelium through the binding of integrins to members of the immunoglobulin 

superfamily of adhesion proteins: vascular-cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 

(ICAM-1). As the eosinophils enter the matrix of the airway through the influence of various chemokines and 

cytokines, their survival is prolonged by interleukin-4 and granulocyte-macrophage colony-stimulating factor 

(GM-CSF). On activation, the eosinophil releases inflammatory mediators, such as leukotrienes and granule 

proteins, to injure airway tissues. In addition, eosinophils can generate GM-CSF to prolong and potentiate their 

survival and contribution to persistent airway inflammation. MCP-1, monocyte chemotactic protein; and MIP-1α, 

macrophage inflammatory protein. 

Reprinted by permission from Busse WW, Lemanske RF. Advances in Immunology N Engl J Med 2001; 344: 350-

62. Copyright © 2001 Massachusetts Medical Society. All rights reserved. 

Mast cells. Activation of mucosal mast cells releases bronchoconstrictor mediators (histamine, 

cysteinyl-leukotrienes, prostaglandin D2) (Boyce 2003; Galli et al. 2005; Robinson 2004). 

Although allergen activation occurs through high-affinity IgE receptors and is likely the most 

relevant reaction, sensitized mast cells also may be activated by osmotic stimuli to account for 

exercise-induced bronchospasm (EIB). Increased numbers of mast cells in airway smooth 

muscle may be linked to airway hyperresponsiveness (Brightling et al. 2002). Mast cells also 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

18 

August 28, 2007 

can release a large number of cytokines to change the airway environment and promote 

inflammation even though exposure to allergens is limited. 

Eosinophils. Increased numbers of eosinophils exist in the airways of most, but not all, 

persons who have asthma (Chu and Martin 2001; Sampson 2000; Williams 2004). These cells 

contain inflammatory enzymes, generate leukotrienes, and express a wide variety of 

pro-inflammatory cytokines. Increases in eosinophils often correlate with greater asthma 

severity. In addition, numerous studies show that treating asthma with corticosteroids reduces 

circulating and airway eosinophils in parallel with clinical improvement. However, the role and 

contribution of eosinophils to asthma is undergoing a reevaluation based on studies with an 

anti-IL-5 treatment that has significantly reduced eosinophils but did not affect asthma control 

(Leckie et al. 2000). Therefore, although the eosinophil may not be the only primary effector cell 

in asthma, it likely has a distinct role in different phases of the disease. 

Neutrophils. Neutrophils are increased in the airways and sputum of persons who have severe 

asthma, during acute exacerbations, and in the presence of smoking. Their pathophysiological 

role remains uncertain; they may be a determinant of a lack of response to corticosteroid 

treatment (Fahy et al. 1995). The regulation of neutrophil recruitment, activation, and alteration 

in lung function is still under study, but leukotriene B4 may contribute to these processes 

(Jatakanon et al. 1999; Wenzel et al. 1997; Wenzel 2006). 

Dendritic cells. These cells function as key antigen-presenting cells that interact with allergens 

from the airway surface and then migrate to regional lymph nodes to interact with regulatory 

cells and ultimately to stimulate Th2 cell production from naïve T cells (Kuipers and Lambrecht 

2004). 

Macrophages. Macrophages are the most numerous cells in the airways and also can be 

activated by allergens through low-affinity IgE receptors to release inflammatory mediators and 

cytokines that amplify the inflammatory response (Peters-Golden 2004). 

Resident cells of the airway. Airway smooth muscle is not only a target of the asthma 

response (by undergoing contraction to produce airflow obstruction) but also contributes to it 

(via the production of its own family of pro-inflammatory mediators). As a consequence of 

airway inflammation and the generation of growth factors, the airway smooth muscle cell can 

undergo proliferation, activation, contraction, and hypertrophy—events that can influence airway 

dysfunction of asthma. 

Epithelial cells. Airway epithelium is another airway lining cell critically involved in asthma 

(Polito and Proud 1998). The generation of inflammatory mediators, recruitment and activation 

of inflammatory cells, and infection by respiratory viruses can cause epithelial cells to produce 

more inflammatory mediators or to injure the epithelium itself. The repair process, following 

injury to the epithelium, may be abnormal in asthma, thus furthering the obstructive lesions that 

occur in asthma. 

Inflammatory Mediators 

Chemokines are important in recruitment of inflammatory cells into the airways and are mainly 

expressed in airway epithelial cells (Zimmermann et al. 2003). Eotaxin is relatively selective for 

eosinophils, whereas thymus and activation-regulated chemokines (TARCs) and 

macrophage-derived chemokines (MDCs) recruit Th2 cells. There is an increasing appreciation 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

19 

August 28, 2007 

for the role this family of mediators has in orchestrating injury, repair, and many aspects of 

asthma. 

Cytokines direct and modify the inflammatory response in asthma and likely determine its 

severity. Th2-derived cytokines include IL-5, which is needed for eosinophil differentiation and 

survival, and IL-4 which is important for Th2 cell differentiation and with IL-13 is important for 

IgE formation. Key cytokines include IL-1β and tumor necrosis factor-α (TNF-α), which amplify 

the inflammatory response, and granulocyte-macrophage colony-stimulating factor (GM-CSF), 

which prolongs eosinophil survival in airways. Recent studies of treatments directed toward 

single cytokines (e.g., monoclonal antibodies against IL-5 or soluble IL-4 receptor) have not 

shown benefits in improving asthma outcomes. 

Cysteinyl-leukotrienes are potent bronchoconstrictors derived mainly from mast cells. They 

are the only mediator whose inhibition has been specifically associated with an improvement in 

lung function and asthma symptoms (Busse 1996; Leff 2001). Recent studies have also shown 

leukotriene B4 can contribute to the inflammatory process by recruitment of neutrophils (Gelfand 

and Dakhama 2006). 

Nitric oxide (NO) is produced predominantly from the action of inducible NO synthase in airway 

epithelial cells; it is a potent vasodilator (Deykin et al. 2002; Strunk et al. 2003). Measurements 

of fractional exhaled NO (FeNO) may be useful for monitoring response to asthma treatment 

because of the purported association between FeNO and the presence of inflammation in 

asthma (Green et al. 2002). 

Immunoglobulin E 

IgE is the antibody responsible for activation of allergic reactions and is important to the 

pathogenesis of allergic diseases and the development and persistence of inflammation. IgE 

attaches to cell surfaces via a specific high-affinity receptor. The mast cell has large numbers of 

IgE receptors; these, when activated by interaction with antigen, release a wide variety of 

mediators to initiate acute bronchospasm and also to release pro-inflammatory cytokines to 

perpetuate underlying airway inflammation (Boyce 2003; Sporik et al. 1995). Other cells, 

basophils, dendritic cells, and lymphocytes also have high-affinity IgE receptors. 

The development of monoclonal antibodies against IgE has shown that the reduction of IgE is 

effective in asthma treatment (Busse et al. 2001; Holgate et al. 2005). These clinical 

observations further support the importance of IgE to asthma. 

Implications of Inflammation for Therapy 

Recent scientific investigations have focused on translating the increased understanding of the 

inflammatory processes in asthma into therapies targeted at interrupting these processes 

(Barnes 2002). Some investigations have yielded promising results, such as the development 

leukotriene modifiers and anti-IgE monoclonal antibody therapy. Other studies, such as those 

directed at IL-4 or IL-5 cytokines, underscore the relevance of multiple factors regulating 

inflammation in asthma and the redundancy of these processes. All of these clinical studies 

also indicate that phenotypes of asthma exist, and these phenotypes may have very specific 

patterns of inflammation that require different treatment approaches. Current studies are 

investigating novel therapies targeted at the cytokines, chemokines, and inflammatory cells 

farther upstream in the inflammatory process. For example, drugs designed to inhibit the 

Th2 inflammatory pathway may cause a broad spectrum of effects such as airway 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

20 

August 28, 2007 

hyperresponsiveness and mucus hypersecretion. Further research into the mechanisms 

responsible for the varying asthma phenotypes and appropriately targeted therapy may enable 

improved control for all manifestations of asthma, and, perhaps, prevention of disease 

progression. 

PATHOGENESIS 

What initiates the inflammatory process in the first place and makes some persons susceptible 

to its effects is an area of active investigation. There is not yet a definitive answer to this 

question, but new observations suggest that the origins of asthma primarily occur early in life. 

The expression of asthma is a complex, interactive process that depends on the interplay 

between two major factors—host factors (particularly genetics) and environmental exposures 

that occur at a crucial time in the development of the immune system (figure 2–4). 

FIGURE 2–4. HOST FACTORS AND ENVIRONMEN TAL EXPOSURES 

Genetic

Factors

• Cytokine

response

profiles

Environment

• Allergens

• Pollution

• Infections

• Microbes

• Stress

Age

Altered Innate and

Adaptive Immune Responses

Persistent wheezing and asthma

LRI

• RSV/PIV

• Adenovirus

• Chlamydia

• Mycoplasma

Lower Airway

Targeting

Key: LRI, lower respiratory illnesses; RSV, respiratory syncytial virus; PIV, parainfluenza virus 

Host Factors 

Innate immunity. There is considerable interest in the role of innate and adaptive immune 

responses associated with both the development and regulation of inflammation (Eder et al. 

2006). In particular, research has focused on an imbalance between Th1 and Th2 cytokine 

profiles and evidence that allergic diseases, and possibly asthma, are characterized by a shift 

toward a Th2 cytokine-like disease, either as overexpression of Th2 or underexpression of 

Th1 (figure 2–5). Airway inflammation in asthma may represent a loss of normal balance 

between two “opposing” populations of Th lymphocytes. Two types of Th lymphocytes have 

been characterized: Th1 and Th2. Th1 cells produce IL-2 and interferon-γ (IFN-γ), which are 

critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a 

family of cytokines (IL-4, -5, -6, -9, and -13) that can mediate allergic inflammation. The current 

“hygiene hypothesis” of asthma illustrates how this cytokine imbalance may explain some of the 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

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August 28, 2007 

FIGURE 2–5. CYTOKINE BALANCE 

Numerous factors, including alterations in the number or type of infections early in life, the widespread use of 

antibiotics, adoption of the Western lifestyle, and repeated exposure to allergens, may affect the balance between 

Th1-type and Th2-type cytokine responses and increase the likelihood that the immune response will be dominated 

by Th2 cells and thus will ultimately lead to the expression of allergic diseases such as asthma. 

Reprinted by permission from Busse WW, Lemanske RF. Advances in Immunology N Engl J Med 2001; 344: 350-

62. Copyright © 2001 Massachusetts Medical Society. All rights reserved. 

dramatic increases in asthma prevalence in westernized countries. This hypothesis is based on 

the assumption that the immune system of the newly born is skewed toward Th2 cytokine 

generation. Following birth, environmental stimuli such as infections will activate Th1 responses 

and bring the Th1/Th2 relationship to an appropriate balance. Evidence indicates that the 

incidence of asthma is reduced in association with certain infections (M. tuberculosis, measles, 

or hepatitis A), exposure to other children (e.g., presence of older siblings and early enrollment 

in childcare), and less frequent use of antibiotics (Eder et al. 2006; Gern et al. 1999; Gern and 

Busse 2002; Horwood et al. 1985; Sears et al. 2003). Furthermore, the absence of these 

lifestyle events is associated with the persistence of a Th2 cytokine pattern. Under these 

conditions, the genetic background of the child who has a cytokine imbalance toward Th2 will 

set the stage to promote the production of IgE antibodies to key environmental antigens, such 

as house-dust mite, cockroach, Alternaria, and possibly cat. Therefore, a gene-by-environment 

interaction occurs in which the susceptible host is exposed to environmental factors that are 

capable of generating IgE, and sensitization occurs. Precisely why the airways of some 

individuals are susceptible to these allergic events has not been established. 

There also appears to be a reciprocal interaction between the two subpopulations in which 

Th1 cytokines can inhibit Th2 generation and vice versa. Allergic inflammation may be the 

result of an excessive expression of Th2 cytokines. Alternatively, recent studies have 

suggested the possibility that the loss of normal immune balance arises from a cytokine 

dysregulation in which Th1 activity in asthma is diminished. The focus on actions of cytokines 

and chemokines to regulate and activate the inflammatory profile in asthma has provided 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

22 

August 28, 2007 

ongoing and new insight into the pattern of airway injury that may lead to new therapeutic 

targets. 

Genetics. It is well recognized that asthma has an inheritable component to its expression, but 

the genetics involved in the eventual development of asthma remain a complex and incomplete 

picture (Holgate 1999; Ober 2005). To date, many genes have been found that either are 

involved in or linked to the presence of asthma and certain of its features. The complexity of 

their involvement in clinical asthma is noted by linkages to certain phenotypic characteristics, 

but not necessarily the pathophysiologic disease process or clinical picture itself. The role of 

genetics in IgE production, airway hyperresponsiveness, and dysfunctional regulation of the 

generation of inflammatory mediators (such as cytokines, chemokines, and growth factors) has 

appropriately captured much attention. In addition, studies are investigating genetic variations 

that may determine the response to therapy. The relevance of polymorphisms in the betaadrenergic and corticosteroid receptors in determining responsiveness to therapies is of 

increasing interest, but the widespread application of these genetic factors remains to be fully 

established. 

Sex. In early life, the prevalence of asthma is higher in boys. At puberty, however, the sex ratio 

shifts, and asthma appears predominantly in women (Horwood et al. 1985). How specifically 

sex and sex hormones, or related hormone generation, are linked to asthma has not been 

established, but they may contribute to the onset and persistence of the disease. 

Environmental Factors 

Two major environmental factors have emerged as the most important in the development, 

persistence, and possibly severity of asthma: airborne allergens and viral respiratory infections. 

In the susceptible host, and at a critical time of development (e.g., immunological and 

physiological), both respiratory infections and allergens have a major influence on asthma 

development and its likely persistence. It is also apparent that allergen exposure, allergic 

sensitization, and respiratory infections are not separate entities but function interactively in the 

eventual development of asthma. 

Allergens. The role of allergens in the development of asthma has yet to be fully defined or 

resolved, but it is obviously important. Sensitization and exposure to house-dust mite and 

Alternaria are important factors in the development of asthma in children. Early studies showed 

that animal danders, particularly dog and cat, were associated with the development of asthma. 

Recent data suggest that, under some circumstances, dog and cat exposure in early life may 

actually protect against the development of asthma. The determinant of these diverse 

outcomes has not been established. Studies to evaluate house-dust mite and cockroach 

exposure have shown that the prevalence of sensitization and subsequent development of 

asthma are linked (Huss et al. 2001; Sporik et al. 1990; Wahn et al. 1997). Exposure to 

cockroach allergen, for example, a major allergen in inner-city dwellings, is an important cause 

of allergen sensitization, a risk factor for the development of asthma (Rosenstreich et al. 1997). 

In addition, allergen exposure can promote the persistence of airway inflammation and 

likelihood of an exacerbation. 

Respiratory infections. During infancy, a number of respiratory viruses have been associated 

with the inception or development of the asthma. In early life, respiratory syncytial virus (RSV) 

and parainfluenza virus in particular, cause bronchiolitis that parallels many features of 

childhood asthma (Gern and Busse 2002; Sigurs et al. 2000). A number of long-term 

prospective studies of children admitted to hospital with documented RSV have shown that 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

23 

August 28, 2007 

approximately 40 percent of these infants will continue to wheeze or have asthma in later 

childhood (Sigurs et al. 2000). Symptomatic rhinovirus infections in early life also are emerging 

as risk factors for recurrent wheezing. On the other hand, evidence also indicates that certain 

respiratory infections early in life—including measles and even RSV (Stein et al. 1999) or 

repeated viral infections (other than lower respiratory tract infections) (Illi et al. 2001; Shaheen 

et al. 1996)—can protect against the development of asthma. The “hygiene hypothesis” of 

asthma suggests that exposure to infections early in life influences the development of a child’s 

immune system along a “nonallergic” pathway, leading to a reduced risk of asthma and other 

allergic diseases. Although the hygiene hypothesis continues to be investigated, this 

association may explain observed associations between large family size, later birth order, 

daycare attendance, and a reduced risk of asthma (Eder et al. 2006; Illi et al. 2001). 

The influence of viral respiratory infections on the development of asthma may depend on an 

interaction with atopy. The atopic state can influence the lower airway response to viral 

infections, and viral infections may then influence the development of allergic sensitization. The 

airway interactions that may occur when individuals are exposed simultaneously to both 

allergens and viruses are of interest but are not defined at present. 

Other environmental exposures. Tobacco smoke, air pollution, occupations, and diet have 

also been associated with an increased risk for the onset of asthma, although the association 

has not been as clearly established as with allergens and respiratory infections (Malo et al. 

2004; Strachan and Cook 1998a; Strachan and Cook 1998b). 

In utero exposure to environmental tobacco smoke increases the likelihood for wheezing in the 

infant, although the subsequent development of asthma has not been well defined. In adults 

who have asthma, cigarette smoking has been associated with an increase in asthma severity 

and decreased responsiveness to inhaled corticosteroids (ICSs) (Dezateux et al. 1999). 

The role of air pollution in the development of asthma remains controversial and may be related 

to allergic sensitization (American Thoracic Society 2000). One recent epidemiologic study 

showed that heavy exercise (three or more team sports) outdoors in communities with high 

concentration of ozone was associated with a higher risk of asthma among school-age children 

(McConnell et al. 2002). The relationship between increased levels of pollution and increases in 

asthma exacerbations and emergency care visits has been well documented. 

An association of low intake of antioxidants and omega-3 fatty acids has been noted in 

observational studies, but a direct link as a causative factor has not been established. 

Increasing rates of obesity have paralleled increasing rates in asthma prevalence, but the 

interrelation is uncertain (Ford 2005). Obesity may be a risk factor for asthma due to the 

generation of unique inflammatory mediators that lead to airway dysfunction. 

In summary, our understanding of asthma pathogenesis and underlying mechanisms now 

includes the concept that gene-by-environmental interactions are critical factors in the 

development of airway inflammation and eventual alteration in the pulmonary physiology that is 

characteristic of clinical asthma. 

Natural History of Asthma 

If the persistence and severity of asthma involves a progression of airway inflammation to 

airway remodeling and some eventual irreversible airway obstruction, then an important 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

24 

August 28, 2007 

question is whether anti-inflammatory medication (i.e., ICSs), given early in the course of 

disease might interrupt this process and prevent permanent declines in lung function. For early 

initiation of ICSs to be more beneficial than delayed initiation, two assumptions must be valid: 

(1) as a group, people who have mild or moderate persistent asthma experience a progressive 

decline in lung function that is measurable and clinically significant, and (2) treatment with ICSs 

prevents or slows this decline, in addition to providing long-term control of asthma. Reviews 

were conducted in 2002 (EPR⎯Update 2002) and for the current report to evaluate the 

literature on the effect of intervention with ICSs in altering the progression of disease. 

NATURAL HISTORY OF PERSISTENT ASTHMA 

Children 

It is well established that asthma is a variable disease. Asthma can vary among individuals, and 

its progression and symptoms can vary within an individual’s experience over time. The course 

of asthma over time, either remission or increasing severity, is commonly referred to as the 

natural history of the disease. It has been postulated that the persistence or increase of asthma 

symptoms over time is accompanied by a progressive decline in lung function. Recent research 

suggests that this may not be the case. Rather, the course of asthma may vary markedly 

between young children, older children and adolescents, and adults, and this variation is 

probably more dependent on age than on symptoms. 

A prospective cohort study in which followup began at birth revealed that, in children whose 

asthma-like symptoms began before 3 years of age, deficits in lung growth associated with the 

asthma occurred by 6 years of age (Martinez et al. 1995). Continued followup on lung function 

measures taken at 11–16 years of age found that, compared to the group of children who 

experienced no asthma symptoms for the first 6 years of life, the group of children whose 

asthma symptoms began before 3 years of age experienced significant deficits in lung function 

at 11–16 years of age; however, no further loss in forced expiratory volume in 1 second (FEV1) 

occurred compared to children who did not have asthma (Morgan et al. 2005). The group 

whose asthma symptoms began after 3 years of age did not experience deficits in lung function. 

A longitudinal study of children 8–10 years of age found that bronchial hyperresponsiveness 

was associated with declines in lung function growth in both children who have active symptoms 

of asthma and children who did not have such symptoms (Xuan et al. 2000). Thus, symptoms 

neither predicted nor determined lung function deficits in this age group. 

A study by Sears and colleagues (2003) assessed lung function repeatedly from ages 9 to 26 in 

almost 1,000 children from a birth cohort in Dunedin, New Zealand. They found that children 

who had asthma had persistently lower levels of FEV1/forced vital capacity (FVC) ratio during 

the followup. Regardless of the severity of their symptoms, however, their levels of lung 

function paralleled those of children who did not have asthma, and no further losses of lung 

function were observed after age 9. 

Baseline data from the Childhood Asthma Management Program (CAMP) study support the 

finding that the individual’s age at the time of asthma onset influences declines in lung function 

growth. At the time of enrollment of children who had mild or moderate persistent asthma at 

5–12 years of age, an inverse association between lung function and duration of asthma was 

noted (Zeiger et al. 1999). Although the analysis did not distinguish between age of onset and 

duration of asthma, it can be inferred that, because the average duration of asthma was 5 years 

and the average age of the children was 9 years, most children who had the longer duration of 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

25 

August 28, 2007 

asthma started experiencing symptoms before 3 years of age. The data suggest that these 

children had the lowest lung function levels. After 4–6 years of followup, the children in the 

CAMP study, on average, did not experience deficits in lung growth (as defined by 

postbronchodilator FEV1), regardless of their symptom levels or the treatment they received 

(CAMP 2000). However, a followup analysis of the CAMP data showed that a subgroup of the 

children experienced progressive (at least 1 percent a year) reductions in lung growth, 

regardless of treatment group (Covar et al. 2004). Predictors of this progressive reduction, at 

baseline of the study, were male sex and younger age. 

The CAMP study noted that when measures other than FEV1 are used to assess lung function 

measures over time in childhood asthma, progressive declines are observed: the FEV1/FVC 

ratio before bronchodilator use was smaller at the end of the treatment period than at the start in 

all three treatment groups; the decline in the ICS group was less than that of the placebo group 

(0.2 percent versus 1.8 percent) (CAMP 2000). In a comparison of lung function measures of 

CAMP study participants with lung function measures of children who did not have asthma, by 

year from ages 5 through 18, the FEV1/FVC ratio was significantly lower for the children who 

had asthma compared to those who did not have asthma at age 5 (mean difference 7.3 percent 

for boys and 7.1 percent for girls), and the difference increased with age (9.8 percent for boys 

and 9.9 percent for girls) (Strunk et al. 2006). 

Cumulatively, these studies suggest that most of the deficits in lung function growth observed in 

children who have asthma occur in children whose symptoms begin during the first 3 years of 

life, and the onset of symptoms after 3 years of age usually is not associated with significant 

deficits in lung function growth. Thus, a promising target for interventions designed to prevent 

deficits in lung function, and perhaps the development of more severe symptoms later in life, 

would be children who have symptoms before 3 years of age and seem destined to develop 

persistent asthma. However, it is important to distinguish this group from the majority of 

children who wheeze before 3 years of age and do not experience any more symptoms after 

6 years of age (Martinez et al. 1995). Until recently, no validated algorithms were available to 

predict which children among those who had asthma-like symptoms early in life would go on to 

have persistent asthma. Data obtained from long-term longitudinal studies of children who were 

enrolled at birth have generated such a predictive index. The studies first identified an index of 

risk factors for developing persistent asthma symptoms among children younger than 3 years of 

age who had more than three episodes of wheezing during the previous year. The index was 

then applied to a birth cohort that was followed through 13 years of age. Seventy-six percent of 

the children who were diagnosed with asthma after 6 years of age had a positive asthma 

predictive index before 3 years of age; 97 percent of the children who did not have asthma after 

6 years of age had a negative asthma predictive index before 3 years of age (Castro-Rodriguez 

et al. 2000). The index was subsequently refined and tested in a clinical trial to examine if 

treating children who had a positive asthma predictive index would prevent development of 

persistent wheezing (Guilbert et al. 2006). The asthma predictive index generated by these 

studies identifies the following risk factors for developing persistent asthma among children 

younger than 3 years of age who had four or more episodes of wheezing during the previous 

year: either (1) one of the following: parental history of asthma, a physician diagnosis of atopic 

dermatitis, or evidence of sensitization to aeroallergens, or (2) two of the following: evidence of 

sensitization to foods, ≥4 percent peripheral blood eosinophilia, or wheezing apart from colds. 

Adults 

Accelerated loss of lung function appears to occur in adults who have asthma. In a study of 

adults who have asthma and who received 2 weeks of high-dose prednisone if airflow 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

26 

August 28, 2007 

obstruction persisted after 2 weeks of bronchodilator therapy, the degree of persistent airflow 

obstruction correlated with both the severity and the duration of their asthma (Finucane et al. 

1985). 

Two large, prospective epidemiological studies evaluated the rate of decline in pulmonary 

function in adults who had asthma. In an 18-year prospective study of 66 nonsmokers who had 

asthma, 26 smokers who had asthma, and 186 control participants who had no asthma, 

spirometry was performed at 3-year intervals (Peat et al. 1987). Seventy-three percent of the 

study group underwent at least six spirometric evaluations. The slope for decline in lung 

function (FEV1) was approximately 40 percent greater for the participants who had asthma than 

for those who had no asthma. This did not appear to result from extreme measurement 

produced by a few participants, because fewer than 25 percent of the participants who had 

asthma were measured with a slope less steep than the mean for those who did not have 

asthma. In another study, three spirometry evaluations were performed in 13,689 adults 

(778 had asthma, and 12,911 did not have asthma) over a 15-year period (Lange et al. 1998). 

The average decline in FEV1 was significantly greater (38 mL per year) in those who had 

asthma than in those who did not have asthma (22 mL per year). Although, in this study, 

asthma was defined simply by patient report, the researchers noted that, because the 6 percent 

prevalence rate for asthma did not increase in this cohort as they increased in age, it is likely 

that the subjects who reported having asthma did indeed have asthma rather than chronic 

obstructive pulmonary disease (COPD). It is not possible to determine from these studies 

whether the loss of pulmonary function occurred in those who had mild or moderate asthma or 

only in those who had severe asthma. Nevertheless, the data support the likelihood of potential 

accelerated loss of pulmonary function in adults who have asthma. 

New studies have addressed this issue since the “Expert Panel Review—Update 2002” 

(EPR⎯Update 2002). James and colleagues (2005) reanalyzed the data from the study of 

decline in lung function from Busselton, Australia (Peat et al. 1987), after adding a new survey 

in 1994–1995. Subjects (N = 9,317) had participated as adults (19 years or older) in one or 

more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the 

followup study of 1994–1995. Using the whole data sample, James and colleagues found that 

subjects who had asthma showed significantly lower lung function during the whole followup 

period, but most of the differences were due to deficits in lung function present at the beginning 

of followup (when subjects were age 19). Once the effect of smoking was taken into account, 

the excess decline in FEV1 attributable to asthma was 3.78 mL per year for women and 3.69 mL 

per year for men. Although these results were statistically significant, their clinical relevance is 

debatable. Sherrill and coworkers (2003) reanalyzed the data from the Tucson Epidemiologic 

Study of Airway Obstructive Disease. A total of 2,926 subjects, with longitudinal data for lung 

function assessed in up to 12 surveys spanning a period of up to 20 years, were included. They 

found that, unlike subjects who had a diagnosis of COPD, in those who had diagnosis of 

longstanding asthma, FEV1 did not decline at a more rapid rate than normal. This was also true 

for subjects who had asthma and COPD. Griffith and colleagues (2001) studied decline in lung 

function in 5,242 participants in the Cardiovascular Health Study who were over age 65 at 

enrollment. Each participant had up to three lung function measurements over a 7-year interval. 

Subjects who had asthma had lower levels of FEV1 than those who reported no asthma. 

However, after adjustment for emphysema and chronic bronchitis, there were no significant 

increases in the rate of decline in FEV1 in participants who had asthma. 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

27 

August 28, 2007 

Summary 

Taken together, these longitudinal epidemiological studies and clinical trials indicate that the 

progression of asthma, as measured by declines in lung function, varies in different age groups. 

Declines in lung function growth observed in children appear to occur by 6 years of age and 

occur predominantly in those children whose asthma symptoms started before 3 years of age. 

Children 5–12 years of age who have mild or moderate persistent asthma, on average, do not 

appear to experience declines in lung function through 11–17 years of age, although a subset of 

these children experience progressive reductions in lung growth as measured by FEV1. 

Furthermore, there is emerging evidence of reductions in the FEV1/FVC ratio, apparent in young 

children who have mild or moderate asthma compared to children who do not have asthma, that 

increase with age. There is also evidence of progressively declining lung function in adults who 

have asthma, but the clinical significance and the extent to which these declines contribute to 

the development of fixed airflow obstruction are unknown. 

EFFECT OF INTERVENTIONS ON NATURAL HISTORY OF ASTHMA 

Data on the effect of interventions on the progression of asthma, as measured by declines in 

lung function, airway hyperresponsiveness, or the severity of symptoms, were evaluated for 

EPR—Update 2002 and the current update. The Expert Panel does not recommend using ICSs 

for the purpose of modifying the underlying disease process (e.g., preventing persistent 

asthma). Evidence to date indicates that daily long-term control medication does not alter the 

underlying severity of the disease. Although a preliminary study suggests that appropriate 

control of childhood asthma may prevent more serious asthma or irreversible obstruction in later 

years (Agertoft and Pedersen 1994), these observations were not verified in a recent long-term 

randomized control trial (RCT) in 1,041 children 5–12 years of age (CAMP 2000). This study 

does not support the assumption that, on average, children 5–12 years of age who have mild or 

moderate persistent asthma have a progressive decline in lung function. Children in the 

placebo group did not experience a decline in postbronchodilator FEV1 over the 5-year 

treatment period, and they had postbronchodilator FEV1 levels similar to children in the ICS and 

nedocromil treatment groups at the end of the study. Observational prospective data from other 

studies of large groups of children suggest that the timing of the CAMP intervention was too 

late, as most loss of lung function in childhood asthma appears to occur in the first 3–5 years of 

life (Martinez et al. 1995). However, in a recent randomized, controlled prospective study, 

children 2–3 years of age who were at high risk of developing persistent asthma were treated 

for 2 years with ICSs and observed for 1 additional year after treatment was discontinued. That 

study demonstrated that the intervention group had lung function and asthma symptom levels 

similar to the placebo group at the end of the study (Guilbert et al. 2006). 

Two recent studies addressed the possibility that ICSs may prevent the putative declines in lung 

function believed to occur shortly after the beginning of the disease in adults who have 

late-onset asthma. A retrospective study (Selroos et al. 2004) reported the results of an 

observational study of adults who had mild-to-moderate asthma and were treated for 5 years 

with an ICS. One group, treated early in the disease (less than 2 years after diagnosis), had 

better outcomes in terms of lung function than those who started treatment more than 2 years 

after diagnosis. The group in which treatment was started more than 2 years after diagnosis, 

however, had lower levels of lung function at the beginning of the trial. Therefore, it is not 

possible to determine from these data what the results would have been in a randomized trial. 

Two recent long-term observational studies report an association between ICS therapy and 

reduced decline in FEV1 in adults who have asthma (Dijkstra et al. 2006; Lange et al. 2006). 

However, long-term RCTs will be necessary to confirm a causal relationship. 
Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma 

28 

August 28, 2007 

The START study (Pauwels et al. 2003) enrolled 7,241 subjects, 5–66 years of age, who had 

mild asthma of less than 2 years’ duration, according to each subject’s report. Participants were 

randomized to a low-dose ICS or placebo and were followed prospectively for 3 years. The 

study found a slightly better level of postbronchodilator lung function in participants in the active 

arm than in the placebo arm, but the difference was more prominent after 1 year of treatment 

(+1.48 percent predicted FEV1) than at the end of the treatment period (+0.88 percent predicted 

FEV1), suggesting no effect in the putative progressive loss in lung function in these subjects. 

With respect to the potential role of ICSs in changing the natural course of asthma, the relevant 

clinical question is: Are ICSs associated with less disease burden after discontinuation of 

therapy? The best available evidence in children 5–12 years of age (CAMP 2000) and 

2–3 years of age (Guilbert et al. 2006) demonstrated that, although ICSs provide superior 

control and prevention of symptoms and exacerbations during treatment, symptoms and airway 

hyperresponsiveness worsen when treatment is withdrawn (EPR⎯Update 2002; Guilbert et al. 

2006). This evidence suggests that currently available therapy controls but does not modify the 

underlying disease process. 

IMPLICATIONS OF CURRENT INFORMATION ABOUT PATHOPHYSIOLOGY 

AND PATHOGENESIS, AND NATURAL HISTORY FOR ASTHMA 

MANAGEMENT 

Airway inflammation is a major factor in the pathogenesis and pathophysiology of asthma. The 

importance of inflammation to central features of asthma continues to expand and underscore 

this characteristic as a primary target of treatment. It has also become apparent, however, that 

airway inflammation is variable in many aspects including intensity, cellular/mediator pattern, 

and response to therapy. As knowledge of the various phenotypes of inflammation become 

apparent, it is likely that treatment also will also have greater specificity and, presumably, 

effectiveness. 

It is also apparent that asthma, and its persistence, begin early in life. Although the factors that 

determine persistent versus intermittent asthma have yet to be ascertained, this information will 

become important in determining the type of treatment, its duration, and its effect on various 

outcomes of asthma. Early studies have indicated that although current treatment is effective in 

controlling symptoms, reducing airflow limitations, and preventing exacerbations, present 

treatment does not appear to prevent the underlying severity of asthma. 

Despite these unknowns, the current understanding of basic mechanisms in asthma has greatly 

improved appreciation of the role of treatment. The Expert Panel’s recommendations for 

asthma treatment, which are directed by knowledge of basic mechanisms, should result in 

improved control of asthma and a greater understanding of therapeutic effectiveness.

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Section 3, The Four Components of Asthma Management 

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SECTION 3, THE FOUR COMPONENTS OF ASTHMA MANAGEMENT 

Introduction 

The Expert Panel Reports presenting clinical practice guidelines for the diagnosis and 

management of asthma have organized recommendations for asthma care around four 

components considered essential to effective asthma management: 

 Measures of assessment and monitoring, obtained by objective tests, physical examination, 

patient history and patient report, to diagnose and assess the characteristics and severity of 

asthma and to monitor whether asthma control is achieved and maintained 

 Education for a partnership in asthma care 

 Control of environmental factors and comorbid conditions that affect asthma 

 Pharmacologic therapy 

This section updates information on each of these four components, based on the Expert 

Panel’s review of the scientific literature. The sections that follow present specific clinical 

recommendations for managing asthma long term and for managing exacerbations that 

incorporate the four components
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

36 

August 28, 2007 

SECTION 3, COMPONENT 1: MEASURES OF ASTHMA ASSESSMENT AND 

MONITORING 

Introduction 

See section 1, “Overall Methods Used To Develop This Report,” for literature search strategy 

and tally of results for the EPR—3: Full Report 2007 on this component, Measures of Asthma 

Assessment and Monitoring. Two Evidence Tables were prepared: 1, Predictors of 

Exacerbation; and 2, Usefulness of Peak Flow Measurement. 

Recommendations for “Component 1: Measures of Asthma Assessment and Monitoring” are 

presented in five sections: “Overview of Assessing and Monitoring Severity, Control, and 

Responsiveness in Managing Asthma;” “Diagnosis of Asthma;” “Initial Assessment: 

Characterization of Asthma and Classification of Asthma Severity;” “Periodic Assessment and 

Monitoring of Asthma Control Essential for Asthma Management;” and “Referral to an Asthma 

Specialist for Consultation or Comanagement.” The recommendations are based on the opinion 

of the Expert Panel and review of the scientific literature. 

Overview of Assessing and Monitoring Asthma Severity, Control, and 

Responsiveness in Managing Asthma 

KEY POINTS: OVERVIEW OF MEASURES OF ASTHMA 

ASSESSMENT AND MONITORING 

 The functions of assessment and monitoring are closely linked to the concepts of severity, 

control, and responsiveness to treatment: 

— Severity: the intrinsic intensity of the disease process. Severity is measured most easily 

and directly in a patient not receiving long-term-control therapy. 

— Control: the degree to which the manifestations of asthma (symptoms, functional 

impairments, and risks of untoward events) are minimized and the goals of therapy are 

met. 

— Responsiveness: the ease with which asthma control is achieved by therapy. 

 Both severity and control include the domains of current impairment and future risk: 

— Impairment: frequency and intensity of symptoms and functional limitations the patient is 

experiencing or has recently experienced 

— Risk: the likelihood of either asthma exacerbations, progressive decline in lung function 

(or, for children, reduced lung growth), or risk of adverse effects from medication 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

37 

August 28, 2007 

 The concepts of severity and control are used as follows for managing asthma: 

— During a patient’s initial presentation, if the patient is not currently taking long-term 

control medication, asthma severity is assessed to guide clinical decisions on the 

appropriate medication and other therapeutic interventions. 

— Once therapy is initiated, the emphasis thereafter for clinical management is changed to 

the assessment of asthma control. The level of asthma control will guide decisions 

either to maintain or adjust therapy. 

— For population-based evaluations, clinical research, or subsequent characterization of 

the patient’s overall severity, asthma severity can be inferred after optimal therapy is 

established by correlating levels of severity with the lowest level of treatment required to 

maintain control. For clinical management, however, the emphasis is on assessing 

asthma severity for initiating therapy and assessing control for monitoring and adjusting 

therapy. 

KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 The key elements of assessment and monitoring are refined to include the separate, but 

related, concepts of severity, control, and responsiveness to treatment. Classifying severity 

is emphasized for initiating therapy; assessing control is emphasized for monitoring and 

adjusting therapy. Asthma severity and control are defined in terms of two domains: 

impairment and risk. 

 The distinction between the domains of impairment and risk for assessing asthma severity 

and control emphasizes the need to consider separately asthma’s effects on quality of life 

and functional capacity on an ongoing basis (i.e., in the present) and the risks it presents for 

adverse events in the future, such as exacerbations and progressive loss of pulmonary 

function. These domains of asthma may respond differentially to treatment. 

Diagnosing a patient as having asthma is only the first step in reducing the symptoms, 

functional limitations, impairment in quality of life, and risk of adverse events that are associated 

with the disease. The ultimate goal of treatment is to enable a patient to live with none of these 

manifestations of asthma, and an initial assessment of the severity of the disease allows an 

estimate of the type and intensity of treatment needed. Responsiveness to asthma treatment is 

variable; therefore, to achieve the goals of therapy, followup assessment must be made and 

treatment should be adjusted accordingly. Even patients who have asthma that is well 

controlled at the time of a clinical assessment must be monitored over time, for the processes 

underlying asthma can vary in intensity over time, and treatment should be adjusted 

accordingly. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

38 

August 28, 2007 

The functions of assessment and monitoring are closely linked to the concepts of severity, 

control, and responsiveness to treatment: 

 Severity: the intrinsic intensity of the disease process. Severity is most easily and directly 

measured in a patient who is not currently receiving long-term control treatment. 

 Control: the degree to which the manifestations of asthma (symptoms, functional 

impairments, and risks of untoward events) are minimized and the goals of therapy are met. 

 Responsiveness: the ease with which control is achieved by therapy. 

An important point linking asthma severity, control, and responsiveness is that the goals are 

identical for all levels of baseline asthma severity. A patient who has severe persistent asthma 

compared to a patient who has mild persistent asthma, or a patient who is less responsive to 

therapy may require more intensive intervention to achieve well-controlled asthma; however, the 

goals are the same: in well-controlled asthma, the manifestations of asthma are minimized by 

therapeutic intervention. 

Although the severity of disease is most accurately assessed in patients before initiating 

long-term control medication, many patients are already receiving treatment when first seen by 

a new health care provider. In such cases, severity can be inferred from the least amount of 

treatment required to maintain control. This approach presumes that the severity of asthma is 

closely related to its responsiveness to treatment. Although this assumption may not be true for 

all forms of asthma and all treatments, it does focus attention on what is important in managing 

patients who have asthma: achieving a satisfactory level of control. 

Both asthma severity and asthma control can be broken down into two domains: impairment 

and risk. Impairment is an assessment of the frequency and intensity of symptoms and 

functional limitations that a patient is experiencing or has recently experienced. Risk is an 

estimate of the likelihood of either asthma exacerbations or of progressive loss of pulmonary 

function over time. 

 An assessment of the impairment domain for determining the severity of disease (in patients 

on no long-term-control treatment before treatment is initiated) or the level of control (after 

treatment is selected) usually can be elicited by careful, directed history and lung function 

measurement. Standardized questionnaires like the Asthma Control Test (ACT) (Nathan et 

al. 2004), the Childhood Asthma Control Test (Liu et al. 2007), the Asthma Control 

Questionnaire (Juniper et al. 1999b), the Asthma Therapy Assessment Questionnaire 

(ATAQ) control index (Vollmer et al. 1999), and others have been developed to facilitate and 

standardize the assessment of the impairment domain of asthma control. Some patients, 

however, appear to perceive the severity of airflow obstruction poorly (Bijl-Hofland et al. 

2000; Kikuchi et al. 1994). These patients may have unconsciously accommodated to their 

symptoms, or perhaps they have mistakenly attributed these symptoms to other causes, like 

aging, obesity, or lack of fitness, so that they do not report them readily. For these patients, 

some other measure, such as spirometry, may identify that the degree of airflow obstruction 

is poorly recognized or perceived by the patient. A trial of therapy can be initiated and lead 

to unexpected improvement in quality of life (“I did not realize how much better I could feel 

until my asthma was treated.”).

 Assessment of the risk domain—that is, of adverse events in the future, especially of 

exacerbations and of progressive, irreversible loss of pulmonary function—is more 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

problematic. Some assessment of the risk of exacerbations can be inferred from the 

medical history. Patients who have had exacerbations requiring emergency department 

(ED) visits, hospitalization, or intensive care unit (ICU) admission, especially in the past 

year, have a great risk of exacerbations in the future (Adams et al. 2000; Eisner et al. 2001; 

Lieu et al. 1998). Conversely, the achievement of good control of asthma symptoms and 

airflow obstruction from treatment with an inhaled corticosteroid (ICS) lowers the risk for 

asthma exacerbations in the future (Bateman et al. 2004). It is not known, however, 

whether the minimum treatment to control symptoms necessarily reduces the risk of 

exacerbations. Some patients who have few current symptoms or impairment of quality of 

life may still be at grave risk of severe, even life-threatening exacerbations (Ayres et al. 

2004). Finally, little is known about the prevalence of a heightened risk of progressive loss 

of pulmonary function among patients who have asthma or whether any current treatment 

can prevent it. 

 The test most used for assessing the risk of future adverse events is spirometry, especially 

forced expiratory volume in 1 second (FEV1) expressed as a percent of the predicted value 

or as a proportion of the forced vital capacity (FVC) or FEV1/FVC. The need for a simple, 

easily applied, more accurate test has prompted study of “biomarkers” whose deviations 

from normal might correlate with the severity of risk. Many biomarkers have been 

proposed—airway hyperresponsiveness, blood or sputum eosinophils or eosinophilic 

cationic protein (ECP), fractional exhaled nitric oxide concentration (FeNO), serum 

immunoglobulin E (IgE), number of positive skin tests, concentration of hydrogen ion, 

inflammatory mediators, or various metabolites in an exhaled breath condensate (EBC). 

Few studies, however, have validated or “anchored” assessment of these markers by 

analyzing their relationship to the rate of adverse events or decline in pulmonary function 

over time. Further complicating the matter is that the relationship between normalization of 

a biomarker and normalization of risk of an adverse event may depend on the specific 

treatment given. What is found true for treatment with an ICS may not be true for treatment 

with a leuktotriene receptor antagonist (LTRA) or an inhaled long-acting beta2-agonist 

(LABA), or vice versa. 

In the future, assessment of a combination of historical features and of biomarkers may 

allow accurate estimation of the risk of future adverse events, but it must be kept in mind 

that laboratory tests only indirectly estimate control of risk. In the end, only symptoms, 

exacerbations, and quality of life over time are the measures of asthma control. 

 Assessment of response to therapy is important, but there is inconsistency about the 

definition and measurement of “response.” In general, response to therapy describes the 

ease with which adequate control is achieved by therapy. In a randomized controlled trial 

(RCT) of interventions to achieve asthma control, decreased symptoms, decreased use of 

short-acting beta2-agonist (SABA) for quick relief, improved functioning, improvement in 

FEV1, reduction in exacerbations, fewer ED visits, and decreased side effects from 

medication were equally weighted to develop a composite score that defines a responder to 

therapy (Bateman et al. 2004). The investigators observed that a composite definition of a 

responder correlates with asthma control. In a recent editorial, Stempel and Fuhlbrigge 

(2005) noted that, in published clinical trials, response to therapy based on pre- or 

postbronchodilator FEV1 varied widely in statistical significance, depending on the research 

design and number of subjects included to attain statistical power. Furthermore, when 

response is defined solely by FEV1, it can be influenced by disease activity independent of 

the intervention. It may be significant to characterize other responses, such as decreased 

airway responsiveness as measured by the response to methacholine, frequency of 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

40 

August 28, 2007 

exacerbations, and decrease in nighttime awakening. This area of work is currently 

developing and will be influenced by the outcome measures chosen by researchers 

conducting intervention studies. Agreement is needed on what clinically significant 

outcomes characterize response to therapy. Agreement is also needed on the time needed 

to assess response accurately (Zhang et al. 2002), but this time may vary according to 

treatment. It will take longer to determine whether a patient has responded to a treatment 

whose principal benefit is reduction in the rate of exacerbations, such as an anti-IgE 

monoclonal antibody (Bousquet et al. 2004), than to a treatment that acts as an acute 

bronchodilator. 

Another concept closely related to assessing and predicting response to therapy is resistance to 

therapy. Of adult patients who have asthma, approximately 5 percent have poorly controlled 

asthma, with frequent symptoms and exacerbations despite use of high-dose ICS (Barnes and 

Woolcock 1998). Little is known about why some patients who have asthma do not respond 

well to therapy. A high prevalence of comorbidity—such as uncontrolled gastroesophageal 

reflux disease (GERD), allergic rhinitis, and psychiatric illness—has been described in this 

population (Heaney et al. 2003). Patients who have a poor response to appropriate therapy 

require referral to and consultation with an asthma specialist. 

Diagnosis of Asthma 

KEY POINTS: DIAGNOSIS OF ASTHMA 

 To establish a diagnosis of asthma, the clinician should determine that (EPR⎯2 1997): 

— Episodic symptoms of airflow obstruction or airway hyperresponsiveness are present. 

— Airflow obstruction is at least partially reversible. 

— Alternative diagnoses are excluded. 

 Recommended methods to establish the diagnosis are (EPR⎯2 1997): 

— Detailed medical history. 

— Physical exam focusing on the upper respiratory tract, chest, and skin. 

— Spirometry to demonstrate obstruction and assess reversibility, including in children 

5 years of age or older. Reversibility is determined either by an increase in FEV1 of 

≥12 percent from baseline or by an increase ≥10 percent of predicted FEV1 after 

inhalation of a short-acting bronchodilator. 

— Additional studies as necessary to exclude alternate diagnoses. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 Discussions have been added on the use of spirometry, especially in children, and on the 

criteria for reversibility. 

 Information has been added on vocal cord dysfunction (VCD) and cough variant asthma as 

an alternative diagnosis. Reference has been added to updated information in another 

component on comorbid conditions that may complicate diagnosis and treatment of asthma 

(e.g., allergic bronchopulmonary aspergillosis (ABPA), obstructive sleep apnea (OSA), and 

GERD). 

The Expert Panel recommends that the clinician trying to establish a diagnosis of asthma 

should determine that (EPR⎯2 1997):

 Episodic symptoms of airflow obstruction are present. 

 Airflow obstruction is at least partially reversible. 

 Alternative diagnoses are excluded. 

Box 3–1 lists key indicators for considering a diagnosis of asthma. A careful medical history, 

physical examination, pulmonary function tests, and additional tests will provide the information 

needed to ensure a correct diagnosis of asthma. Each of these methods of assessment is 

described in this section. 

Clinical judgment is needed in conducting the assessment for asthma. Patients who have 

asthma are heterogeneous and present signs and symptoms that vary widely from patient to 

patient as well as within each patient over time. 

MEDICAL HISTORY 

The Expert Panel recommends that a detailed medical history of the new patient who is 

thought to have asthma should address the items listed in figure 3–1 (EPR⎯2 1997). The 

medical history can help: 

 Identify the symptoms likely to be due to asthma. See figure 3–2 for sample questions. 

 Support the likelihood of asthma (e.g., patterns of symptoms, family history of asthma or 

allergies). 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

BOX 3–1. KEY INDICATORS FOR CONSIDERING A DIAGNOSIS OF 

ASTHMA 

Consider a diagnosis of asthma and performing spirometry if any of these indicators is present.* 

These indicators are not diagnostic by themselves, but the presence of multiple key indicators 

increases the probability of a diagnosis of asthma. Spirometry is needed to establish a 

diagnosis of asthma. 

 Wheezing—high-pitched whistling sounds when breathing out—especially in children. (Lack 

of wheezing and a normal chest examination do not exclude asthma.) 

 History of any of the following: 

— Cough, worse particularly at night 

— Recurrent wheeze 

— Recurrent difficulty in breathing 

— Recurrent chest tightness 

 Symptoms occur or worsen in the presence of: 

— Exercise 

— Viral infection 

— Animals with fur or hair 

— House-dust mites (in mattresses, pillows, upholstered furniture, carpets) 

— Mold 

— Smoke (tobacco, wood) 

— Pollen 

— Changes in weather 

— Strong emotional expression (laughing or crying hard) 

— Airborne chemicals or dusts 

— Menstrual cycles 

 Symptoms occur or worsen at night, awakening the patient. 

*Eczema, hay fever, or a family history of asthma or atopic diseases are often associated with asthma, but they are 

not key indicators. 

PHYSICAL EXAMINATION 

The upper respiratory tract, chest, and skin are the focus of the physical examination for 

asthma. Physical findings that increase the probability of asthma are listed below. The 

absence of these findings does not rule out asthma, because the disease is by definition 

variable, and signs of airflow obstruction are often absent between attacks. 

 Hyperexpansion of the thorax, especially in children; use of accessory muscles; appearance 

of hunched shoulders; and chest deformity. 

 Sounds of wheezing during normal breathing, or a prolonged phase of forced exhalation 

(typical of airflow obstruction). Wheezing may only be heard during forced exhalation, but it 

is not a reliable indicator of airflow limitation. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

 Increased nasal secretion, mucosal swelling, and/or nasal polyps.

 Atopic dermatitis/eczema or any other manifestation of an allergic skin condition. 

PULMONARY FUNCTION TESTING (SPIROMETRY) 

The Expert Panel recommends that spirometry measurements—FEV1, forced expiratory 

volume in 6 seconds (FEV6), FVC, FEV1/FVC—before and after the patient inhales a 

short-acting bronchodilator should be undertaken for patients in whom the diagnosis of 

asthma is being considered, including children ≥5 years of age (EPR⎯2 1997). These 

measurements help to determine whether there is airflow obstruction, its severity, and whether it 

is reversible over the short term (Bye et al. 1992; Li and O'Connell 1996). (See box 3–2 for 

further information.) Patients’ perception of airflow obstruction is highly variable, and spirometry 

sometimes reveals obstruction much more severe than would have been estimated from the 

history and physical examination. 

BOX 3–2. IMPORTANCE OF SPIROMETRY IN ASTHMA DIAGNOSIS 

Objective assessments of pulmonary function 

are necessary for the diagnosis of asthma 

because medical history and physical 

examination are not reliable means of 

excluding other diagnoses or of characterizing 

the status of lung impairment. Although 

physicians generally seem able to identify a 

lung abnormality as obstructive (Russell et al. 

1986), they have a poor ability to assess the 

degree of airflow obstruction (Nair et al. 2005; 

Shim and Williams 1980) or to predict whether 

the obstruction is reversible (Russell et al. 

1986). Furthermore, pulmonary function 

measures often do not correlate directly with 

symptoms. One study reports that one-third of 

the children who had moderate-to-severe 

asthma were reclassified to a more severe 

asthma category when pulmonary function 

reports of FEV1 were considered in addition to 

symptom frequency (Stout et al. 2006). 

Conversely, a majority of children in another 

study who had mild-to-moderate asthma 

classified by symptoms had normal FEV1

(Bacharier et al. 2004). These findings 

emphasize the importance of using multiple 

measures and the value of pulmonary function 

testing in a comprehensive assessment of 

asthma. 

For diagnostic purposes, spirometry is 

generally recommended over measurements 

by a peak flow meter in the clinician’s office 

because there is wide variability even in the 

published predicted peak expiratory flow (PEF) 

reference values. Reference values need to 

be specific to each brand of peak flow meter, 

and such normative brand-specific values 

currently are not available for most brands. 

Peak flow meters are designed as monitoring, 

not as diagnostic, tools in the office. 

Spirometry typically measures the maximal volume of air forcibly exhaled from the point of 

maximal inhalation (FVC) and the volume of air exhaled during the first second of this maneuver 

(FEV1). Spirometry is generally valuable in children ≥5 years of age, although some children 

cannot conduct the maneuver adequately until after age 7. Healthy young children complete 

exhalation of their entire vital capacity in a few seconds, but it can take older patients much 

longer, especially patients who have airflow obstruction, because expiratory flow is so low at low 

lung volumes. In these patients, sustaining a maximal expiratory effort for the time necessary 

for complete exhalation may be more than 12 or 15 seconds—long enough for some patients to 

find the maneuver uncomfortable or associated with light headedness. This accounts for the 

interest in measurement of the FEV6 as a substitute for measurement of FVC in adults. In 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

44 

August 28, 2007 

adults, FEV6 has been shown to be equivalent to FVC for identifying obstructive and restrictive 

patterns, using the American Thoracic Society (ATS) algorithm, and to be more reproducible 

and less physically demanding than FVC (Swanney et al. 2004). Airflow obstruction is indicated 

by a reduction in the values for both the FEV1 and the FEV1/FVC (or FEV1/ FEV6) relative to 

reference or predicted values. See figure 3–3a and 3–3b for an example of a spirometric curve 

for this test. Predicted values for FEV1/FVC are based on National Health and Nutrition 

Examination Survey (NHANES) data, National Center for Health Statistics, Centers for Disease 

Control and Prevention (CDC). 

Significant reversibility is indicated by ATS standards as an increase in FEV1 of >200 mL and 

≥12 percent from the baseline measure after inhalation of a short-acting bronchodilator (e.g., 

albuterol, 2–4 puffs of 90 mcg/puff) (ATS 1995; ATS/ERS et al. 2005; Pellegrino et al. 2005). 

Some studies indicate that an increase ≥10 percent of the predicted FEV1 after inhalation of a 

short-acting bronchodilator may be less subject to bias than measuring percent change from 

baseline and may have a higher likelihood of separating patients who have asthma from those 

who have chronic obstructive pulmonary disease (COPD) (Appleton et al. 2005; Brand et al. 

1992; Dales et al. 1988; Meslier et al. 1989). Some patients who have signs and symptoms of 

asthma may not demonstrate reversibility until after a 2- to 3-week trial of oral corticosteroid 

therapy is administered to help improve their asthma control. Furthermore, the spirometry 

measured after a single treatment with SABA or after a short course of oral systemic 

corticosteroid treatment plus acute administration of a bronchodilator may not indicate the 

patient’s best achievable lung function; thus, followup spirometry measures are indicated as 

asthma control improves. 

Abnormalities of lung function are categorized as restrictive and obstructive defects. A reduced 

ratio of FEV1/FVC or FEV1/FEV6 indicates obstruction to the flow of air from the lungs, whereas 

a proportionately reduced FVC (or FEV6 in adults) with a normal or increased FEV1/FVC (or 

FEV1/FEV6) ratio suggests a restrictive pattern. The severity of abnormality of spirometric 

measurements is evaluated by comparison of the patient’s results with reference values based 

on age, height, sex, and race (ATS 1995). Furthermore, chronic asthma may be associated 

with decreased lung function with a loss of response to bronchodilator. Although asthma is 

typically associated with an obstructive impairment that is reversible, neither this finding nor any 

other single test or measure is adequate to diagnose asthma. Many diseases are associated 

with this pattern of abnormality. The patient’s pattern of symptoms (along with other information 

from the patient’s medical history) and exclusion of other possible diagnoses also are needed to 

establish a diagnosis of asthma. In severe cases, the FVC also may be reduced due to trapping 

of air in the lungs. 

When pulmonary function measures are obtained, measuring pulmonary function before and 

after bronchodilator treatment to determine reversibility is recommended. The degree of airway 

reversibility correlates with airway inflammation, as measured by sputum eosinophilia and FeNO 

(Covar et al. 2004a). In addition, those patients who have the greatest degree of reversibility in 

response to SABA may be at the greatest risk of developing fixed airflow obstruction and have 

the greatest loss of lung function (Ulrik and Backer 1999). The postbronchodilator FEV1

measure can then be used to follow lung growth patterns over time (Covar et al. 2004b). 

The Expert Panel recommends that office-based physicians who care for asthma patients 

should have access to spirometry, which is useful in both diagnosis and periodic 

monitoring. Spirometry should be performed using equipment and techniques that meet 

standards developed by the ATS (EPR⎯2 1997). Correct technique, calibration methods, 

and maintenance of equipment are necessary to achieve consistently accurate test results 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

(ATS/ERS et al. 2005). Maximal effort by the patient in performing the test is required to avoid 

important errors in diagnosis and management. Training courses in the performance of 

spirometry that are approved by the National Institute for Occupational Safety and Health are 

available (800–35–NIOSH). 

The Expert Panel recommends that when office spirometry shows severe abnormalities, 

or if questions arise regarding test accuracy or interpretation, further assessment should 

be performed in a specialized pulmonary function laboratory (EPR⎯2 1997).

DIFFERENTIAL DIAGNOSIS OF ASTHMA 

The Expert Panel recommends consideration of alternative diagnoses, as appropriate. 

Box 3–3 lists examples of possible alternative diagnoses for asthma that may be 

considered during the evaluation of medical history, physical examination, and 

pulmonary function. Additional studies are not routinely necessary but may be useful 

when considering alternative diagnoses (EPR⎯2 1997):

 Additional pulmonary function studies (e.g., measurement of lung volumes and evaluation of 

inspiratory loops) may be indicated, especially if there are questions about possible 

coexisting COPD, a restrictive defect, VCD, or possible central airway obstruction. A 

diffusing capacity test is helpful in differentiating between asthma and emphysema in 

patients, such as smokers and older patients, who are at risk for both illnesses. 

 Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge may be 

useful when asthma is suspected and spirometry is normal or near normal. For safety 

reasons, bronchoprovocation testing should be carried out by a trained individual in an 

appropriate facility and is not generally recommended if the FEV1 is <65 percent predicted. 

A positive methacholine bronchoprovocation test is diagnostic for the presence of airway 

hyperresponsiveness, a characteristic feature of asthma that also can be present in other 

conditions (e.g., allergic rhinitis, cystic fibrosis, COPD, among others). Thus, although a 

positive test is consistent with asthma, a negative bronchoprovocation may be more helpful 

to rule out asthma. 

 Chest x ray may be needed to exclude other diagnoses. 

 Allergy testing (see component 3—Control of Environmental Factors and Comorbid 

Conditions That Affect Asthma). 

 Biomarkers of inflammation. The usefulness of measurements of biomarkers of 

inflammation (e.g., total and differential cell count and mediator assays) in sputum, blood, 

urine, and exhaled air as aids to the diagnosis and assessment of asthma is currently being 

evaluated in clinical research trials (see “Monitoring Asthma Control With Minimally Invasive 

Markers and Pharmacogenetics,” in the following section on “Periodic Assessment and 

Monitoring of Asthma Control Essential for Asthma Management”). 

Recurrent episodes of cough and wheezing are due most often to asthma in both children and 

adults. Underdiagnosis of asthma is a frequent problem, especially in children who wheeze 

when they have respiratory infections. These children are often labeled as having bronchitis, 

bronchiolitis, or pneumonia even though the signs and symptoms are most compatible with a 

diagnosis of asthma. The clinician needs, however, to be aware of other causes of airway 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

BOX 3–3. DIFFERENTIAL DIAGNOSTIC POSSIBILITIES FOR 

ASTHMA 

Infants and Children 

Upper airway diseases 

 Allergic rhinitis and sinusitis 

Obstructions involving large airways 

 Foreign body in trachea or bronchus 

 Vocal cord dysfunction 

 Vascular rings or laryngeal webs 

 Laryngotracheomalacia, tracheal stenosis, or bronchostenosis 

 Enlarged lymph nodes or tumor 

Obstructions involving small airways 

 Viral bronchiolitis or obliterative bronchiolitis 

 Cystic fibrosis 

 Bronchopulmonary dysplasia 

 Heart disease 

Other causes 

 Recurrent cough not due to asthma 

 Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux 

Adults 

 COPD (e.g., chronic bronchitis or emphysema) 

 Congestive heart failure 

 Pulmonary embolism 

 Mechanical obstruction of the airways (benign and malignant tumors) 

 Pulmonary infiltration with eosinophilia 

 Cough secondary to drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors) 

 Vocal cord dysfunction 

obstruction leading to wheezing (See box 3–3.). See also “Diagnosis and Prognosis of Asthma 

in Children” in the section “Managing Asthma Long Term in Children 0–4 Years of Age and 

5–11 Years of Age,” for more detailed discussion about the diagnosis of asthma in young 

children. 

Cough variant asthma. Although chronic cough can be a sign of many health problems, it may 

be the principal—or only—manifestation of asthma, especially in young children. This has led to 

the term “cough variant asthma.” Monitoring of PEF or methacholine inhalation challenge, to 

clarify whether there is bronchial hyperresponsiveness consistent with asthma, may be helpful 

in diagnosis. The diagnosis of cough variant asthma is confirmed by a positive response to 

asthma medication (Dicpinigaitis 2006). Treatment should follow the stepwise approach to 

long-term management of asthma. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

Vocal cord dysfunction often mimics asthma. VCD is characterized by episodic dyspnea and 

wheezing caused by intermittent paradoxical vocal cord adduction during inspiration (sometimes 

with abnormal adduction during expiration as well). The cause of VCD is not well understood, 

although some patients develop VCD in response to irritant triggers, such as fumes, cold air, 

and exercise. Although VCD is clearly distinct from asthma, it is often confused with asthma, 

leading to inappropriate medication of affected individuals with anti-asthma medications. 

Asthma medications typically do little, if anything, to relieve symptoms if the patient has pure 

VCD. VCD should be considered in the differential of difficult-to-treat, atypical asthma patients. 

It is important to note, however, that VCD and asthma may coexist and that VCD may 

complicate asthma management. Elite athletes, in particular, are prone to both exerciseinduced bronchospasm (EIB) and VCD, so careful workup is warranted for athletes who present 

with exercise-related breathlessness (Rundell and Spiering 2003). During severe VCD 

episodes, respiratory distress may be severe and lead to intubation. Once the trachea is 

intubated, the wheezing and distress abate in VCD but not in asthma. 

VCD can be difficult to diagnose. Variable flattening of the inspiratory flow loop on spirometry is 

strongly suggestive of the diagnosis, but abnormalities of the inspiratory loop may well be 

absent between episodes. The diagnosis of VCD comes from indirect or direct vocal cord 

visualization during an episode, during which the abnormal adduction can be documented. 

Therapy generally consists of speech therapy and relaxation techniques (Bucca et al. 1995; 

Christopher et al. 1983; Newman et al. 1995). 

Several conditions that may coexist with asthma can complicate diagnosis: ABPA, OSA, and 

GERD (See “Component 3: Control of Environmental Factors and Comorbid Conditions That 

Affect Asthma.”). 

Initial Assessment: Characterization of Asthma and Classification of 

Asthma Severity 

KEY POINTS: INITIAL ASSESSMENT OF ASTHMA 

 Once the diagnosis has been established, information obtained from the diagnostic 

evaluation, and additional information, if necessary, should be used to characterize the 

patient’s asthma in order to guide decisions for therapy (EPR⎯2 1997): 

— Identify precipitating factors (e.g., exposure at home, work, daycare, or school to 

inhalant allergens, or irritants such as tobacco smoke, or viral respiratory infections) 

(Evidence A) 

— Identify comorbidities that may aggravate asthma (e.g., sinusitis, rhinitis, GERD) 

(Evidence B) 

— Classify asthma severity, using measures in both the impairment (Evidence B) and risk 

domains (Evidence C) 

 Measures of pulmonary function, using spirometry, are recommended for assessing asthma 

severity. Low FEV1 indicates current obstruction (impairment domain) and risk for future 

exacerbation (risk domain) (Evidence C). For children, FEV1/FVC appears to be a more 

sensitive measure of severity in the impairment domain; FEV1 is a useful measure of risk for 

exacerbations (Evidence C). 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 The severity classification for asthma changed the category of mild intermittent to 

intermittent in order to emphasize that even patients who have intermittent asthma can have 

severe exacerbations. A note of emphasis has also been added that acute exacerbations 

can be mild, moderate, or severe in any category of persistent asthma. 

 Severity classification is defined in terms of two domains—impairment and risk—to 

emphasize the need to consider separately asthma’s effects on quality of life and functional 

capacity on an ongoing basis (i.e., in the present) and the risks asthma presents for adverse 

events in the future, such as exacerbations and progressive loss of pulmonary function. 

These domains of asthma may respond differentially to treatment. 

 A new emphasis on using FEV1/FVC has been added for to classifying severity in children 

because it may be a more sensitive measure than FEV1. 

The Expert Panel recommends that clinicians use information obtained from the 

diagnostic evaluation, and any additional information, if necessary, to (EPR⎯2 1997):

 Identify precipitating factors 

 Identify comorbid conditions that may aggravate asthma 

 Assess the patient’s knowledge and skills for self-management 

 Classify asthma severity 

Once the diagnosis of asthma has been established, the next step in the initial assessment is to 

characterize the patient’s asthma in order to guide decisions for selecting therapy. This 

characterization is a basic description of the patient’s asthma phenotype. 

As noted earlier, the usefulness of measurements of biomarkers of inflammation (e.g., total and 

differential cell count and mediator assays) in sputum, blood, urine, and exhaled air as aids to 

the diagnosis and assessment of asthma is currently being evaluated in clinical research trials 

(See “Monitoring Asthma Control With Minimally Invasive Markers and Pharmacogenetics,” in 

the following section on “Periodic Assessment and Monitoring of Asthma Control Essential for 

Asthma Management.”). 

IDENTIFY PRECIPITATING FACTORS 

The identification of factors that precipitate worsening of asthma—such as exposure to 

allergens (e.g., pets, molds, seasonal pollens), irritants (e.g., environmental tobacco smoke 

(ETS) and industrial pollutants (such as sulfur dioxide and ozone), or respiratory viruses 

(including “common cold” viruses)—can assist in educating the patient to avoid unnecessary 

exposures or at least to be alert to exposures that might indicate a need for increased 

treatment. Information obtained from the medical history (See figure 3–1.) will aid this 

assessment. See “Component 3: Control of Environmental Factors and Comorbid Conditions 

That Affect Asthma” for additional tools to assess allergies and other relevant exposures, as 

well as key messages for patient education on this topic. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

IDENTIFY COMORBID CONDITIONS THAT MAY AGGRAVATE ASTHMA 

It is also important to identify whether the patient has chronic comorbid conditions that may 

complicate the presentation or the treatment of asthma, such as sinusitis, rhinitis, GERD, OSA, 

or ABPA (See “Component 3: Control of Environmental Factors and Comorbid Conditions That 

Affect Asthma.”). Identification of these comorbid conditions is helpful, because treating them 

adequately may improve overall control of asthma and lessen requirements for asthma 

medications. 

ASSESS THE PATIENT’S KNOWLEDGE AND SKILLS FOR SELF-MANAGEMENT 

Successful management of asthma requires that the patient or patient’s caregiver have a 

fundamental understanding of and skills for following the therapeutic recommendations, 

including pharmacotherapy and measures to control factors that contribute to asthma severity. 

Initial assessment of the patient, therefore, should include an evaluation of the patient’s selfmanagement skills. This evaluation will guide decisions about appropriate educational training. 

See component 2—Education for a Partnership in Asthma Care for detailed discussion and 

tools for integrating assessment and education into all phases of clinical management, including 

the initial patient assessment. 

CLASSIFY ASTHMA SEVERITY 

The Expert Panel recommends that clinicians classify asthma severity by using the 

domains of current impairment and future risk (Evidence B—secondary analyses of 

clinical trials, and Evidence C—observational studies, for assessing impairment; 

Evidence C, for distinguishing intermittent versus persistent asthma by risk of 

exacerbations; Evidence D, for distinguishing different categories of persistent asthma 

by varying frequencies of exacerbations).

Asthma severity is the intrinsic intensity of disease. Initial assessment of patients who have 

confirmed asthma begins with a severity classification because the selection of type, amount, 

and scheduling of therapy should then correspond to the level of asthma severity. This initial 

assessment of asthma severity is made immediately after diagnosis, or when the patient is first 

encountered, generally before the patient is taking some form of long-term control medication. 

Assessment is made on the basis of current spirometry and the patient’s recall of symptoms 

over the previous 2–4 weeks, because detailed recall of symptoms decreases over time. If the 

assessment is made during a visit in which the patient is treated for an acute exacerbation, then 

asking the patient to recall symptoms in the period before the onset of the current exacerbation 

will suffice until a followup visit can be made. 

For population-based evaluations, clinical research, or subsequent characterization of the 

patient’s overall severity, asthma severity can be inferred after optimal therapy is established by 

correlating levels of severity with the lowest level of treatment required to maintain control. For 

clinical management, however, the emphasis is to assess asthma severity prior to initiating 

therapy and, then, assess control for monitoring and adjusting therapy. 

The severity classification of asthma shown in figures 3–4 a, b, and c uses the two domains of 

current impairment and future risk. The specific measures for classifying severity—symptoms, 

use of SABA for quick relief, exacerbations, and pulmonary function—that were presented in 

EPR—2 remain in the current report, although they have been organized into the new 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

50 

August 28, 2007 

framework of measures of impairment and risk. As noted in the “Overview” section of this 

component, the distinction between impairment and risk emphasizes the need to consider 

separately asthma’s effects on quality of life and functional capacity on an ongoing basis (i.e., in 

the present) and the risks asthma presents for adverse events in the future, such as 

exacerbations and progressive loss of pulmonary function. Clinical trial data demonstrate that 

these “domains” of asthma may respond differentially to treatment. Data further suggest that, in 

estimating severity or control in either domain, different manifestations of asthma must be 

assessed, because they do not necessarily correlate with each other (Bacharier et al. 2004; 

Colice et al. 1999; Fuhlbrigge et al. 2002; Strunk et al. 2002). Thus, a composite of measures, 

with a distinction between domains of impairment and risk, will be useful in classifying severity. 

Assessment of Impairment 

Assessment of severity requires assessing the following components of current impairment: 

 Symptoms 

— Nighttime awakenings 

— Need for SABA for quick relief of symptoms 

— Work/school days missed 

— Ability to engage in normal daily activities or in desired activities 

— Quality-of-life assessments 

 Lung function, measured by spirometry: FEV1, FVC (or FEV6), FEV1/FVC (or FEV6 in 

adults). Spirometry is the preferred method for measuring lung function to classify severity. 

Peak flow has not been found to be a reliable variable for classifying severity (Eid et al. 

2000; Llewellin et al. 2002), but it may serve as a useful tool for monitoring trends in asthma 

control over time (See section, “Monitoring Lung Function.”). 

Secondary analyses of clinical trial data and observational studies using the EPR—2 1997 or 

similar Global Initiative for Asthma (GINA) criteria have confirmed that the parameters for the 

impairment domain (symptom, activity levels, and pulmonary function) reflect increasing 

gradients of severity in adults (Antonicelli et al. 2004; Diette et al. 2004; EPR⎯2 1997; Schatz 

et al. 2003, 2005b). 

Whether the ranges of pulmonary function for severity of asthma previously defined in 

guidelines (EPR⎯2 1997) apply well to children has been questioned in cross-sectional studies 

that found normal FEV1 values (many over 90 percent predicted) in a majority of the children, 

5–18 years of age, regardless of their asthma severity as classified on the basis of symptoms 

(Bacharier et al. 2004; Paull et al. 2005; Spahn et al. 2004). Two of those studies reported that, 

in contrast to FEV1 measures, FEV1/FVC decreased with increasing asthma severity and thus 

appeared to be a more sensitive measure of severity (Bacharier et al. 2004; Paull et al. 2005). 

On the other hand, analysis of a large, longitudinal study of children confirmed a relationship 

between the severity of airflow obstruction and the risk of exacerbations (Fuhlbrigge et al. 

2001). Increasing risk correlated with the FEV1 cutoffs for increasing levels of severity as 

defined in EPR—2 (Fuhlbrigge et al. 2006). It is emphasized that these studies also found that 

even children who had normal values of lung function experienced exacerbations. In addition, 

children who have low lung function are at greatest risk of developing fixed airflow obstruction 

over time (Rasmussen et al. 2002). Cumulatively, these studies underscore the importance of 

measuring several variables in the assessment of asthma. Making treatment decisions for 

children should be based on frequency and severity of past exacerbations and symptoms, with 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

51 

August 28, 2007 

pulmonary function measures as an additional guide. FEV1 appears to be a useful measure 

indicating risk for exacerbations; FEV1/FVC appears to be a more sensitive measure of severity 

in the impairment domain. The Expert Panel has updated the pulmonary function measures for 

assessing asthma severity and control in children by adding suggested ranges for FEV1/FVC. 

Assessment of Risk 

A closely related and second dimension of severity is the concept of risk of adverse events, 

including exacerbations and risk of death. Assessment of the risk of future adverse events 

requires careful medical history, observation, and clinician judgment. Documentation of warning 

signs and adverse events will be necessary when a patient is felt to be at increased risk. 

Patients who are deemed at increased risk of adverse outcomes will need close monitoring and 

frequent assessment by their clinicians. 

 Exacerbations of asthma are acute or subacute episodes of progressively worsening 

shortness of breath, cough, wheezing, and chest tightness—or some combination of these 

symptoms. Exacerbations are characterized by decreases in expiratory airflow that can be 

documented and quantified by simple measurement of lung function (spirometry or PEF). 

Exacerbations of asthma can vary widely among individuals and within individuals, from very 

rare to frequent. Although the classification of severity focuses on the frequency of 

exacerbations, it is important to note that the severity of disease does not necessarily 

correlate with the intensity of exacerbations, which can vary from mild to very severe and 

life-threatening. Patients at any level of severity, even intermittent asthma, can have severe 

exacerbations. For example, a person who has intermittent asthma can have a severe 

exacerbation during a viral illness or when exposed to allergens to which he or she is 

sensitized or to noxious fumes and irritants. Accordingly, the Expert Panel has modified the 

designation of “mild intermittent asthma” in the previous guidelines (EPR⎯2 1997; 

EPR⎯Update 2002) to become “intermittent asthma” to emphasize that patients at any level 

of severity—including intermittent—can have severe exacerbations. The duration of 

exacerbations may vary from a few hours to a few days. These unpredictable variations in 

exacerbations can present treatment dilemmas for the clinician who strives to prevent future 

exacerbations and considers when to initiate chronic anti-inflammatory therapy. 

The frequency of exacerbations requiring intervention with oral systemic corticosteroids has 

been correlated in observational studies with the designation of persistent, rather than 

intermittent, asthma (Fuhlbrigge et al. 2001, 2006). Determination of whether the level of 

severity is mild, moderate, or severe will depend on consideration of both the frequency and 

the intensity of the exacerbations. No data are available to correspond specific numbers 

with each severity category. In general, the more frequent and the more intense the 

exacerbations (e.g., requiring urgent, unscheduled clinical care, hospitalization, or ICU 

admission), the greater the degree of underlying disease severity. 

 Predictors that have been reported to be associated with increased risk of exacerbations 

(See Evidence Table 1, Predictors of Exacerbations.) or death include: 

— Severe airflow obstruction, as detected by spirometry (Adams et al. 2000; Connolly et al. 

1998; Fuhlbrigge et al. 2001, 2006; Kitch et al. 2004). 

— Persistent severe airflow obstruction (Kitch et al. 2004). 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

52 

August 28, 2007 

— Two or more ED visits or hospitalizations for asthma in the past year; any history of 

intubation or ICU admission, especially if in the past 5 years (Belessis et al. 2004; Cowie 

et al. 2001). 

— Patients report that they feel in danger or frightened by their asthma (Janson-Bjerklie et 

al. 1993; Ng 2000). 

— Certain demographic or patient characteristics: female, nonwhite (Diette et al. 2002), 

nonuse of ICS therapy, and current smoking (Eisner et al. 2001). 

— Psychosocial factors: depression (Eisner et al. 2005; Goodwin et al. 2004), increased 

stress (Goodwin et al. 2004), socioeconomic factors (Griswold et al. 2005). 

— Attitudes and beliefs about taking medications (Adams et al. 2000; Apter and Szefler 

2004). 

For population-based management, risk stratification is used to identify patients at increased 

risk of morbidity and health care resource use. Several validated psychometric instruments 

have been shown to predict future risk of hospitalization and ED visits (Schatz et al. 2005a). 

Periodic Assessment and Monitoring of Asthma Control Essential for 

Asthma Management 

KEY POINTS: PERIODIC ASSESSMENT OF ASTHMA 

CONTROL 

 The goals of therapy are to achieve asthma control by (Evidence A): 

— Reducing impairment: 

♦ Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the 

daytime, in the night, or after exertion) 

♦ Require infrequent use (≤2 days a week) of inhaled SABA for quick relief of 

symptoms 

♦ Maintain (near) “normal” pulmonary function 

♦ Maintain normal activity levels (including exercise and other physical activity and 

attendance at work or school) 

♦ Meet patients’ and families’ expectations of and satisfaction with asthma care 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

— Reducing risk: 

♦ Prevent recurrent exacerbations of asthma and minimize the need for ED visits or 

hospitalizations 

♦ Prevent progressive loss of lung function; for children, prevent reduced lung growth 

♦ Provide optimal pharmacotherapy with minimal or no adverse effects 

 Periodic assessments (at 1- to 6-month intervals) and ongoing monitoring of asthma control 

are recommended to determine if the goals of therapy are being met and if adjustments in 

therapy are needed (Evidence B, extrapolation from clinical trials; and Evidence C, 

observational studies). Measurements of the following are recommended: 

— Signs and symptoms of asthma 

— Pulmonary function 

— Quality of life/functional status 

— History of asthma exacerbations 

— Pharmacotherapy (checking for adherence to therapy and potential side effects from 

medication) 

— Patient–provider communication and patient satisfaction 

 Clinician assessment and patient self-assessment are the primary methods for monitoring 

asthma. Population-based assessment is used by health organizations, such as managed 

care organizations and disease management programs (EPR⎯2 1997). 

 The following frequencies for spirometry tests are recommended: (1) at the time of initial 

assessment (Evidence C), (2) after treatment is initiated and symptoms and PEF have 

stabilized, (3) during periods of progressive or prolonged loss of asthma control, and (4) at 

least every 1–2 years (Evidence D). 

 Use of minimally invasive markers (“biomarkers”) to monitor asthma control and guide 

treatment decisions for therapy is of increasing interest. Some markers, such as spirometry 

measures, are currently and widely used in clinical care; others, such as sputum eosinophils 

and FeNO, may also be useful, but they require further evaluation in both children and 

adults before they can be recommended as clinical tools for routine asthma management 

(Evidence D). 

 Provide to all patients a written asthma action plan based on signs and symptoms and/or 

PEF; written action plans are particularly recommended for patients who have moderate or 

severe persistent asthma, a history of severe exacerbations, or poorly controlled asthma 

(Evidence B). 

 Whether peak flow monitoring, symptom monitoring (available data show similar benefits for 

each), or a combination of approaches is used, self-monitoring is important to the effective 

self-management of asthma (Evidence A). 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

54 

August 28, 2007 

 Patients should be taught to recognize symptom patterns indicating inadequate asthma 

control and the need for additional therapy (Evidence A). 

 Consider peak flow monitoring for patients who have moderate or severe persistent asthma, 

patients who have a history of severe exacerbations (Evidence B), and patients who poorly 

perceive airflow obstruction and worsening asthma (Evidence D). Long-term daily peak flow 

monitoring can be helpful to (Evidence B): 

— Detect early changes in asthma control that require adjustment in treatment. 

— Evaluate responses to changes in treatment. 

— Provide a quantitative measure of impairment. 

KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 Periodic assessment of asthma control is emphasized. 

 This update (EPR—3: Full Report 2007) makes a stronger distinction than previous 

guidelines between classifying asthma severity and assessing asthma control. 

Interpretation of previous asthma guidelines raised questions about applying the severity 

classifications once treatment is established and also resulted in placing more emphasis on 

severity than on ongoing monitoring of whether therapeutic goals were met. This update 

(EPR—3: Full Report 2007) clarifies the issue: 

— For initiating treatment, asthma severity should be classified, and the initial treatment 

should correspond to the appropriate severity category. 

— Once treatment is established, the emphasis is on assessing asthma control to 

determine if the goals for therapy have been met and if adjustments in therapy (step up 

or step down) would be appropriate. 

 Assessment of asthma control includes the two domains of impairment and risk. 

 Peak flow monitoring: The recommendation to assess diurnal variation was deleted. New 

text was added regarding the patients most likely to benefit from routine peak flow 

monitoring. Emphasis was added that evidence suggests equal benefits to either peak flow 

or symptom-based monitoring; the important issue continues to be having a monitoring plan 

in place. 

 Parameters for lung function, specifically FEV1/FVC, were added as measures of asthma 

control for children. 

 Minimally invasive markers and pharmacogenetic approaches for monitoring asthma. New 

text was added. These approaches have gained increasing attention in clinical research, 

and some applications may be useful in the near future for the clinical management of 

asthma. The concepts are introduced here, although most require further evaluation before 

they can be recommended as tools for routine asthma management. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

55 

August 28, 2007 

GOALS OF THERAPY: ASTHMA CONTROL 

The purpose of periodic assessment and ongoing monitoring is to determine whether the goals 

of asthma therapy are being achieved and asthma is controlled. When asthma is not controlled, 

it is associated with significant asthma burden (Fuhlbrigge et al. 2002), decreased quality of life 

(Schatz et al. 2005b), and increased health care utilization (Schatz et al. 2005a; Vollmer et al. 

2002). The level of asthma control (well controlled, not well controlled, or poorly controlled) is 

the degree to which both dimensions of the manifestations of asthma—impairment and 

risk—are minimized by therapeutic intervention. The level of control at the time of followup 

assessment will determine clinical actions—that is, whether to maintain or adjust therapy. In 

previous guidelines (EPR⎯2 1997; GINA 2002), parameters for control were selected on the 

basis of research that used individual outcomes for evaluating the effectiveness of asthma 

treatments. The composite list of goals reflected the Panel’s opinions of a complete list of 

relevant outcomes that could define asthma control. A recent large international trial 

demonstrated that significant reductions in the rate of severe exacerbations and improvements 

in quality of life were achieved by aiming at achieving guideline-defined asthma control and by 

adjusting therapy to achieve it. At the end of 1 year, 30 percent of the patients achieved total 

control (i.e., the absence of any sign or symptom of asthma), and 60 percent had achieved wellcontrolled asthma (Bateman et al. 2004). 

Interpretation of previous asthma guidelines, in which severity classifications before treatment 

corresponded to recommended steps of treatment, has raised questions about applying severity 

classifications once treatment is established and what elements of asthma should be used to 

monitor asthma during clinical followup (Graham 2006; Wolfenden et al. 2003). This update 

(EPR—3: Full Report 2007) clarifies the issue. For initiating treatment, asthma severity should 

be classified, and the initial treatment should correspond to the appropriate category of severity. 

Once treatment is established, the emphasis is on assessing asthma control to determine if the 

goals for therapy have been met and if adjustments in therapy (step up or step down) would be 

appropriate. 

The Expert Panel recommends that asthma control be defined as follows (Evidence A):

Asthma Control 

 Reduce impairment 

— Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the 

daytime, in the night, or after exertion) 

— Require infrequent use (<2 days a week) of SABA for quick relief of symptoms 

— Maintain (near) “normal” pulmonary function 

— Maintain normal activity levels (including exercise and other physical activity and 

attendance at work or school) 

— Meet patients’ and families’ expectations of and satisfaction with asthma care 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

56 

August 28, 2007 

 Reduce risk 

— Prevent recurrent exacerbations of asthma and minimize the need for ED visits or 

hospitalizations 

— Prevent progressive loss of lung function; for children, prevent reduced lung growth 

— Provide optimal pharmacotherapy with minimal or no adverse effects 

See figures 3–5a, b, and c for classification of asthma control in three different age groups. 

Specific discussion of measures for assessment are in the following section. In general: 

 Assessment of impairment is in the form of questions, such as those presented in figure 3–6 

and within figure 3–7. The focus of these questions is to assess the degree of asthma 

control in the present. The key elements include current pulmonary function and patient’s 

recall of symptoms, physical activity, quality of life, and need for SABA for quick relief of 

symptoms over the previous 2–4 weeks. 

 Assessing the risk of exacerbations is through questions regarding the use of medications, 

particularly oral corticosteroids, or urgent care visits. Low FEV1 is associated with increased 

risk for severe exacerbations (Fuhlbrigge et al. 2001). 

 Assessment of the risk of progressive loss function, or, for children, the risk of reduced lung 

growth (measured by prolonged failure to attain predicted lung function values for age) 

requires longitudinal assessment of lung function, preferably using spirometry. 

 Assessment of the risk of side effects from medication does not directly correspond to the 

varying levels of asthma control. For example, a patient might have well-controlled asthma 

with high doses of ICS and chronic oral corticosteroids but is likely to experience some 

adverse effects from this intense therapy. The risk of side effects can vary in intensity from 

none to very troublesome and worrisome; see component 4—Medications for discussion of 

potential adverse effects associated with different asthma medications. Although not 

directly correlated to control, the risk or evidence of side effects should be included in the 

overall assessment of the risk domain of asthma control. 

 Future work on assessment of asthma control tools will define the relative value of including 

specific biological markers and test how well the tool predicts the risk of exacerbations. 

MEASURES FOR PERIODIC ASSESSMENT AND MONITORING OF ASTHMA CONTROL 

The Expert Panel recommends that ongoing monitoring of asthma control be performed 

to determine whether all the goals of therapy are met—that is, reducing both impairment 

and risk (Evidence B); see figures 3–5 a, b, and c for assessing asthma control for 

different age groups.

The Expert Panel recommends that the frequency of visits to a clinician for review of 

asthma control is a matter of clinical judgment; in general, patients who have intermittent 

or mild persistent asthma that has been under control for at least 3 months should be 

seen by a clinician about every 6 months, and patients who have uncontrolled and/or 

severe persistent asthma and those who need additional supervision to help them follow 

their treatment plan need to be seen more often (EPR⎯2 1997).
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August 28, 2007 

The assessment measures for control monitor six areas described in this section and are 

recommended based on the opinion of the Expert Panel and review of the scientific literature. A 

seventh area, monitoring asthma control with minimally invasive markers, is of increasing 

interest, but many of these markers require further evaluation before they can be recommended 

widely for routine asthma care. 

 Monitoring signs and symptoms of asthma 

 Monitoring pulmonary function 

— Spirometry 

— Peak flow monitoring 

 Monitoring quality of life 

 Monitoring history of asthma exacerbations 

 Monitoring pharmacotherapy for adherence and for potential side effects 

 Monitoring patient–provider communication and patient satisfaction 

 Monitoring asthma control with minimally invasive markers and pharmacogenetics (requires 

further evaluation) 

Monitoring Signs and Symptoms of Asthma 

The Expert Panel recommends that every patient who has asthma should be taught to 

recognize symptom patterns that indicate inadequate asthma control (Evidence A) (See 

also “Component 2: Education for a Partnership in Asthma Care.”). Either symptom and/or 

PEF monitoring should be used as a means to determine the need for intervention, including 

additional medication, in the context of a written asthma action plan. 

The Expert Panel recommends that symptoms and clinical signs of asthma should be 

assessed at each health care visit through physical examination and appropriate 

questions (EPR⎯2 1997). This is important for optimal asthma care. 

The Expert Panel recommends that the detailed symptoms history should be based on a 

short (2–4 weeks) recall period (EPR⎯2 1997). Patients’ detailed recall of symptoms 

decreases over time; therefore, the clinician may choose to assess over a 2-week, 3-week, or 

4-week recall period. Symptom assessment for periods longer than 4 weeks should reflect 

more global symptom assessment, such as inquiring whether the patient’s asthma has been 

better or worse since the last visit and inquiring whether the patient has encountered any 

particular difficulties during specific seasons or events. Figure 3–7 provides an example of a set 

of questions that can be used to characterize both global (long-term recall) and recent 

(short-term recall) asthma symptoms. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

The Expert Panel recommends that assessment of the patient’s symptom history should 

include at least four key symptom expressions (Evidence B, extrapolation from clinical 

trials; and Evidence C, from observational studies):

 Daytime asthma symptoms (including wheezing, cough, chest tightness, or shortness of 

breath) 

 Nocturnal awakening as a result of asthma symptoms 

 Frequency of use of SABA for relief of symptoms 

 Inability or difficulty performing normal activities (including exercise) because of asthma 

symptoms 

Monitoring Pulmonary Function 

The Expert Panel recommends that, in addition to assessing symptoms, it is also 

important to assess pulmonary function periodically (Evidence B, extrapolation from 

clinical trials; and Evidence C, from observational studies). The main methods are 

spirometry and peak flow monitoring. 

Low FEV1 is associated with increased risk of severe asthma exacerbations (Fuhlbrigge et al. 

2001). Regular monitoring of pulmonary function is particularly important for asthma patients 

who do not perceive their symptoms until airflow obstruction is severe. There is no readily 

available method of detecting the “poor perceivers.” The literature reports that patients who had 

a near-fatal asthma exacerbation, as well as older patients, are more likely to have poor 

perception of airflow obstruction (Connolly et al. 1992; Kikuchi et al. 1994). 

Spirometry 

The Expert Panel recommends the following frequencies for spirometry measurements: 

(1) at the time of initial assessment (Evidence C); (2) after treatment is initiated and 

symptoms and PEF have stabilized, to document attainment of (near) “normal” airway 

function; (3) during a period of progressive or prolonged loss of asthma control; and 

(4) at least every 1–2 years to assess the maintenance of airway function (Evidence B, 

extrapolation from clinical trials). Spirometry may be indicated more often than every 1–

2 years, depending on the clinical severity and response to management (Evidence D). 

These spirometry measures should be followed over the patient’s lifetime to detect 

potential for decline and rate of decline of pulmonary function over time (Evidence C). 

As noted previously, adjusting therapy according to the level of asthma control improves the 

patient’s quality of life and reduces morbidity due to asthma (Bateman et al. 2004). Measures of 

control in this and related studies, as well as in numerous clinical trials that examine drug 

efficacy, include measures of lung function obtained by spirometry. Lung function declines in 

adults as they grow older, and adults who have asthma have greater declines, on average, than 

adults who do not have asthma and do not smoke. For children, lung function increases as they 

grow older, until maximal lung function is achieved, which occurs for most individuals by 20 

years of age. Children who have asthma may have reductions in lung growth compared to 

children who do not have asthma. The postbronchodilator FEV1 measure can be used to follow 

lung growth patterns over time (Covar et al. 2004a). Observations of reduced lung growth may 

reflect a progressive worsening of asthma control that should be treated accordingly. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

Spirometry with measurement of the FEV1 is also useful: 

 As a periodic (e.g., yearly) check on the accuracy of the peak flow meter (Miles et al. 1995) 

for patients who are monitoring PEF. 

 When more precision is desired in measuring lung function (e.g., when evaluating response 

to bronchodilator or nonspecific airway responsiveness or when assessing response to a 

“step down” in pharmacotherapy). 

 When PEF results are unreliable (e.g., in some very young or elderly patients, when 

neuromuscular or orthopedic problems are present, or technical artifact is suspected (see 

below)) and the physician needs the quality checks that are available only with spirometry 

(Hankinson and Wagner 1993). 

Peak Flow Monitoring 

The Expert Panel recommends the following: 

 If peak flow monitoring is performed, the written asthma action plan should use the 

patient’s personal best peak flow as the reference value (EPR⎯Update 2002). 

 Consider long-term daily peak flow monitoring for: 

— Patients who have moderate or severe persistent asthma (Evidence B). 

— Patients who have a history of severe exacerbations (Evidence B). 

— Patients who poorly perceive airflow obstruction and worsening asthma 

(Evidence D). 

— Patients who prefer this monitoring method (Evidence D). 

 Long-term daily peak flow monitoring can be helpful to (EPR⎯Update 2002): 

— Detect early changes in disease states that require treatment. 

— Evaluate responses to changes in therapy. 

— Afford a quantitative measure of impairment. 

 Peak flow monitoring during exacerbations will help determine the severity of the 

exacerbations and guide therapeutic decisions in the home, school, clinicians’ office, 

or ED (See “Component 2: Education for a Partnership in Asthma Care” and 

section 5, “Managing Exacerbations of Asthma.”). 

 Consider home peak flow monitoring during exacerbations of asthma for: 

— Patients who have a history of severe exacerbations (Evidence B). 

— Patients who have moderate or severe persistent asthma (Evidence B). 

— Patients who have difficulty perceiving signs of worsening asthma (Evidence D). 

PEF measurements, using either handheld mechanical or electronic metered devices, provide a 

means to obtain simple, quantitative, and reproducible assessments of the existence and 

severity of airflow obstruction. It must be stressed that peak flow meters function best as tools 

for ongoing monitoring, not diagnosis. Because the measurement of PEF is dependent on 

effort and technique, patients need instructions, demonstrations, and frequent reviews of 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

technique. See “Component 2: Education for a Partnership in Asthma Care” for detailed 

instructions on using peak flow meters. The accuracy of peak flow monitoring devices may 

decrease over time (Irvin et al. 1997); therefore, measurements that are at odds with the clinical 

status of the patient may be related to technical and not physiologic factors, and consideration 

should be given to reviewing technique with the patient or replacing the device the patient is 

currently using. The patient’s measured personal best peak flow is the most appropriate 

reference value for the patient’s action plan. 

In clinical trials, peak flow values have been used as major outcome measures to monitor both 

asthma control and treatment responses, short (Lazarus et al. 2001) and long term (Boushey et 

al. 2005). In the context of both impairment and risk domains for asthma severity reviewed 

previously, it should be noted that peak flow values may not correlate with other asthma 

outcome measures such as treatment failure (Leone et al. 2001) or asthma exacerbations 

(Lazarus et al. 2001). Although peak flow monitoring to guide chronic asthma management has 

been reported to be valuable in studies more reflective of clinical practice, the results are not 

consistent enough for this tool to be recommended uniformly for all asthma patients (Jain et al. 

1998) (See Evidence Table 2, Usefulness of Peak Flow Measurement, and EPR—Update 

2002.). Thus, the relative usefulness of peak flow measurements as monitoring tools can be 

individualized, based on the patient’s age (decreased utility in preschool children and the 

elderly), socioeconomic status (minority and poor children show greatest benefit) (Yoos et al. 

2002), asthma pattern (of questionable utility to monitor individuals who have histories of rapid 

onset of severe airflow obstruction), asthma severity (Llewellin et al. 2002), ability to perceive 

signs and symptoms of early worsening of asthma (Jain et al. 1998), and the clinician’s and 

patient’s opinions as to their contribution in achieving and maintaining acceptable asthma 

control. 

Peak Flow Versus Symptom-Based Monitoring Action Plan 

A systematic review of the evidence in 2002 concluded that, although studies available at that 

time were limited, studies did not clearly show that a peak flow monitoring-based action plan 

was better than a symptom monitoring-based plan in improving outcomes but that it did show 

similar benefits. 

Evidence generated since the 2002 review does not change these recommendations. 

The Expert Panel recommends the following:

 Either peak flow monitoring or symptom monitoring, if taught and followed correctly, 

may be equally effective (Evidence B). 

 Whether peak flow monitoring, symptom monitoring, or a combination of approaches 

is used, self-monitoring is important to the effective self-management of asthma 

(Evidence A). The nature and intensity of self-monitoring should be individualized, based 

on such factors as asthma severity, the patient’s ability to perceive airflow obstruction, 

availability of peak flow meters, and patient preferences. Patient preferences for objective 

measures or certain patient circumstances, such as inability either to perceive or to report 

signs and symptoms of worsening asthma, warrant the use of peak flow monitoring and 

justify the associated time, energy, and costs to the clinician and patient (Evidence D). 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

 Provide to all patients a written asthma action plan that includes daily treatment and 

recognizing and handing worsening asthma, including self-adjustment of medications 

in response to acute symptoms or changes in PEF measures. Written action plans 

are particularly recommended for patients who have moderate or severe persistent 

asthma, a history of severe exacerbations, or poorly controlled asthma (Evidence B). 

Either peak flow or symptom self-monitoring appears to increase patients’ awareness of the 

disease status and control, thereby helping patients “tune in” to their disease; and action 

plans enhance clinician–patient communication. Thus, the nature of the plan, whether it is 

based on symptoms or based on peak flow, is not the important issue; rather, it is having a 

plan in place versus not having one at all. For additional discussion of written asthma action 

plans, see component 2—Education for Partnership in Asthma Care and section 4, 

“Managing Asthma Long Term in Children, School Issues.” 

Monitoring Quality of Life 

The Expert Panel recommends that several key areas of quality of life and related loss of 

physical function should be assessed periodically for each person who has asthma 

(Evidence C). These include:

 Any work or school missed because of asthma 

 Any reduction in usual activities (either home/work/school or recreation/exercise) 

 Any disturbances in sleep due to asthma 

 Any change in caregivers’ activities due to a child’s asthma (for caregivers of children who 

have asthma) 

See figure 3–7 for sample questions that characterize quality-of-life concerns for persons who 

have asthma. 

The goals of asthma treatment include improving quality of life for people who have asthma in 

addition to controlling symptoms, reducing the risk of exacerbations, and preventing 

asthma-related death. It is important, therefore, to examine how the disease expression and 

control are affecting the patient’s quality of life. Several dimensions of quality of life may be 

important to track; these include physical function, role function, and mental health function. 

Clinical asthma status parameters correlate only moderately with quality-of-life measures. 

Correlations between symptoms and quality of life are often in the low-to-moderate range, while 

correlations with pulmonary function measures are quite weak. These observations suggest 

that perceptions and experiences of patients must be assessed directly and not imputed from 

measures of clinical status. Quality of life appears to be a distinct component of asthma health 

status, along with nighttime symptoms, daytime symptoms, and SABA use (Juniper et al. 2004). 

In general, the impact of asthma is greater on the physical functioning component of life quality 

than on mental functioning (Adams et al. 2006; Graham et al. 2000; Stahl et al. 2003). 

However, when loss of physical functioning in valued life activities occurs, a higher correlation 

with quality of life is found among adults who have asthma. Valued life activities are those that 

individuals find most meaningful or pleasurable, and loss of these has been found to have a 

significant association with an increase in clinical asthma severity, patients’ perception of 

asthma severity, and decrease in general physical function (Katz et al. 2004). Similarly, among 

adolescents who have asthma, quality of life was found to correlate with shortness of breath 

during exercise (Hallstrand et al. 2003). In contrast, in younger children (mean age of 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

62 

August 28, 2007 

9.3 ± 2.2 years), quality of life was more associated with the level of anxiety (Annett et al. 2001). 

Significant reduction in quality of life is also apparent when people who have asthma also have 

comorbid chronic conditions, such as diabetes, arthritis, heart disease, stroke, cancer, and 

osteoporosis (Adams et al. 2006). 

The predictors of quality of life among people who have asthma may be related to levels of 

asthma severity. Lung function, however, was not found to be an independent predictor of 

quality of life at any level of severity, whereas shortness of breath was found to predict quality of 

life at all levels of asthma severity (Moy et al. 2001; Wijnhoven et al. 2001). Asthma symptom 

frequency has been found to be the most significant determinant of the subjective experience of 

asthma and perception of quality of life (Schatz et al. 2005a). Another important reason to 

monitor health-related quality of life is that it predicts health care utilization among patients who 

have asthma (Eisner et al. 2002; Magid et al. 2004) and for this reason may be a useful method 

of identifying patients who are at risk of exacerbation. Patients’ reports of impaired quality of life 

to their primary care providers (PCPs) also were found to result in increased interventions, 

especially patient education and counseling, as well as medication changes (Jacobs et al. 

2001). 

Quality of life, perceptions of asthma control, and depression are psychosocial factors worth 

assessing over time, because they may affect directly the ability to engage in self-management 

of asthma and affect indirectly asthma morbidity and mortality outcomes. Both asthma-specific 

and generic quality-of-life measures are associated with patients’ perceived control of asthma 

(Katz et al. 2002). The coping resources and specific coping style used by patients who have 

respiratory disease have been associated with quality of life. Among patients who have asthma, 

a more emotional or avoidant coping style, low self-efficacy, and low mastery feelings were 

found to be independently associated with poor quality of life (Hesselink et al. 2004). 

Many instruments have been developed and tested to assess quality of life among persons who 

have asthma in all age groups. Both asthma-specific and generic quality-of-life instruments 

have been tested and validated (See box 3–4.). Specific measures are more useful for 

assessing an individual’s response to treatment and are more sensitive than generic measures 

in detecting the impact of changes in asthma severity or control (Graham et al. 2000). Generic 

measures are more useful in assessing the broad impact of asthma on the quality of life and 

functioning in a population of people (Graham et al. 2000; Noonan et al. 1995) and for 

comparing populations across diagnoses of chronic illness (Graham et al. 2000; Mancuso et al. 

2001). 

BOX 3–4. INSTRUMENTS FOR ASSESSING ASTHMA-SPECIFIC 

AND GENERIC QUALITY OF LIFE 

Asthma-Specific Quality of Life 

 Mini Asthma Quality of Life Questionnaire (Juniper et al. 1999a) 

 Asthma Quality of Life Questionnaire (Katz et al. 1999; Marks et al. 1993) 

 ITG Asthma Short Form (Bayliss et al. 2000) 

 Asthma Quality of Life for Children (Juniper et al. 1996) 

Generic Quality of Life 

 SF-36 (Bousquet et al. 1994) 

 SF-12 (Ware et al. 1996) 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

Most of these instruments, however, are more suited for use in research studies than in clinical 

settings. Certain concerns preclude the Expert Panel’s recommendation of the general 

adoption of these instruments at this time for routine encounters. These concerns include lack 

of experience with the use of the instruments in clinical practice and the time involved in 

administering the surveys. A few questionnaires have been shortened (Juniper et al. 1996) or 

tested by alternate methods of administration, such as telephone surveys (Pinnock et al. 2005). 

Still, the importance of this concept to people who have asthma warrants that clinicians assess 

and monitor the effect of asthma on quality of life. See figure 3–7 for sample questions that may 

be used in the clinical setting for characterizing quality-of-life concerns for persons who have 

asthma. 

Monitoring History of Asthma Exacerbations 

The Expert Panel recommends that, during periodic assessments, clinicians should 

question the patient and evaluate any records of patient self-monitoring (figure 3–7) to 

detect exacerbations, both those that are self-treated and those treated by other health 

care providers (Evidence C). Exacerbations of asthma are episodes of marked increases in 

symptoms and reductions in lung function that interfere with the ability to perform usual activities 

unless quick relief therapy, such as SABA and additional corticosteroid treatment, is used. (See 

section 5 on “Managing Exacerbations of Asthma,” for the classification of severity of 

exacerbations.) The most common cause of severe exacerbations is infection with a respiratory 

virus, especially rhinovirus, but exacerbations may be brought on by exposures to allergens or 

irritants, air pollutants, certain medications, and, possibly, emotional stress. Exacerbations also 

can be triggered by withdrawal of ICS or other long-term-control therapy. (See “Component 3: 

Control of Environmental Factors and Comorbid Conditions That Affect Asthma” for a review of 

literature on causes of exacerbations.) 

It is important to evaluate the frequency, rate of onset, severity, and causes of exacerbations. A 

history of previous exacerbations, especially in the past year, is the strongest predictor of future 

severe exacerbations leading to ED visits and hospitalizations (Adams et al. 2000; Eisner et al. 

2001; Ford et al. 2001; Lieu et al. 1998). The patient should be asked about precipitating 

exposures and other factors. Specific inquiry into unscheduled visits to health care providers, 

telephone calls for assistance, and use of urgent or emergency care facilities is helpful. 

Severity of the exacerbation can be estimated by the increased need for oral corticosteroids. 

Finally, any hospitalizations should be documented, including the facility, duration of stay, and 

any use of critical care or intubation. To facilitate continuity of care, the clinician then can 

request summaries of all care received. 

Monitoring Pharmacotherapy for Adherence and Potential Side Effects 

The Expert Panel recommends monitoring the following factors at each visit: patient’s 

adherence to the regimen, inhaler technique, and side effects of medications 

(Evidence C). See sample questions in figure 3–7 for assessing the patient’s adherence to, 

concerns about, or adverse experiences with the drug regimen. See component 2—Education 

for a Partnership in Asthma Care for further discussion of patient’s adherence to treatment. 

Monitoring Patient–Provider Communication and Patient Satisfaction 

The Expert Panel recommends that health care providers should routinely assess the 

effectiveness of patient–clinician communication (Evidence D). (See figure 3–7 for sample 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

questions.) Open and unrestricted communication among the clinician, the patient, and the 

patient’s family is essential to ensure successful self-management by the patient who has 

asthma. A patient’s negative attitude toward medication and/or reluctance toward selfmanagement are risk factors for severe exacerbations (Adams et al. 2000). Every effort should 

be made to encourage open discussion of concerns and expectation of therapy. See 

“Component 2: Education for a Partnership in Asthma Care” for specific strategies to enhance 

communication and patient adherence to the treatment plan. 

The Expert Panel recommends that two aspects of patient satisfaction should be 

monitored: satisfaction with asthma control and satisfaction with the quality of care 

(Evidence D). Patients’ satisfaction with their asthma care and resolution of fears and concerns 

are important goals and will increase adherence to the treatment plan (Haynes et al. 1979; 

Meichenbaum and Turk 1987). See figures 3–2, 3–7, and 3–8 for examples of questions to use 

in monitoring patient satisfaction. 

Monitoring Asthma Control With Minimally Invasive Markers and Pharmacogenetics 

The Expert Panel recommends some minimally invasive markers for monitoring asthma 

control—such as spirometry and airway hyperresponsiveness—that are appropriately 

used, currently and widely, in asthma care (Evidence B). Other markers, such as sputum 

eosinophils and FeNO, are increasingly used in clinical research and will require further 

evaluation in adults and children before they can be recommended as a clinical tool for 

routine asthma management (Evidence D). 

The interest in minimally invasive markers of asthma control arises from concerns over the 

possible dissociation between the severity of symptoms and impairments in function in the 

present, and the severity of the risk of exacerbations or progressive loss of pulmonary function 

in the future. For example, in a patient who reported daily symptoms, twice weekly nocturnal 

awakenings from asthma, shortness of breath on climbing stairs, and two exacerbations 

requiring ED treatment in the previous 12 months when first seen, does the resolution of all 

symptoms while taking treatment with a low dose of an ICS necessarily mean that his/her risk of 

exacerbations in the future is now acceptably low? A similar question might be asked of a 

patient treated with a high dose of an ICS and a LABA. If symptoms are completely controlled, 

can treatment be tapered without jeopardizing the patient’s protection against future 

exacerbations? Must high-dose therapy for asthma be continued in a patient whose symptoms 

and function are well controlled but whose spirometry reveals a severely reduced but stable 

airflow obstruction (e.g., FEV1 = 55 percent predicted)? Thus, although direct questioning is the 

best approach for assessing impairment, measurements of “biomarkers” are being examined as 

a way of assessing risk and thereby guiding adjustments in treatment. 

The goal is to find a marker for asthma akin to hemoglobin A1C for diabetes (Its elevation is an 

index of the control of diabetes, and its reduction by therapy is known to reduce the risks of 

cardiovascular and renal complications.). To be practical, the marker should be measurable 

with minimal discomfort and risk to the patient and at minimal cost. 

Spirometry: Perhaps the oldest marker of asthma impairment and risk is maximal expiratory 

flow, most commonly measured as FEV1 and expressed as a percentage of predicted. Two 

large, retrospective cohort studies have shown that a reduction in FEV1 at an annual visit is 

associated with increases in the risk of an attack of wheezing and shortness of breath over the 

next 12 or 36 months for pediatric and adult cohorts, respectively, and that the risk is greatest 

for those who have values consistent with “severe asthma,” as described by the guidelines 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

(<60 percent predicted); the risk is next greatest for those who have an FEV1 qualifying as 

“moderate asthma” (60–79 percent predicted); and the risk is least for those who have an FEV1

for “mild asthma” (80–100 percent predicted) (Fuhlbrigge et al. 2001; Fuhlbrigge et al. 2006; 

Kitch et al. 2004). The validity is less well established of using a reduction in FEV1 as a marker 

of increased risk of progressive loss of pulmonary function in patients. 

Airway responsiveness is measured by delivering serially increasing doses of a provocative 

agent, like methacholine, and calculating the “provocative dose” causing a 20 percent fall in 

FEV1 (“PC20”). Making this measurement is time consuming, expensive, and so far has been 

disappointing in predicting exacerbations in patients weaned from ICS treatment (Deykin et al. 

2005). More promising, but still under investigation, is measurement of the PD15 to mannitol 

(Leuppi et al. 2005), possibly because it provokes bronchoconstriction indirectly, through the 

activation of mast cells in the bronchial mucosa. A system for delivering progressively 

increasing doses from simple inhaler devices has been developed (Leuppi et al. 2002), but at 

the time of this writing, the system has been approved for use only in Australia. 

Sputum eosinophils: Two approaches to measuring the intensity of eosinophilic inflammation 

deserve mention. One is to analyze the cells and mediators in the sputum induced by inhalation 

of hypertonic saline aerosol (Djukanovic et al. 2002). The other is to measure the concentration 

of gases or volatile substances in exhaled air. 

Analysis of induced sputum has attracted much attention, and analysis of the number or 

proportion of eosinophils in the sample holds up well in distinguishing patients who have or do 

not have asthma in repeatability, in association with other markers of asthma severity, and in 

predicting responsiveness to starting or withdrawing ICS treatment (Deykin et al. 2005). Its 

principal drawbacks are the difficulties in standardizing the methods for obtaining, preparing, 

and analyzing the samples, even across specialized centers, and the demands on the time of 

highly trained technical staff for obtaining and processing the samples. Still, a controlled 

prospective study has shown that adjusting ICS treatment to control sputum eosinophilia—as 

opposed to controlling symptoms, SABA use, nocturnal awakenings, and pulmonary 

function—significantly reduced both the rate of exacerbations and the cumulative dose of ICS 

(Green et al. 2002). 

Fractional exhaled nitric oxide: Increases in FeNO are thought to reflect the intensity of 

eosinophilic inflammation of the bronchial mucosa. Like sputum eosinophil counts, 

measurement of FeNO distinguishes patients who do or do not have asthma, is repeatable, is 

associated with other markers of asthma severity, and, in some but not all studies, predicts 

responsiveness to starting or withdrawing ICS or oral corticosteroid treatment (Kharitonov et al. 

1997; Pijnenburg et al. 2005; Taylor 2006). A device for measuring FeNO has been approved 

by the U.S. Food and Drug Administration (FDA); and a prospective, controlled study has shown 

that when ICS treatment was adjusted to control FeNO, as opposed to controlling the standard 

indices of asthma, the cumulative dose of ICS was reduced, with no worsening of the frequency 

of asthma exacerbations (Smith et al. 2005). 

Other methods include measurement of compounds, like hydrogen ion (pH), 

isoprostanes, leukotriene metabolites, and products of nitrosylation in EBC (Hunt 2002). 

The condensate is collected by passing exhaled air through a cold tube for 10–20 minutes. 

Several studies have shown differences in the concentrations of various compounds in the EBC 

of healthy persons and those who have asthma, but work remains to be done to establish the 

range of normal values, repeatability, association with other markers of asthma severity, and 

responsiveness to treatment. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

A recent study in children suggests that low pulmonary function and high indicators of markers 

of allergic airway inflammation—such as FeNO, blood eosinophil count, and IgE—predict 

greater response to ICS than to LTRAs in children (Szefler et al. 2005). Several studies indicate 

that monitoring biomarkers—such as measures of hyperresponsiveness, sputum eosinophils, 

and FeNO—can be used to guide treatment decisions (Green et al. 2002; Smith et al. 2005; 

Sont et al. 1999). Each of these studies has shown a reduction in asthma exacerbations with 

the biomarker-based treatment approach, as compared to treatment based on symptoms and 

pulmonary function, although the trend toward decreased exacerbations did not reach statistical 

significance in one of the studies (Smith et al. 2005). In addition, FeNO and sputum 

eosinophilis may be used in diagnosing asthma, as their sensitivity and specificity approach that 

of methacholine challenges, and both have sensitivities greater than SABA reversibility (Dupont 

et al. 2003; Smith et al. 2004). 

Once these tools are refined for application to the clinical setting, they could be useful in guiding 

treatment selection to achieve and monitor asthma control quickly. It is important that tools for 

using biomarkers to diagnose or monitor asthma be tested in both children and adults, because 

the presentation of the disease may differ between age groups. 

Pharmacogenetics in Managing Asthma 

Pharmacogenetics is the study of the genetic causes of between-person variation in drug 

treatment response. To date, three genes have been identified that influence response to 

specific asthma medications: LTRA (Alox 5) (Drazen 1999; Lima et al. 2006), SABA (B2AR) 

(Israel et al. 2000, 2004; Silverman et al. 2003; Taylor et al. 2000), and ICS (CRHR1) (Tantisira 

et al. 2004). It is not clear that the functional variants responsible for these associations have 

been identified. The ADRB2 gene has been studied the most. Multiple studies have shown that 

individuals homozygous for Arg/Arg at position 16 of the protein have about a 3 percent 

reduction in peak flow when compared to Gly/Gly homozygotes. Because individuals having 

Arg/Arg homozygotes account for only 16 percent of the Caucasian population in the United 

States, this is a small amount of variability in the clinical phenotype in a small percentage of the 

population and thus is of questionable clinical significance. Studies of the influence of the 

homozygous Arg-16 genetic variant on response to LABA are inconclusive. Some studies show 

reduced lung function and increased symptoms (Wechsler et al. 2006); others show no adverse 

effects (Bleecker et al. 2006; Taylor et al. 2000) (see component 4—Medications). None of 

these genotypes, in isolation, explains a sufficient amount of variation in the drug-response 

phenotype to warrant clinical testing at this time. It is likely, however, that prediction of 

response to asthma treatment will be a clinical reality in the near future. 

METHODS FOR PERIODIC ASSESSMENT AND MONITORING OF ASTHMA CONTROL 

Each of the key measures used in the periodic assessment of asthma (i.e., signs and 

symptoms, pulmonary function, quality of life, history of exacerbations, pharmacotherapy, and 

patient–provider communication and patient satisfaction) can be obtained by several methods. 

The principal methods include the clinician’s assessment and the patient’s (and/or parent’s or 

caregiver’s) self-assessment. In addition, population-based assessment of asthma care is 

being developed in the managed care field. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

67 

August 28, 2007 

Clinician Assessment 

The Expert Panel recommends that patients who have intermittent or mild or moderate 

persistent asthma (i.e., requiring steps 1, 2, 3, or 4 treatment) that has been under control 

for at least 3 months should be seen by a clinician about every 6 months. Patients who 

have uncontrolled and/or severe persistent asthma (i.e., requiring steps 5 or 6 treatment) 

and those who need additional supervision to help them follow their treatment plan 

should be seen more often (EPR⎯2 1997).

The frequency of visits to a clinician for review of asthma control is a matter of clinical judgment. 

Clinical assessment of asthma should be obtained through medical history and physical 

examination with appropriate pulmonary function testing. Optimal followup assessment of 

medical history may be achieved best via a consistent set of questions (figure 3–7). 

Patient Self-Assessment 

The Expert Panel recommends that clinicians should encourage patients to use selfassessment tools to determine from the perspective of the patient and/or the patient’s 

family whether the asthma is well controlled (EPR⎯2 1997). The two general methods are 

(1) a daily diary and (2) a periodic self-assessment form to be filled out by the patient and/or 

family member, usually at the time of the followup visits to the clinician. Patients are less likely 

to see completion of diaries and forms as a burden if they receive feedback from the clinician 

that allows them to see value in self-monitoring. 

 The daily diary should include the key factors to be monitored at home: symptoms and/or 

peak flow, medication use, and restricted activity (See “Component 2: Education for a 

Partnership in Asthma Care.”). Monitoring with a daily diary will be most useful to patients 

whose asthma is not yet under control and who are trying new treatments. It is also useful 

for those who need help in identifying environmental or occupational exposures that make 

their asthma worse. 

 The self-assessment questionnaires that can be completed at office visits are intended to 

capture the patient’s and family’s impression of asthma control, self-management skills, and 

overall satisfaction with care. Several multidimensional instruments have been developed to 

assess control. Four of those that have been validated in more than one study for their 

psychometric quality are listed in figure 3–8. Two that have given permission are 

reproduced in that figure. Each of these four validated tools includes the impairment domain 

by measuring the dimension of symptoms, activity limitations, and need for quick relief 

medication, but not all include the physiological dimension of lung function. Only one 

includes a biological marker. Most of the questionnaires do not assess the risk domain of 

asthma control. Figure 3–9 is a sample self-assessment tool that incorporates both 

impairment and risk domains; however, this instrument has not had standardized 

assessment for validity and reliability. 

Population-Based Assessment 

Asthma care is of increasing interest in various health care settings. Important regulatory 

organizations for the health care industry (e.g., the National Committee on Quality Assurance) 

have included the care of persons who have asthma as a key indicator of the quality of 

managed care. In this context, periodic population-based assessment of asthma care has 

begun to emerge as an issue for patients and their clinical care providers. This type of 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

assessment often uses population experience, such as hospitalization or ED visit rates, to 

examine care within different clinical settings and among different providers. Complex, 

standardized population surveys (including lengthy health-status instruments) are being tested 

experimentally in the managed care setting. 

Referral to an Asthma Specialist for Consultation or Comanagement 

The Expert Panel recommends referral for consultation or care to a specialist in asthma 

care (usually, a fellowship-trained allergist or pulmonologist; occasionally, other 

physicians who have expertise in asthma management, developed through additional 

training and experience) when (Evidence D):

 Patient has had a life-threatening asthma exacerbation. 

 Patient is not meeting the goals of asthma therapy after 3–6 months of treatment. An earlier 

referral or consultation is appropriate if the physician concludes that the patient is 

unresponsive to therapy. 

 Signs and symptoms are atypical, or there are problems in differential diagnosis. 

 Other conditions complicate asthma or its diagnosis (e.g., sinusitis, nasal polyps, 

aspergillosis, severe rhinitis, VCD, GERD, COPD). 

 Additional diagnostic testing is indicated (e.g., allergy skin testing, rhinoscopy, complete 

pulmonary function studies, provocative challenge, bronchoscopy). 

 Patient requires additional education and guidance on complications of therapy, problems 

with adherence, or allergen avoidance. 

 Patient is being considered for immunotherapy. 

 Patient requires step 4 care or higher (step 3 for children 0–4 years of age). Consider 

referral if patient requires step 3 care (step 2 for children 0–4 years of age). 

 Patient has required more than two bursts of oral corticosteroids in 1 year or has an 

exacerbation requiring hospitalization. 

 Patient requires confirmation of a history that suggests that an occupational or 

environmental inhalant or ingested substance is provoking or contributing to asthma. 

Depending on the complexities of diagnosis, treatment, or the intervention required in the 

work environment, it may be appropriate in some cases for the specialist to manage the 

patient over a period of time or to comanage with the PCP. 

In addition, patients who have significant psychiatric, psychosocial, or family problems that 

interfere with their asthma therapy may need referral to an appropriate mental health 

professional for counseling or treatment. These problems have been shown to interfere with a 

patient’s ability to adhere to treatment (Strunk et al. 1985, 1987). 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

FIGURE 3–1. SUGGESTED IT EMS FOR MEDICAL HISTORY* 

A detailed medical history of the new patient who is known or thought to have asthma should address the 

following items: 

1. Symptoms 

Cough 

Wheezing 

Shortness of breath 

Chest tightness 

Sputum production 

2. Pattern of symptoms 

Perennial, seasonal, or both 

Continual, episodic, or both 

Onset, duration, frequency (number of days or nights, per 

week or month) 

Diurnal variations, especially nocturnal and on awakening in 

early morning 

3. Precipitating and/or aggravating factors 

Viral respiratory infections 

Environmental allergens, indoor (e.g., mold, house-dust mite, 

cockroach, animal dander or secretory products) and 

outdoor (e.g., pollen) 

Characteristics of home including age, location, cooling and 

heating system, wood-burning stove, humidifier, carpeting 

over concrete, presence of molds or mildew, characteristics 

of rooms where patient spends time (e.g., bedroom and 

living room with attention to bedding, floor covering, stuffed 

furniture) 

Smoking (patient and others in home or daycare) 

Exercise 

Occupational chemicals or allergens 

Environmental change (e.g., moving to new home; going on 

vacation; and/or alterations in workplace, work processes, 

or materials used) 

Irritants (e.g., tobacco smoke, strong odors, air pollutants, 

occupational chemicals, dusts and particulates, vapors, 

gases, and aerosols) 

Emotions (e.g., fear, anger, frustration, hard crying or 

laughing) 

Stress (e.g., fear, anger, frustration) 

Drugs (e.g., aspirin; and other nonsteroidal anti-inflammatory 

drugs, beta-blockers including eye drops, others) 

Food, food additives, and preservatives (e.g., sulfites) 

Changes in weather, exposure to cold air 

Endocrine factors (e.g., menses, pregnancy, thyroid disease) 

Comorbid conditions (e.g. sinusitis, rhinitis, GERD) 

4. Development of disease and treatment 

Age of onset and diagnosis 

History of early-life injury to airways (e.g., bronchopulmonary 

dysplasia, pneumonia, parental smoking) 

Progression of disease (better or worse) 

Present management and response, including plans for 

managing exacerbations 

Frequency of using SABA 

Need for oral corticosteroids and frequency of use 

5. Family history 

History of asthma, allergy, sinusitis, rhinitis, 

eczema, or nasal polyps in close relatives 

6. Social history 

Daycare, workplace, and school characteristics 

that may interfere with adherence 

Social factors that interfere with adherence, 

such as substance abuse 

Social support/social networks 

Level of education completed 

Employment 

7. History of exacerbations 

Usual prodromal signs and symptoms 

Rapidity of onset 

Duration 

Frequency 

Severity (need for urgent care, hospitalization, 

ICU admission) 

Life-threatening exacerbations (e.g., intubation, 

intensive care unit admission) 

Number and severity of exacerbations in the 

past year. 

Usual patterns and management (what works?) 

8. Impact of asthma on patient and family 

Episodes of unscheduled care (ED, urgent care, 

hospitalization) 

Number of days missed from school/work 

Limitation of activity, especially sports and 

strenuous work 

History of nocturnal awakening 

Effect on growth, development, behavior, school 

or work performance, and lifestyle 

Impact on family routines, activities, or dynamics 

Economic impact 

9. Assessment of patient’s and family’s 

perceptions of disease 

Patient’s, parents’, and spouse’s or partner’s 

knowledge of asthma and belief in the 

chronicity of asthma and in the efficacy of 

treatment 

Patient’s perception and beliefs regarding use 

and long-term effects of medications 

Ability of patient and parents, spouse, or partner 

to cope with disease 

Level of family support and patient’s and 

parents’, spouse’s, or partner’s capacity to 

recognize severity of an exacerbation 

Economic resources 

Sociocultural beliefs 

* This list does not represent a standardized assessment or diagnostic instrument. The validity and reliability of this list have not been 

assessed. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

70 

August 28, 2007 

FIGURE 3–2. SAMPLE QUESTI ONS* FOR THE DIAGNOSIS AND 

INITIAL ASSESSMENT OF ASTHMA 

A “yes” answer to any question suggests that an asthma diagnosis is likely. 

In the past 12 months... 

 Have you had a sudden severe episode or recurrent episodes of coughing, wheezing 

(high-pitched whistling sounds when breathing out), chest tightness, or shortness of 

breath? 

 Have you had colds that “go to the chest” or take more than 10 days to get over? 

 Have you had coughing, wheezing, or shortness of breath during a particular season or 

time of the year? 

 Have you had coughing, wheezing, or shortness of breath in certain places or when 

exposed to certain things (e.g., animals, tobacco smoke, perfumes)? 

 Have you used any medications that help you breathe better? How often? 

 Are your symptoms relieved when the medications are used? 

In the past 4 weeks, have you had coughing, wheezing, or shortness of breath... 

 At night that has awakened you? 

 Upon awakening? 

 After running, moderate exercise, or other physical activity? 

* These questions are examples and do not represent a standardized assessment or diagnostic instrument. The 

validity and reliability of these questions have not been assessed. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

FIGURE 3–3a. SAMPLE SPIROME TRY VOLUME TIME AND FLOW 

VOLUME CURVES 

Key: FEV1, forced expiratory volume in 1 second 

FIGURE 3–3b. REPORT OF SPIR OMETRY FINDINGS PRE- AND 

POSTBRONCHODILATOR 

Prebronchodilator Postbronchodilator 

Study: 

bronch 

Age: 59 

ID: 

Height: 

175 cm 

Test 

date: 

8/7/06 

Sex: M 

Time: 

9:38 a.m. 

System: 

7 20 17 

 

Study: 

bronch 

Age: 59 

ID: 

Height:

175 cm 

Test 

date: 

8/7/06 

Sex: M 

Time: 

9:58 a.m. 

System: 

7 20 17 

 Trial FVC FEV1

FEV1/ 

FVC (%) 

 

Trial FVC FEV1

FEV1/ 

FVC (%) 

 1 4.34 2.68 61.8% 1 4.73 2.94 62.2% 

 

 2 4.44 2.62 58.9% 2 4.76 3.07 64.5% 

 3 4.55 2.71 59.6% 3 4.78 3.04 63.5% 

Best Values 4.56 2.71 59.4% Best Values 4.78 3.07 64.3% 

Predicted 

Values* 

4.23 3.40 80.5% Reference 

Values 

4.56 2.71 

Percent 

Predicted 

107.8% 79.7% 73.8% Difference (L) 0.22 0.36 

 Difference (%) 4.8% 13.4%

Interpretations: 

FEV1 and FEV1/FVC are below normal range. The reduced 

rate at which air is exhaled indicates obstruction to airflow. 

*Predicted values from Knudson et al. (1983) 

 Interpretations: 

Significant increases in FEV1, with bronchodilator (≥12% 

increase after bronchodilator indicates a significant change). 

Key: FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

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August 28, 2007 

FIGURE 3–4a. CLASSIFYING AS THMA SEVERITY IN CHILDREN 

0–4 YEARS OF AGE 

 Classifying severity in children who are not currently taking long-term control 

medication. 

Consider severity and interval since last exacerbation.

Frequency and severity may fluctuate over time.

None Minor limitation Some limitation Extremely limited Interference with 

normal activity

Several times per 

day Daily >2 days/weekbut not daily ≤2 days/week

Short-acting

beta2-agonist use 

for symptom 

control (not 

prevention of EIB)

Exacerbations of any severity may occur in patients in any severity category

Exacerbations 

requiring oral 

systemic

corticosteroids

Risk

Impairment

0 1−2x/month 3−4x/month >1x/week Nighttime

awakenings

Classification of Asthma Severity

(Children 0−4 years of age)

Persistent

Components of

Severity

≥2 exacerbations in 6 months requiring oral steroids,

or ≥4 wheezing episodes/1 year lasting >1 day

AND risk factors for persistent asthma

0−1/year

Throughout

the day Daily >2 days/weekbut not daily Symptoms ≤2 days/week

Intermittent Mild Moderate Severe

 Level of severity is determined by both impairment and risk. Assess impairment domain by caregiver’s recall of previous 2–4 weeks. 

Assign severity to the most severe category in which any feature occurs. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. For treatment 

purposes, patients who had ≥2 exacerbations requiring oral corticosteroids in the past 6 months, or ≥4 wheezing episodes in the past 

year, and who have risk factors for persistent asthma may be considered the same as patients who have persistent asthma, even in the 

absence of impairment levels consistent with persistent asthma. 

 Classifying severity in patients after asthma becomes well controlled, by lowest level 

of treatment required to maintain control.* 

Mild Moderate Severe

Classification of Asthma Severity

Lowest level of Intermittent Persistent

treatment required

to maintain control

(See figure 4−1a for

treatment steps.) Step 1 Step 2 Step 3 or 4 Step 5 or 6

Key: EIB, exercise-induced bronchospasm 

*Notes:

 For population-based evaluations, clinical research, or characterization of a patient’s overall asthma severity after control is achieved. 

For clinical management, the focus is on monitoring the level of control (See figure 3–5a.), not the level of severity, once treatment is 

established. 

 See figure 3–5a for definition of asthma control. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

73 

August 28, 2007 

FIGURE 3–4b. CLASSIFYING AS THMA SEVERITY IN CHILDREN 

5–11 YEARS OF AGE 

 Classifying severity in children who are not currently taking long-term control 

medication. 

• Normal FEV1

between 

exacerbations

Extremely 

limited None Minor limitation Some limitation Interference with normal activity

Several times 

per day Daily >2 days/weekbut not daily ≤2 days/week

Short-acting

beta2-agonist use

for symptom

control (not 

prevention of EIB)

• FEV1 <60% 

predicted

• FEV1 = 60−80% 

predicted

• FEV1 = >80% 

predicted

• FEV1 >80% 

predicted

≥2 in 1 year (see note)

Relative annual risk of exacerbations may be related to FEV1

Classification of Asthma Severity

(Children 5−11 years of age)

Consider severity and interval since last exacerbation. Frequency and 

severity may fluctuate over time for patients in any severity category.

Impairment

Risk

Persistent

Components of 

Severity

0−1/year (see note) Exacerbations 

requiring oral 

systemic 

corticosteroids

• FEV1/FVC 

<75%

• FEV1/FVC =

75−80%

• FEV1/FVC 

>80%

• FEV1/FVC >85%

Lung function

Often 

7x/week

>1x/week but

not nightly ≤2x/month 3−4x/month Nighttimeawakenings

Throughout

the day

>2 days/week Daily

but not daily

≤2 days/week Symptoms

Mild Moderate Severe

Intermittent

 Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of the previous 

2–4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, 

more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater 

underlying disease severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the 

past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with 

persistent asthma. 

 Classifying severity in patients after asthma becomes well controlled, by lowest level 

of treatment required to maintain control.* 

Mild Moderate Severe

Classification of Asthma Severity

Lowest level of Intermittent Persistent

treatment required

to maintain control

(See figure 4−1b

for treatment steps.) Step 1 Step 2 Step 3 or 4 Step 5 or 6

Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in second; FVC, forced vital capacity; ICU, intensive 

care unit 

*Notes: 

 For population-based evaluations, clinical research, or characterization of a patient’s overall asthma severity after control is achieved. 

For clinical management, the focus is on monitoring the level of control (See figure 3–5b.), not the level of severity, once treatment is 

established. 

 See figure 3–5b for definition of asthma control. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

74 

August 28, 2007 

FIGURE 3–4c. CLASSIFYING AS THMA SEVERITY IN YOUTHS 

≥ 12 YEARS OF AGE AND ADULTS 

 Classifying severity for patients who are not currently taking long-term control 

medications. 

• Normal FEV1

between 

exacerbations

None Minor limitation Some limitation Extremely limited Interference with 

normal activity

Several times

per day

>2 days/week Daily

but not 

>1x/day

Short-acting ≤2 days/week

beta2-agonist use 

for symptom control 

(not prevention

of EIB)

≥2/year (see note) 0−1/year

(see note)

• FEV1 <60% 

predicted

• FEV1 >60% but 

<80% predicted

• FEV1 ≥80% 

predicted

• FEV1 >80% 

predicted

• FEV1/FVC

reduced >5%

• FEV1/FVC 

reduced 5%

• FEV1/FVC 

normal

• FEV1/FVC 

normal

Risk

Relative annual risk of exacerbations may be related to FEV1

Classification of Asthma Severity

(Youths ≥12 years of age and adults)

Consider severity and interval since last exacerbation. Frequency and

severity may fluctuate over time for patients in any severity category.

Impairment

Normal FEV1/FVC:

8−19 yr 85%

20 −39 yr 80%

40 −59 yr 75%

60 −80 yr 70%

Persistent

Components of 

Severity

Exacerbations

requiring oral 

systemic 

corticosteroids

Lung function

>1x/week but Often 7x/week

not nightly Nighttime ≤2x/month 3−4x/month

awakenings

Throughout 

the day

>2 days/week Daily

but not daily

≤2 days/week Symptoms

Intermittent Mild Moderate Severe

 Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of 

previous 2–4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, 

more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater 

underlying disease severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the 

past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with 

persistent asthma. 

 Classifying severity in patients after asthma becomes well controlled, by lowest level 

of treatment required to maintain control.* 

Mild Moderate Severe

Classification of Asthma Severity

Lowest level of Intermittent Persistent

treatment required

to maintain control

(See figure 4−5

for treatment steps.) Step 1 Step 2 Step 3 or 4 Step 5 or 6

Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive 

care unit 

*Notes: 

 For population-based evaluations, clinical research, or characterization of a patient’s overall asthma severity after control is achieved. 

For clinical management, the focus is on monitoring the level of control (See figure 3–5c.), not the level of severity, once treatment is 

established. 

 See figure 3–5c for definition of asthma control. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

75 

August 28, 2007 

FIGURE 3–5a. ASSESSING ASTHMA CONTROL IN CHILDREN 

0–4 YEARS OF AGE 

0−1/year 2−3/year >3/year

Exacerbations 

requiring oral systemic 

corticosteroids

Risk

≤2 days/week >2 days/week Several times per day

Short-acting

beta2-agonist use

for symptom control 

(not prevention

of EIB)

None Some limitation Extremely limited Interference with 

normal activity

Medication side effects can vary in intensity from none to very 

troublesome and worrisome. The level of intensity does not 

correlate to specific levels of control but should be considered

in the overall assessment of risk.

Classification of Asthma Control

(Children 0−4 years of age)

Impairment

Components of Control

Treatment-related 

adverse effects

>1x/month >1x/week

Symptoms ≤2 days/week >2 days/week Throughout the day

Very Poorly 

Controlled

Not Well 

Controlled

Well 

Controlled

Key: EIB, exercise-induced bronchospasm; ICU, intensive care unit 

Notes: 

 The level of control is based on the most severe impairment or risk category. Assess 

impairment domain by caregiver’s recall of previous 2–4 weeks. Symptom assessment for 

longer periods should reflect a global assessment, such as inquiring whether the patient’s 

asthma is better or worse since the last visit. 

 At present, there are inadequate data to correspond frequencies of exacerbations with 

different levels of asthma control. In general, more frequent and intense exacerbations (e.g., 

requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer 

disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral 

systemic corticosteroids in the past year may be considered the same as patients who have 

not-well-controlled asthma, even in the absence of impairment levels consistent with 

persistent asthma. 

 Nighttime awakenings ≤1x/month
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

76 

August 28, 2007 

FIGURE 3–5b. ASSESSING ASTH MA CONTROL IN CHILDREN 

5–11 YEARS OF AGE 

Impairment

Exacerbations requiring 0−1/year ≥2/year (see note) oral systemic 

corticosteroids

Lung function

<60% predicted/

personal best

60−80% predicted/

personal best

>80% predicted/

personal best

 FEV1 or peak flow

Evaluation requires long-term followup.

Medication side effects can vary in intensity from none to very 

troublesome and worrisome. The level of intensity does not correlate 

to specific levels of control but should be considered in the overall 

assessment of risk.

Treatment-related 

adverse effects

Consider severity and interval since last exacerbation

Risk

≤2 days/week >2 days/week Several times per day

Short-acting

beta2-agonist use

for symptom control

(not prevention of EIB)

None Some limitation Extremely limited Interference with

normal activity

Classification of Asthma Control

(Children 5−11 years of age) Components of Control

Reduction in lung growth

 FEV1/FVC >80% 75−80% <75%

≤1x/month ≥2x/month ≥2x/week Nighttime

awakenings

Throughout the day

>2 days/week or 

multiple times on

≤2 days/week

≤2 days/week but 

not more than 

once on each day

Symptoms

Very Poorly 

Controlled

Not Well 

Controlled Well Controlled

Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive 

care unit 

Notes: 

 The level of control is based on the most severe impairment or risk category. Assess 

impairment domain by patient’s/caregiver’s recall of previous 2–4 weeks and by 

spirometry/or peak flow measures. Symptom assessment for longer periods should reflect a 

global assessment, such as inquiring whether the patient’s asthma is better or worse since 

the last visit. 

 At present, there are inadequate data to correspond frequencies of exacerbations with 

different levels of asthma control. In general, more frequent and intense exacerbations 

(e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer 

disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral 

systemic corticosteroids in the past year may be considered the same as patients who have 

not-well-controlled asthma, even in the absence of impairment levels consistent with 

not-well-controlled asthma. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

77 

August 28, 2007 

FIGURE 3–5c. ASSESSIN G ASTHMA CONTROL IN 

YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

Consider severity and interval since last exacerbation

Evaluation requires long-term followup care

Medication side effects can vary in intensity from none to very 

troublesome and worrisome. The level of intensity does not correlate to 

specific levels of control but should be considered in the overall 

assessment of risk.

Treatment-related adverse 

effects

Progressive loss of lung 

Risk function

Validated Questionnaires

≥2/year (see note)

Symptoms ≤2 days/week >2 days/week Throughout the day

Impairment

3–4

N/A

≤15 

1–2

≥1.5

16−19 

0

≤0.75*

≥20

ATAQ

ACQ

ACT

<60% predicted/

personal best

60−80% predicted/

personal best

>80% predicted/

personal best

FEV1 or peak flow

Short-acting beta2-agonist use ≤2 days/week >2 days/week Several times per day

for symptom control (not 

prevention of EIB)

0−1/year

Exacerbations

Classification of Asthma Control

(Youths ≥12 years of age and adults)

Components of Control

Interference with normal None Some limitation Extremely limited

activity

Nighttime awakening ≤2x/month 1−3x/week ≥4x/week

Very Poorly

Controlled

Not

Well-Controlled Well-Controlled

*ACQ values of 0.76–1.4 are indeterminate regarding well-controlled asthma. 

Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second. See figure 3–8 for full name and source of 

ATAQ, ACQ, ACT. 

Notes: 

 The level of control is based on the most severe impairment or risk category. Assess 

impairment domain by patient’s recall of previous 2–4 weeks and by spirometry/or peak flow 

measures. Symptom assessment for longer periods should reflect a global assessment, 

such as inquiring whether the patient’s asthma is better or worse since the last visit. 

 At present, there are inadequate data to correspond frequencies of exacerbations with 

different levels of asthma control. In general, more frequent and intense exacerbations 

(e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer 

disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral 

systemic corticosteroids in the past year may be considered the same as patients who have 

not-well-controlled asthma, even in the absence of impairment levels consistent with 

not-well-controlled asthma. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

78 

August 28, 2007 

FIGURE 3–6. SAMPLE QUES TIONS FOR ASSESSING AND 

MONITORING ASTHMA CONTROL 

Monitoring Asthma Control 

Ask the patient: 

 Has your asthma awakened you at night or early morning? 

 Have you needed more quick-relief bronchodilator medication (inhaled shortacting beta2-agonist) than usual? 

 Have you needed any urgent medical care for your asthma, such as unscheduled 

visits to your doctor, an urgent care clinic, or the emergency department? 

 Are you participating in your usual and desired activities? 

 If you are measuring your peak flow, has it been below your personal best?

Actions to consider: 

 Assess whether the medications are being taken as prescribed. 

 Assess whether the medications are being inhaled with correct technique. 

 Assess lung function with spirometry and compare to previous measurement. 

 Adjust medications, as needed; either step up if control is inadequate or step 

down if control is maximized, to achieve the best control with the lowest dose of 

medication.

Source: Adapted and reprinted from “Global Initiative for Asthma: Pocket Guide for Asthma Management 

and Prevention.” NIH Publication No. 96-3659B. Bethesda, MD: Department of Health and Human 

Services, National Institutes of Health, National Heart, Lung, and Blood Institute. 1995 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

79 

August 28, 2007 

FIGURE 3–7. COMPONENTS OF THE CLINICIAN’S FOLLOWUP 

ASSESSMENT: SAMPLE ROUTINE CLINICAL ASSESSMENT 

QUESTIONS* 

Monitoring Signs and Symptoms 

(Global assessment) “Has your asthma been better or 

worse since your last visit?” 

“Has your asthma worsened during specific seasons 

or events?” 

(Recent assessment) “In the past 2 weeks, how many 

days have you: 

 Had problems with coughing, wheezing, 

shortness of breath, or chest tightness during the 

day?” 

 Awakened at night from sleep because of 

coughing or other asthma symptoms?” 

 Awakened in the morning with asthma symptoms 

that did not improve within 15 minutes of inhaling 

a short-acting beta2-agonist?” 

 Had symptoms while exercising or playing?” 

 Been unable to perform a usual activity, including 

exercise, because of asthma?” 

Monitoring Pulmonary Function 

Lung Function 

“What is the highest and lowest your peak flow has 

been since your last visit?” 

“Has your peak flow dropped below ___ L/min 

(80 percent of personal best) since your last visit?” 

“What did you do when this occurred?” 

Peak Flow Monitoring Technique 

“Please show me how you measure your peak flow.” 

“When do you usually measure your peak flow?” 

Monitoring Quality of Life/Functional Status 

“Since your last visit, how many days has your asthma 

caused you to: 

 Miss work or school?” 

 Reduce your activities?” 

 (For caregivers) Change your activity because of 

your child’s asthma?” 

“Since your last visit, have you had any unscheduled 

or emergency department visits or hospital stays?” 

Monitoring Exacerbation History 

“Since your last visit, have you had any 

episodes/times when your asthma symptoms were 

a lot worse than usual?” 

If yes, “What do you think caused the 

symptoms to get worse?” 

If yes, “What did you do to control the 

symptoms?” 

“Have there been any changes in your home or work 

environment (e.g., new smokers or pets)?” 

Monitoring Pharmacotherapy 

Medications 

“What medications are you taking?” 

“How do you feel about taking medication?” 

“How often do you take each medication?” 

“How much do you take each time?” 

“Have you missed or stopped taking any regular doses of 

your medications for any reason?” 

“Have you had trouble filling your prescriptions (e.g., for 

financial reasons, not on formulary)?” 

“How many puffs of your inhaled short-acting beta2-agonist 

(quick-relief medicine) do you use per day?” 

“How many [name inhaled short-acting beta2-agonist] 

inhalers [or pumps] have you been through in the past 

month?” 

“Have you tried any other medicines or remedies?” 

Side Effects 

“Has your asthma medicine caused you any problems?” 

 Shakiness, nervousness, bad taste, sore throat, cough, 

upset stomach, hoarseness, skin changes (e.g., 

bruising) 

Inhaler Technique 

“Please show me how you use your inhaler.” 

Monitoring Patient–Provider Communication and 

Patient Satisfaction 

“What questions have you had about your asthma daily 

self-management plan and action plan?” 

“What problems have you had following your daily selfmanagement plan? Your action plan?” 

“How do you feel about making your own decisions about 

therapy?” 

“Has anything prevented you from getting the treatment you 

need for your asthma from me or anyone else?” 

“Have the costs of your asthma treatment interfered with 

your ability to get asthma care?” 

“How satisfied are you with your asthma care?” 

“How can we improve your asthma care?” 

“Let’s review some important information: 

 When should you increase your medications? Which 

medication(s)?” 

 When should you call me [your doctor or nurse 

practitioner]? Do you know the after-hours phone 

number?” 

 If you can’t reach me, what emergency department 

would you go to?” 

* These questions are examples and do not represent a standardized assessment instrument. The validity and reliability of these 

questions have not been assessed. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

80 FIGURE 3–8. VALIDATED INST RUMENTS FOR ASSESSMENT AN D MONITORIN Asthma Control Questionnaire (Juniper et al. 1999b)  Asthma Therapy Assessment Questionnaire (Vollmer et al. 1999) (See below.)  Asthma Control Test (Nathan et al. 2004) (See below.)  Asthma Control score (Boulet et al. 2002) 

ASTHMA THERAPY ASSESSMENT QUESTIONNAIRE© (ATAQ) 1. In the past 4 weeks did you miss any work, school, or normal daily 

activities because of your asthma? (1 point for YES) 

2. In the past 4 weeks, did you wake up at night because of your 

asthma? (1 point for YES) 

3. Do you believe your asthma was well controlled in the past 4 weeks? 

(1 point for NO) 

4. Do you use an inhaler for quick relief from asthma symptoms? If yes, 

what is the highest number of puffs in 1 day you took of this inhaler? (1 point for more than 12) 

Total points = 0–4, with more points indicating more control problems Source: Adapted and reprinted with permission from Merck and Co., Inc. Copyright © 1997, 1998, 1999 Merck and Co., Inc. All Rights Reserved. 

CAUTION: The sample questionnaires in figure 3–8 assess only the impairment domain of asthma control and NOT the risk d

risk, such as exacerbations, urgent care, hospitalizations, and declines in lung function, are important elements of assessing control. 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

81 

August 28, 2007 

FIGURE 3–9. SAMPLE PATIEN T SELF-ASSESSMENT SHEET FOR 

FOLLOWUP VISITS *

Name: Date: 

Your Asthma Control 

How many days in the past week have you 

had chest tightness, cough, shortness of 

breath, or wheezing (whistling in your 

chest)? 

_____ 0 _____ 1 _____ 2 _____ 3 _____ 4 _____ 5 _____ 6 _____ 7 

How many nights in the past week have you 

had chest tightness, cough, shortness of 

breath, or wheezing (whistling in your 

chest)? 

_____ 0 _____ 1 _____ 2 _____ 3 _____ 4 _____ 5 _____ 6 _____ 7 

Do you perform peak flow readings at 

home? 

______ yes ______ no 

If yes, did you bring your peak flow chart? ______ yes ______ no 

How many days in the past week has 

asthma restricted your physical activity? 

_____ 0 _____ 1 _____ 2 _____ 3 _____ 4 _____ 5 _____ 6 _____ 7 

Have you had any asthma attacks since 

your last visit? 

______ yes ______ no 

Have you had any unscheduled visits to a 

doctor, including to the emergency 

department, since your last visit? 

______ yes ______ no 

____very well controlled 

____somewhat controlled 

____not well controlled 

How well controlled is your asthma, in your 

opinion? 

Average number of puffs per day 

Taking your medicine

What problems have you had taking your medicine or following your asthma action plan? 

Please ask the doctor or nurse to review how you take your medicine. 

Your questions 

What questions or concerns would you like to discuss with the doctor? 

How satisfied are you with your 

asthma care? 

____very satisfied 

____somewhat satisfied 

____not satisfied 

* These questions are examples and do not represent a standardized assessment instrument. Other examples of asthma control 

questions: Asthma Control Questionnaire (Juniper); Asthma Therapy Assessment Questionnaire (Volmer); Asthma Control Test 

(Nathan); Asthma Control Score (Boulet) 
Section 3, Component 1: Measures of Asthma Assessment and Monitoring 

82 

August 28, 2007 

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SECTION 3, COMPONENT 2: EDUCATION FOR A PARTNERSHIP IN 

ASTHMA CARE 

KEY POINTS: EDUCATION FOR A PARTNERSHIP IN 

ASTHMA CARE 

 Asthma self-management education is essential to provide patients with the skills necessary 

to control asthma and improve outcomes (Evidence A). 

 Asthma self-management education should be integrated into all aspects of asthma care, 

and it requires repetition and reinforcement. It should: 

— Begin at the time of diagnosis and continue through followup care (Evidence B). 

— Involve all members of the health care team (Evidence B). 

— Introduce the key educational messages by the principal clinician, and negotiate 

agreements about the goals of treatment, specific medications, and the actions patients 

will take to reach the agreed-upon goals to control asthma (Evidence B). 

— Reinforce and expand key messages (e.g., the patient’s level of asthma control, inhaler 

techniques, self-monitoring, and use of a written asthma action plan) by all members of 

the health care team (Evidence B). 

— Occur at all points of care where health professionals interact with patients who have 

asthma, including clinics, medical offices, EDs and hospitals, pharmacies, homes, and 

community sites (e.g., schools, community centers) (Evidence A or B, depending on 

point of care). 

♦ Strong evidence supports self-management education in the clinic setting 

(Evidence A). 

♦ Observational studies and limited clinical trials support consideration of focused, 

targeted patient education in the ED setting (e.g., teaching inhaler technique and 

providing an ED asthma discharge plan with instructions for discharge medications 

and for increasing medication or seeking medical care if asthma should worsen). 

Studies demonstrate the benefits of education in the hospital setting (Evidence B). 

♦ Studies of pharmacy-based education directed toward understanding medications 

and teaching inhaler and self-monitoring skills show the potential of using community 

pharmacies as a point of care for self-management education. Studies report 

difficulties in implementation, but they also demonstrate benefits in improving asthma 

self-management skills and asthma outcomes (Evidence B). 

♦ Studies demonstrate the benefits of programs provided in the patient’s home for 

multifaceted allergen control, although further evaluation of cost-effectiveness and 

feasibility for widespread implementation will be helpful (Evidence A). 
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♦ Some, but not all, school-based programs have demonstrated success in reducing 

symptoms and urgent health care use and in improving school attendance and 

performance. Proven school-based programs should be considered for 

implementation because of their potential to reach large numbers of children who 

have asthma and provide an “asthma-friendly” learning environment for students who 

have asthma (Evidence B). 

♦ Emerging evidence suggests the potential for using computer and Internet programs 

incorporated into asthma care (Evidence B). 

 Provide all patients with a written asthma action plan that includes two aspects: (1) daily 

management and (2) how to recognize and handle worsening asthma. Written action plans 

are particularly recommended for patients who have moderate or severe persistent asthma, 

a history of severe exacerbations, or poorly controlled asthma (Evidence B). 

 Regular review, by an informed clinician, of the status of the patient’s asthma control is an 

essential part of asthma self-management education (Evidence B). Teach and reinforce at 

every opportunity (EPR⎯2 1997): 

— Basic facts about asthma 

— What defines well-controlled asthma and the patient’s current level of control 

— Roles of medications 

— Skills: e.g., inhaler technique, use of a valved holding chamber (VHC) or spacer, and 

self-monitoring 

— When and how to handle signs and symptoms of worsening asthma 

— When and where to seek care

— Environmental exposure control measures 

 Develop an active partnership with the patient and family by (EPR⎯2 1997): 

— Establishing open communications. 

— Identifying and addressing patient and family concerns about asthma and asthma 

treatment. 

— Identifying patient/parent/child treatment preferences regarding treatment and barriers to 

its implementation. 

— Developing treatment goals together with patient and family. 

— Encouraging active self-assessment and self-management of asthma. 
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 Encourage adherence by: 

— Choosing a treatment regimen that achieves outcomes and addresses preferences that 

are important to the patient/caregiver (Evidence B). 

— Reviewing the success of the treatment plan with the patient/caregiver at each visit and 

making adjustments as needed (Evidence B). 

 Tailor the asthma self-management teaching approach to the needs of each patient. 

Maintain sensitivity to cultural beliefs and ethnocultural practices (Evidence C). 

 Encourage development and evaluation of community-based interventions that provide 

opportunities to reach a wide population of patients and their families, particularly those 

patients at high risk of asthma morbidity and mortality (Evidence D). 

 Asthma self-management education that is provided by trained health professionals should 

be considered for policies and reimbursements as an integral part of effective asthma care; 

the education improves patient outcomes (Evidence A) and can be cost-effective in 

improving patient outcomes (Evidence B). 

KEY POINTS: PROVIDER EDUCATION 

 Implement multidimensional, interactive clinician education in asthma care including, for 

example, case discussions involving active participation by the learners (Evidence B). 

 Consider participation in programs to enhance skills in communicating with patients 

(Evidence B). 

 Encourage development and use of clinical pathways for management of acute asthma 

(Evidence B). 

 Develop, implement, and evaluate system-based interventions to support clinical 

decisionmaking and to support quality care for asthma (Evidence B). 

KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

Patient Education: 

 Emphasis on the many potential points of care and sites available in which to provide 

asthma education, including review of new evidence regarding the efficacy of asthma selfmanagement education outside the usual office setting. 

 Greater emphasis on the two aspects of the written asthma action plan—(1) daily 

management, and (2) how to recognize and handle worsening asthma. Use of the 

terminology “written asthma action plan” encompasses both aspects. This change 

addresses confusion over the previous guidelines’ use of different terms. One term is now 

used for the written asthma action plan, although in some studies cited, investigators may 

have used a variation of this term. 

 New sections on the impact of cultural and ethnic factors and health literacy that affect 

delivery of asthma self-management education. 
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Provider Education: 

 New section with review of system-based interventions to improve the quality of asthma 

care, to support clinical decisionmaking, and to enhance clinical information systems 

 Review of tested programs that use effective strategies to provide clinician education in 

asthma care, e.g., multidimensional approaches, interactive formats, and practice-based 

case studies 

Introduction 

See section 1, “Overall Methods Used To Develop This Report,” for literature search strategy 

and tally of results for EPR—3: Full Report 2007 on this component, Education for a 

Partnership in Asthma Care. Six Evidence Tables were prepared: 3, Asthma Self-Management 

Education for Adults; 4, Asthma Self-Management Education for Children; 5, Asthma 

Self-Management Education in Community Settings; 6, Cost-Effectiveness of Asthma 

Self-Management Education; 7, Methods for Improving Clinical Behaviors: Implementing 

Guidelines; 8, Methods for Improving Systems Support. 

Education for a Partnership in Asthma Care requires education for the patient or caregiver about 

asthma self-management as well as education for clinicians to enhance skills in teaching 

patients self-management and provide support to implement guidelines-recommended 

practices. In this component, recommendations are presented on asthma self-management 

education at multiple points of care, tools for asthma self-management, and provider education. 

Evidence is now abundant that asthma self-management education is effective in improving 

outcomes of chronic asthma. Specific training in self-management skills is necessary to 

produce behavior that modifies the outcomes of chronic illnesses such as asthma. Expert care, 

with regular review by health professionals, is necessary but not sufficient to improve outcomes. 

Patients must actively participate in their own care, which means consciously using strategies 

and taking actions to minimize exposure to factors that make asthma harder to control and 

adjusting treatments to improve disease control. 

The ultimate goal of both expert care and patient self-management is to reduce the impact of 

asthma on related morbidity, functional ability, and quality of life. The benefits of educating 

people who have asthma in the self-management skills of self-assessment, use of medications, 

and actions to prevent or control exacerbations, include reduction in urgent care visits and 

hospitalizations, reduction of asthma-related health care costs, and improvement in health 

status (Bartholomew et al. 2000; Cicutto et al. 2005; Cordina et al. 2001; Cowie et al. 1997; 

Gibson et al. 2000; Guevara et al. 2003; Krieger et al. 2005; Krishna et al. 2003; Madge et al. 

1997; MeGhan [sic] et al. 2003; Morgan et al. 2004; Powell and Gibson 2003; Teach et al. 2006; 

Wesseldine et al. 1999). Other benefits of value from self-management education are reduction 

in symptoms, less limitation of activity, improvement in quality of life and perceived control of 

asthma, and improved medication adherence (Bonner et al. 2002; Christiansen et al. 1997; 

Clark et al. 2004; Evans et al. 1999a; Janson et al. 2003; McLean et al. 2003; Perneger et al. 

2002; Saini et al. 2004; Thoonen et al. 2003). Cost-analysis studies have shown that asthma 

education can be delivered in a cost-effective manner and that morbidity is reduced as a result, 

especially in high-risk subjects (Gallefoss and Bakke 2001; Kattan et al. 1997; Powell and 

Gibson 2003; Schermer et al. 2002; Sullivan et al. 2002). 
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Although not all controlled trials of asthma self-management education have shown positive 

results, it is notable that controlled studies have demonstrated benefit from patient education 

programs delivered in a wide range of points of care, including clinics, EDs, hospitals, 

pharmacies, doctors’ offices, schools, and community settings. These results have been 

achieved through face-to-face educational strategies and the use of new electronic 

technologies. Referenced studies are from multiple countries. Some outcomes may be 

dependent on the context of care and may not be completely generalizable. 

Asthma Self-Management Education at Multiple Points of Care 

The Expert Panel recommends that patients be educated at multiple points of care where 

health professionals and health educators may interact with patients who have asthma 

(Evidence A or B, depending on point of care). For people who have asthma, many points of 

care exist outside traditional clinic, office, or hospital settings. An emerging body of evidence 

suggests that educating people at these points of care creates opportunities to provide an 

essential link between the patient and the primary clinician, forming a network of support for the 

patient and clinician outside the clinician’s office. In this way, a network of asthma education 

capability is built that ensures no person who has asthma is left without knowledge or skills. 

Although it is beyond the scope of this document to address the issues of asthma education of 

persons who are not family members and are not health care professionals, those individuals 

who come into contact with persons with asthma on a regular basis (e.g., teachers, coaches, 

daycare workers, employers, etc.) should receive some basic education about asthma. 

Education of these individuals about asthma may help reduce asthma morbidity and mortality 

and may contribute to earlier diagnosis of this disease. Teachers and coaches should know 

how to recognize worsening asthma, administer quick-relief medications, and know how and 

when to call for emergency services. 

CLINIC/OFFICE-BASED EDUCATION 

Adults—Teach Asthma Self-Management Skills To Promote Asthma Control 

The Expert Panel recommends that: 

 Clinicians provide to patients asthma self-management education that includes the 

following essential items: asthma information and training in asthma management 

skills (Evidence A), self-monitoring (either symptom– or peak flow–based) 

(Evidence A), written asthma action plan (Evidence B), and regular assessment by a 

consistent clinician (Evidence B). (See Evidence Table 3: Asthma Self-Management 

Education for Adults.) 

 Clinicians involve patients in decisions about the type of self-monitoring of asthma 

control that they will do (Evidence B) 

 Clinicians provide all patients with a written asthma action plan that includes 

instructions for (1) daily management, and (2) recognizing and handling worsening 

asthma, including self-adjustment of medications in response to acute symptoms or 

changes in PEF measures. Written asthma action plans are particularly 

recommended for patients who have moderate or severe persistent asthma, a history 

of severe exacerbations, or poorly controlled asthma (Evidence B). 
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 Clinicians involve adult patients in the treatment decisionmaking within the context of 

a therapeutic partnership (Evidence B). 

 Health professionals and others trained in asthma self-management education be 

used to implement and teach asthma self-management programs (Evidence B). 

 Because poor attendance at multiple sessions may be a problem in some 

populations, consider introducing key messages and essential skills of selfmanagement in the first session and adjusting subsequent sessions to the needs of 

the patients in the groups (Evidence D). Research comparing lengthy versus 

condensed or shorter sessions is encouraged. (See Evidence Table 3, Asthma SelfManagement for Adults.) 

Written Asthma Action Plans, Clinician Review, and Self-Monitoring 

In a large, scientific review of 36 RCTs involving 6,090 adults who had asthma, asthma 

self-management—accompanied by regular review of medications and asthma control by a 

medical practitioner—improved health outcomes significantly more than usual care (Gibson et 

al. 2003). All interventions included education, while 15 tested “optimal self-management” that 

included self-monitoring of symptoms and/or peak flow, regular review by a clinician, and a 

written asthma action plan. These intervention trials were conducted in primary care, specialty 

care, hospital inpatient, or community settings. The results of the statistical analysis overall, 

including meta-analysis where possible, showed self-management education significantly 

reduced hospitalizations, unscheduled acute visits, and missed work days, as well as improving 

quality of life. Subgroup analyses compared the intensity of the intervention (optimal 

self-management with regular review, self-monitoring, and a written asthma action plan versus 

self-monitoring and regular review versus self-monitoring only versus regular review only versus 

written asthma action plan with either self-monitoring or regular review). Optimal 

self-management, including self-monitoring of symptoms and/or peak flow and a written asthma 

action plan, significantly reduced hospitalizations and ED visits for asthma. There was 

insufficient power to compare the subgroups with less intensive interventions. There was little 

effect on lung function: FEV1 did not change. A statistically significant small mean increase 

(14.5 L/min, p <0.05) in PEF occurred, however. 

Self-management education that included a written asthma action plan appeared more effective 

than other forms of self-management education. The intensity (number of sessions) of teaching 

and the number of different components taught had little impact. 

Regular review of progress by a concerned clinician is the basis for the patient–clinician 

partnership necessary to achieve asthma control. In another scientific review, the equivalence 

and efficacy of different options for asthma self-management were analyzed in 15 RCTs (Powell 

and Gibson 2003). In six studies, regular clinical review by physicians who adjusted ICS 

medications was compared to self-management education allowing self-adjustment of 

medications by using a written asthma action plan. These two methods for achieving asthma 

control were found to be equivalent. No significant differences in hospitalization, ED visits, 

unscheduled doctor’s visits, or frequency of nocturnal asthma symptoms were found between 

patients who self-adjusted their medication and those whose medications were adjusted by their 

physicians. Two of three studies found no difference between clinician review and 

self-management in the days lost from work or school, while the third study reported a 

significant effect of peak-flow-based self-management on work or school absenteeism. Lung 
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function, as measured by FEV1, was not significantly improved with peak-flow-based 

self-adjustment of medications as compared to physician adjustment of medications. 

The evidence from this analysis indicates that these two methods of adjusting medications for 

asthma control (change by physician during office visit or patient self-management according to 

a written asthma action plan) are equivalent, and the choice depends on the comfort and 

agreement between the clinician and the patient. Patient self-monitoring is an important tool for 

patients to assess the level of their asthma control and to adjust treatment according to their 

action plan. 

When self-management is the chosen method for maintaining asthma control, peak-flow-based 

self-management is equivalent to symptom-based self-management as long as either method 

also includes a written asthma action plan with instructions on how to recognize and handle 

worsening asthma, including self-adjustment of medications. In three studies, both methods 

were found to have an equal impact on ED visits, and one study found peak flow monitoring was 

more effective in reducing ED visits (Powell and Gibson 2003). As noted in “Component 1: 

Measures of Asthma Assessment,” the important point is for patients to have a plan for 

monitoring their asthma, regardless of whether it is peak flow or symptom based. Therefore, the 

Expert Panel recommends that clinicians involve patients in decisions about the type of selfmonitoring they will do. All patients may benefit from a written asthma action plan that includes 

instructions for (1) daily management, and (2) recognizing and handling worsening asthma, 

including self-adjustment of medications in response to acute symptoms or changes in PEF 

measures. Written action plans are particularly recommended for patients who have moderate 

or severe asthma, a history of severe exacerbations, or poorly controlled asthma. (See 

“Component 1: Measures of Asthma Assessment” for further discussion of tools for assessing 

asthma control.) 

Other studies offer evidence of varying effectiveness of patient education. Those studies 

conducted as RCTs with positive findings confirm the results of the large scientific reviews 

(Janson et al. 2003; Magar et al. 2005; Marabini et al. 2002; Perneger et al. 2002; Thoonen et 

al. 2003). In these trials, one conducted across multiple practices in primary care settings 

(Thoonen et al. 2003), providing self-management education including an asthma action plan for 

exacerbations resulted in reduced symptoms, fewer days of restricted activity, and improvement 

in quality of life. Self-management education also resulted in improved self-confidence to 

manage asthma (Perneger et al. 2002) and improved adherence to ICS therapy (Janson et al. 

2003; Magar et al. 2005) (Evidence B). 

Education that provides information only, without skills training, improves knowledge but does 

not reduce hospitalizations, ED visits, unscheduled doctor’s visits, or lost work days; nor does it 

improve lung function and medication use (Gibson et al. 2002). In this review, patients’ reports 

of symptoms improved in only 2 of the 12 RCTs of information-only programs. 

Patient–Provider Partnership 

The value of establishing the patient–clinician partnership when teaching asthma 

self-management was shown in another RCT of asthma education (Marabini et al. 2002) in 

which investigators purposely formed partnerships with patients in the intervention group. The 

control group received education on medication use, role of environmental triggers, and 

metered-dose inhaler (MDI) technique but no partnership. The educational intervention 

delivered in the context of the therapeutic relationship produced improved symptom control, 

quality of life, and lung function measured as FEV1 in patients in the group who had moderate or 
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severe asthma only. This finding suggests asthma self-management education, reinforced in 

the context of a therapeutic partnership between clinician and patient, may be especially 

valuable in patients who have moderate or severe asthma. 

Another recent RCT (Wilson et al. 2005, 2006) used the context of the patient-clinician 

partnership to test the impact of shared decisionmaking about asthma treatment, compared to 

guideline-based clinician decisionmaking and usual care, in adults who had poorly controlled 

asthma. Clinician care managers (nurse practitioners, pharmacists, respiratory therapists) met 

with the patients to adjust therapy in two visits, 1 month apart, followed by three brief telephone 

calls (at 3, 6, and 9 months) to assess patients’ progress in both intervention groups. The 

unique features of shared decisionmaking included identifying patients’ goals and preferences 

regarding treatment and negotiating a treatment regimen to accommodate best each patient’s 

goals and preferences. Establishing rapport, providing educational information, teaching inhaler 

technique, writing the prescription, and preparing a written asthma action plan for the patient 

occurred in both the guidelines and shared-decision groups. The shared-decision group had 

significantly greater adherence to long-term control medication compared to the guidelines 

group, and both interventions produced significantly better adherence to asthma control 

medications than usual care over 12 months of followup. 

The results of these two important RCTs suggest the value of shared decisionmaking about 

asthma treatment in adults. Therefore, the Expert Panel concludes that clinicians should 

involve adult patients in the treatment decisionmaking within the context of a therapeutic 

partnership. 

Health Professionals Who Teach Self-Management 

A variety of health professionals deliver health education effectively. Recent studies have 

focused on nurse-educators. Often, specially trained nurses provide asthma education. Three 

RCTs and three observational studies used advanced practice nurses trained in asthma to 

deliver self-management education to adults in outpatient settings. In one RCT, a 

hospital-based nurse specialist delivered self-management education during three sessions 

(Levy et al. 2000). Compared to patients receiving usual care, the educated patients 

significantly increased use of ICS; decreased use of SABA for quick relief of symptoms; 

achieved higher mean and less variable PEF; and had significantly lower symptom scores, 

doctor visits, and urgent care visits for asthma after 6 months. The reduction in asthma 

morbidity in this study may have been related to the strong emphasis, during the educational 

sessions, placed on improving asthma self-management skills during exacerbations. In another 

RCT, self-management education with peak flow monitoring and a written asthma action plan, 

individualized to the patient’s severity, was delivered in one session that was then reinforced 

in two subsequent visits (Janson et al. 2003). Compared to the control condition (monitoring 

only), self-management education significantly improved adherence to ICS medications, quality 

of life, and perceived control of asthma. In an attempt to reduce high hospitalization rates and 

health care utilization, another RCT (Urek et al. 2005) examined the effectiveness of three 

educational interventions in adults: “asthma school,” an educational booklet, and individual 

verbal instruction. Asthma school, which included three 4-hour sessions of group education, 

produced the most significant improvement in quality of life; individual verbal instruction 

produced the best overall response in terms of both asthma control and quality of life. 

Hopman and colleagues (2004) used nurse specialists to educate children and adults who had 

asthma through a standardized 2-hour asthma education program given across seven clinical 

centers in a large, multisite observational study. The program resulted in significant 
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improvements (decreases) in hospital utilization and missed activity days over 6 months. Two 

other observational studies of adults who had asthma, in which patients were taught and cared 

for by specially trained asthma nurses (Lindberg et al. 2002), showed significantly reduced 

symptoms and days of activity limitation as well as significantly decreased markers of airway 

inflammation (Janson et al. 2001). In an attempt to reduce sick days lost from work, a 4-week 

inpatient asthma rehabilitation program was tested in an observational study that included 

asthma education, pharmacological optimization, physical training, and coping skill training. 

The program resulted in significantly reduced sick leave over 3 years (Nathell 2005). 

Rehabilitation programs that require patients to live in the treatment setting are expensive and 

rare in the United States, but such programs may be useful for those who have severe asthma 

and are significantly limited by their asthma. 

Respiratory therapists also provide asthma education in hospital, ED, and clinic settings and 

may direct clinical pathways and algorithms in hospital settings. There are no published RCTs 

of asthma education programs delivered by respiratory therapists. An observational trial of 

60 pediatric patients who attended a special clinic focusing on inhaler technique demonstrated 

that MDI technique improved significantly after MDI demonstration, teaching, and reinforcement 

(Minai et al. 2004). Respiratory therapists also participate actively in clinical protocols or 

pathways that are implemented in acute care settings for management of acute exacerbations 

in hospitalized patients. Studies of the efficacy and value of clinical pathways is reviewed in the 

“Provider Education Section: Methods of Improving System Supports—Clinical Pathways.” 

The Expert Panel encourages using health professionals and others trained in asthma 

self-management education to implement and teach asthma self-management programs. 

Education With Multiple Sessions 

Negative studies that found little or no benefit of asthma self-management education frequently 

contained significant design flaws or methodological errors. Several were underpowered to 

detect significant differences between groups (Couturaud et al. 2002; Cowie et al. 2002; Neri et 

al. 2001) due to small sample size and significant attrition. (See Evidence Table 3, Asthma 

Self-Management for Adults.) Cowie and colleagues (2002) modified the education according to 

age level but found no incremental benefit from this adjustment. Many of these patients were 

recruited from EDs immediately after treatment for an acute exacerbation, when they were 

presumably more open to education, but significant attrition from or no attendance at the 

educational sessions scheduled outside of the medical care context occurred (Bolton et al. 

1991; Ford et al. 1997). Taken together, these studies demonstrate the problems that are 

created when education programs are not integrated into the patient’s regular medical care as 

well as the low participation of intervention patients in educational programs designed with 

multiple sessions over time. Because poor attendance at multiple sessions may be a problem 

in some populations, the Expert Panel’s opinion is that the key messages and essential skills of 

self-management should be introduced in the first session and that subsequent sessions should 

be adjusted to the needs of the patients in the groups. 

Children—Teach Asthma Self-Management Skills To Promote Asthma Control 

The Expert Panel recommends that asthma self-management education be incorporated 

into routine care for children who have asthma (Evidence A). (See Evidence Table 4, 

Asthma Self-Management Education for Children.) 
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A meta-analysis of 32 controlled trials of educational interventions for self-management in 

children and adolescents, involving 3,706 patients, showed significant effects of education in 

improving the child’s self-efficacy and lung function as well as in reducing days with restricted 

activity, school absences, and ED visits (Guevara et al. 2003). No effects were seen on 

hospitalizations (Guevara et al. 2003; Wolf et al. 2003). The authors conducted subgroup 

analyses to determine the effect of peak flow versus symptom-based monitoring strategies, 

individual versus group format, single versus multiple sessions, and moderate or severe asthma 

versus mild or moderate asthma, but the small number of studies in each subgroup did not 

provide sufficient statistical power to detect significant differences. 

Several other controlled studies have also shown positive effects for self-management 

education in children. A multicenter RCT of education delivered by asthma counselors through 

group sessions, individual meetings, and telephone followup showed that education significantly 

reduced days with asthma symptoms (Evans et al. 1999a). An RCT of education that combined 

group sessions, individual meetings, and having the family accompany the patient during doctor 

visits both decreased frequency of symptoms and activity restriction and increased the families’ 

ability and confidence to self-manage asthma (Bonner et al. 2002). A small RCT (N = 33) with 

minority families found that group education that emphasized collaborative learning and use of 

cultural resources increased asthma knowledge and reduced ED visits significantly compared to 

more didactic group education and to a no-intervention control (La Roche et al. 2006). A trial of 

training to improve children’s technique in using a breath-activated inhalation device showed 

that individual training provided by nurses in a single visit improved inhalation technique and 

that instructions to practice at home for 2 weeks resulted in further improvements (Agertoft and 

Pedersen 1998). These studies provide strong evidence for the benefit of providing structured 

self-management education to children who have asthma as well as their families in conjunction 

with ambulatory care for asthma. 

EMERGENCY DEPARTMENT/HOSPITAL-BASED EDUCATION 

Adults 

The Expert Panel recommends that:

 At the time of discharge from the ED, clinicians offer brief and focused asthma 

education (Evidence D) and provide patients with an ED asthma discharge plan with 

instructions to the patients and family for how to use it (Evidence B). 

 Before patients are discharged home, assess inhaler techniques for all prescribed 

medications and reinforce correct technique (Evidence B). 

 At the time of discharge from the ED, patients be referred for followup asthma care 

appointment (either PCP or asthma specialist) within 1–4 weeks (Evidence B). If 

appropriate, consider referral to an asthma self-management education program 

(Evidence B). 

 Before patients are discharged from a hospitalization for asthma exacerbations, give 

them asthma self-management education (Evidence B). 
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Emergency Department Asthma Education 

Visits to the ED for asthma exacerbation have been characterized as a moment of opportunity 

for providing asthma education, inhaler technique training, and referral for followup with the 

PCP; yet there are very few RCTs of asthma education in the ED for patients who have 

exacerbations. Previous asthma guidelines (EPR 1991; EPR⎯2 1997) have recommended at 

least some asthma education at the time of discharge from the ED for an exacerbation. One 

observational study conducted in the EDs of a province of Canada found that only 78 percent of 

patients received even brief education, and the focus was usually on medicines (46 percent) or 

inhaler technique (73 percent). Only 38 percent were counseled on triggers of exacerbations, 

and only 32 percent were referred to an asthma education program (Gervais et al. 2005). 

Patients who present to the ED with acute asthma are a source for identifying self-management 

problems. Observational studies (Griswold et al. 2005; Radeos et al. 2001) show that many of 

these patients have poor knowledge of self-management and have a high frequency of ED visits 

(Boulet et al. 1996; Griswold et al. 2005). Moreover, many adults seem to delay seeking care 

for acute asthma for a variety of reasons, including fear of being treated with systemic steroids 

(Janson and Becker 1998). These observations suggest a role for asthma education, yet there 

is little evidence from RCTs of the benefit of targeted education in the ED setting. A survey of 

77 asthma researchers based in EDs showed that, despite agreeing that patient education was 

very important, few EDs have or use asthma education programs (Emond et al. 2000). 

Targeting high-risk patients for asthma education at the ED visit has been explored in two RCTs 

(Bolton et al. 1991; Cote et al. 2001) and in two observational studies (Kelso et al. 1995, 1996). 

In one RCT, limited education in the ED in inhaler technique and use of a written asthma action 

plan was compared to a comprehensive, structured educational program and usual care (Cote 

et al. 2001). ED revisits were not different among the groups in the first 6 months after the 

intervention, but revisits declined significantly more in the structured education group by 

12 months; however, reinforcement of self-management education was provided at the 6-month 

point only to the structured education group. In a second RCT, Bolton and coworkers (1991) 

provided three asthma education sessions to patients after a visit to the ED. Despite significant 

attrition from attendance at sessions, followup was completed with 76 percent of the study 

sample, and, adjusting for baseline differences, the intervention group had fewer ED visits than 

controls at 12-month followup (p = .06). In a race-specific reanalysis of the Bolton and 

colleagues (1991) study data, Ford and coworkers (1997) found that African American and 

Caucasian patients experienced similar benefits from the program. 

Teaching Inhaler Technique in the Emergency Department 

Most other RCTs of education for adults in the ED setting focus on teaching inhaler technique 

for delivery of SABA. Numata and coworkers (2002) conducted an RCT in the ED to compare 

teaching MDI technique to 61 adults who had asthma and nebulizer delivery of bronchodilator to 

32 adults who had COPD. Median teaching time required to teach and administer MDIdelivered bronchodilator medication was 6.5 minutes. The authors concluded that teaching use 

of MDI with spacer delivery of bronchodilator is feasible in the ED for treatment of acute asthma 

exacerbation. This study suggests that patients can learn about and use MDIs in the acute care 

setting and that the ED provides an opportunity to teach correct inhaler technique. 

Despite being provided with MDIs and instructions for using them, a significant proportion of 

children continue to use nebulizers at home after discharge from the ED (Cheng et al. 2002). 

Use of MDIs by children may be complicated, however, by numerous errors in technique, 
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potentially rendering the devices ineffective. Scarfone and colleagues (2002) evaluated 

children’s skills in using an MDI and a peak flow meter in the ED and found a significant 

proportion were using these devices incorrectly with a large number of errors. Dry-powder 

inhaler (DPI) use appears to be associated with a rate of poor inhalation technique similar to 

that of the use of MDIs (Melani et al. 2004). Inhaler technique may be improved with tailored 

educational interventions aimed at specific problems (Hesselink et al. 2004). 

The Expert Panel concludes that it is important to assess inhaler techniques for all prescribed 

medications and reinforce correct technique before patients are discharged home. 

Referral for Followup Care 

ED clinicians encourage patients seen for acute exacerbation to follow up with their PCPs, and 

ED clinicians often encourage participation in an asthma education program. Robichaud et al. 

(2004) found that ED clinicians can motivate some patients to attend an asthma educational 

program following discharge from the ED by giving a brief educational message and facilitating 

followup attendance at the educational program. However, others have found that ED 

discharge instructions that include recommending attendance at an educational session and 

keeping an appointment with a PCP are not adhered to in any consistent way, and even when 

appointments are kept, there is no impact on long-term outcomes (Baren et al. 2001, 2006). In 

one RCT, however, the short-term outcome of contact with the PCP did improve (Baren et al. 

2001). These studies refer specifically to referral to the PCP. 

The findings may not be true for facilitated referrals to an asthma specialist. Both an 

observational study (Schatz et al. 2005) and an interventional study (Zeiger et al. 1991) suggest 

that better outcomes may result for patients referred from the ED to asthma specialists. 

Although evidence from RCTs is limited regarding the optimal referral site (e.g., PCP or asthma 

specialist), the Expert Panel concludes that patients should be referred for a followup asthma 

care appointment within 1–4 weeks of discharge from the ED. The followup appointment should 

include patient education; if appropriate, consider referral to an asthma self-management 

education program. Because there are so few studies of self-management education in the ED 

setting, and because the several interventions to improve patient followup have not 

demonstrated benefit, more research is needed to understand how to make education effective 

at this point of care. 

Hospital-Based Asthma Education 

Patients who are admitted to the hospital for acute severe asthma exacerbations represent 

another opportunity for teaching asthma self-management. Castro and colleagues (2003) 

conducted an RCT to determine if an intensive asthma intervention program led by specially 

trained nurses could prevent readmissions of adult patients who were noted to be high users of 

health care. The multiple-component intervention included asthma education, a written asthma 

action plan, extra social support, and telephone followup calls after discharge. The combination 

of all of these produced a significant decrease in readmissions for asthma and in total 

hospitalizations compared to patients in usual care. The effect of the individual components of 

the intervention was not determined. Similarly, another hospital-based randomized trial of an 

inpatient education program (George et al. 1999) targeted to young, economically 

disadvantaged adults who were admitted with acute asthma showed that inpatient asthma 

education, assistance with discharge planning, postdischarge followup telephone calls, and 

scheduled followup clinic visits had an impact after discharge. Patients who received the 
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intervention had a higher followup rate, fewer subsequent ED visits, and fewer repeat 

hospitalizations. 

In another RCT of asthma self-management education during hospital admission, 80 patients 

admitted with acute asthma received two 30-minute self-management education sessions and a 

written asthma action plan (Morice and Wrench 2001). The education group improved 

knowledge of asthma management compared to controls, but no significant differences between 

groups occurred in number of readmissions. Using a brief self-management intervention during 

hospital admission was found to reduce patients’ daytime wheezing, nighttime awakenings, 

activity limitations, and hospital readmission (Osman et al. 2002). The session was 

40–60 minutes of self-management education and included a written asthma action plan. All of 

these outcomes were improved compared to control patients but were more significant in 

patients for whom it was a first-time admission. The results of these trials suggest that asthma 

education at the time of hospitalization can have a significant effect in reducing repeat 

hospitalizations for asthma exacerbations. 

Children 

The Expert Panel recommends that asthma education programs that have been shown to 

be effective be delivered to children during or following discharge from the ED or the 

hospital (Evidence B). More research is needed to understand how to make education 

maximally effective at this point of care. 

The Expert Panel recommends that: 

 At the time of discharge from the ED, clinicians offer brief and focused asthma 

education (Evidence D) and provide patients with an ED asthma discharge plan with 

instructions to the patients and family for how to use it (Evidence B). 

 Before patients are discharged home, assess inhaler techniques for all prescribed 

medications and reinforce correct technique (Evidence B). 

 At the time of discharge from the ED, patients be referred for followup asthma care 

appointment (either PCP or asthma specialist) within 1–4 weeks (Evidence B). If 

appropriate, consider referral to an asthma self-management education program 

(Evidence B). 

 Before patients are discharged from a hospitalization for asthma exacerbations, give 

them asthma self-management education (Evidence B).

A meta-analysis of eight controlled studies of educational interventions for children or 

adolescents following ED visits or hospital admissions found no significant benefit for health 

status or readmission and concluded that more research is needed (Haby et al. 2001). The 

authors of the meta-analysis noted trends toward clinically relevant, yet not statistically 

significant, decreases in ED visits, unscheduled visits, and hospitalizations. Haby and 

colleagues recommended more studies with larger sample sizes to assess adequately the 

effectiveness of educational interventions after use of emergency care. Two successful studies 

included in this meta-analysis showed very different approaches. An RCT of a nurse-led 

discharge program (consisting of a 20-minute patient education program and a written asthma 

action plan) significantly reduced unscheduled doctor visits, ED visits, and readmissions to 

hospital over 12 months (Wesseldine et al. 1999). In another RCT, a nurse-led training program 
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administered during admission with one outpatient followup visit to the nurse resulted in reduced 

hospital admissions in the following 14 months (Madge et al. 1997). 

Five recent RCTs show mixed results for the effectiveness of education postdischarge from the 

ED. Walders and colleagues (2006) provided all participants with medical care by a specialist, 

including written asthma action plans, peak flow meters, and spacer devices. Participants who 

also received an intervention that included an asthma education session, a session on 

problem-solving based on an individualized asthma risk profile, and access to an asthma advice 

telephone service had significantly fewer ED visits at 12-month followup than the controls who 

received no education (Walders et al. 2006). Teach and coworkers (2006) scheduled a followup 

visit, within 2 weeks, to a specialized asthma clinic located in the ED, where followup care and 

education were provided. The intervention group received a written asthma action plan and 

referrals to ongoing primary care, plus education about asthma self-monitoring and 

management as well as environmental modification and trigger control. Compared with 

controls, the intervention group had significantly greater ICS use, fewer ED visits, and improved 

quality of life in the 6-month followup period (Teach et al. 2006). Sockrider and colleagues 

(2006) provided children and their families with tailored education, including a customized 

asthma action plan and an educational summary, before discharge from the ED for an acute 

episode of asthma. At 2-week followup, intervention families had significantly greater 

confidence than controls in their ability to manage asthma. At 9-month followup, among 

participants who had intermittent asthma, children whose families received education had 

significantly fewer ED visits than controls, but there was no difference between groups for 

children who had persistent asthma (Sockrider et al. 2006). Two other controlled trials of brief 

education, by telephone postdischarge from the ED (Khan et al. 2004) and by a combination of 

computer instruction and interaction with a nurse practitioner (Sundberg et al. 2005), did not 

improve patients’ health status. 

Two recent controlled trials to see if telephone reminders after discharge from the ED increased 

followup appointments with primary care showed positive findings at short-term but not 

long-term followup. In one study, appointment rates, quality of life, and asthma symptoms 

improved relative to controls at 6 months, but no difference was found at 12 months (Sin et al. 

2004). In the second study, the number of appointments was higher and symptoms were lower 

at 2 weeks, but these differences had disappeared at 12 months (Smith et al. 2004). 

In an RCT (Zorc et al. 2003), followup primary care appointments for children seen in the ED for 

acute asthma were scheduled by ED staff, but patients had no higher rate of attendance than 

when visits were simply requested. Furthermore, there was no change in return visits to the ED, 

missed school, or use of long-term control medications. 

Based on these findings, the Expert Panel concludes that asthma education programs that have 

been shown to be effective should be delivered to children during or following discharge from 

the ED or the hospital. More research is needed to understand how to make education 

maximally effective at this point of care. 

EDUCATIONAL INTERVENTIONS BY PHARMACISTS 

The Expert Panel recommends that use of interventions provided by pharmacists be 

considered; such programs are feasible, and they merit further studies of effectiveness 

(Evidence B). 
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Controlled trials of asthma education delivered by pharmacists have shown mixed results 

(Barbanel et al. 2003; Basheti et al. 2005; Bynum et al. 2001; Cordina et al. 2001; McLean et al. 

2003; Saini et al. 2004; Stergachis et al. 2002). Four of these RCTs recruited community 

pharmacies, provided training for their pharmacists, and evaluated the impact of pharmacist 

teaching on patient outcomes (Cordina et al. 2001; McLean et al. 2003; Saini et al. 2004; 

Stergachis et al. 2002). All of these studies involved repeated contacts with patients. One 

study showed reduced hospitalizations and improved inhaler technique (Cordina et al. 2001). A 

second study found reduced asthma severity, better lung function, less use of albuterol, and 

better perceived control of asthma (Saini et al. 2004). The third study showed reductions in 

daytime and nighttime symptoms, use of SABA, and doctor visits, as well as improvements in 

PEF and quality of life (McLean et al. 2003). The fourth study found no differences between 

intervention patients and controls on any measure (Stergachis et al. 2002). These studies 

noted difficulties in providing asthma education in a community pharmacy, but they 

demonstrated that community pharmacies may serve as effective venues for scheduled 

followup visits for specialized asthma care. A small study of patients randomized within a single 

pharmacy found significant reduction in symptoms for the intervention group (Barbanel et al. 

2003). Another small study found that counseling by a pharmacist improved inhaler technique 

(Basheti et al. 2005). Finally, another study evaluated interactive telepharmacy video 

counseling, using compressed video, connecting adolescents in schools with pharmacists 

working from a remote site; this study found improvements in inhaler technique (Bynum et al. 

2001). 

The Expert Panel concludes that, despite the difficulties observed, use of interventions provided 

by pharmacists is feasible, may help improve self-management skills and asthma outcomes, 

and merits more clinical studies of pharmacists’ providing education interventions. 

EDUCATIONAL INTERVENTIONS IN SCHOOL SETTINGS 

The Expert Panel recommends that implementation of school-based asthma education 

programs proven to be effective be considered to provide to as many children who have 

asthma as possible the opportunity to learn asthma self-management skills and to help 

provide an “asthma-friendly” learning environment for students who have asthma 

(Evidence B). 

Several studies suggest that comprehensive school-based asthma education programs can 

improve health and quality of life in students who have persistent asthma. Five controlled trials 

of education in schools for children who have asthma have shown reduced symptoms for 

children receiving asthma education (Butz et al. 2005; Christiansen et al. 1997; Cicutto et al. 

2005; Clark et al. 2004; MeGhan [sic] et al. 2003). Three of these studies have also shown 

reductions in the use of acute health care services (Butz et al. 2005; Cicutto et al. 2005; 

MeGhan [sic] et al. 2003). One program provided education for elementary school children, 

plus educational components for principals, custodians, and other school staff, resulting in 

reduced asthma morbidity, improved asthma management, and decreased school absences 

(Clark et al. 2004). A secondary analysis of this trial found that the program also had effects on 

students who had moderate or severe symptoms but no diagnosis; effects included reductions 

in daytime and nighttime symptoms and in days with restricted activity (Joseph et al. 2005). 

Two studies have shown that parents who did not attend the educational sessions had improved 

asthma management skills after completing learning assignments with children at home (Clark 

et al. 2004; Evans et al. 2001). 
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An innovative trial of peer education in the schools, in which older students were trained to 

deliver education to younger students, improved quality of life in participating students (Shah et 

al. 2001). Teacher-led asthma education interventions have been successful in improving 

asthma outcomes in secondary schools and in improving school policies. In a very large trial, 

teachers were trained to deliver asthma education to students who had and did not have 

asthma. This study revealed positive changes in students’ knowledge of asthma, their 

perception that asthma could be controlled, and their tolerance of asthma in others (Henry et al. 

2004). Five-year followup showed that this program was still being taught by 71 percent of the 

teachers who had been trained. 

Three other RCTs of school-based education showed no significant effect on student health 

(Patterson et al. 2005; Velsor-Friedrich et al. 2005) or school staff efforts to communicate with 

community physicians about students’ symptoms (Halterman et al. 2005). Another RCT tested 

the effectiveness of an asthma educational intervention in improving asthma knowledge, 

self-efficacy, and quality of life in rural families (Butz et al. 2005). Children 6–12 years of age 

who had persistent asthma were recruited from rural elementary schools and randomized into 

the control (standard asthma education) group or into an interactive educational intervention 

consisting of three educational workshops, an asthma coloring book, and parental educational 

workshops. Parent/caregiver and child asthma knowledge, self-efficacy, and quality of life were 

assessed at baseline and at 10 months after enrollment. Children’s self-efficacy, children’s 

asthma knowledge, and parental asthma knowledge increased significantly in the intervention 

group, but no significant increase in parental self-efficacy or children’s or parental quality of life 

was found at followup. 

Asthma education video gaming media were shown to be useful in improving asthma 

self-management knowledge and asthma quality of life for high-risk, low-income, inner-city 

children who have asthma (Shames et al. 2004). 

Taken together, these studies suggest that asthma education delivered in schools can improve 

health and quality of life in students who have asthma. 

COMMUNITY-BASED INTERVENTIONS 

Asthma Education 

It is the opinion of the Expert Panel that, although studies of community-based asthma 

education do not demonstrate benefits in health status, they do show that asthma 

education programs delivered by trained community residents are feasible, can result in 

behavior change and improved quality of life, and deserve further research (Evidence C). 

(See Evidence Table 5, Asthma Self-Management Education in Community Settings.) 

Community-based asthma interventions (those delivered in various community settings) can 

positively affect large numbers of persons who have asthma, especially in poor, inner-city 

communities. A controlled trial of asthma outreach and education, delivered by trained 

community residents in a community center, found no difference in acute care visits between 

intervention and comparison communities, but the study found reduced numbers of acute care 

visits for those who had high levels of participation in the program (Fisher et al. 2004). 

Surprisingly, socially isolated residents were more likely to participate in program activities than 

those who were socially active. An observational study of education for caregivers of children 

who had asthma, delivered by trained, community peer educators, found significant increases in 

asthma knowledge, management behavior, and quality of life; these increases were sustained 
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at 3, 6, and 12 months (Bryant-Stephens and Li 2004). An asthma education program that 

included the interventions of group and individual education sessions taught by a nurse and a 

physiotherapist resulted in significantly fewer primary care visits and less absenteeism from 

work (Gallefoss and Bakke 2001). In an observational study, hospital inpatient asthma 

education combined with outpatient followup asthma education in the community for children 

and families improved asthma knowledge (Ochsner et al. 2002). The inclusion of a child-life 

specialist in community-based and family-support interventions appears to be beneficial in 

promoting psychological adjustment of children who have chronic health conditions, such as 

asthma, especially if the child has low self-esteem (Chernoff et al. 2002). 

HOME-BASED INTERVENTIONS 

Home-Based Asthma Education for Caregivers 

The Expert Panel recommends that asthma education delivered in the homes of 

caregivers of young children be considered and that this area needs more research 

(Evidence C). 

A controlled trial of a home-based asthma education intervention for caregivers of young 

children showed that the intervention significantly reduced the amount of reported bother from 

asthma symptoms and increased symptom-free days and caregiver quality of life for children 1–

3 years of age (Brown et al. 2002). The age of the children who had asthma appeared to 

moderate the intervention effect of home-based asthma education for caregivers in relation to 

both asthma morbidity and caregivers’ quality of life. A single-group study of home-based 

asthma education intervention for Latino caregivers of children who have asthma (average age, 

7 years) showed reductions in bedroom allergens and increases in allergen-control devices 

(e.g., mattress covers) at followup (Jones et al. 2001). These studies suggest that the home 

may be a useful point of care for education interventions. 

Home-Based Allergen-Control Interventions 

The Expert Panel recommends that multifaceted allergen education and control 

interventions delivered in the home setting and that have been shown to be effective in 

reducing exposures to cockroach, rodent, and dust-mite allergen and associated asthma 

morbidity be considered for asthma patients sensitive to those allergens (Evidence A). 

Further research to evaluate the cost-effectiveness and the feasibility of widespread 

implementation of those programs will be helpful. 

Avoiding allergens is often difficult (Leickly et al. 1998). The home may be a useful point of care 

for educational interventions to reduce household allergens and to increase the use of 

allergen-control devices in the home. Eight controlled trials have evaluated allergen-control 

interventions that combined education for families about implementing allergen-control 

strategies with provision of tools and supplies needed to carry them out (Carter et al. 2001; 

Custovic et al. 2000; Eggleston et al. 2005; Klinnert et al. 2005; Krieger et al. 2005; McConnell 

et al. 2005; Morgan et al. 2004; Woodcock et al. 2003). Some of these studies added 

professional allergen-reduction services (Carter et al. 2001; Custovic et al. 2000; Eggleston et 

al. 2005; Morgan et al. 2004), and several provided broader education about asthma 

management as well (Klinnert et al. 2005; Krieger et al. 2005). Four of the studies delivered 

allergen-control education through multiple home visits (Eggleston et al. 2005; Klinnert et al. 

2005; Krieger et al. 2005; Morgan et al. 2004). 
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In general, the aim of these trials was to test multifaceted strategies to reduce the burden of 

allergens in the homes of asthma patients and to improve health outcomes rather than the 

efficacy of specific allergen-control techniques by themselves. An innovative trial of home 

intervention to control allergens included both a placebo control and a “no-visit” control to 

assess the relative effect of the intervention versus home visits to prompt allergen-control 

measures by families of children who have asthma (Carter et al. 2001). The intervention and 

placebo control (permeable mattress covers and instructions to wash bedding in cold water) 

groups did not differ significantly, but both groups had reduced acute care visits when compared 

to the no-visit control group, suggesting that the home visit itself resulted in improved asthma 

control. This study did not provide information about how families in the no-visit control group 

reduced allergens or improved asthma control. 

Another trial evaluated allergen-control measures in the homes of infants who had atopic 

parents and no pets; measures included using impermeable bedding covers, replacing carpet 

with vinyl flooring in the infant’s room, and asking participants to wash bed linens in hot water. 

Over the 1-year followup, the intervention group had significantly less wheeze with shortness of 

breath, less wheeze after vigorous activity, and less medicine prescribed by PCPs for control of 

wheezy attacks (Custovic et al. 2000). This study suggests that prenatal intervention in 

high-risk infants can reduce the risk of asthma symptoms during the first year of life. 

One large trial relied primarily on repeated home visits to educate the family in allergen-control 

techniques and to provide them with HEPA-filter vacuum cleaners and mattress covers. The 

intervention was tailored to the child’s allergen-sensitivity profile, and professional pest control 

was applied for children allergic to cockroach (Morgan et al. 2004). Over the 2-year followup 

period, significant reductions occurred in cat, dust-mite, and cockroach allergens in the child’s 

bedroom, and these were associated with reductions in daytime and nighttime symptoms, fewer 

school absences in both years, and reductions in ED visits in the first followup year. This study 

suggests that education about relevant environmental control in the home, coupled with the 

provision of tools for allergen control, can enable families to reduce allergen levels and asthma 

morbidity effectively. 

A clinical RCT of home environmental intervention with inner-city children who had mild 

persistent asthma demonstrated that tailored, multifaceted environmental treatment and 

education can reduce airborne particulate matter in inner-city homes, resulting in a modest 

effect on asthma morbidity, with decreased asthma symptoms, but no improvement in lung 

function (Eggleston et al. 2005). The intervention group received home-based education, 

cockroach and rodent extermination, allergen-proof mattress and pillow encasings, and 

HEPA-filter air cleaners. Outcomes were measured by home evaluations at 6 and 12 months, 

clinic evaluation at 12 months, and multiple telephone interviews. 

Three RCTs, assessing the effect of home-based education on allergens and control 

interventions, used community health workers. One RCT showed that a home-based 

allergen-control and education intervention (delivered by trained community health workers to 

families of children who had asthma), focusing on training residents to apply cockroach-control 

measures themselves during a five-visit period, could successfully reduce the number of 

cockroaches in the home and cockroach-allergen levels in the children’s bedding (McConnell et 

al. 2005). No measures of health outcomes were reported. A second trial provided 

allergen-control education, as well as resources and support for behavior change, by trained 

community heath workers in seven visits (Krieger et al. 2005). This study found reductions in 

the use of emergency health care services by children who had asthma and improvements in 

the quality of life of their caregivers. A third trial of allergen control and both allergen-specific 
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and general asthma education with children relied on 15 home visits over a period of 12 months 

by nurses trained in community outreach (Klinnert et al. 2005). Compared to controls, this 

intervention significantly reduced cockroach-allergen and children’s cotinine levels but had no 

effect on health outcomes. 

In adults, a trial of dust-mite-allergen control that relied on allergen-impermeable bed covers 

alone, without instructions to wash linens in hot water or any other education, found no 

significant differences in mattress dust, morning PEF, or percent of patients who were able to 

control asthma without ICSs (Woodcock et al. 2003). This study, which involved no educational 

component, suggests that the role of education in maintaining allergen control is important. 

Several studies with strong education components were successful in reducing allergen 

exposures in the home and/or reducing asthma morbidity, whether education was delivered by 

community workers or research staff. More research is needed to increase our understanding 

about how the combination of home-based education interventions and the provision of tools for 

allergen control in high-risk asthma populations can reduce the burden of allergen exposure and 

affect asthma morbidity. Studies are also needed to evaluate the cost-effectiveness and 

feasibility of widespread implementation of all allergen-control interventions delivered in 

patients’ homes. 

Summary statement on asthma self-management education at points of care outside the 

health care system: 

According to the review of RCTs, asthma education can be delivered at multiple points of care 

other than clinics, EDs, and hospitals. With the support of clinicians, effective educational 

interventions should be provided at points of care outside the traditional health care setting, 

including schools (Butz et al. 2005; Christiansen et al. 1997; Cicutto et al. 2005; Clark et al. 

2004; MeGhan [sic] et al. 2003), pharmacies (Cordina et al. 2001; McLean et al. 2003; Saini et 

al. 2004), and homes. For example, pharmacy-based education directed toward understanding 

medications and teaching inhaler skills as well as home-based interventions to increase patient 

and family capacity to control allergen and irritant exposure (Custovic et al. 2000; Eggleston et 

al. 2005; Klinnert et al. 2005; Krieger et al. 2005; McConnell et al. 2005; Morgan et al. 2004) are 

strategies that will enhance overall asthma self-management support. 

OTHER OPPORTUNITIES FOR ASTHMA EDUCATION 

Education for Children Using Computer-Based Technology 

The Expert Panel recommends that computer-based programs that are incorporated into 

asthma care be considered for adolescents and children (Evidence B). 

Four controlled trials have tested the ability of interactive computer asthma-education programs 

to improve children’s asthma self-management behavior, health outcomes, and use of 

emergency health services. Two studies of computer-based asthma-education programs that 

children completed over a series of clinic visits reported positive results including: reduced 

symptoms and hospitalizations, and increased clinic followup visits (Bartholomew et al. 2000); 

reduced symptoms and ED visits, and less use of ICSs (Krishna et al. 2003). In two other trials 

of computer-based education, no improvements were found in health status or use of 

emergency health services. One study involved three opportunities to complete the program 

over three clinic visits (Homer et al. 2000); the other study involved a single 20-minute 

opportunity to complete the program at home with guidance from a nurse (Huss et al. 2003). 
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Two other trials tested computer-based programs to facilitate recording symptoms, 

communicating with health care providers, and making decisions about treatment. A trial of a 

device used at home to monitor symptoms and medication use, obtain immediate programmed 

feedback, and communicate results to health care providers over a telephone link found 

reductions in days with activity limitation, reports of peak flow in yellow or red zones, and urgent 

telephone calls to the doctor (Guendelman et al. 2002). A trial that tested an interactive, 

Internet-based system, allowing specialists to monitor patient diaries of symptoms and peak 

flow and to adjust therapy quickly, rapidly improved patients’ control of symptoms and quality of 

life (Rasmussen et al. 2005). 

An observational study found that asking children and adolescents to videotape their 

asthma-management practices at home provided detailed evidence of problems with adherence 

and inhaler technique (Rich et al. 2000). Reviewing these videotape narratives with the patient 

may help clinicians improve teaching and care of patients. 

Taken together, these studies suggest that new technologies, including computer and 

Internet-based education and communication with physicians, can improve patients’ control of 

asthma. More research is needed in these areas. 

Education on Tobacco Avoidance for Women Who Are Pregnant and Members of 

Households With Infants and Young Children 

The Expert Panel recommends that all patients who have asthma and women who are 

pregnant be advised not to smoke and not to be exposed to ETS (Evidence C). Query 

patients about their smoking status, and consider specifically referring to smoking 

cessation programs adults who smoke and have young children who have asthma in the 

household (Evidence B). 

Several studies strongly suggest that maternal smoking during pregnancy results in harmful in 

utero exposure of the fetus and increases the risk of the child’s developing recurrent wheezing 

and asthma in the first 5 years of life (Agabiti et al. 1999; Gergen et al. 1998; Gilliland et al. 

2001). Children exposed in utero to maternal smoking demonstrate persistent deficits in lung 

function measured by spirometry (Kelso et al. 1995). Children not exposed in utero but exposed 

postnatally to tobacco smoke in the home also have an increased risk of wheezing and asthma 

by age 5 (Gergen et al. 1998). Heavy postnatal tobacco smoke markedly increases the risk for 

persistent asthma in the child (Infante-Rivard et al. 1999). In addition, children 4–16 years of 

age who were exposed to pre- and postnatal tobacco smoke and had high cotinine levels were 

found to have increased wheezing, increased school absences, and decreased lung function 

(Mannino et al. 2001). 

It is now well established that exposure to ETS increases the severity of asthma, increases the 

risk of asthma-related ED visits and hospitalizations, and decreases the quality of life in both 

children and adults (Eisner 2002; Mannino et al. 2002; Morkjaroenpong et al. 2002). In adult, 

nonsmoking persons who have asthma, recent secondhand smoke exposure (as directly 

measured by 7-day nicotine badge) and long-term 3-month exposure (as measured by levels of 

both nicotine and cotinine in hair) are associated with increased asthma severity and poorer 

asthma outcomes (Eisner et al. 2005). In terms of public health, these results support efforts to 

prohibit smoking in public places. 
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An important RCT (Wilson et al. 2001) used three nurse-led education sessions with parents 

who were smokers; the sessions incorporated behavior change strategies, asthma education, 

and repeated feedback of their children’s urinary cotinine levels. The intervention significantly 

reduced medical visits for acute asthma in these tobacco-exposed, low-income, minority 

children. 

Because of the marked impact of tobacco as an irritant for most people who have asthma plus 

the negative health consequences of smoking to the smoker, the smoking status of all patients 

should be obtained, and appropriate advice and support should be offered to all patients who 

smoke. 

Case Management for High-Risk Patients 

The Expert Panel recommends that case or care management by trained health 

professionals be considered for patients who have poorly controlled asthma and have 

recurrent visits to the ED or hospital (Evidence B). 

Case or care management is the strategy of using expert guidelines to focus management of 

patients who have asthma and have high levels of health care service use on specific, stepwise 

goals to reduce morbidity and costs, as well as the risk of mortality from asthma. Three RCTs 

(Greineder et al. 1999; Hughes et al. 1991; Kelly et al. 2000) found that case management 

reduced ED visits, hospitalizations, and health care costs among children who had asthma and 

were high users of health care resources. In all three trials, the intervention included intensive 

education of patients combined with case management by nurses. One study (Greineder et al. 

1999) found a 39 percent reduction in ED use in the group that received asthma education 

alone, but the extent to which this was attributable to the education rather than to developmental 

changes cannot be determined. However, case management with education resulted in a 

73 percent decrease in ED visits—a reduction of 34 percentage points compared with education 

alone (p = 0.0002). Hospitalizations were reduced by 43 percent in the control group and by 

84 percent in the case-management group. Total use of services outside the study group health 

plans was reduced 28 percent in control and 82 percent in case-management groups. All 

between-group differences were statistically significant. The positive effect of asthma education 

was significantly enhanced by followup case management, with continued contact with the 

nurse case manager. Care-management processes are tools to improve the efficiency and 

quality of primary care delivery. These tools are often used by organizations that provide care 

for chronic illnesses, such as asthma and diabetes, to low-income populations. 

Another study (Delaronde 2002) explored using case management to increase use of ICSs 

among 249 persons who had asthma, were in a managed care program, were identified as 

receiving three or more SABA prescriptions for 3 consecutive months, but had no prescription 

for anti-inflammatory medications. The results of this study and another observational study 

with more intensive followup (Delaronde et al. 2005) showed that case management may 

improve medication use by patients who do not use asthma medications as prescribed. 

Patients who received intensive case-management intervention were four times more likely to 

be prescribed anti-inflammatory medications. 

Taken together, the findings of these studies suggest that case (or care) management can be 

effective in improving asthma control in selected populations of individuals who have poorly 

controlled asthma. 
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COST-EFFECTIVENESS 

The Expert Panel recommends that asthma self-management education that is provided 

by trained health professionals be considered for policies and reimbursements as an 

integral part of effective asthma care; the education improves patient outcomes 

(Evidence A) and can be cost-effective (Evidence B). (See Evidence Table 6, 

Cost-Effectiveness of Asthma Self-Management Education.) 

Cost-effectiveness analyses provide evidence of the financial impact of interventions as well as 

their clinical benefits. The analyses relate costs to a measure of clinical effectiveness of the 

intervention. The cost-effectiveness ratio is the ratio of the difference in costs between two 

alternatives to the difference in effectiveness between the same two alternatives. When an 

intervention that has a certain cost improves a significant clinical outcome and total costs are 

decreased, the intervention is considered cost-effective. For example, if self-management 

education improves overall control of asthma, with fewer days of symptoms, fewer ED visits, 

and fewer hospitalizations, then the intervention may result in lower overall direct medical costs. 

If these educated patients also have fewer missed work or school days, then indirect costs are 

reduced as well. 

The cost-effectiveness and/or cost savings of asthma self-management education has been 

shown in six RCTs (Gallefoss and Bakke 2001; Kamps et al. 2004; Kauppinen et al. 1999; 

Schermer et al. 2002; Sullivan et al. 2002, 2005) and one observational study (Tinkelman and 

Wilson 2004). Sullivan and colleagues (2002) conducted a prospective cost analysis of an 

inner-city asthma-management program being studied in an RCT of 1,033 inner-city children 

who had asthma. The primary efficacy end point was the mean number of days with asthma 

symptoms self-reported over a 2-week period. Masters-level social workers worked with adult 

family members to improve asthma-management skills. Children attended two child-only group 

sessions for skill development. Compared with usual care, the intervention improved outcomes 

at average cost of $9.20 per symptom-free day. Cost savings increased as severity of a child’s 

asthma increased. Cost-effectiveness was greater in subgroups of children who had more 

severe asthma because, for the modest increase in cost of the intervention, substantial 

reductions occurred in the total cost of medical care. Later, Sullivan and colleagues (2005) 

evaluated the cost-effectiveness of interventions designed to improve the quality of care 

delivered to children who had asthma and their outcomes. In this three-arm, cluster RCT, 

peer-led physician education was compared to combined peer-led education with a multilevel, 

nurse-led educational intervention to improve asthma care and compared to usual care. The 

primary clinical outcome, symptom-free days, was highest (13.3 days) for the combined 

intervention compared to peer-led education alone (6.5 days) and compared to usual care, but 

this outcome was achieved at an increased cost of asthma care (cost-effectiveness ratio of 

$18/symptom-free day for peer-led education and $68/symptom-free day for the combined 

intervention). The higher costs were attributable to the cost of implementing and maintaining 

the interventions. 

Two other RCTs demonstrate the cost-effectiveness of self-management education (Gallefoss 

and Bakke 2001; Schermer et al. 2002). Both studies showed that guided self-management 

education improved quality of life, lung function, and compliance with ICS medication while 

reducing rates of physician consultation and absenteeism from work due to asthma. A key part 

of the intervention was teaching how to change medication during symptom episodes of 

asthma. Both studies showed a reduction in total direct and indirect costs while improving 

asthma outcomes, thus making the cost of the self-management interventions cost-effective. 
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In an earlier study, Kauppinen and coworkers (1999) conducted an RCT in newly diagnosed 

adults who had asthma, comparing the long-term cost-effectiveness of intensive patient 

education combined with supervision of self-management to a control group who received 

conventional brief education at the initial visit. After 3 years, a significant improvement in lung 

function and a significant reduction in sick days occurred in the self-management group. 

Quality-of-life scores did not differ between groups, and the difference in costs was not 

statistically significant, although costs were consistently lower in the self-management group. 

Kamps and colleagues (2004) conducted an RCT of outpatient asthma management of children, 

who were 2–18 years of age and had asthma, by trained nurses compared to pediatricians. 

After all patients were seen for the first asthma-education visit with a nurse educator, the 

patients were randomly assigned to either a pediatrician or an experienced asthma nurse 

educator. Costs of followup care were less for the nurse than for the pediatrician due to lower 

salary costs. In this population of patients who had mild asthma, nurse-led outpatient 

management of childhood asthma was provided at a lower cost, with no difference in health 

care utilization, compared to medical care by pediatricians. Similar results were shown by 

Lindberg and coworkers (2002) in a comparative cohort study of adult patients cared for by 

trained asthma nurses versus physicians. The average costs of care were significantly less for 

the group of patients managed by nurses. 

In an observational study, Tinkelman and Wilson (2004) reported a disease-management 

intervention that was effective in achieving cost savings in asthma care. Patients served as 

their own controls and showed a significant improvement, between baseline and 

postintervention, in costs of care. 

Taken together, the analyses of costs in both randomized and observation trials demonstrate 

the cost-effectiveness of education in those asthma self-management programs that improve 

patients’ skills and decrease health care utilization. (See Evidence Table 6, Cost-Effectiveness 

of Asthma Self-Management Education.) 

Tools for Asthma Self-Management 

ROLE OF WRITTEN ASTHMA ACTION PLANS FOR PATIENTS WHO HAVE ASTHMA 

The Expert Panel recommends that clinicians provide to all patients who have asthma a 

written asthma action plan that includes instructions for (1) daily management and (2) 

recognizing and handling worsening asthma, including adjustment of dose of 

medications. Written action plans are particularly recommended for patients who have 

moderate or severe persistent asthma, a history of severe exacerbations, or poorly 

controlled asthma (Evidence B). Written asthma action plans may be based on PEF 

measurements or symptoms or both, depending on the preference of the patient and 

clinician (Evidence B). A peak-flow-based plan may be particularly useful for patients 

who have difficulty perceiving signs of worsening asthma (Evidence D). 

The Expert Panel prefers to use one term—“written asthma action plan”—to encompass 

instructions both for daily actions to keep asthma controlled and for actions to adjust treatment 

when symptoms or exacerbations occur. Using one term addresses the confusion over 

previous guidelines’ use of several different terms for asthma management plans and 

emphasizes the importance of giving patients instructions for managing both the acute and longterm aspects of asthma. Therefore, this report uses one term “written asthma action plan,” 

although in some studies investigators used a variation of this term. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

Written asthma action plans provide a way to involve the patient directly in self-management by 

writing down the treatment plan the clinician and patient agree on together and by giving clear 

instructions that the patient can use at home. The asthma action plan should be reviewed and 

refined at the patient’s followup visits. Clinicians should choose an action plan that suits 

their practice, patients, and style. Examples of asthma action plans are provided in 

figures 3–10 a, b, and c to demonstrate the range of possibilities; they can be modified as 

appropriate. 

Written asthma action plans include two important elements: 

 Daily management 

— What medicine to take daily, including the specific names of the medications 

— What actions to take to control environmental factors that worsen the patient’s asthma 

 How to recognize and handle worsening asthma 

— What signs, symptoms, and PEF measurements (if peak flow monitoring is used) 

indicate worsening asthma 

— What medications to take in response to these signs 

— What symptoms and PEF measurements indicate the need for urgent medical attention 

— Emergency telephone numbers for the physician, ED, and person or service to transport 

the patient rapidly for medical care 

systematic reviews and in five individual studies. A recent systematic review of 36 RCTs 

showed that self-management education that included self-monitoring by either PEF or 

symptoms, coupled with regular medical review and a written asthma action plan, reduced 

hospitalizations, urgent care visits, ED visits, work absences, and nocturnal asthma in adults 

(Gibson et al. 2003). Although subgroup analyses were not able to isolate the specific 

contribution of written plans to these outcomes, the authors conclude that education 

programs that enable people to adjust their medication using a written asthma action plan 

appear to be more effective than other forms of asthma self-management. 

In a later systematic review (Toelle and Ram 2004), three RCTs tested the effect of written 

plans versus no written plans and found no consistent evidence that written plans produced 

better patient outcomes than outcomes with no written plan. The trials were too small and the 

results too inconsistent to reach a firm conclusion about the contribution of written asthma 

action plans to asthma education. 

Five individual studies (including four RCTs, and one with an additional, extended followup) and 

one case-control study have examined the contributions of written asthma action plans to the 

control of asthma (Abramson et al. 2001; Baldwin et al. 1997; Cowie et al. 1997; Jones et al. 

1995; Klein et al. 2001; van der Palen et al. 2001). Two RCTs showed no effect for written 

asthma action plans compared to no written plans for measures of asthma morbidity or health 

care utilization (Baldwin et al. 1997; Jones et al. 1995). The individual benefit of including an 

asthma action plan for self-management of exacerbations was shown in a 2-year RCT 

 The effectiveness of written asthma action plans has been addressed in several recent 
Section 3, Component 2: Education for a Partnership in Asthma Care 

117 

August 28, 2007 

FIGURE 3–10a. SAMPLE ASTHMA ACTION PLAN 

Source: Adapted and reprinted with permission from the Regional Asthma Management and Prevention (RAMP) Initiative, a program of the Public 

Health Institute. http://www.calasthma.org/uploads/resources/actionplanpdf.pdf; San Francisco Bay Area Regional Asthma Management Plan, 

http://www.rampasthma.org 
Section 3, Component 2: Education for a Partnership in Asthma Care 

118 

August 28, 2007 

FIGURE 3–10b. SAMPLE ASTHMA ACTION PLAN 

Adapted and reprinted with permission from the Regional Asthma Management and Prevention (RAMP) Initiative, a program of the Public Health 

Institute. 

Source: http://www.calasthma.org/uploads/resources/actionplanpdf.pdf; San Francisco Bay Area Regional Asthma Management Plan, 

http://www.rampasthma.org 
Section 3, Component 2: Education for a Partnership in Asthma Care 

119 

August 28, 2007 

FIGURE 3–10c. SAMPLE ASTHMA ACTION PLAN 

Source: National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services. 

NIH Publication No 07-5251, October 2006. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

120 

August 28, 2007 

(van der Palen et al. 2001). The self-management action plan significantly improved selfperceived asthma control, confidence (self-efficacy) for self-management, and self-treatment 

and self-management behavior during a hypothetical asthma exacerbation. These subjective 

outcomes were confirmed after 2 years of followup, but no significant effect on asthma clinical 

status was detected (Klein et al. 2001). Another RCT (Cowie et al. 1997) provided education for 

all patients during ED visits for asthma exacerbations and randomly assigned patients to three 

study arms: no written plan, a symptom-based written plan, and a peak flow-based written plan. 

Over the 6-month followup period, all groups improved their asthma control, but patients who 

received a peak flow-based written plan had significantly (p = 0.002) fewer urgent care visits (5 

for 46 patients) compared with patients who received a symptom-based plan (45 visits for 48 

patients) or no written plan (55 visits for 48 patients). A case-control study by Abramson and 

colleagues (2001) compared patients who died from exacerbation of asthma with controls who 

had severe asthma exacerbations successfully treated in the ED. After adjustment for 

demographic, psychosocial, and disease severity factors, having a written asthma action plan at 

the time of the exacerbation was significantly associated with a 70 percent reduction in the risk 

of death (RR = 0.29 (0.09, 0.93)). 

Although the results of these studies are mixed, they suggest that the use of written plans may 

help patients improve control of their asthma, particularly in preventing or managing asthma 

exacerbations. A scientific review (Powell and Gibson 2003) examined several options for the 

use of written plans in asthma management. The review found no difference in outcomes when 

patients self-adjusted medication by using a written asthma action plan compared to when 

clinicians adjusted treatment. These two methods for achieving asthma control were found to 

be equivalent. This finding suggests that it is safe and effective for patients to use written 

asthma action plans for self-management of their asthma. 

Adams and colleagues (2001) showed that a comprehensive program, with monthly telephone 

contact to discuss the asthma action plans directed by either symptoms or peak flow, was 

equally effective in improving outcomes. The key factor in this study was the monthly contact to 

provide reinforcement for the educational endeavor. Only patients who had higher levels of 

denial of the disease and lower self-confidence had increased numbers of ED visits for asthma 

flares. 

ROLE OF PEAK FLOW MONITORING 

The Expert Panel recommends that:

 Written asthma action plans can be based on either symptoms or peak flow 

measurements (Evidence B). 

 Long-term daily peak flow monitoring be considered for patients who have moderate 

or severe persistent asthma (Evidence B), poor perception of airflow obstruction or 

worsening asthma, unexplained response to environmental or occupational 

exposures, and others at the discretion of the clinician and the patient (EPR⎯2 1997). 

Several studies reviewed in the National Asthma Education and Prevention Program (NAEPP) 

“Expert Panel Report—Update 2002: Guidelines for the Diagnosis and Management of 

Asthma” show that peak flow and symptom-based action plans are equally effective in adults 

(EPR⎯Update 2002). The choice should be left to the discretion of the patient and the health 

care clinician. When peak-flow-guided action plans are chosen, the patient’s personal best 

peak flow must be known. Reddel and colleagues (2004) reported that personal best PEF is a 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

useful concept for written asthma action plans and can be determined by using the highest PEF 

over the previous 2 weeks. Additionally, the patient must be educated, understand how to use 

the action plan, and be willing to incorporate peak flow monitoring into asthma care. Use of 

peak flow monitoring should not replace symptom recognition but should facilitate additional 

discussion with the health care provider. 

Peak flow monitoring for self-management of asthma may be less effective for children. In a 

small RCT of peak flow monitoring and diary recording in children, Kamps and coworkers (2001) 

found low levels of adherence over a 4-week period of monitoring peak flow twice daily. 

Children and their parents were not told the electronic monitor was recording date and time of 

measurement. Actual compliance recorded electronically was significantly lower than reported 

compliance in both study groups, and 50 percent of the values were either recorded incorrectly 

or invented. Eid and colleagues (2000) showed that PEF monitoring in children may be 

inaccurate compared to FEV1, especially as the severity of airway obstruction increases. The 

addition of peak flow monitoring to symptom-based guided self-management was not shown to 

contribute to self-management decisionmaking in children 7–14 years of age in another RCT 

(Wensley and Silverman 2004). During acute episodes of asthma, children responded to 

increased symptoms by taking more ICS when PEF was greater than 70 percent of personal 

best. In contrast to the finding of Eid and colleagues (2000), these investigators found no 

evidence that FEV1 was more sensitive than PEF in detecting airflow obstruction. In the findings 

of an RCT comparing symptom monitoring to PEF monitoring only when symptoms occurred, to 

daily and symptom-time PEF monitoring, children and their parents perceived benefit from 

symptom monitoring whether or not it was accompanied by peak flow measurement (McMullen 

et al. 2002). These investigators found no evidence of benefit from more intensive daily 

monitoring. 

Periodic daily peak flow monitoring may be useful to evaluate responses to changes in 

treatment, identify the temporal relationship between environmental or occupational exposures 

and bronchospasm, and provide guidance for patients who have poor perception of airflow 

obstruction. 

See “Component 1: Assessment and Monitoring” for additional discussion. See “How To Use 

Your Peak Flow Meter” (figure 3–11) for a sample handout for patients. 

GOALS OF ASTHMA SELF-MANAGEMENT EDUCATION AND KEY EDUCATIONAL 

MESSAGES 

Patient education is an essential component of successful asthma management. Current 

management approaches require patients and families to effectively carry out complex 

pharmacologic regimens, institute environmental control strategies, detect and self-treat most 

asthma exacerbations, and communicate appropriately with health care providers. Patient 

education is the mechanism through which patients learn to accomplish those tasks 

successfully. It is also a powerful tool for helping patients gain the motivation, skill, and 

confidence to control their asthma (Butz et al. 2005; Gibson et al. 2000; Guevara et al. 2003; 

Levy et al. 2000; Perneger et al. 2002). Research shows that asthma education can be 

cost-effective and can reduce morbidity for both adults and children, especially among high-risk 

patients (Gallefoss and Bakke 2001; Gibson et al. 2000, 2003; Guevara et al. 2003; Schermer 

et al. 2002; Sullivan et al. 2002). 

This section covers strategies for enhancing the delivery of patient education and improving the 

likelihood that patients will follow clinical recommendations. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

122 

August 28, 2007 

FIGURE 3–11. HOW TO USE YOUR PEAK FLOW METER 

A peak flow meter is a device that measures how 

well air moves out of your lungs. During an 

asthma episode, the airways of the lungs usually 

begin to narrow slowly. The peak flow meter may 

tell you if there is narrowing in the airways 

hours—sometimes even days—before you have 

any asthma symptoms. 

By taking your medicine(s) early (before 

symptoms), you may be able to stop the episode 

quickly and avoid a severe asthma episode. 

Peak flow meters are used to check your asthma 

the way that blood pressure cuffs are used to 

check high blood pressure. 

The peak flow meter also can be used to help you 

and your doctor: 

 Learn what makes your asthma worse. 

 Decide if your treatment plan is working well. 

 Decide when to add or stop medicine. 

 Decide when to seek emergency care. 

A peak flow meter is most helpful for patients who 

must take asthma medicine daily. Patients age 5 

and older are usually able to use a peak flow 

meter. Ask your doctor or nurse to show you how 

to use a peak flow meter. 

How To Use Your Peak Flow Meter 

 Do the following five steps with your peak 

flow meter: 

1. Move the indicator to the bottom of the 

numbered scale. 

2. Stand up. 

3. Take a deep breath, filling your lungs 

completely.

4. Place the mouthpiece in your mouth and 

close your lips around it. Do not put your 

tongue inside the hole. 

5. Blow out as hard and fast as you can in a 

single blow. 

 Write down the number you get. But if you 

cough or make a mistake, don’t write down 

the number. Do it over again. 

 Repeat steps 1 through 5 two more times, 

and write down the best of the three blows in 

your asthma diary. 

Find Your Personal Best Peak Flow 

Number 

Your personal best peak flow number is the 

highest peak flow number you can achieve over a 

2-week period when your asthma is under good 

control. Good control is when you feel good and 

do not have any asthma symptoms. 

Each patient’s asthma is different, and your best 

peak flow may be higher or lower than the peak 

flow of someone of your same height, weight, and 

sex. This means that it is important for you to find 

your own personal best peak flow number. Your 

treatment plan needs to be based on your own 

personal best peak flow number. 

To find out your personal best peak flow number, 

take peak flow readings: 

 At least twice a day for 2 to 3 weeks. 

 When you wake up and in late afternoon or 

early evening. 

 15–20 minutes after you take your inhaled 

short-acting beta2-agonist for quick relief. 

 As instructed by your doctor. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

FIGURE 3–11. HOW TO USE YOUR PEAK FLOW METER 

(CONTINUED) 

The Peak Flow Zone System 

Once you know your personal best peak flow 

number, your doctor will give you the numbers 

that tell you what to do. The peak flow numbers 

are put into zones that are set up like a traffic 

light. This will help you know what to do when 

your peak flow number changes. For example: 

Green Zone (more than __L/min [80 percent of 

your personal best number]) signals good control. 

No asthma symptoms are present. Take your 

medicines as usual. 

Yellow Zone (between __L/min and __L/min 

[50 to less than 80 percent of your personal best 

number]) signals caution. If you remain in the 

yellow zone after several measures of peak flow, 

take an inhaled short-acting beta2-agonist. If you 

continue to register peak flow readings in the 

yellow zone, your asthma may not be under good 

control. Ask your doctor if you need to change or 

increase your daily medicines. 

Red Zone (below __L/min [less than 50 percent 

of your personal best number]) signals a medical 

alert. You must take an inhaled short-acting 

beta2-agonist (quick-relief medicine) right away. 

Call your doctor or emergency room and ask what 

to do, or go directly to the hospital emergency 

room. 

Record your personal best peak flow number and 

peak flow zones in your asthma diary. 

Use the Diary To Keep Track of Your Peak 

Flow 

Measure your peak flow when you wake up, 

before taking medicine. Write down your peak 

flow number in the diary every day, or as 

instructed by your doctor. 

Actions To Take When Peak Flow 

Numbers Change 

 PEF goes between __L/min and __L/min 

(50 to less than 80 percent of personal best, 

yellow zone). 

ACTION: Take an inhaled short-acting 

beta2-agonist (quick-relief medicine) as 

prescribed by your doctor. 

 PEF increases 20 percent or more when 

measured before and after taking an inhaled 

short-acting beta2-agonist (quick-relief 

medicine). 

ACTION: Talk to your doctor about adding 

more medicine to control your asthma better 

(for example, an anti-inflammatory 

medication). 

Source: Adapted from Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. National Asthma 

Education and Prevention Program, National Heart, Lung, and Blood Institute, 1997. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

124 

August 28, 2007 

Establish and Maintain a Partnership 

The Expert Panel recommends that a 

partnership between patient and clinician be 

established to promote effective asthma 

management (Evidence A).

Building a partnership requires that clinicians 

promote open communication and ensure that 

patients have a basic and accurate foundation 

of knowledge about asthma, understand the 

treatment approach, and have the selfmanagement skills necessary to monitor the 

disease objectively and take medication 

effectively (Clark et al. 1995, 1998, 2000; Evans 

et al. 1997; Love et al. 2000; Marabini et al. 

2002; Smith et al. 2005; Wilson et al. 2005, 

2006). 

The Expert Panel recommends that when 

nurses, pharmacists, respiratory therapists, 

and other health care professionals are 

available to provide and support patient 

self-management education, a team 

approach through multiple points of care 

should be used (NHLBI 1995b,c). The 

principal clinician, care manager, or any other 

health professional trained in asthma 

management and self-management education 

can introduce the key educational messages 

(See figure 3–12.) and negotiate agreements 

with patients about the goals of treatment, 

medications to use, and the actions the patient 

will take to promote asthma control (Clark et al. 

1995, 1998, 2000; Marabini et al. 2002; Wilson 

et al. 2005, 2006). All health care professionals 

who encounter patients who have asthma are 

members of the health care team and should 

reinforce and expand these messages during 

clinic visits, ED visits, pharmacy visits, 

telephone calls, and in community centers and 

schools. National certification for asthma 

educators is available in the United States. Although no published data are available comparing 

certified to noncertified educators, certification requires a minimum number of hours of 

experience and passing a standardized test. 

It is the opinion of the Expert Panel that the health professional team members 

should consider documenting in the patient’s record the key educational points (See 

figure 3–12.), patient concerns, and actions the patient agrees to take (Evidence C). This 

record will enable all members of the team to be consistent and to reinforce the educational 

points and the progress being made. Communication strategies that unite the network of health 

care professionals should be developed and strengthened. See further discussion in the 

section on “Communication Techniques.” 

FIGURE 3–12. KEY 

EDUCATIONAL MESSAGES: 

TEACH AND REINFORCE AT 

EVERY OPPORTUNITY 

Basic Facts About Asthma 

 The contrast between airways of a person who 

has and a person who does not have asthma; the 

role of inflammation

 What happens to the airways in an asthma attack 

Roles of Medications: Understanding the 

Difference Between: 

 Long-term-control medications: prevent 

symptoms, often by reducing inflammation. Must 

be taken daily. Do not expect them to give quick 

relief. 

 Quick-relief medications: short-acting 

beta2-agonists relax muscles around the airway 

and provide prompt relief of symptoms. Do not 

expect them to provide long-term asthma control. 

Using quick-relief medication on a daily basis 

indicates the need for starting or increasing longterm control medications. 

Patient Skills 

 Taking medications correctly 

— Inhaler technique (demonstrate to patient and 

have the patient return the demonstration) 

— Use of devices, such as prescribed valved 

holding chamber (VHC), spacer, nebulizer 

 Identifying and avoiding environmental exposures 

that worsen the patient’s asthma; e.g., allergens, 

irritants, tobacco smoke 

 Self-monitoring to: 

— Assess level of asthma control 

— Monitor symptoms and, if prescribed, peak 

flow 

— Recognize early signs and symptoms of 

worsening asthma 

 Using written asthma action plan to know when 

and how to: 

— Take daily actions to control asthma 

— Adjust medication in response to signs of 

worsening asthma 

— Seek medical care as appropriate 
Section 3, Component 2: Education for a Partnership in Asthma Care 

125 

August 28, 2007 

TEACH ASTHMA SELF-MANAGEMENT 

The Expert Panel recommends that:

 Clinicians teach patients and families the basic facts about asthma (especially the 

role of inflammation), medication skills, and self-monitoring techniques (Evidence A).

 Provide all patients with a written asthma action plan that includes daily management 

and how to recognize and handle worsening asthma. Written action plans are 

particularly recommended for patients who have moderate or severe persistent 

asthma, a history of severe exacerbations, or poorly controlled asthma (Evidence B).

 Clinicians teach patients environmental control measures (See “Component 3: 

Control of Environmental Factors and Comorbid Conditions That Affect Asthma” for 

evidence ranking on different control measures.).

Self-management education should include the following key points, adapted to meet the 

individual patient’s needs: 

 Figure 3–13 illustrates how education can be delivered across initial patient visits and 

followup visits. 

 Teach basic facts about asthma so that the patient and family understand the rationale for 

needed actions. Give a brief verbal description of what asthma is, emphasizing the role of 

inflammation, and the intended role of each medication. Do not overwhelm the patient with 

too much information all at once, but repeat the important messages at each visit. Ask the 

patient to bring all medications to each appointment for review. 

 Teach the patient necessary medication skills, such as correct use of the inhaler (See 

figure 3–14.) and VHC or spacer and knowing when and how to take quick-relief 

medications. 

 Teach self-monitoring skills: symptom monitoring; peak flow monitoring, as appropriate; and 

recognizing early signs of deterioration. 

 Identify current level of asthma control, goals for improvement, and teach how to 

self-manage worsening asthma by adjusting medications to regain asthma control. 

 Teach relevant environmental control/avoidance strategies (See figure 3–15, “How To 

Control Things That Make Your Asthma Worse.”). Teach how environmental allergens and 

irritants can make the patient’s asthma worse at home, school, and work as well as how to 

recognize both immediate and delayed reactions. Teach patients strategies for removing 

allergens and irritants to which they are sensitive from their living spaces. If possible, refer 

them to evaluated, effective, home-based education programs for allergen and irritant 

control. 

 Advise all patients not to smoke tobacco and to avoid secondhand tobacco smoke. 

Emphasize the importance of not smoking for women who are pregnant and for parents of 

small children. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

FIGURE 3–13. DELIVERY OF ASTH MA EDUCATION BY CLINICIANS 

DURING PATIENT CARE VISITS 

Assessment Questions Information Skills 

Recommendations for Initial Visit 

Focus on: 

 Expectations of visit 

 Asthma control 

 Patients’ goals of treatment 

 Medications 

 Quality of life 

“What worries you most about your 

asthma?” 

“What do you want to accomplish at 

this visit?” 

“What do you want to be able to do 

that you can’t do now because of 

your asthma?” 

“What do you expect from 

treatment?” 

“What medicines have you tried?” 

“What other questions do you have 

for me today?” 

“Are there things in your environment 

that make your asthma worse?” 

Teach in simple language: 

 What is asthma? Asthma is a 

chronic lung disease. The 

airways are very sensitive. They 

become inflamed and narrow; 

breathing becomes difficult. 

 The definition of asthma control: 

few daytime symptoms, no 

nighttime awakenings due to 

asthma, able to engage in 

normal activities, normal lung 

function. 

 Asthma treatments: two types of 

medicines are needed: 

— Long-term control: 

medications that prevent 

symptoms, often by 

reducing inflammation. 

— Quick relief: short-acting 

bronchodilator relaxes 

muscles around airways. 

 Bring all medications to every 

appointment. 

 When to seek medical advice. 

Provide appropriate telephone 

number. 

Teach or review and demonstrate: 

 Inhaler (see figure 3–14) and 

spacer or valved holding 

chamber (VHC) use. Check 

performance. 

 Self-monitoring skills that are 

tied to a written action plan: 

— Recognize intensity and 

frequency of asthma 

symptoms. 

— Review the signs of 

deterioration and the need 

to reevaluate therapy: 

 Waking at night or early 

morning with asthma 

 Increased medication 

use 

 Decreased activity 

tolerance 

 Use of a written asthma action 

plan (See figure 3–10.) that 

includes instructions for daily 

management and for recognizing 

and handling worsening asthma.

Recommendations for First Followup Visit (2 to 4 weeks or sooner as needed) 

Focus on: 

 Expectations of visit 

 Asthma control 

 Patients’ goals of treatment 

 Medications 

 Patient treatment preferences 

 Quality of life 

Ask relevant questions from previous 

visit and also ask: 

“What medications are you taking?” 

“How and when are you taking 

them?” 

“What problems have you had using 

your medications?” 

“Please show me how you use your 

inhaled medications.” 

Teach in simple language: 

 Use of two types of medications. 

 Remind patient to bring all 

medications and the peak flow 

meter, if using, to every 

appointment for review. 

 Self-assessment of asthma 

control using symptoms and/or 

peak flow as a guide. 

Teach or review and demonstrate: 

 Use of written asthma action 

plan. Review and adjust as 

needed. 

 Peak flow monitoring if indicated 

(See figure 3–11.). 

 Correct inhaler and spacer or 

VHC technique. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

127 

August 28, 2007 

FIGURE 3–13. DELIVERY OF ASTH MA EDUCATION BY CLINICIANS 

DURING PATIENT CARE VISITS (CONTINUED) 

Assessment Questions Information Skills 

Recommendations for Second Followup Visit 

Focus on: 

 Expectations of visit 

 Asthma control 

 Patients’ goals of treatment 

 Medications 

 Quality of life 

Ask relevant questions from previous 

visits and also ask: 

“Have you noticed anything in your 

home, work, or school that makes 

your asthma worse?” 

“Describe for me how you know 

when to call your doctor or go to 

the hospital for asthma care.” 

“What questions do you have about 

the asthma action plan?” “Can we 

make it easier?” 

“Are your medications causing you 

any problems?” 

“Have you noticed anything in your 

environment that makes your 

asthma worse?” 

“Have you missed any of your 

medications?” 

Teach in simple language: 

 Self-assessment of asthma 

control, using symptoms and/or 

peak flow as a guide. 

 Relevant environmental 

control/avoidance strategies 

(See figure 3–15.): 

— How to identify home, work, 

or school exposures that 

can cause or worsen 

asthma 

— How to control house-dust 

mites, animal exposures if 

applicable 

— How to avoid cigarette 

smoke (active and passive) 

 Review all medications.

Teach or review and demonstrate: 

 Inhaler/spacer or VHC 

technique. 

 Peak flow monitoring technique. 

 Use of written asthma action 

plan. Review and adjust as 

needed. 

 Confirm that patient knows what 

to do if asthma gets worse.

Recommendations for All Subsequent Visits 

Focus on: 

 Expectations of visit 

 Asthma control 

 Patients’ goals of treatment 

 Medications 

 Quality of life 

Ask relevant questions from previous 

visits and also ask: 

“How have you tried to control things 

that make your asthma worse?” 

“Please show me how you use your 

inhaled medication.” 

Teach in simple language: 

 Review and reinforce all: 

— Educational messages 

— Environmental control 

strategies at home, work, or 

school 

— Medications 

— Self-assessment of asthma 

control, using symptoms 

and/or peak flow as a guide

Teach or review and demonstrate: 

 Inhaler/spacer or VHC 

technique. 

 Peak flow monitoring technique, 

if appropriate. 

 Use of written asthma action 

plan. Review and adjust as 

needed. 

 Confirm that patient knows what 

to do if asthma gets worse.

Sources: Adapted from Guevara et al. 2003; Janson et al. 2003; Powell and Gibson 2003; Wilson et al. 1993. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

128 

August 28, 2007 

FIGURE 3–14. HOW TO USE YOUR METERED-DOSE INHALER 

HOW TO USE YOUR METERED-DOSE INHALER

Using an inhaler seems simple, but most patients do not use it the right way. When you use your inhaler the wrong 

way, less medicine gets to your lungs. 

For the next few days, read these steps aloud as you do them or ask someone to read them to you. Ask your doctor 

or nurse to check how well you are using your inhaler. 

Use your inhaler in one of the three ways pictured below. A or B are best, but C can be used if you have trouble with 

A and B. Your doctor may give you other types of inhalers. 

Steps for Using Your Inhaler 

Getting ready 1. Take off the cap and shake the inhaler. 

2. Breathe out all the way. 

3. Hold your inhaler the way your doctor said (A, B, or C 

below). 

Breathe in slowly 4. As you start breathing in slowly through your mouth, press 

down on the inhaler one time. (If you use a holding 

chamber, first press down on the inhaler. Within 5 

seconds, begin to breathe in slowly.) 

5. Keep breathing in slowly, as deeply as you can. 

Hold your breath 6. Hold your breath as you count to 10 slowly, if you can. 

7. For inhaled quick-relief medicine (beta2-agonists), wait 

about 15–30 seconds between puffs. There is no need to 

wait between puffs for other medicines. 

A. Hold inhaler 1 to 2 

inches in front of 

your mouth (about 

the width of two 

fingers). 

B. Use a spacer/holding 

chamber. These come in 

many shapes and can be 

useful to any patient. 

C. Put the inhaler in your 

mouth. Do not use for 

steroids. 

Clean your inhaler as needed, and know when to replace your inhaler. For instructions, read the package 

insert or talk to your doctor, other health care provider, or pharmacist. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

129 

August 28, 2007 

FIGURE 3–15. HOW TO CONTRO L THINGS THAT MAKE YOUR 

ASTHMA WORSE 

You can help prevent asthma episodes by staying 

away from things that make your asthma worse. This 

guide suggests many ways to help you do this. 

You need to find out what makes your asthma worse. 

Some things that make asthma worse for some 

people are not a problem for others. You do not need 

to do all of the things listed in this guide. 

Look at the things listed in dark print below. Put a 

check next to the ones that you know make your 

asthma worse, particularly if you are allergic to the 

things. Then, decide with your doctor what steps you 

will take. Start with the things in your bedroom that 

bother your asthma. Try something simple first. 

Tobacco Smoke 

 If you smoke, ask your doctor for ways to 

help you quit. Ask family members to quit 

smoking, too. 

 Do not allow smoking in your home, car, or 

around you. 

 Be sure no one smokes at a child’s daycare 

center or school. 

Dust Mites 

Many people who have asthma are allergic to dust mites. 

Dust mites are like tiny “bugs” you cannot see that live in 

cloth or carpet. 

Things that will help the most:

 Encase your mattress in a special dust miteproof cover.* 

 Encase your pillow in a special dust mite-proof 

cover* or wash the pillow each week in hot 

water. Water must be hotter than 130 °F to kill 

the mites. Cooler water used with detergent 

and bleach can also be effective. 

 Wash the sheets and blankets on your bed 

each week in hot water. 

Other things that can help: 

 Reduce indoor humidity to or below 60 percent; 

ideally 30–50 percent. Dehumidifiers or central 

air conditioners can do this. 

 Try not to sleep or lie on cloth-covered cushions 

or furniture. 

 Remove carpets from your bedroom and those 

laid on concrete, if you can. 

 Keep stuffed toys out of the bed, or wash the 

toys weekly in hot water or in cooler water with 

detergent and bleach. Placing toys weekly in a 

dryer or freezer may help. Prolonged exposure 

to dry heat or freezing can kill mites but does 

not remove allergen. 

*To find out where to get products mentioned in this guide, call: 

Asthma and Allergy Foundation of America 

(800–727–8462) 

Allergy and Asthma Network/Mothers of 

Asthmatics, Inc. (800–878–4403) 

 American Academy of Allergy, Asthma, and Immunology 

(800–822–2762) 

National Jewish Medical and Research Center 

(Lung Line) (800–222–5864) 

American College of Allergy, Asthma, and Immunology 

(800–842–7777)
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

FIGURE 3–15. HOW TO CONTRO L THINGS THAT MAKE YOUR 

ASTHMA WORSE (CONTINUED) 

Animal Dander 

Some people are allergic to the flakes of skin or dried 

saliva from animals. 

The best thing to do: 

 Keep animals with fur or hair out of your 

home. 

If you can’t keep the pet outdoors, then: 

 Keep the pet out of your bedroom, and keep 

the bedroom door closed. 

 Remove carpets and furniture covered with 

cloth from your home. If that is not possible, 

keep the pet out of the rooms where these 

are. 

Cockroach 

Many people with asthma are allergic to the dried 

droppings and remains of cockroaches. 

 Keep all food out of your bedroom. 

 Keep food and garbage in closed containers 

(never leave food out). 

 Use poison baits, powders, gels, or paste (for 

example, boric acid). You can also use traps. 

 If a spray is used to kill roaches, stay out of 

the room until the odor goes away. 

Vacuum Cleaning 

 Try to get someone else to vacuum for you 

once or twice a week, if you can. Stay out of 

rooms while they are being vacuumed and for 

a short while afterward. 

 If you vacuum, use a dust mask (from a 

hardware store), a central cleaner with the 

collecting bag outside the home, or a vacuum 

cleaner with a HEPA filter or a double-layered 

bag.* 

Indoor Mold 

 Fix leaking faucets, pipes, or other sources of 

water. 

 Clean moldy surfaces. 

 Dehumidify basements if possible. 

Pollen and Outdoor Mold 

During your allergy season (when pollen or mold spore 

counts are high): 

 Try to keep your windows closed. 

 If possible, stay indoors with windows closed 

during the midday and afternoon, if you can. 

Pollen and some mold spore counts are 

highest at that time. 

 Ask your doctor whether you need to take or 

increase anti-inflammatory medicine before 

your allergy season starts. 

Smoke, Strong Odors, and Sprays 

 If possible, do not use a wood-burning stove, 

kerosene heater, fireplace, unvented gas 

stove, or heater. 

 Try to stay away from strong odors and 

sprays, such as perfume, talcum powder, hair 

spray, paints, new carpet, or particle board. 

Exercise or Sports 

 You should be able to be active without 

symptoms. See your doctor if you have 

asthma symptoms when you are active—such 

as when you exercise, do sports, play, or work 

hard. 

 Ask your doctor about taking medicine before 

you exercise to prevent symptoms. 

 Warm up for a period before you exercise. 

 Check the air quality index and try not to work 

or play hard outside when the air pollution or 

pollen levels (if you are allergic to the pollen) 

are high. 

Other Things That Can Make 

Asthma Worse 

 Sulfites in foods: Do not drink beer or wine or 

eat shrimp, dried fruit, or processed potatoes if 

they cause asthma symptoms. 

 Cold air: Cover your nose and mouth with a 

scarf on cold or windy days. 

 Other medicines: Tell your doctor about all 

the medicines you may take. Include cold 

medicines, aspirin, and even eye drops. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

JOINTLY DEVELOP TREATMENT GOALS 

The Expert Panel recommends that clinicians determine the patient’s personal treatment 

goals and preferences for treatment; review the general goals of asthma treatment; and 

agree on the goals of treatments (Evidence B).

Fundamental to building a partnership is that clinicians and patients jointly develop and agree 

on both short- and long-term treatment goals. Such agreements can encourage active 

participation, enhance the partnership, and improve asthma management (Clark et al. 1995, 

2000; Marabini et al. 2002; Wilson et al. 2005, 2006). 

 Determine the patient’s personal treatment goals and preferences for treatment. Ask 

how asthma interferes with the patient’s life (e.g., inability to sleep through the night, play a 

sport), and incorporate the responses into personal treatment goals. Involve the patient in 

decisionmaking about treatment. 

 Share the general goals of asthma treatment with the patient and family. Tell patients, 

“Our measures of control are to have you: 

— Be free from troublesome symptoms day and night, including sleeping through the 

night.” 

— Have the best possible lung function.” 

— Be able to participate fully in any activities of your choice.” 

— Not miss work or school because of asthma symptoms.” 

— Need fewer or no urgent care visits or hospitalizations for asthma.” 

— Use medications to control asthma with as few side effects as possible.” 

— Be satisfied with your asthma care.” 

 Agree on the goals of treatment. The clinicians, the patient, and, when appropriate, the 

patient’s family should agree on the goals of asthma management, which include both the 

patient’s personal goals and the general goals (see list above) suggested by the clinicians. 

Negotiate the treatment plans to accomplish joint goals of treatment. 

 Provide a written asthma action plan that reflects the agreed upon goals for 

treatment. See earlier discussion, “The Role of Written Asthma Action Plans for Patients 

Who Have Asthma.” 

ASSESS AND ENCOURAGE ADHERENCE TO RECOMMENDED THERAPY 

The Expert Panel recommends that clinicians assess and encourage adherence during 

all asthma visits (Evidence C).

An important part of patient education is encouraging adherence. In a meta-analysis of 

methods to improve adherence to medical regimens, Roter and colleagues (1998) used multiple 

measures of compliance (health outcomes; direct indicators, such as urine and blood tracers; 

indirect indicators, such as pill and refill counts; subjective patient reports; and utilization, such 

as appointment keeping) to identify successful adherence strategies. The authors found that no 

single strategy or programmatic focus showed any clear advantage but that comprehensive 

interventions combining multiple strategies with cognitive, behavioral, and affective components 

were more likely to be effective than those using a single focus. Magar and coworkers (2005) 

showed that a multifocused strategy that tailored asthma education goals and messages to the 

individual patient improved outcomes. Other studies in small numbers of adults have shown 

that self-management education programs in asthma led to improved adherence over periods of 
Section 3, Component 2: Education for a Partnership in Asthma Care 

132 

August 28, 2007 

7 weeks to 6 months (Janson et al. 2003; Schaffer and Tian 2004). Onyirimba and colleagues 

(2003) found that direct clinician-to-patient discussion and feedback of adherence rates 

improved use of ICSs over a 10-week period. 

Evidence concerning the optimal frequency for assessing and encouraging adherence among 

asthma patients is lacking, and no evidence from adherence studies identifies any single 

successful method. Evidence from studies in multiple diseases and in asthma, however, 

indicates that repetition is important, perhaps especially so in a variable, chronic disease such 

as asthma, and that consideration of the following strategies would be helpful for assessing and 

improving adherence within the context of clinical visits. 

 Use effective techniques to promote open communication. Studies of physicians’ 

communication styles suggest that being willing to address all questions, active listening, 

and using good communication techniques can improve patient adherence and/or 

satisfaction with care (Brown et al. 2004; Clark et al. 1998, 2000; Smith et al. 2005). 

 Start each visit by asking about the patient’s or parent’s concerns and goals for the visit. 

Studies of adults and children have shown the most common concerns of patients and 

families include: fear and misunderstanding of effects of medications, including concerns of 

becoming “dependent” on asthma medications (Bender and Bender 2005; Janson and 

Becker 1998; Leickly et al. 1998; Muntner et al. 2001; Yawn 2003), and uncertainty of when 

to seek help (Bender and Bender 2005; Janson and Becker 1998). Open-ended questions, 

such as “What worries you most about your asthma?,” may encourage patients and families 

to voice issues, personal beliefs, or concerns they may be apprehensive about discussing or 

may think are not of interest to the clinician. Most nonadherence originates in personal 

beliefs or concerns about asthma that have not been discussed with the clinician (Bender 

and Bender 2005; Janson and Becker 1998; Janz et al. 1984; Korsch et al. 1968; Yawn 

2003). Until such fears and worries are identified and addressed, patients will not be able to 

adhere to the clinician’s recommendations (Adams et al. 2003; Colland et al. 2004; Cowie et 

al. 2004; Gibson et al. 2002, 2005; Janson and Becker 1998; Korsch et al. 1968; Levy et al. 

2000; Lindberg et al. 1999). 

 Ask specifically about any concerns patients or parents have about medicines (e.g., safety, 

impact, convenience, and cost) (Bender and Bender 2005; Janson and Becker 1998; Leickly 

et al. 1998; Muntner et al. 2001; Yawn 2003). 

 Assess the patient’s and family’s perceptions of the severity level of the disease and how 

well it is controlled. Beliefs that the asthma is not really severe have been shown to affect 

adherence adversely (Bender and Bender 2005; Muntner et al. 2001). Ask questions such 

as “How much danger do you believe you are in from your asthma?” Identifying patients 

who are overwhelmed by fear of death offers the opportunity to put their fears in perspective 

with the results of objective assessments and expert opinion. A written asthma action plan 

that directs the patient how to respond to worsening asthma (figure 3–10a, b, and c) may 

also be helpful in reducing anxiety and directing appropriate use of health care resources 

(Bender and Bender 2005; Janson-Bjerklie et al. 1992; Janz et al. 1984; Muntner et al. 

2001). 

 Assess the patient’s and family’s level of social support, and encourage family involvement. 

Ask “Who among your family or friends can you turn to for help if your asthma worsens?” 

Counsel patients to identify an asthma “partner” among their family or friends who is willing 

to be educated and provide support. Include at least one of these individuals in followup 

appointments with the patient so that he or she can hear what is expected of the patient in 

following the self-management and action plans (Graham et al. 1990). 
Section 3, Component 2: Education for a Partnership in Asthma Care 

133 

August 28, 2007 

 Assess levels of stress, family disruption, anxiety, and depression associated with asthma 

and asthma management. Although stress, anxiety, and depression do not cause asthma, 

they can make management more difficult (Busse et al. 1995) and can complicate an 

individual’s attempts at self-management. Use tools to formally assess these conditions 

(USPSTF 2004) and, when appropriate, refer the patient to a psychologist, social worker, 

psychiatrist, or other licensed professional when stress seems to interfere unduly with daily 

asthma management. Referral to a local support group also may be useful. 

 Assess ability to adhere to the written asthma action plan. Adherence to the action plan is 

enhanced when the plan is simplified, the number of medications and frequency of daily 

doses are minimized, the medication doses and frequency fit into the patient’s and family’s 

daily routine (Bender et al. 1998; Bender and Bender 2005; Clark et al. 1995; Eisen et al. 

1990; Evans 1993; Haynes et al. 2005; Janson and Becker 1998; Meichenbaum and Turk 

1987), and the plan considers the patient’s ability to afford the medications (Bender and 

Bender 2005; Hindi-Alexander et al. 1987). 

TAILOR EDUCATION TO THE NEEDS OF THE INDIVIDUAL PATIENT 

The Expert Panel recommends that:

 Asthma education interventions be tailored as much as possible to an individual’s 

underlying knowledge and beliefs about the disease (Evidence C). 

 Health care professionals who develop asthma education programs consider the 

needs of patients who have limited literacy (Evidence C). 

 Clinicians consider assessing cultural or ethnic beliefs or practices that may 

influence self-management activities, and modify educational approaches as needed 

(Evidence C). 

Knowledge and Beliefs 

People who have asthma have different levels of knowledge about the disease and diverse 

underlying asthma-related beliefs. African Americans and other minorities who have asthma 

often accept suboptimal levels of asthma control because they are not aware of the effect that 

proper asthma management can have on their quality of life. Incorrect underlying beliefs about 

asthma may constitute a major obstacle to adherence to daily anti-inflammatory therapy and 

other self-management behavior, and such beliefs thereby may contribute to poor asthma 

outcomes. Studies have highlighted the lack of appreciation, on the part of people who have 

asthma and/or their caregivers, of the importance of the use of ICSs on days when the asthma 

is asymptomatic. This behavior appears to be based on the belief that asthma is absent if overt 

asthma symptoms are absent, and therefore asthma medications are only necessary when an 

acute episode occurs (Halm et al. 2006; Riekert et al. 2003). Doubts about the usefulness of 

anti-inflammatory asthma medications and concerns about the long-term side effects of these 

medications also contribute to this pattern of behavior (George et al. 2003; Leickly et al. 1998; 

Mansour et al. 2000; Van Sickle and Wright 2001). Moreover, African Americans are 

significantly more likely than Caucasians to report distrust of the health care system (George et 

al. 2003; Halbert et al. 2006). 

A recent study demonstrated how underlying beliefs about asthma may serve as an obstacle to 

adherence with daily anti-inflammatory therapy and other self-management behaviors in 

high-risk patients who have moderate or severe persistent asthma (Halm et al. 2006). This 

prospective, longitudinal, observational cohort study assessed disease beliefs and 
Section 3, Component 2: Education for a Partnership in Asthma Care 

134 

August 28, 2007 

self-management behaviors. In this group of low-income, high-risk, predominantly Latino and 

African American people, more than half of the persons who had asthma believed they have 

asthma only when they have symptoms. This “no symptoms, no asthma” belief was associated 

with one-third lower odds of adherence to ICS use when the asthma was asymptomatic. One 

study suggested that, if enough time is taken to explain the function and use of ICSs, adherence 

to therapy might be improved in African American patients who have asthma (Apter et al. 2003). 

Another study demonstrated that education focusing on changing behavior, rather than 

providing information alone, improved quality of life. Perceived control of asthma and 

asthma-specific quality of life significantly improved after patients who have asthma completed a 

behavior modification-based asthma education program for adults. The authors concluded that 

assessment of perceived control of asthma may enable educators to target and tailor 

educational interventions for individuals who perceive a lack of control over their asthma and to 

monitor the effectiveness of asthma education (Olajos-Clow et al. 2005). Qualitative research is 

one important methodology for understanding the health beliefs and attitudes of patients and for 

formulating hypotheses for improving ICS adherence that can be tested in the future by using 

quantitative research methods (George et al. 2003). 

Health Literacy 

Nationally, almost one-quarter of the adult population cannot read and understand basic written 

material (Kirsh et al. 1993). Traditional patient education relies largely on printed materials that 

are often written at too high a level for patients who have a low level of literacy to read and 

adequately comprehend. Inadequate literacy is a barrier to asthma knowledge and self-care 

(Williams et al. 1998). Asthma education programs may not adequately reach those patients 

who suffer the greatest morbidity and mortality from asthma. Some asthma education 

strategies may not reach a large number of patients who have asthma and poor reading skills. 

Therefore, it is important that health education literature meet the readability standards (of 

5th-grade level or lower) recommended by health education experts (Doak et al. 1996). 

Knowledge of asthma may affect health behaviors and disease outcomes. Patients need to 

understand proper health behaviors and acquire self-management skills. Correcting knowledge 

and behavior deficits through asthma instructional programs has been shown to be 

cost-effective (Neri et al. 1996) and to reduce physician visits and hospitalizations (Kelso et al. 

1996; Patel et al. 2004). 

Self-management skills and asthma knowledge are poorer among patients who have limited 

reading ability. In a cross-sectional survey, using multivariate analysis, a patient’s reading level 

was the strongest predictor of asthma knowledge score and the strongest predictor of skills in 

use of MDI (Williams et al. 1998). A prospective cohort study examined the relationship 

between inadequate health literacy and the capacity to learn and retain instructions about 

discharge medications and appropriate MDI technique. Before instruction, inadequate health 

literacy was associated with lower asthma medication knowledge and worse MDI technique; 

after instruction, it was demonstrated that inadequate health literacy was not associated with 

difficulty in learning or retaining instructions. This study demonstrated that tailored education 

can successfully overcome barriers related to inadequate health literacy and improve asthma 

self-management skills (Paasche-Orlow et al. 2005). 

Overcoming the barrier of inadequate literacy may be facilitated by structuring asthma education 

programs for low literacy levels and by developing systematic approaches to tailor asthma 

education to patients. Additional studies are needed to determine whether tailored asthma 

education provided to vulnerable populations will result in long-term gains in asthma 

self-management. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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Cultural/Ethnic Considerations 

Cultural variables may affect patient understanding of and adherence to medical regimens 

(Kleinman et al. 1978; Pachter and Weller 1993). Moudgil and colleagues (2000) have 

suggested that using a culturally sensitive patient education approach directed toward altering 

attitudes and beliefs, as well as toward physical management of the disease is a more 

successful approach to improving asthma health outcomes. Improved understanding is needed 

concerning how ethnocultural practices, independent of socioeconomic variables, may influence 

asthma care and the use of health care services. Open-ended questions such as “In your 

community, what does having asthma mean?” can elicit informative responses. The culturally 

sensitive clinician should attempt to find ways to incorporate harmless or potentially beneficial 

remedies with the pharmacologic plan. 

For example, a prevalent ethnocultural belief among the Latino population is that illnesses are 

either “hot” or “cold” (Pachter et al. 2002; Risser and Mazur 1995). Asthma is viewed as a 

“cold” illness amenable to “hot” treatment. Suggesting that asthma medications be taken with 

hot tea or hot water incorporates this belief into the therapeutic regimen and helps build the 

therapeutic partnership. In a study of Dominican Americans, most of the mothers of persons 

who had asthma used folk remedies called “zumos” instead of prescription medicines. These 

folk remedies were derived from their folk beliefs about health and illness. In this study, most of 

the mothers said that prescribed medications are overused in this country and that physicians 

hide therapeutic information from them (Bearison et al. 2002). It is important to be aware of 

potential barriers posed by ethnocultural beliefs within racial/ethnic minority communities about 

the practice of traditional Western medicine. When harmful home remedies are being used, 

clinicians should discourage their use by suggesting a culturally acceptable alternative as a 

replacement or recommending a safer route of administration (Pachter et al. 1995). These and 

other strategies may be useful in working with ethnic minorities (NHLBI 1995a). 

Every effort should be made to discuss asthma care, especially the asthma action plan, in the 

patient’s native language so that educational messages are fully understood. It is the opinion of 

the Expert Panel that, for some ethnic groups, the word “action” may require additional 

explanation to patients and their families when used in the context of a medical treatment plan. 

Research suggests that lack of language concordance between the clinician and the patient 

affects adherence and appropriate use of health care services (Manson 1988). Language is a 

significant barrier for Latinos seeking health care for asthma. In a study assessing risk factors 

for inadequate asthma therapy in children, the risk of receiving inadequate asthma therapy 

when Spanish was the preferred language was 1.4 times greater than if English was the 

preferred language (Halterman et al. 2000). In a study of Latinos attending an inner-city 

pediatric clinic, immigrant parents cited language as the greatest barrier to health care access 

for their children (Flores et al. 1998). Language barriers also may complicate the assessment of 

cultural differences. Often, medical interpreters are not used; when used, they sometimes lack 

formal training in this skill (Baker et al. 1996). If interpreters are used, they should be equally 

competent in both English and the patient’s language as well as knowledgeable about medical 

terms (Woloshin et al. 1995). 

MAINTAIN THE PARTNERSHIP 

As part of ongoing care, the clinician should continue to build the partnership by being a 

sympathetic coach and by helping the patient follow the written asthma action plan and take 

other needed actions. Educational efforts should be continuous, because it may take up to 6 

months for the effect of education to be evident (Gallefoss and Bakke 2001; Gibson et al. 2003; 

Toelle et al. 1993). Furthermore, it is necessary to review periodically the information and skills 
Section 3, Component 2: Education for a Partnership in Asthma Care 

136 

August 28, 2007 

covered previously, because patients’ self-management behavior is likely to decline over time 

(Cote et al. 2001; Ries et al. 1995). 

The Expert Panel recommends that clinicians demonstrate, review, evaluate, and correct 

inhaler technique and, if appropriate, the use of a VHC or spacer at each visit, because 

these skills can deteriorate rapidly (Evidence C). Written instructions are helpful (See 

figure 3–14.) but insufficient (Nimmo et al. 1993; Wilson et al. 1993). Research suggests that 

patients who use inhalers tend to make specific mistakes that need to be corrected (Hanania et 

al. 1994; Hesselink et al. 2004; Kesten et al. 1993; Larsen et al. 1994; Scarfone et al. 2002). 

Patients especially need to be reminded to inhale slowly, to activate the inhaler only once for 

each breath (Rau et al. 1996), and to use DPI devices correctly (Melani et al. 2004). Inhaler 

technique may be improved with educational interventions (Agertoft and Pedersen 1998; 

Hesselink et al. 2004). 

The Expert Panel recommends that clinicians continue to promote open communication 

with the patient and family by addressing, as much as possible, the following elements in 

each followup visit (Evidence B unless otherwise noted) (See also figure 3–13.): 

 Continue asking patients early in each visit what concerns they have about their 

asthma and what they especially want addressed during the visit. 

 Review the short-term goals agreed on in the initial visit. Assess how well the goals are 

being achieved (e.g., was the patient’s wish to engage in physical activity achieved?). 

Revise the goals as needed. Achievement of short-term goals should be discussed as 

indicators that the patient is moving toward long-term goals. Give positive verbal 

reinforcement for achievement of a goal, and recognize the patient’s success in moving 

closer to full control of the disease (Clark et al. 1998, 2000; Evans et al. 1997). 

 Review the written asthma action plan and the steps the patient is to take. Adjust the 

plan as needed. For example, give recommendations on how to use medicines if the dose 

or type is not working, and confirm that the patient knows what to do if his or her asthma 

gets worse. Identify other problems the patient has in following the agreed-on steps (e.g., 

disguising the bad taste of medicine). Treat these as areas that need more work, not as 

adherence failures (Clark et al. 1995, 1998, 2000). 

 Either encourage parents to take a copy of the child’s written asthma action plan to 

the child’s school or childcare setting, or obtain parental permission and send a copy 

to the school nurse or designee (Evidence C) (See figures 3–16a, b.). 

 Continue teaching and reinforcing key educational messages (See figure 3–12.). 

Provide information and teach skills over several visits so as not to overwhelm the patient 

with too much information at one time. Repeat important points often. 

 Give patients simple, brief, written materials that reinforce the actions recommended 

and skills taught (Gibson et al. 2000). See “Asthma Education Resources” for a list of 

organizations that distribute patient education materials. Many of these organizations also 

have some Spanish-language materials. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

FIGURE 3–16a. SCHOOL ASTHMA ACTION PLAN 

Source: Reprint with permission from the Asthma and Allergy Foundation of America. Copyright © 2006 The Asthma and Allergy 

Foundation of America. For more information on asthma and allergies, visit http://www.aafa.org. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

138 

August 28, 2007 

FIGURE 3–16a. SCHOOL ASTHMA ACTION PLAN (CONTINUED) 

Source: Reprint with permission from the Asthma and Allergy Foundation of America. Copyright © 2006 The Asthma and Allergy 

Foundation of America. For more information on asthma and allergies, visit http://www.aafa.org. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

139 

August 28, 2007 

FIGURE 3–16b. SCHOOL ASTHMA ACTION PLAN 

Source: California Asthma Public Health Initiative, California Department of Public Health. http://www.cdph.ca.gov/healthinfo/discond/pages/asthma.aspx. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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August 28, 2007 

ASTHMA EDUCATION RESOURCES 

ALLERGY AND ASTHMA NETWORK 1–800–878–4403 

MOTHERS OF ASTHMATICS 1–703–641–9595 

2751 Prosperity Avenue, Suite 150 

Fairfax, VA 22030 

www.breatherville.org

AMERICAN ACADEMY OF ALLERGY, ASTHMA, AND IMMUNOLOGY 1–414–272–6071 

555 East Wells Street 

Suite 1100

Milwaukee, WI 53202-3823 

www.aaaai.org

AMERICAN ASSOCIATION FOR RESPIRATORY CARE 1–972–243–2272 

9125 North MacArthur Boulevard, Suite 100 

Irving, TX 75063 

www.aarc.org

AMERICAN COLLEGE OF ALLERGY, ASTHMA, 1–800–842–7777 

 AND IMMUNOLOGY 1–847–427–1200 

85 West Algonquin Road, Suite 550 

Arlington Heights, IL 60005 

www.acaai.org

AMERICAN LUNG ASSOCIATION 1–800–586–4872 

61 Broadway 

New York, NY 10006 

www.lungusa.org

ASSOCIATION OF ASTHMA EDUCATORS 1–888–988–7747 

1215 Anthony Avenue 

Columbia, SC 29201 

www.asthmaeducators.org

ASTHMA AND ALLERGY FOUNDATION OF AMERICA 1–800–727–8462 

1233 20th Street, NW., Suite 402 

Washington, DC 20036 

www.aafa.org

CENTERS FOR DISEASE CONTROL AND PREVENTION 1–800–311–3435 

1600 Clifton Road 

Atlanta, GA 30333

http://www.cdc.gov

FOOD ALLERGY & ANAPHYLAXIS NETWORK 1–800–929–4040 

11781 Lee Jackson Highway, Suite 160 

Fairfax, VA 22033 

www.foodallergy.org

NATIONAL HEART, LUNG, AND BLOOD INSTITUTE 1–301–592–8573 

 HEALTH INFORMATION CENTER 

P.O. BOX 30105 

Bethesda, MD 20824-0105 

www.nhlbi.nih.gov

NATIONAL JEWISH MEDICAL AND RESEARCH CENTER 1–800–222–LUNG 

1400 Jackson Street 

Denver, CO 80206 

www.njc.org

U.S. ENVIRONMENTAL PROTECTION AGENCY 1–800–490-9198 

P.O. BOX 42419 

Cincinnati, OH 45242-0419 

www.airnow.gov
Section 3, Component 2: Education for a Partnership in Asthma Care 

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Provider Education 

METHODS OF IMPROVING CLINICIAN BEHAVIORS 

Implementing Guidelines—Recommended Practices 

The Expert Panel recommends the use of multifaceted, clinician education programs that 

reinforce guidelines-based asthma care and are based on interactive learning strategies 

(Evidence B). (See Evidence Table 7, Methods for Improving Clinician Behaviors.) 

In an attempt to improve and standardize the quality of care given to people with asthma, 

several studies have focused on methods of implementing guideline-based practice. This 

process of implementation is designed to change the behavior of clinicians. Eight RCTs and 

one trial’s secondary analysis (Baker et al. 2003; Brown et al. 2004; Cabana et al. 2006; Clark 

et al. 2000; Finkelstein et al. 2005; Kattan et al. 2006; Lagerlov et al. 2000; White et al. 2004) 

show the variable effects of interventions designed to change clinicians’ use of recommended 

asthma guidelines. Lagerlov and colleagues (2000) provided 199 general practitioners with two 

evening meetings, 1 week apart, lasting almost 3 hours each. At the first meeting, participants 

discussed how they diagnosed asthma and the treatment they prescribed. At the second 

meeting, guidelines were presented, and the group agreed on quality criteria for prescribing 

based on the guidelines. The educational sessions resulted in a small (6 percent) but 

statistically significant increase in the mean proportion of acceptably treated patients compared 

to controls. In peer groups of doctors, combining feedback about prescribing behavior along 

with guideline recommendations improved the quality of care of their patients who had asthma. 

Clark and coworkers (2000) evaluated the long-term impact of an interactive seminar for 

pediatricians that focused on teaching and communication skills in managing asthma according 

to published guidelines. Two years after the intervention, physicians who attended the seminar 

were more likely than controls to deliver asthma education, supply patients with written 

directions for adjusting medications when symptoms change, and offer more guidance for 

modifying therapy. Children seen by physicians in the intervention group had fewer 

hospitalizations and ED visits. Notably, no differences were found between intervention 

physicians and controls in time they spent with patients at 1-year followup (Clark et al. 1998). In 

a reanalysis of the trial by Clark and coworkers, Brown and colleagues (2004) found the 

program was more effective for children in low-income families than children in families with 

greater income. Cabana and coworkers (2006) replicated the intervention by Clark and 

colleagues in a large RCT to test whether the seminar could be delivered effectively by local 

faculty trained by the investigators. One year postintervention, physicians who attended the 

seminar were more likely than physicians in the control group to ask about patients’ concerns 

about asthma, to encourage patients to be more physically active, and set goals for successful 

treatment. Compared with patients in the control group, patients of physicians who attended the 

seminar had greater decreases in ED visits and in days with limited activity at 1-year followup 

(Cabana et al. 2006). 

On the other hand, two trials of methods to increase use of guidelines (Baker et al. 2003; White 

et al. 2004) had negative results. In an RCT designed to impart techniques for teaching patients 

about their asthma, White and colleagues (2004) compared a standard didactic lecture for 

physicians to problem-based learning. Groups did not differ in knowledge gained, but 

problem-based learning was perceived to have more educational value than the lectures. Baker 

and coworkers (2003) showed that neither distribution of evidence-based guidelines alone, nor 
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presentation of guidelines in a prioritized format (with or without performance feedback), led to 

increased implementation of the guideline recommendations. 

To promote use of asthma guidelines, Lozano and colleagues (2004) conducted a 2-year RCT 

of 422 primary care pediatric practices using two different asthma care improvement strategies. 

Peer leader education (training one physician per practice in asthma guidelines) was compared 

to peer leader education combined with nurse-driven organizational change through planned 

visits focused on assessment, care planning, and self-management support. Children in the 

planned care approach had significantly reduced symptoms and lower rates of oral steroid 

bursts, as well as greater adherence to controller medications. The comprehensive approach 

was an effective model for improving asthma care. A large, 1-year RCT (n = 937) aimed at 

inner-city PCPs working with 5- to 11-year-old children who had moderate or severe asthma 

evaluated the benefit of sending timely clinical information regarding the patient’s asthma status 

in a single-page letter to the physicians in the intervention group. The computer-generated 

letter summarized the results of bimonthly telephone calls to the child’s caretaker; provided 

information on the child’s asthma symptoms, health service use, and medication use; and 

included a corresponding recommendation to step up or step down the child’s medication. The 

letter served as a prompt to the clinician to change treatment. Children who were in the 

intervention group had significantly more scheduled preventative asthma visits, resulting in 

appropriate medication changes, and fewer ED visits and fewer school absences as compared 

with children who were controls (Kattan et al. 2006). 

An observational study was conducted to see whether an organized citywide 

asthma-management program delivered by PCPs would increase adherence to the asthma 

guidelines (Cloutier et al. 2005). Among the 3,748 children enrolled in the disease-management 

program, prescriptions for ICS increased by providers’ adherence to the guidelines, and overall 

hospitalization rates and ED visits decreased. 

Finkelstein and coworkers (2005) randomized primary care practices to one of two 

care-improvement strategies—physician peer leaders alone or in combination with asthma 

education nurses—or to usual care. The primary outcome, prescription of at least one 

long-term-control medication, improved in all arms of the study, but there were no differences 

among groups overall except a slight increase in ambulatory visits for asthma. 

Observational studies support the value of targeting physicians to participate in workshops. 

Rossiter and colleagues (2000) conducted a unique study in recruiting physicians to enroll in 

communication workshops using multimedia and adult learning techniques to improve 

communication skills. Hands-on workshops that included negotiating treatment plans for 

asthma were incorporated in the 6-hour sessions. Free continuing medical education, a 

discount on malpractice insurance, and free patient-education materials were used as 

incentives. Medicaid claims for ED care for asthma were reduced, with a marked increase in 

guideline-based asthma prescriptions. Doctors also got feedback reports identifying patients in 

need of followup because of poor asthma outcomes in terms of emergency room (ER) visits. 

However, only 33 percent of physicians from the community participated in the intervention. 

Reasons for lack of adherence to guidelines were shown in an observational study (Cabana et 

al. 2001) that is enlightening on the barriers to pediatricians’ adherence to asthma guidelines. 

Lack of time, lack of educational materials, lack of support staff, and lack of reimbursement 

were cited as major reasons for not adopting guidelines; notably, these are similar to reasons 

for patients’ nonadherence. This study reinforces the need for multifaceted interventions to 

address characteristic barriers for each guideline component. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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Taken together, these findings suggest that multifaceted clinician education programs based on 

interactive learning strategies (Cabana et al. 2006; Clark et al. 1998, 2000; Kattan et al. 2006; 

Lagerlov et al. 2000) can improve quality of care and patient outcomes. In the absence of 

multifaceted tailored interventions, a prioritized guideline format, with or without feedback, is 

unlikely to promote change in general practice care. However, it is acknowledged that 

practice-level interventions may have significant effects on subgroups of patients, but these 

effects are difficult to detect. More research is needed to understand how to increase 

adherence to guidelines and improved quality of care for asthma. From available evidence, 

multifaceted clinician education programs based on interactive learning strategies are a 

promising alternative to noninteractive educational sessions that provide information only. 

Communication Techniques 

The Expert Panel recommends that: 

 Clinicians consider participating in programs designed to enhance their skills in 

communicating with patients (Evidence B). 

 Clinicians consider documenting communication and negotiated agreements 

between patients and clinicians during medical encounters and that the level of 

asthma control be documented in the medical record of a patient at every visit to 

facilitate communication with patients during subsequent visits (Evidence C). 

 Communication skills-building programs include strategies to increase competence 

in caring for multicultural populations (Evidence D). 

The RCT reported on by Clark and colleagues (1998, 2000) and Brown and coworkers (2004) 

demonstrated that a physician education program could improve the communication skills of 

pediatricians caring for children and adolescents who have asthma and could result in improved 

patient outcomes. The program involved two educational sessions, each 2.5 hours long, and 

combined didactic sessions with interactive role playing. Bratton and coworkers (2006) have 

replicated this study in a population of physicians providing care to Medicaid patients. Data 

from providers indicate that the intervention improved providers’ use of communication skills, 

efforts to counsel patients in self-management strategies, and provision of written asthma action 

plans (Bratton et al. 2006). The results among pediatricians suggest that physicians can be 

taught improved communication skills that enhance patient adherence as well as asthma 

self-management and control. Love and coworkers (2000) showed that continuity of clinicians’ 

care can improve patient adherence and quality of life but not other outcomes. In qualitative 

work, Yawn (2003) reported that parents of children who have asthma were frustrated by lack of 

clear communication with health professionals, especially regarding changes in diagnosis, 

classification of asthma severity, and methods for asthma management. 

In a slightly different variation of patient–health professional communication, Cabana and 

colleagues (2003, 2005) and Yawn (2004) have shown that the documentation of the content of 

medical visits for asthma, if not the actual communication that occurs at those visits, frequently 

lacks information that is necessary to assess either asthma severity or asthma control as 

well as current adherence to asthma therapy. These studies suggest a need to document 

patient–clinician communications that occur in the context of asthma care. Such documentation 

may improve the content of subsequent communication during asthma care visits. 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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Wondering whether asthma severity was documented in medical records and whether such 

documentation prompted actions, Cabana and colleagues (2003) conducted an observational 

review of outpatient pediatric medical records. Only 34 percent of charts showed 

documentation of asthma severity during the previous 2 years. Documentation of severity, 

when identified, was associated with use of written asthma action plans and documented 

asthma education. Documentation of severity appeared to be associated with markers of 

improved long-term management of asthma.

In a large, prospective cohort 1-year study of 1,663 children receiving Medicaid in five large, 

nonprofit health plans, Lieu and coworkers (2004) demonstrated that, at sites that promoted 

cultural competence combined with physician feedback and improved access to care, improved 

use of long-term control medications and better ratings of care, according to the parents, 

resulted. 

METHODS OF IMPROVING SYSTEM SUPPORTS 

Clinical Pathways 

The Expert Panel recommends that clinical pathways be considered for the inpatient 

setting for patients who are admitted to hospital with asthma exacerbations (Evidence B).

Clinical pathways are tools, ideally based on clinical guidelines, that outline a sequence of 

evaluations and interventions to be carried out by clinicians for patients who have asthma. 

These pathways are designed to improve and maintain the quality of care while containing 

costs. Three studies described below reported the outcomes of implementing clinical pathways 

to guide patient care either in the ED or in the hospital setting. 

In an RCT, Johnson and colleagues (2000) demonstrated that, for children hospitalized for 

asthma, a clinical pathway directed by nurses can safely and reliably wean children from acute 

treatments and thereby significantly decrease the length of hospitalizations, the cost associated 

with the hospital admission, and the overall amount of nebulized beta2-agonist used. 

In another RCT, directed at children 2–18 years of age presenting to the ED with acute asthma, 

Zorc and coworkers (2003) used a clinical pathway to improve followup with PCPs. They found, 

however that even when followup appointments with the PCP 3–5 days later were scheduled 

by the ED staff, there was no effect on ED return visits, missed school days, or use of long-term 

control medications in the 4 weeks after the initial ED visit. The only positive outcome identified 

was an increased likelihood that urban children who had asthma would keep their followup 

appointment with the PCP. However, only 29 percent of children in the intervention group saw 

their PCP within 5 days after their ED visit, as requested, compared to 23 percent in the control 

group. Overall, 63 percent in the intervention group saw a PCP within 4 weeks versus 44 

percent in the control group. No information was provided about the reasons for missed 

followup visits. This study illustrates the difficulties in scheduling followup appointments after 

acute exacerbation as well as the problem of ensuring that patients go to PCPs as requested. 

A recent observational study showed that education of general practitioners in an asthma 

clinical pathway for children who have persistent asthma decreased prescription rates of oral 

beta2-agonists compared to rates prescribed by clinicians who were not educated in the 

pathway (Mitchell et al. 2005). Three other observational studies of pediatric patients show that 

implementation of an asthma clinical pathway may reduce hospital length of stay and costs 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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without increasing morbidity or rates of readmission (Kelly et al. 2000; McDowell et al. 1998; 

Wazeka et al. 2001). 

These studies show mixed results for the effectiveness of clinical pathways, depending on the 

outcomes chosen and the setting. 

Clinical Decision Supports 

The Expert Panel recommends that: 

 Prompts encouraging guideline-based care be integrated into system-based 

interventions focused on improving the overall quality of care rather than used as a 

single intervention strategy (Evidence B).

 System-based interventions that address multiple dimensions of the organization and 

delivery of care and clinical decision support be considered to improve and maintain 

quality of care for patients who have asthma (Evidence B and C).

(See Evidence Table 8, Methods for Improving Systems Support.) 

Some investigators have studied the use of computer-based prompts to encourage the use of 

guidelines in asthma management. McCowan and colleagues (2001) conducted an RCT of a 

software decision-support system to prompt use of asthma guidelines. The system had a 

positive effect resulting in reduction of exacerbations in patients whose physicians used the 

system, but the system had no effect on reported symptoms, physicians’ prescribing of longterm-control medications, or use of hospital services by patients. In another RCT (Tierney et al. 

2005), care suggestions were delivered by computerized prompts to physicians and 

pharmacists in the intervention group. The prompts did not result in improved medication 

adherence, quality of life, patient satisfaction with care, ED visits, or hospitalizations. 

Intervention physicians had higher health care costs for asthma care of their patients, but care 

suggestions had no effect on the delivery or the outcomes of care. The results of these two 

trials suggest that, although the use of computerized prompts is intuitively appealing, there is 

insufficient evidence that prompts result in improved asthma care. 

In a retrospective analysis of administrative claims data, Dombkowski and colleagues (2005) 

found that adherence to national asthma guidelines varied widely among health care plans 

covering 3,970 children who had persistent asthma and were enrolled in Medicaid. After 

low-income families who had children who had asthma enrolled in a statewide insurance plan, 

Szilagyi and coworkers (2006) interviewed parents at baseline and 1 year later. They found 

improvements in access to care and a decrease in asthma exacerbations and hospitalizations 

for the enrolled children. Quality of asthma care improved for most general measures. Taken 

together, these observational studies suggest opportunities for population-based health care 

plan interventions to improve access and quality of asthma care. 

In one RCT, Lozano and colleagues (2004) demonstrated that multidimensional system-based 

interventions improved patient outcomes. Observational analysis (Patel et al. 2004) of a large 

database of 3,400 patients who had asthma and were in a medical group practice that initiated a 

multidisciplinary asthma disease-management program showed that the program worked in 

several, but not all, areas: documentation of diagnoses and patient education improved, and 

ED visits and hospitalizations were reduced. A multidimensional approach, utilizing all staff to 

assist in implementation of the program, was an important part of the intervention. The key to 
Section 3, Component 2: Education for a Partnership in Asthma Care 

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clinicians’ ownership of the program included having clinicians lead the design process, using 

physician champions who had both formal and informal influence, and using rewards and 

recognition. In a comprehensive program to restructure health care delivery for all patients who 

had asthma, one large organization serving children instituted a systemwide restructured plan, 

including a new inpatient unit, standardized treatment protocol, direct admission policies for 

PCPs with optional specialist consultation, and use of case managers to help families address 

barriers to care and facilitate adherence (Evans et al. 1999b). The restructured program 

resulted in significant reductions in ED visits and length of hospital stays, as well as fewer 

readmissions to the hospital, while maintaining high quality of care and parental satisfaction with 

care. 

Taken together, these system-based interventions for large populations of low-income children 

and adults who have asthma demonstrate effectiveness in improving quality of care and 

reducing use of health resources. Compared to provider-dependent strategies, these 

systemwide interventions may be more likely to result in consistent improved health outcomes 

for large populations of patients who have asthma. 

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SECTION 3, COMPONENT 3: CONTROL OF ENVIRONMENTAL FACTORS 

AND COMORBID CONDITIONS THAT AFFECT ASTHMA 

KEY POINTS: CONTROL OF ENVIRONMENTAL FACTORS 

AND COMORBID CONDITIONS THAT AFFECT ASTHMA 

 Exposure of patients who have asthma to allergens (Evidence A) or irritants (EPR⎯2 1997) 

to which they are sensitive has been shown to increase asthma symptoms and precipitate 

asthma exacerbations. 

 For at least those patients who have persistent asthma, the clinician should evaluate the 

potential role of allergens, particularly indoor inhalant allergens (Evidence A): 

— Use the patient’s medical history to identify allergen exposures that may worsen the 

patient’s asthma. 

— Use skin testing or in vitro testing to reliably determine sensitivity to perennial indoor 

inhalant allergens to which the patient is exposed. 

— Assess the significance of positive tests in the context of the patient’s medical history. 

— Use the patient’s history to assess sensitivity to seasonal allergens. 

 Patients who have asthma at any level of severity should: 

— Reduce, if possible, exposure to allergens to which the patient is sensitized and 

exposed. 

— Know that effective allergen avoidance requires a multifaceted, comprehensive 

approach; individual steps alone are generally ineffective (Evidence A). 

— Avoid exposure to environmental tobacco smoke and other respiratory irritants, including 

smoke from wood-burning stoves and fireplaces and, if possible, substances with strong 

odors (Evidence C). 

— Avoid exertion outdoors when levels of air pollution are high (Evidence C). 

— Avoid use of nonselective beta-blockers (Evidence C). 

— Avoid sulfite-containing and other foods to which they are sensitive (Evidence C). 

— Consider allergen immunotherapy when there is clear evidence of a relationship 

between symptoms and exposure to an allergen to which the patient is sensitive 

(Evidence B). If use of allergen immunotherapy is elected, it should be administered 

only in a physician’s office where facilities and trained personnel are available to treat 

any life-threatening reaction that can, but rarely does, occur. 
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 Adult patients who have severe persistent asthma, nasal polyps, or a history of sensitivity to 

aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) should be counseled regarding the 

risk of severe and even fatal exacerbations from using these drugs (Evidence C). 

 Clinicians should evaluate a patient for the presence of a chronic comorbid condition when 

the patient’s asthma cannot be well controlled. Treating the conditions may improve asthma 

management: ABPA (Evidence A), gastroesophageal reflux (Evidence B), obesity 

(Evidence B, limited studies), OSA (Evidence D), rhinitis/sinusitis (Evidence B), chronic 

stress/depression (Evidence D). 

 Consider inactivated influenza vaccination for patients who have asthma. It is safe for 

administration to children more than 6 months of age and adults (Evidence A). The 

Advisory Committee on Immunization Practices of the CDC recommends vaccination for 

persons who have asthma, because they are considered to be at risk for complications from 

influenza. However, the vaccine should not be given with the expectation that it will reduce 

either the frequency or severity of asthma exacerbations during the influenza season 

(Evidence B). 

 Use of humidifiers and evaporative (swamp) coolers is not generally recommended in 

homes of patients who have asthma and are sensitive to house-dust mites or mold 

(Evidence C). 

 Employed persons who have asthma should be queried about possible occupational 

exposures, particularly those who have new-onset disease (EPR⎯2 1997). 

 There is insufficient evidence to recommend any specific environmental strategies to 

prevent the development of asthma. 

KEY DIFFERENCES FROM 1997 EXPERT PANEL REPORT 

 Evidence strengthens recommendations that reducing exposure to inhalant indoor allergens 

can improve asthma control and notes that a multifaceted approach is required; single steps 

to reduce exposure are generally ineffective. 

 Formaldehyde and volatile organic compounds (VOCs) have been implicated as potential 

risk factors for asthma and wheezing. 

 Evidence shows that influenza vaccine, while having other benefits, does not appear to 

reduce either the frequency or severity of asthma exacerbations during the influenza 

season. 

 The section has been expanded to include discussion of ABPA, obesity, OSA, and stress as 

chronic comorbid conditions, in addition to rhinitis, sinusitis, and gastroesophageal reflux, 

that may interfere with asthma management. 
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Introduction 

See section 1, “Overall Methods Used To Develop This Report,” for literature search strategy 

and tally of results for the EPR—3: Full Report 2007 on this component, “Control of 

Environmental Factors and Comorbid Conditions That Affect Asthma.” Two Evidence Tables 

were prepared: 9, Allergen Avoidance; and 10, Immunotherapy. 

For successful long-term management of asthma, it is essential to identify and reduce 

exposures to relevant allergens and irritants and to control other factors that have been shown 

to increase asthma symptoms and/or precipitate asthma exacerbations. These factors are in 

five categories: inhalant allergens, occupational exposures, irritants, comorbid conditions, and 

other factors. Ways to reduce the effects of these factors on asthma are discussed in this 

component of asthma management. 

Inhalant Allergens 

The Expert Panel recommends that patients who have asthma at any level of severity 

should be queried about exposures to inhalant allergens, particularly indoor inhalant 

allergens, and their potential effect on the patient’s asthma (Evidence A). Exposure of a 

person who has asthma to inhalant allergens to which the person is sensitive increases airway 

inflammation and symptoms. Substantially reducing such exposure may significantly reduce 

inflammation, symptoms, and need for medication (See a summary of the evidence in box 3–5.). 

DIAGNOSIS—DETERMINE RELEVANT INHALANT SENSITIVITY 

Demonstrating a patient’s relevant sensitivity to inhalant allergens will enable the clinician to 

recommend specific environmental controls to reduce exposures. It will also help the patient 

understand the pathogenesis of asthma and the value of allergen avoidance. 

The Expert Panel recommends that, given the importance of allergens and their control 

to asthma morbidity and asthma management, patients who have persistent asthma 

should be evaluated for the role of allergens as possible contributing factors as follows 

(EPR⎯2 1997):

 Determine the patient’s exposure to allergens, especially indoor inhalant allergens. 

(See relevant questions in figure 3–17.) 

 Assess sensitivity to the allergens to which the patient is exposed. 

— Use the patient’s medical history, which is usually sufficient, to determine 

sensitivity to seasonal allergens. 

— Use skin testing or in vitro testing to determine the presence of specific IgE 

antibodies to the indoor allergens to which the patient is exposed year round. 

(See figure 3–18 for a comparison of skin and in vitro tests.) Allergy testing is the 

only reliable way to determine sensitivity to perennial indoor allergens (See 

box 3–6 for further explanation.). 

— For selected patients who have asthma at any level of severity, detection of 

specific IgE sensitivity to seasonal or perennial allergens may be indicated as a 

basis for education about the role of allergens for avoidance and for 

immunotherapy. 

 Assess the clinical significance of positive allergy tests in the context of the patient’s 

medical history (See figure 3–19.). 
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BOX 3–5. THE STRONG ASSOCIATION BETWEEN SENSITIZATION 

TO ALLERGENS AND ASTHMA: A SUMMARY OF THE EVIDENCE 

The association of asthma and allergy has long been recognized. Recent studies confirm that 

sensitization among genetically susceptible populations to certain indoor allergens such as 

house-dust mite, animal dander, and cockroach or to the outdoor fungus Alternaria is a risk for 

developing asthma in children (Halonen et al. 1997; Sears et al. 1993; Sporik et al. 1990). 

Sensitization to outdoor pollens carries less risk for asthma (Sears et al. 1989), although 

exposure to grass (Reid et al. 1986) and ragweed (Creticos et al. 1996) pollen has been 

associated with seasonal asthma. It is widely accepted that the importance of inhalant 

sensitivity as a cause of asthma declines with advancing age (Pollart et al. 1989). 

An allergic reaction in the airways, caused by natural exposure to allergens, has been shown to 

lead to an increase in inflammatory reaction, increased airway hyperresponsiveness (Boulet et 

al. 1983; Peroni et al. 1994; Piacentini et al. 1993), and increased eosinophils in 

bronchoalveolar lavage (Rak et al. 1991). Other research has demonstrated that asthma 

symptoms, pulmonary function, and need for medication in mite-sensitive asthma patients 

correlate with the level of house-dust mite exposure (Custovic et al. 1998; Huss et al. 2001; 

Sporik et al. 1990; Vervloet et al. 1991) and that reducing house-dust mite exposure reduces 

asthma symptoms, nonspecific bronchial hyperresponsiveness, and evidence of active 

inflammation (Morgan et al. 2004; Peroni et al. 2002; Piacentini et al. 1993; Simon et al. 1994). 

Inhalant allergen exposure to seasonal outdoor fungal spores (O'Hollaren et al. 1991; Targonski 

et al. 1995) and to indoor allergens (Call et al. 1994) has also been implicated in fatal 

exacerbations of asthma. These reports emphasize that allergen exposure must be considered 

in the treatment of asthma. 

The important allergens for children and adults appear to be those that are inhaled. Food 

allergens are not a common precipitant of asthma symptoms. Foods are an important cause of 

anaphylaxis in adults and children (Golbert et al. 1969; Sampson et al. 1992), but significant 

lower respiratory tract symptoms are uncommon even with positive double-blind food 

challenges (James et al. 1994). However, asthma is a risk factor for fatal anaphylactic reactions 

to food or immunotherapy (Bernstein et al. 2004; Reid et al. 1993). 
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BOX 3–6. RATIONALE FOR ALLERGY TESTING FOR PERENNIAL 

INDOOR ALLERGENS

Determination of sensitivity to a perennial indoor allergen is usually not possible with a patient’s 

medical history alone (Murray and Milner 1995). Increased symptoms during vacuuming or bed 

making and decreased symptoms when away from home on a business trip or vacation are 

suggestive but not sufficient. Allergy skin or in vitro tests are reliable in determining the 

presence of specific IgE (Dolen 2001; Yunginger et al. 2000), but these tests do not determine 

whether the specific IgE is responsible for the patient’s symptoms. That is why patients should 

be tested only for sensitivity to the allergens to which they may be exposed, and why the third 

step in evaluating patients for allergen sensitivity calls for assessing the clinical relevance of the 

sensitivity. 

The recommendation to do skin or in vitro tests for patients who have persistent asthma and are 

exposed to perennial indoor allergens will result in a limited number of allergy tests for about 

half of all asthma patients. This estimate is based on the prevalence of persistent asthma and 

the level of exposure to indoor allergens. Based on data on children in the United States, it is 

estimated that at least 70 percent of all patients who have asthma have persistent asthma 

(Squillace et al. 1997; Taylor and Newacheck 1992). About 80 percent of the U.S. population is 

exposed to house-dust mites (Arbes et al. 2003; Nelson and Fernandez-Caldas 1995), 60 

percent to cat or dog, and a much smaller percentage to both animals (Ingram et al. 1995). 

Cockroaches are a consideration primarily in the inner-city and southern parts of the United 

States. 

Skin or in vitro tests are necessary to educate patients about the role of allergens in their 

disease. Education is an essential prerequisite for convincing patients about the need for 

specific allergen avoidance. Current recommendations for avoidance measures for dust-mite, 

cat, or cockroach allergens are allergen specific, and it is only possible to convince patients to 

undertake the measures once they know to what they are allergic. 

MANAGEMENT—REDUCE EXPOSURE 

The Expert Panel recommends that patients should reduce exposure, as much as 

possible, to allergens to which the patient is sensitized and exposed: 

 The first and most important step in controlling allergen-induced asthma is to advise 

patients to reduce exposure to relevant indoor and outdoor allergens to which the 

patient is sensitive (Evidence A) (See Evidence Table 9, Allergen Avoidance.). 

 Effective allergen avoidance requires a multifaceted, comprehensive approach; 

individual steps alone are generally ineffective (Evidence A). 

 Consider multifaceted allergen-control education interventions provided in the home 

setting that have been proven effective for reducing exposures to cockroach, dustmite, and rodent allergens for patients sensitive to those allergens (Evidence A). 

Further research to evaluate the feasibility of widespread implementation of such 

programs will be helpful (see “Component 2: Education for a Partnership in Asthma 

Care.”). 
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Effective ways patients can reduce their exposures to indoor and outdoor allergens are 

discussed below and summarized in figure 3–20, which also addresses irritants. Although these 

recommendations focus on the home environment, reductions in exposures to allergens and 

irritants are also appropriate in other environments where the patient spends extended periods 

of time, such as school, work, or daycare. For information about companies that distribute 

products to help reduce allergen exposure, contact the Asthma and Allergy Foundation of 

America toll-free hotline at 800–727–8462 or the Allergy and Asthma Network/Mothers of 

Asthmatics at 800–878–4403. 

See “Component 2: Education for a Partnership in Asthma Care” for a description of 

allergen-control education programs that are delivered in patients’ homes. Multifaceted 

programs that focus on educating patients and providing tools for reducing exposure to 

cockroach, dust-mite, and rodent allergens have demonstrated success in reducing exposure 

and reducing asthma morbidity. Further evaluation is needed of the cost-effectiveness and 

feasibility for widespread implementation of these interventions; however, the efficacy of the 

interventions warrants their consideration, if available, for patients sensitive to these allergens. 

Animal allergens. The Expert Panel recommends the following actions to control animal 

antigens (Evidence D):

 If the patient is sensitive to an animal, the treatment of choice is removal of the 

exposure from the home. 

 If removal of the animal is not acceptable: 

— Keep the pet out of the patient’s bedroom. 

— Keep the patient’s bedroom door closed. 

— Remove upholstered furniture and carpets from the home, or isolate the pet from 

these items to the extent possible. 

— Mouse allergen exposure can be reduced by a combination of blocking access, 

low-toxicity pesticides, traps, and vacuuming and cleaning. 

All warm-blooded animals, including pets and rodents, produce dander, urine, feces, and saliva 

that can cause allergic reactions (de Blay et al. 1991b; Swanson et al. 1985). Given recent 

evidence that exposure to cat allergens can be significant in homes, schools, and offices without 

animals, the issue of allergen avoidance in sites without animals has become more relevant. 

Successful controlled trials of animal dander avoidance have now been reported for schools and 

for homes without an animal (Popplewell et al. 2000). Studies suggest that mouse and rat 

allergen exposure and sensitization are common in urban children who have asthma 

(Phipatanakul et al. 2004). 

High-efficiency particulate air (HEPA) cleaners reduce airborne Can f 1 in homes with dogs. 

Furthermore, preventing the dog from having access to the bedroom, and possibly the living 

room, may reduce the total allergen load inhaled (Green et al. 1999). Weekly washing of the 

pet will remove large quantities of dander and dried saliva that will otherwise accumulate in the 

house; however, the role of washing in allergen avoidance is not established (Avner et al. 1997, 

de Blay et al. 1991a, Klucka et al. 1995). 
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House-dust mite allergen. The Expert Panel recommends the following mite-control 

measures; effective allergen avoidance requires a multifaceted approach (Evidence A).

 Recommended actions to control mites include: 

— Encase the mattress in an allergen-impermeable cover. 

— Encase the pillow in an allergen-impermeable cover or wash it weekly. 

— Wash the sheets and blankets on the patient’s bed weekly in hot water. 

— A temperature of >130 °F is necessary for killing house-dust mites. Prolonged 

exposure to dry heat or freezing can also kill mites but does not remove allergen. 

If high temperature water is not available, a considerable reduction in live mites 

and mite allergens can still be achieved with cooler water and using detergent 

and bleach. 

 Actions to consider to control mites include: 

— Reduce indoor humidity to or below 60 percent, ideally between 30 and 

50 percent. 

— Remove carpets from the bedroom. 

— Avoid sleeping or lying on upholstered furniture. 

— Remove from the home carpets that are laid on concrete. 

— In children’s beds, minimize the number of stuffed toys, and wash them weekly. 

House-dust mites are universal in areas of high humidity (most areas of the United States) but 

are usually not present at high altitudes or in arid areas unless moisture is added to the indoor 

air (Platts-Mills et al. 1997). Mites depend on atmospheric moisture and human dander for 

survival. High levels of mites can be found in dust from mattresses, pillows, carpets, 

upholstered furniture, bed covers, clothes, and soft toys. The patient’s bed is the most 

important source of dust mites to control. Washing bedding is advised, preferably in hot water, 

but cold water, detergent, and bleach can also be effective (Arlian et al. 2003; McDonald and 

Tovey 1992). Several recent studies support the efficacy of allergen avoidance in the treatment 

of asthma (Carter et al. 2001; Halken et al. 2003; Htut et al. 2001; Morgan et al. 2004; Peroni et 

al. 2002; Rijssenbeek-Nouwens et al. 2003; van der Heide et al. 1997). Other studies provide 

important insight into the details of allergen avoidance. For example, three studies reported that 

mattress covers without other measures were not effective (Luczynska et al. 2003; Terreehorst 

et al. 2003; Woodcock et al. 2003). Likewise, two well-conducted studies failed to show an 

effect of HEPA filters alone (Francis et al. 2003; Wood et al. 1998). Thus, the conclusion 

remains that effective allergen avoidance requires a comprehensive approach, and that 

individual steps alone are generally ineffective (Platts-Mills et al. 2000). 

Chemical agents are available for killing mites and denaturing the antigen; however, the effects 

are not dramatic and do not appear to be maintained for long periods. Therefore, use of these 

agents in the homes of persons who have asthma and are sensitive to house-dust mites should 

not be recommended routinely (Woodfolk et al. 1995). Vacuuming removes mite allergen from 

carpets but is inefficient at removing live mites. 
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Room air-filtering devices are not recommended for control of mite allergens, because the 

allergens are associated with large particles which remain airborne for only a few minutes after 

disturbance. They are, therefore, not susceptible to removal by air filtration. 

Cockroach allergen. The Expert Panel recommends that cockroach control measures 

should be instituted if the patient is sensitive to cockroaches and infestation is present 

in the home (Evidence B).

Cockroach sensitivity and exposure are common among patients who have asthma and live in 

inner cities (Call et al. 1992; Gelber et al. 1993; Huss et al. 2001; Kang et al. 1993). In a study 

of asthma in an inner-city area, asthma severity increased with increasing levels of cockroach 

antigen in the bedrooms of children who were sensitized (Rosenstreich et al. 1997). Another 

major study demonstrated efficacy of cockroach avoidance as part of an overall plan for allergen 

avoidance (Morgan et al. 2004). Patients should not leave food or garbage exposed. Poison 

baits, boric acid, and traps are preferred to other chemical agents, because the latter can be 

irritating when inhaled by persons who have asthma. If volatile chemical agents are used, the 

home should be well ventilated, and the person who has asthma should not return to the home 

until the odor has dissipated. Care should be taken so that young children do not have access 

to cockroach baits and poisons. 

Indoor fungi (molds). The Expert Panel recommends consideration of measures to 

control indoor mold (Evidence C). Indoor fungi are particularly prominent in humid 

environments and homes that have problems with dampness. Children who live in homes with 

dampness problems have increased respiratory symptoms (Institute of Medicine 2004; Verhoeff 

et al. 1995), but the relative contribution of fungi, house-dust mites, or irritants is not clear. 

Because an association between indoor fungi and respiratory and allergic disease is suggested 

by some studies (Bjornsson et al. 1995; Smedje et al. 1996; Strachan 1988), measures to 

control dampness or fungal growth in the home may be beneficial. 

Outdoor allergens (tree, grass, and weed pollen; seasonal mold spores). The Expert 

Panel recommends that patients who are sensitive to seasonal outdoor allergens 

consider staying indoors, if possible, during peak pollen times—particularly midday and 

afternoon (EPR⎯2 1997). The strongest associations between mold-spore exposure and 

asthma have been with the outdoor fungi, such as Alternaria (Halonen et al. 1997; O'Hollaren et 

al. 1991; Targonski et al. 1995). Patients can reduce exposure during peak pollen season by 

staying indoors with windows closed in an air-conditioned environment (Solomon et al. 1980), 

particularly during the midday and afternoon when pollen and some spore counts are highest 

(Long and Kramer 1972; Mullins et al. 1986; Smith and Rooks 1954). Conducting outdoor 

activities shortly after sunrise will result in less exposure to pollen. These actions may not be 

realistic for some patients, especially children. 

IMMUNOTHERAPY 

The Expert Panel recommends that allergen immunotherapy be considered for patients 

who have persistent asthma if evidence is clear of a relationship between symptoms and 

exposure to an allergen to which the patient is sensitive (Evidence B) (see Evidence 

Table 10, Immunotherapy).

Immunotherapy is usually reserved for patients whose symptoms occur all year or during a 

major portion of the year and in whom controlling symptoms with pharmacologic management is 

difficult because the medication is ineffective, multiple medications are required, or the patient is 
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not accepting the use of medication. Reports, however, that immunotherapy can prevent the 

development of new sensitivities in monosensitized children and adults (Des Roches et al. 

1997; Pajno et al. 2001; Purello-D'Ambrosio et al. 2001) and that immunotherapy with birch and 

timothy pollen extracts can prevent the development of asthma in children who have allergic 

rhinitis (Moller et al. 2002), along with evidence of persisting effect for at least 3 years after 

discontinuation (Durham et al. 1999), suggest that immunotherapy should be considered when 

there is a significant allergic contribution to the patient’s symptoms. Specific immunotherapy 

has been shown to induce a wide range of immunologic responses that include the modulation 

of T- and B-cell responses by the generation of allergen-specific Treg cells; increases in 

allergen-specific IgG4, IgG1, and IgA; decrease in IgE and decreased tissue infiltration of mast 

cells and eosinophils. The relevance of these immunologic changes to the clinical efficacy of 

specific immunotherapy has yet to be established (Akdis and Akdis 2007). 

Controlled studies of immunotherapy, usually conducted with single allergens, have 

demonstrated reduction in asthma symptoms caused by exposure to grass, cat, house-dust 

mite, ragweed, Cladosporium, and Alternaria (Creticos et al. 1996; Horst et al. 1990; Malling et 

al. 1986; Olsen et al. 1997; Reid et al. 1986; Varney et al. 1997). A meta-analysis of 75 

randomized, placebo-controlled studies has confirmed the effectiveness of immunotherapy in 

asthma, with a significant reduction in asthma symptoms and medication and with improvement 

in bronchial hyperreactivity (Abramson et al. 2003). This meta-analysis included 36 trials for 

allergy to house dust mites, 20 for pollen allergy, and 10 for animal dander. On the other hand, 

only three trials for mold allergy and only six trials with multiple allergen therapy were included. 

In the United States, standardized extracts are available for house-dust mites, grasses, short 

ragweed, and cat, and there are unstandardized extracts of other pollens and for dog that 

appear to have similar potency (Nelson 2007). Available extracts for cockroach and mold, on 

the other hand, are of very variable allergen content and allergenic potency, and their 

effectiveness in specific immunotherapy has not been demonstrated (Nelson 2007). Few 

studies have been reported on multiple-allergen mixes that are commonly used in clinical 

practice. One, which included high doses of all allergens to which the children were sensitive 

(Johnstone and Dutton 1968), demonstrated reduction in asthma symptoms compared to lower 

doses of the same allergens or placebo. Another study, in which the children were given 

optimal medical therapy and in which the only perennial allergen administered was house-dust 

mite, demonstrated no improvement in asthma symptoms between active and placebo therapy 

(Adkinson et al. 1997). 

The course of allergen immunotherapy is typically of 3–5 years’ duration. Severe and 

sometimes fatal reactions to immunotherapy, especially severe bronchoconstriction, are more 

frequent among patients who have asthma, particularly those who have poorly controlled 

asthma, compared with those who have allergic rhinitis (Bernstein et al. 2004; Reid et al. 1993). 

If use of allergen immunotherapy is elected, it should be administered only in a physician’s 

office where facilities and trained personnel are available to treat any life-threatening reaction 

that can, but rarely does, occur (AAAI Board of Directors 1994). For this reason, enthusiasm for 

the use of immunotherapy in asthma differs considerably among experts (Abramson et al. 2003; 

Canadian Society of Allergy and Clinical Immunology 1995; Frew 1993). 

In Europe, interest has increased in high-dose sublingual immunotherapy (Canonica and 

Passalacqua 2003). It has been reported to be effective in asthma, with benefit persisting 

4–5 years after its discontinuation (Di Rienzo et al. 2003), and to be free of systemic reactions, 

thus allowing home administration. Comparative studies suggest it is less effective, however, 

than immunotherapy administered by subcutaneous injection (Khinchi et al. 2004; Lima et al. 

2002). 
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ASSESSMENT OF DEVICES THAT MAY MODIFY INDOOR AIR 

The Expert Panel recommends the following actions to modify indoor air:

 Vacuuming carpets once or twice a week to reduce accumulation of house dust. 

Patients sensitive to components of house dust should avoid using conventional 

vacuum cleaners, and these patients should stay out of rooms where a vacuum 

cleaner is being or has just been used (EPR⎯2 1997; Murray et al. 1983). If patients 

vacuum, they can use a dust mask, a central cleaner with the collecting bag outside the 

home, or a cleaner fitted with a HEPA filter or with a double bag (Popplewell et al. 2000; 

Woodfolk et al. 1993). 

 Air conditioning during warm weather, if possible, for patients who have asthma and 

are allergic to outdoor allergens (Evidence C), because air conditioning allows windows 

and doors to stay closed, thus preventing entry of outdoor allergens (Solomon et al. 1980). 

Regular use of central air conditioning also will usually control humidity sufficiently to reduce 

house-dust mite growth during periods of high humidity (Arlian et al. 2001). Reducing 

relative humidity is a practical way to control house-dust mites and their allergens in homes 

in temperate climates (Arlian et al. 2001). 

 Use of a dehumidifier to reduce house-dust mite levels in areas where the humidity of 

the outside air remains high for most of the year (EPR⎯2 1997). House-dust mite 

levels can be reduced by use of dehumidifiers to maintain levels to or below 60 percent, 

ideally 30–50 percent, relative humidity (Cabrera et al. 1995). 

 There is insufficient evidence to recommend indoor air cleaning devices. They may 

reduce some, but not all airborne allergens, but evidence is limited regarding their 

impact on asthma control. Indoor air-cleaning devices cannot substitute for the more 

effective dust-mite and cockroach control measures described previously, because these 

heavy particles do not remain airborne (Custis et al. 2003). However, air-cleaning devices 

(i.e., HEPA and electrostatic precipitating filters) have been shown to reduce airborne dog 

allergen (Green et al. 1999), cat dander (de Blay et al. 1991a; Francis et al. 2003; Wood et 

al. 1998), mold spores (Maloney et al. 1987), and particulate tobacco smoke (EPA 1990). 

Use of an air cleaning device containing a HEPA filter may reduce exposure, especially if 

added to other avoidance measures (Green et al. 1999). However, most studies of air 

cleaners have failed to demonstrate an effect on asthma symptoms or pulmonary function 

(Nelson et al. 1988; Reisman et al. 1990; Warburton et al. 1994; Warner et al. 1993; Wood 

et al. 1998). Air cleaners that are designed to work by the generation of ozone and that emit 

ozone into the air should be avoided by persons who have asthma. 

 There is insufficient evidence to recommend cleaning air ducts of 

heating/ventilation/air conditioning systems (Evidence D). Cleaning has been reported 

to decrease levels of airborne fungi in residences (Garrison et al. 1993). The effect on 

levels of house-dust mite or animal dander has not been studied. Limited evidence 

continues to preclude the Expert Panel’s making a recommendation in this area. 

The Expert Panel does not generally recommend use of humidifiers and evaporative 

(swamp) coolers for use in the homes of house-dust mite-sensitive patients who have 

asthma (Evidence C). If use of a humidifier is desired to avoid excessive dryness, the relative 

humidity in the home should be maintained at or below 60 percent, ideally between 30 and 

50 percent. These machines are potentially harmful because increased humidity may 
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encourage the growth of both mold (Solomon 1976) and house-dust mites (Ellingson et al. 

1995; McConnell et al. 2002). In addition, humidifiers may pose a problem because, if not 

properly cleaned, they can harbor and aerosolize mold spores (Solomon 1974). 

Occupational Exposures 

The Expert Panel recommends that clinicians query patients who are employed and have 

asthma about possible occupational exposures, particularly those who have new-onset 

disease (EPR⎯2 1997). Early recognition and control of exposures are particularly important 

in occupationally induced asthma, because the likelihood of complete resolution of symptoms 

decreases with time (Pisati et al. 1993). Occupational asthma is suggested by a correlation 

between asthma symptoms and work, as well as with improvement when away from work for 

several days. Other indications of workplace exposure are listed in figure 3–21. The patient 

may fail to recognize the relationship with work, because symptoms often begin several hours 

after exposure. Recently, common jobs—such as domestic cleaner, laboratory technician, and 

house painter—have been associated with the disease (Moscato et al. 1995). Serial peak flow 

records at work and away from work can confirm the association between work and asthma 

(Nicholson et al. 2005). 

Workplace exposure to sensitizing chemicals, allergens, or dusts can induce asthma which 

often persists after the exposures are terminated (Pisati et al. 1993). This effect should be 

distinguished from allergen- or irritant-induced aggravation of preexisting asthma. 

Patient confidentiality issues are particularly important in work-related asthma. Because even 

general inquiries about the potential adverse health effects of work exposures may occasionally 

result in reprisals against the patient (e.g., job loss), patients who have asthma need to be 

informed of this possibility and be full partners in the decision to approach management 

regarding the effects or control of workplace exposures. This situation may require referral to 

an occupational asthma specialist. 

Irritants 

The Expert Panel recommends that clinicians query patients who have asthma at any 

level of severity about exposures to irritants that may cause their asthma to worsen, and 

advise them accordingly about reducing relevant exposures (EPR⎯2 1997). Sample 

assessment questions are in figure 3–17. 

ENVIRONMENTAL TOBACCO SMOKE 

The Expert Panel recommends that clinicians advise persons who have asthma not to 

smoke or be exposed to ETS (Evidence C). Query patients about their smoking status 

and specifically consider referring to smoking cessation programs adults who smoke 

and have young children who have asthma in the household (Evidence B).

Exposure to ETS is common in the United States (Gergen et al. 1998). ETS is associated with 

increased symptoms, decreased lung function, and greater use of health services among those 

who have asthma (Sippel et al. 1999) in all age groups, although exact negative effects may 

vary by age (Mannino et al. 2001). Exposure to maternal smoking has been shown to be a risk 

factor for the development of asthma in infancy and childhood (Henderson et al. 1995; Martinez 

et al. 1995; Soyseth et al. 1995). Effects of ETS on a child’s asthma are greater when the 

mother smokes than when others in the household smoke (Agabiti et al. 1999; Austin and 
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Russell 1997; Ehrlich et al. 2001). Heavy smokers may be more unaware than those who 

smoke less of the effects of ETS exposure on children (Crombie et al. 2001). The primary 

modes of exposure to ETS for adults who have asthma may be when they are at work (Radon 

et al. 2002) or traveling (Eisner and Blanc 2002). ETS exposure operates as a cofactor in 

wheezing, along with other insults such as infections (Gilliland et al. 2001). Smoking out of 

doors to avoid exposing others may not adequately reduce exposure for children (Bahceciler et 

al. 1999). See ”Component 2: Education for a Partnership in Asthma Care” for discussion of 

programs to encourage parents of children who have asthma not to smoke. 

As a routine part of their asthma care, patients should be counseled concerning the negative 

effects of smoking and ETS. 

INDOOR/OUTDOOR AIR POLLUTION AND IRRITANTS 

The Expert Panel recommends that clinicians advise patients to avoid, to the extent 

possible, exertion or exercise outside when levels of air pollution are high (Evidence C).

Increased pollution levels—especially of particulate matter ≤10 micrometers (PM10) (Abbey et 

al. 1993; Atkinson et al. 2001; Gent et al. 2003; Koenig et al. 1993; Ostro et al. 1995; Pope et al. 

1991; Schwartz et al. 1993; Slaughter et al. 2003; Walters et al. 1994) and ozone (Abbey et al. 

1993; Cody et al. 1992; Kesten et al. 1995; Ostro et al. 1995; Ponka 1991; Romieu et al. 1995; 

Thurston et al. 1992; White et al. 1994), but also of SO2 (Moseholm et al. 1993) and nitric oxide 

(NO2) (Kesten et al. 1995; Moseholm et al. 1993)—have been reported to precipitate symptoms 

of asthma (Abbey et al. 1993; Koenig et al. 1987; Moseholm et al. 1993; Pope et al. 1991), 

increase SABA use (Gent et al. 2003), and increase ED visits and hospitalizations for asthma 

(Cody et al. 1992; Kesten et al. 1995; Ponka 1991; Romieu et al. 1995; Schwartz et al. 1993; 

Thurston et al. 1992; Walters et al. 1994; White et al. 1994). 

High exposure to NO2 in the week before the start of a respiratory viral infection, at levels within 

current air quality standards, may increase the severity of virus-induced asthma exacerbations 

(Chauhan et al. 2003). 

Exposure to pollutants may increase airway inflammation (Hiltermann et al. 1999) and enhance 

the risk of allergic sensitization through simultaneous exposure to aeroallergens (Diaz-Sanchez 

et al. 1999; Fujieda et al. 1998; Jenkins et al. 1999). The propensity for particulate pollution to 

enhance allergic sensitization may be genetically regulated (Gilliland et al. 2004; Peden 2005). 

Formaldehyde and Volatile Organic Compounds 

Formaldehyde and VOCs—which can arise from sources such as new linoleum flooring, 

synthetic carpeting, particleboard, wall coverings, furniture, and recent painting—have been 

implicated as potential risk factors for the onset of asthma and wheezing (Garrett et al. 1999; 

Jaakkola et al. 2004; Rumchev et al. 2004). Clinicians should advise patients to be aware of the 

potential irritating effects of newly installed furnishings and finishes. 

Gas Stoves and Appliances 

The Expert Panel recommends that clinicians advise patients to avoid, if possible, 

exposure to gas stoves and appliances that are not vented to the outside, fumes from 

wood-burning appliances or fireplaces, sprays, or strong odors (Evidence C).
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Use of unvented gas stoves and appliances results in increased indoor levels of NO2. Use of 

gas stoves for cooking has been associated with increased respiratory symptoms, including 

wheezing in school children (Garrett et al. 1998; Withers et al. 1998) and increased prevalence 

of bronchial hyperresponsiveness in atopic adults (Kerkhof et al. 1999). However, data from the 

National Health and Nutrition Examination Survey III (NHANES III) did not suggest any impact 

of gas-stove use on pulmonary function or respiratory symptoms in adults who have asthma 

(Eisner and Blanc 2003). Infants at high risk for asthma who were exposed to higher levels of 

NO2—but levels which currently are not considered to be harmful—had increased days of 

wheezing and shortness of breath (van Strien et al. 2004). In school-aged children, increased 

levels of NO2 were associated with increased bronchitis, wheeze, and asthma in girls but not 

boys (Shima and Adachi 2000). When unflued gas heaters in schools were replaced, 

NO2 levels decreased by two-thirds, accompanied by significant reduction in both daytime and 

nighttime asthma symptoms (Pilotto et al. 2004). Exposure to gas heaters and appliances in 

infancy has been found to be a risk for wheezing, asthma, and bronchial hyperresponsiveness 

as well as sensitization to house-dust mites in school-aged children (Phoa et al. 2004; 

Ponsonby et al. 2000, 2001). Current use of gas appliances also was found to be a risk for 

decreased FEV1 in children sensitized to house-dust mites (Glasgow et al. 2001). Fumes from 

wood-burning appliances or fireplaces can precipitate symptoms in persons who have asthma 

(Ostro et al. 1994). Sprays and strong odors, particularly perfumes, can also irritate the lungs 

and precipitate asthma symptoms. 

Comorbid Conditions 

The Expert Panel recommends that clinicians evaluate a patient for presence of a chronic 

comorbid condition when the patient’s asthma cannot be well controlled. Treating the 

following conditions may improve asthma management: ABPA (Evidence A), 

gastroesophageal reflux (Evidence B), obesity (Evidence B, limited studies), OSA 

(Evidence D), rhinitis/sinusitis (Evidence B), chronic stress/depression (Evidence D). 

Several chronic comorbid conditions have been demonstrated to impede asthma management. 

Evidence suggests that if the conditions are treated appropriately, asthma control can improve, 

although clearly some conditions are more readily addressed than others. Clinical judgment is 

needed to weigh the level of asthma control and patient circumstances to determine the 

appropriate approach. 

ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS 

The Expert Panel recommends that ABPA should be suspected in patients who have 

asthma and have the presence or a history of pulmonary infiltrates. It should also be 

specifically considered in patients who have evidence of IgE sensitization to Aspergillus 

(positive prick skin test or in vitro tests) and in corticosteroid-dependent patients who 

have asthma (Evidence A). ABPA complicates both asthma and cystic fibrosis (Greenberger 

2002). The fungus grows saphrophytically in bronchial mucus in the bronchi. Although there is 

no tissue invasion, a surrounding, predominantly eosinophilic inflammation occurs and often 

leads to damage to the bronchial wall and development of the typical proximal bronchiectasis, 

which may be varicose (beaded), cylindrical, or saccular (cystic). The classic clinical 

presentation includes transient migratory lung shadows on chest x ray or computer tomography 

(CT), peripheral blood eosinophilia, pyrexia, and sputum containing brown plugs or flecks. 

Occasionally, the same presentation is produced by another organism, usually another fungus. 

Clear diagnostic criteria for ABPA are lacking; minimum criteria for the diagnosis of ABPA 

complicating asthma include (Greenberger 2002): 
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 Positive immediate skin test to Aspergillus

 Total serum IgE >417 IU (1,000 ng/mL) 

 Elevated serum IgE and/or immunoglobulin G (IgG) to Aspergillus

 Central bronchiectasis (inner two-thirds of the chest CT fields) 

An earlier form of the disease, before it has progressed to produce central bronchiectasis, can 

be diagnosed based on the first three criteria above in patients who have asthma. Additional 

supporting findings for a diagnosis of ABPA include a history of pulmonary infiltrates, serum 

precipitating antibodies to Aspergillus, peripheral blood eosinophilia, and production of mucus 

plugs containing Aspergillus.

The standard treatment for ABPA is prednisone, initially 0.5 mg per kilogram, with gradual 

tapering monitored by repeat chest x rays and measurement of total serum IgE concentrations 

(Greenberger 2002). Azole antifungal agents have also been tried as adjunctive treatment in 

patients who are stable and who have ABPA (Wark et al. 2003). Itraconazole administered 

orally for 16 weeks reduced sputum eosinophilia, serum IgE and IgG levels, and the number of 

exacerbations requiring oral corticosteroids (Stevens et al. 2000). 

GASTROESOPHAGEAL REFLUX DISEASE 

The Expert Panel recommends that medical management of GERD be instituted for 

patients who have asthma and complain of frequent heartburn or pyrosis, particularly 

those who have frequent episodes of nocturnal asthma (Evidence B).

For patients who have poorly controlled asthma, particularly with a nocturnal component, 

investigation for GERD may be warranted even in the absence of suggestive symptoms (Irwin et 

al. 1989; Kiljander et al. 1999). 

Medical management of GERD includes: 

 Avoiding heavy meals, fried food, caffeine, and alcohol. 

 Avoiding food and drink within 3 hours of retiring (Nelson 1984). 

 Elevating the head of the bed on 6- to 8-inch blocks (Nelson 1984). 

 Using appropriate pharmacologic therapy (Harding 1999). 

For patients who have persistent reflux symptoms following optimal therapy, further evaluation 

is indicated. 

The symptoms of GERD are common in both children and adults who have asthma (Harding 

1999). Reflux during sleep can contribute to nocturnal asthma (Avidan et al. 2001; Cibella and 

Cuttitta 2001; Davis et al. 1983; Martin et al. 1982). Although a systematic review concluded 

that there was no overall improvement in asthma following medical treatment for GERD (Gibson 

et al. 2003), treatment with a proton pump inhibitor was reported to reduce nocturnal symptoms 

(Kiljander et al. 1999), reduce asthma exacerbations, and improve quality of life related to 

asthma (Littner et al. 2005). Surgical treatment has been reported to reduce the symptoms of 

asthma and the requirement for medication (Field et al. 1999; Perrin-Fayolle et al. 1989; Sontag 

et al. 2003). 
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OBESITY 

The Expert Panel recommends that clinicians consider advising asthma patients who are 

overweight or obese that weight loss, in addition to improving overall health, might also 

improve their asthma control (Evidence B, limited studies).

Obesity has been associated with asthma persistence and severity in both children and adults 

(Camargo et al. 1999; Schaub and von Mutius 2005; Shore and Fredberg 2005; Weiss 2005; 

Weiss and Shore 2004). Although obesity itself causes alterations in pulmonary physiology that 

can lead to dyspnea, studies have documented specific increases in asthma among overweight 

and obese persons. 

Increased risk from obesity appears to be greatest in postpubertal women and is associated 

with more severe symptoms, enhanced airway inflammation, and new-onset or persistent 

disease (Camargo et al. 1999; Guerra et al. 2004). Presently, the relationship of obesity to 

allergy is controversial. 

The effects of obesity on asthma appear to be independent of diet and physical activity, 

although these three factors are clearly interrelated. Many epidemiologic studies have 

controlled for potential effects of diet and physical activity when examining the relationship of 

obesity to asthma onset (Camargo et al. 1999). 

The few RCTs that have been done are small, but they show that weight loss in adults resulted 

in improvement in pulmonary mechanics, improved FEV1, reductions in exacerbations and 

courses of oral corticosteroids, and improved quality of life (Stenius-Aarniala et al. 2000). 

Weight loss following gastric bypass surgery improved self-reported asthma severity (Simard et 

al. 2004). 

OBSTRUCTIVE SLEEP APNEA 

The Expert Panel recommends that clinicians consider evaluating patients who have 

unstable, not-well-controlled asthma, particularly those who are overweight or obese, to 

ascertain whether they have symptoms that suggest OSA (Evidence D).

OSA and nocturnal asthma are distinct entities that fall within the broad classification of 

sleep-disordered breathing. Patients who have OSA and nocturnal asthma may have similar 

clinical presentations. Both conditions may involve repetitive sleep arousals associated with 

changes in oronasal airflow, ventilatory effort, and decreases in oxygen saturation (SaO2) during 

sleep. Consequently, each of these disorders may be mistaken for the other in some patients. 

Moreover, asthma and OSA may coexist in a significant number of patients. Congestion of the 

nasopharynx, with resultant mouth breathing, may heighten the expression of both conditions. 

OSA-induced hypoxemia may predispose to increased bronchial reactivity, and vagal tone is 

increased during obstructive apneas (Denjean et al. 1988; Tilkian et al. 1978). On the other 

hand, sleep disruption secondary to nocturnal asthma could cause periodic breathing and 

decreased upper airway muscle activity, contributing to upper airway obstruction during sleep. 

A high prevalence of OSA has been reported in patients who have unstable asthma (Yigla et al. 

2003). 

Patients who have unstable asthma and sleep apnea demonstrated improvement when treated 

with nasal continuous positive airway pressure (CPAP). Morning and evening PEF before and 

after SABA significantly improved (Chan et al. 1988). However, nocturnal nasal CPAP in 
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individuals who have asthma and who do not have apnea is associated with disrupted sleep 

architecture (Martin and Pak 1991). Thus, confirmation of diagnosis is important. 

RHINITIS/SINUSITIS 

The Expert Panel recommends that clinicians evaluate patients who have asthma 

regarding the presence of rhinitis/sinusitis diagnosis or symptoms (Evidence B). It is 

important for clinicians to appreciate the connection between upper and lower airway 

conditions and the part the connection plays in asthma management. 

There is considerable evidence for the interrelationship of the upper and lower airway and the 

concept of the airway as a continuum. Varied epidemiologic studies support a substantial 

association between allergic rhinitis and asthma (Guerra et al. 2002; Leynaert et al. 1999; 

Linneberg et al. 2002). Those persons who treat asthma need to concern themselves with the 

best therapy for the upper airway to optimize overall therapy for their patients. 

In addition to the general similarity of normal nasal and bronchial mucosa, these mucosa may 

show similar changes when inflamed, including erosion of the epithelium, thickening of the 

basement membrane, and cellular infiltrate that is often eosinophilic (Ponikau et al. 2003). In 

patients who have allergic rhinitis, nasal allergen challenge has been shown to induce adhesion 

molecule expression and inflammatory mediators in bronchial mucosa and sputum (Beeh et al. 

2003; Braunstahl et al. 2001). Segmental bronchial allergen challenge causes inflammatory 

changes in both nasal and bronchial mucosa (Braunstahl et al. 2000, 2001). 

Treatment of allergic rhinitis and asthma with intranasal corticosteroids has decreased exhaled 

NO and H2O2, markers of lower airway inflammation (Sandrini et al. 2003). Review of the 

literature on antihistamine therapy in the treatment of asthma reveals positive results (Nelson 

2003). Both intranasal steroids and second-generation antihistamines with or without 

decongestants have been reported to decrease ED visits for asthma (Adams et al. 2002; Corren 

et al. 2004; Crystal-Peters et al. 2002). However, the validity of the statistical approach used to 

arrive at this conclusion, in at least one of these articles, has been questioned (Suissa and Ernst 

2005). Immunotherapy may also be considered for the treatment of allergic rhinitis (See 

previous section “Immunotherapy.”) 

A similar manifestation of “the airway as a continuum” exists in patients who have sinusitis and 

asthma. A direct relationship can be seen between severity of CT of sinus, markers of lower 

airway inflammation including eosinophils in peripheral blood and sputum, level of exhaled NO, 

as well as decreases in pulmonary function (ten Brinke et al. 2002). In children who have 

asthma and are treated with intranasal corticosteroids and antibiotics for rhinosinusitis, 

improvement in respiratory symptoms has been shown to be accompanied by decreases in 

inflammatory cells and mediators in the nose (Tosca et al. 2003). Studies of sinus surgery in 

patients who have chronic rhinosinusitis and asthma have shown mixed results (Dunlop et al. 

1999; Uri et al. 2002). 

STRESS, DEPRESSION, AND PSYCHOSOCIAL FACTORS IN ASTHMA 

The Expert Panel recommends that clinicians consider inquiring about the potential role 

of chronic stress or depression in complicating asthma management for patients whose 

asthma is not well controlled (Evidence C); additional patient education may be helpful 

(Evidence D). Clinical trials are needed to evaluate the effect of stress and stress reduction on 

asthma control, but observational studies demonstrate an association between increased stress 
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and worsening asthma. See ”Component 2: Education for a Partnership in Asthma Care” for 

strategies to help improve patients’ coping skills and support for asthma management. 

The role of stress and psychological factors in asthma is important but not fully defined. 

Emerging evidence indicates that stress can play an important role in precipitating 

exacerbations of asthma and possibly act as a risk factor for an increase in prevalence of 

asthma (Busse et al. 1995; Sandberg et al. 2004; Wright et al. 2002). Chronic stressors 

increase the risk of asthma exacerbations, especially in children who have severely negative life 

events and those who have brittle asthma (Miles et al. 1997; Sandberg et al. 2000). 

The mechanisms involved in this process have yet to be fully established and may involve 

enhanced generation of pro-inflammatory cytokines (Friedman et al. 1994). In a prospective 

study of a birth cohort predisposed to atopy, higher caregiver stress in the first 6 months after 

birth was significantly associated with an increased atopic immune profile in the children (high 

total IgE level, increased production of tumor necrosis factor-alpha (TNF-α) and a suggested 

trend between higher stress and reduced interferon-gamma (IFN-γ production) (Wright et al. 

2004a). Equally important are psychosocial factors that are associated with poor outcome (e.g., 

conflict between patients and family and the medical staff, inappropriate asthma self-care, 

depressive symptoms, behavioral problems, emotional problems, and disregard of perceived 

asthma symptoms) (Brush and Mathé 1993; Strunk et al. 1985; Strunk 1993). Asthma severity 

can be affected by personal or parental factors, and both should be evaluated in cases of poorly 

controlled asthma. For example, maternal depression is common among inner-city mothers of 

children who have asthma and has been associated with increased ED visits and poor 

adherence to therapy by these children (Bartlett et al. 2001, 2004). Furthermore, in a large 

prospective study of inner-city children who had asthma, increased exposure to violence, as 

reported by caretakers, predicted a higher number of symptom days in their children, with 

caregivers’ perceived stress mediating some, although not all, of this effect (Wright et al. 

2004b). It may also be important to evaluate psychosocial and socioenvironmental factors in 

children who have repeated hospitalizations; however, it is not clear whether psychosocial 

factors affect or result from the frequent hospitalizations (Chen et al. 2003). 

Other Factors 

MEDICATION SENSITIVITIES 

Aspirin 

The Expert Panel recommends that clinicians query adult patients who have asthma 

regarding precipitation of bronchoconstriction by aspirin and other NSAIDs (Evidence C). 

If patients have experienced a reaction to any of these drugs, they should be informed of 

the potential for all of these drugs to precipitate severe and even fatal exacerbations. 

Adult patients who have severe persistent asthma or nasal polyps should be counseled 

regarding the risk of using these drugs (Evidence C). Alternatives to aspirin that usually do 

not cause acute bronchoconstriction in aspirin-sensitive patients include acetaminophen 

(7 percent cross-sensitivity) (Jenkins et al. 2004), salsalate (Settipane et al. 1995; Szczeklik et 

al. 1977), or the COX-2 inhibitor celecoxib (Gyllfors et al. 2003). Aspirin desensitization 

treatment, followed by daily aspirin, is a potential option to decrease disease activity and reduce 

corticosteroid requirements (Berges-Gimeno et al. 2003a,b). 

As many as 21 percent of adults and 5 percent of children who have asthma have 

aspirin-induced asthma, especially when identified through oral provocation testing rather than 
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verbal history (Jenkins et al. 2004). In one study, 39 percent of adults who had asthma and 

were admitted to an asthma-referral hospital were reported to experience severe and even fatal 

exacerbations of asthma after taking aspirin or certain other NSAIDs (Spector et al. 1979). The 

prevalence of aspirin sensitivity increases with increasing age and severity of asthma (Chafee 

and Settipane 1974; Spector et al. 1979). 

Beta-Blockers 

The Expert Panel recommends that clinicians advise asthma patients to avoid 

nonselective beta-blockers, including those in ophthalmological preparations 

(Evidence B). Nonselective beta-blockers can cause asthma symptoms (Odeh et al. 1991; 

Schoene et al. 1984), although cardioselective beta-blockers, such as betaxolol, may be 

tolerated (Dunn et al. 1986). A recent systematic review, primarily of single dose or short-term 

studies in younger subjects, indicates that patients who have mild to moderate airway 

obstruction can tolerate cardioselective beta-blockers; therefore, if needed for managing 

cardiovascular disorders, these agents may be administered after careful evaluation (Salpeter et 

al. 2002). 

SULFITE SENSITIVITY 

The Expert Panel recommends that clinicians advise patients who have asthma 

symptoms associated with eating processed potatoes, shrimp, or dried fruit or with 

drinking beer or wine to avoid these products (Evidence C). These products contain 

sulfites, which are used to preserve foods and beverages. Sulfites have caused severe asthma 

exacerbations, particularly in patients who have severe persistent asthma (Taylor et al. 1988). 

INFECTIONS 

Viral Respiratory Infections 

It is well established that viral respiratory infections can exacerbate asthma, particularly in 

children under age 10 who have asthma (Busse et al. 1993). Respiratory syncytial virus (RSV), 

rhinovirus, and influenza virus have been implicated (Busse et al. 1993), with rhinovirus being 

implicated in the majority of the exacerbations of asthma in children (Johnston et al. 1995). The 

role of infections causing exacerbations of asthma also appears to be important in adults 

(Nicholson et al. 1993). Rhinovirus, considered to be mainly an upper airway pathogen, has 

recently been demonstrated in the lower airways in patients who have asthma (Mosser et al. 

2005). Rhinovirus infections in patients who have asthma may induce exacerbations due to 

abnormalities in epithelial cells’ innate immune responses to infection (Wark et al. 2005). 

Viral infections are the most frequent precipitants of wheezing during infancy and asthma 

exacerbations during childhood. Many infants and toddlers who wheeze with viral infections are 

predisposed to have bronchial obstruction during these illnesses because of very small airway 

size (Martinez et al. 1995), and they will not have further exacerbations during later childhood. 

However, chronic asthma also may start as early as the first year of life among infants who have 

a family history of asthma, persistent rhinorrhea, atopic dermatitis, or high IgE levels. Early 

identification of these infants would allow institution of environmental controls to reduce 

exposure to tobacco smoke, animal dander, and house-dust mites and, thus, potentially reduce 

symptoms. RSV infections severe enough to require hospitalization during infancy and early 

childhood may be a risk factor for subsequent chronic asthma (Sigurs et al. 2005). 
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Bacterial Infections 

Recent studies in both children and adults suggest that infections with both Mycoplasma and 

Chlamydia, in addition to viral infections, may contribute to exacerbation rates and disease 

chronicity and severity (Cunningham et al. 1998; Esposito et al. 2000; Kraft et al. 2002). 

Studies to confirm and expand upon these initial observations have been impeded due to the 

lack of definitive serologic markers to document current or past infection, as well as the inherent 

difficulties in obtaining biologic specimens from the lower airway to confirm the presence of 

these infectious agents (Martin et al. 2001). 

Influenza Infection 

The Expert Panel recommends that clinicians consider inactivated influenza vaccination 

for patients who have asthma. It is safe to administer in children over 6 months and 

adults who have asthma (Evidence A), and the Advisory Committee on Immunization 

Practices of the CDC recommends the vaccine for persons who have asthma because 

they may be at increased risk for complications from influenza. However, the vaccine 

should not be given with the expectation that it will reduce either the frequency or 

severity of asthma exacerbations during the influenza season (Evidence B).

Recent evaluations in both children and adults have yielded inconsistent and unconvincing 

results regarding the ability of influenza vaccination to reduce either overall rates of asthma 

exacerbations or exacerbations specifically related to influenza infection during the influenza 

season (Abadoglu et al. 2004; Bueving et al. 2004; Cates et al. 2004; Kramarz et al. 2001). The 

Advisory Committee on Immunization Practices recommends inactivated influenza vaccine for 

persons who have chronic disorders of the pulmonary systems, including asthma, because they 

are considered to be at increased risk for complications from influenza, such as hospitalizations 

and increased requirements for antibiotics (CDC 2006). 

Administration of partially inactivated influenza vaccine is safe in both adults and children who 

have asthma (American Lung Association Asthma Clinical Research Centers 2001). 

Vaccination with cold-adapted, live, attenuated influenza vaccine has also been demonstrated 

to be safe in school-aged, adolescent, and adult patients who have asthma (Belshe et al. 2004). 

However, the observation of an increased risk of asthma/reactive airway disease in children 

<36 months of age is of potential concern (Bergen et al. 2004). In patients who have 

documented histories of anaphylactic reactions after ingestion of egg protein and documented 

evidence of current allergic sensitization to eggs (skin testing or in vitro antigen-specific IgE 

antibody testing), the risk/benefit ratio of administration of influenza vaccine should be reviewed 

carefully. If the decision is made to administer the live, attenuated vaccine, a subspecialist 

familiar with appropriate challenge testing and published safe administration protocols should be 

consulted prior to administration (Zeiger 2002). 

FEMALE HORMONES AND ASTHMA 

In the opinion of the Expert Panel, no recommendation can be made at this time 

regarding female hormones and asthma.

There is considerable interest in the effects of female hormones on asthma severity. Studies 

are not totally concordant in their findings, but most evidence suggests that some women have 

worsening of their asthma during the premenstrual and menstrual times of the cycle (Haggerty 

et al. 2003; Shames et al. 1998). Two ED studies, however, suggest that many women 
Section 3, Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma

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experience asthma exacerbations during the preovulatory phase (Brenner et al. 2005; 

Zimmerman et al. 2000). Studies on hormone replacement therapy (HRT) after menopause 

also demonstrate apparent discordance. A cross-sectional study reported better pulmonary 

function and less frequent asthma exacerbations (Kos-Kudla et al. 2001), whereas a 

prospective cohort study found higher risk of adult-onset asthma (Barr et al. 2004). 

Although associations between female hormones and asthma severity are not uniform or clear, 

it may be useful for clinicians, as they develop action plans with their patients, to appreciate the 

role that female hormone levels may have in the course of asthma. 

DIET 

In the opinion of the Expert Panel, there is insufficient evidence to make specific 

recommendations with regard to dietary constituents that should be consumed or 

avoided to affect asthma.

Patients have great interest in whether dietary factors may influence the onset, persistence, or 

severity of asthma. Although people who have asthma frequently experience 

bronchoconstriction as part of an acute IgE-mediated reaction to a food, food allergy is rarely 

the main aggravating factor in chronic asthma in children and even more rarely in adults 

(Sampson 2003). 

Preliminary evidence suggests that antioxidant vitamins (Currie et al. 2005; Devereux et al. 

2002; Kaur et al. 2001; Martindale et al. 2005; McKeever et al. 2004; Pearson et al. 2004; 

Shaheen et al. 2001) and omega-3 fatty acids (Broadfield et al. 2004; Dunstan et al. 2003; 

Kompauer et al. 2004; Mihrshahi et al. 2003, 2004; Peat et al. 2004; Woods et al. 2004) reduce 

asthma development and symptom severity, but no conclusive evidence shows that any dietary 

factors prevent or exacerbate the disease. 

Physicians and patients are encouraged to promote a varied diet consistent with the Dietary 

Guidelines for Americans (DHHS and USDA 2005). In brief, most Americans need to consume 

diets with more fruits, vegetables, and whole grains, and eat less solid fats (saturated fat, trans

fat), salt, and added sugars. 

Primary Prevention of Allergic Sensitization and Asthma 

In the opinion of the Expert Panel, there is insufficient evidence to recommend any 

specific strategies to prevent the development of asthma.

Primary prevention of asthma—preventing initial development—is an active area of 

investigation. Although a number of trials have investigated dietary and environmental 

manipulations as preventive measures for asthma and allergy, clinical trials have not been 

uniform in their approaches, making firm conclusions difficult. Also, most of these interventions 

have been evaluated over a relatively short period of time, thus limiting their weight for any 

long-term implications. 

Evaluations of dust-mite mitigation in homes of children of atopic parents show effectiveness of 

interventions in decreasing dust-mite levels as well as decreased incidence of wheezing 

(Custovic et al. 2001; Tsitoura et al. 2002). Prospective assessment of dust-mite reduction and 

cow’s milk avoidance (breastfeeding or hydrolysate) appears to show protective effects at 
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8-year followup (Arshad et al. 2003), while breastfeeding, dust-mite and pet avoidance, and 

tobacco smoke avoidance were protective at 7-year followup (Chan-Yeung et al. 2005). 

Trials evaluating breastfeeding have generally shown protective benefit (Chandra 1997; 

Gdalevich et al. 2001; Oddy et al. 1999), although there are conflicting studies (Sears et al. 

2003; Wright et al. 2001). Pet exposure as preventive or provocative is controversial (Celedon 

et al. 2002; Ownby et al. 2002). Although interesting data support the development of tolerance 

rather than clinical disease after exposure to cat (Platts-Mills et al. 2001), there is also contrary 

information (Brussee et al. 2005). 

Dietary modification or supplementation with antioxidants or omega-3 polyunsaturated fatty 

acids to reduce the likelihood of asthma and allergic diseases requires further research 

(Devereux and Seaton 2005). Preliminary studies with probiotics show promise (Kalliomaki et 

al. 2001; Rautava et al. 2005) but require further study. 

Several recent studies have suggested that acetaminophen may contribute to the pathogenesis 

of asthma and asthma-related symptoms. The effect has been observed in both children and 

adults in population-based, birth-cohort, and case-control studies. A comprehensive review of 

this topic has been published (Eneli et al. 2005). However, one potential limitation of many 

studies on intake of commonly available over-the-counter analgesics, such as acetaminophen, 

is the potential for confounding by indication (Signorello et al. 2002). In summary, preliminary 

evidence appears to indicate a possible association between acetaminophen intake and 

wheeze, but the data are limited and potentially confounded. Although choice of 

analgesic/antipyretic should always be made carefully, at the current time, it would be 

premature to recommend avoidance of acetaminophen. 

Exposure to daycare in early childhood may be beneficial, while tobacco smoke exposure both 

in utero and in early childhood is a risk factor for asthma (Becker et al. 2004; Gergen et al. 

1998; Gilliland et al. 2001). Larger family size may be preventive, with the incidence of asthma 

decreasing with an increasing number of siblings (Bodner et al. 1998; Mattes et al. 1999; Rona 

et al. 1997). The weight of evidence regarding larger family size, daycare exposure with more 

likelihood of respiratory infection, and country living is in keeping with the hygiene hypothesis of 

the origin of atopy and asthma. This hypothesis purports that more developed societies are 

more prone to higher incidence of allergy and asthma because their cleanliness downregulates 

immune processes for fighting infection in favor of those that cause atopic disease. Rural 

lifestyle may be protective compared to urban living (Bibi et al. 2002; Kauffmann et al. 2002). 
Section 3, Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma

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FIGURE 3–17. ASSESSMENT QUES TIONS* FOR ENVIRONMENTAL 

AND OTHER FACTORS THAT CAN MAKE ASTHMA WORSE 

Inhalant Allergens 

Does the patient have symptoms year round? (If yes, 

ask the following questions. If no, see next set of 

questions.) 

 Does the patient keep pets indoors? What type? 

 Does the patient have moisture or dampness in any 

room of his or her home (e.g., basement)? 

(Suggests house-dust mites, molds.) 

 Does the patient have mold visible in any part of his 

or her home? (Suggests molds.) 

 Has the patient seen cockroaches or rodents in his 

or her home in the past month? (Suggests 

significant cockroach exposure.) 

 Assume exposure to house-dust mites unless 

patient lives in a semiarid region. However, if a 

patient living in a semiarid region uses a swamp 

cooler, exposure to house-dust mites must still be 

assumed. 

Do symptoms get worse at certain times of the year? 

(If yes, ask when symptoms occur.) 

 Early spring? (trees) 

 Late spring? (grasses) 

 Late summer to autumn? (weeds) 

 Summer and fall? (Alternaria, Cladosporium, mites) 

 Cold months in temperate climates? (animal dander) 

Tobacco Smoke 

 Does the patient smoke? 

 Does anyone smoke at home or work? 

 Does anyone smoke at the child’s daycare? 

Indoor/Outdoor Pollutants and Irritants 

 Is a wood-burning stove or fireplace used in the 

patient’s home? 

 Are there unvented stoves or heaters in the patient’s 

home? 

 Does the patient have contact with other smells or 

fumes from perfumes, cleaning agents, or sprays? 

 Have there been recent renovations or painting in 

the home? 

Workplace Exposures 

 Does the patient cough or wheeze during the week, 

but not on weekends when away from work? 

 Do the patient’s eyes and nasal passages get 

irritated soon after arriving at work? 

 Do coworkers have similar symptoms? 

 What substances are used in the patient’s worksite? 

(Assess for sensitizers.) 

Rhinitis 

 Does the patient have constant or seasonal nasal 

congestion, runny nose, and/or postnasal drip? 

Gastroesophageal Reflux Disease (GERD) 

 Does the patient have heartburn? 

 Does food sometimes come up into the patient’s 

throat? 

 Has the patient had coughing, wheezing, or 

shortness of breath at night in the past 4 weeks? 

 Does the infant vomit, followed by cough, or have 

wheezy cough at night? Are symptoms worse after 

feeding? 

Sulfite Sensitivity 

 Does the patient have wheezing, coughing, or 

shortness of breath after eating shrimp, dried fruit, or 

processed potatoes or after drinking beer or wine? 

Medication Sensitivities and Contraindications 

 What medications does the patient use now 

(prescription and nonprescription)? 

 Does the patient use eyedrops? What type? 

 Does the patient use any medications that contain 

beta-blockers? 

 Does the patient ever take aspirin or other 

nonsteroidal anti-inflammatory drugs? 

 Has the patient ever had symptoms of asthma after 

taking any of these medications? 

* These questions are examples and do not represent a standardized assessment or diagnostic instrument. The validity and 

reliability of these questions have not been assessed. 
Section 3, Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma 

187 

August 28, 2007 

FIGURE 3–18. COMPARISON OF SKIN TESTS WITH IN VITRO 

TESTS 

Advantages of Skin Tests 

 Less expensive than in vitro tests. 

 Results are available within 1 hour. 

 Equally sensitive as in vitro tests. 

 Results are visible to the patient. This may 

encourage compliance with environmental control 

measures. 

Advantages of RAST and Other In Vitro Tests 

 Do not require knowledge of skin testing technique. 

 Do not require availability of allergen extracts. 

 Can be performed on patients who are taking 

medications that suppress the immediate skin test 

(antihistamines, antidepressants). 

 No risk of systemic reactions. 

 Can be done for patients who have extensive 

eczema. 

FIGURE 3–19. PATIENT INTERVIE W QUESTIONS* FOR ASSESSING 

THE CLINICAL SIGNIFICANCE OF POSITIVE ALLERGY TESTS 

 Animal dander. If pets are in the patient’s home and the patient is sensitive to dander of that species of animal, 

the likelihood that animal dander allergy is contributing to asthma symptoms is increased if answers to the 

following questions are affirmative. However, absence of positive responses does not exclude a contribution of 

animal dander to the patient’s symptoms. 

— Do nasal, eye, or chest symptoms appear when the patient is in a room where carpets are being or have just 

been vacuumed? 

— Do nasal or chest symptoms improve when the patient is away from home for a week or longer? 

— Do the patient’s symptoms become worse during the first 24 hours after returning home? 

 House-dust mites. Mite allergy is more likely to be a contributing factor to asthma severity if answers to the 

following questions are affirmative. However, absence of a positive response does not exclude a contribution of 

mite allergen to the patient’s symptoms. 

— Do nasal, eye, or chest symptoms appear when the patient is in a room where carpets are being or have just 

been vacuumed? 

— Does making a bed cause nasal or chest symptoms in the patient? 

— Does the patient sneeze repeatedly in the morning? 

 Indoor fungi (molds). Contribution of indoor molds in causing asthma symptoms is suggested by a positive 

answer to this question: 

— Do nasal, eye, or chest symptoms appear when the patient is in damp or moldy rooms, such as basements? 

 Outdoor allergens (pollens and outdoor molds). Contribution of pollens and outdoor molds in causing 

asthma symptoms is suggested by a positive answer to this question: 

— Is asthma worse in a specific season or at a time when the patient has hay fever symptoms in spring, 

summer, fall, or parts of the growing season? 

— Usually, if pollen or mold spores are causing increased asthma symptoms, the patient will also have 

symptoms of allergic rhinitis—sneezing, itching nose and eyes, runny and obstructed nose. 

* These questions are provided as examples for the clinician. The validity and reliability of these questions have not been assessed.
Section 3, Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma

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FIGURE 3–20. SUMMARY OF MEASURES TO CONTROL 

ENVIRONMENTAL FACTORS THAT CAN MAKE ASTHMA WORSE 

Allergens 

Reduce or eliminate exposure to the allergen(s) the patient is sensitive to, including: 

 Animal dander: Remove animal from house or, at a minimum, keep animal out of the patient’s bedroom. 

 House-dust mites: 

— Recommended: Encase mattress in an allergen-impermeable cover; encase pillow in an 

allergen-impermeable cover or wash it weekly; wash sheets and blankets on the patient’s bed in hot water 

weekly (water temperature of >130 °F is necessary for killing mites): cooler water and detergent and bleach 

will still reduce live mites and allergen level. Prolonged exposure to dry heat or freezing can also kill mites 

but does not remove allergen. 

— Desirable: Reduce indoor humidity to or below 60 percent, ideally 30–50 percent; remove carpets from the 

bedroom; avoid sleeping or lying on upholstered furniture; remove carpets that are laid on concrete. 

 Cockroaches: Use poison bait or traps to control insects, but intensive cleaning is necessary to reduce 

reservoirs. Do not leave food or garbage exposed. 

 Pollens (from trees, grass, or weeds) and outdoor molds: If possible, adults who have allergies should stay 

indoors, with windows closed, during periods of peak pollen exposure, which are usually during the midday and 

afternoon. 

 Indoor mold: Fix all leaks and eliminate water sources associated with mold growth; clean moldy surfaces. 

Consider reducing indoor humidity to or below 60 percent, ideally 30–50 percent. Dehumidify basements if 

possible. 

 It is recommended that allergen immunotherapy be considered for patients who have asthma if evidence is clear 

of a relationship between symptoms and exposure to an allergen to which the patient is sensitive. 

Tobacco Smoke 

Advise patients and others in the home who smoke to stop smoking or to smoke outside the home. Discuss ways to 

reduce exposure to other sources of tobacco smoke, such as from daycare providers and the workplace. 

Indoor/Outdoor Pollutants and Irritants 

Discuss ways to reduce exposures to the following: 

 Wood-burning stoves or fireplaces 

 Unvented gas stoves or heaters 

 Other irritants (e.g., perfumes, cleaning agents, sprays) 

 Volatile organic compounds (VOCs) such as new carpeting, particle board, painting 
Section 3, Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma 

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August 28, 2007 

FIGURE 3–21. EVALUATION AND MANAGEMENT OF WORKAGGRAVATED ASTHMA AND OCCUPATIONAL ASTHMA 

Evaluation 

Potential for workplace-related symptoms: 

 Recognized sensitizers (e.g., isocyanates, plant or animal products). 

 Irritants* or physical stimuli (e.g., cold/heat, dust, humidity). 

 Coworkers may have similar symptoms. 

Patterns of symptoms (in relation to work exposures): 

 Improvement occurs during vacations or days off (may take a week or more). 

 Symptoms may be immediate (<1 hour), delayed (most commonly, 2–8 hours after exposure), or nocturnal. 

 Initial symptoms may occur after high-level exposure (e.g., spill). 

Documentation of work-relatedness of airflow limitation: 

 Serial charting for 2–3 weeks (2 weeks at work and up to 1 week off work, as needed to identify or exclude 

work-related changes in PEF): 

— Record when symptoms and exposures occur. 

— Record when a bronchodilator is used. 

— Measure and record peak flow (or FEV1) every 2 hours while awake. 

 Immunologic tests. 

 Referral for further confirmatory evaluation (e.g., bronchial challenges). 

Management 

Work-aggravated asthma: 

 Work with onsite health care providers or managers/supervisors. 

 Discuss avoidance, ventilation, respiratory protection, tobacco smoke-free environment. 

Occupationally induced asthma: 

 Recommend complete cessation of exposure to initiating agent. 

*Material Safety Data Sheets may be helpful for identifying respiratory irritants, but many sensitizers are not listed. 

Key: FEV1, forced expiratory volume in 1 second; PEF, peak expiratory flow 
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SECTION 3, COMPONENT 4: MEDICATIONS 

KEY POINTS: MEDICATIONS 

Medications for asthma are categorized into two general classes: long-term control medications 

used to achieve and maintain control of persistent asthma and quick-relief medications used to 

treat acute symptoms and exacerbations. 

Long-term control medications (listed in alphabetical order)

 Corticosteroids: Block late-phase reaction to allergen, reduce airway 

hyperresponsiveness, and inhibit inflammatory cell migration and activation. They are the 

most potent and effective anti-inflammatory medication currently available (Evidence A). 

ICSs are used in the long-term control of asthma. Short courses of oral systemic 

corticosteroids are often used to gain prompt control of the disease when initiating long-term 

therapy; long-term oral systemic corticosteroid is used for severe persistent asthma. 

 Cromolyn sodium and nedocromil: Stabilize mast cells and interfere with chloride 

channel function. They are used as alternative, but not preferred, medication for the 

treatment of mild persistent asthma (Evidence A). They can also be used as preventive 

treatment prior to exercise or unavoidable exposure to known allergens. 

 Immunomodulators: Omalizumab (anti-IgE) is a monoclonal antibody that prevents 

binding of IgE to the high-affinity receptors on basophils and mast cells. Omalizumab is 

used as adjunctive therapy for patients ≥12 years of age who have allergies and severe 

persistent asthma (Evidence B). Clinicians who administer omalizumab should be prepared 

and equipped to identify and treat anaphylaxis that may occur (see discussion in text). 

 Leukotriene modifiers: Include LTRAs and a 5-lipoxygenase inhibitor. Two LTRAs are 

available—montelukast (for patients >1 year of age) and zafirlukast (for patients ≥7 years of 

age). The 5-lipoxygenase pathway inhibitor zileuton is available for patients ≥12 years of 

age; liver function monitoring is essential. LTRAs are alternative, but not preferred, therapy 

for the treatment of mild persistent asthma (Step 2 care) (Evidence A). LTRAs can also be 

used as adjunctive therapy with ICSs, but for youths ≥12 years of age and adults they are 

not the preferred adjunctive therapy compared to the addition of LABAs (Evidence A). 

Zileuton can be used as alternative but not preferred adjunctive therapy in adults (Evidence 

D). 

 LABAs: Salmeterol and formoterol are bronchodilators that have a duration of 

bronchodilation of at least 12 hours after a single dose. 

— LABAs are not to be used as monotherapy for long-term control of asthma (Evidence A). 

— LABAs are used in combination with ICSs for long-term control and prevention of 

symptoms in moderate or severe persistent asthma (step 3 care or higher in children 

≥5 years of age and adults) (Evidence A for ≥12 years of age, Evidence B for 5–11 years 

of age). 
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— Of the adjunctive therapies available, LABA is the preferred therapy to combine with ICS 

in youths ≥12 years of age and adults (Evidence A). 

— In the opinion of the Expert Panel, the beneficial effects of LABA in combination therapy 

for the great majority of patients who require more therapy than low-dose ICS alone to 

control asthma (i.e., require step 3 care or higher) should be weighed against the 

increased risk of severe exacerbations, although uncommon, associated with the daily 

use of LABAs (see discussion in text). 

♦ For patients ≥5 years of age who have moderate persistent asthma or asthma 

inadequately controlled on low-dose ICS, the option to increase the ICS dose should 

be given equal weight to the option of adding LABA. 

♦ For patients ≥5 years of age who have severe persistent asthma or asthma 

inadequately controlled on step 3 care, the combination of LABA and ICS is the 

preferred therapy. 

— LABA may be used before exercise to prevent EIB (Evidence A), but duration of action 

does not exceed 5 hours with chronic regular use. Frequent and chronic use of LABA 

for EIB is discouraged, because this use may disguise poorly controlled persistent 

asthma (Evidence D). 

— In the opinion of the Expert Panel, the use of LABA for the treatment of acute symptoms 

or exacerbations is not currently recommended (Evidence D). 

 Methylxanthines: Sustained-release theophylline is a mild to moderate bronchodilator 

used as alternative, not preferred, adjunctive therapy with ICS (Evidence A). Theophylline 

may have mild anti-inflammatory effects. Monitoring of serum theophylline concentration is 

essential. 

Quick-relief medications (listed in alphabetical order)

 Anticholinergics: Inhibit muscarinic cholinergic receptors and reduce intrinsic vagal tone of 

the airway. Ipratropium bromide provides additive benefit to SABA in moderate-to-severe 

asthma exacerbations. May be used as an alternative bronchodilator for patients who do 

not tolerate SABA (Evidence D). 

 SABAs: Albuterol, levalbuterol, and pirbuterol are bronchodilators that relax smooth 

muscle. Therapy of choice for relief of acute symptoms and prevention of EIB (Evidence A). 

 Systemic corticosteroids: Although not short acting, oral systemic corticosteroids are 

used for moderate and severe exacerbations as adjunct to SABAs to speed recovery and 

prevent recurrence of exacerbations (Evidence A). 
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 KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 Information about asthma medications has been updated based on review of evidence 

published since 1997. This updated report (EPR—3: Full Report 2007) continues to 

emphasize that the most effective medications for long-term therapy are those shown to 

have anti-inflammatory effects.

 New medications—immunomodulators—are available for long-term control of asthma. 

 New data on the safety of LABAs are discussed, and the position of LABA in therapy has 

been revised (see text). The most significant difference is that for youths ≥12 years of age 

and adults who have moderate persistent asthma or asthma inadequately controlled on 

low-dose ICS, the option of increasing the dose of medium-dose ICS should be given equal 

weight to the option of adding LABA to low-dose ICS. 

 The estimated clinical comparability of different ICS preparations has been updated. (See 

Section 4, “Managing Asthma Long-Term,” figures 4–4b and 4–8b.) The significant role of 

ICSs in asthma therapy continues to be supported. 

Introduction 

See Section 1, “Overall Methods Used To Develop This Report,” for the literature search 

strategies and tallies of results used to update each class of medication discussed in this 

section. Evidence Tables were prepared for: 11, Inhaled Corticosteroids: Combination 

Therapy; 12, Inhaled Corticosteroids: Dosing Strategies; 13, Immunomodulators: Anti-IgE; 

14, Leukotriene Receptor Antagonists: Monotherapy/Effectiveness Studies; 

15, Bronchodilators: Safety of Long-Acting Beta2-Agonists; 16, Bronchodilators: Levalbuterol. 

Pharmacologic therapy is used to prevent and control asthma symptoms, improve quality of life, 

reduce the frequency and severity of asthma exacerbations, and reverse airflow obstruction. 

Recommendations in this “Component 4: Medications,” reflect the scientific concepts that 

asthma is a chronic disorder with recurrent episodes of airflow limitation, mucus production, and 

cough and that the severity of the underlying asthma may vary over time. Asthma medications 

are categorized into two general classes: long-term control medications taken daily on a longterm basis to achieve and maintain control of persistent asthma (these medications are also 

known as long-term preventive, controller, or maintenance medications) and quick-relief 

medications taken to provide prompt reversal of acute airflow obstruction and relief of 

accompanying bronchoconstriction (these medications are also known as reliever or rescue 

medications). Patients who have persistent asthma require both classes of medication. 

Figures 3–22 and 3–23 present summaries of the indications, mechanisms, potential adverse 

effects, and therapeutic issues for currently available long-term control and quick-relief 

medications. The discussion in this component includes the following: an overview of asthma 

medications—both long-term control and quick-relief—and an overview of complementary 

alternative medicine strategies. 
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Overview of the Medications 

LONG-TERM CONTROL MEDICATIONS 

The Expert Panel recommends that long-term control medications be taken daily on a 

long-term basis to achieve and maintain control of persistent asthma. The most effective 

long-term-control medications are those that attenuate the underlying inflammation 

characteristic of asthma (Evidence A).

Long-term control medications include ICSs, inhaled long-acting bronchodilators, leukotriene 

modifiers, cromolyn, theophylline, and immunomodulators. Because eosinophilic and 

lymphocytic inflammation is a constant feature of the mucosa of the airways in asthma, the most 

effective long-term control medications are those that attenuate inflammation (Haahtela et al. 

1991; Kerrebijn et al. 1987; Van Essen-Zandvliet et al. 1992). The Expert Panel defines 

anti-inflammatory medications as those that cause a reduction in the markers of airway 

inflammation in airway tissue or airway secretions (e.g., eosinophils, mast cells, activated 

lymphocytes, macrophages, and cytokines; or ECP and tryptase; or extravascular leakage of 

albumin, fibrinogen, or other vascular protein) and thus decrease the intensity of airway 

hyperresponsiveness. Because many factors contribute to the inflammatory response in 

asthma, many drugs may be considered anti-inflammatory. It is not yet established, however, 

which anti-inflammatory actions are responsible for therapeutic effects, such as reduction in 

symptoms, improvement in expiratory flow, reduction in airway hyperresponsiveness, prevention 

of exacerbations, or prevention of airway wall remodeling. 

Inhaled Corticosteroids 

Mechanism 

The Expert Panel concludes that ICSs are the most potent and consistently effective 

long-term control medication for asthma (Evidence A). The broad action of ICSs on the 

inflammatory process may account for their efficacy as preventive therapy. Their clinical effects 

include reduction in severity of symptoms; improvement in asthma control and quality of life; 

improvement in PEF and spirometry; diminished airway hyperresponsiveness; prevention of 

exacerbations; reduction in systemic corticosteroid courses, ED care, hospitalizations, and 

deaths due to asthma; and possibly the attenuation of loss of lung function in adults (Barnes et 

al. 1993; Barnes and Pedersen 1993; Dahl et al. 1993; Fabbri et al. 1993; Gustafsson et al. 

1993; Haahtela et al. 1991; Jeffery et al. 1992; Kamada et al. 1996; Pauwels et al. 2003; 

Rafferty et al. 1985; Suissa et al. 2000; Van Essen-Zandvliet et al. 1992). 

Which of these clinical effects depend on specific anti-inflammatory actions of corticosteroids is 

not yet clear. Corticosteroids suppress the generation of cytokines, recruitment of airway 

eosinophils, and release of inflammatory mediators. These anti-inflammatory actions of 

corticosteroids have been noted in clinical trials and analyses of airway histology (Booth et al. 

1995; Busse 1993; Djukanovic et al. 1992; Duddridge et al. 1993; Laitinen et al. 1991, 1992; 

Levy et al. 1995; McGill et al. 1995). The anti-inflammatory effects of corticosteroids are 

mediated through receptors that modulate inflammatory gene expression. 

ICSs do not have the same bioavailability as oral systemic corticosteroids; hence, the risk of 

potential side effects is substantially reduced with ICSs. 
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Inhaled Corticosteroid Insensitivity 

The Expert Panel concludes that sensitivity and consequently clinical response to ICS 

can vary among patients (Evidence B).

Variation in sensitivity to ICS therapy may be related to high levels of inflammation, 

corticosteroid-insensitive pathways, or structural changes refractory to corticosteroid therapy 

(Leung and Bloom 2003). Corticosteroid responsiveness is decreased in smokers (Chalmers et 

al. 2002; Chaudhuri et al. 2003) and persons who have asthma with predominantly neutrophilic 

inflammation (Gauvreau et al. 2002; Green et al. 2002). Also, African American children who 

have poor control of their asthma appear to have an increased risk for corticosteroid 

insensitivity; this could be related to diminished glucocorticoid responsiveness at the cellular 

level, specifically T lymphocytes (Chan et al. 1998; Federico et al. 2005). 

Efficacy of Inhaled Corticosteroids as Compared to Other Long-Term Control 

Medications as Monotherapy 

The Expert Panel concludes that studies demonstrate that ICSs improve asthma 

control more effectively in both children and adults than LTRAs or any other single 

long-term control medication (Evidence A). 

For the EPR—3: Full Report 2007, the evidence of the efficacy of ICS therapy compared to 

other single daily long-term control medications in patients ≥5 years of age was obtained from 

nine randomized trials, most of which compared ICS to LTRA; five of these trials had placebo 

control groups (Garcia-Garcia et al. 2005; Ostrom et al. 2005; Szefler et al. 2002, 2005; Zeiger 

et al. 2006). These studies confirm findings discussed in EPR—Update 2002. Patients who 

have mild or moderate persistent asthma and are treated with ICS, compared to other single 

long-term control medications, demonstrate greater improvements in prebronchodilator FEV1; 

reduced airway hyperresponsiveness, symptom scores, exacerbation rates, and symptom 

frequency; as well as less use of supplemental SABA, fewer courses of oral systemic 

corticosteroids, and less use of hospitalization. The evidence does not suggest, however, that 

ICS use is associated with improved long-term postbronchodilator FEV1 (CAMP 2000). 

Studies comparing ICS to cromolyn or theophylline are limited, but available evidence shows 

that neither of these long-term control medications appears to be as effective as ICS in 

improving asthma outcomes. 

Efficacy of Inhaled Corticosteroid and Adjunctive Therapy (Combination Therapy) 

The Expert Panel recommends that when patients ≥12 years of age require more than 

low-dose ICS alone to control asthma (i.e., step 3 care or higher), a therapeutic option is 

to add LABA to ICS (Evidence A). Alternative, but not preferred adjunctive therapies 

include LTRA (Evidence B), theophylline (Evidence B), or, in adults, zileuton 

(Evidence D). (See Evidence Table 11, Inhaled Corticosteroids: Combination Therapy.) 

For children 0–11 years of age, LABA, LTRA, and, in children 5–11 years of age, 

theophylline may be considered as adjunctive therapies in combination with ICS 

(Evidence B, based on extrapolation from studies in older children and adults; see also 

section 4, “Managing Asthma Long Term” for recommendations on adjunctive therapies 

at different steps of care for different age groups in children).
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Although numerous studies have examined adjunctive therapy in adults, adjunctive therapy has 

not been studied adequately in children 5–11 years of age, and it has not been evaluated at all 

in children less than 4 years of age. An extensive review of the literature on this topic, 

conducted for the EPR—Update 2002, concluded that strong evidence in adults and older 

children indicates that the combination of ICS and LABA leads to improvements in lung function 

and symptoms and reduced need for quick-relief SABA. Adding an LTRA or theophylline to ICS 

or doubling the dose of ICS also was shown to improve outcomes, but the evidence was not as 

substantial as with the addition of LABA (EPR⎯Update 2002). 

The current review of the evidence supports this conclusion. The 2006 evidence review 

included studies comparing the combination of ICS and LABA to either baseline dose of ICS 

(two articles) or increasing doses of ICS (eight articles); comparing the combination of ICS and 

LTRA to baseline doses of ICS (three articles) or increasing doses of ICS (one article); 

comparing the combination of ICS and LABA to ICS and LTRA (seven articles); and comparing 

the combination of ICS and one LABA to another LABA (two articles), as well as three Cochrane 

Review meta-analyses (See Evidence Table 11, Inhaled Corticosteroids: Combination Therapy 

for complete citations.). The weight of the evidence reviewed continues to demonstrate that the 

addition of LABA to ICS leads to greater improvement in lung function, symptoms, and less use 

of SABA than increasing the dose of ICS or using LTRA as adjunctive therapy. Studies on the 

addition of LTRA to ICS have limitations that preclude conclusions, although the studies reveal 

a trend showing that LTRA improved lung function and some but not all trials report 

improvements in some measures of asthma control (See also the section below on “Leukotriene 

Modifiers.”). Recent data indicate potential risks that need to be considered for uncommon but 

life-threatening exacerbations associated with the daily use of LABAs (See the section below on 

“Safety of Inhaled Long-Acting Beta2-Agonists.”). See also section 4 on “Managing Asthma 

Long Term” for a discussion of issues to consider regarding combination therapy compared to 

increasing the dose of ICS. 

Dose-Response and Delivery Device 

The Expert Panel concludes that dosages for ICSs vary, depending upon the specific 

product and delivery devices. (See figure 3–24 for issues on delivery devices; see 

figures 4–4b, and 4–8b in section 4, “Managing Asthma Long Term,” for comparative ICS 

dosages.) For all ICS preparations, the dose-response relationship appears to flatten in 

patients who have mild or moderate asthma for most clinical parameters and lung 

function in the low- to medium-dose range (Evidence C).

Although most of the benefits of treatment are achieved with a low dose, the dose-response to 

ICS may vary, based on the response measured (e.g., improvement in lung function, prevention 

of exacerbations, or improvement in bronchial hyperresponsiveness, individual variability in 

response to ICS, and disease severity). Several studies show that for patients who have mild or 

moderate persistent asthma, use of higher doses improves asthma control modestly if at all 

(Bousquet et al. 2002; Holt et al. 2001; Kemp et al. 2000; Masoli et al. 2004a; Nayak et al. 2000; 

Powell and Gibson 2003; Szefler and Eigen 2002). However, the dose-response continued to 

improve at a higher dose for patients who have severe asthma (Masoli et al. 2004b). This 

efficacy of low-dose ICS therapy may account for the success of once-per-day treatment of 

patients who have mild or moderate persistent asthma, using several ICS preparations—both 

ICS alone (Casale et al. 2003; Jonasson et al. 2000; Jones et al. 1994; Noonan et al. 2001; 

Pincus et al. 1995) and in combination with LABA (Buhl et al. 2003). This efficacy may also 

account for the finding that mild and moderate asthma are as well controlled by starting 

treatment with a low, standard dose of an ICS as by starting with a high dose (Chanez et al. 
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2001; Reddel et al. 2000). These generalizations may not apply to patients who have more 

severe, uncontrolled asthma or to patients who have frequent, severe exacerbations. In these 

patients, twice-daily therapy with a higher dose may be necessary (Noonan et al. 1995; Pauwels 

et al. 1997), although control is achieved in a higher proportion of patients, and at a lower ICS 

dose, when it is given in combination with a LABA (Bateman et al. 2003, 2004). 

Variability in Response and Adjustable Dose Therapy 

The Expert Panel recommends that, given the variations over time in the severity 

of the pathophysiologic processes underlying asthma, it may be useful to adjust 

anti-inflammatory therapy accordingly (Evidence B). (See Evidence Table 12, Inhaled 

Corticosteroids: Dosing Strategies.) 

Several studies have shown that, for most patients whose asthma has been well controlled for 

at least 2 months by a high dose of an ICS alone, a 50 percent reduction in dose does not lead 

to loss of control (Aalbers et al. 2004; Hawkins et al. 2003; Leuppi et al. 2003; Thoonen et al. 

2003). This finding does not mean, however, that treatment with an ICS can be stopped 

altogether, for studies show that asthma control in most patients can worsen within a few weeks 

when treatment is discontinued (CAMP 2000; Dahl et al. 2002). Trials are now focusing on 

clinical features or “biomarkers” to distinguish between those patients who need continued 

treatment and those in whom it can be reduced or discontinued (Deykin et al. 2005; Leuppi et al. 

2003). 

Whether ICS treatment should be increased temporarily in response to some index of 

worsening asthma is also being examined. The effectiveness of this adjustable dose approach 

may be a function of timing or of dose. When asthma symptoms have worsened to the point of 

qualifying as an asthma exacerbation (See section 5 on “Managing Exacerbations of Asthma” 

for definition.), simply doubling the regular maintenance dose of ICS treatment does not appear 

to be effective (FitzGerald et al. 2004; Harrison et al. 2004). Studies that have shown benefit to 

patients from treatment with an adjustable dose regimen have employed greater increase in the 

dose of ICS (e.g., fourfold) and/or have made this adjustment earlier, at the first appearance of 

worsening symptoms (Aalbers et al. 2004; Boushey et al. 2005; Foresi et al. 2000; Harrison et 

al. 2004; Ind et al. 2004; Leuppi et al. 2003; Reddel and Barnes 2006; Thoonen et al. 2003). An 

interesting application of this approach was made possible by the development of an inhaler 

containing both budesonide (an ICS) and formoterol (a LABA with a rapid onset of action). 

Although this product does not have approved labeling for use as an acute quick-relief 

medication, one study has shown that use of a low dose of budesonide from this combination 

inhaler twice daily (maintenance therapy) plus additional use for relief of symptoms (adjustable 

therapy) was associated with a lower rate of asthma exacerbations and a lower cumulative dose 

of budesonide than was twice daily treatment with a fourfold greater dose of budesonide alone 

(Bisgaard et al. 2006; O'Byrne et al. 2005; Rabe et al. 2006). 

Another approach to adjustable therapy with an ICS is to link the dose adjustments to 

measurement of a biomarker of airway inflammation. Three biomarkers have been examined: 

bronchial reactivity to methacholine (Sont et al. 1999), sputum eosinophils (Green et al. 2002), 

and the concentration of nitric oxide in exhaled air (FeNO) (Smith et al. 2005). In these studies, 

biomarker-adjusted therapy reduced the rate of asthma exacerbations. In two of the studies 

(Green et al. 2002; Smith et al. 2005), the cumulative dose of ICS was reduced as well as in 

comparison to standard maintenance therapy alone. 
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Safety of Inhaled Corticosteroids 

KEY POINTS: SAFETY OF INHALED CORTICOSTEROIDS 

 ICSs are the most effective long-term therapy available for mild, moderate, or severe 

persistent asthma; in general, ICSs are well tolerated and safe at the recommended 

dosages (Evidence A). 

 The potential but small risk of adverse events from the use of ICS treatment is well balanced 

by their efficacy (Evidence A). 

 The dose-response curve for ICS treatment begins to flatten for many measures of efficacy 

at low to medium doses, although some data suggest that higher doses may reduce the risk 

of exacerbations. Most benefit is achieved with relatively low doses, whereas the risk of 

adverse effects increases with dose (Evidence B). 

 To reduce the potential for adverse effects, the following measures are recommended: 

— Spacers or valved holding chambers (VHCs) used with non-breath-activated MDIs 

reduce local side effects (Evidence A), but there are no data on use of spacers with ultra 

fine particle hydrofluoroalkane (HFA) MDIs. 

— Advise patients to rinse their mouths (rinse and spit) after inhalation (Evidence B). 

— Use the lowest dose of ICS that maintains asthma control. Evaluate patient adherence 

and inhaler technique as well as environmental factors that may contribute to asthma 

severity before increasing the dose of ICS (Evidence B). 

— To achieve or maintain control of asthma, consider adding a LABA to a low or medium 

dose of ICS rather than using a higher dose of ICS (Evidence A). 

— For children, monitor growth (Evidence A). See “Key Points: Inhaled Corticosteroids 

and Linear Growth in Children.” 

— In adult patients, consider supplements of calcium (1,000–1,500 mg per day) and 

vitamin D (400–800 units a day), particularly in perimenopausal women (Evidence D). 

Bone-sparing therapy (e.g., bisphosphonate), where appropriate, may be considered for 

patients on medium or high doses of ICS, particularly for those who are at risk of 

osteoporosis or who have low bone mineral density (BMD) scores by dual energy x ray 

absorptiometry (or DEXA) scan (Evidence C). In children, age-appropriate dietary intake 

of calcium and exercise should be reviewed with the child’s caregivers (Evidence D). 

The Expert Panel concludes that ICSs are the most effective long-term therapy available 

for patients who have persistent asthma and, in general, ICSs are well tolerated and safe 

at the recommended dosages (Evidence A). Systemic activity has been identified, 

particularly at high doses (See figures 4–4b and 4–8b.), for a definition of high-, medium-, and 

low-dose ICSs), but their clinical significance remains unclear (Leone et al. 2003). Furthermore, 

there may be interindividual variations in dose-response effects; thus, some patients may 
Section 3, Component 4: Medications 

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experience effects at lower doses. See Key Points, above, for a summary of recommendations 

to minimize the potential for adverse effects. In general, the potential for adverse effects must 

be weighed against the risk of uncontrolled asthma; to date, evidence supports the use of ICS, 

especially at low and medium doses (Barnes et al. 1993; CAMP 2000; EPR⎯Update 2002; 

Leone et al. 2003; Tinkelman et al. 1993; Van Essen-Zandvliet et al. 1992). 

The Expert Panel recommends the following actions to minimize potential adverse 

effects of ICS. Specific recommendations and evidence rank are presented under 

“Prevention and Treatment.” 

Local Adverse Effects 

Oral candidiasis (thrush) is one of the most common adverse effects of ICSs. Positive throat 

cultures of Candida can be identified in about 45–58 percent of patients, whereas clinical thrush 

is diagnosed in only 0–34 percent of patients (Rinehart et al. 1975; Shaw and Edmunds 1986; 

Toogood et al. 1980). With lower dosages of ICS, candidiasis is uncommon (5 percent) 

(Rinehart et al. 1975), although it is more frequent in adults than in children. Prevention and 

Treatment: Use a spacer or VHC with a non-breath-activated MDI to reduce the incidence of 

colonization and clinical thrush; rinse mouth with water after inhalation (Selroos and Halme 

1991). No data are available on the use of spacers or VHCs with ultrafine-particle-generated 

HFA MDIs. Administer ICS less frequently (bid versus qid). Topical or oral antifungal agents 

should be used to treat active infections (EPR⎯2 1997). 

Dysphonia is reported in 5–50 percent of patients who use an ICS and is associated with vocal 

stress and increasing dosages of ICS (Toogood et al. 1980). Prevention and Treatment: Use 

a spacer or VHC with a non-breath-activated MDI, temporarily reduce dosage, or rest for vocal 

stress (EPR⎯2 1997). 

Reflex cough and bronchospasm. Prevention and Treatment: These effects can be reduced 

by slower rates of inspiration and/or use of a spacer or valved holding chamber or by 

pretreatment with SABA. There is no convincing evidence that the routine use of a SABA 

before each dose of ICS increases intrapulmonary delivery of the ICS or reduces dosage 

requirement (EPR⎯2 1997). 

Systemic Adverse Effects 

Linear growth. A reduction in growth velocity may occur in children or adolescents as a result 

of inadequate control of chronic diseases such as asthma or from the use of corticosteroids for 

treatment. Overall, however, the available cumulative data about children suggest that, 

although low or medium doses of ICS may have the potential of decreasing growth velocity, the 

effects are small, nonprogressive, and may be reversible (CAMP 2000; Guilbert et al. 2006; 

Leone et al. 2003). Furthermore, studies of early intervention with low- or medium-dose ICS 

showed significantly improved asthma outcomes, despite a small reduction in growth velocity 

(Guilbert et al. 2006; Pauwels et al. 2003). 

The long-term prospective studies on growth involved budesonide, the retrospective analyses 

included studies on beclomethasone, and several shorter term studies have been performed on 

a variety of moieties, but the results have been generalized to include all ICS preparations. 

Although different preparations and delivery devices may have a systemic effect at different 

doses, all short-term studies on numerous preparations suggest that the effect of ICS on growth 

is a drug-class effect. When high doses of ICS are necessary to achieve satisfactory asthma 
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control, the use of adjunctive long-term control therapy should be initiated to reduce the dose of 

ICS and thus minimize possible dose-related long-term effects on growth. Prevention and 

Treatment: Physicians should monitor the growth of children and adolescents who are taking 

corticosteroids by any route and should weigh the benefits of corticosteroid therapy and asthma 

control against the possibility of growth suppression or delay if a child’s or an adolescent’s 

growth appears slowed (Evidence D). 

KEY POINTS: INHALED CORTICOSTEROIDS AND LINEAR 

GROWTH IN CHILDREN 

In the opinion of the Expert Panel: 

 The potential risks of ICSs are well balanced by their benefits. 

 Growth rates are highly variable in children. Short-term evaluations may not be predictive of 

final adult height attained. 

 Poorly controlled asthma may delay growth in children. 

 In general, children who have asthma tend to have longer periods of reduced growth rates 

before puberty (males more than females). 

 The potential for adverse effects on linear growth from ICS appears to be dose dependent. 

In treatment of children who have mild or moderate persistent asthma, low- to medium-dose 

ICS therapy may be associated with a possible, but not predictable, adverse effect on linear 

growth. The clinical significance of this potential systemic effect has yet to be determined. 

High doses of ICS have greater potential for growth suppression. 

 Use of high doses of ICS by children who have severe persistent asthma has significantly 

less potential than use of oral systemic corticosteroids for having an adverse effect on linear 

growth. 

 Studies in which growth has been carefully monitored suggest the growth-velocity effect of 

ICS occurs in the first several months of treatment and is generally small and 

nonprogressive. 

 In general, the efficacy of ICSs is sufficient to outweigh any concerns about growth or other 

systemic effects. However, ICSs, as with any medications, should be titrated to as low a 

dose as needed to maintain good control of the child’s asthma. 

Bone mineral density. Low and medium doses of ICS appear to have no serious adverse 

effects on BMD in children (CAMP 2000; Roux et al. 2003). A small, dose-dependent reduction 

in BMD may be associated with ICS use in patients older than 18 years of age (Ip et al. 1994; 

Israel et al. 2001), but the clinical significance of these findings is not clear. A large 

observational study of older patients (>65 years of age) with prolonged use of ICS showed that, 

at <2,000 mcg/day of beclomethasone or equivalent, there was no increase in the risk of 

fractures (Suissa et al. 2004). Data in adults suggest a cumulative dose relationship to the 
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effects of ICS on BMD (Wong et al. 2000). Prevention and Treatment: In patients who have 

risk factors for osteoporosis or low BMD scores, consideration can be given to bone-protecting 

therapies (e.g., bisphosphonates), although data are mixed in supporting the use of these 

therapies specifically in asthma patients who are taking ICS (Campbell et al. 2004; Kasayama et 

al. 2005) (Evidence C). Measuring BMD may be considered every 1–2 years, depending on 

duration and dose of ICS and oral corticosteroid treatment as well as previous BMD scores 

(Evidence D). 

Disseminated varicella. Although high doses of ICS theoretically present risks similar to those of 

systemic corticosteroid treatment, the reports of disseminated varicella in patients receiving only ICS 

are rare, causality is not clear, and there is no evidence that recommended doses of the ICSs are 

immunosuppressive. Cases have been reported of children who have severe persistent asthma, and 

are taking immunosuppressive doses of systemic corticosteroids, developing fatal disseminated 

disease from varicella infection (Kasper and Howe 1990; Silk et al. 1988). Other case reports 

indicate complications for patients who have Strongyloides or tuberculosis and who take high 

doses of systemic corticosteroids. Prevention and Treatment of Varicella: Children who require 

episodic therapy with systemic corticosteroids and who have not had clinical varicella should 

receive the varicella vaccine (EPR⎯2 1997). The vaccine should not be administered to 

patients who are receiving immunosuppressive doses of systemic corticosteroids (2 mg/kg or more 

of prednisone equivalent or 20 mg/day of prednisone for more than 1 month), unless this dosage is 

discontinued for at least 1 month. Children who have completed a short prednisone course may 

receive varicella vaccine without delay (American Academy of Pediatrics 1995; CDC 1994). 

Children and adults on treatment with immunosuppressive doses of corticosteroids who have not 

been immunized against varicella and are exposed to varicella infection are candidates for oral 

antiviral therapy (e.g., valacyclovir). If they develop clinical varicella, intravenous antiviral 

therapy should be given (EPR⎯2 1997). 

Dermal thinning and increased ease of skin bruising. These effects have been observed in 

patients treated with ICS. The effect is dose dependent, but the threshold dose is variable 

(Capewell et al. 1990). 

Ocular effects. In children, low- and medium-dose ICS therapy appears to have no significant 

effects on the incidence of subcapsular cataracts or glaucoma (CAMP 2000). In adults, high 

cumulative lifetime exposure (greater than 2,000 mg of beclomethasone dipropionate or 

equivalent) to ICS may increase the prevalence of cataracts, as suggested in three 

retrospective studies of adult and elderly patients (Evidence C) (Cumming et al. 1997; Garbe et 

al. 1998; Jick et al. 2001). A retrospective, case-control study showed an association between 

long-term ICS use and the development of glaucoma (Garbe et al. 1997). A subsequent 

cross-sectional, retrospective study in adults reported an association between elevated 

intraocular pressure and glaucoma in patients who had a family history of glaucoma and used 

ICS, particularly at higher doses (defined in this study as more than 4 puffs per day). There was 

no increase in risk in ICS users who did not have a family history of glaucoma (Mitchell et al. 

1999). Prevention and Treatment: These data suggest the advisability of periodic 

assessments and treatments, if indicated, for increased intraocular pressures in asthma patients 

who use ICS, particularly at higher doses, and have a family history of glaucoma (Evidence C). 

Hypothalamic-pituitary-adrenal axis function. The available evidence indicates that, on 

average, children may experience only clinically insignificant, if any, effects of low- or 

medium-dose ICS on the hypothalamic-pituitary-adrenal (HPA) axis (Leone et al. 2003). Rarely, 

however, some individuals may be more susceptible to the effects of ICS even at conventional 

doses. 
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Glucose metabolism. In a study of children, ICS at dosages from 400 to 1,000 mcg/day 

(budesonide) did not affect fasting glucose or glycosolated hemoglobin. At 1,000 mcg/day, a 

significantly greater rise in fasting serum insulin levels and glucose during a glucose tolerance 

test was noted, but results remained within normal limits (Turpeinen et al. 1991). 

Oral Systemic Corticosteroids 

The Expert Panel recommends that chronic administration of oral systemic 

corticosteroids as a long-term-control medication be used only for the most severe, 

difficult-to-control asthma because of well-documented risk for side effects (EPR⎯2 

1997). 

The Expert Panel recommends that, because the magnitude of adverse effects is often 

related to the dose, frequency of administration, and the duration of corticosteroid use 

(Evidence A), every consideration should be given to minimize systemic corticosteroid 

doses and maximize other modes of therapy (Evidence D). It is necessary, therefore, to 

monitor for the development and progression of adverse effects and to take appropriate 

steps to minimize the risk and impact of adverse corticosteroid effects (Evidence D).

Oral systemic corticosteroids suppress, control, and reverse airway inflammation. However, 

side effects with chronic administration include adrenal suppression, growth suppression, 

dermal thinning, hypertension, Cushing’s syndrome, cataracts, and muscle weakness. Chronic 

corticosteroid use can also result in immunologic attenuation with loss of delayed-type 

hypersensitivity, diminished immunoglobulin G (IgG) levels without change in functional 

antibody response, potential for reactivation of latent tuberculosis infection, and possible 

increased risk for infection, especially the development of severe varicella (Spahn et al. 2003). 

Cromolyn Sodium and Nedocromil 

Cromolyn and nedocromil are alternative, not preferred, medications for the treatment of 

mild persistent asthma (Evidence A). They can also be used as preventive treatment 

before exercise or unavoidable exposure to known allergens (EPR⎯2 1997). Although 

cromolyn and nedocromil have distinct properties (Clark 1993), they have similar 

anti-inflammatory actions. The mechanism of cromolyn and nedocromil appears to involve the 

blockade of chloride channels (Alton and Norris 1996) and modulate mast cell mediator release 

and eosinophil recruitment (Eady 1986). The two compounds are equally effective against 

allergen challenge (Gonzalez and Brogden 1987), although nedocromil appears to be more 

potent than cromolyn in inhibiting bronchospasm provoked by exercise (de Benedictis et al. 

1995; Novembre et al. 1994), by cold dry air (Juniper et al. 1987), and by bradykinin aerosol 

(Dixon and Barnes 1989). 

Dosing recommendations for both nedocromil and cromolyn are for administration four times a 

day, although nedocromil has been shown to be clinically effective with twice-daily dosing 

(Creticos et al. 1995; EPR⎯2 1997). 

Cromolyn sodium and nedocromil have been shown to provide symptom control greater than 

placebo in some but not all clinical trials (Konig 1997; Petty et al. 1989; Tasche et al. 2000) and 

to confer protection against exacerbations of asthma leading to hospitalization, particularly in 

children (Donahue et al. 1997), and ED visits (Adams et al. 2001). These results, along with the 

excellent safety profile, justify consideration of cromolyn and nedocromil as treatment options. 

However, a systematic review (van der Wouden et al. 2003) concluded that insufficient evidence 

existed to conclude that cromolyn had a beneficial effect on maintenance treatment of childhood 
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asthma. Compared to placebo, nedocromil reduces both urgent care visits as well as the need 

for prednisone, which are meaningful clinical outcomes. However, nedocromil is no different 

than placebo on all other outcome measures (CAMP 2000). Overall, nedocromil is significantly 

less effective than ICS in improving outcomes measures (CAMP 2000). Nedocromil has not 

been studied adequately in children younger than 5 years of age. As a result of these disparate 

findings (i.e., some, but limited, effectiveness and strong safety profile), the Expert Panel’s 

opinion is that cromolyn for children of all ages and nedocromil for children ≥5 years of age 

could be considered in the treatment of persistent asthma for children of all ages, but they are 

not preferred therapies. The Expert Panel’s review of the literature in 2006 found that no new 

studies have been published that would change these conclusions. 

Immunomodulators 

Many different pharmaceutical agents have been tested for their ability to provide long-term 

control and/or steroid-sparing effects. These agents are loosely defined as immunomodulators. 

New information is available and discussed here on methotrexate, soluble interleukin-4 (IL-4) 

receptor, anti-IL-5, recombinant IL-12, cyclosporin A, intravenous immunoglobulin (IVIG), 

clarithromycin, omalizumab (anti-IgE), and others. For discussion of immunotherapy as an 

asthma management strategy, see “Component 3: Control of Environmental Factors and 

Comorbid Conditions That Affect Asthma.” 

Omalizumab 

The Expert Panel recommends that omalizumab may be considered as adjunctive 

therapy in step 5 or 6 care for patients who have allergies and severe persistent asthma 

that is inadequately controlled with the combination of high-dose ICS and LABA 

(Evidence B). (See Evidence Table 13, Immunomodulators: Anti-IgE.) 

Omalizumab, a recombinant DNA-derived humanized monoclonal antibody to the Fc portion of 

the IgE antibody, binds to that portion preventing the binding of IgE to its high-affinity receptor 

(FcεRI) on mast cells and basophils. The decreased binding of IgE on the surface of mast cells 

leads to a decrease in the release of mediators in response to allergen exposure. Omalizumab 

also decreases FcεRI expression on basophils and airway submucosal cells (Djukanovic et al. 

2004; Lin et al. 2004). That study also showed significant decreases in sputum and bronchial 

eosinophils as well as in CD3+, CD4+, and CD8+ T cells in bronchial biopsy (Djukanovic et al. 

2004). The vast majority of patients in clinical trials of omalizumab had moderate or severe 

persistent asthma incompletely controlled with ICS (Walker et al. 2004); all had atopy and IgE 

≥30 IU/mL. Adding omalizumab to ICS therapy generally produced a significant reduction in 

asthma exacerbations (Busse et al. 2001a; Soler et al. 2001; Vignola et al. 2004) but not always 

(Holgate et al. 2004; Milgrom et al. 2001). (See Evidence Table 13, Immunomodulators: AntiIgE.) Omalizumab, added to ICS, was associated with a small but significant improvement in 

lung function (Busse et al. 2001a; Soler et al. 2001). In two trials, one open-label, in patients 

who had severe persistent asthma inadequately controlled on ICS plus LABAs, omalizumab 

reduced asthma exacerbations and ED visits (Ayres et al. 2004; Humbert et al. 2005). 

Omalizumab appears to have a modest steroid-sparing effect, allowing a median reduction of 25 

percent over that of placebo in the trials (Busse et al. 2001a; Holgate et al. 2004; Milgrom et al. 

2001; Soler et al. 2001). Omalizumab has not been compared in clinical trials to the other 

adjunctive therapies for moderate persistent asthma (LABAs, leukotriene modifiers, and 

theophylline), all of which improve outcomes and allow reduction of ICS dose. Omalizumab is 

the only adjunctive therapy, however, to demonstrate added efficacy to high-dose ICS plus 

LABA in patients who have severe persistent allergic asthma (Humbert et al. 2005). In studies 
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of patients who have severe persistent asthma, omalizumab resulted in clinically relevant 

improvements in quality-of-life scores in significantly more patients (approximately 60 percent) 

than did placebo (approximately 43 percent) (Holgate et al. 2004; Humbert et al. 2005). 

Omalizumab is approved for patients 12 years and older who have proven sensitivity to 

aeroallergens: studies have been done in patients who have sensitivity to dust mite, cockroach, 

cat, or dog. One study of omalizumab in children 6–12 years of age demonstrated 

nonsignificant reductions in exacerbations and no improvement in lung function but did show 

small but significant reduction in ICS dose compared to placebo (Milgrom et al. 2001). 

Urticaria and anaphylactic reactions have been reported in 0.1 percent of cases (Berger et al. 

2003; FDA 2003; Holgate et al. 2004; Lanier et al. 2003). Postmarketing surveys have identified 

anaphylaxis in an estimated 0.2 percent of treated patients, which resulted in an FDA alert (FDA 

2007). Most of these reactions occurred within 2 hours of the omalizumab injection, and after 

the first, second, or third injections. However, reactions have occurred after many injections 

and after many hours. Therefore, clinicians who administer omalizumab are advised to be 

prepared and equipped for the identification and treatment of anaphylaxis that may occur, to 

observe patients for an appropriate period of time following each injection (the optimal length of 

the observation is not established), and to educate patients about the risks of anaphylaxis and 

how to recognize and treat it if it occurs (e.g., using prescription auto injectors for emergency 

self-treatment, and seeking immediate medical care) (FDA 2007). 

Adverse effects reported from omalizumab in the trials have also included injection-site pain and 

bruising in up to 20 percent of patients (Holgate et al. 2004). In the trials reported to the FDA, 

twice as many patients receiving omalizumab had malignancies (20 of 48,127, or 0.5 percent) 

as did those receiving placebo (5 of 2,236, or 0.2 percent), but there were no trends for a 

specific tumor type. 

Antibiotics 

In the opinion of the Expert Panel, the data at present are insufficient to support a 

recommendation about the use of macrolide in chronic asthma.

Some, but not all, data—including a recent controlled trial—have shown an effect of the 

macrolide antibiotic, clarithromycin, in the treatment of asthma (Kostadima et al. 2004; Kraft et 

al. 2002). Although it has been shown that clarithromycin can interfere with the clearance of 

methylprednisolone (Fost et al. 1999), this did not appear to be the mode of action. Preliminary 

data suggest that clarithromycin may enhance glucocorticoid effect on lymphocyte activation 

(Spahn et al. 2001). 

Recent evidence suggesting that telithromycin may provide benefit in recovery from acute 

exacerbations has not linked the benefit with antibiotic activity of the drug (Johnston et al. 2006). 

Macrolide antibiotics, however, have potential risk for liver toxicity. 

Others 

The Expert Panel concludes that current evidence does not support the use of 

methotrexate, soluble IL-4 receptor, humanized monoclonal antibody against IL-5 or 

IL-12, cyclosporin A, IVIG, gold, troleandomycin (TAO), or colchicine for asthma 

treatment (Evidence B).
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For methotrexate, the evidence from a new meta-analysis does not support use of the 

treatment, given the side effects of the drug (Aaron et al. 1998; Davies et al. 2000). 

Use of soluble IL-4 receptor gave promising initial results on moderate to severe asthma (Borish 

et al. 1999), but subsequent trials were less successful, and it is unlikely to be marketed (Borish 

et al. 2001). 

A humanized monoclonal antibody directed against IL-5 depleted eosinophils from blood and 

induced sputum but had no effect on airway hyperresponsiveness, on the late asthmatic 

reaction to inhaled allergen, or in patients who have severe persistent asthma (Flood-Page et al. 

2003; Kips et al. 2003; Leckie et al. 2000). Recombinant IL-12 also reduced blood and sputum 

eosinophils, but it had no significant effects on airway hyperresponsiveness or the late 

asthmatic reaction to allergen (Bryan et al. 2000). These findings suggest that neither biological 

will be useful in clinical asthma. 

Despite further interesting studies on the mechanism of action of cyclosporin A (Khan et al. 

2000), data from controlled trials are not convincing (Evans et al. 2001); given the toxicity of the 

drug, the data make it difficult to recommend. 

Data from open-label trials of IVIG have shown clinical and biomarker benefit in steroiddependent asthma (Landwehr et al. 1998; Mazer and Gelfand 1991; Spahn et al. 1999). Two 

controlled trials, however, have failed to establish a clinical benefit of IVIG in such patients 

(Kishiyama et al. 1999; Niggemann et al. 1998) and showed significant adverse effects. The 

Expert Panel concludes, from available data, that the use of IVIG in asthma is not 

recommended. 

Trials have suggested limited or no usefulness for oral gold (Bernstein et al. 1996), TAO 

(Nelson et al. 1993), and colchicine (Fish et al. 1997; Newman et al. 1997). 

Leukotriene Modifiers 

The Expert Panel recommends that LTRAs are an alternative, not preferred, treatment 

option for mild persistent asthma (Step 2 care) (Evidence A). LTRAs can also be used as 

adjunct therapy with ICS, but for youths ≥12 years of age and adults they are not the 

preferred, adjunct therapy compared to the addition of LABAs (Evidence A). A 

5-lipoxygenase inhibitor (zileuton) is an alternative treatment option that is less desirable 

than LTRAs due to more limited efficacy data and the need for liver function monitoring 

(Evidence D). (See Evidence Table 14, Leukotriene Receptor Antagonists: 

Monotherapy/Effectiveness Studies.) 

Leukotrienes are potent biochemical mediators—released from mast cells, eosinophils, and 

basophils—that contract airway smooth muscle, increase vascular permeability, increase mucus 

secretions, and attract and activate inflammatory cells in the airways of patients who have 

asthma (Henderson 1994). 

Three leukotriene modifiers—montelukast, zafirlukast, and zileuton—are available as oral 

tablets for the treatment of asthma. Leukotriene modifiers comprise two pharmacologic classes 

of compounds: 5-lipoxygenase pathway inhibitors (e.g., zileuton), and LTRAs (e.g., montelukast 

and zafirlukast, which block the effects of the CysLT1 receptor). Only montelukast (for children 

as young as 1 year of age) and zafirlukast (for children as young as 7 years of age) are 

approved for use in children. 
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Leukotriene receptor antagonists. The LTRAs have been demonstrated to provide 

statistically significant but modest improvement in lung function when used as monotherapy in 

both adults and children as young as 5 years of age as well as in asthma control outcomes 

other than lung function in patients as young as 2 years of age (Bisgaard et al. 2005; Bleecker 

et al. 2000; Busse et al. 2001b,c; Garcia-Garcia et al. 2005; Jenkins et al. 2005; Ostrom et al. 

2005; Pearlman et al. 2000; Szefler et al. 2005; Zeiger et al. 2005, 2006) (see Evidence 

Table 14). In general, these studies included patients who had either mild or moderate 

persistent asthma, although the classification of severity was not always clear in the studies, nor 

was it consistently applied. When comparing overall efficacy of LTRA to ICS in both children 

and adult patients who have persistent asthma, most outcome measures (e.g., reduction in 

exacerbations, improvements in symptom-free days and FEV1) significantly and clearly favored 

ICS (Busse et al. 2001b,c; Ducharme et al. 2003; Garcia-Garcia et al. 2005; Jenkins et al. 2005; 

Ostrom et al. 2005; Sorkness et al. 2007; Zeiger et al. 2006). See Evidence Table 14: 

Leukotriene Receptor Antagonists: Monotherapy/Effectiveness Studies. 

Three randomized, controlled, double-blind studies in children 5–15 years of age demonstrated 

the greater effectiveness of ICS (fluticasone) compared to montelukast (Garcia-Garcia et al. 

2005; Ostrom et al. 2005; Sorkness et al. 2007). All three reported significantly greater 

improvements in lung function and total symptom scores as well as reduction in exacerbations; 

one demonstrated that montelukast was not inferior to fluticasone in rescue-free days (defined 

in the study as any day without asthma rescue medication and with no asthma-related resource 

use) (Garcia-Garcia et al. 2005), but the other two showed superiority of fluticasone compared 

to montelukast for percentage of rescue-free days. 

A randomized, cross-over, double-blind study of 140 children 6–17 years of age, in which 

children received either ICS or LTRA (montelukast) for 8 weeks followed by 8 weeks of the 

other medication, examined what factors might predict individual variation in response to 

different medications. The study suggests that children who have higher levels of 

eosinophilic/allergic airway inflammation (nitric oxide, IgE levels, total eosinophil levels) or low 

pulmonary function (measured by FEV1/FVC or FEV1) are more likely to respond favorably to 

ICS than to LTRA. Children who do not have these markers appeared to respond equally to 

treatment with ICS or LTRA (Szefler et al. 2005; Zeiger et al. 2006). 

LTRAs have been demonstrated to attenuate EIB (Mastalerz et al. 2002; Moraes and 

Selvadurai 2004). 

LTRAs may be considered as an alternative treatment option for patients whose response to 

ICSs may be compromised. For example, a controlled trial noted that active cigarette smoking 

impairs the efficacy of short-term ICS treatment in adults who had mild asthma (Chalmers et al. 

2002). However, patients who smoke should be advised to quit smoking. See “Component 3: 

Control of Environmental Factors and Comorbid Conditions That Affect Asthma” and 

“Component 2: Education for a Partnership in Care.” 

Zafirlukast, an LTRA, has been demonstrated to attenuate the late response to inhaled allergen 

and post-allergen-induced bronchial responsiveness (Dahlen et al. 1994; Taylor et al. 1991). A 

study comparing zafirlukast to placebo in patients who have mild or moderate asthma 

demonstrated that patients treated with zafirlukast experienced modest improvement in FEV1 

(mean improvement of 11 percent above placebo), had improved symptom scores, and reduced 

albuterol use (average decline of 1 puff/day) (Spector et al. 1994). Zafirlukast can cause a 

significant increase in the half-life of warfarin. Consequently, for those individuals receiving 

zafirlukast and warfarin, it will be necessary to closely monitor prothrombin times and adjust 
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doses of warfarin accordingly. Cases of hepatic dysfunction have occurred with zafirlukast. 

Although most patients improved with discontinuation of zafirlukast, some have gone on to 

fulminate hepatic failure resulting in receiving a transplant or in death. Patients should be 

advised to be alert for signs and symptoms of hepatitis (anorexia, abdominal pain, nausea, 

jaundice, and pruritis); if these occur, they should discontinue zafirlukast and have liver 

enzymes (ALT) monitored. 

The use of LTRA as adjunctive therapy in moderate or severe asthma has not been studied 

adequately in children 5–11 years of age and has not been studied at all in children less than 

4 years of age. Limitations in the studies comparing addition of LTRA to a fixed dose of ICS 

(i.e., adding LTRA when patients are not adequately controlled with ICS alone) preclude 

definitive conclusions, although they reveal a trend showing that LTRA improved lung function 

and some but not all measures of asthma control (Laviolette et al. 1999; Robinson et al. 2001; 

Simons et al. 2001; Vaquerizo et al. 2003). One study in adults compared the combination of 

LTRA and ICS to increasing the dose of ICS and reported similar outcomes for the two 

approaches (Price et al. 2003). In a 24-week trial in patients who had poorly controlled asthma, 

the addition of theophylline or montelukast led to small improvement in lung function but did not 

improve episodes of poor asthma control, symptoms, or quality of life (American Lung 

Association Asthma Clinical Research Centers 2007). Studies comparing LTRA to LABA as 

adjunctive therapy in adults show significantly greater improvement in lung function and other 

asthma control measures with the LABA adjunctive therapy (EPR⎯Update 2002; Ram et al. 

2005). 

5-lipoxygenase inhibitor. Zileuton has not been studied in patients less than 12 years of age. 

It has been demonstrated to provide immediate and sustained improvements in FEV1 (mean 

increase of 15 percent above placebo) in placebo-controlled trials in patients who have mild or 

moderate asthma (Israel et al. 1993, 1996). Compared to placebo, the patients who had 

moderate asthma treated with zileuton experienced significantly fewer exacerbations requiring 

oral systemic corticosteroids (Israel et al. 1996), thus suggesting anti-inflammatory action. 

Zileuton is capable of attenuating bronchoconstriction from exercise (Meltzer et al. 1996) and 

from aspirin in aspirin-sensitive individuals (Israel et al. 1993). One large, randomized, open 

label, study in adults who had asthma (Lazarus et al. 1998) and one small cross-over study in 

aspirin-sensitive adults who had asthma (Dahlen et al. 1998) demonstrated clinical benefits to 

adding zileuton to existing therapy; the large trial also reported elevated liver enzymes. 

Because liver toxicity has been found in some subjects receiving zileuton, it is recommended 

that hepatic enzymes (ALT) be monitored in patients who take this medication. Furthermore, 

zileuton is a microsomal cytochrome P450 enzyme inhibitor that can inhibit the metabolism of 

warfarin and theophylline; doses of these drugs should be monitored accordingly. Due to the 

limited efficacy data and the need for liver function monitoring, zileuton is a less desirable 

alternative than LTRAs. 

Inhaled Long-Acting Beta2-Agonists 

The principal action of beta2-agonists is to relax airway smooth muscle by stimulating 

beta2-receptors, which increases cyclic AMP and produces functional antagonism to 

bronchoconstriction. Due to their increased lipophilicity prolonging retention in lung tissue, the 

LABAs have a duration of bronchodilation of at least 12 hours after a single dose (Kips and 

Pauwels 2001). The LABAs effectively block EIB for 12 hours after a single dose; however, with 

chronic regular administration, this effect does not exceed 5 hours (Ramage et al. 1994; Simons 

et al. 1997). 
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The Expert Panel concludes the following regarding the use of LABAs:

 LABAs are used as an adjunct to ICS therapy for providing long-term control of 

symptoms (Evidence A). Of the adjunctive therapies available, LABA is the preferred 

treatment to combine with ICS in youths ≥12 years of age and adults (Evidence A).

 LABAs are not recommended for use as monotherapy for long-term control of 

persistent asthma (Evidence A). 

 Use of LABA is not currently recommended to treat acute symptoms or exacerbations 

of asthma (Evidence D). Studies are underway examining the potential use of formoterol 

in acute exacerbations and in adjustable-dose therapy in combination with ICS; see the 

discussion below in the section on “Quick-Relief Medications” and on “Inhaled Short-Acting 

Beta2-Agonists.” 

 LABA may be used before exercise to prevent EIB (Evidence B), but frequent and 

chronic use of LABA for EIB may indicate poorly controlled asthma which should be 

managed with daily anti-inflammatory therapy.

 Safety issues have been raised regarding LABAs. The Expert Panel reviewed the 

safety data provided to the FDA Pulmonary and Allergy Drugs Advisory Committee as 

well as the extensive accumulation of clinical trials and meta-analyses on the use of 

LABA, both as monotherapy and in conjunction with ICS. The Expert Panel 

concluded that LABAs should not be used as monotherapy as long-term control 

medication in persistent asthma but that LABAs should continue to be considered for 

adjunctive therapy in patients ≥5 years of age who have asthma that requires more 

than low-dose ICS. For patients inadequately controlled on low-dose ICS, the option 

to increase the ICS dose should be given equal weight to the addition of a LABA. For 

patients who have more severe persistent asthma (i.e., those who require step 4 care 

or higher), the Expert Panel continues to endorse the use of a combination of LABA 

and ICS as the most effective therapy. The basis of this opinion is discussed below. 

(See Evidence Table 15, Bronchodilators: Safety of Long-Acting Beta2-Agonists.) 
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Safety of Long-Acting Beta2-Agonists

KEY POINTS: SAFETY OF INHALED LONG-ACTING 

BETA 2 -AGONISTS 

 The addition of LABA (salmeterol or formoterol) to the treatment of patients whose asthma is 

not well controlled on low- or medium-dose ICS improves lung function, decreases 

symptoms, and reduces exacerbations and use of SABA for quick relief in most patients 

(EPR⎯Update 2002; Greenstone et al. 2005; Masoli et al. 2005). 

 A large clinical trial comparing daily treatment with salmeterol or placebo added to usual 

asthma therapy (Nelson et al. 2006) resulted in an increased risk of asthma-related deaths 

in patients treated with salmeterol (13 deaths out of 13,176 patients treated for 28 weeks 

with salmeterol versus 3 deaths out of 13,179 patients with placebo). In addition, increased 

numbers of severe asthma exacerbations were noted in the pivotal trials submitted to the 

FDA for formoterol approval, particularly in the higher dose formoterol arms of the trials 

(Mann et al. 2003). Thus the FDA determined that a Black Box warning was warranted on 

all preparations containing a LABA. 

 The Expert Panel recommends that the established, beneficial effects of LABA for the great 

majority of patients whose asthma is not well controlled with ICS alone should be weighed 

against the increased risk for severe exacerbations, although uncommon, associated with 

the daily use of LABAs. 

 Therefore, the Expert Panel has modified its previous recommendation (EPR⎯Update 

2002) and has now concluded that, for patients who have asthma not sufficiently controlled 

with ICS alone, the option to increase the ICS dose should be given equal weight to the 

option of the addition of a LABA to ICS. 

 Daily use of LABA generally should not exceed 100 mcg salmeterol or 24 mcg formoterol. 

 It is not currently recommended that LABA be used for treatment of acute symptoms or 

exacerbations. 

 LABAs are not to be used as monotherapy for long-term control. Patients should be 

instructed not to stop ICS therapy while taking salmeterol or formoterol even though their 

symptoms may significantly improve. 

General Safety. LABAs induce sustained relaxation of airway smooth muscle that allows 

twice-daily administration. The two LABAs currently available for the treatment of asthma are 

salmeterol and formoterol. They have slightly different properties in that salmeterol is a partial 

agonist and formoterol is a full agonist, but the only clinically relevant difference is that 

formoterol has a more rapid onset of bronchodilation (similar to albuterol) (Kips and Pauwels 

2001). Both are highly selective beta2-adrenergic receptor agonists that produce clinically 

relevant cardiovascular effects (tachycardia, QTc interval prolongation, and hypokalemia) at 

doses approximately 4–5 times those recommended (Guhan et al. 2000; Ostrom 2003; 
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Palmqvist et al. 1999). Other dose-dependent sympathomimetic effects include tremor and 

hyperglycemia. Because the LABAs are devoid of any clinically apparent anti-inflammatory 

activity (Currie et al. 2003; Lazarus et al. 2001), they should not be used as monotherapy for 

long-term control of persistent asthma. Discontinuation of ICS therapy following initiation of 

LABA results in an increase in asthma exacerbations (Lemanske et al. 2001). Of greatest 

concern have been the reports of an increased risk of severe asthma exacerbations, both 

life-threatening and fatal, associated with regular LABA use (Mann et al. 2003; Nelson et al. 

2006) that has resulted in a Black Box Warning label for products in the United States 

containing either salmeterol or formoterol. 

Early recognition of the potential dangers of LABAs followed a large, randomized, prospective 

postmarketing study in approximately 25,000 patients in the United Kingdom. The study 

reported an increased (although not statistically significant) number of deaths in patients treated 

with salmeterol (42 mcg/day) versus albuterol (180 mcg four times/day) added to usual asthma 

therapy (12 of 16,787 patients taking salmeterol versus 2 of 8,393 patients on albuterol) (Castle 

et al. 1993). However, an observational, prescription-event monitoring program in the United 

Kingdom evaluating 15,407 patients taking salmeterol found no evidence that salmeterol 

contributed to the death of any of the patients (Mann et al. 1996). Similarly, a retrospective 

review of a large, health insurance claims database in the United States, comparing a cohort of 

2,708 patients receiving salmeterol to 3,825 recipients of sustained release theophylline, found 

no increase in ED visits, hospitalizations, or ICU admissions among those receiving salmeterol 

during the year following initiation of therapy (Lanes et al. 1998). 

Due to the concerns generated by the initial United Kingdom study, a large, randomized, 

placebo-controlled, 28-week trial of salmeterol versus placebo added to usual care in adults 

who had asthma was performed to assess the safety of salmeterol (Nelson et al. 2006). The 

goal was to enroll approximately 60,000 patients, and the primary outcome variable was 

combined respiratory-related deaths or respiratory-related, life-threatening experiences; 

secondary end points included all-cause deaths, asthma-related deaths, and combined 

asthma-related deaths or life-threatening experiences. A planned interim analysis of more than 

26,000 patients found no increase in the primary outcome but did find an increased risk of 

asthma-related deaths and combined asthma-related death or life-threatening experiences in 

the total population. Although the study was not designed to assess subgroups, a subgroup 

analysis reported that African Americans, who were 18 percent of the total population, 

experienced a significant increased risk for the primary end point as well as combined 

asthma-related death or life-threatening experiences. In addition, an analysis of serious asthma 

exacerbations in the pivotal trials submitted to the FDA for marketing approval of formoterol 

revealed an increased number of these events in patients receiving formoterol, particularly at 

the higher dose of 48 mcg daily that exceeds current labeling (Chowdhury 2005; Mann et al. 

2003). A followup analysis of the same data reiterated the potential risks (Salpeter et al. 2006). 

The data from the Salmeterol Multicenter Asthma Research Trial (SMART), Chowdhury, and 

Mann and colleagues prompted the FDA to convene a meeting of the Pulmonary and Allergy 

Drugs Advisory Committee (www.fda.gov/cder/drug/advisory/LABA.htm) (FDA 2005). This 

group, in conjunction with the FDA, determined that these data represented a serious safety 

concern for the use of LABAs but that the significant benefit provided by these agents to a large 

number of patients, particularly in conjunction with ICS therapy, warranted continued use of 

LABA as adjunctive therapy for patients who have asthma that is not well controlled with ICS 

alone. 

A meta-analysis of trials, performed for the EPR—Update 2002, reported greater benefit in 

measures of asthma control with the addition of a LABA compared to doubling the dose of ICS 
Section 3, Component 4: Medications 

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(EPR⎯Update 2002). A Cochrane Library systematic review of 85 RCTs (60 studies with 

salmeterol and 25 studies with formoterol) comparing LABA with a placebo in chronic asthma 

(Walters et al. 2003) reported a decrease in severe asthma exacerbations (defined as requiring 

intervention other than as-needed SABA) associated with LABA use. Additional meta-analyses 

showed that the addition of LABA compared to increasing the ICS dose improved lung function 

and symptom control (Ni et al. 2005), reduced exacerbations (Masoli et al. 2005), and did not 

increase serious asthma exacerbations or participant withdrawals due to worsening asthma. A 

recent case-control study of 532 asthma patients who died from asthma did not find a positive 

association between LABA use and death (Anderson et al. 2005). A more recent large, 

postmarketing study (2,085 patients) of adding formoterol, either 24 mcg or 12 mcg twice daily, 

to usual care (65 percent receiving concomitant anti-inflammatory therapy) failed to detect an 

increase risk of serious asthma exacerbations (Wolfe et al. 2006). 

A mechanism for a direct effect of LABAs in producing exacerbations has not been established. 

The primary hypotheses for LABAs’ increasing the risk of severe, life-threatening asthma 

exacerbations include: (1) a direct adverse effect of LABA on bronchial smooth muscle, 

resulting in more severe obstruction following any bronchoconstrictive stimulus, or 

(2) maintenance of lung function in the face of worsening underlying inflammation, leading either 

to a catastrophic increase in obstruction or to patients’ delaying seeking appropriate medical 

attention for a severe exacerbation. Clinical trials clearly demonstrate that, in patients who have 

persistent asthma, discontinuation of ICS after starting LABA results in increased markers of 

inflammation and increased risk of exacerbations (Lazarus et al. 2001; Lemanske et al. 2001; 

Mcivor et al. 1998). In patients who have mild asthma, the increase in exacerbations occurs 

despite benefits in measures of daily asthma control such as symptoms, as-needed use of 

SABA, and PEFs (Lazarus et al. 2001). Unlike regular use of SABA, the regular daily 

administration of LABA has not produced an increase in bronchial hyperresponsiveness 

(Cheung et al. 1992; Lazarus et al. 2001; Simons 1997; Van Schayck et al. 2002; Walters et al. 

2003). 

Genetic studies assessing the role of the polymorphism at codon 16 of the beta2-adrenergic 

receptor gene have produced inconclusive results. A cross-over study by Taylor and coworkers 

(2000) reported that, during 24 weeks of treatment with placebo, albuterol, and salmeterol, the 

number of major exacerbations was significantly increased for homozygous Arg-16 subjects 

(only 17 subjects) during albuterol treatment compared with placebo but not during salmeterol 

treatment. In addition, researchers found no adverse effect of salmeterol on morning peak flow 

in the homozygote Arg-16 subjects compared with placebo or compared to homozygous 

Gly-16 subjects. More recently, Wechsler and colleagues (2006) reported that homozygote 

Arg-16 subjects (n = 8) who were taking salmeterol and an ICS had lower FEV1, increased 

symptom scores, and increased use of SABA compared with Gly/Gly subjects (n = 22) taking 

the same combination therapy. On the other hand, Bleecker (2006) reported that, in a study of 

patients receiving LABA and ICS (N = 183), there were no differences in clinical response 

between Arg/Arg or Gly/Gly genotypes. 

Studies assessing the qualitative nature of exacerbations have shown no difference in the 

rapidity of onset or severity of obstruction, reporting of symptoms, or use of SABA whether 

patients who had asthma were receiving LABA or not (Matz et al. 2001; Tattersfield et al. 1999). 

However, the patients in these studies were all receiving ICS as well as LABA. No studies have 

specifically addressed whether patients who take LABA delay seeking medical attention for 

deterioration of asthma, but this effect would be difficult to assess. 
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What ameliorative role, if any, the concomitant administration of ICS has on the potential for 

severe asthma exacerbations associated with LABA use has not been studied adequately. In a 

meta-analysis, the addition of LABA to ICS produced a significant reduction in severe 

exacerbations, but only a borderline significant decrease occurred in studies of patients who 

were not receiving ICS (Walters et al. 2003). In large clinical trials of at least 1 year duration, 

with severe exacerbations as a primary end point, LABA added to low- to medium-dose ICS 

significantly reduced the number of severe exacerbations in patients who had moderate asthma 

(O'Byrne et al. 2001; Pauwels et al. 1997) and reduced the number of patients who withdrew 

from the study because of an excessive number of exacerbations (Tattersfield et al. 1999). 

These results have been confirmed in a recent meta-analysis (Masoli et al. 2005). Although the 

study was not designed to assess subgroups or to assess concomitant medication use during 

the trial, no increase in the primary outcome of asthma deaths or life-threatening experiences 

was seen in association with salmeterol in the 12,265 patients who self-reported taking ICS at 

baseline in the SMART trial; however, this finding should not be considered conclusive (Nelson 

et al. 2006). 

On the other hand, there did not appear to be a protective effect of ICS in the number of serious 

exacerbations reported in the formoterol pivotal trials. Although not statistically significant, an 

increased number of exacerbations were observed in the formoterol group (Chowdhury 2005). 

Thus, while the data do not necessarily support an increased risk of severe or serious 

exacerbations in patients who are taking LABA and are receiving concomitant ICS, data are 

also insufficient to establish definitively that ICS therapy completely obviates the risk. Further 

research is urgently needed to clarify this issue. 

Methylxanthines 

The Expert Panel recommends that sustained-release theophylline is an alternative but 

not preferred treatment for mild persistent asthma (Step 2 care) (Evidence A); it may also 

be used as alternative but not preferred adjunctive therapy with ICS (Evidence B). 

Theophylline, the principally used methylxanthine, provides mild or moderate bronchodilation in 

persons who have asthma. Theophylline is a nonselective phosphodiesterase inhibitor; as 

such, it has exhibited mild anti-inflammatory activity according to some but not all studies (Jaffar 

et al. 1996; Kidney et al. 1995; Page et al. 1998). 

Theophylline produces minimal to no effect on airway reactivity and significantly less control of 

asthma than low-dose ICS does (Dahl et al. 2002; Reed et al. 1998). The addition of 

theophylline to ICS produces a small improvement in lung function similar to doubling the dose 

of ICS (Evans et al. 1997; Lim et al. 2000; Suessmuth et al. 2003). In a 24-week randomized, 

placebo-controlled trial in patients who had poorly controlled asthma, the addition of 

theophylline or montelukast led to small improvement in lung function but did not improve 

episodes of poor asthma control, symptoms, or quality of life (American Lung Association 

Asthma Clinical Research Centers 2007). Thus, the main use of theophylline is as adjunctive 

therapy to ICS. Sustained-release theophylline may be considered as a nonpreferred 

alternative long-term preventive therapy when issues arise concerning cost or a patient’s 

aversion to inhaled medication. Monitoring serum concentrations of theophylline is essential to 

ensure that toxic concentrations are avoided. For sustained-release theophyllines, the serum 

concentration is obtained in the middle of the dosing interval, at least 3–5 days after initiation of 

theophylline and then at least 2 days after initiation of any factor known to affect theophylline 

clearance significantly. If patients experience signs and symptoms of toxicity (e.g., severe 

headache, tachycardia, nausea and vomiting), theophylline should be discontinued and a serum 

concentration obtained. 
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Tiotropium Bromide 

Tiotropium bromide is a new, long-acting inhaled anticholinergic indicated once daily for COPD; 

this drug has not been studied in the long-term management of asthma (Gross 2004), and it has 

not received FDA-approved labeling for use in treating asthma. Ipratropium bromide, a shortacting anticholinergic, also has not demonstrated effectiveness in long-term management of 

asthma (Kerstjens et al. 1992). 

QUICK-RELIEF MEDICATIONS 

Quick-relief medications are used to provide prompt relief of bronchoconstriction and its 

accompanying acute symptoms such as cough, chest tightness, and wheezing. These 

medications include SABAs and anticholinergics (ipratropium bromide). Although the onset of 

action is slow (>4 hours), systemic corticosteroids are important in the treatment of moderate or 

severe exacerbations because these medications prevent progression of the exacerbation, 

speed recovery, and prevent relapses. 

Anticholinergics 

The Expert Panel concludes that ipratropium bromide, administered in multiple doses 

along with SABA in moderate or severe asthma exacerbations in the ED, provides 

additive benefit (Evidence B). Patients who have more severe obstruction of airways appear 

to benefit the most (Rodrigo and Castro-Rodriguez 2005). Ipratropium bromide has been used, 

with some success, as a quick-relief medication to avoid use of as-needed albuterol in clinical 

research trials in patients who have mild asthma (Israel et al. 2004). It has not been compared 

adequately to SABAs, however, nor does it have FDA-approved labeling for use in treatment of 

asthma. 

Inhaled Short-Acting Beta2-Agonists 

The Expert Panel recommends that SABAs are the drug of choice for treating acute 

asthma symptoms and exacerbations and for preventing EIB (Evidence A). The SABAs 

(albuterol, levalbuterol, pirbuterol, etc.) relax airway smooth muscle and cause a prompt (within 

3–5 minutes) increase in airflow. All synthetic beta2-agonists exist chemically as racemic 

mixtures; however, the therapeutic activity primarily resides in the (R)-enantiomers and not the 

(S)-enantiomers. Due to the stereoselectivity of biological systems, the (R)-enantiomers are 

more active than the (S)-enantiomers. In vitro studies have suggested a possible deleterious 

effect of the (S)-enantiomer of albuterol on airway smooth muscle responsiveness and other 

airway cells (Berger 2003; Waldeck 1999). Therefore, a product containing only the active 

enantiomer of albuterol (levalbuterol) was developed and approved for clinical use. Some 

clinical studies suggested an improved efficacy of levalbuterol over racemic albuterol (Carl et al. 

2003; Nelson et al. 1998) when administered in equal (R)-albuterol doses; however, other trials 

have failed to detect any advantage of levalbuterol over racemic albuterol (Cockcroft and 

Swystun 1997; Lotvall et al. 2001; Qureshi et al. 2005). (See also Evidence Table 16, 

Bronchodilators: Levalbuterol.) Concerns about the safety of SABAs are discussed below. 

Formoterol, a LABA, has an onset of action similar to the SABAs (within 5 minutes) due to its 

lower lipophilicity than salmeterol (onset at 15 minutes) (Grembiale et al. 2002; Kips and 

Pauwels 2001). In acute bronchospasm induced by methacholine or exercise, formoterol 

improves FEV1 as rapidly as inhaled albuterol or terbutaline (Hermansen et al. 2006; Politiek et 

al. 1999). In a large, 12-week comparison trial in patients receiving ICS therapy, formoterol was 
Section 3, Component 4: Medications 

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as effective as terbutaline when used by outpatients as a quick-relief medication; fewer patients 

in the group that used formoterol experienced severe asthma exacerbations (Tattersfield et al. 

2001). Initial studies of formoterol delivered by DPI showed rapid improvement in lung function 

in patients who presented in the ED with acute exacerbation (Bateman et al. 2006; Boonsawat 

et al. 2003). The onset of action and efficacy is comparable when formoterol is administered 

with budesonide in combination inhalers (Balanag et al. 2006; Bateman et al. 2006). This result 

has led numerous investigators to assess the efficacy of the combination inhaler for adjustable 

therapy in conjunction with standard administration (see discussion in the section above on 

“Inhaled Corticosteroids, Variability in Response and Adjustable Dose Therapy.”) Although the 

Expert Panel is not currently recommending the use of formoterol as therapy for acute 

exacerbations, nor is formoterol approved for this indication, this area of research clearly 

warrants further investigation. 

Safety of Inhaled Short-Acting Beta2-Agonists 

KEY POINTS: SAFETY OF INHALED SHORT-ACTING 

BETA 2 -AGONISTS 

 SABAs are the most effective medication for relieving acute bronchospasm (Evidence A). 

 Increasing use of SABA treatment or using SABA >2 days a week for symptom relief (not 

prevention of EIB) generally indicates inadequate control of asthma and the need for 

initiating or intensifying anti-inflammatory therapy (Evidence C). 

 Regularly scheduled, daily, chronic use of SABA is not recommended (Evidence A). 

The Expert Panel recommends the use of SABA as the most effective medication for 

relieving acute bronchoconstriction; SABAs have few negative cardiovascular effects 

(Evidence A).

The Expert Panel does not recommend regularly scheduled, daily, long-term use of 

SABA (Evidence A).

SABAs are the mainstay of treatment for acute symptoms of bronchospasm. This is true both in 

routine outpatient management of persons who have asthma and for their treatment in the clinic 

or ED. The main SABAs in use today (i.e., albuterol, levalbuterol, and pirbuterol) are effective 

agonists and have few negative cardiovascular effects. In contrast, in the past, two SABAs 

(isoprenaline and fenoterol) which were less selective or used at higher doses have been 

associated with severe and fatal attacks of asthma. In addition, regular use of fenoterol 

produced a significant diminution in control of asthma and in objective measurements of 

pulmonary function (Sears et al. 1990). Regularly scheduled use of albuterol in patients who 

have mild or moderate asthma, compared to use of albuterol on an as-needed basis, resulted in 

no significant differences between groups in levels of asthma control. The regularly scheduled 

use of albuterol produced neither demonstrable benefits nor harmful effects (Dennis et al. 2000; 

Drazen et al. 1996). On the basis of these and other studies (Cockcroft et al. 1993; Ernst et al. 

1993; Mullen et al. 1993; O'Connor et al. 1992; Suissa et al. 1994; Van Schayck et al. 1991), 

the regularly scheduled daily use of SABA is not recommended. 
Section 3, Component 4: Medications 

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The frequency of SABA use can be clinically useful as a barometer of disease activity, because 

increasing use of SABA has been associated with increased risk for death or near death in 

patients who have asthma (Spitzer et al. 1992). Use of more than one SABA canister every 

1–2 months is also associated with an increased risk of an acute exacerbation that requires an 

ED visit or hospitalization (Crystal-Peters et al. 2002; Lieu et al. 1998; Schatz et al. 2005). 

Thus, the use of more than one SABA canister (e.g., albuterol, 200 puffs per canister), 

predominantly for quick-relief treatment during a 1-month period, most likely indicates 

overreliance on this drug and suggests inadequate control of asthma (Spitzer et al. 1992). 

Over the last few years, further studies have identified problems with chronic use of albuterol, 

especially when used without ICS (Eisner et al. 2001; Lemaitre et al. 2002). The possibility that 

regular albuterol use may be deleterious in some patients who have asthma was supported by 

studies that showed an increased risk of exacerbations in subjects who had elevated markers of 

inflammation as well as in those not taking ICS (Wraight et al. 2003, 2004). 

Several different mechanisms have been proposed for the adverse effects of regular use of 

SABA. Evidence has been reported for increased expression of CxCL8 (Gordon et al. 2003) 

and increased response to allergen challenge (Swystun et al. 2000) and exercise (Hancox et al. 

2002). In addition, decreases in lung function after stopping chronic use have been reported 

with regular use of SABAs (Hancox et al. 2000; Israel et al. 2000; Van Schayck et al. 2002). It 

is not possible to state with confidence which of these mechanisms is responsible for the 

increased exacerbation rate seen in large-scale observational studies. 

Sequencing of the beta2-agonist receptor gene has made it possible to identify polymorphisms, 

some of which may be relevant to the function of the receptor. Two studies have shown that 

subjects who are homozygous for arginine at position 16 (Arg/Arg 16) are more likely than 

patients who are homozygous for glycine (Gly/Gly 16) to experience decline in lung function 

when taking regularly scheduled daily albuterol treatment (Israel et al. 2000, 2004), although, as 

noted in “Component 1: Measures of Asthma Assessment and Monitoring,” the clinical 

significance of the difference in lung function has not been established. In addition, a 

retrospective genetic analysis reported that patients who have Arg/Arg 16 and regularly 

received albuterol experienced increased exacerbations compared to patients who had Arg/Gly 

and Gly/Gly (Taylor et al. 2000). Due to the complex genetic nature of the beta2-agonist 

receptor and its response, the current findings are not definitive in identifying the functional 

variant responsible for this adverse effect or the number of individuals in whom this effect may 

occur. The current data leave little doubt, however, that regularly scheduled administration of 

SABA can result in deleterious effects on lung function and asthma control in a subset of 

patients who have asthma. Although the mechanism of this effect is not clear, its association 

with polymorphisms of the beta2-receptor is becoming more clear. 

Systemic Corticosteroids 

The Expert Panel recommends the use of oral systemic corticosteroids in moderate or 

severe exacerbations (Evidence A).

The Expert Panel recommends that multiple courses of oral systemic corticosteroids, 

especially more than three courses per year, should prompt a reevaluation of the asthma 

management plan for a patient (Evidence C). The risk of adverse effects from systemic 

corticosteroids depends on dose and duration. Systemic corticosteroids can speed resolution of 

airflow obstruction and reduce the rate of relapse (Rowe et al. 2001a, b; Rowe et al. 2004; 

Scarfone et al. 1993; Smith et al. 2003). Common adverse effects of systemic corticosteroids 
Section 3, Component 4: Medications 

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include the potential for growth suppression, osteoporosis, cataracts, myopathy, adrenal 

suppression, increased appetite with weight gain, and development of cushingoid habitus 

consisting of moon facies, buffalo hump, central obesity with wasting of extremities, atrophy of 

the skin with the development of striae, and hirsutism. Psychologic disturbances—from 

increased emotional lability to frank psychosis—can occur, as well as hypertension, peptic ulcer 

disease, atherosclerosis, aseptic necrosis of bone, and diabetes mellitus. High-dose systemic 

corticosteroids can be immunosuppressive; if such treatment is used, appropriate steps should 

be taken to monitor and prevent infection (Spahn et al. 2003). 

In regard to risk of adverse effects related to short courses of systemic corticosteroids, little 

information is available, and available studies used different products at varying doses. One 

epidemiologic study suggests that children, 4–17 years of age, who require more than four 

courses of oral corticosteroids (average duration 6.4 days) as treatment for underlying disease 

have an increased risk of fracture (van Staa et al. 2003). Another study concluded that multiple 

short courses of oral corticosteroids (median four courses in the preceding year) in the 

treatment of asthma in children 2–17 years of age were not associated with any lasting effect on 

bone metabolism, bone mineralization, or adrenal function (Ducharme et al. 2003). In another 

study, children who received four or more bursts of oral corticosteroids for acute asthma 

exacerbations in the previous year demonstrated a subnormal response of the HPA axis to 

hypoglycemic stress or ACTH (Dolan et al. 1987). 

ROUTE OF ADMINISTRATION 

Medications for asthma can be administered by either inhaled or systemic routes. Systemic 

routes are oral (ingested) or parenteral (subcutaneous, intramuscular, or intravenous). The 

major advantages of delivering drugs directly into the lungs via inhalation are that higher 

concentrations can be delivered more effectively to the airways and that systemic side effects 

are lessened (Newhouse and Dolovich 1986). Some drugs are therapeutically active in asthma 

only when inhaled (e.g., most ICS preparations, cromolyn, salmeterol). 

Inhaled medications, or aerosols, are available in a variety of devices that differ in technique 

required and quantity of drug delivered to the lung. See figure 3–24 for a summary of issues to 

consider for different devices including inhalers, spacers, and nebulizers. Whatever device is 

selected, patients should be instructed in its use, and their technique should be checked 

regularly. 

Alternatives to CFC-Propelled MDIs 

Many inhaled medications currently used for asthma are available in MDIs. Historically, MDI 

technology has utilized chlorofluorocarbons (CFCs) as propellants. CFCs usually constitute 

95 percent or more of the formulation emitted from an MDI. CFCs are metabolically stable, and 

even the portion of an actuation that is systemically absorbed is quickly excreted unchanged via 

exhalation. CFCs have been found to deplete stratospheric ozone, however, and have been 

banned internationally. Although a temporary medical exemption has been granted, it is 

expected that MDIs with CFC propellant will be phased out completely. For example, albuterol 

CFC will be phased out by the end of 2008. Alternatives include MDIs with other propellants 

(nonchlorinated propellants such as HFA 134a do not have ozone-depleting properties); 

multidose, breath-activated DPIs; and other handheld devices with convenience and delivery 

characteristics similar to current MDIs. MDIs with HFA 134a have been approved for use with 

albuterol, levalbuterol, beclomethasone dipropionate, and fluticasone propionate. Additional 

non-CFC products and delivery systems are expected in the future. Albuterol MDIs with HFA 
Section 3, Component 4: Medications 

239 

August 28, 2007 

propellant deliver comparable doses to the lung and produce comparable efficacy and safety as 

albuterol CFC-MDIs (Lumry et al. 2001; Ramsdell et al. 1999; Shapiro et al. 2000a,b). 

Beclomethasone dipropionate with HFA propellant delivers a significantly greater dose to the 

lungs than its respective CFC-MDIs, however, resulting in lower recommended doses 

(figures 4–4a, b, c; 4–8a, b, c) (Busse et al. 1999; Leach et al. 1998; Richards et al. 2001), 

whereas fluticasone propionate with HFA propellant delivers slightly less drug to the lungs than 

the CFC-MDI but dosage recommendations are unchanged. During the phaseout of CFC 

products, clinicians will need to be informed of the alternatives and assist their patients in the 

transition to non-CFC products. 

Spacers and Valved Holding Chambers 

“Spacer” is a generic term that refers to simple open tubes that are placed on the mouthpiece of 

an MDI to extend it away from the mouth of the patient. Spacers have consisted of 

manufactured and homemade devices such as plastic bottles, corrugated ventilation tubing, 

toilet tissue cores, etc. Spacers have also been integrated with the MDI (triamcinolone 

acetonide, flunisolide HFA). 

VHCs are manufactured devices (Aerochamber, Optichamber, Prochamber, Vortex) that have 

one-way valves that do not allow the patient to exhale into the device. Thus, patients—either 

very young children or infants or those who for some other reason are unable to cooperate—

can breathe normally and have someone else actuate the device without loss of the actuated 

dose and obviating the need for coordinating actuation and inhalation. 

Both spacers and VHCs are intended to retain large particles emitted from the MDI so they do 

not deposit in the oropharynx and thereby lead to a higher proportion of small, respirable 

particles being inhaled. They perform this function to various degrees, however, depending 

upon their size and shape as well as the formulation of the MDI (drug, propellant, and/or 

excipients). Thus, a spacer or VHC can increase lung delivery of a drug from one MDI and 

decrease lung delivery from another (Ahrens et al. 1995; Dolovich 2000). In addition, in vitro 

and in vivo studies comparing various spacers and VHCs with the same MDI have 

demonstrated a two- to six-fold variation in the respirable dose emitted from the devices and 

two- to five-fold difference in systemic availability of the drug (Asmus et al. 2004; Liang et al. 

2002). 

VHCs are preferred over spacers because the vast majority of controlled clinical trials 

demonstrating safety and efficacy of drugs administered by MDIs that do not have integrated 

spacers and use an add-on device have been performed with VHCs (Dolovich et al. 2005). 

However, due to the significant variation found between the performance of specific VHCs and 

MDIs, it may be preferable to use the same combination of MDI and VHC reported in the 

individual drug study to achieve comparable results. No specific combination of MDI and VHC 

currently has been specifically approved by the FDA for use together. 
Section 3, Component 4: Medications 

240 

August 28, 2007 

Complementary and Alternative Medicine 

KEY POINTS: COMPLEMENTARY AND ALTERNATIVE 

MEDICINE 

 It is recommended that the clinician ask patients about all medications and treatments they 

are using for asthma and advise the patients that complementary and alternative medicines 

and treatments are not a substitute for the clinician’s recommendations for asthma treatment 

(Evidence D). 

 Evidence is insufficient to recommend or not recommend most complementary and 

alternative medicines or treatments. 

 Acupuncture is not recommended for the treatment of asthma (Evidence B). 

 Patients who use herbal treatments for asthma should be cautioned that there is the 

potential for harmful ingredients in herbal treatments and for interactions with recommended 

asthma medications (Evidence D). 

Alternative healing methods are not substitutes for recommended asthma management 

strategies (i.e., pharmacologic therapy, environmental control measures, or patient education). 

Although alternative healing methods may be popular, clinical trials that adequately address 

safety and efficacy are limited, and their scientific basis has not been established. 

The most widely known complementary and alternative medicine methods are acupuncture, 

homeopathy, herbal medicine, and Ayurvedic medicine (which includes transcendental 

meditation, herbs, and yoga). 

Because complementary and alternative medicine is reported to be used by as much as onethird of the U.S. population (Eisenberg et al. 1993), it is important to inquire about all the 

medications and interventions a patient uses and advise the patient accordingly (See 

“Component 2: Education for a Partnership in Asthma Care.”). 

ACUPUNCTURE 

The Expert Panel does not recommend the use of acupuncture for the treatment of 

asthma (Evidence B). Acupuncture involves the superficial insertion of thin needles along 

acupuncture points or acupoints on the body. (Acupressure is an alternative method of 

stimulating the same acupoints.) Two Cochrane database systematic reviews (Linde et al. 

2000; McCarney et al. 2004) of 7 and 11 randomized trials (with 174 and 324 participants, 

respectively) using real acupuncture and sham acupuncture to treat asthma or asthma-like 

symptoms found no statistically significant or clinically relevant effects for acupuncture 

compared to sham acupuncture. Both reviews concluded that adequate evidence to make 

recommendations about the value of acupuncture in asthma treatment is lacking. A 

meta-analysis of 11 RCTs published in the period 1970–2000, comparing real acupuncture with 

placebo acupuncture, found no evidence of an effect of acupuncture in reducing asthma 

symptoms (Martin et al. 2002). 
Section 3, Component 4: Medications 

241 

August 28, 2007 

CHIROPRACTIC THERAPY 

The Expert Panel concludes that there is insufficient evidence to recommend the use of 

chiropractic or related techniques in the treatment of asthma.

Chiropractic therapy and other forms of spinal or bodily manipulation or massage have been 

reported anecdotally to benefit patients who have asthma. Systematic reviews of chiropractic 

techniques in asthma (Balon and Mior 2004) and related therapies, such as the Alexander 

technique (Dennis 2000), found few randomized, controlled studies. Those studies, where 

available, showed mixed results, with perhaps some benefit in symptoms or health-related 

quality-of-life measures but no definitive improvement on more objective measures of asthma 

outcomes. 

HOMEOPATHY AND HERBAL MEDICINE 

The Expert Panel concludes that there is insufficient evidence to support effectiveness of 

homeopathy and that more clinical trial and observational data are necessary.

The Expert Panel concludes that there is insufficient evidence to recommend herbal 

products for treating asthma. Furthermore, because herbal products are not 

standardized, one must be aware that some may have harmful ingredients and that some 

may interact with other pharmaceutical products that the patient may be taking 

(Evidence D). 

Homeopathy deals with the use of diluted substances which cause symptoms in the undiluted 

form. A systematic review of homeopathy for asthma included six RCTs. The trials were of 

variable quality and used different homeopathic treatments, which limit the ability to reliably 

assess the possible role of homeopathy in asthma (McCarney et al. 2004). 

A variety of herbal products have been used alone and as adjunctive therapy for asthma with 

positive results in small trials that have not been duplicated (Gupta et al. 1998; Khayyal et al. 

2003; Lee et al. 2004; Urata et al. 2002). The National Center for Complementary and 

Alternative Medicine of the National Institutes of Health encourages the development of welldesigned clinical trials to assess with clarity the role of herbal products. 

BREATHING TECHNIQUES 

The Expert Panel concludes there is insufficient evidence to suggest that breathing 

techniques provide clinical benefit to patients who have asthma. Controlled studies have 

been conducted with breathing exercises (Holloway and Ram 2004), inspiratory muscle training 

(Ram et al. 2003; Weiner et al. 2002), and Buteyko breathing (Cooper et al. 2003) (raising blood 

PCO2 through hypoventilation). A systematic review of breathing exercises identified seven 

studies meeting inclusion criteria (Holloway and Ram 2004). Treatment interventions and 

outcome measurements varied greatly in these studies. Thus, although there was a suggestion 

of improvement in such outcomes as SABA use, quality of life, and exacerbations in persons 

who have asthma, no reliable conclusions could be drawn regarding the use of breathing 

exercises for treatment of asthma in clinical practice (Holloway and Ram 2004). Inspiratory 

muscle training has also been examined in a systematic review (Ram et al. 2003). In three 

studies in which the maximum inspiratory pressure (PImax) was reported, it was significantly 

improved compared to controls. In one study, increased PImax in women was accompanied by 

decreased perception of dyspnea and decreased SABA use (Weiner et al. 2002). A recent 
Section 3, Component 4: Medications 

242 

August 28, 2007 

randomized, double-blind, controlled study of 57 patients assessed the impact of two different 

breathing techniques on the use of SABA, controlling for the advice given to patients regarding 

the use of either breathing technique before using SABA. A marked reduction in SABA use was 

observed with both breathing techniques, but no significant changes occurred in the quality of 

life or in any physiological markers. This study suggests that, in mild persistent asthma, using 

breathing techniques before using SABA might curb overuse of SABA, and that the process of 

practicing breathing techniques may be more important than the type of breathing technique 

used (Slader et al. 2006). Larger studies are needed to confirm study findings. 

RELAXATION TECHNIQUES 

The Expert Panel concludes that, despite some encouraging data from small studies, 

further positive data from randomized, controlled studies will be necessary before 

relaxation techniques can be recommended in the treatment of asthma. Recent controlled 

studies have been conducted to investigate whether relaxation techniques, including 

biofeedback and hypotherapy, may be beneficial in asthma. Preliminary data suggest that 

relaxation techniques may help improve not only symptoms (which in studies appeared to 

improve nonspecifically) but also lung function (Lehrer et al. 2004; Loew et al. 2001). Due to 

limitations of size and clearly prespecified hypotheses, these studies would need further 

confirmation. A systematic review of RCTs of relaxation techniques (Huntley et al. 2002) 

concluded that there was a lack of data from well-conducted studies of relaxation therapies to 

recommend them in the treatment of asthma. This review did find some evidence, however, 

that muscle relaxation techniques in particular may lead to improvements in lung function. 

YOGA 

There is a paucity of well-controlled studies on the effects of yoga on asthma outcomes. 

A recent, well-controlled pilot study of one type of yoga (Iyengar) showed no significant effects 

on physiologic or health-related quality-of-life measures (Sabina et al. 2005). 
Section 3, Component 4: Medications 

243 

August 28, 2007 

FIGURE 3–22. LONG-TER M CONTROL MEDICATIONS 

Name/Products 

(Listed Alphabetically) Indications/Mechanisms Potential Adverse Effects 

Therapeutic Issues 

(Not All Inclusive) 

Corticosteroids 

(Glucocorticoids) 

Inhaled (ICS): 

Beclomethasone 

dipropionate 

Budesonide 

Flunisolide 

Fluticasone 

propionate 

Mometasone furoate 

Triamcinolone 

acetonide 

Indications 

 Long-term prevention of 

symptoms; suppression, 

control, and reversal of 

inflammation. 

 Reduce need for oral 

corticosteroid. 

Mechanisms 

 Anti-inflammatory. 

Block late reaction to 

allergen and reduce 

airway 

hyperresponsiveness. 

Inhibit cytokine 

production, adhesion 

protein activation, and 

inflammatory cell 

migration and activation. 

 Reverse beta2-receptor 

downregulation. Inhibit 

microvascular leakage. 

 Cough, dysphonia, oral thrush 

(candidiasis). 

 In high doses (see figures 4-

4b and 4–8b), systemic 

effects may occur, although 

studies are not conclusive, 

and clinical significance of 

these effects has not been 

established (e.g., adrenal 

suppression, osteoporosis, 

skin thinning, and easy 

bruising) (Barnes and 

Pedersen 1993; Kamada et 

al. 1996). In low-to-medium 

doses, suppression of growth 

velocity has been observed in 

children, but this effect may 

be transient, and the clinical 

significance has not been 

established (CAMP 2000; 

Guilbert et al. 2006). 

 Spacer/holding chamber 

devices with nonbreathactivated MDIs and mouth 

washing after inhalation 

decrease local side effects. 

 Preparations are not 

absolutely interchangeable 

on a mcg or per puff basis 

(see figures 4–4b and 4–8b 

for estimated clinical 

comparability). New 

delivery devices may 

provide greater delivery to 

airways; this change may 

affect dose. 

 The risks of uncontrolled 

asthma should be weighed 

against the limited risks of 

ICS therapy. The potential 

but small risk of adverse 

events is well balanced by 

their efficacy. (See text.) 

 “Adjustable dose” approach 

to treatment may enable 

reduction in cumulative dose 

of ICS treatment over time 

without sacrificing 

maintenance of asthma 

control. 

 Dexamethasone is not 

included as an ICS for longterm control because it is 

highly absorbed and has 

long-term suppressive side 

effects. 

Systemic: 

Methylprednisolone 

Prednisolone 

Prednisone 

Indications 

 For short-term (3–10 

days) “burst”: to gain 

prompt control of 

inadequately controlled 

persistent asthma. 

 For long-term prevention 

of symptoms in severe 

persistent asthma: 

suppression, control, and 

reversal of inflammation. 

Mechanisms 

 Same as inhaled. 

 Short-term use: reversible 

abnormalities in glucose 

metabolism, increased 

appetite, fluid retention, 

weight gain, mood alteration, 

hypertension, peptic ulcer, 

and rarely aseptic necrosis. 

 Long-term use: adrenal axis 

suppression, growth 

suppression, dermal thinning, 

hypertension, diabetes, 

Cushing’s syndrome, 

cataracts, muscle weakness, 

and—in rare instances—

impaired immune function. 

 Consideration should be 

given to coexisting conditions 

that could be worsened by 

systemic corticosteroids, such 

as herpes virus infections, 

varicella, tuberculosis, 

hypertension, peptic ulcer, 

diabetes mellitus, 

osteoporosis, and 

Strongyloides.

 Use at lowest effective 

dose. For long-term use, 

alternate-day a.m. dosing 

produces the least toxicity. 

If daily doses are required, 

one study shows improved 

efficacy with no increase in 

adrenal suppression when 

administered at 3 p.m. 

rather than in the morning 

(Beam et al. 1992). 
Section 3, Component 4: Medications 

244 

August 28, 2007 

FIGURE 3–22. LONG-TER M CONTROL MEDICATIONS 

(CONTINUED) 

Name/Products 

(Listed Alphabetically) Indications/Mechanisms Potential Adverse Effects Therapeutic Issues (Not All Inclusive)

Cromolyn Sodium 

and Nedocromil 

Indications 

 Long-term prevention of 

symptoms in mild persistent 

asthma; may modify 

inflammation. 

 Preventive treatment prior to 

exposure to exercise or 

known allergen. 

Mechanisms 

 Anti-inflammatory. Blocks 

early and late reaction to 

allergen. Interferes with 

chloride channel function. 

Stabilizes mast cell 

membranes and inhibits 

activation and release of 

mediators from eosinophils 

and epithelial cells. 

 Inhibits acute response to 

exercise, cold dry air, and 

SO2. 

 Cough and irritation. 

 15–20 percent of patients 

complain of an unpleasant 

taste from nedocromil.

 Therapeutic response to 

cromolyn and nedocromil 

often occurs within 2 

weeks, but a 4- to 6-week 

trial may be needed to 

determine maximum 

benefit. 

 Dose of cromolyn by MDI 

(1 mg/puff) may be 

inadequate to affect 

airway 

hyperresponsiveness. 

Nebulizer delivery 

(20 mg/ampule) may be 

preferred for some 

patients. 

 Safety is the primary 

advantage of these 

agents. 

Immunomodulators 

Omalizumab 

(Anti-IgE) 

For subcutaneous use 

Indications 

 Long-term control and 

prevention of symptoms in 

adults (≥12 years old) who 

have moderate or severe 

persistent allergic asthma 

inadequately controlled with 

ICS. 

Mechanisms 

 Binds to circulating IgE, 

preventing it from binding to 

the high-affinity (FcεRI) 

receptors on basophils and 

mast cells. 

 Decreases mast cell mediator 

release from allergen 

exposure. 

 Decreases the number of 

FcεRIs in basophils and 

submucosal cells. 

 Pain and bruising of 

injection sites has been 

reported in 5–20 percent of 

patients. 

 Anaphylaxis has been 

reported in 0.2 percent of 

treated patients. 

 Malignant neoplasms were 

reported in 0.5 percent of 

patients compared to 0.2 

percent receiving placebo; 

relationship to drug is 

unclear. 

 Monitor patients following 

injection. Be prepared 

and equipped to identify 

and treat anaphylaxis that 

may occur. 

 The dose is administered 

either every 2 or 4 weeks 

and is dependent on the 

patient’s body weight and 

IgE level before therapy. 

 A maximum of 150 mg 

can be administered in 

one injection. 

 Needs to be stored under 

refrigeration at 2–8 °C. 

 Whether patients will 

develop significant 

antibody titers to the drug 

with long-term 

administration is 

unknown. 
Section 3, Component 4: Medications 

245 

August 28, 2007 

FIGURE 3–22. LONG-TER M CONTROL MEDICATIONS 

(CONTINUED) 

Name/Products 

(Listed Alphabetically) Indications/Mechanisms Potential Adverse Effects 

Therapeutic Issues 

(Not All Inclusive)

Leukotriene Receptor Mechanisms 

Antagonists (LTRAs)  Leukotriene receptor 

antagonist; selective 

competitive inhibitor of 

CysLT1 receptor.

 May attenuate EIB in some 

patients, but less effective 

than ICS therapy (Vidal et al. 

2001). 

 Do not use LTRA + LABA as 

a substitute for ICS + LABA. 

Montelukast tablets and Indications 

granules  Long-term control and 

prevention of symptoms in 

mild persistent asthma for 

patients ≥1 year of age. 

May also be used with ICS 

as combination therapy in 

moderate persistent 

asthma. 

 No specific adverse 

effects have been 

identified. 

 Rare cases of ChurgStrauss have occurred, 

but the association is 

unclear. 

 A flat dose-response curve, 

without further benefit, if dose 

is increased above those 

recommended. 

Zafirlukast 

tablets 

 Long-term control and 

prevention of symptoms in 

mild persistent asthma for 

patients ≥7 years of age. May 

also be used with ICS as 

combination therapy in 

moderate persistent 

asthma.

 Postmarketing 

surveillance has reported 

cases of reversible 

hepatitis and, rarely, 

irreversible hepatic 

failure resulting in death 

and liver transplantation. 

 Administration with meals 

decreases bioavailability; 

take at least 1 hour before or 

2 hours after meals. 

 Zafirlukast is a microsomal 

P450 enzyme inhibitor that 

can inhibit the metabolism of 

warfarin. INRs should be 

monitored during 

coadministration. 

 Patients should be warned to 

discontinue use if they 

experience signs and 

symptoms of liver dysfunction 

(right upper quadrant pain, 

pruritis, lethargy, jaundice, 

nausea), and patients’ ALTs 

should be monitored. 

5-Lipoxygenase 

Inhibitor 

Mechanisms 

 Inhibits the production of 

leukotrienes from 

arachidonic acid, both LTB4

and the cysteinyl 

leukotrienes.

 

Zileuton tablets Indications 

 Long-term control and 

prevention of symptoms in 

mild persistent asthma for 

patients ≥12 years of age. 

 May be used with ICS as 

combination therapy in 

moderate persistent asthma 

in patients ≥12 years of age.

 Elevation of liver 

enzymes has been 

reported. Limited case 

reports of reversible 

hepatitis and 

hyperbilirubinemia. 

 Zileuton is microsomal P450 

enzyme inhibitor that can 

inhibit the metabolism of 

warfarin and theophylline. 

Doses of these drugs should 

be monitored accordingly. 

 Monitor hepatic enzymes 

(ALT). 
Section 3, Component 4: Medications 

246 

August 28, 2007 

FIGURE 3–22. LONG-TER M CONTROL MEDICATIONS 

(CONTINUED) 

Name/Products 

(Listed Alphabetically) Indications/Mechanisms Potential Adverse Effects Therapeutic Issues (Not All Inclusive)

Long-Acting 

Beta2-Agonists 

(LABA) 

Inhaled LABA: 

Formoterol 

Salmeterol 

Indications 

 Long-term prevention of 

symptoms, added to ICS 

 Prevention of EIB. 

 Not to be used to treat acute 

symptoms or exacerbations. 

Mechanisms 

 Bronchodilation. Smooth 

muscle relaxation following 

adenylate cyclase activation 

and increase in cyclic AMP, 

producing functional 

antagonism of 

bronchoconstriction. 

 Compared to SABA, 

salmeterol (but not formoterol) 

has slower onset of action 

(15–30 minutes). Both 

salmeterol and formoterol 

have longer duration (>12 

hours) compared to SABA. 

 Tachycardia, skeletal 

muscle tremor, 

hypokalemia, 

prolongation of QTc 

interval in overdose. 

 A diminished 

bronchoprotective effect 

may occur within 1 week 

of chronic therapy. 

Clinical significance has 

not been established. 

 Potential risk of 

uncommon, severe, lifethreatening or fatal 

exacerbation; see text for 

additional discussion 

regarding safety of 

LABAs. 

 Not to be used to treat acute 

symptoms or exacerbations. 

 Should not be used as 

monotherapy for long-term 

control of asthma or as 

anti-inflammatory therapy. 

 May provide more effective 

symptom control when added 

to standard doses of ICS 

compared to increasing the 

ICS dosage. 

 Clinical significance of 

potentially developing 

tolerance is uncertain, 

because studies show 

symptom control and 

bronchodilation are 

maintained. 

 Decreased duration of 

protection against EIB may 

occur with regular use. 

Oral: 

Albuterol, 

sustained-release 

 Inhaled route is preferred 

because LABAs are longer 

acting and have fewer side 

effects than oral sustainedrelease agents. Oral agents 

have not been adequately 

studied as adjunctive therapy 

with ICS. 

Methylxanthines 

Theophylline, 

sustained-release 

tablets and capsules 

Indications 

 Long-term control and 

prevention of symptoms in 

mild persistent asthma or as 

adjunctive with ICS, in 

moderate or persistent 

asthma. 

Mechanisms 

 Bronchodilation. Smooth 

muscle relaxation from 

phosphodiesterase inhibition 

and possibly adenosine 

antagonism. 

 May affect eosinophilic 

infiltration into bronchial 

mucosa as well as 

decreases T-lymphocyte 

numbers in epithelium. 

 Increases diaphragm 

contractility and mucociliary 

clearance. 

 Dose-related acute 

toxicities include 

tachycardia, nausea and 

vomiting, 

tachyarrhythmias (SVT), 

central nervous system 

stimulation, headache, 

seizures, hematemesis, 

hyperglycemia, and 

hypokalemia. 

 Adverse effects at usual 

therapeutic doses include 

insomnia, gastric upset, 

aggravation of ulcer or 

reflux, increase in 

hyperactivity in some 

children, difficulty in 

urination in elderly males 

who have prostatism. 

 Maintain steady-state serum 

concentrations between 5 and 

15 mcg/mL. Routine serum 

concentration monitoring is 

essential due to significant 

toxicities, narrow therapeutic 

range, and individual 

differences in metabolic 

clearance. Absorption and 

metabolism may be affected 

by numerous factors which 

can produce significant 

changes in steady-state serum 

theophylline concentrations. 

 Patients should be told to 

discontinue if they experience 

toxicity. 

 Not generally recommended 

for exacerbations. There is 

minimal evidence for added 

benefit to optimal doses of 

SABA. Serum concentration 

monitoring is mandatory. 

Key: anti-IgE, anti-immunoglobulin E, EIB, exercise-induced bronchospasm; INR, International Normalized Ratio; LABA, long-acting 

beta2-agonist; MDI, metered-dose inhaler; SABA, inhaled short-acting beta2-agonist 
Section 3, Component 4: Medications 

247 

August 28, 2007 

FIGURE 3–23. QUICK- RELIEF MEDICATIONS 

Name/Products Indications/Mechanisms Potential Adverse Effects Therapeutic Issues 

Short-Acting Beta2-

Agonists (SABA) 

Inhaled SABA: 

Albuterol 

Levalbuterol 

Pirbuterol 

Indications

 Relief of acute symptoms;

quick-relief medication. 

 Preventive treatment for EIB 

prior to exercise. 

Mechanisms 

 Bronchodilation. Binds to 

the beta2-adrenergic 

receptor, producing smooth 

muscle relaxation following 

adenylate cyclase activation 

and increase in cyclic AMP 

producing functional 

antagonism of 

bronchoconstriction. 

 Tachycardia, skeletal 

muscle tremor, 

hypokalemia, increased 

lactic acid, headache, 

hyperglycemia. Inhaled 

route, in general, 

causes few systemic 

adverse effects. 

Patients with 

preexisting 

cardiovascular disease, 

especially the elderly, 

may have adverse 

cardiovascular 

reactions with inhaled 

therapy.

 Drugs of choice for acute 

bronchospasm. Inhaled 

route has faster onset, fewer 

adverse effects, and is more 

effective than systemic 

routes. The less 

beta2-selective agents 

(isoproterenol, 

metaproterenol, isoetharine, 

and epinephrine) are not 

recommended due to their 

potential for excessive 

cardiac stimulation, 

especially in high doses. 

Oral systemic beta2-agonists 

are not recommended. 

 For patients who have 

intermittent asthma, 

regularly scheduled daily 

use neither harms nor 

benefits asthma control 

(Drazen et al. 1996). 

Regularly scheduled daily 

use is not recommended. 

 Regular use >2 days/week 

for symptom control (not 

prevention of EIB), 

increasing use, or lack of 

expected effect indicates 

inadequate asthma control. 

 For patients frequently using 

SABA, anti-inflammatory 

medication should be 

initiated or intensified. 

 Levalbuterol at one-half the 

mcg dose produces 

clinically comparable 

bronchodilation and 

systemic side effects as 

racemic albuterol. 
Section 3, Component 4: Medications 

248 

August 28, 2007 

FIGURE 3–23. QUICK-RELIEF MEDICATIONS (CONTINUED) 

Name/Products Indications/Mechanisms Potential Adverse Effects Therapeutic Issues 

Anticholinergics 

Ipratropium 

bromide 

Indications 

 Relief of acute 

bronchospasm (See 

Therapeutic Issues 

column.). 

Mechanisms 

 Bronchodilation. 

Competitive inhibition of 

muscarinic cholinergic 

receptors. 

 Reduces intrinsic vagal 

tone of the airways. May 

block reflex 

bronchoconstriction 

secondary to irritants or to 

reflux esophagitis. 

 May decrease mucous 

gland secretion. 

 Drying of mouth and 

respiratory secretions, 

increased wheezing in 

some individuals, blurred 

vision if sprayed in eyes. 

If used in the ED, 

produces less cardiac 

stimulation than SABAs.

 Reverses only cholinergically 

mediated bronchospasm; 

does not modify reaction to 

antigen. Does not block EIB. 

 Multiple doses of ipratropium 

in the ED provide additive 

effects to SABA. 

 May be alternative for 

patients who do not tolerate 

SABA. 

 Treatment of choice for 

bronchospasm due to 

beta-blocker medication. 

 Has not proven to be 

efficacious as long-term 

control therapy for asthma. 

Corticosteroids 

Systemic: 

Methylprednisolone 

Prednisolone 

Prednisone 

Indications 

 For moderate or severe 

exacerbations to prevent 

progression of 

exacerbation, reverse 

inflammation, speed 

recovery, and reduce rate 

of relapse. 

Mechanisms

 Anti-inflammatory. 

See figure 3–22. 

 Short-term use: reversible 

abnormalities in glucose 

metabolism, increased 

appetite, fluid retention, 

weight gain, facial 

flushing, mood alteration, 

hypertension, peptic ulcer, 

and rarely aseptic 

necrosis. 

 Consideration should be 

given to coexisting 

conditions that could be 

worsened by systemic 

corticosteroids, such as 

herpes virus infections, 

varicella, tuberculosis, 

hypertension, peptic ulcer, 

diabetes mellitus, 

osteoporosis, and 

Strongyloides. 

 Short-term therapy should 

continue until patient’s 

symptoms resolve. This 

usually requires 3–10 days 

but may require longer. 

— Action may begin within 

an hour. 

 There is no evidence that 

tapering the dose following 

improvement is useful in 

preventing a relapse in 

asthma exacerbations. 

 Other systemic 

corticosteroids such as 

hydrocortisone and 

dexamethasone given in 

equipotent daily doses are 

likely to be as effective as 

prednisolone. 

Key: ED, emergency department; EIB, exercise-induced bronchospasm 
Section 3, Component 4: Medications 

249 

August 28, 2007 

FIGURE 3–24. AEROSO L DELIVERY DEVICES 

Device/Drugs Population Optimal Technique* Therapeutic Issues 

Metered-dose inhaler 

(MDI) 

 Beta2-agonists 

 Corticosteroids 

 Cromolyn sodium 

 Anticholinergics 

≥5 years old 

(<5 with spacer or 

valved holding 

chamber (VHC) 

mask) 

Actuation during a slow (30 L/min 

or 3–5 seconds) deep inhalation, 

followed by 10-second breathhold. 

Under laboratory conditions, openmouth technique (holding MDI 

2 inches away from open mouth) 

enhances delivery to the lung. This 

technique, however, has not been 

shown to enhance clinical benefit 

consistently compared to closedmouth technique (inserting MDI 

mouthpiece between lips and 

teeth). 

Slow inhalation and coordination of 

actuation during inhalation may be 

difficult, particularly in young 

children and elderly. Patients may 

incorrectly stop inhalation at 

actuation. Deposition of 50–80 

percent of actuated dose in 

oropharynx. Mouth washing and 

spitting is effective in reducing the 

amount of drug swallowed and 

absorbed systemically (Selroos and 

Halme 1991). 

Lung delivery under ideal conditions 

varies significantly between MDIs 

due to differences in formulation 

(suspension versus solution), 

propellant (chlorofluorocarbon 

(CFC) versus hydrofluoralkane 

(HFA)), and valve design (Dolovich 

2000). For example, inhaled 

corticosteroid (ICS) delivery varies 

from 5–50 percent (Kelly 2003). 

Breath-actuated MDI 

 Beta2-agonist 

≥5 years old Tight seal around mouthpiece and 

slightly more rapid inhalation than 

standard MDI (see above) followed 

by 10-second breathhold. 

May be particularly useful for 

patients unable to coordinate 

inhalation and actuation. May also 

be useful for elderly patients 

(Newman et al. 1991). Patients 

may incorrectly stop inhalation at 

actuation. Cannot be used 

with currently available 

spacer/valved-holding chamber 

(VHC) devices. 

Dry powder inhaler 

(DPI) 

 Beta2-agonists 

 Corticosteroids 

 Anticholinergics 

≥4 years old Rapid (60 L/min or 1–2 seconds), 

deep inhalation. Minimally effective 

inspiratory flow is device 

dependent. 

Most children <4 years of age may 

not generate sufficient inspiratory 

flow to activate the inhaler. 

Dose is lost if patient exhales 

through device after actuating. 

Delivery may be greater or lesser 

than MDI, depending on device and 

technique. Delivery is more flow 

dependent in devices with highest 

internal resistance. Rapid inhalation 

promotes greater deposition in 

larger central airways (Dolovich 

2000). Mouth washing and spitting 

is effective in reducing amount of 

drug swallowed and absorbed 

(Selroos and Halme 1991). 
Section 3, Component 4: Medications 

250 

August 28, 2007 

FIGURE 3–24. AEROSOL DELI VERY DEVICES (CONTINUED) 

Device/Drugs Population Optimal Technique* Therapeutic Issues 

≥4 years old Slow (30 L/min or 3–5 seconds) 

deep inhalation, followed by 10-

second breathhold immediately 

following actuation. 

Actuate only once into spacer/VHC 

per inhalation (O'Callaghan et al. 

1994). 

Spacer or valved holding 

chamber (VHC) 

<4 years old VHC 

with face mask 

If face mask is used, it should have 

a tight fit and allow 3–5 inhalations 

per actuation (Amirav and 

Newhouse 2001; Everard et al. 

1992). 

Rinse plastic VHCs once a month 

with low concentration of liquid 

household dishwashing detergent 

(1:5,000 or 1–2 drops per cup of 

water) and let drip dry (Pierart et al. 

1999; Wildhaber et al. 2000). 

Indicated for patients who have 

difficulty performing adequate MDI 

technique. 

May be bulky. Simple tubes do not 

obviate coordinating actuation and 

inhalation. The VHCs are preferred. 

Face mask allows MDIs to be used 

with small children. However, use 

of a face mask reduces delivery to 

lungs by 50 percent (Wildhaber et 

al. 1999). The VHC improves lung 

delivery and response in patients 

who have poor MDI technique. 

The effect of a spacer or VHC on 

output from an MDI depends on 

both the MDI and device type; thus 

data from one combination should 

not be extrapolated to all others 

(Ahrens et al. 1995; Dolovich 2000). 

Spacers and/or VHCs decrease 

oropharyngeal deposition and thus 

decrease risk of topical side effects 

(e.g., thrush) (Salzman and 

Pyszczynski 1988; Toogood et al. 

1984). 

Spacers will also reduce the 

potential systemic availability of 

ICSs with higher oral absorption 

(Brown et al. 1990; Selroos and 

Halme 1991). However, 

spacer/VHCs may increase 

systemic availability of ICSs that are 

poorly absorbed orally by enhancing 

delivery to lungs (Dempsey et al. 

1999; Kelly 2003). 

No clinical data are available on use 

of spacers or VHCs with ultrafineparticle-generated HFA MDIs. 

Use antistatic VHCs or rinse plastic 

nonantistatic VHCs with dilute 

household detergents to enhance 

delivery to lungs and efficacy 

(Lipworth et al. 2002; Pierart et al. 

1999; Wildhaber et al. 2000). This 

effect is less pronounced for 

albuterol MDIs with HFA propellant 

than for albuterol MDIs with CFC 

propellant (Chuffart et al. 2001). 

As effective as nebulizer for 

delivering SABAs and 

anticholinergics in mild to moderate 

exacerbations; data in severe 

exacerbations are limited. 
Section 3, Component 4: Medications 

251 

August 28, 2007 

FIGURE 3–24. AEROSOL DELI VERY DEVICES (CONTINUED) 

Device/Drugs Population Optimal Technique* Therapeutic Issues 

Nebulizer 

 Beta2-agonists 

 Corticosteroids 

 Cromolyn sodium 

 Anticholinergics 

Patients of any 

age who cannot 

use MDI with VHC 

and face mask. 

Slow tidal breathing with occasional 

deep breaths. Tightly fitting face 

mask for those unable to use 

mouthpiece. 

Using the “blow by” technique (i.e., 

holding the mask or open tube near 

the infant’s nose and mouth) is not 

appropriate. 

Less dependent on patient’s 

coordination and cooperation. 

Delivery method of choice for 

cromolyn sodium in young children. 

May be expensive; time consuming; 

bulky; output is dependent on 

device and operating parameters 

(fill volume, driving gas flow); 

internebulizer and intranebulizer 

output variances are significant 

(Dolovich 2000). Use of a face 

mask reduces delivery to lungs by 

50 percent (Wildhaber et al. 1999). 

Nebulizers are as effective as MDIs 

plus VHCs for delivering 

bronchodilators in the ED for mild to 

moderate exacerbations; data in 

severe exacerbations are limited. 

Choice of delivery system is 

dependent on resources, 

availability, and clinical judgment of 

the clinician caring for the patient 

(Cates et al. 2002; Dolovich et al. 

2005). 

Potential for bacterial infections if 

not cleaned properly. 

Key: ED, emergency department; SABAs, inhaled short-acting beta2-agonists 

*See figures in “Component 2: Education for a Partnership in Asthma Care” for description of MDI and DPI techniques. 
Section 3, Component 4: Medications 

252 

August 28, 2007 

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SECTION 4, MANAGING ASTHMA LONG TERM: OVERVIEW 

KEY POINTS: MANAGING ASTHMA LONG TERM 

 The goal for therapy is to control asthma by (Evidence A): 

— Reducing impairment 

♦ Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the 

daytime, in the night, or after exertion) 

♦ Require infrequent use (≤2 days a week) of inhaled short-acting beta2-agonist 

(SABA) for quick relief of symptoms (not including prevention of exercise-induced 

bronchospasm (EIB)) 

♦ Maintain (near) normal pulmonary function 

♦ Maintain normal activity levels (including exercise and other physical activity and 

attendance at work or school) 

♦ Meet patients’ and families’ expectations of and satisfaction with asthma care 

— Reducing risk 

♦ Prevent recurrent exacerbations of asthma and minimize the need for emergency 

department (ED) visits or hospitalizations 

♦ Prevent progressive loss of lung function; for children, prevent reduced lung growth 

♦ Provide optimal pharmacotherapy with minimal or no adverse effects 

 A stepwise approach to pharmacologic therapy is recommended to gain and maintain 

control of asthma in both the impairment and risk domains (Evidence A): 

— The type, amount, and scheduling of medication is dictated by asthma severity for 

initiating therapy and the level of asthma control for adjusting therapy (Evidence A). 

— Step-down therapy is essential to identify the minimum medication necessary to 

maintain control (Evidence D). 

 Monitoring and followup is essential (Evidence B). 

— When initiating therapy, monitor at 2- to 6-week intervals to ensure that asthma control is 

achieved (Evidence D). 

— Regular followup contacts at 1- to 6-month intervals, depending on level of control, are 

recommended to ensure that control is maintained and the appropriate adjustments in 

therapy are made: step up if necessary or step down if possible. Consider 3-month 

intervals if a step down in therapy is anticipated (Evidence D). 
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 Because asthma is a chronic inflammatory disorder of the airway, persistent asthma is most 

effectively controlled with daily long-term control medication directed toward suppression of 

airway inflammation (Evidence A). 

 Therapeutic strategies should be considered in concert with clinician-patient partnership 

strategies; education of patients is essential for achieving optimal pharmacologic therapy 

(Evidence A). 

 At each step, patients should be advised to avoid or control allergens (Evidence A), irritants, 

or comorbid conditions that make the patient’s asthma worse (Evidence B). 

 A written asthma action plan detailing for the individual patient the daily management 

(medications and environmental control strategies) and how to recognize and handle 

worsening asthma is recommended for all patients; it is particularly recommended for 

patients who have moderate or severe asthma, a history of severe exacerbations, or poorly 

controlled asthma (Evidence B). The written asthma action plan can be either symptom or 

peak-flow based; evidence shows similar benefits for each (Evidence B). 

 Referral to an asthma specialist for consultation or comanagement of the patient is 

recommended if there are difficulties achieving or maintaining control of asthma; if additional 

education is needed to improve adherence; if the patient requires step 4 care or higher 

(step 3 care or higher for children 0–4 years of age); or if the patient has had an 

exacerbation requiring hospitalization. Consider referral if a patient requires step 3 care 

(step 2 care for children 0–4 years of age) or if additional testing for the role of allergy is 

indicated (Evidence D). 

KEY DIFFERENCES FROM 1997 AND 2002 

EXPERT PANEL REPORTS 

 Recommendations for managing asthma in children 0–4 and 5–11 years of age are 

presented separately from recommendations for managing asthma in youths ≥12 years of 

age and adults. 

 Treatment decisions for initiating long-term control therapy are based on classifying severity 

(considering both the impairment and risk domains) and selecting a corresponding step for 

treatment. Recommendations on when to initiate therapy in children 0–4 years of age have 

been revised. 

 Treatment decisions for adjusting therapy and maintaining control are based on assessing 

the level of asthma control (considering both the impairment and risk domains). 

 The distinction between the domains of impairment and risk for assessing asthma control 

and guiding decisions for therapy emphasizes the need to consider separately asthma’s 

effects on quality of life and functional capacity on an ongoing basis (i.e., in the present) and 

the risks it presents for adverse events in the future, such as exacerbations and progressive 

reduction in lung growth or lung function. These domains of asthma may respond 

differentially to treatment. 
Section 4, Managing Asthma Long Term: Overview 

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August 28, 2007 

 Stepwise approach to managing asthma has been expanded to include six steps of care to 

simplify the actions within each step. For example, previous guidelines had several 

progressive actions within step 3, whereas the current guidelines separate the actions into 

different steps. 

 Treatment options within the steps have been revised, especially: 

— For patients not well controlled on low-dose inhaled corticosteroid (ICS), increasing the 

dose of ICSs to medium dose is recommended before adding adjunctive therapy in the 

0–4 years age group; for other age groups (children 5–11 years of age and youths 

≥12 years of age and adults), increasing the dose of ICS to medium dose or adding 

adjunctive therapy to a low dose of ICS are considered as equal options. 

— Evidence for the selection of adjunctive therapy is limited in children under 12 years of 

age; recommendations vary according to the assessment of impairment or risk. 

— Steps 5–6 for youths ≥12 years of age and adults include consideration of omalizumab. 

 Managing special situations has been expanded to include racial and ethnic disparities. 

Introduction 

The literature searches and results for all four components of asthma management (See 

section 3.) provided the foundation for the update of this section: “Managing Asthma Long 

Term.” The Expert Panel’s recommendations for managing asthma long term integrate the 

four components of therapy into a stepwise therapeutic approach for managing asthma long 

term, in which medications are increased as necessary and decreased if possible to achieve 

and maintain control of asthma. The general stepwise approach is applicable to all patients who 

have asthma. Adaptations are required, however, to tailor the approach to the needs of 

different patient groups. For example, it is important to consider the age of the patient, because 

the course of the disease may change over time, and the relevance of different assessment 

measures and potential short- and long-term impact of medications may be age related. Thus, 

the Expert Panel’s recommendations are presented for three different age groups: children 0–4 

years of age, children 5–11 years of age, and youths ≥12 years of age and adults, based on the 

following considerations: 

 Evidence available demonstrating safety and efficacy for many medications is age 

dependent (e.g., many clinical trials have enrolled patients ≥12 years of age only, and it is 

unknown if these results are applicable to children 5–11 years of age; furthermore, few trial 

data are available for children <5 years of age). 

 Issues related to drug delivery are often age dependent (e.g., the ability of a child and/or 

their caregivers to use nebulizers versus metered dose inhalers (MDIs) versus dry powder 

inhaler (DPI) devices). 

 Approval of medications by the U.S. Food and Drug Administration (FDA) is based on age. 

 Lung function measurements, used to classify asthma severity (impairment domain) and 

control (risk domain), are usually not possible in children <5 years of age, and 
Section 4, Managing Asthma Long Term: Overview 

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August 28, 2007 

interpretations of these tests may require special considerations for children 5–11 years of 

age. 

 The characterization of various wheezing phenotypes is frequently age dependent, with 

different patterns among children 0–4 years of age compared to children 5–11 years of age 

or children 12 years of age or older and adults (e.g., severe episodes of virus-induced 

wheezing (risk domain) with periods of no symptoms in between episodes (impairment 

domain) are most frequently seen in preschool children). 

Furthermore, situations arise which require special consideration of therapeutic options within 

the stepwise care: EIB, surgery, pregnancy, and racial and ethnic disparity. 

This section, “Managing Asthma Long Term,” will present recommendations for each group 

separately: managing asthma long term in children (ages 0–4 years and 5–11 years), 

managing asthma long term in youths ≥12 years of age and adults, and managing special 

situations in asthma. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

SECTION 4, MANAGING ASTHMA LONG TERM IN CHILDREN 0–4 YEARS 

OF AGE AND 5–11 YEARS OF AGE 

Diagnosis and Prognosis of Asthma in Children 

Long-term management decisions begin with diagnosis and an appreciation for factors that may 

influence the prognosis for asthma in children. 

DIAGNOSIS OF ASTHMA 

0–4 Years of Age: The Expert Panel recommends that essential elements in the 

evaluation include the history, symptoms, physical examination, and assessment of 

quality of life, as discussed in “Component 1: Measures of Asthma Assessment and 

Monitoring.” A therapeutic trial with medications listed in figure 4–1a will also aid in the 

diagnosis.

Several studies show that as many as 50–80 percent of children who have asthma develop 

symptoms before their fifth birthdays. Diagnosis can be difficult in this age group and has 

important implications. On the one hand, asthma in early childhood is frequently 

underdiagnosed (receiving such inappropriate labels as chronic bronchitis, wheezy bronchitis, 

reactive airway disease (RAD), recurrent pneumonia, gastroesophageal reflux, and recurrent 

upper respiratory tract infections). Therefore, many infants and young children do not receive 

adequate therapy. On the other hand, not all wheeze and cough are caused by asthma, and 

caution is needed to avoid giving infants and young children inappropriate prolonged asthma 

therapy. Episodic or chronic wheeze, cough, and breathlessness also may be seen in other, 

less common, conditions, including cystic fibrosis, vascular ring, tracheomalacia, primary 

immunodeficiency, congenital heart disease, parasitic disease, and foreign-body aspiration. 

Diagnosis is complicated by the difficulty in obtaining objective measurements of lung function in 

this age group. 

5–11 Years of Age: The Expert Panel recommends that the diagnosis in children 5 years 

of age and older should follow the same procedures recommended in “Component 1: 

Measures of Asthma Assessment and Monitoring.” 

PROGNOSIS OF ASTHMA 

Although asthma clearly has been demonstrated to be associated with airway inflammation and 

structural changes in adult patients, the age when these changes begin in asthma has not yet 

been defined precisely. Elevations in both inflammatory cells and mediators have been 

demonstrated in bronchoalveolar lavage specimens obtained from preschool children who have 

recurrent wheezing (Krawiec et al. 2001). Recently, endobronchial biopsy specimens from 

infants who have wheezing and documented airflow obstruction that was both reversible and 

nonreversible following the administration of bronchodilator were compared to four other groups 

of subjects: infants who had wheezing without airflow obstruction, school-aged children who 

had difficult-to-control asthma, and both school-aged children and adults who did not have 

asthma (Saglani et al. 2005). In the infants who had wheezing, regardless of bronchodilator 

reversibility or atopic status, the characteristic histopathologic features of thickening of the 

laminar reticularis and eosinophil inflammation were absent. Taken together, these data 

indicate that the airway inflammatory responses and structural changes that are characteristic of 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

asthma develop during the preschool years and may follow, and not precede, the physiologic 

changes associated with asthma. 

Among children 5 years of age and younger, the most common cause of asthma symptoms is 

viral respiratory infection. At present, the relative contributions of airway inflammation, bronchial 

smooth muscle abnormalities, or other structural factors in producing wheeze with acute viral 

upper respiratory infections are unknown. Two general patterns of illness appear in infants and 

children who have wheezing with acute viral upper respiratory infections: a remission of 

symptoms in the preschool years and persistence of asthma throughout childhood. No absolute 

markers are available to predict the prognosis of an individual child; however, an asthma 

predictive index has been developed that identifies risk factors for developing persistent asthma. 

Children under 3 years of age who had four or more episodes of wheezing in the past year that 

lasted more than 1 day and affected sleep are significantly likely to have persistent asthma after 

the age of 5 years if they also have either (1) one of the following: parental history of asthma, a 

physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens, OR (2) 

two of the following: evidence of sensitization to foods, ≥4 percent peripheral blood 

eosinophilia, or wheezing apart from colds (See section 2, “Definition and Pathophysiology and 

Pathogenesis of Asthma, and Natural History of Asthma.”). 

PREVENTION OF ASTHMA PROGRESSION 

The Expert Panel concludes that evidence to date does not support the previously 

hypothesized contention that early intervention with an ICS, either continuously (CAMP 

2000; Guilbert et al. 2006) or intermittently (Bisgaard and Szefler 2006), may alter the 

underlying severity or progression of the disease. ICSs should be used to control 

asthma symptoms and to improve the child’s quality of life, but their use should not be 

initiated or prolonged for the purpose of changing the natural history of the disease (i.e., 

the underlying severity or progression of asthma) (Evidence A).

Although a preliminary, retrospective study suggested that appropriate control of childhood 

asthma may prevent more serious asthma or irreversible obstruction in later years (Agertoft and 

Pedersen 1994), these observations were not verified in a more recent long-term randomized 

controlled trial (RCT) in children 5–12 years of age (CAMP 2000) (Evidence A). The best 

available evidence does not support the assumption that children 5–12 years of age who have 

mild or moderate persistent asthma, on average, have a progressive decline in lung function. A 

followup analysis from the Childhood Asthma Management Program (CAMP) study indicates, 

however, that a subset of participants in both treatment and placebo groups experienced 

progressive reductions in lung growth compared to predicted measures (Covar et al. 2004). 

Further studies are needed to assess this risk fully. 

Observational prospective data from other large groups of children suggest that the timing of the 

CAMP intervention was too late, as most loss of lung function in early childhood asthma 

appears to occur during the first 3–5 years of life (Martinez et al. 1995; Morgan et al. 2005). A 

recent study enrolled children 2–3 years of age who were at high risk of developing persistent 

asthma and compared ICS therapy to placebo. The study demonstrated that this intervention 

clearly reduced symptom burden and the frequency of exacerbations while the ICS was 

administered daily for 2 years, but this therapy did not prevent the reappearance of persistent 

symptoms in the year of followup after discontinuing therapy (Guilbert et al. 2006). 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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MONITORING ASTHMA PROGRESSION 

The Expert Panel recommends that the following measures be monitored over the course 

of children’s followup visits, especially in those children who have moderate or severe 

persistent asthma (require Step 3 care or higher), to assess both impairment and risk 

domains for the development of progressive disease: course of medications, including 

increasing use of SABAs and escalation of long-term control medications; episodes of 

severe exacerbations requiring systemic corticosteroids, urgent care visits, or 

hospitalizations; pulmonary function measures including prebronchodilator forced 

expiratory volume in 1 second/forced vital capacity (FEV1/FVC) and FEV1 (percent 

predicted) and postbronchodilator FEV1 (percent predicted) (Evidence B). If these 

measures so indicate, therapy should be stepped up to ensure adequate asthma control. 

See box 4–1 for a sample patient record for monitoring asthma progression in children. 

BOX 4–1. SAMPLE RECORD FOR MONITORING THE RISK DOMAIN 

IN CHILDREN: RISK OF ASTHMA PROGRESSION (INCREASED 

EXACERBATIONS OR NEED FOR DAILY MEDICATION, OR LOSS OF 

LUNG FUNCTION), AND POTENTIAL ADVERSE EFFECTS OF 

CORTICOSTEROID THERAPY 

Patient name: 

Date 

Long-term control medication 

ICS daily dose* 

LTRA 

LABA 

Theophylline 

Other 

Significant exacerbations 

Exacerbations 

(number/month) 

 

Oral systemic 

corticosteroids 

(number/year)* 

Hospitalization 

(number/year) 

Pulmonary function 

Prebronchodilator 

FEV1/FVC 

 

Prebronchodilator 

FEV1 percent predicted 

Postbronchodilator 

FEV1 percent predicted 

Percent bronchodilator 

reversibility 

Potential risk of adverse corticosteroid effects (as indicated by corticosteroid dose and duration of 

treatment) 

Height, cm 

Percentile 

Plots of growth velocity 

 

FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; LABA, long-acting beta2-agonist; 

LTRA, leukotriene receptor antagonist 

*Consider ophthalmologic exam and bone density measurement in children using high doses of ICS or multiple courses of oral 

corticosteroids. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

Although there is no indication that treatment alters the progression of asthma severity in 

children, asthma is highly variable over time (see sections on “Natural History” and 

“Pathophysiology”), and treatment may have to be adjusted accordingly. 

Treatment: Principles of Stepwise Therapy in Children 

The Expert Panel recommends that the goal of asthma therapy is to maintain long-term 

control of asthma with the least amount of medication and hence minimal risk for 

adverse effects. Control of asthma may be viewed in the context of two domains—

impairment and risk—and within these domains, defined as follows (Evidence A).

 Reducing impairment 

— Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the 

daytime, in the night, or after exertion) 

— Require infrequent use (≤2 days a week) of SABA for quick relief of symptoms (not 

including prevention of EIB) 

— Maintain (near) normal pulmonary function 

— Maintain normal activity levels (including exercise and other physical activity and 

attendance at work or school) 

— Meet patients’ and families’ expectations of and satisfaction with asthma care 

 Reducing risk 

— Prevent recurrent exacerbations of asthma and minimize the need for ED visits or 

hospitalizations 

— Prevent progressive loss of lung function; for children, prevent reduced lung growth 

— Provide optimal pharmacotherapy with minimal or no adverse effects 

The Expert Panel recommends that the stepwise approach to therapy, in which the dose 

and number of medications and frequency of administration are increased as necessary 

(Evidence B, extrapolated from studies in older children and adults) and decreased when 

possible (Evidence D), is used to achieve and maintain this control.

The distinction between assessing impairment and risk to make treatment decisions draws 

attention to the multifaceted nature of asthma and the need to consider all manifestations of the 

disease. Assessing both domains emphasizes the need to consider separately asthma’s effects 

on quality of life and functional capacity on an ongoing basis (i.e., at present) and the risks 

asthma presents for adverse events in the future, such as exacerbations or progressive 

reduction in lung growth. These domains may respond differentially to treatment. For example, 

a large study of children who had asthma revealed that 30 percent of the low-dose ICS 

treatment group, whose levels of impairment (symptoms, SABA use, lung function) improved, 

remained at risk of exacerbations requiring oral systemic corticosteroids (CAMP 2000). 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

The steps of care for managing asthma to achieve and maintain this control are presented in 

figures 4–1a and 4–1b. Deciding which step of care is appropriate for a patient depends on 

whether long-term control therapy is being initiated for the first time or whether therapy is being 

adjusted (i.e., stepped up to regain control or stepped down, for patients who have maintained 

control for a sufficient length of time, to determine the minimal amount of medication required to 

maintain control and/or reduce the risk of side effects). The classification of asthma severity, 

which considers the severity of both impairment and risk domains, provides a guide for 

initiating therapy for patients who are not currently taking long-term control medications. (See 

figures 4–2a and 4–2b for children 0–4 years of age and 5–11 years of age, respectively.) Once 

therapy is selected, or if the patient is already taking long-term control medication, the patient’s 

response to therapy will guide decisions about adjusting therapy based on the level of control 

achieved in both the impairment and risk domains (figure 4–3a for children 0–4 years of age and 

figure 4–3b for children 5–11 years of age). 

ACHIEVING CONTROL OF ASTHMA 

Selecting Initial Therapy 

0–4 Years of Age: Initiating Long-Term Control Therapy. The Expert Panel concludes 

that initiating daily long-term control therapy:

 Is recommended for reducing impairment and risk of exacerbations in infants and 

young children who had four or more episodes of wheezing in the past year that 

lasted more than 1 day and affected sleep AND who have risk factors for developing 

persistent asthma: either (1) one of the following: parental history of asthma, a 

physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens 

OR (2) two of the following: evidence of sensitization to foods, ≥4 percent peripheral 

blood eosinophilia, or wheezing apart from colds (Evidence A). 

 Should be considered for reducing impairment in infants and young children who 

consistently require symptomatic treatment more than 2 days per week for a period of 

more than 4 weeks (Evidence D). 

 Should be considered for reducing risk in infants and young children who have a 

second asthma exacerbation requiring systemic corticosteroids within 6 months 

(Evidence D). Recognition of these children and treatment with daily low-dose ICS therapy 

can significantly reduce overall symptom burden and the frequency of exacerbations, even 

though such treatment will not alter the underlying severity of asthma in later childhood 

(Guilbert et al. 2006). 

 May be considered for use only during periods of previously documented risk for a 

child (Evidence D). If daily long-term control therapy is discontinued after the season 

of increased risk, written asthma action plans indicating specific signs of worsening 

asthma and actions to take should be reviewed with the caregivers, and a clinic 

contact should be scheduled 2–6 weeks after discontinuation of therapy to ascertain 

whether adequate control is maintained satisfactorily (Evidence D). Because of 

seasonal variations in exacerbations among children, such as during the seasons of 

increased upper respiratory infections (Johnston et al. 2006), it is possible, although not yet 

evaluated systematically, that some of the children described above may require daily 

therapy only during previously documented periods of increased risk of exacerbations for 

that individual. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

5–11 Years of Age: Initiating Long-Term Control Therapy. The Expert Panel 

recommends daily long-term control therapy for children who have persistent asthma 

(Evidence A). In deciding when to initiate daily long-term control therapy, the clinician must 

weigh the possible long-term effects of inadequately controlled asthma versus the possible 

adverse effects of medications given over prolonged periods. Long-term studies in children 5–

12 years of age at the time of enrollment conclude that ICSs improve health outcomes for 

children who have mild or moderate persistent asthma, and that the potential albeit small risk of 

delayed growth from the use of ICSs is well balanced by their effectiveness (Evidence A) 

(CAMP 2000). Furthermore, available long-term data indicate that most children treated with 

recommended doses of ICSs achieve their predicted adult heights (Agertoft and Pedersen 

2000). It is noted that the long-term prospective studies on growth involved budesonide, and 

retrospective analyses included studies on beclomethasone, but the results have been 

generalized to include all ICS preparations. Although different preparations and delivery 

devices may have a systemic effect at different doses, all short-term studies on numerous 

preparations suggest that the effect of ICSs on growth is a drug-class effect. 

Adjusting Therapy 

The Expert Panel recommends that, if a child is already taking long-term control 

medication, treatment decisions are based on the level of asthma control that has 

been achieved: therapy should be stepped up if necessary to achieve control 

(Evidence B—extrapolated from studies in youths and adults) (See figures 4–3a and 

4–3b.). After identifying the patient’s treatment step, based on the patient’s or parents’ report of 

what medications the patient is currently taking, classify the level of control by measuring 

impairment based on symptoms, SABA use, and lung function (in children 5–11 years of age) 

and risk based on previous exacerbations and potential side effects. In general, the 

assessment leads to the following sequence of actions. 

 Address the impairment domain. Consider factors related to the different age groups. 

— 0–4 years of age: The level of impairment generally is judged on the most severe 

symptom. The risk domain is usually more strongly associated with asthma morbidity 

than the impairment domain, because children are often symptom free between 

exacerbations. 

— 5–11 years of age: The level of impairment generally is judged on the most severe 

measure among symptom report, asthma control score (using validated tools if 

available), and pulmonary function measures. For patients at step 3 or higher care, if 

office spirometry is feasible and suggests poorer control than does the assessment of 

impairment based on other measures, consider fixed airway obstruction as the 

explanation and reassess the other measures of impairment. If fixed airway obstruction 

does not appear to be the explanation, consider a step up in therapy, because low FEV1

is a predictor of risk for exacerbations in children. (See “Component 1: Measures of 

Asthma Assessment and Monitoring.”) 

— The Expert Panel recommends the following actions if control of the impairment 

domain is not achieved and maintained at any step of care: 

♦ Patient adherence and technique in using medications correctly should 

be assessed and addressed as appropriate (Evidence C). See 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

“Component 2: Education for a Partnership in Asthma Care” for discussion on 

assessing adherence. Key questions to ask the child and parent include: 

• Which medicines is your child currently taking? How often? 

• Who is responsible for administering the child’s medicine? 

• Please show me how the child takes the medicine. 

• How many times a week does the child miss taking the medication? 

• What problems have you/your child had taking the medicine (cost, time, lack of 

perceived need)? 

• What concerns do you have about your asthma medicines? 

♦ Other factors that diminish control of asthma impairment should be addressed 

as possible reasons for poor response to therapy and targets for intervention 

(Evidence C). These factors include the presence of a coexisting condition (e.g., 

sinusitis), a new or increased exposure to allergens or irritants, or psychosocial 

problems. In some cases, alternative diagnoses, such as vocal cord dysfunction 

(VCD), should be considered. 

♦ If patient adherence, inhaler technique, and environmental control measures 

are adequate, and asthma is not well controlled, a step up in treatment may be 

needed (Evidence B—extrapolated). For patients who have asthma that is not well 

controlled, in general step up one treatment step. For patients who have very poor

asthma control, consider increasing treatment by two steps, a course of oral 

corticosteroids, or both (Evidence D). 

 Address the risk domain. 

— The Expert Panel recommends the following actions if control of the risk of 

exacerbations is not achieved or maintained (Evidence D):

♦ 0–4 years of age: If there is a history of one or more exacerbations, review 

adherence to medications and control of environmental exposures, review the 

patient’s written asthma action plan to confirm that it includes oral prednisone for 

patients who have histories of severe exacerbations, and consider stepping up 

therapy to the next level (Evidence D). 

♦ 5–11 years of age: If the history of exacerbations suggests poorer control than 

does the assessment of impairment, the following actions are recommended: 

reassess the impairment domain, review adherence to medications and control of 

environmental exposures, review the patient’s written asthma action plan to confirm 

that it includes oral prednisone for patients who have a history of severe 

exacerbations, and consider a step up in therapy, especially for children who have 

reduced lung function (Fuhlbrigge et al. 2001, 2006). 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

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August 28, 2007 

— Address the risk domain with regard to side effects. 

The Expert Panel recommends consideration of alternative and/or adjunctive 

therapies within the step of care the patient is receiving if the patient experiences 

troublesome or debilitating side effects. In addition, confirm efforts to control 

environmental exposures (Evidence D). 

 Consider referral to an asthma specialist. The Expert Panel recommends referral to 

an asthma specialist for consultation or comanagement of the patient if (Evidence D):

— There are difficulties achieving or maintaining control of asthma.

— A child 0–4 years of age requires step 3 care or higher (step 4 care or higher for 

children 5–11 years of age) to achieve and maintain control or if additional 

education is indicated to improve the patients’ management skills or adherence. 

Referral may be considered if a child 0–4 years of age requires step 2 care or a 

child 5–11 years of age requires step 3 care.

— The patient has had an exacerbation requiring hospitalization.

— Immunotherapy or other immunomodulators are considered, or additional tests 

are indicated, to determine the role of allergy.

MAINTAINING CONTROL OF ASTHMA 

The Expert Panel recommends that regular followup contact is essential (Evidence B). 

Contact at 1- to 6-month intervals is recommended, depending on the level of control; 

consider a 3-month interval if a step down in therapy is anticipated (Evidence D). 

Clinicians need to assess whether control of asthma has been maintained and whether a step 

up or down in therapy is appropriate. Clinicians also need to monitor and review the written 

asthma action plan, which includes the medications, and the patient’s self-management 

behaviors for daily management and handling worsening asthma (e.g., inhaler and peak flow 

monitoring techniques, actions to control factors that aggravate his or her asthma) (See 

“Component 2: Education for a Partnership in Asthma Care,” figures 3–11 and 3–15, 

respectively.). 

The Expert Panel recommends that once well-controlled asthma is achieved and 

maintained for at least 3 months, a reduction in pharmacologic therapy—a step down—

can be considered helpful to identify the minimum therapy for maintaining 

well-controlled asthma (Evidence D). The opinion of the Expert Panel is that the dose of 

ICS may be reduced about 25–50 percent every 3 months to the lowest dose possible 

required to maintain control (Evidence D). Reduction in therapy should be gradual, because 

asthma control can deteriorate at a highly variable rate and intensity. The patient should be 

instructed to contact the clinician if and when asthma worsens. Guidelines for the rate of 

reduction and intervals for evaluation have not been validated, and clinical judgment of the 

individual patient’s response to therapy is important. Patients may relapse when the ICS is 

completely discontinued (CAMP 2000; Guilbert et al. 2006; Waalkens et al. 1993); however, 

giving daily therapy only during periods of documented risk for a child (e.g., seasons of viral 

respiratory infections) may be considered (Evidence D). 
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August 28, 2007 

KEY POINTS: INHALED CORTICOSTEROIDS IN CHILDREN 

 ICSs are the preferred therapy for initiating long-term control therapy in children of all ages 

(Evidence A). 

 ICSs, especially at low doses and even for extended periods of time, are generally safe 

(Evidence A). 

 The potential for the adverse effect of low- to medium-dose ICS on linear growth is usually 

limited to a small reduction in growth velocity, approximately 1 cm in the first year of 

treatment, that is generally not progressive over time (Evidence A). Children receiving ICS 

should be monitored, by using a stadiometer, for changes in growth (Evidence D). 

 The potential risks of ICSs are well balanced by their benefits. 

 High doses of ICS administered for prolonged periods of time (for example, more than 

1 year), particularly in combination with frequent courses of systemic corticosteroid therapy, 

may be associated with adverse growth effects and risk of posterior subcapsular cataracts 

or reduced bone density. Age-appropriate dietary intake of calcium and vitamin D should be 

reviewed with the child’s caregivers (Evidence D). Slit-lamp eye exam and bone 

densitometry should be considered (Evidence D). 

 See also section 3, component 4—Medications. 

KEY POINTS: MANAGING ASTHMA IN CHILDREN 

0–4 YEARS OF AGE 

 Diagnosing asthma in infants is often difficult. Underdiagnosis and undertreatment are key 

problems in this age group. However, not all wheeze and cough are caused by asthma, and 

caution is needed to avoid giving inappropriate prolonged asthma therapy (EPR⎯2 1997). 

Thus, a diagnostic trial of asthma medications may be helpful. 

 Treatment for young children, especially infants, who have asthma has not been studied 

adequately. Most recommendations for treatment are based on limited data and 

extrapolations from studies in older children and adults. 

 The initiation of long-term control therapy: 

— Is recommended for reducing impairment and risk of exacerbations in infants and young 

children who had four or more episodes of wheezing in the past year that lasted more 

than 1 day and affected sleep AND who have either (1) one of the following: a parental 

history of asthma, a physician’s diagnosis of atopic dermatitis, or evidence of 

sensitization to aeroallergens OR (2) two of the following: evidence of sensitization to 

foods, ≥4 percent peripheral blood eosinophilia, or wheezing apart from colds 

(Evidence A). 
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August 28, 2007 

— Should be considered for reducing impairment in infants and young children who 

consistently require symptomatic treatment more than 2 days per week for a period of 

more than 4 weeks (Evidence D). 

— Should be considered for reducing risk in infants and young children who have two 

exacerbations requiring systemic corticosteroids within 6 months (Evidence D). 

— May be considered for use only during periods, or seasons, of previously documented 

risk for a child (Evidence D). 

 When initiating daily long-term control therapy, daily ICS is the preferred treatment 

(Evidence A). Alternative treatment options (listed here in alphabetical order) include 

cromolyn (Evidence B—extrapolated from studies in older children) or leukotriene receptor 

antagonist (LTRA) (montelukast). The initial choice of long-term control medication includes 

consideration of treatment effectiveness, the domain of particular relevance for the individual 

patient (impairment, risk, or both), the patient’s history of previous response to therapies, the 

ability of the patient and family to use the medication correctly, and anticipated patient and 

family adherence to the treatment regimen (Evidence D). 

 Response to therapy should be carefully monitored. If there is a clear and positive response 

for at least 3 months, a careful step down in therapy should be attempted to identify the 

lowest dose required to maintain control. If clear benefit is not observed within 4–6 weeks 

and patient/family medication technique and adherence are satisfactory, the therapy should 

be discontinued and alternative therapies or diagnoses should be considered (Evidence D). 

 Administration of an ICS early in the course of the disease will not alter the underlying 

progression of the disease (Evidence A). ICSs should be used to control symptoms, 

prevent exacerbations, and improve the child’s quality of life, but their use should not be 

initiated or prolonged for the purpose of changing the progression or underlying severity of 

the disease. 

The following recommendations for different steps of pharmacologic therapy to gain and 

maintain asthma control are intended to be general guidelines for making therapeutic decisions. 

They are not intended to be prescriptions for individual treatment. Specific therapy should be 

tailored to the needs and circumstances of individual patients. Pharmacologic therapy must be 

accompanied at every step by measures to control those environmental factors and comorbid 

conditions that can impede asthma control and by patient education (See section 3, 

“Component 2: Education for a Partnership in Asthma Care” and “Component 3: Control of 

Environmental Factors and Comorbid Conditions That Affect Asthma.”). 

Treatment: Pharmacologic Issues for Children 0–4 Years of Age 

The Expert Panel recommends that treatment of young children is often in the form of a 

therapeutic trial; therefore, it is essential to monitor the child’s response to therapy. If 

there is no clear response within 4–6 weeks, the therapy should be discontinued and 

alternative therapies or alternative diagnoses considered (Evidence D). If there is a clear 

and positive response for at least 3 months, a step down in therapy should be 

undertaken to the lowest possible doses of medication required to maintain asthma 

control (Evidence D). 
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Treatment for young children, especially infants, has not been studied adequately. 

Recommendations are based on expert opinion, limited data, and extrapolations from studies in 

older children and adults (Baker et al. 1999; Kemp et al. 1999). 

FDA APPROVAL 

The following long-term control medications are approved by the FDA for young children: 

 ICS budesonide nebulizer solution (approved for children 1–8 years of age) 

 ICS fluticasone DPI (approved for children 4 years of age and older) 

 Long-acting inhaled beta2-agonist (LABA) salmeterol DPI and combination product 

(salmeterol + fluticasone) DPI (approved for children 4 years of age and older) 

 LTRA montelukast, based on safety data rather than efficacy data, in a 4 mg chewable 

tablet (approved for children 2–6 years of age) and in 4 mg granules (approved down to 

1 year of age) 

 Cromolyn nebulizer (approved for children ≥2 years of age) 

DELIVERY DEVICES 

Several delivery devices are available for infants and young children. The dose received 

may vary considerably among devices and age groups. (See “Component 4: Medications,” 

figure 3–24, for a summary of therapeutic issues regarding aerosol delivery devices.) In 

general, children less than 4 years of age will have less difficulty with an MDI plus valved 

holding chamber (VHC) with a face mask or a nebulizer with a face mask. The child’s 

caregivers must be instructed in the proper use of nebulizers, appropriate size of face masks, 

and how to use VHCs with and without face masks for medication delivery to be effective and 

efficient. Using the “blow by” technique, holding the mask or open tube near the infant’s nose 

and mouth, is not appropriate. For younger children, nebulizer therapy is an option for 

administering budesonide and cromolyn. Children between 3 and 5 years old may begin 

therapy with an MDI and spacer or VHC alone, but if the desired therapeutic effects are not 

achieved, they may require a nebulizer or an MDI plus spacer or VHC and face mask. 

Treatment: Pharmacologic Steps for Children 0–4 Years of Age 

Figure 4–1a presents treatment options within the stepwise approach to therapy. Selection of 

the step of care for a patient depends on whether long-term control therapy is being initiated for 

the first time or therapy is being adjusted. Classifying severity in patients not currently taking 

long-term control medication will guide decisions for initiating therapy (See figure 4–2a.). 

Assessing the level of asthma control in patients taking long-term control medication will guide 

decisions for adjusting therapy (See figure 4–3a.). Figures 4–4a, b, and c list usual dosages of 

asthma medications. 
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INTERMITTENT ASTHMA 

Step 1 Care, Children 0–4 Years of Age 

The Expert Panel recommends the following treatment for intermittent asthma: 

 SABA taken as needed to treat symptoms is usually sufficient therapy for intermittent 

asthma (EPR⎯2 1997). If effective in relieving symptoms, intermittent use of SABA can 

continue on an as-needed basis. Increasing use, however, may indicate more severe or 

inadequately controlled asthma and thus a need to step up therapy. 

 The Expert Panel recommends the following actions for managing exacerbations due 

to viral respiratory infections, which are especially common in children (EPR⎯2 

1997). These exacerbations may be intermittent yet severe.

— If the symptoms are mild, SABA (every 4–6 hours for 24 hours, longer with a physician 

consult) may be sufficient to control symptoms and improve lung function. If this therapy 

needs to be repeated more frequently than every 6 weeks, consider a step up in 

long-term care. 

— If the viral respiratory infection provokes a moderate-to-severe exacerbation, a short 

course of oral systemic corticosteroids should be considered (1 mg/kg/day prednisone or 

equivalent for 3–10 days). 

— For those patients who have a history of severe exacerbations with viral respiratory 

infections, consider initiating oral systemic corticosteroids at the first sign of the infection. 

 The Expert Panel recommends that a detailed written asthma action plan be 

developed for those patients who have intermittent asthma and a history of severe 

exacerbations (Evidence B) (See “Component 2: Education for a Partnership in 

Asthma Care.”). Intermittent asthma—infrequent exacerbations separated by periods of no 

symptoms and normal pulmonary function—is often mild. Some patients, however, who 

have intermittent asthma experience sudden, severe, and life-threatening exacerbations. It 

is essential to treat these exacerbations accordingly. The patient’s written asthma action 

plan should include indicators of worsening asthma (specific symptoms) as well as specific 

recommendations for using SABAs, early administering of oral systemic corticosteroids, and 

seeking medical care. 

Furthermore, periodic monitoring (See “Component 1: Measures of Asthma Assessment 

and Monitoring.”) of the patient is appropriate to evaluate whether the patient’s asthma is 

indeed intermittent. The occurrence of two or more severe exacerbations within 6 months 

without symptoms in between them is an example of a child’s having minimal or intermittent 

impairment, but a persistent, high risk of exacerbation. In the opinion of the Expert Panel, 

this child should be considered to have persistent asthma (See figure 4–2a.). Such children 

can benefit from daily long-term control therapy (Bisgaard et al. 2004, 2005). 
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August 28, 2007 

PERSISTENT ASTHMA 

The Expert Panel recommends the following therapy for persistent asthma: 

 Daily long-term control medication at step 2 or above is recommended for children 

who had four or more wheezing episodes in 1 year and risk factors for persistent 

asthma (Evidence A). Consider daily therapy for children who have a second 

exacerbation requiring oral systemic corticosteroids in 6 months or children who 

consistently require symptomatic treatment >2 days a week for > 4 weeks (Evidence 

D). 

 Quick-relief medication must be available. SABA should be taken as needed to 

relieve symptoms (EPR⎯2 1997). The intensity of treatment will depend on the severity of 

the exacerbation (See section 5, “Managing Exacerbations of Asthma.”). Use of SABA 

more than 2 days a week for symptom control (not prevention of EIB), or increasing use, 

indicates the need for additional long-term control therapy. 

 To gain more rapid control of asthma, a course of oral systemic corticosteroids may 

be necessary for the patient who has an exacerbation at the time long-term control 

therapy is started or in patients who have moderate or severe asthma with frequent 

interference with sleep or normal activity (EPR⎯2 1997).

 Close monitoring of the child’s response to therapy is recommended (EPR⎯2 1997); 

treatment recommendations are based on limited data in this age group, and thus 

treatment is often in the form of a therapeutic trial. If no clear response occurs within 

4–6 weeks and medication technique and adherence are satisfactory, the treatment 

should be discontinued and a change in therapy or alternative diagnoses should be 

considered. If there is a clear and positive response for at least 3 months, a step 

down in therapy should be undertaken to the lowest possible doses of medication 

required to maintain asthma control (Evidence D). 

 Giving daily therapy only during specific periods of previously documented risk for a 

child may be considered (Evidence D). Although this approach is not yet evaluated, it is 

possible that children who have specifically defined periods of increased risk for symptoms 

and exacerbations (e.g., during the seasons in which viral respiratory infections are 

common) may require daily long-term control therapy only during this historically 

documented period of risk. If long-term control therapy is discontinued, then written action 

plans for recognizing and handling signs of worsening asthma should be reviewed with the 

caregivers, and followup appointments 2–6 weeks later should be conducted to ensure that 

asthma control is maintained. 

Step 2 Care, Children 0–4 Years of Age 

 Preferred treatment for step 2 care is daily ICS at a low dose (Evidence A based on 

studies of individual drug efficacy in this age group; comparator trials are not 

available). 

 Alternative, but not preferred, treatments include (listed in alphabetical order) 

cromolyn (Evidence B—extrapolated from studies in older children) and montelukast 

(Evidence A). If an alternative treatment is selected and adequate asthma control is 
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not achieved and maintained in 4–6 weeks, then discontinue that treatment and use 

the preferred medication before stepping up therapy. 

 Theophylline is not recommended as alternative treatment (EPR⎯2 1997) because of 

its erratic metabolism during viral infections and febrile illness in children less than 5 years of 

age and the need to closely monitor and control serum concentrations. 

At present, few studies of medications have been conducted in children younger than 3 years of 

age. ICSs have been shown to be effective in long-term clinical studies with infants and young 

children (Bisgaard et al. 2004; Guilbert et al. 2006). In contrast, cromolyn has demonstrated 

inconsistent symptom control in children younger than 5 years of age (Tasche et al. 2000). 

Montelukast has shown some effectiveness in children 2–5 years of age (Knorr et al. 2001) and, 

in young children who have a history of exacerbations, can reduce symptoms associated with 

exacerbations and the amount of ICSs used during exacerbations, although montelukast was 

not shown to reduce requirements for oral systemic corticosteroid to control exacerbations 

(Bisgaard et al. 2005). 

Therefore, it is the opinion of the Expert Panel that low-dose ICS is the preferred daily long-term 

control therapy for infants and young children who have never before been treated with longterm control therapy. This medication should be prescribed in the form of a therapeutic trial, 

and response should be monitored carefully. Treatment should be stopped if a clear beneficial 

effect is not obvious within 4–6 weeks and the patient/family medication technique and 

adherence are satisfactory. If a clear and positive response exists for at least 3 months (and 

given the high rates of spontaneous remission of symptoms in this age group), the need for ICS 

therapy should be reevaluated. A step down to intermittent therapy, as needed for symptoms, 

may then be considered (Evidence D). If long-term control therapy is discontinued, then written 

asthma action plans for recognizing and handling signs of worsening asthma should be 

reviewed with the caregivers, and followup appointments should be conducted 2–6 weeks later 

to ensure that asthma control is maintained. 

A trial of montelukast in children 2 years of age or older can be considered in situations in which 

inhaled medication delivery is suboptimal due to poor technique or adherence. 

Step 3 Care, Children 0–4 Years of Age 

 Medium-dose ICS is the preferred step 3 treatment (Evidence D). The Expert Panel 

recommends increasing the dose of ICS, for children 0–4 years of age whose asthma 

is not well controlled on low doses of ICS, to ensure that an adequate dose is 

delivered (due to the inherent difficulty and variability of delivering aerosols) before 

adding adjunctive therapy (Evidence D). 

Only a few data are available to address step 3 care in children from 0 to 4 years of age in 

regard to the various options that have been studied in older children and adults (See the 

section on “Managing Asthma Long Term—Youths ≥12 Years of Age and Adults.”). The pivotal 

trials for budesonide nebulizer solution included children 6 months to 8 years of age and failed 

to detect a significant dose-dependent effect, from doses ranging from 0.25 mg twice daily to 

1.0 mg twice daily, on either impairment or risk domains (Szefler and Eigen 2002). In children 

<5 years of age, ICS clearly reduced risk and impairment compared to placebo (Bisgaard 1999; 

Roorda et al. 2001; Szefler and Eigen 2002). One trial in 237 children 1–4 years of age 

suggested a dose-dependent decrease in exacerbations (risk domain), some symptoms, and 

as-needed albuterol use (impairment domain) from fluticasone propionate 100 mcg/day and 
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200 mcg/day by MDI plus VHC (Bisgaard 1999), although the 100 mcg/day did not lower 

exacerbations differently from placebo. Some trials comparing budesonide nebulizer solution 

0.25 mg twice daily to 1.0 mg daily in infants 5–40 months old have shown improved symptom 

control with the higher dose; other trials show no difference (Szefler and Eigen 2002). 

Few data are available on the addition of LABA in step 3 care in this age group. The only data 

are those involving 4 year olds who have asthma that is not well controlled on low-dose ICS; 

there are no data for children under 4 years of age. The LABA DPI preparation (either alone or 

as a combination product) currently available and approved for use in the United States has a 

delivery system that is difficult to administer correctly to the majority of children less than 4 

years of age. Data from studies and clinical experience are needed to determine how 

conveniently the newly released LABA hydrofluoroalkane (HFA) preparation can be delivered to 

this age group. FDA approval for the combination of LABA and ICS in children 4–11 years of 

age is based primarily on safety data and extrapolation of efficacy data from adolescents and 

adults (Malone et al. 2005; Van den Berg et al. 2000). Two studies in children 4–11 years of 

age whose asthma was not completely controlled on ICS have demonstrated that the addition of 

LABA improved lung function and symptom control compared to placebo (Russell et al. 1995; 

Zimmerman et al. 2004). To date, studies have not shown a reduction in significant asthma 

exacerbations with the addition of LABA to ICS (Bisgaard 2003) in young children. Although 

4-year-old children were included in these study populations, the small numbers enrolled 

preclude any accurate extrapolation from these findings to the larger population of children 0–4 

years of age. No other studies have evaluated adjunctive therapies in this 0–4 years of age 

group. 

In summary, few studies in this age group are available, and they have mixed findings. Some 

data show improvement in both the impairment and risk domains with increasing the dose of 

ICS in children 1–4 years of age. Data from studies including only small numbers of 4-year-old 

children show improvement in the impairment domain with the use of ICS plus LABA, but no 

studies show improvement in the risk domain with combination therapy. 

Step 4 Care, Children 0–4 Years of Age 

 Medium-dose ICS AND either (listed in alphabetical order) LABA or montelukast is the 

preferred treatment for step 4 (Evidence D). Theophylline is not recommended as 

add-on therapy (EPR⎯2 1997). 

No data were found on add-on therapy in children 0–4 years of age whose asthma is not well 

controlled on medium-dose ICS. In the opinion of the Expert Panel, and extrapolating from 

studies in older children and adults, adding a noncorticosteroid long-term control medication to 

the medium dose of ICS may be considered before increasing the dose of ICS to high dose, to 

avoid the potential risk of side effects with high doses of medication. The LABA DPI preparation 

is difficult to administer correctly to the majority of children less than 4 years of age; studies are 

needed to determine if the recently released LABA HFA will be convenient to administer in this 

age group. Montelukast (an LTRA) in combination with lower doses of an ICS can be 

considered for add-on therapy in these children. 

Theophylline is not recommended as add-on therapy due to the erratic metabolism of 

theophylline during viral infections and febrile illness (See figure 4–4a.), which are common in 

this age group, and the need for careful monitoring of serum concentration levels. 
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Step 5 Care, Children 0–4 Years of Age 

 High-dose ICS AND either LABA or montelukast is the preferred treatment 

(Evidence D). 

Step 6 Care, Children 0–4 Years of Age 

 High-dose ICS AND either LABA or montelukast AND oral systemic corticosteroids 

may be given for step 6 (Evidence D). 

Before oral systemic corticosteroids are given for prolonged periods as a long-term control 

medication, consider a 2-week course of oral systemic corticosteroids to confirm clinical 

reversibility and the possibility of an effective response to therapy or, in 4-year-old children, 

consider high-dose ICS in combination with both an LTRA and a LABA. 

For patients who require long-term oral systemic corticosteroids: 

 Use the lowest possible dose (single dose daily or on alternative days). 

 Monitor patients closely for corticosteroid adverse effects (See component 4—Medications.). 

 When control of asthma symptoms is achieved, make persistent attempts to reduce oral 

systemic corticosteroids. High doses of ICS are preferable because they have fewer side 

effects than oral systemic corticosteroids. 

 Recommend consultation with an asthma specialist. 

KEY POINTS: MANAGING ASTHMA IN CHILDREN 

5–11 YEARS OF AGE 

 Classification of severity, considering the new dimensions of both the impairment and risk 

domains, should guide decisions for initiating therapy in children not currently taking 

long-term control medications (EPR⎯2 1997). 

 Assessment of asthma control, considering both the impairment and risk domains, should 

guide decisions for adjusting therapy—either stepping up (Evidence A) or stepping down 

(Evidence D). 

 When initiating daily long-term control therapy for persistent asthma, daily ICS is the 

preferred treatment (Evidence A); alternative treatment options include cromolyn, LTRA, and 

theophylline (Evidence B). The choice of medication includes consideration of treatment 

effectiveness, the domain of particular relevance to the individual patient (impairment, risk, 

or both), the individual patient’s history of previous response to therapies, the ability of the 

patient and family to use the medication correctly, and anticipated patient and family 

adherence with the treatment regime and cost (Evidence D). 
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 Administration of ICS early in the course of the disease will not alter the underlying 

progression of the disease. ICSs should be used to control symptoms, prevent 

exacerbations, and improve the child’s quality of life, but their use should not be initiated or 

prolonged for the purpose of changing the progression or underlying severity of the disease 

(Evidence A). 

 Children should be directly involved as much as possible in establishing goals for therapy 

and developing their written asthma action plans. 

 Active participation in physical activities, exercise, and sports should be promoted (EPR⎯2 

1997). Treatment immediately before vigorous activity or exercise usually prevents EIB. If 

symptoms occur during usual play activities, a step up in treatment is warranted (EPR⎯2 

1997). 

 A written asthma action plan should be prepared for the student’s school, extended care, or 

camp, including the clinician’s recommendation regarding self-administration of medication. 

Either encourage parents to take a copy to the child’s school or obtain parental permission 

and send a copy to the school nurse or designee (Evidence C). 

The following recommendations for pharmacologic therapy to gain and maintain asthma control 

(See figures 4–1b, 4–3b, 4–4a, b, and c.) are intended to be general guidelines for making 

therapeutic decisions. They are not intended to be prescriptions for individual treatment or to 

replace clinical judgment. Specific therapy should be tailored to the need and circumstances of 

individual patients. Pharmacologic therapy must be accompanied at every step by patient 

education and measures to control those environmental factors and comorbid conditions that 

can impede asthma control. 

Treatment: Special Issues for Children 5–11 Years of Age 

PHARMACOLOGIC ISSUES 

The Expert Panel recommends that, when initiating daily long-term control therapy for 

mild or moderate persistent asthma, the choice of medication includes consideration of 

treatment effectiveness, the domain of particular relevance to the patient’s asthma 

(impairment, risk, or both), the individual patient’s history of previous response to 

therapies, the ability of the patient and family to use the medication correctly, anticipated 

patient and family adherence to the treatment regimen, and cost (Evidence D).

The Expert Panel recommends that children ≥10 years of age (and younger children as 

appropriate) be directly involved in developing their written asthma action plans (EPR⎯2 

1997). Children entering puberty may experience more difficulties than younger children in 

adhering to a written asthma action plan because they may fail to recognize the danger of 

poorly controlled asthma (Strunk et al. 1985), they may not accept having a chronic illness, or 

they may view the plan as infringing upon their emerging independence and adulthood. In 

teaching these children the same asthma self-management techniques expected of adults, the 

clinician should address developmental issues, such as building a positive self-image and 

confidence, increasing personal responsibility, and gaining problem-solving skills. To 

accomplish this, it is often helpful to see the child initially without parents present and to involve 
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the child directly in setting goals for therapy, choosing the appropriate treatment, and reviewing 

the effectiveness of the written asthma action plan at repeated visits. The parents can be 

brought in at the end of the visit to review the plan together and to emphasize the parents’ 

important role in supporting the child’s efforts. 

SCHOOL ISSUES 

The Expert Panel recommends that the clinician prepare a written asthma action plan for 

the student’s school or childcare setting. Either encourage parents to take a copy to the 

child’s school or obtain parental permission and send a copy to the school nurse or 

designee (Evidence C). The written asthma action plan should include the following 

information (See “Component 2: Education for a Partnership in Asthma Care,” figure 3–16.): 

instructions for handling exacerbations (including the clinician’s recommendation regarding selfadministration of medication); recommendations for long-term control medications and 

prevention of EIB, if appropriate; and identification of those factors that make the student’s 

asthma worse, so the school may help the student avoid exposure. Nonrandomized studies 

and observational studies have demonstrated the usefulness of written asthma action plans and 

peak flow monitoring in schools (Barbot et al. 2006; Borgmeyer et al. 2005; Byrne et al. 2006; 

Erickson et al. 2006). 

It is preferable to schedule daily, long-term medications so that they are not taken at school, 

even if this results in unequal dosing intervals throughout the day. In school districts that have 

more comprehensive school nurse coverage, however, children who would benefit from close 

supervision to promote adherence may be given medications at school. In this way, daily 

medication can be administered, and patient education can be supplemented most days of the 

week. 

Students who have asthma often require medication during school to treat acute symptoms or to 

prevent EIB that may develop during physical education class, school recess, or organized 

sports. Reliable, prompt access to medication is essential, but it may be difficult because of 

school rules that preclude the child from carrying medications. The NAEPP and several 

member organizations have adopted resolutions that endorse allowing students to carry and 

self-administer medications when the physician and parent consider this appropriate. Many 

State governments have passed legislation that allows self-administration of asthma medication 

in schools. It may be helpful for some children to have a compressor-driven nebulizer and 

medication available at the school. See also “Component 2: Education for a Partnership in 

Asthma Care,” for a discussion of school-based asthma programs that promote effective 

management of asthma in the school setting. 

SPORTS AND EXERCISE ISSUES 

The Expert Panel recommends that physical activity at play or in organized sports is an 

essential part of a child’s life, and full participation in physical activities should be 

encouraged (EPR⎯2 1997). Many children who have asthma experience cough, wheeze, or 

excessive fatigue when they exercise. Treatment immediately before vigorous activity or 

exercise usually prevents EIB. If symptoms occur during usual play activities, a step up in 

long-term therapy is warranted. Poor endurance or EIB can be an indication of poorly controlled 

persistent asthma; appropriate use of long-term control medication can reduce EIB (See the 

section on “Managing Special Situations in Asthma—Exercise-Induced Bronchospasm.”). 

Activity should be limited or curtailed only as a last resort. 
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Treatment: Pharmacologic Steps for Children 5–11 Years of Age 

Figure 4–1b presents treatment options within the stepwise approach to therapy. Selection of 

the step of care for a patient depends on whether long-term control therapy is being initiated for 

the first time or whether therapy is being adjusted. Classifying severity in patients not currently 

taking long-term control medication is a guide for initiating therapy (See figure 4–2b.); assessing 

the level of asthma control in patients taking long-term control medication will guide decisions 

for adjusting therapy (See figure 4–3b.). Figures 4–4a, b, and c list usual dosages of asthma 

medications. Note that the recommendations in stepwise therapy are meant to assist, not 

replace, the clinical decisionmaking required to meet the individual patient’s needs. 

INTERMITTENT ASTHMA 

Step 1 Care, Children 5–11 Years of Age 

The Expert Panel recommends the following therapy for intermittent asthma 

(step 1 care): 

 SABA, taken as needed to treat symptoms, is usually sufficient therapy for 

intermittent asthma. 

If a child requires increasing amounts of as-needed SABA, this may indicate more severe or 

poorly controlled asthma and thus the need to step up therapy (See figures 4–1b and 4–

2b.). 

 Manage moderate or severe exacerbations due to viral respiratory infections, 

especially common in children, with a short course of oral systemic corticosteroids. 

Consider initiating systemic corticosteroids at the first sign of infection in children 

who have a history of severe exacerbations with viral respiratory infections 

(Evidence D). 

 Provide a detailed written asthma action plan for those patients who have intermittent 

asthma and a history of severe exacerbations (Evidence B). Intermittent asthma—

infrequent exacerbations separated by periods of no symptoms and normal pulmonary 

function—is often mild. However, some patients who have intermittent asthma experience 

sudden, severe, and life-threatening exacerbations, and it is essential to treat these 

exacerbations accordingly. The patient’s written asthma action plan should include 

indicators of worsening asthma (specific symptoms and peak expiratory flow (PEF) 

measurement), specific recommendations for using SABA, early administration of systemic 

corticosteroids, and seeking medical care. Recommendations regarding avoidance or 

control of allergies, irritants, or comorbid conditions that affect the child’s asthma should also 

be included. Periodic monitoring is important to evaluate whether the patient’s asthma is 

indeed intermittent. The occurrence of more than two exacerbations a year that require oral 

systemic corticosteroids, without symptoms between them, is an example of a child’s having 

minimal or intermittent impairment, but a persistent risk of exacerbation. In the opinion of 

the Expert Panel, this child should be considered to have persistent asthma (See 

figure 4–2b.). 
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August 28, 2007 

PERSISTENT ASTHMA 

The Expert Panel recommends the following therapy for persistent asthma:

 Use daily long-term control medication. The most effective long-term control 

medications are those with anti-inflammatory effects, that is, those that diminish 

chronic airway inflammation and airway hyperresponsiveness (Evidence A).

 Quick-relief medication must be available. SABA, taken as needed to relieve 

symptoms, is recommended (Evidence A). The intensity of treatment will depend on the 

severity of the exacerbation (See section 5 on “Managing Exacerbations of Asthma.”). 

Increasing use of SABA or use more than 2 days week for symptom control (not prevention 

of EIB) indicates the need to step up therapy. 

 To gain more rapid control of asthma, consider a course of oral systemic 

corticosteroids for the patient who has an exacerbation at the time long-term control 

therapy is started or in patients who have moderate or severe asthma with frequent 

interference with sleep or normal activity (EPR⎯2 1997). 

 Giving daily therapy only during specific periods of previously documented risk for a 

child may be considered (Evidence D). Although this approach is not yet evaluated, it is 

possible that children who have specifically defined periods of increased risk for symptoms 

and exacerbations (e.g., during the seasons in which viral respiratory infections are 

common) may require daily long-term control therapy only during this historically 

documented period of risk. If long-term control therapy is discontinued, then written action 

plans for recognizing and handling signs of worsening asthma should be reviewed with the 

caregivers, and followup appointments 2–6 weeks later should be conducted to ensure that 

asthma control is maintained. 

 Consider treating patients who had two or more exacerbations requiring oral 

systemic corticosteroids in the past year the same as patients who have persistent 

asthma, even in the absence of an impairment level consistent with persistent asthma 

(Evidence D).

Step 2 Care, Children 5–11 Years of Age 

 Daily low-dose ICS is the preferred step 2 treatment (Evidence A). High-quality 

evidence demonstrates the effectiveness of ICS as initial therapy for children who have 

persistent asthma (See “Component 4: Medications.”). This approach is also the preferred 

treatment for stepping down treatment of patients who are well controlled on a higher 

treatment step. 

 Alternative treatments at this step include (listed in alphabetical order) cromolyn, 

LTRA, nedocromil, and theophylline (Evidence B). Three comparator studies in children 

5–17 years of age demonstrated that montelukast is not as efficacious as ICS on a range of 

asthma outcomes (Garcia-Garcia et al. 2005; Ostrom et al. 2005; Sorkness et al. 2007) (See 

“Component 4: Medications” and Evidence Table 14, Leukotriene Receptor Antagonist: 

Monotherapy/Effectiveness Studies.). One study that examined factors that might predict 

response to therapy found that children who had lower lung function (impairment domain) 

and/or higher levels of markers of allergic airway inflammation were more likely to respond 

favorably to ICS and not respond to montelukast in the impairment domain of FEV1. 
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Children who did not have these characteristics may respond equally well to both 

medications (Szefler et al. 2005). Montelukast, then, is an appropriate treatment option. Of 

the LTRAs, montelukast may be more desirable, as it requires only once daily dosing; 

furthermore, zafirlukast has several potential drug interactions and a small risk for 

hepatotoxicity. Cromolyn and nedocromil, although having excellent safety profiles, require 

administration four times per day and have shown benefit inconsistently. Theophylline is 

less desirable because of its safety profile and the need to adjust dose based on diet, drug 

interactions, and variable metabolism with age (See figure 4–4a.). Theophylline may be 

considered, however, when cost and adherence to inhaled medications are concerns. 

If an alternative treatment is selected and well-controlled asthma is not achieved and 

maintained, then discontinue that treatment and use the preferred medication before 

stepping up treatment. 

Step 3 Care, Children 5–11 Years of Age 

 Low-dose ICS plus the addition of some form of adjunctive therapy or medium-dose 

ICS are equivalent options in step 3 care, based on extrapolation from studies in 

adults (Evidence B—extrapolation). Because of the lack of comparative data in this 

age group, however, the adjunctive therapies are listed in alphabetical order: LABA, 

LTRA, or, with appropriate monitoring, theophylline. 

In adult patients whose asthma is not well controlled on low-dose ICS, the clinician has 

several options: (1) increasing the ICS dose, (2) adding a LABA, (3) adding a leukotriene 

modifier, or (4) adding theophylline. Based on considerable available evidence, the first two 

are preferred. In children, none of these options has been studied adequately or compared 

in the age range of 5–11 years, and the options have not been studied at all in those <5 

years of age. 

— Low-dose ICS plus the addition of adjunctive therapy (listed alphabetically): 

♦ Adding LABA to ICS: Two trials demonstrated that children 4–11 years of age who 

had asthma not completely controlled by ICS achieved improved lung function and 

symptom control with the addition of LABA compared to placebo (Russell et al. 1995; 

Zimmerman et al. 2004). FDA approval for the combination in 4- to 11-year-old 

children, however, is based primarily on safety and extrapolation of efficacy from 

adolescents and adults (Malone et al. 2005; Van den Berg et al. 2000). To date, 

studies have not shown a reduction in significant asthma exacerbations from the 

addition of LABA to ICS treatment in children (Bisgaard 2003). One negative study 

of LABA in combination with ICS in children who had mild or moderate persistent 

asthma failed to establish a need in the study participants, at baseline, for more 

therapy than low-dose ICS, and thus did not sufficiently address the question of 

combination therapy with LABA (Verberne et al. 1998). 

♦ Adding LTRA to ICS: One trial of medications for children compared the addition of 

montelukast to budesonide, 400 mcg/day, and reported a slight increase in lung 

function (PEF, although not FEV1) and a reduction in as-needed SABA use (Simons 

et al. 2001). 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

302 

August 28, 2007 

♦ Adding theophylline: A small trial in 36 children, 6–18 years of age, reported a 

small improvement in PEF, but not FEV1 or bronchial reactivity, from the addition of 

theophylline to ICS (Suessmuth et al. 2003). Because of the risk of toxicity, multiple 

drug interactions, and the need to monitor serum concentrations regularly, with no 

significant beneficial effect over other adjunctive treatments, theophylline would be 

considered the less desirable option for adjunctive therapy. 

— Increasing the dose of ICS to medium dose: A recent systematic review in children 

4–16 years of age (Masoli et al. 2004) reported that the dose-response to fluticasone 

propionate for improvement in lung function and symptom control (in the impairment 

domain) appears to plateau between 100–200 mcg/day (low dose), although patients 

who have severe asthma may achieve additional response at 400 mcg/day (medium 

dose). A large prospective trial of budesonide in children 4–8 years of age who had 

moderate to severe asthma showed similar improvements in symptom control with low 

and high doses, with small improvements in lung function upon increasing the daily dose 

fourfold from 200 mcg/day to 800 mcg/day (medium dose) (Shapiro et al. 1998). None 

of these studies, however, evaluated whether patients not initially controlled on low-dose 

ICS had an improved response after increasing the dose. In adult studies, increasing 

the dose from 200 mcg budesonide further reduced exacerbations (Pauwels et al. 1997). 

The Expert Panel concludes that, while the benefits from ICS in the impairment domain 

may begin to plateau at low doses, increasing the dose for children who have asthma 

not well controlled at low dose ICS may benefit children who have more severe 

impairment and may also reduce the risk of exacerbations. Increasing the dose of ICS 

may increase the risk of systemic activity, although the clinical significance of the 

potential systemic effects is unclear (See component 4—Medications.). 

In summary, based on the small amount of data available concerning asthma in children 5–11 

years of age, as well as the lack of comparison studies for various long-term control regimens, it 

is not possible to recommend firmly whether administering higher doses of ICS or maintaining 

the low dose of ICS and adding adjunctive therapy is the best treatment approach for step 3 

care. Thus, the Expert Panel considers increasing the dose of ICS to the medium-dose range 

or using lower doses of ICS plus adjunctive therapy to be equivalent options. Decisions at this 

juncture should consider which component of control (impairment or risk) is more affected. For 

the impairment domain, based on studies in older children and adults, children who have low 

lung function and >2 days/week impairment may be better served by adding LABA to a 

low-dose of ICS. One study in children suggests some benefit in the impairment domain with 

adding LTRA. Studies in children show that increasing the dose of ICS to medium dose can 

improve symptoms and lung function in those children who have greater levels of impairment. 

For the risk domain, studies have not demonstrated that adding LABA or LTRA reduces 

exacerbations in children. Adding LABA has the potential risk of rare life-threatening or fatal 

exacerbations. Studies in older children and adults show that increasing the dose of ICS can 

reduce the risk of exacerbations, but this may require up to a fourfold increase in the dose. This 

may increase the potential risk of systemic effects, although within the medium-dose range the 

risk is small. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

303 

August 28, 2007 

Step 4 Care, Children 5–11 Years of Age 

 Medium-dose ICS AND LABA is the preferred step 4 treatment (Evidence B—

extrapolated from studies in youths ≥12 years and adults). 

Many children who have asthma that is not well controlled on step 3 therapy have low lung 

function contributing to their impairment; thus, extrapolating from studies on LABA as 

adjunctive therapy for older children and adults is particularly relevant, because the data 

show that a key benefit of adding LABA is improvement in lung function. 

 Alternative, but not preferred, treatment is medium-dose ICS AND either LTRA or 

theophylline (Evidence B—extrapolated from studies in youths ≥12 years of age and 

adults).

No data specifically address the comparative effects of the various choices of treatments to 

add on to ICS in children <11 years of age. Based on comparative studies in older children 

and adults (Evidence A), the preferred add-on treatment is LABA. If the physician has 

concerns regarding use of LABA, an LTRA can be given a therapeutic trial first. If a trial of 

LTRA is deemed ineffective, then the LTRA should be discontinued, and theophylline could 

be added. Theophylline is a less desirable option because of its safety profile and the need 

to monitor serum concentration levels. Cromolyn has not been demonstrated to be effective 

as add-on therapy. 

 In the opinion of the Expert Panel, if the add-on therapy initially administered does not lead 

to improvement in asthma control, discontinue it and use a trial of a different add-on therapy 

before stepping up. 

Step 5 Care, Children 5–11 Years of Age 

 High-dose ICS AND LABA is the preferred step 5 treatment based on extrapolation 

from studies in older children and adults (Evidence B—extrapolated). 

 Alternative, but not preferred, add-on treatments include LTRA or theophylline 

(Evidence B—extrapolated). 

Step 6 Care, Children 5–11 Years of Age 

 High-dose ICS AND LABA AND oral systemic corticosteroids long term is the 

preferred treatment (Evidence D). 

 Alternative, but not preferred, add-on treatments are either an LTRA or theophylline 

AND oral systemic corticosteroids (Evidence D). 

Before maintenance prednisone therapy is initiated, consider a 2-week course of oral 

corticosteroids to confirm clinical reversibility and the possibility of effective response to therapy. 

At this level of treatment, it is strongly recommended to add measures of pulmonary function to 

assess response to oral corticosteroid therapy. If response is poor, a careful review for other 

pulmonary conditions or concomitant medical conditions should be conducted to ensure the 

primary diagnosis is indeed severe asthma. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

304 

August 28, 2007 

For patients who require long-term oral systemic corticosteroids: 

 Use the lowest possible dose (single dose daily or on alternate days). 

 Monitor patients closely for corticosteroid adverse side effects (See box 4–1, “Patient 

Record: Monitoring Risk of Asthma Progression and Potential Adverse Effects of 

Corticosteroid Therapy.”). 

 When well-controlled asthma is achieved, make persistent attempts to reduce oral systemic 

corticosteroids. High-dose ICS therapy is preferable to oral systemic corticosteroids. 

 Recommend consultation with an asthma specialist. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

305 

August 28, 2007 

FIGURE 4–1a. STEPWI SE APPROACH FOR MA NAGING ASTHMA IN 

CHILDREN 0–4 YEARS OF AGE 

Intermittent

Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 3 care or higher is required.

Consider consultation at step 2.

Quick-Relief Medication for All Patients

• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms. 

• With viral respiratory infection: SABA q 4–6 hours up to 24 hours (longer with physician consult). Consider short course of oral 

systemic corticosteroids if exacerbation is severe or patient has history of previous severe exacerbations.

• Caution: Frequent use of SABA may indicate the need to step up treatment. See text for recommendations on initiating daily 

long-term-control therapy.

Step 1

Preferred:

SABA PRN

Step 2

Preferred:

Low-dose ICS

Alternative:

Cromolyn or 

Montelukast

Step 3

Preferred:

Medium-dose 

ICS

Step 5

Preferred:

High-dose ICS + 

either

LABA or 

Montelukast

Step 6

Preferred:

High-dose ICS + 

either

LABA or 

Montelukast

Oral systemic 

corticosteroids

Step up if 

needed

(first, check 

adherence, 

inhaler 

technique, and 

environmental 

control)

Step down if 

possible

(and asthma is 

well controlled 

at least

3 months) Patient Education and Environmental Control at Each Step

Step 4

Preferred:

Medium-dose 

ICS + either

LABA or 

Montelukast

Assess 

control

Key: Alphabetical order is used when more than one treatment option is listed within either preferred or 

alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; SABA, inhaled shortacting beta2-agonist 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual 

patient needs. 

 If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before 

stepping up. 

 If clear benefit is not observed within 4–6 weeks and patient/family medication technique and adherence are 

satisfactory, consider adjusting therapy or alternative diagnosis. 

 Studies on children 0–4 years of age are limited. Step 2 preferred therapy is based on Evidence A. All other 

recommendations are based on expert opinion and extrapolation from studies in older children. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

306 

August 28, 2007 

FIGURE 4–1b. STEPWI SE APPROACH FOR MA NAGING ASTHMA IN 

CHILDREN 5–11 YEARS OF AGE 

Intermittent

Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.

Consider consultation at step 3.

Step 1

Preferred:

SABA PRN

Step 2

Preferred:

Low-dose ICS

Alternative:

Cromolyn, LTRA,

Nedocromil, or

Theophylline

Step 3

Preferred:

EITHER: 

Low-dose ICS + 

either LABA, 

LTRA, or 

Theophylline

OR

Medium-dose 

ICS

Step 5

Preferred:

High-dose ICS + 

LABA

Alternative:

High-dose ICS + 

either LTRA or 

Theophylline

Step 6

Preferred:

High-dose ICS

+ LABA + oral 

systemic 

corticosteroid

Alternative:

High-dose ICS + 

either LTRA or 

Theophylline + 

oral systemic 

corticosteroid

Step up if 

needed

(first, check 

adherence, 

inhaler 

technique, 

environmental 

control, and 

comorbid

conditions)

Step down if 

possible

(and asthma is 

well controlled 

at least

3 months)

Each step: Patient education, environmental control, and management of comorbidities.

Steps 2−4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma 

(see notes).

Step 4

Preferred:

Medium-dose 

ICS + LABA

Alternative:

Medium-dose 

ICS + either 

LTRA or 

Theophylline

Assess 

control

Quick-Relief Medication for All Patients

• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute 

intervals as needed. Short course of oral systemic corticosteroids may be needed.

• Caution: Increasing use of SABA or use >2 days a week for symptom relief (not prevention of EIB) generally indicates 

inadequate control and the need to step up treatment.

Key: Alphabetical order is used when more than one treatment option is listed within either preferred or 

alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist, LTRA, leukotriene 

receptor antagonist; SABA, inhaled short-acting beta2-agonist 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual 

patient needs. 

 If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before 

stepping up. 

 Theophylline is a less desirable alternative due to the need to monitor serum concentration levels. 

 Step 1 and step 2 medications are based on Evidence A. Step 3 ICS + adjunctive therapy and ICS are based on 

Evidence B for efficacy of each treatment and extrapolation from comparator trials in older children and adults—

comparator trials are not available for this age group; steps 4–6 are based on expert opinion and extrapolation 

from studies in older children and adults. 

 Immunotherapy for steps 2–4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence 

is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. 

The role of allergy in asthma is greater in children than in adults. Clinicians who administer immunotherapy should 

be prepared and equipped to identify and treat anaphylaxis that may occur. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

307 

August 28, 2007 

FIGURE 4–2a. CLASSIFYING ASTHMA SEVERITY AND INITIATING 

TREATMENT IN CHILDREN 0–4 YEARS OF AGE 

Assessing severity and initiating therapy in children who are not currently taking long-term control 

medication 

Step 3 and consider short course of 

oral systemic corticosteroids

Recommended Step for Step 1 Step 2 Initiating Therapy

(See figure 4−1a for

treatment steps.)

In 2−6 weeks, depending on severity, evaluate level of asthma control that is 

achieved. If no clear benefit is observed in 4−6 weeks, consider adjusting 

therapy or alternative diagnoses.

None Minor limitation Some limitation Extremely limited Interference with 

normal activity

Several times

per day Daily >2 days/weekbut not daily ≤2 days/week

Short-acting

beta2-agonist use 

for symptom 

control (not 

prevention of EIB)

Consider severity and interval since last exacerbation.

Frequency and severity may fluctuate over time.

Exacerbations of any severity may occur in patients in any severity category.

Exacerbations

requiring oral 

systemic 

corticosteroids

Risk

Impairment

0 1−2x/month 3−4x/month >1x/week Nighttime

awakenings

Classification of Asthma Severity

(0−4 years of age)

Persistent

Components of

Severity

≥2 exacerbations in 6 months requiring oral systemic 

corticosteroids, or ≥4 wheezing episodes/1 year lasting

>1 day AND risk factors for persistent asthma

0−1/year

Throughout

the day Daily >2 days/week

but not daily Symptoms ≤2 days/week

Intermittent Mild Moderate Severe

Key: EIB, exercise-induced bronchospasm 

Notes 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual 

patient needs. 

 Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s/caregiver’s 

recall of previous 2–4 weeks. Symptom assessment for longer periods should reflect a global assessment such as 

inquiring whether the patient’s asthma is better or worse since the last visit. Assign severity to the most severe 

category in which any feature occurs. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma 

severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the 

past 6 months, or ≥4 wheezing episodes in the past year, and who have risk factors for persistent asthma may be 

considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent 

with persistent asthma. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

308 

August 28, 2007 

FIGURE 4–2b. CLASSIFYING ASTH MA SEVERITY AND INITIATING 

TREATMENT IN CHILDREN 5–11 YEARS OF AGE 

Assessing severity and initiating therapy in children who are not currently taking long-term control 

medication 

None Minor limitation Some limitation Extremely limited Interference with

normal activity

Step 1 and consider short course of

oral systemic corticosteroids

Step 3, mediumdose ICS option

In 2−6 weeks, evaluate level of asthma control that is achieved, and adjust therapy 

accordingly.

Step 3, medium-dose 

ICS option, or step 4

Risk

Exacerbations

requiring oral 

systemic 

corticosteroids

• FEV1 • FEV1/FVC >85% • FEV1/FVC >80% • FEV1/FVC = 75−80% /FVC <75%

• FEV1 <60% 

predicted

• FEV1 = 60−80% 

predicted

• FEV1 = >80% 

predicted

• FEV1 >80% 

predicted

Lung function

0−1/year (see note) ≥2/year (see note)

• Normal FEV1

between 

exacerbations

Several times

per day Daily >2 days/week

but not daily ≤2 days/week

Short-acting

beta2-agonist use for 

symptom control (not 

prevention of EIB)

Consider severity and interval since last exacerbation.

Frequency and severity may fluctuate over time for patients in any severity category.

Step 2

Classification of Asthma Severity

(5−11 years of age)

Impairment

Recommended Step for 

Initiating Therapy

(See figure 4−1b for

treatment steps.)

Persistent

Components of 

Severity

Relative annual risk of exacerbations may be related to FEV1.

Often 7x/week >1x/week but

not nightly ≤2x/month 3−4x/month Nighttime

awakenings

Throughout

the day

>2 days/week but Daily

not daily

≤2 days/week Symptoms

Intermittent Mild Moderate Severe

Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; 

ICS, inhaled corticosteroids 

Notes 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual 

patient needs. 

 Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s/caregiver’s 

recall of the previous 2–4 weeks and spirometry. Assign severity to the most severe category in which any feature 

occurs. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma 

severity. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, 

hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients 

who had ≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as 

patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

309 

August 28, 2007 

FIGURE 4–3a. ASSESSING ASTH MA CONTROL AND ADJUSTING 

THERAPY IN CHILDREN 0–4 YEARS OF AGE 

• Consider short course of 

oral systemic 

corticosteroids,

• Step up (1−2 steps), and

• Reevaluate in 2 weeks. 

• If no clear benefit in 4−6 

weeks, consider alternative 

diagnoses or adjusting 

therapy.

• For side effects, consider 

alternative treatment 

options.

• Step up (1 step) and

• Reevaluate in

2−6 weeks.

• If no clear benefit in 

4−6 weeks, consider 

alternative diagnoses 

or adjusting therapy.

• For side effects, 

consider alternative 

treatment options.

• Maintain current 

treatment.

• Regular followup

every 1−6 

months.

• Consider step 

down if well 

controlled for at 

least 3 months.

Recommended Action

for Treatment

(See figure 4−1a for

treatment steps.)

0−1/year 2−3/year >3/year

Exacerbations requiring 

oral systemic 

corticosteroids

Risk

≤2 days/week >2 days/week Several times per day

Short-acting

beta2-agonist use

for symptom control 

(not prevention of EIB)

None Some limitation Extremely limited Interference with 

normal activity

Medication side effects can vary in intensity from none to very troublesome and 

worrisome. The level of intensity does not correlate to specific levels of control 

but should be considered in the overall assessment of risk.

Classification of Asthma Control (0−4 years of age)

Impairment

Components of Control

Treatment-related 

adverse effects

Nighttime awakenings ≤1x/month >1x/month >1x/week

Symptoms ≤2 days/week >2 days/week Throughout the day

Very Poorly Controlled Not Well 

Controlled

Well

Controlled

Key: EIB, exercise-induced bronchospasm 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual 

patient needs. 

 The level of control is based on the most severe impairment or risk category. Assess impairment domain by 

caregiver’s recall of previous 2–4 weeks. Symptom assessment for longer periods should reflect a global 

assessment such as inquiring whether the patient’s asthma is better or worse since the last visit. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma 

control. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, 

hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had 

≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients 

who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled 

asthma. 

 Before step up in therapy: 

— Review adherence to medications, inhaler technique, and environmental control. 

— If alternative treatment option was used in a step, discontinue it and use preferred treatment for that step. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

310 

August 28, 2007 

FIGURE 4–3b. ASSESSING ASTH MA CONTROL AND ADJUSTING 

THERAPY IN CHILDREN 5–11 YEARS OF AGE 

Consider severity and interval since last exacerbation

• Consider short course of oral 

systemic corticosteroids, 

• Step up 1−2 steps, and

• Reevaluate in 2 weeks.

• For side effects, consider 

alternative treatment options.

• Step up at least 

1 step and

• Reevaluate in 

2−6 weeks.

• For side effects: 

consider alternative 

treatment options.

• Maintain current step.

• Regular followup

every 1−6 months.

• Consider step down if 

well controlled for at 

least 3 months.

Recommended Action

for Treatment

(See figure 4−1b for

treatment steps.)

Lung function

<60% predicted/

personal best

60−80% predicted/

personal best

>80% predicted/

personal best

• FEV1 or peak flow

Evaluation requires long-term followup.

Medication side effects can vary in intensity from none to very troublesome and worrisome. 

The level of intensity does not correlate to specific levels of control but should be 

considered in the overall assessment of risk.

Treatment-related 

adverse effects

Exacerbations requiring 0−1/year ≥2/year (see note)

oral systemic 

corticosteroids

Risk

≤2 days/week >2 days/week Several times per day

Short-acting

beta2-agonist use

for symptom control

(not prevention of EIB)

None Some limitation Extremely limited Interference with normal 

activity

Classification of Asthma Control (5−11 years of age)

Impairment

Components of Control

Reduction in

lung growth

• FEV >80% 75−80% <75% 1/FVC

≤1x/month ≥2x/month ≥2x/week Nighttime

awakenings

Throughout the day

>2 days/week or 

multiple times on

≤2 days/week

≤2 days/week but not 

more than once on each 

day

Symptoms

Very Poorly Controlled Not Well 

Controlled

Well

Controlled

Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual 

patient needs. 

 The level of control is based on the most severe impairment or risk category. Assess impairment domain by 

patient’s/caregiver’s recall of previous 2–4 weeks and by spirometry/or peak flow measures. Symptom 

assessment for longer periods should reflect a global assessment such as inquiring whether the patient’s asthma 

is better or worse since the last visit. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma 

control. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, 

hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had 

≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients 

who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma. 

 Before step up in therapy: 

— Review adherence to medications, inhaler technique, environmental control, and comorbid conditions. 

— If alternative treatment option was used in a step, discontinue it and use preferred treatment for that step. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

311 

August 28, 2007 

FIGURE 4–4a. USUAL DOSAGE S FOR LONG-TERM CONTROL 

MEDICATIONS IN CHILDREN* 

Medication 

Dosage 

Form 0–4 years 5–11 years Comments 

Inhaled Corticosteroids (ICSs) (See figure 4–4b, Estimated Comparative Daily Dosages for ICSs in Children.)

Systemic Corticosteroids (Applies to all three corticosteroids) 

Methylprednisolone 2, 4, 8, 16, 

32 mg tablets 

Prednisolone 5 mg tablets, 

5 mg/5 cc, 

15 mg/5 cc 

Prednisone 1, 2.5, 5, 10, 

20, 50 mg 

tablets; 

5 mg/cc, 

5 mg/5 cc 

0.25–2 mg/kg 

daily in single 

dose in a.m. or 

qod as needed 

for control 

Short-course 

“burst”: 1–2 

mg/kg/day, 

maximum 

60 mg/day for 

3–10 days 

0.25–2 mg/kg 

daily in single 

dose in a.m. or 

qod as needed 

for control 

Short-course 

“burst”: 1–2 

mg/kg/day, 

maximum 

60 mg/day for 3–

10 days 

 For long-term treatment of severe 

persistent asthma, administer single 

dose in a.m. either daily or on 

alternate days (alternate-day therapy 

may produce less adrenal 

suppression). 

 Short courses or “bursts” are effective 

for establishing control when initiating 

therapy or during a period of gradual 

deterioration. 

 There is no evidence that tapering the 

dose following improvement in 

symptom control and pulmonary 

function prevents relapse. 

 Patients receiving the lower dose 

(1 mg/kg/day) experience fewer 

behavioral side effects (Kayani and 

Shannon 2002), and it appears to be 

equally efficacious (Rachelefsky 

2003). 

 For patients unable to tolerate the 

liquid preparations, dexamethasone 

syrup at 0.4 mg/kg/day may be an 

alternative. Studies are limited, 

however, and the longer duration of 

activity increases the risk of adrenal 

suppression (Hendeles 2003). 

Long-Acting Beta2-Agonists (LABAs)  Should not be used for symptom 

relief or exacerbations. Use only 

with ICSs. 

Salmeterol DPI 50 mcg/ 

blister 

Safety and 

efficacy not 

established in 

children 

<4 years 

1 blister q 

12 hours 

 Decreased duration of protection 

against EIB may occur with regular 

use. 

 Most children <4 years of age cannot 

provide sufficient inspiratory flow for 

adequate lung delivery. 

 Do not blow into inhaler after dose is 

activated. 

Formoterol DPI 12 mcg/ 

single-use 

capsule 

Safety and 

efficacy not 

established in 

children 

<5 years 

1 capsule q 

12 hours  Most children <4 years of age cannot 

provide sufficient inspiratory flow for 

adequate lung delivery. 

 Each capsule is for single use only; 

additional doses should not be 

administered for at least 12 hours. 

 Capsules should be used only with 

the inhaler and should not be taken 

orally. 

*Dosages are provided for those products that have been approved by the U.S. Food and Drug Administration or have sufficient 

clinical trial safety and efficacy data in the appropriate age ranges to support their use. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

312 

August 28, 2007 

FIGURE 4–4a. USUAL DOSAGE S FOR LONG-TERM CONTROL 

MEDICATIONS IN CHIL DREN* (CONTINUED) 

Medication Dosage Form 0–4 years 5–11 years Comments 

Combined Medication 

Fluticasone/ 

Salmeterol 

DPI 100 mcg/ 

50 mcg 

Safety and 

efficacy not 

established in 

children 

<4 years 

1 inhalation bid  There have been no clinical trials in 

children <4 years of age. 

 Most children <4 years of age cannot 

provide sufficient inspiratory flow for 

adequate lung delivery. 

 Do not blow into inhaler after dose is 

activated. 

Budesonide/ 

Formoterol 

HFA MDI 

80 mcg/4.5 mcg 

Safety and 

efficacy not 

established 

 2 puffs bid  There have been no clinical trials in 

children <4 years of age. 

 Currently approved for use in youths 

≥12. Dose for children 5–12 years of 

age based on clinical trials using DPI 

with slightly different delivery 

characteristics (Pohunek et al. 2006; Tal 

et al. 2002; Zimmerman et al. 2004). 

Cromolyn/Nedocromil 

Cromolyn MDI 

0.8 mg/puff 

Safety and 

efficacy not 

established 

2 puffs qid 

 Nebulizer 

20 mg/ampule 

1 ampule qid 

Safety and 

efficacy not 

established 

<2 years 

1 ampule qid 

Nedocromil MDI 

1.75 mg/puff 

Safety and 

efficacy not 

established 

<6 years 

2 puffs qid 

 4–6 week trial may be needed to 

determine maximum benefit. 

 Dose by MDI may be inadequate to 

affect hyperresponsiveness. 

 One dose before exercise or allergen 

exposure provides effective prophylaxis 

for 1–2 hours. Not as effective as 

inhaled beta2-agonists for EIB. 

 Once control is achieved, the frequency 

of dosing may be reduced. 

Leukotriene Receptor Antagonists (LTRAs) 

Montelukast 4 mg or 5 mg 

chewable tablet 

4 mg granule 

packets 

4 mg qhs 

(1–5 years of 

age) 

5 mg qhs 

(6–14 years of 

age) 

 Montelukast exhibits a flat doseresponse curve. 

 No more efficacious than placebo in 

infants 6–24 months (van Adelsberg et 

al. 2005). 

Zafirlukast 10 mg tablet Safety and 

efficacy not 

established 

10 mg bid 

(7–11 years of 

age) 

 For zafirlukast, administration with meals 

decreases bioavailability; take at least 

1 hour before or 2 hours after meals. 

 Monitor for signs and symptoms of 

hepatic dysfunction. 

Methylxanthines 

Theophylline Liquids, 

sustained-release 

tablets, and 

capsules 

Starting dose 10 

mg/kg/day; 

usual maximum: 

 <1 year of 

age: 0.2 (age 

in weeks) + 5 

= mg/kg/day 

 ≥1 year of 

age: 16 

mg/kg/day 

Starting dose 

10 mg/kg/day; 

usual maximum: 

16 mg/kg/day 

 Adjust dosage to achieve serum 

concentration of 5–15 mcg/mL at 

steady-state (at least 48 hours on same 

dosage). 

 Due to wide interpatient variability in 

theophylline metabolic clearance, routine 

serum theophylline level monitoring is 

essential. 

 See next page for factors that can affect 

theophylline levels. 

Key: DPI, dry powder inhaler; EIB, exercise-induced bronchospasm; HFA, hydrofluoroalkane (inhaler propellant); MDI, metered 

dose inhaler 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

313 

August 28, 2007 

FIGURE 4–4a. USUAL DOSAGE S FOR LONG-TERM CONTROL 

MEDICATIONS IN CHIL DREN* (CONTINUED) 

Factors Affecting Serum Theophylline Concentrations†

Factor 

Decreases Theophylline 

Concentrations 

Increases Theophylline 

Concentrations Recommended Action 

Food È or delays absorption of 

some sustained-release 

theophylline (SRT) 

products 

Ç rate of absorption 

(fatty foods) 

Select theophylline preparation 

that is not affected by food. 

Diet Ç metabolism (high protein) È metabolism (high 

carbohydrate) 

Inform patients that major 

changes in diet are not 

recommended while taking 

theophylline. 

Systemic, febrile 

viral illness (e.g., 

influenza) 

È metabolism Decrease theophylline dose 

according to serum 

concentration. Decrease dose 

by 50 percent if serum 

concentration measurement is 

not available. 

Hypoxia, cor 

pulmonale, and 

decompensated 

congestive heart 

failure, cirrhosis 

È metabolism Decrease dose according to 

serum concentration. 

Age Ç metabolism (1–9 years) È metabolism (<6 

months, elderly) 

Adjust dose according to serum 

concentration. 

Phenobarbital, 

phenytoin, 

carbamazepine 

Ç metabolism Increase dose according to 

serum concentration. 

Cimetidine È metabolism Use alternative H2 blocker (e.g., 

famotidine or ranitidine). 

Macrolides: 

erythromycin, 

clarithromycin, 

troleandomycin 

È metabolism Use alternative macrolide 

antibiotic, azithromycin, or 

alternative antibiotic or adjust 

theophylline dose. 

Quinolones: 

ciprofloxacin, 

enoxacin, 

perfloxacin 

È metabolism Use alternative antibiotic or 

adjust theophylline dose. 

Circumvent with ofloxacin if 

quinolone therapy is required. 

Rifampin Ç metabolism Increase dose according to 

serum concentration. 

Ticlopidine È metabolism Decrease dose according to 

serum concentration. 

Smoking Ç metabolism Advise patient to stop smoking; 

increase dose according to 

serum concentration. 

†

This list is not all inclusive; for discussion of other factors, see package inserts.
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

314 

August 28, 2007 

FIGURE 4–4b. ESTIMATED CO MPARATIVE DAILY DOSAGES FOR 

INHALED CORTICOSTEROIDS IN CHILDREN 

Low Daily Dose Medium Daily Dose High Daily Dose 

Drug Child 0–4 Child 5–11 Child 0–4 Child 5–11 Child 0–4 Child 5–11 

Beclomethasone 

HFA 

 

40 or 80 mcg/puff NA 80–160 mcg NA >160–320 mcg NA >320 mcg 

Budesonide DPI 

90, 180, or 200 

mcg/inhalation 

NA 180–400 

mcg 

NA >400–800 mcg NA >800 mcg 

Budesonide 

inhaled 

 

Inhalation 

suspension for 

nebulization (child 

dose) 

0.25–0.5 

mg 

0.5 mg >0.5–1.0 mg 1.0 mg >1.0 mg 2.0 mg 

Flunisolide 

250 mcg/puff NA 500–750 

mcg 

NA 1,000–1,250 

mcg 

NA >1,250 mcg 

Flunisolide HFA 

80 mcg/puff NA 160 mcg NA 320 mcg NA ≥640 mcg 

Fluticasone 

HFA/MDI: 44, 110, 

or 

220 mcg/puff 

176 mcg 88–176 mcg >176–352 mcg >176–352 mcg >352 mcg >352 mcg 

DPI: 50, 100, or 

250 mcg/inhalation

NA 100–200 

mcg 

NA >200–400 mcg NA >400 mcg 

Mometasone DPI 

200 mcg/inhalation NA NA NA NA NA NA 

Triamcinolone 

acetonide 

 

75 mcg/puff NA 300–600 

mcg 

NA >600–900 mcg NA >900 mcg 

Key: HFA, hydrofluoroalkane; NA, not approved and no data available for this age group 

Notes: 

 The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy. The clinician must monitor the 

patient’s response on several clinical parameters and adjust the dose accordingly. The stepwise approach to therapy emphasizes that once control of asthma 

is achieved, the dose of medication should be carefully titrated to the minimum dose required to maintain control, thus reducing the potential for adverse effect. 

 Some doses may be outside package labeling, especially in the high-dose range. Budesonide nebulizer suspension is the only ICS with FDA approved labeling 

for children <4 years of age. 

 Metered-dose inhaler (MDI) dosages are expressed as the actuator dose (the amount of the drug leaving the actuator and delivered to the patient), which is the 

labeling required in the United States. This is different from the dosage expressed as the valve dose (the amount of drug leaving the valve, not all of which is 

available to the patient), which is used in many European countries and in some scientific literature. Dry powder inhaler (DPI) doses are expressed as the 

amount of drug in the inhaler following activation. 

 For children <4 years of age: The safety and efficacy of ICSs in children <1 year has not been established. Children <4 years of age generally require delivery 

of ICS (budesonide and fluticasone HFA) through a face mask that should fit snugly over nose and mouth and avoid nebulizing in the eyes. Wash face after 

each treatment to prevent local corticosteroid side effects. For budesonide, the dose may be administered 1–3 times daily. Budesonide suspension is 

compatible with albuterol, ipratropium, and levalbuterol nebulizer solutions in the same nebulizer. Use only jet nebulizers, as ultrasonic nebulizers are 

ineffective for suspensions. 

 For fluticasone HFA, the dose should be divided 2 times daily; the low dose for children <4 years is higher than for children 5–11 years of age due to lower 

dosedelivered with face mask and data on efficacy in young children.
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

315 

August 28, 2007 

FIGURE 4–4b. ESTIMATED CO MPARATIVE DAILY DOSAGES FOR 

INHALED CORTICOSTEROIDS IN CHILDREN (CONTINUED) 

 Comparative dosages are based on published comparative clinical trials (Adams et al. 2005; Barnes et al. 1998; Kelly 

1998; Lasserson et al. 2005; Pedersen and O'Byrne 1997). The rationale for some key comparisons is summarized as 

follows: 

— The high dose is the dose that appears likely to be the threshold beyond which significant hypothalamic-pituitaryadrenal (HPA) axis suppression is produced, and, by extrapolation, the risk is increased for other clinically significant 

systemic effects if used for prolonged periods of time (Martin et al. 2002; Szefler et al. 2002). 

— The low- to medium-doses reflect findings from dose-ranging studies in which incremental efficacy within the low- to 

medium dose ranges was established without increased systemic effect as measured by overnight cortisol excretion. 

The studies demonstrated a relatively flat dose-response curve for efficacy at the medium-dose range; that is, 

increasing the dose of high-dose range did not significantly increase efficacy but did increase systemic effect (Adams 

et al. 2001; Martin et al. 2002; Szefler et al. 2002). 

— The doses for budesonide and fluticasone MDI or DPI are based on recently available comparative data. These new 

data, including meta-analyses, show that fluticasone requires one-half the microgram dose of budesonide DPI to 

achieve comparable efficacy (Adams et al. 2005; Barnes et al. 1998; Nielsen and Dahl 2000). 

— The dose for beclomethasone in HFA inhaler should be approximately one-half the dose for beclomethasone 

chlorofluorocarbon (CFC) inhaler for adults and children, based on studies demonstrating that the different 

pharmaceutical properties of the medications result in enhanced lung delivery for the HFA (a less forceful spray from 

the HFA propellant and a reengineered nozzle that allows a smaller particle size) and clinical trials demonstrating 

similar potency to fluticasone at 1:1 dose ratio (Boulet et al. 2004; Busse et al. 1999; Gross et al. 1999; Lasserson et al. 

2005; Leach et al. 1998; Pedersen et al. 2002; Szefler et al. 2002; Thompson et al. 1998). 

— The dose for budesonide nebulizer suspension is based on efficacy and safety studies (Baker et al. 1999; Kemp et al. 

1999; Shapiro et al. 1998). It is noted that the efficacy studies did not demonstrate a clear or consistent doseresponse, although the high dose of 2.0 mg was effective in a placebo-controlled study in 40 infants who had severe 

asthma (de Blic et al. 1996). In a small, open-label, long-term safety study, the ACTH-stimulated cortisols appeared 

lower in the 13 infants receiving a high dose of 2.0 mg budesonide compared to infants receiving lower doses, but this 

result was not statistically significant, perhaps due to the small study size (Scott and Skoner 1999). 

— The dose for flunisolide HFA is based on product information and current literature (Corren et al. 2001; Gillman et al. 

2002; Richards et al. 2001). 

— The dose of budesonide/formoterol in children is based on product information and current literature (Pohunek et al. 

2006; Tal et al. 2002; Zimmerman et al. 2004).

— The dose for fluticasone HFA in children <5 years of 

age is based on clinical studies demonstrating efficacy 

at this dose of 176 mcg/day (Bisgaard et al. 2004; 

Guilbert et al. 2006). 

 Bioavailability

Both the relative potency and the relative bioavailability 

(systemic availability) determine the potential for systemic 

activity of an ICS preparation. As illustrated here, the 

bioavailability of an ICS is dependent on the absorption of 

the dose delivered to the lungs and the oral bioavailability 

of the swallowed portion of the dose received. 

— Absorption of the dose delivered to the lungs: 

♦ Approximately 10–50 percent of the dose from the 

MDI is delivered to the lungs. This amount varies 

among preparations and delivery devices. 

♦ Nearly all of the amount delivered to the lungs is 

bioavailable. 

Inactivation in gut 

Inactivation in the 

liver or gut wall 

“first pass” 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

316 

August 28, 2007 

FIGURE 4–4b. ESTIMATED CO MPARATIVE DAILY DOSAGES FOR 

INHALED CORTICOSTEROIDS IN CHILDREN (CONTINUED) 

— Oral bioavailability of the swallowed portion of the dose received: 

♦ Approximately 50–80 percent of the dose from the MDI without a spacer or valved holding chamber is swallowed. 

♦ The oral bioavailability of this amount varies: 

Either a high first-pass metabolism or the use of a spacer/holding chamber with an MDI can decrease oral 

bioavailability, thus enhancing safety (Lipworth 1995). 

The approximate oral bioavailability of ICS has been reported as: beclomethasone dipropionate, 20 percent; 

flunisolide, 21 percent; triamcinolone acetonide, 10.6 percent; budesonide, 11 percent; fluticasone propionate, 

1 percent; mometasone, <1 percent (Affrime et al. 2000; Chaplin et al. 1980; Check and Kaliner 1990; Clissold and 

Heel 1984; Davies 1993; Harding 1990; Heald et al. 1995; Martin et al. 1974; Mollmann et al. 1985; Szefler 1991; 

Wurthwein and Rohdewald 1990).

Potential drug interactions 

 A number of the ICSs, including fluticasone, budesonide, and mometasone, are metabolized in the gastrointestinal tract 

and liver by CYP 3A4 isoenzymes. Potent inhibitors of CYP 3A4, such as ritonavir and ketoconazole, have the potential 

for increasing systemic concentrations of these ICSs by increasing oral availability and decreasing systemic clearance. 

Some cases of clinically significant Cushing syndrome and secondary adrenal insufficiency have been reported (Johnson 

et al. 2006; Samaras et al. 2005). 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

317 

August 28, 2007 

FIGURE 4–4c. USUAL DOSAGES FOR QUICK-RELIEF 

MEDICATIONS IN CHILDREN* 

Medication Dosage Form 0–4 Years 5–11 Years Comments 

Inhaled Short-Acting Beta2-Agonists 

MDI 

Albuterol CFC 90 mcg/puff, 

200 puffs/canister

1–2 puffs 

5 minutes before

exercise 

2 puffs 5 minutes 

before exercise 

Albuterol HFA 90 mcg/puff, 

200 puffs/canister 

2 puffs every 4–6 

hours as needed 

2 puffs every 4–6 

hours as needed 

 Differences in potencies exist, but 

all products are essentially 

comparable on a per puff basis. 

 An increasing use or lack of 

expected effect indicates 

diminished control of asthma. 

 Not recommended for long-term 

daily treatment. Regular use 

exceeding 2 days/week for 

symptom control (not prevention of 

EIB) indicates the need for 

additional long-term control 

therapy. 

 May double usual dose for mild 

exacerbations. 

Levalbuterol HFA 45 mcg/puff, 

200 puffs/canister 

Safety and 

efficacy not 

established in 

children <4 years 

2 puffs every 

4–6 hours as 

needed 

 Should prime the inhaler by 

releasing 4 actuations prior to use. 

 Periodically clean HFA actuator, as 

drug may plug orifice. 

Pirbuterol CFC 

Autohaler 

200 mcg/puff, 

400 puffs/canister 

Safety and 

efficacy not 

established 

Safety and 

efficacy not 

established 

 Children <4 years may not generate 

sufficient inspiratory flow to activate 

an auto-inhaler. 

 Nonselective agents (i.e., 

epinephrine, isoproterenol, 

metaproterenol) are not 

recommended due to their potential 

for excessive cardiac stimulation, 

especially in high doses. 

Nebulizer solution 

Albuterol 0.63 mg/3 mL 

1.25 mg/3 mL 

2.5 mg/3 mL 

5 mg/mL (0.5%) 

0.63–2.5 mg in 

3 cc of saline 

q 4–6 hours, as 

needed

1.25–5 mg in 

3 cc of saline 

q 4–8 hours, as 

needed 

 May mix with cromolyn solution, 

budesonide inhalant suspension, or 

ipratropium solution for 

nebulization. May double dose for 

severe exacerbations. 

Levalbuterol 

(R-albuterol) 

0.31 mg/3 mL 

0.63 mg/3 mL 

1.25 mg/0.5 mL 

1.25 mg/3 mL 

0.31–1.25 mg in 

3 cc q 4–6 hours, 

as needed 

0.31–0.63 mg, 

q 8 hours, as 

needed 

 Does not have FDA-approved 

labeling for children <6 years of 

age. 

 The product is a sterile-filled 

preservative-free unit dose vial. 

 Compatible with budesonide 

inhalant suspension. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

318 

August 28, 2007 

FIGURE 4–4c. USUAL DOSAGES FOR QUICK-RELIEF 

MEDICATIONS IN CHIL DREN* (CONTINUED) 

Medication 

Dosage 

Form 0–4 Years 5–11 Years Comments 

Anticholinergics 

MDI 

Ipratropium HFA 17 mcg/puff, 

200 puffs/ 

canister 

Safety and 

efficacy not 

established 

Safety and 

efficacy not 

established 

Nebulizer 

solution 

 

0.25 mg/mL 

(0.025%) 

Safety and 

efficacy not 

established 

Safety and 

efficacy not 

established 

 Evidence is lacking for anticholinergics 

producing added benefit to beta2-agonists 

in long-term control asthma therapy. 

 See “Management of Acute Asthma” for 

dosing in ED. 

Systemic Corticosteroids Applies to the first three corticosteroids 

Methylprednisolone 2, 4, 6, 8, 

16, 32 mg 

tablets 

Short course 

“burst”: 1–2 

mg/kg/day, 

maximum 

60 mg/day, for

3–10 days 

Short course 

“burst”: 1-2

mg/kg/day, 

maximum

60 mg/day, for

3–10 days

Prednisolone 5 mg 

tablets, 

5 mg/5 cc, 

15 mg/5 cc 

 

Prednisone 1, 2.5, 5, 10, 

20, 50 mg 

tablets; 5 

mg/cc, 5 

mg/5 cc 

 

 Short courses or “bursts” are effective for 

establishing control when initiating therapy 

or during a period of gradual deterioration. 

 The burst should be continued until patient 

achieves 80% PEF personal best or 

symptoms resolve. This usually requires 

3–10 days but may require longer. There 

is no evidence that tapering the dose 

following improvement prevents relapse. 

Repository 

injection 

 

(Methylprednisolone 

acetate) 

40 mg/mL 

80 mg/mL 

7.5 mg/kg IM 

once 

240 mg IM 

once 

 May be used in place of a short burst of 

oral steroids in patients who are vomiting 

or if adherence is a problem. 

Key: CFC, chlorofluorocarbon; ED, emergency department; EIB, exercise-induced bronchospasm; HFA, hydrofluoroalkane; 

IM, intramuscular; MDI, metered-dose inhaler; PEF, peak expiratory flow 

*Dosages are provided for those products that have been approved by the U.S. Food and Drug Administration or have 

sufficient clinical trial safety and efficacy data in the appropriate age ranges to support their use. 
Section 4, Managing Asthma Long Term in Children 0–4 Years of Age and 5–11 Years of Age 

319 

August 28, 2007 

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SECTION 4, MANAGING ASTHMA LONG TERM IN YOUTHS ≥12 YEARS OF 

AGE AND ADULTS 

KEY POINTS: MANAGING ASTH MA LONG TERM IN YOUTHS 

≥ 12 YEARS OF AGE AND ADULTS 

 The goal for therapy is to control asthma by (Evidence A): 

— Reducing impairment 

♦ Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the 

daytime, in the night, or after exertion) 

♦ Require infrequent use (≤2 days a week) of SABA for quick relief of symptoms 

♦ Maintain (near) normal pulmonary function 

♦ Maintain normal activity levels (including exercise and other physical activity and 

attendance at work or school) 

♦ Meet patients’ and families’ expectations of and satisfaction with asthma care 

— Reducing risk 

♦ Prevent recurrent exacerbations of asthma and minimize the need for ED visits or 

hospitalizations 

♦ Prevent progressive loss of lung function; for youths, prevent reduced lung growth 

♦ Provide optimal pharmacotherapy with minimal or no adverse effects 

 A stepwise approach to pharmacologic therapy is recommended to gain and maintain 

control of asthma in both the impairment and risk domains (Evidence A): 

— The type, amount, and frequency of medication is determined by asthma severity for 

initiating therapy and by the level of asthma control for adjusting therapy (Evidence A). 

— Step-down therapy is essential to identify the minimum medication necessary to 

maintain control (Evidence D). 

 Monitoring and followup is essential (Evidence B). 

— When initiating therapy, monitor at 2- to 6-week intervals to ensure that asthma control is 

achieved (Evidence D). 

— Regular followup contacts at 1- to 6-month intervals, depending on the level of control, 

are recommended to ensure that control is maintained and appropriate adjustments in 

therapy are made—step up if necessary and step down if possible. Consider 3-month 

intervals if a step down in therapy is anticipated (Evidence D). 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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 Because asthma is a chronic inflammatory disorder of the airways with recurrent 

exacerbations, persistent asthma is most effectively controlled with daily long-term control 

medication, specifically, anti-inflammatory therapy (Evidence A). 

— ICSs are the preferred treatment option for initiating long-term control therapy 

(Evidence A). 

— Selection of an alternative treatment option includes consideration of treatment 

effectiveness, the domain of particular relevance to the patient (impairment, risk, or 

both), the individual patient’s history of previous response to therapies, the ability of the 

patient and family to use the medication correctly, and anticipated patient’s and family’s 

adherence to the treatment regime (Evidence D). 

 Therapeutic strategies should be considered in concert with clinician-patient partnership 

strategies; education of patients is essential for achieving optimal pharmacologic therapy 

(Evidence A). 

 At each step, patients should be advised to avoid or control allergens (Evidence A), irritants, 

or comorbid conditions that make the patient’s asthma worse (Evidence B). 

 A written asthma action plan detailing for the individual patient daily management 

(medications and environmental control strategies) and how to recognize and handle 

worsening asthma is recommended for all patients; written asthma action plans are 

particularly recommended for patients who have moderate or severe persistent asthma, a 

history of severe exacerbations, or poorly controlled asthma (Evidence B). The written 

asthma action plan can be either symptom or peak-flow based; evidence shows similar 

benefits for each (Evidence B). 

 Referral to an asthma specialist for consultation or comanagement is recommended if there 

are difficulties achieving or maintaining control of asthma; if the patient requires step 4 care 

or higher; if immunotherapy or omalizumab are considered; or if the patient has had an 

exacerbation requiring hospitalization. Consider referral if the patient requires step 3 care 

(Evidence D). 

 Special considerations for youths (EPR⎯2 1997): 

— Pulmonary function testing should use appropriate reference populations. Adolescents 

compare better to childhood than to adult predicted norms. 

— Adolescents (and younger children as appropriate) should be directly involved in 

establishing goals for therapy and developing their asthma management plans. 

— Active participation in physical activities, exercise, and sports should be promoted. 

— A written asthma management plan should be prepared for the student’s school, 

including plans to ensure reliable, prompt access to medications. Either encourage 

parents to take a copy to the child’s school or obtain parental permission and send a 

copy to the school nurse or designee. 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

 Special considerations for older adults (EPR⎯2 1997): 

— Chronic bronchitis/emphysema may coexist with asthma. A trial of systemic 

corticosteroids will determine the presence of reversibility and the extent of therapeutic 

benefit. 

— Asthma medications may aggravate coexisting medical conditions (e.g., cardiac disease, 

osteoporosis); adjustments in the medication plan may be necessary. 

— Be aware of increased potential for adverse drug/disease interaction (e.g., aspirin, 

beta-blockers). 

— Review of patient technique in using medications and devices is essential; physical (e.g., 

arthritis or visual) or cognitive impairments may make proper technique difficult. 



SECTION 4, STEPWISE APPROACH FOR MANAGING ASTHMA IN YOUTHS 

≥12 YEARS OF AGE AND ADULTS 

Treatment: Principles of Stepwise Therapy in Youths ≥12 Years of Age and 

Adults 

The Expert Panel recommends that the goal of asthma therapy is to maintain control of 

asthma with the least amount of medication and hence minimal risk for adverse effects 

(Evidence A). Control of asthma is viewed in the context of two domains, impairment 

and risk, and is defined as:

 Reducing impairment 

— Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the 

daytime, in the night, or after exertion) 

— Require infrequent use (≤2 days a week) of SABA for quick relief of symptoms 

— Maintain (near) normal pulmonary function 

— Maintain normal activity levels (including exercise and other physical activity and 

attendance at work or school) 

— Meet patients’ and families’ expectations of and satisfaction with asthma care 

 Reducing risk 

— Prevent recurrent exacerbations of asthma, and minimize the need for ED visits or 

hospitalizations 

— Prevent progressive loss of lung function; for youths, prevent reduced lung growth 

— Provide optimal pharmacotherapy with minimal or no adverse effects 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

The stepwise approach to therapy, in which the dose and number of medications and frequency 

of administration are increased as necessary and decreased when possible, is used to achieve 

and maintain this control. This approach is illustrated in figure 4–5. Because asthma is a 

chronic inflammatory disorder of the airways with recurrent exacerbations, therapy for persistent 

asthma must emphasize efforts to suppress inflammation over the long term and to prevent 

exacerbations. Recommendations in the stepwise approach to therapy are based on the Expert 

Panel’s review of the literature (See “Component 4: Medications.”) and the Expert Panel’s 

experience. 

The steps of care for managing asthma are presented in figure 4–5. Deciding which step of 

care is appropriate for a patient depends on whether long-term control therapy is being initiated 

for the first time or whether therapy is being adjusted. Care is stepped up to regain control, and 

it is stepped down for patients who have maintained control for a sufficient length of time to 

determine the minimal amount of medication required to maintain control and/or reduce the risk 

of side effects. The classification of asthma severity (figure 4–6), which considers the severity 

of both impairment and risk domains, provides a guide for initiating therapy for patients who are 

not currently taking long-term control medications. Once therapy is selected, or if the patient is 

already taking long-term control medication, the patient’s response to therapy will guide 

decisions about adjusting therapy based on the level of control achieved in both the impairment 

and risk domains (See figure 4–7.). 

ACHIEVING CONTROL OF ASTHMA 

Selecting Initial Therapy for Patients Not Currently Taking Long-Term Control 

Medications 

The Expert Panel recommends the following actions to achieve asthma control in 

patients who are not currently taking long-term control medications.

 Assess asthma severity (EPR⎯2 1997). Asthma severity is based on measurements of 

impairment and risk; see figure 4–6 and the discussion in “Component 1: Measures of 

Asthma Assessment and Monitoring.”

 Select treatment that corresponds to the patient’s level of asthma severity (EPR⎯2 

1997). See figure 4–6 for the recommended step of care at different levels of severity, and 

see figure 4–5 for treatment options at each step of care. See figures 4–8 a, b, and c for 

usual dosages of medications. However, the clinician must also judge the individual 

patient’s needs and circumstances to determine at what step to initiate therapy. For 

example, patients who have moderate or severe asthma that frequently interferes with sleep 

or normal activity often benefit from a course of oral corticosteroids to gain control of asthma 

more rapidly. Each patient’s response to treatment must also be assessed. 

 If at a followup visit in 2–6 weeks after starting treatment, depending on severity, 

asthma is not well controlled (see below), then treatment should be advanced to the 

next step. If uncontrolled asthma persists, then the diagnosis should be reevaluated, 

and, if confirmed, treatment should be advanced another step (Evidence D). 

Adjusting Therapy 

The Expert Panel recommends that, once therapy is selected, or if the clinician sees a 

patient for the first time who is already taking a long-term control medication, treatment 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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decisions are based on the level of the patient’s asthma control (See figure 4–7.) 

(Evidence A). 

 Assess asthma control. As in assessment of asthma severity, asthma control can be 

considered in terms of impairment and risk domains (Evidence C). Both domains should be 

addressed to select appropriate therapy; the level of control is generally judged on the most 

severe indicator of impairment or risk (Evidence D). 

Impairment Domain 

This domain is multifactorial because the different manifestations of asthma do not necessarily 

correlate with each other, and each factor should be assessed if possible (Evidence C). 

Symptoms. Three types of symptom assessments each appear to provide unique information 

regarding asthma control: symptom frequency, nighttime awakening, and activity limitation 

(Fuhlbrigge et al. 2002; Nathan et al. 2004; Vollmer et al. 1999). Frequency of shortness of 

breath appears to be particularly related to asthma control (Nathan et al. 2004) and quality of life 

(Moy et al. 2001). 

SABA use. Frequency of SABA use is a good measure of short-term (past month) (Nathan et 

al. 2004; Vollmer et al. 1999) and long-term (past year) asthma control (Schatz et al. 2006). 

Frequent use of SABA before exercise may confound these measures unless quick relief and 

prophylactic use can be separated. 

Pulmonary function. Office spirometry (prebronchodilator) or home peak flow measures 

reflect control in treated patients (Bateman et al. 2004; Juniper et al. 1999, 2001). Pulmonary 

function measures may be poorly correlated with asthma symptoms (Shingo et al. 2001; Stahl 

2000). 

Validated questionnaires. Several validated tools have been developed to measure asthma 

control (Juniper et al. 1999; Nathan et al. 2004; Vollmer et al. 1999) and can be used to classify 

asthma control. (See “Component 1: Measures of Asthma Assessment and Monitoring,” 

figure 3–8.) 

Risk Domain 

The risk domain includes frequency and severity of exacerbations and the occurrence of 

treatment-related adverse effects. Patients at any level of control of impairment may experience 

severe exacerbations. A history of previous exacerbations, especially exacerbations leading to 

ED visits or hospitalizations in the previous year, significantly increases the risk of subsequent 

exacerbations (Adams et al. 2000; Cowie et al. 2001; Eisner et al. 2001; Lieu et al. 1998; Schatz 

et al. 2004; Yurk et al. 2004). This highlights the need to obtain a history of previous 

exacerbations requiring hospitalization (including need for intensive care unit (ICU) admission or 

intubation), ED visits, and other unscheduled physician visits. In addition, increasing 

exacerbation rates are noted with decreasing FEV1 categories >80 percent, 60–79 percent, and 

<60 percent predicted (Fuhlbrigge et al. 2001, 2006; Kitch et al. 2004). 

It is generally hoped that control of impairment will reduce the risk of exacerbations (Schatz et 

al. 2005; Vollmer et al. 1999), but there may be a disassociation between the two. It has been 

demonstrated that control based on bronchial hyperreactivity (Sont et al. 1999), sputum 

eosinophilia (Green et al. 2002), or possibly fractional exhaled nitric oxide (FeNO) (Smith et al. 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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2005) is more effective in reducing exacerbations than control based on clinical markers alone, 

but more studies are needed, and only FeNO monitoring may become practical enough to be 

used clinically for this purpose. 

 Adjust therapy based on level of asthma control (Evidence A). The following 

considerations will guide selection of therapy based on level of asthma control. Classify 

current level of asthma control, generally, by the most severe indicator of impairment or risk 

(figure 4–7) (Evidence D). 

— If the patient’s asthma is not well controlled: 

♦ Identify the patient’s current treatment step (figure 4–5), based on what he or she is 

actually taking. In general, step up one step for patients whose asthma is not well 

controlled. For patients who have very poorly controlled asthma, consider increasing 

by two steps, a course of oral corticosteroids, or both. Before increasing 

pharmacologic therapy, consider poor inhaler technique, adverse environmental 

exposures, poor adherence, or comorbidities as targets for intervention. 

♦ If the office spirometry suggests worse control than does the assessment of 

impairment based on other measures, (1) consider fixed airway obstruction as the 

explanation (Aburuz et al. 2005) (See “Component 1: Measures of Asthma 

Assessment and Monitoring”.), and use changes from percent personal best rather 

than percent predicted to guide therapy; (2) reassess the other measures of 

impairment; and (3) if fixed airway obstruction does not appear to be the explanation, 

consider a step up in therapy, especially if the patient has a history of frequent 

moderate or severe exacerbations. 

♦ If the history of exacerbations suggests poorer control than does the assessment of 

impairment, (1) reassess impairment; (2) review control of factors capable of making 

asthma worse (e.g., lack of adherence, adverse environmental exposure, or 

comorbidities); (3) review the written action plan, and be sure it includes oral 

prednisone for patients who have histories of severe exacerbations; and (4) consider 

a step up in therapy, especially if the patient has reduced FEV1. 

♦ For troublesome or debilitating side effects, explore a change in therapy. In addition, 

confirm maximal efforts to control factors capable of making asthma worse (See 

“Component 3: Control of Environmental Factors and Comorbid Conditions That 

Affect Asthma.”). 

♦ After treatment is adjusted, reevaluate in 2–6 weeks, depending on the level of 

control. 

— If the patient’s asthma is well controlled, see the following section on “Maintaining 

Control of Asthma.” 

MAINTAINING CONTROL OF ASTHMA 

The Expert Panel recommends that regular followup contact is essential (Evidence B). 

Contact at 1- to 6-month intervals is recommended, depending on the level of control; 

consider 3-month intervals if a step down in therapy is anticipated (Evidence D). 

Clinicians need to assess whether control of asthma has been maintained and whether a step 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

up or down in therapy is appropriate. Clinicians also need to monitor and review the patient’s 

written asthma action plan, the medications, and the patient’s self-management behaviors (e.g., 

inhaler and peak flow monitoring techniques, actions to control factors that aggravate 

their asthma) (See “Component 2: Education for a Partnership in Asthma Care,” figures 3–11 

and 3–15.). 

The Expert Panel recommends that, once asthma is well controlled and the control is 

achieved and maintained for at least 3 months, a reduction in pharmacologic therapy—a 

step down—can be considered. This will be helpful to identify the minimum therapy for 

maintaining good control of asthma (Evidence D). Reduction in therapy should be gradual 

and closely monitored, because asthma can deteriorate at a highly variable rate and intensity. 

The patient should be instructed to contact the clinician if and when asthma worsens. 

Guidelines for the rate of reduction and intervals for evaluation have not been validated, and 

clinical judgment of the individual patient’s response to therapy is important. The opinion of the 

Expert Panel is that the dose of ICS may be reduced about 25–50 percent every 3 months to 

the lowest dose possible that is required to maintain control (Hawkins et al. 2003; Lemanske et 

al. 2001). Patients may relapse when the ICS is completely discontinued (Lemanske et al. 

2001; Waalkens et al. 1993). 

The Expert Panel recommends that, if asthma control is not achieved and maintained at 

any step of care (See figure 4–7.), several actions may be considered: 

 Patient adherence and technique in using medications correctly should be assessed 

(Evidence B). See “Component 2: Education for a Partnership in Asthma Care” for 

discussion on assessing adherence. Key questions to consider asking patients include: 

— Which medicines are you currently taking? How often? 

— Please show me how you take the medicine. 

— How many times a week do you miss taking the medication? 

— What problems have you had taking the medicine (cost, time, lack of perceived need)? 

— What concerns do you have about your asthma medicines? 

 A temporary increase in anti-inflammatory therapy may be indicated to reestablish 

asthma control (Evidence D). A deterioration of asthma may be characterized by gradual 

reduction in PEF (approximately 20 percent), by failure of SABA bronchodilators to produce 

a sustained response, by a reduced tolerance to activities or exercise, and by the 

development of increasing symptoms or nocturnal awakenings from asthma. To regain 

control of asthma, a short course of oral prednisone (See figure 4–8a.) is often effective. If 

asthma symptoms do not recur and pulmonary functions remain normal, no additional 

therapy is necessary. However, if the prednisone burst does not control symptoms, is 

effective only for a short period of time (e.g., less than 1–2 weeks), or is repeated frequently, 

the patient should be managed according to the next higher step of care. 

 Other factors that diminish control may have to be identified and addressed 

(Evidence C). These factors include the presence of a coexisting condition (e.g., 

rhinitis/sinusitis, gastroesophageal reflux, obesity), a new or increased exposure to allergens 

or irritants, patient or family barriers to adequate self-management behaviors, or 

psychosocial problems. In some cases, alternative diagnoses, such as VCD, should be 

considered. 

 A step up to the next higher step of care may be necessary (Evidence A). 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

 Consultation with an asthma specialist may be indicated (See “Component 1: 

Measures of Asthma Assessment and Monitoring.”) (Evidence D). The Expert Panel 

recommends referral to an asthma specialist for consultation or comanagement if: 

there are difficulties achieving or maintaining control of asthma; immunotherapy or 

omalizumab is being considered; the patient requires step 4 care or higher; or 

the patient has had an exacerbation requiring a hospitalization. (See 

“Component 1: Measures of Asthma Assessment and Monitoring.”). Referral may be 

considered if a patient requires step 3 care (Evidence D). 

Treatment: Pharmacologic Steps 

The Expert Panel recommends that specific therapy should be tailored to the needs and 

circumstances of individual patients. Pharmacologic therapy must be accompanied at 

every step by patient education and measures to control those environmental factors or 

comorbid conditions that can make asthma worse (EPR⎯2 1997). See “Component 3: 

Control of Environmental Factors and Comorbid Conditions That Affect Asthma” which includes 

discussion of the role of allergen immunotherapy, and “Component 2: Education for a 

Partnership in Asthma Care.” Figure 4–5 presents treatment options for the stepwise approach 

for managing asthma youths ≥12 years of age and adults. The recommendations for steps of 

pharmacologic therapy are intended to be general guidelines for assisting, not replacing, clinical 

decisionmaking. The recommendations are not intended to be prescriptions for individual 

treatment. 

INTERMITTENT ASTHMA 

The Expert Panel recommends the following therapy for intermittent asthma: 

Step 1 Care 

 SABA taken as needed to treat symptoms is usually sufficient therapy for intermittent 

asthma (EPR⎯2 1997). If effective in relieving infrequent symptoms and normalizing 

pulmonary function, intermittent use of SABA can continue on an as-needed basis. If 

significant symptoms recur or SABA is required for quick-relief treatment more than 2 days a 

week (with the exception of using SABA for exacerbations caused by viral infections and for 

EIB), the patient should be treated for persistent asthma (See below.). 

 Patients who have intermittent asthma and experience EIB benefit from taking SABA, 

cromolyn, or nedocromil shortly before exercise (EPR⎯2 1997) (See in 

“Exercise-Induced Bronchospasm” in “Managing Special Situations in Asthma.”). 

Cromolyn or nedocromil may be beneficial if taken before unavoidable exposure to an 

aeroallergen known to exacerbate the patient’s asthma (Cockcroft and Murdock 1987). 

 The following actions for managing exacerbations due to viral respiratory infections 

are recommended (EPR⎯2 1997). If the symptoms are mild, SABA (every 4–6 hours for 

24 hours, longer with a physician consult) may be sufficient to control symptoms and 

improve lung function. If this therapy must be repeated more frequently than every 6 weeks, 

a step up in long-term care is recommended. If the viral respiratory infection provokes a 

moderate-to-severe exacerbation, a short course of systemic corticosteroids should be 

considered. For those patients who have a history of severe exacerbations with viral 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

334 

August 28, 2007 

respiratory infections, systemic corticosteroids should be considered at the first sign of the 

infection. 

 A detailed written asthma action plan is recommended for those patients who have 

intermittent asthma and particularly those who have a history of severe exacerbations 

(Evidence B) (See “Component 2: Education for a Partnership in Asthma Care.”). 

Intermittent asthma—infrequent exacerbations separated by periods of no symptoms and 

normal pulmonary function—is often mild. Some patients who have intermittent asthma 

experience sudden, severe, and life-threatening exacerbations. It is essential to treat these 

exacerbations accordingly. The patient’s written asthma action plan should include 

indicators of worsening asthma (specific symptoms and PEF measurements), as well as 

specific recommendations for using SABA, early administering a course of oral systemic 

corticosteroids, and seeking medical care. Furthermore, periodic monitoring (See 

“Component 1: Measures of Asthma Assessment and Monitoring.”) of the patient is 

appropriate to evaluate whether the patient’s asthma is indeed intermittent or whether a 

stepup in long-term therapy is warranted. 

PERSISTENT ASTHMA 

The Expert Panel recommends the following therapy for persistent asthma: 

 Daily long-term control medication is recommended for patients who have persistent 

asthma. The long-term control medication should be one with anti-inflammatory 

effects. Of the available medications, ICSs are the most effective single agents 

(Evidence A) (see component 4—Medications). 

 Quick-relief medication must be available to all patients who have persistent asthma. 

SABA should be taken as needed to relieve symptoms (EPR⎯2 1997). The intensity of 

treatment will depend on the severity of the exacerbation (See section 5, “Managing 

Exacerbations of Asthma.”). Increasing use of SABA or use more than 2 days a week for 

symptom control (not for preventing EIB) indicates the need to step up therapy. 

 Consider treating patients who may have seasonal asthma (asthma symptoms only in 

relation to certain seasonal molds or pollens with few symptoms the rest of the year) 

as having persistent asthma during the season and as having intermittent asthma the 

rest of the year. Confirm characteristics of intermittent asthma out of season 

(Evidence D). Some patients experience asthma symptoms only in relationship to certain 

pollens and molds. Asthma exacerbations in children are common in the fall and seem to 

correlate with increased exposure to viral respiratory infections in the school environment 

(Hammerman et al. 2002; Johnston et al. 2005). 

 Consider treating patients who had two or more exacerbations requiring oral 

corticosteroids in the past year the same as patients who have persistent asthma, 

even in the absence of an impairment level consistent with persistent asthma 

(Evidence D).
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

Step 2 Care, Long-Term Control Medication 

 Preferred treatment for step 2 care is daily ICS at a low dose (Evidence A). 

 Alternative, but not preferred, treatments include (listed alphabetically) cromolyn, 

LTRA, nedocromil (Evidence A), and sustained release theophylline (Evidence B). 

There is insufficient evidence to recommend LABA in combination with ICS for step 2 

therapy. 

— Cromolyn and nedocromil have some, but limited, effectiveness and a strong safety 

profile. 

— LTRAs (montelukast and zafirlukast) provide long-term control, prevent symptoms, and 

are alternative, but not preferred, therapies for patients who have mild persistent 

asthma, because studies comparing overall efficacy of ICS and LTRA favor ICS on most 

asthma outcome measures (Evidence A). (See section 3, “Component 4: 

Medications.”) Zileuton, a leukotriene inhibitor, is not recommended in step 2 care, 

because no studies of zileuton specifically in patients who have mild persistent asthma 

have been reported, and zileuton requires liver function test monitoring (Evidence D). 

— Sustained-release theophylline is an alternative, but not preferred, long-term control 

medication. It is not preferred because the modest clinical effectiveness (theophylline 

is primarily a bronchodilator and its anti-inflammatory activity demonstrated thus far is 

modest) must be balanced against concerns about potential toxicity (See “Component 4: 

Medications.”). Theophylline remains a therapeutic option for certain patients due to 

expense or need for tablet-form medication. Sustained-release theophylline is given to 

achieve a serum concentration of between 5 and 15 mcg/mL. Periodic theophylline 

monitoring is necessary to maintain a therapeutic—but not toxic—level. 

— Insufficient evidence is available to recommend LABA in combination with ICS in 

step 2 care (O'Byrne et al. 2001). In steroid naïve patients who have mild persistent 

asthma, the initiation of an ICS in combination with a LABA does not significantly reduce 

the rate of exacerbations or the use of SABA for quick relief over that achieved with ICS 

alone, although the combination therapy can improve lung function and symptom days 

compared to ICS alone (Ni et al. 2005). Thus, there is insufficient efficacy evidence to 

recommend this combination therapy in step 2 care. In addition, the possibility of rare 

but potentially life-threatening outcomes with LABAs (See “Component 4: Medications.”) 

supports this recommendation. 

— A recent study has suggested that some patients who have mild persistent asthma may 

be successfully managed with intermittent use of low-dose ICS, because study 

participants taking daily budesonide, daily zafirlukast, or intermittent treatment with ICS 

and SABA (according to a symptom-based action plan) had similar improvement in 

morning PEF and a similarly low number of exacerbations (Boushey et al. 2005). 

However, other outcomes in this study were significantly better in patients taking regular 

versus intermittent ICS therapy (symptom-free days, prebronchodilator FEV1, airway 

hyperresponsiveness, and inflammatory markers). Currently, data are insufficient to 

recommend intermittent use of ICS for most patients who have mild persistent asthma, 

although it may be considered as a step-down therapy strategy for patients who are well 

controlled on step 2 therapy. Further studies are needed to evaluate the use of 

intermittent therapy with either ICSs or leukotriene modifiers. 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

Step 3 Care, Long-Term Control Medications 

 Consultation with an asthma specialist may be considered because the therapeutic 

options at this juncture pose a number of challenging risk/benefit considerations 

(Evidence D). Before increasing therapy, however, the clinician should review the 

patient’s inhaler technique and adherence to therapy (Evidence B), as well as 

determine whether environmental factors, particularly allergens (Evidence A), or 

comorbid conditions are contributing to the patient’s worsening asthma (Evidence C). 

 Preferred step 3 care options: Two equally acceptable options are available, given 

the consideration of both benefits and risks for each. 

— Add a LABA to a low dose of ICS (Evidence A). Studies on LABAs as adjunctive 

therapy have revealed both benefit and some risk. See “Component 4: Medications,” 

section on “Safety of Long-Acting Beta2-Agonists,” for a complete discussion. In 

summary: 

♦ Studies demonstrate the addition of a LABA (salmeterol or formoterol) to medications 

for patients whose asthma is not well controlled on a low to medium dose of ICSs 

improves lung function, decreases symptoms, and reduces exacerbations and use of 

quick-relief medication in most patients who have asthma (Bateman et al. 2004; 

EPR⎯2 1997; Greenstone et al. 2005; Masoli et al. 2005). See also Evidence Table 

11: Inhaled Corticosteroids—Combination Therapy. 

♦ A large clinical trial comparing daily treatment with salmeterol or placebo added to 

usual asthma therapy (Nelson et al. 2006) demonstrated an increased risk of 

asthma-related deaths in patients treated with salmeterol (13 deaths out of 13,176 

patients treated for 28 weeks with salmeterol versus 3 deaths out of 13,179 patients 

treated with placebo). In addition, an increased number of severe asthma 

exacerbations were noted in the pivotal trials submitted to the FDA for formoterol 

approval, particularly in the higher dose formoterol arms of the trials (Mann et al. 

2003). Thus the FDA determined that a Black Box warning was warranted on all 

preparations containing a LABA. 

♦ The Expert Panel recommends that the established, beneficial effects of LABAs for 

the great majority of patients who have asthma not sufficiently controlled with ICS 

therapy alone be weighed carefully against the increased risk for potentially 

deleterious, although uncommon, side effects associated with the daily use of 

LABAs. 

♦ Therefore, the Expert Panel has modified its previous recommendation 

(EPR⎯Update 2002) and has now concluded that, for patients who have asthma not 

sufficiently controlled with a low-dose ICS alone, the step-up option to increase the 

ICS dose should be given equal weight to that of the addition of a LABA to ICS. 

OR 

— Continue the ICS as monotherapy by increasing the dose to the medium-dose 

range (Evidence A). Studies of adults in whom the dose of ICS was at least doubled 

demonstrate some improvements in lung function and other outcomes in those patients 

who have asthma not completely controlled on a low-to-medium dose of ICS, although 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

these results are generally less effective than adding a LABA (Ind et al. 2003). In the 

GOAL study of 3,421 patients who had uncontrolled asthma, a substantial proportion of 

the patients who received a dose escalation of ICS achieved well-controlled (59 percent) 

or totally controlled (28 percent) asthma (Bateman et al. 2004). Furthermore, a study of 

2,670 patients showed similar rates of exacerbations and nighttime awakenings among 

the daily medium-dose ICS and daily combination low-dose (ICS/formoterol) study 

treatment groups (O'Byrne et al. 2005). Both studies confirm the benefits of increasing 

the dose of ICS (see below for further discussion on weighing the benefits and risks of 

different step 3 care options). 

Based on review of the evidence and in consideration of the potential benefits for improvements 

in the asthma control domains of impairment and risk, as well as consideration of the potential 

for adverse effects that exist for each therapeutic option, the Expert Panel recommends that 

either increasing the dose of the ICS to medium dose or adding LABA to low-dose ICS is an 

equally acceptable step-up option for patients whose asthma is not adequately controlled on a 

low dose of ICS. 

Overall, the results of the Expert Panel’s review of the evidence indicate that the choice one 

makes at this juncture of stepping up therapy should be based on which therapeutic outcome 

should be the focus for each individual patient: that is, the desired degree of asthma control in 

the domains of either impairment or risk, or both, weighed against the relative risks of side 

effects for the therapeutic options. 

 For the impairment domain, adding LABA, rather than increasing the dose of ICS, more 

consistently results in improvements in the impairment domain (EPR⎯Update 2002). 

 If the risk domain is of particular concern, then a balance of potential risks needs to be 

considered (See also “Component 4: Medications.”). 

— Adding LABA to low-dose ICS reduces the frequency of exacerbations to a greater 

extent than doubling the dose of ICS (Masoli et al. 2005), but adding LABA has the 

potential risk of rare life-threatening or fatal exacerbations. 

— Increasing the dose of ICS can significantly reduce the risk of exacerbations, but this 

benefit may require up to a fourfold increase in the ICS dose (Pauwels et al. 1997). This 

may increase the potential risk of systemic effects, although within the medium-dose 

range the risk is small. 

 Alternative, but not preferred, step 3 therapy is to add (listed alphabetically) an LTRA 

(Evidence A), theophylline (Evidence B), or zileuton (Evidence D) to low-dose ICS. 

Considerations favoring one of these alternative combinations would be the patient’s lack of 

response to or intolerance of the side effects of the LABA if that option was tried; marked 

preference for oral therapy; previous demonstration of superior responsiveness to the 

alternative class of drug; and/or financial considerations (theophylline is the least 

expensive). 

The addition of either LTRA, theophylline, or zileuton has produced modest improvement in 

lung function and some other outcomes in patients who have asthma that is not completely 

controlled by an ICS. The addition of theophylline, however, has not been shown to be 

more effective than doubling the dose of the ICS (Evans et al. 1997; Ukena et al. 1997). 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

LTRAs have produced improvements in lung function and in some but not all measures of 

asthma control in both adults (Laviolette et al. 1999) and children (Simons et al. 2001) 

whose asthma is not well controlled by ICSs. When the addition of the LTRA to an ICS has 

been compared with doubling the dose of the ICS, similar results were observed for a 

number of outcome measures (Price et al. 2003). Direct comparisons of the addition of an 

LTRA or a LABA to therapy for patients whose asthma is not well controlled by ICS show 

significantly greater improvement in lung function and other measures of asthma control for 

patients receiving the LABA and ICS combination (Ram et al. 2005). Because efficacy data 

are limited for zileuton as add-on therapy (Dahlen et al. 1998; Lazarus et al. 1998), and 

zileuton requires monitoring of liver function tests, the Expert Panel considers zileuton a less 

desirable alternative than LTRA or theophylline for step 3 add-on therapy. 

 If an alternative, but not preferred, treatment is initially administered and does not 

lead to improvement in asthma control, discontinue it and use a preferred step 3 

option before stepping up to step 4 (Evidence D). 

Step 4 Care, Long-Term Control Medications 

 The preferred option is to increase the dose of ICS to the medium-dose range AND 

add a LABA (Evidence B). This step is recommended for patients who have asthma not 

controlled by step 3 therapy. This approach is also recommended for those patients who 

experience recurring severe exacerbations requiring oral prednisone, ED visits, or 

hospitalizations. In a 1-year trial of combination therapy, the addition of a LABA to either 

low-dose or high-dose ICS significantly reduced both mild and severe exacerbation 

(Pauwels et al. 1997). In addition, fewer exacerbations occurred in the group receiving 

high-dose ICS compared with the group receiving the lower dose, although statistical 

analysis was not done. See also the discussion on LABA and combination therapy in 

“Component 4: Medications.” 

 Alternative, but not preferred, step 4 therapy includes medium-dose ICS AND either 

LTRA or theophylline (Evidence B), or zileuton (Evidence D). 

 If the add-on therapy initially administered does not lead to improvement in asthma control, 

discontinue it and consider a trial of a different add-on therapy before stepping up 

(Evidence D). 

Step 5 Care, Long-Term Control Medications 

 High-dose ICS and LABA is the preferred treatment (Evidence B). 

 Omalizumab may be considered at this step for patients who have sensitivity to 

relevant perennial allergens (e.g., dust mites, cockroach, cat, or dog) (Evidence B) 

(Bousquet et al. 2004; Humbert et al. 2005). 

 Clinicians who administer omalizumab are advised to be prepared and equipped for 

the identification and treatment of anaphylaxis that may occur, to observe patients for 

an appropriate period of time following each omalizumab injection (the optimal length 

of the observation is not established), and to educate patients about the risks of 

anaphylaxis and how to recognize and treat it if it occurs (e.g., using prescription 

auto injectors for emergency self-treatment, and seeking immediate medical care) 

(FDA 2007). 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

 Consultation with an asthma specialist is recommended for patients who require this 

step of therapy (Evidence D). 

Step 6 Care, Long-Term Control Medications 

 Add oral corticosteroids to step 5 therapy. Patients who are not controlled on 

step 5 therapy may require regular oral corticosteroids to achieve well-controlled 

asthma (EPR⎯2 1997). 

— Two studies have examined the benefit of LTRA as adjunctive therapy in patients who 

have asthma that is not controlled by ICS and LABA. One 2-week study found no 

benefit for the addition of an LTRA to high-dose ICS and, for most patients in the study, 

another medication (either theophylline, a LABA, oral corticosteroid, or a combination) 

(Robinson et al. 2001). Nathan et al. (2005) reported that adding montelukast for 

patients who had mild or moderate persistent asthma treated with combined fluticasone 

(100 mcg)–salmeterol did not improve asthma outcome compared to adding placebo. 

Studies are not available of other long-term control medications added to the 

combination of medium- to high-dose ICS and LABA in severe persistent asthma. 

These data are not definitive; therefore, due to the side effects associated with chronic 

oral corticosteroid therapy, before maintenance prednisone therapy is initiated, the 

following may be considered: a 2-week course of oral corticosteroids to confirm 

reversibility; or a combination of high-dose ICS + LABA + trial of either LTRA, low-dose 

theophylline, or zileuton (Evidence D). 

— For patients who require long-term systemic corticosteroids: 

♦ Use the lowest possible dose (single dose daily or on alternate days). 

♦ Monitor patients closely for corticosteroid adverse side effects (See “Component 4: 

Medications.”). 

♦ When well-controlled asthma is achieved, make persistent attempts to reduce 

systemic corticosteroids. High-dose ICS therapy is preferable to oral systemic 

corticosteroids because ICSs have fewer systemic effects. 

♦ Consultation with an asthma specialist is recommended. 

SPECIAL ISSUES FOR ADOLESCENTS 

The Expert Panel recommends that the pharmacologic management of asthma in 

school-age children and adolescents follows the same basic principles as those for 

adults, but the special circumstances of school and social development require special 

consideration (EPR⎯2 1997). 

Assessment Issues 

The Expert Panel recommends that pulmonary function testing should be performed by 

using comparison data from an appropriate reference population (ATS 1995; EPR⎯2 

1997). Adolescents generally compare better to childhood norms than to adult predicted norms. 

Testing in a laboratory or clinic that specializes in children can result in higher pulmonary 

function values and more consistent data. Technicians who conduct pulmonary function testing 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

for children should have special training in achieving the best possible effort from young 

patients. 

Treatment Issues 

The Expert Panel recommends that adolescents (and younger children as appropriate) be 

directly involved in developing their written asthma action plans (See “Component 2: 

Education for a Partnership in Asthma Care.”). Adolescents may experience more 

difficulties than younger children in adhering to a medication plan because they may fail to 

recognize the danger of poorly controlled asthma (Strunk et al. 1985), they may not accept 

having a chronic illness, or they may view the plan as infringing on their emerging independence 

and adulthood. In teaching adolescents the same asthma self-management techniques 

expected of adults, the clinician should address adolescent developmental issues, such as 

building a positive self-image and confidence, increasing personal responsibility, and gaining 

problem-solving skills. To accomplish this approach, it is often helpful to see the adolescent 

initially without parents present and to involve the adolescent directly in setting goals for 

therapy, developing an appropriate asthma action plan, and reviewing the effectiveness of the 

plan at repeated visits. The parents can be brought in at the end of the visit to review the plan 

together and to emphasize the parents’ important role in supporting the adolescent’s efforts. 

School Issues 

The Expert Panel recommends that the clinician prepare a written asthma action plan for 

the student’s school. Either encourage the youth or the parents to take a copy of the 

plan to the youth’s school or obtain parental permission and send a copy to the school 

nurse or designee (Evidence C). The written asthma action plan should include the following 

information: instructions for handling exacerbations (including the clinician’s recommendation 

regarding self-administration of medication); recommendations for long-term control medications 

and prevention of EIB, if appropriate; and identification of those factors that make the student’s 

asthma worse, so the school may help the student avoid exposure. For a sample plan, See 

figure 3–16a, b. 

It is preferable to schedule daily, long-term medications so that they are not taken at school, 

even if this results in unequal dosing intervals throughout the day. In school districts that have 

more comprehensive school nurse coverage, however, youths who would benefit from close 

supervision to promote adherence may be given medications at school. In this way, daily 

medication can be administered, and patient education can be supplemented most days of the 

week. 

Students who have asthma often require medication during school to treat acute symptoms or to 

prevent EIB that may develop during physical education class, school recess, or organized 

sports. Reliable, prompt access to medication is essential, but it may be difficult because of 

school rules that preclude the student from carrying medications. The NAEPP and several 

member organizations have adopted resolutions that endorse allowing students to carry and 

self-administer medications when the physician and parent consider this appropriate. It may be 

helpful for some children to have a compressor-driven nebulizer available at the school. 

Sports Issues 

The Expert Panel recommends that clinicians encourage full participation in physical 

activities; physical activity at play or in organized sports is an essential part of a child’s 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

life (EPR⎯2 1997). Many children who have asthma experience cough, wheeze, or excessive 

fatigue when they exercise. Treatment immediately before vigorous activity or exercise usually 

prevents EIB. If symptoms occur during usual play activities, a step up in long-term therapy is 

warranted. Poor endurance or EIB can be an indication of poorly controlled persistent asthma; 

appropriate use of long-term control medication can reduce EIB (See “Exercise-Induced 

Bronchospasm.”). Activity should be limited or curtailed only as a last resort. 

SPECIAL ISSUES FOR OLDER ADULTS 

Assessment Issues 

The Expert Panel recommends that the extent of reversible airflow obstruction be 

determined because of the high prevalence of other obstructive lung disease (e.g., 

chronic bronchitis, emphysema) among the elderly (EPR⎯2 1997). Careful evaluation is 

required, because the precise cause of severe airflow obstruction can be difficult to identify in 

older patients who have asthma. A 2- to 3-week trial of therapy with systemic corticosteroids 

can help detect the presence of significant reversibility of the airway disease. Long-term control 

asthma medication can then be offered. 

Treatment Issues 

The Expert Panel recommends that adjustments in therapy may be necessary because 

asthma medications may have increased adverse effects in the elderly patient (EPR⎯2 

1997). 

 Airway response to bronchodilators may change with age, although this is not clearly 

established. Older patients, especially those with preexisting ischemic heart disease, may 

also be more sensitive to beta2-agonist side effects, including tremor and tachycardia. 

Concomitant use of an anticholinergic and a SABA may be beneficial to the older patient 

(Barros and Rees 1990; Gross et al. 1989; Ullah et al. 1981). 

 Theophylline clearance is reduced in elderly patients (Nielsen-Kudsk et al. 1988), causing 

increased blood levels of theophylline. In addition, age is an independent risk factor for 

developing life-threatening events from iatrogenic chronic theophylline overdose (patients 

75 years of age or older have a 16-fold greater risk of death from theophylline overdose 

than do 25-year-old patients) (Shannon and Lovejoy 1990). The potential for drug 

interaction—especially with antibiotics and H2-histamine antagonists such as cimetidine—is 

greater because of the increased use of medications in this age group. Theophylline and 

epinephrine may exacerbate underlying heart conditions. 

 Systemic corticosteroids can provoke confusion, agitation, and changes in glucose 

metabolism. 

 Inhaled corticosteroid. Consider concurrent treatments with calcium supplements and 

vitamin D, and bone-sparing medications (e.g., bisphosphonates) in patients who 

have risk factors for osteoporosis or low bone mineral density (Evidence D). ICS use 

may be associated with a dose-dependent reduction in bone mineral content, although low 

or medium doses appear to have no major adverse effect. Elderly patients may be more at 

risk due to preexisting osteoporosis, changes in estrogen levels that affect calcium 

utilization, and a sedentary lifestyle. The risk of not adequately controlling asthma may limit 

unnecessarily the patient’s mobility and activities (See “Component 4: Medications.”). An 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

approach for identifying patients at risk for accelerated bone loss from high-dose ICS 

therapy is to conduct bone densitometry when treatment begins and again 6 months later 

(NHLBI 1996), although the benefits of this approach have not yet been evaluated in clinical 

trials. 

The Expert Panel recommends that medications taken for other diseases and conditions 

be adjusted as necessary, because some medications may exacerbate asthma (EPR⎯2 

1997). Nonsteroidal anti-inflammatory agents for treating arthritis, beta-blockers for treating 

hypertension (particularly nonselective beta-blockers), or beta-blockers found in some eye 

drops used to treat glaucoma may exacerbate asthma. See “Component 4: Medications” for 

more details on drugs that can complicate asthma management. 

The Expert Panel recommends that review of the patient’s technique in using 

medications and devices is essential (Evidence B). Observation of technique for use of 

inhaler devices, peak flow meters, and spirometry is especially important in the elderly because 

physical (e.g., arthritis, visual) and cognitive impairments (recognized or unrecognized) can 

make acquisition and retention of proper technique difficult (Allen et al. 2003; Barr et al. 2002; 

Pezzoli et al. 2003; Wolfenden et al. 2002). 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

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August 28, 2007 

FIGURE 4–5. STEPWISE APPROA CH FOR MANAGING ASTHMA IN 

YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

Intermittent

Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.

Consider consultation at step 3.

Step 1

Preferred:

SABA PRN

Step 2

Preferred:

Low-dose ICS

Alternative:

Cromolyn, LTRA,

Nedocromil, or 

Theophylline

Step 3

Preferred:

Low-dose

ICS + LABA

OR

Medium-dose ICS

Alternative:

Low-dose ICS + 

either LTRA, 

Theophylline, or 

Zileuton

Step 5

Preferred:

High-dose 

ICS + LABA

AND

Consider 

Omalizumab for 

patients who have 

allergies

Step 6

Preferred:

High-dose

ICS + LABA + oral 

corticosteroid

AND

Consider 

Omalizumab for 

patients who have 

allergies

Step up if 

needed

(first, check 

adherence, 

environmental 

control, and 

comorbid

conditions)

Step down if 

possible

(and asthma is 

well controlled 

at least

3 months)

Step 4

Preferred:

Medium-dose ICS 

+ LABA

Alternative:

Medium-dose ICS 

+ either LTRA, 

Theophylline, or 

Zileuton

Assess 

control

Quick-Relief Medication for All Patients

• SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals 

as needed. Short course of oral systemic corticosteroids may be needed. 

• Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step 

up treatment.

Each step: Patient education, environmental control, and management of comorbidities.

Steps 2−4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

— Key: Alphabetical order is used when more than one treatment option is listed within either preferred or 

alternative therapy. EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting inhaled beta2-

agonist; LTRA, leukotriene receptor antagonist; SABA, inhaled short-acting beta2-agonist 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient 

needs. 

 If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before 

stepping up. 

 Zileuton is a less desirable alternative due to limited studies as adjunctive therapy and the need to monitor liver 

function. Theophylline requires monitoring of serum concentration levels. 

 In step 6, before oral systemic corticosteroids are introduced, a trial of high-dose ICS + LABA + either LTRA, 

theophylline, or zileuton may be considered, although this approach has not been studied in clinical trials. 

 Step 1, 2, and 3 preferred therapies are based on Evidence A; step 3 alternative therapy is based on Evidence A for 

LTRA, Evidence B for theophylline, and Evidence D for zileuton. Step 4 preferred therapy is based on Evidence B, 

and alternative therapy is based on Evidence B for LTRA and theophylline and Evidence D for zileuton. Step 5 

preferred therapy is based on Evidence B. Step 6 preferred therapy is based on (EPR⎯2 1997) and Evidence B for 

omalizumab. 

 Immunotherapy for steps 2–4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence 

is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens. The 

role of allergy in asthma is greater in children than in adults. 

 Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to identify and treat 

anaphylaxis that may occur. 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

344 

August 28, 2007 

FIGURE 4–6. CLASSIFYING ASTH MA SEVERITY AND INITIATING 

TREATMENT IN YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

— Assessing severity and initiating treatment for patients who are not currently taking long-term control 

medications 

and consider short course of

oral systemic corticosteroids

Step 3 Step 4 or 5

Step 1 Step 2 Recommended Step

for Initiating Treatment

(See figure 4−5 for treatment steps.) In 2−6 weeks, evaluate level of asthma control that is achieved and adjust therapy 

accordingly. 

• Normal FEV1

between 

exacerbations

Interference with None Minor limitation Some limitation Extremely limited

normal activity

Several times

per day

>2 days/week Daily

but not daily, and 

not more than

1x on any day

Short-acting ≤2 days/week

beta2-agonist use for 

symptom control (not 

prevention of EIB)

≥2/year (see note) 0−1/year (see 

note)

• FEV1 <60% 

predicted

• FEV1 >60% but 

<80% predicted

• FEV1 >80% 

predicted

• FEV1 >80% 

predicted

• FEV1/FVC

reduced >5%

• FEV1/FVC reduced 

5%

• FEV1 • FEV /FVC normal 1/FVC normal

Risk

Relative annual risk of exacerbations may be related to FEV1. 

Classification of Asthma Severity

≥12 years of age

Consider severity and interval since last exacerbation.

Frequency and severity may fluctuate over time for patients in any severity category.

Impairment

Normal FEV1/FVC:

8−19 yr 85%

20 −39 yr 80%

40 −59 yr 75%

60 −80 yr 70%

Persistent Components of Severity

Exacerbations

requiring oral 

systemic 

corticosteroids

Lung function

>1x/week but Often 7x/week

not nightly

Nighttime ≤2x/month 3−4x/month

awakenings

>2 days/week but Daily Throughout the day

not daily

≤2 days/week Symptoms

Intermittent Mild Moderate Severe

— 

Key: FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive care unit 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient 

needs. 

 Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by 

patient’s/caregiver’s recall of previous 2–4 weeks and spirometry. Assign severity to the most severe category in 

which any feature occurs. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma 

severity. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, 

hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients 

who had ≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as 

patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma. 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

345 

August 28, 2007 

FIGURE 4–7. ASSESSING ASTH MA CONTROL AN D ADJUSTING 

THERAPY IN YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 



0−1/year ≥2/year (see note)

• Consider short course of 

oral systemic 

corticosteroids,

• Step up 1−2 steps, and

• Reevaluate in 2 weeks.

• For side effects, 

consider alternative 

treatment options.

• Step up 1 step and

• Reevaluate in 

2−6 weeks.

• For side effects, 

consider alternative 

treatment options.

• Maintain current step.

• Regular followups

every 1−6 months to 

maintain control.

• Consider step down if 

well controlled for at 

least 3 months.

Recommended Action

for Treatment

(see figure 4−5 for treatment steps)

Evaluation requires long-term followup care

Medication side effects can vary in intensity from none to very troublesome 

and worrisome. The level of intensity does not correlate to specific levels of 

control but should be considered in the overall assessment of risk.

Treatment-related adverse effects

Risk Progressive loss of lung function

Validated questionnaires

Symptoms ≤2 days/week >2 days/week Throughout the day

Impairment

3–4

N/A

≤15 

1–2

≥1.5

16−19 

0

≤0.75*

≥20

ATAQ

ACQ

ACT

<60% predicted/

personal best

60−80% predicted/

personal best

>80% predicted/

personal best

FEV1 or peak flow

Short-acting beta ≤2 days/week >2 days/week Several times per day 2-agonist use for 

symptom control (not prevention of EIB)

Consider severity and interval since last exacerbation

Exacerbations requiring oral systemic 

corticosteroids

Classification of Asthma Control

(≥12 years of age) Components of Control

Interference with normal activity None Some limitation Extremely limited

Nighttime awakenings ≤2x/month 1−3x/week ≥4x/week

Very Poorly

Controlled

Not

Well Controlled Well Controlled

— *ACQ values of 0.76–1.4 are indeterminate regarding well-controlled asthma. 

— Key: EIB, exercise-induced bronchospasm; ICU, intensive care unit 

Notes: 

 The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient 

needs. 

 The level of control is based on the most severe impairment or risk category. Assess impairment domain by patient’s recall 

of previous 2–4 weeks and by spirometry/or peak flow measures. Symptom assessment for longer periods should reflect a 

global assessment, such as inquiring whether the patient’s asthma is better or worse since the last visit. 

 At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In 

general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU 

admission) indicate poorer disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral 

systemic corticosteroids in the past year may be considered the same as patients who have not-well-controlled asthma, 

even in the absence of impairment levels consistent with not-well-controlled asthma. 

 Validated Questionnaires for the impairment domain (the questionnaires do not assess lung function or the risk domain) 

ATAQ = Asthma Therapy Assessment Questionnaire© (See sample in “Component 1: Measures of Asthma 

Assessment and Monitoring.”) 

ACQ = Asthma Control Questionnaire© (user package may be obtained at www.qoltech.co.uk or 

juniper@qoltech.co.uk) 

ACT = Asthma Control TestTM (See sample in “Component 1: Measures of Asthma Assessment and Monitoring.”) 

Minimal Important Difference: 1.0 for the ATAQ; 0.5 for the ACQ; not determined for the ACT. 

 Before step up in therapy: 

— Review adherence to medication, inhaler technique, environmental control, and comorbid conditions. 

— If an alternative treatment option was used in a step, discontinue and use the preferred treatment for that step. 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

346 

August 28, 2007 

FIGURE 4–8a. USUAL DOSAGE S FOR LONG-TERM CONTROL 

MEDICATIONS FOR YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

Medication Dosage Form Adult Dose Comments 

Inhaled Corticosteroids (ICS) (See figure 4–8b, “Estimated Comparative Daily Dosages for Inhaled 

Corticosteroids.”) 

Systemic Corticosteroids (Applies to all three corticosteroids) 

Methylprednisolone 2, 4, 8, 16, 32 mg 

tablets 

Prednisolone 5 mg tablets, 

5 mg/5 cc, 

15 mg/5 cc 

Prednisone 1, 2.5, 5, 10, 20, 50 mg 

tablets; 

5 mg/cc, 

5 mg/5 cc 

7.5–60 mg daily in a 

single dose in a.m. or 

qod as needed for 

control 

Short-course “burst”: to 

achieve control, 40–60 

mg per day as single or 

2 divided doses for 3–

10 days 

 For long-term treatment of severe 

persistent asthma, administer single 

dose in a.m. either daily or on 

alternate days (alternate-day therapy 

may produce less adrenal 

suppression). Short courses or 

“bursts” are effective for establishing 

control when initiating therapy or 

during a period of gradual 

deterioration. 

 There is no evidence that tapering 

the dose following improvement in 

symptom control and pulmonary 

function prevents relapse. 

Inhaled Long-Acting Beta2-Agonists (LABA)  Should not be used for symptom 

relief or exacerbations. Use with 

ICS. 

Salmeterol DPI 50 mcg/ 

blister 

1 blister q 12 hours  Decreased duration of protection 

against EIB may occur with regular 

use. 

Formoterol DPI 12 mcg/ 

single-use capsule 

1 capsule q 12 hours  Each capsule is for single use only; 

additional doses should not be 

administered for at least 12 hours. 

 Capsules should be used only with 

the AerolizorTM inhaler and should not 

be taken orally. 

Combined Medication 

Fluticasone/Salmeterol DPI 

100 mcg/50 mcg, 

250 mcg/50 mcg, or 

500 mcg/50 mcg 

HFA 

45 mcg/21 mcg 

115 mcg/21 mcg 

230 mcg/21 mcg 

1 inhalation bid; dose 

depends on severity of 

asthma 

 100/50 DPI or 45/21 HFA for 

patient not controlled on low- to 

medium-dose ICS 

250/50 DPI or 115/21 HFA for 

patients not controlled on medium- to 

high-dose ICS 

Budesonide/ 

Formoterol 

HFA MDI 

80 mcg/4.5 mcg 

160mcg/4.5 mcg 

2 inhalations bid; dose 

depends on severity of 

asthma 

 80/4.5 for patients who have asthma 

not controlled on low- to mediumdose ICS 

 160/4.5 for patients who have asthma 

not controlled on medium- to highdose ICS 


Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

347 

August 28, 2007 

FIGURE 4–8a. USUAL DOSAGE S FOR LONG-TERM CONTROL 

MEDICATIONS FOR YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

(CONTINUED) 

Medication Dosage Form Adult Dose Comments 

Cromolyn and Nedocromil 

MDI 

0.8 mg/puff 

Cromolyn 2 puffs qid 

Nebulizer 

20 mg/ampule 

1 ampule qid 

Nedocromil MDI 

1.75 mg/puff 

2 puffs qid 

 4–6 week trial may be needed to 

determine maximum benefit. 

 Dose by MDI may be inadequate to 

affect hyperresponsiveness. 

 One dose before exercise or 

allergen exposure provides effective 

prophylaxis for 1–2 hours. Not as 

effective for EIB as SABA. 

 Once control is achieved, the 

frequency of dosing may be 

reduced. 

Leukotriene Modifiers 

Leukotriene Receptor Antagonists

Montelukast 4 mg or 5 mg 

chewable tablet 

10 mg tablet 

10 mg qhs  Montelukast exhibits a flat doseresponse curve. Doses >10 mg will 

not produce a greater response in 

adults. 

Zafirlukast 10 or 20 mg tablet 40 mg daily 

(20 mg tablet bid) 

 For zafirlukast, administration with 

meals decreases bioavailability; take 

at least 1 hour before or 2 hours 

after meals. 

 Monitor for signs and symptoms of 

hepatic dysfunction. 

5-Lipoxygenase Inhibitor 

Zileuton 600 mg tablet 2,400 mg daily 

(give tablets qid) 

 For zileuton, monitor hepatic 

enzymes (ALT). 

Methylxanthines 

Theophylline Liquids, sustainedrelease tablets, and 

capsules 

Starting dose 10 mg/ 

kg/day up to 300 mg 

maximum; usual 

maximum 

800 mg/day  Due to wide interpatient variability in 

theophylline metabolic clearance, 

routine serum theophylline level 

monitoring is important. 

 See next page for factors that can 

affect theophylline levels. 

Immunomodulators 

Omalizumab Subcutaneous injection, 

150 mg/1.2 mL following 

reconstitution with 1.4 mL 

sterile water for injection 

150–375 mg SC q 

2–4 weeks, depending 

on body weight and 

pretreatment serum 

IgE level 

 Do not administer more than 150 mg 

per injection site. 

 Monitor for anaphylaxis for 2 hours 

following at least the first 3 

injections. 

Key: DPI, dry powder inhaler; EIB, exercise-induced bronchospasm; HFA, hydrofluoroalkane; IgE, immunoglobulin E; 

MDI, metered-dose inhaler; SABA, short-acting beta2-agonist 

 Adjust dosage to achieve serum 

 concentration of 5–15 mcg/mL at 

 steady-state (at least 48 hours on same 

 dosage). 


Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

348 

August 28, 2007 

FIGURE 4–8a. USUAL DOSAGE S FOR LONG-TERM CONTROL 

MEDICATIONS FOR YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

(CONTINUED) 

Factors Affecting Serum Theophylline Concentrations* 

Factor 

Decreases Theophylline 

Concentrations 

Increases Theophylline 

Concentrations Recommended Action 

Food È or delays absorption of 

some sustained-release 

theophylline (SRT) 

products 

Ç rate of absorption (fatty 

foods) Select theophylline preparation 

that is not affected by food. 

Diet Ç metabolism (high protein) È metabolism (high 

carbohydrate) Inform patients that major 

changes in diet are not 

recommended while taking 

theophylline. 

Systemic, febrile 

viral illness (e.g., 

influenza) 

È metabolism Decrease theophylline dose 

according to serum 

concentration. Decrease dose 

by 50 percent if serum 

concentration measurement is 

not available. 

Hypoxia, cor 

pulmonale, and 

decompensated 

congestive heart 

failure, cirrhosis 

È metabolism Decrease dose according to 

serum concentration. 

Age Ç metabolism (1–9 years) È metabolism (<6 months, 

elderly) Adjust dose according to 

serum concentration. 

Phenobarbital, 

phenytoin, 

carbamazepine 

Ç metabolism Increase dose according to 

serum concentration. 

Cimetidine È metabolism Use alternative H2 blocker 

(e.g., famotidine or ranitidine). 

Macrolides: 

erythromycin, 

clarithromycin, 

troleandomycin 

È metabolism Use alternative macrolide 

antibiotic, azithromycin, or 

alternative antibiotic or adjust 

theophylline dose. 

Quinolones: 

ciprofloxacin, 

enoxacin, 

perfloxacin 

È metabolism Use alternative antibiotic or 

adjust theophylline dose. 

Circumvent with ofloxacin if 

quinolone therapy is required. 

Rifampin Ç metabolism Increase dose according to 

serum concentration. 

Ticlopidine È metabolism Decrease dose according to 

serum concentration. 

Smoking Ç metabolism Advise patient to stop smoking; 

increase dose according to 

serum concentration. 

*This list is not all inclusive; for discussion of other factors, see package inserts. 


Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

349 

August 28, 2007 

FIGURE 4–8b. ESTIMATED CO MPARATIVE DAILY DOSAGES FOR 

INHALED CORTICOSTEROIDS FOR YOUTHS ≥ 12 YEARS OF AGE 

AND ADULTS 

Drug Low Daily Dose Medium Daily Dose High Daily Dose 

Adult Adult Adult 

Beclomethasone HFA 

40 or 80 mcg/puff 80–240 mcg >240–480 mcg >480 mcg 

Budesonide DPI 

90, 180, or 200 mcg/inhalation 180–600 mcg >600–1,200 mcg >1,200 mcg 

Flunisolide 

250 mcg/puff 500–1,000 mcg >1,000–2,000 mcg >2,000 mcg 

Flunisolide HFA 

80 mcg/puff 320 mcg >320–640 mcg >640 mcg 

Fluticasone 

HFA/MDI: 44, 110, or 

220 mcg/puff 

88–264 mcg >264–440 mcg >440 mcg 

DPI: 50, 100, or

250 mcg/inhalation 

100–300 mcg >300–500 mcg >500 mcg 

Mometasone DPI 

200 mcg/inhalation 200 mcg 400 mcg >400 mcg 

Triamcinolone acetonide 

75 mcg/puff 300–750 mcg >750–1,500 mcg >1,500 mcg 

Key: DPI, dry powder inhaler; HFA, hydrofluoroalkane; MDI, metered-dose inhaler 

Notes: 

 The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to 

therapy. The clinician must monitor the patient’s response on several clinical parameters and adjust the dose 

accordingly. The stepwise approach to therapy emphasizes that once control of asthma is achieved, the dose of 

medication should be carefully titrated to the minimum dose required to maintain control, thus reducing the potential for 

adverse effect. 

 Some doses may be outside package labeling, especially in the high-dose range. 

 MDI dosages are expressed as the actuator dose (the amount of the drug leaving the actuator and delivered to the 

patient), which is the labeling required in the United States. This is different from the dosage expressed as the valve 

dose (the amount of drug leaving the valve, not all of which is available to the patient), which is used in many European 

countries and in some scientific literature. DPI doses are expressed as the amount of drug in the inhaler following 

activation. 

 Comparative dosages are based on published comparative clinical trials (Adams et al. 2005; Barnes et al. 1998; Kelly 

1998; Lasserson et al. 2005; Pedersen and O'Byrne 1997). The rationale for some key comparisons is summarized as 

follows: 

— The high dose is the dose that appears likely to be the threshold beyond which significant hypothalamic-pituitaryadrenal (HPA) axis suppression is produced, and, by extrapolation, the risk is increased for other clinically 

significant systemic effects if used for prolonged periods of time (Martin et al. 2002; Szefler et al. 2002). 

— The low- and medium-doses reflect findings from dose-ranging studies in which incremental efficacy within the 

low- to medium-dose ranges was established without increased systemic effect as measured by overnight cortisol 

excretion. The studies demonstrated a relatively flat dose-response curve for efficacy at the medium-dose range; 

that is, increasing the dose of high-dose range did not significantly increase efficacy but did increase systemic 

effect (Adams et al. 2001; Martin et al. 2002; Szefler et al. 2002). 

— The dose for budesonide and fluticasone MDI or DPI are based on recently available comparative data. These new 

data, including meta-analyses, show that fluticasone requires one-half the microgram dose of budesonide DPI to 

achieve comparable efficacy (Adams et al. 2005; Barnes et al. 1998; Nielsen and Dahl 2000). 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

350 

August 28, 2007 

FIGURE 4–8b. ESTIMATED CO MPARATIVE DAILY DOSAGES FOR 

INHALED CORTICOSTEROIDS FOR YOUTHS ≥ 12 YEARS OF AGE 

AND ADULTS (CONTINUED) 

— The dose for beclomethasone in HFA inhaler should be approximately one-half the dose for beclomethasone in 

chlorofluorocarbon (CFC) inhaler for adults and children, based on studies demonstrating that the different 

pharmaceutical properties of the medications result in enhanced lung delivery for the HFA (a less forceful spray 

from the HFA propellant and a reengineered nozzle that allows a smaller particle size) and clinical trials 

demonstrating similar potency to fluticasone at 1:1 dose ratio (Boulet et al. 2004; Busse et al. 1999; Gross et al. 

1999; Lasserson et al. 2005; Leach et al. 1998; Pedersen et al. 2002; Szefler et al. 2002; Thompson et al. 1998). 

— The dose for mometasone DPI is based on product information and current literature (Bousquet et al. 2000; 

Fardon et al. 2004; Kemp et al. 2000; O'Connor et al. 2001). Mometasone is approved for once daily 

administration. Mometasone furoate by dry powder achieved effects similar to twice the dose of budesonide by 

dry powder (Bousquet et al. 2000) and comparable to a slightly higher dose of fluticasone propionate by dry 

powder (O'Connor et al. 2001). 

— The dose for flunisolide HFA is based on product information and current literature (Corren et al. 2001; Gillman et 

al. 2002; Richards et al. 2001).

 Bioavailability 

Both the relative potency and the relative 

bioavailability (systemic availability) determine the 

potential for systemic activity of an ICS 

preparation. As illustrated here, the bioavailability 

of an ICS is dependent on the absorption of the 

dose delivered to the lungs and the oral 

bioavailability of the swallowed portion of the dose 

received. 

— Absorption of the dose delivered to the lungs: 

♦ Approximately 10–50 percent of the 

dose from the MDI is delivered to the 

lungs. This amount varies among 

preparations and delivery devices. 

♦ Nearly all of the amount delivered to the 

lungs is bioavailable. 

— Oral bioavailability of the swallowed portion 

of the dose received: 

♦ Approximately 50–80 percent of the dose from the MDI without a spacer/holding chamber is swallowed. 

♦ The oral bioavailability of this amount varies: 

Either a high first-pass metabolism or the use of a spacer/holding chamber with an MDI can decrease oral 

bioavailability, thus enhancing safety (Lipworth 1995). 

The approximate oral bioavailability of ICSs has been reported as: beclomethasone dipropionate 20 percent; 

flunisolide, 21 percent; triamcinolone acetonide, 10.6 percent; budesonide, 11 percent; fluticasone propionate, 

1 percent; mometasone, <1 percent (Affrime et al. 2000; Chaplin et al. 1980; Check and Kaliner 1990; 

Clissold and Heel 1984; Davies 1993; Harding 1990; Heald et al. 1995; Martin et al. 1974; Mollmann et al. 

1985; Szefler 1991; Wurthwein and Rohdewald 1990).

 Potential drug interactions 

A number of the ICSs, including fluticasone, budesonide, and mometasone, are metabolized in the gastrointestinal tract 

and liver by CYP 3A4 isoenzymes. Potent inhibitors of CYP 3A4, such as ritonavir and ketoconazole, have the 

potential for increasing systemic concentrations of these ICSs by increasing oral availability and decreasing systemic 

clearance. Some cases of clinically significant Cushing syndrome and secondary adrenal insufficiency have been 

reported (Johnson et al. 2006; Samaras et al. 2005). 

Inactivation in the 

liver or gut wall 

“first pass” 

Inactivation in gut 
Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

351 

August 28, 2007 

FIGURE 4–8c.USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS 

FOR YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

Medication Dosage Form Adult Dose Comments 

Inhaled Short-Acting Beta2-Agonists (SABA) 

MDI Applies to all four SABAs 

Albuterol CFC 90 mcg/puff, 

200 puffs/canister 

Albuterol HFA 90 mcg/puff, 

200 puffs/canister 

Pirbuterol CFC 200 mcg/puff, 

400 puffs/canister 

Levalbuterol HFA 45 mcg/puff, 

200 puffs/canister 

 2 puffs 

5 minutes before 

exercise 

 2 puffs every 4–6 

hours as needed 

 An increasing use or lack of expected 

effect indicates diminished control of 

asthma. 

 Not recommended for long-term daily 

treatment. Regular use exceeding 

2 days/week for symptom control (not 

prevention of EIB) indicates the need 

to step up therapy. 

 Differences in potency exist, but all 

products are essentially comparable 

on a per puff basis. 

 May double usual dose for mild 

exacerbations. 

 Should prime the inhaler by releasing 

4 actuations prior to use. 

 Periodically clean HFA activator, as 

drug may block/plug orifice. 

 Nonselective agents (i.e., epinephrine, 

isoproterenol, metaproterenol) are not 

recommended due to their potential for 

excessive cardiac stimulation, 

especially in high doses. 

Nebulizer solution 

Albuterol 0.63 mg/3 mL 

1.25 mg/3 mL 

2.5 mg/3 mL 

5 mg/mL (0.5%)

1.25–5 mg in 3 cc of saline 

q 4–8 hours as needed 

 May mix with budesonide inhalant 

suspension, cromolyn or ipratropium 

nebulizer solutions. May double dose 

for severe exacerbations. 

 

Levalbuterol 

(R-albuterol) 

0.31 mg/3 mL 

0.63 mg/3 mL 

1.25 mg/0.5 mL 

1.25 mg/3 mL 

0.63 mg–1.25 mg q 8 

hours as needed 

 Compatible with budesonide inhalant 

suspension. The product is a sterilefilled, preservative-free, unit dose vial. 


Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

352 

August 28, 2007 

FIGURE 4–8c. USUAL DOSAGES FOR QUICK-RELIEF 

MEDICATIONS FOR YOUTHS ≥ 12 YEARS OF AGE AND ADULTS 

(CONTINUED) 

Medication Dosage Form Adult Dose Comments 

Anticholinergics 

MDI 

Ipratropium HFA 17 mcg/puff, 

200 puffs/canister

2–3 puffs q 6 hours 

Nebulizer solution 

0.25 mg/mL (0.025%) 0.25 mg q 6 hours 

 Evidence is lacking for 

anticholinergics producing added 

benefit to beta2-agonists in long-term 

control asthma therapy. 

MDI 

Ipratropium with 

albuterol 

18 mcg/puff of 

ipratropium bromide and 

90 mcg/puff of albuterol 

2–3 puffs 

q 6 hours 

 200 puffs/canister 

Nebulizer solution 

0.5 mg/3 mL ipratropium 

bromide and 

2.5 mg/3 mL albuterol 

3 mL 

q 4–6 hours 

 Contains EDTA to prevent 

discoloration of the solution. This 

additive does not induce 

bronchospasm. 

Systemic 

Corticosteroids 

Applies to the first three 

corticosteroids 

Methylprednisolone 2, 4, 6, 8, 16, 32 mg 

tablets 

 Short course “burst”: 

40–60 mg/day as single 

or 2 divided doses for 

3–10 days

 Short courses or “bursts” are 

effective for establishing control when 

initiating therapy or during a period of 

gradual deterioration. 

Prednisolone 5 mg tablets, 

5 mg/5 cc, 

15 mg/5 cc 

Prednisone 1, 2.5, 5, 10, 20, 50 mg 

tablets; 5 mg/cc, 5 mg/5 

cc 

 The burst should be continued until 

symptoms resolve and the PEF is at 

least 80 percent of personal best. 

This usually requires 3–10 days but 

may require longer. There is no 

evidence that tapering the dose 

following improvement prevents 

relapse. 

Repository injection 

(Methylprednisolone 

acetate) 

40 mg/mL 

80 mg/mL 

240 mg IM once  May be used in place of a short burst 

of oral steroids in patients who are 

vomiting or if adherence is a problem. 

Key: CFC, chlorofluorocarbon; EIB, exercise-induced bronchospasm; HFA, hydrofluoroalkane; IM, intramuscular; MDI, 

metered-dose inhaler; PEF, peak expiratory flow 


Section 4, Managing Asthma Long Term—Youths ≥12 Years of Age and Adults 

353 

August 28, 2007 

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Section 4, Managing Asthma Long-Term—Special Situations in Asthma 

363 

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SECTION 4, MANAGING ASTHMA LONG TERM—SPECIAL 

SITUATIONS 

Introduction 

Patients who have asthma may encounter situations that will require adjustments to their 

asthma management to keep their asthma under control. Special situations described in 

this section include: EIB, pregnancy, and surgery. 

Exercise-Induced Bronchospasm 

The Expert Panel concludes that exercise may be the only precipitant of asthma 

symptoms for some patients. These patients should be monitored regularly to 

ensure that they have no symptoms of asthma or reductions in PEF in the 

absence of exercise, because EIB is often a marker of inadequate asthma 

management and responds well to regular anti-inflammatory therapy (EPR⎯2 

1997). 

EIB—which can limit and disrupt otherwise normal lives if not treated—should be 

anticipated in all asthma patients. EIB is a bronchospastic event that is caused by a loss 

of heat, water, or both from the lung during exercise because of hyperventilation of air 

that is cooler and dryer than that of the respiratory tree. Some, but not all, studies 

suggest that release of inflammatory mediators is involved in the etiology of EIB 

(Anderson 2004; Anderson and Brannan 2004; Carlsen and Carlsen 2002; Jarjour and 

Calhoun 1992; McFadden and Gilbert 1994; Tan and Spector 2002). EIB usually occurs 

during or minutes after vigorous activity, reaches its peak 5–10 minutes after stopping 

the activity, and resolves in another 20–30 minutes. Some reports indicate that there is 

a refractory period of less than 1 hour after EIB that allows for an asthma-symptom-free 

interval after warmup exercises (Edmunds et al. 1978). There is uncertainty, however, 

concerning the existence of a late-phase reaction hours after exercise (Chhabra and 

Ojha 1998). 

DIAGNOSIS 

The Expert Panel recommends that a history of cough, shortness of breath, chest 

pain or tightness, wheezing, or endurance problems during exercise suggests 

EIB. An exercise challenge can be used to establish the diagnosis (EPR⎯2 1997). Use 

of history alone has been shown both to underdiagnose and overdiagnose the problem 

(McKenzie et al. 2002; Tan and Spector 2002). VCD, in particular, can be confused with 

EIB (Huggins et al. 2004; Sullivan et al. 2001). An exercise challenge, useful for 

establishing the diagnosis, can be performed in a formal laboratory setting or as a 

free-run challenge sufficiently strenuous to increase the baseline heart rate to 80 percent 

of maximum for 4–6 minutes. Alternatively, the patient may simply undertake the task 

that previously caused the symptoms. A 15-percent decrease in PEF or FEV1 (with 

measurements taken before and after exercise at 5-minute intervals for 20–30 minutes) 

is compatible with EIB. 
Section 4, Managing Asthma Long-Term—Special Situations in Asthma 

364 

August 28, 2007 

MANAGEMENT STRATEGIES 

The Expert Panel recommends that an important dimension of adequate asthma 

control is a patient’s ability to participate in any activity he or she chooses without 

experiencing asthma symptoms. EIB should not limit either participation or 

success in vigorous activities. Recommended treatments include: 

 Long-term control therapy, if appropriate (Evidence A). There is evidence that 

appropriate long-term control of asthma with anti-inflammatory medication will reduce 

airway responsiveness, and this is associated with a reduction in the frequency and 

severity of EIB (Vathenen et al. 1991; Vidal et al. 2001). Frequent, severe EIB may 

indicate poorly controlled asthma and thus a need to initiate or increase daily longterm control therapy. 

 Pretreatment before exercise: 

— Inhaled beta2-agonists will prevent EIB in more than 80 percent of patients 

(Evidence A). 

♦ SABA used shortly before exercise (or as close to exercise as possible) may 

be helpful for 2–3 hours. 

♦ LABAs can be protective up to 12 hours (Ferrari et al. 2002; Newnham et al. 

1993; Richter et al. 2002; Shapiro et al. 2002). When LABAs are 

administered on a daily basis, however, there is some shortening of the 

duration of protection, even in patients using ICSs (Simons et al. 1997). 

Frequent and chronic use of LABAs for EIB should be discouraged. Such 

use may disguise poorly controlled persistent asthma, which should be 

managed with daily anti-inflammatory therapy. 

— LTRAs can attenuate EIB in up to 50 percent of patients (Evidence B). The 

onset of action is generally hours after administration. Few comparisons with 

other protective agents are currently available (Mastalerz et al. 2002; Moraes and 

Selvadurai 2004; Steinshamn et al. 2002). 

— Cromolyn or nedocromil taken shortly before exercise is an alternative 

treatment to prevent EIB, but it is not as effective as SABAs (Spooner et al. 

2003) (Evidence B). The addition of cromolyn to a SABA is helpful in some 

individuals who have EIB (Spooner et al. 2003). These studies (Spooner et al. 

2003) indicate that anticholinergics may also attenuate EIB, but they are less 

likely to be protective than either mast cell stabilizers or SABAs. 

— A warmup period before exercise may reduce the degree of EIB (de Bisschop 

et al. 1999) (Evidence C). 

— A mask or scarf over the mouth may attenuate cold-induced EIB (Beuther 

and Martin 2006) (Evidence C). 

The Expert Panel recommends that teachers and coaches be notified that a child 

has EIB, that the child should be able to participate in activities, and that the child 

may need inhaled medication before activity (Evidence D). Individuals involved in 
Section 4, Managing Asthma Long-Term—Special Situations in Asthma 

365 

August 28, 2007 

competitive athletics need to be aware that their medication use should be disclosed, 

and they should adhere to standards set by the sports-governing bodies (Anderson et al. 

2003). The U.S. Anti-Doping Agency Drug Reference Line is 1–800–233–0393. 

Surgery and Asthma 

The Expert Panel recommends consideration that patients who have asthma are at 

risk for specific complications during and after surgery (EPR⎯2 1997). These 

complications include acute bronchoconstriction triggered by intubation, hypoxemia and 

possible hypercapnia, impaired effectiveness of cough, atelectasis, and respiratory 

infection (Kingston and Hirshman 1984); latex exposure (Slater 1994; Sussman and 

Beezhold 1995); and even some anesthetic agents (Nishiyama and Hanaoka 2001). 

The likelihood of these complications depends on the severity of the patient’s airway 

hyperresponsiveness, airflow obstruction, mucus hypersecretions, latex sensitivity, and 

history of prior surgeries, because the latter is a risk factor for both latex and anesthetic 

agent sensitivities. 

The Expert Panel recommends the following actions to reduce risk of 

complications during surgery (EPR⎯2 1997): 

 Patients who have asthma should have an evaluation before surgery that 

includes a review of symptoms, medication use (particularly the use of oral 

systemic corticosteroids for longer than 2 weeks in the past 6 months), and 

measurement of pulmonary function. 

 If possible, attempts should be made to improve lung function preoperatively 

(FEV1 or peak expiratory flow rate [PEFR]) to either their predicted values or 

their personal best level. A short course of oral systemic corticosteroids may 

be necessary to optimize lung function. 

 For patients who have received oral systemic corticosteroids during the past 

6 months and for selected patients on a long-term high dose of an ICS, give 

100 mg hydrocortisone every 8 hours intravenously during the surgical period 

and reduce the dose rapidly within 24 hours after surgery. Stress doses of 

corticosteroids may be considered for select patients treated with prior 

high-dose ICS therapy as well, because clinically important adrenal 

suppression has been reported in such patients, particularly children (Todd et 

al. 2002a, b). 

Pregnancy and Asthma 

The NAEPP “Working Group Report on Managing Asthma During Pregnancy: 

Recommendations for Pharmacologic Treatment—Update 2004” (NAEPP 2005) 

emphasizes that maintaining adequate control of asthma during pregnancy is 

important for the health and well-being of both the mother and her baby. Maternal 

asthma increases the risk of perinatal mortality, preeclampsia, preterm birth, and 

low-birth-weight infants. More severe asthma is associated with increased risks, while 

better-controlled asthma is associated with decreased risks. It is safer for pregnant 

women who have asthma to be treated with asthma medications than to have asthma 

symptoms and exacerbations. Monitoring and making appropriate adjustments in 
Section 4, Managing Asthma Long-Term—Special Situations in Asthma 

366 

August 28, 2007 

therapy may be required to maintain lung function and, hence, blood oxygenation that 

ensures oxygen supply to the fetus. 

The following is a summary of the recommendations made in the 2004 update. See that 

report for evidence reviews. 

 Monitoring of asthma status during prenatal visits is encouraged. Because the 

course of asthma improves for about one-third of women and worsens for about 

one-third of women during pregnancy, monthly evaluations of asthma history and 

pulmonary function (spirometry is preferred, but measurement with a peak flow meter 

is generally sufficient) are recommended. This evaluation will allow the opportunity 

to step down treatment, if possible, or to increase treatment if necessary. 

 Albuterol is the preferred SABA because it has an excellent safety profile and the 

most data related to safety during human pregnancy are available for this 

medication. 

 ICSs are the preferred treatment for long-term control medication. Budesonide 

is the preferred ICS because more data are available on using budesonide in 

pregnant women than are available on other ICSs, and the data are reassuring. 

Preference for ICSs is based on strong data on effectiveness in nonpregnant women 

as well as effectiveness and safety data in pregnant women; the data show no 

increased risk of adverse perinatal outcomes. Although budesonide is the preferred 

ICS, it is important to note that no data indicate that the other ICS preparations are 

unsafe during pregnancy. Cromolyn has an excellent safety profile but has limited 

effectiveness compared with ICSs. Minimal published data are available on the use 

of LTRAs during pregnancy; however, animal safety data submitted to the FDA are 

reassuring. Data are limited describing the effectiveness and/or safety of LABAs 

during pregnancy, although there is justification for expecting LABAs to have a safety 

profile similar to that of albuterol, for which there are data related to safety during 

pregnancy. 

 For the treatment of comorbid conditions, intranasal corticosteroids are 

recommended for treatment of allergic rhinitis because they have a low risk of 

systemic effect. LTRAs can also be used, but minimal data are available on 

their use during pregnancy. The current second-generation antihistamines of 

choice are loratadine or cetirizine. 

For more information, see the NAEPP “Working Group Report on Managing Asthma 

During Pregnancy: Recommendations for Pharmacologic Treatment—Update 2004” 

(NAEPP 2005).

Racial and Ethnic Disparity in Asthma 

The Expert Panel recommends heightened awareness of cultural barriers between 

the clinician and patient that may influence asthma management as well as 

modification of educational/communication strategies to address these barriers 

(Evidence D) (See “Component 3: Education for a Partnership in Asthma Care.”). 

Aggressive efforts have been made to understand better the growing problem of racial 

and ethnic disparity in asthma. It has been documented that racial and ethnic minorities 
Section 4, Managing Asthma Long-Term—Special Situations in Asthma 

367 

August 28, 2007 

tend to receive lower quality health care than whites even when insurance status, age, 

income, and severity of conditions are comparable (Institute of Medicine 2002). The 

paradox is that, despite our increased understanding of asthma and the availability of 

highly effective drugs for controlling asthma, no substantial improvement in asthma 

morbidity and mortality has occurred among certain racial and ethnic minority 

populations. Multiple initiatives have been launched recently to develop strategies to 

eliminate disparities in asthma care that are based on race and culture (AHRQ 2003; 

NIH 2004). Assessment of asthma status, health care use, and processes of asthma 

care among children in managed Medicaid programs demonstrated that Black and 

Hispanic children had worse asthma than white children, but the minorities used less 

anti-inflammatory medication (Lieu et al. 2002). This study and other studies suggest 

that underutilization of preventive therapy, especially ICSs, contributes to disparities in 

asthma and care for asthma (Halterman et al. 2000, 2002; Ortega et al. 2002; Warman 

et al. 2001). These studies suggest that lack of adherence—due to cost, inadequate 

literacy, or multiple competing priorities for the patient—may contribute to underuse of 

medication, but other factors are equally important. 

Less than optimal use of preventive asthma medications may be due to nonfinancial 

barriers to optimal asthma care. A study of Medicaid pediatric patients who have 

asthma showed that black and hispanic children were much less likely than whites to 

receive followup care in a timely fashion after being seen in the ED for asthma (Shields 

et al. 2004), demonstrating important differences in the process of care. A prospective 

cohort study of Medicaid-insured children who had asthma found that practice-site 

policies predicted higher quality care for these children; policies included presence of 

ethnically diverse or bilingual clinicians, cross-cultural or diversity training, continuity in 

care, and use of feedback to clinicians about prescribing of medication (Lieu et al. 2004). 

Such observations have stimulated great interest in the study of culturally influenced 

health beliefs and attitudes, demonstrated the importance of cultural competency for 

health care providers, and shown the need for improved communication between 

provider and patient or family regarding use of asthma medication. 

A large proportion of ethnic and racial minorities live in urban areas where exposure to 

indoor allergens (e.g., cockroach and mold) can be high; efforts to mitigate these 

allergens can reduce symptoms successfully and significantly for urban children who 

have asthma (Morgan et al. 2004). 

Multivariate analysis models have been used in an attempt to disentangle the effects of 

race, ethnicity, income, and other individual-level risk factors that influence the 

expression of asthma in various populations. The influence of race versus 

socioeconomic status on asthma morbidity and mortality remains controversial. Some 

studies suggest that differences in patterns of asthma-related health care are driven 

largely by ethnicity and only partially by financial barriers (Boudreaux et al. 2003; Grant 

et al. 2000; Higgins et al. 2005; Miller 2000; Zoratti et al. 1998). On the other hand, 

some studies suggest that low socioeconomic status, not race, is largely responsible for 

poor asthma health outcomes and health care-seeking behavior (Apter et al. 1997; Haas 

et al. 1994). 

Accumulating evidence suggests that biological and pathophysiological differences 

between ethnic groups may contribute to racial and ethnic disparities in the expression 

of asthma, and these differences may be independent of socioeconomic and educational 

influences. For example, there appears to be a significant racial difference between total 
Section 4, Managing Asthma Long-Term—Special Situations in Asthma 

368 

August 28, 2007 

serum IgE and airway hyperresponsiveness, and a significant positive relationship 

between total serum IgE and reactivity to methacholine has been demonstrated in White 

children but not in Black children (Joseph et al. 2000). This difference supports the 

hypothesis that Black children may be predisposed to more severe asthma or that racial 

differences may predispose to more severe asthma. 

While biological and pathophysiological differences between population groups may 

contribute to the heterogeneity of asthma and its variable expression, gene by 

environmental influences are not exclusive variables that affect the expression of this 

disease. The significance of social and geographical environmental differences and the 

significance of ethnocultural influences on the expression of asthma warrant additional 

investigations, especially with regard to their effect on asthma outcomes and asthma 

disparities. 

Hispanic populations are characterized by diverse racial, ethnic, national, and cultural 

expressions. Among Hispanics, the highest mortality rates from asthma occur among 

Puerto Ricans, followed by Cuban Americans and Mexican Americans (Homa et al. 

2000; Sly 2006). These differences cannot be explained by geographic location; neither 

can they be explained by other demographic variables (Ledogar et al. 2000). Our 

evolving understanding of the natural history of asthma may eventually confirm or 

challenge some current notions about how asthma is expressed in various populations. 

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Section 5, Managing Exacerbations of Asthma 

373 

August 28, 2007 

SECTION 5, MANAGING EXACERBATIONS OF ASTHMA 

KEY POINTS: MANAGING EXACERBATIONS OF ASTHMA 

 Early treatment of asthma exacerbations is the best strategy for management. Important 

elements of early treatment at the patient’s home include (EPR⎯2 1997): 

— Patient education, including a written asthma action plan to guide patient 

self-management of exacerbations at home, especially for patients who have moderate 

or severe persistent asthma and any patient who has a history of severe exacerbations 

(Evidence B). A peak-flow-based plan may be particularly useful for patients who have 

difficulty perceiving airflow obstruction and worsening asthma (Evidence D). 

— Recognition of early signs of worsening asthma and taking prompt action (Evidence A). 

— Appropriate intensification of therapy by increasing inhaled short-acting beta2-agonist 

(SABA) and, in some cases, adding a short course of oral systemic corticosteroids 

(Evidence A). 

— Removal or withdrawal of the environmental factor contributing to the exacerbation. 

— Prompt communication between patient and clinician about any serious deterioration in 

symptoms or peak flow, decreased responsiveness to SABAs, or decreased duration of 

effect. 

 Management of asthma exacerbations requiring urgent medical care (e.g., in the urgent care 

setting or emergency department (ED)) includes: 

— Oxygen to relieve hypoxemia in moderate or severe exacerbations (EPR⎯2 1997). 

— SABA to relieve airflow obstruction, with addition of inhaled ipratropium bromide in 

severe exacerbations (Evidence A). 

— Systemic corticosteroids to decrease airway inflammation in moderate or severe 

exacerbations or for patients who fail to respond promptly and completely to a SABA 

(Evidence A). 

— Consideration of adjunct treatments, such as intravenous magnesium sulfate or heliox, 

in severe exacerbations unresponsive to the initial treatments listed above (Evidence B). 

— Monitoring response to therapy with serial measurements of lung function (Evidence B). 

— Preventing relapse of the exacerbation or recurrence of another exacerbation by 

providing: referral to followup asthma care within 1–4 weeks; an ED asthma discharge 

plan with instructions for medications prescribed at discharge and for increasing 

medications or seeking medical care if asthma worsens; review of inhaler techniques 

whenever possible; and consideration of initiating inhaled corticosteroids (ICSs) 

(Evidence B). 
Section 5, Managing Exacerbations of Asthma 

374 

August 28, 2007 

KEY DIFFERENCES FROM 1997 AND 2002 EXPERT PANEL 

REPORTS 

 For the assessment of exacerbations, the current update (EPR—3: Full Report 2007): 

— Simplifies classification of severity of asthma exacerbations. 

— Reinstates, for use in the urgent or emergency care setting, the 1991 cut points of forced 

expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) to indicate the goal 

for discharge from the urgent care or emergency care setting (≥70 percent predicted 

FEV1 or PEF); patients for whom response to therapy is incomplete and who usually 

require continued treatment in the ED (40–69 percent predicted); and the exacerbation 

severity level where adjunct therapies may be considered (<40 percent predicted). 

These cut points differ from those used to determine long-term asthma control and 

treatments, thus underscoring the distinction between acute and chronic asthma 

management. 

— Acknowledges the limited value of pulmonary function measures in very severe 

exacerbations. 

 For the treatment of exacerbations, the current update: 

— Adds levalbuterol as a SABA treatment for asthma exacerbations. 

— For home management of exacerbations, no longer recommends doubling the dose of 

ICSs. 

— For prehospital management (e.g., emergency transport), encourages standing orders 

for albuterol and—for prolonged transport—repeated treatments and protocols to allow 

consideration of ipratropium and oral corticosteroids. 

— For ED management, reduces dose and frequency of administration of oral 

corticosteroids in severe exacerbations, adds consideration of magnesium sulfate or 

heliox for severe exacerbations, and adds consideration of initiating an ICS upon 

discharge. 

— For hospital management, no longer recommends ipratropium bromide. 

— 

Introduction 

In this section, recommendations are presented for the assessment and treatment of 

exacerbations in the home, ED, and hospital. See section 1, “Overall Methods Used To 

Develop This Report,” for literature search strategy and tally of results for this EPR—3: Full 

Report 2007 section on “Managing Exacerbations of Asthma.” Four Evidence Tables were 

prepared: 17, Increasing the Dose of Inhaled Corticosteroids; 18, IV Aminophylline; 19, 

Magnesium Sulfate; and 20, Heliox. 

Asthma exacerbations are acute or subacute episodes of progressively worsening shortness of 

breath, cough, wheezing, and chest tightness—or some combination of these symptoms. 
Section 5, Managing Exacerbations of Asthma 

375 

August 28, 2007 

Exacerbations are characterized by decreases in expiratory airflow that can be documented and 

quantified by simple measurement of lung function (spirometry or PEF). These objective 

measures more reliably indicate the severity of an exacerbation than does the severity of 

symptoms. In general, milder exacerbations may be managed “at home” (i.e., outside the 

health care system), whereas more serious exacerbations may require an unscheduled 

(“urgent”) office visit, an ED visit, or a hospital admission (see figure 5–1). The most severe 

exacerbations require admission to the intensive care unit (ICU) for optimal monitoring and 

treatment. Although assessment and treatment of young children pose unique challenges, the 

management of asthma exacerbations in older children and adults is fairly similar. 

Individuals who have their asthma under control with ICSs will decrease the risk of 

exacerbations. Nonetheless, patients in good control can still be vulnerable to exacerbations, 

for example, when they have clinical respiratory infections (Reddel et al. 1999). Diurnal 

variability, a marker of poor control, may not change during an exacerbation; thus, clinicians 

may fail to detect important changes in lung function. The striking difference between PEF 

FIGURE 5–1. CLASSIFYIN G SEVERITY OF ASTHMA 

EXACERBATIONS IN THE URGENT OR EMERGENCY CARE 

SETTING 

Note: Patients are instructed to use quick-relief medications if symptoms occur or if PEF drops below 80 percent 

predicted or personal best. If PEF is 50–79 percent, the patient should monitor response to quick-relief medication 

carefully and consider contacting a clinician. If PEF is below 50 percent, immediate medical care is usually required. 

In the urgent or emergency care setting, the following parameters describe the severity and likely clinical course of an 

exacerbation. 

Symptoms and Signs Initial PEF (or FEV1) Clinical Course 

Mild Dyspnea only with 

activity (assess 

tachypnea in young 

children) 

PEF ≥70 percent 

predicted or personal 

best 

 Usually cared for at home 

 Prompt relief with inhaled SABA 

 Possible short course of oral 

systemic corticosteroids

Moderate Dyspnea interferes with 

or limits usual activity 

PEF 40−69 percent 

predicted or personal 

best 

 Usually requires office or ED visit 

 Relief from frequent inhaled SABA 

 Oral systemic corticosteroids; 

some symptoms last for 1–2 days 

after treatment is begun

Severe Dyspnea at rest; 

interferes with 

conversation 

PEF <40 percent 

predicted or personal 

best 

 Usually requires ED visit and likely 

hospitalization 

 Partial relief from frequent inhaled 

SABA 

 Oral systemic corticosteroids; 

some symptoms last for >3 days 

after treatment is begun 

 Adjunctive therapies are helpful 

Subset: Life 

threatening

Too dyspneic to speak; 

perspiring 

PEF <25 percent 

predicted or personal 

best 

 Requires ED/hospitalization; 

possible ICU 

 Minimal or no relief from frequent 

inhaled SABA 

 Intravenous corticosteroids 

 Adjunctive therapies are helpful 

Key: ED, emergency department; FEV1, forced expiratory volume in 1 second; ICU, intensive care unit; PEF, peak 

expiratory flow; SABA, short-acting beta2-agonist 
Section 5, Managing Exacerbations of Asthma 

376 

August 28, 2007 

variations during exacerbations, as compared with during poor asthma control, suggests 

differences in beta2-adrenoceptor function between these conditions. The decrease in 

responsiveness to SABA during some severe exacerbations may help to explain the benefit of 

ipratropium bromide and other “alternative” approaches to bronchodilation. 

General Considerations 

Based on the scientific literature and the opinion of the Expert Panel, the Panel 

recommends that clinicians consider the following general principles and goals for 

managing asthma exacerbations: early treatment, special attention to patients who are 

at high risk of asthma-related death, and special attention to infants (EPR⎯2 1997). 

 Early treatment is the best strategy for management of asthma exacerbations. 

Important elements of early treatment include: 

— A written asthma action plan (See “Component 2: Education for a Partnership in 

Asthma Care,” figure 3–10) to guide patient self-management, especially for patients 

who have moderate or severe persistent asthma and any patient who has a history of 

severe exacerbations. 

— Recognition of early indicators of an exacerbation, including worsening PEF. 

Patients are instructed to recognize early signs and symptoms of worsening asthma and 

to use quick-relief medications if symptoms occur or if PEF drops below 80 percent 

predicted or personal best. If PEF is 50–79 percent, the patient should carefully monitor 

the response to quick-relief medication and, based on the response, consider contacting 

a clinician. If PEF is below 50 percent, immediate medical care is usually required (See 

sample written asthma action plans, figures 3–10a, b, and c.). In the urgent or 

emergency care setting, different parameters are used to classify the severity of the 

exacerbation and determine the clinical course; see figure 5–1. The Panel chose cut 

points of 40 percent and 70 percent of predicted (or personal best) because 40 percent 

denotes an exacerbation severity below which several adjunct therapies are effective, 

and 70 percent is a posttreatment goal for discharge from the ED or hospital. 

— Appropriate intensification of therapy, often including a short course of systemic 

corticosteroids. 

— Removal of or withdrawal from allergens or precipitating irritants in the 

environment that may be contributing to the exacerbation. 

— Prompt communication between patient and clinician about any serious 

deterioration in symptoms or peak flow, decreased responsiveness to SABA 

treatment, or decreased duration of effect. 

 Patients who are at high risk for asthma-related death require special attention—

particularly intensive education, monitoring, and care. Such patients should be counseled to 

seek medical care early during an exacerbation and instructed about the availability of 

ambulance services. Such patients include those who have identifiable risk factors (See 

figure 5–2a.). 

 Infants require special attention, especially due to their greater risk for respiratory failure 

(See figure 5–2b.). 
Section 5, Managing Exacerbations of Asthma 

377 

August 28, 2007 

FIGURE 5–2a. RISK FACTOR S FOR DEATH FROM ASTHMA 

Asthma history 

Previous severe exacerbation (e.g., intubation or ICU admission for asthma) 

Two or more hospitalizations for asthma in the past year 

Three or more ED visits for asthma in the past year 

Hospitalization or ED visit for asthma in the past month 

Using >2 canisters of SABA per month 

Difficulty perceiving asthma symptoms or severity of exacerbations 

Other risk factors: lack of a written asthma action plan, sensitivity to Alternaria

Social history 

Low socioeconomic status or inner-city residence 

Illicit drug use 

Major psychosocial problems 

Comorbidities 

Cardiovascular disease 

Other chronic lung disease 

Chronic psychiatric disease 

Key: ED, emergency department; ICU, intensive care unit; SABA, short-acting beta2-agonist 

Sources: Abramson et al. 2001; Greenberger et al. 1993; Hardie et al. 2002; Kallenbach et al. 1993; Kikuchi et al. 

1994; O’Hollaren et al. 1991; Rodrigo and Rodrigo 1993; Strunk and Mrazek 1986; Suissa et al. 1994
Section 5, Managing Exacerbations of Asthma 

378 

August 28, 2007 

FIGURE 5–2b. SPEC IAL CONSIDERATIONS FOR INFANTS 

 Assessment depends on physical examination rather than objective measurements. Use of 

accessory muscles, inspiratory and expiratory wheezing, paradoxical breathing, cyanosis, 

and a respiratory rate >60 are key signs of serious distress. 

 Objective measurements, such as oxygen saturation (SaO2) of <90 percent, also indicate 

serious distress. 

 Response to SABA therapy can be variable and may not be a reliable predictor of 

satisfactory outcome. However, because infants are at greater risk for respiratory failure, a 

lack of response noted by either physical examination or objective measurements should be 

an indication for hospitalization. 

 Use of oral systemic corticosteroids early in the episode is essential but should not 

substitute for careful assessment by a physician. 

 Most acute wheezing episodes result from viral infections and may be accompanied by 

fever. Antibiotics generally are not required. 

Key: SABA, short-acting beta2-agonist 

Source: EPR—2 1997. 

— 

Treatment Goals 

The principal goals and Expert Panel recommendations for treating asthma 

exacerbations are: 

 Correction of significant hypoxemia, in moderate or severe exacerbations, by 

administering supplemental oxygen. In rare instances, alveolar hypoventilation requires 

mechanically assisted ventilation (EPR⎯2 1997). 

 Rapid reversal of airflow obstruction (Evidence A). This is best achieved by: 

— Repetitive or continuous administration of a SABA (Camargo et al. 2003b; Karpel et al. 

1997; McFadden 2003; Travers et al. 2001) 

AND 

— Early in the course of treatment, administration of systemic corticosteroids to patients 

who have moderate or severe exacerbations or to patients who fail to respond promptly 

and completely to SABA treatment (McFadden 2003; Rachelefsky 2003; Rowe et al. 

2004). 

 Reduction of the likelihood of relapse of the exacerbation or future recurrence of 

severe airflow obstruction by intensifying therapy (Evidence A). Often, a short course 

of systemic corticosteroids is useful (Rachelefsky 2003; Rowe et al. 2004). 
Section 5, Managing Exacerbations of Asthma 

379 

August 28, 2007 

 Achieving these goals requires careful assessment and monitoring (Evidence B). The 

ability to predict care requirements, including the need for hospitalization, is based on 

repeated clinical assessments. In adults, repeated measurements of lung function are often 

helpful. The specific measurements chosen for monitoring will depend on the age of the 

patient and the available resources. 

— Children. In children, no single assessment tool appears to be the best for assessing 

the severity of the exacerbation or for monitoring response to treatment and predicting 

hospital admission (Chey et al. 1999; Gorelick et al. 2004a,b; Keahey et al. 2002; Keogh 

et al. 2001; Smith et al. 2002; Sole et al. 1999; Wright et al. 1997). 

♦ Serial measurements of lung function. Lung function measures using either FEV1

or PEF may be useful for many children 5 years of age or older. However, neither 

maneuver may be obtainable during an exacerbation. Gorelick and colleagues 

(2004a) found that only 65 percent of children 5–18 years of age could complete 

either measurement during an acute exacerbation, and for children less than 5 years 

old, the maneuvers were almost impossible. 

♦ Pulse oximetry. An initial pulse oximetry in infants and young children might be 

useful for assessing exacerbation severity but not for predicting the need for hospital 

admission (Keahey et al. 2002; Kelly et al. 2004; Keogh et al. 2001; Sole et al. 1999; 

Wright et al. 1997). However, a repeat pulse oximetry of <92–94 percent (sea level) 

at 1 hour was a better predictor of need for hospitalization, and it may be useful to 

move those infants and children into the hospital and out of the ED at that time (Kelly 

et al. 2004; Sole et al. 1999; Wright et al. 1997). 

♦ Signs and symptoms scores. Several severity assessment scores have been 

developed and tested in children to help predict the need for hospitalization early in 

the course of ED treatment (Gorelick et al. 2004b; Keogh et al. 2001; Rodrigo and 

Rodrigo 1998b; Smith et al. 2002). None is 100 percent predictive, but the 

assessments may help to determine who should be transferred from the ED to the 

hospital after an initial 1- to 2-hour period of treatment, leaving the ED resources for 

those who are more likely to be able to go home after extended ED treatment and 

observation. These assessment scores combine physician- or nurse-observed signs 

and symptoms—such as shortness of breath, chest tightness, ability to speak in 

sentences or phrases, emotional impact, and alertness—plus respiratory rate, use of 

intercostals muscles, timing and volume of wheezes as well as pulse oximetry and, if 

available and feasible, FEV1 or PEF. One score (Gorelick et al. 2004b) has added a 

parental assessment of asthma control over the past several months and history of 

previous exacerbations requiring ED or hospital management. Others add the 

continuing need for hourly SABA 4 or more hours after the administration of oral 

systemic corticosteroids. 

A recent study suggests that most children who require hospitalization can be 

identified by a repeat assessment 1 hour after initial treatment (Kelly et al. 2004). 

After 1 hour, those children who continue to meet the criteria for a severe 

exacerbation have >86 percent chance of requiring hospitalization; those who meet 

the criteria for moderate exacerbation at 1 hour have an 84 percent chance of 

requiring hospitalization; and those whose assessment has remained the same or 

dropped to the mild level have only an 18 percent chance of requiring hospitalization. 

These severity assessment studies highlight the importance of regular, multifaceted 

assessments and close observation of children and adolescents who present to the 

office or ED with acute asthma exacerbations (See figures 5–1 and 5–3.). 
Section 5, Managing Exacerbations of Asthma 

380 

August 28, 2007 

FIGURE 5–3. FORMAL EVALUATION OF ASTHMA EXACERBATION 

SEVERITY IN THE URGENT OR EMERGENCY CARE SETTING 

 Mild Moderate Severe 

Subset: Respiratory 

Arrest Imminent 

Symptoms

Breathlessness While walking While at rest (infant—

softer, shorter cry, 

difficulty feeding) 

While at rest (infant—

stops feeding) 

Can lie down Prefers sitting Sits upright 

Talks in Sentences Phrases Words 

Alertness May be agitated Usually agitated Usually agitated Drowsy or confused 

Signs 

Respiratory rate Increased Increased Often >30/minute 

Guide to rates of breathing in awake children: 

 Age Normal rate 

 <2 months 

2–12 months 

1–5 years 

6–8 years 

<60/minute 

<50/minute 

<40/minute 

<30/minute 

Use of accessory 

muscles; suprasternal 

retractions 

Usually not Commonly Usually Paradoxical 

thoracoabdominal 

movement 

Wheeze Moderate, often only 

end expiratory 

Loud; throughout 

exhalation 

Usually loud; 

throughout inhalation 

and exhalation 

Absence of wheeze 

Pulse/minute <100 100–120 >120 Bradycardia 

Guide to normal pulse rates in children:: 

 Age Normal rate 

 2–12 months 

1–2 years 

2–8 years 

<160/minute 

<120/minute 

<110/minute 

Pulsus paradoxus Absent <10 mmHg May be present 

10–25 mmHg 

Often present 

>25 mmHg (adult) 

20–40 mmHg (child) 

Absence suggests 

respiratory muscle 

fatigue 

Functional Assessment 

PEF 

percent predicted or 

percent personal best 

≥70 percent Approx. 40–69 

percent or response 

lasts <2 hours 

<40 percent <25 percent 

Note: PEF testing 

may not be needed in 

very severe attacks 

PaO2 (on air) Normal (test not 

usually necessary) 

≥60 mmHg 

(test not usually 

necessary) 

<60 mmHg: possible 

cyanosis 

and/or 

PCO2 <42 mmHg (test not 

usually necessary) 

<42 mmHg (test not 

usually necessary) 

≥42 mmHg: possible 

respiratory failure 

(See pages 393–394, 

399.) 

SaO2 percent (on air) 

at sea level 

>95 percent (test not 

usually necessary) 

90–95 percent (test 

not usually necessary) 

<90 percent 

Hypercapnia (hypoventilation) develops more readily in young children than in adults and 

adolescents. 

Key: PaO2, arterial oxygen pressure; PCO2, partial pressure of carbon dioxide; PEF, peak expiratory flow; SaO2, oxygen saturation 

Notes: 

 The presence of several parameters, but not necessarily all, indicates the general classification of the exacerbation. 

 Many of these parameters have not been systematically studied, especially as they correlate with each other. Thus, they serve 

only as general guides (Cham et al. 2002; Chey et al. 1999; Gorelick et al. 2004b; Karras et al. 2000; Kelly et al. 2002b and 

2004; Keogh et al. 2001; McCarren et al. 2000; Rodrigo and Rodrigo 1998b; Rodrigo et al. 2004; Smith et al. 2002). 

 The emotional impact of asthma symptoms on the patient and family is variable but must be recognized and addressed and can 

affect approaches to treatment and followup (Ritz et al. 2000; Strunk and Mrazek 1986; von Leupoldt and Dahme 2005). 
Section 5, Managing Exacerbations of Asthma 

381 

August 28, 2007 

— Adults

♦ Serial measurements of lung function. FEV1 or PEF appear to be more useful in 

adults for categorizing the severity of the exacerbation and the response to treatment 

and in predicting the need for hospitalization. Repeated measurements of PEF or 

FEV1 in adults at 1 hour and beyond are useful as isolated assessments in 

determining who will require hospitalization and who is likely to have sufficient 

response to treatment to allow continued ED care. Indeed, repeated FEV1 or PEF 

measures at presentation to the ED and 1 hour after treatment were the strongest 

single predictor of hospitalization among adults who present to the ED with an 

asthma exacerbation (Karras et al. 2000; Kelly et al. 2004; McCarren et al. 2000; 

Rodrigo et al. 2004; Weber et al. 2002). 

When FEV1 is unavailable, PEF may be substituted. Although percentage of 

personal best PEF or FEV1 would be ideal for patient management, individuals may 

report erroneous values (Diner et al. 2001). Interpretation of percentage of predicted 

values is complicated by differences between formulas in the literature (Radeos and 

Camargo 2004). Regardless of the calculation chosen, for severe exacerbations 

with obvious airway compromise and even cyanosis, the immediate testing of FEV1

or PEF provides little additional information, and the maneuver can be very 

uncomfortable for acutely ill patients (Kelly et al. 2004). 

♦ Pulse oximetry is indicated for patients who are in severe distress, have FEV1 or 

PEF <40 percent of predicted, or are unable to perform lung function measures. 

♦ Signs and symptoms scores. As in children, some multifaceted prediction models 

have been tested and shown to improve slightly on the accuracy of the FEV1 or PEF 

alone (Chey et al. 1999; Kelly et al. 2002b and 2004; McFadden 2003; Weber et al. 

2002). Kelly and colleagues (2004) used multiple signs and symptoms to determine 

the level of the severity of the exacerbation at 1 hour after the first ED treatment as 

well as the duration of symptoms (either <6 hours or ≥6 hours) before the patient’s 

arrival at the ED (Kelly et al. 2002b) and found the additional measures improved the 

prediction rate by 5–10 percent. (See paragraph above related to the same model 

used in children.) For EDs that have limited resources, the presence of drowsiness in 

a patient is a useful predictor of impending respiratory failure and reason to consider 

immediate transfer of the patient to a facility equipped to deal with ventilatory support 

(Cham et al. 2002). As in the case with children, the ability to predict future care 

requirements is based on repeated clinical assessments, and, in adults, repeated 

measures of FEV1 or PEF (See figure 5–3.). 

Home Management of Asthma Exacerbations 

Beginning treatment at home avoids treatment delays, prevents exacerbations from becoming 

severe, and also adds to patients’ sense of control over their asthma. The degree of care 

provided in the home depends on the patients’ (or parents’) abilities and experience and on the 

availability of emergency care. General guidelines for managing exacerbations at home are 

presented in figure 5–4. 

The Expert Panel recommends preparing patients for home management of asthma 

exacerbations by taking the following actions (Also see “Component 1: Measures of 

Asthma Assessment and Monitoring,” and “Component 2: Education for a Partnership in 

Asthma Care.”).
Section 5, Managing Exacerbations of Asthma 

382 

August 28, 2007 

FIGURE 5–4. MANAGEMENT OF ASTHMA EXACERBATIONS: HOME 

TREATMENT 

— 

Assess Severity

 Patients at high risk for a fatal attack (see figure 5–2a) require immediate medical attention 

after initial treatment.

 Symptoms and signs suggestive of a more serious exacerbation such as marked breathlessness, 

inability to speak more than short phrases, use of accessory muscles, or drowsiness (see 

figure 5–3) should result in initial treatment while immediately consulting with a clinician.

 Less severe signs and symptoms can be treated initially with assessment of response to therapy 

and further steps as listed below.

 If available, measure PEF—values of 50–79% predicted or personal best indicate the need for 

quick-relief mediation. Depending on the response to treatment, contact with a clinician may also 

be indicated. Values below 50% indicate the need for immediate medical care. 

Initial Treatment

 Inhaled SABA: up to two treatments 20 minutes apart of 2–6 puffs 

by metered-dose inhaler (MDI) or nebulizer treatments.

 Note: Medication delivery is highly variable. Children and 

individuals who have exacerbations of lesser severity may need 

fewer puffs than suggested above.

Good Response

No wheezing or dyspnea

(assess tachypnea in young 

children).

PEF ≥80% predicted or 

personal best.

 Contact clinician for 

followup instructions and 

further management.

 May continue inhaled 

SABA every 3–4 hours for 

24–48 hours.

 Consider short course of 

oral systemic 

corticosteroids.

Incomplete Response

Persistent wheezing and 

dyspnea (tachypnea).

PEF 50–79% predicted or 

personal best.

 Add oral systemic 

corticosteroid.

 Continue inhaled SABA.

 Contact clinician urgently 

(this day) for further 

instruction.

Poor Response

Marked wheezing and dyspnea.

PEF <50% predicted or 

personal best.

 Add oral systemic 

corticosteroid.

 Repeat inhaled SABA 

immediately.

 If distress is severe and 

nonresponsive to initial 

treatment:

—Call your doctor AND

—PROCEED TO ED;

—Consider calling 9–1–1 

(ambulance transport).

 To ED.

Key: ED, emergency department; MDI, metered-dose inhaler; PEF, peak expiratory flow; SABA, short-acting 

beta2-agonist (quick-relief inhaler) 
Section 5, Managing Exacerbations of Asthma 

383 

August 28, 2007 

 Teach all patients how to monitor signs and symptoms so they can recognize early 

signs of deterioration and take appropriate action (Evidence A) (See “Component 2: 

Education for a Partnership in Asthma Care.”), particularly since many fatal asthma 

exacerbations occur out of hospital (Krishnan et al. 2006). Patients should be taught how to 

adjust their medications early in an exacerbation (Kelly et al. 2002b) and when to call for 

further help or seek medical care. Patients should seek medical help earlier if the 

exacerbation is severe; treatment does not give rapid, sustained improvement; or there is 

further deterioration. 

 Consider teaching how to monitor lung function, by using PEF to facilitate early and 

accurate assessment of exacerbations and response to treatment, to patients and 

parents of children who have moderate or severe persistent asthma or a history of 

severe exacerbations (Evidence B) and patients who are poor perceivers of airflow 

obstruction (Evidence D). Signs and symptoms imperfectly mirror airflow obstruction; 

therefore, other tools may be required, especially in the group of people who are “poor 

perceivers” and have failed to recognize previous exacerbations or symptom deteriorations 

early (Hardie et al. 2002; Kikuchi et al. 1994). Exacerbations recognized and treated within 

6 hours of onset may be less likely to result in hospitalizations (Kelly et al. 2002b). When 

using PEF expressed only as a percent of personal best, the impact of any irreversible 

airflow obstruction must be considered. For example, in a person whose personal best is 

only 160 L/min, a drop to 60 percent of personal best represents life-threatening airflow 

obstruction. 

 Provide to all patients a written asthma action plan that includes daily management 

and recognizing and handling worsening asthma, including self-adjustment of 

medications in response to acute symptoms or changes in PEF measures in the event 

of an exacerbation. A written asthma action plan is particularly recommended for 

patients who have moderate or severe persistent asthma and any patient who has a 

history of severe exacerbations or poorly controlled asthma (Evidence B). A peakflow-based plan may be particularly useful for patients who have difficulty perceiving 

airflow obstruction and worsening asthma (Evidence D). See component 2—

Education for a Partnership in Asthma Care, figure 3–10 for a sample plan. Children 

should also receive a plan appropriate to the school setting (See “Component 2: Education 

for a Partnership in Asthma Care,” figure 3–16.). The plan should direct the patient to adjust 

medications in response to particular signs, symptoms, and peak flow measurements and 

should state when to seek medical help. Review the plan with the patient and family. The 

clinician should tailor the plan to the needs of individual patients. Patients who are at risk for 

asthma death (See figure 5–2a.) require especially close monitoring. 

 Advise patients who have moderate or severe persistent asthma or a history of 

severe exacerbations to have the medication (e.g., corticosteroid tablets or liquid) 

and equipment (e.g., peak flow meter, compressor-driven nebulizer for young 

children) for treating exacerbations at home (Evidence A). 

The Expert Panel recommends the following pharmacologic therapy for home 

management of exacerbations: 

 Increase the frequency of SABA treatment (Evidence A). 

 Initiate oral systemic corticosteroid treatment under certain circumstances 

(Evidence A). Short courses or “bursts” of oral corticosteroids reduce the duration and may 
Section 5, Managing Exacerbations of Asthma 

384 

August 28, 2007 

prevent hospitalizations and relapse following an acute exacerbation (McFadden 2003; 

Rachelefsky 2003; Rowe et al. 2004). The Expert Panel recommends that, unless 

working from a defined action plan, individuals contact their health care provider 

before instituting a course of oral systemic corticosteroids (Evidence D). 

 Doubling the ICS dose is not sufficient (Evidence B) (See Evidence Table 17, Increasing 

the Dose of Inhaled Corticosteroids.). Doubling the dose of an ICS in those patients already 

receiving ICS therapy has not been effective at reducing the severity or preventing 

progression of exacerbations (FitzGerald et al. 2004; Garrett et al. 1998; Harrison et al. 

2004; Rice-McDonald et al. 2005). However, higher doses of an ICS may be effective in the 

ED management of acute asthma exacerbations. For example, preliminary evidence 

indicates that quadrupling the dose of an ICS for 7 days, starting at the first appearance of 

worsening symptoms, may prevent exacerbations requiring oral systemic corticosteroids 

(Foresi et al. 2000). For patients who experience substantial adverse effects with oral 

systemic corticosteroids (e.g., mood changes, worsening diabetes), high-dose ICS may be 

an effective alternative for mild to moderate exacerbations. 

 Continue more intensive treatment for several days (EPR⎯2 1997). Recovery from an 

exacerbation varies, with symptom relief in 1–2 days for moderate exacerbations but in 3 or 

more days for severe exacerbations (See figure 5–1.). For many persons, the improvement 

is quite gradual. Even when symptoms have resolved, evidence of inflammation in the 

airways may continue for up to 2–3 weeks (McFadden 1975). In managing an exacerbation 

at home, patients’ greater use of SABA should be continued until symptoms and PEF are 

stable. That said, patients should seek medical care rather than rely on bronchodilator 

therapy in excessive doses or for prolonged periods (e.g., >12 puffs/day for more than 

24 hours). 

The Expert Panel does not recommend the following home management techniques, 

because no studies have demonstrated effectiveness, and it is the opinion of the Panel 

that these techniques may delay patients from obtaining necessary care (EPR⎯2 1997).

 Drinking large volumes of liquids or breathing warm, moist air (e.g., the mist from a hot 

shower). 

 Using over-the-counter products such as antihistamines or cold remedies. Over-the-counter 

bronchodilators may provide transient bronchodilation, but their use should not delay 

seeking medical care. 

The Expert Panel also notes that although pursed-lip and other forms of controlled breathing 

may help to maintain calm during respiratory distress, these methods do not bring about 

improvement in lung function. 

Prehospital Management of Asthma Exacerbations 

The Expert Panel recommends that emergency medical services (EMS) providers 

administer supplemental oxygen and SABA to patients who have signs or symptoms of 

an asthma exacerbation (Evidence A).

Prehospital administration of SABA reduces airflow obstruction and relieves symptoms 

(Fergusson et al. 1995; Markenson et al. 2004; Richmond et al. 2005). Ideally, all EMS 

providers would receive a standing order to allow them to provide albuterol to their patients who 
Section 5, Managing Exacerbations of Asthma 

385 

August 28, 2007 

have asthma exacerbations. Such an order would be consistent with their legally authorized 

scope of practice and local medical direction (Camargo 2006). In such settings, EMS providers 

should have available a nebulizer and/or an inhaler plus spacer/holding chamber for SABA 

administration (see figure 5–5 for dosages). If these are not available, subcutaneous 

epinephrine or terbutaline should be given for severe exacerbations (See figure 5–5.) (Sly et al. 

1977; Smith et al. 1977). 

When initiating bronchodilatory use, EMS personnel should not delay transport of the patient to 

the appropriate medical facility. The treatment, however, may be repeated while transporting 

the patient. Prolonged transport times (e.g., in a rural setting or during transport on congested 

urban streets) may necessitate multiple inhaled SABA treatments before arrival at the medical 

facility (Crago et al. 1998). Patients should receive a maximum of three inhaled SABA 

treatments in the first hour, and then one per hour thereafter (consistent with practice in the ED 

setting; see figures 5–5 and 5–6). After each treatment, EMS personnel should reassess and 

record the patient’s vital signs and lung sounds. 

Ambulance services should develop prehospital protocols for the treatment of acute asthma in 

children and adults (Markenson et al. 2004; Stead and Whiteside 1999). With medical 

oversight, these protocols can allow for more frequent administration of several established 

acute asthma treatments, such as ipratropium bromide and oral systemic corticosteroids (Knapp 

and Wood 2003). The latter medication is particularly important during prolonged transport 

times. All prehospital providers should receive training in how to respond to the clinical signs 

and symptoms of severe airway obstruction and imminent respiratory failure (Camargo 2006). 

Emergency Department and Hospital Management of Asthma 

Exacerbations 

Severe exacerbations of asthma are potentially life threatening. Care must be prompt. 

Effective initial therapies (i.e., SABA and the means of giving it by aerosol and a source of 

supplemental oxygen) should be available in a physician’s office. Serious exacerbations, 

however, require close observation for deterioration, frequent treatment, and repetitive 

measurement of lung function. Therefore, most severe exacerbations of asthma require prompt 

transfer to an ED for more complete therapy (McFadden 2003; Rowe et al. 2001). Despite 

appropriate therapy, approximately 10–25 percent of ED patients who have acute asthma will 

require hospitalization (Pollack et al. 2002; Weber et al. 2002). In the hospital, multidisciplinary 

(e.g., nursing and respiratory care) clinical pathways for asthma appear to be effective in 

reducing hospital length-of-stay and inpatient costs, but they have less clear impact on clinical 

outcomes (Banasiak and Meadows-Oliver 2004). An overview of the treatment strategies in 

EDs and hospitals is presented in figure 5–6 and detailed below. 

ASSESSMENT 

The Expert Panel recommends the following activities to assess exacerbations: 

 All clinicians treating patients who have asthma should be prepared to treat an 

asthma exacerbation, be familiar with the symptoms and signs of severe and lifethreatening exacerbations (figures 5–1, 5–2a, and 5–3), and have procedures for 

facilitating immediate patient transfer to an emergency care facility (EPR⎯2 1997). 
Section 5, Managing Exacerbations of Asthma 

386 

August 28, 2007 

FIGURE 5–5. DOSAGES OF DRUG S FOR ASTHMA EXACERBATIONS

 Dosages 

Medication Child Dose* Adult Dose Comments 

Inhaled Short-Acting Beta2-Agonists (SABA) 

Albuterol 

Nebulizer solution 

(0.63 mg/3 mL, 

1.25 mg/3 mL, 

2.5 mg/3 mL, 

5.0 mg/mL) 

0.15 mg/kg (minimum dose 

2.5 mg) every 20 minutes for 

3 doses then 0.15–0.3 mg/kg 

up to 10 mg every 1–4 hours 

as needed, or 0.5 mg/kg/hour 

by continuous nebulization. 

2.5–5 mg every 20 minutes 

for 3 doses, then 2.5–10 

mg every 1–4 hours as 

needed, or 10–15 mg/hour 

continuously. 

Only selective 

beta2-agonists are 

recommended. For optimal 

delivery, dilute aerosols to 

minimum of 3 mL at gas 

flow of 6–8 L/min. Use 

large volume nebulizers for 

continuous administration. 

May mix with ipratropium 

nebulizer solution. 

MDI 

(90 mcg/puff) 4–8 puffs every 20 minutes 

for 3 doses, then every 1–4 

hours inhalation maneuver as 

needed. Use VHC; add mask 

in children <4 years. 

4–8 puffs every 20 minutes 

up to 4 hours, then every 

1–4 hours as needed. 

In mild-to-moderate 

exacerbations, MDI plus 

VHC is as effective as 

nebulized therapy with 

appropriate administration 

technique and coaching by 

trained personnel. 

Bitolterol 

Nebulizer solution 

(2 mg/mL) 

See albuterol dose; thought to 

be half as potent as albuterol 

on mg basis. 

See albuterol dose. Has not been studied in 

severe asthma 

exacerbations. Do not mix 

with other drugs. 

MDI 

(370 mcg/puff) 

See albuterol MDI dose. See albuterol MDI dose. Has not been studied in 

severe asthma 

exacerbations. 

Levalbuterol 

(R-albuterol) 

Nebulizer solution 

(0.63 mg/3 mL, 

1.25 mg/0.5 mL 

1.25 mg/3 mL) 

0.075 mg/kg (minimum 

dose 1.25 mg) every 

20 minutes for 3 doses, then 

0.075–0.15 mg/kg up to 

5 mg every 1–4 hours as 

needed. 

1.25–2.5 mg every 

20 minutes for 3 doses, 

then 1.25–5 mg every 

1–4 hours as needed. 

MDI 

(45 mcg/puff) 

See albuterol MDI dose. See albuterol MDI dose. 

Levalbuterol administered 

in one-half the mg dose of 

albuterol provides 

comparable efficacy and 

safety. Has not been 

evaluated by continuous 

nebulization. 

Pirbuterol 

MDI 

(200 mcg/puff) 

See albuterol MDI dose; 

thought to be half as potent 

as albuterol on a mg basis. 

See albuterol MDI dose. Has not been studied in 

severe asthma 

exacerbations. 

Systemic (Injected) Beta2-Agonists 

Epinephrine 0.3–0.5 mg every 

20 minutes for 3 doses sq. 

1:1,000 (1 mg/mL) 

0.01 mg/kg up to 0.3–0.5 mg 

every 20 minutes for 3 doses 

sq. 

No proven advantage of 

systemic therapy over 

aerosol. 

Terbutaline 0.25 mg every 20 minutes 

for 3 doses sq. 

(1 mg/mL) 

0.01 mg/kg every 20 minutes 

for 3 doses then every 

2–6 hours as needed sq. 

No proven advantage of 

systemic therapy over 

aerosol. 
Section 5, Managing Exacerbations of Asthma 

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August 28, 2007 

FIGURE 5–5. DOSAGES OF DRUGS FOR ASTHMA 

EXACERBATIONS (CONTINUED) 

Dosages 

Medication Child Dose* Adult Dose Comments 

Anticholinergics 

Ipratropium bromide 

Nebulizer solution 

(0.25 mg/mL) 

0.25–0.5 mg every 20 minutes 

for 3 doses, then as needed 

0.5 mg every 20 minutes 

for 3 doses then as 

needed 

May mix in same nebulizer with 

albuterol. Should not be used 

as first-line therapy; should be 

added to SABA therapy for 

severe exacerbations. The 

addition of ipratropium has not 

been shown to provide further 

benefit once the patient is 

hospitalized. 

MDI 

(18 mcg/puff) 

4–8 puffs every 20 minutes as 

needed up to 3 hours 

8 puffs every 20 minutes 

as needed up to 3 hours 

Should use with VHC and face 

mask for children <4 years. 

Studies have examined 

ipratropium bromide MDI for up 

to 3 hours. 

Ipratropium with 

albuterol 

 

Nebulizer solution 

(Each 3 mL vial 

contains 0.5 mg 

ipratropium bromide 

and 2.5 mg 

albuterol.) 

1.5-3 mL every 20 minutes for 

3 doses, then as needed 

3 mL every 20 minutes for 

3 doses, then as needed 

May be used for up to 3 hours 

in the initial management of 

severe exacerbations. The 

addition of ipratropium to 

albuterol has not been shown to 

provide further benefit once the 

patient is hospitalized. 

MDI 

(Each puff contains 

18 mcg ipratropium 

bromide and 90 

mcg of albuterol.) 

4–8 puffs every 20 minutes as 

needed up to 3 hours 

8 puffs every 20 minutes 

as needed up to 3 hours 

Should use with VHC and face 

mask for children <4 years. 

Systemic Corticosteroids 

(Applies to all three corticosteroids) 

Prednisone 40–80 mg/day in 1 or 2 

divided doses until PEF 

reaches 70% of predicted 

or personal best 

Methylprednisolone 

Prednisolone 

1-2 mg/kg in 2 divided doses 

(maximum = 60 mg/day) until 

PEF is 70% of predicted or 

personal best 

For outpatient “burst,” use 

40–60 mg in single or 2 divided 

doses for total of 5–10 days in 

adults (children: 1–2 mg/kg/day 

maximum 60 mg/day for 

3–10 days). 

*Children ≤ 12 years of age 

Key: ED, emergency department; MDI, metered-dose inhaler; PEF, peak expiratory flow; VHC, valved holding chamber 

Notes: 

 There is no known advantage for higher doses of corticosteroids in severe asthma exacerbations, nor is there any advantage for

intravenous administration over oral therapy provided gastrointestinal transit time or absorption is not impaired. 

 The total course of systemic corticosteroids for an asthma exacerbation requiring an ED visit of hospitalization may last from 3 to 

10 days. For corticosteroid courses of less than 1 week, there is no need to taper the dose. For slightly longer courses (e.g., up 

to 10 days), there probably is no need to taper, especially if patients are concurrently taking ICSs. 

 ICSs can be started at any point in the treatment of an asthma exacerbation. 
Section 5, Managing Exacerbations of Asthma 

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August 28, 2007 

FIGURE 5–6. MANAGEMENT OF A S T H M A E X A C E R B A T I O N S : 

EMERGENCY DEPARTMENT AND HOSPITAL-BASED CARE 

Initial Assessment (see figures 5–1, 5–3)

Brief history, physical examination (auscultation, use of accessory muscles, heart rate, respiratory rate), 

PEF or FEV1, oxygen saturation, and other tests as indicated.

FEV1 or PEF ≥40% (Mild-to-Moderate)

 Oxygen to achieve SaO2 ≥90%

 Inhaled SABA by nebulizer or MDI with 

valved holding chamber, up to 3 doses 

in first hour

 Oral systemic corticosteroids if no 

immediate response or if patient 

recently took oral systemic 

corticosteroids

FEV1 or PEF <40% (Severe)

 Oxygen to achieve SaO2

≥90%

 High-dose inhaled SABA plus 

ipratropium by nebulizer or 

MDI plus valved holding 

chamber, every 20 minutes or 

continuously for 1 hour

 Oral systemic corticosteroids

Impending or Actual 

Respiratory Arrest

 Intubation and mechanical 

ventilation with 100% 

oxygen

 Nebulized SABA and 

ipratropium

 Intravenous corticosteroids

 Consider adjunct therapies

Repeat Assessment 

Symptoms, physical examination, PEF, O2 saturation, other tests as needed

Admit to Hospital Intensive Care

(see box below)

Severe Exacerbation

FEV1 or PEF <40% predicted/personal best

Physical exam: severe symptoms at rest, accessory muscle use, 

chest retraction

History: high-risk patient

No improvement after initial treatment

 Oxygen

 Nebulized SABA + ipratropium, hourly or continuous

 Oral systemic corticosteroids

 Consider adjunct therapies

Moderate Exacerbation

FEV1 or PEF 40–69% 

predicted/personal best

Physical exam: moderate symptoms

 Inhaled SABA every 60 minutes

 Oral systemic corticosteroid

 Continue treatment 1–3 hours, 

provided there is improvement; 

make admit decision in <4 hours

Incomplete Response 

 FEV1 or PEF 40–69%

 Mild-to-moderate symptoms

Poor Response 

 FEV1 or PEF <40%

 PCO2 ≥42 mm Hg

 Physical exam: 

symptoms severe, 

drowsiness, confusion Individualized decision re: 

hospitalization (see text)

Discharge Home

 Continue treatment with inhaled SABA.

 Continue course of oral systemic 

corticosteroid.

 Consider initiation of an ICS.

 Patient education

− Review medications, including inhaler 

technique.

− Review/initiate action plan.

− Recommend close medical followup.

Admit to Hospital Ward

 Oxygen

 Inhaled SABA

 Systemic (oral or 

intravenous) corticosteroid

 Consider adjunct therapies

 Monitor vital signs, FEV1 or 

PEF, SaO2

Admit to Hospital Intensive Care

 Oxygen

 Inhaled SABA hourly or 

continuously 

 Intravenous corticosteroid

 Consider adjunct therapies

 Possible intubation and 

mechanical ventilation

Improve Improve

Discharge Home

 Continue treatment with inhaled SABAs.

 Continue course of oral systemic corticosteroid.

 Continue on ICS. For those not on long-term control therapy, consider 

initiation of an ICS.

 Patient education (e.g., review medications, including inhaler technique and, 

whenever possible, environmental control measures; review/initiate action 

plan; recommend close medical followup).

 Before discharge, schedule followup appointment with primary care provider 

and/or asthma specialist in 1–4 weeks.

Good Response

 FEV1 or PEF ≥70%

 Response sustained 60 minutes 

after last treatment

 No distress

 Physical exam: normal

Key: FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; MDI, metered dose inhaler; PCO2, partial pressure 

carbon dioxide; PEF, peak expiratory flow; SABA, short-acting beta2-agonist; SaO2, oxygen saturation 
Section 5, Managing Exacerbations of Asthma 

389 

August 28, 2007 

 Initial assessment should include a brief history, brief physical examination, and, for 

most patients, objective measures of lung function. Initial laboratory studies may be 

helpful, but they are not required for most patients, and they should not delay 

initiation of asthma treatment (EPR⎯2 1997).

 In the ED, all patients presenting with a reported asthma exacerbation must be 

evaluated and triaged immediately, based on at least vital signs and an overall 

physical assessment (e.g., ability to breathe well enough to talk). Treatment should 

begin immediately following recognition of a moderate, severe, or life-threatening 

exacerbation by assessment of symptoms, signs, or, when possible, lung function 

(EPR⎯2 1997). 

 While treatment is given, obtain a brief, focused history and physical examination 

pertinent to the exacerbation (See figure 5–3.). Take a more detailed history and 

complete physical examination and perform laboratory studies only after initial 

therapy has been completed (Evidence D). 

 The objectives of functional assessment (the frequency and number of 

measurements) will depend on the severity of the exacerbation and the response to 

treatment (See figure 5–6.) are to: 

— Obtain objective lung function measurements. 

♦ FEV1 or PEF values provide important information about the level of airflow 

obstruction both initially and in response to treatment. Because low PEF values 

cannot distinguish between poor effort, restrictive ventilatory disorders (e.g., 

neuromuscular weakness, pneumonia), and obstructive ventilatory disorders (e.g., 

asthma), FEV1 measurements are preferable if they are readily available 

(Evidence D). 

♦ In the initial assessment of a life-threatening asthma exacerbation, FEV1 or PEF are 

not indicated (Evidence D). 

♦ Very severe exacerbations may preclude performance of a maximal expiratory 

maneuver and, in such cases, the clinical presentation should suffice for clinical 

assessment and prompt initiation of therapy (Evidence D). 

♦ In less severe exacerbations, in the office or ED, FEV1 or PEF should be obtained on 

arrival and 30–60 minutes after initial treatment (Evidence B). 

♦ In the hospital, FEV1 or PEF should be measured on admission and 15–20 minutes 

after bronchodilator therapy during the acute phase and at least daily thereafter until 

discharge (Evidence C). 

♦ Any FEV1 or PEF value <25 percent of predicted that improves by <10 percent after 

treatment or values that fluctuate widely are potential indications for ICU admission 

and close monitoring for respiratory failure (Evidence C). 

♦ Flow-volume loops should be obtained to distinguish between upper and lower 

airway obstruction in patients who have atypical asthma symptoms (e.g., dysphonia) 
Section 5, Managing Exacerbations of Asthma 

390 

August 28, 2007 

or findings on exam (e.g., stridor) or if response to therapy is inadequate 

(Evidence D). 

— Monitor oxygen saturation. 

♦ Pulse oximetry is indicated for children unable to perform FEV1 or PEF or for any 

patient who is in severe distress or has an FEV1 or PEF <40 percent of predicted to 

assess the adequacy of arterial oxygen saturation (SaO2) (Connett and Lenney 

1993; Geelhoed et al. 1994; Sole et al. 1999; Wright et al. 1997) (Evidence C). 

♦ Serial pulse oximetry measurements can be useful to assess both the severity of the 

exacerbation and improvement with treatment (Evidence B). By contrast, a single 

pulse oximetry value on admission is of relatively little value for predicting hospital 

admission (Boychuk et al. 2006; Keahey et al. 2002; Wright et al. 1997). 

 Objectives of the brief history are to determine (EPR⎯2 1997): 

— Time of onset and any potential causes of current exacerbation. 

— Severity of symptoms, especially compared with previous exacerbations, and response 

to any treatment given before admission to ED. 

— All current medications and time of last dose, especially of asthma medications. 

— Estimate of number of previous unscheduled office visits, ED visits, and hospitalizations 

for asthma, particularly within the past year. 

— Any prior episodes of respiratory insufficiency due to asthma (loss of consciousness or 

intubation and mechanical ventilation). 

— Other potentially complicating illness, especially other pulmonary or cardiac disease or 

diseases that may be aggravated by systemic corticosteroid therapy (such as diabetes, 

peptic ulcer, hypertension, and psychosis). 

 Objectives of the initial brief physical examination are to (EPR⎯2 1997): 

— Assess the severity of the exacerbation, as indicated by the findings listed in figure 5–3. 

— Assess overall patient status, including level of alertness, fluid status, and presence of 

cyanosis, respiratory distress, and wheezing. Wheezing can be an unreliable indicator 

of obstruction; in rare cases, extremely severe obstruction may be accompanied by a 

“silent chest” (Shim and Williams 1980). 

— Identify possible complications (e.g., pneumonia, pneumothorax, or 

pneumomediastinum); although rare, these will influence management of the asthma 

exacerbation. 

— Rule out upper airway obstruction. Both intrathoracic and extrathoracic central airway 

obstruction can cause severe dyspnea and may be diagnosed as asthma. 
Section 5, Managing Exacerbations of Asthma 

391 

August 28, 2007 

♦ Causes include upper airway foreign bodies, epiglottitis, organic diseases of the 

larynx, vocal cord dysfunction, and extrinsic and intrinsic tracheal narrowing (See 

“Component 1: Measures of Asthma Assessment and Monitoring.”). 

♦ Clues to the presence of alternative reasons for dyspnea include dysphonia, 

inspiratory stridor, monophonic wheezing loudest over the central airway, normal 

values for PO2, and unexpectedly complete resolution of airflow obstruction with 

intubation. 

♦ When upper airway obstruction is suspected, further evaluation is indicated by 

flow-volume curves and by referral for laryngoscopy (See “Component 1: Measures 

of Asthma Assessment and Monitoring.”). 

 Laboratory studies. Most patients who have an asthma exacerbation do not require any 

initial laboratory studies. If laboratory studies are ordered, they must not delay initiation of 

asthma treatment (EPR⎯2 1997). The most important objective of laboratory studies is 

detection of actual or impending respiratory failure. Other objectives include detection of 

theophylline toxicity or conditions that complicate the treatment of asthma exacerbations 

(such as cardiovascular disease, pneumonia, or diabetes). For example: 

— Consider arterial blood gas (ABG) measurement for evaluating arterial carbon dioxide 

tension (PCO2) in patients who have suspected hypoventilation, severe distress, or FEV1

or PEF ≤25 percent of predicted after initial treatment. (Note: Respiratory drive is 

typically increased in asthma exacerbations, so a “normal” PCO2 of 40 mmHg indicates 

severe airflow obstruction and a heightened risk of respiratory failure.) 

— Venous levels of PCO2 have been tested as a substitute for arterial measurements, and 

a venous PCO2 of >45 mmHg may serve as a screening test but cannot substitute for 

the ABG evaluation of respiratory function (Kelly et al. 2002a). 

— Complete blood count (CBC) is not required routinely but may be appropriate in patients 

who have fever or purulent sputum. Keep in mind that modest leukocytosis is common 

in asthma exacerbations and that corticosteroid treatment causes a further outpouring of 

polymorphonuclear leukocytes within 1–2 hours of administration. 

— Measure serum theophylline concentration in patients who have taken theophylline 

before presentation. 

— It may be prudent to measure serum electrolytes in patients who have been taking 

diuretics regularly and in patients who have coexistent cardiovascular disease, because 

frequent SABA administration can cause transient decreases in serum potassium, 

magnesium, and phosphate. 

— Chest radiography is not recommended for routine assessment but should be obtained 

for patients suspected of a complicating cardiopulmonary process, such as congestive 

heart failure, or another pulmonary process such as pneumothorax, 

pneumomediastinum, pneumonia, or lobar atelectasis. 

— Electrocardiograms are not required routinely, but a baseline electrocardiogram and 

continual monitoring of cardiac rhythm are appropriate in patients older than 50 years of 

age and in those who have coexistent heart disease or chronic obstructive pulmonary 
Section 5, Managing Exacerbations of Asthma 

392 

August 28, 2007 

disease (COPD). The electrocardiogram may show a pattern of right ventricular strain 

that reverses promptly with treatment of airflow obstruction. 

 Assessment considerations unique to children and infants are as follows: 

— It is often difficult for physicians and parents to determine the severity of the airway 

obstruction in infants and small children who have asthma. However, using a 

combination of the subjective and objective parameters in figure 5–3 permits a fairly 

accurate assessment to guide initial therapy. Many of these parameters have not been 

studied systematically, so they serve only as general guides. 

— The differences in the anatomy and physiology of the lungs of infants place them at 

greater risk for respiratory failure. These differences include greater peripheral airway 

resistance, fewer collateral channels of ventilation, further extension of airway smooth 

muscle into the peripheral airways, less elastic recoil, and mechanical disadvantage of 

the diaphragm. Viral infections, particularly respiratory syncytial virus (RSV), are the 

most common cause of acute wheezing illness in infants. The edematous inflammatory 

response in the airways leads to air trapping and hyperinflation, atelectasis, increased 

respiratory rate, and wheezing. This sequence of changes can rapidly progress to 

respiratory failure, and close monitoring is critical. 

— It is particularly important to monitor SaO2 by pulse oximetry in infants because their 

ventilation/perfusion characteristics lead them to become hypoxemic more readily than 

adults. SaO2 should be normal for altitude (>95 percent at sea level). Decreased SaO2

is often an early sign of severe airway obstruction, and an SaO2 <92 percent of room air 

1 hour after initial treatment is a good predictor of the need for hospitalization in small 

infants (Connett and Lenney 1993; Geelhoed et al. 1994; Sole et al. 1999). 

— Capillary or ABG measurements should be performed on infants suspected of 

respiratory failure. PCO2 is the best measurement of ventilation in infants, as it is in 

adults. Children who have a normal PCO2 but are in obvious respiratory distress are at 

high risk for respiratory failure. 

— After initial treatment is begun, it is important to consider possible coexisting conditions, 

as is done in adults. In infants, considerations should include RSV infection, foreign 

body aspiration, history of bronchopulmonary dysplasia (prematurity) or cystic fibrosis. 

TREATMENT 

The Expert Panel recommends as initial treatments: oxygen for most patients, SABA for 

all patients; adding multiple doses of ipratropium bromide for ED patients who have 

severe exacerbations (but ipratropium bromide is not recommended during 

hospitalization); and systemic corticosteroids for most patients. For severe 

exacerbations unresponsive to the initial treatments, adjunct treatments (magnesium 

sulfate or heliox) merit consideration to decrease the likelihood of intubation. (See the 

following discussion for evidence levels.) 

The Expert Panel does not recommend: methylxanthines, antibiotics (except as needed 

for comorbid conditions), aggressive hydration, chest physical therapy, mucolytics, or 

sedation. (For evidence levels, see the following discussion.) 
Section 5, Managing Exacerbations of Asthma 

393 

August 28, 2007 

In the ED and hospital, tailor the intensity of treatment and surveillance to the severity of the 

exacerbation. The primary therapies—the administration of oxygen, SABA, and systemic 

corticosteroids—are constant, but the dose and frequency with which they are given and the 

frequency with which the patient’s response is assessed may vary. Thus, for patients 

presenting with a severe exacerbation, give SABA therapy at the higher dose plus ipratropium 

bromide (figure 5–5) either repeatedly (three treatments in the first hour) or continuously (by 

nebulization) (Evidence A). Give systemic corticosteroids immediately, and watch closely for 

signs of worsening airflow obstruction or fatigue. For patients who have mild exacerbations, 

give SABA therapy and assess the patient’s response before deciding whether additional 

therapy is necessary. When SaO2 monitoring is not available, give supplemental oxygen to 

patients who have significant hypoxemia and to patients who have FEV1 or PEF <40 percent of 

predicted. 

The Expert Panel recommends the following treatments: 

 Oxygen is recommended for most patients (EPR⎯2 1997). Administer supplemental 

oxygen (by nasal cannulae or mask, whichever is best tolerated) to maintain an SaO2

>90 percent (>95 percent in pregnant women and in patients who have coexistent heart 

disease). Monitor SaO2 until a clear response to bronchodilator therapy has occurred. 

 SABA treatment is recommended for all patients (Evidence A) (For recommended 

doses, see figure 5–5.). 

— The repetitive or continuous administration of SABAs is the most effective means of 

reversing airflow obstruction (Camargo et al. 2003b; Karpel et al. 1997; McFadden 2003; 

Travers et al. 2001). 

— In the ED, three treatments of SABA spaced every 20–30 minutes can be given safely 

as initial therapy. Thereafter, the frequency of administration varies according to the 

improvement in airflow obstruction and associated symptoms and the occurrence of side 

effects. Continuous administration of SABA may be more effective in more severely 

obstructed patients (Camargo et al. 2003b; Papo et al. 1993). 

— Because of the risk of cardiotoxicity, use only selective SABA (albuterol, levalbuterol, 

pirbuterol) in high doses. 

— In mild or moderate exacerbations, equivalent bronchodilation can be achieved either by 

high doses (4–12 puffs) of a SABA by MDI with a valved holding chamber (VHC) in 

infants, children, and adults under the supervision of trained personnel or by nebulizer 

therapy (Cates et al. 2003; Dolovich et al. 2005). However, nebulizer therapy may be 

preferred for patients who are unable to cooperate effectively in using an MDI because 

of their age, agitation, or severity of the exacerbation. 

— The onset of action for SABAs is less than 5 minutes; repetitive administration produces 

incremental bronchodilation. In about 60–70 percent of patients, response to the initial 

three doses in the ED will be sufficient to discharge them, and most patients will have a 

significant response after the first dose (Karpel et al. 1997; Rodrigo and Rodrigo 1998b; 

Strauss et al. 1997). 
Section 5, Managing Exacerbations of Asthma 

394 

August 28, 2007 

— Duration of action of bronchodilation from SABAs in severe asthma exacerbations is not 

precisely known, but duration can be significantly shorter than that observed in stable 

asthma. 

— A recent meta-analysis of six trials suggests that the use of nebulized magnesium 

sulfate in combination with SABAs may result in further improvements in pulmonary 

function (Blitz et al. 2005), but further research is needed. 

 Inhaled ipratropium bromide. 

— In the ED: recommended (Evidence A). Adding multiple high doses of ipratropium 

bromide (0.5 mg nebulizer solution or 8 puffs by MDI in adults; 0.25–0.5 mg nebulizer 

solution or 4–8 puffs by MDI in children) to a selective SABA produces additional 

bronchodilation, resulting in fewer hospital admissions, particularly in patients who have 

severe airflow obstruction (Plotnick and Ducharme 2000; Rodrigo and Castro-Rodriguez 

2005). 

— In the hospital: not recommended (Evidence A). Two controlled clinical trials failed 

to detect a significant benefit from the addition of ipratropium to treatment after 

hospitalization for severe acute asthma (Craven et al. 2001; Goggin et al. 2001). 

Studies of hospitalized adults are not available.

 Systemic corticosteroids are recommended for most patients (For recommended 

doses, See figure 5–5.): 

— In the ED: Give systemic corticosteroids to patients who have moderate or severe 

exacerbations and patients who do not respond completely to initial SABA 

therapy (Evidence A). These medications speed the resolution of airflow obstruction 

and reduce the rate of relapse and may reduce hospitalizations (Edmonds et al. 2003; 

Rowe et al. 2001; Rowe et al. 2004). 

♦ Oral administration of prednisone has been shown to have effects equivalent 

to those of intravenous methylprednisolone (Evidence A) (Harrison et al. 1986; 

Ratto et al. 1988) and, in the opinion of the Expert Panel, is usually preferred 

because it is less invasive. 

♦ Give a 5- to 10-day course following ED discharge to prevent early relapse 

(EPR⎯2 1997). 

♦ Intramuscular depot injections of corticosteroids may be considered as an 

alternative to oral corticosteroids for patients who are at high risk of 

nonadherence (Evidence D). Intramuscular depot injections may be as effective as 

oral corticosteroids for preventing relapse after discharge from the ED (Lahn et al. 

2004; Rowe et al. 2001; Schuckman et al. 1998). 

♦ Give supplemental doses of oral corticosteroids to patients who take them 

regularly, even if the exacerbation is mild (Evidence D). 

— In the hospital: Give systemic corticosteroids to patients who are admitted to the 

hospital (Evidence A), because oral systemic corticosteroids speed the resolution of 

asthma exacerbations (Manser et al. 2001; Smith et al. 2003). 
Section 5, Managing Exacerbations of Asthma 

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August 28, 2007 

 High doses of an ICS may be considered in the ED, although current evidence is 

insufficient to permit conclusions about using ICSs rather than oral systemic 

corticosteroids in the ED (Evidence B). (See Evidence Table 17, Increasing the Dose of 

Inhaled Corticosteroids.) Although simply doubling the dose of the ICS that a patient is 

taking for long-term therapy at the onset of an exacerbation does not appear to be effective 

(FitzGerald et al. 2004; Garrett et al. 1998; Harrison et al. 2004; Rice-McDonald et al. 2005), 

there is increasing evidence that multiple high doses of an ICS (6 mg flunisolide over 

3 hours) (Rodrigo and Rodrigo 1998a) or 3 mg fluticasone/hour for 3 hours (Rodrigo 2005) 

are beneficial when initiated in adults early in the ED (See Evidence Table 17.). The data 

on ICS use in children are inconsistent (Rowe et al. 2004). This may be a result of the 

inconsistency of dosing. One trial reporting greater efficacy for oral corticosteroids used a 

single high dose of an ICS (2 mg fluticasone) (Schuh et al. 2000), whereas a trial giving 

multiple doses of budesonide (1.2 mg total) reported increased efficacy for the inhaled route 

(Singhi et al. 1999). The level of acute asthma severity also may explain apparent 

discrepancies found in the literature. Although the data are suggestive, a meta-analysis 

concluded that evidence was insufficient for firm conclusions (Edmonds et al. 2003). 

Further investigations with greater attention to dosing and acute asthma severity level are 

required. 

 For severe exacerbations unresponsive to the initial treatments listed above, whether 

given before arrival at the acute care setting or in the ED, adjunct treatments may be 

considered to decrease the likelihood of intubation: intravenous magnesium or 

heliox may be useful (Evidence B). These therapies are discussed below, in the 

subsection on “Impending Respiratory Failure.” 

The following treatments are NOT recommended:

 Methylxanthines are not recommended (Evidence A). (See Evidence Table 18, 

IV Aminophylline.)

— In the ED: Theophylline/aminophylline is not recommended because it appears to 

provide no additional benefit to optimal SABA therapy and increases the frequency of 

adverse effects (Parameswaran et al. 2000). 

— If patients are currently taking a theophylline-containing preparation, determine serum 

theophylline concentration to prevent theophylline toxicity. 

— In the hospital: Therapy with oral or intravenous methylxanthines does not improve 

lung function or other outcomes in hospitalized adults (Parameswaran et al. 2000). Most 

studies show no benefit, but increased toxicity, with theophylline in children who are 

hospitalized with severe asthma (Mitra et al. 2005). The meta-analysis, however, 

reported that those patients receiving intravenous aminophylline had a small 

(8–9 percent) but significant greater improvement in percent predicted FEV1. This 

difference was due to the weight of one study (Yung and South 1998), and this 

difference in lung function did not result in significant differences in length of stay, ICU 

admission or stay, or symptoms; however, significantly greater numbers of patients in 

the theophylline group had therapy discontinued due to adverse effects. 

 Antibiotics are not generally recommended for the treatment of acute asthma 

exacerbations except as needed for comorbid conditions (Evidence B). Bacterial, 

Chlamydia, or Mycoplasma infections infrequently contribute to exacerbations of asthma; 
Section 5, Managing Exacerbations of Asthma 

396 

August 28, 2007 

therefore, the use of antibiotics is generally reserved for patients who have fever and 

purulent sputum and for patients who have evidence of pneumonia (EPR⎯Update 2002). 

When the presence of bacterial sinusitis is strongly suspected, treat with antibiotics. 

 Aggressive hydration is not recommended for older children and adults but may be 

indicated for some infants and young children (Evidence D). Intravenous or oral 

administration of large volumes of fluids does not play a role in the management of severe 

asthma exacerbations. Some infants and young children may become dehydrated, 

however, as a result of increased respiratory rate and decreased oral intake. In these 

patients, clinicians should make an assessment of fluid status (urine output, urine specific 

gravity, mucus membrane moisture, electrolytes) and provide appropriate corrections. The 

placement of intravenous lines is not without complication, and the emotional impact of this 

procedure may prove counterproductive. Oral routes of hydration are preferable except in 

very severe exacerbations with the possibility of endotracheal intubation. 

 Chest physical therapy is not generally recommended (Evidence D). For most 

exacerbations, chest physiotherapy is not beneficial and is unnecessarily stressful for the 

breathless asthma patient. Because mucus plugging is a major contributing cause of fatal 

asthma (Kuyper et al. 2003), further studies are needed on the role of improved airway 

clearance in near-fatal exacerbations. 

 Mucolytics are not recommended (Evidence C). Avoid mucolytic agents (e.g., 

acetylcysteine, potassium iodide) because they may worsen cough or airflow obstruction. 

 Sedation is not generally recommended (Evidence D). Anxiolytic and hypnotic drugs are 

contraindicated in severely ill asthma patients because of their respiratory depressant effect. 

In asthmatic patients who have severe emotional impact, and possible comorbid anxiety 

disorder, therapy should stay focused on the asthma exacerbation; the benefit of shortacting sedatives is not known. 

REPEAT ASSESSMENT 

The Expert Panel recommends that repeat assessment of patients who have severe 

exacerbations be made after the initial dose of a SABA and that repeat assessment of all 

patients be made after three doses of a SABA (60–90 minutes after initiating treatment) 

(Evidence A). 

The response to initial treatment in the ED is a better predictor of the need for hospitalization 

than is the severity of an exacerbation on presentation (Cham et al. 2002; Chey et al. 1999; 

Gorelick et al. 2004b; Karras et al. 2000; Kelly et al. 2002b and 2004; McCarren et al. 2000; 

Rodrigo and Rodrigo 1993, 1998c; Smith et al. 2002). The elements to be evaluated include the 

patient’s subjective response, physical findings, FEV1 or PEF, and measurement of pulse 

oximetry or ABG (if the patient meets the criteria described in the earlier discussion of laboratory 

studies). 

HOSPITALIZATION 

The Expert Panel recommends that the decision to hospitalize a patient be based on 

duration and severity of symptoms, severity of airflow obstruction, response to ED 

treatment (See earlier section on monitoring in “Treatment Goals.”), course and severity 

of prior exacerbations, medication use at the time of the exacerbation, access to medical 
Section 5, Managing Exacerbations of Asthma 

397 

August 28, 2007 

care and medications, adequacy of support and home conditions, and presence of 

psychiatric illness (Evidence C) (Pollack et al. 2002; Weber et al. 2002.). 

In general, the principles of care in the hospital and recommendation for treatment 

resemble those for care in the ED and involve both treatment (with oxygen, aerosolized 

SABA, and systemic corticosteroids and, perhaps, adjunct therapies) and frequent 

assessment, including clinical assessment of respiratory distress and fatigue as well as 

objective measurement of airflow (PEF or FEV1) and oxygen saturation (EPR⎯2 1997). 

IMPENDING RESPIRATORY FAILURE 

The Expert Panel recommends that intubation not be delayed once it is deemed 

necessary; exactly when to intubate is based on clinical judgment (Evidence D). Most 

patients respond well to therapy. However, a small minority will show signs of worsening 

ventilation, whether from worsening airflow obstruction, worsening respiratory muscle fatigue, or 

a combination of the two. Signs of impending respiratory failure include inability to speak, 

altered mental status, intercostal retraction (Cham et al. 2002), worsening fatigue, and a PCO2

of ≥42 mmHg. Because respiratory failure can progress rapidly and can be difficult to reverse, 

early recognition and treatment are critically important. 

The Expert Panel recommends that adjunct treatments such as magnesium sulfate or 

heliox may be considered to avoid intubation, but intubation should not be delayed once 

it is deemed necessary (Evidence B). Because intubation of a severely ill asthma patient is 

difficult and associated with complications, additional treatments are sometimes attempted. 

 Intravenous magnesium sulfate. Consider intravenous magnesium sulfate in patients 

who have life-threatening exacerbations and in those whose exacerbations remain in 

the severe category after 1 hour of intensive conventional therapy (Evidence B). (See 

Evidence Table 19, Magnesium Sulfate.) Meta-analyses of studies of both children and 

adults (Cheuk et al. 2005; Rowe et al. 2000) show that intravenous magnesium sulfate (2 

grams in adults and 25–75 mg/kg up to 2 grams in children) added to conventional therapy 

reduces hospitalization rates in ED patients who present with severe asthma exacerbations 

(PEF <40 percent). However, not all individual studies have found positive results 

(Boonyavorakul et al. 2000; Porter et al. 2001; Scarfone et al. 2000). The treatment has no 

apparent value in patients who have exacerbations of lesser severity, and one study 

(Silverman et al. 2002) found that intravenous magnesium sulfate improved pulmonary 

function only in patients whose initial FEV1 was <25 percent predicted, and the treatment did 

not improve hospital admission rates. 

 Heliox. Consider heliox-driven albuterol nebulization for patients who have 

life-threatening exacerbations and for those patients whose exacerbations remain in 

the severe category after 1 hour of intensive conventional therapy (Evidence B). (See 

Evidence Table 20, Heliox.)

Because of helium’s low density, a mixture of helium and oxygen (heliox) could improve gas 

exchange in patients who have airway obstruction (Gupta and Cheifetz 2005). However, a 

meta-analysis of six studies (four in adults, two in pediatric patients) performed between 

1996 and 2002 did not find a statistically significant improvement in pulmonary function or 

other measured outcomes in patients receiving heliox compared to oxygen or air (Ho et al. 

2003). Likewise, a more recent study did not demonstrate a statistically significant benefit in 

children who had moderately severe asthma and received standard initial therapy followed 
Section 5, Managing Exacerbations of Asthma 

398 

August 28, 2007 

by continuous albuterol nebulization with heliox compared to air/oxygen (Rivera et al. 2006). 

In contrast, another recent study (Kim et al. 2005) did report a significant improvement in 

pulmonary index and a trend toward reduced hospitalizations in children who had 

moderate-to-severe exacerbations and received heliox-driven albuterol nebulization 

compared to children who received oxygen-driven nebulization. Other investigators recently 

described two randomized controlled trials (RCTs) of adults that demonstrated more rapid 

and greater improvements in peak flow and dyspnea scores in patients who presented with 

severe exacerbations and received initial treatment with heliox versus oxygen-driven 

albuterol therapy (Lee et al. 2005). The discrepancy in findings may result from small 

sample sizes. More importantly, however, some studies have neglected to account for the 

different effect of heliox versus oxygen (or room air) on respirable mass (Hess et al. 1999). 

For example, failure to increase the gas flow rate for those on heliox greatly complicates 

interpretation (and synthesis) of the literature. 

 Other adjunct therapies to avoid intubation include intravenous beta2-agonists, 

intravenous leukotriene receptor antagonists (LTRAs), and noninvasive ventilation; 

however, insufficient data are available to make recommendations regarding these 

possible adjunct therapies (Evidence D). 

— Intravenous beta2-agonists remain a largely unproven treatment. Current evidence does 

not suggest an improved benefit from intravenous beta2-agonists compared to aerosol 

administration (Travers et al. 2001), but data are sparse (Browne et al. 1997) on the 

benefit of adding an intravenous beta2-agonist to high-dose nebulized therapy. 

Nevertheless, the Expert Panel does not recommend use of intravenous isoproterenol in 

the treatment of asthma because of the danger of myocardial toxicity (Evidence B) 

(Maguire et al. 1991). 

— Intravenous LTRAs could provide another pathway to rapid bronchodilation during 

impending respiratory failure. A randomized trial of intravenous montelukast in 

moderate and severe exacerbations demonstrated significant improvement in pulmonary 

function within 10 minutes of administration (Camargo et al. 2003a). The oral 

formulation LTRA would not be expected to provide benefit for at least 90 minutes 

(Dockhorn et al. 2000). 

— Noninvasive ventilation is another experimental approach for treatment of respiratory 

failure due to severe asthma exacerbation, but data are very limited (Ram et al. 2005). 

— Review of other experimental adjunct therapies is beyond the scope of this report. 

The Expert Panel recommends the following actions regarding intubation: 

 Patients who present with apnea or coma should be intubated immediately (EPR⎯2 

1997). There are no other absolute indications for endotracheal intubation, but persistent or 

increasing hypercapnia, exhaustion, and depression of mental status strongly suggest the 

need for ventilatory support (Evidence D). 

 Intubate semielectively, before the crisis of respiratory arrest, because intubation is 

difficult in patients who have asthma (EPR⎯2 1997). 
Section 5, Managing Exacerbations of Asthma 

399 

August 28, 2007 

 Intubation should be performed by a physician who has extensive experience in 

intubation and airway management (EPR⎯2 1997). 

— Because intubation should not be delayed once it is deemed necessary, it is often 

performed in the ED or inpatient ward, and the patient is subsequently transferred to an 

ICU appropriate to the patient’s age. 

— Children who are intubated for asthma should be admitted to a pediatric ICU or 

transferred to a facility that has such a unit. 

— Even without intubation, patients who have severe exacerbations and are slow to 

respond to therapy may benefit from admission to an ICU, where they can be monitored 

closely and intubated if it is indicated. 

— Despite theoretical benefits from using ketamine as a premedication for intubation, 

clinical trials in nonintubated patients who have severe exacerbations have not shown 

clinical benefit (Allen and Macias 2005; Howton et al. 1996). Studies of intubated 

patients are not available. 

— Although many issues require consideration at the time of intubation, clinicians should 

pay close attention to maintaining or replacing intravascular volume, because 

hypotension commonly accompanies the initiation of positive pressure ventilation. 

 “Permissive hypercapnia” or “controlled hypoventilation” is the recommended 

ventilator strategy (Evidence C). Permissive hypercapnia provides adequate oxygenation 

and ventilation while minimizing high airway pressures and barotrauma (Darioli and Perret 

1984; Menitove and Goldring 1983; Tuxen 1994). It involves administration of as high a 

fraction of inspired oxygen as is necessary to maintain adequate arterial oxygenation, 

acceptance of hypercapnia, and treatment of respiratory acidosis with intravenous 

sodium bicarbonate. Adjustments are made to the tidal volume, ventilator rate, and 

inspiration-to-expiration ratio to minimize airway pressures. Consultation with or 

comanagement by physicians who have expertise in ventilator management is appropriate, 

because mechanical ventilation of patients who have severe refractory asthma is 

complicated and fraught with risk. Continuation of a SABA in ventilated patients is 

recommended, although no RCTs provide evidence for or against this practice (Dhand and 

Tobin 1997; Jones et al. 2001). This ventilator strategy is not uniformly successful in 

critically ill asthma patients, and additional therapies are being evaluated. Their review is 

beyond the scope of this report. 

PATIENT DISCHARGE 

The Expert Panel recommends that clinicians, before patients’ discharge from the ED or 

hospital, provide patients with necessary medications and education on how to use 

them, a referral for a followup appointment, and instruction in an ED asthma discharge 

plan for recognizing and managing relapse of the exacerbation or recurrence of airflow 

obstruction (Evidence B).
Section 5, Managing Exacerbations of Asthma 

400 

August 28, 2007 

The Expert Panel recommends the following actions for discharging patients from the 

ED: 

 Release of the patient from the ED depends on the patient’s response to treatment 

(EPR⎯2 1997). 

— In general, discharge is appropriate if FEV1 or PEF has returned to ≥70 percent of 

predicted or personal best and symptoms are minimal or absent. Patients who have an 

incomplete response to therapy (FEV1 or PEF 50–69 percent of predicted or personal 

best) and with mild symptoms should be assessed individually for their suitability for 

discharge home, with consideration given to factors listed in figure 5–2a (Evidence C). 

— The Expert Panel’s opinion is that patients who have a rapid response should be 

observed for 30–60 minutes after the most recent dose of bronchodilator to ensure their 

stability of response before discharge to home. 

— Extended treatment and observation in a holding area, clinical decision unit, or overnight 

unit to determine the need for hospitalization may be appropriate, provided there is 

sufficient monitoring and nursing care (McCarren et al. 2000). 

 Prescribe sufficient medications for the patient to continue treatment after discharge.

— Patients given systemic corticosteroids should continue oral systemic 

corticosteroids for 3–10 days (Evidence A). The need for further corticosteroid 

therapy should be assessed at a followup visit. For corticosteroid courses of less than 

1 week, there is no need to taper the dose. For 10-day courses, there remains no need 

to taper if patients are concurrently taking ICSs (O'Driscoll et al. 1993). 

— Consider initiating an ICS at discharge, in addition to oral systemic 

corticosteroids (Evidence B). A retrospective review of a large patient database found 

a significant reduction in the risk of subsequent ED visits among patients using ICS 

therapy after ED discharge (Sin and Man 2002). A clinical RCT comparing ED patients 

discharged with and without ICSs demonstrated that ICSs added to oral systemic 

corticosteroids halved patients’ risk of relapse events (Rowe et al. 1999). A Cochrane 

review (Edmonds et al. 2000) noted that two other relapse trials did not report similar 

benefit, but the review found that the combined estimate of the three available trials had 

borderline statistical significance (odds ratio 0.68; 95 percent CI 0.46 to 1.02). The 

Expert Panel concludes that initiating ICS therapy (e.g., providing a 1–2 month supply) 

at discharge from ED should be considered, given the potential for ICSs is to reduce 

subsequent ED visits, the strong evidence that long-term-control ICS therapy reduces 

exacerbations in patients who have persistent asthma, and the opinion of the Expert 

Panel that the initiation (and continuation) of ICS therapy at ED discharge can be an 

important effort to bridge the gap between emergency and primary care for asthma. 

Patients already taking ICS therapy should continue it following discharge. 

 Emphasize the need for continual, regular care in an outpatient setting, and refer the 

patient for a followup asthma care appointment (either primary care provider (PCP) or 

asthma specialist) within 1–4 weeks (Evidence B). If appropriate, consider referral to 

an asthma self-management education program (Evidence B). A visit to the ED is often 

an indication of inadequate long-term management of asthma or inadequate plans for 

handling exacerbations. Having fewer general practice contacts in the previous year has 
Section 5, Managing Exacerbations of Asthma 

401 

August 28, 2007 

been independently associated with an increased risk of fatal asthma (Sturdy et al. 2005), 

and an observational study found that having followup appointments within 30 days of an 

asthma-related ED visit was associated with a reduced 90-day readmission rate (Sin et al. 

2002). Likewise, referral of patients in the ED to an asthma specialist for consultation was 

associated with a reduced rate of subsequent ED visits (Zeiger et al. 1991). These results 

contrast, however, with two recent randomized trials that found that facilitated referral of ED 

patients to the PCP did not alter long-term asthma outcomes (Baren et al. 2006; Smith et al. 

2004). Although the evidence from RCTs regarding optimal referral practice is limited (e.g., 

PCP or asthma specialist), the ED and hospital staff should notify the patient’s health care 

professional (or provide a referral to one if the patient does not name a source of asthma 

care) and encourage the patient to contact his/her health care provider (e.g., by telephone) 

for asthma-related problems during the first 3–5 days after ED or hospital discharge. The 

ED and hospital staff should instruct the patient to seek a followup medical appointment 

within 1–4 weeks. Whenever possible, the ED should schedule such an appointment before 

the patient is discharged, because this action will increase the likelihood that the patient 

actually receives an appointment and attends the followup (Baren et al. 2006; Zorc et al. 

2003). At the followup appointment, the health care provider should try to ascertain the 

cause of the exacerbation and institute appropriate, specific, preventative therapy if 

possible. The followup visit should also include a detailed review of the patient’s 

medications, inhaler and peak flow meter technique, and development of a comprehensive 

written asthma action plan that will help prevent subsequent exacerbations and urgent or 

emergency care visits (See section 3, “Component 2: Education for a Partnership in Asthma 

Care,” figures 3–10a, b, and c; 3–11; and 3–14.). If appropriate, consider referring the 

patient to an asthma self-management education program. 

 Review discharge medications with the patient and provide patient education on 

correct use of an inhaler (Evidence B) (See section 3, “Component 2: Education for a 

Partnership in Asthma Care,” figures 3–12 and 3–14.). 

 Give the patient an ED asthma discharge plan with instruction for medications 

prescribed at discharge and for increasing medications or seeking medical care if 

asthma should worsen (Evidence B). Although evidence from RCTs is limited, for many 

patients, a thoughtful, asthma-oriented ED discharge plan will suffice. If local staff and 

resources permit, however, the provision of a more detailed plan may be appropriate, 

especially for patients who had severe exacerbations or who do not have regular asthma 

care. See figure 5–7 for a sample ED asthma discharge plan and “Component 2: 

Education for a Partnership in Asthma Care.” 

 Consider issuing a peak flow meter and giving appropriate education on how to 

measure and record PEF to patients who have difficulty perceiving airflow 

obstruction or symptoms of worsening asthma (Evidence D). Studies document that 

some patients are unable to perceive signs of deterioration that would indicate a need to 

increase medication (Hardie et al. 2002; Kikuchi et al. 1994). These “poor perceivers” may 

particularly benefit from action plans based on peak flow monitoring, because this tool may 

prevent delays in treating exacerbations. Although clinical trials have not yet evaluated 

issuing peak flow meters at discharge from ED, it is the opinion of the Expert Panel that this 

approach warrants consideration. See “Component 1: Measures of Asthma Assessment 

and Monitoring” and “Component 2: Education for a Partnership in Asthma Care” for 

discussions of the advantages and disadvantages of peak flow monitoring. 
Section 5, Managing Exacerbations of Asthma 

402 

August 28, 2007 

FIGURE 5–7. EMERGENCY D EPARTMENT—ASTHMA DISCHARGE 

PLAN 

Reprinted by permission from Carlos Camargo, M.D., Principal Investigator of Agency for Health Care Research and Quality. Grant No. R13H31094. 

Source: Camargo CA Jr, Emond SD, Boulet L, Gibson PG, Kolbe J, Wagner CW, Brenner BE. Emergency Department⎯Asthma Discharge Plan. 

Developed at "Asthma Education in the Adult Emergency Department: A Multidisciplinary Consensus Conference," New York Academy of Medicine, 

New York, NY; 2001 April 1–5. Boston, MA: Massachusetts General Hospital, 2001. 2 pp. 
Section 5, Managing Exacerbations of Asthma 

403 

August 28, 2007 

FIGURE 5–7b. EMERGENCY D EPARTMENT—ASTHMA DISCHARGE 

PLAN: HOW TO USE YOUR METERED-DOSE INHALER 

Using an inhaler seems simple, but most patients do not use it the right way. When you use your inhaler the wrong 

way, less medicine gets to your lungs. 

For the next few days, read these steps aloud as you do them or ask someone to read them to you. Ask your doctor, 

nurse, other health care provider, or pharmacist to check how well you are using your inhaler. 

Use your inhaler in one of the three ways pictured below. A or B are best, but C can be used if you have trouble with 

A and B. Your doctor may give you other types of inhalers. 

Steps for Using Your Inhaler 

Getting ready 1. Take off the cap and shake the inhaler. 

2. Breathe out all the way. 

3. Hold your inhaler the way your doctor said (A, B, or C 

below). 

Breathe in slowly 4. As you start breathing in slowly through your mouth, 

press down on the inhaler one time. (If you use a 

holding chamber, first press down on the inhaler. Within 

5 seconds, begin to breathe in slowly.) 

5. Keep breathing in slowly, as deeply as you can. 

Hold your breath 6. Hold your breath as you count to 10 slowly, if you can. 

7. For inhaled quick-relief medicine (short-acting 

beta2-agonists), wait about 15–30 seconds between puffs. 

There is no need to wait between puffs for other 

medicines. 

inches in front of 

your mouth (about 

the width of two 

fingers). 

chamber. These come in 

many shapes and can be 

useful to any patient. 

mouth. Do not use for 

steroids. 

Clean your inhaler as needed, and know when to replace your inhaler. For instructions, read the package 

insert or talk to your doctor, other health care provider, or pharmacist. 

A. Hold inhaler 1 to 2 B. Use a spacer/holding C. Put the inhaler in your 
Section 5, Managing Exacerbations of Asthma 

404 

August 28, 2007 

The Expert Panel recommends the following actions for discharging patients from the 

hospital: 

 Prior to discharge, adjust the patient’s medication to an outpatient regimen (EPR⎯2 

1997). During the first 24 hours after this medication adjustment, observe the patient for 

possible deterioration. 

 Discharge medications should include a SABA and sufficient oral systemic 

corticosteroids to complete the course of therapy (Evidence A) and instructions to 

continue long-term control therapy until the followup appointment (Evidence B). 

Consider initiating ICS therapy for patients who did not use an ICS prior to the 

hospital admission (Evidence B). If the decision is made to start the patient on an ICS, 

the ICS should be started before the course of oral corticosteroids is completed, because 

their onset of action is gradual (Kraan et al. 1988). Starting the ICS therapy before 

discharge gives the patient additional time to learn and demonstrate appropriate technique. 

 Provide patient education: 

— Review patient understanding of the causes of asthma exacerbations, the 

purposes and correct uses of treatment (including inhaler technique), and the 

actions to be taken for worsening symptoms or peak flow measures (Evidence B) 

(See “Component 2: Education for a Partnership in Asthma Care.”). An 

exacerbation severe enough to require hospitalization may reflect a failure of the 

patient’s self-management, particularly in patients who have low levels of health literacy 

(Paasche-Orlow et al. 2005). Some studies report that 35 percent of adult patients 

presenting to the ED are current smokers (Silverman et al. 2003). It would be 

appropriate to query patients hospitalized for asthma about their smoking status and 

encourage smoking cessation along with their asthma discharge plan. Hospitalized 

patients may be particularly receptive to information and advice about their illness (See 

“Component 2: Education for a Partnership in Asthma Care.”). 

— Educate patients about their discharge medications and the importance of taking 

medications as prescribed and attending their followup visit (Evidence B). Low 

levels of adherence to asthma medications are common, even in patients recently 

hospitalized for severe asthma exacerbations (Krishnan et al. 2004). 

— Referral to an asthma specialist should be considered for patients who have a 

history of life-threatening exacerbations or multiple hospitalizations (Evidence B) 

(Harish et al. 2001; Mahr and Evans 1993; Mayo et al. 1990; Sperber et al. 1995). 

— Consider issuing a peak flow meter and giving appropriate education on peak flow 

monitoring to patients who are ≥5 years of age (and parents) who have a history of 

severe exacerbations or who have moderate or severe persistent asthma 

(Evidence B) and those who poorly perceive airflow obstruction or worsening 

asthma (Evidence D). 
Section 5, Managing Exacerbations of Asthma 

405 

August 28, 2007 

 Review or develop a written plan for managing either relapse of the exacerbation of 

recurrent symptoms or exacerbations (Evidence B). The plan should describe the signs, 

symptoms, and/or peak flow values that should prompt increases in self-medication, contact 

with a health care provider, or return for emergency care. The plan given at discharge from 

the ED may be quite simple (e.g., instructions for discharge medications and returning for 

care if asthma worsens; see figure 5–7). The preparation for discharge from the hospital 

should be more complete (See figure 5–8.). A detailed written asthma action plan for 

comprehensive long-term management and handling of exacerbations should be developed 

by the regular provider at a followup visit (See figure 3–10a, b, and c; “Component 2: 

Education for a Partnership in Asthma Care.”). 

FIGURE 5–8. CHECKLIST FOR HOSPITAL DISCHARGE OF 

PATIENTS WHO HAVE ASTHMA 

Intervention Dose/Timing Education/Advice M.D./R.N. Initials 

Inhaled medications 

(e.g., MDI with valved holding 

chamber (VHC or spacer); 

nebulizer) 

Select agent, dose, and 

frequency (e.g., albuterol) 

 SABA 2–6 puffs every 3–4 hours as 

needed 

 Corticosteroids Medium dose 

 Teach purpose 

 Teach and check technique 

 For MDIs, emphasize the 

importance of VHC or 

spacer 

Oral medications Select agent, dose, and 

frequency (e.g., prednisone 

50 mg qd for 5 days) 

 Teach purpose 

 Teach side effects 

Peak flow meter For selected patients: measure 

a.m. and p.m. PEF, and record 

best of three tries each time 

 Teach purpose 

 Teach technique 

 Distribute peak flow diary 

Followup visit Make appointment for followup 

care with primary clinician or 

asthma specialist 

Advise patient (or caregiver) 

of date, time, and location of 

appointment, ideally within 7 

days of hospital discharge 

Action plan Before or at discharge Instruct patient (or caregiver) 

on simple plan for actions to 

be taken when symptoms, 

signs, or PEF values suggest 

airflow obstruction 

Key: MDI, metered-dose inhaler; PEF, peak expiratory flow; SABA, short-acting beta2-agonist. 
Section 5, Managing Exacerbations of Asthma 

406 

August 28, 2007 

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Revised June 2002, August 2007 
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