U.S. DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Public Health Service

National Institutes of Health

National Heart, Lung, and Blood Institute

NIH Publication No. 95-0000

July 1995

U.S. DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Public Health Service

National Institutes of Health

National Heart, Lung, and Blood Institute

NIH Publication No. 97-4051

July 1997
NIH PUBLICATION

NO. 97-4051

JULY 1997

NATIONAL INSTITUTES

O F HEALTH

National Heart, Lung, 

and Blood Institute

CLINICAL PRACTICE

GUIDELINES

E XPERT PANEL REPORT 2

Guidelines 

for the 

Diagnosis and 

Management of Asthma

Archive

for historical Reference Only
iii

Second Expert Panel on the Management of Asthma ........vii 

National Asthma Education and Prevention Program

Coordinating Committee....................................................ix

National Asthma Education and Prevention Program

Science Base Committee......................................................x

PREFACE ..........................................................................xi

INTRODUCTION .....................................................1

METHODS USED TO DEVELOP THIS REPORT...........2

OVERVIEW OF THE REPORT ........................................3

Pathogenesis and Definition ...........................................3

Component 1: Measures of Assessment 

and Monitoring ...........................................................3

Initial Assessment and Diagnosis of Asthma................3

Periodic Assessment and Monitoring ...........................4

Component 2: Control of Factors Contributing to

Asthma Severity ..........................................................4

Component 3: Pharmacologic Therapy .........................4

Component 4: Education for a Partnership 

in Asthma Care ...........................................................5

Box 1. Major Events in the Development of EPR-2...........3 

REFERENCES....................................................................5

PATHOGENESIS AND DEFINITION......................7

Key Points ..........................................................................7

Differences From 1991 Expert Panel Report .......................7

AIRWAY PATHOLOGY AND ASTHMA.........................8

Child-Onset Asthma ....................................................10

Adult-Onset Asthma....................................................10

RELATIONSHIP OF AIRWAY INFLAMMATION 

AND LUNG FUNCTION...............................................10

Airway Hyperresponsiveness ........................................10

Airflow Obstruction .....................................................11

RELEVANCE OF CHRONIC AIRWAY 

INFLAMMATION TO ASTHMA THERAPY.................11

Figure 1. Mechanisms Underlying the Definition of

Asthma ..........................................................................8

Figure 2. Cellular Mechanisms Involved in Airway

Inflammation .................................................................9

REFERENCES..................................................................12

COMPONENT 1:

MEASURES OF ASSESSMENT 

AND MONITORING ..........................................................15

INITIAL ASSESSMENT AND 

DIAGNOSIS OF ASTHMA ......................................15

Key Points ........................................................................15

Differences From 1991 Expert Panel Report .....................15

MEDICAL HISTORY ......................................................17

PHYSICAL EXAMINATION..........................................17

PULMONARY FUNCTION TESTING 

(SPIROMETRY)...........................................................17

ADDITIONAL STUDIES................................................19

DIFFERENTIAL DIAGNOSIS OF ASTHMA .................22

GENERAL GUIDELINES FOR REFERRAL TO AN

ASTHMA SPECIALIST....................................................23

Box 1. Key Indicators for Considering a Diagnosis 

of Asthma ....................................................................16

Box 2. Importance of Spirometry in Asthma Diagnosis ...20

Figure 1-1. Suggested Items for Medical History.............18

Figure 1-2. Sample Questions for the Diagnosis 

and Initial Assessment of Asthma.................................19

Figure 1-3. Classification of Asthma Severity...................20

Figure 1-4a. Sample Spirometry Volume Time and 

Flow Volume Curves.....................................................21

Figure 1-4b. Report of Spirometry Findings Pre and 

Post Bronchodilator......................................................21

Figure 1-5. Differential Diagnostic Possibilities 

for Asthma ...................................................................22

REFERENCES..................................................................23

CONTENTS Archive

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iv

PERIODIC ASSESSMENT AND MONITORING:

ESSENTIAL FOR ASTHMA MANAGEMENT ........25

Key Points ........................................................................25

Differences From 1991 Expert Panel Report .....................25

GOALS OF THERAPY....................................................26

ASSESSMENT MEASURES .............................................26

Monitoring Signs and Symptoms of Asthma ................26

Monitoring Pulmonary Function ..................................28

Spirometry.................................................................28

Peak Flow Monitoring ...............................................28

Monitoring Quality of Life/Functional Status ...............34

Monitoring History of Asthma Exacerbations...............35

Monitoring Pharmacotherapy.......................................35

Monitoring Patient-Provider Communication 

and Patient Satisfaction .............................................35

ASSESSMENT METHODS..............................................35

Clinician Assessment ....................................................35

Patient Self-Assessment ................................................38

Population-Based Assessment.......................................38

Box 1. Peak Flow Monitoring Literature Review..............31

Box 2. Differences in Peak Flow Across Racial 

and Ethnic Populations.................................................34

Figure 1-6. Components of the Clinician’s Followup 

Assessment: Sample Routine Clinical Assessment 

Questions .....................................................................27

Figure 1-7. How To Use Your Peak Flow Meter 

(Patient Handout) ........................................................29

Figure 1-8. Sample Patient Self-Assessment Sheet 

for Followup Visits .......................................................36

Figure 1-9. Patient Self-Assessment: Example of 

Patient Diary................................................................37

REFERENCES..................................................................38

COMPONENT 2:

CONTROL OF FACTORS CONTRIBUTING 

TO ASTHMA SEVERITY ....................................................41

Key Points ........................................................................41

Differences From 1991 Expert Panel Report .....................41

INHALANT ALLERGENS ..............................................42

Diagnosis—Determine Relevant Inhalant Sensitivity ...42

Management—Reduce Exposure..................................43

Immunotherapy ...........................................................47

Assessment of Devices That May Modify Indoor Air ....48

OCCUPATIONAL EXPOSURES.....................................48

IRRITANTS .....................................................................49

Environmental Tobacco Smoke.....................................49

Indoor/Outdoor Air Pollution and Irritants ..................49

OTHER FACTORS THAT CAN INFLUENCE 

ASTHMA SEVERITY ......................................................50

Rhinitis/Sinusitis...........................................................50

Gastroesophageal Reflux ..............................................50

Aspirin Sensitivity ........................................................50

Sulfite Sensitivity..........................................................51

Beta-Blockers ...............................................................51

Infections .....................................................................51

PREVENTING THE ONSET OF ASTHMA...................51

Box 1. The Strong Association Between Sensitization to 

Allergens and Asthma: A Summary of the Evidence ....42

Box 2. Rationale for Allergy Testing for Perennial 

Indoor Allergens...........................................................45

Figure 2-1. Assessment Questions for Environmental 

and Other Factors That Can Make Asthma Worse ......44

Figure 2-2. Comparison of Skin Tests With 

In Vitro Tests................................................................45

Figure 2-3. Patient Interview Questions for Assessing the 

Clinical Significance of Positive Allergy Tests................46

Figure 2-4. Summary of Control Measures for 

Environmental Factors That Can Make 

Asthma Worse..............................................................47

Figure 2-5. Evaluation and Management of WorkAggravated Asthma and Occupational Asthma............49

REFERENCES..................................................................51

COMPONENT 3:

PHARMACOLOGIC THERAPY............................................57

Key Points ........................................................................57

Differences From 1991 Expert Panel Report .....................58

PHARMACOLOGIC THERAPY: 

THE MEDICATIONS...............................................59

Contents

Archive

for historical Reference Only
Contents

v

OVERVIEW OF THE MEDICATIONS ..........................59

Long-Term-Control Medications...................................59

Corticosteroids...........................................................60

Cromolyn Sodium and Nedocromil ...........................60

Long-Acting Beta2-Agonists (Beta-Adrenergic 

Agonists) ................................................................60

Methylxanthines........................................................65

Leukotriene Modifiers................................................65

Quick-Relief Medications..............................................66

Short-Acting Beta2-Agonists .....................................66

Anticholinergics.........................................................66

Systemic Corticosteroids ............................................66

Medications To Reduce Oral Systemic 

Corticosteroid Dependence ........................................66

Troleandomycin, Cyclosporine, Methotrexate, 

Gold, Intravenous Immunoglobulin, Dapsone, 

and Hydroxychloroquine ........................................66

Complementary Alternative Medicine ..........................66

ROUTE OF ADMINISTRATION ...................................67

SPECIAL ISSUES REGARDING SAFETY ......................67

Short-Acting Inhaled Beta2-Agonists ...........................67

Long-Acting Inhaled Beta2-Agonists............................70

Inhaled Corticosteroids.................................................70

Local Adverse Effects.................................................71

Systemic Adverse Effects............................................71

Figure 3-1. Long-Term-Control Medications....................61

Figure 3-2. Quick-Relief Medications ..............................64

Figure 3-3. Aerosol Delivery Devices...............................68

REFERENCES..................................................................73

PHARMACOLOGIC THERAPY:

MANAGING ASTHMA LONG TERM ....................81

STEPWISE APPROACH FOR MANAGING 

ASTHMA IN ADULTS AND CHILDREN OLDER 

THAN 5 YEARS OF AGE...............................................81

Gaining Control of Asthma..........................................82

Maintaining Control of Asthma....................................82

Pharmacologic Steps.....................................................87

Intermittent Asthma .................................................92

Persistent Asthma......................................................93

SPECIAL CONSIDERATIONS FOR MANAGING 

ASTHMA IN DIFFERENT AGE GROUPS ....................94

Infants and Young Children (5 Years of Age 

and Younger).............................................................94

Diagnosis...................................................................94

Treatment..................................................................95

School-Age Children (Older Than 5 Years of Age) and 

Adolescents................................................................97

Assessment ................................................................97

Treatment..................................................................97

School Issues..............................................................98

Sports ........................................................................98

Older Adults ................................................................98

MANAGING SPECIAL SITUATIONS IN 

ASTHMA.........................................................................99

Seasonal Asthma ..........................................................99

Cough Variant Asthma.................................................99

Exercise-Induced Bronchospasm.................................100

Diagnosis.................................................................100

Management Strategies ...........................................100

Surgery and Asthma...................................................100

Pregnancy and Asthma ..............................................101

Stress and Asthma......................................................101

Figure 3-4a. Stepwise Approach for Managing 

Asthma in Adults and Children Older Than 

5 Years of Age ..............................................................83

Figure 3-4b. Stepwise Approach for Managing 

Asthma in Adults and Children Older Than 

5 Years of Age: Treatment...........................................84

Figure 3-5a. Usual Dosages for Long-Term-Control

Medications..................................................................86

Figure 3-5b. Estimated Comparative Daily Dosages 

for Inhaled Corticosteroids............................................88

Figure 3-5c. Estimated Clinical Comparability of 

Doses for Inhaled Corticosteroids .................................89

Figure 3-5d. Usual Dosages for Quick-Relief

Medications..................................................................91

Figure 3-6. Stepwise Approach for Managing 

Infants and Young Children (5 Years of Age and

Younger) With Acute or Chronic Asthma Symptoms ..96

REFERENCES................................................................101

Archive

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vi

PHARMACOLOGIC THERAPY:

MANAGING EXACERBATIONS OF ASTHMA ...105

GENERAL CONSIDERATIONS ...................................105

TREATMENT GOALS ..................................................106

HOME MANAGEMENT OF ASTHMA

EXACERBATIONS........................................................107

PREHOSPITAL EMERGENCY MEDICINE/

AMBULANCE MANAGEMENT OF ASTHMA 

EXACERBATIONS........................................................110

EMERGENCY DEPARTMENT AND HOSPITAL 

MANAGEMENT OF ASTHMA EXACERBATIONS ...110

Assessment.................................................................110

Treatment...................................................................114

Repeat Assessment .....................................................116

Hospitalization...........................................................116

Impending Respiratory Failure ...................................116

Patient Discharge .......................................................117

From the Emergency Department ...........................117

From the Hospital ...................................................119

Figure 3-7a. Risk Factors for Death From Asthma.........106

Figure 3-7b. Special Considerations for Infants..............106

Figure 3-8. Management of Asthma Exacerbations: 

Home Treatment........................................................108

Figure 3-9. Classifying Severity of Asthma

Exacerbations........................................................109

Figure 3-10. Dosages of Drugs for Asthma 

Exacerbations in Emergency Medical Care

or Hospital.................................................................111

Figure 3-11. Management of Asthma Exacerbations: 

Emergency Department and Hospital-Based Care......112

Figure 3-12. Hospital Discharge Checklist for Patients 

With Asthma Exacerbations.......................................118

REFERENCES................................................................119

COMPONENT 4:

EDUCATION FOR A PARTNERSHIP IN 

ASTHMA CARE.............................................................123

Key Points ......................................................................123

Differences From 1991 Expert Panel Report ...................123

ESTABLISH A PARTNERSHIP .....................................124

Teach Asthma Self-Management ................................125

Jointly Develop Treatment Goals ...............................129

Provide the Patient With Tools for Self-Management .129

Encourage Adherence.................................................132

Tailor Education to the Needs of the Individual 

Patient.....................................................................133

MAINTAIN THE PARTNERSHIP................................133

SUPPLEMENT PATIENT EDUCATION 

DELIVERED BY CLINICIANS .....................................134

PROVIDE PATIENT EDUCATION IN 

OTHER CLINICAL SETTINGS ....................................134

Box 1. Patient Education for Non-CFC Inhalers ............125

Figure 4-1. Key Educational Messages for Patients........124

Figure 4-2. Delivery of Asthma Education by 

Clinicians During Patient Care Visits..........................126

Figure 4-3. Steps for Using Your Inhaler

(Patient Handout) ......................................................128

Figure 4-4. Asthma Daily Self-Management Plan

(Patient Handout) ......................................................130

Figure 4-5. Asthma Action Plan

(Patient Handout) ......................................................138

Figure 4-6. Promoting Open Communication 

To Encourage Patient Adherence ................................132

Figure 4-7. School Self-Management Plan

(Patient Handout) ......................................................144

Figure 4-8. Sources of Patient Education 

Programs and Materials..............................................146

REFERENCES................................................................134

Contents

Archive

for historical Reference Only
vii

*Shirley Murphy, M.D., Chair

Professor and Chair

Department of Pediatrics

University of New Mexico 

School of Medicine

Albuquerque, New Mexico

Eugene R. Bleecker, M.D.

Professor of Medicine

School of Medicine

University of Maryland

Baltimore, Maryland

*Homer Boushey, M.D.

Chief, Asthma Clinical 

Research Center

and Division of Allergy and

Immunology

Professor of Medicine

Department of Medicine

University of California at 

San Francisco

San Francisco, California

*A. Sonia Buist, M.D.

Professor of Medicine and Physiology

Head, Pulmonary and 

Critical Care Division

Oregon Health Sciences University

Portland, Oregon

*William Busse, M.D.

Professor of Medicine

Medicine/Allergy and 

Immunology Department

University of Wisconsin

Madison, Wisconsin

Noreen M. Clark, Ph.D.

Professor and Dean

University of Michigan School 

of Public Health

Ann Arbor, Michigan

Howard Eigen, M.D.

Director

Section of Pulmonology and 

Intensive Care

Professor and Associate Chairman 

for Clinical Affairs

Department of Pediatrics

Riley Hospital for Children

Indianapolis, Indiana

Jean G. Ford, M.D.

Chief, Division of Pulmonary Medicine

Harlem Hospital Center

Assistant Professor of Medicine and

Public Health (Environmental Health

Sciences)

Columbia University

New York, New York

*Susan Janson, D.N.Sc., R.N.

Professor

Department of Community Health 

School of Nursing

University of California, San Francisco

San Francisco, California

*H. William Kelly, Pharm.D.

Professor of Pharmacy and Pediatrics

College of Pharmacy

University of New Mexico

Albuquerque, New Mexico

Robert F. Lemanske, Jr., M.D.

Professor of Medicine and Pediatrics

University of Wisconsin 

Hospital and Clinics

Madison, Wisconsin

Carolyn C. Lopez, M.D.

Chief, Department of Family Practice

Cook County Hospital

Associate Professor, Department 

of Family Medicine

Rush Medical College

Chicago, Illinois

Fernando Martinez, M.D.

Associate Professor of Pediatrics

Director, Respiratory Sciences Center

University of Arizona Medical Center

Tucson, Arizona

*Harold S. Nelson, M.D.

Senior Staff Physician

Department of Medicine

National Jewish Medical and 

Research Center

Denver, Colorado

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

Vice Chairman

Department of Emergency Medicine

Henry Ford Hospital

Detroit, Michigan

* Executive Committee Member

SECOND EXPERT PANEL ON THE MANAGEMENT OF ASTHMA

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

Director

UVA Asthma and Allergy Disease

Center

Head, Division of Allergic and 

Clinical Immunology

University of Virginia School 

of Medicine

Charlottesville, Virginia

Gail G. Shapiro, M.D.

Clinical Professor of Pediatrics

University of Washington 

School of Medicine

Seattle, Washington

Stuart Stoloff, M.D.

Private Family Practice

Clinical Associate Professor of Family

and Community Medicine

University of Nevada

School of Medicine

Reno, Nevada

Kevin Weiss, M.D., M.P.H.

Director

Center for Health Services Research

Rush Primary Care Institute

Chicago, Illinois

FEDERAL LIAISON

REPRESENTATIVES

Clive Brown, M.B.B.S., M.P.H.

Epidemiologist

Air Pollution and Respiratory 

Health Branch

Centers for Disease Control 

and Prevention

Atlanta, Georgia

Peter J. Gergen, M.D.

(formerly with the National Institute 

of Allergy and Infectious Diseases)

Medical Officer

Center for Primary Care Research

Agency for Health Care 

Policy and Research 

Bethesda, Maryland

Edward L. Petsonk, M.D.

Clinical Section Chief

Clinical Investigations Branch

Division of Respiratory Disease Studies

National Institute for Occupational

Safety and Health

Morgantown, West Virginia

Archive

for historical Reference Only
viii

ACKNOWLEDGMENTS

The Expert Panel acknowledges the following 

consultants for their review of an early draft of the

report: David Evans, Ph.D.; James Fish, M.D.; 

Mark Liu, M.D.; Guillermo Mendoza, M.D.; 

Gary Rachelefsky, M.D.; Albert Sheffer, M.D.; 

Stanley Szefler, M.D.; and Pamela Wood, M.D.

NATIONAL HEART, LUNG, AND BLOOD

INSTITUTE STAFF

Ted Buxton, M.P.H.

Special Expert

National Asthma Education and Prevention Program

Robinson Fulwood, M.S.P.H.

Coordinator

National Asthma Education and Prevention Program

Michele Hindi-Alexander, Ph.D.

Health Scientist Administrator

Division of Lung Diseases

Suzanne S. Hurd, Ph.D.

Director 

Division of Lung Diseases

Virginia S. Taggart, M.P.H.

Health Scientist Administrator

Division of Lung Diseases

R.O.W. SCIENCES, INC., SUPPORT STAFF

Ruth Clark

Cathy Hageman

Lisa Marcellino

Maria New

Donna Selig

Keith Stanger

Donna Tharpe

Sonia Van Putten

Eileen Zeller, M.P.H.

Archive

for historical Reference Only
ix

Claude Lenfant, M.D., Chair

National Heart, Lung, and Blood Institute

Lynn A. Bosco, M.D., M.P.H.

Agency for Health Care Policy and Research

Nancy J. Sander

Allergy and Asthma Network/Mothers of

Asthmatics, Inc.

Albert L. Sheffer, M.D.

American Academy of Allergy, Asthma, and

Immunology

Gary S. Rachelefsky, M.D.

American Academy of Pediatrics

Barbara Senske Heier, PA-C

American Academy of Physician Assistants

Thomas J. Kallstrom, R.R.T.

American Association for Respiratory Care

Eloise Branche, R.N., C.O.H.N.-S.

American Association of Occupational

Health Nurses

Allan T. Luskin, M.D.

American College of Allergy, Asthma, and

Immunology

Robert A. Barbee, M.D., F.C.C.P.

American College of Chest Physicians

Richard M. Nowak, M.D., M.B.A., F.A.C.E.P.

American College of Emergency Physicians

Noreen M. Clark, Ph.D.

American Lung Association

Paul V. Williams, M.D.

American Medical Association

Barbara M. Santamaria, R.N., M.P.H., C.F.N.P.

American Nurses Association, Inc.

Dennis M. Williams, Pharm.D.

American Pharmaceutical Association

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

American Public Health Association

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

American School Health Association

Leslie Hendeles, Pharm.D.

American Society of Health-System Pharmacists

A. Sonia Buist, M.D.

American Thoracic Society

Barbara L. Hager, M.P.H., C.H.E.S.

Association of State and Territorial Directors

of Health Promotion and Public Health Education

Mary E. Worstell, M.P.H.

Asthma and Allergy Foundation of America

Mary Vernon, M.D., M.P.H.

Centers for Disease Control and Prevention

Vivian Haines, R.N., M.A., S.N.P.

National Association of School Nurses

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

National Black Nurses Association, Inc.

Ruth A. Etzel, M.D., Ph.D.

National Center for Environmental Health

Kathryn Silbersiepe, M.D., M.S.

National Center for Health Statistics

Ruth I. Quartey, M.A., R.R.T.

NHLBI Ad Hoc Committee on Minority Populations

Gregory R. Wagner, M.D.

National Institute for Occupational Safety and Health

Lawrence J. Prograis, Jr., M.D.

National Institute of Allergy and Infectious Diseases

Sheila A. Newton, Ph.D.

National Institute of Environmental Health Sciences

Michael Lenoir, M.D.

National Medical Association

L. Kay Bartholomew, Ed.D., M.P.H.

Society for Public Health Education

Kimberly Green Goldsborough, M.S.

U.S. Environmental Protection Agency

John K. Jenkins, M.D.

U.S. Food and Drug Administration

Olivia Carter-Pokras, Ph.D.

U.S. Public Health Service

NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM

COORDINATING COMMITTEE Archive

for historical Reference Only
Albert L. Sheffer, M.D., Chair

Brigham and Women’s Hospital

Boston, Massachusetts

A. Sonia Buist, M.D.

Oregon Health Sciences University

Portland, Oregon

William Busse, M.D.

University of Wisconsin

Madison, Wisconsin

Noreen M. Clark, Ph.D.

University of Michigan 

Ann Arbor, Michigan

Romain Pauwels, M.D., Ph.D., Chair

University Hospital

Ghent, Belgium

Jean Bousquet, M.D., Ph.D.

Hopital Arnaud de Villeneuve

Montpellier, France

Timothy J. H. Clark, M.D.

National Heart and Lung Institute

London, England

Leonardo M. Fabbri, M.D.

University of Ferrara

Ferrara, Italy

Stephen T. Holgate, M.D., D.Sc.

Southampton General Hospital

Southampton, England

Martyn R. Partridge, M.D.

Whipps Cross Hospital

London, England

Søren Pedersen, M.D.

Kolding Hospital

Kolding, Denmark

Ann J. Woolcock, A.O., M.D., F.R.A.C.P.

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM

SCIENCE BASE COMMITTEE

x

Shirley Murphy, M.D.

University of New Mexico

Albuquerque, New Mexico

Harold S. Nelson, M.D.

National Jewish Medical and Research Center

Denver, Colorado

Kevin Weiss, M.D., M.P.H.

Rush Primary Care Institute

Chicago, Illinois

INTERNATIONAL SCIENCE BASE COMMITTEE

Archive

for historical Reference Only
xi

I

n 1991, under the auspices of the National Asthma

Education and Prevention Program (NAEPP), the

first Expert Panel on the Management of Asthma

published Expert Panel Report: Guidelines for the

Diagnosis and Management of Asthma. This landmark

report redefined commonly held beliefs about asthma

care, thus setting the stage for nationwide improvements in the clinical management of asthma and

stimulating a variety of novel research. An enormous

amount of work has been done since the release of the

report to deepen our understanding of the pathogenesis of asthma and increase our knowledge about

effective approaches to asthma diagnosis, monitoring,

pharmacologic and environmental management, and

patient education. Accordingly, the decision was

made to update and revise the 1991 report to identify

progress made over the last 6 years.

Expert Panel Report 2: Guidelines for the Diagnosis and

Management of Asthma (EPR-2) is the culmination of

more than 3 years of preparatory analysis, meetings,

and writing and review cycles involving many individuals, not the least of whom were the members of

the second Expert Panel. Under the able leadership

of Dr. Shirley Murphy, Panel chair, the second Expert

Panel diligently met its charge of producing an accurate, up-to-date source of information for clinicians on

asthma diagnosis and management. Panel members

conducted their work not only with skill and a depth

of clinical and academic knowledge, but also with a

commitment to quality and an impressive spirit of

collaboration. The National Heart, Lung, and Blood

Institute and the organizations that comprise the

NAEPP Coordinating Committee sincerely appreciate

the work of Dr. Murphy, the Expert Panel, and all

others who participated in the preparation of this

report.

The task before us is to explore innovative methods

to broadly disseminate and encourage implementation of these updated asthma care recommendations.

The first steps will be to adapt the EPR-2 into formats that meet the needs of various health professionals and then to disseminate these materials.

However, these national-level efforts will have an

impact on asthma care only if they occur in concert

with local activities to encourage use of EPR-2 materials. Ultimately, broad change in clinical practice

depends on the influence of local 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. 

We are optimistic that over the next several years, 

the joint efforts of the NAEPP, its Coordinating

Committee member organizations, and committed

professionals at the local level will result in extensive

implementation of the recommendations in the 

EPR-2. We ask for the assistance of every reader in

reaching our ultimate goal: improving asthma care

and the quality of life for every patient with asthma

and their families. 

Publications from the National Asthma Education

and Prevention Program can be ordered through 

the National Heart, Lung, and Blood Institute

Information Center, P.O. Box 30105, Bethesda,

MD 20824-0105. Publications are also

available through the Internet at

http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm.

Claude Lenfant, M.D., Director

National Heart, Lung, and Blood Institute

Chair, National Asthma Education and

Prevention Program Coordinating Committee

PREFACE Archive

for historical Reference Only
1

Asthma is a chronic inflammatory disease

of the airways. In the United States,

asthma affects 14 million to 15 million

persons. It is the most common chronic

disease of childhood, affecting an estimated 4.8 

million children (Adams and Marano 1995; Centers

for Disease Control and Prevention 1995). 

People with asthma collectively have more than 

100 million days of restricted activity and 470,000

hospitalizations annually. More than 5,000 people

die of asthma annually. Asthma hospitalization

rates have been highest among blacks and children,

while death rates for asthma were consistently highest

among blacks aged 15 to 24 years (Centers for

Disease Control and Prevention 1996). These rates

have increased or remained stable over the past

decade. This report describes the appropriate use of

the available therapies in the management of asthma.

To help health care professionals bridge the gap

between current knowledge and practice, the

National Heart, Lung, and Blood Institute’s

(NHLBI) National Asthma Education and

Prevention Program (NAEPP) has convened two

Expert Panels to prepare guidelines for the diagnosis and management of asthma. The NAEPP

Coordinating Committee, under the leadership of

Claude Lenfant, M.D., director of the NHLBI, convened the first Expert Panel in 1989. The charge

to this Panel was to develop a report that would

provide a general approach to diagnosing and managing asthma based on current science. The Expert

Panel Report: Guidelines for the Diagnosis and

Management of Asthma (NAEPP 1991) was published in 1991, and the recommendations for the

treatment of asthma were organized 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

■ Comprehensive pharmacologic therapy for longterm management designed to reverse and prevent

the airway inflammation characteristic of asthma as

well as pharmacologic therapy to manage asthma

exacerbations

■ Patient education that fosters a partnership among

the patient, his or her family, and clinicians

The principles addressed within these four components of asthma management served as the starting

point for the development of two additional reports

prepared by asthma experts from many countries in

cooperation with the NHLBI: the International

Consensus Report on Diagnosis and Management of

Asthma (NHLBI 1992) and the Global Initiative for

Asthma (NHLBI/WHO 1995). The Expert Panel

Report 2: Guidelines for the Diagnosis and Management

of Asthma (EPR-2) is the latest report from the

National Asthma Education and Prevention

Program and updates the 1991 Expert Panel

Report. The second Expert Panel critically

reviewed and built upon the reports listed above.

This report presents basic 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 with asthma will be

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

document of any Government agency.

INTRODUCTION Archive

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2

METHODS USED TO DEVELOP 

THIS REPORT

The NAEPP Coordinating Committee established

a Science Base Committee of U.S. asthma experts

who began work in early 1994 to monitor the scientific literature and advise the Coordinating

Committee when an update of the 1991 Expert

Panel Report: Guidelines for the Diagnosis and

Management of Asthma was needed. The Science

Base Committee, along with international members of the Global Initiative for Asthma, examined

all the relevant literature on asthma in human subjects published in English between 1991 and mid1995, obtained through a series of MEDLINE

database searches. More than 5,000 abstracts were

reviewed. In 1995, the Science Base Committee

recommended to the NAEPP Coordinating

Committee that sufficient new information had

been published since 1991 to convene a panel of

experts to update the first Expert Panel Report.

The second Expert Panel is a multidisciplinary

group of clinicians and scientists with expertise in

asthma management. The Panel includes health

professionals in the areas of general medicine, family practice, pediatrics, emergency medicine, allergy,

pulmonary medicine, nursing, pharmacy, and

health education. Among the Panel members are

individuals who served on either the Science Base

Committee or the 1991 Expert Panel. Other

members were chosen based on names submitted

by NAEPP Coordinating Committee member

organizations. Several Expert Panel members are

themselves members of the Coordinating

Committee. Representatives from several Federal

agencies also have participated.

The charge to the Panel was to prepare recommendations for use by clinicians working in diverse

health care settings that address the practical 

decisionmaking issues in the diagnosis and management of asthma. The Panel also was requested

to develop specific aids to facilitate implementation

of the recommendations. 

Panel members were asked to base their recommendations on their review of the scientific 

literature and to cite studies that support the recommendations. When a clear recommendation

could not be extracted from the studies (e.g., 

studies were not available, were conflicting, or

were equivocal), the Panel was asked to label the

recommendation as “based on the opinion of the

Expert Panel,” “recommended by the Expert

Panel,” or similar terminology. When a whole 

section was “based on the opinion of the Expert

Panel,” this was indicated at the beginning of the

section (e.g., see component 1-Initial Assessment

and Diagnosis).

This report was prepared in a systematic and iterative process. In addition to the Science Base

Committee review of the scientific literature, the

Panel conducted in-depth reviews of the literature

in selected areas it considered controversial. In

interpreting the literature, the Panel considered the

nature and quality of the study designs and analyses. Given the complexities of several issues, the

Panel chose not to use the strict evidence ranking

system used in the guidelines development procedures of the U.S. Preventive Services Task Force.

However, this procedure was applied in the area of

peak flow monitoring. The Panel submitted their

interpretation of the literature and related recommendations for multiple reviews by their fellow

Expert Panel members and outside reviewers. 

The development of EPR-2 was directed by an

Executive Committee; each member of the Executive

Committee headed a subcommittee assigned to prepare a specific chapter. Each member of the Panel

was assigned to one of the subcommittees. The subcommittees were responsible for reviewing the pertinent literature and drafting the recommendations

with the supporting evidence for the full Panel to

review. Once the subcommittee reports were prepared, the full Panel critically reviewed the evidence

and rationale for each recommendation, discussed

revisions, and reached final agreement on each recommendation. A vote was taken to confirm the consensus of the Panel. The final report was approved

by the NAEPP Coordinating Committee via mail.

Box 1 summarizes the draft, review, and consensusbuilding process. 

The development of this report was entirely funded

by the National Heart, Lung, and Blood Institute,

National Institutes of Health. Panel members and

reviewers participated as volunteers and were compensated only for travel expenses related to the two

Expert Panel meetings and the Executive

Committee meetings.

Introduction

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Introduction

3

The goal of the Expert Panel Report 2: Guidelines for

the Diagnosis and Management of Asthma is to serve

as a comprehensive guide to diagnosing and 

managing asthma. Implementation of EPR-2 

recommendations is likely to increase some costs of

asthma care by increasing the number of primary

care visits for asthma and the use of asthma medications, environmental control products and services, and equipment (e.g., spacer/holding chamber

devices). However, asthma diagnosis and management are expected to improve, which should

reduce the numbers of lost school and work days,

hospitalizations and emergency department visits,

and deaths due to asthma. A net reduction in total

health care costs should result. The NAEPP

encourages research to evaluate the impact of

implementing the recommendations in this report. 

OVERVIEW OF THE REPORT

Each section of EPR-2 begins with a list of 

“Key Points” and “Differences From 1991 Expert

Panel Report.” A brief overview of each section is

provided below.

Pathogenesis and Definition

In the 1991 Expert Panel Report, the role of

inflammation in the pathogenesis of asthma was

emphasized although the scientific evidence for the

involvement of inflammation in asthma was just

emerging. Now in 1997, although the role of

inflammation is still evolving as a concept, a much

firmer scientific basis exists to indicate that asthma

results from complex interactions among inflammatory cells, mediators, and the cells and tissues

resident in the airways.

Thus, asthma is now defined as a chronic inflammatory disorder of the airways in which many cells and

cellular elements play a role, in particular, mast 

cells, eosinophils, T lymphocytes, neutrophils, and 

epithelial cells. In susceptible individuals, this

inflammation causes recurrent episodes of wheezing,

breathlessness, chest tightness, and cough, particularly at night and 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.

COMPONENT 1:

Measures of Assessment and Monitoring 

Initial Assessment and Diagnosis of Asthma

Making the correct diagnosis of asthma is extremely important. Clinical judgment is required

because signs and symptoms vary widely from

patient to patient as well as within each patient

over time. To establish the diagnosis of asthma,

the clinician must determine that:

■ Episodic symptoms of airflow obstruction are 

present.

■ Airflow obstruction is at least partially reversible.

■ Alternative diagnoses are excluded.

This section differs from the 1991 Expert Panel

Report in several ways. Asthma severity classifications have been changed from mild, moderate, and

severe to mild intermittent, mild persistent, moderate persistent, and severe persistent to more

accurately reflect the clinical manifestations of

BOX 1. MAJOR EVENTS IN THE DEVELOPMENT OF EPR-2

First Expert Panel meeting June 1995

Executive Committee meeting November 1995

Executive Committee meeting (by phone) February 1996

Second Expert Panel meeting and review by outside experts May 1996

Review by NAEPP Coordinating Committee member organizations August 1996 

Executive Committee meeting October 1996

Mail Review, Expert Panel December 1996

Mail Review and Approval, NAEPP Coordinating Committee January 1997

Archive

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4

asthma. The Panel emphasizes that patients at any

level of severity can have mild, moderate, or severe

exacerbations. In addition, information on wheezing in infancy and vocal cord dysfunction has been

expanded in the differential diagnosis section in

component 1. Situations that may warrant referral

to an asthma specialist have been refined with

input from specialty and primary care physicians.

Periodic Assessment and Monitoring

To establish whether the goals of asthma therapy

have been achieved, ongoing monitoring and 

periodic assessment are needed. The goals of 

asthma therapy are to:

■ Prevent chronic and troublesome symptoms

■ Maintain (near) “normal” pulmonary function

■ Maintain normal activity levels (including exercise

and other physical activity)

■ Prevent recurrent exacerbations of asthma and

minimize the need for emergency department visits or hospitalizations

■ Provide optimal pharmacotherapy with minimal or

no adverse effects

■ Meet patients’ and families’ expectations of and

satisfaction with asthma care

Several types of monitoring are recommended:

signs and symptoms, pulmonary function, quality

of life/functional status, history of asthma exacerbations, pharmacotherapy, and patient-provider

communication and patient satisfaction.

The Panel recommends that patients, especially

those with moderate-to-severe persistent asthma or

a history of severe exacerbations, be given a written

action plan based on signs and symptoms and/or

peak expiratory flow. As in the 1991 report, daily

peak flow monitoring is recommended for patients

with moderate-to-severe persistent asthma. In

addition, the Panel states that any patient who

develops severe exacerbations may benefit from

peak flow monitoring. A complete review of the

literature on peak flow monitoring was conducted,

evidence tables were prepared, and the results of

this analysis are summarized in the report.

COMPONENT 2: 

Control of Factors Contributing 

to Asthma Severity

Exposure of sensitive patients to inhalant allergens

has been shown to increase airway inflammation,

airway hyperresponsiveness, asthma symptoms,

need for medication, and death due to asthma.

Substantially reducing exposures significantly

reduces these outcomes. Environmental tobacco

smoke is a major precipitant of asthma symptoms

in children, increases symptoms and the need for

medications, and reduces lung function in adults.

Increased air pollution levels of respirable particulates, ozone, SO2, and NO2 have been reported to

precipitate asthma symptoms and increase emergency department visits and hospitalizations for

asthma. Other factors that can contribute to 

asthma severity include rhinitis and sinusitis, 

gastroesophageal reflux, some medications, and

viral respiratory infections. EPR-2 discusses 

environmental control and other measures to

reduce the effects of these factors.

COMPONENT 3: 

Pharmacologic Therapy

EPR-2 offers an extensive discussion of the pharmacologic management of patients at all levels of

asthma severity. It is noted that asthma pharmacotherapy should be instituted in conjunction with

environmental control measures that reduce 

exposure to factors known to increase the patient’s

asthma symptoms. 

As in the 1991 report, a stepwise approach to

pharmacologic therapy is recommended, with the

type and amount of medication dictated by asthma

severity. EPR-2 continues to emphasize that persistent asthma requires daily long-term therapy in

addition to appropriate medications to manage

asthma exacerbations. To clarify this concept, the

EPR-2 now categorizes medications into two 

general classes: long-term-control medications to

achieve and maintain control of persistent asthma

and quick-relief medications to treat symptoms and

exacerbations. 

Observations into the basic mechanisms of asthma

have had a tremendous influence on therapy.

Because inflammation is considered an early and

persistent component of asthma, therapy for persistent asthma must be directed toward long-term

Introduction

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Introduction

5

suppression of the inflammation. Thus, EPR-2

continues to emphasize that the most effective

medications for long-term control are those shown

to have anti-inflammatory effects. For example,

early intervention with inhaled corticosteroids can

improve asthma control and normalize lung function, and preliminary studies suggest that it may

prevent irreversible airway injury. 

An important addition to EPR-2 is a discussion of

the management of asthma in infants and young

children that incorporates recent studies on wheezing in early childhood. Another addition is 

discussions of long-term-control medications that

have become available since 1991—long-acting

inhaled beta2-agonists, nedocromil, zafirlukast, 

and zileuton.

Recommendations for managing asthma exacerbations are similar to those in the 1991 Expert Panel

Report. However, the treatment recommendations

are now on a much firmer scientific basis because

of the number of studies addressing the treatment

of asthma exacerbations in children and adults in

the past 6 years. 

COMPONENT 4: 

Education for a Partnership in Asthma Care

As in the 1991 Expert Panel Report, education for

an active partnership with patients remains the

cornerstone of asthma management and should be

carried out by health care providers delivering

asthma care. Education should start at the time of

asthma diagnosis and be integrated into every step

of clinical asthma care. Asthma self-management

education should be tailored to the needs of each

patient, maintaining a sensitivity to cultural beliefs

and practices. New emphasis is placed on evaluating outcomes in terms of patient perceptions of

improvement, especially quality of life and the ability to engage in usual activities. Health care

providers need to systematically teach and frequently review with patients how to manage and

control their asthma. Patients also should be 

provided with and taught to use a written daily

self-management plan and an action plan for exacerbations. It is especially important to give a 

written action plan to patients with moderate-tosevere persistent asthma or a history of severe 

exacerbations. Appropriate patients should also

receive a daily asthma diary. Adherence should be

encouraged by promoting open communication;

individualizing, reviewing, and adjusting plans as

needed; emphasizing goals and outcomes; and

encouraging family involvement. 

In summary, the 1997 Expert Panel Report 2:

Guidelines for the Diagnosis and Management of

Asthma reflects the experience of the past 6 years 

as well as the increasing scientific base of published

articles on asthma. The Expert Panel hopes this

new report will assist the clinician in forming a

valuable partnership with patients to achieve 

excellent asthma control and outcomes.

REFERENCES

Adams PF, Marano MA. Current estimates from the National

Health Interview Survey, 1994. Vital Health Stat

1995;10:94.

Centers for Disease Control and Prevention. Asthma mortality

and hospitalization among children and young adults—

United States, 1990-1993. MMWR 1996;45:350-353.

Centers for Disease Control and Prevention. Asthma-United

States, 1989-1992. MMWR 1995;43:952-5.

National Asthma Education and Prevention Program. Expert Panel

Report: Guidelines for the Diagnosis and Management of Asthma.

National Institutes of Health pub no 91-3642. Bethesda,

MD, 1991.

National Heart, Lung, and Blood Institute. International Consensus

Report on Diagnosis and Management of Asthma. National

Institutes of Health pub no 92-3091. Bethesda, MD, 1992.

National Heart, Lung, and Blood Institute and World Health

Organization. Global Initiative for Asthma. National Institutes

of Health pub no 95-3659. Bethesda, MD, 1995.

U.S. Preventive Services Task Force. Guide to Clinical Preventive

Health Services. Baltimore: Williams and Wilkins, 1989.

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7

KEY POINTS

■ Asthma, whatever the severity, is a chronic inflammatory disorder of the airways. This has implications for the

diagnosis, management, and potential prevention of the disease.

■ The immunohistopathologic features of asthma include:

— Denudation of airway epithelium

— Collagen deposition beneath basement membrane

— Edema

— Mast cell activation

— Inflammatory cell infiltration

– Neutrophils (especially in sudden-onset, fatal asthma exacerbations)

– Eosinophils

– Lymphocytes (TH2-like cells)

■ Airway inflammation contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, 

and disease chronicity.

■ Airway inflammation also contributes to several forms of airflow limitation, including acute bronchoconstriction,

airway edema, mucus plug formation, and airway wall remodeling. These features lead to bronchial obstruction.

■ Atopy, the genetic predisposition for the development of an IgE-mediated response to common aeroallergens, 

is the strongest identifiable predisposing factor for developing asthma.

DIFFERENCES FROM 1991 EXPERT PANEL REPORT 

■ The critical role of inflammation in asthma has been further substantiated by research. It is recognized that 

asthma results from complex interactions among inflammatory cells, mediators, and other cells and tissues 

resident in the airway.

■ Evidence indicates that subbasement membrane fibrosis may occur in some patients and that these changes 

contribute to persistent abnormalities in lung function. The importance of airway remodeling and the 

development of persistent airflow limitation need further exploration and may have significant implications 

for the treatment of asthma.

PATHOGENESIS AND DEFINITION Archive

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8

The clinician, physiologist, immunologist, and pathologist all may have different perspectives on asthma

based on their individual viewpoints and experience.

The merging of these different perspectives into an

acceptable definition of asthma has begun to occur

and is important for more specific and effective treatment of this disease and for investigation into its

pathogenesis. Furthermore, even though this disorder

affects virtually the entire spectrum of life, asthma

has certain age-specific characteristics and differential

diagnosis issues that need to be considered in both its

treatment and its etiology.

Based on current knowledge, a working definition

of asthma is: 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 (NHLBI 1995). Moreover, recent evidence

indicates that subbasement membrane fibrosis may

occur in some patients with asthma and that these

changes contribute to persistent abnormalities in

lung function (Roche 1991).

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

from studying how airway changes in asthma relate

to various factors associated with the development

of allergic inflammation (e.g., allergens, respiratory

viruses, and some occupational exposures, as illustrated in figure 1). From this approach has come

a more comprehensive understanding of asthma

pathogenesis, the development of persistent airway

inflammation, and the profound implications these

issues have for the diagnosis, treatment, and potential prevention of asthma.

AIRWAY PATHOLOGY AND ASTHMA

Until recently, information on airway pathology in

asthma has come largely from post-mortem examination (Dunnill 1960), which shows that both

large and small airways often contain plugs composed of mucus, serum proteins, inflammatory cells,

and cellular debris. Viewed microscopically, airways

are infiltrated with eosinophils and mononuclear

cells, and there is vasodilation and evidence of

microvascular leakage and epithelial disruption. The

airway smooth muscle is often hypertrophied, which

is characterized by new vessel formation, increased

numbers of epithelial goblet cells, and deposition of

interstitial collagens beneath the epithelium. These

features of airway wall remodeling further underscore the importance of chronic, recurrent inflammation in asthma and its effects on the airway.

Moreover, these morphologic changes may not be

completely reversible. Consequently, research is currently focused on determining whether these

changes can be prevented or modified by early diagnosis, avoidance of factors that contribute to asthma

severity, and pharmacologic therapy directed at suppressing airway inflammation.

Establishing the relationship between the pathologic changes and the clinical features of asthma

has been difficult. Fiberoptic bronchoscopy with

lavage and biopsy provide new insight into mechanisms of airway disease and features that link

altered lung function to a specific type of mucosal

inflammation (Laitinen et al. 1985; Beasley et al.

1989; Jeffery et al. 1989). From such studies, evidence has emerged that mast cells, eosinophils,

epithelial cells, macrophages, and activated T cells

are key features of the inflammatory process of

asthma (Djukanovic et al. 1990), as illustrated in

figure 2. These cells can influence airway function

through secretion of preformed and newly synthePathogenesis and Definition

INFLAMMATION

Environmental risk factors (causes)

Airway

hyperresponsiveness

Airflow

limitation

Precipitants

Symptoms

FIGURE 1. MECHANISMS UNDERLYING

THE DEFINITION OF ASTHMA

Adapted with permission from Stephen T. Holgate, M.D., D.Sc.

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Pathogenesis and Definition

9

sized mediators that act either directly on the airway or indirectly through neural mechanisms

(Emanuel and Howarth 1995). Furthermore, with

the use of cellular and molecular biological techniques, subpopulations of T lymphocytes (TH2)

have been identified as important cells that may

regulate allergic inflammation in the airway

through the release of selective cytokines and also

establish disease chronicity (Robinson et al. 1992).

In addition, constituent cells of the airway, including fibroblasts, endothelial cells, and epithelial

cells, also contribute to this process by releasing

cytokines and chemokines.

The above factors may be important in both initiating and maintaining the level of airway inflammation (Robinson et al. 1993). It is hypothesized that

airway inflammation can be acute, subacute, and

chronic. The acute inflammatory response is represented by the early recruitment of cells to the airway. In the subacute phase, recruited and resident

cells are activated to cause a more persistent pattern

of inflammation. Chronic inflammation is characterized by a persistent level of cell damage and an

ongoing repair process, changes that may cause 

permanent abnormalities in the airway. 

Finally, it is recognized that specific adhesion proteins, found in the vascular tissue, lung matrix, and

bronchial epithelium, may be critical in directing

and anchoring cells in the airway, thus causing the

inflammatory changes noted (Albelda 1991). From

these studies of the histological features associated

with asthma has come evidence of an association

between airway inflammation and markers of airway

disease severity and an indication that this process is

multicellular, redundant, and self-amplifying.

Cell-derived mediators can influence airway smooth

muscle tone, modulate vascular permeability, activate neurons, stimulate mucus secretion, and produce characteristic structural changes in the airway

(Horwitz and Busse 1995). These mediators can

target ciliated airway epithelium to cause injury or

disruption. As a consequence, epithelial cells and

myofibroblasts—present beneath the epithelium—

proliferate and begin to deposit interstitial collagens

in the lamina reticularis of the basement membrane.

This may explain apparent basement membrane

thickening and the irreversible airway changes that

may occur in some asthma patients (Roche 1991).

Other changes, including hypertrophy and hyperplasia of airway smooth muscle, increases in goblet cell

number, enlargement of submucous glands, and

remodeling of the airway connective tissue, are 

MAST CELL

EOSINOPHIL

Acute

BRONCHOSPASM

Subacute

INFLAMMATION

Chronic

Cytokines

Proinflammatory

ANTIGEN

Figure 2.

Cellular Mechanisms Involved in Airway Inflammation

IL-4

IgE

IL-5

IL-5

IL-8

B CELL

Proinflammatory

Cytokines

MACROPHAGES

MACROPHAGES

T CELL

NEUTROPHILS

Tryptase

Activated

Histamine

Leukotrienes

Chemokines

LTB-4

Cytokines, IL-4

FIGURE 2. CELLULAR MECHANISMS INVOLVED IN AIRWAY INFLAMMATION Archive

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10

components of asthma that need to be recognized 

in both its pathogenesis and treatment. This

inflammatory process is redundant in its ability to

alter airway physiology and architecture.

Child-Onset Asthma

Asthma often begins in childhood, and when it

does, it is frequently found in association with

atopy, which is the genetic susceptibility to produce IgE directed toward common environmental

allergens, including house-dust mites, animal 

proteins, and fungi (Larsen 1992). With the production of IgE antibodies, mast cells and possibly

other airway cells (e.g., lymphocytes) are sensitized

and become activated when they encounter specific

antigens. Although atopy has been found in 30 to

50 percent of the general population, it is frequently found in the absence of asthma. Nevertheless,

atopy is one of the strongest predisposing factors in

the development of asthma (Sporik et al. 1990).

Furthermore, among infants and young children

who have wheezing with viral infections, allergy or

family history of allergy is the factor that is most

strongly associated with continuing asthma

through childhood (Martinez et al. 1995).

Adult-Onset Asthma

Although asthma begins most frequently in childhood and adolescence, it can develop at anytime in

life. Adult-onset asthma can occur in a variety of

situations. In adult-onset asthma, allergens may

continue to play an important role. However, in

some adults who develop asthma, IgE antibodies to

allergens or a family history of asthma are not

detected. These individuals often have coexisting

sinusitis, nasal polyps, and sensitivity to aspirin or

related nonsteroidal anti-inflammatory drugs. The

mechanisms of nonallergic, or intrinsic, asthma are

less well established, although the inflammatory

process is similar (but not identical) to that seen in

atopic asthma (Walker et al. 1992).

Occupational exposure to workplace materials (animal products; biological enzymes; plastic resin;

wood dusts, particularly cedar; and metals) (see

component 2) can cause airway inflammation,

bronchial hyperresponsiveness, and clinical signs of

asthma (Chan-Yeung and Malo 1994; Fabbri et al.

1994). Identification of the causative agent and its

removal from the workplace can reduce symptoms;

however, some individuals will have persistent

asthma even though exposure to the causative

agent is eliminated. The mechanisms of this 

form of asthma are not clearly established.

RELATIONSHIP OF AIRWAY 

INFLAMMATION AND LUNG 

FUNCTION

Airway Hyperresponsiveness

An important feature of asthma is an exaggerated

bronchoconstrictor response to a wide variety of

stimuli. The propensity for airways to narrow 

too easily and too much is a major, but not 

necessarily unique, feature of asthma. Airway

hyperresponsiveness leads to clinical symptoms of

wheezing and dyspnea after exposure to allergens,

environmental irritants, viral infections, cold air, 

or exercise. Research indicates that airway 

hyperresponsiveness is important in the pathogenesis of asthma and that the level of airway responsiveness usually correlates with the clinical severity

of asthma.

Airway hyperresponsiveness can be measured by

inhalation challenge testing with methacholine or

histamine, as well as after exposure to such nonpharmacologic stimuli as hyperventilation with

cold dry air, inhalation of hypotonic or hypertonic

aerosols, or after exercise (O’Connor et al. 1989).

In addition, variability between morning and

evening peak expiratory flow (PEF) appears to

reflect airway hyperresponsiveness and may serve

as a measure of airway hyperresponsiveness, 

asthma instability, or asthma severity.

The factors contributing to airway inflammation in

asthma are multiple and involve a variety of different inflammatory cells (as illustrated in figure 2)

(Busse et al. 1993). It is also apparent that asthma

is not caused by either a single cell or a single inflammatory mediator but rather results from complex

interactions among inflammatory cells, mediators,

and other cells and tissues resident in airways. An

initial trigger in asthma may be the release of 

inflammatory mediators from bronchial mast cells,

macrophages, T lymphocytes, and epithelial cells.

These substances direct the migration and activation

of other inflammatory cells, such as eosinophils and

neutrophils, to the airway where they cause injury,

such as alterations in epithelial integrity, abnormalities

in autonomic neural control of airway tone, mucus

hypersecretion, change in mucociliary function, and

increased airway smooth muscle responsiveness.

Pathogenesis and Definition

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Pathogenesis and Definition

11

The importance of the airway inflammatory

response to airway hyperresponsiveness is substantiated by several observations. First, airway markers of inflammation correlate with bronchial hyperresponsiveness. Second, treatment of asthma and

modification of airway inflammatory markers not

only reduce symptoms but also diminish airway

responsiveness. However, the relationship between

airway inflammation and airway responsiveness is

complex. Some investigations have shown that

although anti-inflammatory therapy reduced airway hyperresponsiveness, it did not eradicate it. 

A small study found that control of airway inflammation did not control bronchial hyperresponsiveness (Lundgren et al. 1988). Thus, factors in 

addition to inflammation may contribute to 

airway hyperresponsiveness.

Airflow Obstruction

Airflow limitation in asthma is recurrent and

caused by a variety of changes in the airway. 

These include:

■ Acute bronchoconstriction. Allergen-induced

acute bronchoconstriction results from an IgEdependent release of mediators from the mast cell

that include histamine, tryptase, leukotrienes, and

prostaglandins (Marshall and Bienenstock 1994),

which directly contract airway smooth muscle.

Aspirin and other nonsteroidal anti-inflammatory

drugs (see component 2) 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

(Fischer et al. 1994). 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

(Busse et al. 1993). There is emerging evidence

that stress can play a role in precipitating asthma

exacerbations. The mechanisms involved have yet

to be established and may include enhanced generation of proinflammatory cytokines (Friedman et

al. 1994).

■ Airway edema. Airway wall edema, even without

smooth muscle contraction or bronchoconstriction,

limits airflow in asthma. Increased microvascular

permeability and leakage caused by released mediators also contribute to mucosal thickening and

swelling of the airway. As a consequence, swelling

of the airway wall causes the airway to become

more rigid and interferes with airflow.

■ Chronic mucus plug formation. In severe

intractable asthma, airflow limitation is often persistent. In part, this change may arise as a consequence of mucus secretion and the formation of

inspissated mucus plugs.

■ Airway remodeling. In some patients with 

asthma, airflow limitation may be only partially

reversible. The etiology of this component is not

as well studied as other features of asthma but may

relate to structural changes in the airway matrix

that may accompany longstanding and severe airway inflammation. There is evidence that a histological feature of asthma in some patients is an

alteration in the amount and composition of the

extracellular matrix in the airway wall (Djukanovic

et al. 1990; Laitinen and Laitinen 1994). As a

consequence of these changes, airway obstruction

may be persistent and not responsive to treatment.

Regulation of this 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. Although

yet to be fully explored, the importance of airway

remodeling and the development of persistent 

airflow limitation suggest a rationale for early 

intervention with anti-inflammatory therapy.

RELEVANCE OF CHRONIC 

AIRWAY INFLAMMATION TO 

ASTHMA THERAPY

Although inflammation can be used to describe a

variety of conditions in various diseases, the inflammatory response in asthma has special features that

include eosinophil infiltration, mast cell degranulation, interstitial airway wall injury, and lymphocyte

activation. Furthermore, there is evidence that a

TH2 lymphocyte cytokine profile (i.e., IL-4 and IL-5)

is instrumental in initiating and sustaining the

inflammatory process (James and Kay 1995; Ricci et

al. 1993) (see figure 2). These observations also have

become important in directing treatment in asthma.

It is hypothesized that inflammation is an early and

persistent component of asthma. As a consequence, therapy to suppress the inflammation must

be long term. Furthermore, preliminary evidence

suggests that early intervention with anti-inflamArchive

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12

matory therapy may modify the disease process

(Agertoft and Pedersen 1994; Laitinen et al. 1992;

Djukanovic et al. 1992).

Observations into the basic mechanisms of asthma

have had tremendous impact and influence on

therapy. Studies have shown that improvements in

asthma control achieved with high doses of inhaled

corticosteroids are associated with improvement in

markers of airway inflammation (Laitinen et al.

1992; Djukanovic et al. 1992). These observations

indicate that a strong link may exist between features of airway inflammation, bronchial hyperresponsiveness, and asthma symptoms and severity.

Furthermore, insight into the mechanisms of asthma

with airway inflammation and bronchial wall repair

has become a driving factor in designing logical, and

hopefully effective, treatment paradigms.

Another area that needs clarification is the classification of compounds as anti-inflammatory in

nature. Because many factors contribute to the

inflammatory response in asthma, many drugs may

fit this category. At present, corticosteroids are the

anti-inflammatory compounds that have been

demonstrated to modify histopathological features

of asthma (Barnes 1995). It may be necessary to

evaluate each new compound for the specificity of

its “anti-inflammatory” action and determine from

appropriate observations whether the compound is

indeed anti-inflammatory and what consequences

this has on the clinical features of the disease.

REFERENCES

Agertoft L, Pedersen S. Effects of long-term treatment with an

inhaled corticosteroid on growth and pulmonary function

in asthmatic children. Respir Med 1994;88:373-81.

Albelda SM. Endothelial and epithelial cell adhesion molecules. Am J Respir Cell Mol Biol 1991;4:195-203.

Barnes PJ. Inhaled glucocorticosteroid for asthma. N Engl J

Med 1995;332:868-75.

Beasley R, Roche WR, Roberts TA, Holgate ST. Cellular

events in the bronchi in mild asthma and bronchial provocation. Am Rev Respir Dis 1989;139:806-17.

Busse WW, Calhoun WJ, Sedgwick JD. Mechanisms of airway

inflammation in asthma. Am Rev Respir Dis 1993;147:S20-

S24.

Chan-Yeung M, Malo JL. Aetiological agents in occupational

asthma. Eur Respir J 1994;7:346-71.

Djukanovic R, Roche WR, Wilson JW, et al. Mucosal inflammation in asthma. Am Rev Respir Dis 1990;142:434-57.

Djukanovic R, Wilson TW, Britten KM, et al. Effect of an

inhaled corticosteroid on airway inflammation and symptoms of asthma. Am Rev Respir Dis 1992;145:669-74.

Dunnill MS. The pathology of asthma, with special reference

to changes in the bronchial mucosa. J Clin Pathol

1960;13:27-33.

Emanuel MB, Howarth PH. Asthma and anaphylaxis: a relevant

model for chronic disease? An historical analysis of directions

in asthma research. Clin Exp Allergy 1995;25:15-26.

Fabbri LM, Maestrelli P, Saetta M, Mapp CM. Mechanisms of

occupational asthma. Clin Exp Allergy 1994;24:628-35.

Fischer AR, Rosenberg MA, Lilly CM, et al. Direct evidence

for a role of the mast cell in the nasal response to aspirin in

aspirin-sensitive asthma. J Allergy Clin Immunol

1994;94:1046-56.

Friedman EM, Coe CL, Ershler WB. Bidirectional effects of

interleukin-1 on immune responses in rhesus monkeys.

Brain Behav Immunol 1994;8:87-99.

Horwitz RJ, Busse WW. Inflammation and asthma. Clin Chest

Med 1995;16:583-602.

James DG, Kay AB. Are you TH-1 or TH-2? [editorial] Clin

Exp Allergy 1995;25:389-90.

Jeffery PK, Wardlaw AJ, Nelson FC, Collins JV, Kay AB.

Bronchial biopsies in asthma. An ultrastructural, qualitative study and correlation with hyperreactivity. Am Rev

Respir Dis 1989;140:1745-53.

Laitinen A, Laitinen LA. Airway morphology: endothelium/

basement membrane. Am J Respir Crit Care Med

1994;150:S14-S17.

Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T.

Damage of the airway epithelium and bronchial reactivity

in patients with asthma. Am Rev Respir Dis 1985;131:599-

606.

Laitinen LA, Laitinen A, Haahtela T. A comparative study of the

effects of an inhaled corticosteroid, budesonide, and a 

β2-agonist, terbutaline, on airway inflammation in newly

diagnosed asthma: a randomized, double-blind, parallelgroup controlled trial. J Allergy Clin Immunol 1992;90:32-42.

Larsen GL. Asthma in children. N Engl J Med 1992;326:1540-5.

Lundgren R, Söderberg M, Horstedt P, et al. Morphological

studies of bronchial biopsies from asthmatics before and

after 10 years of treatment with inhaled steroids. Eur Respir

J 1988;1:883-9.

Marshall JS, Bienenstock J. The role of mast cells in inflammatory reactions of the airways, skin and intestine. Curr Opin

Immunol 1994;6:853-9.

Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen

M, Morgan WJ, Group Health Medical Associates. Asthma

and wheezing in the first six years of life. N Engl J Med

1995;332:133-8.

National Heart, Lung, and Blood Institute. Global Initiative for

Asthma. National Institutes of Health pub no 95-3659.

1995.

O’Connor GT, Sparrow D, Weiss ST. The role of allergy and

nonspecific airway hyperresponsiveness in the pathogenesis

of chronic obstructive pulmonary disease. Am Rev Respir Dis

1989;140:225-52.

Ricci M, Rossi O, Bertoni M, Matucci A. The importance of

TH2-like cells in the pathogenesis of airway allergic

inflammation. Clin Exp Allergy 1993;23:360-9.

Pathogenesis and Definition

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Pathogenesis and Definition

13

Robinson DS, Durham SR, Kay AB. Cytokines in asthma.

Thorax 1993;48:845-53.

Robinson DS, Hamid Q, Ying S, et al. Predominant TH2-like

broncheoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992;326:298-304.

Roche WR. Fibroblasts and asthma. Clin Exp Allergy

1991;21:545-8.

Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure

to house-dust mite allergen (Der pI) and the development

of asthma in childhood. A prospective study. N Engl J Med

1990;323:502-7.

Walker C, Bode E, Boer L, Hausel TT, Blaser K, Virchow JC

Jr. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in

peripheral blood and bronchoalveolar lavage. Am Rev Respir A

Dis 1992;146:109-15. rchive

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15

KEY POINTS

■ To establish a diagnosis of asthma, the clinician should determine that:

— Episodic symptoms of airflow obstruction are present.

— Airflow obstruction is at least partially reversible.

— Alternative diagnoses are excluded.

■ Recommended mechanisms to establish the diagnosis are:

— Detailed medical history

— Physical exam focusing on the upper respiratory tract, chest, and skin

— Spirometry to demonstrate reversibility

■ Additional studies may be considered to:

— Evaluate alternative diagnoses

— Identify precipitating factors

— Assess severity

— Investigate potential complications

■ Recommendations are presented for referral for consultation or care to a specialist in asthma care.

DIFFERENCES FROM 1991 EXPERT PANEL REPORT

■ Severity classifications were changed from mild, moderate, and severe to mild intermittent, mild persistent,

moderate persistent, and severe persistent.

■ Examples of questions to use for diagnosis and initial assessment of asthma were added.

■ Information on wheezing in infancy and vocal cord dysfunction was expanded in the differential diagnosis

section.

■ Criteria for referral were refined with input from specialty and primary care physicians.

■ More specific recommendations for measuring peak expiratory flow (PEF) diurnal variation are made.

COMPONENT 1: 

MEASURES OF ASSESSMENT AND MONITORING

Initial Assessment and Diagnosis of Asthma Archive

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16

The guidelines to help establish a diagnosis of asthma

presented in this component are based on the opinion

of the Expert Panel.

The clinician trying to establish a diagnosis of

asthma should determine that: 

■ Episodic symptoms of airflow obstruction are

present.

■ Airflow obstruction is at least partially

reversible.

■ Alternative diagnoses are excluded.

A careful medical history, physical examination, 

pulmonary function tests, and additional tests will

provide the information needed to ensure a correct

diagnosis of asthma (see box 1). Each of these 

methods of assessment is described in this section.

Clinical judgment is needed in conducting the assessment for asthma. Patients with asthma are heterogeneous and present signs and symptoms that vary

widely from patient to patient as well as within each

patient over time.

Component 1: Measures of Assessment and Monitoring

BOX 1. KEY INDICATORS FOR CONSIDERING A DIAGNOSIS OF ASTHMA

Consider asthma and performing spirometry if any of these indicators are 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

■ Reversible airflow limitation and diurnal variation as measured by using a peak flow meter, for example:

— Peak expiratory flow (PEF) varies 20 percent or more from PEF measurement on arising in the morning 

(before taking an inhaled short-acting beta2-agonist) to PEF measurement in the early afternoon

(after taking an inhaled short-acting beta2-agonist).

■ Symptoms occur or worsen in the presence of:

— Exercise

— Viral infection

— Animals with fur or feathers

— 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

— Menses

■ 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.

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17

MEDICAL HISTORY

A detailed medical history of the new patient

known or thought to have asthma should address

the items listed in figure 1-1. The medical history

can help:

■ Identify the symptoms likely to be due to asthma. 

See figure 1-2 for sample questions.

■ Support the likelihood of asthma (e.g., patterns of

symptoms, family history of asthma or allergies).

■ Assess the severity of asthma (e.g., symptom frequency

and severity, exercise tolerance, hospitalizations,

current medications). See figure 1-3 for a description of the levels of asthma severity.

■ Identify possible precipitating factors (e.g., viral respiratory infections; exposure at home, work, day care,

or school to inhalant allergens or irritants such as

tobacco smoke). See component 2, Control of

Factors Contributing to Asthma Severity, for 

more details.

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 include:

■ 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 during forced exhalation

is not a reliable indicator of airflow limitation. 

In mild intermittent asthma, or between 

exacerbations, wheezing may be absent.

■ Increased nasal secretion, mucosal swelling, and nasal

polyps. 

■ Atopic dermatitis/eczema or any other manifestation

of an allergic skin condition.

PULMONARY FUNCTION TESTING

(SPIROMETRY)

Spirometry measurements (FEV1, 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 (Bye et al. 1992; Li and

O’Connell 1996). This helps determine whether

there is airflow obstruction and whether it is

reversible over the short term (see box 2 for further

information). Spirometry is generally valuable in children over age 4; however, some children cannot conduct the maneuver adequately until after age 7.

Spirometry typically measures the maximal volume 

of air forcibly exhaled from the point of maximal

inhalation (forced vital capacity, FVC) and the volume

of air exhaled during the first second of the FVC

(forced expiratory volume in 1 second, FEV1).

Airflow obstruction is indicated by reduced FEV1 and

FEV1/FVC values relative to reference or predicted

values. Significant reversibility is indicated by an

increase of >_12 percent and 200 mL in FEV1 after

inhaling a short-acting bronchodilator (American

Thoracic Society 1991) (see figure 1-4 for example of

a spirometric curve for this test). A 2- to 3-week trial

of oral corticosteroid therapy may be required to

demonstrate reversibility. The spirometry measures

that establish reversibility may not indicate the

patient’s best lung function.

Abnormalities of lung function are categorized as

restrictive and obstructive defects. A reduced ratio of

FEV1/FVC (i.e., <65 percent) indicates obstruction to

the flow of air from the lungs, whereas a reduced

FVC with a normal FEV1/FVC 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 (American Thoracic 

Society 1991).

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 may

also be reduced, due to trapping of air in the lungs.

Initial Assessment and Diagnosis 

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Component 1: Measures of Assessment and Monitoring

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)

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)

Emotional expressions (e.g., fear, anger, frustration, hard 

crying or laughing)

Drugs (e.g., aspirin; beta-blockers, including eye drops; 

nonsteroidal anti-inflammatory drugs; others)

Food, food additives, and preservatives (e.g., sulfites)

Changes in weather, exposure to cold air

Endocrine factors (e.g., menses, pregnancy, thyroid 

disease)

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)

Progress of disease (better or worse)

Present management and response, including plans for 

managing exacerbations

Need for oral corticosteroids and frequency of use

Comorbid conditions

5. Family history

History of asthma, allergy, sinusitis, rhinitis, or nasal 

polyps in close relatives

6. Social history

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 day care)

Day care, 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 (if employed, characteristics of work 

environment)

7. Profile of typical exacerbation

Usual prodromal signs and symptoms 

Usual patterns and management (what works?)

8. Impact of asthma on patient and family

Episodes of unscheduled care (emergency department, 

urgent care, hospitalization)

Life-threatening exacerbations (e.g., intubation, intensive 

care unit admission)

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, parental, and spouse’s or partner’s knowledge of 

asthma and belief in the chronicity of asthma and in 

the efficacy of treatment

Patient 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

FIGURE 1-1. SUGGESTED ITEMS FOR MEDICAL HISTORY*

A detailed medical history of the new patient who is known or thought to have asthma should address the following items:

*This list does not represent a standardized assessment or diagnostic instrument. The validity and reliability of this list have not been assessed.

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19

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 American Thoracic Society

(1995). Correct technique, calibration methods, and

maintenance of equipment are necessary to achieve

consistently accurate test results. Maximal patient

effort 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 

(800-35NIOSH). When office spirometry shows

severe abnormalities, or if questions arise regarding test accuracy or interpretation, the Expert

Panel recommends further assessment in a 

specialized pulmonary function laboratory.

ADDITIONAL STUDIES

Even though additional studies are not routine, they

may be considered. No one test or set of tests is appropriate for every patient. However, the following procedures may be useful when considering alternative 

diagnoses, identifying precipitating factors, assessing

severity, and investigating potential complications:

■ Additional pulmonary function studies (e.g., lung 

volumes and inspiratory and expiratory flow volume loops) may be indicated, especially if there are

questions about coexisting chronic obstructive pulmonary disease, a restrictive defect, or possible 

central airway obstruction. A diffusing capacity test

is helpful in differentiating between asthma and

emphysema in patients at risk for both illnesses,

such as smokers and older patients.

■ Assessment of diurnal variation in peak expiratory flow

over 1 to 2 weeks is recommended when patients

have asthma symptoms but normal spirometry

(Enright et al. 1994). PEF is generally lowest on

Initial Assessment and Diagnosis 

FIGURE 1-2. SAMPLE QUESTIONS* 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), 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?

■ In the early morning?

■ 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.

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Component 1: Measures of Assessment and Monitoring

Clinical Features Before Treatment*

Symptoms** Nighttime Symptoms Lung Function

STEP 4 ■ Continual symptoms Frequent ■ FEV1 or PEF <_ 60% predicted

Severe ■ Limited physical activity ■ PEF variability >30%

Persistent ■ Frequent exacerbations

STEP 3 ■ Daily symptoms >1 time a week ■ FEV1 or PEF >60% –<80% predicted

Moderate ■ Daily use of inhaled short-acting ■ PEF variability >30%

Persistent beta2-agonist

■ Exacerbations affect activity

■ Exacerbations >_ 2 times a week; 

may last days

STEP 2 ■ Symptoms >2 times a week but >2 times a month ■ FEV1 or PEF >_ 80% predicted

Mild <1 time a day ■ PEF variability 20–30%

Persistent ■ Exacerbations may affect activity

STEP 1 ■ Symptoms <_ 2 times a week <_ 2 times a month ■ FEV1 or PEF >_ 80% predicted

Mild ■ Asymptomatic and normal PEF ■ PEF variability <20%

Intermittent between exacerbations

■ Exacerbations brief (from a few hours 

to a few days); intensity may vary

FIGURE 1-3. CLASSIFICATION OF ASTHMA SEVERITY

* The presence of one of the features of severity is sufficient to place a patient in that category. An individual should be assigned to the 

most severe grade in which any feature occurs. The characteristics noted in this figure are general and may overlap because asthma is 

highly variable. Furthermore, an individual’s classification may change over time.

** Patients at any level of severity can have mild, moderate, or severe exacerbations. Some patients with intermittent asthma experience 

severe and life-threatening exacerbations separated by long periods of normal lung function and no symptoms.

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

(Shim and Williams 1980) or to predict whether the

obstruction is reversible (Russell et al. 1986). 

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 best published peak expiratory flow 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 (see 

component 1-Periodic Assessment and Monitoring).

However, peak flow monitoring can establish peak

flow variability and thus aid in the determination of

asthma severity when patients have asthma symptoms

and normal spirometry (see Additional Studies section,

page 19).

BOX 2. IMPORTANCE OF SPIROMETRY IN ASTHMA DIAGNOSIS

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Initial Assessment and Diagnosis 

21

first awakening and highest several hours before the

midpoint of the waking day (e.g., between noon and

2 p.m.) (Quackenboss et al. 1991). Optimally, PEF

should be measured close to those two times, before

taking an inhaled short-acting beta2-agonist in the

morning and after taking one in the afternoon. A 20

percent difference between morning and afternoon

measurements suggests asthma. Measuring PEF on

waking and in the evening may be more practical

and feasible, but values will tend to underestimate

the actual diurnal variation. 

■ Bronchoprovocation with methacholine, histamine, 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 negative bronchoprovocation may be helpful to rule out asthma.

■ Chest x ray may be needed to exclude other diagnoses. 

■ Allergy testing (see component 2).

■ Evaluation of the nose for nasal polyps and sinuses for

sinus disease.

■ Evaluation for gastroesophageal reflux (Harding and

Richter 1992) (see component 2).

FIGURE 1-4a. SAMPLE SPIROMETRY VOLUME TIME AND FLOW VOLUME CURVES

FIGURE 1-4b. REPORT OF SPIROMETRY FINDINGS PRE AND POST BRONCHODILATOR

Pre Bronchodilator

Interpretations: Pre-shift

FEV1/FVC are below normal range. The reduced rate which air is

exhaled indicates obstruction to airflow.

1- Predicted values from Knudson et al., Am Rev Respir Dis 1983.

2- LLN is the Lower Limit of the Normal range (95th percentile).

Interpretations: Bronchodilator Response

Significant increases in FEV1, with bronchodilator (>_12% increase

after bronchodilator indicates a significant change).

Study: bronch ID: Test date: 8/7/96 Time: 9:38 am

Age: 59 Height: 175 cm Sex: M System: 7 20 17

Trial FVC FEV1 FEV1/FVC%

1 4.34 2.68 61.8%

2 4.40 2.59 58.9%

3 4.44 2.62 58.9%

4 4.56 2.69 58.9%

5 4.55 2.71 59.6%

Best Values 4.56 2.71 59.4%

Predicted Values-1 4.23 3.40 80.5%

LLN-2 3.10 2.62 69.9%

Percent Predicted 107.8% 79.7% 73.8%

Post Bronchodilator

Study: bronch ID: Test date: 8/7/96 Time: 11:42 am

Age: 59 Height: 175 cm Sex: M System: 7 20 17

Trial FVC FEV1 FEV1/FVC%

1 4.68 3.00 64.0%

2 4.73 2.94 62.2%

3 4.59 2.95 64.3%

4 4.76 3.07 64.5%

5 4.78 3.04 63.5%

Best values 4.78 3.07 64.3%

Reference Values 4.56 2.71

Difference (L) 0.22 0.36

Difference (%) 4.8% 13.4%

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22

The usefulness of measurements of biomarkers of

inflammation (e.g., total and differential cell count

and mediator assays) in sputum, blood, or urine as

aids to the diagnosis of asthma is currently being

evaluated in clinical research trials.

DIFFERENTIAL DIAGNOSIS 

OF ASTHMA

Recurrent episodes of cough and wheezing are almost always

due 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. However, the clinician needs to be aware

of other causes of airway obstruction leading to

wheezing (see figure 1-5).

There are two general patterns of wheezing in infancy:

nonallergic and allergic. Nonallergic infants wheeze

when they have an acute upper respiratory viral infection, but as their airways grow larger in the preschool

years the wheezing disappears. Allergic infants also

wheeze with viral infections, but they are more likely

to have asthma that will continue throughout childhood. This group may have eczema, allergic rhinitis,

or food allergy as other manifestations of allergy.

Both groups may benefit from asthma treatment 

(see Infants and Young Children section, page 94, 

in component 3-Managing Asthma Long Term).

Vocal cord dysfunction often mimics asthma. Patients

with vocal cord dysfunction can present with recurrent

severe shortness of breath and wheezing. Vocal cord

dysfunction may even cause alveolar hypoventilation,

with increases in PCO2 that prompt urgent intubation

and mechanical ventilation. Vocal cord dysfunction that

mimics asthma is more common in young adults with

psychological disorders. It should be suspected when

physical examination reveals a monophonic wheeze

heard loudest over the glottis. Further evaluation by

flow-volume curve revealing inspiratory flow limitation

strongly supports the diagnosis of vocal cord dysfunction. Definitive diagnosis—and exclusion of organic

causes of vocal cord narrowing—requires direct visualization of the vocal cords. Treatment with speech therapy that teaches techniques for relaxed throat breathing

is often effective (Newman et al. 1995; Bucca et al.

1995; Christopher et al. 1983).

Component 1: Measures of Assessment and Monitoring

FIGURE 1-5. 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

■ Chronic obstructive pulmonary disease 

(chronic bronchitis or emphysema)

■ Congestive heart failure

■ Pulmonary embolism

■ Laryngeal dysfunction

■ Mechanical obstruction of the airways 

(benign and malignant tumors)

■ Pulmonary infiltration with eosinophilia

■ Cough secondary to drugs (angiotensinconverting enzyme [ACE] inhibitors)

■ Vocal cord dysfunction

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Initial Assessment and Diagnosis 

23

GENERAL GUIDELINES FOR REFERRAL

TO AN ASTHMA SPECIALIST

Criteria for the referral of an asthma patient have been

developed (Spector and Nicklas 1995; Shuttari 1995).

Based on the opinion of the Expert Panel, referral

for consultation or care to a specialist in asthma

care (usually, a fellowship-trained allergist or pulmonologist; occasionally, other physicians with expertise

in asthma management developed through additional

training and experience) is recommended when:

■ Patient has had a life-threatening asthma 

exacerbation.

■ Patient is not meeting the goals of asthma therapy

(see component 1-Periodic Assessment and

Monitoring) after 3 to 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, vocal cord dysfunction, gastroesophageal

reflux, chronic obstructive pulmonary disease).

■ 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 has severe persistent asthma, requiring step

4 care (referral may be considered for patients

requiring step 3 care; see component 3-Managing

Asthma Long Term).

■ Patient requires continuous oral corticosteroid

therapy or high-dose inhaled corticosteroids or has

required more than two bursts of oral corticosteroids in 1 year. 

■ Patient is under age 3 and requires step 3 or 4 care

(see component 3-Managing Asthma Long Term).

When patient is under age 3 and requires step 2

care or initiation of daily long-term therapy, referral should be considered.

■ 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

comanage with the primary care provider.

In addition, patients with 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 characteristics have been shown to

interfere with a patient’s ability to adhere to treatment (Strunk 1987; Strunk et al. 1985)

REFERENCES

American Thoracic Society. Lung function testing: selection of reference values and interpretive strategies. Am Rev Respir Dis

1991;144:1202-18.

American Thoracic Society. Standardization of spirometry: 1994

update. Am J Respir Crit Care Med 1995;152:1107-36.

Bucca C, Rolla G, Brussino L, De Rose V, Bugiani M. Are asthma-like symptoms due to bronchial or extrathoracic airway

dysfunction? Lancet 1995;346:791-5.

Bye MR, Kerstein D, Barsh E. The importance of spirometry in

the assessment of childhood asthma. Am J Dis Child

1992;146:977-8.

Christopher KL, Wood RP 2nd, Eckert RC, Blager FB, Raney RA,

Souhrada JF. Vocal cord dysfunction presenting as asthma. N

Engl J Med 1983;308:1566-70.

Enright PL, Lebowitz MD, Cockroft DW. Physiologic measures:

pulmonary function tests. Asthma outcome. Am J Respir Crit

Care Med 1994;149:S9-18.

Harding SM, Richter JE. Gastroesophageal reflux disease and

asthma. Semin Gastrointest Dis 1992;3:139-50.

Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in

the normal maximal expiratory flow-volume curve with

growth and aging. Am Rev Respir Dis 1983;127:725-34.

Li JT, O’Connell EJ. Clinical evaluation of asthma. Ann Allergy

Asthma Immunol 1996;76:1-13.

Newman KB, Mason UG 3rd, Schmaling KB. Clinical features of

vocal cord dysfunction. Am J Respir Crit Care Med

1995;152:1382-6.

Archive

for historical Reference Only
24

Quackenboss JJ, Lebowitz MD, Krzyzanowski M. The normal

range of diurnal changes in peak expiratory flow rates.

Relationship to symptoms and respiratory disease. Am Rev

Respir Dis 1991;143:323-30.

Russell NJ, Crichton NJ, Emerson PA, Morgan AD. Quantitative

assessment of the value of spirometry. Thorax 1986;41:360-3.

Shim CS, Williams MH Jr. Evaluation of the severity of asthma:

patients versus physicians. Am J Med 1980;68:11-13.

Shuttari MF. Asthma: diagnosis and management. Am Fam

Physician 1995;52:2225-35.

Spector SL, Nicklas RA, eds. Practice parameters for the diagnosis

and treatment of asthma. J Allergy Clin Immunol

1995;96:729-31.

Strunk RC. Asthma deaths in childhood: identification of patients

at risk and intervention. J Allergy Clin Immunol

1987;80:472-7.

Strunk RC, Mrazek DA, Wolfson Fuhrmann GS, LaBrecque JF.

Physiologic and psychological characteristics associated with

deaths due to asthma in childhood. A case-controlled study.

JAMA 1985;254:1193-8.

Component 1: Measures of Assessment and Monitoring

Archive

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25

Periodic Assessment and Monitoring: 

Essential for Asthma Management

KEY POINTS

■ The goals of therapy are to:

— Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the night, in the early 

morning, or after exertion)

— Maintain (near) “normal” pulmonary function 

— Maintain normal activity levels (including exercise and other physical activity)

— Prevent recurrent exacerbations of asthma and minimize the need for emergency department visits or 

hospitalizations

— Provide optimal pharmacotherapy with least amount of adverse effects

— Meet patients’ and families’ expectations of and satisfaction with asthma care 

■ Periodic assessments and ongoing monitoring of asthma are recommended to determine if the goals of therapy are 

being met. Measurements of the following are recommended:

— Signs and symptoms of asthma

— Pulmonary function

— Quality of life/functional status

— History of asthma exacerbations

— Pharmacotherapy

— Patient-provider communication and patient satisfaction

■ Clinician assessment and patient self-assessment are the primary methods for monitoring asthma. Populationbased assessment is beginning to be used by managed care organizations.

■ Spirometry tests are recommended (1) at the time of initial assessment, (2) after treatment is initiated and symptoms and PEF have stabilized, and (3) at least every 1 to 2 years.

■ Patients should be given a written action plan based on signs and symptoms and/or PEF; this is especially important for patients with moderate-to-severe persistent asthma or a history of severe exacerbations.

■ Patients should be trained to recognize symptom patterns indicating inadequate asthma control and the need for

additional therapy.

■ Recommendations on how and when to do peak flow monitoring are presented.

DIFFERENCES FROM 1991 EXPERT PANEL REPORT

■ The new report includes an additional goal of therapy (meet patients’ and families’ expectations of and satisfaction

with asthma care) that was not listed in the 1991 report.

■ Periodic assessment of six domains of patient health that correspond with the goals of asthma therapy are now recommended, including signs and symptoms, pulmonary function, quality of life, history of exacerbations, pharmacotherapy, and patient-provider communication and patient satisfaction.

■ The following changes affecting peak flow monitoring have been made: 

— The recommendation for peak flow monitoring was changed from twice daily to morning. If the morning 

reading is less than 80 percent of personal best PEF, more frequent peak flow monitoring may be desired.

Archive

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26

GOALS OF THERAPY

The purpose of periodic assessment and ongoing

monitoring is to determine whether the goals of 

asthma therapy are being achieved. The goals of

therapy are as follows:

■ Prevent chronic and troublesome symptoms 

(e.g., coughing or breathlessness in the night, in

the early morning, or after exertion)

■ Maintain (near) “normal” pulmonary function 

■ Maintain normal activity levels (including exercise

and other physical activity)

■ Prevent recurrent exacerbations of asthma and

minimize the need for emergency department 

visits or hospitalizations

■ Provide optimal pharmacotherapy with minimal or

no adverse effects

■ Meet patients’ and families’ expectations of and

satisfaction with asthma care 

ASSESSMENT MEASURES

The Expert Panel recommends ongoing monitoring in the six areas listed below to determine

whether the goals of therapy are being met. The

assessment measures for monitoring these six areas are

described in this section and are recommended

based on the opinion of the Expert Panel.

■ Monitoring signs and symptoms of asthma

■ Monitoring pulmonary function

— Spirometry

— Peak flow monitoring

■ Monitoring quality of life/functional status

■ Monitoring history of asthma exacerbations

■ Monitoring pharmacotherapy

■ Monitoring patient-provider communication and

patient satisfaction 

Monitoring Signs and Symptoms of Asthma

Every patient with asthma should be taught to

recognize symptom patterns that indicate inadequate asthma control (see Patient Self-Assessment

section, page 38, and component 4). Symptom monitoring should be used as a means to determine the

need for intervention, including additional medication,

in the context of an action plan (see figure 4-5).

Symptoms and clinical signs of asthma should be

assessed at each health care visit through physical

examination and appropriate questions. This is

crucial to optimal asthma care. A description of the

important elements of an asthma-related physical

examination can be found in component 1-Initial

Assessment and Diagnosis, which also discusses the

variability in the types of symptoms associated with

asthma.

Detailed patient recall of symptoms decreases over

time; therefore, the Expert Panel recommends that

any detailed symptoms history be based on a

short (2 to 4 weeks) recall period. For example,

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 1-6 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.

In addition, any assessment of the patient’s 

symptom history should include at least three 

key symptom expressions:

■ Daytime asthma symptoms (including wheezing,

cough, chest tightness, or shortness of breath)

Component 1: Measures of Assessment and Monitoring

— Discussion of inconsistencies in measurement among peak flow meters was added.

— Use of the individual patient’s personal best PEF is emphasized strongly.

■ The recommendation for patients at all severity levels to monitor symptoms to recognize early signs of 

deterioration is emphasized.

■ Sample questions to use in periodic assessments were added. Archive

for historical Reference Only
Periodic Assessment and Monitoring

27

FIGURE 1-6. 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?”

(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 shortacting inhaled beta2-agonist?”

■ Had symptoms while exercising or playing?”

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 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 short-acting inhaled beta2-agonist 

(quick-relief medicine) do you use per day?”

“How many [name short-acting inhaled 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

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 

self-management plan? Your action plan?”

“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. 

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28

■ Nocturnal awakening as a result of asthma 

symptoms

■ Asthma symptoms early in the morning that are

not improved 15 minutes after inhaling a shortacting beta2-agonist

Monitoring Pulmonary Function

In addition to assessing symptoms, it is also important

to periodically assess pulmonary function. The main

methods are spirometry and peak flow monitoring.

Regular monitoring of pulmonary function is

particularly important for asthma patients who do not

perceive their symptoms until airflow obstruction is

severe. Currently, 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

(Kikuchi et al. 1994; Connolly et al. 1992).

Spirometry

The Expert Panel recommends that spirometry

tests be done (1) at the time of initial assessment;

(2) after treatment is initiated and symptoms and

peak expiratory flow (PEF) have stabilized, to

document attainment of (near) “normal” airway

function; and (3) at least every 1 to 2 years to

assess the maintenance of airway function.

Spirometry may be indicated more often than every 

1 to 2 years, depending on the clinical severity and

response to management. 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)

■ 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 or when neuromuscular or

orthopedic problems are present) and the physician

needs the quality checks that are available only with

spirometry (Hankinson and Wagner 1993).

For routine monitoring at most outpatient visits,

measurement of PEF with a peak flow meter is generally a sufficient assessment of pulmonary function,

particularly in mild intermittent, mild persistent, 

and moderate persistent asthma.

Peak Flow Monitoring

Peak expiratory flow provides a simple, quantitative,

and reproducible measure of the existence and severity of airflow obstruction. PEF can be measured with

inexpensive and portable peak flow meters. It must be

stressed that peak flow meters are designed 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 technique (see figure 1-7, the patient 

handout How To Use Your Peak Flow Meter).

Peak flow monitoring can be used for short-term monitoring, managing exacerbations, and daily long-term

monitoring. When used in these ways, the patient’s

measured personal best is the most appropriate reference value. Four studies (Woolcock et al. 1988;

Ignacio-Garcia and Gonzalez-Santos 1995; Lahdensuo

et al. 1996; Beasley et al. 1989) have found that comprehensive asthma self-management programs, in

which peak flow monitoring was a component,

achieved significant improvements in health outcomes.

Thus far, the few studies that have isolated a comparison of peak flow and symptom monitoring have not

been sufficient to assess the relative contributions of

each to asthma management (see box 1, Peak Flow

Monitoring Literature Review). The literature does

suggest which patients may benefit most from peak

flow monitoring. The Expert Panel concludes, on the

basis of this literature and the Panel’s opinion, that:

■ Patients with moderate-to-severe persistent

asthma should learn how to monitor their PEF

and have a peak flow meter at home.

■ Peak flow monitoring during exacerbations of

asthma is recommended for patients with

moderate-to-severe persistent asthma to:

— Determine severity of the exacerbation

— Guide therapeutic decisions (see 

component 3-Managing Exacerbations and 

figure 4-5) in the home, clinician’s office, 

or emergency department

Component 1: Measures of Assessment and Monitoring

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29

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- to 3-

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 between noon and 

2:00 p.m.

■ Before and after you take your short-acting

inhaled beta2-agonist for quick relief, if you take

this medicine.

■ As instructed by your doctor.

Figure 1-7

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30

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. You must

take a short-acting inhaled beta2-agonist right

away. Also, your asthma may not be under

good day-to-day control. Ask your doctor if you

need to change or increase your daily medicines.

Red Zone (below ___ L/min [50 percent of

your personal best number]) signals a medical

alert. You must take a short-acting inhaled

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 a short-acting inhaled beta2-

agonist (quick-relief medicine) as prescribed by 

your doctor.

■ PEF increases 20 percent or more when measured before and after taking a short-acting

inhaled 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: 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.

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31

Periodic Assessment and Monitoring

Seven intervention studies on the use of daily peak

flow monitoring for asthma management were identified, six through a MEDLINE search from 1980

to 1995 and reviews of reference lists and one from

the 1996 literature.

Three randomized controlled trials (Woolcock et al.

1988, N=24; Ignacio-Garcia and Gonzalez-Santos

1995, N=70; Lahdensuo et al. 1996, N=115) and

an uncontrolled pretest/posttest study (Beasley et al.

1989, N=36) tested comprehensive asthma interventions that included self-management medication

plans, medications, education, and peak flow monitoring. These studies reported significant improvements in lung function, symptoms, and medication

use after 6 months (Beasley et al. 1989; IgnacioGarcia and Gonzalez-Santos 1995) and 18 months

(Woolcock et al. 1988). However, these studies could

not determine the relative importance of peak flow

monitoring to the effectiveness of the comprehensive

asthma intervention.

Three randomized controlled trials compared the

use of daily peak flow monitoring with symptom

monitoring (Charlton et al. 1990, N=115 adults

and children) or usual care (Grampian Asthma

Study 1994, N=569 adults; Jones et al. 1995,

N=72 adults). These studies found no significant

differences between the experimental and control

groups in the outcomes measured: lung function,

symptom frequency, quality of life, hospitalizations,

medication use, and medical consultations. However,

one of these studies involved patients with mild asthma

(Jones et al. 1995), a population not expected to benefit

as much from peak flow monitoring.

Almost all the peak flow monitoring studies 

available had study design and execution problems

(e.g., selection bias, unequal control and experimental groups, small sample sizes, high loss to 

followup). More studies of daily long-term peak

flow monitoring among patients with moderate 

and severe persistent asthma are urgently needed.

Nonetheless, some issues suggested by the few 

studies available warrant consideration:

■ Among patients with mild intermittent or mild 

persistent asthma, there appears to be no significant

advantage of peak flow monitoring over usual care

without peak flow monitoring (Jones et al. 1995).

■ Patients with moderate-to-severe persistent asthma or unstable asthma are more likely to benefit

from long-term daily peak flow monitoring. For

example, the Grampian study authors conducted

an observational study of 89 patients disqualified

from the original study because their asthma was

too severe and found that those who used peak

flow meters took oral corticosteroids more often

(action plan told patients to take oral corticosteroids at specific PEF levels) and had significantly fewer days of limited activity than those

who did not use a peak flow meter.

■ Short-term daily peak flow monitoring is helpful

for assessing the severity of a patient’s asthma

and evaluating response to chronic maintenance

therapy.

■ Short-term peak flow monitoring is also helpful

during exacerbations for assessing the severity of

acute airflow obstruction and evaluating the

patient’s response to bronchodilator therapy.

Janson-Bjerklie and Shnell (1988) found that

patients used medications less frequently when

they monitored PEF during symptomatic periods.

■ Additional studies are needed to clarify the role

of long-term daily peak flow monitoring in

detecting early signs of deterioration, especially

for patients with moderate-to-severe persistent

asthma. Studies have found that 15 percent of

asthma patients (Rubinfeld and Pain 1976), 24

to 27 percent of elderly patients (Connolly et al.

1992), and patients who had near-fatal asthma

exacerbations (Kikuchi et al. 1994) could not

perceive significant reductions in FEV1 provoked

by methacholine challenge. A recent study in a

general community setting found that for 60

percent of patients, their PEF did not correlate

with the perception of how well their asthma

was controlled (i.e., patients felt their asthma

was better than the PEF readings indicated)

(Kendrick et al. 1993). However, symptom

monitoring and peak flow monitoring were

found to be equally effective in identifying

exacerbations that were confirmed by FEV1

measurements in a randomized controlled,

crossover study (Malo et al. 1993). Although

peak flow monitoring for children may be 

BOX 1. PEAK FLOW MONITORING LITERATURE REVIEW Archive

for historical Reference Only
■ Long-term daily peak flow monitoring is 

helpful in managing patients with moderateto-severe persistent asthma to:

— Detect early changes in disease status 

that require treatment

— Evaluate responses to changes in therapy

— Provide assessment of severity for 

patients with poor perception of airflow 

obstruction

— Afford a quantitative measure of 

impairment

■ If long-term daily peak flow monitoring is not

used, a short-term (2 to 3 weeks) period of

peak flow monitoring is recommended to:

— Evaluate responses to changes in chronic 

maintenance therapy

— Identify temporal relationship between 

changes in PEF and exposure to 

environmental or occupational irritants 

or allergens. It may be necessary to 

record PEF four or more times a day 

(Chan-Yeung 1995).

— Establish the individual patient’s personal

best PEF

■ The Expert Panel does not recommend long-term

daily peak flow monitoring for patients with mild

intermittent or mild persistent asthma unless the

patient/family and/or clinician find it useful in

guiding therapeutic decisions. Any patient who

develops severe exacerbations may benefit from

peak flow monitoring.

Limitations of long-term peak flow monitoring include:

■ Difficulty in maintaining adherence to monitoring

(Reeder et al. 1990; Chmelik and Doughty 1994;

Malo et al. 1993), often due to inconvenience, lack

of required level of motivation, or lack of a specific

treatment plan based on PEF

■ Potential for incorrect readings related to poor

technique, misinterpretation, or device failure

32

Component 1: Measures of Assessment and Monitoring

helpful, one study points out that the variability

of individual PEF measurements between different brands of peak flow meters and in comparison to spirometry warrants caution about teaching how to use peak flow meters and interpret

the measurements. Emphasis should be placed

on observing differences between readings over

time rather than on a single reading (Sly et al.

1994).

■ Patient preferences regarding peak flow monitoring vary. One study found that most patients

felt that peak flow monitoring was helpful (Jones

et al. 1995), another found that most patients

felt symptom monitoring was helpful (Garrett et

al. 1994), and another study found that most

patients felt that both forms of monitoring combined were helpful (D’Souza et al. 1994). In an

observational study of children attending a 

community clinic, 70 percent of the parents of

children using peak flow monitoring reported it

to be very useful, especially for judging the

severity of an exacerbation and the child’s

response to inhaled short-acting beta2-agonist

(Lloyd and Ali 1992).

■ Linking peak flow monitoring to specific asthma

management plans and providing appropriate

instruction and feedback to the patient will

influence the effectiveness and perceived 

usefulness of peak flow monitoring.

Due to the limited number and quality of the studies on peak flow monitoring reported thus far, the

Expert Panel believes that more research is urgently

needed in this area. Recent studies do offer some

guidance on which patients are most likely to 

benefit from daily peak flow monitoring; see text 

of the report for recommendations.

BOX 1. PEAK FLOW MONITORING LITERATURE REVIEW (CONTINUED) Archive

for historical Reference Only
33

Whether peak flow monitoring, symptom monitoring,

or a combination of approaches is used, the Expert

Panel believes that self-monitoring is important to the

effective self-management of asthma. The nature and

intensity of self-monitoring should be individualized,

based on such factors as asthma severity, patient’s ability

to perceive airflow obstruction, availability of peak flow

meters, and patient preferences.

It is the opinion of the Expert Panel that, regardless of the type of monitoring used, patients

should be given a written action plan and be

instructed to use it (see figure 4-5). The Panel

believes it is especially important to give a written

action plan to patients with moderate-to-severe persistent asthma and any patient with a history of

severe exacerbations. The action plan will describe

the actions patients should take based on their signs

and symptoms and/or PEF. The clinician should 

periodically review the plan, revise it as necessary, and

confirm that the patient knows what to do if his or

her asthma gets worse. 

Recommendations on How To Monitor 

Peak Flow. The Expert Panel recommends that

patients who are using a peak flow meter be

instructed on how to establish their personal best

peak expiratory flow (figure 1-7) and use it as the

basis of their action plan (figure 4-5). Meters

used to measure PEF should meet American

Thoracic Society recommendations for monitoring

devices (American Thoracic Society 1995).

The patient’s personal best PEF can be estimated

after a 2- to 3-week period in which the patient

records PEF two to four times per day. The personal

best value is usually achieved in the early afternoon

measurement after maximal therapy has stabilized the

patient (Quackenboss et al. 1991). A course of oral

corticosteroids may be needed to establish the personal best PEF. The patient’s personal best value should

be reassessed periodically to account for progression of

disease in children and adults and for growth in children. Occasionally, a PEF value is recorded that is

markedly higher than other values. This may be due

to “spitting” (especially if the peak flow meter mouthpiece is small) or coughing into the peak flow meter,

as well as other reasons that are not well understood.

Therefore, caution should be used in establishing a

personal best value when an outlying value is

observed. Children with moderate-to-severe

persistent asthma should repeat the short-term 

monitoring period every 6 months to establish

changes in personal best PEF that occur with growth.

Patients requiring daily peak flow monitoring

should measure their PEF on waking from sleep

in the morning before taking a bronchodilator, if

the patient uses a bronchodilator (Reddel et al. 1995;

Morris et al. 1994). When the morning PEF is below

80 percent of the patient’s personal best, PEF should

be measured more than once a day (again, before taking a bronchodilator). This recommendation is based

not on scientific data, but on the logic of reducing

delays in treatment. The additional measurements of

PEF during the day will enable patients to detect if

their asthma is continuing to worsen or is improving

after taking medication. If their asthma is worsening,

they will have the opportunity to quickly respond to

this. In addition, periodically having patients take

their PEF first thing in the morning and in the early

afternoon for 1 to 2 weeks will assess airflow variability, which is an indicator of the current level of the

patient’s asthma severity (see figure 1-3 and

Additional Studies section, page 19).

It is the Expert Panel’s opinion that, in general,

PEF below 80 percent of the patient’s personal

best before bronchodilator inhalation indicates a

need for additional medication. PEF below 50

percent indicates a severe asthma exacerbation

(see component 3 for recommended treatment).

These cutpoints of 80 and 50 percent of the personal

best are somewhat arbitrary. The emphasis is not on

a specific PEF value but, rather, on a patient’s change

from personal best or from one reading to the next.

Cutpoints should be tailored to individual patients’

needs and PEF patterns.

Cutpoints may be easier to use and remember when

they are adapted to a traffic light system (see figure

4-5) (Lewis et al. 1984; Mendoza et al. 1988; Plaut

1995). In this system, for example, the green zone

(80 to 100 percent of personal best) signals good 

control, the yellow zone (50 to less than 80 percent 

of personal best) signals caution, and the red zone

(below 50 percent of personal best) signals a medical

alert (see figure 1-7). Because the yellow zone

includes a wide spectrum of asthma severity, clinicians

may consider recommending different interventions

for a high yellow zone (e.g., 65 to less than 80 percent of personal best) and a low yellow zone (e.g., 50

to less than 65 percent of personal best).

Periodic Assessment and Monitoring 

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34

The Expert Panel recommends that patients use

the same peak flow meter over time and bring

their peak flow meter for use at every followup visit.

Using the same brand of meter is recommended

because different brands of meters can give significantly different values (Jackson 1995; Enright et al.

1995; Hegewald et al. 1995; Sly et al. 1994; Miller et

al. 1992) and because lung function varies across

racial and ethnic populations. (See box 2, Differences

in Peak Flow Across Racial and Ethnic Populations.)

Thus, there is no universal normative standard for PEF.

In addition, brand-specific normative values are not

available for most peak flow meters.

Despite this variability across different brands of peak

flow meters, measurements from the same meter and

meters of the same brand are fairly consistent in measuring PEF (Jackson 1995; Enright et al. 1995;

Hegewald et al. 1995; Sly et al. 1994; Miller et al.

1992). Thus, once patients establish their personal

best PEF on their own meter, they can obtain reliable

and clinically meaningful readings of their PEF.

However, at each visit, the patient’s peak flow meter

should be inspected. At least once a year, or any time

there is a question about the validity of peak flow

meter readings, PEF values from the portable peak

flow meter and from laboratory spirometry should 

be compared.

When patients replace their peak flow meter, it is prudent to have them reestablish their personal best PEF

with the new meter, regardless of whether the replacement meter is the same brand as the original. Action

plan cutpoints also may need to be modified. The durability and consistency over time of peak flow meters

have not been adequately studied to provide guidance

on when a peak flow meter needs to be replaced. 

Monitoring Quality of 

Life/Functional Status

To determine whether the goals of asthma therapy are

being met, it is crucial 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, including physical function,

role function, and mental health function. Several

comprehensive survey instruments, such as the SF-36

(Stewart et al. 1988 for adult measure; Landgraf et al.

1996 for child measure), have been developed for

general use for patient populations. In addition, a

number of asthma-specific quality-of-life survey

instruments have been developed (Creer et al. 1989;

Hyland et al. 1991; Juniper et al. 1992; Marks et al.

1993; Richards and Hemstreet 1994), several of

which appear promising. However, certain concerns

preclude the Expert Panel from recommending the

general adoption of these instruments at this time,

such as the lack of experience with the use of the

instruments in clinical practice and the time involved

in administering the surveys. The Expert Panel

does recommend that at least several key areas of

quality of life be periodically assessed for each

person with asthma. These include:

■ Any missed work or school due to asthma

■ Any reduction in usual activities (either

home/work/school or recreation/exercise)

■ Any disturbances in sleep due to asthma

■ Any change in caregiver activities due to a child’s

asthma (for caregivers of children with asthma)

Component 1: Measures of Assessment and Monitoring

BOX 2. DIFFERENCES IN PEAK FLOW

ACROSS RACIAL AND ETHNIC 

POPULATIONS

Currently available normative standards for PEF

use standing height as well as age and sex as predictors. However, for a given height, African

Americans have longer legs, shorter trunks, and

smaller thoracic diameters (Woolcock et al. 1972;

Coultas et al. 1994). The normal ranges of lung

function in Hispanics, Asians, and Native

Americans have received less attention (Coultas et

al. 1994). Differences have been reported among

Caucasians and Japanese Americans (Marcus et al.

1988; Coultas et al. 1994), Native Americans

(Wall et al. 1982; Crapo et al. 1988; Marcus et al.

1988), and Latinos (Hsu et al. 1979; Coultas et al.

1988, 1994). But these results are inconsistent,

especially for Hispanics and Native Americans

(Coultas et al. 1994). In general, lung function

for these groups tends to be intermediate between

those of Caucasians and African Americans.

Because predicted normal lung function varies

across racial and ethnic populations, it is the opinion of the Expert Panel that (1) normative standards for PEF derived from a given racial or ethnic

group cannot be readily extrapolated to other

groups and that (2) the most clinically useful standard for ongoing monitoring of asthma is the

patient’s personal best PEF value.

Archive

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35

Figure 1-6 provides a set of questions that the Expert

Panel recommends for use in characterizing qualityof-life concerns for persons with asthma (also see 

figure 4-2).

Monitoring History of Asthma Exacerbations

Exacerbations of asthma are characterized by periods

of increased symptoms and reduced lung function,

which may result in diminished ability to perform

usual activities. Exacerbations may be brought on by

exposures to irritants or sensitizers in the home, work,

or general environment. Infections, certain medications, and a number of other medical conditions, as

well as insufficient or ineffective therapy, also may

trigger exacerbations (see component 2).

During periodic assessments, clinicians should

question the patient and evaluate any records of

patient self-monitoring (figures 1-8 and 1-9) to

detect exacerbations, both self-treated and those

treated by other health care providers. It is important to evaluate the frequency, severity, and causes of

exacerbations. The patient should be asked about precipitating exposures and other factors. Specific inquiry

into unscheduled visits to providers, telephone calls for

assistance, and use of urgent or emergency care facilities may be helpful. Severity can be estimated by the

increased need for oral corticosteroids. Control of

asthma can be assessed by the increased need for

short-acting beta2-agonist. Finally, any hospitalizations should be documented, including the facility,

duration of stay, and any use of critical care or intubation. The clinician then can request summaries of all

care received to facilitate continuity of care.

Monitoring Pharmacotherapy

To ensure the effectiveness of pharmacotherapy, it is

essential that the drug regimen be based on a sound

rationale and that it be monitored on an ongoing

basis. Based on the opinion of the Expert Panel,

the following factors should be monitored:

patient adherence to the regimen, inhaler 

technique, level of usage of as-needed inhaled

short-acting beta2-agonist, frequency of oral 

corticosteroid “burst” therapy, changes in dosage

of inhaled anti-inflammatory or other longterm-control medications, and side effects of

medications (see assessment questions in figure 1-6).

It is also critical that the clinician determine that the

patient is on the appropriate step of pharmacotherapy

(see component 3-Managing Asthma Long Term) and

has an up-to-date, written daily self-management

plan and action plan (see figures 4-4 and 4-5).

Monitoring Patient-Provider Communication

and Patient Satisfaction

Health care providers should routinely assess the

effectiveness of patient/provider communication

(see figure 1-6). Open and unrestricted communication among the clinician, the patient, and the family

is essential to ensure successful self-management by

the patient with asthma. Every effort should be made

to encourage open discussion of concerns and expectation of therapy. See component 4 for specific strategies to enhance communication and patient adherence

to the treatment plan.

Patient 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). Two

aspects of patient satisfaction should be monitored: satisfaction with asthma control and

satisfaction with the quality of care. See 

figures 1-6, 1-8, and 4-2 for examples of questions to

use in monitoring patient satisfaction.

ASSESSMENT METHODS

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 

clinician assessment and patient (and/or parent or

caregiver) self-assessment. In addition, populationbased assessment of asthma care is being developed 

in the managed care field.

Clinician Assessment

Clinical assessment of asthma should be obtained via

medical history and physical examination with appropriate pulmonary function testing. Optimal history

assessment may be best achieved via a consistent set

of questions (figure 1-6); physical examination for

asthma is reviewed in component 1-Initial Assessment

and Diagnosis. Patients with mild 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. This is a rough

guideline based on the opinion of the Expert Panel.

Periodic Assessment and Monitoring

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36

Component 1: Measures of Assessment and Monitoring

How many days in the past week ______ 0 ______ 1 ______ 2 ______ 3 ______ 4 ______ 5 ______ 6 ______ 7

have you had chest tightness, 

cough, shortness of breath, or 

wheezing (whistling in your chest)?

How many nights in the past week ______ 0 ______ 1 ______ 2 ______ 3 ______ 4 ______ 5 ______ 6 ______ 7

have you had chest tightness, 

cough, shortness of breath, or 

wheezing (whistling in your chest)?

Do you perform peak flow ______ yes ______ no

readings at home?

If yes, did you bring your ______ yes ______ no

peak flow chart?

How many days in the past week ______ 0 ______ 1 ______ 2 ______ 3 ______ 4 ______ 5 ______ 6 ______ 7

has asthma restricted your

physical activity?

Have you had any asthma attacks ______ yes ______ no

since your last visit?

Have you had any unscheduled ______ yes ______ no

visits to a doctor, including to 

the emergency department, since 

your last visit?

How many puffs of your short-acting ___________________________________________

inhaled beta2-agonist (quick-relief medicine) Average number of puffs per day

do you use per day?

How many of your short-acting inhaled ___________________________________________ beta2-agonist inhalers did you go through Number of inhalers in past month

over the past month?

What questions or concerns would you like to discuss with the doctor?

How well controlled is your ______ very well controlled

asthma in your opinion? ______ somewhat controlled

______ not well controlled

How satisfied are you with your ______ very satisfied

asthma care? ______ somewhat satisfied

______ not satisfied

* These questions are examples and do not represent a standardized assessment instrument. The validity and reliability of these questions

have not been assessed.

FIGURE 1-8. SAMPLE* PATIENT SELF-ASSESSMENT SHEET FOR FOLLOWUP VISITS

Name:A_______________________________________________________________________________________________________ Date:__________________________________________________________

rchive

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Periodic Assessment and Monitoring

37

FIGURE 1-9. PATIENT SELF-ASSESSMENT: EXAMPLE OF PATIENT DIARY Wheeze Cough Activity Sleep Quick Relief: Beta2 – Agonist Cromolyn/Nedocromil Inhaled Steroids Other – Inhaled Oral Steroids Theophylline

AM

Wheeze

Cough

Activity

Sleep

None

None

Normal

Fine

=

=

=

=

0

0

0

0

=

=

=

=

1

1

1

1

=

=

=

=

2

2

2

2

=

=

=

=

3

3

3

3

Some

Occasional

Can run short 

distance or climb

3 flights of stairs

Slept well, slight 

wheeze or cough

Medium

Frequent

Can walk only

Awake 2-3 times,

wheeze or cough

Severe

Continuous

Missed school or 

work or stayed 

indoors

Bad night, awake

most of the time

PM

Other

Date Times Comments

Peak Flow

Adapted with permission from Plaut 1991.

This diary is provided as an example for clinicians.

*

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38

The exact frequency of clinician visits is a matter of

clinical judgment. Patients with uncontrolled

and/or severe persistent asthma and those

needing additional supervision to help them follow their treatment plan need to be seen more

often.

Patient Self-Assessment

Self-assessment by the patient and/or family is important to determine from their perspective whether the

asthma is well controlled. Two methods are recommended: a daily diary (see figure 1-9 for an example)

and a periodic self-assessment form to be filled out by

the patient and/or family member at the time of the

followup visits to the clinician (figure 1-8).

■ The daily diary should include the key factors to

be monitored at home: symptoms and/or peak

flow, medication use, and restricted activity.

■ The periodic self-assessment sheet completed at

office visits is intended to capture the patient’s and

family’s impression of asthma control, self-management skills, and overall satisfaction with care.

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 selfmonitoring. 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 identifying 

environmental or occupational exposures that 

make their asthma worse.

Population-Based Assessment

Asthma care is of increasing interest in various health

care settings. Important regulatory organizations for

the industry (e.g., the National Committee on

Quality Assurance) have included the care of persons

with asthma as a key indicator of 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 providers. This

type of assessment often uses population experience,

such as hospitalization or emergency department 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.

REFERENCES

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Charlton I, Charlton G, Broomfield J, Mullee MA. Evaluation of

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Crapo RO, Lockey J, Aldrich V, Jensen RL, Elliott CG. Normal

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care: trial of a “credit card” asthma self- management plan.

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Enright PL, Sherrill DL, Lebowitz MD. Ambulatory monitoring

of peak expiratory flow. Reproducibility and quality control.

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Garrett J, Fenwick JM, Taylor G, Mitchell E, Rea H. Peak expiratory flow meters (PEFMs)—who uses them and how does

education affect the pattern of utilisation? Aust N Z J Med

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Grampian Asthma Study of Integrated Care. Effectiveness of routine self-monitoring of peak flow in patients with asthma.

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Hankinson JL, Wagner GR. Medical screening using periodic

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Hegewald MJ, Crapo RO, Jensen RL. Intraindividual peak flow

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Hsu KH, Jenkins DE, Hsi BP, et al. Ventilatory functions of normal children and young adults—Mexican American, white,

and black. I. Spirometry. J Pediatr 1979;95:14-23.

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Hyland ME, Finnis S, Irvine SH. A scale for assessing quality of life

in adult asthma sufferers. J Psychosom Res 1991;35:99-110.

Ignacio-Garcia JM, Gonzalez-Santos P. Asthma self-management

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patterns of self-care in adult asthma. Heart Lung

1988;17:543-9.

Jones KP, Mullee MA, Middleton M, Chapman E, Holgate ST.

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Research Committee. Thorax 1995;50:851-7.

Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller

TK. Evaluation of impairment of health related quality of

life in asthma: development of a questionnaire for use in

clinical trials. Thorax 1992;47:76-83.

Kendrick AH, Higgs CM, Whitfield MJ, Laszlo G. Accuracy of

perception of severity of asthma: patients treated in general

practice. BMJ 1993;307:422-4.

Kikuchi Y, Okabe S, Tamura G, et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal

asthma. N Engl J Med 1994;330:1329-34.

Lahdensuo A, Haahtela T, Herrala J, et al. Randomised comparison of guided self management and traditional treatment of

asthma over one year. BMJ 1996;312:748-52.

Landgraf JM, Abetz L, Ware JE. The CHQ User’s Manual. First

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Medical Center, 1996.

Lewis CE, Rachelefsky G, Lewis MA, de la Sota A, Kaplan M. A

randomized trial of A.C.T. (Asthma Care Training) for kids.

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symptoms with a simple diary in the management of asthma? J Allergy Clin Immunol 1993;91:702-9.

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Buist AS. Reference values for FEV1 in Japanese-American

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Marks GB, Dunn SM, Woolcock AJ. An evaluation of an asthma

quality of life questionnaire as a measure of change in adults

with asthma. J Clin Epidemiol 1993;46:1103-11.

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Quackenboss JJ, Lebowitz MD, Krzyzanowski M. The normal

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peak expiratory flow is most useful in the management of

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flow meters: are they monitoring tools or training devices? J

Asthma 1990;27:219-27.

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Stewart AL, Hays RD, Ware JE Jr. The MOS short-form general

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Archive

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KEY POINTS

■ Exposure of asthma patients to irritants or allergens to which they are sensitive has been shown to increase asthma

symptoms and precipitate asthma exacerbations.

■ For at least those patients with persistent asthma on daily medications, the clinician should:

— Identify allergen exposures

— Use the patient’s history to assess sensitivity to seasonal allergens

— Use skin testing or in vitro testing to assess sensitivity to perennial indoor allergens

— Assess the significance of positive tests in context of patient’s medical history

■ Patients with asthma at any level of severity should avoid:

— Exposure to allergens to which they are sensitive.

— Exposure to environmental tobacco smoke.

— Exertion when levels of air pollution are high.

— Use of beta-blockers.

— Sulfite-containing and other foods to which they are sensitive.

■ Adult patients with severe persistent asthma, nasal polyps, or a history of sensitivity to aspirin or nonsteroidal 

anti-inflammatories should be counseled regarding the risk of severe and even fatal exacerbations from using 

these drugs.

■ Patients should be treated for rhinitis, sinusitis, and gastroesophageal reflux, if present.

■ Patients with persistent asthma should be given an annual influenza vaccine.

DIFFERENCES FROM 1991 EXPERT PANEL REPORT

■ Skin testing or in vitro testing is now specifically recommended for at least those patients with persistent asthma

exposed to perennial indoor allergens.

■ Adult patients with severe persistent asthma, nasal polyps, or a history of sensitivity to aspirin or nonsteroidal 

anti-inflammatories are to be counseled regarding the risk of severe and even fatal exacerbations from using 

these drugs. In the 1991 report, all asthma patients were recommended to avoid aspirin.

■ Routine use of chemicals to kill house-dust mites and denature the antigen is no longer recommended as a 

control measure.

■ The discussion of tartrazine sensitivity in the 1991 version was deleted. 

■ Annual influenza vaccinations are now specifically recommended for patients with persistent asthma. 

The recommendation to consider pneumococcal vaccine was deleted.

COMPONENT 2: 

CONTROL OF FACTORS CONTRIBUTING TO ASTHMA SEVERITY Archive

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42

For successful long-term asthma management, 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 fall into four categories: inhalant allergens,

occupational exposures, nonallergic factors, and other

factors. Ways to reduce the effects of these factors 

on asthma are discussed in this component.

■ Inhalant allergens:

— Animal allergens

— House-dust mites

— Cockroach allergens

— Indoor fungi (molds)

— Outdoor allergens

■ Occupational exposures

■ Irritants:

— Tobacco smoke

— Indoor/outdoor pollution and irritants

■ Other factors that can influence asthma severity:

— Rhinitis/sinusitis

— Gastroesophageal reflux

— Sensitivity to aspirin, other nonsteroidal antiinflammatory drugs, and sulfites

— Topical and systemic beta-blockers

— Viral respiratory infections

INHALANT ALLERGENS

Exposure of an asthma patient to inhalant allergens 

to which the patient is sensitive increases airway 

inflammation and symptoms. Substantially reducing

such exposure will result in significantly reduced

inflammation, symptoms, and need for medication

(see a summary of the evidence in box 1). In the

opinion of the Expert Panel, patients with 

asthma at any level of severity should be 

queried about exposures to inhalant allergens.

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. Given the importance of allergens and

Component 2: Control of Factors Contributing to Asthma Severity

BOX 1. THE STRONG ASSOCIATION

BETWEEN SENSITIZATION TO 

ALLERGIES 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 (Peat et al. 1993, 1994; Sears et al. 1993a,

1993b; Sporik et al. 1990). Sensitization to outdoor pollens carries less risk for asthma (Sears et al.

1989), although grass (Reid et al. 1986) and ragweed (Creticos et al. 1996) pollen exposure 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

(Vervloet et al. 1991; Zock et al. 1994) and that

reducing house-dust mite exposure reduces asthma

symptoms, nonspecific bronchial hyperresponsiveness, and evidence of active inflammation (Peroni et

al. 1994; Piacentini et al. 1993; Simon et al. 1994).

Inhalant allergen exposure to seasonal outdoor fungal spores (Targonski et al. 1995; O’Hollaren et al.

1991) 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).

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43

their control to asthma morbidity and asthma

management, the Expert Panel recommends that

patients with persistent asthma who require daily

therapy be evaluated for allergens as possible

contributing factors as follows: 

1. Determine the patient’s exposure to allergens

(see relevant questions in figure 2-1).

2. 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 2-2 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 2

for further explanation).

(For selected patients with asthma at any level

of severity, detection of specific IgE sensitivity

to seasonal or perennial allergens may be indicated as a basis for avoidance, for immunotherapy, or to characterize the patient’s atopic status.)

3. Assess the clinical significance of positive 

allergy tests in the context of the patient’s

medical history (see figure 2-3).

Management—Reduce Exposure

The first and most important step in controlling allergen-induced asthma is to reduce exposure to relevant

indoor and outdoor allergens. Effective ways patients

can reduce their exposures to indoor and outdoor allergens are discussed below and summarized in figure 2-4,

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 day

care. For information about companies that distribute

products to help reduce allergen exposure, contact the

Asthma and Allergy Foundation of America at 800-

727-8462 or the Allergy and Asthma Network/Mothers

of Asthmatics at 800-878-4403.

■ Animal Allergens. All warm-blooded pets, including small rodents and birds, produce dander, urine,

feces, and saliva that can cause allergic reactions

(Swanson et al. 1985; de Blay et al. 1991a). No

studies have been published on the effect of animal

allergen avoidance on asthma symptoms; however,

based on the opinion of the Expert Panel, the

following actions to control animal antigens

are recommended:

— If the patient is sensitive, remove the 

animal and products made of feathers 

from the home to eliminate exposure.

— If removal of the animal is not acceptable:

– Keep the pet out of the patient’s bedroom.

– Keep the patient’s bedroom door closed.

Consider placing dense filtering material

over forced air outlets to trap airborne 

dander particles.

– Remove upholstered furniture and carpets from the home or isolate the pet

from them to the extent possible.

Weekly washing of the pet may decrease the

amount of dander and dried saliva the animal

contributes to the environment (de Blay et al.

1991b; Klucka et al. 1995).

■ House-Dust Mite Allergen. 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. 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. Recommended mite control measures are

listed below (Platts-Mills et al. 1982).

Essential 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.

Control of Factors Contributing to Asthma Severity

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44

Component 2: Control of Factors Contributing to Asthma Severity

* 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.

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 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)

Tobacco Smoke

■ Does the patient smoke?

■ Does anyone smoke at home or work?

■ Does anyone smoke at the child’s day care?

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?

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 and/or postnasal drip?

Gastroesophageal Reflux

■ 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?

FIGURE 2-1. ASSESSMENT QUESTIONS* FOR ENVIRONMENTAL AND OTHER FACTORS 

THAT CAN MAKE ASTHMA WORSE Archive

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Control of Factors Contributing to Asthma Severity

45

FIGURE 2-2. COMPARISON OF SKIN TESTS WITH IN VITRO TESTS

■ Less expensive than in vitro tests

■ Results are available within 1 hour.

■ More sensitive than in vitro tests

■ Results are visible to the patient. 

This may encourage compliance with 

environmental control measures.

Advantages of skin tests: 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 with extensive

eczema

BOX 2. RATIONALE FOR ALLERGY TESTING FOR PERENNIAL INDOOR ALLERGENS

Determination of sensitivity to a perennial indoor allergen is usually not possible with a patient 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 (Adinoff et al. 1990), but these tests do not

determine whether the specific IgE is responsible for the patient’s symptoms. That is why patients should only

be tested for sensitivity to the allergens to which they are 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 with persistent asthma exposed to perennial indoor

allergens will result in a limited number of allergy tests for about half of all asthma patients. This is based on

the prevalence of persistent asthma and the level of exposure to indoor allergens. It is estimated that about half

of all asthma patients have persistent asthma based on data on children in the United States (Taylor and

Newacheck 1992) and on adults in Australia (Boston Consulting Group 1992). About 80 percent of the U.S.

population is exposed to house-dust mites (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 only in the

inner city and southern parts of the United States.

Skin or in vitro tests for patients exposed to perennial allergens are essential to justify the expense and effort

involved in implementing environmental controls. In addition, patient adherence to maintaining environmental

controls (e.g., with regard to pets) is likely to be poor without proof of the patient’s sensitivity. 

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— 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.

Desirable actions to control mites include:

— Reduce indoor humidity to less than 

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 the toys weekly 

in hot water.

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 house-dust mite-sensitive asthma

patients should not be recommended routinely

(Woodfolk et al. 1995). Vacuuming removes mite

allergen from carpets but is inefficient at removing

live mites.

■ Cockroach Allergen. Cockroach sensitivity and exposure are common among patients with asthma who

live in inner cities (Kang et al. 1993; Call et al.

1992). In an inner-city asthma study, asthma

severity increased with increasing levels of cockroach antigen in the bedroom of sensitized children

(Rosenstreich et al. 1997). Although no studies

have been published that report the effect of cockroach reduction on asthma symptoms, it is the

opinion of the Expert Panel that control measures need to be instituted when the patient is

sensitive to cockroaches and infestation is present in the home. Patients should not leave food or

garbage exposed. Poison baits, boric acid, and traps

are preferred to chemical agents because the latter

can be irritating when inhaled by asthma patients.

If chemical agents are used, the home should be well

ventilated and the patient should not return to the

home until the odor has dissipated.

46

Component 2: Control of Factors Contributing to Asthma Severity

FIGURE 2-3. PATIENT INTERVIEW 

QUESTIONS* FOR ASSESSING THE 

CLINICAL SIGNIFICANCE OF 

POSITIVE ALLERGY TESTS

■ Animal Dander. If there are pets 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 in a room where carpets are being or have just

been vacuumed?

— Do nasal, eye, or chest symptoms improve when away from home for a week or longer?

— Do the symptoms become worse 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 in a room where carpets are being or have just

been vacuumed?

— Does making a bed cause nasal, eye, or chest symptoms?

■ 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 consistently worse 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.

■ 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 in damp or moldy rooms, such as basements?

* These questions are provided as examples for the clinician.

The validity and reliability of these questions have not been

assessed.

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Control of Factors Contributing to Asthma Severity

47

■ Indoor Fungi (Molds). Indoor fungi are particularly

prominent in humid environments and homes that

have dampness problems. Children living in

homes with dampness have increased respiratory

symptoms (Cuijpers et al. 1995; 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 Pollens and

Seasonal Mold Spores). Patients can reduce exposure

by staying indoors with windows closed in an airconditioned environment (Solomon et al. 1980),

particularly during the midday and afternoon

when pollen and some spore counts are highest

(Long and Kramer 1972; Smith and Rooks 1954;

Mullins et al. 1986). Conducting outdoor activities shortly after sunrise will result in less pollen

exposure. These actions may not be realistic for

some patients, especially children.

Immunotherapy

Allergen immunotherapy may be considered for

asthma patients when (1) there is clear evidence

of a relationship between symptoms and exposure to an unavoidable allergen to which the

patient is sensitive, (2) symptoms occur all year

or during a major portion of the year, and (3)

there is difficulty controlling symptoms with

pharmacologic management either because the

medication is ineffective, multiple medications are

required, or the patient is not accepting of medication. This recommendation is based on the opinion of

the Expert Panel and the evidence described below. 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; Frew 1993).

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 (Reid et al. 1986; Malling et al. 1986;

Creticos et al. 1996; Horst et al. 1990). A metaanalysis of 20 randomized, placebo-controlled studies

has confirmed the effectiveness of immunotherapy in

asthma (Abramson et al. 1995). Few studies have

FIGURE 2-4. SUMMARY OF CONTROL

MEASURES FOR 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 patient’s bedroom

and seal or cover with a filter air ducts that lead to

bedroom.

■ House-dust mites: 

—Essential: Encase mattress in an allergenimpermeable 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). 

—Desirable: Reduce indoor humidity to less

than 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. Do not leave food or garbage exposed.

■ Pollens (from trees, grass, or weeds) and outdoor molds: To avoid exposures, adults should

stay indoors with windows closed during the

season in which they have problems with outdoor allergens, especially during the afternoon.

■ Indoor mold: Fix all leaks and eliminate water

sources associated with mold growth; clean

moldy surfaces. Consider reducing indoor

humidity to less than 50 percent.

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 day care providers and the workplace.

Indoor/Outdoor Pollutants and Irritants: 

Discuss ways to reduce exposures to the following:

■ Wood-burning stoves or fireplaces

■ Unvented stoves or heaters

■ Other irritants (e.g., perfumes, cleaning agents,

sprays)

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48

been reported on multiple allergen mixes, which are

commonly employed in clinical practice.

The course of allergen immunotherapy is typically of

3 to 5 years’ duration. Reactions to immunotherapy,

especially bronchoconstriction, are more frequent

among patients with asthma, particularly those with

poorly controlled asthma, compared with those with

allergic rhinitis (Reid et al. 1993). For this reason,

enthusiasm for the use of immunotherapy differs considerably among experts (Abramson et al. 1995;

Canadian Society of Allergy and Clinical Immunology

1995; Frew 1993).

Assessment of Devices That May 

Modify Indoor Air

■ Vacuuming carpets once or twice a week is

essential 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 (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

(high-efficiency particulate air) filter or with a double bag (Woodfolk et al. 1993).

■ Humidifiers and evaporative (swamp) coolers

are not recommended for use in the homes of

house-dust mite-sensitive patients with asthma. These are potentially harmful because

increased humidity may encourage the growth of

both mold (Solomon 1976) and house-dust mites

(Ellingson et al. 1995). In addition, humidifiers

may pose a problem if not properly cleaned

because they can harbor and aerosolize mold spores

(Solomon 1974).

■ Air conditioning during warm weather is recommended for asthma patients because it allows

windows and doors to stay closed, which prevents

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 (Lintner and Brame 1993).

■ Use of a dehumidifier will reduce house-dust

mite levels in areas where the humidity of the

outside air remains high for most of the year

(Cabrera et al. 1995).

■ Indoor air-cleaning devices cannot substitute

for the more effective measures described previously (see page 43, Management—Reduce

Exposure). However, air-cleaning devices 

(i.e., HEPA and electrostatic precipitating filters)

have been shown to reduce airborne cat dander 

(de Blay et al. 1991b), mold spores (Maloney et al.

1987), and particulate tobacco smoke (U.S.

Environmental Protection Agency 1990). Air

cleaners cannot significantly reduce exposure to

house-dust mite and cockroach allergens because

these heavy particles do not remain airborne 

(de Blay et al. 1991a). 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; Warner et al. 1993;

Warburton et al. 1994).

■ Air-duct cleaning of heating/ventilation/air conditioning systems 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 precludes the Expert Panel from making

a recommendation in this area.

OCCUPATIONAL EXPOSURES

Early recognition and control of exposures are particularly important in occupationally induced asthma,

because the likelihood of complete resolution of

symptoms decreases with time (Chan-Yeung et al.

1987; Pisati et al. 1993). Occupational asthma is

suggested by a correlation between asthma symptoms

and work, with improvement when away from work

for several days. Other indications of workplace

exposure are listed in figure 2-5. The patient may fail

to recognize the work relationship, because symptoms

often begin several hours after exposure. Serial peak

flow records at work and away from work can confirm the work association (Moscato et al. 1995).

Workplace exposure to sensitizing chemicals or dusts

can induce asthma, which often persists after the

exposures are terminated (Chan-Yeung et al. 1987;

Pisati et al. 1993). This should be distinguished from

allergen- or irritant-induced aggravation of preexisting asthma. Acute exposure to irritant gases, dusts,

or fumes can cause an asthma-like condition (reactive

airway dysfunction syndrome) (Brooks et al. 1985).

Patient confidentiality issues are particularly important

in work-related asthma. Because even general

Component 2: Control of Factors Contributing to Asthma Severity

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Control of Factors Contributing to Asthma Severity

49

inquiries about the potential adverse health effects of

work exposures may occasionally result in reprisals

against the patient (e.g., job loss), asthma patients

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.

IRRITANTS

In the opinion of the Expert Panel, patients with

asthma at any level of severity should be queried

about exposures to irritants. Sample assessment

questions are in figure 2-1.

Environmental Tobacco Smoke

Asthma patients should not smoke or be exposed

to environmental tobacco smoke (Marquette et al.

1992). Tobacco smoke is the most important environmental indoor irritant and is a major precipitant of

asthma symptoms in children and adults (Abbey et al.

1993; Greer et al. 1993; Jindal et al. 1994;

Leuenberger et al. 1994). Jindal and colleagues

(1994) found that exposure of adults to environmental tobacco smoke is associated with decreased levels

of pulmonary function, increased requirements for

medication, and more frequent absences from work.

In addition, exposure to maternal smoke has been

shown to be a risk factor for the development of asthma in infancy (Arshad and Hide 1992) and childhood

(Frischer et al. 1992; Schmitzberger et al. 1993;

Gortmaker et al. 1982; Henderson et al. 1995;

Soyseth et al. 1995; Martinez et al. 1995; Agudo et

al. 1994), although not for persistence of childhood

asthma into adulthood (Roorda et al. 1993).

Indoor/Outdoor Air Pollution and Irritants

Asthma patients should avoid exertion or exercise

outside to the extent possible when levels of air

pollution are high. Increased pollution levels, particularly of respirable particulates (Abbey et al. 1993;

Koenig et al. 1993; Pope et al. 1991; Walters et al.

1994; Schwartz et al. 1993; Ostro et al. 1995) and

ozone (Abbey et al. 1993; Cody et al. 1992; Ponka

1991; Thurston et al. 1992; Ostro et al. 1995;

Romieu et al. 1995; Kesten et al. 1995; White et al.

1994), but also of SO2 (Moseholm et al. 1993) and

NO2 (Moseholm et al. 1993; Kesten et al. 1995),

have been reported to precipitate symptoms of 

asthma (Abbey et al. 1993; Koenig et al. 1987;

Moseholm et al. 1993; Pope et al. 1991) and to

increase emergency department visits and hospitalizaFIGURE 2-5. 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 during vacations or days off 

(may take a week or more).

■ Symptoms may be immediate (<1 hour),

delayed (most commonly, 2 to 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 to 3 weeks (2 weeks at

work and up to 1 week off work as needed to

identify or exclude work-related changes in

peak expiratory flow):

— Record when symptoms and exposures occur.

— Record when a bronchodilator is used.

— Measure and record peak flow 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.

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50

tions for asthma (Walters et al. 1994; Schwartz et al.

1993; Cody et al. 1992; Ponka 1991; Thurston et al.

1992; Romieu et al. 1995; Kesten et al. 1995; White

et al. 1994).

Patients also should avoid exposure to fumes

from unvented gas, oil, or kerosene stoves; woodburning appliances or fireplaces (Ostro et al.

1994); sprays; and strong odors because they irritate the lungs and can precipitate asthma symptoms.

OTHER FACTORS THAT CAN 

INFLUENCE ASTHMA SEVERITY

Rhinitis/Sinusitis

Treatment of upper respiratory tract symptoms is an

integral part of asthma management. Intranasal

corticosteroids are recommended for the 

treatment of chronic rhinitis in patients with 

persistent asthma. Antihistamine/decongestant

combinations also may be used; they provide 

symptomatic relief but have not been shown to have 

a protective effect on the lower airways secondary to

their action on the nose. Intranasal corticosteroids

reduce nasal inflammation, obstruction, and discharge

and have been shown to reduce lower airway hyperresponsiveness and asthma symptoms (Aubier et al.

1992; Watson et al. 1993; Corren et al. 1992; Welsh

et al. 1987). Intranasal cromolyn has been shown 

to reduce symptoms of asthma during the ragweed 

season, but to a lesser extent than intranasal 

corticosteroids in the same study (Welsh et al. 1987).

Treatment of sinusitis includes medical measures

to promote drainage (Zeiger 1992) and the use of

antibiotics when complicating acute bacterial

infection is present (Wald 1992; Gwaltney et al.

1992). In cases of subacute or chronic sinusitis,

physicians need to make a judgment regarding the

appropriateness of antibiotic therapy. Antibiotic therapy was not shown to be of clear benefit in children

who had nasal symptoms or cough for longer than 

3 weeks and who had abnormal sinus x rays but no

fever (Dohlman et al. 1993).

Asthma is commonly associated with perennial and

seasonal rhinitis and sinusitis. Studies indicate that

inflammation of the upper airway contributes to

lower airway hyperresponsiveness and asthma symptoms (Watson et al. 1993; Corren et al. 1992; Welsh

et al. 1987). The histopathology in the chronically

thickened mucosa of the paranasal sinuses is similar to

that in the nose and bronchi, with a primarily

eosinophilic infiltrate that, in most patients, is notably

lacking in neutrophils (Harlin et al. 1988; Demoly et

al. 1994).

Gastroesophageal Reflux

Medical management of gastroesophageal reflux

should be instituted for any patients with asthma

complaining of frequent heartburn or pyrosis,

particularly those with frequent episodes of 

nocturnal asthma. Medical management of 

gastroesophageal reflux includes:

■ 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 

(Hixson et al. 1992)

For patients who have persistent symptoms following

optimal therapy, further evaluation is indicated.

For patients with poorly controlled asthma, particularly with a nocturnal component, investigation for

gastroesophageal reflux may be warranted even in the

absence of suggestive symptoms (Irwin et al. 1989).

The symptoms of gastroesophageal reflux are common

in both children and adults with asthma (Nelson 1984).

Reflux during sleep can contribute to nocturnal asthma

(Martin et al. 1982; Davis et al. 1983). Both medical

(Ekstrom et al. 1989) and surgical (Perrin-Fayolle et al.

1989) therapy of gastroesophageal reflux have been

reported to reduce the symptoms of asthma.

Aspirin Sensitivity

Adult patients with asthma should be questioned

regarding precipitation of bronchoconstriction by

aspirin and other nonsteroidal anti-inflammatory

drugs. If they have experienced a reaction to any

of these drugs, they should be informed of the

potential for all these drugs to precipitate severe

and even fatal exacerbations. Adult patients with

severe persistent asthma or nasal polyps should

be counseled regarding the risk of using these

drugs. Usually safe alternatives to aspirin include

acetaminophen or salsalate (Szczeklik et al. 1977;

Settipane et al. 1995).

Component 2: Control of Factors Contributing to Asthma Severity

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Control of Factors Contributing to Asthma Severity

51

From 3 percent of patients with asthma seen in a private allergy practice (Chafee and Settipane 1974) to

39 percent of adults with asthma admitted to an

asthma referral hospital (Spector et al. 1979) have

been reported to experience severe and even fatal

exacerbations of asthma after taking aspirin or certain

other nonsteroidal anti-inflammatory drugs. The

prevalence of aspirin sensitivity increases with 

increasing age and severity of asthma (Chafee and

Settipane 1974; Spector et al. 1979).

Sulfite Sensitivity

Patients who have asthma symptoms associated

with eating processed potatoes, shrimp, or dried

fruit or with drinking beer or wine should avoid

these products (Taylor et al. 1988). These products

contain sulfites, which are used to preserve foods and

beverages. They have caused severe asthma exacerbations, particularly in patients with severe persistent

asthma.

Beta-Blockers

Nonselective beta-blockers, including those in

ophthalmological preparations, can cause asthma

symptoms and should be avoided by asthma

patients (Odeh et al. 1991; Schoene et al. 1984),

although cardioselective beta-blockers, such as 

betaxolol, may be tolerated (Dunn et al. 1986).

Infections

Annual influenza vaccinations are recommended

for patients with persistent asthma (Bell et al.

1978; CDC 1993). It is well established that viral

respiratory infections can exacerbate asthma, particularly in children with asthma under the age of 10

(Busse et al. 1993). Respiratory syncytial virus, 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).

Viral infections are the most frequent precipitants of

asthma exacerbations in infancy. In the majority of

cases, young children are predisposed to have

bronchial obstruction during viral infections because

of very small airway size (Martinez et al. 1995) and

will not have further exacerbations after infancy.

However, chronic asthma also may start as early as

the first year of life among infants with a family history of asthma, persistent rhinorrhea, atopic dermatitis,

or high IgE levels. Early identification of these infants

allows institution of environmental controls to reduce

exposure to tobacco smoke, animal dander, and

house-dust mites.

PREVENTING THE ONSET OF ASTHMA

Primary prevention of asthma (preventing initial 

development) is an accepted approach for occupational asthma (Venables 1994; Chan-Yeung et al. 1987)

but remains unproven outside the workplace. Recent 

studies indicate that exposures to high levels of housedust mite antigen (Sporik et al. 1990; Peat et al.

1993, 1994) and environmental tobacco smoke

(Martinez et al. 1995; Kuehr et al. 1995) are associated with an increased incidence of asthma among

infants. This suggests that reducing these exposures

may result in reduction in the incidence of asthma.

Prolonged breast feeding and avoidance of early introduction of allergenic foods have been reported to

reduce eczema and food sensitization but not to

reduce the prevalence of asthma (Zeiger 1994).

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Woodfolk JA, Hayden ML, Couture N, Platts-Mills TAE. Chemical

treatment of carpets to reduce allergen: comparison of the effects

of tannic acid and other treatments on proteins derived from

dust mites and cats. J Allergy Clin Immunol 1995;96:325-33.

Woodfolk JA, Luczynska CM, de Blay F, Chapman MD, PlattsMills TAE. The effect of vacuum cleaners on the concentration

and particle size distribution of airborne cat allergen. J Allergy

Clin Immunol 1993;91:829-37.

Zeiger RS. Dietary manipulations in infants and their mothers and

the natural course of atopic disease. Pediatr Allergy Immunol

1994;5:33-43.

Zeiger RS. Prospects for ancillary treatment of sinusitis in the1990s.

J Allergy Clin Immunol 1992;90:478-95.

Zock JP, Brunekreef B, Hazebroek-Kampschreur AA, Roosjen CW.

House dust mite allergen in bedroom floor dust and respiratory health of children with asthmatic symptoms. Eur Respir J

1994;7:1254-9.

Archive

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57

KEY POINTS

■ Underdiagnosis and inappropriate therapy are major contributors to asthma morbidity and mortality.

■ Goals of asthma therapy are:

— Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the night, in the early morning,

or after exertion)

— Maintain (near) “normal” pulmonary function 

— Maintain normal activity levels (including exercise and other physical activity)

— Prevent recurrent exacerbations of asthma and minimize the need for emergency department 

visits or hospitalizations

— Provide optimal pharmacotherapy with minimal or no adverse effects

— Meet patients’ and families’ expectations of and satisfaction with asthma care

■ Persistent asthma is most effectively controlled with daily anti-inflammatory therapy.

■ A stepwise approach to pharmacologic therapy is recommended:

— The amount and frequency of medication is dictated by asthma severity and directed toward suppression of

increasing airway inflammation.

— Initiate therapy at a higher level at the onset to establish prompt control and then step down.

— Continual monitoring is essential to ensure that asthma control is achieved.

— Step down therapy cautiously once control is achieved and sustained.

— Step-down therapy is necessary to identify the minimum medication necessary to maintain control.

■ Regular followup visits (at 1- to 6-month intervals) are essential to maintain control and consider appropriate step

down in therapy.

■ Therapeutic strategies should be considered in concert with clinician-patient partnership strategies; education of

patients is essential for achieving optimal asthma control.

■ At each step, patients should be advised to avoid or control allergens, irritants, or other factors that make the

patient’s asthma worse.

■ Referral to an asthma specialist for consultation or comanagement is recommended if there are difficulties achieving

or maintaining control of asthma or if the patient requires step 4 care. Referral may be considered for patients who

require step 3 care. For patients younger than 3 years of age, referral is recommended if the patient requires step 3 or

4 care and should be considered if the patient requires step 2 care.

■ New medications are available.

— Long-acting inhaled beta2-agonists

– Effective 12-hour bronchodilator

– Adjunctive therapy to inhaled corticosteroids for maintaining control, especially helpful for 

nighttime symptoms

– Not to be used to treat acute symptoms or exacerbations

— Nedocromil

– Similar role in therapy as cromolyn sodium, with similar safety profile

— Leukotriene modifiers

– Zafirlukast, leukotriene receptor antagonist, and zileuton, 5-lipoxygenase inhibitor

– May be considered alternative daily long-term-control medications for patients with mild persistent asthma 

who are 12 years of age and older, but further clinical experience and study are needed to establish 

their roles in therapy

COMPONENT 3: 

PHARMACOLOGIC THERAPY Archive

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58

Component 3: Pharmacologic Therapy

■ Increased understanding of inhaled corticosteroids notes that:

— Inhaled corticosteroids are the most potent inhaled anti-inflammatory agent currently available.

— Early intervention with inhaled corticosteroids can improve asthma control and normalize lung function and

may prevent irreversible airway injury.

— Higher doses of inhaled corticosteroids may be associated with possible, but not predictable, growth retardation

in children. The clinical significance of this potential systemic effect has yet to be determined.

— Issues regarding clinical comparability and bioavailability of different preparations and different delivery systems

indicate the need to adjust doses accordingly.

■ Management of asthma exacerbations includes:

— Inhaled beta2-agonist to provide prompt relief of airflow obstruction

— Systemic corticosteroid, for moderate-to-severe exacerbations, to suppress and reverse airway inflammation

— Oxygen to relieve hypoxia for moderate-to-severe exacerbations

— Monitoring response to therapy with serial measurements of lung function

DIFFERENCES FROM 1991 EXPERT PANEL REPORT

■ Medications are now 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.

However, the updated report continues to emphasize that the most effective medications for long-term therapy are those shown to

have anti-inflammatory effects.

■ New medications are available—long-acting inhaled beta2-agonists, nedocromil, zafirlukast, and zileuton—

that have positions in therapy for long-term control and prevention of symptoms.

■ There is an increased understanding of inhaled corticosteroids and their significant role in asthma therapy. 

An estimated clinical comparability of different inhaled corticosteroid preparations is presented.

■ The stepwise approach to asthma therapy emphasizes initiating higher level therapy at the onset to establish

prompt control and then stepping down.

■ A new section on asthma in infants and young children incorporates recent studies on wheezing in early childhood.

Selecting the appropriate pharmacologic therapy to

achieve and maintain control of asthma involves several considerations: the medications and their routes

of administration, a stepwise approach to managing

asthma long term as a chronic disorder, and a protocol for managing exacerbations. Each will be discussed in this component. In addition, substantial

reports in the literature since publication of the

1991 Expert Panel Report have commented on the

safety of regular administration of inhaled beta2-

agonists and the potential adverse effects of inhaled

corticosteroids. Because of the importance of these

two classes of compounds in the treatment of 

asthma, it is the opinion of the Panel that special

emphasis should be given to these issues. 

A summary is presented in this component.

The therapeutic strategies provided in this component should be considered in concert with the 

clinician-patient partnership strategies provided in

component 4. Effective communication with, and

education of, patients will increase the benefits of

the therapeutic regimen.

Archive

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59

OVERVIEW OF THE MEDICATIONS

Pharmacologic therapy is used to prevent and control

asthma symptoms, reduce the frequency and severity

of asthma exacerbations, and reverse airflow obstruction. Recommendations in this component reflect the

scientific concept that asthma is a chronic disorder

with recurrent episodes of airflow limitation, mucus

production, and cough. Asthma medications are thus

categorized into two general classes: long-term-control

medications taken daily on a long-term 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 acute rescue medications). Patients with persistent asthma require both

classes of medication. Figures 3-1 and 3-2 present

summaries of the indications, mechanisms, potential

adverse effects, and therapeutic issues for currently

available long-term-control and quick-relief 

medications. 

Long-Term-Control Medications

Long-term-control medications are taken daily on a

long-term basis to achieve and maintain control of

persistent asthma. They include anti-inflammatory

agents, long-acting bronchodilators, and leukotriene

modifiers. Because eosinophilic 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

eosinophilic cationic protein 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

KEY POINTS: THE 

MEDICATIONS

Long-term-control medications

■ Corticosteroids: Most potent and effective antiinflammatory medication currently available.

Inhaled form is used in the long-term control of

asthma. Systemic corticosteroids are often used to

gain prompt control of the disease when initiating

long-term therapy.

■ Cromolyn sodium and nedocromil: Mild-tomoderate anti-inflammatory medications. May be

used as initial choice for long-term-control therapy

for children. Can also be used as preventive treatment prior to exercise or unavoidable exposure to

known allergens. 

■ Long-acting beta2-agonists: Long-acting bronchodilator used concomitantly with anti-inflammatory medications for long-term control of symptoms,

especially nocturnal symptoms. Also prevents exercise-induced bronchospasm (EIB).

■ Methylxanthines: Sustained-release theophylline is a

mild-to-moderate bronchodilator used principally as

adjuvant to inhaled corticosteroids for prevention of

nocturnal asthma symptoms. May have mild antiinflammatory effect.

■ Leukotriene modifiers: Zafirlukast, a leukotriene

receptor antagonist, or zileuton, a 5-lipoxygenase

inhibitor, may be considered an alternative therapy

to low doses of inhaled corticosteroids or cromolyn

or nedocromil for patients >_12 years of age with

mild persistent asthma, although further clinical

experience and study are needed to establish their

roles in asthma therapy.

Quick-relief medications

■ Short-acting beta2-agonists: Therapy of choice 

for relief of acute symptoms and prevention of EIB.

■ Anticholinergics: Ipratropium bromide may provide some additive benefit to inhaled beta2-agonists

in severe exacerbations. May be an alternative bronchodilator for patients who do not tolerate inhaled 

beta2-agonists.

■ Systemic corticosteroids: Used for moderate-tosevere exacerbations to speed recovery and prevent 

recurrence of exacerbations.

Pharmacologic Therapy:

The Medications Archive

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60

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. 

Corticosteroids

Corticosteroids are the most potent and consistently

effective long-term-control medication for asthma.

Their broad action on the inflammatory process may

account for their efficacy as preventive therapy. Their

clinical effects include reduction in severity of symptoms, improvement in peak expiratory flow and

spirometry, diminished airway hyperresponsiveness,

prevention of exacerbations, and possibly the prevention of airway wall remodeling (Barnes et al. 1993;

Jeffery et al. 1992; Dahl et al. 1993; Fabbri et al.

1993; Gustafsson et al. 1993; Haahtela et al. 1991;

Kamada et al. 1996; Rafferty et al. 1985; van EssenZandvliet 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 (Busse 1993; Booth et al. 1995;

Laitinen et al. 1992; Djukanovic et al. 1992;

Duddridge et al. 1993; Laitinen et al. 1991; Levy et

al. 1995; McGill et al. 1995).

Dosages for inhaled corticosteroids vary depending

upon the specific product and delivery devices (see

figure 3-5b). For many patients, a twice-a-day dosing

schedule maintains control of asthma; even high doses

of some preparations are effective when given twice a

day (Noonan et al. 1995). Some studies show that

once-daily dosing is effective in mild persistent asthma (Jones et al. 1994; Pincus et al. 1995).

Cromolyn Sodium and Nedocromil

Although cromolyn and nedocromil have distinct

properties (Clark 1993), they have similar antiinflammatory actions. Their mechanism appears to

involve the blockade of chloride channels (Alton and

Norris 1996), and they modulate mast cell mediator

release and eosinophil recruitment (Eady 1986). They

also inhibit the early and late asthmatic response to

allergen challenge and exercise-induced bronchospasm

(EIB) (Novembre et al. 1994; Alton and Norris 1996;

Thompson 1989; Gonzalez and Brogden 1987).

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 (Novembre et al. 1995; deBenedictis et al.

1995), by cold dry air (Juniper et al. 1987), and by

bradykinin aerosol (Dixon and Barnes 1989).

Both compounds have been shown to reduce asthma

symptoms, improve morning peak flow, and reduce

need for quick-relief beta2-agonists (Lal et al. 1993;

Schwartz et al. 1996). Two large clinical trials comparing nedocromil MDI 4 mg qid to cromolyn MDI

2 mg qid demonstrated that they are generally comparable in mild allergic patients and that nedocromil

was more effective than cromolyn in nonallergic

patients using inhaled corticosteroids. Furthermore,

nedocromil may have a modest effect in helping

reduce the dose requirements for inhaled corticosteroids (Lal et al. 1993; O’Hickey and Rees 1994;

Svendsen and Jorgensen 1991), although some studies

did not demonstrate this effect (Wong et al. 1993).

Dosing recommendations for both drugs are for

administration four times a day, although nedocromil

has been shown to be clinically effective with twicedaily dosing (Creticos et al. 1995).

The clinical response to cromolyn and nedocromil is

less predictable than the response to inhaled corticosteroids. Both compounds have a strong safety profile.

Long-Acting Beta2-Agonists 

(Beta-Adrenergic 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. Long-acting

inhaled beta2-agonists have a duration of bronchodilation of at least 12 hours after a single dose (Becker

and Simons 1989; D’Alonzo et al. 1994). This class

of medication is not to be used for exacerbations.

Rather, it is used as an adjunct to anti-inflammatory

therapy for providing long-term control of symptoms,

especially nocturnal symptoms (Yates et al. 1995) and

to prevent exercise-induced bronchospasm. The use

and safety of beta2-agonists are discussed on page 67,

Special Issues Regarding Safety.

Component 3: Pharmacologic Therapy

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61

FIGURE 3-1. LONG-TERM-CONTROL MEDICATIONS

Name/Products

Corticosteroids

(Glucocorticoids)

Inhaled:

Beclomethasone 

dipropionate 

Budesonide 

Flunisolide 

Fluticasone 

propionate 

Triamcinolone 

acetonide

Systemic:

Methylprednisolone

Prednisolone

Prednisone

Indications/Mechanisms

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 

down-regulation. Inhibit

microvascular leakage.

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.

Potential Adverse Effects

■ Cough, dysphonia, oral thrush

(candidiasis).

■ In high doses (see figure 3-5b),

systemic effects may occur,

although studies are not conclusive, and clinical significance

of these effects has not been

established (e.g., adrenal suppression, osteoporosis, growth

suppression, and skin thinning

and easy bruising) (Barnes and

Pedersen 1993; Kamada et al.

1996).

■ Short-term use: reversible,

abnormalities in glucose metabolism, increased appetite, fluid

retention, weight gain, mood

alteration, hypertension, peptic

ulcer, and rarely aseptic necrosis

of femur.

■ 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, and Strongyloides.

Therapeutic Issues

■ Spacer/holding chamber

devices and mouth washing

after inhalation decrease local

side effects and systemic

absorption.

■ Preparations are not absolutely

interchangeable on a mcg or

per puff basis (see figure 3-5c

for estimated clinical comparability). New delivery devices

may provide greater delivery

to airways, which may affect

dose.

■ The risks of uncontrolled asthma should be weighed against

the limited risks of inhaled

corticosteroids. The potential

but small risk of adverse

events is well balanced by

their efficacy. (See text.)

■ Dexamethasone is not 

included because it is highly

absorbed and has long-term

suppressive side effects.

Use at lowest effective dose. 

For long-term use, alternate-day

a.m. dosing produces 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).

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62

Component 3: Pharmacologic Therapy

FIGURE 3-1. LONG-TERM-CONTROL MEDICATIONS (CONTINUED)

Cromolyn Sodium

and Nedocromil

Long-Acting

Beta2-Agonists

Inhaled:

Salmeterol

Oral:

Albuterol, 

sustained-release 

Indications

■ Long-term prevention of 

symptoms; may modify 

inflammation.

■ Preventive treatment prior to

exposure to exercise or known

allergen.

Mechanisms

■ Anti-inflammatory. Block

early and late reaction to allergen. Interfere with chloride

channel function. Stabilize

mast cell membranes and

inhibit activation and release of

mediators from eosinophils and

epithelial cells.

■ Inhibit acute response to 

exercise, cold dry air, and SO2.

Indications

■ Long-term prevention of 

symptoms, especially nocturnal

symptoms, added to 

anti-inflammatory therapy

■ Prevention of exercise-induced 

bronchospasm.

■ 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.

■ In vitro, inhibit mast cell

mediator release, decrease 

vascular permeability, and

increase mucociliary clearance.

■ Compared to short-acting

inhaled beta2-agonist, salmeterol (but not formoterol) has

slower onset of action (15 to 30

minutes) but longer duration

(>12 hours).

15 to 20 percent of patients

complain of an unpleasant taste

from nedocromil.

■ 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.

■ See text for additional 

discussion.

■ 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 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.

■ Not to be used to treat acute

symptoms or exacerbations.

■ Clinical significance of potentially developing tolerance is

uncertain because studies show

symptom control and bronchodilation are maintained.

■ Should not be used in place of

anti-inflammatory therapy.

■ May provide more effective

symptom control when added 

to standard doses of inhaled

corticosteriod compared to

increasing the corticosteriod

dosage.

■ Inhaled long-acting beta2-agonists

are preferred because they are

longer acting and have fewer side

effects than oral sustained-release

agents.

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The Medications

FIGURE 3-1. LONG-TERM-CONTROL MEDICATIONS (CONTINUED)

Methylxanthines

Theophylline, 

sustained-release

tablets and capsules

Leukotriene

Modifiers

Zafirlukast

tablets

Zileuton tablets

Indications

■ Long-term control and prevention of symptoms, especially

nocturnal symptoms.

Mechanisms

■ Bronchodilation. Smooth 

muscle relaxation from phosphodiesterase inhibition and possibly

adenosine antagonism

■ May affect eosinophilic infiltration into bronchial mucosa as

well as decrease T-lymphocyte

numbers in epithelium.

■ Increases diaphragm contractility and mucociliary clearance.

Indications

■ Long-term control and prevention of symptoms in mild

persistent asthma for patients

>_ 12 years of age.

Mechanisms

■ Leukotriene receptor antagonist; selective competitive

inhibitor of LTD4 and LTE4

receptors.

Indications

■ Long-term control and prevention of symptoms in mild persistent asthma for patients >_12

years of age.

Mechanisms

■ 5-lipoxygenase inhibitor.

■ 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 with prostatism.

■ No specific adverse effects to

date. As with any new drug,

there is possibility of rare

hypersensitivity or idiosyncratic reactions that cannot

usually be detected in initial

premarketing trials. One

reported case of reversible

hepatitis and hyperbilirubinemia; high concentrations may

develop in patients with liver

impairment.

■ Elevation of liver enzymes has

been reported. Limited case

reports of reversible hepatitis

and hyperbilirubinemia.

■ 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 (see figure 3-5a), which

can produce significant changes

in steady-state serum theophylline concentrations.

■ Not generally recommended

for exacerbations. There is

minimal evidence for added

benefit to optimal doses of

inhaled beta2-agonists. Serum 

concentration monitoring is

mandatory.

■ Administration with meals

decreases bioavailability; take

at least 1 hour before or 2

hours after meals.

■ Inhibits the metabolism of

warfarin and increases prothrombin time; it is a competitive inhibitor of the

CYP2C9 hepatic microsomal

isozymes. (It has not affected

elimination of terfenadine,

theophylline, or ethinyl estradiol drugs metabolized by the

CYP3A4 isozymes.)

■ Zileuton is microsomal

CYP3A4 enzyme inhibitor that

can inhibit the metabolism of

terfenadine, warfarin, and theophylline. Doses of these drugs

should be monitored accordingly. 

■ Monitor hepatic enzymes

(ALT).

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Component 3: Pharmacologic Therapy

FIGURE 3-2. QUICK-RELIEF MEDICATIONS

Short-Acting

Inhaled Beta2- Agonists

Albuterol

Bitolterol

Pirbuterol

Terbutaline

Anticholinergics

Ipratropium

bromide

Indications

■ Relief of acute symptoms;

quick-relief medication.

■ Preventive treatment prior to

exercise for exercise-induced

bronchospasm.

Mechanisms

■ Bronchodilation. Smooth

muscle relaxation following

adenylate cyclase activation

and increase in cyclic AMP

producing functional antagonism of bronchoconstriction.

Indications

■ Relief of acute bronchospasm

(see Therapeutic Issues 

column).

Mechanisms

■ Bronchodilation.

Competitive inhibition of

muscarinic cholinergic 

receptors.

■ Reduces intrinsic vagal tone

to the airways. May block

reflex bronchoconstriction 

secondary to irritants or to

reflux esophagitis.

■ May decrease mucus gland

secretion.

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.

Drying of mouth and respiratory

secretions, increased wheezing in

some individuals, blurred vision if

sprayed in eyes.

■ 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. Albuterol liquid is not recommended.

■ For patients with mild intermittent asthma, regularly

scheduled daily use neither

harms nor benefits asthma

control (Drazen et al. 1996).

Regularly scheduled daily 

use is not generally recommended.

■ Increasing use or lack of

expected effect indicates 

inadequate asthma control. 

>1 canister a month 

(e.g., albuterol-200 puffs 

per canister) may indicate 

overreliance on this drug; 

>_ 2 canisters in 1 month

poses additional adverse risks.

■ For patients frequently using

beta2-agonist, anti-inflammatory medication should be 

initiated or intensified.

■ Reverses only cholinergically

mediated bronchospasm; does

not modify reaction to antigen. Does not block exerciseinduced bronchospasm.

■ May provide additive effects

to beta2-agonist but has 

slower onset of action.

■ Is an alternative for patients

with intolerance to beta2-

agonists.

■ Treatment of choice for 

bronchospasm due to betablocker medication.

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65

FIGURE 3-2. QUICK-RELIEF MEDICATIONS (CONTINUED)

Corticosteroids

Systemic:

Methylprednisolone

Prednisolone

Prednisone

Indications

■ For moderate-to-severe exacerbations to prevent progression of exacerbation, reverse

inflammation, speed recovery,

and reduce rate of relapse.

Mechanisms

■ Anti-inflammatory.

See figure 3-1.

■ Short-term use: reversible

abnormalities in glucose

metabolism, increased

appetite, fluid retention,

weight gain, mood alteration,

hypertension, peptic ulcer,

and rarely aseptic necrosis of

femur.

■ Consideration should be

given to coexisting conditions

that could be worsened by

systemic corticosteroids, 

such as herpes virus infections, varicella, tuberculosis,

hypertension, peptic ulcer,

and Strongyloides.

■ Short-term therapy should

continue until patient

achieves 80% PEF personal

best or symptoms resolve.

This usually requires 3 to 10

days but may require longer.

■ There is no evidence that

tapering the dose following

improvement prevents

relapse.

Methylxanthines

Theophylline, the principally used methylxanthine,

provides mild-to-moderate bronchodilation in asthma.

Although its mechanism of action has yet to be established (Weinberger and Hendeles 1996; Hendeles et

al. 1995), recent evidence suggests that low serum

concentrations of theophylline are mildly antiinflammatory (Sullivan et al. 1994; Kidney et al.

1995; Pauwels 1989). Sustained-release theophylline’s main use is as adjuvant therapy, and it is

particularly effective for controlling nocturnal asthma

symptoms. Sustained-release theophylline may be

considered as an alternative, but not preferred, longterm preventive therapy when issues arise concerning

cost or adherence to regimens using inhaled medication. Monitoring serum concentration levels is essential to ensure that therapeutic, but not toxic, doses

are achieved. 

Leukotriene Modifiers

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 with asthma (Henderson 1994). Two

leukotriene modifiers—zafirlukast and zileuton—

have recently become available as oral tablets for the

treatment of asthma. 

From the information currently available, it appears

that leukotriene modifiers improve lung function

(Gaddy et al. 1992) and diminish symptoms and the

need for short-acting inhaled beta2-agonists. The

majority of trials have been conducted in mildto-moderate asthma, and the improvements noted

have been modest. Leukotriene modifiers may be

considered an alternative to low-dose inhaled corticosteroid therapy for patients with mild persistent asthma, although increased clinical experience and further

study in a wide range of patients are needed to determine those patients most likely to benefit from

leukotriene modifiers and to establish a more specific

role for leukotriene modifiers in asthma therapy.

Zafirlukast, a leukotriene receptor antagonist, 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).

Studies comparing zafirlukast to placebo in patients

with mild-to-moderate asthma demonstrated that

patients treated with zafirlukast experienced modest

improvement in FEV1 (mean improvement of 11 percent above placebo), improved symptom scores, and

reduced albuterol use (average decline of 1 puff/day)

(Spector et al. 1994). In a small study of healthy

Name/ProductsAIndications/Mechanisms Potential Adverse Effects Therapeutic Issues

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males, 60 mg a day of zafirlukast caused 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 doses of warfarin accordingly.

Zileuton, a 5-lipoxygenase inhibitor, has been demonstrated to provide immediate and sustained improvements in FEV1 (mean increase of 15 percent above

placebo) in placebo-controlled trials in patients with

mild-to-moderate asthma (Israel et al. 1993, 1996).

Compared to placebo, the patients with moderate

asthma treated with zileuton experienced significantly

fewer exacerbations requiring oral corticosteroids

(Israel et al. 1996), thus suggesting anti-inflammatory action. Finally, zileuton is capable of attenuating

bronchoconstriction from exercise (Meltzer et al.

1996) and from aspirin in aspirin-sensitive individuals

(Israel et al. 1993). 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. Zileuton is a

microsomal CYP3A4 enzyme inhibitor that can

inhibit the metabolism of terfenadine, warfarin, and

theophylline. Doses of these drugs should be monitored accordingly.

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. They include short-acting beta2-agonists

and anticholinergics. Although the onset of action is

slow (>4 hours), systemic corticosteroids are 

important in the treatment of moderate-to-severe 

exacerbations because they prevent progression of the

exacerbation, speed recovery, and prevent early relapses.

Short-Acting Beta2-Agonists

Short-acting beta2-agonists relax airway smooth muscle and cause a prompt (within 30 minutes) increase

in airflow. Inhaled short-acting beta2-agonists are the

drug of choice for treating acute asthma symptoms

and exacerbations and for preventing EIB. Concerns

about the safety of short-acting beta2-agonists are 

discussed in another section of this component (see

page 67, Special Issues Regarding Safety).

Anticholinergics

Cholinergic innervation is an important factor in the

regulation of airway smooth muscle tone. Ipratropium bromide is a quaternary derivative of atropine

that does not have atropine’s side effects. Ipratropium bromide may provide some additive benefit

with inhaled beta2-agonists in severe asthma exacerbations. Its effectiveness in long-term management

of asthma has not been demonstrated (Kerstjens et al.

1992; Gross 1988; Storms et al. 1986).

Systemic Corticosteroids

Systemic corticosteroids can speed resolution of airflow obstruction and reduce the rate of relapse (Fanta

et al. 1983; Rowe et al. 1992; Scarfone et al. 1993;

Connett et al. 1994; Chapman et al. 1991).

Medications To Reduce Oral Systemic

Corticosteroid Dependence

Troleandomycin, Cyclosporine, Methotrexate, 

Gold, Intravenous Immunoglobulin, Dapsone, and 

Hydroxychloroquine

These regimens to reduce oral systemic corticosteroid

dependence should be used only in selected patients

who are under the supervision of an asthma specialist.

Although some of the compounds have corticosteroidsparing effects, their use in asthma remains complicated because of highly variable effects, potential 

toxicity, and limited clinical experience (Bernstein et

al. 1996; Jarjour et al. 1996; Mullarkey et al. 1988;

Shiner et al. 1990; Erzurum et al. 1991; Muranaka et

al. 1978; Klaustermeyer et al. 1987; Kamada et al.

1993; Nelson et al. 1993; Alexander et al. 1992; Mazer

and Gelfand 1991). Colchicine is not considered effective in reducing need for oral systemic or high doses of

inhaled corticosteroids (Newman et al. 1997).

Complementary Alternative Medicine

Alternative healing methods are not substitutes for

recommended pharmacologic therapy. Although

alternative healing methods may be popular with

selected patients and of some interest to investigators,

their scientific basis has not been established.

The most widely known complementary alternative

medicine methods are acupuncture, homeopathy,

herbal medicine, and Ayurvedic medicine (which

includes transcendental meditation, herbs, and yoga).

Component 3: Pharmacologic Therapy

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A review of multiple trials on the use of acupuncture

in asthma concluded that the trials lacked quality and

that the effectiveness of acupuncture in treating asthma has not been established (Kleijnen et al. 1991).

One trial, however, demonstrated benefit in EIB

(Fung et al. 1986). Homeopathy, based on the “law

of similars” and the use of infinitesimally small doses,

is as yet unproven for asthma (Reilly et al. 1986);

some homeopathic remedies may contain potent

unidentified pharmacologic agents (Morice 1986).

No controlled clinical trials have been reported on

herbal medicines, and the claims of effectiveness of

western plant derivatives for asthma remain unsubstantiated (Dorsch and Wagner 1991; Ziment and

Stein 1993). Because complementary alternative

medicine is reported to be used by as much as onethird of the U.S. population (Eisenberg et al. 1993), it

may be important to inquire about all the medications a patient uses and advise the patient accordingly

(see component 4).

ROUTE OF ADMINISTRATION

Medications for asthma can be administered either by

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

avoided or minimized (Newhouse and Dolovich

1986). Furthermore, the onset of action of inhaled

bronchodilators is substantially shorter than that of

oral bronchodilators.

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 3-3

for a summary of issues to consider for different devices.

Whatever device is selected, patients should be instructed in its use and their technique checked regularly.

Most inhaled medications currently used for asthma

are available as metered-dose inhalers (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. However, CFCs have been found to deplete

stratospheric ozone and have been banned internationally. Although a temporary medical exemption

has been granted, it is expected that CFC-propelled

MDIs will eventually be phased out completely.

Alternatives include MDIs with other propellants

(nonchlorinated propellants such as hydrofluoroalkane

[HFA] 134a do not have ozone-depleting properties),

multidose dry powder inhalers, and other hand-held

devices with convenience and delivery characteristics

similar to current MDIs. An MDI for albuterol with

HFA 134a has been approved for use; additional nonCFC products and delivery systems are expected in

the future. The Food and Drug Administration

approval process requires that the replacement products demonstrate comparability to the corresponding

CFC products so that clinicians and patients can

anticipate similar effectiveness and safety with the

new products. 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 (see component 4).

SPECIAL ISSUES REGARDING SAFETY

Short-Acting Inhaled Beta2-Agonists

Short-acting inhaled beta2-agonists (e.g., albuterol) are

the medications of choice for treating exacerbations of

asthma and for preventing EIB. Prior to 1990, many

clinicians prescribed short-acting beta2-agonists on a

regularly scheduled basis in the belief that this treatment regimen improved overall asthma symptom control. Some recent reports, however, have modified these

beliefs. For example, in moderate asthma, regular use of

a potent inhaled beta2-agonist (fenoterol) produced a

significant diminution in asthma control and objective

measurements of pulmonary function (Sears et al.

1990). In mild asthma, regularly scheduled use of

albuterol compared to use on an as-needed basis only

resulted in no significant differences in a variety of 

KEY POINTS: SHORT-ACTING INHALED

BETA 2 -AGONISTS

■ Short-acting beta2-agonists are the most 

effective medication for relieving acute 

bronchospasm.

■ Increasing use of short-acting beta2-agonists or

the use of more than one canister in 1 month

indicates inadequate control of asthma and 

the need for initiating or intensifying 

anti-inflammatory therapy.

■ Regularly scheduled, daily use of short-acting

beta2-agonists is generally not recommended.

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Component 3: Pharmacologic Therapy

FIGURE 3-3. AEROSOL DELIVERY DEVICES

Device/Drugs Population Optimal Technique* Therapeutic Issues

Slow inhalation may be difficult. Difficulty with 

coordination of actuation and inhalation, particularly in

young children and elderly. Patients may incorrectly

stop inhalation at actuation. Deposition of 80 percent 

of actuated dose in oropharynx. Mouth washing is 

effective in reducing systemic absorption (Selroos 

and Halme 1991).

Indicated for patients unable to coordinate inhalation and

actuation. May be particularly useful in elderly

(Newman et al. 1991). Slow inhalation may be difficult

and patients may incorrectly stop inhalation at actuation.

Requires more rapid inspiration to activate than is 

optimal for deposition. Cannot be used with currently

available spacer/holding chamber devices.

Dose lost if patient exhales through device. Delivery

may be >_ MDI depending on device and technique.

Can be used in children 4 years old, but effects are

more consistent with children >5 (Pedersen et al. 1990;

Goren et al. 1994; Kemp et al. 1989; Kesten et al.

1994). Most appear to have similar delivery efficiency

as MDI either with or without spacer/holding chamber,

but some may have delivery >MDI (Thorsson et al.

1994; Agertoft and Pedersen 1993; Kemp et al. 1989;

Melchor et al. 1993; Vidgren et al. 1983). Mouth

washing is effective in reducing systemic absorption

(Selroos and Halme 1991).

Metered-dose

inhaler (MDI)

Beta2-agonists

Corticosteroids

Cromolyn sodium 

and nedocromil

Anticholinergics

Breath-actuated

MDI

Beta2-agonists

Dry powder

inhaler (DPI)

Beta2-agonists

Corticosteroids

>5 years

>5 years

Actuation during a slow

(30 L/min or 3-5 seconds)

deep inhalation, followed

by 10-second breathholding.

Under laboratory 

conditions, open-mouth

technique (holding MDI

2 inches away from open

mouth) enhances delivery

to the lung. However, it

has not consistently been

shown to enhance clinical 

benefit compared to

closed-mouth technique

(closing lips around MDI

mouthpiece).

Slow (30 L/min 

or 3-5 seconds) inhalation

followed by 10-second

breath-holding.

Rapid (60 L/min 

or 1-2 seconds), deep

inhalation. Minimally

effective inspiratory flow

is device dependent.

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69

FIGURE 3-3. AEROSOL DELIVERY DEVICES (CONTINUED)

Device/Drugs Population Optimal Technique* Therapeutic Issues

Easier to use than MDI alone. With a face mask,

enables MDI to be used with small children (Everard et

al. 1992; Connett et al. 1993). Simple tubes do not

obviate coordinating actuation and inhalation. Bulky.

Output may be reduced in some devices after cleaning.

The larger volume spacers/holding chambers (>600 cc)

may increase lung delivery over MDI alone in patients

with poor MDI technique. The effect of a spacer/holding

chamber on output from an MDI is dependent on both

MDI and spacer type; thus data from one combination

should not be extrapolated to all others (Ahrens et al.

1995; Kim et al. 1987).

Spacers/holding chambers decrease oropharyngeal deposition and will reduce potential system absorption of

inhaled corticosteroid preparations that have higher oral

bioavailability (Newman et al. 1984; Brown et al. 1990;

Lipworth 1995; Selroos and Halme 1991). Spacers/

holding chambers are recommended for all patients on

medium-to-high doses of inhaled corticosteroids.

May be as effective as nebulizer in delivering high doses

of beta2-agonists during severe exacerbations.

Less dependent on patient coordination or cooperation.

Delivery method of choice for cromolyn in children and

for high-dose beta2-agonists and anticholinergics in

moderate-to-severe exacerbations in all patients.

Expensive; time consuming; bulky; output is device

dependent; and there are significant internebulizer and

intranebulizer output variances.

* See figure 4-3 for description of MDI and DPI techniques.

Sources: Agertoft and Pedersen 1993; Ahrens et al. 1995; Brown et al. 1990; Connett et al. 1993; Higgins et al. 1987; Crompton and

Duncan 1989; Everard et al. 1992; Fuglsang and Pedersen 1986; Goren et al. 1994; Kemp et al. 1989; Kesten et al. 1994; Kim et al. 1987;

Lipworth 1995; Melchor et al. 1993; Newman et al. 1981, 1984, 1991; O’Callaghan et al. 1994; Pedersen et al. 1990; Pedersen and

Mortensen 1990; Prahl and Jenson 1987; Rossing et al. 1980; Ruggins et al. 1993; Schecker et al. 1993; Selroos and Halme 1991; Selroos et

al. 1995; Thorsson et al. 1994; Vidgren et al. 1983.

Spacer/holding 

chamber

Nebulizer

Beta2-agonists

Cromolyn

Anticholinergics

Corticosteroids

>4 years

<_4 years with 

face mask

<_2 years

Patients of any

age who cannot use MDI

with spacer/

holding chamber or spacer

and face mask 

(e.g., during 

exacerbations)

Slow (30 L/min or 3-5

seconds) inhalation 

or tidal breathing 

immediately following 

actuation.

Actuation only once into

spacer/holding chamber

per inhalation (O’Callaghan et al. 1994). If face

mask is used, allow 3-5

inhalations per actuation

(Everard et al. 1992).

Slow tidal breathing with

occasional deep breaths.

Tightly fitting face mask

for those unable to use

mouthpiece.

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70

outcome indices. Although regularly scheduled use of

beta2-agonists in mild asthma produced no harmful

effects in a 4-month period, it also produced no demonstrable benefits (Drazen et al. 1996). Similar findings

were noted in studies with moderate asthma (D’Alonzo

et al. 1994; Pearlman et al. 1992). Based on these and

other observations (Cockcroft et al. 1993; van Schayck

et al. 1991; O’Connor et al. 1992; Mullen et al. 1993;

Ernst et al. 1993; Suissa et al. 1994), the regularly

scheduled, daily use of short-acting beta2-agonists is not 

generally recommended.

The frequency of beta2-agonist use can be clinically

useful as a barometer of disease activity because

increasing use of beta2-agonists has been associated

with increased risk for death or near death in patients

with asthma (Spitzer et al. 1992). The use of more

than one beta2-agonist 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 asthma control (Spitzer et al. 1992). 

Long-Acting Inhaled Beta2-Agonists

Long-acting beta2-agonists have several beneficial

clinical properties. They attenuate EIB for longer

time periods than do short-acting beta2-agonists

(Green and Price 1992; Henriksen et al. 1992) and

improve nocturnal asthma symptoms (Fitzpatrick et

al. 1990; Maesen et al. 1990). Recent studies suggest

that for patients with inadequate symptom control

who are receiving low-to-medium doses of inhaled

corticosteroids, it may be more beneficial to add 

salmeterol than to increase the dose of inhaled 

corticosteroids (Greening et al. 1994; Woolcock et al.

1996). Furthermore, in one study, salmeterol resulted

in statistically significant increases in overall quality

of life (Juniper et al. 1995) although the clinical significance of the reported differences is not certain. 

Several studies report that patients do not appear to

develop a tolerance to the bronchodilator action of

salmeterol even after months of regular treatment

(D’Alonzo et al. 1994; Lotvall et al. 1992; Pearlman

et al. 1992; Ullman et al. 1990). In contrast, in

bronchoprovocation studies following chronic administration of either short-acting or long-acting beta2-

agonists, a decrease was demonstrated in the bronchoprotective effect against exercise (Ramage et al.

1994), allergen (Cockcroft et al. 1993, 1995; Bhagat

et al. 1996), and methacholine (Bhagat et al. 1996;

Cheung et al. 1992). However, the bronchoprotective

effect over time, although diminished, was still significantly greater than placebo. Thus, the clinical

importance of the reported decrease in bronchoprotective effect remains uncertain (McFadden 1995).

Following the introduction of salmeterol into clinical

practice, case reports of sudden severe attacks of asthma

(Clark et al. 1993) raised concerns that in certain asthma patients, under certain conditions, the use of salmeterol may cause a sudden worsening of symptoms and

possibly death. A recent randomized study in England

compared more than 16,000 patients who received regular salmeterol for a 16-week period with more than

8,000 patients receiving regular (qid) albuterol therapy.

The study found more deaths in the salmeterol group;

however, the differences did not reach statistical significance (Castle et al. 1993). Nor did a prescription-event

monitoring survey demonstrate a statistically significant

difference in deaths (Mann et al. 1996). Several large

studies have demonstrated that, overall, patients taking

salmeterol do not experience an increase in the frequency of exacerbations (Britton et al. 1992; Lundback et al.

1993; Greening et al. 1994; Pearlman et al. 1992;

Woolcock et al. 1996). There are ongoing longitudinal

studies to determine if there might be risk for special

populations. The potential for patients to incorrectly

use salmeterol as a quick-relief medication warrants special attention by the clinician and appropriate patient

education. Based on current information, long-acting

inhaled beta2-agonists should be used only in conjunction with anti-inflammatory medication. When added

to inhaled corticosteroids, long-acting inhaled beta2-

agonists are helpful long-term-control therapy.

Component 3: Pharmacologic Therapy

KEY POINTS: LONG-ACTING INHALED

BETA 2 -AGONISTS

■ Long-acting beta2-agonists (salmeterol) can be

beneficial to patients when added to inhaled

corticosteroid therapy, especially to control

nighttime symptoms (Greening et al. 1994;

Woolcock et al. 1996). Daily use of long-acting beta2-agonists should generally not exceed

84 mcg (salmeterol; four puffs). 

■ Salmeterol is not to be used for treatment of acute 

symptoms or exacerbations.

■ Patient education regarding correct use of salmeterol is critical.

■ Patients should be instructed not to stop antiinflammatory therapy while taking salmeterol

even though their symptoms may significantly

improve.

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Inhaled Corticosteroids

Inhaled corticosteroids are the most effective longterm therapy available for patients with persistent

asthma. In general, inhaled corticosteroids are well

tolerated and safe at the recommended dosages

(Barnes 1995; van Essen-Zandvliet et al. 1992;

Tinkelman et al. 1993). Systemic effects have been

identified, particularly at high doses (see figure 3-5b 

for a definition of high-, medium-, and low-dose

inhaled corticosteroids), but their clinical significance remains unclear. Furthermore, there may be

interindividual variations in dose-response effects,

and thus some patients may 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

inhaled corticosteroids, especially at low and medium doses.

Local Adverse Effects

Oral candidiasis (thrush) is one of the most common

adverse effects of inhaled corticosteroids. Positive

throat cultures of Candida can be identified in about

45 to 58 percent of patients, whereas clinical thrush is

diagnosed in only 0 to 34 percent of patients (Rinehart et al. 1975; Toogood et al. 1980; Shaw and

Edmunds 1986). With lower dosages of inhaled corticosteroids, 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/holding chamber to reduce the incidence

of colonization and clinical thrush, rinse mouth with

water after inhalation (Selroos and Halme 1991), and

administer inhaled corticosteroids less frequently 

(bid vs. qid). Topical or oral antifungal agents should

be used to treat active infections.

Dysphonia is reported in 5 to 50 percent of patients

using inhaled corticosteroids and is associated with

vocal stress and increasing dosages of inhaled 

corticosteroids (Toogood et al. 1980). Prevention

and treatment: Use a spacer/holding chamber, 

temporarily reduce dosage, or rest for vocal stress.

Reflex cough and bronchospasm can be reduced by slower

rates of inspiration and/or use of a spacer/holding

chamber or pretreatment with an inhaled beta2-

agonist. There is no convincing evidence that the

routine use of an inhaled beta2-agonist prior to 

each dose of inhaled corticosteroids increases 

intrapulmonary delivery of the inhaled corticosteroid

or reduces dosage requirement.

Systemic Adverse Effects

Linear Growth. The potential effects of inhaled 

corticosteroids on children’s growth are important

because the drugs are more likely to be used for

longer periods of time, although it is recognized that

poorly controlled asthma itself may result in retarded

linear growth. Growth in children with asthma who

have not received any form of corticosteroid therapy

may be influenced by concomitant atopy, asthma

severity, and being male, among other factors

(Kamada and Szefler 1995; Allen 1996). Indeed,

childhood asthma appears to be associated with

KEY POINTS: INHALED 

CORTICOSTEROIDS

■ Inhaled corticosteroids are the most effective

long-term therapy available for mild, moderate, or severe persistent asthma; in general,

inhaled corticosteroids are well tolerated and

safe at the recommended dosages.

■ The potential but small risk of adverse events

from the use of inhaled corticosteroids is well

balanced by their efficacy.

■ To reduce the potential for adverse effects, 

the following measures are recommended:

— Administer inhaled corticosteroids with 

spacers/holding chambers.

— Advise patients to rinse their mouths 

(rinse and spit) following inhalation.

— Use the lowest possible dose of inhaled 

corticosteroid to maintain control.

— To maintain control of asthma (especially

for nocturnal symptoms), consider adding a

long-acting inhaled beta2-agonist to a lowto-medium dose of inhaled corticosteroid

rather than using a higher dose of inhaled

corticosteroid. 

— For children, monitor growth (see box on

page 72).

— For postmenopausal women, consider supplements of calcium (1,000 to 1,500 mg

per day) and vitamin D (400 units a day).

Estrogen replacement therapy, where

appropriate, may be considered for patients

on doses that exceed 1,000 mcg of inhaled

corticosteroid a day.

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72

delayed maturation and a longer period of reduced

growth prior to puberty. Although this could be

viewed as growth suppression, these delays do not

appear to compromise the attainment of final predicted adult heights (Balfour-Lynn 1986; Allen 1996).

Because of these numerous confounding factors, 

evaluating the effects of systemic or inhaled corticosteroids on growth in children with asthma has been

challenging and has led to contradictory findings.

A few studies of children with asthma have identified

some growth delay in those treated with inhaled corticosteroids, suggesting that some caution may be

prudent until this important issue can be studied further. A 1-year controlled trial comparing children

with mild-to-moderate asthma receiving either

inhaled beclomethasone (400 mcg per day, administered without a spacer/holding chamber) or oral theophylline demonstrated slower growth in children

receiving beclomethasone (Tinkelman et al. 1993).

In a placebo-controlled, community-based 7-month

study of 7- to 9-year-old children to determine the

effect on growth during treatment with beclomethasone at 400 mcg/day, growth was significantly

decreased in both males and females, and there was

no evidence of catchup growth during a 5-month

washout period (Doull et al. 1995). However, the

results of this short-term study may not reflect effects

on long-term growth.

A recent meta-analysis of the influence of inhaled

beclomethasone in the attainment of expected adult

height did not find any significant adverse effects

regardless of dose, duration of asthma, or disease

severity (Allen et al. 1994). An uncontrolled followup study (mean duration of 2.7 years, range of 1

to 5 years) of prepubertal children with moderate

asthma found no effect of inhaled budesonide (800

mcg mean daily dose) on long-term growth (Ninan

and Russell 1992). A majority of studies do not

demonstrate a negative effect on growth with dosages

of 400 to 800 mcg a day (Wolthers 1996; Kamada et

al. 1996; Kamada and Szefler 1995; Barnes and

Pederson 1993). 

Bone Metabolism/Osteoporosis. The few published

observations regarding the effect of inhaled corticosteroids on bone metabolism and osteoporosis are

complicated by oral corticosteroid use and small

patient populations (Jennings et al. 1991a, 1991b;

Toogood et al. 1991). The effects of inhaled

corticosteroid on markers of skeletal metabolism—

serum osteocalcin, serum alkaline phosphatase, and

urinary hydroxyproline:creatinine ratio—are equivocal

(Hodsman et al. 1991; Jennings et al. 1991a; Ali et

al. 1991). The clinical implications in terms of risk 

of osteoporosis and fracture after long-term use of

inhaled corticosteroids are still unknown (Jennings et

al. 1991b; Pouw et al. 1991). Although low and

medium dosages of inhaled corticosteroids appear to

have no major adverse effects on any clinically important measure of bone metabolism (Toogood et al.

1991, 1995), a dose-dependent, yet significant,

reduction in bone mineral content of subjects with

asthma has been associated with inhaled corticosteroid

use (Packe et al. 1992; Puolijoki et al. 1992; Toogood

Component 3: Pharmacologic Therapy

KEY POINTS: INHALED

CORTICOSTEROIDS AND LINEAR

GROWTH IN CHILDREN

■ The potential risks of inhaled corticosteroids

are well balanced by their benefits.

■ Growth rates are highly variable in children.

Short-term evaluations may not be predictive

of attaining final adult height.

■ Poorly controlled asthma may delay growth in

children.

■ In general, children with asthma tend to have

longer periods of reduced growth rates prior to

puberty (males > females).

■ The potential for adverse effects on linear

growth from inhaled corticosteroids appears to

be dose dependent. In treating children with

mild-to-moderate persistent asthma, medium-dose

inhaled corticosteroid 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 inhaled 

corticosteroids have greater potential for

growth suppression.

■ Use of high doses of inhaled corticosteroids

with children with severe persistent asthma has

significantly less potential for having an

adverse effect on linear growth than oral 

systemic corticosteroids.

■ A majority of studies of the use of inhaled 

corticosteroids by children have not demonstrated an effect on growth, but a few have

identified growth delay. Some caution (e.g.,

monitoring growth, stepping down therapy

when possible) is suggested while this issue is

studied further.

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73

et al. 1988). Elderly female patients may be more at

risk due to preexisting osteoporosis, previous use of

oral corticosteroids, a sedentary lifestyle, and the normal changes of estrogen in aging that affect calcium

utilization. However, the risk of uncontrolled asthma, which may unnecessarily limit the patient’s

mobility and activities, must be weighed against 

the limited risks of using inhaled corticosteroids. 

Prevention and treatment: Concurrent treatment

with calcium supplements and vitamin D (and estrogen replacement where appropriate) is reasonable.

Disseminated Varicella. Although high doses of

inhaled corticosteroids theoretically present risks similar to those of systemic corticosteroids, the reports of

disseminated varicella in patients receiving only

inhaled corticosteroids are rare, causality is not clear,

and there is no evidence that recommended doses of

inhaled corticosteroids are immunosuppressive. Cases

have been reported of children with severe persistent

asthma on 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 with Strongyloides or tuberculosis

who take high doses of systemic corticosteroids.

Prevention and treatment: Children who require

episodic therapy with systemic corticosteroids who

have not had clinical varicella should receive the varicella vaccine. 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 zoster immunoglobulin and therapy with

oral acyclovir. Should they develop clinical varicella,

intravenous acyclovir with or without zoster immunoglobulin should be given.

Dermal thinning and increased ease of skin

bruising have been observed in elderly subjects treated with inhaled corticosteroids. The effect is dose

dependent, but the threshold dose is variable

(Capewell et al. 1990).

Hypothalamic Pituitary Axis (HPA) Function.

The issue of inhaled corticosteroid effects on HPA

function is complex and requires further study.

Several studies indicate that low-to-medium doses of

inhaled corticosteroids do not appear to have significant effects on HPA function (Doull et al. 1995;

Goldstein and Konig 1983). However, some studies

showed that, compared with placebo, both beclomethasone and budesonide reduced the 24-hour urinary cortisol excretion even in doses as low as 400 to

500 mcg daily (Tabachnik and Zadik 1991; Prahl

1991). At higher doses, there appears to be a dosedependent effect on different measures of HPA function (Kamada et al. 1996; Brown et al. 1993).

Fluticasone caused greater adrenal suppression at

doses of 400 to 2,000 mcg than budesonide in equivalent doses (Clark et al. 1996; Boorsma et al. 1996).

The clinical significance, if any, of these findings 

is not known.

Cataracts. Although cataracts are a documented

adverse effect of systemic corticosteroids, there

appears to be no association between inhaled corticosteroids and posterior subcapsular cataracts in adults

(Toogood et al. 1993) or children (Simons et al. 1993;

Rooklin et al. 1979).

Glucose Metabolism. In a study of children, inhaled

corticosteroids at dosages from 400 to 1,000 mcg/day

(budesonide) failed to affect fasting glucose or glycated hemoglobin (Turpeinen et al. 1991). 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.

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1993;92:783-9.

Schwartz HJ, Blumenthal M, Brady R, et al. A comparative

study of the clinical efficacy of nedocromil sodium and

placebo. Chest 1996;109:945-52.

Sears MR, Taylor DR, Print CG, et al. Regular inhaled betaagonist treatment in bronchial asthma. Lancet

1990;336:1391-6.

Selroos O, Pietinalho A, Lofroos A, Riska H. Effect of early

vs. late intervention with inhaled corticosteroids in asthma. Chest 1995;108:1228-34.

Selroos O, Halme M. Effect of a volumatic spacer and mouth

rinsing on systemic absorption of inhaled corticosteroids

from a metered dose inhaler and dry powder inhaler.

Thorax 1991;46:891-4.

Shaw NJ, Edmunds AT. Inhaled beclomethasone and oral

candidiasis. Arch Dis Child 1986;61:788-90.

Shiner RJ, Nunn AJ, Chung KF, Gedder DM. Randomised,

double-blind, placebo-controlled trial of methotrexate in

steroid-dependent asthma. Lancet 1990;336:137-40.

Silk HJ, Guay-Woodford L, Perez-Atayde AR, Geha RS, Broff

MD. Fatal varicella in steroid-dependent asthma. J

Allergy Clin Immunol 1988;81:47-51.

Simons FE, Persaud MP, Gillespie CA, Cheang M, Shuckett

EP. Absence of posterior subcapsular cataracts in young

patients treated with inhaled glucocorticoids. Lancet

1993;342:776-8.

Spector SL, Smith LJ, Glass M. Effects of 6 weeks of therapy

with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. Am J

Respir Crit Care Med 1994;150:618-23.

Spitzer WO, Suissa S, Ernst P, et al. The use of beta-agonist

and the risk of death and near death from asthma. N

Engl J Med 1992;326:501-6.

Storms WW, Bodman SF, Nathan RA, et al. Use of ipratropium bromide in asthma. Am J Med 1986;81:61-6.

Suissa S, Ernst P, Boivin JP, et al. A cohort analysis of excess

mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med 1994;149:604-10.

Sullivan P, Bekir S, Jaffar Z, Page C, Jeffrey P, Costello J.

Anti-inflammatory effects of low-dose oral theophylline

in atopic asthma. Lancet 1994;343:1006-8.

Svendsen UG, Jorgensen H. Inhaled nedocromil sodium as

additional treatment to high dose inhaled corticosteroids

in the management of bronchial asthma. Eur Respir J

1991;4:992-9.

Tabachnik E, Zadik Z. Diurnal cortisol secretion during therapy with inhaled beclomethasone dipropionate in children with asthma. J Pediatr 1991;118:294-7.

Taylor IK, O’Shaughensessy KM, Fuller RW, Dollery CT.

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Tinkelman DG, Reed CE, Nelson HS, Offord KP. Aerosol

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treatment of asthma. J Allergy Clin Immunol

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with doubling of the dose of inhaled steroid. Am J Respir

Crit Care Med 1996;153:1481-8.

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Regular formoterol treatment in mild asthma. Effect on

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The Medications

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81

KEY RECOMMENDATIONS FOR 

MANAGING ASTHMA LONG TERM

■ Persistent asthma is most effectively controlled

with daily long-term-control medication, 

specifically, anti-inflammatory therapy.

■ A stepwise approach to pharmacologic therapy is

recommended to gain and maintain control of

asthma:

— The amount and frequency of medication is

dictated by asthma severity and directed

toward suppression of airway inflammation.

— Therapy should be initiated at a higher level

than the patient’s step of severity at the onset

to establish prompt control and then stepped

down.

— Continual monitoring is essential to ensure

that asthma control is achieved.

— Step-down therapy is essential to identify the

minimum medication necessary to maintain

control.

■ Regular followup visits (at 1- to 6-month intervals) are essential to ensure that control is maintained and the appropriate step down in therapy is 

considered.

■ Therapeutic strategies should be considered in 

concert with clinician-patient partnership strategies; education of patients is essential for achieving optimal pharmacologic therapy.

■ At each step, patients should be advised to avoid

or control allergens, irritants, or other factors that

make the patient’s asthma worse.

■ Referral to an asthma specialist for consultation or

comanagement of the patient is recommended if

there are difficulties achieving or maintaining 

control of asthma or if the patient requires step 4

care (see component 1-Initial Assessment and

Diagnosis). Referral may be considered if the

patient requires step 3 care. For infants and

young children, referral is recommended if the

patient requires step 3 or 4 care and should be

considered if the patient requires step 2 care.

STEPWISE APPROACH FOR 

MANAGING ASTHMA IN ADULTS 

AND CHILDREN OLDER THAN 

5 YEARS OF AGE

The aim of asthma therapy is to maintain control of

asthma with the least amount of medication and

hence minimal risk for adverse effects. Control of

asthma is defined as:

■ Preventing chronic and troublesome symptoms

(e.g., coughing or breathlessness in the night, in

the early morning, or after exertion)

■ Maintaining (near) “normal” pulmonary function

■ Maintaining normal activity levels (including 

exercise and other physical activity)

■ Preventing recurrent exacerbations of asthma and

minimizing the need for emergency department

visits or hospitalizations

■ Providing optimal pharmacotherapy with minimal

or no adverse effects

■ Meeting patients’ and families’ expectations of and

satisfaction with asthma care

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 this control. This is illustrated in figures 3-4a and 3-4b. Figures 3-5a and 

3-5d present usual medication dosages for therapy.

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 prevent exacerbations. Recommendations in the stepwise approach

to therapy are based on the Expert Panel’s review of

the literature (see component 3-Medications) and the

Expert Panel’s experience and opinion.

Pharmacologic Therapy:

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82

two approaches—the traditional step-up care (low

dose to high) vs. step-down care (initial high dose to

low). However, there is evidence supporting a more

aggressive initial approach. First, asthma symptoms

and altered pulmonary function are related to the

level of ongoing airway inflammation. Suppression of

airway inflammation is more likely to occur with

higher doses of corticosteroids. Furthermore, studies

indicate that the dose of inhaled or systemic corticosteroids can be reduced and the clinical benefits sustained once the disease is controlled (Haahtela et al.

1994; Agertoft and Pedersen 1994). A preliminary

observation in a retrospective study of children suggests that initiating inhaled corticosteroids early in

the course of the disease results in better clinical benefit and less accumulated corticosteroid dose over the

long term (Agertoft and Pedersen 1994). Therefore,

it is conceivable that a more aggressive approach in

initial therapy will more rapidly suppress airway

inflammation, restore pulmonary function, and allow

for eventual asthma control at lower doses of antiinflammatory therapy.

Continual monitoring is essential to ensure that

asthma control is achieved. Control is indicated by,

for example, peak expiratory flow (PEF) values indicating less than 10 to 20 percent variability or PEF

consistently greater than 80 percent of the patient’s

personal best, minimal symptoms, minimal need for

short-acting inhaled beta2-agonist, absence of 

nighttime awakenings, and no activity limitations.

If control is not achieved with initial therapy

(e.g., within 1 month), the pharmacologic management plan, and possibly the diagnosis, should

be reevaluated (see Pharmacologic Steps, page 87).

Maintaining Control of Asthma

Once control is achieved and sustained for several

weeks or months, a reduction in pharmacologic

therapy—a step down—is appropriate and helpful to identify the minimum therapy for maintaining control. Reduction in therapy should be

gradual because asthma can deteriorate at a highly

variable rate and intensity.

In general, the last medication added to the medical

regimen should be the first medication reduced.

Although guidelines for the rate of reduction and

intervals for evaluation have not been established, the

opinion of the Expert Panel is that the dose of

inhaled corticosteroids may be reduced about 

Component 3: Pharmacologic Therapy

Gaining Control of Asthma

The clinician must judge individual patient needs

and circumstances to determine at what step to

initiate therapy. There are two appropriate

approaches to gaining control of asthma:

■ Start treatment at the step appropriate to the

severity of the patient’s disease at the time of 

evaluation and gradually step up if control is 

not achieved.

OR

■ At the onset, administer therapy at a level higher

than the patient’s step of severity to gain rapid 

control. This can be accomplished by either a short

course of systemic corticosteroids (see figure 3-5a)

along with inhaled corticosteroids or initiating a

medium-to-high dose of inhaled corticosteroids.

Once control is gained, step down the therapy.

The two approaches are illustrated by the solid and

broken lines in the following diagram.

The more aggressive approach of gaining prompt

control with a higher level of therapy is preferred, in the opinion of the Expert Panel. At

present, there are no studies directly comparing the

STEP 1

STEP 2

STEP 4

1 STEP 3 2

TWO APPROACHES TO GAINING 

CONTROL OF ASTHMA: (1) START WITH

HIGH-DOSE THERAPY AND 

STEP DOWN OR (2) GRADUALLY 

STEP UP THERAPY

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Managing Asthma Long Term

83

FIGURE 3-4a. STEPWISE APPROACH FOR MANAGING ASTHMA IN ADULTS

AND CHILDREN OLDER THAN 5 YEARS OF AGE

* The presence of one of the features of severity is sufficient to place a patient in that category. An individual should be assigned to the

most severe grade in which any feature occurs. The characteristics noted in this figure are general and may overlap because asthma is

highly variable. Furthermore, an individual’s classification may change over time.

** Patients at any level of severity can have mild, moderate, or severe exacerbations. Some patients with intermittent asthma experience

severe and life-threatening exacerbations separated by long periods of normal lung function and no symptoms.

Goals of Asthma Treatment

■ Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the night, in the early 

morning, or after exertion)

■ Maintain (near) “normal” pulmonary function

■ Maintain normal activity levels (including exercise and other physical activity)

■ Prevent recurrent exacerbations of asthma and minimize the need for emergency department visits or 

hospitalizations

■ Provide optimal pharmacotherapy with minimal or no adverse effects

■ Meet patients’ and families’ expectations of and satisfaction with asthma care

Clinical Features Before Treatment*

Symptoms** Nighttime Symptoms Lung Function

STEP 4 ■ Continual symptoms Frequent ■ FEV1 or PEF <60% predicted _

Severe Persistent ■ Limited physical activity ■ PEF variability >30%

■ Frequent exacerbations

STEP 3 ■ Daily symptoms >1 time a week ■ FEV1 or PEF >60% –<80%

Moderate Persistent ■ Daily use of inhaled short-acting predicted

beta2-agonist ■ PEF variability >30%

■ Exacerbations affect activity

■ Exacerbations >_2 times a week; 

may last days

STEP 2 ■ Symptoms >2 times a week but >2 times a month ■ FEV1 or PEF >_ 80% predicted

Mild Persistent <1 time a day ■ PEF variability 20–30%

■ Exacerbations may affect activity

STEP 1 ■ Symptoms <2 times a week _ <2 times a month _ ■ FEV1 or PEF >_80% predicted

Mild Intermittent ■ Asymptomatic and normal PEF ■ PEF variability <20%

between exacerbations

■ Exacerbations brief (from a few 

hours to a few days); intensity 

may vary

Classify Severity of Asthma

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84

Component 3: Pharmacologic Therapy

Long-Term Control

Daily medications:

■ Anti-inflammatory: inhaled 

corticosteroid (high dose)

AND

■ Long-acting bronchodilator:

either long-acting inhaled

beta2-agonist, sustainedrelease theophylline, or 

long-acting beta2-agonist

tablets

AND

■ Corticosteroid tablets or syrup

long term (make repeat

attempts to reduce systemic

steroids and maintain control

with high dose inhaled steroids)

Daily medication:

■ Either

Anti-inflammatory: inhaled 

corticosteroid (medium 

dose)

OR

Inhaled corticosteroid 

(low-medium dose) and add 

a long-acting bronchodilator,

especially for nighttime

symptoms; either long-acting

inhaled beta2-agonist, 

sustained-release thephylline,

or long-acting beta2-agonist

tablets.

■ If needed

Anti-inflammatory: inhaled

corticosteroids (mediumhigh dose)

AND

Long-acting bronchodilator, especially for nighttime

symptoms; either long-acting

inhaled beta2-agonist,

sustained-release theophylline, 

or long-acting beta2-agonist

tablets.

Quick Relief

■ Short-acting bronchodilator:

inhaled beta2-agonists as

needed for symptoms.

■ Intensity of treatment will

depend on severity of 

exacerbation; see component 

3-Managing Exacerbations.

■ Use of short-acting inhaled

beta2-agonists on a daily basis,

or increasing use, indicates the

need for additional longterm-control therapy.

■ Short-acting bronchodilator:

inhaled beta2-agonists as

needed for symptoms.

■ Intensity of treatment will

depend on severity of 

exacerbation; see component 

3-Managing Exacerbations.

■ Use of short-acting inhaled

beta2-agonists on a daily basis,

or increasing use, indicates the

need for additional longterm-control therapy.

Education

Steps 2 and 3 actions plus:

■ Refer to individual

education/counseling

Step 1 actions plus:

■ Teach self-monitoring

■ Refer to group education if

available

■ Review and update selfmanagement plan

STEP 4

Severe

Persistent

STEP 3

Moderate

Persistent

FIGURE 3-4b. STEPWISE APPROACH FOR MANAGING ASTHMA IN ADULTS 

AND CHILDREN OLDER THAN 5 YEARS OF AGE: TREATMENT APreferred treatments are in bold print.

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Managing Asthma Long Term 

85

Long-Term Control

One daily medication:

■ Anti-inflammatory: either

inhaled corticosteroid (low

doses) or cromolyn or

nedocromil (children usually

begin with a trial of cromolyn

or nedocromil).

■ Sustained-release theophylline

to serum concentration of 5-15

mcg/mL is an alternative, but

not preferred, therapy.

Zafirlukast or zileuton may

also be considered for patients 

>_12 years of age, although

their position in therapy is not

fully established.

■ No daily medication needed.

Quick Relief

■ Short-acting bronchodilator: 

inhaled beta2-agonists as

needed for symptoms.

■ Intensity of treatment 

will depend on severity of

exacerbation; see component

3-Managing Exacerbations.

■ Use of short-acting inhaled

beta2-agonists on a daily basis,

or increasing use, indicates the

need for additional long-termcontrol therapy.

■ Short-acting bronchodilator:

inhaled beta2-agonists as

needed for symptoms.

■ Intensity of treatment will

depend on severity of 

exacerbation; see component

3-Managing Exacerbations.

■ Use of short-acting inhaled

beta2-agonists more than 

2 times a week may indicate

the need to initiate long-termcontrol therapy.

Education

Step 1 actions plus:

■ Teach self-monitoring

■ Refer to group education if

available

■ Review and update selfmanagement plan

■ Teach basic facts about asthma

■ Teach inhaler/spacer/holding

chamber technique

■ Discuss roles of medications

■ Develop self-management plan

■ Develop action plan for when

and how to take rescue actions,

especially for patients with a

history of severe exacerbations

■ Discuss appropriate environmental control measures to

avoid exposure to known 

allergens and irritants

(See component 4.)

STEP 2

Mild Persistent

STEP 1

Mild

Intermittent

NOTE:

■ The stepwise approach presents general guidelines to assist clinical decisionmaking; it is not intended to be a specific prescription. Asthma is highly

variable; clinicians should tailor specific medication plans to the needs and circumstances of individual patients.

■ Gain control as quickly as possible; then decrease treatment to the least medication necessary to maintain control. Gaining control may be accomplished by either

starting treatment at the step most appropriate to the initial severity of the condition or starting at a higher level of therapy (e.g., a course of systemic corticosteroids or higher dose of inhaled corticosteroids).

■ A rescue course of systemic corticosteroids may be needed at any time and at any step.

■ Some patients with intermittent asthma experience severe and life-threatening exacerbations separated by long periods of normal lung function and no symptoms.

This may be especially common with exacerbations provoked by respiratory infections. A short course of systemic corticosteroids is recommended.

■ At each step, patients should control their environment to avoid or control factors that make their asthma worse (e.g., allergens, irritants); this requires specific

diagnosis and education.

■ Referral to an asthma specialist for consultation or comanagement is recommended if there are difficulties achieving or maintaining control of asthma or if the patient

requires step 4 care. Referral may be considered if the patient requires step 3 care (see also component 1-Initial Assessment and Diagnosis).

FIGURE 3-4b. STEPWISE APPROACH FOR MANAGING ASTHMA IN ADULTS 

AND CHILDREN OLDER THAN 5 YEARS OF AGE: TREATMENT (CONTINUED)

Step down

Review treatment every 1 to 6 months; a gradual

stepwise reduction in treatment may be possible.

Step up

If control is not maintained, consider step up. First, review patient 

medication technique, adherence, and environmental control (avoidance

of allergens or other factors that contribute to asthma severity).

APreferred treatments are in bold print.

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86

Component 3: Pharmacologic Therapy

Medication Dosage Form Adult Dose Child Dose Comments

FIGURE 3-5a. USUAL DOSAGES FOR LONG-TERM-CONTROL MEDICATIONS

Inhaled Corticosteroids (see figures 3-5b and 3-5c)

Systemic Corticosteroids (Applies to all three systemic corticosteroids)

Methylprednisolone

Prednisolone

Prednisone

Cromolyn 

Nedocromil

Salmeterol

Sustained-Release 

Albuterol

Theophylline

Zafirlukast

Zileuton

2, 4, 8, 16, 32 mg

tablets

5mg tablets,

5mg/5 cc,

15mg/5 cc

1, 2.5, 5, 10, 20,

25 mg tablets; 

5 mg/cc, 5mg/5 cc

MDI 1 mg/puff

Nebulizer solution

20 mg/ampule

MDI 1.75 mg/puff

Inhaled

MDI 21 mcg/puff,

60 or 120 puffs

DPI 50 mcg/

blister

Tablet

4 mg tablet

Liquids, sustainedrelease tablets, and

capsules

20 mg tablet

300 mg tablet

600 mg tablet

■ 7.5–60 mg daily

in a single dose

or qod as needed

for control

■ Short-course

“burst”: 40–60

mg per day as

single or 2 divided doses for 

3–10 days

2–4 puffs tid-qid

1 ampule tid-qid

2–4 puffs bid-qid

2 puffs q 12 hours

1 blister q 12

hours

4 mg q 12 hours

Starting dose 10

mg/kg/day up to

300 mg max;

usual max 800

mg/day

40 mg daily 

(1 tablet bid)

2,400 mg daily

(two 300 mg

tablets or one 600

mg tablet, qid)

■ 0.25–2 mg/kg

daily in single

dose or qod as

needed for 

control

■ Short course

“burst”: 1–2

mg/kg/day, 

maximum 60

mg/day, for 3–10

days

1–2 puffs tid-qid

1 ampule tid-qid

1–2 puffs bid-qid

1–2 puffs q 12

hours

1 blister q 12

hours

0.3–0.6

mg/kg/day, not to

exceed 8 mg/day

Starting dose 10

mg/kg/day; usual

max:

■ <1 year of age:

0.2 (age in

weeks) + 5 =

mg/kg/day

■ >1 year of age: _

16 mg/kg/day

■ 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). If daily

doses are required, one study suggests

improved efficacy and no increase in

adrenal suppression when administered

at 3:00 p.m. (Beam et al. 1992).

■ 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.

■ One dose prior to exercise or allergen

exposure provides effective prophylaxis for 1–2 hours.

■ See cromolyn above.

■ May use one dose nightly for 

symptoms.

■ Should not be used for symptom

relief or for exacerbations.

■ 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 important. ■ See factors on page 87 that can affect

levels.

■ For zafirlukast, administration with

meals decreases bioavailability; take

at least 1 hour before or 2 hours after

meals.

■ For zileuton, monitor hepatic

enzymes (ALT).

Long-Acting Beta2-Agonists

Methylxanthines 

Leukotriene Modifiers

Cromolyn and Nedocromil

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Managing Asthma Long Term

87

25 percent every 2 to 3 months to the lowest dose

possible required to maintain control. It is likely

that most patients with persistent asthma will continue to benefit from daily medication to suppress

underlying airway inflammation. Patients may

relapse when inhaled corticosteroids are completely

discontinued (Waalkens et al. 1993).

Regular followup visits (at 1- to 6-month intervals) are essential. Clinicians need to assess whether

control of asthma has been maintained and if a step

down in therapy is appropriate. Clinicians also need

to monitor and review the daily self-management and

action plans, the medications, and the patient’s selfmanagement behaviors (e.g., inhaler and peak flow

monitoring techniques, actions to control factors that

aggravate their asthma) (see figure 4-2).

The Expert Panel recommends referral to an asthma specialist for consultation or comanagement

of the patient if: there are difficulties achieving

or maintaining control of asthma; immunotherapy is being considered; the patient requires step 

4 care (step 3 or 4 care for infants and young

children); or the patient has had a life-threatening exacerbation (see component 1-Initial Assessment and Diagnosis). Referral may be considered if a

patient requires step 3 care (or step 2 care for infants

and young children).

Pharmacologic Steps

The following recommendations for pharmacologic

therapy at different steps of asthma severity (see figures 3-4a and 3-4b) are intended to be general guidelines for making therapeutic decisions. They are not

Factor

Food

Diet

Systemic, febrile viral illness 

(e.g., influenza)

Hypoxia, cor pulmonale, and 

decompensated congestive heart 

failure, cirrhosis

Age

Phenobarbital, phenytoin, 

carbamazepine

Cimetidine

Macrolides: TAO, erythromycin, 

clarithromycin

Quinolones: ciprofloxacin, enoxacin,

pefloxacin

Rifampin

Ticlopidine

Smoking

Decreases Theophylline 

Concentrations

or delays absorption of some sustainedrelease theophylline (SRT) products

metabolism (high protein)

metabolism (1 to 9 years)

metabolism

metabolism

metabolism

Increases Theophylline 

Concentrations

rate of absorption (fatty foods) 

products

metabolism (high carbohydrate)

metabolism

metabolism

metabolism (<6 months, elderly)

metabolism

metabolism

metabolism

metabolism

Recommended Action

Select theophylline preparation that is

not affected by food.

Inform patients that major changes in

diet are not recommended while taking

theophylline.

Decrease theophylline dose according

to serum concentration level. Decrease

dose by 50 percent if serum concentration measurement is not available.

Decrease dose according to serum

concentration level.

Adjust dose according to serum 

concentration level.

Increase dose according to serum 

concentration level.

Use alternative H2 blocker 

(e.g., famotidine or ranitidine).

Use alternative antibiotic or adjust

theophylline dose.

Use alternative antibiotic or adjust

theophylline dose. Circumvent with

ofloxacin if quinolone therapy is

required.

Increase dose according to serum 

concentration level.

Decrease dose according to serum

concentration level.

Advise patient to stop smoking;

increase dose according to serum 

concentration level.

Factors Affecting Serum Theophylline Concentrations*

➞

➞

➞

➞

➞

➞

➞

➞

➞

➞

➞

➞ ➞ ➞

➞

FIGURE 3-5a. USUAL DOSAGES FOR LONG-TERM-CONTROL MEDICATIONS (CONTINUED)

* This list is not all-inclusive; for discussion of other factors, see package inserts.

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88

Component 3: Pharmacologic Therapy

FIGURE 3-5b. ESTIMATED COMPARATIVE DAILY DOSAGES FOR INHALED

CORTICOSTEROIDS

Adults

Drug

Beclomethasone dipropionate

42 mcg/puff

84 mcg/puff

Budesonide 

DPI: 200 mcg/dose

Flunisolide

250 mcg/puff

Fluticasone

MDI: 44, 110, 220 mcg/puff

DPI: 50, 100, 250 mcg/dose

Triamcinolone acetonide

100 mcg/puff

Children

Drug

Beclomethasone dipropionate

42 mcg/puff

84 mcg/puff

Budesonide 

DPI: 200 mcg/dose

Flunisolide

250 mcg/puff

Fluticasone

MDI: 44, 110, 220 mcg/puff

DPI: 50, 100, 250 mcg/dose

Triamcinolone acetonide

100 mcg/puff

Low Dose

168-504 mcg

(4-12 puffs — 42 mcg)

(2-6 puffs — 84 mcg)

200-400 mcg

(1-2 inhalations)

500-1,000 mcg

(2-4 puffs)

88-264 mcg

(2-6 puffs — 44 mcg) OR

(2 puffs — 110 mcg)

(2-6 inhalations — 50 mcg)

400-1,000 mcg

(4-10 puffs)

Low Dose

84-336 mcg

(2-8 puffs — 42 mcg)

(1-4 puffs — 84 mcg)

100-200 mcg

500-750 mcg

(2-3 puffs)

88-176 mcg

(2-4 puffs — 44 mcg)

(2-4 inhalations — 50 mcg)

400-800 mcg

(4-8 puffs)

Medium Dose

504-840 mcg

(12-20 puffs — 42 mcg)

(6-10 puffs — 84 mcg)

400-600 mcg

(2-3 inhalations)

1,000-2,000 mcg

(4-8 puffs)

264-660 mcg

(2-6 puffs — 110 mcg)

(3-6 inhalations — 100 mcg)

1,000-2,000 mcg

(10-20 puffs)

Medium Dose

336-672 mcg

(8-16 puffs — 42 mcg)

(4-8 puffs — 84 mcg)

200-400 mcg

(1-2 inhalations — 200 mcg)

1,000-1,250 mcg

(4-5 puffs)

176-440 mcg

(4-10 puffs — 44 mcg) OR

(2-4 puffs — 110 mcg)

(2-4 inhalations — 100 mcg)

800-1,200 mcg

(8-12 puffs)

High Dose

>840 mcg

(>20 puffs — 42 mcg)

(>10 puffs — 84 mcg)

>600 mcg

(>3 inhalations)

>2,000 mcg

(>8 puffs)

>660 mcg

(>6 puffs — 110 mcg) OR

(>3 puffs — 220 mcg)

(>6 inhalations — 100 mcg) OR

(>2 inhalations — 250 mcg)

>2,000 mcg

(>20 puffs)

High Dose

>672 mcg

(>16 puffs — 42 mcg)

(>8 puffs — 84 mcg)

>400 mcg

(>2 inhalations — 200 mcg)

>1,250 mcg

(>5 puffs)

>440 mcg

(>4 puffs — 110 mcg) OR 

(>2 puffs — 220 mcg)

(>4 inhalations — 100 mcg) OR 

(>2 inhalations — 250 mcg)

>1,200 mcg

(>12 puffs)

Note:

■ 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. 

■ See figure 3-5c for an explanation of the rationale used for the comparative dosages. The reference point for the range in the dosages for children is data

on the safety of inhaled corticosteroids in children, which, in general, suggest that the dose ranges are equivalent to beclomethasone dipropionate 200-400

mcg/day (low dose), 400-800 mcg/day (medium dose), and >800 mcg/day (high dose).

■ Some dosages may be outside package labeling.

■ Metered-dose inhaler (MDI) dosages are expressed as the actuater dose (the amount of drug leaving the actuater 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, all of which is

not available to the patient), which is used in many European countries and in some of the scientific literature. Dry powder inhaler (DPI) doses are

expressed as the amount of drug in the inhaler following activation.

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89

FIGURE 3-5c. ESTIMATED CLINICAL COMPARABILITY OF DOSES FOR INHALED

CORTICOSTEROIDS 

Data from in vitro and clinical trials suggest that the different inhaled corticosteroid preparations are not equivalent on a per

puff or microgram basis. However, it is not entirely clear what implications these differences have for dosing recommendations in clinical practice because there are few data directly comparing the preparations. Relative dosing for clinical comparability is affected by differences in topical potency, clinical effects at different doses, delivery device, and bioavailability. The

Expert Panel developed recommended dose ranges (see figure 3-5b) for different preparations based on available data and the following

assumptions and cautions about estimating relative doses needed to achieve comparable clinical effect.

■ Relative topical potency using human skin blanching

— The standard test for determining relative topical anti-inflammatory potency is the topical vasoconstriction (MacKenzie

skin blanching) test.

— The MacKenzie topical skin blanching test correlates with binding affinities and binding half-lives for human lung 

corticosteroid receptors (see table below) (Dahlberg et al. 1984; Högger and Rohdewald 1994).

— The relationship between relative topical anti-inflammatory effect and clinical comparability in asthma management is 

not certain. However, recent clinical trials suggest that different in vitro measures of anti-inflammatory effect correlate 

with clinical efficacy (Barnes and Pedersen 1993; Johnson 1996; Kamada et al. 1996; Ebden et al. 1986; Leblanc et al. 

1994; Gustafsson et al. 1993; Lundback et al. 1993; Barnes et al. 1993; Fabbri et al. 1993; Langdon and Capsey 

1994; Ayres et al. 1995; Rafferty et al. 1985; Bjorkander et al. 1982; Stiksa et al. 1982; Willey et al. 1982).

* Numbers are assigned in reference to dexamethasone, which has a value of “1” in the MacKenzie test. 

■ Relative doses to achieve similar clinical effects

— Clinical effects are evaluated by a number of outcome parameters (e.g., changes in spirometry, peak flow rates, 

symptom scores, quick-relief beta2-agonist use, frequency of exacerbations, airway responsiveness). 

— The daily dose and duration of treatment may affect these outcome parameters differently (e.g., symptoms and peak 

flow may improve at lower doses and over a shorter treatment time than bronchial reactivity) (van Essen-Zandvliet et 

al. 1992; Haahtela et al. 1991).

— Delivery systems influence comparability. For example, the DPI delivery device for budesonide delivers approximately 

twice the amount of drug to the airway as the MDI, thus enhancing the clinical effect (Thorsson et al. 1994; Agertoft 

and Pedersen 1993). 

— Individual patients may respond differently to different preparations, as noted by clinical experience.

Clinical trials comparing effects in reducing symptoms and improving peak expiratory flow demonstrate:

— BDP and BUD achieved comparable effects at similar microgram doses by MDI (Bjorkander et al. 1982; Ebden et al. 

1986; Rafferty et al. 1985).

— BDP achieved effects similar to twice the dose of TAA on a microgram basis.

— FP achieved effects similar to twice the dose of BDP and BUD via an MDI on a microgram basis (Gustaffson et al. 

1993; Fabbri et al. 1993; Barnes et al. 1993; Dahl et al. 1993; Ayres et al. 1995).

— BUD by dry powder inhaler achieved effects similar to twice the dose delivered by MDI, thus implying greater 

bronchial delivery by the delivery device (Thorsson et al. 1994; Agertoft and Pedersen 1993).

Medication

Beclomethasone dipropionate 

(BDP)

Budesonide (BUD)

Flunisolide (FLU)

Fluticasone propionate (FP)

Triamcinolone acetonide (TAA)

Topical Potency 

(Skin Blanching)*

600

980

330

1,200

330

Corticosteroid Receptor 

Binding Half-Life

7.5 hours

5.1 hours

3.5 hours

10.5 hours

3.9 hours

Receptor

Binding Affinity

13.5

9.4

1.8

18.0

3.6

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Component 3: Pharmacologic Therapy

FIGURE 3-5c. ESTIMATED CLINICAL COMPARABILITY OF DOSES FOR INHALED

CORTICOSTEROIDS (CONTINUED)

■ Bioavailability

Both the relative potency and the relative

bioavailability (systemic availability) determine

the potential for systemic activity of an inhaled

corticosteroid preparation. As illustrated here,

the bioavailability of an inhaled corticosteroid 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 to 30 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 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 liver 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 inhaled corticosteroids has been reported as: BDP 20%; 

FLU 21%; TAA 10.6%; BUD 11%; FP 1% (Chaplin et al. 1980; Check and Kaliner 1990; Clissold and 

Heel 1984; Davies 1993; Harding 1990; Heald et al. 1995; Martin et al. 1974; Mollman et al. 1985; Szefler 1991; 

Wurthwein andRohdewald 1990).

Although few clinical trials are available that compare systemic activity among preparations (Kamada et al. 1996), studies

have found:

— As suggested by one cross-over comparison study, BDP, FLU, and TAA appear to have equivalent dose-dependent 

systemic activity, as measured by 24-hour urinary free cortisol excretion (McCubbin et al. 1995).

— Inconsistent results comparing BDP and BUD. Some show equivalent systemic activity (Kamada et al. 1996; Prahl 

1991; Prahl et al. 1987); others show BUD having slightly less systemic activity than BDP (Barnes and 

Pedersen 1993; Pedersen and Fuglsang 1988; Bisgaard et al. 1988).

— FP had greater adrenal suppression at doses of 400 to 2,000 micrograms than BUD in equivalent microgram doses 

delivered by MDI and accompanied by mouth washing to prevent oral bioavailability (Clark et al. 1996). This 

confirms that there are differences in microgram potencies among preparations and that absorption through the lung 

can result in systemic activity.

Mouth

and 

Pharynx

Lung

Swallowed

fraction

Lung deposit

Absorption

from the gut

Active drug

from the gut

Absorption

from the lung

(A)

(B)

Inactivation

in the liver

“first pass”

GI tract

Liver

Systemic Circulation

Systemic Concentration = A+B

Adapted with permission from Barnes 1995.

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91

FIGURE 3-5d. USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS

Short-Acting Inhaled Beta2-Agonists

Albuterol

Albuterol HFA

Bitolterol

Pirbuterol

Terbutaline

Albuterol Rotahaler

Albuterol

Bitolterol

Anticholinergics

Ipratropium

Methylprednisolone

Prednisolone

Prednisone

MDI

90 mcg/puff, 200 puffs

90 mcg/puff, 200 puffs

370 mcg/puff, 300 puffs

200 mcg/puff, 400 puffs

200 mcg/puff, 300 puffs

DPI

200 mcg/capsule

Nebulizer solution

5 mg/mL (0.5%)

2 mg/mL (0.2%)

MDI

18 mcg/puff, 200 puffs

Nebulizer solution

.25 mg/mL (0.025%)

2, 4, 8, 16, 32 mg

tablets

5 mg tabs, 5 mg/5 cc, 

15 mg/5 cc

1, 2.5, 5, 10, 20, 

25 mg tabs; 5 mg/cc, 

5 mg/5 cc

■ 2 puffs 5 minutes

prior to exercise

■ 2 puffs tid-qid prn

1-2 capsules q 4-6

hours as needed and

prior to exercise

1.25-5 mg (.25-1 cc)

in 2-3 cc of saline q 

4-8 hours

0.5-3.5mg (.25-1 cc)

in 2-3 cc of saline q 4-

8 hours

2-3 puffs q 6 hours

0.25 mg q 6 hours

■ Short course “burst”:

40-60 mg/day as

single or 2 divided

doses for 3-10 days

■ 1-2 puffs 5 

minutes prior to

exercise

■ 2 puffs tid-qid prn

1 capsule q 4-6 hours

as needed and prior to

exercise

0.05 mg/kg (min 1.25

mg, max 2.5 mg) in

2-3 cc of saline q 4-6

hours

Not established

1-2 puffs q 6 hours

0.25-0.5 mg q 6 hours

■ Short course “burst”:

1-2 mg/kg/day, 

maximum 

60 mg/day, for 

3-10 days

■ An increasing use or lack of

expected effect indicates 

diminished control of asthma.

■ Not generally recommended for

long-term treatment. Regular use

on a daily basis indicates the need

for additional long-term-control

therapy.

■ Differences in potency exist so that

all products are essentially equipotent on a per puff basis.

■ May double usual dose for mild

exacerbations.

■ Nonselective agents (i.e., 

epinephrine, isoproterenol,

metaproterenol) are not recommended due to their potential for

excessivecardiac stimulation, 

especially in high doses.

May mix with cromolyn or ipratropium nebulizer solutions. May double dose for mild exacerbations.

May not mix with other nebulizer

solutions.

Evidence is lacking for 

anticholinergics producing added

benefit to beta2-agonists in longterm asthma therapy.

■ 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.

(Applies to all three systemic corticosteroids)

Medication Dosage Form Adult Dose Child Dose Comments

Systemic Corticosteroids

Managing Asthma Long Term

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Component 3: Pharmacologic Therapy

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 patient

education and measures to control those factors that

contribute to the severity of the asthma (see components 2 and 4).

If optimal control of asthma is not achieved and

sustained at any step of care (nocturnal symptoms, urgent care visits, or an increased need for

short-acting beta2-agonists are key indications

that asthma is not optimally controlled), several

actions may be considered:

■ Patient adherence and technique in using

medications correctly should be assessed.

■ A temporary increase in anti-inflammatory therapy may be indicated to reestablish 

control. A deterioration of asthma may be 

characterized by gradual reduction in PEF 

(approximately 20 percent), by failure of inhaled

bronchodilators to produce a sustained response, 

by a reduced tolerance to activities or exercise, 

and by the development of increasing nocturnal 

symptoms. To regain control of asthma, a short

course of oral prednisone (see figure 3-5a) 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 to 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 need

to be identified and addressed. These factors

include the presence of a coexisting condition (e.g.,

sinusitis), 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

may need to be considered, such as vocal cord 

dysfunction.

■ A step up to the next higher step of care may

be necessary.

■ Consultation with an asthma specialist may be

indicated (see component 1-Initial Assessment

and Diagnosis).

Intermittent Asthma

Step 1: Mild Intermittent Asthma. Short-acting

inhaled beta2-agonists taken as needed to treat

symptoms are usually sufficient therapy for mild,

intermittent asthma. If effective in relieving 

symptoms and normalizing pulmonary function,

intermittent use of short-acting inhaled beta2-agonists

can continue to be used on an as-needed basis. If 

significant symptoms reoccur or beta2-agonist is

required for quick-relief treatment more than two times

a week (with the exception of using beta2-agonist for

exacerbations caused by viral infections and for 

exercise-induced bronchospasm [EIB]), the patient

should be moved to the next step of care.

Patients with intermittent asthma who experience

EIB benefit from taking inhaled beta2-agonists, 

cromolyn, or nedocromil shortly before exercise (see

Exercise-Induced Bronchospasm, page 100).

Cromolyn or nedocromil taken before unavoidable

exposure to an aeroallergen known to exacerbate the

patient’s asthma may be beneficial (Cockcroft and

Murdock 1987).

The Expert Panel recommends the following

actions for managing exacerbations due to viral

respiratory infections, which are especially common in children. If the symptoms are mild, inhaled

beta2-agonist (every 4 to 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, a step up in long-term care is recommended.

If the viral respiratory infection provokes a moderateto-severe exacerbation, a short course of systemic corticosteroids should be considered. For those patients

with a history of severe exacerbations with viral respiratory infections, systemic corticosteroids should be

initiated at the first sign of the infection.

The Expert Panel recommends that a detailed

written action plan be developed for those

patients with intermittent asthma who have a 

history of severe exacerbations (see figure 4-5).

Intermittent asthma—infrequent exacerbations 

separated by periods of no symptoms and normal 

pulmonary function—is often mild. However, some

patients with intermittent asthma experience sudden,

severe, and life-threatening exacerbations. It is essential to treat these exacerbations accordingly. The

patient’s action plan should include indicators of

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Managing Asthma Long Term

93

surements), as well as specific recommendations for

using beta2-agonist rescue therapy, early administration of systemic corticosteroids, and seeking medical

care. Furthermore, periodic monitoring (see 

component 1-Periodic Assessment and Monitoring) 

of the patient is appropriate to evaluate whether the

patient’s asthma is indeed intermittent or whether 

a step up in long-term therapy is warranted.

Persistent Asthma

The Expert Panel recommends that patients with

persistent asthma, either mild, moderate, or

severe, receive 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 from clinical trials supports this 

recommendation (van Essen-Zandvliet et al. 1992;

Kerstjens et al. 1992).

Step 2: Mild Persistent Asthma. The main 

characteristics of step 2 care are as follows:

■ Step 2 care long-term-control medication is

daily anti-inflammatory medication: either

inhaled corticosteroids at a low dose (see 

figure 3-5b), cromolyn, or nedocromil.

For children, a trial of cromolyn or nedocromil is

often the initial long-term therapy due to the 

safety profiles of these medications.

■ Sustained-release theophylline is an alternative,

but not preferred, long-term-control medication. It is not preferred because its 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 3-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.

■ Zafirlukast or zileuton may also be considered

an alternative long-term-control medication

for patients 12 years of age and older, although

their position in therapy is not yet fully established. Initial experience in clinical trials and possible patient requirements for tablet-form medication make these new medications a therapeutic

option. Further clinical experience and additional

data are needed to establish the role of zafirlukast

and zileuton in stepwise therapy.

■ Quick-relief medication must be available.

Inhaled short-acting beta2-agonists should be

taken as needed to relieve symptoms. The

intensity of treatment will depend on the severity

of the exacerbation (see component 3-Managing

Exacerbations). Use of inhaled short-acting 

beta2-agonists on a daily basis, or increasing use,

indicates the need for additional long-termcontrol therapy.

Step 3: Moderate Persistent Asthma. Consultation with an asthma specialist may be considered

because the therapeutic options at this juncture pose a

number of challenging risk/benefit outcomes. There

are at least three options for initiating step 3 therapy.

■ Increase inhaled corticosteroids to medium

dose. This strategy will benefit many patients.

Adverse effects, although infrequent, may arise 

(see component 3-Medications).

OR

■ Add a long-acting bronchodilator to a low-tomedium dose of inhaled corticosteroids. The

long-acting bronchodilator may be either a longacting inhaled beta2-agonist (e.g., salmeterol)

(Greening et al. 1994; Woolcock et al. 1996) or

sustained-release theophylline (Nassif et al. 1981);

although not preferred, long-acting beta2-agonist

tablets may be considered. This approach has been

shown to improve symptom control and may be

especially beneficial in patients who have significant nocturnal symptoms. Improved asthma control has been demonstrated with an inhaled longacting beta2-agonist and a medium-dose inhaled

corticosteroid compared to a doubled dose of

inhaled corticosteroid (Woolcock et al. 1996), 

but the potential for incorrectly using long-acting

inhaled beta2-agonists as a quick-relief medication

needs to be considered. The approach of adding

theophylline has the potential for adverse reactions

related to fluctuations in theophylline serum 

concentrations.

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Component 3: Pharmacologic Therapy

OR

■ Establish control with medium-dose inhaled

corticosteroids, then lower the dose (but still

within the medium-dose range) and add

nedocromil. Nedocromil has a notable safety profile, and some studies (Lal et al. 1993; O’Hickey

and Rees 1994; Svendsen and Jorgensen 1991) have

shown that it has some, albeit modest, inhaled corticosteroid-sparing effects in adults. Other studies

(e.g., Wong et al. 1993) did not demonstrate this.

Therefore, this treatment option is not preferred.

Furthermore, adding another inhaler into the

patient’s medication schedule may affect patient

adherence. It will also affect the total cost of care.

If the patient’s asthma is not optimally controlled

with initial step 3 therapy, and medications are

used correctly, additional step 3 therapy is 

recommended.

■ Increase daily long-term-control medications

to a high dose of inhaled corticosteroids, 

AND

■ Add a long-acting bronchodilator, especially to

control nocturnal symptoms. The long-acting 

bronchodilator can be either long-acting inhaled

beta2-agonist or sustained-release theophylline. An

evening dose of either bronchodilator may alleviate

and prevent nocturnal symptoms and thus improve

adherence to the overall therapeutic regimen.

Step 4: Severe Persistent Asthma. Patients

whose asthma is not controlled on high doses of

inhaled corticosteroids and the addition of longacting bronchodilators will also need oral systemic corticosteroids on a regularly scheduled,

long-term basis. 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 3-Medications).

■ When control of asthma is achieved, make 

persistent attempts to reduce systemic corticosteroids. High doses of inhaled corticosteroids are

preferable to systemic corticosteroids because

inhaled corticosteroids have fewer systemic effects.

■ Consultation with an asthma specialist is 

recommended.

SPECIAL CONSIDERATIONS FOR 

MANAGING ASTHMA IN 

DIFFERENT AGE GROUPS

Infants and Young Children 

(5 Years of Age and Younger)

Diagnosis

Several studies show that as many as 50 to 80 percent of children with asthma develop symptoms

before their fifth birthday. 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 labels as

chronic bronchitis, wheezy bronchitis, recurrent

pneumonia, gastroesophageal reflux, and recurrent

upper respiratory tract infections), and thus 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 inappropriately prolonged asthma therapy. Episodic or

KEY RECOMMENDATIONS FOR

MANAGING ASTHMA IN INFANTS AND

YOUNG CHILDREN

■ Diagnosing asthma in infants is often 

difficult, yet underdiagnosis and undertreatment are key problems in this age group.

Thus, a diagnostic trial of inhaled bronchodilators and anti-inflammatory medications may 

be helpful.

■ In general, infants and young children consistently requiring symptomatic treatment more

than two times per week should be given daily

anti-inflammatory therapy.

■ When initiating daily anti-inflammatory 

therapy, a trial of cromolyn or nedocromil 

is often given due to the safety profile of these

medications.

■ Response to therapy should be carefully 

monitored. Once control of asthma 

symptoms is established and sustained, a 

careful step down in therapy should be

attempted. If clear benefit is not observed,

alternative therapies or diagnoses should 

be considered.

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95

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.

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. There appear to be two general patterns of

illness 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. There are no clear

markers to predict the prognosis for an individual child;

however, the factors more strongly associated with continuing asthma are allergy, a family history of allergy or

asthma, and perinatal exposure to passive smoke and

aeroallergens (Pullan and Hey 1982; Sporik et al. 1991;

Martinez et al. 1995; Martinez 1995).

Diagnosis is complicated by the difficulty in obtaining

objective measurements of lung function in this age

group. Essential elements in the evaluation include

the history, symptoms, physical examination, and

assessment of quality of life. A therapeutic trial with

medications listed in figure 3-5d will also aid in the

diagnosis.

Treatment

Figure 3-6 illustrates the Expert Panel’s recommendations for a stepwise approach to managing

acute and chronic asthma symptoms, regardless

of the prognosis for the wheezing infant or 

young child.

It is the opinion of the Expert Panel that, in 

general, infants and young children consistently

requiring symptomatic treatment more than two

times per week should be given daily antiinflammatory medication.

At present there are few studies of medications in

children younger than 3 years of age. A therapeutic

trial of anti-inflammatory medications should be

monitored carefully. Treatment should be stopped if a

clear beneficial effect is not obvious. Although only

inhaled corticosteroids have been shown to be effective in long-term clinical studies with infants

(Ilangovan et al. 1993; Gleeson and Price 1988;

Bisgaard et al. 1990), cromolyn has demonstrated

symptom control and reduced airway hyperresponsiveness in a number of pediatric studies (GellerBernstein and Sneh 1980; Hilman et al. 1987;

Miraglia del Giudice et al. 1982; Shapiro and Konig

1985; Silverman et al. 1972; Bertelsen et al. 1986;

Glass et al. 1981). Fewer studies are available on

nedocromil, but benefit has been demonstrated

(Brogden and Sorkin 1993). Sustained-release theophylline, an alternative long-term-control medication

for older children, may have particular risks of adverse

side effects in infants, who frequently have febrile 

illnesses which increase theophylline concentrations.

Theophylline should be considered only if serum 

concentration levels will be carefully monitored.

In deciding when to initiate daily long-term-control

therapy, the clinician must weigh the possible longterm effects of inadequately controlled asthma vs. the

possible adverse effects of medications given over prolonged periods. 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). There is

evidence that anti-inflammatory treatment can reduce

morbidity from wheezing in early childhood (Connett

et al. 1993). Studies in older children suggest that

the potential but small risk of delayed growth from

the use of inhaled corticosteroids is balanced by their

efficacy (see component 3-Medications). Furthermore, there are options (cromolyn and nedocromil)

for initiating anti-inflammatory therapy.

Recommendations for treating infants and young

children at different steps of care include:

■ The patient’s response to therapy should be

monitored carefully. When benefits are sustained, a step down in therapy should be attempted. If there are no clear benefits, treatment

should be stopped and alternative therapies or

diagnoses should be considered.

■ Daily long-term-control therapy often begins

with cromolyn or nedocromil.

■ When inhaled corticosteroids are introduced in

step 2 care, doses may range from 100 to 400

mcg/day; this generally translates to a dose of 15

mcg/kg up to 400 mcg/day beclomethasone (Allen

and Lemanske 1993). See figures 3-5b and 3-5c for

discussion of equivalency among preparations.

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96

Component 3: Pharmacologic Therapy

■ Daily anti-inflammatory medicine

— High-dose inhaled corticosteroid with 

spacer/holding chamber and face mask

— If needed, add systemic corticosteroids

2 mg/kg/day and reduce to lowest daily or

alternate-day dose that stabilizes symptoms

■ Daily anti-inflammatory medication. Either:

— Medium-dose inhaled corticosteroid with 

spacer/holding chamber and face mask

OR, once control is established:

— Medium-dose inhaled corticosteroid and 

nedocromil

OR

— Medium-dose inhaled corticosteroid and 

long-acting bronchodilator (theophylline)

■ Daily anti-inflammatory medication. Either:

— Cromolyn (nebulizer is preferred; or MDI) 

or nedocromil (MDI only) 

— Infants and young children usually begin 

with a trial of cromolyn or nedocromil

OR

— Low-dose inhaled corticosteroid with 

spacer/holding chamber and face mask

■ No daily medication needed.

STEP 4

Severe 

Persistent

STEP 3

Moderate

Persistent

STEP 2

Mild Persistent

STEP 1

Mild Intermittent

NOTE:

■ The stepwise approach presents guidelines to assist clinical decisionmaking. Asthma is highly variable; clinicians should tailor specific 

medication plans to the needs and circumstances of individual patients.

■ Gain control as quickly as possible; then decrease treatment to the least medication necessary to maintain control. Gaining control may be accomplished

by either starting treatment at the step most appropriate to the initial severity of their condition or by starting at a higher level of therapy (e.g., a course

of systemic corticosteroids or higher dose of inhaled corticosteroids).

■ A rescue course of systemic corticosteroid (prednisolone) may be needed at any time and step.

■ In general, use of short-acting beta2-agonist on a daily basis indicates the need for additional long-term-control therapy.

■ It is important to remember that there are very few studies on asthma therapy for infants.

■ Consultation with an asthma specialist is recommended for patients with moderate or severe persistent asthma in this age group. Consultation should be

considered for all patients with mild persistent asthma.

FIGURE 3-6. STEPWISE APPROACH FOR MANAGING INFANTS AND YOUNG CHILDREN

(5 YEARS OF AGE AND YOUNGER) WITH ACUTE OR CHRONIC ASTHMA SYMPTOMS 

Step down

Review treatment every 1 to 6 months. If control is sustained for at least 3 months, a gradual stepwise reduction

in treatment may be possible.

Step up

If control is not achieved, consider step up. But first: review patient

medication technique, adherence, and environmental control (avoidance

of allergens or other precipitant factors).

Long-Term Control Quick Relief

■ Bronchodilator as needed for symptoms (see step 1) 

up to 3 times a day

■ Bronchodilator as needed for symptoms (see step 1) 

up to 3 times a day

■ Bronchodilator as needed for symptoms (see step 1)

■ Bronchodilator as needed for symptoms ≤2 times a week.

Intensity of treatment will depend upon severity of exacerbation (see component 3-Managing Exacerbations). Either:

— Inhaled short-acting beta2-agonist by nebulizer or face

mask and spacer/holding chamber

OR

— Oral beta2-agonist for symptoms

■ With viral respiratory infection

— Bronchodilator q 4-6 hours up to 24 hours (longer

with physician consult) but, in general, repeat no more

than once every 6 weeks

— Consider systemic corticosteroid if

• Current exacerbation is severe

OR

• Patient has history of previous severe 

exacerbations

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Managing Asthma Long Term

97

■ When step 3 care is required, it is the opinion

of the Expert Panel that control should be

established promptly with higher doses of

inhaled corticosteroid and then therapy should

be stepped down after 2 to 3 months to maintain

control (Pedersen and Hansen 1995). For some

patients, control of asthma may be maintained by

using a lower dose of inhaled corticosteroid (e.g., the

minimum dose in the medium-dose range) along

with the addition of either nedocromil or theophylline. Some, but not all, studies with nedocromil

in adults have demonstrated its potential corticosteroid-sparing effect. There are no studies demonstrating this effect with cromolyn. Studies in infants

and young children are necessary. Some clinicians

prefer gradually increasing medication to establish

control—for example, adding nedocromil or theophylline before increasing the dose of inhaled corticosteroid beyond low-dose therapy.

■ Exacerbations caused by viral respiratory infections

may be intermittent yet severe. Consider 

systemic corticosteroids if the exacerbation is

moderate to severe or at the onset of a viral

respiratory infection if the patient has a history

of severe exacerbations.

■ Consultation with an asthma specialist should

be considered for infants and young children

requiring step 2 care; consultation is recommended for those requiring step 3 or step 4 care.

■ Several delivery devices are available for infants

and young children. The dose received may vary

considerably among devices and age groups. (See

figure 3-3 for a summary of therapeutic issues

regarding aerosol delivery devices.) The child’s

caregivers must be instructed in the proper use of

appropriately sized face masks, spacers/holding

chambers with face masks, and spacers/holding

chambers for medication delivery to be effective

and efficient. For children younger than 2 years of

age, nebulizer therapy may be preferred for administering cromolyn and for high doses of beta2-

agonists during exacerbations. Children between 

3 and 5 years may begin therapy with MDI and

spacer/holding chamber alone, but if the desired

therapeutic effects are not achieved, they may

require a nebulizer or an MDI plus spacer/holding

chamber and face mask.

School-Age Children 

(Older Than 5 Years of Age) 

and Adolescents

The pharmacologic management of school-age 

children and adolescents follows the same basic 

principles as those for adults, but the special 

circumstances of growth, school, and social 

development require special consideration.

Assessment

Pulmonary function testing should be performed

using comparison data from an appropriate reference population (American Thoracic Society 1991).

Adolescents generally compare better to childhood

than to adult predicted norms. Testing in a laboratory or clinic specializing in children can result in higher

pulmonary function values and more consistent data.

Technicians who conduct pulmonary function testing

for children should have special training in achieving

the best possible effort from young patients.

Treatment

For children with mild or moderate persistent

asthma, cromolyn or nedocromil are often 

effective anti-inflammatory therapies and have no

known long-term systemic effects. However, for

KEY RECOMMENDATIONS FOR

MANAGING ASTHMA IN SCHOOL-AGE

CHILDREN AND ADOLESCENTS

■ Pulmonary function testing should use 

appropriate reference populations. 

Adolescents compare better to childhood 

than to adult predicted norms.

■ When initiating daily anti-inflammatory 

therapy for mild-to-moderate persistent 

asthma, a trial of cromolyn or nedocromil 

is often given.

■ 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.

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98

children with severe persistent asthma, and for

many children with moderate persistent asthma,

cromolyn and nedocromil do not provide adequate control and thus inhaled corticosteroids are

necessary for long-term therapy (see figure 3-4b). 

The Expert Panel recommends that adolescents

(and younger children as appropriate) be directly

involved in developing their asthma management

plans. 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 upon 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 problemsolving skills. To accomplish this, 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 treatment 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 emphasize the parents’

important role in supporting the adolescent’s efforts.

School Issues

The clinician should prepare a written asthma

management plan for the student’s school (see 

figure 4-7) that includes the following information: an action plan for handling exacerbations

(including the clinician’s recommendation regarding

self-administration of medication and plans to ensure

prompt, reliable access to medications); recommendations for long-term-control medications and prevention of exercise-induced bronchospasm (EIB), if

appropriate; and identification of those factors that

make the student’s asthma worse so the school may

help the student avoid exposure.

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.

However, in school districts that have more comprehensive school nurse coverage, 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 with 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 National Asthma

Education and Prevention Program 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

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. Many children with asthma experience cough,

wheeze, or excessive fatigue when they exercise.

Treatment immediately prior to 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,

page 100). Activity should be limited or curtailed 

only as a last resort.

Older Adults

Component 3: Pharmacologic Therapy

KEY RECOMMENDATIONS FOR 

MANAGING ASTHMA IN OLDER ADULTS

■ 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 need to be made.

■ 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.

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99

Because of the high prevalence of other 

obstructive lung disease (e.g., chronic bronchitis,

emphysema) among the elderly, it is important 

to determine the extent of reversible airflow

obstruction. Careful evaluation is required because

the precise cause of severe airflow obstruction can be

difficult to identify in older patients with 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-termcontrol asthma medication can then be offered.

Asthma medications may have increased adverse

effects in the elderly patient; adjustments in the

medication plan may be necessary.

■ 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 anticholinergics and beta2-

agonists may be beneficial to the older patient (Ullah

et al. 1981; Barros and Rees 1990; Gross et al. 1989).

■ Theophylline clearance is reduced in the elderly

patient (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-olds)

(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.

■ A dose-dependent reduction in bone mineral content may be associated with inhaled corticosteroid

use, 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. However, the

risk of not adequately controlling asthma may

unnecessarily limit the patient’s mobility and

activities. Concurrent treatment with calcium

supplements and vitamin D, and estrogen

replacement when appropriate, are recommended. At the present time, the optimal

approach for identifying patients at risk for accelerated bone loss from high-dose corticosteroid 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.

Medications employed for other diseases may

exacerbate asthma; adjustments may need to be

made. Nonsteroidal anti-inflammatory agents for

treating arthritis, nonselective beta-blockers for treating hypertension, or beta-blockers found in some eye

drops used to treat glaucoma may exacerbate asthma.

See component 2 for more details on drugs that can

complicate asthma management.

For more information on asthma in older patients, 

see NAEPP Working Group Report: Considerations for

Diagnosing and Managing Asthma in the Elderly

(NHLBI 1996).

MANAGING SPECIAL SITUATIONS 

IN ASTHMA

Seasonal Asthma

Some patients experience asthma symptoms only in

relationship to certain pollens and molds. Such seasonal asthma should be treated according to the stepwise approach to long-term management of asthma.

If the patient has seasonal asthma on a predictable

basis, daily, long-term anti-inflammatory therapy

(inhaled corticosteroids, cromolyn, or nedocromil)

should be initiated prior to the anticipated onset of

symptoms and continued through the season.

Cough Variant Asthma

Cough variant asthma is seen especially in young

children. Cough is the principal symptom; because

this frequently occurs at night, examinations during

the day may be normal. Monitoring of morning and

afternoon PEF variability and/or therapeutic trials

with anti-inflammatory or bronchodilator medication

may be helpful in diagnosis. Once the diagnosis is

established, treat according to the stepwise approach

to long-term management of asthma.

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100

Component 3: Pharmacologic Therapy

Exercise-Induced Bronchospasm

Exercise-induced bronchospasm—which untreated

can limit and disrupt otherwise normal lives—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 (Anderson 1985; Godfrey

1986; McFadden and Gilbert 1994). EIB usually

occurs during or minutes after vigorous activity, reaches

its peak 5 to 10 minutes after stopping the activity, and

usually resolves in another 20 to 30 minutes.

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.

Diagnosis

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. This 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 to 6

minutes. Alternatively, the patient may simply

undertake the task that previously caused the symptoms. A 15 percent decrease in PEF or FEV1 (measurements taken before and after exercise at 5-minute 

intervals for 20 to 30 minutes) is compatible with EIB.

Management Strategies

One goal of management is to enable patients to 

participate in any activity they choose without experiencing asthma symptoms. EIB should not limit

either participation or success in vigorous activities.

Recommended treatments include:

■ Beta2-agonists will prevent EIB in more than 

80 percent of patients.

— Short-acting inhaled beta2-agonists used shortly before exercise (or as close to exercise as possible) may be helpful for 2 to 3 hours.

— Salmeterol has been shown to prevent EIB for

10 to 12 hours (Kemp et al. 1994). 

■ Cromolyn and nedocromil, taken shortly before

exercise, are also acceptable for preventing EIB

(Tullett et al. 1985; Woolley et al. 1990; Albazzaz

et al. 1989; de Benedictis et al. 1995).

■ A lengthy warmup period before exercise may

benefit patients who can tolerate continuous exercise with minimal symptoms. The warmup may

preclude a need for repeated medications.

■ Long-term-control therapy, if appropriate.

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).

Teachers and coaches need to be notified that a

child has EIB, should be able to participate in activities, and may need inhaled medication before activity.

Individuals involved in competitive athletics need to

be aware that their medication use should be disclosed and should adhere to standards set by the 

U.S. Olympic Committee (Nastasi et al. 1995). 

The U.S. Olympic Committee’s Drug Control Hotline

is 1-800-233-0393.

Surgery and Asthma

Asthma patients are at risk for specific complications

during and after surgery: acute bronchoconstriction

triggered by intubation, hypoxemia and possible

hypercapnia, impaired effectiveness of cough, atelectasis and respiratory infection (Kingston and Hirshman

1984), and latex exposure (Slater 1994; Sussman and

Beezhold 1995). The likelihood of these complications depends on the severity of the patient’s airway

hyperresponsiveness, airflow obstruction, mucus

hypersecretions, and latex sensitivity.

Recommended actions include:

■ Patients with asthma should have an evaluation before surgery that includes a review of

symptoms, medication use (particularly the use

of systemic corticosteroids for longer than 2 weeks

in the past 6 months), and measurement of pulmonary function.

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■ If possible, attempts should be made to

improve lung function (FEV1 or PEF) to their

predicted values or their personal best level. A

short course of systemic corticosteroids may be

necessary to optimize pulmonary function.

■ For patients who have received systemic corticosteroids during the past 6 months, give 100

mg hydrocortisone every 8 hours intravenously

during the surgical period and reduce dose

rapidly within 24 hours following surgery.

Pregnancy and Asthma

Maintaining sufficient lung function and blood

oxygenation to ensure adequate oxygen supply to

the fetus is essential. Poorly controlled asthma during pregnancy can result in increased perinatal mortality, increased prematurity, and low birth weight

(Nelson and Weber 1988). For most drugs used to

treat asthma and rhinitis, with the exception of

brompheniramine, epinephrine, and alpha-adrenergic

compounds (other than pseudoephedrine), there is little to suggest an increased risk to the fetus (Schatz et

al. 1988; Federal Register 1979; Briggs et al. 1986).

Other classes of drugs with some possibility of risk to

the fetus include decongestants (other than pseudoephedrine), antibiotics (tetracycline, sulfonamides,

and ciprofloxacin), live virus vaccines, immunotherapy

(if doses are increased), and iodides.

For more information on asthma and pregnancy, see

Executive Summary: Management of Asthma During

Pregnancy (NHLBI 1992).

Stress and Asthma

The role of stress and psychological factors in asthma

is important but not fully defined. There is emerging

evidence 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). The mechanisms involved in this

process have yet to be fully established and may

involve enhanced generation of proinflammatory

cytokines (Friedman et al. 1994). 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) (Strunk et al. 1985; Strunk 1993; Brush and

Mathé 1993).

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Pharmacologic Therapy:

Managing Exacerbations of Asthma

Asthma exacerbations 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 peak 

expiratory flow [PEF]). These objective measures

more reliably indicate the severity of an exacerbation

than does the severity of symptoms.

GENERAL CONSIDERATIONS

The Expert Panel recommends that clinicians consider

the following general principles and goals for 

managing asthma exacerbations, based on the 

scientific literature and the opinion of the Panel.

■ Early treatment is the best strategy for 

management of asthma exacerbations. Important

elements of early treatment include:

— A written action plan (see figure 4-5) to 

guide patient self-management, especially 

for patients with moderate-to-severe 

persistent asthma and any patient with a 

history of severe exacerbations

— Recognition of early indicators of an 

exacerbation, including worsening 

FEV1 or PEF

— Prompt communication between patient 

and clinician about any serious deterioration 

in symptoms or peak flow, decreased 

responsiveness to inhaled beta2-agonist, 

or decreased duration of effect

— Appropriate intensification of therapy, often

including a short course of systemic 

corticosteroids

— Removal of or withdrawal from allergic or 

irritant precipitants in the environment that 

may be contributing to the exacerbation

■ Patients at high risk of asthma-related death

require special attention—particularly intensive

education, monitoring, and care. They should be

counseled to seek medical care early during an

exacerbation and instructed about the availability

of ambulance services. Such patients include those

with identifiable risk factors (see figure 3-7a).

KEY POINTS

■ Early treatment of asthma exacerbations is the

best strategy for management. Important 

elements of early treatment include:

— A written action plan to guide patient 

self-management of exacerbations at 

home, especially for patients with 

moderate-to-severe persistent asthma 

and any patient with a history of severe 

exacerbations

— Recognition of early signs of worsening 

asthma

— Appropriate intensification of therapy

— Prompt communication between patient

and clinician about any serious 

deterioration in symptoms or peak flow, 

decreased responsiveness to inhaled 

beta2-agonists, or decreased duration 

of effect

■ Management of asthma exacerbations

includes:

— Inhaled beta2-agonist to provide prompt

relief of airflow obstruction

— Systemic corticosteroids, for moderateto-severe exacerbations or for patients 

who fail to respond promptly and 

completely to an inhaled beta2-agonist, 

to suppress and reverse airway 

inflammation

— Oxygen to relieve hypoxemia for 

moderate-to-severe exacerbations

— Monitoring response to therapy with 

serial measurements of lung function

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■ Infants require special attention, especially due

to their greater risk for respiratory failure 

(see figure 3-7b).

TREATMENT GOALS

The principal goals for treating asthma exacerbations are:

■ Correction of significant hypoxemia by administering supplemental oxygen. In rare instances,

alveolar hypoventilation requires mechanically

assisted ventilation.

■ Rapid reversal of airflow obstruction. This is

best achieved by

— Repetitive or continuous administration of 

an inhaled beta2-agonist (Brenner 1983b; 

Lipworth et al. 1988; McFadden 1989; Lin 

et al. 1993; Rudnitsky et al. 1993; Papo et 

al. 1993)

AND

— Early in the course of treatment, administration of systemic corticosteroids to patients with

moderate-to-severe exacerbations or to patients

who fail to respond promptly and completely

to an inhaled beta2-agonist (Fanta et al. 1983;

Littenberg and Gluck 1986; Rowe et al. 1992;

Scarfone et al. 1993; Connett et al. 1994).

■ Reduction of the likelihood of recurrence of

severe airflow obstruction by intensifying 

therapy. Often, a short course of systemic 

corticosteroids is useful (Fanta et al. 1983;

Littenberg and Gluck 1986; Rowe et al. 1992;

Scarfone et al. 1993; Connett et al. 1994).

Achieving these goals requires close monitoring

by serial measurements of lung function to quantify the severity of airflow obstruction and its

response to treatment. The improvement in FEV1

Component 3: Pharmacologic Therapy

FIGURE 3-7a. RISK FACTORS FOR 

DEATH FROM ASTHMA

■ Past history of sudden severe exacerbations

■ Prior intubation for asthma

■ Prior admission for asthma to an intensive care

unit

■ Two or more hospitalizations for asthma in the

past year

■ Three or more emergency care visits for asthma

in the past year

■ Hospitalization or an emergency care visit for 

asthma within the past month

■ Use of >2 canisters per month of inhaled

short-acting beta2-agonist

■ Current use of systemic corticosteroids or

recent withdrawal from systemic corticosteroids

■ Difficulty perceiving airflow obstruction or its

severity

■ Comorbidity, as from cardiovascular diseases or

chronic obstructive pulmonary disease

■ Serious psychiatric disease or psychosocial 

problems

■ Low socioeconomic status and urban residence

■ Illicit drug use

■ Sensitivity to Alternaria

Sources: Kallenbach et al. 1993; Rodrigo and Rodrigo 1993; Suissa et

al. 1994; Greenberger et al. 1993; O’Hollaren et al. 1991

FIGURE 3-7b. SPECIAL 

CONSIDERATIONS FOR INFANTS

■ Assessment depends on physical examination

rather than objective measurements. Use of

accessory muscles, paradoxical breathing,

cyanosis, and a respiratory rate >60 are key

signs of serious distress.

■ Objective measurements such as oxygen saturation of <91 percent also indicate serious distress.

■ Response to beta2-agonist 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 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 are generally not required.

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107

Managing Exacerbations of Asthma

after 30 minutes of treatment correlates significantly

with a broad range of indices of the severity of asthma

exacerbations (Rodrigo and Rodrigo 1993), and

repeated measurement of airflow in the emergency

department can help reduce unnecessary admissions

(Taylor 1994). Use PEF or FEV1 values to guide

treatment decisions, along with the patient’s history,

current symptoms, and physical findings. In using

PEF expressed as a percentage of personal best, it is

important to consider the impact of irreversible airflow obstruction. For a patient whose best PEF is

160 L/min, for example, a fall of 40 percent represents severe, potentially life-threatening obstruction.

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 3-8.

The Expert Panel recommends the following

actions to prepare patients for home management of

asthma exacerbations, based on scientific literature

(see component 1-Periodic Assessment and Monitoring and component 4) and the opinion of the Panel.

■ Teach all patients how to monitor symptoms to

recognize early signs of deterioration (see component 1-Periodic Assessment and Monitoring and

component 4) and how to adjust their medications

accordingly.

■ Teach patients with moderate-to-severe persistent asthma and those with a history of severe

exacerbations how to monitor their peak flow

to assess the severity of an exacerbation and the

response to therapy (see component 1-Periodic

Assessment and Monitoring). In the absence of

PEF measurement, severity can be judged only

from the presence and intensity of signs and symptoms (see figure 3-9), which correlate imperfectly

with the severity of airflow obstruction. This is

especially true in a subgroup of patients (“poor

perceivers”) who do not sense airway narrowing

until it is far advanced (Kikuchi et al. 1994).

■ Give a written asthma action plan to be followed in the event of an exacerbation (see figure 

4-5), especially to patients with moderate-to-severe

persistent asthma and any patient with a history of

severe exacerbations. Children should also receive

a plan appropriate to the school setting (see figure

4-7). 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 at risk for asthma death (see figure 3-7a)

require especially close monitoring.

■ Teach patients to seek medical help early if 

(1) an asthma exacerbation is severe, (2) therapy does not give rapid, sustained improvement, or (3) there is further deterioration.

■ Advise patients with moderate-to-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.

The Expert Panel recommends the following

pharmacologic therapy, based on the scientific 

literature, for home management of exacerbations:

■ Increase the frequency of inhaled beta2-agonist.

■ Initiate or increase corticosteroid treatment

under certain circumstances. For mild exacerbations in patients already taking an inhaled 

corticosteroid, many experts prescribe doubling 

the dose until peak flow returns to predicted or

personal best. Although this practice has not been

proved in a clinical trial, a few studies suggest 

its benefit (Lahdensuo et al. 1996; Wilson and

Silverman 1990). For moderate-to-severe 

exacerbations (see figure 3-9), and for mild 

exacerbations that persist despite an increased dose

of inhaled corticosteroids, a course of oral 

corticosteroids is necessary (Chapman et al. 1991; 

Fiel et al. 1983; Harris et al. 1987; Deshpande and

McKenzie 1986; Loren et al. 1980; Rowe et al. 1992).

■ Continue more intensive treatment for several

days. Recovery from an exacerbation is often

gradual. Greater use of medication should be

continued until symptoms and PEF are stable, but

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108

Component 3: Pharmacologic Therapy

FIGURE 3-8. MANAGEMENT OF ASTHMA EXACERBATIONS: HOME TREATMENT

Assess Severity

Measure PEF: Value <50% personal best or predicted

suggests severe exacerbation.

Note signs and symptoms: Degrees of cough,

breathlessness, wheeze, and chest tightness correlate 

imperfectly with severity of exacerbation. Accessory 

muscle use and suprasternal retractions suggest 

severe exacerbation.

Initial Treatment

● Inhaled short-acting beta2-agonist: up to three 

treatments of 2-4 puffs by MDI at 20-minute 

intervals or single nebulizer treatment.

Incomplete Response

Moderate Exacerbation

PEF 50-80% predicted or 

personal best

Persistent wheezing and shortness

of breath

● Add oral corticosteroid.

● Continue beta2-agonist.

Good Response

Mild Exacerbation

PEF >80% predicted or 

personal best

No wheezing or shortness of breath

Response to beta2-agonist 

sustained for 4 hours

● May continue beta2-agonist

every 3-4 hr for 24-48 hours.

● For patients on inhaled corticosteroids, double dose for 7-10 days.

Poor Response

Severe Exacerbation

PEF <50% predicted or personal best

Marked wheezing and shortness 

of breath

● Add oral corticosteroid. 

● Repeat beta2-agonist immediately.

● If distress is severe and nonresponsive,

call your doctor and proceed to 

emergency department; consider 

calling ambulance or 9-1-1.

● Contact clinician for followup

instructions.

● Contact clinician urgently (this day) 

for instructions.

● Proceed to emergency department.

Note:

Patients at high risk of asthma-related death (see figure 3-7a) should receive immediate attention clinical attention after initial treatment.

Additional therapy may be required.

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Managing Exacerbations of Asthma

FIGURE 3-9. CLASSIFYING SEVERITY OF ASTHMA EXACERBATIONS

Respiratory

Mild Moderate Severe Arrest Imminent

Symptoms

Breathlessness While walking While talking While at rest

(infant—softer, (infant—stops

shorter cry; feeding)

difficulty 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/min

Guide to rates of breathing in awake children:

Age Normal rate

<2 months <60/minute

2-12 months <50/minute

1-5 years <40/minute

6-8 years <30/minute

Use of accessory Usually not Commonly Usually Paradoxical

muscles; suprasternal thoracoabdominal

retractions movement

Wheeze Moderate, often only Loud; throughout Usually loud; throughout Absence of wheeze

end expiratory exhalation inhalation and exhalation

Pulse/minute <100 100-120 >120 Bradycardia

Guide to normal pulse rates in children:

Age Normal rate 

2-12 months <160/minute

1-2 years <120/minute

2-8 years <110/minute

Pulsus paradoxus Absent <10 mm Hg May be present Often present >25 mm Hg Absence suggests respiratory

10-25 mm Hg (adult) 20-40 mm Hg (child) muscle fatigue

Functional Assessment

PEF >80% Approx. 50-80% <50% predicted or personal best

% predicted or or response lasts <2 hrs

% personal best

PaO2 (on air) Normal >60 mm Hg <60 mm Hg: possible cyanosis

(test not usually necessary) (test not usually necessary)

and/or

PCO2 <42 mm Hg (test not <42 mm Hg >_ 42 mm Hg: possible

usually necessary) (test not usually necessary) respiratory failure (see text)

SaO2% (on air) >95% 91-95% <91%

at sea level (test not usually necessary)

Hypercapnia (hypoventilation) develops more readily in young children than in adults and adolescents.

Note:

■ 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, so they serve only as general guides.

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110

patients should seek medical care rather than rely

on bronchodilator therapy in excessive doses or for

prolonged periods.

The Expert Panel does not recommend the following

home management techniques because there are no

studies demonstrating effectiveness and it is the opinion of the Panel that these techniques may delay

patients from obtaining necessary care.

■ 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, cold remedies, and bronchodilators.

Over-the-counter metered-dose inhalers may provide transient bronchodilation, but their use should

not be permitted to 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, they do not

bring about improvement in lung function.

PREHOSPITAL EMERGENCY 

MEDICINE/AMBULANCE 

MANAGEMENT OF ASTHMA 

EXACERBATIONS

The Expert Panel recommends that prehospital

providers administer supplemental oxygen and

inhaled short-acting bronchodilators to patients

who have signs or symptoms of asthma. Prehospital administration of inhaled bronchodilators

reduces airflow obstruction and relieves symptoms

(Fergusson et al. 1995). Thus, advanced life 

support units should have available an inhaler plus

spacer/holding chamber and/or nebulizer for beta2-

agonist administration (see figure 3-10 for dosages).

If these are not available, subcutaneous epinephrine or

terbutaline should be given for severe exacerbations

(see figure 3-10) (Sly et al. 1977; Smith et al. 1977).

Ambulance services should develop prehospital 

protocols for the treatment of acute asthma in 

children and adults. Prehospital providers should

receive training in how to respond to the clinical 

signs and symptoms of severe airway obstruction 

and imminent respiratory failure. 

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., a short-acting beta2-agonist and the

means of giving it by aerosol and a source of supplemental oxygen) should be available in a physician’s

office. However, serious exacerbations require close

observation for deterioration, frequent treatment, and

repetitive measurement of lung function. Therefore,

most severe exacerbations of asthma require prompt

transfer to an emergency department for a complete

course of therapy (Brenner 1983a). An overview of the

treatment strategies in emergency departments and

hospitals is presented in figure 3-11 and detailed below.

Assessment

The Expert Panel recommends that all clinicians

treating asthma exacerbations be familiar with

the characteristics of patients at risk for lifethreatening deterioration (see figures 3-7a and 

3-7b). In the emergency department, treatment

should be started as soon as an asthma exacerbation is recognized and an assessment of lung

function is made.

While treatment is given, obtain a brief, focused

history and physical examination pertinent to the

exacerbation (see figure 3-9). Take a more detailed

history and complete physical examination and

perform laboratory studies only after initial therapy has been completed.

■ The objectives of functional assessment are to:

— Obtain objective information on the severity of

airflow obstruction (FEV1 or PEF) and the

patient’s response to treatment. In the emergency

department, obtain FEV1 or PEF on presentation, after initial treatment, and at frequent

intervals thereafter, depending on the patient’s

response to therapy. Rarely, a patient’s airflow

obstruction may be so severe as to prevent performance of a maximal expiratory maneuver.

In the hospital, measure FEV1 or PEF before and

15 to 20 minutes after bronchodilator therapy

during the acute phase of the exacerbation.

Thereafter, measure FEV1 or PEF at least daily

until discharge. Values <30 percent of predicted that improve by <10 percent after

Component 3: Pharmacologic Therapy

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Managing Exacerbations of Asthma

FIGURE 3-10. DOSAGES OF DRUGS FOR ASTHMA EXACERBATIONS

IN EMERGENCY MEDICAL CARE OR HOSPITAL

Dosages

Medications Adult Dose Child Dose Comments

Inhaled Short-Acting Beta2-Agonists

Albuterol

Nebulizer solution (5 mg/mL) 2.5-5 mg every 20 minutes for 3 0.15 mg/kg (minimum dose 2.5 Only selective beta2-agonists are doses, then 2.5-10 mg every 1-4 mg) every 20 minutes for 3 doses, recommended. For optimal

hours as needed, or 10-15 then 0.15-0.3 mg/kg up to 10 delivery, dilute aerosols to

mg/hour continuously mg every 1-4 hours as needed, minimum of 4 mL at gas flow of or 0.5 mg/kg/hour by 6-8 L/min.

continuous nebulization

MDI (90 mcg/puff) 4-8 puffs every 20 minutes up to 4-8 puffs every 20 minutes for As effective as nebulized therapy 4 hours, then every 1-4 hours 3 doses, then every 1-4 hours if patient is able to coordinate

as needed as needed inhalation maneuver. Use

spacer/holding chamber.

Bitolterol

Nebulizer solution (2 mg/mL) See albuterol dose See albuterol dose; thought to Has not been studied in severe be half as potent as albuterol asthma exacerbations. Do not 

on a mg basis mix with other drugs.

MDI (370 mcg/puff) See albuterol dose See albuterol dose Has not been studied in severe asthma exacerbations.

Pirbuterol

MDI (200 mcg/puff) See albuterol dose See albuterol dose; thought to be Has not been studied in severe half as potent as albuterol on asthma exacerbations.

a mg basis

Systemic (Injected) Beta2-Agonists

Epinephrine 0.3-0.5 mg every 20 minutes for 0.01 mg/kg up to 0.3-0.5 mg No proven advantage of systemic

1:1000 (1 mg/mL) 3 doses sq every 20 minutes for 3 doses sq therapy over aerosol.

Terbutaline 0.25 mg every 20 minutes for 3 0.01 mg/kg every 20 minutes for No proven advantage of systemic

(1 mg/mL) doses sq 3 doses then every 2-6 hours therapy over aerosol. as needed sq

Anticholinergics

Ipratropium bromide 0.5 mg every 30 minutes for 3 .25 mg every 20 minutes for May mix in same nebulizer with

Nebulizer solution doses then every 2-4 hours 3 doses, then every 2 to 4 hours albuterol. Should not be used as

(.25 mg/mL) as needed first-line therapy; should be added to beta2-agonist therapy.

MDI (18 mcg/puff) 4-8 puffs as needed 4-8 puffs as needed Dose delivered from MDI is low and has not been studied in

asthma exacerbations.

Corticosteroids

Prednisone 120-180 mg/day in 3 or 4 1 mg/kg every 6 hours for 48 For outpatient “burst” use 40-60

Methylprednisolone divided doses for 48 hours, hours then 1-2 mg/kg/day mg in single or 2 divided doses

Prednisolone then 60-80 mg/day until PEF (maximum = 60 mg/day) in 2 for adults (children: 1-2 reaches 70% of predicted or divided doses until PEF 70% mg/kg/day, maximum 60 

personal best of predicted or personal best mg/day) for 3-10 days 

Note:

■ No advantage has been found for higher dose 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 usual regimen is to continue the frequent multiple daily dosing until the patient

achieves an FEV1 or PEF of 50 percent of predicted or personal best and then lower the dose to twice daily. This usually occurs within 48 hours. Therapy following a hospitalization or emergency department visit may last from 3 to 10 days. If patients are then started on inhaled corticosteroids, studies indicate there is

no need to taper the systemic corticosteroid dose. If the followup systemic corticosteroid therapy is to be given once daily, one study indicates that it may be

more clinically effective to give the dose in the afternoon at 3:00 p.m., with no increase in adrenal suppression (Beam et al. 1992).

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Component 3: Pharmacologic Therapy

FIGURE 3-11. MANAGEMENT OF ASTHMA EXACERBATIONS: EMERGENCY DEPARTMENT

AND HOSPITAL-BASED CARE

Initial Assessment (see figure 3)

History, physical examination (auscultation, use of accessory muscles, heart rate, respiratory rate), PEF or FEV1, oxygen saturation, and other tests as indicated

Repeat Assessment

Symptoms, physical examination, PEF, O2 saturation, other tests as needed

Moderate Exacerbation

FEV1 or PEF 50-80% predicted/personal best

Physical exam: moderate symptoms

● Inhaled short-acting beta2-agonist every 60 minutes

● Systemic corticosteroid

● Continue treatment 1-3 hours, provided there is improvement

Good Response

● FEV1 or PEF ≥70%

● Response sustained 60 minutes after last 

treatment

● No distress

● Physical exam: normal

Impending or Actual

Respiratory Arrest

● Intubation and mechanical ventilation 

with 100% O2

● Nebulized beta2-agonist and anticholinergic

● Intravenous corticosteroid

Admit to Hospital Intensive Care

(see box below)

FEV1 or PEF >50% ● Inhaled beta2-agonist by metered-dose inhaler or 

nebulizer, up to three doses in first hour

● Oxygen to achieve O2 saturation ≥90%

● Oral systemic corticosteroids if no immediate response or 

if patient recently took oral systemic corticosteroid

FEV1 or PEF <50% (Severe Exacerbation) ● Inhaled high-dose beta2-agonist and

anticholinergic by nebulization every

20 minutes or continuously for 1 hour

● Oxygen to achieve O2 saturation ≥90%

● Oral systemic corticosteroid

Severe Exacerbation

FEV1 or PEF <50% predicted/personal best

Physical exam: severe symptoms at rest, accessory muscle use, chest retraction

History: high-risk patient

No improvement after initial treatment

● Inhaled short-acting beta2-agonist, hourly or continuous + inhaled anticholinergic

● Oxygen

● Systemic corticosteroid

Incomplete Response

● FEV1 or PEF ≥50% but <70%

● Mild-to-moderate symptoms

Poor Response

● FEV1 or PEF <50%

● PCO2 ≥42 mm Hg

● Physical exam: symptoms severe, 

drowsiness, confusion

Admit to Hospital Ward

● Inhaled beta2-agonist + inhaled

anticholinergic

● Systemic (oral or intravenous) 

corticosteroid

● Oxygen

● Monitor FEV1 or PEF, O2 saturation, pulse

Admit to Hospital Intensive Care

● Inhaled beta2-agonist hourly or 

continuously + inhaled anticholinergic

● Intravenous corticosteroid

● Oxygen

● Possible intubation and mechanical 

ventilation

Improve

Individualized decision re:

hospitalization (see text)

Discharge Home

● Continue treatment with inhaled beta2-agonist

● Continue course of oral systemic corticosteroid

● Patient education

— Review medicine use

— Review/initiate action plan

— Recommend close medical followup

Discharge Home

● Continue treatment with inhaled beta2-agonist

● Continue course of oral systemic corticosteroid

● Patient education

— Review medicine use

— Review/initiate action plan

— Recommend close medical followup

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Managing Exacerbations of Asthma

bronchodilator therapy or that fluctuate widely

over 24 hours indicate a heightened risk of 

life-threatening deterioration.

—In patients with severe distress or with FEV1

or PEF <50 percent of predicted, assess the 

adequacy of arterial oxygen saturation by 

pulse oximetry (Connett and Lenney 1993; 

Geelhoed et al. 1994).

■ Objectives of the brief history are to determine:

—Time of onset and cause of current 

exacerbation

— Severity of symptoms, especially compared 

with previous exacerbations

— All current medications and time of last dose

— Prior hospitalizations and emergency 

department visits for asthma, particularly 

within the past year

— 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 physical examination are to:

— Assess the severity of the exacerbation as indicated by the findings listed in figure 3-9.

— 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 complications (e.g., pneumonia, pneumothorax, or pneumomediastinum).

— Identify other diseases that may affect asthma

(e.g., allergic rhinitis, rhinitis, sinusitis).

— Rule out upper airway obstruction. Both

intrathoracic and extrathoracic central airway

obstruction can cause severe dyspnea and may

be diagnosed as asthma. Causes include

epiglottitis, organic diseases of the larynx, vocal

cord dysfunction, and extrinsic and intrinsic

tracheal narrowing (see component 1-Initial

Assessment and Diagnosis). Clues as to their

presence 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, obtain further evaluation by

flow-volume curves and by referral for laryngoscopy (see component 1-Initial Assessment

and Diagnosis).

■ The most important objective of laboratory studies is

detection of actual or impending respiratory failure; other objectives include detection of theophylline toxicity and of conditions that complicate

the treatment of asthma exacerbations. Do not 

permit these studies to delay initiation of treatment. 

For example, 

— Consider arterial blood gas (ABG) measurement

for evaluating arterial carbon dioxide tension

(PCO2) in patients with suspected hypoventilation, with severe distress, or with FEV1 or PEF

30 percent of predicted after initial treatment.

(NOTE: Respiratory drive is typically increased

in asthma exacerbations, so a “normal” PCO2 of

40 mm indicates severe airflow obstruction and

a heightened risk of respiratory failure.)

—Complete blood count (CBC) may be appropriate

in patients with 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 to 2 hours

of administration.

— Measure serum theophylline concentration in patients

taking theophylline prior to presentation.

— It may be prudent to measure serum electrolytes

in patients who have been taking diuretics regularly and in patients with coexistent cardiovascular disease, because frequent beta2-agonist

administration can cause transient decreases in

serum potassium, magnesium, and phosphate.

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114

—Chest radiography is not recommended for 

routine assessment but should be obtained in

patients suspected of a complicating cardiopulmonary process, such as pneumothorax, 

pneumomediastinum, pneumonia, lobar

atelectasis, or congestive heart failure.

—Electrocardiograms need not be routinely

obtained, but a baseline electrocardiogram and

continual monitoring of cardiac rhythm are

appropriate in patients older than 50 years of

age and in those with coexistent heart disease

or chronic obstructive pulmonary disease. 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 with asthma.

However, using a combination of the subjective

and objective parameters in figure 3-9 permits

a fairly accurate assessment to guide initial

therapy. Many of these parameters have not

been systematically studied, 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, 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. Close monitoring is critical.

— It is particularly important to monitor O2

saturation 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 oxygen

saturation is often an early sign of severe 

airway obstruction, and an SaO2 <91 percent

on room air is a good predictor of the need for

hospitalization in small infants (Connett and

Lenney 1993; Geelhoed et al. 1994).

— Capillary or ABG measurements should be 

performed in infants suspected of respiratory

failure. PCO2 is the best measurement of ventilation in infants, as it is in adults. Children

with a normal PCO2 but in obvious respiratory

distress are at high risk for respiratory failure.

Treatment

In the emergency department and hospital, tailor the

intensity of treatment and surveillance to the severity

of the exacerbation. The primary therapies—the

administration of oxygen, inhaled beta2-agonist, 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 inhaled beta2-agonist therapy at

the higher dose (figure 3-10) either repeatedly (three

treatments in the first hour) or continuously (by nebulization), give systemic corticosteroids immediately,

and watch closely for signs of worsening airflow

obstruction or fatigue. For patients with mild exacerbations, give inhaled beta2-agonist therapy and assess

the patient’s response before deciding whether additional therapy is necessary. Give supplemental 

oxygen to patients with significant hypoxemia and to

patients with FEV1 or PEF <50 percent of predicted

when arterial oxygen monitoring is not available.

The following recommendations are based on 

scientific evidence (key studies are cited) and the

opinion of the Expert Panel:

■ Oxygen is recommended for most patients.

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 with coexistent heart

disease). Monitor oxygen saturation until a clear

response to bronchodilator therapy has occurred.

■ Inhaled short-acting beta2-agonists are 

recommended for all patients (for recommended

doses, see figure 3-10).

Component 3: Pharmacologic Therapy

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115

■ Systemic corticosteroids are recommended for

most patients (for recommended doses, see figure

3-10).

—In the emergency department: Give systemic

corticosteroids to patients who have moderate-to-severe exacerbations and patients

who do not respond completely to initial

beta2-agonist therapy. These medications

appear to speed the resolution of airflow

obstruction and reduce the rate of relapse

(Fanta et al. 1983; Rowe et al. 1992; Scarfone

et al. 1993; Connett et al. 1994; Chapman et

al. 1991).

- Oral administration of prednisone has been 

shown to have effects equivalent to those of 

intravenous methylprednisolone (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 supplemental doses of oral corticosteroids to patients who take them regularly,

even if the exacerbation is mild.

- In infants and children, it is especially 

important to give corticosteroids early in the 

course of an asthma exacerbation (Harris et 

al. 1987).

—In the hospital: Give systemic corticosteroids to patients admitted to the 

hospital, because they speed the resolution 

of asthma exacerbations (Connett et al. 

1994; Rowe et al. 1992; Singh and Kum

ar 1993).

■ Methylxanthines are not generally recommended.

—In the emergency department: Theophylline/aminophylline is not recommended because it appears

to provide no additional benefit to optimal

inhaled beta2-agonist therapy and may increase

adverse effects (Fanta et al. 1986; Rossing et al.

1980; Murphy et al. 1993; Rodrigo and Rodrigo

1994; Coleridge et al. 1993).

— In patients currently taking a theophyllinecontaining preparation, determine serum 

theophylline concentration to rule out 

theophylline toxicity.

Managing Exacerbations of Asthma

— The repetitive or continuous administration of

inhaled short-acting beta2-agonists is the most

effective means of reversing airflow obstruction

(Lipworth et al. 1988; Lin et al. 1993; Rudnitsky et al. 1993).

—In the emergency department, three treatments of

beta2-agonists spaced every 20 to 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 beta2-agonists may be more effective

in children and severely obstructed adults (Lin

et al. 1993; Rudnitsky et al. 1993; Papo et al.

1993; Kelly and Murphy 1992). 

— Because of the risk of cardiotoxicity, use only

selective beta2-agonists (albuterol, terbutaline,

pirbuterol, bitolterol) in high doses.

— Studies show that equivalent bronchodilation

can be achieved by either high doses (6 to 12

puffs) of a beta2-agonist by MDI with a spacer/holding chamber under the supervision of

trained personnel or by nebulizer therapy (Idris

et al. 1993; Colacone et al. 1993; Kerem et al.

1993). However, nebulized therapy is more

effective in patients who are unable to coordinate inhalation of medication from an MDI

because of their age, agitation, or severity of

the exacerbation.

— The onset of action for inhaled beta2-agonist is

less than 5 minutes; repetitive administration

produces incremental bronchodilation (Lipworth et al. 1988).

— Duration of action of bronchodilation from

beta2-agonists in severe asthma exacerbations is

not precisely known.

■ Anticholinergics may be considered. Adding

high doses of ipratropium bromide (0.5 mg in

adults, 0.25 mg in children) to an aerosolized solution of a selective beta2-agonist has been shown to

cause additional bronchodilation, particularly in

those with severe airflow obstruction (Schuh et al.

1995; Reisman et al. 1988; O’Driscoll et al. 1989;

Kelly and Murphy 1991), although some studies did

not demonstrate this effect (Karpel et al. 1996).

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116

—In the hospital: Therapy with oral or intravenous methylxanthines does not benefit children hospitalized with severe asthma (Strauss et

al. 1994; Carter et al. 1993; DiGiulio et al.

1993). The addition of intravenous theophylline in hospitalized adults remains controversial (Huang et al. 1993; Self et al. 1990).

■ Antibiotics are not recommended for asthma

treatment but may be necessary for comorbid

conditions. Bacterial, chlamydia, and mycoplasma

respiratory tract infections are thought to 

contribute only infrequently to exacerbations of

asthma. The use of antibiotics is generally reserved

for those patients with fever and purulent sputum

(discolored because of polymorphonuclear leukocytes, not eosinophils) and for patients with evidence of pneumonia. When the presence of 

bacterial sinusitis is suspected, treat with antibiotics. 

■ Aggressive hydration is not recommended for

older children and adults but may be indicated

for infants and young children. Intravenous or

oral administration of large volumes of fluids does

not play a role in the management of severe asthma

exacerbations. However, infants and young children may become dehydrated as a result of

increased respiratory rate and decreased oral

intake. In these patients, make an assessment of

fluid status (urine output, urine specific gravity,

mucus membrane moisture, electrolytes) and 

provide appropriate corrections.

■ Chest physical therapy is not generally 

recommended. In general, chest physiotherapy 

is not beneficial and is unnecessarily stressful for

the breathless asthma patient.

■ Mucolytics are not recommended. Avoid

mucolytic agents (e.g., acetylcysteine, potassium

iodide) because they may worsen cough or airflow

obstruction.

■ Sedation is not recommended. Anxiolytic and

hypnotic drugs are contraindicated in severely ill

asthma patients because of their respiratory

depressant effect.

Repeat Assessment

The Expert Panel recommends that repeat assessment of patients with severe exacerbations be

made after the initial dose of inhaled bronchodilator and that repeat assessment of all

patients be made after three doses of inhaled 

bronchodilator (60 to 90 minutes after initiating

treatment). The response to initial treatment in the

emergency department is a better predictor of the need

for hospitalization than is the severity of an exacerbation

on presentation (Rodrigo and Rodrigo 1993). The elements to be evaluated include the patient’s subjective

response, physical findings, measurement of airflow, and

measurement of ABG if the patient now meets the criteria described in the discussion of laboratory studies in

the Assessment section, page 110.

Hospitalization

The decision to hospitalize a patient should be based

on duration and severity of symptoms, severity of airflow obstruction, course and severity of prior exacerbations, medication use at the time of the exacerbation, access to medical care and medications, 

adequacy of support and home conditions, and presence of psychiatric illness. In general, the principles

of care in the hospital resemble those for care in the

emergency department and involve both treatment

with oxygen, aerosolized bronchodilators, and systemic corticosteroids and frequent assessment, including clinical assessment of respiratory distress and

fatigue and objective measurement of airflow (PEF 

or FEV1) and oxygen saturation. 

Impending Respiratory Failure

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 a declining mental clarity, worsening

fatigue, and a PCO2 of >_ 42 mm Hg. Exactly when

to intubate is based on clinical judgment; however,

the Expert Panel recommends that intubation not

be delayed once it is deemed necessary. Because

respiratory failure can progress rapidly and can be 

difficult to reverse, early recognition and treatment

are critically important.

Because intubation of a severely ill asthma patient is

difficult, additional treatments are sometimes

attempted, such as intravenous administration of magnesium sulfate (Kuitert and Kletchko 1991; Skorodin

et al. 1995; Tiffany et al. 1993; Green and Rothrock

1992) and substituting a mixture of helium and

Component 3: Pharmacologic Therapy

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Managing Exacerbations of Asthma

oxygen (“heliox”) for oxygen-enriched air (Manthous et

al. 1995; Gluck et al. 1990). Although limited observations suggest that these therapies may be effective, 

possibly among certain subgroups (Bloch et al. 1995),

they have not yet been proven consistently effective.

Intravenous administration of a beta2-agonist also falls

into this category of unproven treatment. Recent 

studies suggest that albuterol is more effective and has

fewer side effects when it is given by aerosol than when

given intravenously (Salmeron et al. 1994), but the

efficacy of adding an intravenous beta2-agonist to 

high-dose nebulized therapy has not been studied. 

Do not use intravenous isoproterenol in the treatment

of asthma because of the danger of myocardial toxicity

(Maguire et al. 1991).

The Expert Panel recommends the following

actions regarding intubation:

■ Patients presenting with apnea or coma should

be intubated immediately. 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.

■ Consultation with or comanagement by physicians expert in ventilator management is appropriate because mechanical ventilation of patients

with severe refractory asthma is complicated and

fraught with risk.

■ Because intubation is difficult in asthma

patients, it is best done semi-electively, before

the crisis of respiratory arrest.

■ Intubation should be performed in a controlled

setting by a physician with extensive experience

in intubation and airway management.

— It is preferable that patients with severe exacerbations who are slowly responsive to therapy be

admitted to an intensive care unit where they

can be monitored closely and intubated if it is

indicated.

— Because intubation should not be delayed once

it is deemed necessary, it may be performed in

the emergency department or inpatient ward

and the patient transferred to an intensive care

unit appropriate to the patient’s age.

— Children intubated for asthma should be

admitted to a pediatric intensive care unit or

transferred to a facility that has such a unit.

■ Issues to consider at the time of intubation include

the following:

— Close attention should be given to maintaining

or replacing intravascular volume, because

hypotension commonly accompanies the initiation of positive pressure ventilation.

— Once mechanical ventilation has been started,

it is important to avoid high ventilator pressures and the associated risks of barotrauma.

■ “Permissive hypercapnia” or “controlled

hypoventilation” is the recommended ventilator strategy to provide adequate oxygenation and

ventilation while minimizing high airway pressures

and barotrauma (Tuxen 1994; Darioli and Perret

1984; Menitove and Goldring 1983). It involves

administration of as high an FiO2 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 I:E ratio to minimize airway pressures.

Bronchodilators are continued, and even in ventilated patients, aerosol delivery is the route of

choice (Dhand and Tobin 1996).

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

Before discharge, provide patients with necessary

medications and education in how to use them,

instruction in self-assessment (e.g., by monitoring

symptoms and peak flow), a followup appointment, and instruction in an action plan for managing recurrence of airflow obstruction. To ensure

that these steps are taken, a discharge checklist may

be useful (see example in figure 3-12).

From the Emergency Department

■ Release of the patient from the emergency

department depends on the patient’s response

to treatment.

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118

— 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 with an incomplete response

to therapy (FEV1 or PEF >_50 but <70 percent

predicted or personal best) and with mild

symptoms should be assessed individually for

their suitability for discharge home, with consideration of factors listed in figure 3-7a.

— The Panel’s opinion is that patients with a

rapid response should be observed for 30 to 60

minutes after the most recent dose of bronchodilator to ensure 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. 

■ Prescribe sufficient medications for the patient

to continue treatment after discharge. Patients

given systemic corticosteroids should continue oral

systemic corticosteroids for 3 to 10 days. The need

for further corticosteroid therapy should be assessed

at a followup visit. If the patient is receiving

inhaled corticosteroids, it is not necessary to taper

the dose gradually when the course is completed

(O’Driscoll et al. 1993).

■ Emphasize the need for continual, regular care

in an outpatient setting. Refer the patient to a

followup medical appointment. A visit to the

emergency department is often an indication of

inadequate long-term management of asthma or

inadequate plans for handling exacerbations.

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 instruct the

patient to seek a followup medical appointment

within 3 to 5 days. When possible, schedule such

an appointment prior to the patient’s discharge.

The followup visit should include a detailed review

of the patients’ medications, inhaler and peak flow

meter technique, and development of comprehensive daily management and action plans that will

help prevent exacerbations and urgent care visits

(see figures 4-4 and 4-5). Referral to an asthma

specialist for consultation should be considered

because this has been reported to reduce the rate

of subsequent emergency department visits (Zeiger

et al. 1991).

Component 3: Pharmacologic Therapy

FIGURE 3-12. HOSPITAL DISCHARGE CHECKLIST FOR PATIENTS

WITH ASTHMA EXACERBATIONS

Intervention Dose/Timing Education/Advice M.D./R.N. Initials

Inhaled medications Select agent, dose, and Teach purpose (MDI + spacer/holding chamber) frequency (e.g., albuterol) Teach technique

Beta2-agonist 2-6 puffs q 3-4 hr prn Emphasize need for spacer/ holding chamber Corticosteroids Medium dose Check patient technique

Oral medications Select agent, dose, and frequency Teach purpose

(e.g., prednisone 20 mg bid Teach side effects

for 3-10 days)

Peak flow meter Measure a.m. and p.m. PEF and record Teach purpose

best of three tries each time Teach technique Distribute peak flow diary

Followup visit Make appointment for followup care Advise patient (or caregiver) 

with primary clinician or asthma of date, time, and location of

specialist appointment 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, and PEF values suggest

recurrent airflow obstruction

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119

Managing Exacerbations of Asthma

■ Review written discharge medications and,

whenever possible, provide patient education on

avoidance of asthma triggers and correct use of an

inhaler (see figure 4-3).

■ Instruct the patient in a simple action plan for

increasing medications or returning for care should

asthma worsen.

■ Consider issuing a peak flow meter and providing patient education on how to measure and

record daily PEF rates.

From the Hospital

■ Prior to discharge, adjust the patient’s medication to an oral and/or inhaled regimen. The optimal timing of this transition is not precisely established, but the general approach is to wait until the

patient is minimally symptomatic from asthma and

has little wheezing on chest examination. Usually

this clinical status corresponds to a PEF or FEV1 of

>_70 percent of predicted or personal best. During

the first 24 hours after this medication adjustment,

observe the patient for possible deterioration.

■ Discharge medications should include a shortacting inhaled beta2-agonist and sufficient oral

corticosteroid to complete the course of therapy

or to continue therapy until the followup appointment. If the decision is made to start the patient

on inhaled corticosteroids, they should be started

before the course of oral corticosteroids is completed, because their onset of action is gradual (Kraan

et al. 1988). Starting the inhaled corticosteroid

therapy before discharge gives the patient additional time to learn and demonstrate appropriate

technique.

■ Provide patient education:

— An exacerbation severe enough to require hospitalization may reflect a failure of the patient’s

self-management plan. Hospitalized patients

may be particularly receptive to information and

advice about their illness; take the opportunity to

review patient understanding of the causes of

asthma exacerbations, the purposes and correct

uses of treatment, and the actions to be taken for

worsening symptoms or peak flow values.

— Educate patients about their discharge medications and the importance of a followup medical

visit. Referral to an asthma specialist should be

considered for patients with a history of lifethreatening exacerbations or multiple hospitalizations (see component 1, page 23) (Mayo et

al. 1990).

— Educate patients older than 5 years of age in

the use of peak flow meters to monitor their

lung function at home.

—Review or develop an action plan for management of

recurrent symptoms or exacerbations. 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 emergency

department may be quite simple (e.g., instructions for discharge medications and returning

for care should asthma worsen). The plan

developed for discharge from the hospital

should be more complete (see figure 3-12). 

A detailed plan for comprehensive long-term

management and handling exacerbations

should be developed by the regular provider at

a followup visit (see figure 4-5).

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Kraan J, Koeter GH, van der Mark TW, et al. Dosage and time

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Managing Exacerbations of Asthma

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KEY POINTS

■ Patient education should begin at the time of diagnosis and be integrated into every step of clinical asthma care.

■ It is essential that education be provided by all members of the health care team. The principal clinician should

introduce the key educational messages and negotiate agreements with patients; these messages should be 

reinforced and expanded by all members of the health care team.

■ Teach asthma self-management, tailoring the approach to the needs of each patient. Maintain a sensitivity 

to cultural beliefs and practices.

■ Teach and reinforce at every opportunity:

— Basic facts about asthma

— Roles of medications

— Skills: inhaler/spacer/holding chamber use, self-monitoring

— Environmental control measures 

— When and how to take rescue actions

■ Jointly develop treatment goals. 

■ To encourage an active partnership, provide all patients with a written daily self-management plan and an action

plan for exacerbations. Action plans are especially important for patients with moderate-to-severe asthma and

patients with a history of severe exacerbations. Provide appropriate patients with a daily asthma diary.

■ Encourage adherence by promoting open communication; individualizing, reviewing, and adjusting plans as 

needed; emphasizing goals and outcomes; and encouraging family involvement.

DIFFERENCES FROM 1991 EXPERT PANEL REPORT

■ Emphasis is on patient education by the principal clinician as well as other members of the health care team.

■ To enhance the delivery of education, detailed questions to elicit information and educational messages for each 

visit are provided in chart form. Reinforcement of key messages is emphasized.

■ Additional emphasis is placed on evaluating outcomes in terms of patient perceptions of improvement, especially

quality of life and the ability to engage in desired activities.

■ Roles of written materials and formal education programs are clarified with emphasis that they can supplement 

but not replace education by clinicians. A list of sources for asthma education programs and materials is provided.

■ Renewed emphasis is placed on providing patients with both a written treatment plan for daily self-management

and a written action plan for management of exacerbations. Examples are provided that are applicable to both

children and adults.

■ New section on assessing and responding to cultural and language differences was added.

■ New section on patient education for non-chlorofluorocarbon inhalers was added.

COMPONENT 4: 

EDUCATION FOR A PARTNERSHIP IN ASTHMA CARE Archive

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124

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

successfully accomplish those tasks. It is also a 

powerful tool for helping patients gain the motivation, skill, and confidence to control their asthma 

(Feldman et al. 1987; Mellins 1989). Research shows

that asthma education can be cost-effective and can

reduce morbidity for both adults and children, 

especially among high-risk patients (Trautner et al.

1993; Bolton et al. 1991; Fireman et al. 1981; 

Hindi-Alexander and Cropp 1984; Lewis et al. 1984;

Clark et al. 1986).

This component covers strategies for enhancing the

delivery of patient education and improving the 

likelihood that patients will follow clinical recommendations, as well as key messages to communicate to the

patient. When references are not cited, recommendations are based on the opinion of the Expert Panel.

ESTABLISH A PARTNERSHIP

Patient education should begin at the time of

diagnosis and be integrated into every step of

medical care, in the context of medical appointments and other clinician-patient communication. When clinicians take the time to provide education, it sends a powerful message to patients and

families about the importance of being knowledgeable

self-management of asthma. Specific educational

messages delivered in the context of a medical care

appointment clearly communicate the importance of

collaboration in the treatment of asthma (Mayo et al.

1990; Ignacio-Garcia and Gonzales-Santos 1995). 

From the time of diagnosis, the clinician and other

members of the health care team should begin to

build a partnership with the patient and family.

Building the 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 self-management skills necessary to

monitor the disease objectively and take medication

effectively (Evans et al. 1997).

When nurses, pharmacists, respiratory therapists,

and other health care professionals are available

to support and expand patient education (NHLBI

1995a, 1995b), a team approach should be used.

The principal clinician should introduce the key

educational messages (see figure 4-1) and negotiate

agreements with patients (Mayo et al. 1990; Kotses

et al. 1996). Different members of the health care

team should reinforce and expand these messages

during office visits and telephone calls or in more

formal educational sessions.

Communication and coordination within the team are

critical. Team members should document in the

patient’s record the key educational points (see

figure 4-1), patient concerns, and actions the

Component 4: Education for a Partnership in Asthma Care

FIGURE 4-1. KEY EDUCATIONAL 

MESSAGES FOR PATIENTS

Check off or document that the following key messages 

have been covered:

Basic Facts About Asthma

■■The contrast between asthmatic and normal

airways

■■What happens to the airways in an asthma

attack

Roles of Medications

■■How medications work

– Long-term control: medications that 

prevent symptoms, often by reducing

inflammation

– Quick relief: short-acting bronchodilator

relaxes muscles around airways

■■Stress the importance of long-term-control

medications and not to expect quick relief from

them.

Skills

■■Inhaler use (patient demonstrate)

■■Spacer/holding chamber use

■■Symptom monitoring, peak flow monitoring,

and recognizing early signs of deterioration

Environmental Control Measures

■■Identifying and avoiding environmental 

precipitants or exposures

When and How To Take Rescue Actions

■■Responding to changes in asthma severity

(daily self-management plan and action plan)

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125

Education for a Partnership in Asthma Care

patient agrees to take. This will enable all members

of the team to be consistent and to reinforce the 

educational points and the progress being made.

Teach Asthma Self-Management

The Expert Panel recommends that clinicians

teach patients and families the essential information, medication skills, self-monitoring techniques, and environmental control measures

outlined in figure 4-2 (Bailey et al. 1990; IgnacioGarcia and Gonzales-Santos 1995; Kotses et al. 1995,

1996; Wilson et al. 1993). These key points should

be adapted to meet the individual patient’s needs.

Clinicians should:

■ 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 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 

4-3) and spacer/holding chamber and knowing

when and how to take quick- relief medications. (Also see box 1, Patient Education for 

Non-CFC Inhalers.)

■ Teach self-monitoring skills: symptom 

monitoring, peak flow monitoring as 

appropriate (see component 1-Periodic

Assessment and Monitoring), and recognizing

early signs of deterioration.

■ Teach relevant environmental control/avoidance strategies (see figure 2-4). Teach how 

environmental precipitants or exposures can make 

the patient’s asthma worse (e.g., allergens and 

irritants) at home, school, and work and how to

recognize both immediate and delayed reactions.

BOX 1. PATIENT EDUCATION FOR NON-CFC INHALERS

Clinicians need to be aware that metered-dose inhalers (MDIs) containing chlorofluorocarbons (CFCs) contribute

to the depletion of stratospheric ozone. As a result of the consequent health hazards, CFCs have been internationally banned. Although a temporary medical exemption has been granted, MDIs with CFC propellants will

eventually have to be replaced with alternative aerosol products, including MDIs with non-CFC propellants.

Other non-CFC options include multidose dry powder inhalers and hand-held mini-nebulizers.

When first prescribing any of these new alternative products to patients accustomed to a CFC-containing MDI, the Expert Panel recommends that clinicians review with the patient the appropriate inhalation

technique and care of the device to ensure proper use and optimum device performance. For alternative

propellant MDIs, the patient may perceive differences in the aerosol delivery compared to their CFC-containing

MDI. The patient should be given the following messages about these differences:

■ All FDA-approved alternative propellant inhalers will have been demonstrated to be comparably safe

and effective as their usual CFC-propelled medication in clinical trials. However, individual differences in tolerability may be observed. 

■ Clinicians should familiarize patients with any differences in the care and use of non-CFC devices.

■ The alternative propelled MDIs may taste different or feel different due to differences in the 

propellant and formulations. However, patients should be assured that these differences should not

lead to important differences in their use or benefit. 

For alternate propellant MDIs that deliver a less forceful aerosol plume, patients may believe that this less forceful

spray may not reach their lungs as effectively as their CFC product. Clinicians should reassure patients that medication delivery is assured by proper inhalation technique and that a less forceful spray does not equate with less

efficacy. This is an opportunity to train patients in the use of non-CFC devices.

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126

Component 4: Education for a Partnership in Asthma Care

FIGURE 4-2. DELIVERY OF ASTHMA EDUCATION BY CLINICIANS DURING PATIENT

CARE VISITS

Assessment Questions Information Skills

“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?”

What is asthma?

A chronic lung disease. The airways

are very sensitive. They become

inflamed and narrow; breathing

becomes difficult.

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.

Inhaler (see figure 4-3) and

spacer/holding chamber use. 

Check performance.

Self-monitoring skills that are tied to

an action plan:

■ Recognize intensity and frequency

of asthma symptoms

■ Review the signs of deterioration

and the need to reevaluate therapy:

•Waking at night with asthma

•Increased medication use

•Decreased activity tolerance

Use of a simple, written self-management plan (see figure 4-4) and action

plan (see figure 4-5)

Recommendations for First Followup Visit (2 to 4 weeks or sooner as needed)

Focus on: Teach in simple language: Teach or review and demonstrate:

■ Expectations of visit

■ Goals of treatment

■ Medications

■ 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.”

Use of two types of medications.

Remind patient to bring all medications and the peak flow meter to

every appointment for review.

Self-evaluation of progress in asthma

control using symptoms and peak

flow as a guide.

Use of a daily self-management plan. 

Review and adjust as needed.

Use of an action plan. 

Review and adjust as needed.

Peak flow monitoring (see figure 1-7) 

and daily diary recording (see figure

1-9).

Correct inhaler and spacer/holding 

chamber technique.

Recommendations for Initial Visit 

Focus on: Teach in simple language: Teach or review and demonstrate:

■ Expectations of visit

■ Goals of treatment

■ Medications

■ Quality of life Archive

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127

FIGURE 4-2. DELIVERY OF ASTHMA EDUCATION BY CLINICIANS DURING PATIENT

CARE VISITS (CONTINUED)

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 action plan?” “Can we make 

it easier?”

“Are your medications causing you any 

problems?”

Relevant environmental

control/avoidance strategies 

(see figure 2-4).

■ 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.

Review and interpret from daily

diary:

■ Peak flow measure

■ Symptom scores

Inhaler/spacer/holding chamber 

technique.

Peak flow monitoring technique.

Use of daily self-management plan. 

Review and adjust as needed.

Review use of action plan. Confirm

that patient knows what to do if

asthma gets worse.

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.”

Review and reinforce all:

■ Educational messages

■ Environmental control strategies

at home, work, or school

■ Medications

Review and interpret from daily

diary:

■ Peak flow measures

■ Symptom scores

Inhaler/spacer/holding chamber 

technique. 

Peak flow monitoring technique.

Use of daily self-management plan.

Review and adjust as needed.

Review use of action plan. Confirm

that patient knows what to do if

asthma gets worse. Periodically

review and adjust written action

plan.

Recommendations for All Subsequent Visits

Focus on: Teach in simple language: Teach or review and demonstrate:

■ Expectations of visit

■ Goals of treatment

■ Medications

■ Quality of life

Education for a Partnership in Asthma Care

Assessment Questions Information Skills

Recommendations for Second Followup Visit 

Focus on: Teach in simple language: Teach or review and demonstrate:

■ Expectations of visit

■ Goals of treatment

■ Medications

■ Quality of lifeArchive

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128

Figure 4-3.

Please demonstrate your inhaler technique at every visit.

1. Remove the cap and hold inhaler upright.

2. Shake the inhaler.

3. Tilt your head back slightly and breathe out slowly.

4. Position the inhaler in one of the following ways (A or B is optimal, but C is acceptable for those who

have difficulty with A or B. C is required for breath-activated inhalers):

5. Press down on the inhaler to release medication as you start to breathe in slowly.

6. Breathe in slowly (3 to 5 seconds).

7. Hold your breath for 10 seconds to allow the medicine to reach deeply into your lungs.

8. Repeat puff as directed. Waiting 1 minute between puffs may permit second puff to penetrate your

lungs better.

9. Spacers/holding chambers are useful for all patients. They are particularly recommended for young

children and older adults and for use with inhaled corticosteroids.

Avoid common inhaler mistakes. Follow these inhaler tips:

■ Breathe out before pressing your inhaler.

■ Inhale slowly.

■ Breathe in through your mouth, not your nose.

■ Press down on your inhaler at the start of inhalation (or within the first second of inhalation).

■ Keep inhaling as you press down on inhaler.

■ Press your inhaler only once while you are inhaling (one breath for each puff).

■ Make sure you breathe in evenly and deeply.

NOTE: Other inhalers are becoming available in addition to those illustrated above. Different types of inhalers may require different techniques.

Source: 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.

A. Open mouth with

inhaler 1 to 2 inches

away.

B. Use spacer/holding chamber

(that is recommended especially

for young children and for 

people using corticosteroids).

C. In the mouth. 

Do not use for corticosteroids.

D. NOTE: Inhaled dry

powder capsules require

a different inhalation

technique. To use a dry

powder inhaler, it is

important to close the

mouth tightly around

the mouthpiece of the

inhaler and to inhale

rapidly.

STEPS FOR USING YOUR INHALER Archive

for historical Reference Only
Education for a Partnership in Asthma Care

129

Jointly Develop Treatment Goals

Fundamental to building a partnership is for clinicians

and patients to 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

(Schulman 1979; Clark 1989; Clark et al. 1995). 

It is the opinion of the Expert Panel that 

clinicians should:

■ Determine the patient’s personal treatment

goals. 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. Asthma-specific

quality-of-life instruments (Juniper et al. 1992;

Marks et al. 1993) may be useful.

■ Share the general goals of asthma treatment

with the patient and family. Tell patients, 

“Our goals are to have you:

— Be free from severe 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.

Provide the Patient With Tools for 

Self-Management

It is the opinion of the Expert Panel that, at the

first visit, clinicians should develop a written,

individualized, daily self-management plan (see

figure 4-4) in consultation with the patient.

Include the recommended doses and frequencies of

daily medications and the daily self-management

activities needed to achieve the agreed-on goals.

Review and refine the plan at subsequent followup

visits. List the treatment goals in the plan and

explain how following the plan will help the patient

reach those goals. Emphasizing the patient’s personal

goals is essential to enhancing adherence. For example, ask, “Have you had any problems taking your

bronchodilator immediately before playing basketball? Has it helped you stay in the game?”

Discuss the long-term benefits of following the

written, daily self-management plan (Plaut 1996).

For some patients, focusing on long-term treatment

goals and discussing the “big picture” of asthma control and how medications can be adjusted over time

may improve adherence (Mellins 1996).

Also at the first visit, jointly develop a written

action plan to help the patient manage asthma

exacerbations (see figure 4-5, pages 138-143) for

examples). This is especially important for patients

with moderate-to-severe persistent asthma and

patients with a history of severe exacerbations.

Review and refine the plan at followup visits. The

action plan directs the patient to adjust medicines at

home in response to particular signs, symptoms, and

peak flow measurements. It should also list the PEF

levels and symptoms indicating the need for acute

care and emergency telephone numbers for the physician, emergency department, rapid transportation,

and family/friend for aid and support. A number of

action plans have been published (Woolcock et al.

1988; Beasley et al. 1989; D’Souza et al. 1994;

Charlton et al. 1990; Mellins and Evans, in press;

NHLBI 1995d; NHLBI 1995e). Those tested in randomized clinical trials were effective in decreasing

asthma exacerbations (Woolcock et al. 1988; Charlton

et al. 1990). Clinicians should choose an action plan

that suits their practice, patients, and style. The

examples in figure 4-5 are not endorsed by the Expert

Panel; rather, they are provided to demonstrate a

range of possibilities and should be modified as appropriate.

It is the opinion of the Expert Panel that clinicians should provide an asthma diary to appropriate patients for self-monitoring symptoms,

peak flow measurements, frequency of daily

quick-relief inhaler medication use, and activity

restriction (see figure 1-9).

Archive

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130

ASTHMA SELF-MANAGEMENT PLAN FOR 

(Name)

YOUR TREATMENT GOALS

■ Be free from severe 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

■ Not need emergency visits or hospitalizations for asthma

■ Use asthma medications to control asthma with as few side effects as possible

Add personal goals here:

___________________________________________________________________________________________________

___________________________________________________________________________________________________

___________________________________________________________________________________________________

___________________________________________________________________________________________________

YOUR DAILY MEDICATIONS

Daily Medication How Much To Take When To Take It

___________________________________________________________________________________________________

___________________________________________________________________________________________________

___________________________________________________________________________________________________

___________________________________________________________________________________________________ 

RECORD DAILY SELF-MONITORING ACTIONS in the asthma diary your doctor gives you.

Peak flow: At least every morning when you wake up, before taking your medication, measure your peak flow and record it in

your diary. Bring these records to your next appointment with your doctor.

Symptoms: Note if you had asthma symptoms (shortness of breath, wheezing, chest tightness, or cough) and 

rate how severe they were during the day or night: mild, moderate, severe.

Use of your quick-relief inhaler (bronchodilator): Keep a record of the number of puffs you needed to use 

each day or night to control your symptoms.

Actual use of daily medications:

Activity restriction:

This plan is provided as an example to clinicians.

Figure 4-4.

ASTHMA DAILY SELF-MANAGEMENT PLAN (EXAMPLE 1)

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131

LONG-TERM SELF-MANAGEMENT PLAN FOR PERSISTENT ASTHMA

Introduction: This long-term plan provides four benefits to the clinician and patient, who complete it together during an early visit and review it

periodically. The chart (1) reflects the step-up/step-down concept of pharmacotherapy; (2) enables patient and clinician to negotiate which medicines will be used and how often; (3) combines symptoms and/or peak flow monitoring as the basis for patient’s adding or deleting medicines at

home and self-adjusting doses; and (4) gives the patient a view of what the clinician recommends over the long-term—under what future circumstances the clinician intends that the regimen be increased or decreased.

Directions: The clinician writes the patient’s medicines in the first column. Based on the symptoms and peak flow specified in the top row, the

clinician then writes the doses and frequency of administration for each medication. (Some clinicians may prefer to print standard recommendations on the form to save time.) 

Medication At the FIRST If cough or If cough or As soon as When there is When there is Before exercise For rapidly sign of a cold wheeze is wheeze cough and no cough or no cough or or physical worsening 

or exposure present worsen wheeze have wheeze for 2 wheeze for activity asthma (severe

to known stopped weeks, even ____ months exacerbation)

trigger with activity OR OR OR OR OR

peak flow is peak flow is peak flow is peak flow is peak flow is

between 50 below 50% above 80% above 80% above 80%

and 80% of of personal of personal of personal of personal 

personal best best best best for best for 2 weeks ___ months

Times 

per day

Source: Mellins 1996.

This plan is provided as an example to clinicians.

Please note that the following long-term plan is included only as an example of how to fill out the plan. The treatment regimen itself does not

correspond to recommendations made in the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma.

LONG-TERM SELF-MANAGEMENT PLAN FOR PERSISTENT ASTHMA (EXAMPLE ONLY)

Medication At the FIRST If cough or If cough or As soon as When there When there Before exercise For rapidly sign of a cold wheeze is wheeze worsen cough and is no cough is no cough or physical worsening

or exposure to present wheeze or wheeze for or wheeze for activity asthma

known trigger have stopped 2 weeks, even ____ months (severe with activity exacerbation) OR OR OR OR OR

peak flow is peak flow is peak flow is peak flow is peak flow is

between 50 below 50% above 80% above 80% above 80%

and 80% of of personal of personal of personal best of personal best personal best best best for 2 weeks for___ months 

Short-acting 2 puffs 2 puffs 2 puffs 2 puffs 0 0 2 puffs 2-4 puffs beta2-agonist

Nonsteroidal 2 puffs 2 puffs 2 puffs 2 puffs 2 puffs 2 puffs 0 0 antiinflammatory

Inhaled 2 puffs 4 puffs 4 puffs 2 puffs 2 puffs 0 0 0 corticosteroid

TIMES PER 3 4 4 3 3 3 5-10 minutes every 20 

DAY (every 4 hrs) (every 4 hrs) before exercise minutes for 3 doses*

Oral 0 0 2 mg/kg/day x 0 0 0 0 0 corticosteroid 2 days then

1 mg/kg/day

x 3 days

* If there is not a good response, seek emergency care immediately. If there is a good response, return to the third column.

Figure 4-4.

ASTHMA DAILY SELF-MANAGEMENT PLAN (EXAMPLE 2)

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132

Encourage Adherence

An important part of patient education is encouraging adherence.

■ Use effective techniques to promote open

communication. Research suggests that certain

clinician behaviors are associated with patient

adherence and/or satisfaction with care (Clark et al.

1995). Not all are appropriate for cultural 

subgroups, but the items listed in figure 4-6 

are general guidelines.

■ Early in each visit, elicit the patient’s concerns,

perceptions, and unresolved questions about

his or her asthma (see figure 4-2). A question such

as “What worries you most about your asthma?,”

which cannot be answered yes or no, encourages

patients and families to voice issues, personal beliefs,

or concerns they may be apprehensive about discussing or may not think are of interest to the clinician. These potential barriers to adherence can be

dealt with only if they are identified. By asking

about and discussing such concerns, clinicians build

trust and a sense of partnership with the patient.

Most nonadherence originates in personal beliefs or

concerns about asthma that have not been discussed

with the clinician (Korsch et al. 1968; Janz et al.

1984). Until such fears and worries are identified and

addressed, patients will not be able to adhere to the

clinician’s recommendations (Korsch et al. 1968).

■ Assess the patient’s and family’s perceptions of

the severity level of the disease. Two questions

may prove useful: “How severe do you think your

asthma is?” and “How much danger do you

believe you are in from your asthma?” When

patients are identified who are overwhelmed by

fear of death, put their fears in perspective by providing them with the results of objective assessments and expert opinion. A clearly written,

detailed action plan that directs the patient how to

respond to worsening asthma may be extremely

helpful in reducing anxiety (figure 4-5). Patients’

perceptions about their disease severity and its

threat to their well-being influence self-management behavior and use of the health care system

(Janson-Bjerklie et al. 1992; Janz et al. 1984).

■ Assess the patient’s and family’s level of social

support. 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).

■ Encourage or enlist family involvement. Ask

patients to identify ways their family members can

help them follow the plans. Ask the patient to

share the plans with family members, elicit their

input, and agree on actions they can help with. 

It may be helpful for children and parents to 

discuss this with a clinician present.

■ Consider referral to a psychologist, social worker,

psychiatrist, or other licensed professional when

stress seems to unduly interfere with daily asthma

management. As with other chronic diseases,

emotional and social stress may be a confounding

factor for many patients struggling with asthma

control. Although stress does not cause asthma, 

it can play a role in precipitating asthma exacerbations (Busse et al. 1995) and can complicate an

individual’s attempts at self-management. 

Referral to a local support group may be useful.

Component 4: Education for a Partnership in Asthma Care

FIGURE 4-6. PROMOTING OPEN

COMMUNICATION TO ENCOURAGE

PATIENT ADHERENCE

Friendly Manner:

■ Show attentiveness (eye contact, attentive 

listening, etc.)

■ Give encouragements with nonverbal 

communication (nodding agreement, 

smiling, etc.)

■ Give verbal praise for effective 

management strategies

■ Use interactive conversation (e.g., 

asking open-ended questions)

Reassuring Communication:

■ Elicit patient’s underlying concerns 

about asthma

■ Allay fears with specific reassuring 

information

Adapted with permission from Clark et al. 1995.

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133

■ Use methods to increase the chances that the

patient will adhere to the written, daily selfmanagement plan. For instance, adherence to

the self-management plan is enhanced when the

plan is simplified as much as possible, when the

number of medications and frequency of daily

doses are minimized, when the medication doses

and frequency fit into the patient’s and family’s

daily routine (Clark et al. 1995; Haynes et al.

1979; Eisen et al. 1990; Evans 1993; Meichenbaum and Turk 1987), and when the plan considers the patient’s ability to afford the medications

(Hindi-Alexander and Throm 1987). Because

nonadherence is difficult for clinicians to detect

(Haynes et al. 1979; Charney et al. 1967; Mushlin

and Appel 1977), it is prudent to explore potential

barriers to adherence with every patient by asking

what concerns they have about medicines (e.g.,

safety) or other aspects of treatment.

Tailor Education to the Needs of the

Individual Patient

Assess cultural or ethnic beliefs or practices that

may influence self-management activities and

modify educational approaches, as needed.

Cultural variables may affect patient understanding of

and adherence to medical regimens (Pachter and

Weller 1993; Kleinman et al. 1978). 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 belief among the Latino population is that illnesses are either “hot” or “cold” (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. 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 1995c).

Every effort should be made to discuss asthma care,

especially the self-management plan, in the patient’s

native language so that educational messages are fully

understood. 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 barriers also may complicate the assessment of cultural differences. If interpreters are used, they should be equally competent in

both English and the patient’s language and 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 self-management plan

and take other needed actions. Educational efforts

should be continuous, because it may take up to 6

months for the impact of education to be evident (Toelle

et al. 1993). Furthermore, it is necessary to periodically

review information and skills covered previously because

patient self-management behavior is likely to decline

over time (Reis et al. 1995).

In particular, it is essential that clinicians demonstrate, review, evaluate, and correct inhaler/spacer/

holding chamber technique at each visit because

these skills deteriorate rapidly (Keston et al. 1993).

Written instructions are helpful (see figure 4-3), but

insufficient (Nimmo et al. 1993; Wilson et al. 1993).

Research suggests that patients tend to make specific

mistakes in using inhalers that need to be corrected

(Larsen et al. 1994; Dolovich et al. 1981; Kesten et al.

1993; Hanania et al. 1994). Patients especially need to

be reminded to inhale slowly and to activate the inhaler

only once for each breath (Rau et al. 1996).

Clinicians should continue to promote open 

communication with the patient and family by

addressing the following elements (see figure 4-2)

in each followup visit:

■ 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 they 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.

Education for a Partnership in Asthma Care

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134

■ Review the daily self-management plan and

the steps the patient was to take (Clark et al.

1995). Adjust the plan as needed (e.g., the

recommendations of how to use medicines if the

dose or type is not working). Identify other problems the patient has in following the agreed-on

steps (e.g., disguising the bad taste of medicine);

treat these as areas needing more work, not as

adherence failures. Write a self-management plan

to help school personnel manage a child’s asthma

(see figure 4-7, page 144, for an example).

■ Periodically review the asthma action plan and

revise as necessary. Confirm that the patient

knows what to do if his or her asthma gets worse.

■ Continue teaching and reinforcing key educational messages (see figure 4-1). 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 (Morris et al. 1986; Ley 1972; 

Davis et al. 1990; Estey et al. 1991). Figure 4-8

(page 146) lists organizations that distribute

patient education materials; many of these organizations also have some Spanish-language materials.

SUPPLEMENT PATIENT EDUCATION

DELIVERED BY CLINICIANS

All patients may benefit from a formal asthma education

program that has been evaluated and reported in the literature to be effective. These programs should be

taught by qualified asthma educators who are knowledgeable about asthma and experienced in patient education. Communication among the asthma educator,

the clinicians providing direct care, and the patient/family is critical. When formal programs are available in

local communities, they can supplement, but not replace,

patient education provided in the office. Individual and

group programs have been developed and tested for

patients of all ages, including parents of very young

children (birth to 4 years) (Clark et al. 1986; Creer et al.

1988; Evans et al. 1987; Lewis et al. 1984; NHLBI

1984a, 1984b, 1984c, 1985; Taggart et al. 1991;

Wilson-Pessano et al. 1987; Wilson-Pessano and

McNabb 1985; Bailey et al. 1990; Kotses et al. 1995;

Wilson et al. 1996; Lahdensuo et al. 1996). A list of

organizations distributing programs that have been validated in the literature can be found in figure 4-8.

These patient education programs should be delivered

as designed. Some validity and effectiveness may be

compromised when segments of various programs are

pieced together or when programs are condensed. 

In the interest of saving time, educators should not

delete educational strategies, such as using small

groups or scheduling multiple sessions spaced with

“homework” assignments, because these strategies

have demonstrated effectiveness in motivating 

individuals to make significant behavior changes 

(Thapar 1994; Wilson et al. 1993; Kotses et al. 1995;

Bailey et al. 1990).

A variety of other educational formats, such as videotapes (Yoon et al. 1993) and interactive computer

software (Osman et al. 1994), also may enhance, but

not replace, education delivered by clinicians.

PROVIDE PATIENT EDUCATION IN

OTHER CLINICAL SETTINGS

Patient education also should be delivered in the

context of emergency department visits and hospitalizations. Asthma exacerbations may represent

teachable moments when patients are more receptive

to educational messages. Research on adults with

asthma who are referred by emergency department

providers to an asthma education program shows that

education can decrease utilization of emergency services (Bolton et al. 1991). Educational programs

delivered to hospitalized children and adult asthma

patients show increased knowledge and use of selfmanagement behaviors (Taggart et al. 1991), reduced

length of hospital stay, and overall reduction in asthma readmissions (Mayo et al. 1996).

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Mushlin AL, Appel FA. Diagnosing potential noncompliance.

Physicians’ ability in a behavioral dimension of medical care.

Arch Intern Med 1977;137(3):318-21.

National Heart, Lung, and Blood Institute. Asthma Management

and Prevention: A Practical Guide for Public Health Officials and

Health Care Professionals. National Institutes of Health pub.

no. 96-3659A. Bethesda, MD, 1995d.

National Heart, Lung, and Blood Institute. Asthma Management in

Minority Children: Practical Insights for Clinicians, Researchers,

and Public Health Planners. National Institutes of Health

pub. no. 95-3675. Bethesda, MD, 1995c.

National Heart, Lung, and Blood Institute. Air Power: SelfManagement of Asthma Through Group Education. National

Institutes of Health pub no 85-2362. Bethesda, MD, 1984c.

National Heart, Lung, and Blood Institute. Air Wise: Management

of Asthma Through Individual Education. National Institutes of

Health pub no 84-2363. Bethesda, MD, 1984a.

National Heart, Lung, and Blood Institute. Global Initiative for

Asthma. Global Strategy for Asthma Management and Prevention.

NHLBI/WHO Workshop Report. National Institutes of Health

pub no 95-3659. Bethesda, MD, 1995e.

National Heart, Lung, and Blood Institute. Living With Asthma:

Manual for Teaching Families the Self-Management of Childhood

Asthma. National Institutes of Health pub no 85-2364.

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National Heart, Lung, and Blood Institute. Nurses: Partners in

Asthma Care. National Institutes of Health pub no 95-3308.

Bethesda, MD, 1995a.

National Heart, Lung, and Blood Institute. Open Airways/Respiro

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National Heart, Lung, and Blood Institute. The Role of the

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Nimmo CJR, Chen DNM, Martinusen SM, Ustad TL, Ostrow

DN. Assessment of patient acceptance and inhalation technique of a pressurized aerosol inhaler and two breach-actuated devices. Ann Pharmacother 1993;27:922-7.

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Component 4: Education for a Partnership in Asthma Care

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Education for a Partnership in Asthma Care

137

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138

Name Date 

It is important in managing asthma to keep track of your symptoms, medications, and peak expiratory flow (PEF). 

You can use the colors of a traffic light to help learn your asthma medications:

A. GREEN means Go Use preventive (anti-inflammatory) medicine

B. YELLOW means Caution Use quick-relief (short-acting bronchodilator) medicine in addition to the preventive medicine.

C. RED means STOP! Get help from a doctor.

A Your GREEN ZONE is___________80 to 100% of your personal best. GO!

Breathing is good with no cough, wheeze, or chest tightness during work, school, exercise, or play.

ACTION:

■■Continue with medications listed in your daily treatment plan.

B. Your YELLOW ZONE is___________50 to less than 80% of your personal best. CAUTION!

Asthma symptoms are present (cough, wheeze, chest tightness).

Your peak flow number drops below___________or you notice:

■■Increased need for inhaled quick-relief medicine

■■Increased asthma symptoms upon awakening

■■Awakening at night with asthma symptoms

■■____________________________________________________________________

ACTIONS:

■■Take ______ puffs of your quick-relief (bronchodilator) medicine________________________________. 

Repeat ______ times.

■■Take ______ puffs of _________________________ (anti-inflammatory) ______ times/day.

■■Begin/increase treatment with oral steroids:

Take ______ mg of __________________________ every a.m. ______ p.m.______ . 

■■Call your doctor (phone) __________________ or emergency room ____________________________. 

C. Your RED ZONE is ___________50% or less of your best. DANGER!!

Your peak flow number drops below ______ , or you continue to get worse after increasing treatment according to the directions above.

ACTIONS:

■■Take ______ puffs of your quick-relief (bronchodilator) medicine________________________________. Repeat ______ times.

■■Begin/increase treatment with oral steroids. Take ______ mg now.

■■Call your doctor now (phone __________________ ). If you cannot contact your doctor, go directly to the emergency room (phone 

_______________ ).

Other important phone numbers for transportation________________________________. .

AT ANY TIME, CALL YOUR DOCTOR IF:

■■Asthma symptoms worsen while you are taking oral steroids, or

■■Inhaled bronchodilator treatments are not lasting 4 hours, or

■■Your peak flow number remains or falls below ___________ in spite of following the plan.

Physician Signature –––––––––––––––––––––––––––––––––––– Patient’s/Family Member’s Signature ––––––––––––––––––––––––– 

This plan is provided as an example to clinicians.

Figure 4-5.

ASTHMA ACTION PLAN (EXAMPLE 1)

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139

Figure 4-5.

ASTHMA ACTION PLAN (EXAMPLE 2)

Action

Plan

Asthma

Name:

Doctor’s Name:

Doctor’s Phone:

Baseline/Personal Best Peak Flow:

Medicines:

ZONE ACTIONS GREEN YELLOW RED

Adapted with permission from Cecilia Vicu ̃na-Kneady, R.N.This plan is provided as an example to clinicians.

Archive

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140

Figure 4-5.

ASTHMA ACTION PLAN (EXAMPLE 3)

Adapted with permission from National Jewish Medical and Research Center.

This plan is provided as an example to clinicians.

Archive

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141

Adapted with permission from Kaiser Permanente Center for Health Research, Portland, OR.This plan is provided as an example to clinicians.

Figure 4-5.

ASTHMA ACTION PLAN (EXAMPLE 4)

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142

Adapted with permission from Kaiser Permanente Center for Health Research, Portland, OR.This plan is provided as an example to clinicians.

Figure 4-5.

ASTHMA ACTION PLAN (EXAMPLE 5)

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143

Adapted with permission from Plaut and Brennan 1996.

This plan is provided as an example to clinicians.

Figure 4-5.

ASTHMA ACTION PLAN (EXAMPLE 6)

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144

Figure 4-7.

SCHOOL SELF-MANAGEMENT PLAN

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145

Figure 4-7.

SCHOOL SELF-MANAGEMENT PLAN (CONTINUED)

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146

Component 4: Education for a Partnership in Asthma Care

FIGURE 4-8. SOURCES OF PATIENT EDUCATION PROGRAMS AND MATERIALS

Organization Other written and

audiovisual patient

education materials?

(in other languages?)

Local support groups?

American Lung Association

For the affiliate nearest you, call

(800) LUNG-USA [800-586-4872]

Asthma and Allergy Foundation of America

1125 15th Street, N.W., Suite 502

Washington, DC 20005

(800) 7-ASTHMA [800-727-8462]

National Technical Information Service

5285 Port Royal Road

Springfield, VA 22161

(703) 487-4650

National Asthma Education and 

Prevention Program

National Heart, Lung, and Blood Institute

Information Center

P.O. Box 30105

Bethesda, MD 20824-0105

(301) 251-1222

Allergy and Asthma Network/Mothers of 

Asthmatics, Inc.

3554 Chain Bridge Road, Suite 200

Fairfax, VA 22030-2709

(800) 878-4403

American Academy of Allergy, Asthma, and 

Immunology

611 East Wells Street

Milwaukee, WI 53202

(800) 822-ASTHMA [800-822-2762]

American College of Allergy, Asthma, 

and Immunology

85 West Algonquin Road

Arlington Heights, IL 60005

(800) 842-7777

National Jewish Medical and Research Center

1400 Jackson Street

Denver, CO 80206

(800) 423-8891

Open Airways at School; 8-11 years

(Evans et al. 1987)

Asthma Care Training for Kids

(A.C.T.); 7-12 years (Lewis et al.1984)

You Can Control Asthma; 8-12

years (Taggart et al. 1991)

Air Power; 9-13 years

(Wilson-Pessano and McNabb 1985;

NHLBI 1984c)

Air Wise; 8-13 years 

(McNabb et al. 1985; NHLBI 1984a)

Living With Asthma; 8-13 years

(Creer et al. 1988; NHLBI 1985)

Open Airways; 4-12 years 

(Clark et al. 1986; NHLBI 1984a)

Breathe Easier; adult

(Wilson et al. 1993)

No validated programs

No validated programs

No validated programs

No validated programs

Yes (Yes)

Yes (Yes)

Yes (Yes)

Yes (Yes)

Yes (Yes)

Yes (No)

Yes (No)

Yes (No)

Yes

Yes 

No 

No

No

No

No

No

Validated Program(s); A

Age Group

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Discrimination Prohibited:

Under provisions of applicable

public laws enacted by Congress

since 1964, no person in the

United States shall, on the

grounds of race, color, national

origin, handicap, or age, be

excluded from participation in,

be denied the benefits of, or be

subjected to discrimination under

any program or activity (or, on

the basis of sex, with respect to

any education program or activity) receiving Federal financial

assistance. In addition, Executive

Order 11141 prohibits discrimination on the basis of age by contractors and subcontractors in the

performance of Federal contracts,

and Executive Order 11246

states that no federally funded

contractor may discriminate

against any employee or applicant

for employment because of race,

color, religion, sex, or national

origin. Therefore, the National

Heart, Lung, and Blood Institute

must be operated in compliance

with these laws and Executive

Orders.

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U.S. DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Public Health Service

National Institutes of Health

National Heart, Lung, and Blood Institute

NIH Publication No. 95-0000

July 1995

U.S. DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Public Health Service

National Institutes of Health

National Heart, Lung, and Blood Institute

NIH Publication No. 97-4051

July 1997

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