Clinical Practice Guideline 

Management of  

Asthma in Children and Adults

 2009

VA/DoD Evidence Based Practice
VA/DoD CLINICAL PRACTICE GUIDELINE FOR

MANAGEMENT OF ASTHMA IN CHILDREN AND ADULTS

Department of Veterans Affairs

Department of Defense

Prepared by:

The Management of Asthma Working Group

With support from:

The Office of Quality and Performance, VA, Washington, DC

& 

Quality Management Division, United States Army MEDCOM

QUALIFYING STATEMENTS

The Department of Veterans Affairs (VA) and the Department of Defense (DoD) guidelines are based on the 

best information available at the time of publication. They are designed to provide information and assist 

decision-making. They are not intended to define a standard of care and should not be construed as one. 

Neither should they be interpreted as prescribing an exclusive course of management.

Variations in practice will inevitably, and appropriately, occur when providers take into account the needs of 

individual patients, available resources, and limitations unique to an institution or type of practice. Every 

healthcare professional making use of these guidelines is responsible for evaluating the appropriateness of 

applying them in the setting of any particular clinical situation.

Version 2.0 – 2009 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Introduction – Page 2 

INTRODUCTION

The Clinical Practice Guideline for Management of Asthma in Children and Adults was developed under the 

auspices of the Veterans Health Administration (VHA) and the Department of Defense (DoD) pursuant to 

directives from the Department of Veterans Affairs (VA). VHA and DoD define clinical practice guidelines as:

“Recommendations for the performance or exclusion of specific procedures or services 

derived through a rigorous methodological approach that includes:

• Determination of appropriate criteria such as effectiveness, efficacy, population 

benefit, or patient satisfaction; and

• Literature review to determine the strength of the evidence in relation to these 

criteria.”

The intent of these guidelines is to:

• Reduce current practice variation and provide facilities with a structured framework to help 

improve patient outcomes

• Provide evidence-based recommendations to assist providers and their patients in the decisionmaking process concerning the diagnosis and management of patients with asthma

• Identify outcome measures to support the development of practice-based evidence that can 

ultimately be used to improve patient healthcare outcomes. 

2009 UPDATED VERSION OF THE GUIDELINE

This clinical practice guideline updates the 1999 version of the DoD/VA Guideline on Management of Asthma

for Adults and Children Age 6 years and over. The current guideline incorporates the two sections of the 1999 

guideline into one document. Where evidence suggests differences in the management between adults and 

children, age-specific recommendations are provided. The objective of the DoD/VA Working Group in 

developing this guideline was to incorporate information from existing national recommendations into a 

format that would maximally facilitate clinical decision-making. 

This effort drew heavily from the National Heart, Lung and Blood Institute's (NHLBI) National Asthma

Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of 

Asthma, published in 2007, and the Global Initiative for Asthma (GINA), Global Strategy for Asthma 

Management and Prevention, published in 2007.

The DoD/VA Working Group (WG) reviewed these two guidelines and made the decision to adopt several of 

their recommendations. The Working Group developed a revised comprehensive clinical algorithm that 

incorporates the diagnosis and management of asthma in both children and adults. Additional 

recommendations were added addressing specific issues that the Working Group considered to be of 

importance to patients in the healthcare system of the VA and DoD. Hence, this DoD/VA updated version of 

the Asthma guideline includes evidence-based recommendations for routine primary care and additional 

recommendations suggesting specific actions for diagnosis and treatment of exercise-induced asthma in active 

young adults. These specific recommendations may better serve providers caring for service persons with 

asthma among the active duty population.

The guideline/algorithms are designed to be adapted to an individual facility’s needs and resources. They will 

also be updated periodically or when relevant research results become available. The guideline should be 

used as a starting point for innovative plans that improve collaborative efforts and focus on key aspects of 

care. Except in very unusual circumstances, the recommendations outlined in this guideline should also serve 

as a framework to the care that is provided or recommended in specialty care settings.
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Introduction – Page 3 

BACKGROUND

Asthma is a chronic inflammatory disease of the lungs characterized by episodic and reversible airway 

obstruction. During the 1990s, rates of asthma increased in all age and racial groups, from an average of 30.7 

per thousand to 53.8 per thousand in 1994. In 1998, asthma affected an estimated 17.3 million people in the 

United States, including over 4.8 million children. 1

In 1995, asthma accounted for more than 5,000 deaths, 1.87 million emergency department visits, and over 

100 million restricted activity days. There have been important gains since and the number of deaths due to 

asthma has declined, even in the face of an increasing prevalence of the disease (NHIS 2005). Fewer patients 

who have asthma report limitations to activities, and an increasing proportion of people who have asthma 

receive formal patient education (Department of Health and Human Services [DHHS], Healthy People 2010 

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

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

that improved recognition of asthma among young children contributes to these rates. However, the burden 

of avoidable hospitalizations remains. 

In 2005, asthma affected more than 22 million persons. In 

children, asthma is one of the most common chronic diseases, affecting more than 6 million children (current 

asthma estimates, 2006 National Health Interview Survey (NHIS), Centers for Disease Control and Prevention 

(CDC). [http://www.cdc.gov/asthma/nhis/06/table3-1.htm] 

With the appropriate use of available therapies, asthma exacerbations and their consequences can be 

effectively controlled. The purpose of this clinical practice guideline is to help clinicians and patients make 

appropriate decisions about asthma care. This guideline can assist primary care providers or specialists in the 

diagnosis and initial management of symptoms, follow-up management, assessment of the ongoing clinical 

situation, emergency management of acute exacerbations, determination of appropriate treatment, and 

delivery of individualized interventions. 

Goals of the Guideline

• Update the recommendations for the diagnosis of asthma in children and adults

• Update the recommendations for the management of asthma in children and adult.

• Address the diagnosis and management of asthma in the active duty population (including 

deployed, non-deployed)

• Review the evidence regarding the assessment of severity definition of disease control (addressing 

risk and impairment) and the use of peak flow meters 

• Review the evidence regarding intervention for asthma (new treatment strategies, combination 

therapies, non-pharmacologic treatment, education, and written ongoing treatment plans involving 

the patient)

• Review the evidence and address the management of exercise-induced bronchospasm (EIB)

• Review the evidence regarding outpatient management of acute exacerbation of asthma. 

 

1 Centers for Disease Control. Forecasted state-specific estimates of self-reported asthma prevalence -- United 

States, 1998. MMWR Morb Mortal Wkly Rep. 1998;47:1022-1025.
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Introduction – Page 4 

Target population

The guideline will offer best practice advice on the following:

• Diagnosis and management of asthma in adults: 

- Special consideration for active duty members

- Special consideration for diagnosis and management in the elderly (over age 65) or other comorbidities

• Diagnosis and management of asthma in children. 

Audiences

Primary care and allied health professionals who have direct contact with patients with asthma (in the 

outpatient setting), and make decisions concerning routine management of their care. 

Development Process

The development process of this guideline follows a systematic approach described in “Guideline-forGuidelines,” an internal working document of VHA’s National Clinical Practice Guideline Counsel. Appendix A

clearly describes the guideline development process.

The literature was critically analyzed and evidence was graded using a standardized format. The evidence 

rating system for this document is based on the system used by the U.S. Preventative Services Task Force

(USPSTF). (See Appendix A – Development Process.)

Evidence Rating System

A A strong recommendation that the clinicians provide the intervention to eligible patients. 

Good evidence was found that the intervention improves important health outcomes and concludes that 

benefits substantially outweigh harm. 

B A recommendation that clinicians provide (the service) to eligible patients.

At least fair evidence was found that the intervention improves health outcomes and concludes that 

benefits outweigh harm.

C No recommendation for or against the routine provision of the intervention is made.

At least fair evidence was found that the intervention can improve health outcomes, but concludes that the 

balance of benefits and harms is too close to justify a general recommendation.

D Recommendation is made against routinely providing the intervention to patients.

At least fair evidence was found that the intervention is ineffective or that harms outweigh benefits.

I The conclusion is that the evidence is insufficient to recommend for or against routinely providing the 

intervention.

Evidence that the intervention is effective is lacking, or poor quality, or conflicting, and the balance of 

benefits and harms cannot be determined.

Lack of Evidence – Consensus of Experts

Where existing literature was ambiguous or conflicting, or where scientific data were lacking on an issue, 

recommendations were based on the clinical experience of the Working Group. These recommendations are 

indicated in the evidence tables as based on “Working Group Consensus.”

This Guideline is the product of many months of diligent effort and consensus building among knowledgeable 

individuals from the VA, DoD, and academia, and a guideline facilitator from the private sector. An 

experienced moderator facilitated the multidisciplinary Working Group. The draft document was discussed in 

two face-to-face group meetings. The content and validity of each section was thoroughly reviewed in a series 

of conference calls. The final document is the product of those discussions and has been approved by all 

members of the Working Group.

The list of participants is included in Appendix H to the guideline.
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Introduction – Page 5 

Implementation

This guideline is not intended to be construed or to serve as a standard of medical care. Standards of care are

determined on the basis of all clinical data available for an individual patient and are subject to change as 

scientific knowledge and technology advance and patterns of care evolve.

The guideline and algorithm should serve as a guide that providers can use to determine best interventions 

and timing of care for their patients to optimize quality of care and clinical outcomes. This should not prevent 

providers from using their own clinical expertise in the care of an individual patient. Guideline 

recommendations are intended to support clinical decision-making but should never replace sound clinical 

judgment. The ultimate judgment regarding a particular clinical procedure or treatment plan must be made

by the provider, following discussion of the options with the patient or parent, in light of the diagnostic and

treatment choices available. 

Although this guideline represents the state of the art practice at the time of its publication, medical practice 

is evolving and this evolution will require continuous updating of published information. New technology and 

more research will affect and improve patient care in the future. The clinical practice guideline can assist in 

identifying priority areas for research and optimal allocation of resources. Future studies examining the 

results of clinical practice guidelines such as these may lead to the development of new practice-based 

evidence.

Outcomes

• Control Symptoms: Nighttime awakenings; need for Short-Acting Beta Agonists (SABA) for quick 

relief of symptoms; work/school days missed; ability to engage in normal daily 

activities/desired activities

• Optimize (normal) lung function: Forced Expiratory Volume in 1 Second (FEV1); FEV1/Forced Vital 

Capacity (FVC); peak flow

• Reduce risk of exacerbation

• Minimize adverse effects

• Utilization of healthcare

• Working knowledge of the asthma action plan

• Patient satisfaction
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Introduction – Page 6 

Content of the Guideline

The guideline consists of an algorithm that describes the step-by-step process of the clinical decision-making 

and intervention that should occur throughout the diagnosis, treatment, and follow-up of asthma patients. 

General and specific recommendations for each step are included in the annotation section. The links to these 

recommendations are embedded in the relevant specific steps in the algorithm. 

Each annotation includes a brief background, discussion of the research supporting the recommendations and 

the rationale behind the grading of the evidence as well as the determination of the strength of the 

recommendations (SR). The SR is indicated in brackets for each of these recommendations. Readers should 

note that the grade relates to the strength of the evidence and not necessarily to the clinical importance of 

the recommendation. 

Recommendations that are based on the clinical experience of the Working Group are not followed by an “SR” 

grade. A complete bibliography of the references used in this guideline can be found in Appendix I. 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Introduction – Page 7 

Guideline Update Working Group* 

VA DoD

Donald Curran, MD Arthur Blain, MD Kristina Orio, Maj, MC, USAF

Carlos Daughaday, MD Deborah Bray, RN, MSN Lawrence Potter, LCDR, MC, USN

Debbie Khachikian, PharmD Christina Colluraburke, LCDR, MC, USN James Quinn, Col, MC, USAF

Michael Littner, MD Darrel Dodson, LTC, MC, USA Nancy Radebaugh, BPharm 

Gregory Sees, RRT, RPSGT Trina Davenport, HM2, USN Kristie Robson, LCDR, MC, USN

Daniel P. Hsu, LTC, MC, USA Christopher Roach, HM2, RCP, CRT, USN 

Rees Lee, CDR, MC, USN Wayne Schriner, DO, MPH

Julie Liss, PharmD Mark Tucker, LCDR, MC, USN

John Manning, CDR, NC, USN Henry Wojtczak, CAPT, MC, USN

Michael Morris, COL, MC, USA Jane Jacknewitz-Woolard, RN

Jack M. Markusfeld, COL, MC, USA

Office of Quality and 

Performance, VHA

Carla Cassidy, RN, MSN, NP

Quality Management Division

U.S. Army Medical Command

Ernest Degenhardt, RN, MSN, ANP-FNP 

Angela Klar, RN, MSN, ANP-CS

Facilitator

Oded Susskind, MPH

Research Team – Evidence Appraisal

RTI International North Carolina

Linda Lux, MPA

Meera Viswanathan, PhD

Kathleen Lohr, PhD

Healthcare Quality Informatics, Inc. 

Rosalie Fishman, RN, MSN, CPHQ

Joanne Marko, MS, SLP

* Bolded names are Co-Chair of the Guideline Working Group. 

 Additional contributor contact information is available in Appendix H. 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Table of Contents – Page 8 

TABLE OF CONTENTS BY TOPICS 

INTRODUCTION ............................................................................................................................................................. 2

Guideline Update Working Group ....................................................................................................................... 7

 Algorithms................................................................................................................................................................. 13

 Annotations...............................................................................................................................................................16

1. DEFINITIONS ....................................................................................................................................................16

ALGORITHM A: ASSESSMENT AND DIAGNOSIS ................................................................................................ 17

2. ESTABLISHING THE DIAGNOSIS OF ASTHMA ...................................................................................................17

2.1 Medical History and Physical Exam ..........................................................................................................17

2.2 Chest Radiograph ......................................................................................................................................18

2.3 Exclude Alternative Diagnoses ..................................................................................................................19

2.3.1 Full Pulmonary Function Testing (Exclude Alternative Diagnoses).........................................................22

2.3.2 Spirometry with Bronchodilators (Airflow is partially reversible) ..........................................................24

2.3.3 Bronchoprovocation Testing – Airway Hyperresponsiveness ................................................................26

2.3.4 Other Diagnostic Tests............................................................................................................................27

2.3.5 Allergy Testing ........................................................................................................................................27

2.4 Indication for Specialty Consultation.........................................................................................................29

ALGORITHM B: INITIATION OF THERAPY......................................................................................................... 31

3. CO-MORBIDITIES FOR ASTHMA.......................................................................................................................31

3.1 Gastroesophageal Reflux Disease (GERD)..................................................................................................31

3.2 Allergic Rhinitis/Sinusitis............................................................................................................................32

3.3 Obesity.......................................................................................................................................................33

3.4 Obstructive Sleep Apnea ...........................................................................................................................34

4. SEVERITY CLASSIFICATION ...............................................................................................................................35

5. INITIAL TREATMENT.........................................................................................................................................38

5.1 Establishing Patient-Provider Partnership ................................................................................................. 38

5.2 Reduction of Exposure to Risk ...................................................................................................................38

5.3 Co-morbid Conditions................................................................................................................................40

5.4 Medication.................................................................................................................................................41

5.5 Patient Education.......................................................................................................................................43

5.6 Plan for Improving Activity Level (Asthma at Work/School/Daycare).......................................................44

5.7 Psychosocial Assessment...........................................................................................................................46 
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Asthma in Children and Adults

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ALGORITHM C: FOLLOW-UP ............................................................................................................................47

6. MONITORING FOR CONTROL AND FOLLOW-UP.............................................................................................47

6.1 Assessment of Control...............................................................................................................................47

6.2 Adjustment of Treatment..........................................................................................................................50

7. FOLLOW-UP OF PATIENT WITH STABLE ASTHMA............................................................................................52

7.1 Indications for Consultation/Referral to Specialist....................................................................................53

INTERVENTIONS............................................................................................................................................... 54

8. PHARMACOTHERAPY.......................................................................................................................................54

8.1 Step Care Approach ...................................................................................................................................54

8.2. Medication................................................................................................................................................55

8.2.1 Quick Relief.............................................................................................................................................55

8.2.2 Long-term Controllers.............................................................................................................................56

8.2.3 Combination ...........................................................................................................................................62

8.3 Use of Devices (MDI without Chambers), Training Technique ..................................................................63

9. ENVIRONMENTAL CONTROL............................................................................................................................65

9.1 Inhaled Allergens.......................................................................................................................................65

9.2 Inhaled Irritants .........................................................................................................................................67

9.3 Occupational Exposure ..............................................................................................................................67

10. OTHER INTERVENTIONS................................................................................................................................. 69

10.1 Smoking Cessation...................................................................................................................................69

10.2 Nutrition ..................................................................................................................................................70

10.3 Weight loss ..............................................................................................................................................71

10.4 Complementary and Alternative Medicine (Meditation, Acupuncture)..................................................72

11. SELF-MANAGEMENT/PATIENT EDUCATION ..................................................................................................73

11.1 Patient and Family Education (Self-Management)..................................................................................73

11.2 Strategies to Deliver Patient and Family Education.................................................................................75

11.3 Optimal Self-Management Tools ............................................................................................................76

12. ACUTE EXACERBATION ..................................................................................................................................79

12.1 Indication for Immediate Triage ..............................................................................................................79

12.2 Assessing Severity of Exacerbation..........................................................................................................80

12.3 Non-Urgent Management of Acute Exacerbations (Home or Office)......................................................82

12.4. Management of Exacerbation in the Emergency Department...............................................................83

12.5 Follow-up in Primary Care after Discharge from Emergency Department..............................................84

13. EXERCISE-INDUCED BRONCHOSPASM...........................................................................................................85
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Table of Contents – Page 10 

13.1 EIB in the Patient with Asthma ................................................................................................................85

13.2 EIB in the Athlete .....................................................................................................................................86

13.3 Bronchoprovocation Testing....................................................................................................................87

13.4. EIB Treatment.........................................................................................................................................88

14. MILITARY (ACTIVE DUTY)-SPECIFIC ISSUES ....................................................................................................90

APPENDICES......................................................................................................................................................... 91

 Appendix A Guideline Development Process...........................................................................................................91

 Appendix B-1 Details of a Comprehensive History ..................................................................................................96

 Appendix B-2 Details of a Comprehensive Physical Exam .......................................................................................98

 Appendix C DoD Service-Specific Regulation Concerning Asthma.........................................................................100

 Appendix D Medication Tables ..............................................................................................................................101

 Appendix E Environmental Control........................................................................................................................105

 Appendix F Questions for Literature Search ..........................................................................................................107

 Appendix G Acronym List.......................................................................................................................................109

 Appendix H Participant List....................................................................................................................................111

 Appendix I Bibliography .........................................................................................................................................117

TABLES

 Table 1. Clinical Features Differentiating COPD and Asthma 20

 Table 2. Identifying Alternative Diagnoses Based on Symptoms and Tests 21

 Table 3. Identifying Alternative Diagnoses Based on Symptoms and Tests – Pediatric-Specific 22

 Table 4. Co-morbidities of Asthma in Adults and Children 31

 Table 5. Initial Assessment of Asthma Severity 37

 Table 6. Asthma Control (All Ages) 49

 Table 7. Step Care for Medications Required to Maintain Long-Term Control 51

 Table 8. Comparison of Inhaler Devices 64

 Table 9. Core Education and Self-Management Concepts 74

 Table 10. Information Included in Written Asthma Action Plans 77

 Table 11. Classification of Acute Exacerbation: Severity and Treatment 81
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Table of Contents – Page 11 

TABLE OF CONTENTS BY ANNOTATIONS

INTRODUCTION ..................................................................................................................................................... 2

Guideline Update Working Group...................................................................................................................... 7

Algorithms........................................................................................................................................................... 13

Annotations......................................................................................................................................................... 16

1. DEFINITIONS ................................................................................................................................................16

ALGORITHM A: ASSESSMENT AND DIAGNOSIS ................................................................................................ 17

Annotation A-1 Patient with Symptoms or Recurrent Episodes of Cough, Wheeze, or SOB...................17

2. ESTABLISHING THE DIAGNOSIS OF ASTHMA ...............................................................................................17

Annotation A-2 Obtain History and Physical Examination .......................................................................17

Annotation A-3 Consider X-ray in New Onset if Not Previously Obtained...............................................18

Annotation A-4 Non-Asthma Cause of Symptoms Identified...................................................................19

Annotation A-5 Assess Airway Obstruction (Spirometry) ........................................................................24

Annotation A-6 Refer to Specialist for Evaluation and Diagnosis............................................................29

ALGORITHM B: INITIATION OF THERAPY......................................................................................................... 31

Annotation B-1 Assess Asthma Triggers, Allergies and Co-morbidities ...................................................31

3. CO-MORBIDITIES FOR ASTHMA ...................................................................................................................31

Annotation B-2 Assess and Determine Initial Asthma Severity (Impairment and Risk)...........................35

4. SEVERITY CLASSIFICATION ...........................................................................................................................35

5. INITIAL TREATMENT.....................................................................................................................................38

Annotation B-3 Establish Partnership and Goals.....................................................................................38

Annotation B-4 Manage Triggers and Allergens.......................................................................................38

Annotation B-5 Manage Co-morbidities ..................................................................................................40

Annotation B-6 Manage Medication........................................................................................................41

Annotation B-7 Educate Patient and Family ............................................................................................43

Annotation B-8 Educate About Asthma During Activities........................................................................44

Annotation B-9 Assess Needs for Family Support and Mental Health Services ; 

 Assess Quality of Life of the Patient...............................................................................46
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ALGORITHM C: FOLLOW-UP............................................................................................................................. 47

6. MONITORING FOR CONTROL AND FOLLOW-UP.........................................................................................47

Annotation C-1 Reassess Symptom Control.............................................................................................47

Annotation C-2 Adjust/Decrease Medication as Indicated .....................................................................50

Annotation C-3 Schedule Follow-up Visit................................................................................................. 52

7. FOLLOW-UP OF PATIENT WITH STABLE ASTHMA........................................................................................52

Annotation C-4 Reassess Diagnosis, Consider Consultation or Referral ..................................................53

D. INTERVENTIONS........................................................................................................................................... 54

8. PHARMACOTHERAPY................................................................................................................................... 54

9. ENVIRONMENT CONTROL............................................................................................................................65

10. OTHER INTERVENTIONS.............................................................................................................................69

11. SELF-MANAGEMENT/PATIENT EDUCATION ..............................................................................................73

12. ACUTE EXACERBATION ..............................................................................................................................79

13. EXERCISE-INDUCED BRONCHOSPASM.......................................................................................................85

Annotation E-1 High Suspicion of Asthma or EIB? ......................................................................................85

Annotation E-2 Consider Bronchoprovocation Testing ...............................................................................86

Annotation E-3 Manage Exercise-Induced Bronchospasm (EIB)................................................................. 88

14. MILITARY (ACTIVE DUTY)-SPECIFIC ISSUES ................................................................................................90
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 13 

Algorithms 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 14 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 15 
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Algorithms and Annotations - Page 16 

Annotations

1. DEFINITIONS 

Asthma is a chronic inflammatory disorder of the airways. 

Chronically inflamed airways are hyperresponsive; they become obstructed and airflow is limited when 

airways are exposed to various risk factors. These episodes are usually associated with widespread but 

variable airflow obstruction, which is often reversible either spontaneously, or with treatment. 

Control is the degree to which the manifestations of asthma (symptoms, functional impairments, and risks of 

untoward events) are minimized and the goals of therapy are met. 

Exercise-induced asthma involves episodes of airway obstruction in individuals who have the underlying 

chronic condition that is triggered by exercise. 

Exercise-induced bronchospasm or hyperreactivity is a disorder of the airways as a result of exercise in

patients who have normal baseline spirometry and are not considered to have chronic inflammation of the 

airways. 

Impairment involves functional limitations the patient is currently experiencing or has recently experienced. 

Severity refers to the intrinsic intensity of the disease process. Severity is most easily and directly measured in 

a patient who is not currently receiving long-term control treatment.

Risk is the likelihood of either asthma exacerbations, progressive decline in lung function (or, for children, 

reduced lung growth), or risk of adverse effects from medication. 
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 17 

ALGORITHM A: ASSESSMENT AND DIAGNOSIS

Annotation A-1 Patient with Symptoms or Recurrent Episodes of Cough, Wheeze, or Shortness of 

Breath

2. ESTABLISHING THE DIAGNOSIS OF ASTHMA

Establishing the diagnosis of asthma primarily rests on obtaining a solid clinical history suggestive of airway 

hyperreactivity that includes symptoms such as shortness of breath (SOB), cough, wheezing, or chest tightness 

and objective evidence of reversible airway obstruction by either spirometry or bronchoprovocation testing. 

Since many disease processes share similar clinical symptoms, the clinician should not rely solely on symptoms 

for diagnosing asthma and should always consider alternative diagnoses that mimic asthma. Additional 

imaging studies, pulmonary function testing, or biomarkers of inflammation are often required to rule out 

other causes. Diseases such as chronic obstructive pulmonary disease (COPD), sarcoidosis, congestive heart 

failure, and vocal cord dysfunction require a much different approach for diagnosis and treatment. It is 

imperative that the clinician carefully examine the clinical history, spirometric findings, and response to 

treatment to reach the correct diagnosis and to provide the proper long-term care of patients with asthma. 

Some evidence suggests that many patients are incorrectly diagnosed and treated for asthma when they have 

an alternative diagnosis.

Annotation A-2 Obtain History and Physical Examination

2.1 Medical History and Physical Exam

(Episodic symptoms of airflow obstruction or airway hyper-responsiveness are present) 

BACKGROUND

A complete history and physical exam is the first step in establishing the diagnosis of asthma. Characteristic 

symptoms of shortness of breath, wheezing, cough, chest tightness, or nocturnal awakenings may suggest the 

diagnosis. The history should emphasize recurrence of symptoms with associated factors such as exercise, 

viral infections, or environmental exposures. Physical exam may demonstrate wheezing or suggest other 

diagnoses. For pediatric patients, a thorough history and physical exam is particularly important. For children 

too young to perform spirometry, the diagnosis of asthma is often solely based on the history and physical 

exam without the benefit of objective evidence. Waiting to diagnose asthma until the child is old enough to 

perform spirometry or other objective measures is inappropriate and unnecessarily delays treatment. 

ACTION STATEMENT

Complete and document a thorough history of asthma symptoms and physical examination in all patients 

suspected of having asthma.

RECOMMENDATIONS

1. During the diagnostic evaluation a thorough history should be performed to include focus on the 

following elements (see Appendix B-1 for expanded details of the history): 

a. Characterization of symptoms related to airway obstruction or airway hyper-responsiveness 

to include cough, wheezing, shortness of breath, chest tightness, and sputum production

b. In children, cough may be the only presenting symptom, while wheezing may not be present 

in some patients with asthma
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Algorithms and Annotations - Page 18 

c. The pattern of symptoms should be characterized to include onset, duration, frequency, 

diurnal variation, and seasonality

d. Precipitating and aggravating factors (including occupational exposure)

e. Prior diagnosis, prior symptoms, prior exacerbations, and prior therapies

f. Review of all current medications including over-the-counter and supplements

g. Family and social history. 

2. In children, a thorough birth history must also be obtained. Important factors in a birth history 

would include evidence of maternal smoking, prematurity, chronic lung disease, bronchopulmonary 

dysplasia, and postnatal smoke exposure. 

3. Careful review of systems for any condition which can mimic asthma, such as pulmonary emboli, 

congestive heart failure, congenital heart disease, viral syndromes, or hypersensitivity pneumonitis.

4. During the diagnostic evaluation, a thorough physical examination should be performed, 

emphasizing findings in the following areas (see Appendix B-2 for expanded details of the physical 

exam): 

a. Upper respiratory tract, including presence of increased nasal secretions, mucosal swelling, or 

nasal polyps 

b. Chest, including wheezing during normal breathing or prolonged forced exhalation, 

hyperexpansion of the thorax, use of accessory muscles, or chest deformity

c. Skin, including the presence of atopic dermatitis or eczema 

d. Absence of the above findings does not exclude the diagnosis of asthma and the examination 

should include findings that may support alternative diagnoses (see Appendix B-2) 

e. Consider cardiac evaluation of all murmurs or evidence of cardiovascular disease before 

initiating, or concurrent with initiating, asthma therapy. 

DISCUSSION

The symptom complex in any patient suspected of having asthma is paramount in recognizing and establishing 

treatment options for any patient. The episodic nature of asthma symptoms helps to differentiate asthma 

from other respiratory disorders. 

The presenting symptom complex serves as the basis for the future diagnostic evaluation and for defining the 

severity of impairment and risk for any individual patient. 

Annotation A-3 Consider X-ray in New Onset if Not Previously Obtained

2.2 Chest Radiograph (Exclude alternative diagnoses)

BACKGROUND

The chest radiograph may be an invaluable tool for excluding other diagnoses that masquerade or complicate 

the diagnosis and/or treatment of asthma. A chest radiograph can provide key information regarding heart 

anatomy, lung parenchyma, and mediastinal structures not readily detected by physical exam. Every patient 

diagnosed with asthma should have at least one chest radiograph during their initial evaluation to help 

exclude other diagnoses. In children, chronic wheezing and cough may represent a vascular ring (suggested by 

a right-sided aorta), congestive heart failure, pneumonia, or a variety of other non-asthmatic diagnoses. 

ACTION STATEMENT

Obtain a chest radiograph during the initial evaluation for asthma if not done recently.
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Algorithms and Annotations - Page 19 

RECOMMENDATIONS

1. In the pediatric and adolescent patients, a chest radiograph should be considered during the initial 

treatment period to rule out other diagnoses. 

2. In the adult patient with new symptoms suggestive of asthma, a chest radiograph should always be 

obtained during the initial evaluation.

DISCUSSION

The prevalence of other diseases in a pediatric patient with cough or wheezing makes a chest radiograph less 

useful during the evaluation and initial treatment of asthma in the pediatric patient. 

There is a higher likelihood of other diseases found in the adult population being evaluated for asthma. In 

most cases, a chest radiograph during the initial evaluation will be normal but may exclude other diagnoses.

EVIDENCE STATEMENTS 

o Relatively few new tests have been developed that facilitate the diagnosis of asthma in children 3 

years of age or younger. In clinical practice, 3 evaluations—chest radiography, sweat chloride testing, 

and allergy skin testing—generally serve as standards of cost-effective assessment for eliminating 

other illnesses and confirming a diagnosis in the asthmatic child (Strunk, 2002). 

o The routine use of spirometry and bronchoprovocation testing is warranted, but other tests, such as 

full PFT, CXR, and cardiac and laboratory evaluations, have limited diagnostic value in the active duty 

patient population (Morris et al., 2002).

o The chest radiograph is generally normal in patients with asthma and therefore not useful as an 

asthma outcome measure (O’Connor, 1994).

Annotation A-4 Non-Asthma Cause of Symptoms Identified

2.3 Exclude Alternative Diagnoses (Additional studies) 

BACKGROUND

A fundamental tenet of the diagnosis of asthma is a thorough evaluation and exclusion of alternative 

diagnoses that may masquerade as asthma or that may co-exist and complicate the evaluation and treatment 

of asthma. The accurate diagnosis of asthma requires the exclusion of alternative diagnoses that may present 

with shortness of breath (SOB), wheezing, cough, or other symptoms suggestive of asthma. 

Exclusion/inclusion of alternative diagnoses starts with a thorough history and physical exam from which a 

differential diagnosis and a rational approach to additional testing can be developed. 

ACTION STATEMENT 

Consider differential diagnoses when diagnosing asthma. Refer to a specialist when symptoms, examination, 

or testing suggests alternative diagnoses. 

RECOMMENDATIONS 

1. Alternative diagnoses should be considered in all patients, and in particular those over age 30 and 

under age two with new symptoms suggestive of asthma. (see Tables 2 and 3) 

2. A significant history of smoking exceeding 20 pack years makes the diagnosis of COPD more likely 

than asthma. 
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3. Absence of airway obstruction on initial spirometry should prompt consideration for alternative 

diagnoses and additional testing. 

4. Abnormalities found on Chest X-Ray (CXR) screening should prompt referral to a specialist for 

further evaluation.

5. When there is no clear response to initial therapy, other significant causes of airway obstruction 

must be considered. 

DISCUSSION

COPD and asthma are frequently distinguishable based on history (and examination) in untreated patients 

presenting for the first time. Features from the history and examination (such as those listed in Table 1) 

should be used to differentiate COPD from asthma whenever possible. 

Table 1. Clinical Features Differentiating COPD and Asthma

Clinical Features COPD Asthma 

Smoker or ex-smoker Nearly all Possibly

Symptoms under age 35 Rare Often

Chronic productive cough Common Uncommon

Breathlessness Persistent and progressive Variable

Nighttime waking with breathlessness and/or wheeze Uncommon Common

Commonly associated with atopic symptoms and seasonal allergies Uncommon Common

Significant diurnal or day-to-day variability of symptoms Uncommon Common

Favorable response to inhaled glucocorticoids Inconsistent Consistent 
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Table 2. Identifying Alternative Diagnoses Based on Symptoms and Tests

Diagnosis Symptoms Test: Results Radiographic Findings 

(CT, CXR)

Pulmonary Function 

Tests

Chronic Obstructive 

Pulmonary Disease 

(COPD) 

• See VA/DoD CPG for COPD, 

Sec. 2.4

(see Table 1)

• ABG: hypercapnia • Bullous disease

• Hyperinflation

• Lack of reversibility

Allergic Rhinitis • Seasonal or chronic 

rhinorrhea/nasal obstruction

• Daytime and/or morning 

cough

• Trial of

antihistamines

• Allergy testing

• Nasal steroids

N/A • Normal for 

allergies

• Allergic rhinitis 

common comorbid condition 

in asthma

Gastro-esophageal 

Reflux (GERD)

• Heartburn

• Irritable after feeding 

[children]

• Commonly asymptomatic

• Trial of H2-blocker 

or proton pump 

inhibitors

• Consider GI referral 

for pH probe: reflux

N/A N/A

Congestive Heart 

Failure / Coronary 

Artery Disease (CAD)

• Fatigue

• Orthopnea

• Paroxysmal nocturnal 

dyspnea

• Dyspnea on exertion

• Edema

• Weight gain

• Hypertension

• Diabetes

• Coronary Artery Disease 

• Echocardiogram: 

- low LVEF 

- diastolic 

dysfunction

- BNP: Elevated

• Cardiomegaly

• Pulmonary 

congestion

• Pleural effusion

• Reversible 

obstruction 

uncommon

Vocal cord dysfunction

(VCD)

• Poor response to asthma Rx

• Inspiratory wheeze/stridor

• Episodic dyspnea

• Rapid onset/relief

• Emotional trigger

• Laryngoscopy: 

inspiratory vocal 

cord closure

• Normal • Usually normal; 

25% may have 

blunted inspiratory 

flow volume loop 

Allergic 

bronchopulmonary 

aspergillosis (ABPA) 

• Brownish sputum, wheezing, 

SOB, fever, malaise

• Blood: eosinophilia

• Serum precipitins 

to aspergillus

• Very elevated IgE

• Recurrent fleeting 

infiltrates, 

bronchiectasis

• Obstruction

Sarcoidosis – 

Multisystem 

inflammatory disorder; 

granulomatous 

changes primarily 

found in lung

• Asymptomatic, SOB,

wheezing, cough

• ACE level: Elevated 

hypercalcemia

• Non-caseating 

granulomas on 

biopsy

• Stage 0 –None

• Stage 1 –Hilaradenopathy

• Stage II–Adenopathy 

+ infiltrates

• Stage III-Infiltrates

• Normal, restriction, 

20% show 

obstruction

Bronchiectasis – 

Airway enlargement 

due to previous 

infections

• Chronic productive cough, 

wheezing, SOB

None • High Resolution CT: 

Localized 

infiltrates, airway 

enlargement 

• Normal or mild 

obstruction

Pulmonary embolus

(PE)

• Unresponsive to 

bronchodilator

• Hemodynamic compromise

• Sudden chest pain 

• Presence of risk factors

• Tachycardia

• D-dimer: elevated

• ABG: hypoxemia

• CT: chest PE 

protocol

• Ventilation/

Perfusion (V/Q) 

mismatch

• CXR normal

N/A

Cystic Fibrosis • Recurrent productive cough • Sweat chloride 

test: abnormal

• Hyperinflation, 

cystic changes

• Lack of 

reversibility

Key: ABG Arterial Blood Gas; ACE-Angiotensin-converting Enzyme; BNP-b-type Natriuretic Peptide; CT-Computed Tomography; CXRChest X-Ray; gE-Immunoglobulin E LVEF-Left Ventricular Ejection Fraction.
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Table 3. Identifying Alternative Diagnoses Based on Symptoms and Tests – Pediatric-Specific

2.3.1 Full Pulmonary Function Testing (Exclude Alternative Diagnoses)

BACKGROUND

Full pulmonary function testing including flow volume loops, lung volumes, and diffusing capacity of the lung 

for carbon monoxide (DLCO) may be indicated in evaluating patients suspected of having asthma. Full 

pulmonary function testing can assist in clarifying the differential diagnosis when spirometry demonstrates a 

restrictive rather than obstructive process. Full pulmonary function testing can assist in the differentiating 

elements of COPD, interstitial lung disease, and restrictive lung disease due to chest wall mechanics. 

ACTION STATEMENT

Consider full pulmonary function testing for patients with significant pulmonary symptoms and restrictive 

spirometry, and in many cases, those with normal spirometry.

Diagnosis Symptoms Test Radiographic Finding (CT, 

CXR) 

Foreign Body • Unilateral wheeze 

• Sudden onset 

• Choking history 

• Age: 6 months-6 years 

• Bronchoscopy • CXR – Unilateral 

hyperinflation or 

atelectasis 

• Failure to deflate on 

expiratory or 

decubitus CXR 

Bronchopulmonary 

dysplasia (BPD) 

• Premature birth:

• Hx prolonged mechanical 

ventilation/oxygen 

requirement in neonatal 

period. If responsive to 

bronchodilators and 

steroids, treat as asthma 

N/A • CXR: May appear 

identical to asthma 

patients 

Laryngomalacia • Inspiratory wheeze 

• Onset prior to 6 weeks of 

age

• Improves when prone

• No bronchodilator 

response 

• Laryngoscopy N/A 

Subglottic stenosis • Hx of intubation

• Biphasic wheeze, loudest in 

neck

• No bronchodilator 

response 

• Bronchoscopy N/A 

Tracheo/ bronchomalacia • Inspiratory or expiratory 

monophonic wheeze 

• No bronchodilator 

response 

• Bronchoscopy N/A 

Bronchiolitis (asthma 

exacerbation caused by 

viruses)

• Diffused wheeze and/or 

bronchi

• No response to beta-2 

agonist

• Respiratory Syncytial 

Virus testing 

N/A

Recurrent upper 

respiratory infection

• Common cold symptoms • Reduction of 

respiratory symptoms 

after bulb suction or 

decongestion 

N/A
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RECOMMENDATIONS

1. The presence of restrictive indices on spirometry (reduction in both FEV1 and FVC) should prompt 

the clinician to perform full pulmonary function testing to include lung volumes and diffusing 

capacity. 

2. In those patients with confirmed restriction on full pulmonary function testing, referral to specialty

care is indicated.

3. In those patients with normal spirometry and significant pulmonary symptoms, consideration 

should also be given to full pulmonary function testing to exclude mild reductions in vital capacity

or diffusing capacity.

4. Careful review of the flow volume loop should be performed on all spirometric exams to look for 

the presence of truncated or flattened loops suggestive of possible upper airway obstruction.

RATIONALE

Spirometric evidence of asthma in an actively symptomatic patient is characterized by the presence of 

obstructive indices (a reduction in FEV1/FVC ratio below 95th percentile). Absence of this finding or the 

presence of restrictive indices suggests other causes of lung disease that can be better characterized by lung 

volumes and DLCO. 

Normal spirometric indices may be seen in mild lung disease or in association with a secondary process (ABPA, 

sarcoidosis, obesity). Full studies may elucidate the presence of hyperinflation (due to COPD or asthma) or a 

reduction in diffusing capacity not typical for asthma. In differentiating COPD from severe asthma, the DLCO is 

generally not reduced in patients with severe asthma.

Normal spirometry in a patient with active symptoms typical of asthma may actually represent vocal cord 

dysfunction. An abnormal inspiratory flow volume loop with normal spirometry is suggestive, but not 

diagnostic of vocal cord dysfunction.

EVIDENCE STATEMENTS

o Paradoxical inspiratory vocal cord closure is a frequent occurrence in patients with symptoms of 

exertional dyspnea, and should be strongly considered in their evaluation. In a cross-sectional, 

controlled study, fifteen percent of patients studied prospectively were found to have VCD, whereas 

all control subjects were negative for VCD. There was minimal difference in pulmonary function 

testing between VCD-positive and VCD-negative patients, whereas control subjects had higher 

spirometric values. Twenty percent of VCD-positive patients had abnormal flow-volume loops 

compared with 14 percent of patients without VCD, but after methacholine, 60 percent of VCDpositive patients developed abnormal flow-volume loops. In the VCD-positive group, 60 percent had 

a positive methacholine response, but there was less decrease in FEV1/FVC ratio compared with 

either VCD-negative patients or control subjects (Morris et al., 1999).

o “Vocal cord dysfunction often mimics asthma. VCD is characterized by episodic dyspnea and 

wheezing caused by intermittent paradoxical vocal cord adduction during inspiration (sometimes 

with abnormal adduction during expiration as well). The cause of VCD is not well understood, 

although some patients develop VCD in response to irritant triggers, such as fumes, cold air, and 

exercise. Although VCD is clearly distinct from asthma, it is often confused with asthma, leading to 

inappropriate medication of affected individuals with anti-asthma medications. Asthma medications 

typically do little, if anything, to relieve symptoms if the patient has pure VCD. VCD should be 

considered in the differential of difficult-to-treat, atypical asthma patients. It is important to note, 

however, that VCD and asthma may coexist and that VCD may complicate asthma management.” 

(NHLBI Asthma Guidelines 2007 – page 47) 
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Annotation A-5 Assess Airway Obstruction (Spirometry)

2.3.2 Spirometry with Bronchodilators (Airflow is partially reversible)

BACKGROUND

While the diagnosis of asthma may be based on history and physical examination alone, the confidence in the 

diagnosis is substantially enhanced by objective techniques such as spirometry. Spirometry should be 

obtained on all patients older than five years of age. The classic spirometric finding in asthma is obstructive 

airflow changes that partially or completely normalize after bronchodilator treatment. For the purpose of 

diagnosis, spirometry is an essential technique that allows documentation of airflow reversibility and 

demonstrates baseline function prior to treatment.

ACTION STATEMENT

Perform spirometry (with bronchodilators if indicated) in all adult patients and older children suspected of 

having asthma, to establish the presence of airway obstruction as a diagnostic study, preferably prior to 

initiation of treatment. 

RECOMMENDATIONS

1. Spirometry should be performed in accordance with published standards and documented in the 

medical record. In general, there is no minimum age for spirometry, but patients under age 5 may 

not be able to perform breathing maneuvers correctly. [A]

2. A diagnosis of expiratory airflow limitation can be made in accordance with validated reference 

values (such as National Health and Nutrition Examination Survey (NHANES) III as recommended by 

the ATS/ERS guidelines). 

3. The presence of obstruction should be based on a forced expiratory volume in 1 second/forced 

vital capacity (FEV1/FVC) value less than the fifth percentile and not on the percent reduction of 

the FEV1. (Healthcare providers not trained in the interpretation of spirometry should have the 

results reviewed by a specialist.) [B]

4. If airway obstruction is present or there is suspicion of asthma, spirometry should be repeated 

post-bronchodilators to establish the presence and degree of reversibility of the FEV1. [B]

5. A 10-12 percent increase in the FEV1 (and > 200 ml in adults) may be considered significant airway 

reversibility. [C]

DISCUSSION

Evidence of Reversible Obstruction (in order of preference): 

• Improved spirometry following bronchodilator (>12% FEV1 improvement in children and adults; for 

adults, FEV1 increase must also exceed 200 ml)

• Physical exam changes following bronchodilator documented by healthcare provider (examples: 

improved aeration and increased expiratory time on auscultation, changes in wheezing, decreased 

retractions/work of breathing)

• Historical improvement in respiratory symptoms following bronchodilator described by patient or 

caregiver (example: decreased cough, dyspnea, or audible wheeze; decrease in nighttime awakenings 

due to respiratory problems). 

The diagnosis of asthma should be made in conjunction with an objective measurement of airway obstruction 

(if feasible based on age) with reversibility.

A baseline spirometry value establishes the severity of obstruction to guide future treatment strategies.
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Current guidelines recommend the NHANES III reference values with interpretation based on the 95th 

percentile rather than previous reference values and methods of interpretation that were not normalized for 

race and ethnicity. 

In patients who are not able to perform a spirometry test, the diagnosis of asthma can still be made based on 

history and physical examination findings suggesting airway hyperreactivity (such as decreased respiratory 

effort following a bronchodilator or improvement of symptoms following a bronchodilator). 

Evidence of reversibility with borderline airway obstruction may be considered diagnostic for the presence of 

asthma.

EVIDENCE STATEMENTS

o “Spirometry can demonstrate obstruction and assess reversibility in patients greater than 5 years of

age. Patients’ perceptions of airflow obstruction are highly variable. Spirometry is an essential 

objective measure to establish the diagnosis of asthma, because the medical history and physical 

examination are not reliable means of excluding other diagnoses or of assessing lung status. 

Spirometry is generally recommended, rather than measurements by a peak flow meter, due to wide 

variability in peak flow meters and reference values. Peak flow meters are designed for monitoring, 

not as diagnostic tools.” (NHLBI 2007: Summary Guidelines – page 11)

o Objective assessments of pulmonary function are necessary for the diagnosis of asthma because 

medical history and physical examination are not reliable means of excluding other diagnoses or of 

characterizing the status of lung impairment. Although physicians generally seem able to identify a 

lung abnormality as obstructive (Russell et al., 1986), they have a poor ability to assess the degree of 

airflow obstruction (Nair et al., 2005; Shim and Williams, 1980) or to predict whether the obstruction 

is reversible (Russell et al., 1986). Furthermore, pulmonary function measures often do not correlate 

directly with symptoms. One study reports that one-third of the children who had moderate-tosevere asthma were reclassified to a more severe asthma category when pulmonary function reports 

of FEV1 were considered in addition to symptom frequency (Stout et al., 2006). Conversely, a 

majority of children in another study who had mild-to-moderate asthma classified by symptoms had 

normal FEV1 (Bacharier et al., 2004). These findings emphasize the importance of using multiple 

measures and the value of pulmonary function testing in a comprehensive assessment of asthma.” 

(NHLBI 2007: Asthma Guidelines – page 43)

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Performance of spirometry ATS/ERS, 2005

NHLBI, 2007

III Fair Substantial A 

2 Spirometry interpretation ATS/ERS, 2005

Hankinson et al., 1999 

II-2 Poor Small B 

3 Post-spirometry bronchodilator use ATS/ERS, 2005 III Fair Mod C 

4 Bronchodilator reversibility Dales et al., 1988 II-2 Fair Mod C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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2.3.3 Bronchoprovocation Testing – Airway Hyperresponsiveness

BACKGROUND

Bronchoprovocation testing may be a useful tool when attempting to demonstrate airway 

hyperresponsiveness in a patient with symptoms suggestive of asthma and normal baseline spirometry. A 

common diagnosis in adolescents and young adults who exercise regularly is exercise-induced bronchospasm

(EIB). Common methods of assessing airway hyperresponsiveness include methacholine challenge testing, 

exercise spirometry, or eucapnic voluntary hyperventilation. These tests in particular should be conducted on 

patients who exhibit symptoms consistent with asthma, but the diagnosis is not established by baseline 

spirometry and bronchodilator studies. Bronchoprovocation testing is usually performed by a specialist 

familiar with the procedure and knowledgeable on indications and pitfalls with each type of testing procedure.

ACTION STATEMENT

Consider referral for bronchoprovocation testing for those patients with symptoms suggestive of asthma with 

1) normal baseline spirometry (no evidence of obstruction) and/or minimal clinical response to initial 

treatment; or 2) symptoms primarily associated with exertion.

For further discussion of EIB, see Annotations E-1, E-2, E-3.

RECOMMENDATIONS

1. Refer patients to a pulmonary function laboratory capable of performing bronchoprovocation 

testing in accordance with American Thoracic Society (ATS) standards.

2. The preferred method for bronchoprovocation testing is histamine or methacholine challenge 

testing. Other established methods are less commonly available such as cold air or eucapnic

hyperventilation.

3. Exercise challenge testing is a less sensitive test for detecting the presence of airway 

hyperreactivity and may be considered for symptoms primarily associated with exertion.

DISCUSSION

Normal spirometry with negative response to bronchodilator medications may be indicative of mild

intermittent disease or the lack of airway hyperreactivity. 

Confirmation of airway hyperreactivity by bronchoprovocation testing can help clarify the presence of asthma.

Testing should be performed by a qualified physical fitness test (PFT) laboratory and interpreted by an 

appropriately credentialed or trained physician for the level of bronchial hyperresponsiveness. 

A positive methacholine or histamine test is usually indicative of airway hyperreactivity. A negative test 

excludes asthma as the underlying cause of symptoms.

A negative exercise challenge test does not exclude the presence of asthma or exercise-induced 

bronchospasm. 

EVIDENCE STATEMENTS

o “Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge may be useful 

when asthma is suspected and spirometry is normal or near normal. For safety reasons, 

bronchoprovocation should be carried out only by a trained individual. A positive test is diagnostic 

for airway hyperresponsiveness, which is a characteristic feature of asthma but can also be present in 

other conditions. Thus, a positive test is consistent with asthma, but a negative test may be more 

helpful to rule out asthma.” ( NHLBI Summary Guidelines, 2007)
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2.3.4 Other Diagnostic Tests

BACKGROUND

Multiple biomarkers such as exhaled nitric oxide, sputum eosinophils, and serum arginase levels are available 

measurements of airway inflammation. However, no specific biomarkers have been validated prospectively in 

regards to impacting either diagnosis or response to therapy. Furthermore, the equipment required for such 

measurements is prohibitively expensive and performed in specialized clinical settings. 

RECOMMENDATIONS

1. Biomarkers such as nitric oxide are not currently validated clinical indicators of asthma severity or 

control and should not be used in the primary care setting as a means of diagnosis or evaluating 

response to therapy. 

2. Biomarker evaluation is best performed in specialty clinics where such testing is frequently 

conducted and interpreted.

RATIONALE

No definitive studies exist that validate the use of biomarkers to confirm asthma diagnosis or to monitor 

response to treatment. The NHLBI guidelines (2007) regard biomarkers as having the potential to impact 

asthma care in the future but do not routinely recommend these tests outside specialized clinical settings.

EVIDENCE TABLE

Evidence Source LE QE SR

1 Exhaled nitric oxide is not indicated 

in the primary care setting for 

diagnosis of asthma

Petsky et al., 2008 I Fair I 

2 Exhaled nitric oxide measurements 

are not recommended in the 

primary care setting for asthma 

monitoring

Petsky et al., 2008 I Fair I 

3 Measurements of sputum 

eosinophils are not indicated to 

confirm the diagnosis of asthma or 

measure the response to therapy

Gogate & Katial, 

2008

III Poor I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

2.3.5 Allergy Testing

BACKGROUND

Allergy testing is an important tool in the evaluation and management of patients with asthma. Assessing for 

specific IgE can assist in demonstrating the presence or absence of atopy as well as identifying specific

antigens that may trigger or contribute to symptoms. The presence of atopy is common and an important risk 

factor for the development of asthma. The absence of atopy, especially in children with other atypical 

features, may lead to a more aggressive pursuit of alternative diagnosis. Identification of atopy, specific 

allergic sensitization, and co-morbid allergic rhinitis can help focus strategies for education and avoidance 

techniques. They may also assist to identify or strengthen indications for selection of medication and 

immunotherapy, and may play a role in identifying patients at risk of severe or fatal episodes.
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ACTION STATEMENT

Consider allergy testing to assist in the diagnosis of asthma.

RECOMMENDATIONS

1. Consider allergy testing in patients with asthma with symptoms suggesting significant co-morbid 

allergic rhinoconjunctivitis or if recommended by specialty referral.

2. Allergy testing may be useful in the diagnostic evaluation of asthma to: [B]

a. Identify atopy and co-morbid allergic rhinoconjunctivitis as risk factors for the development of 

asthma

b. Identify precipitating factors and/or triggers related to asthma symptoms and worsening comorbid allergic rhinoconjunctivitis

c. Allergy testing in children is less sensitive. 

DISCUSSION

Allergy testing can be accomplished by either prick/puncture skin testing or serologic methods. Established 

practice parameters identify prick/puncture skin tests as the preferred techniques for assessing IgE-mediated 

hypersensitivity. Serologic testing for allergen-specific IgE can demonstrate correlation of higher kIU levels to 

clinical sensitivity for some allergens that is equivalent to prick/puncture tests. However, skin prick/puncture 

tests generally have better overall predictability and are the preferred initial diagnostic approach.

The most appropriate age to undertake allergy testing is not well defined in the literature and is often best 

decided in the context of the patient’s clinical presentation. Studies have identified that even children under 

the age of two at high risk of atopy can demonstrate allergic sensitization. Nevertheless, the use of 

aeroallergen skin testing to confirm and identify specific sensitizations in children under age 2 has limited 

application and is generally not undertaken. Skin testing for aeroallergens, in patients 5 years of age and 

older, has greater clinical applicability and begins to have more robust supportive data in the literature. 

Unfortunately, the evidence that early intervention can prevent sensitization has not been convincing. While 

data may include younger children, a substantial portion of the referenced literature is limited or weighted to 

children age 5 and above. Additionally, the identification of sensitization in patients with asthma has greater 

benefit and greater clinical applicability in patients with perennial symptoms. 

The appropriate number of allergens to use in testing is not well defined in the literature and is often best 

decided with an understanding of regional botany and in the context of the patient’s clinical presentation. 

Nevertheless, large panels of indiscriminate tests are not supported in the literature or general standards of 

care. Committees of a national specialty organization have identified a panel of important relevant North 

American allergens that contain fewer than 40 allergens.
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EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Atopy and allergic sensitization 

are risk factors for the 

development of asthma

Hagy et al., 1976 

NHLBI, 2007

Sears et al., 2003 

Sporik et al., 1990 

I Good Mod B 

2 Allergic sensitization is 

commonly associated with 

asthma

Call et al., 1992 

Gruchalla et al., 2002 

Huss et al., 2001 

NHLBI, 2007

Pollart et al., 1989 

Reid et al., 1993 

Rosenstreich et al., 1997 

II-1 Good Mod B 

3 Allergy testing can identify 

triggers associated with asthma 

morbidity and mortality

Call et al., 1992

Gruchalla et al., 2002 

NHLBI, 2007

Pulimood et al., 2007 

Reid et al., 1993 

Rosenstreich et al., 1997 

Targonski et al., 1995 

II-1 Good Mod B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Annotation A-6 Refer to Specialist for Evaluation and Diagnosis

2.4 Indication for Specialty Consultation

BACKGROUND

While the majority of patients with asthma should be diagnosed and treated at the primary care level, some 

patients with more severe asthma or those whose symptoms present a diagnostic dilemma may benefit from 

an evaluation by a pulmonologist, allergist, or other asthma specialist. 

ACTION STATEMENT

Refer patients with atypical presentation for evaluation and diagnosis to a specialist. 

RECOMMENDATIONS

1. Patients who are under consideration for an asthma diagnosis by their primary care provider should 

be referred to a subspecialist (Allergist / Immunologist, Pulmonologist, Gastroenterologist, 

Otolaryngologist) if any of the following are present: [C]

a. Findings NOT consistent with typical asthma diagnosis that should prompt referral to 

specialty: 

• Poor growth / failure-to-thrive (especially in infants and children) 

• Cyanosis at feeding (infants and children) 

• Vomiting at feeding (infants and children) 

• Clubbing 

• Stridor / upper airway wheeze 

• Hemoptysis 
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• Any significant chest radiograph abnormality 

• Lymphadenopathy 

• Persistent oxygen requirement

• Chest pain 

• Pneumothorax 

• Recurrent bacterial pneumonia

• Monophonic or unilateral wheeze

• Recurrent bronchitis (only for adults) 

• History of anaphylaxis

• Chronic productive cough or irreversible airway obstruction on spirometry in the

absence of a diagnosis of COPD

b. Signs and symptoms are atypical, or there are problems in differential diagnosis such that the 

primary care provider is uncertain of making an asthma diagnosis 

c. Patient requires confirmation of a history that suggests that an occupational or environmental 

inhalant or ingested substance is provoking or contributing to asthma.

2. Patients who have significant psychiatric, substance abuse, psychosocial, or family problems that 

interfere with their asthma therapy may need referral to an appropriate mental health professional 

for counseling or treatment. [B]

3. Patient/parent requests for consultation with subspecialist.

DISCUSSION

Most patients with asthma can be successfully managed by the primary care provider, but patients with 

asthma are in a continuum of severity and vary in their response to medications. Situations may arise in either 

establishing a diagnosis or selecting the best therapy when the specialist will be of assistance. 

EVIDENCE STATEMENTS

o Patients with symptoms suggestive of asthma with atypical features may require referral to an 

asthma specialist for accurate diagnosis.

o Significant psychiatric, substance abuse, psychosocial, or family problems that interfere with their 

asthma therapy have been shown to interfere with a patient’s ability to adhere to treatment (Strunk 

et al., 1985, 1987).

EVIDENCE TABLE

Evidence Source LE QE SR

1 Specialist referral assists in 

diagnosis of asthma or alternative 

diagnoses

AAAAI, 2006

NHLBI EPR3 2007 

III Fair C 

2 Referral of patients with significant

mental health illnesses to an 

appropriate mental health 

professional for counseling to 

improve adherence

Strunk et al., 1985, 

1987

II Good B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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ALGORITHM B: INITIATION OF THERAPY

Annotation B-1 Assess Asthma Triggers, Allergies and Co-morbidities

3. CO-MORBIDITIES FOR ASTHMA

BACKGROUND

Patients diagnosed with asthma should be investigated for co-morbidities regardless of age. Patients with 

asthma commonly have other diagnoses that exacerbate their respiratory complaints or act to trigger asthma 

symptoms. Failure to identify these co-morbidities may lead to difficulty fully controlling respiratory 

symptoms resulting in increased asthma symptoms and exacerbations. Evidence suggests that appropriate 

treatment of these co-morbidities can improve asthma control. A thorough history, physical exam, and 

focused review of systems should be obtained to determine if these co-morbidities are present and contribute 

significantly in an individual patient (see Table 4). 

Table 4. Co-morbidities of Asthma in Adults and Children

Children Adults 

Allergic rhinitis and sinusitis 

Gastroesophageal Reflux Disease (GERD )

Allergic bronchopulmonary aspergillosis (ABPA)

Gastroesophageal Reflux Disease (GERD)

Allergic rhinitis and sinusitis 

Allergic bronchopulmonary aspergillosis (ABPA)

Obstructive Sleep Apnea (OSA)

3.1 Gastroesophageal Reflux Disease (GERD)

BACKGROUND

Gastroesophageal reflux disease (GERD) is the retrograde regurgitation of stomach contents into the 

esophagus and, in some individuals, the upper airway. Acid stimulation of the esophagus has been 

demonstrated to cause bronchospasm and involvement of the upper airway may cause laryngospasm or even 

aspiration events. Investigation for GERD should be a routine part of an initial asthma evaluation in all 

patients, regardless of age, and should be particularly addressed in those patients with frequent heartburn or 

nocturnal asthma symptoms.

ACTION STATEMENT

Obtain a detailed history of the frequency of heartburn symptoms and treat for GERD if symptoms or 

nocturnal asthma is significant.

RECOMMENDATIONS

1. Patients with asthma should be questioned about the frequency of heartburn symptoms, 

effectiveness of previous treatments, and the presence of symptoms such as nocturnal cough or 

wheezing, morning hoarseness, or sore throat even in the absence of heartburn. [B]

2. Parents of children under age 5 should be questioned about irritability after feeds, regurgitation 

while supine, or complaints of chest pain that may be a manifestation of GERD. [B]

3. Treatment should include specific food avoidance (especially caffeine and alcohol), avoidance of 

food and drink 3 hours before bedtime, elevation of head of bed, and appropriate pharmacologic 

therapy. [C]
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DISCUSSION

GERD symptoms are prevalent in children and adults with asthma and nocturnal reflux can contribute to 

nocturnal asthma symptoms. Although there is no overall improvement in asthma following medical 

treatment, use of proton pump inhibitors decreases nocturnal symptoms, reduces exacerbations, decreases 

cough, and improves quality of life. Surgical treatment is reported to reduce asthma symptoms and

medication use.

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 GERD is a common finding in 

patients with asthma

Harding, 1999 II-2 Good Mod B 

2 GERD contributes to nocturnal 

asthma symptoms 

Avidan et al., 2001

Cibella & Cuttitta, 

2001

II-2 

II-1 

Fair

Good

Mod B 

3 Medical treatment for GERD 

reduces symptoms and 

exacerbations

Gibson et al., 2003 

Kiljander et al., 1999

Littner et al., 2005

I Good Small-Mod C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

3.2 Allergic Rhinitis/Sinusitis

BACKGROUND

There is a strong association between allergic rhinitis and asthma. The majority of school-age children with 

asthma have co-morbid allergic rhinitis; the association remains strong in adults and wanes in the elderly. 

Consistent with the concept of the airway as a continuum, treatment of allergic rhinitis can improve asthma 

outcomes. Accumulation of fluid in the sinuses with resultant chronic nasal drainage and post-nasal drip is a 

common complication in asthma patients, even in young children. A common misperception among 

physicians is that children do not get sinusitis. In fact, the maxillary and ethmoid sinuses are present at birth 

and sinusitis as a co-morbidity must be considered in all patients regardless of age.

ACTION STATEMENT

Evaluate patients with asthma who have chronic nasal drainage, nasal congestion, or postnasal drip for the 

presence of allergic rhinitis or chronic sinusitis as a co-morbidity affecting asthma control. 

RECOMMENDATIONS

1. Patients with asthma should undergo an assessment for allergic rhinitis or sinusitis that is either 

seasonal or year-round in variation. This assessment should include a history of seasonal 

variations, specific triggers, diurnal variation, and changes in the workplace. [B]

2. Physical examination of all patients with asthma should include evaluation for the presence of 

conjunctival inflammation, nasal mucosal inflammation, nasal discharge, polyps, and post nasal 

drip. [B]

3. Consideration for allergy testing should be given to patients with asthma who have allergic rhinitis 

and who experience year-round symptoms or difficulty controlling asthma. [B]

4. Adequate treatment of allergic rhinitis or sinusitis should be undertaken in an effort to improve 

asthma outcomes. Treatment may include allergen avoidance, medications, immunotherapy, or 

surgical therapy. [B]
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RATIONALE

There is considerable evidence for the relationship of the upper and lower airways and the concept of the 

airway as a continuum. Epidemiologic studies support a substantial association between allergic rhinitis and 

asthma.

In patients with allergic rhinitis, nasal allergen challenge has been shown to induce adhesion molecule 

expression and inflammatory mediators in bronchial mucosa and sputum.

Treatment of allergic rhinitis and asthma with intranasal corticosteroids decreases exhaled nitric oxide and 

other markers of lower airway inflammation. Antihistamine therapy in the treatment of asthma reveals 

positive results, and intranasal steroids and second-generation antihistamines have been reported to decrease 

emergency department visits for asthma.

A similar manifestation of airway continuum exists in patients with sinusitis and asthma. A direct relationship 

can be seen between severity of sinusitis and markers of lower airway inflammation as well as decreases in 

pulmonary function. Improvement in respiratory symptoms in children, who have asthma and are treated 

with intranasal corticosteroids and antibiotics for rhinosinusitis, is accompanied by decreases in inflammatory 

cells and mediators in the nose. 

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Allergic rhinitis/sinusitis is a 

common finding in patients with 

asthma

Guerra et al., 2002

Linneberg et al., 2002

II-2 Good Mod B 

2 Allergy testing should be 

considered in patients with asthma

who have allergic rhinitis symptoms

Dolen, 2001

Pulimood, 2007

Yunginger et al., 2000

II-1 Good Mod B 

3 Treatment for allergic 

rhinitis/sinusitis improves 

respiratory symptoms

Nelson, 2003

Sandrini et al., 2003

ten Brinke et al., 2002

Tosca et al., 2003

II-1 Good Mod B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

3.3 Obesity

BACKGROUND

Obesity is an increasing problem in industrialized nations and has a significant effect on the development of 

asthma and asthma control. There is a higher prevalence of asthma in the overweight pediatric population. 

Weight loss is associated with improved asthma control and should be highly encouraged in patients with 

asthma. 

ACTION STATEMENT

Clinicians advising patients with asthma who are overweight or obese should recommend weight loss to 

improve overall health and possibly asthma control.

RECOMMENDATIONS

1. Weight loss should be highly encouraged in patients with asthma who are overweight or obese to 

improve pulmonary mechanics, decrease exacerbations, and reduce the use of steroids, especially 

in children who are more likely to have asthma persistence. [C]
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RATIONALE 

Obesity has been associated with asthma persistence and severity in both children and adults. Although 

obesity itself causes alterations in pulmonary physiology that can lead to dyspnea, studies have documented 

specific increases in asthma among overweight and obese persons.

Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma. 

Obese and non-obese patients with asthma have similar lung function abnormalities, but co-morbidities and 

altered responses to medications may significantly affect asthma control in obese people. 

Obesity increases the prevalence, incidence, and possibly severity of asthma, while weight loss in the obese 

improves asthma outcomes. Obesity also influences asthma control and the response to standard asthma 

therapeutics.

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Obesity is associated with 

asthma persistence and 

severity

Flaherman & Rutherford, 2006

Schaub & von Mutius, 2005 

Shore, 2007

Weiss, 2005

I Good Mod B 

2 Weight loss in overweight 

patients with asthma

improves outcomes

Dixon et al., 2006 

Simard et al., 2004

Stenius-Aarniala et al., 2000

II-2 Fair Small C 

3 The effects of obesity on 

asthma appear to be 

independent of diet and 

physical activity

Camargo et al., 1999 II-2 Fair Small C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

3.4 Obstructive Sleep Apnea

BACKGROUND

Obesity is associated with persistent asthma and severity in both children and adults. Sleep disturbances in 

patients with asthma are common. In the patients with uncontrolled asthma, recurrent cough and wheeze 

may interrupt sleep. Obstructive sleep apnea (OSA) as a cause for sleep disordered breathing is also relatively 

common. In children, OSA is often a manifestation of tonsillar and adenoidal hypertrophy and surgery may be 

curative. Addressing OSA effectively can dramatically improve the quality of sleep and a patient’s daytime 

academic / work performance.

ACTION STATEMENT

Clinicians evaluating patients who are overweight or obese and have unstable or poorly controlled asthma 

(particularly those with nocturnal asthma or awakenings) should assess for the presence of obstructive sleep 

apnea. 

RECOMMENDATIONS

1. Overweight patients with asthma should be questioned about their sleep habits and hygiene and in 

particular a history of loud snoring, excessive daytime somnolence, and witnessed apneas. 

2. Patients with excessive daytime somnolence or witnessed apneas should be referred for sleep 

testing (polysomnography). [B]
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3. Patients with unstable uncontrolled asthma and sleep apnea should be treated with continuous 

positive airway pressure (CPAP). Weight loss, dental appliances, and evaluation for surgery may be 

considered in selected patients. [C]

RATIONALE

Patients who have OSA and nocturnal asthma may have similar clinical presentations to include conditions 

such as repetitive sleep arousals associated with changes in airflow, ventilatory effort, and decreases in 

oxygen saturation during sleep. Moreover, asthma and OSA may coexist in a significant number of patients. 

Patients who have unstable asthma and sleep apnea demonstrate improved peak expiratory flow when 

treated with nasal continuous positive airway pressure (CPAP). 

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Overweight patients with asthma

with excessive daytime somnolence 

or nocturnal awakening should be 

evaluated for obstructive sleep 

apnea

Yigla et al., 2003 II-2 Good Mod B 

2 Treatment with CPAP improves 

patients with asthma with OSA

Chan et al., 1988 II-2 Fair Mod C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Annotation B-2 Assess and Determine Initial Asthma Severity (Impairment and Risk)

4. SEVERITY CLASSIFICATION

BACKGROUND

Asthma is a heterogeneous disorder with a wide range of severity. An assessment of severity is essential for 

determining appropriate initial therapy and need for specialty referral. The system for assessing severity has 

been refined from previous guidelines. It now includes the domain of risk as well as current impairment from 

asthma. Asthma severity is classified using standardized, widely accepted terminology. This allows for clear 

communication among medical providers and gives a uniform framework for the assessment of asthma.

NHLBI and GINA classifications of asthma severity are based on expert consensus. In order to provide a clear 

and practical initial assessment of severity, elements of both guidelines were adopted in constructing the VADoD severity classification table (Table 5).

ACTION STATEMENT

Assess current impairment and risk of exacerbation as part of initial evaluation, to determine and classify the 

severity of the asthma.

RECOMMENDATIONS

1. Current impairment and risk of exacerbations should be assessed in the initial evaluation of asthma 

to classify severity (see Table 5). 

2. A history of asthma symptoms, nighttime awakenings, need for SABA for relief of symptoms and 

interference with activities should be used to assess current impairment. 
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3. The frequency and severity of asthma exacerbations should be used in assessing the domain of risk. 

Lung function and psychosocial factors may also help predict risk. 

4. Spirometry should be used in the initial assessment of all patients who are capable of performing 

an adequate expiratory maneuver. Lung function is a measure of impairment but may also predict 

risk. 

5. Classification of severity of the disease should be based on initial assessment of the patient who is 

not on long-term control therapy. 

RATIONALE

Classification of severity may be helpful in guiding initial management, but ongoing management should be 

based on periodic assessment of asthma control. 

EVIDENCE STATEMENTS

o An assessment of severity based on impairment and risk should be made to determine initial therapy, 

but periodic assessment of asthma control should be used to determine ongoing management 

(NHBLI, 2007; GINA, 2007).

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Classification of Severity GINA, 2007 

NHLBI , 2007 

III Poor Unknown I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Table 5. Initial Assessment of Asthma Severity

SEVERITY

(Assess over a period of at least 4-6 weeks)

Classifying Asthma Severity and Initiating Therapy

Intermittent Persistent

Mild Moderate Severe

Impairment

Symptoms < 2 days/week > 2 days/week but not daily Daily Throughout the day

Nighttime awakenings < 2 x/month > 2x/month > 1x/week but not 

nightly Nightly

Use of quick-relief for 

symptom control < 2 days/week

> 2 days/week but not daily, 

and not more than once on 

any day

Daily Several times/day

Interference with 

normal activity None Minor limitation Some limitation Extremely limited

Lung Function:

Normal 

FEV1/FVC:

 < 19 yr - 85%

20-39 yr - 80%

40-59 yr - 75%

FEV1

 > 80% predicted

Normal between 

exacerbations 

 > 80% predicted

Normal between 

exacerbations 

60-80% predicted <60% predicted

FEV1/FVC Normal Normal Abnormal Abnormal

Risk Exacerbations 

requiring systemic 

corticosteroids

(consider severity and 

interval since last 

episode) 

0-1 x/year Age 0-4 years: 

> 2 exacerbations in 6 months requiring oral or intravenous corticosteroids, OR

> 4 wheezing episodes/1 year, lasting >1 day AND risk factors for persistent 

asthma

Age ≥5 years and adult: 

> 2 exacerbations per year requiring oral or intravenous corticosteroids 

Modified from NHLBI 2007 and GINA 2007 guidelines.
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5. INITIAL TREATMENT

Annotation B-3 Establish Partnership and Goals

5.1 Establishing Patient-Provider Partnership 

BACKGROUND

A proactive partnership between the patient and provider that identifies the patient’s perception of their 

asthma control and quality of life will enable the development of a treatment plan that emphasizes long-term 

control through medications, avoidance mechanisms, and asthma self-management.

ACTION STATEMENT

Establish an interactive partnership with patient and caregiver to optimize the patient self-management of 

asthma.

RECOMMENDATIONS

1. Patient and parent education on asthma self-management should begin at diagnosis and be 

reviewed regularly. 

2. Patients and parents should be familiar with, and receive education from, the entire healthcare

team: physicians, nurses, pharmacists, respiratory therapists, etc. 

3. Communication with the patient/parents should focus on patient-centered goals of treatment; at 

every visit, reinforce self-management of asthma. 

4. Written asthma action plans, developed jointly between patient and provider, should focus on daily 

management and techniques to manage exacerbations for all patients with asthma. 

RATIONALE

Reviews of NHLBI 2007 and Cochrane Review of 36 trials show that self-management education, to include a 

written asthma action plan, not only reduced hospitalizations, emergency department visits, and unscheduled

visits to the physicians, but improved outcomes.

EVIDENCE STATEMENTS

o NHLBI (2007) clearly supports the need for a proactive partnership between patient (and/or parent) 

and provider. 

o Review of current evidence reveals no changes to NHLBI 2007 recommendations.

Annotation B-4 Manage Triggers and Allergens

5.2 Reduction of Exposure to Risk

BACKGROUND

Asthma symptoms may be triggered by a wide variety of occupational and aeroallergen exposures or

exacerbated by certain medications. Education that addresses recognition and avoidance of these triggers will 
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help improve long-term asthma control and decrease the frequency and severity of exacerbations. Patients 

with chronic asthma are at increased risk for complications from influenza and pneumococcal pneumonia.

RECOMMENDATIONS

1. Patients with persistent asthma should be evaluated for possible allergen and environmental 

triggers that can be avoided (see Section 9 - Environmental Control), including outdoor activity if 

levels of air pollution are high. 

2. Patients should be advised to avoid non-selective beta-blocker therapy. [B]

3. Encourage avoidance of sulfite-containing foods or other foods determined by history to trigger 

exacerbations. [B]

4. NSAID and aspirin use in patients with nasal polyps, severe persistent asthma, or known NSAID/ASA 

sensitivity should be strictly avoided. [B]

5. All patients with asthma who are older than 6 months of age should receive inactivated flu vaccine 

to decrease the risk of complications from infection with influenza. Patient or parents should be 

counseled that the vaccination will not decrease the frequency or severity of exacerbations during 

the flu season. [A]

6. Pneumococcal polysaccharide vaccine should be administered to adults with chronic persistent 

asthma. [B]

RATIONALE

Asthma control cannot be achieved with medications alone. Avoidance of identified triggers is essential to 

successful management. Patients with chronic asthma are at increased risk for complications from influenza 

and pneumococcal pneumonia.

EVIDENCE STATEMENTS

o Environmental triggers, including sulfites in food, should be identified and incorporated into patient 

education about avoidance (NHLBI, 2007)

o Nonselective beta-blocker drugs aggravate asthma symptoms in patients with persistent asthma 

(NHLBI, 2007)

o A subgroup of patients with asthma may have acute attacks precipitated by ingestion of aspirin 

and/or NSAIDS (NHLBI, 2007) 

o Influenza and other viral respiratory infections are associated with acute exacerbations and influenza 

vaccine may prevent some cases of influenza, although it may not prevent the number of 

exacerbations during the flu season (NHLBI, 2007)

o Pneumococcal polysaccharide vaccine is safe and appropriate for all adults with chronic respiratory 

diseases, including asthma (ACIP, 2008). The ACIP recommends that asthma should be included 

among the chronic pulmonary diseases (such as COPD and emphysema) that are indications for 

pneumococcal polysaccharide vaccine in adults aged 19 through 64. 
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Algorithms and Annotations - Page 40 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Allergen avoidance is effective in 

improving asthma control (see Section 9) 

NHLBI, 2007 II Fair B 

2 Nonselective beta-blocker drugs, including 

eye drops, may precipitate asthma attacks

NHLBI, 2007 II Fair B 

3 Sulfite avoidance prevents exacerbations 

in patients identified with sensitivity

NHLBI, 2007 II Fair B 

4 NSAID and ASA avoidance prevents 

attacks in sensitive patients

NHLBI, 2007 II Fair B 

5 Inactivated influenza vaccine is safe in 

patients > 6 months of age with asthma 

ACIP, 2008

NHLBI, 2007 

I Good A 

6 Inactivated influenza prevents 

complications of influenza in patients with 

asthma, but has no effect on the 

frequency of exacerbations during the flu 

season 

NHLBI, 2007 II Fair B 

7 Pneumococcal Polysaccharide vaccine is 

appropriate for adult patients with 

chronic asthma

ACIP, 2008 II Poor B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Annotation B-5 Manage Co-morbidities

5.3 Co-morbid Conditions 

BACKGROUND

Multiple conditions exist that can provoke or exacerbate asthma symptoms if left untreated. Inadequate 

treatment of co-morbid conditions may result in false assessments of asthma severity and control, thus 

complicating the long-term management and increasing the risk of treatment failure (see Annotation B-1). 

RECOMMENDATIONS

1. Patients who do not respond to typical asthma therapy should be reevaluated for the presence of

unmanaged co-morbid conditions.

2. Identify and treat conditions such as allergic rhinitis, sinusitis, gastro-esophageal reflux, obstructive 

sleep apnea, obesity, substance abuse, depression, or other mental health disorders to ensure 

optimal control of asthma.

RATIONALE

While the association between allergen exposure and asthma symptoms is well documented, measures to 

avoid allergens and other triggers may decrease attacks. However, the studies of specific avoidance 

interventions have generally been inconclusive with regard to asthma symptoms. The treatment of other comorbid conditions may improve the response to medications as well as adherence. 
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Algorithms and Annotations - Page 41 

EVIDENCE STATEMENTS

o Since the 2007 NHLBI guidelines were published, no new studies were found that provided any 

significant new recommendations concerning identification and treatment of co-morbid conditions.

o The NHLBI guideline recommendations are incorporated into this document for identification and 

treatment of co-morbidities. 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Co-morbid conditions should be identified 

and treated to ensure optimal asthma 

control

NHLBI, 2007 & 1997 I Fair B 

2 Treatment of GERD with Proton Pump 

Inhibitor (PPI) improves asthma symptoms

Gibson et al., 2003

Havemann et al., 2007 

Littner et al., 2005 

Sharma et al., 2007 

I Fair C 

3 Treatment of allergic rhinitis and 

rhinosinusitis is recommended to improve 

asthma control

Sandrini et al., 2003

Nelson, 2003

Rabago et al., 2006 

I Good A 

4 Allergen avoidance remains recommended; 

however, current evidence indicates a low 

likelihood of significant asthma control with 

avoidance measures for house dust mites

NHLBI, 2007

Sheikh et al., , 2007 

I Good A 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Annotation B-6 Manage Medications

5.4 Medication

BACKGROUND

The goals of therapy are to prevent or reduce the frequency and intensity of symptoms, prevent recurrent 

exacerbations, prevent decline in lung function, and improve quality of life. Medications to treat asthma are 

categorized into long-term control medications and quick relief medications. Long-term control medications 

are taken daily to achieve and maintain control of persistent asthma. Quick relief medications are used to 

treat acute symptoms and exacerbations. The initial medication regimen is based on asthma severity, optimal 

delivery devices, and safety.

(For detailed recommendations and discussion of evidence, see Section 8: Intervention – Pharmacotherapy.) 

RECOMMENDATIONS

1. Patients diagnosed with persistent asthma require treatment with an inhaled corticosteroid to 

reduce inflammation. Additional long-term control medications such as long-acting beta agonists 

(LABAs) or leukotriene inhibitors may be added based on initial asthma severity and subsequent 

assessment of control to relieve bronchospasm. Patients must never be treated solely with longacting beta2-agonists.

2. Short-Acting Beta Agonists (SABAs) should be used for relief of acute asthma symptoms. An 

asthma action plan is needed to guide home use of SABAs. Two to six puffs of SABA may be used in
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accordance with the asthma action plan. Patients who do not experience relief after 3 doses in a 

one hour period OR who need a dose more frequently than every 4 hours, should seek medical 

care.

3. To ensure adequate medication delivery, an appropriate inhaler device should be used. Device 

selection must include consideration of the patient’s developmental age and ability to perform 

proper technique (see Table 8 Comparison of Inhaler Devices). 

4. A large volume spacer such as the Aerochamber should be used in patients who have difficulty 

using metered-dose inhalers.

(For detailed recommendations, see Section 8: Intervention – Pharmacotherapy.) 

RATIONALE

Review of NHLBI (2007) and GINA (2007) guidelines and several randomized controlled clinical trials strongly 

support the use of inhaled steroids as the preferred first-line agent. 

A Cochrane review validates the use of MDI and VHC/spacer devices in lieu of nebulized therapy in the acute 

setting and for administration of daily controller medications. 

EVIDENCE STATEMENTS

o Published guidelines have recommended the initiation of inhaled controller medications for all 

patients diagnosed with persistent asthma (NHLBI, 2007; GINA, 2007).

o The recent GINA and NHLBI guidelines also support the use of MDI/HFA and other delivery devices for 

effective medication delivery in lieu of nebulized medication in both the daily and acute 

administration setting (NHLBI, 2007; GINA, 2007). 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Use of inhaled corticoid steroids (ICS) in 

persistent asthma is beneficial

GINA, 2007

NHLBI, 2007 

I Good A 

2 Additional long-acting beta agonists in 

conjunction with ICS may be beneficial in 

controlling symptoms

GINA, 2007

NHLBI, 2007

I Good A 

3 SABAs are effective for acute asthma 

symptoms

GINA, 2007

NHLBI, 2007 

I Good A 

3 Medication delivery is improved by the use 

of an appropriate device

GINA, 2007

NHLBI, 2007

I Good A 

4 Holding Chambers are as effective as 

nebulizers for beta-agonist treatment of 

acute asthma in children age < 5

Cates et al., 2006 I Good A 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Annotation B-7 Educate Patient and Family

5.5 Patient Education 

BACKGROUND

Asthma self-management education is imperative and effective in attaining validated patient outcomes and 

improved asthma control. Targeted asthma education provided to patients and their caregivers affords 

asthma knowledge, skill sets for home management, action steps for changes in asthma control, and 

empowerment. Integration of self-management educational components by patients and their providers 

reduces urgent care clinic visits and hospitalizations, improves health status, reduces symptoms, lessens 

limitation of activity, improves quality of life and perceived control of asthma, and improves medication 

adherence. Reinforcement of asthma self-management education is essential at all points of contact with the 

patient and their caregivers. 

See Section 10: Intervention: Smoking Cessation, Nutrition, Weight loss, and Complementary Alternative 

Medicine.

 See Section 11: Self-Management/Patient Education. 

ACTION STATEMENT

Provide formal asthma education to all patients diagnosed with asthma and reinforce self-management skills 

of patients and caregivers as part of each follow-up visit.

RECOMMENDATIONS

1. Patients and their caregivers should be educated regarding the essential and basic facts about 

asthma that includes: [B]

a. What defines well-controlled asthma

b. Roles of medications

c. Appropriate technique in using inhaler devices 

d. Self-monitoring (either symptom or peak flow-based)

e. Identification of triggers and environmental exposure control measures

f. When and how to handle signs and symptoms of worsening asthma

g. When and where to seek care. 

2. Asthma self-management education should be incorporated into all points of contact with the 

patient and his/her caregivers. [B]

RATIONALE

Asthma patient education programs have been proven effective in improving asthma outcomes. The NHLBI 

(2007) guidelines recommendations were adopted. 

EVIDENCE STATEMENTS 

o Recent meta-analysis reaffirmed the positive impact of asthma education at repeated asthma visits 

on outcomes such as emergency department utilization rates (Coffman et al., 2008).
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EVIDENCE TABLE

Evidence Source LE QE NE SR 

1 Assessment of asthma control and its 

impact on optimal treatment strategy

Lundback & Dahl, 

2007 

III Fair Mod B 

2 Inhaler technique and adherence to 

therapy

Blaiss et al., 2007 III Fair Mod B 

3 Determining personal best peak flow Reddell et al., 2004 II-2 Good Mod B 

4 Traditional and new approaches in 

asthma monitoring

Sorkness, 2008 III Fair Significant B 

5 The effects of a peak flow-based action 

plan in preventing exacerbations of 

asthma

Cowie et al., 1997 I Good Mod B 

6 Effects of Asthma Education on 

Children’s use of Acute Care Services: A 

Meta Analysis

Coffman et al., 2008 I Good Significant A 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Annotation B-8 Educate About Asthma During Activities

5.6 Plan for Improving Activity Level (Asthma at Work/School/Daycare) 

BACKGROUND

A major goal of asthma therapy should be maintenance of normal, age-appropriate activity levels (this 

includes routine exercise as well as desired extracurricular activities). Patients should exhibit minimal, if any, 

symptoms during exercise and should experience regular attendance at work or school.

ACTION STATEMENT

Explain exercise-induced asthma (EIA) and the plan for improving activity level, and provide a letter for 

school/day care.

RECOMMENDATIONS

1. Patients should be encouraged to continue regular exercise and activities of daily living. [A] 

2. Ensure family members, teachers, coaches, and school nurses are aware of the basic principles of 

asthma symptom recognition and management for acute exacerbation.

3. All patients should have a written asthma action plan that includes instructions for recognition of 

worsening conditions along with actions to take at home/work/school/daycare. [A]

4. Patients should be educated about the instructions included in the action plan.

a. Education regarding exercise-induced asthma: [A] 

• Explain that pharmacologic therapies and other strategies may improve exercise 

tolerance and decrease the occurrence of exercise-related symptoms 

• Use SABA 20 minutes prior to planned exertion; if symptoms appear during activity, a 

repeated dose of SABA may be offered as addressed in the written asthma action plan 

• Extend warm-up periods prior to exercise. 

b. Education regarding occupational asthma: [B] 

• Obtaining serial peak flow values both at work and away from work may suggest a 

relationship between work and asthma 
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• Patients with occupation-related asthma may require referral to an occupational 

health specialist. 

5. Managing asthma during school/day care activities: 

a. The asthma action plan for children should be provided to the school and/or daycare [C] 

b. Establish a partnership with schools and/or daycare centers to provide education programs 

for staff and/or peers [B]

c. Use of medication:

• Controller medication: 

o If possible, schedule controller medications to be given at home and not at school or 

daycare 

o If patient adherence is questionable, medication may need to be given at school to 

ensure compliance during the school year 

o When daily controller medication is required at school/daycare, the ability of 

school/daycare personnel to administer the medication should be determined.

• Rescue medication: 

o Rescue medications should be available at school/daycare

o For school-age children, determine availability of rescue medication; some school 

systems do not allow children to personally carry any medication 

o For daycare or young school-age children, the ability of the staff to administer 

medication should be determined.

EVIDENCE STATEMENTS

o Strong evidence supports the use of written asthma action plans (Gibson et al., 2003; NHLBI, 2007). 

o A proactive partnership with schools and/or daycare centers should be established to improve 

asthma management and control in children (Gerald et al., 2006; Haltlerman et al., 2004; NHLBI, 

2007). 

o Evidence supports the use of SABA prior to exercise for those patients with exercise-induced asthma 

(NHLBI, 2007).

o Patients with occupational asthma may require management from an occupational asthma specialist 

(NHLBI, 2007).

EVIDENCE TABLE

Evidence Source LE QE SR

1 Written asthma action plans should be provided 

to all patients

Gibson et al., 2003 

NHLBI, 2007

I Good A 

2 Establish a partnership with schools and/or 

daycare centers 

Gerald et al., 2006

Halterman et al., 2004

NHLBI, 2007

I Good B 

3 Use of SABA prior to exercise for patients with EIA NHLBI, 2007 I Good A 

4 Patients with occupational asthma may require 

referral to an occupational asthma specialist

NHLBI, 2007 I Good B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Annotation B-9 Assess Needs for Family Support and Mental Health Services ; Assess Quality of Life of 

the Patient 

5.7 Psychosocial Assessment

BACKGROUND

Psychosocial factors such as socioeconomic status, educational level of caregivers, and the presence of 

emotional or psychiatric disorders among family members may adversely affect asthma care. Cultural and 

ethnic beliefs or perceptions about asthma or other chronic illnesses may also impact compliance with an 

asthma care plan. Patients with depression or other psychiatric disorders often report impairments that are 

more significant. Social or mental health services may improve not only symptom treatment, but also patient 

perception of symptom control. 

ACTION STATEMENT

Develop and tailor the comprehensive asthma treatment plan to the individual needs of the patient with 

specific sensitivity to cultural, ethnic, educational, or other social or psychological barriers to care. 

RECOMMENDATIONS

1. Asthma care should be provided in an environment that is culturally and ethnically sensitive and at 

an educational level appropriate to the patient and caregivers. [A] 

2. Socio-economic barriers to patient adherence to asthma care should be identified with the patient 

and caregivers, and addressed by education or appropriate referrals. [B]

3. Psychiatric disorders, to include chronic stress or depression, should be identified and patients 

referred as appropriate. [B]

RATIONALE

The NHLBI guidelines (2007) have expanded the importance of providing asthma care that is culturally and 

ethnically sensitive respecting the educational level of the patient and caregiver. Literature reveals that the 

home environment may impact asthma care and compliance with therapy. Patients with asthma have been 

found to be at higher risk for depression and other behavioral disorders that require psychiatric intervention.

EVIDENCE STATEMENTS

o Overwhelming evidence reported outcome improvements with asthma education that is culturally

and ethnically sensitive, and appropriate to educational age (NHLBI, 2007).

o Expert opinion and emerging evidence suggests that psychosocial conditions may play an important 

role in asthma management (NHLBI, 2007; Strine et al., 2008).

o Research indicates that patients with asthma are at higher risk for depressive and/or behavioral 

disorders requiring treatment interventions (Kuehn, 2008; NHLBI, 2007).

EVIDENCE TABLE

Evidence Source LE QE SR

1 Psychosocial conditions impact asthma care 

and severity

NHLBI, 2007

Strine et al., 2008 

II Fair B 

2 Patients with asthma are at higher risk for 

depressive or behavioral disorders

Kuehn, 2008

NHLBI, 2007

II Good B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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ALGORITHM C: FOLLOW-UP

6. MONITORING FOR CONTROL AND FOLLOW-UP

BACKGROUND

A stepwise approach to therapy is recommended, in which the dose and number of medications and 

frequency of administration are increased as necessary and decreased when possible, to achieve and maintain 

control of asthma. Assessing both the domains of impairment and risk emphasizes the need to separately 

consider asthma’s effects on quality of life and functional capacity on an ongoing basis (impairment), as well 

as the risks asthma presents for adverse events in the future. These include exacerbations, or progressive 

reduction in lung growth in children. The two domains may respond differently to treatment. For example, a 

large study of children with asthma revealed that 30 percent of the low-dose ICS treatment group, whose 

levels of impairment (symptoms, SABA use, and lung function) improved, remained at risk for exacerbations 

requiring oral systemic corticosteroids.

The goal for therapy is to control asthma by: (NHLBI, 2007)

Reducing Impairment

o Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness during the day, at 

night, or after exertion)

o Require infrequent use (< 2 days /week) of SABA for quick relief of symptoms, not including 

prevention of exercise-induced bronchospasm (EIB)

o Maintain (near) normal pulmonary function

o Maintain normal activity levels (including exercise and other physical activity and attendance at 

work or school)

o Meet patient and family expectations of, and satisfaction with, asthma care. 

Reducing Risk

o Prevent recurrent exacerbations of asthma and minimize the need for emergency department 

(ED) visits or hospitalizations

o Prevent progressive loss of lung function; for children, prevent reduced lung growth

o Provide optimal pharmacotherapy with minimal or no adverse effects. 

Annotation C-1 Reassess Symptom Control

6.1 Assessment of Control

BACKGROUND

Since asthma is a dynamic condition, ongoing monitoring is essential to maintain control and establish the 

lowest step and dose of treatment. Through proper monitoring, the control of asthma can be reassessed and 

the responsiveness to therapy noted. The severity and control of asthma can be further broken down into the 

domains of asthma impairment and risk. Specific assessment measures can be utilized in the monitoring 

process, including the monitoring of signs/symptoms of asthma, pulmonary function, missing days of

school/work/duty, quality of life, history of asthma exacerbations, adherence to and adverse effects from 

prescribed medical regimens, and patient satisfaction with current asthma treatment.

ACTION STATEMENT

Continue monitoring asthma symptoms to maintain control and establish the lowest step and dose of 

treatment.
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RECOMMENDATIONS

1. Patients with a new diagnosis of asthma, regardless of initial severity, should be seen frequently 

until they are on an effective regimen and demonstrate sufficient understanding of their disease 

management. Thereafter, patients with intermittent and mild persistent asthma should be seen at 

least every 6 months. Those asthma patients with more labile or persistent symptoms should have 

more frequent follow up. [B]

2. Every patient with asthma should be taught to recognize their asthma symptoms, and a written 

asthma action plan, developed in partnership with the patient, should detail the daily management 

(medications and environmental control strategies), and how to recognize and handle worsening 

asthma. The action plan is particularly recommended for patients who have moderate or severe 

asthma, a history of severe exacerbations, or poorly controlled asthma. The written plan can be 

either symptom or peak flow-based; evidence shows similar benefits for each. [B]

3. Periodic pulmonary function tests or spirometry to assess asthma control should be performed: [A]

a. At the initial evaluation

b. After treatment and stabilization

c. If symptoms worsen

d. If change of medication is considered.

4. Periodic spirometry should be considered in patients with controlled symptoms to assess changes 

in airways function.

5. Providers should consider giving patients a peak flow device and including peak flow values in 

written action plans for adults. Peak flow devices would be especially useful in patients with 

moderate-severe asthma, poor perceivers of symptoms, and those with frequent asthma 

exacerbations. Peak flow devices may help the patient and provider assess changes in therapy and 

detect changes in disease state.

6. Self-assessment tools should be considered in monitoring patients with asthma. 

Examples include: [B]

a. Asthma Control Test (ACT) scores used for assessment of symptoms over the past 4 weeks

b. Quality of life monitors to determine a patient’s satisfaction with asthma control and care.

7. Patient adherence and inhaler technique should be evaluated at every asthma visit.

8. Adherent patients with poorly controlled asthma or intolerance of medications should be referred 

to a specialist.

EVIDENCE TABLE

Evidence Source QE Overall 

Quality

NE SR

1 Asthma monitoring Sorkness et al., 2008 III Fair Small B 

2 Peak flow and asthma 

action plans

Cowie et al., 1997

Reddell et al., 2004

I 

II-2 

Good Mod B 

3 Asthma control tests (ACT) Schatz et al., 2006 II-1 Good Mod B

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Table 6. Asthma Control (All Ages)

Components of Control Assessing Asthma Control and Adjusting Therapy

All Ages

Controlled Not Controlled

Impairment

Normal

FEV1/FVC: 

<19 yr – 85%

20-39 yr – 80%

40-59 yr – 75%

Daytime Symptoms ≤ 2 brief symptomatic 

episodes per week

> 2 symptomatic 

episodes per week

Nighttime awakening ≤ 2 nights/month > 2 nights/month

Interference with normal activities None Some Limitation

SABA use for symptom control 

(not for prevention of EIB)

≤ 2 treatments/week > 2 treatments/week 

Spirometry (if obtained)

* predicted/personal best

FEV1 ≥ 80% AND

FEV1/FVC normal

FEV1 ≤ 80% OR

abnormal FEV1/FVC 

Asthma Control Test (ACT) Score

ages ≥4 years ≥ 20 ≤ 19

Risk

Exacerbation requiring oral 

systemic steroids

0-1x/year ≥ 2/year 

Progressive loss of lung function Evaluation requires long-term follow-up and is best assessed by spirometry 

conducted at regular intervals (at least every 1-2 years)

Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome 

and worrisome. The level of intensity does not correlate to specific levels 

of control but should be considered in the overall assessment of risk

Action for 

Treatment

Maintain current therapy 

step

Follow up every 1-6 months

Consider step down

Step up therapy; Reevaluate in 2-6 weeks

- Consider a 5 to 10-day course of oral 

steroids if acute exacerbation and 

reevaluate in 1-2 weeks

- If persistently uncontrolled or 

worsening, consider referral to specialist

Modified from the NHLBI (2007) and GINA (2007) guidelines 
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Annotation C-2 Adjust Medication as Indicated

6.2 Adjustment of Treatment

BACKGROUND

With routine monitoring, proper adjustments can be made to a patient’s asthma treatment plan. The goal is 

to ‘step up’ or ‘step down’ therapy based on the interim symptoms and current control of asthma. When it 

appears that the patient has optimal control of his/her asthma through routine monitoring, he/she may be 

able to ‘step down’ the medical management. Conversely, if it appears the patient is more symptomatic 

during reassessment, he/she may need to ‘step up’ asthma therapy in order to help control the asthma. 

Whenever there is any change made to a patient’s asthma therapy, closer follow-up should be implemented 

to assure the asthma remains under control.

ACTION STATEMENT

Adjust treatment using a step-wise approach to maximize asthma control.

RECOMMENDATIONS

1. Ongoing monitoring is essential to maintain control of asthma. Patients should be monitored at 2-6 

week intervals after initial evaluation and treatment to re-evaluate their response and current 

symptoms.

2. Regular follow-up contacts at 1 to 6-month intervals, depending on level of control, are 

recommended to ensure that control is maintained. A closer follow-up and objective measurement 

of airway obstruction should be obtained whenever the patient’s asthma medication regimen is 

changed. 

3. When adjusting medications: (see Table 7) 

a. If asthma is not controlled on current regimen, a ‘step up’ in therapy is indicated after assuring 

that the patient has good adherence and technique with the medication

b. If asthma is partially controlled, the provider should consider ‘stepping up’ the patient’s 

medication until control is achieved 

c. If the patient is able to maintain control of asthma symptoms for at least 3-6 months on their 

medicine regimen, a ‘step down’ or decrease in their asthma control medication may be 

considered. 
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Table 7. Step Care for Medications Required to Maintain Long-Term Control

Initial

Severity

Use of Quick

relief [b]

Activity 

limits

Symptoms FEV1 Daily Medications [a]

Day Night Preferred Alternative

Step 1

Intermittent < 2 days/week NONE < 2 days/week < 2x/month > 80% SABA PRN --

Step 2

Mild

> 2 days/week, 

not daily 

Minor 

limitation

> 2 days/week, 

not daily [c] > 2x/month > 80% Low-dose ICS --

Step 3

Moderate

Not more than 

once a day

Minor 

limitation

> 2 days/week, 

not daily [c]

> 1x/week, 

not nightly

60-

80% 

Age 0-4: Medium-dose ICS or

Low-dose ICS +LTRA --

Age ≥ 5 

to Adult: 

Low-dose ICS + LABA or

Medium-dose ICS Low-dose ICS + LTRA

Step 4

Severe Daily Some 

limitations Daily [c] Nightly < 60%

0-4: Medium-dose ICS + LTRA Consider referral to specialist 

Age ≥ 5 

to Adult:

Medium-dose ICS + LABA Medium-dose ICS + LTRA

Step 5

Severe

Several times a 

day

Extremely 

limited

Throughout 

the day [c] Nightly < 60%

Age 0-4: Medium-dose ICS + LABA + 

LTRA Refer to specialist

Age ≥ 5 

to Adult:

High-dose ICS + LABA

Consider oral corticosteroids

Medium-dose ICS + LABA + LTRA

Consider referral to specialist

Step 6

Severe

Several times a 

day

Extremely 

limited

Several times a 

day [c] Nightly < 60%

Age 0-4: High-dose ICS + LABA + LTRA

(Consider 5-10 day course of 

oral corticosteroids)

Refer to specialist

Age ≥ 5 

to Adult: 

High-dose ICS + LABA + oral 

corticosteroids

High-dose ICS + LABA + LTRA 

Refer to specialist

[a] Every step: Patient education, environmental control, and management of co-morbidities.

Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma.

Steps 4-6: Consider referral to specialist for evaluation and/or management. 

Steps 5-6: Consider Omalizumab for patients with allergies and elevated IgE. 

[b] Quick-relief medications for all patients: 

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20 minute-intervals, as needed. Short course of oral 

systemic corticosteroids may be needed.

[c] More than 2 exacerbations per year (requiring oral systemic steroids) should prompt step up in therapy 

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs. 
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Annotation C-3 Schedule Follow-up Visit

7. FOLLOW-UP OF PATIENT WITH STABLE ASTHMA

BACKGROUND

Appropriate follow-up visits and management for stable asthma patients should be arranged. Care should be 

focused on preventive visits rather than waiting for symptoms to arise or asthma getting out of control. The 

follow-up visits should include assessment of control, adherence to treatment and reinforcement of selfmanagement skills. Patient education and written Action Plans should be reviewed and updated. Close 

follow-up may minimize need for emergency department visits and/or admissions, preventing progressive loss 

of lung function, and providing optimal pharmacotherapy with minimal adverse effects. 

ACTION STATEMENT

Schedule routine follow-up visits for evaluating asthma control and monitoring disease progression and 

response to treatment. 

RECOMMENDATIONS

1. Stable asthma patients with persistent mild, moderate, or severe asthma should be seen for a visit 

every 6 months unless symptoms warrant sooner follow-up.

2. Stable asthma patients with persistent mild, moderate, or severe asthma should receive spirometry 

at initial evaluation, after treatment and stabilization, if they experience worsening of symptoms, 

and at least every 1-2 years.

3. Aspects of the follow-up visit should include:

a. An interim focused history, review of signs and symptoms, and physical exam

b. Obtaining history of acute exacerbations

c. Assessing the impact of co-morbid conditions affecting asthma control

d. Identifying new environmental triggers

e. Reviewing spirometry and peak flow monitoring

f. Assessing adherence to treatment, spacer use or MDI technique

g. Assessing indications for step-down or step-up therapy

h. Reviewing and updating patient education and written Action Plans

i. Preventive health maintenance, including smoking status of patients and family members

j. Scheduling the next follow-up visit.

RATIONALE

Asthma is a chronic disease with significant morbidity and mortality if left untreated and unmonitored. Stable 

asthma patients require periodic follow-up visits to ensure acceptable asthma control.

EVIDENCE TABLE

Evidence Source LE QE SR

1 Frequency of follow-up visits NHLBI 2007 III Poor I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Annotation C-4 Reassess Diagnosis, Consider Consultation or Referral

7.1 Indications for Consultation/Referral to Specialist 

RECOMMENDATIONS

1. Patients may benefit from referral for assistance in asthma management in the following 

circumstances: 

a. Patient has had a life-threatening asthma exacerbation

b. Patient is not meeting the goals of asthma therapy after 3–6 months of treatment. An earlier 

referral or consultation is appropriate if the primary care provider concludes that the patient 

is unresponsive to therapy

c. Patient requires step 4 care or higher (step 3 for children 0–4 years of age). Consider referral 

if patient requires step 3 care (step 2 for children 0–4 years of age)

d. Patient required more than two bursts of oral corticosteroids in 1 year or had an exacerbation 

requiring hospitalization

e. Other conditions that complicate asthma or its diagnosis (e.g., recurrent sinusitis, nasal 

polyps, aspergillosis, severe rhinitis, VCD, GERD, COPD) that do not respond to appropriate 

management 

f. Additional diagnostic testing is indicated (e.g., allergy skin testing, rhinoscopy, complete 

pulmonary function studies, bronchoscopy)

g. Patient is being considered for immunotherapy or specialized medication such as omalizumab

h. Patient requires additional education and guidance on complications of therapy, problems 

with adherence, or allergen avoidance (Asthma Educator) 

i. Patient / parent requests consultation with a subspecialist.

RATIONALE

Most patients with asthma can be successfully managed by the primary care provider but patients with 

asthma are in a continuum of severity and vary in their response to medications. Situations may arise in either 

establishing a diagnosis or selecting the best therapy, when the specialist will be of assistance. 

EVIDENCE STATEMENT

Patients with asthma that do not respond to standard treatment may benefit from referral to an asthma 

specialist (BTS, 2008; NHLBI, 2007).
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INTERVENTIONS

8. PHARMACOTHERAPY

8.1 Step Care Approach

BACKGROUND

While there are differences in the implementation of step care in children and adults, the basic principles are 

similar. The goal of asthma therapy is to maintain long-term control of asthma with the least amount of 

medication and minimal risk for adverse effects (NHLBI, 2007). 

To achieve and maintain control of asthma, a stepwise approach to therapy is recommended, in which the 

dose and number of medications and frequency of administration are increased as necessary and decreased 

when possible. Assessing both domains (impairment and risk) emphasizes the need to separately consider 

asthma’s effects on quality of life and functional capacity on an ongoing basis (i.e., at present) and the risks 

asthma presents for adverse events in the future, such as exacerbations or progressive reduction in lung 

growth. These domains may respond differentially to treatment. For example, a large study of children with 

asthma revealed that 30 percent of the low-dose ICS treatment group, whose levels of impairment 

(symptoms, SABA use, lung function) improved, remained at risk for exacerbations requiring oral systemic 

corticosteroids (CAMP, 2000). 

Deciding which step of care is appropriate for a patient depends on whether long-term control therapy is 

being initiated for the first time or whether therapy is being adjusted. The classification of asthma severity, 

which considers the severity of both impairment and risk domains, provides a guide for initiating therapy for 

patients who are not currently taking long-term control medications. Once therapy is initiated, or if the 

patient is already taking long-term control medication, the patient’s response to therapy will guide decisions 

about adjusting therapy based on the level of control achieved in both the impairment and risk domains. 

Therapy may be stepped up to regain control, or stepped down for patients who have maintained control for a 

sufficient length of time, to determine the minimal amount of medication required to maintain control and/or 

reduce the risk of side effects.

As indicated, a key to implementing step care involves assessing asthma control. Implementation involves 

assessing severity and monitoring response to therapy with appropriate follow-up. Determining the severity 

in response to treatment can be accomplished by assessment of the number of recent exacerbations, 

frequency of use of rescue medication, impairment of daily activities, nighttime symptoms, and pulmonary 

function levels. In children, this may mean questioning the child’s parents. Another monitoring activity 

involves determining the patient’s acceptance and adherence to the medication regimen and the avoidance of 

asthma triggers such as exposure to plants, pets, or cigarette smoke. 

ACTION STATEMENT

Use the step-up and step-down approaches to initiate and adjust pharmacotherapy for the treatment of 

intermittent and persistent asthma (see Table 7: Step Care for Medications Required to Maintain Long-Term 

Control).

RECOMMENDATIONS

1. Always prescribe an inhaled short-acting bronchodilator for use as needed for intermittent 

symptoms.

2. Always prescribe an anti-inflammatory controller medication for use in persistent asthma. 

3. Inhaled corticosteroids are the preferred anti-inflammatory controller. 
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4. Alternative anti-inflammatory controllers include anti-leukotriene, and cromolyn sodium 

medications. 

5. Consider prescribing a long-acting bronchodilator controller medication for use in persistent 

asthma in addition to an anti-inflammatory controller. 

6. The preferred long-acting bronchodilator controller is an inhaled long-acting beta2-agonist.

7. Alternative controller medications include oral theophylline, oral beta2-agonists, and anti-IgE 

antibody injections. 

8. The dosage of inhaled corticosteriods and added use of combination controller therapy is 

determined by the degree of initial and ongoing impairment and risk. 

9. Step-care includes both stepping up and stepping down the dosage and use of combination 

controller therapy. Stepping down therapy may be considered after a minimum period of stability 

(3-6 months).

8.2. Medication

8.2.1 Quick Relief

Short Acting β2-adrenergic Agonists (SABAs) are bronchodilators that relax smooth muscle and are the 

treatment of choice for relief of acute symptoms, exacerbations of asthma, and prevention of EIB. SABAs 

should only be used on an as-need basis at the lowest dose and frequency required. Increasing use of SABA 

treatment or the use of SABA >2 days a week for symptom relief (not prevention of EIB) indicates inadequate 

asthma control and the need for initiating or intensifying anti-inflammatory therapy. Equally, failure to 

achieve a quick and sustained response during an exacerbation mandates medical attention. Regularly 

scheduled, daily, chronic use of SABA is not recommended.

RECOMMENDATIONS

1. All patients should have a SABA as needed for acute relief of symptoms. [A]

2. SABAs should not be used on a scheduled basis for maintenance therapy. 

3. Providers should evaluate frequency of SABA use. Use of SABA more than 2 days/week for 

symptom control, increasing use, or lack of expected response may indicate inadequate asthma 

control and the need to intensify maintenance drug therapy. 

4. Clinical efficacy and safety are comparable between racemic and non-racemic agents; therefore, 

the least costly agent may be selected. 

EVIDENCE STATEMENTS

Short Acting β2-adrenergic Agonists (SABAs) have a rapid onset of effect and are safe, well tolerated and easy 

to use for relief of acute bronchospasm. 

o The NHLBI reviewed several studies that showed regularly scheduled use of albuterol offered no 

clinical advantage over use on an as-needed basis. 

o Randomized controlled trials in both chronic and acute asthma have shown no clear benefit for nonracemic over racemic SABAs in clinical efficacy or β-adrenergic mediated adverse effects such as 

tachycardia, tremor, and nervousness (Berger et al., 2006; Hamilos et al., 2007; Hardasmalani et al., 

2005; Lotvall et al., 2001; Nowak et al., 2006; Qureshi et al., 2005). However, one study (Carl et al., 

2003) suggested a decrease in hospitalization rate in the emergency department setting with the use 

of non-racemic SABAs. 

Systemic Corticosteroids reduce airway hyperresponsiveness, inhibit inflammatory cell migration and 

activation, and block late-phase reaction to allergen. While not short acting, oral corticosteroids are used for 
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moderate to severe exacerbations in addition to SABAs to accelerate recovery and prevent recurrent 

exacerbations. 

8.2.2 Long-term Controllers

Inhaled Corticosteroids 

Inhaled Corticosteroids (ICS) reduce airway hyperresponsiveness, inhibit inflammatory cell migration and 

activation, and block late-phase reaction to an allergen. ICS do not appear to alter progression or underlying 

severity of asthma but do reduce impairment and risk of exacerbations. Currently, ICS are the most effective 

anti-inflammatory medications for long-term control of persistent asthma across all age groups and in all the 

therapy care steps. 

RECOMMENDATIONS

1. ICS should be used as first-line therapy to control persistent asthma. [A] 

2. ICS initial dosing should be based on the asthma severity. 

3. ICS should be integrated into a step care approach. [A]

4. ICS treatment should be monitored for adverse effects and the patient/parent should be counseled 

regarding management adverse effects. 

5. ICS delivery via nebulization should be administered using specific nebulizer equipment.

RATIONALE

Asthma is predominately a disease of inflammation of the airway that produces airway edema, smooth muscle 

hypertrophy, mucus gland hyperplasia, and airway remodeling such as basement membrane thickening. 

Control of the inflammatory process leads to improvement in airway size and function, typically resulting in 

relief of symptoms, reduction in asthma exacerbations, and improvement in quality of life.

EVIDENCE STATEMENTS

o The pathophysiology of asthma is characterized by a complex inflammatory response within the 

airways. Medications that target inflammation are the most effective agents in the long-term control 

of asthma. 

o ICS are anti-inflammatory medications that are the most viable and effective options for long-term 

control of asthma. 

o ICS are safe and well tolerated; however, adverse effects of the medications are possible, especially 

with escalating doses. 

o Children with asthma require special monitoring for adverse effects of ICS therapy, particularly in the 

aspect of linear growth. ICS appears to affect linear growth in the first few months after initiation of 

therapy, and does not appear to affect final adult height. Poorly controlled asthma can affect linear 

growth. 
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EVIDENCE TABLE

Evidence Source LE QE NE SR

1 ICS should be used as first-line 

therapy to control persistent 

asthma

Durchame et al., 2004

Ng et al., 2004 

NHLBI, 2007

I Good Substantial A 

2 ICS initial dosing should be based 

on asthma severity

NHLBI, 2007 III Poor Mod I 

3 ICS dosing should be integrated into 

a step care approach

Adams et al., 2006

Gibson et al., 2007

NHLBI, 2007

I Good Substantial A 

4 Patient/parent counseling and 

monitoring for ICS adverse effects 

should be performed

NHLBI, 2007 III Poor Substantial I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Long Acting β2-adrenergic 

Long Acting β2-adrenergics (LABAs) do not have anti-inflammatory activity. LABAs are bronchodilators that

act by increasing cyclic adenosine monophosphate in airway smooth muscle, thereby causing bronchodilation. 

A LABA is always used in combination with an anti-inflammatory agent, preferably an inhaled corticosteroid, in 

maintenance treatment of asthma. 

RECOMMENDATIONS (ADULTS)

1. LABAs are not recommended for treatment of acute symptoms or exacerbations. [I] 

2. LABAs must NOT to be used as monotherapy for maintenance treatment of asthma. [D] 

3. LABAs are the preferred agents for add-on therapy to ICS. [A]

4. LABAs should be integrated into a step care approach: [A]

a. For patients who are not adequately controlled on low-dose ICS, consider increasing the dose 

of ICS or adding a LABA. Strong preference should be given to increasing the dose of inhaled 

corticosteroid due to safety concerns, while recognizing that efficacy is greater with the 

addition of a LABA. 

b. For patients who are not adequately controlled on moderate/high-dose ICS, the addition of a 

LABA is preferred to further increasing the ICS dose.

c. Combining a LABA + ICS is preferred to combining a LABA + leukotriene receptor antagonist 

(LTRA) for greater efficacy.

5. Patient/parent counseling and monitoring for LABA adverse effects should be performed.

EVIDENCE STATEMENTS

o The onset of action of salmeterol is slower than SABAs; therefore, it is inappropriate for use in 

management of acute symptoms. While formoterol has an onset of action similar to SABAs, it is not 

approved in the U.S. for acute use.

o Monotherapy with LABAs should not be used for maintenance of asthma regardless of asthma 

severity. 

o Several randomized controlled trials comparing LABA+ICS to same dose ICS or LABA alone have 

shown that LABA monotherapy was inferior to combination ICS +LABA for improvement in pulmonary 
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function and asthma symptoms, decrease in rescue SABA use and resulted in more episodes of 

asthma worsening and exacerbations. In these same studies, outcomes with monotherapy ICS was

better than, or similar to LABAs (Corren et al., 2007; Kavuru et al., 2000; Murray et al., 2004; Nathan 

et al., 2006; Noonan et al., 2006; Pearlman et al., 2004; Shapiro et al., 2000).

o Discontinuation of ICS after initiation of LABA results in increased asthma exacerbations (Lazarus et 

al., 2001; Lemanske et al., 2001).

o The FDA has issued a Black Box warning regarding increased risk of severe asthma exacerbations and 

asthma-related deaths with use of LABAs. The reasons for increased risk are unknown, but may, in 

part, be explained by a lack of concomitant inhaled corticosteroid therapy, genetic factors, reliance 

on bronchodilators in the face of worsening airway inflammation, or the underlying severity of 

asthma (Castle et al., 1993; Nelson et al., 2006). These safety concerns have been reinforced by FDA 

advisory committees (2008), including the FDA safety committee, leading to a recommendation that 

the indication for LABAs as monotherapy for treatment of asthma be withdrawn.

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 LABAs are NOT recommended for 

treatment of acute symptoms or 

exacerbations

NHLBI, 2007 III Poor Zero/Neg I 

2 LABAs are NOT to be used as 

monotherapy for maintenance 

treatment of asthma

NHLBI, 2007 I Good Substantial D 

3 LABAs are the preferred agents for 

add-on therapy to ICS

NHLBI, 2007 

 Adult I Good Substantial A 

 Child III Poor Mod I 

Ducharme et al., 2004 I Good Substantial A 

4 LABAs should be integrated into a 

step care approach but should not 

be used as monotherapy

Gibson et al., 2007

NHLBI, 2007

I Good Substantial A 

5 Patient/parent counseling and 

monitoring for LABA adverse effects 

should be performed

NHLBI, 2007 III Poor Substantial I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Leukotriene Modifiers 

Leukotriene Modifiers interferes with the pathway of leukotriene mediators released from mast cells, 

eosinophils, and basophils. Leukotriene modifiers have a small and variable bronchodilator effect and reduce 

airway inflammation. These drugs can be further classified as leukotriene receptor antagonists (LTRA)

(montelukast, zafirlukast) and 5-lipoxygenase inhibitors (zileuton). In children with allergies, there may be 

some benefit for the use of Leukotriene.

RECOMMENDATIONS

1. Monotherapy with leukotriene modifiers may be considered as an alternative (not preferred) to ICS 

for mild persistent asthma. [A] 
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2. Leukotriene modifiers may be used as an alternative (not preferred) to LABA for add-on therapy to 

ICS. [A] 

3. Zileuton is NOT recommended for use in children < 12 years of age, and is discouraged from use in 

adults due to safety concerns (liver toxicity). [D] 

4. Leukotriene modifiers should be integrated into a step care approach. [B]

EVIDENCE STATEMENTS 

o Several randomized controlled trials have shown that monotherapy with leukotriene modifiers 

improve pulmonary function, asthma symptoms, as needed SABA use, nighttime awakening due to 

asthma, and asthma exacerbations compared to placebo (Altman et al., 1998; Baumgartner et al., 

2003; Busse et al., 2001; Fish et al., 1997; Malmstrom et al., 1999; Nelson et al., 2007; Noonan et al., 

1998; Reiss et al., 1998). 

o A Cochrane meta-analysis showed that monotherapy with leukotriene modifiers is less effective than 

monotherapy with ICS for improvement in pulmonary function, symptoms, rescue SABA use, quality 

of life, and exacerbations (Ducharme et al., 2004). This finding was also supported in a 1-year trial 

comparing montelukast and low-dose ICS (Zeiger et al., 2005). 

o There are limited data comparing the leukotriene modifiers to theophylline or mast cell stabilizers as 

monotherapy; therefore, selection of one of these agents as non-preferred should take into account 

safety and patient-specific variables (Nathan et al., 1999; Schwartz et al., 1998; Yurdakul et al., 2003). 

o Serum alanine aminotransferase (ALT) concentrations should be monitored before treatment with 

zileuton is initiated - monthly for the first 3 months, every 2-3 months for the reminder of the first 

year, and then periodically thereafter. Periodic monitoring may be considered for zafirlukast.

o In clinical trials using zileuton immediate-release, the overall rate of elevation in ALT > 3 x ULN was 

3.2%. One patient developed symptomatic hepatitis with jaundice (Zyflo product labeling).

o In a 12-month safety surveillance study, 4.4% of patients receiving zileuton immediate-release had 

elevation in ALT ≥ 3 x ULN compared to 1% in the usual care group. Elevation in ALT ≥ 8 x ULN 

occurred in 1.3% and 0.2% respectively. Two-thirds of the cases in the zileuton group occurred in the 

first 3 months. No patient in this study developed jaundice or hepatic failure (Lazarus et al., 1998; 

Watkins et al., 2007). 

o In a 6-month trial using zileuton controlled-release, 1.8% of patients had an elevation in ALT ≥ 3 x ULN 

compared to 0.7% of those receiving placebo. Eighty-two percent of the cases occurred within the 

first 3 months. There were no cases of jaundice or hepatic failure in this study (Wenzel et al., 2007). 

EVIDENCE TABLE 

Evidence Source LE QE NE SR

1 Monotherapy with leukotriene 

modifiers may be considered as an 

alternative (not preferred) to ICS for 

mild persistent asthma

NHLBI, 2007 

Durchame et al., 2004

I Good Substantial A 

2 Leukotriene modifiers may be used 

as an alternative (not preferred) to 

LABA for add-on therapy to ICS

NHLBI, 2007 

 Adult

 Child

Durchame et al., 2004 

I 

I 

I 

Good

Fair

Good 

Mod 

Mod 

Substantial 

A 
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3 Zileuton may be less preferable 

than the LTRA due to the need for 

liver function monitoring and drug 

interactions

NHLBI, 2007

Watkins et al., 2007

I 

II-1 

Good Substantial A 

4 Zileuton is not recommended for 

use in children < 12 years of age

NHLBI, 2007 I Good Substantial D 

5 Leukotriene modifiers should be 

integrated into a step care 

approach

NHLBI, 2007

 Adult

 Child 

I 

I 

Good

Fair

Mod 

Mod 

B 

C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Cromolyn sodium 

Cromolyn sodium stabilizes mast cells and interferes with chloride channel function. Its anti-inflammatory 

effect is weak and considered less effective than low-dose ICS. Mast cell stabilizers for the long-term 

treatment of asthma are considered as an alternative medication (not preferred) for mild persistent asthma 

(step 2). It can be used before unavoidable exposure to known allergens or as preventative treatment before 

exercise. Cromolyn is no longer available in a metered-dose inhaler; however, it remains available as a 

solution for nebulizer use.

RECOMMENDATIONS 

1. Cromolyn may be considered as an alternative for mild persistent asthma when other preferred 

options have not been successful. [A] 

2. Consult a specialist if the use of cromolyn is being considered. [I]

EVIDENCE STATEMENTS

o A Cochrane Systematic Review found that ICS were superior to cromolyn for improvement in 

pulmonary function, symptoms scores, and exacerbation rates in children and adults with asthma 

(Guevara et al., 2006).

o There are insufficient data directly comparing cromolyn to leukotriene inhibitors (Nathan et al., 

1999); however, the leukotriene inhibitors are the preferred second-line agents based on the relative 

volume of literature supporting their use compared to cromolyn for maintenance monotherapy. 

Furthermore, adherence to cromolyn is expected to be poor due to its four times daily 

administration.

o There are insufficient data evaluating cromolyn as add-on therapy to other agents. The NHLBI 

recommends that cromolyn not be used as add-on therapy. 

EVIDENCE TABLE: CROMOLYN SODIUM 

Evidence Source LE QE NE SR

1 Monotherapy with cromolyn may 

be considered as an alternative (not 

preferred) to ICS for mild persistent 

asthma

Guevara et al., 2006

NHLBI, 2007

I Good Substantial A 

2 Cromolyn should not be used as 

add-on therapy

NHLBI, 2007 III Poor Small I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Xanthine

Xanthine derivatives are mild to moderate bronchodilators and may have mild anti-inflammatory effects. 

Patient-specific variables should be reviewed due to potential toxicity and significant interactions with other 

drugs. When reference is made to theophylline, it is to the long-acting/slow-release formulations, unless 

otherwise stated.

RECOMMENDATIONS

1. Theophylline may be considered as an alternative for maintenance of mild persistent asthma when 

other preferred options have not been successful. Consult a specialist if maintenance therapy with 

theophylline is being considered.

2. Theophylline may be considered as an adjunctive therapy with ICS for maintenance of moderate or 

persistent asthma.

3. Patients on theophylline should be maintained at a serum level of 5-15 mcg/ml with routine 

monitoring of serum level. 

EVIDENCE TABLE: XANTHINE (THEOPHYLLINE)

Evidence Source LE QE NE SR

1 Consult a specialist if maintenance 

therapy with theophylline is being 

considered

Working Group 

Consensus

III Poor Zero/Neg I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Immunomodulators anti-IgE (Omalizumab)

Immunomodulators anti-IgE (Omalizumab) is a monoclonal antibody that prevents binding of IgE to highaffinity receptors on basophils and mast cells. Omalizumab may be used as adjunctive therapy for severe 

persistent asthma (step 5 or 6) in patients with sensitivity to a relevant allergen (e.g., dust mite, cockroach, 

cat, or dog). Anaphylaxis may occur, therefore clinicians administering omalizumab (prescribed by a specialist)

should be prepared and equipped to identify and treat anaphylaxis. 

RECOMMENDATIONS

1. Omalizumab may be considered, in consultation with a specialist, as adjunctive therapy for severe 

persistent asthma (step 5 or 6) in patients with sensitivity to relevant allergens. [I]

EVIDENCE TABLE: IMMUNOMODULATORS ANTI-IGE (OMALIZUMAB) 

Evidence Source LE QE NE SR

1 Consult Specialist for use of this 

agent in allergic asthma

Working Group 

Consensus

III Poor Zero/Neg I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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Oral systemic Corticosteroids 

Oral Systemic Corticosteroids reduce airway hyperresponsiveness, inhibit inflammatory cell migration and 

activation, and block late-phase reaction to allergen.

RECOMMENDATIONS

1. Consult a specialist if maintenance therapy with an oral corticosteroid is being considered. 

EVIDENCE TABLE: ORAL SYSTEMIC CORTICOSTEROIDS 

Evidence Source LE QE SR

1 Consult a specialist on the use of 

an oral corticosteroid for 

maintenance 

Working Group 

Consensus

III Poor I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

8.2.3 Combination

BACKGROUND

Combination therapy is used to take advantage of the different mechanisms of action of each drug class. 

When single-agents do not provide adequate control, combining agents from different therapeutic classes 

may result in added efficacy. 

RECOMMENDATIONS

1. Combination ICS with LABA is preferred over ICS and LTRA, or zileuton or theophylline for the 

treatment of moderate persistent asthma. [A]

2. Combination of low-dose ICS with LABA may be considered equivalent to medium dose ICS for the 

treatment of moderate persistent asthma. [C]

3. Combination of high-dose ICS with LABA is the preferred therapy for severe persistent asthma. [A]

4. Addition of LABA is preferred to further increasing the ICS dose for patients who are not adequately 

controlled on medium-dose ICS. [A]

EVIDENCE STATEMENTS

o A number of studies as summarized in the NHLBI 2007 report provide evidence from randomized 

controlled trials that combining a LABA and ICS provide greater benefits with respect to pulmonary 

function, reduction in exacerbations and improvement in asthma symptoms compared to any dose of 

ICS alone in adults. Compared to a combination of ICS with a leukotriene modifier or theophylline, a 

LABA and ICS provided greater benefit with respect to pulmonary function and improvement in 

asthma symptoms. There were inconsistent findings with respect to a reduction in asthma 

exacerbations with the trend toward improvement. These combinations have not been well studied

in children ages 5 to 11 and not at all in children age 4 and under (NHLBI 2007). 

o Although evidence supports a greater efficacy of adding a LABA to low-dose ICS over medium-dose 

ICS, the two approaches are considered equal due to the concern for potential adverse effects from a 

LABA (NHLBI, 2007 p. 230). In addition, a meta-analysis by Greenstone et al. (2005) indicated that 

there was no difference between a LABA and ICS (400 beclomethasone equivalent) compared to 1000 

ICS beclomethasone equivalent (non-HFA equivalent). In patients with steroid-naïve mild to 
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Algorithms and Annotations - Page 63 

moderate asthma, a LABA and low to medium-dose ICS is equivalent to ICS alone with respect to 

exacerbations, and slightly inferior with respect to symptom-free days and pulmonary function 

(Greenstone et al., 2005). However, a meta-analysis by Masoli et al. indicated that the addition of a 

LABA to a medium ICS dose provided greater efficacy than doubling the dose of ICS in symptomatic 

asthma patients (Masoli et al., 2005).

EVIDENCE TABLE 

Evidence Source LE QE NE SR

1 Combination ICS with LABA is 

preferred over ICS and LTRA or 

zileuton or theophylline for 

treatment of moderate persistent 

asthma 

NHLBI, 2007 I Good Substantial A 

2 Combination of low-dose ICS with 

LABA may be considered 

equivalent to medium-dose ICS 

for the treatment of moderate 

persistent asthma

NHLBI, 2007 

Greenstone et al., 2005

I 

I 

Good

Good

Small

Mod 

C 

B 

3 High-dose ICS with LABA is the 

preferred therapy for severe 

persistent asthma

NHLBI, 2007 I Good Substantial A 

4 Addition of a LABA is preferred to 

further increasing the ICS dose for 

patients who are not adequately 

controlled on moderate/highdose ICS 

Adults:

 NHLBI, 2007

 Greenstone et al., 2005

 Masoli et al., 2005

Children:

I 

III

Good

Poor

Substantial

I 

A 

I 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

8.3 Use of Devices (MDI without Chambers), Training Technique

BACKGROUND

Inhaled medications for the treatment of asthma are typically delivered through metered dose inhalers 

(MDIs), or air powered nebulizer units. The MDIs are used with or without valved holding chambers (VHC). 

The most effective delivery of inhaled medication via MDI is with a VHC. Use of a VHC should be the primary 

method of MDI delivery, especially for inhaled corticosteroids, in all patients. Optimal medication delivery is 

dependent upon the patient's ability at the time of treatment to physically coordinate and manipulate the 

delivery device, the ability to reproduce optimal delivery technique, and the availability of any additional 

required resources (i.e., electrical power). Additional considerations include the patient's attitude and 

compliance with the need to properly clean and maintain the selected device. 

Regardless of the delivery device selected, detailed education on the use, care and maintenance of the 

delivery device is essential. The patient should demonstrate proper technique initially and with each followup visit to ensure proper (optimal) medication delivery.

The use of a VHC eliminates most physical coordination and manipulation issues associated with MDI-only 

therapy and can be carried easily by the patient. MDIs with VHC do not require filters, batteries, or access to 

electrical power. This delivery combination requires little cleaning and maintenance and is easily replaced. 

Studies show that when compared to nebulized medication delivery, the use of MDIs in conjunction with VHC 

demonstrated a reduced admission rate in pediatrics (over age 5) and no negative impact on adults (Castro et 
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Algorithms and Annotations - Page 64 

al., 2004, Cates et al., 2006). These same studies suggest that severity scores by patients improved when

using the MDIs with VHC in both adults and pediatrics (Castro et al., 2004). MDIs with VHC are recommended 

as the primary delivery system for inhaled medications in the treatment of asthma (see Table 8: Comparison 

of Inhaler Devices).

ACTION STATEMENT

Metered Dose Inhalers (MDIs) in conjunction with Valved Holding Chambers (VHC) are recommended as the 

primary delivery system for inhaled medications in both pediatric and adult patients.

RECOMMENDATIONS

1. Metered Dose Inhalers with Valved Holding Chambers are as effective as nebulizer therapy for 

delivery of aerosolized medications (quick relief) in the adult and pediatric patient. [B] 

Table 8. Comparison of Inhaler Devices

Device Advantages Disadvantages 

Metered Dose Inhaler 

(MDI)

Beta2–Agonists

Corticosteroids

Cromolyn Sodium

Anticholinergics

• Portable – compact

• Little or no preparation time

• Short treatment time

• High dose-to-dose reproducibility

• No content contamination

• Requires significant breath and actuation 

coordination

• Physical dexterity for actuation required

• Not all inhaled medications available in this 

form

• Few with dose counters

Metered Dose Inhaler 

(MDI) with Valved 

Holding Chamber (VHC)

See above

• Portable

• Little or no preparation time

• Short treatment time

• High dose-to-dose reproducibility

• Less pharyngeal deposition vs. MDI

• Reduced coordination vs. MDI

• No content contamination

• Less compact vs. MDI only

• Physical dexterity for actuation required

• Not all inhaled medications available in this 

form

• Few with dose counters

Dry Powder Inhaler 

(DPI)

Beta2–Agonists

Corticosteroids

Anticholinergics

• Portable – compact

• Little or no preparation time

• Short treatment time

• Breath actuated

• Less patient coordination

• Propellant not required

• Most have dose counters

• Requires 30-60 lpm inspiratory flow for 

optimal delivery

• Some units require loading with each dose

• Not all medications available in this form

Small Volume Jet 

Nebulizer

Beta2–Agonists

Corticosteroids

Cromolyn Sodium

Anticholinergics

• Patient coordination minimal

• Effective with tidal breathing

• Can be used with supplemental 

oxygen

• Lengthy treatment time

• Contamination possible

• Device cleaning required

• Pressurized gas source required

• Limited portability

• Not all medications available in this form

• Device preparation required

• Performance variability

Adapted from Dolovich et al., 2005
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9. ENVIRONMENTAL CONTROL

9.1 Inhaled Allergens

BACKGROUND

There is an important association between inhaled allergens and asthma. The presence of IgE-mediated 

sensitization to inhaled allergens is a risk factor for the development of asthma. Furthermore, allergic 

sensitization and exposure to elevated levels of inhaled allergens have been linked to airway hyperreactivity 

and a variety of adverse asthma outcomes including fatal asthma. These links have been shown for indoor 

environmental allergens such as dust mites, animal dander, cockroaches and molds as well as outdoor 

allergens including grass, ragweed, and molds. As a result, the approach to every patient with asthma should 

include a thorough history to assess for associations between inhaled allergens and their asthma symptoms. 

A thorough history and knowledge of specific sensitizations can be used to determine the relevant inhaled 

allergen exposures and serve as the foundation for patient education on triggers, avoidance, and possibly 

immunotherapy when indicated. The role of specific strategies for avoidance of indoor inhaled allergens is 

controversial. 

Understanding potential triggers and associations of symptoms with inhaled allergen exposure can also serve 

an important role in patient selection for consideration of immunotherapy. 

RECOMMENDATIONS

1. For all patients with asthma at any level of severity [B]:

a. Use the patient’s medical history to identify allergen exposures that may trigger the patient’s 

asthma

b. Use the patient’s history to assess sensitivity to seasonal allergens

c. Educate the patient and consider measures to reduce exposure to the identified inhaled 

allergen(s).

2. For patients with persistent asthma and indoor-related symptoms, the investigation of the 

potential role of allergens should be considered [C]:

a. Allergy testing should be performed to reliably determine sensitivity to common inhalant 

allergens to which the patient is exposed (skin testing or serum-specific IgE [i.e., RAST] testing)

b. The patient’s history should be used to assess the significance of positive allergen-specific IgE 

tests

c. Educate the patient and consider measures to reduce exposure to the identified allergens.

3. A comprehensive approach to inhaled allergen avoidance in sensitized patients should be 

employed rather than implementing a single specific environmental avoidance strategy or regimen. 

[C]

4. Consider allergen immunotherapy when there is clear evidence of a relationship between 

symptoms and exposure to an allergen to which the patient is sensitive. [B]

DISCUSSION

While there is insufficient evidence to recommend any single specific environmental avoidance strategy or 

regimen for the varied inhaled allergens, the NHLBI 2007 report outlined a set of sensible strategies for 

common inhaled allergens based on existing literature (see Appendix E).

Several studies demonstrate the ability to significantly lower the levels of several indoor inhaled allergens 

using differing methods requiring differing levels of cost and effort. However, there are limited and 

contradictory findings in the literature that examine improvement in asthma outcomes with avoidance 
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measures for indoor inhaled allergens. Strategies that take comprehensive approaches to avoidance of 

inhaled allergens such as dust mites, cockroaches, and animal dander have shown clinical benefit in some 

smaller well-designed studies. Limited and/or single strategy approaches to indoor inhaled allergens, such as 

bedding covers alone for dust mites, or HEPA filtration alone in a home where the pet remains, are not reliably 

effective. A Cochrane analysis (Gøtzsche et al., 2007) concluded that dust mite interventions were not 

effective in improving asthma outcomes. However, this meta-analysis included negative trials with limited 

approaches and non-sensitized individuals while it excluded some well designed, though smaller, positive trials 

with multiply sensitized patients.

Patients with persistent symptoms or prolonged seasonal symptoms who have sensitization to relevant

inhaled allergens have been shown to benefit from immunotherapy. Controlled studies have demonstrated 

improved asthma outcomes when treated for symptoms caused by grass, ragweed, house dust mites, cats and 

molds. A meta-analysis (Abramson et al., 2003) and the updated NHLBI 2007 Guidelines support the role for 

immunotherapy in asthma.

For more details on allergens, see Appendix E.

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Exposure to inhaled allergens in 

sensitized individuals results in 

airway inflammation and asthma 

symptoms

Call et al., 1992 & 1994

Custovic et al., 1998

GINA, 2007

Gruchalla, 2002 

Huss et al., 2001

NHLBI, 2007

Pulimood et al., 2007 

Rosenstreich et al., 1997

Sporik et al., 1990

I Good Mod B 

2 Limited avoidance measures to 

reduce inhaled indoor allergens 

do not reduce allergen levels or 

improve asthma outcomes

De Blay et al., 1991

Francis et al., 2003

GINA, 2007 

Gotzche et al., 2007 

Lusczynska et al., 2003

NHLBI, 2007

Terreehorst et al., 2002 

Woodcock et al., 2003

I Fair Small C 

3 Comprehensive measures to 

reduce inhaled indoor allergens 

improve airway inflammation 

and asthma outcomes

Carter et al., 2001 

Halken et al., 2003

Morgan et al., 2004

NHLBI, 2007

Peroni et al., 2002

Platts-Mills et al., 2000

Popplewell et al., 2000

Van der Heide et al., 1997

II-1 Fair Small C 

4 Immunotherapy is effective for 

patients with persistent asthma 

who have symptoms consistent 

with identified inhaled allergen 

sensitivities

Abrahamson et al., 2003 

NHLBI, 2007

I Good Mod B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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9.2 Inhaled Irritants

BACKGROUND

There are convincing links and concerning associations between a variety of environmental irritants and 

asthma. Understanding possible associations between asthma and the environmental tobacco smoke, 

particulate air pollution, nitrogen dioxide (NO2), sulfur dioxide (SO2), diesel exhaust, volatile organic 

compounds, formaldehyde, fumes from wood burning stoves and fireplaces, and gas appliances can be 

important in developing plans for avoidance and treatment of patients with asthma.

RECOMMENDATIONS

1. Patients who have asthma at any level of severity should: [C]

a. Avoid exposure to environmental tobacco smoke and other respiratory irritants, including smoke 

from wood-burning stoves and fireplaces and, if possible, substances with strong odors

b. Avoid exertion outdoors when levels of air pollution are high.

2. There is insufficient evidence to recommend any specific environmental strategies to prevent the 

development of asthma.

EVIDENCE STATEMENT

o Other guidelines (NHLBI, 2007 and GINA, 2007) have suggested that irritant identification and 

avoidance could be beneficial in controlling asthma in susceptible patients.

EVIDENCE TABLE

Evidence Source LE QE SR

1 Avoid respiratory irritants NHLBI, 2007 I Good C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

9.3 Occupational Exposure

BACKGROUND

Certain occupations may expose patients to inhaled allergens, inhaled irritants, or other unique substances 

that may contribute to or even be the proximate cause of their asthma. Early diagnosis and intervention can 

be important to reduce the risk of worsening or inducing a more persistent/permanent element to the 

patient’s asthma. History to include exposures to allergens, irritants, chemicals, dusts and the links of the 

workplace with symptoms and/or objective measures of lung function can be crucial. 

RECOMMENDATIONS

1. Patients who have asthma and are employed, particularly those who have new-onset disease, 

should be queried about possible occupational exposures that may include allergens, irritants, or 

other exposures.[C]

2. Specialist care management over a period of time, or co-management with the primary care 

provider, should be considered when history suggests that an occupational or environmental 

inhalant or ingested substance is provoking or contributing to asthma. Treatment or intervention 

may be required in the work environment. 
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RATIONALE

Identification of occupational exposures and modification of work environment can be beneficial in controlling 

asthma symptoms. 

EVIDENCE STATEMENT

o “Early recognition and control of exposures are particularly important in occupationally induced 

asthma, because the likelihood of complete resolution of symptoms decreases with time (Pisati et al., 

1993). Occupational asthma is suggested by a correlation between asthma symptoms and work, as 

well as with improvement when away from work for several days. The patient may fail to recognize 

the relationship with work, because symptoms often begin several hours after exposure. Recently, 

common jobs—such as domestic cleaner, laboratory technician, and house painter—have been 

associated with the disease (Moscato et al., 1995). Serial peak flow records at work and away from 

work can confirm the association between work and asthma (Nicholson et al., 2005).” (NHLBI 2007 

Page 175) 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Occupational exposures GINA, 2007

NHLBI 2007

I Good C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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10. OTHER INTERVENTIONS

10.1 Smoking Cessation

BACKGROUND

Personal use of tobacco products and exposure to environmental tobacco smoke (ETS) is common in the 

United States and directly affects asthma management. Second hand smoke exposure in all asthma patients is 

associated with increased asthma severity and poorer outcomes, including a decreased responsiveness to 

some asthma medications. Exposure to maternal smoking has been shown to be a risk factor for the 

development of asthma in infancy and childhood.

RECOMMENDATIONS

1. All patients should be asked about tobacco use and should have their tobacco use status 

documented on a regular basis. [A] 

2. All providers should strongly advise every patient who smokes to quit. [A] (See the VA/DoD 

Clinical Practice Guideline for Tobacco Use.) 

3. Asthma patients and their families and/or caregivers should be instructed to avoid ETS. [A] 

4. All pregnant patients should be instructed not to smoke and to avoid exposure to ETS. [A] 

RATIONALE

The negative effects of tobacco use and exposure to ETS in the general population are well documented in the 

medical literature. Particularly in patients with asthma, there is a marked decrease in lung function with 

tobacco use. All patients should be queried about tobacco use and/or ETS and instructed to stop smoking 

and/or avoid exposure at each encounter. Refer to the VA/DoD clinical practice guideline for tobacco use, for 

specific information on counseling and tobacco cessation interventions.

EVIDENCE

o Evidence has shown that clinic-screening systems, such as expanding the vital signs to include 

tobacco use status or the use of other reminder systems such as chart stickers or computer 

prompts, significantly increase rates of clinician intervention (PHS, 2008). [A] 

o Evidence analysis shows that brief physician advice significantly increases long-term smoking 

abstinence rates. Additional studies show that advice to quit given by healthcare providers in 

general does significantly increase quit rates (PHS, 2008). [A] 

o Tobacco smoking is associated with accelerated decline of lung function in patients with asthma 

and increases in asthma severity (GINA, 2007). 

o Exposure to ETS is associated with increased symptoms, decreased lung function, decreased 

quality of life, and increased risk of asthma-related ED visits and hospitalizations in patients with 

asthma (GINA, 2007; NHLBI, 2007). 

o Tobacco use during pregnancy and ETS exposure postnatally increases the risk of childhood 

recurrent wheezing and asthma (GINA, 2007; NHLBI, 2007). Of particular concern are the effects 

of tobacco exposure in utero and in early infancy because of the increased incidence of recurrent 

wheezing and asthma (NHLBI, 2007; GINA, 2007; DiFranza, 2004). 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 70 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Screening for tobacco use 

and advising to quit

PHS, 2008 I Good A 

2 Tobacco use has a 

negative effect on asthma 

GINA, 2007 I Good A 

3 ETS worsens asthma GINA, 2007

NHBLI, 2007

I Good A 

4 Prenatal and postnatal ETS 

increases risk of decreased 

lung function, wheezing, 

and asthma

DiFranza et al., 2004

GINA, 2007

NHLBI, 2007

I Good A 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

10.2 Nutrition

BACKGROUND

A well-balanced diet that includes a variety of foods promotes general good health. In brief, most Americans 

need to consume diets with more fruits, vegetables, and whole grains, and eat less solid fats (saturated fat, 

transfat), salt, and added sugars. While food allergies are rarely an aggravating factor, some asthma patients 

are sensitive to sulfites in foods and are at higher risk for severe reactions to foods to which they are 

sensitized.

RECOMMENDATIONS

1. Advise patients who have asthma symptoms associated with consuming foods to which they are 

sensitized and/or foods high in sulfites (e.g., processed potatoes, shrimp, dried fruit, beer or wine) 

to avoid these products. [C] 

RATIONALE

There is no evidence to support using restrictive diets to control asthma except in the cases of patients with 

proven food sensitivities, to include sulfite-containing products. Asthma patients should follow the same 

dietary recommendations as the rest of the population (NHLBI, 2007).

EVIDENCE STATEMENTS

o Evidence shows that in certain patients with asthma, consuming sulfite-containing products or other 

foods to which they are sensitized can contribute to worsening asthma symptoms.

EVIDENCE TABLE

Evidence Source LE QE SR

1 Avoid sulfite-containing foods or 

those to which a patient is 

sensitized 

NHLBI, 2007 II Fair C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 71 

10.3 Weight loss

BACKGROUND

Obesity has been associated with asthma persistence and severity in both children and adults, with a 

correlation between excess weight and selected inflammatory mediators that may negatively impact asthma 

control. Weight loss in adults can result in improved FEV1, reductions in exacerbations, and improved quality 

of life.

RECOMMENDATIONS

1. Advise patients with asthma who are overweight or obese that excess body weight may have 

negative effects on asthma control and that weight loss may be associated with improvement of 

symptoms. [B] 

2. Encourage all patients with asthma to attain and maintain healthy body weight (see the VA/DoD 

Guidelines for Overweight and Obesity). [B]

RATIONALE

Weight loss in obese patients with asthma can result in improvement in pulmonary mechanics, symptoms and 

quality of life, but the actual mechanisms are unclear. However, there is insufficient evidence to recommend 

severely limited caloric diets and/or bariatric surgery to control asthma.

EVIDENCE STATEMENTS

o A prospective study of obese women enrolled in an intensive weight loss program showed that while 

FVC and FEV1 improved, bronchial reactivity did not significantly change nor did methacholine 

responsiveness (Aaron et al, 2004). 

o The evidence shows that children with high body weight, either at birth or later in childhood, are at 

increased risk for future asthma (Flaherman et al., 2006).

o There is compelling evidence that overweight and obese adults have a higher incidence of asthma 

(Beuther & Sutherland, 2007).

o Weight reduction in obese asthma patients has been demonstrated to improve lung function and 

health status (NHLBI, 2007). 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Calorie controlled diets in chronic 

asthma improve FEV1 and FVC

Cheng et al., 2003 I Fair B 

2 High body weight in children increases 

risk for future asthma

Flaherman et al., 2006 I Fair B 

3 Overweight and obesity in adults are 

associated with increased incidence of 

asthma

Beuther & Sutherland, 

2007

I Fair B 

4 Weight loss in adults results in 

improvement in pulmonary mechanics 

NHLBI - 2007 II Good B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 72 

10.4 Complementary and Alternative Medicine (Meditation, Acupuncture)

BACKGROUND

Increasing numbers of the U.S. population are exploring options in complementary and alternative medicine

(CAM), which includes chiropractic therapy, acupuncture, meditation, breathing or relaxation techniques, 

hypnosis, homeopathy, herbal products and nutritional supplements. While some cultural beliefs and 

practices may be incorporated into evidence-based asthma management, patients and caregivers must be 

educated on the potential dangers associated with utilizing unproven therapies.

RECOMMENDATIONS

1. In the process of interviewing the patient and reconciling medications, query every patient for the 

use of complementary and alternative medicine (CAM). [I]

2. Discourage patients and caregivers from substituting alternative therapies for evidence-based 

conventional asthma management by providing evidence-based information. [D] 

DISCUSSION

The Joint Commission for the Accreditation of Healthcare Organizations includes alternative products in the 

definition of a drug and mandates full reconciliation and communication to all providers involved in patients’ 

care. Complementary and alternative therapies include acupuncture, homeopathy, herbal medicine, 

Ayurvedic medicine, ionizers, osteopathy and chiropractic manipulation and dietary supplements. The 

evidence for these therapies is limited by the small number, and size, of well-designed trials, and the lack of 

clinically significant differences between intervention and control groups. The few trials showing benefits 

were not reproducible and the potential side effects can be problematic and, in some cases, life-threatening if 

these therapies are used in place of conventional treatment. 

EVIDENCE STATEMENTS

o There are many accounts of deleterious effects associated with the use of alternative therapies 

because of product interactions, overlap and/or duplication of effects, or contaminated products.

o There is substantial evidence showing that using CAM in place of traditional therapy causes loss of 

asthma control and, in some cases, serious medical symptoms (NHLBI, 2007; GINA, 2007). 

o A meta-analysis of 15 trials (Markham et al., 2004) and a subsequent systemic review (Passalacqua et 

al., 2006) found insufficient evidence to recommend any of these therapies.

EVIDENCE TABLE

Evidence Source LE QE SR

1 Use of CAM is not proven to be effective 

and can be dangerous

NHLBI, 2007

GINA, 2007

II Good D 

2 Treating asthma with omega-3 fatty 

acids

Reisman et al., 2006 I Poor I 

3 Manual therapy for asthma 

(manipulation or massage) 

Hondras et al., 2005 I Poor I 

Lack of evidence for the use of CAM to 

improve asthma control

Markham et al., 2004

Passalacqua et al., 2006

I Poor D 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 73 

11. SELF-MANAGEMENT/PATIENT EDUCATION

Providing limited asthma education to patients and families does not improve clinical outcomes. There is 

strong evidence that practice models incorporating comprehensive education on asthma self-management, 

including self-adjustment of medications in response to worsening symptoms, regular medical review and 

provision of a written action plan, significantly improve asthma control and quality of life.

11.1 Patient and Family Education (Self-Management)

BACKGROUND

Asthma self-management education is essential to provide patients and their caregivers with the skills 

necessary to control asthma, improve outcomes, and maintain a healthy lifestyle. Patient and family 

involvement is central to optimal asthma control and self-management education must be tailored to literacy 

levels and sensitive to diverse cultural beliefs and backgrounds. Asthma education is most effective when 

initiated at the time of diagnosis and reinforced at every encounter, and when it includes information on daily 

and acute management with self-adjustment of medications. By establishing joint treatment goals and 

demonstrating responsiveness to patient concerns, the primary care manager builds the foundation of a 

strong partnership in asthma management.

RECOMMENDATIONS

1. Assess patient and/or family for educational needs as well as for preferences and/or barriers to 

learning, which may include limited medical and/or English literacy, physical, developmental, 

emotional or psychological challenges as well as specific cultural and/or spiritual beliefs. [A]

2. Provide asthma self-management education at all points of care where health professionals 

interact with patients and their families. [A] Education may be effective at other points of care 

such as pharmacies, hospitals, schools, and emergency departments. [B]

3. Teach and review core asthma education and self-management concepts at every visit with return 

demonstration when appropriate. [B]

4. Encourage a varied diet that is consistent with the Dietary Guidelines for Americans. [B] 

5. Encourage asthma patients to participate in regular exercise to maintain general health and

improve pulmonary conditioning. [B] 

DISCUSSION

The Joint Commission (TJC) mandates that all patients be assessed for cultural and spiritual requirements. 

Exercising and eating a variety of foods are safe for asthma patients and they should be encouraged to 

embrace a healthy lifestyle that includes good nutrition and regular exercise to improve pulmonary 

conditioning (Ram et al., 2005). Evidence is now abundant that asthma self-management education is 

effective in improving asthma outcomes (NHLBI, 2007). It is important to integrate asthma self-monitoring 

and management education into all aspects of asthma care, beginning at the time of diagnosis and continuing 

through follow-up care. The principal clinician should introduce the key educational messages and negotiate 

agreements about the goals of treatment, specific medications, and the actions patients will take to reach the 

agreed-upon goals to control asthma. These core concepts should be emphasized by all members of the 

healthcare team at every encounter.
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 74 

Table 9. Core Education and Self-Management Concepts

Core Education and Self-Management Concepts

o Basic information about asthma (inflammation vs. bronchoconstriction, chronicity of disease, 

definition of good control)

o Components and utility of a written asthma action plan, including recognition of worsening 

conditions along with actions to take at home (monitoring and medication adjustment)

o Triggers, allergen avoidance and environmental controls

o School/daycare-specific instructions

o Medications’ mechanisms of action, roles in management, and possible side effects

o Specific instructions for emergency situations

o Delivery devices and their appropriate use emphasizing that MDI/HFA with spacer device is 

equally effective for administration of nebulized medication. 

o Contact names and telephone numbers for professional support to answer questions about 

home management

o Method of routine monitoring (symptoms and/or peak flow)

o Appointment information for the next visit

EVIDENCE STATEMENTS

o The Joint Commission requires comprehensive cultural and spiritual assessment of all patients 

entering a healthcare system (CAMH, 2008). 

o The evidence supports the provision of individualized culturally sensitive patient and/or caregiver 

education (NHLBI, 2007).

o Strong evidence supports ensuring that asthma self-management education be initiated at the time 

of diagnosis and be repeated and reinforced at every patient encounter with healthcare providers 

(NHLBI, 2007). 

o The evidence shows that regular physical exercise improves pulmonary conditioning and does not 

worsen lung function in patients with asthma (Ram et al., 2005). 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Perform cultural and spiritual assessment CAMH, Provision of 

Care 6.10, 2008

I Good A 

2 Individualized culturally sensitive asthma 

education improves outcomes

Bailey et al., 2008

NHLBI, 2007

I Fair C 

3 Self-management asthma education must 

be initiated at the time of diagnosis and be 

repeated and reinforced

NHLBI EPR-3, 2007 I Good A 

4 A varied diet promotes good health DHHS – Dietary 

Guidelines for 

Americans, 2005

II Good B 

5 Physical training in asthma improves 

cardiopulmonary fitness while lung 

function and wheeze are not worsened

Ram et al., 2005 I Fair B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 75 

11.2 Strategies to Deliver Patient and Family Education

BACKGROUND

Effective patient and/or caregiver education can be accomplished using a variety of instructional methods. 

Comprehensive disease management programs may rely on interdisciplinary teams for patient education and 

include physicians, physician assistants, nurse practitioners, nurses, respiratory therapists, pharmacists and 

asthma educators. Many patients and families may benefit from the myriad of easily accessible emerging 

technologies that include audiovisual materials and internet-based programs. 

RECOMMENDATIONS

1. Utilize a variety of educational strategies to include frequent appointments with asthma educators, 

individualized case management, and/or patient age-appropriate standard curriculums. [B]

2. Consider utilizing interactive, multi-media resources in providing asthma education. [B]

3. Consider providing information on web-based comprehensive education sites that may include 

journaling, bulletin boards, support systems, electronic symptom questionnaires, and/or quality of 

life surveys to track and reinforce patient self-monitoring and management skills. [B]

DISCUSSION

Many patients will benefit from interactive computer games and multi-faceted internet programs that provide 

basic asthma-related information and reinforce self-management techniques and environmental controls. 

There is increasing evidence that incorporating technology into asthma self-management education can 

augment and enhance traditional methods of instruction. In children, Cicutto demonstrated that using games, 

puppetry and model building decreased school absenteeism and activity limitation (Cicutto et al., 2005), while 

Runge showed that adding an internet-based education program improved health outcomes (Runge et al., 

2006). Rasmussen demonstrated a similar effect in adult patients utilizing an internet-based asthma 

management tool (Rasmussen et al.,2005). Compared to both specialty and general practice, these patients 

had significantly fewer asthma symptoms, higher quality of life and better FEV1. Based on patient skill, access

to and interest in using interactive multi-media tools and web-based information and decision tools can 

improve outcomes.

EVIDENCE STATEMENT

o Utilization of a variety of educational techniques has demonstrated improvement in outcomes 

(NHBLI, 2007; Cicutto et al., 2005). 

o Emerging evidence suggests the potential for incorporating internet-based programs into asthma 

education and management (Runge et al., 2006; Rasmussen et al., 2007). 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Innovative educational methods that 

include technology improve outcomes in 

children

Cicutto et al., 2005 I Good B 

2 Incorporating internet-based asthma 

education improves outcomes in children

Runge et al., 2006 I Good B 

3 Using an internet-based asthma 

management tool decreased symptoms 

and increased quality of life in adults

Rasmussen et al., 2007 I Good B 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 76 

11.3 Optimal Self-Management Tools (Use of Symptom or Peak Flow and/or Symptom-Based 

Action Plans)

BACKGROUND

Programs providing limited asthma education (transfer of information only without self-management 

techniques/written action plans) have not had positive effects on clinical outcomes with the exception of 

some possible benefit in the emergency department. Since all individuals diagnosed with asthma are 

susceptible to asthma exacerbations, patients with asthma should know how to prevent and manage these 

episodes. Optimal self-management includes self-monitoring (symptoms or symptoms and peak flow), regular 

medical review and the provision of a written action plan. Previous guidelines emphasized the use of peak 

flow meters, but the most recent evidence shows that symptom-based plans are also effective. In patients 

with asthma, training programs that enable patients and/or caregivers to adjust medication using a written 

plan leads to improved health outcomes.

RECOMMENDATIONS

1. Ensure optimal self-management by providing education on self-monitoring, use of a written 

asthma action plan and regular medical review. [A]

2. Develop asthma action plans that include instructions for daily management and recognition of 

worsening conditions along with actions to take at home (monitoring and medication adjustment) 

based on symptoms or peak expiratory flow (PEF) measurements and symptoms as appropriate. 

[A]

DISCUSSION

Education that is limited to information transfer does not significantly impact outcomes (Gibson et al., 2002). 

However, there is strong evidence that optimal asthma self-management, which includes education, regular 

medical review and use of a written asthma action plan, clearly leads to improved health outcomes in adults 

(Gibson et al., 2003). Agrawal demonstrated similar results in a pediatric population (Agrawal et al., 2005). As 

described in Bhogal, the need for active participation of the patient and/or caregiver to prevent exacerbation 

has resulted in the universal recommendation by national and international guidelines to provide written 

asthma action plans to all asthma patients (Bhogal et al., 2006; GINA, 2007; NHLBI, 2007). The action plan 

must include information on daily management, recognizing and handling worsening symptoms, including selfadjustment of medications when necessary.
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 77 

Table 10. Information Included in Written Asthma Action Plans

Personal Information and Daily Management Worsening Symptoms and Actions to Take at Home

Patient name

Provider/clinic name and contact number

Personal best peak flow (when applicable)

Monitoring method and frequency (symptoms or 

symptoms and peak flow)

Description of optimal control (e.g., no coughing, 

wheezing, shortness of breath, chest tightness, 

interference with activities or sleep, peak flow > 

80% of personal best)

Trigger recognition, mitigation and/or avoidance 

(consider pollen count, air quality, etc.)

Medications (quick relief, long-term controller, 

adjunctive therapies)

Guidance on prophylactic medication prior to trigger 

exposure (exercise, environmental allergens or 

irritants)

Patient-specific asthma symptoms/peak flow values 

requiring action:

- Acute asthma symptoms (e.g., cough, wheeze, 

shortness of breath, chest tightness, etc.)

- Daytime symptoms > 2 times/week

- Nighttime wakenings > 2 times/month

- Increased limitation of normal activity

- Increased use of bronchodilator (> 2 times/week)

- Peak flow value < 80% of personal best

Initial response to increased symptoms

- Stop the provoking activity/move away from 

trigger(s)

- Evaluate symptom severity/peak flow value

Appropriate use of quick-relief medication

When to reassess effectiveness of treatment through 

symptoms/peak flow

When and how to modify medication regimen (add and/or 

increase)

How to continue self-monitoring

How to identify a failure of home treatment if increased 

use of rescue medication is required until symptoms and 

peak flow stabilize

When to call the healthcare provider for evaluation

What symptoms/peak flow values require emergency medical treatment:

- Lack of response to quick-relief medication

- Inability to talk in complete sentences

- Extreme shortness of breath

- Retractions, lips/fingernails are blue

- Increased respiration rate

- Peak flow < 50% of personal best

Directions for accessing emergency care (e.g., 911)

EVIDENCE STATEMENT

o Patients with optimal asthma management, including comprehensive asthma education that 

addresses self-monitoring, regular medical review and a written action plan have better outcomes. 

The action plan must include instructions on daily management and how to recognize and handle 

worsening asthma by self-adjustment of medications (Agrawal et al., 2005; Cicutto et al., 2005; 

Gibson et al., 2003). 
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 78 

o Both symptom or symptom and peak flow-based written action plans can be effective (Bhogal et al., 

2006). 

EVIDENCE TABLE

Evidence Source LE QE SR

1 Education in self-management that includes selfmonitoring, regular medical review and a written 

action plan improves health outcomes for adults

Gibson et al., 2003 I Good A 

2 Comprehensive asthma education that includes 

action plan use decreases urgent care visits, 

school absenteeism and activity limitation in 

children

Cicutto et al., 2005 I Good A 

3 Comprehensive self-management programs that 

include written asthma action plans decrease 

asthma events, missed days of school, nocturnal 

awakenings and symptoms

Agrawal et al., 2005 I Good A 

4 Symptom or symptom and peak flow-based 

asthma action plans are effective

Bhogal et al., 2006 I Good A 

5 Limited asthma education does not decrease 

hospitalizations, asthma therapy or time lost 

from work

Gibson et al., 2002 I Good A 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 79 

12. ACUTE EXACERBATION

BACKGROUND

Exacerbations are characterized by decreases in expiratory airflow that should be documented and quantified 

by simple measurement of lung function (either spirometry, if readily available, or peak expiratory flow). 

Objective measures are a more reliable indicator of the severity of an exacerbation than reported symptoms. 

In general, milder exacerbations may be managed at home without requiring an office visit, whereas 

exacerbations that are more serious may require an office visit, referral to the emergency department, or a 

hospital admission. The most severe exacerbations require admission to the intensive care unit (ICU) for 

optimal monitoring and treatment. Although assessment and treatment of young children, especially infants, 

pose unique challenges, the management of asthma exacerbations in older children and adults is fairly similar.

12.1 Indication for Immediate Triage

BACKGROUND

Patients at high risk for asthma-related death should be managed with special attention. These patients 

should be advised to seek medical attention early during acute exacerbations. In general, primary care 

providers without expertise in asthma management should not attempt to manage these patients at home or 

in the office; they should instead be referred for more intensive treatment and monitoring in an emergency 

department. In the pediatric setting, infants seen by a primary care provider should also be referred 

immediately for acute management.

ACTION STATEMENT

Patients at high risk for hospitalization or complications related to an asthma exacerbation should be referred 

to the nearest emergency department for management.

RECOMMENDATIONS

1. Patients are considered high risk for complications from an acute exacerbation in the following 

situations: [C]

a. Previous severe exacerbation (e.g., intubation or ICU admission for asthma)

b. Two or more hospitalizations or greater than three Emergency Department visits in the past 

year

c. Use of greater than two canisters of short-acting beta-agonist per month

d. Difficulty perceiving airway obstruction or the severity of worsening asthma

e. Recent use of oral glucocorticoids for exacerbation

f. Major psychosocial problems or psychiatric disease (including illicit drug use)

g. Co-morbidities such as cardiovascular disease or other chronic lung disease

h. History of non-compliance with asthma medication plan.

2. Patients in respiratory failure, or at imminent risk of respiratory failure, should be treated very 

aggressively and transported immediately to the emergency department. Treatment using 

continuous nebulized bronchodilators (albuterol or levoalbuterol) and/or systemic bronchodilators 

(subcutaneous epinephrine or terbutaline) should be initiated in the office setting pending 

transport
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Algorithms and Annotations - Page 80 

RATIONALE

o Patients with prior intubations or ICU admissions are at higher risk for repeat episodes due to poor 

perception of asthma severity or rapid decline in airway function with an exacerbation.

o Evidence suggests that near-fatal asthma is found in a higher proportion of patients with recent 

hospitalizations, increased beta-agonist use and recent glucocorticoid use.

EVIDENCE TABLE

Evidence Source LE QE SR

1 Patients with asthma at high 

risk for death or hospitalization

Abramson et al., 2001

Suissa et al., 1994

Turner et al., 1998

II Fair C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

12.2 Assessing Severity of Exacerbation

BACKGROUND

One of the essential steps in managing an acute exacerbation of asthma is to determine the severity of the 

exacerbation. There are several indicators based on history, physical examination, and objective 

measurements of lung function that may guide whether a patient can be effectively managed in a primary 

care setting or should be referred to a higher level of care. Likewise, severity may indicate how quickly a 

patient should be transferred for acute management.

ACTION STATEMENT

An overall assessment of the severity of an asthma exacerbation should guide the location (home, office or 

hospital) and rapidity of treatment.

RECOMMENDATIONS

1. The severity of acute exacerbation should be determined by assessing specific characteristics of the 

symptoms, signs, and by objective measurement of SAO2 and PaCO2 (see Table 11). 

RATIONALE

o The primary step in defining treatment options for any asthma exacerbation is to determine the severity 

of the exacerbation.

o Severity will guide the rapidity of treatment (urgent vs. non-urgent), location (home, office or acute care 

setting), and treatment options.

o Many primary care locations are not equipped to deal with a sudden worsening of an acute exacerbation 

and may not have availability of medications or monitoring capability.
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 81 

Table 11. Classification of Acute Exacerbation: Severity and Treatment

Severity of Asthma Exacerbation

Mild Moderate Severe Respiratory Arrest Imminent

SIGNS / SYMPTOMS

Activity Level: Walks briskly Walks slowly Walks with assistance Unable to walk

Feeding (infant): Normal Difficulty feeding Unable to feed Unable to suck

Talks in: Sentences Phrases Words Too dyspneic to speak; perspiring

Sounds (infant): Normal cry, cooing Short, clipped cry Faint cry, grunting

Alertness: May be agitated Usually agitated Usually agitated Drowsy or confused

Respiratory rate: Increased Increased Often > 30/min

Normal rates of breathing in awake children: 

Age Normal rate

< 2 months < 60/min 

2-12 months < 50/min 

1-5 years < 40/min 

6-8 years < 30/min 

Retractions & 

accessory muscle 

use: 

Usually not Usually Usually Paradoxical thoraco-abdominal 

movement (see-saw breathing) 

Wheeze: Moderate, often 

only end 

expiratory 

Loud expiratory Usually loud, may be 

biphasic (inspiratory 

and expiratory)

Absence of wheeze

Pulse/min. > 8 yrs: < 100 100-120 >120 Bradycardia 

Pulse/min. < 8 yrs: 

Guideline limits of normal pulse rate in children: 

Infants (2-12 months): < 160/min

Preschool (1-2 years): < 120/min

School age (2-8 years): < 110/min 

Pulsus paradoxus: Absent < 10 mm 

Hg 

May be present

10-25 mm Hg 

Often present

> 25 mm Hg (adult) 

20-40 mm Hg (child)

Absence suggests respiratory 

muscle fatigue 

TESTS

SaO2% (on room air) > 95% 91-95% < 90% 

PEF after initial 

bronchodilator 

treatment

Over 80% Approx. 60-80% < 60% predicted 

PaO2 (on room air) Normal 

Test not usually 

necessary 

> 60 mm Hg < 60 mm Hg 

Possible cyanosis

Cyanosis

PaCO2 < 45 mm Hg < 45 mm Hg > 45 mm Hg >50 mm Hg

Note: Hypercapnea (hypoventilation) develops more readily in 

young children than in adolescents and adults. 

INTERVENTION

Response to inhaled 

Short-Acting 

Bronchodilator 

(SABA)

Prompt relief Complete relief 

after multiple 

treatments

Partial relief after 

multiple treatments. 

Requires continuous 

inhaled SABA

Minimal or no relief from inhaled 

SABA. 

Requires systemic bronchodilator 

(subcutaneous epinephrine, 

terbutaline)

Location of care Home 

Management

Office or 

emergency 

department

Emergency 

department; possible 

hospitalization

Hospitalization following 

stabilization in emergency 

department

*Note: The presence of several parameters, but not necessarily all, indicates the general classification of the exacerbation.
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 82 

12.3 Non-Urgent Management of Acute Exacerbations (Home or Office)

BACKGROUND

The general principles and goals for managing asthma exacerbations (AE) defined by the 2007 NHLBI asthma 

guidelines include early treatment of exacerbations, and identification of patients who are at high risk for 

asthma-related deaths, with special attention to infants. In those patients who are not at high-risk for 

hospitalization or death, beginning treatment at home avoids treatment delays, prevents exacerbations from 

becoming severe, and adds to patients’ sense of control over their asthma. The degree of care provided in the 

home depends on the patient’s (or parents’) abilities and experience, and on the availability of emergency 

care.

ACTION STATEMENT

Patients with mild to moderate asthma and without significant risk factors may be able to manage their 

asthma exacerbation at home or during a routine office visit without requiring management in an urgent care 

or emergency department setting.

RECOMMENDATIONS

1. Early treatment of exacerbations is best; patients (or parents) should be able to recognize early 

indicators of an exacerbation to include cough and/or worsening peak expiratory flow.

2. All patients should be provided with – and instructed on how to use – a written asthma action plan 

that includes an individualized daily management plan and instructions on recognizing and handling 

worsening asthma. It should also include self-adjustment of medications in response to acute 

symptoms or changes in peak flow measures in the event of an exacerbation. 

3. Initial adjustments in medication should include an increase in frequency of SABA. [B] [For mild - 

moderate AE, up to 3 treatments within an hour (i.e., to 2-6 puffs per treatment); for severe AE, 4-8 

puffs and seek medical care.] 

4. Addition of a short course of oral systemic corticosteroids may be considered for 4-7 days following 

frequent use of SABA. [A]

5. The dose of inhaled corticosteroids should NOT be doubled [D] and patients should contact their 

healthcare provider before instituting a course of oral systemic corticosteroids.

6. Patients should be advised to withdraw from any environmental allergens or irritants that may 

contribute to the exacerbation.

7. Response to treatment should be monitored and communicated to the provider to determine if an 

office visit or referral to the emergency department is warranted.

RATIONALE

o Early treatment of asthma exacerbations by patients at home is warranted, as this is associated with a 

decrease in hospitalizations.

o In many instances, a peak flow-based plan may be useful for patients with difficulty perceiving airflow 

obstruction and who may be unable to recognize an exacerbation based on symptoms.

o Treatment of an exacerbation in which there is acute bronchoconstriction is best treated by inhaled SABA. 

Once initiated, oral steroids will treat the underlying inflammation leading to acute bronchoconstriction.

o Early treatment of acute asthma symptoms with oral steroids in children with a pattern of recurrent acute 

asthma may decrease the severity of acute asthma episodes and reduce the likelihood of subsequent 

relapses. (Rachelefsky, 2003; Rowe 2001 [Cochrane])
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 83 

o There is no role for home remedies such as increased consumption of liquids, breathing warm, moist air, 

or taking over-the-counter antihistamines or cold remedies.

o In patients who regularly take an inhaled corticosteroid, doubling daily ICS dose alone is not effective for 

the treatment of mild to moderately severe exacerbations of asthma in adults (Harrison et al., 2004; 

FitzGerald et al., 2004, Rice-McDonald et al., 2005).

EVIDENCE TABLE

Evidence Source LE QE SR

1 Administer albuterol by 

emergency teams out of 

hospital

Markenson et al., 2004

Richmond et al., 2005

IIa Fair B 

2 Initiate oral corticosteroids 

treatment

McFadden, 2003

Rachelefsky, 2003

Rowe et al., 2001 (SR)

III

I 

I 

Good A 

3 Doubling dose of ICS is NOT

sufficient

FitzGerald et al., 2004

Harrrison et al., 2004

Rice-McDonald et al., 2005

I Good D

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

12.4. Management of Exacerbation in the Emergency Department

BACKGROUND

The emergency department is the best place for managing moderate to severe asthma exacerbations and for 

patients with a high-risk past medical history. Primary care physicians should notify the closest emergency 

department and arrange for patient ACLS transport. Once in the emergency department, patients will be 

cared for according to their asthma severity. Emergency department interventions for moderate 

exacerbations may include continuous or separate albuterol nebulized treatments, nebulized anticholinergics, 

and systemic steroids. Severe exacerbations may need magnesium, subcutaneous adrenergic agents or 

possibly full airway support. The majority of patients will be sent home on a 5-day course of oral steroids and 

SABA. Following all emergency department visits, patients should be seen by their primary care physician 

within 1-2 days for outpatient evaluation and review of long-term asthma control medications.

RECOMMENDATIONS

1. A brief history and physical examination pertinent to the exacerbation should be conducted 

concurrently with the prompt initiation of therapy. 

2. The history should include: 

a. Severity and duration of symptoms, including exercise limitation and sleep disturbance

b. All current medications, including dose (and device) prescribed, dose usually taken, dose 

taken in response to the deterioration, and the patient’s response (or lack thereof) to this 

therapy

c. Time of onset and cause of the present exacerbation

d. Risk factors for asthma-related death.

3. The physical examination should assess exacerbation severity by evaluating pulse rate, respiratory 

rate, use of accessory muscles, the patient’s ability to complete a sentence, and other signs.

4. Any complicating factors should be identified (e.g., pneumonia, atelectasis, pneumothorax, or 

pneumomediastinum).
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Algorithms and Annotations - Page 84 

5. Without unduly delaying treatment, a baseline PEF or FEV1 measurement should be made before 

treatment is initiated. 

6. Subsequent measurements should be made at intervals until a clear response to treatment has 

occurred. 

7. Oxygen saturation should be closely monitored, preferably by pulse oximetry. This is especially 

useful in children because objective measurements of lung function may be difficult. Oxygen 

saturation in children should normally be greater than 95%, and oxygen saturation less than 92% is 

a good predictor of the need for hospitalization [C].

8. A chest X-ray (CXR) is not routinely required unless there are signs of infection such as fever or 

cough productive of purulent sputum. A patient presenting for the first time with signs and 

symptoms of asthma may require a CXR to rule out other causes of airway hyperreactivity. 

Additionally, if the clinician suspects secondary complications such as pneumothorax based on 

history and physical examination, a CXR should be obtained.

12.5 Follow-up in Primary Care after Discharge from Emergency Department

BACKGROUND

Most patients who fail outpatient therapy after discharge from the emergency department will return to the 

emergency department or make an unscheduled clinic visit within 72 hours. Therefore, patients should be 

evaluated by the primary care provider or asthma specialist after emergency department treatment to assess 

for clinical and subjective improvement or deterioration. 

RECOMMENDATIONS

1. Patients discharged from the emergency department should contact the primary care provider 

within 1-2 days and schedule a follow-up visit as considered appropriate by the provider. 

2. An acute exacerbation episode may indicate a lack of control of the patient's chronic asthma. A 

step-up adjustment of the patient's routine care and/or a consultation with a specialist may be 

considered.

DISCUSSION

Some data suggest that patients discharged from the emergency department do better with follow-up by a 

specialist rather a primary care physician (GINA, 2007).
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Algorithms and Annotations - Page 85 

13. EXERCISE-INDUCED BRONCHOSPASM

BACKGROUND

Exercise-induced bronchospasm (EIB), commonly referred to in the medical literature as exercise-induced 

asthma or exercise-induced bronchoconstriction, can be diagnosed in two distinct groups of patients. The first 

group consists of those patients with established asthma who, during exercise, have a component of 

bronchospasm that limits their activities. It is reported to occur in up to 80% of patients with asthma and is 

usually a self-limited process that resolves with cessation of exercise (see Section 13.1: EIB in the Patient with 

Asthma). 

There is a separate group of patients who do not have underlying asthma but may develop symptomatic 

bronchospasm with prolonged exercise. These patients are generally competitive athletes or active duty 

military who exercise on a regular basis. The evaluation of these patients always demonstrates normal resting 

spirometry but airway hyperreactivity with bronchoprovocation testing (see Section 13.2: EIB in the Athlete). 

Annotation E-1 High Suspicion of Asthma or EIB? 

13.1 EIB in the Patient with Asthma

BACKGROUND

Exercise-induced bronchospasm (EIB) should be anticipated in all asthma patients. It is frequently referred to 

as exercise-induced asthma in the medical literature. A history of cough, shortness of breath, chest pain or 

tightness, wheezing, or endurance problems during exercise suggests EIB in the patient with asthma. An 

exercise challenge (in which there is a 15 percent decrease in PEF or FEV1) can help establish the diagnosis. 

An important dimension of adequate asthma control is a patient’s ability to participate in any activity he or 

she chooses without experiencing asthma symptoms. EIB should not limit either participation or success in 

vigorous activities.

ACTION STATEMENT

Consider the diagnosis of exercise-induced bronchospasm (EIB) in the patient with asthma who has significant 

symptoms associated with exercise. Optimal treatment for such a patient may consist of an increase in longterm controller medications or prophylactic beta-agonist use prior to exercise.

RECOMMENDATIONS

1. All patients with asthma should have a regular exercise program and be asked about any limitations 

to exercise. 

2. Bronchoprovocation testing (exercise spirometry) should be considered if the patient notes 

increased symptoms suggestive of EIB during or immediately following exercise. [C]

3. Primary treatment is a warm-up period prior to exercise and pretreatment with short-acting betaagonists is recommended. [A]

4. Alternative treatments include LTRAs, which can attenuate EIB in up to 50 percent of patients. [C]

5. Cromolyn sodium or nedocromil taken shortly before exercise is an alternative treatment, but it is 

not as effective as SABAs. [C]

6. Consideration for increasing controller medications may be indicated to control or alleviate 

increased asthma symptoms during exercise. 
Clinical Practice Guideline for the Management of

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Algorithms and Annotations - Page 86 

RATIONALE

o Exercise-induced bronchospasm (EIB) can be diagnosed in up to 80% of all patients with asthma. 

o A regular exercise program is indicated in patients with asthma to avoid deconditioning and 

improved cardiovascular health. 

o Exercise spirometry is the easiest and most reliable method recommended by the ATS for 

bronchoprovocation testing. 

o Short-acting beta-agonists are the most investigated and proven method of decreasing EIB in the 

patient with asthma. SABA used shortly before exercise may be helpful for 2–3 hours. 

o Frequent or chronic use of LABA as pretreatment for EIB is discouraged, as it may disguise poorly 

controlled persistent asthma. 

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Regular exercise program NHLBI, 2007 page 38 III Poor Small I 

2 Bronchoprovocation testing Randolph, 1997 III Fair Small C 

3 Short-acting beta-agonist Pearlman et al., 2007 I Good Substantial A 

4 LTRA use Pearlman et al., 2006 I Good Mod C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A)

Annotation E-2 Consider Bronchoprovocation Testing 

13.2 EIB in the Athlete

BACKGROUND

Exercise-induced bronchospasm (EIB) in the athlete is a common pulmonary disease diagnosed primarily in 

competitive athletes at all levels. EIB may also be common in the active duty military population given the 

nature of their duties and requirements for aerobic conditioning. These patients are defined in the following 

manner: 1) symptoms (dyspnea, cough, wheezing, or chest tightness) only associated with exercise with no 

other resting or nocturnal symptoms; 2) normal resting baseline spirometry and examination; 3) nonspecific 

airway hyperreactivity with bronchoprovocation testing; and 4) response to treatment. Optimal treatment for 

these patients has not been well delineated. Treatment usually consists of prophylactic beta-agonist use prior 

to exercise. There is little indication for controller medications as the pathophysiology is strikingly different 

from asthma and resolves spontaneously after cessation of exercise. 

ACTION STATEMENT

In competitive athletes and active duty military with symptoms of exertional dyspnea and a normal baseline 

spirometry, the diagnosis of exercise-induced bronchospasm (EIB) should be actively pursued. 

RECOMMENDATIONS

1. The patient’s history should focus on the correlation of symptoms (dyspnea, wheezing, cough, or 

chest tightness) with exertion during or immediately after prolonged exercise such as running.

2. Normal baseline resting spirometry (no evidence of obstruction or restriction with a normal flow 

volume loop) should prompt referral for bronchoprovocation testing. 
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Algorithms and Annotations - Page 87 

3. The preferred method for bronchoprovocation testing is histamine and methacholine challenge 

testing or eucapneic hyperventilation as other methods are less sensitive for detecting airway 

hyperreactivity. 

RATIONALE

Exercise-induced bronchospasm is caused by osmotic drying of the airways due to a decrease of humidified air 

inhaled during exercise. It resolves rapidly with the cessation of exercise and should not cause rest or 

nocturnal symptoms.

Spirometry may be abnormal if performed immediately post-exercise, but the rapid reversal of osmotic 

changes causes no chronic inflammation or persistent changes in spirometry. 

Bronchoprovocation testing can document the predisposition to airway hyperreactivity usually present in 

these patients even when not actively exercising. 

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Prevalence of EIB Sonna et al., 2001

Wilber et al., 2000

II-2 Fair Small B 

2 Method of bronchoprovocation 

testing

Dickinson et al., 2006

Morris et al., 2002

I 

II

Good

Fair

Mod 

Mod

A 

B

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

13.3 Bronchoprovocation Testing

BACKGROUND

Bronchoprovocation testing is a useful adjunct in establishing the presence or absence of airway 

hyperreactivity in patients being evaluated for asthma or exercise-induced bronchospasm (EIB). Indications 

for testing include patients with asthma symptoms with normal spirometry who are suspected of having mild 

asthma or EIB. There are numerous methods established to include methacholine, histamine, cold air, 

eucapneic hyperventilation, and exercise challenge. The indications for using each specific type of 

bronchoprovocation test depend on the availability of equipment and clinical indication. 

ACTION STATEMENT

Bronchoprovocation testing should be considered for 1) patients with symptoms suggestive of asthma with 

normal spirometry or 2) to establish the diagnosis of exercise-induced bronchospasm in patients with asthma

who exhibit exertional symptoms. 

RECOMMENDATIONS

1. Methacholine or histamine challenge testing is indicated to establish the presence of airway 

hyperreactivity in patients with exertional symptoms (cough, wheezing, dyspnea, chest tightness) 

and normal resting spirometry. [C]

2. Exercise challenge testing is indicated to establish the diagnosis of exercise-induced bronchospasm 

(or exercise-induced asthma) in known patients with asthma who exhibit exertional symptoms. [B]

3. Eucapneic hyperventilation or cold air testing are equivalent to methacholine or histamine 

challenge testing but should be used in laboratories experienced in these techniques. [B]
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Algorithms and Annotations - Page 88 

RATIONALE

Methacholine or histamine challenge testing has been shown to be more sensitive in establishing the presence 

of nonspecific airway hyperreactivity when compared to exercise challenge testing.

A positive methacholine challenge test does not specifically establish the diagnosis of asthma (may be positive 

in allergic rhinitis, cystic fibrosis or COPD), but a negative test excludes the diagnosis of asthma.

Exercise challenge testing is the least sensitive test for airway hyperreactivity and is best utilized to establish 

EIB in known patients with asthma.

Bronchoprovocation testing should be performed and interpreted by trained individuals.

EVIDENCE STATEMENTS

o “Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge may be useful 

when asthma is suspected and spirometry is normal or near normal. For safety reasons, 

bronchoprovocation should be carried out only by a trained individual in an appropriate facility and is 

not generally recommended if the FEV1 is <65 percent predicted. A positive test is diagnostic for 

airway hyperresponsiveness, which is a characteristic feature of asthma but can also be present in 

other conditions. Thus, a positive test is consistent with asthma, but a negative test may be more 

helpful to rule out asthma.” (NHLBI 2007, page 45)

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Histamine or methacholine for EIB 

in athletes

Brown et al., 2004

Eliasson et al., 1992

II-2 

II-1

Fair

Fair

Mod 

Mod

C 

B

2 Exercise spirometry for EIB in 

patients with asthma

ATS Guidelines, 1999 III Fair Mod B 

3 Eucapneic hyperventilation Dickinson et al., 2006

Mannix et al., 1999

I 

II-1 

Good

Good

Mod 

Mod

A 

B

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 

Annotation E-3 Manage Exercise-Induced Bronchospasm (EIB)

13.4. EIB Treatment

BACKGROUND

Optimal treatment for EIB patients has not been well delineated but usually consists of prophylactic betaagonist use prior to exercise. There is little indication for controller medications as the pathophysiology is 

strikingly different from asthma and resolves spontaneously after cessation of exercise. 

ACTION STATEMENT

EIB in the athlete should be treated prior to exercise to improve exercise tolerance and decrease post-exercise 

symptoms related to airway hyperreactivity. 

RECOMMENDATIONS

1. The initial treatment regimen should consist of a warm-up period (gradual increase in exercise) and 

short-acting beta-agonist use 15-20 minutes prior to exercise. [C]
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Algorithms and Annotations - Page 89 

2. The use of LTRA or inhaled cromolyn prior to exercise may be considered. [C]

3. Lack of symptomatic improvement to inhaled beta-agonists or continued poor exercise tolerance 

should prompt referral for further evaluation by a specialist. 

RATIONALE

Exercise-induced bronchospasm (EIB) is caused by osmotic drying of the airways due to a decrease of 

humidified air inhaled during exercise. EIB can resolve rapidly with the cessation of exercise and should not 

cause rest or nocturnal symptoms.

Documentation of decreased symptoms or improved exercise tolerance with treatment is critical in 

establishing the diagnosis of EIB in the athlete. 

EVIDENCE STATEMENTS

o Commonly accepted and long-standing treatment for EIB is short-acting beta-agonist use prior to 

exercise. Beta-agonist use has been shown to decrease symptoms both during and post-exercise 

(Parsons & Mastronarde, 2005). 

o There are no studies that have specifically examined the use of LTRA or cromolyn in patients with EIB 

without underlying asthma. Studies performed in asthma patients with EIB have shown benefit in 

decreasing exercise symptoms (Pearlman et al., 2006).

EVIDENCE TABLE

Evidence Source LE QE NE SR

1 Beta-agonists prior to exercise Parsons & Mastronarde, 2005 III Fair Mod C 

2 LTRA or cromolyn use Pearlman et al., 2006 III Fair Mod C 

LE = Level of Evidence; QE = Quality of Evidence; NE = Net Effect; SR = Strength of Recommendation (See Appendix A) 
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14. MILITARY (ACTIVE DUTY)-SPECIFIC ISSUES

RECOMMENDATIONS

Evaluation for possible asthma

1. Active duty service members should be diagnosed with asthma or exercise-induced bronchospasm 

on the basis of the following criteria: 

a. Chronic symptoms of cough, dyspnea, or wheezing

b. Associated decrease in tolerance of exercise and/or running

c. Normal chest radiograph (should be obtained in all active duty patients)

d. Demonstration of persistent airway hyperreactivity

• Baseline spirometry with reversible airflow obstruction post-bronchodilator 

OR

• Reactive bronchoprovocation testing or lower dose of methacholine (preferred method 

of bronchoprovocation testing). 

See Appendix C - DoD Service-Specific Regulation Concerning Asthma

Deployment issues

2. Guidelines for deploying or redeploying service members with asthma to/from a theater of 

operations:

a. In general, service members should be able to perform all required duties, wear protective 

gear, and have stable disease not requiring frequent treatments or oral corticosteroids

b. Failure to meet these criteria should prompt consideration for redeployment

c. See Appendix C – DoD Service-Specific Regulation Concerning Asthma

d. Army; AR 40-501, Section 5–14. Medical fitness standards for deployment and certain 

geographical areas:

“Asthma. See paragraph 3–27a for profile guidance and for MEB/PEB processing criteria. If it 

is determined that the Soldier can be returned to duty, the Soldier should not deploy if 

he/she cannot wear protective gear, has experienced recent emergency room visits, or 

requires repetitive use of oral corticosteroids.”

e. Navy, Air Force, Coast Guard – No specific regulatory guidance.
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APPENDICES

Appendix A 

Guideline Development Process

The development update of the VA/DoD Clinical Practice Guideline for Management of Asthma in Primary 

Care followed the steps described in “Guideline for Guidelines,” an internal working document of the 

VA/DoD Evidence-Based Practice Working Group, that requires an ongoing review of the work in progress. 

The Asthma Working Group of the VA/DoD was charged to update the evidence-based recommendations. 

The Offices of Quality and Performance and Patient Care Services, in collaboration with the network 

Clinical Managers, the Deputy Assistant Under Secretary for Health, and the Medical Command of the 

DoD identified clinical leaders to champion the guideline development process. During a preplanning 

conference call, the clinical leaders defined the scope of the guideline and identified a group of clinical 

experts from the VA and DoD that formed the Management of Asthma Working Group. Working Group 

members included representatives of the following specialties: Family Practice, Pulmonology, Nursing, 

Emergency Medicine, Internal Medicine, Pediatrics, Allergy Medicine, Respiratory therapy, Pharmacology, 

and Nutrition.

The Working Group defined a set of clinical questions within the area of the guideline. This ensured that 

the guideline development work focused on issues that practitioners considered important, and

generated criteria for conducting a systematic review of the literature.

The Working Group participated in an initial face-to-face meeting to reach consensus about the guideline 

algorithms and recommendations, and to prepare a draft update document. The draft continued to be 

revised by the Working Group at-large through numerous conference calls and individual contributions to 

the document. Following the initial effort, an editorial panel of the Working Group convened to further 

edit the draft document. Recommendations for inclusion of specific procedures or services were derived 

through a rigorous methodological approach that included the following: 

• Determining appropriate criteria, such as effectiveness, efficacy, population benefit, or 

patient satisfaction

• Reviewing the literature to determine the strength of the evidence in relation to these 

criteria

• Formulating the recommendations and grading the level of evidence supporting the 

recommendation

• Reviewing of the final draft by independent experts and incorporating their feedback into 

the final document. 

This update of the Asthma Guideline is the product of many months of diligent effort and consensus 

building among knowledgeable individuals from the VA, DoD, and academia. An experienced moderator 

facilitated the multidisciplinary Working Group. The list of participants is included in Appendix H.
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Formulation of Questions

Literature searches were conducted on all topics identified in the algorithm or recommendations of the 

original guidelines. After reviewing the results of the initial search for systematic reviews and metaanalyses, the Working Group decided to focus the search for individual randomized controlled trials 

(RCTs) on specific interventions. The Working Group developed researchable questions and associated 

key terms for these interventions. The questions specified (adapted from the Evidence-Based Medicine 

toolbox, Center for Evidence-Based Medicine, [http://www.cebm.net]):

• Population – Characteristics of the target patient population 

• Intervention – Exposure, diagnostic, prognostic, or therapeutic interventions 

• Comparison – Intervention, exposure, or control used for comparison 

• Outcome – Outcomes of interest

These specifications served as the preliminary criteria for selecting studies. 

(For list of questions, see Appendix F.) 

Selection of Evidence

The evidence selection was designed to identify the best available evidence to address each key question 

and ensure maximum coverage of studies at the top of the hierarchy of study types. Published, peerreviewed RCTs, as well as meta-analyses and systematic reviews that included randomized controlled 

studies were considered to constitute the strongest level of evidence in support of guideline

recommendations. This decision was based on the judgment that RCTs provide the clearest, scientifically 

sound basis for judging comparative efficacy. The Working Group made this decision recognizing the 

limitations of RCTs, particularly considerations of generalizability with respect to patient selection and 

treatment quality. When available, the search sought out critical appraisals already performed by others 

that described explicit criteria for deciding what evidence was selected and how it was determined to be 

valid. The sources that have already undergone rigorous critical appraisal include Cochrane Reviews, Best 

Evidence, Technology Assessment, and AHRQ systematic evidence reports.

In addition to Medline/PubMed, the following databases were searched: Database of Abstracts of 

Reviews of Effectiveness (DARE) and Cochrane Central Register of Controlled Trials. For Medline/PubMed 

searches, limits were set for language (English), and type of research (RCT, systematic reviews and metaanalysis).

As a result of the literature reviews, articles were identified for possible inclusion. These articles formed 

the basis for formulating the guideline recommendations. The following inclusion criteria were used for 

studies: 

• English-language only of studies performed in United States, United Kingdom, Europe, 

Australia, Japan, New Zealand

• Full articles only

• Randomized controlled trials or prospective studies

• Published from 2004 to February 2008

Admissible evidence (study design and other criteria):

• Original research studies that provide sufficient detail regarding methods and results to 

enable use and adjustment of the data and results.

• Randomized controlled trials (RCTs), systematic reviews (including EPC and HTA reviews), 

and meta-analyses.

• Relevant outcomes must be able to be abstracted from data presented in the articles. 
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• Sample sizes must be appropriate for the study question addressed in the paper. RCTs will 

be included if they are initiated with 30 or more participants.

Preparation of Evidence Tables (Reports) and Evidence Rating

The results of the search were organized and evidence reports as well as copies of the original studies 

were provided to the Working Group for further analysis. Each study was appraised by a group of 

research analysts for scientific merit, clinical relevance, and applicability to the populations served by the 

federal healthcare system. The body of evidence was rated for quality and level of evidence. 

Recommendation and Overall Quality Rating

Evidence-based practice involves integrating clinical expertise with the best available clinical evidence 

derived from systematic research. The Working Group received an orientation and tutorial on the 

evidence USPSTF 2001 rating process, reviewed the evidence and independently formulated Quality of 

Evidence ratings (see Table A-1), a rating of Overall Quality (see Table A-2), and a Strength of 

Recommendation (see Table A-3). 

Table A-1: Quality of Evidence (QE)

I At least one properly done RCT

II-1 Well-designed controlled trial without randomization

II-2 Well-designed cohort or case-control analytic study, preferably from more than one source

II-3 Multiple time series evidence with/without intervention, dramatic results of uncontrolled experiment

III Opinion of respected authorities, descriptive studies, case reports, and expert committees

Table A-2: Overall Quality 

Good High-grade evidence (I or II-1) directly linked to health outcome. 

Fair

High-grade evidence (I or II-1) linked to intermediate outcome;

or

Moderate-grade evidence (II-2 or II-3) directly linked to health outcome. 

Poor Level III evidence or no linkage of evidence to health outcome. 

Table A-3: Net Effect of the Intervention 

Substantia

l 

More than a small relative impact on a frequent condition with a substantial burden of suffering; 

or

A large impact on an infrequent condition with a significant impact on the individual patient level.

Moderate

A small relative impact on a frequent condition with a substantial burden of suffering; 

or

A moderate impact on an infrequent condition with a significant impact on the individual patient 

level.

Small

A negligible relative impact on a frequent condition with a substantial burden of suffering; 

or

A small impact on an infrequent condition with a significant impact on the individual patient level.

Zero or 

Negative

Negative impact on patients; 

or

No relative impact on either a frequent condition with a substantial burden of suffering, or an 

infrequent condition with a significant impact on the individual patient level.
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Table A-4: Final Grade of Recommendation 

The net benefit of the intervention

Quality of 

Evidence Substantial Moderate Small Zero or 

Negative

Good A B C D 

Fair B B C D 

Poor I I I I 

Strength of Recommendations Rating System

A A strong recommendation that the clinicians provide the intervention to eligible 

patients. 

Good evidence was found that the intervention improves important health outcomes 

and concludes that benefits substantially outweigh harm. 

B A recommendation that clinicians provide (the service) to eligible patients.

At least fair evidence was found that the intervention improves health outcomes and 

concludes that benefits outweigh harm.

C No recommendation for or against the routine provision of the intervention is made.

At least fair evidence was found that the intervention can improve health outcomes, 

but concludes that the balance of benefits and harms is too close to justify a general 

recommendation.

D Recommendation is made against routinely providing the intervention to patients.

At least fair evidence was found that the intervention is ineffective or that harms 

outweigh benefits.

I The conclusion is that the evidence is insufficient to recommend for or against 

routinely providing the intervention.

Evidence that the intervention is effective is lacking, or poor quality, or conflicting, 

and the balance of benefits and harms cannot be determined.

Lack of Evidence – Consensus of Experts

Where existing literature was ambiguous or conflicting, or where scientific data was lacking on an issue, 

recommendations were based on the clinical experience of the Working Group.

Algorithm Format

The goal in developing the guideline for management of Asthma was to incorporate the information into a 

format that would maximally facilitate clinical decision-making. The use of the algorithmic format was 

chosen because of the evidence that such a format improves data collection, diagnostic and therapeutic 

decision-making and changes patterns of resource use. However, few guidelines are published in such a 

format. 

The algorithmic format allows the provider to follow a linear approach to critical information needed at 

the major decision points in the clinical process, and includes:

• An ordered sequence of steps of care 

• Recommended observations 
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• Decisions to be considered 

• Actions to be taken

A clinical algorithm diagrams a guideline into a step-by-step decision tree. Standardized symbols are used 

to display each step in the algorithm (Society for Medical Decision-Making Committee, 1992). Arrows 

connect the numbered boxes indicating the order in which the steps should be followed.

Rounded rectangles represent a clinical state or condition.

Hexagons represent a decision point in the guideline, formulated 

as a question that can be answered Yes or No. A horizontal arrow 

points to the next step if the answer is Yes. A vertical arrow 

continues to the next step for a negative answer.

Rectangles represent an action in the process of care.

Ovals represent a link to another section within the guideline.

A letter within a box of an algorithm refers the reader to the corresponding annotation. The annotations 

elaborate on the recommendations and statements that are found within each box of the algorithm. 

Included in the annotations are brief discussions that provide the underlying rationale and specific 

evidence tables. Annotations indicate whether each recommendation is based on scientific data or expert 

opinion. A complete bibliography is included in the guideline.

REFERENCES

Agency for Health Care Policy and Research (AHCPR). Manual for conduction systematic review. Draft. 

August 1996. Prepared by Steven H. Woolf.

Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, Atkins D; Methods Work Group, 

Third U.S. Preventive Services Task Force Current methods of the U.S. Preventive Services Task 

Force: a review of the process. Am J Prev Med 2001 Apr;20(3 Suppl):21-35.

Society for Medical Decision-Making Committee (SMDMC). Proposal for clinical algorithm standards, 

SMDMC on Standardization of Clinical Algorithms. Med Decis Making 1992 Apr-Jun;12(2):149-54.

United States Preventive Service Task Force (USPSTF). Guide to clinical preventive services. 2nd edition. 

Washington, DC: U.S. Department of Health and Human Services, Office of Disease Prevention and 

Health Promotion, 1996.

Woolf SH. Practice guidelines, a new reality in medicine II. Methods of developing guidelines. Arch 

Intern Med 1992 May;152(5):946-52.
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Appendix B-1 

Details of a Comprehensive History

1. The history should focus on the characterization of symptoms related to airway obstruction or airway 

hyperresponsiveness: 

• Cough

• Wheezing

• Shortness of breath

• Chest tightness

• Sputum production.

2. The pattern of symptoms should be characterized: 

• Onset

• Duration

• Frequency

• Diurnal variation

• Seasonality. 

3. Precipitating and aggravating factors should be explored:

• Viral infections 

• Exercise

• Environmental indoor allergens: 

 Mold

 House dust mites 

 Cockroaches

 Pets

 Rodents 

• Environmental outdoor allergens: 

 Pollens

 Molds

• Secondary tobacco exposure

• Occupational chemicals, irritants, or allergens

• Irritants: 

 Strong odors

 Air pollution

 Chemicals

 Dusts/particulates

 Vapors, gases, and aerosols

• Emotions and/or stress

• Drugs (i.e., aspirin, NSAIDs) 

• Sulfites in food

• Cold air

• Characteristics of the home and/or office: 

 Carpeting

 Wood burning stoves

 Chemicals

• Co-morbid conditions (sinusitis, rhinitis, GERD). 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 97 

4. The development of disease and prior symptoms, diagnosis and treatment should be explored:

• Age of onset and/or diagnosis

• Early life airway injury such as BPD or pneumonia

• Present or recent management

 Frequency of SABA use and response 

 Requirement for oral steroids, frequency, and response. 

5. Family history: 

• Asthma

• Allergy

• Rhinitis

• Sinusitis

• Nasal polyps

• Eczema. 

6. Social history: 

• Daycare, workplace, school characteristics

• Social factors interfering with adherence such as substance abuse

• Social support networks

• Level of education

• Employment. 

7. History of prior exacerbations:

• Prodrome

• Rapidity of onset 

• Duration

• Frequency 

• Severity (hospitalizations, ICU admissions, intubations) 

• Life-threatening exacerbations (intubation, ICU)

• Number and severity of exacerbations in last 12 months 

• Usual pattern and management. 

8. Impact of the disease on the patient and family: 

• Unscheduled care (Emergency Deparment, urgent care, hospitalization)

• Missed school days 

• Limitations in activity including work, sports, and play

• Nocturnal awakenings 

• Effect on growth, development, behavior

• Economic impact.

9. The history should include an assessment of the patient’s and family’s perceptions of disease:

• Patient’s, parent’s, spouse’s, partner’s knowledge of and belief in disease and treatment

• Ability of patient and family/support system to cope with disease

• Level of support

• Economic resources

• Sociocultural beliefs. 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 98 

Appendix B-2 

Details of a Comprehensive Physical Exam

Physical examination of the upper respiratory tract, neck, chest, heart and skin may support the diagnosis 

of asthma. However, the absence of supportive findings does not exclude the diagnosis of asthma. 

(*) May suggest an alternative diagnosis or co-morbid condition.

1. Vital signs Hypertension*

Increased Body Mass Index* 

2. Eyes Erythema of the conjunctive

3. Nasopharynx Increased nasal secretions

Mucosal swelling

Nasal polyps

4. Oropharynx Enlarged tonsils*

Cobblestoning of the posterior pharynx

Evidence of upper airway obstruction*

5. Ears Evidence of otitis media in children

6. Neck Adenopathy or mass*

Increased intravenous pyelogram (IVP)* 

Stridor*

7. Chest Wheezing at rest

Prolonged phase of forced exhalation

Hyperexpansion of the thorax

Use of accessory muscles

Chest deformity

Crackles*

Dullness to percussion* 

8. Heart Rate

Rhythm

Presence of murmurs 

Presence of gallops

9. Abdomen Organomegaly* 

10. Skin Presence of atopic dermatitis 

11. Extremities Edema*

Clubbing*

Pulses* 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 99 

Physical Findings in Review of Systems

Physical Findings Asthma Co-morbid Conditions Alternative diagnosis

Eyes Conjunctivitis

Ears Otitis media 

Oropharynx Normal Cobblestoning Evidence of upper airway 

obstruction 

Neck Normal Mass, stridor increased JVP

Chest Wheeze, prolonged 

expiration 

Crackles, dullness to percussion 

Heart Normal Murmurs or gallops

Abdomen Organomegaly mass or bruit 

Skin Atopic dermatitis

Extremities Edema, clubbing
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 100 

Appendix C

DoD Service-Specific Regulation Concerning Asthma 

PPG-TAB A: AMPLIFICATION OF THE MINIMAL STANDARDS OF FITNESS FOR DEPLOYMENT TO THE CENTCOM AOR; 

TO ACCOMPANY MOD 7 TO USCINCCENT INDIVIDUAL PROTECTION AND INDIVIDUAL/UNIT DEPLOYMENT POLICY

1. General. This tab accompanies MOD 7 Para 15.g., and provides amplification of the minimal standards of fitness 

for deployment to the CENTCOM AOR, including a list of medical conditions that should usually be sufficient basis 

to deny medical clearance for or to disapprove deployment of a civilian employee, volunteer, or contractor’s 

employee. The list of conditions is not comprehensive; there are many more conditions that could be cause to 

deny medical clearance for deployment. Possession of one or more of the conditions listed in this chapter does not 

automatically mean that the individual may not deploy. Rather, it imposes the requirement to obtain a 

knowledgeable physician’s opinion as to the deployable status of the individual. “Medical conditions” as used here 

also includes those health conditions usually referred to as dental, oral, psychological and/or emotional conditions. 

(Uniformed service members will be evaluated for fitness according to service regulations and policies, in addition 

to the guidance in the parent PPG Modification (MOD). The services’ parent regulations are as follows. 

• Army: AR 40-501, Standards of Medical Fitness, February 2004; 

• Air Force: AFI 48-123, 22 MAY 2001, Medical Examinations And Standards; 

• Navy: NAVMED P-117, The Manual of the Medical Department; 

• Marine Corps: NAVMED P-117, article 15-5; 

• Coast Guard: Medical Manual, COMDTINST M6000.1B)

Deployment Issues

Documented medical conditions usually precluding medical clearance. While a list of all possible diagnoses and 

their severity that should not be approved would be too expansive to list here, the following conditions, in general, 

should usually not be approved. The medical evaluator must carefully consider whether there is any question 

whether the climate, the altitude, the nature of available food and housing, the availability of medical, behavioral 

health, dental, and surgical services, or whether other environmental and operational factors may be hazardous to

the deploying person’s health because of a known physical condition. 

Usually, medical clearance to deploy for persons with any of the following documented medical conditions should 

be granted only after consultation with theater medical authority. The theater medical authority can determine if 

adequate treatment facilities and specialist support is available at the duty station.

A. Conditions resulting in inability to wear personal protective equipment, including protective mask, ballistic 

helmet, body armor, and chemical/biological protective garments, regardless of the nature of the condition that 

causes the inability.

Service-specific regulations regarding medical standards of fitness for asthma or other deployment issues are 

available on the asthma CPG homepage under resource material at: 

https://www.qmo.amedd.army.mil/asthma/Asthfr.htm 

 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 101 

Appendix D 

Medication Tables

Table D1: Drugs Used in Treatment of Asthma

Drug Class§ Uses Cautions and Monitoring‡ 

Inhaled Corticosteroids

(ICS) 

Beclomethasone 

Budesonide 

Ciclesonide

Flunisolide* 

Fluticasone 

Mometasone 

Triamcinolone* 

(See Table D2 for Dosage)

*CFC MDIs are being phased 

out and will no longer be 

available in the near future

Considered first 

line agents for 

maintenance 

treatment of 

asthma

• Local adverse effects include oral candidiasis, dysphonia, and 

reflex cough/bronchospasm

o Use of a spacer or holding chamber (for non-breath activated 

inhalers) and rinsing mouth after inhalation can reduce the 

incidence of oral candidiasis

o Use of a spacer or holding chamber (for non-breath activated 

inhalers) is used as a measure to prevent dysphonia. To treat 

dysphonia, temporarily reducing the dose of ICS, or rest for 

vocal stress has been used

o Use of a spacer or holding chamber (for non-breath activated 

inhalers), slower inspiration, or pretreatment with a SABA 

may be tried for reflex cough/bronchospasm

• Higher doses have been associated with adrenal suppression, 

glaucoma, cataracts, skin thinning, and bruising

• High dose may increase the risk of developing osteoporosis

• Smoking may decrease the effectiveness of ICS; regardless, 

patients with asthma should be encouraged to stop smoking

Short-acting Betaagonists (SABA)

Albuterol

Levalbuterol

Pirbuterol

Long-acting Betaagonists (LABA)

Formoterol 

Salmeterol

Note: Formoterol and 

arformoterol are available in a 

nebulizer solution approved for 

maintenance therapy for COPD; 

at present, they are not 

approved for use in asthma.

Short-acting 

agents are used 

for acute relief of 

bronchospasm 

and prevention 

of exerciseinduced 

bronchospasm

Long-acting 

agents are used 

as the preferred 

add-on agents 

to inhaled 

corticosteroid

• May cause palpitations, chest pain, rapid heart rate, increased 

blood pressure, tremor, nervousness

• Decreases in potassium levels or hyperglycemia have occurred

• Frequent use of SABA (>2 days/week) may indicate uncontrolled 

asthma and the need to intensify maintenance drug therapy

• 2 to 6 puffs of SABA may be used in accordance with the asthma 

action plan. Patients who do not experience relief after 3 doses in 

a one hour period OR who need a dose more frequently than 

every 4 hours should seek medical care

• Long-acting beta-agonists are CONTRAINDICATED AS 

MONOTHERAPY for maintenance treatment of asthma. If a longacting beta-agonist is used, an inhaled steroid must also be 

prescribed and used by the patient on a daily basis.

• Long-acting beta-2 agonist are not to be used for the acute 

treatment of bronchospasm

• Formoterol: Capsules are for oral inhalation only (capsules should 

not be swallowed). Administer using supplied inhalation device 

(Aerolizer) only
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 102 

Drug Class§ Uses Cautions and Monitoring‡ 

Combination ICS/LABA

Budesonide/formoterol

Fluticasone/salmeterol

• See comments for inhaled corticosteroids and beta-agonists

Leukotriene Modifiers

Montelukast

Zafirlukast

Zileuton extended-release

Monotherapy 

may be 

considered as an 

alternative (not 

preferred) to ICS 

for mild 

persistent 

asthma

May be used as 

an alternative 

(not preferred) 

to a LABA for add 

on therapy to ICS

Montelukast may 

be used for 

prevention of 

exercise-induced 

bronchospasm 

(zafirlukast and 

zileuton are not 

FDA approved)

• Rare cases of Churg-Strauss have occurred with montelukast and 

zafirlukast; however, the association is unclear

• Zafirlukast should be taken at least 1 hour before or 2 hours after 

meals due to decreased bioavailability when taken with meals. 

• Zafirlukast and zileuton can inhibit the metabolism of warfarin. 

INRs should be monitored during co-administration

• Zileuton can inhibit the metabolism of theophylline; therefore, 

monitoring of theophylline levels is recommended

• Zileuton is contraindicated in patients with active liver disease or 

persistent hepatic function enzyme elevation (> 3x ULN)

• Assess hepatic function enzymes prior to initiation of zileuton, 

monthly for the first 3 months, every 2-3 months for the 

remainder of the first year, and periodically thereafter

• Postmarketing surveillance of zafirlukast has reported cases of 

reversible hepatitis and, rarely, irreversible hepatic failure 

resulting in death and liver transplantation Consider periodic 

hepatic enzymes (ALT) monitoring

• Patients and providers should be aware of the potential for 

neuropsychiatric events (e.g., suicidal ideation, depression, 

agitation, aggression, anxiousness, irritability, restlessness, dream 

abnormalities, hallucinations, and insomnia) with these 

medications. Patients should be told to contact their healthcare 

provider if these events occur. Consider discontinuing these 

medications if patients develop neuropsychiatric symptoms

Mast cell stabilizer

Cromolyn Nebulizer solution 

Note: Cromolyn is no longer 

available as a MDI

Monotherapy 

may be 

considered as an 

alternative (not 

preferred) to ICS 

for mild 

persistent 

asthma. 

May be used for 

prevention of 

exercise-induced 

bronchospasm; 

however, 

generally not as 

effective as SABA 

• Generally well tolerated although may cause coughing and 

wheezing

• Improvement can occur in 1-2 weeks; however, maximal benefit 

may not be seen for 4-6 weeks

• Needs to be dosed four times daily (may be reduced to three 

times daily once symptoms have stabilized)

• Cromolyn is no longer available as a MDI; therefore, limiting the 

usefulness of this agent
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 103 

Drug Class§ Uses Cautions and Monitoring‡ 

Methylxanthines

Theophylline 

Aminophylline

May be 

considered as an 

alternative for 

maintenance of 

mild persistent 

asthma when 

other preferred 

options have not 

been successful

May be 

considered as an 

adjunctive 

therapy with ICS 

for maintenance 

of moderate or 

persistent 

asthma.

• Monitor theophylline levels. The usual therapeutic range is 5-

15mcg/mL but some toxicity may be noted at the upper end of 

this range

• Adverse reactions include stomach upset, nausea, insomnia, 

tremors, palpitations, and irritability which may be lessened by 

initiating the dose low and increasing gradually

• Serious adverse events including cardiac arrhythmias and seizures 

can occur at higher concentrations

• Instruct patient not to take extra doses of theophylline for acute 

asthma attack

• Sustained-release products should not be crushed or chewed.

• Scored tablets may be split without affecting absorption 

characteristics

• Several drugs or other factors can influence theophylline 

concentration (list not intended to be inclusive of all interactions)

o Drugs or factors decreasing theophylline clearance: 

cimetidine, ciprofloxacin, clarithromycin, disulfiram, 

enoxacin, erythromycin, mexiletine, pentoxifylline, 

propranolol, ticlopidine, troleandomycin, zileuton, 

allopurinol (≥ 600 mg/day), fluvoxamine, interferon, 

propafenone, tacrine, verapamil, congestive heart 

failure, cor pulmonale, elderly (> 60 yrs.), hepatic 

insufficiency (cirrhosis, acute hepatitis, cholestasis), 

fever (> 24 hrs.)

o Drugs or factors increasing theophylline clearance: 

charcoal-broiled food; low carbohydrate, high protein 

diet; smoking (tobacco or marijuana); phenobarbital; 

phenytoin; rifampin, carbamazepine; isoniazid; 

moricizine

Immunomodulators anti-IgE

Omalizumab

Used as 

adjunctive 

therapy for 

severe persistent 

asthma (Step 5 

or 6) who have a 

positive skin test 

or in vitro

reactivity to a 

perennial 

aeroallergen 

• Not to be used in patients who have had a prior allergic reaction 

to omalizumab

• Patient should have pre-treatment serum IgE 30-700IU/ml and 

positive skin test or in vitro reactivity to common aeroallergen 

(e.g., dust mites, pet dander, cockroach)

• Give patient the omalizumab Medication Guide and instruct them 

to read it before each dose of omalizumab

• Educate patient on signs and symptoms of severe hypersensitivity 

and anaphylaxis

• Patients should carry and know how to initiate emergency selftreatment for anaphylaxis

• Observe patients for an appropriate amount of time after each 

injection. In clinical trials, patients were observed for 2 hours 

after the 1st dose and 1 hour for subsequent doses.

• Healthcare professionals should be prepared to manage lifethreatening anaphylaxis

• If a severe hypersensitivity reaction occurs, omalizumab should be 

discontinued

§ Refer to product package insert or other established resources for dosing recommendations and age specific use

‡ Table is not intended to be inclusive of all cautions and monitoring, but rather to highlight some of the major 

points
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 104 

Table D2: Inhaled Steroids a,b 

PC = Pregnancy Category

a Comparative daily doses adapted from the Global Initiative for Asthma 2007 and NHLBI Guidelines for the Diagnosis and 

Management of Asthma (EPR-3). b For dosing recommendations, refer to the manufacturer’s product package insert. c Doses for budesonide suspension shown in mg.

d Dose of mometasone for children is 110mcg once daily. e CFC MDIs are being phased out and will no longer be available in the near future. 

Inhaled steroid (dose/puff) Dosage 

forms

Usual dosing 

interval

Low dose

mcg/day c

Medium dose 

mcg/day c

High dose

mcg/day c

PC

Beclomethasone 

40mcg 

80mcg 

MDI (HFA) 12h >12 yrs 80-240 

5-11yrs 80-160 

>12 yrs >240-480 

5-11 yrs >160-320 

>12 yrs >480 

5-11yrs >320 

C 

Budesonide 

200mcg (delivered dose 160mcg)

90mcg (delivered dose 80mcg)

180mcg (delivered dose 160mcg)

Budesonide suspension

0.25, 0.5, 1mg/2mL ampule

Must use with PARI nebulizer or 

other high-efficiency nebulizer

DPI

Nebulizer

12h 

24h or 12h

>12 yrs 200-600 

5-11 yrs 180-400 

5-11 yrs 0.5 

0-4 yrs 0.25-0.5 

>12 yrs >600-1200 

5-11 yrs >400-800 

5-11 yrs 1.0 

0-4 yrs >0.5-1.0 

>12 yrs >1200 

5-11 yrs >800 

5-11 yrs 2.0 

0-4 yrs >1.0

B 

Ciclesonide

80mcg 

160mcg 

MDI (HFA) 24h >12 yrs 80-160 >12 yrs >160-320 >12 yrs >320-

1280 C 

Flunisolide e

250mcg MDI (CFC) 12h >12 yrs 500-1000 

5-11 yrs 500-750 

>12 yrs >1000-2000 

5-11 yrs >750-1250 

>12 yrs >2000 

5-11 yrs 

>1250 C 

Fluticasone (MDI/DPI)

44mcg /50mcg

110mcg /100mcg

220mcg/250mcg 

MDI (HFA)

DPI 12h >12 yrs 88-264 0-11 yrs 88-176 

>12 yrs >264-440 

0-11 yrs >176-352 

>12 yrs >440 

0-11 yrs >352 

C 

Mometasone 

220mcg (delivered dose 200mcg)

110mcg (delivered dose 110mcg)d

DPI 24h or 12h >12 yrs 200 >12 yrs 400 >12 yrs >400 C 

Triamcinolone e

100mcg (delivered dose 75mcg) 

MDI with 

built-in spacer 

(CFC) 

6-8h or 12h >12 yrs 300-750 

5-11 yrs 300-600 

>12 yrs >750-1500 

5-11 yrs >600-900 

>12 yrs >1500 

5-11 yrs >900 C 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 105 

 

Appendix E

Environmental Control

House Dust Mite Allergen

The EPR-3 Panel recommends the following mite-control measures. Effective allergen avoidance requires a 

multifaceted approach:

 Recommended actions to control mites include:

 Encase the mattress in an allergen-impermeable cover.

 Encase the pillow in an allergen-impermeable cover or wash it weekly.

 Wash the sheets and blankets on the patient’s bed weekly in hot water.

 A temperature of >130 °F is necessary for killing house dust mites. Prolonged exposure to dry heat or 

freezing temperatures can also kill mites but does not remove allergen. If high-temperature water is not 

available, a considerable reduction in live mites and mite allergens can still be achieved with cooler water 

using detergent and bleach.

 Actions to consider to control mites include:

 Reduce indoor humidity to 60 percent or below, ideally between 30 and 50 percent.

 Remove carpets from the bedroom.

 Avoid sleeping or lying on upholstered furniture.

 Remove from the home carpets that are laid on concrete.

 In children’s beds, minimize the number of stuffed toys, and wash them weekly.

Animal Allergens

The EPR-3 Panel recommends the following actions to control animal antigens:

 If the patient is sensitive to an animal, the treatment of choice is removal of the exposure from the home.

 If removal of the animal is not acceptable:

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

 Keep the patient’s bedroom door closed.

 Remove upholstered furniture and carpets from the home, or isolate the pet from these items to the 

extent possible.

 Mouse allergen exposure can be reduced by a combination of blocking access, low-toxicity pesticides, 

traps, and vacuuming and cleaning.

Cockroach Allergen

The EPR-3 Panel recommends that cockroach control measures be instituted if the patient is sensitive to 

cockroaches and infestation is present in the home:

 Patients should not leave food or garbage exposed. 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 106 

 Poison baits, boric acid, and traps are preferred to other chemical agents, because the latter can be irritating 

when inhaled by persons who have asthma.

 If volatile chemical agents are used, the home should be well-ventilated, and the person who has asthma 

should not return to the home until the odor has dissipated.

 Care should be taken so that young children do not have access to cockroach baits and poisons.

Indoor Fungi (Molds)

The EPR-3 Panel recommends consideration of measures to control indoor mold: 

 Measures to control dampness or fungal growth in the home may be beneficial.

Outdoor Allergens (Tree, Grass, and Weed Pollen; Seasonal Mold Spores)

The EPR-3 Panel recommends that measures be taken to reduce exposure to outdoor allergens if the patient is 

sensitive to outdoor allergens and has symptoms that correlate with exposure: 

 Patients who are sensitive to seasonal outdoor allergens should consider staying indoors, if possible, during 

peak pollen times—particularly midday and afternoon.

 Patients can reduce exposure during peak pollen season by staying indoors with windows closed in an airconditioned environment, particularly during the midday and afternoon when pollen and some spore counts 

are highest.

 Conducting outdoor activities shortly after sunrise will result in less exposure to pollen.

 These actions may not be realistic for some patients, especially children.
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 107 

Appendix F 

Questions for Literature Search 

KEY: A & P – adults and pediatrics; A – adults only; P – pediatrics only

DIAGNOSIS

1. In patients with asthma, does consultation or referral to a subspecialist (pulmonologist/allergist) at the time of 

diagnosis, when admitted to the emergency department with exacerbation or early in treatment vs. no 

consultation/referral improve symptom control, patient satisfaction and increased patient knowledge? [A & P]

2. In patients with asthma, does routine allergy testing (e.g., skin prick testing, aeroallergens, immunotherapy) vs. no 

testing or testing HIGH RISK (severe uncontrolled asthma, family history of allergies) improve outcomes in terms of 

QOL through allergen avoidance or immunotherapy, patient knowledge and adherence? [A & P]

3. In adults with exercise-related symptoms of asthma only and non-diagnostic spirometry, is formal exercise testing 

with pre- and post-PFTs compared to informal exercise testing (methacholine challenge test, bronchoprovocation 

test) better for establishing the diagnosis of EIB or exercise-induced asthma? [A]

4. Does the routine use of office-based spirometry compared to history and physical for both asthma diagnosis and 

monitoring improve outcomes? [P]

5. In adults with exercise-related asthma, is peak flow monitoring to assess variability of airway obstruction 

compared to spirometry a comparable way for diagnosing EIB or exercise-induced asthma? [A]

6. Do biomarkers of inflammation (e.g., total and differential cell count and mediator assays) in sputum, blood, 

urine, and exhaled air aid in the diagnosis and assessment of asthma in the primary care setting? [A & P]

7. Is a thorough history and physical, followed by a therapeutic challenge sufficient to identify co-morbid GERD

compared to a diagnostic test in children with asthma? [P]

8. In pregnant women who were not previously diagnosed with asthma, but who develop symptoms consistent with 

asthma, does assessing PFT compared to a presumptive diagnosis (no PFT) improve patient outcome with no 

harm? [A]

PROGNOSIS

9. In adults with asthma who present with an acute exacerbation, what clinical predictors are best at predicting 

successful outpatient management? [A]

10. In patients with difficult-to-control asthma (adults & children), how frequently does the management of coexisting sinusitis or GERD compared to no management improve the control of asthma? [A & P]

11. In patients with asthma who are obese, does weight loss and exercise compared to no weight loss/exercise 

improve the control of asthma symptoms? [A & P]

MEDICATIONS

12. In children with under-controlled asthma on low-dose ICS, what is the best step-up treatment / add-on therapy to 

gain asthma control (search in age groups 1-5, 5-12, 12-17)? [P] 

13. In active duty personnel with asthma in operational environments, is one controller compared to other controllers 

better apt to control asthma symptoms? [A]

14. In patients with mild persistent asthma and no evidence of allergies as triggers (adults & children), does ICS

compared to Montelukast or Tilade, Intal, or other pulmonary anti-inflammatories lead to better outcome and 

minimize harm? [9] 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 108 

15. In patients with moderate or severe uncontrolled asthma who are taking ICS (adults & children), does increasing 

the dose of ICS compared to adjunctive therapy (LABA, Singulair, Leukotriene) lead to better control of symptoms 

with no harm? [A]

16. In adult patients with asthma, does tiotropium (Spiriva) compared to long-acting inhaled bronchodilators lead to 

comparable improvement in PFT, peak flow measures, and safety? [A]

17. In patients with exercise-induced asthma (bronchospasm) (adults & children), does taking a preventive medication

before exercise compared to continuous daily medication improve symptom control? [A&P]

18. In patients over age 65 with asthma, does the use of long-acting beta adrenergic drugs compared to not using the 

drug reduce adverse cardiovascular events (e.g., sudden death, acute MI, arrhythmias)? [A >65]

19. In patients over age 65 who require long-term systemic corticosteroids, does a reduced dose of corticosteroids

compared to the regular dose reduce the risk for adverse complications (osteoporosis, DM, Vavascular necrosis of 

the femoral head, cataracts)? [A >65]

20. In patients with asthma, how effective is aerosol delivery of asthma medications by pMDI + VHC compared to 

nebulization for quick relief aerosols? [A&P]

21. Do studies show there is an effective pharmacotherapy (PRN SABA, ICS Leukotrine) for the <5-year-old child with 

recurrent wheeze, but no asthma diagnosis? [P]

22. Do studies show an optimal systemic steroid preparation, dosage, and duration of treatment for managing asthma 

in pediatrics? [P]

23. Do studies show that routine initiating LTC ICS in children with persistent asthma at discharge from the 

emergency department is more effective? [P]

MANAGEMENT

24. Does the use of a home peak flow meter-based Asthma Action Plan compared to a symptom-based Asthma 

Action Plan result in better outcomes in patients with asthma? [A&P]

• Do patient questionnaires improve reporting of asthma symptoms and therefore improve asthma severity 

assessment and treatment?

• Do comprehensive approaches to environmental control and avoidance of allergens improve asthma 

outcomes? 

• What evidence is there for poorer asthma outcomes related to specific inhaled irritants/pollutants such as 

tobacco smoke, particulate air pollution, NO2, SO2, diesel exhaust, volatile organic compounds, 

formaldehyde, and fumes? 

25. Which strategy in the outpatient setting leads to better outcomes in terms of decreased frequency of 

exacerbations, emergency department visits, or hospitalization in patients with asthma? [A&P]

• Implementation of comprehensive asthma care (pt. education, action plans and asthma educators) 

compared to usual care

• Implementation of group visits compared to individual patient appointments

• Written action plans compared to not using a written action plan in usual care

• Providing patient education in modality other than written (e.g., media, computer-based, internet). 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 109 

Appendix G 

Acronym List

ABG Arterial Blood Gas

ABPA Allergic Bronchopulmonary Aspergillosis

ACT Asthma Control Test

ALT Alanine Aminotransferase

ATS American Thoracic Society

BNP Brain Natriuretic Peptide 

BPD Bronchopulmonary Dysplasia

CAD Coronary Artery Disease

CAM Complementary and Alternative Medicine

CHF Congestive Heart Failure

COPD Chronic Obstructive Pulmonary Disease

CPAP Continuous Positive Airway Pressure

CT Computed Tomography

CXR Chest X-Ray

DLCO Carbon Monoxide Diffusing Capacity

DPI Dry Powder Inhaler

ED Emergency Department

EIB Exercise-Induced Bronchospasm

ETS Environmental Tobacco Smoke

FEV1 Forced Expiratory Volume in 1 Second

FVC Forced Vital Capacity

GERD Gastroesophageal Reflux Disease

ICS Inhaled Corticoid Steroids

ICU Intensive Care Unit

LABA Long-Acting Beta Agonists

LTRA Leukotriene Receptor Antagonist

MDI Metered Dose Inhalers

NAEPP-3 National Asthma Education and Prevention Program Expert Panel Report 3

OSA Obstructive Sleep Apnea

PEF Peak Expiratory Flow

PFT Pulmonary Function Test 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 110 

PND Post Nasal Drip

PPI Proton Pump Inhibitor

SABA Short-Acting Beta Agonists

SOB Shortness of Breath

VCD Vocal Cord Dysfunction

VHC Valved Holding Chamber
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 111 

Appendix H 

Participant List

Arthur Blain, MD, MBA

Naval Hospital Camp Pendleton

Department of Family Medicine

Camp Pendleton, CA 92055

Phone: 760-725-1176

Email: Arthur.blain@med.navy.mil 

Deborah Bray, BSN, MSN

Pulmonary CNS, Asthma Nurse Educator

Brooke Army Medical Center

3851 Roger Brooke Drive

Fort Sam Houston, TX 78234-6200

Phone: 210-916-0945

Email: Deborah.bray@amedd.army.mil 

Carla Cassidy, RN, MSN, NP

Director, Evidence-Based Practice Program

Department of Veterans Affairs

810 Vermont Avenue

Washington, DC 20420

Phone: 202-266-4502

Email: Carla.cassidy@va.gov

 

Christine Colluraburke, MD

LCDR, MD, USN

Pediatric Allergy

Naval Medical Center Portsmouth

620 John Paul Jones Circle 

Portsmouth, VA 23708

Email: Christina.Colluraburke@med.navy.mil

Darrel W. Dodson, MD, DPM, MPH

LTC, USA

Chief, Department of Medicine 

Carl R. Darnall Army Medical Center

36000 Darnall Loop

Fort Hood, TX 76544

Phone: (254) 288-8090

Email: darrel.w.dodson@us.army.mil

Donald Curran, MD

Veterans Administration

555 Willard Ave

Newington, CT 06111

Phone: 860-694-6393

Email: Donald.curran@va.gov
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 112 

Trina Davenport

HM2

Respiratory Therapist

National Naval Medical Center

8901 Wisconsin Ave

Bethesda, MD 20889

Phone: 301-319-4857

Email: Trina.davenport@med.navy.mil 

Ernest Degenhardt, RN, MSN, ANP-FNP

COL, USA

Chief, Evidence-Based Practice

Quality Management Division

U.S. Army Medical Command

2050 Worth Road, Suite 26

Fort Sam Houston TX 78234

Phone: 210-221-6527 or DSN 471-6527

Email: ernest.degenhardt@amedd.army.mil

Carlos Daughaday, MD

Chief, Pulmonary

915 North Grand Blvd

St. Louis VA Hospital

St. Louis, MO 63106

Phone: 314-652-4100, Ext. 4475

Email: Carlos.Daughaday@med.va.gov 

Daniel P. Hsu, M.D., FS, FAAP

LTC, MC, USA

Flight Commander/Medical Director, Pediatric Subspecialty Clinic

Assistant Chief, Division of Pediatric Pulmonology and Tri-Services Cystic

Fibrosis Center

San Antonio Military Pediatric Center

Rosalie Fishman, RN, MSN, CPHQ

President

Healthcare Quality Informatics, Inc.

2275 Shady Grove Rd, Suite 500

Rockville, MD 20850

Phone: 301-296-4542

Email Rosalie@hqiinc.com

Deborah Khachikian, PharmD

Clinical Pharmacy Specialist

Department of Veterans Affairs

Pharmacy Benefits Management Services

1st Ave-1 Blk N of Cermak Rd Building 37, Room 138

Hines, IL 60141

Phone: 708-786-7874

Email: Debbie.khachikian@va.gov 
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 113 

Angela Klar, RN, MSN, ANP-CS

Chronic Disease CPG Coordinator

U.S. Army Medical Command

2050 Worth Road, Building 2792, Suite 26

Fort Sam Houston, TX 78234

Phone: 210-221-8740

Email: Angela.Klar@amedd.army.mil 

Rees Lee, MD

CDR, MC, USN

Staff Pediatric Pulmonologist, NMCP

Assistant Professor of Pediatrics, USUHS

Naval Center Portsmouth

Dept. of Pediatrics

620 John Paul Jones Circle

Portsmouth, VA 23708

Phone: 757-953-0220 or 953-2955

Email: Rees.Lee@med.navy.mil

Julie Liss, PharmD

Clinical Pharmacy Specialist

Department of Defense (PEC)

2450 Stanley Road, Suite 208

Fort Sam Houston, TX 78234

Phone: 210-295-2787

Email: Julie.Liss@amedd.army.mil 

Michael Littner, MD

Chief, Pulmonary Function laboratory

VA Greater Los Angeles Healthcare System

16111 Plummer Street

Sepulveda, CA 91343

Phone: 818-895-9388

Email: mlittner@ucla.edu

John Manning, RN, MSN, BSN

CDR, NC, USN

Pediatric Nurse Practitioner, AE-C 

Naval Hospital

100 Brewster Blvd

Camp Lejeune, NC 28547

Phone: 910-450-3192

Email: John.Manning@med.navy.mil 

Joanne Marko, MS, SLP

Independent Consultant

17816 Whimsey Court

Olney, MD 20832

Phone: 301-774-5812

Email: nitojo@comcast.net
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 114 

Michael Morris, MD

COL, MC, USA

Staff, Pulmonary Disease/Critical Care Service

Brooke Army Medical Center

3851 Roger Brooke Drive

Fort Sam Houston, TX 78234

Phone: 210-916-3027

Email: micheal.morris@amedd.army.mil 

Jack Markusfeld, MD

COL, MC, USA

Deputy Commander Clinical Services

TF 1125th MED, Internal medicine

TF 115th MED

Camp Cropper

APO AE 09342

Email: Jack.markusfeld@us.army.mil

Kristina Orio, MD

Maj, MC, USAF

Emergency Department

Wilford Hall Medical Center

2200 Bergquist Dr.

Lackland AFB, TX 78236

Email: Kristina.Orio@LACKLAND.af.mil 

Lawrence Potter, MD

LCDR, MC, USN

Pediatrician

NH Jacksonville, FL

2080 Child St

Jacksonville, FL 32214

Phone : 904-542-7302

Email: Lawrence.potter@med.navy.mil

James Quinn, MD

COL, MC, USAF

Allergy Immunology Program Director

Wilford Hall Medical Center

2200 Bergquist Dr.

Lackland AFB, TX 78236

Phone: 210-292-7521

Email: James.Quinn@lackland.af.mil 

Nancy Radebaugh, BPharm

Carl R Darnall Army Medical Center

36000 Darnall Loop

Ft. Hood, TX 76544

Phone: 254-286-7069

Email: Nancy.radenbaugh@amedd.army.mil
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 115 

Patricia A. Rikli, Ph.D, MSN, BSN

Project Manager/Nurse Planner

VA Employee Education System

St. Louis EERC, VA Medical Center Bldg.2

1 Jefferson Barracks Drive

St. Louis, MO 63125-4199

Phone: 314-894-5742

Email: patricia.rikli@va.gov

Kristie Robson, MD

LCDR, MC, USN

Head of Naval Hospital Okinawa Emergency Dept

United States Navy

PSC 482 Box 2552

FPO, AP 96362

Phone: 405-808-8700

Email: Kristie.robson@med.navy.mil

Christopher Roach, RCP, CRT

HM2

Respiratory Therapist

NNMC Bethesda

8901 Wisconsin Ave

Bethesda, MD 20889

Phone: 301-319-8634

Email: Christopher.roach@med.navy.mil

Gregory Sees, RRT, RPSGT

Respiratory Therapist

Harry S. Truman Memorial Veterans Hospital

800 Hospital Dr.

Columbia MO, 65201

Tel: 573-814-6471

Email: Gregory.Sees@va.gov 

Wayne Schriner, DO, MPH

Director, Population Health

Carl R. Darnall Army medical Center

36000 Darnall Loop

Fort Hood, TX 76544

Phone: 254-535-3426

Email: wayne.schimer@amedd.army.mil

Oded Susskind, MPH 

Medical Education Consultant

Brookline MA 02446

Phone: 617- 232-3558

Email: oded@tiac.net
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 116 

Mark Tucker, MD

LCDR, MC, USN

Allergist

Naval Medical Center-San Diego

2051 Cushing Road

San Diego, CA 92106

Phone: 619-524-1519

Email: Mark.Tucker@med.navy.mil

Henry Wojczak, MD

CAPT, MC, USN

Pediatric Pulmonologist

Naval Medical Center San Diego

34800 Bob Wilson Drive

San Diego, CA 92124-5000

Phone: 619-532-6883

Email: henry.wojczak@med.navy.mil

Jane Jacknewitz-Woolard, RN, MSN, P/FNP, CS

Pediatric Nurse Practitioner

Walter Reed Army Medical Center

6900 Georgia Ave, NW

Washington, DC 20307

Phone: 202-682-4498/3405

Email: jane.jacknewitz-woolard@amedd.army.mil
Clinical Practice Guideline for the Management of

Asthma in Children and Adults

Appendices - Page 117 

Appendix I

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