• February 21, 2007, Xolair (Omalizumab): New reports of serious and life-threatening allergic reactions (anaphylaxis) in patients after treatment with Xolair.

• Measures of asthma assessment and monitoring.
• Education for a partnership in asthma care.
• Control of environmental factors and comorbid conditions that affect asthma.
• Medications.
• Managing asthma long term in children 0-4 years of age and 5-11 years of age.
• Managing asthma long term—special situations
• Managing exacerbations of asthma.

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

• The goal for therapy is to control asthma by (Evidence A):
  • Reducing impairment
    • Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the daytime, in the night, or after exertion)
    • Require infrequent use (<2 days a week) of inhaled short-acting beta₂-agonist (SABA) for quick relief of symptoms
    • Maintain (near) normal pulmonary function
    • Maintain normal activity levels (including exercise and other physical activity and attendance at work or school)
    • Meet patients' and families' expectations of and satisfaction with asthma care
  • Reducing risk
    • Prevent recurrent exacerbations of asthma and minimize the need for emergency department (ED) visits or hospitalizations
    • Prevent progressive loss of lung function; for children, prevent reduced lung growth
    • Provide optimal pharmacotherapy with minimal or no adverse effects
• A stepwise approach to pharmacologic therapy is recommended to gain and maintain control of asthma in both the impairment and risk domains (Evidence A):
  • The type, amount, and scheduling of medication is dictated by asthma severity for initiating therapy and the level of asthma control for adjusting therapy (Evidence A).
  • Step-down therapy is essential to identify the minimum medication necessary to maintain control (Evidence D).
• Monitoring and follow up is essential (Evidence B).
  • When initiating therapy, monitor at 2- to 6-week intervals to ensure that asthma control is achieved (Evidence D).
  • Regular follow up contacts at 1- to 6-month intervals, depending on level of control, are recommended to ensure that control is maintained and the appropriate adjustments in therapy are made: step up if necessary or step down if possible. Consider 3-month intervals if a step down in therapy is anticipated (Evidence D).
• Because asthma is a chronic inflammatory disorder of the airways with recurrent exacerbations, persistent asthma is most effectively controlled with daily long-term control medication, specifically, anti-inflammatory therapy (Evidence A).
  • Inhaled corticosteroids (ICSs) are the preferred treatment option for initiating long-term control therapy (Evidence A).
  • Selection of an alternative treatment option includes consideration of treatment effectiveness, the domain of particular relevance to the patient (impairment, risk, or both), the individual patient's history of previous response to therapies, the ability of the patient and family to use the medication correctly, and anticipated patient's and family's adherence to the treatment regime (Evidence D).
• Therapeutic strategies should be considered in concert with clinician-patient partnership strategies; education of patients is essential for achieving optimal pharmacologic therapy (Evidence A).
• At each step, patients should be advised to avoid or control allergens (Evidence A), irritants, or comorbid conditions that make the patient's asthma worse (Evidence B).
• A written asthma action plan detailing for the individual patient the daily management (medications and environmental control strategies) and how to recognize and handle worsening asthma is recommended for all patients; written asthma action plans are particularly recommended for patients who have moderate or severe persistent asthma, a history of severe exacerbations, or poorly controlled asthma (Evidence B). The written asthma action plan can be either symptom or peak-flow based; evidence shows similar benefits for each (Evidence B).
• Referral to an asthma specialist for consultation or comanagement is recommended if there are difficulties achieving or maintaining control of asthma; if the patient requires step 4 care or higher; if immunotherapy or omalizumab are considered; or if the patient has had an exacerbation requiring hospitalization. Consider referral if the patient requires step 3 care (Evidence D).
• Special considerations for youths (EPR—2 1997):
  • Pulmonary function testing should use appropriate reference populations. Adolescents compare better to childhood than to adult predicted norms.
  • Adolescents (and younger children as appropriate) should be directly involved in establishing goals for therapy and developing their asthma management plans.
  • Active participation in physical activities, exercise, and sports should be promoted.
  • A written asthma management plan should be prepared for the student's school, including plans to ensure reliable, prompt access to medications. Either encourage parents to take a copy to the child's school or obtain parental permission and send a copy to the school nurse or designee.
• Special considerations for older adults (EPR—2 1997):
  • Chronic bronchitis/emphysema may coexist with asthma. A trial of systemic corticosteroids will determine the presence of reversibility and the extent of therapeutic benefit.
  • Asthma medications may aggravate coexisting medical conditions (e.g., cardiac disease, osteoporosis); adjustments in the medication plan may be necessary.
  • Be aware of increased potential for adverse drug/disease interaction (e.g., aspirin, beta-blockers).
  • Review of patient technique in using medications and devices is essential; physical (e.g., arthritis or visual) or cognitive impairments may make proper technique difficult.

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

The Expert Panel recommends that the goal of asthma therapy is to maintain control of asthma with the least amount of medication and hence minimal risk for adverse effects (Evidence A). Control of asthma is viewed in the context of two domains, impairment and risk, and is defined as:

• Reducing impairment
  • Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the daytime, in the night, or after exertion)
  • Require infrequent use (<2 days a week) of SABA for quick relief of symptoms
  • Maintain (near) normal pulmonary function
  • Maintain normal activity levels (including exercise and other physical activity and attendance at work or school)
  • Meet patients' and families' expectations of and satisfaction with asthma care
• Reducing risk
  • Prevent recurrent exacerbations of asthma, and minimize the need for ED visits or hospitalizations
  • Prevent progressive loss of lung function; for youths, prevent reduced lung growth
  • Provide optimal pharmacotherapy with minimal or no adverse effects

Achieving Control of Asthma

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

The Expert Panel recommends the following actions to achieve asthma control in patients who are not currently taking long-term control medications.

• Assess asthma severity (EPR—2 1997). Asthma severity is based on measurements of impairment and risk; (See figure 4–6 in the original guideline document and the discussion in the NGC summary of the NAEPP guideline Measures of Asthma Assessment and Monitoring).
• Select treatment that corresponds to the patient's level of asthma severity (EPR—2 1997). (See the following in the original guideline document: figure 4–6 for the recommended step of care at different levels of severity; figure 4–5 for treatment options at each step of care; and figures 4–8 a, b, and c for usual dosages of medications.)
• If at a follow up visit in 2 to 6 weeks after starting treatment, depending on severity, asthma is not well controlled (see below), then treatment should be advanced to the next step. If uncontrolled asthma persists, then the diagnosis should be reevaluated, and, if confirmed, treatment should be advanced another step (Evidence D).

Adjusting Therapy

The Expert Panel recommends that, once therapy is selected, or if the clinician sees a patient for the first time who is already taking a long-term control medication, treatment decisions are based on the level of the patient's asthma control (See figure 4–7 in the original guideline document.) (Evidence A).

• Assess asthma control. As in assessment of asthma severity, asthma control can be considered in terms of impairment and risk domains (Evidence C). Both domains should be addressed to select appropriate therapy; the level of control is generally judged on the most severe indicator of impairment or risk (Evidence D).

Impairment Domain

This domain is multifactorial because the different manifestations of asthma do not necessarily correlate with each other, and each factor should be assessed if possible (Evidence C).

Risk Domain

• Adjust therapy based on level of asthma control (Evidence A). The following considerations will guide selection of therapy based on level of asthma control. Classify current level of asthma control, generally, by the most severe indicator of impairment or risk (See figure 4–7 in the original guideline document.) (Evidence D).
  • If the patient's asthma is not well controlled:
    • Identify the patient's current treatment step (See figure 4–5 in the original guideline document), based on what he or she is actually taking. In general, step up one step for patients whose asthma is not well controlled. For patients who have very poorly controlled asthma, consider increasing by two steps, a course of oral corticosteroids, or both. Before increasing pharmacologic therapy, consider poor inhaler technique, adverse environmental exposures, poor adherence, or comorbidities as targets for intervention.
    • If the office spirometry suggests worse control than does the assessment of impairment based on other measures, (1) consider fixed airway obstruction as the explanation (Aburuz et al., 2005) (See the NGC summary of the NAEPP guideline, Measures of Asthma Assessment and Monitoring), and use changes from percent personal best rather than percent predicted to guide therapy; (2) reassess the other measures of impairment; and (3) if fixed airway obstruction does not appear to be the explanation, consider a step up in therapy especially if the patient has a history of frequent moderate or severe exacerbations.
    • If the history of exacerbations suggests poorer control than does the assessment of impairment, (1) reassess impairment; (2) review control of factors capable of making asthma worse (e.g., lack of adherence, adverse environmental exposure, or comorbidities); (3) review the written action plan, and be sure it includes oral prednisone for patients who have histories of severe exacerbations; and (4) consider a step up in therapy, especially if the patient has reduced forced expiratory volume in 1 second (FEV₁).
    • For troublesome or debilitating side effects, explore a change in therapy. In addition, confirm maximal efforts to control factors capable of making asthma worse. (See the NGC summary of the NAEPP guideline, Control of Environmental Factors and Comorbid Conditions That Affect Asthma).
    • After treatment is adjusted, reevaluate in 2 to 6 weeks, depending on the level of control.
  • If the patient's asthma is well controlled, see the following section on "Maintaining Control of Asthma."

Maintaining Control of Asthma

The Expert Panel recommends that regular follow up contact is essential (Evidence B). Contact at 1- to 6-month intervals is recommended, depending on the level of control; consider 3-month intervals if a step down in therapy is anticipated (Evidence D).

The Expert Panel recommends that, once asthma is well controlled and the control is achieved and maintained for at least 3 months, a reduction in pharmacologic therapy—a step down—can be considered. This will be helpful to identify the minimum therapy for maintaining good control of asthma (Evidence D).

The Expert Panel recommends that, if asthma control is not achieved and maintained at any step of care (See figure 4–7 in the original guideline document.), several actions may be considered:

• Patient adherence and technique in using medications correctly should be assessed (Evidence B). (See the NGC summary of the NAEPP guideline, Education for a Partnership in Asthma Care for discussion on assessing adherence.)
• A temporary increase in anti-inflammatory therapy may be indicated to reestablish asthma control (Evidence D).
• Other factors that diminish control may have to be identified and addressed (Evidence C).
• A step up to the next higher step of care may be necessary (Evidence A).
• Consultation with an asthma specialist may be indicated (See the NGC summary of the NAEPP guideline, Measures of Asthma Assessment and Monitoring) (Evidence D). The Expert Panel recommends referral to an asthma specialist for consultation or comanagement if: there are difficulties achieving or maintaining control of asthma; immunotherapy or omalizumab is being considered; the patient requires step 4 care or higher; or the patient has had an exacerbation requiring a hospitalization. Referral may be considered if a patient requires step 3 care (Evidence D).

Treatment: Pharmacologic Steps

The Expert Panel recommends that specific therapy should be tailored to the needs and circumstances of individual patients. Pharmacologic therapy must be accompanied at every step by patient education and measures to control those environmental factors or comorbid conditions that can make asthma worse (EPR—2 1997). (See the NGC summaries of the NAEPP guidelines, Control of Environmental Factors and Comorbid Conditions That Affect Asthma which includes discussion of the role of allergen immunotherapy, and Education for a Partnership in Asthma Care. Figure 4–5 in the original guideline document presents treatment options for the stepwise approach for managing asthma youths >12 years of age and adults.

Note: The recommendations for steps of pharmacologic therapy are intended to be general guidelines for assisting, not replacing, clinical decision making. The recommendations are not intended to be prescriptions for individual treatment.

Intermittent Asthma

The Expert Panel recommends the following therapy for intermittent asthma:

Step 1 Care

• SABA taken as needed to treat symptoms is usually sufficient therapy for intermittent asthma (EPR—2 1997).
• Patients who have intermittent asthma and experience exercise-induced bronchospasm (EIB) benefit from taking SABA, cromolyn, or nedocromil shortly before exercise (EPR—2 1997) (See "Exercise-Induced Bronchospasm" in the NGC summary of the NAEPP guideline, Managing Asthma Long Term—Special Situations).
• The following actions for managing exacerbations due to viral respiratory infections are recommended (EPR—2 1997).
  • If the symptoms are mild, SABA (every 4 to 6 hours for 24 hours, longer with a physician consult) may be sufficient to control symptoms and improve lung function.
  • If this therapy must be repeated more frequently than every 6 weeks, a step up in long-term care is recommended.
  • If the viral respiratory infection provokes a moderate-to-severe exacerbation, a short course of systemic corticosteroids should be considered.
  • For those patients who have a history of severe exacerbations with viral respiratory infections, systemic corticosteroids should be considered at the first sign of the infection.
• A detailed written asthma action plan is recommended for those patients who have intermittent asthma and particularly those who have a history of severe exacerbations (Evidence B) (See the NGC summary of the NAEPP guideline, Education for a Partnership in Asthma Care).

Persistent Asthma

The Expert Panel recommends the following therapy for persistent asthma:

• Daily long-term control medication is recommended for patients who have persistent asthma. The long-term control medication should be one with anti-inflammatory effects. Of the available medications, ICSs are the most effective single agents (Evidence A) (see the NGC summary of the NAEPP guideline, Medications).
• Quick-relief medication must be available to all patients who have persistent asthma. SABA should be taken as needed to relieve symptoms (EPR—2 1997). The intensity of treatment will depend on the severity of the exacerbation (See the NGC summary of the NAEPP guideline Managing Exacerbations of Asthma).
• Consider treating patients who may have seasonal asthma (asthma symptoms only in relation to certain seasonal molds or pollens with few symptoms the rest of the year) as having persistent asthma during the season and as having intermittent asthma the rest of the year. Confirm characteristics of intermittent asthma out of season (Evidence D).
• Consider treating patients who had two or more exacerbations requiring oral corticosteroids in the past year the same as patients who have persistent asthma, even in the absence of an impairment level consistent with persistent asthma (Evidence D).

Step 2 Care, Long-Term Control Medication

• Preferred treatment for step 2 care is daily ICS at a low dose (Evidence A).
• Alternative, but not preferred, treatments include (listed alphabetically) cromolyn, leukotriene receptor antagonist (LTRA), nedocromil (Evidence A), and sustained release theophylline (Evidence B). There is insufficient evidence to recommend long-acting beta₂-agonists (LABA) in combination with ICS for step 2 therapy.

Step 3 Care, Long-Term Control Medications

• Consultation with an asthma specialist may be considered because the therapeutic options at this juncture pose a number of challenging risk/benefit considerations (Evidence D). Before increasing therapy, however, the clinician should review the patient's inhaler technique and adherence to therapy (Evidence B), as well as determine whether environmental factors, particularly allergens (Evidence A), or comorbid conditions are contributing to the patient's worsening asthma (Evidence C).
• Preferred step 3 care options: Two equally acceptable options are available, given the consideration of both benefits and risks for each.
  • Add a LABA to a low dose of ICS (Evidence A) (See Component 4 Medications, section on "Safety of Long-Acting Beta₂-Agonists," for a complete discussion.
    • The Expert Panel recommends that the established, beneficial effects of LABAs for the great majority of patients who have asthma not sufficiently controlled with ICS therapy alone be weighed carefully against the increased risk for potentially deleterious, although uncommon, side effects associated with the daily use of LABAs.
    • Therefore, the Expert Panel has modified its previous recommendation (EPR—Update 2002) and has now concluded that, for patients who have asthma not sufficiently controlled with a low-dose ICS alone, the step-up option to increase the ICS dose should be given equal weight to that of the addition of a LABA to ICS.

    OR

  • Continue the ICS as monotherapy by increasing the dose to the medium-dose range (Evidence A).
• Alternative, but not preferred, step 3 therapy is to add (listed alphabetically) an LTRA (Evidence A), theophylline (Evidence B), or zileuton (Evidence D) to low-dose ICS.
• If an alternative, but not preferred, treatment is initially administered and does not lead to improvement in asthma control, discontinue it and use a preferred step 3 option before stepping up to step 4 (Evidence D).

Step 4 Care, Long-Term Control Medications

• The preferred option is to increase the dose of ICS to the medium-dose range AND add a LABA (Evidence B).
• Alternative, but not preferred, step 4 therapy includes medium-dose ICS AND either LTRA or theophylline (Evidence B), or zileuton (Evidence D).
• If the add-on therapy initially administered does not lead to improvement in asthma control, discontinue it and consider a trial of a different add-on therapy before stepping up (Evidence D).

Step 5 Care, Long-Term Control Medications

• High-dose ICS and LABA is the preferred treatment (Evidence B).
• Omalizumab may be considered at this step for patients who have sensitivity to relevant perennial allergens (e.g., dust mites, cockroach, cat, or dog) (Evidence B) (Bousquet et al., 2004; Humbert et al., 2005).
• Clinicians who administer omalizumab are advised to be prepared and equipped for the identification and treatment of anaphylaxis that may occur, to observe patients for an appropriate period of time following each omalizumab injection (the optimal length of the observation is not established), and to educate patients about the risks of anaphylaxis and how to recognize and treat it if it occurs (e.g., using prescription auto injectors for emergency self-treatment, and seeking immediate medical care) (see "FDA Warning/Regulatory Alert" field).
• Consultation with an asthma specialist is recommended for patients who require this step of therapy (Evidence D).

Step 6 Care, Long-Term Control Medications

• Add oral corticosteroids to step 5 therapy. Patients who are not controlled on step 5 therapy may require regular oral corticosteroids to achieve well-controlled asthma (EPR—2 1997).

Special Issues for Adolescents

The Expert Panel recommends that the pharmacologic management of asthma in school-age children and adolescents follows the same basic principles as those for adults, but the special circumstances of school and social development require special consideration (EP—2 1997).

Assessment Issues

The Expert Panel recommends that pulmonary function testing should be performed by using comparison data from an appropriate reference population ("Standardization of spirometry," 1995; EPR—2 1997).

Treatment Issues

The Expert Panel recommends that adolescents (and younger children as appropriate) be directly involved in developing their written asthma action plans (See the NGC summary of the NAEPP guideline, Education for a Partnership in Asthma Care).

School Issues

The Expert Panel recommends that the clinician prepare a written asthma action plan for the student's school. Either encourage the youth or the parents to take a copy of the plan to the youth's school or obtain parental permission and send a copy to the school nurse or designee (Evidence C).

Sports Issues

The Expert Panel recommends that clinicians encourage full participation in physical activities; physical activity at play or in organized sports is an essential part of a child's life (EPR—2 1997).

Special Issues for Older Adults

Assessment Issues

The Expert Panel recommends that the extent of reversible airflow obstruction be determined because of the high prevalence of other obstructive lung disease (e.g., chronic bronchitis, emphysema) among the elderly (EPR—2 1997).

Treatment Issues

The Expert Panel recommends that adjustments in therapy may be necessary because asthma medications may have increased adverse effects in the elderly patient (EPR—2 1997).

• Inhaled corticosteroid. Consider concurrent treatments with calcium supplements and vitamin D, and bone-sparing medications (e.g., bisphosphonates) in patients who have risk factors for osteoporosis or low bone mineral density (Evidence D).

The Expert Panel recommends that medications taken for other diseases and conditions be adjusted as necessary, because some medications may exacerbate asthma (EPR—2 1997). (See the NGC summary of the NAEPP guideline, Medications for more details on drugs that can complicate asthma management.)

The Expert Panel recommends that review of the patient's technique in using medications and devices is essential (Evidence B).

Definitions:

Levels of Evidence

The system* used to describe the level of evidence is as follows:

Evidence Category A: Randomized controlled trials (RCTs), rich body of data.
Evidence is from end points of well-designed RCTs that provide a consistent pattern of findings in the population for which the recommendation is made. Category A requires substantial numbers of studies involving substantial numbers of participants.

Evidence Category B: RCTs, limited body of data.
Evidence is from end points of intervention studies that include only a limited number of patients, post hoc or subgroup analysis of RCTs, or meta-analysis of RCTs. In general, category B pertains when few randomized trials exist; they are small in size, they were undertaken in a population that differs from the target population of the recommendation, or the results are somewhat inconsistent.

Evidence Category C: Nonrandomized trials and observational studies.
Evidence is from outcomes of uncontrolled or nonrandomized trials or from observational studies.

Evidence Category D: Panel consensus judgment.
This category is used only in cases where the provision of some guidance was deemed valuable, but the clinical literature addressing the subject was insufficient to justify placement in one of the other categories. The Panel consensus is based on clinical experience or knowledge that does not meet the criteria for categories A through C.

*Source: Jadad AR, Moher M, Browman GP, Booker L, Sigouin C, Fuentes M, Stevens R. Systematic reviews and meta-analyses on treatment of asthma: critical evaluation. BMJ 2000;320(7234):537-40.

Strength of Recommendations

In addition to specifying the level of evidence supporting a recommendation, the Expert Panel agreed to indicate the strength of the recommendation. When a certain clinical practice "is recommended," this indicates a strong recommendation by the panel. When a certain clinical practice "should, or may, be considered," this indicates that the recommendation is less strong.

This distinction is an effort to address nuances of using evidence ranking systems. For example, a recommendation for which clinical RCT data are not available (e.g., conducting a medical history for symptoms suggestive of asthma) may still be strongly supported by the Panel. Furthermore, the range of evidence that qualifies a definition of "B" or "C" is wide, and the Expert Panel considered this range and the potential implications of a recommendation as they decided how strongly the recommendation should be presented.

References open in a new window

Electronic copies: Available from the National Heart, Lung, and Blood Institute Web site.

Print copies: Available from NHLBI Information Center, P.O. Box 30105, Bethesda, MD 20824-0105; e-mail: nhlbiic@dgsys.com.

• Guidelines for the diagnosis and management of asthma. Summary report 2007. Bethesda (MD): National Heart, Lung, and Blood Institute; 2007. Available from the National Heart, Lung, and Blood Institute Web site.
• Overall methods used to develop this report. Electronic copies: Available from the National Heart, Lung, and Blood Institute Web site.
• Search strategies. Electronic copies: Available from the National Heart, Lung, and Blood Institute Web site.
• Evidence tables. Electronic copies: Available from the National Heart, Lung, and Blood Institute Web site.
• Lung diseases information. Information for health professionals. Electronic copies: Available from the National Heart, Lung, and Blood Institute Web site.

Print copies: Available from NHLBI Information Center, P.O. Box 30105, Bethesda, MD 20824-0105; e-mail: nhlbiic@dgsys.com.

Electronic copies: Available from the National Heart, Lung and Blood Institute Web site.

Print copies: Available from NHLBI Information Center, P.O. Box 30105, Bethesda, MD 20824-0105; e-mail: nhlbiic@dgsys.com.

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