Asthma EPR2 Quick Reference-2002 Update

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Originally published by the National Heart, Lung, and Blood Institute (NIH Publication No. 97-4051). U.S. government work, public domain. Reproduced as archived reference, not current guidance.

National Asthma Education and Prevention Program

QUICK REFERENCE

NAEPP Expert Panel Report Guidelines for the Diagnosis and Management of Asthma–Update on Selected Topics 2002*

The National Asthma Education and Prevention Program (NAEPP) keeps clinical practice guidelines up to date by identifying selected topics on asthma that warrant intensive review based on the level of research activity reflected in the published literature or the level of concern in clinical practice. The NAEPP Expert Panel identified key questions about asthma management and used a systematic review of the evidence, conducted by the Agency for Healthcare Research and Quality Evidence Practice Center, to prepare answers and update recommendations for clinical practice.

The NAEPP Expert Panel Report: Guidelines for the Diagnosis and Managment of Asthma—Update on Selected Topics 2002 (EPR—Update 2002) presents up-to-date recommendations on:

Medications—long-term management of asthma in children with mild or moderate persistent asthma, combination therapy in moderate persistent asthma, and use of antibiotics to treat acute exacerbations of asthma

Monitoring—written action plans compared to medical management alone, and peak flow-based compared to symptom-based written action plans

Prevention—effects of early treatment on the progression of asthma

Medications

Long-Term Management of Asthma in Children

Question: Does chronic use of inhaled corticosteroids improve long-term outcomes for children with mild or moderate persistent asthma, compared to other asthma medications?

Answer: Strong evidence from clinical trials has established that inhaled corticosteroids improve control of asthma for children with mild or moderate persistent asthma compared to as-needed beta2-agonists, as measured by prebronchodilator FEV1, reduced airway hyperresponsiveness, improvements in symptom scores and symptom frequency, fewer courses of oral corticosteroids, and fewer urgent care visits or hospitalizations. Studies comparing inhaled corticosteroids to cromolyn, nedocromil, theophylline, or leukotriene receptor antagonists are limited, but available evidence shows that none of these long-term-control medications appears to be as effective as inhaled corticosteroids in improving asthma outcomes. Studies comparing medications in children younger than 5 years of age are not available; recommendations are based on expert opinion and extrapolation from studies in older children. The NAEPP EPR-2 recommendations for treating children with mild or moderate persistent asthma have been revised. (See charts for Stepwise Approach for Managing Asthma.)

*Updates the NAEPP Expert Panel Report 2 (NIH Publication No. 97-4051). Asthma

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES For more information contact: Public Health Service NHLBI Health Information Network

National Institutes of Health

National Heart, Lung, and Blood Institute

Originally printed June 2002

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

Reprinted May 2003

Based on observational studies, it is the opinion of the Expert Panel that the initiation of long-term-control therapy should be considered in infants and young children who have had more than three episodes of wheezing in the past year that lasted more than 1 day and affected sleep and who have risk factors for the development of asthma (parental history of asthma or physician-diagnosed atopic dermatitis or two of the following: physician-diagnosed allergic rhinitis, wheezing apart from colds, peripheral blood eosinophilia). This is in addition to previously recommended indications for starting long-term-control therapy—i.e., in infants and young children requiring symptomatic treatment more than two times per week or experiencing severe exacerbations less than 6 weeks apart.

Question: What are the long-term adverse effects of chronic inhaled corticosteroid use in children on the following outcomes: vertical growth, bone mineral density, ocular toxicity, and suppression of the hypothalamic-pituitary-adrenal (HPA) axis?

Answer: Strong evidence from clinical trials following children for up to 6 years shows that the use of inhaled corticosteroids at recommended doses does not have frequent, clinically significant, or irreversible effects on any of the outcomes reviewed. The NAEPP EPR-2 statements have been updated but not changed: Inhaled corticosteroids improve health outcomes for children with mild or moderate persistent asthma, and the potential but small risk of delayed growth is well balanced by their effectiveness.

Cumulative data in children suggest that low-to-medium doses of inhaled corticosteroids may have the potential of decreasing growth velocity (resulting in a small difference in height averaging 1 cm in the first year of treatment), but this effect on growth velocity is not sustained in subsequent years of treatment, is not progressive, and may be reversible. Cohort studies following children for more than 10 years suggest that final predicted height is attained. Physicians should monitor the growth of children and adolescents taking corticosteroids by any route of administration and, if growth appears slowed, weigh the benefits of asthma control against the possibility of growth suppression or delay.

Studies including 6 years of observation indicate that lowto-medium doses of inhaled corticosteroids have no adverse effects on bone mineral density in children and no significant effects on the incidence of subcapsular cataracts or glaucoma. Studies show that, on average, persons may have only clinically insignificant effects, if any, of inhaled corticosteroids on HPA axis function, although there may be rare individuals who are more susceptible.

Combination Therapy

Question: In patients with moderate persistent asthma who are receiving inhaled corticosteroids, does addition of another long-term-control agent improve outcomes?

Answer: Strong evidence from clinical trials consistently indicates that use of long-acting inhaled beta2- agonists added to low-to-medium doses of inhaled corticosteroids leads to improvements in lung function and symptoms and reduced need for quick relief, shortacting beta2-agonists. Adding a leukotriene modifier or theophylline to inhaled corticosteroids or doubling the dose of inhaled corticosteroids also improves outcomes, but the evidence is not as substantial. The NAEPP EPR-2 recommendations for moderate persistent asthma have been revised: The preferred treatment for adults and children over 5 years of age is the addition of long-acting inhaled beta2-agonists to low-to-medium doses of inhaled corticosteroids. Adjunctive therapy combinations have not been studied in children younger than 5 years of age. For this age group, it is the opinion of the Expert Panel that there are two preferred options for treating moderate asthma: either the addition of long-acting inhaled beta2- agonists to a low dose of inhaled corticosteroids or medium-dose inhaled corticosteroids as monotherapy.

Use of Antibiotics To Treat Acute Asthma Exacerbation

Question: Does adding antibiotics to standard care improve the outcomes of treatment for acute exacerbation of asthma?

Answer: Evidence from clinical trials suggests no benefit from antibiotic therapy for asthma exacerbations, whether administered routinely or when suspicion of bacterial infection is low. No studies have addressed the question of whether the addition of antibiotics to standard care improves the outcomes of treatment for asthma exacerbations when signs and symptoms suggest the possibility—but do not clearly indicate the presence—of bacterial infection. The NAEPP EPR-2 recommendation has not been changed: Antibiotics are not recommended for the treatment of acute asthma exacerbations except as needed for comorbid conditions—e.g., for those patients with fever and purulent sputum, evidence of pneumonia, or suspected bacterial sinusitis.

Monitoring

Written Action Plans Compared to Medical Management Alone

Question: Compared to medical management alone, does the use of a written asthma action plan improve outcomes?

Answer: Data are insufficient to support or refute the benefits of using written asthma action plans compared to medical management alone. Seven studies compared medical management with written action plans to medical management without action plans. Beyond including instructions on the action plan to the intervention groups, four of these studies did not include asthma education for either the intervention or control groups; three of the studies included similar but limited asthma education for both intervention and control groups. Only one study included children. Significant limitations in study designs and methods in these studies preclude conclusions. For example, the studies showing no benefits of written action plans did not have sufficient power for comparisons between treatment and control groups, and the two studies reporting significant improvements with action plans had potential biases in patient selection, withdrawals, data collection, or analysis.

However, a Cochrane review of 25 studies comparing asthma self-management education interventions for adults to medical care without such education also contrasted those studies with self-management interventions that included written action plans to those that did not. The selfmanagement interventions with written action plans had the greatest benefits, including reduced emergency department visits and hospitalizations and improved lung function.

The NAEPP EPR-2 recommendations have not been changed: It is the opinion of the Expert Panel that use of written action plans as part of an overall effort to educate patients in self-management is recommended, especially for patients with moderate or severe persistent asthma and patients with a history of severe exacerbations.

Peak Flow-Based Compared to Symptom-Based Written Action Plans

Question: Compared to a written action plan based on symptoms, does use of a written action plan based on peak flow monitoring improve outcomes?

Answer: Evidence neither supports nor refutes the benefits of written action plans based on peak flow monitoring compared to symptom-based plans in improving health care utilization, symptoms, or lung function. Just four studies, one including children, were available, and these studies had limitations (e.g., inadequate sample sizes and power to detect differences or potential bias in patient selection). The evidence does not clearly show that a peak flow-based action plan is better, but equivalent benefits have been demonstrated. Patient preferences and circumstances (e.g., inability to recognize or report signs and symptoms of worsening asthma) may warrant choosing peak flow monitoring. The NAEPP EPR-2 recommendations have not been changed. It is the opinion of the Expert Panel that peak flow monitoring for patients with moderate or severe persistent asthma should be considered because it may enhance clinician-patient communication and may increase patient and caregiver awareness of the disease status and control.

Prevention

Effects of Early Treatment on Progression of Asthma

Question: For patients with mild or moderate persistent asthma, does early intervention with long-term-control therapy (i.e., inhaled corticosteroids) prevent progression of asthma as indicated by changes in lung function or severity of symptoms?

Answer: Evidence is insufficient to permit conclusions on the benefits of early treatment of asthma in preventing the progression of disease. The NAEPP EPR-2 statements on disease progression have been revised. The assumption that children ages 5 to 12 with mild or moderate persistent asthma have a progressive decline in lung function has not been supported by a large, randomized, controlled clinical trial. The trial found that although inhaled corticosteroids provided superior asthma control during treatment, symptoms and airway hyperresponsiveness returned when treatment was discontinued. This suggests that, for this age group, with mild or moderate asthma, treatment provides control but does not modify the underlying disease process. In contrast, prospective observational studies in other age groups suggest that a loss of lung function in children occurs in the first 3 to 5 years of life and can occur rapidly in adults with asthma. Adequate studies of whether treatment can prevent these declines in lung function have not yet been conducted.

Stepwise Approach for Managing Infants and Young Children (5 Years of Age and Younger) With Acute or Chronic Asthma

Classify Severity: Clinical Features Before Medications Required To Maintain Long-Term Control Treatment or Adequate Control

Symptoms/Day Symptoms/Night Daily Medications

Step 4 Continual ■ Preferred treatment: Frequent – High-dose inhaled corticosteroids

Severe Persistent AND

• Long-acting inhaled beta2-agonists AND, if needed,
• Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not exceed 60 mg per day). (Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.)

Daily ■ Preferred treatments: Step 3 > 1 night/week – Low-dose inhaled corticosteroids and long-acting inhaled beta2-agonists

Moderate Persistent OR

• Medium-dose inhaled corticosteroids.
• Alternative treatment:
• Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (particularly in patients with recurring severe exacerbations):
• Preferred treatment:
• Medium-dose inhaled corticosteroids and long-acting beta2-agonists.
• Alternative treatment:
• Medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline.

> 2/week but < 1x/day ■ Preferred treatment: Step 2

• Low-dose inhaled corticosteroid (with nebulizer or MDI with > 2 nights/month

Mild Persistent holding chamber with or without face mask or DPI).

• Alternative treatment (listed alphabetically):
• Cromolyn (nebulizer is preferred or MDI with holding chamber) OR leukotriene receptor antagonist.

≤ 2 days/week ■ No daily medication needed. Step 1 ≤ 2 nights/month

Mild Intermittent

• Bronchodilator as needed for symptoms. Intensity of treatment will depend upon severity of exacerbation. Quick Relief
• Preferred treatment: Short-acting inhaled beta2-agonists by nebulizer or face mask and space/holding chamber

All Patients – Alternative treatment: Oral beta2-agonist

• With viral respiratory infection
• Bronchodilator q 4–6 hours up to 24 hours (longer with physician consult); in general, repeat no more than once every 6 weeks
• Consider systemic corticosteroid if exacerbation is severe or patient has history of previous severe exacerbations
• Use of short-acting beta2-agonists >2 times a week in intermittent asthma (daily, or increasing use in persistent asthma) may

indicate the need to initiate (increase) long-term-control therapy.

Note

Step down

• The stepwise approach is intended to assist, not replace, the clinical decisionmaking required to

Review treatment every 1 to 6 months; a gradual stepwise

meet individual patient needs.

reduction in treatment may be possible.

• Classify severity: assign patient to most severe step in which any feature occurs.

Step up If control is not maintained, consider step up. First, review patient medication technique, adherence, and environmental control.

■ There are very few studies on asthma therapy for infants. ■ Gain control as quickly as possible (a course of short systemic corticosteroids may be required); then step down to the least medication necessary to maintain control.

• Minimize use of short-acting inhaled beta2-agonists. Overreliance on short-acting inhaled beta2-agonists (e.g., use of approximately one canister a month even if not using it every day)

Goals of Therapy: Asthma Control indicates inadequate control of asthma and the need to initiate or intensify long-term-control

therapy.

• Minimal or no chronic ■ Minimal use of short-acting
• Provide parent education on asthma management and controlling environmental factors that

symptoms day or night inhaled beta -agonist

make asthma worse (e.g., allergies and irritants).

• Minimal or no exacerbations ■ Minimal or no adverse effects
• Consultation with an asthma specialist is recommended for patients with moderate or severe
• No limitations on activities; from medications

persistent asthma. Consider consultation for patients with mild persistent asthma.

no school/parent’s work missed

Stepwise Approach for Managing Asthma in Adults and Children Older Than 5 Years of Age: Treatment

Classify Severity: Clinical Features Before Treatment or Adequate Control

Symptoms/Day PEF or FEV1

Medications Required To Maintain Long-Term Control

PEF Variability Symptoms/Night

Step 4 Continual ≤ 60%

Severe Persistent Frequent > 30%

Daily Medications

• Preferred treatment:
• High-dose inhaled corticosteroids AND
• Long-acting inhaled beta2-agonists AND, if needed,
• Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not exceed 60 mg per day). (Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.)

> 60% – < 80% Daily Step 3 > 1 night/week > 30%

Moderate Persistent

> 2/week but < 1x/day ≥ 80% Step 2 > 2 nights/month 20–30%

Mild Persistent

≤ 2 days/week ≥ 80% Step 1 ≤ 2 nights/month < 20%

Mild Intermittent

• Short-acting bronchodilator: 2–4 puffs Quick Relief
• Preferred treatment:
• Low-to-medium dose inhaled corticosteroids and longacting inhaled beta2-agonists.
• Alternative treatment (listed alphabetically):
• Increase inhaled corticosteroids within medium-dose range OR
• Low-to-medium dose inhaled corticosteroids and either leukotriene modifier or theophylline.

If needed (particularly in patients with recurring severe exacerbations):

• Preferred treatment:
• Increase inhaled corticosteroids within medium-dose range and add long-acting inhaled beta2-agonists.
• Alternative treatment (listed alphabetically):
• Increase inhaled corticosteroids within medium-dose range and add either leukotriene modifier or theophylline.
• Preferred treatment:
• Low-dose inhaled corticosteroids.
• Alternative treatment (listed alphabetically): cromolyn, leukotriene modifier, nedocromil, OR sustained-release theophylline to serum concentration of 5–15 mcg/mL.
• No daily medication needed.
• Severe exacerbations may occur, separated by long periods of normal lung function and no symptoms. A course of systemic corticosteroids is recommended.

short-acting inhaled beta2-agonists as needed for symptoms. Intensity of treatment will depend on severity of exacerbation; up to 3 treatments at 20-minute intervals or a

All Patients

single nebulizer treatment as needed. Course of systemic corticosteroids may be needed.

• agonists >2 times a week in intermittent asthma (daily, or increasing use in persistent asthma) may indicate the need to initiate (increase) long-term-control therapy.

Note

Step down Review treatment every 1 to 6 months; a gradual stepwise reduction in treatment may be possible. Step up If control is not maintained, consider step up. First, review patient medication technique, adherence, and environmental control.

Goals of Therapy: Asthma Control

• Minimal or no chronic ■ Maintain (near) normal pulmonary symptoms day or night function
• Minimal or no exacerbations ■ Minimal use of short-acting inhaled
• No limitations on activities; no beta -agonist school/work missed ■ Minimal or no adverse effects from medications

The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient needs. Classify severity: assign patient to most severe step in which any feature occurs (PEF is % of personal best; FEV1 is % predicted). Gain control as quickly as possible (consider a short course of systemic corticosteroids); then step down to the least medication necessary to maintain control. Minimize use of short-acting inhaled beta2-agonists. Overreliance on short-acting inhaled beta2-agonists (e.g., use of approximately one canister a month even if not using it every day) indicates inadequate control of asthma and the need to initiate or intensify long-term-control therapy. Provide education on self-management and controlling environmental factors that make asthma worse (e.g., allergens and irritants). Refer to an asthma specialist if there are difficulties controlling asthma or if step 4 care is required. Referral may be considered if step 3 care is required.

Usual Dosages for Long-Term-Control Medications

Medication Dosage Form Adult Dose

Inhaled Corticosteroids (See Estimated Comparative Daily Dosages for Inhaled Corticosteroids.)

Child Dose*

(Applies to all three corticosteroids.)

Methylprednisolone 2, 4, 8, 16, 32 mg tablets ■ 7.5–60 mg daily in a single dose Prednisolone 5 mg tablets, in a.m. or qod as needed for control 5 mg/5 cc, ■ Short-course “burst” to achieve 15 mg/5 cc control: 40–60 mg per day Prednisone 1, 2.5, 5, 10, 20, 50 mg tablets; as single or 2 divided doses for 5 mg/cc, 5 mg/5 cc 3–10 days

• 0.25–2 mg/kg daily in single dose in a.m. or qod as needed for control
• Short-course “burst”: 1–2 mg/kg/day, maximum 60 mg/day for 3–10 days

(Should not be used for symptom relief or for exacerbations. Use with inhaled corticosteroids.)

Salmeterol MDI 21 mcg/puff 2 puffs q 12 hours DPI 50 mcg/blister 1 blister q 12 hours Formoterol DPI 12 mcg/single-use capsule 1 capsule q 12 hours

Combined Medication Fluticasone/Salmeterol DPI 100, 250, or 1 inhalation bid; dose depends on 500 mcg/50 mcg severity of asthma

Cromolyn and Nedocromil Cromolyn MDI 1 mg/puff 2–4 puffs tid-qid Nebulizer 20 mg/ampule 1 ampule tid-qid Nedocromil MDI 1.75 mg/puff 2–4 puffs bid-qid

Leukotriene Modifiers Montelukast 4 or 5 mg chewable tablet 10 mg qhs 10 mg tablet

Zafirlukast 10 or 20 mg tablet 40 mg daily (20 mg tablet bid) Zileuton 300 or 600 mg tablet 2,400 mg daily (give tablets qid)

Methylxanthines (Serum monitoring is important [serum concentration of 5–15 mcg/mL at steady state]). Theophylline Liquids, sustained-release Starting dose 10 mg/kg/day up to tablets, and capsules 300 mg max; usual max 800 mg/day

1–2 puffs q 12 hours 1 blister q 12 hours 1 capsule q 12 hours

1 inhalation bid; dose depends on severity of asthma

1–2 puffs tid-qid 1 ampule tid-qid 1–2 puffs bid-qid

4 mg qhs (2–5 yrs) 5 mg qhs (6–14 yrs) 10 mg qhs (> 14 yrs) 20 mg daily (7–11 yrs) (10 mg tablet bid)

Starting dose 10 mg/kg/day; usual max:

• < 1 year of age: 0.2 (age in weeks) + 5 = mg/kg/day
• ≥ 1 year of age: 16 mg/kg/day

Estimated Comparative Daily Dosages for Inhaled Corticosteroids

Low Daily Dose Medium Daily Dose Drug Adult Child* Adult Child*

High Daily Dose Adult Child*

336–672 mcg Beclomethasone CFC 168–504 mcg 84–336 mcg 504–840 mcg 42 or 84 mcg/puff

> 840 mcg > 672 mcg

160–320 mcg Beclomethasone HFA 80–240 mcg 80–160 mcg 240–480 mcg 40 or 80 mcg/puff

> 480 mcg > 320 mcg

400–800 mcg Budesonide DPI 200–600 mcg 200–400 mcg 600–1,200 mcg 200 mcg/inhalation

Inhalation suspension for 0.5 mg 1.0 mg nebulization (child dose)

> 1,200 mcg > 800 mcg

2.0 mg

1,000–1,250 mcg Flunisolide 500– 500–750 mcg 1,000– 250 mcg/puff 1,000 mcg 2,000 mcg

> 2,000 mcg > 1,250 mcg

176–440 mcg Fluticasone 88–264 mcg 88–176 mcg 264–660 mcg MDI: 44, 110, or 220 mcg/puff

> 660 mcg > 440 mcg

200–400 mcg DPI: 50, 100, or 250 mcg/ 100–300 mcg 100–200 mcg 300–600 mcg inhalation

Triamcinolone acetonide 400–1,000 mcg 400–800 mcg 1,000–2,000 mcg

> 600 mcg > 400 mcg

800–1,200 mcg 100 mcg/puff

• Children ≤ 12 years of age

> 2,000 mcg > 1,200 mcg