Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms

INTRODUCTION — Quick-relief (also called rescue or acute symptom relief) medications are primarily taken to relieve the bronchoconstriction that occurs with acute asthma symptoms (eg, wheeze, cough, chest tightness, shortness of breath), although some agents may have additional effects. Quick-relief agents include short-acting beta agonists (SABAs), rapid-onset long-acting beta agonists (LABAs) either alone or in combination with an inhaled glucocorticoid, and an anticholinergic bronchodilator (eg, ipratropium bromide) alone or in combination with a SABA.

Medications initiated by the patient/caregiver for the quick relief of asthma symptoms in children younger than 12 years of age are reviewed here. The recommendations below are based upon National Asthma Education and Prevention Program (NAEPP) expert panel guidelines published in 2007 [1] and updated in 2020 [2] and Global Initiative for Asthma (GINA) 2020 guidelines [3], which are similar to other major published asthma guidelines. (See 'Society guideline links' below.)

Home management of more significant symptoms associated with an asthma exacerbation are reviewed in detail separately. The outpatient and hospital management of acute asthma exacerbations in children are also discussed in detail elsewhere. (See "Acute asthma exacerbations in children younger than 12 years: Overview of home/office management and severity assessment" and "Acute asthma exacerbations in children younger than 12 years: Emergency department management" and "Acute asthma exacerbations in children younger than 12 years: Inpatient management" and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management".)

Prophylactic use of SABAs prior to anticipated triggers (eg, exercise, allergen exposure) is discussed in detail separately. (See "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Use in exercise-induced asthma' and "Exercise-induced bronchoconstriction" and "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Allergen-induced asthma'.)

TYPES OF QUICK-RELIEF MEDICATIONS — Short-acting beta agonists (SABAs) are the most commonly used medications for the quick relief of acute asthma symptoms [1-3]. Other medications used in select patient populations include a combination of an inhaled glucocorticoid and a rapid-onset, long-acting beta agonist (LABA; eg, budesonide-formoterol) and the anticholinergic agent ipratropium bromide in combination with a SABA.

Short-acting beta agonists (SABAs)

Specific preparations

●Racemic albuterol – A racemic mixture of albuterol (salbutamol) is the primary SABA used for quick relief of acute asthma symptoms and exacerbations.

●Levalbuterol – Levalbuterol (Levosalbutamol), the R-enantiomer, is the active isomer of racemic albuterol that confers the bronchodilator effects. Levalbuterol is approved in the United States for treatment of bronchospasm in children ≥4 years of age via hydrofluoroalkane (HFA) metered-dose inhaler (MDI) and ≥6 years of age via solution for nebulization.

Available data do not support widespread use of levalbuterol instead of racemic albuterol as a quick-relief medication. Some studies have demonstrated favorable efficacy and safety profiles for levalbuterol compared with racemic albuterol, including one in which the hospitalization rate was lower among children who received levalbuterol in the emergency department (ED; 36 versus 45 percent) [4-7]. However, overall clinical studies suggest no meaningful benefits of levalbuterol over racemic albuterol [8-11]. The 2007 National Asthma Education and Prevention Program (NAEPP) guidelines suggest that levalbuterol provides clinically comparable bronchodilation and systemic side effects as racemic albuterol [1].

●Other SABAs – Other SABAs used in the management of childhood asthma include terbutaline, clenbuterol, and fenoterol. Inhaled forms of these medications are available in some countries (not the United States), although not all are approved for use in children younger than 12 years.

Route of delivery

●Inhaled – Inhaled SABAs (table 1) have the advantages of lower doses, fewer side effects, and more rapid onset of action than oral agents [12].

Inhaled SABAs are typically administered by an MDI (through a valved holding chamber if an aerosol, but not if an inhalation powder) or by nebulization, along with an infant- or child-sized mask as appropriate for size and developmental age [13]. A number of factors influence the amount of drug actually deposited in the lower airways with either of these methods [14]. In general, administration by MDI is preferred, although this is based upon ED data in which higher doses of SABA are typically used compared with home administration (4 to 12 puffs rather than 2 puffs) [15]. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Inhaled short-acting beta-2 agonists' and "Delivery of inhaled medication in children", section on 'Factors affecting drug deposition' and "Use of medication nebulizers in children" and "The use of inhaler devices in children".)

A dry powder inhaler (DPI) SABA is also available for children ≥4 years of age [16]. However, it is not known whether an acute exacerbation reduces inspiratory flow enough in this age group to reduce drug delivery when using a DPI. Thus, the authors are comfortable with DPI SABA use for prophylactic treatment prior to exercise in those who can demonstrate proper use of the device but would not advise its use in the acute setting as rescue therapy.

It is important for patients who use inhalers to know how to tell when the inhaler is near empty to ensure that they will have access to bronchodilator therapy during an acute exacerbation. Many MDIs now have a built-in counter. Patients should only use the actuator supplied with the MDI (if they have more than one SABA inhaler, such as one for home and one for camp or school) to ensure that the count is accurate. (See "The use of inhaler devices in children", section on 'Determining when an MDI is empty'.)

●Oral – Oral beta agonists (albuterol) are no longer used for quick-relief treatment because they have more frequent and greater systemic effects, such as tachycardia, tremor, and behavioral and sleep disturbance, and a slower onset of action compared with inhaled SABAs.

Dosing — The usual doses of inhaled SABAs used for intermittent asthma symptoms are reviewed in the table (table 1). Higher doses with shorter dosing intervals are often used for more significant acute asthma exacerbations, particularly when administered in the ED or inpatient setting (table 2). Uses of SABAs in these settings is discussed in greater detail separately. (See "Acute asthma exacerbations in children younger than 12 years: Overview of home/office management and severity assessment", section on 'Home management' and "Acute asthma exacerbations in children younger than 12 years: Overview of home/office management and severity assessment", section on 'Outpatient management' and "Acute asthma exacerbations in children younger than 12 years: Inpatient management", section on 'Management of bronchospasm' and "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Inhaled short-acting beta-2 agonists'.)

Use of SABAs for exercise-induced bronchoconstriction is discussed in detail separately. (See "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Use in exercise-induced asthma' and "Exercise-induced bronchoconstriction", section on 'Pre-exercise treatments for EIB'.)

Adverse effects — The most common side effects are tremor, increased heart rate, and palpitations. SABAs should not be prescribed on a regular schedule, because of concerns about a possible relationship between the frequent use of these agents and deteriorating asthma control [1,17]. In addition, scheduled use prevents assessment of frequency of need based upon signs and symptoms, an important element in evaluating the status of an exacerbation. Decreased sensitivity or tolerance to beta agonists with chronic use (tachyphylaxis) is primarily mediated by downregulation of beta-2 adrenergic receptors. Various factors associated with bronchodilator unresponsiveness include genetics [18], obesity [19], and stress [20]. Beta agonist toxicity and tolerance are discussed in detail separately. (See "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Adverse effects' and "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Tolerance' and "Severe asthma phenotypes", section on 'Asthma associated with obesity' and "Genetics of asthma".)

Combination inhaled glucocorticoid and beta agonist — Clinical studies have shown that use of inhaled glucocorticoids in conjunction with beta agonists in patients with acute severe asthma can enhance bronchodilator response to beta agonists by reversing beta receptor desensitization and downregulation [21]. In a reciprocal manner, beta agonists influence the activated glucocorticoid receptors. These findings have led to the use of inhaled glucocorticoids with a SABA or a rapid-onset LABA for acute symptoms in select patient populations with asthma. The inhaled glucocorticoid (table 3) and SABA (table 1) are used at standard doses. The LABA most extensively studied for single maintenance and reliever therapy (SMART) is formoterol, which has a rapid onset of action and a maximum daily dose that allows for more than twice a day use. The maximum daily dose of formoterol in children 4 to 11 years of age is 36 micrograms, equivalent to 8 puffs of budesonide-formoterol MDI. While this dosing is off label, it is supported by national and international guidelines and clinical trials (table 4A-B) [2,3] (see 'Acute symptoms in patients with persistent asthma' below). Other inhaled glucocorticoid-formoterol combinations that are available in some countries but that have not been studied or approved for SMART and have slightly higher doses of formoterol are mometasone-formoterol and beclomethasone-formoterol. Adverse effects from inhaled glucocorticoids are infrequent with intermittent use. The adverse effects of inhaled glucocorticoids are discussed in detail separately. (See "Molecular effects of inhaled glucocorticoid therapy in asthma", section on 'Beta 2-receptor effects' and "Major side effects of inhaled glucocorticoids".)

Ipratropium bromide — Ipratropium bromide is an anticholinergic drug that provides bronchodilation through smooth muscle relaxation [22]. However, it has a slower onset of action than SABAs. It begins to work within 15 to 30 minutes, with a maximum effect seen within one to two hours. Inhaled anticholinergics used on their own are less effective than inhaled beta agonists used alone or in combination with anticholinergics [23]. Ipratropium can be administered via MDI and spacer or via nebulizer. Potential adverse effects of ipratropium bromide include drying of the mouth, blurred vision, urinary retention, tachycardia, and central nervous system effects. Ipratropium is commonly used in combination with a SABA for asthma exacerbations treated in the ED. It is occasionally used in combination with albuterol for quick relief of acute symptoms in patients with asthma who have demonstrated a prior favorable response. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Ipratropium bromide'.)

Nonstandard therapies — Experimental and alternative therapies, including over-the-counter products such as homeopathic treatments [24] and racemic epinephrine inhalers [25-27], are not recommended for routine care of acute asthma symptoms. These therapies are discussed in greater detail separately. (See "Acute exacerbations of asthma in adults: Home and office management", section on 'Risks associated with inhaled epinephrine' and "Investigational agents for asthma" and "Complementary, alternative, and integrative therapies for asthma".)

QUICK-RELIEF TREATMENT

Overview — Short-acting beta agonists (SABAs) such as albuterol (salbutamol) and levalbuterol (levosalbutamol) remain a cornerstone of the treatment of childhood asthma (table 4A-B) [1-3]. SABAs relax airway smooth muscle, reducing constriction, which leads to a prompt increase in airflow [28-33]. These drugs generally provide rapid relief of acute asthma symptoms (eg, coughing, wheezing, chest tightness, and shortness of breath), with a time to onset of action of approximately 5 to 10 minutes, peak effect beginning within approximately 50 minutes, and duration of action of approximately three to six hours. SABAs are the standard emergency treatment for acute asthma exacerbations in all patients based upon adult data, a few early trials in children, and many ensuing years of clinical use. By extrapolation, as-needed use of these drugs is also the primary therapy for acute symptoms in patients with intermittent asthma. (See "Beta agonists in asthma: Acute administration and prophylactic use" and "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Inhaled short-acting beta-2 agonists'.)

Acute symptoms in patients with intermittent asthma/wheezing — We suggest a SABA as needed for acute symptoms in all children with intermittent asthma (table 4A-B) [1-3]. Taking a low-dose inhaled glucocorticoid whenever a SABA is used is an alternative to a SABA alone in children >5 years of age. A short course of a high-dose inhaled glucocorticoid starting at the onset of a respiratory illness for 7 to 10 days in addition to a SABA as needed may be used in patients ≤4 years of age with intermittent virus-induced wheezing. This approach to treatment of recurrent virus-induced wheezing in young children is discussed in greater detail separately. (See "Treatment of recurrent virus-induced wheezing in young children", section on 'Episodic therapy'.)

Acute symptoms in patients with persistent asthma — We recommend an as-needed SABA for quick-relief therapy in the following patients (table 4A-B) [1-3]:

●Children <4 years of age with any severity of persistent asthma

●Children 4 to 11 years of age with mild persistent asthma

●Children 4 to 11 years of age with severe persistent asthma on step 5 or step 6 therapy

For children ≥4 years of age with moderate-to-severe persistent asthma on step 3 or step 4 therapy, we suggest an inhaled glucocorticoid combined with a rapid-onset long-acting beta agonist (LABA; eg, formoterol) for both daily and quick-relief therapy (single maintenance and reliever therapy [SMART]) rather than a SABA for quick-relief therapy. The goal of SMART is to both treat acute symptoms and prevent exacerbations. It is reasonable to continue a SABA for quick-relief therapy in patients whose asthma is adequately controlled on a daily combination inhaled glucocorticoid-LABA.

The recommendations for SMART are largely based upon adolescent and adult data. One post-hoc analysis of data from a larger randomized trial that included 341 children 4 to 11 years of age (118 on budesonide-formoterol 80-4.5 microg once daily with up to seven additional quick-relief puffs daily [SMART]; 117 on budesonide-formoterol 80-4.5 microg once daily with a SABA, terbutaline, as needed for quick relief; and 106 on budesonide 320 microg daily with terbutaline for quick relief) was performed [34,35]. Compared with the other treatment groups, children on SMART had fewer exacerbations (14 versus 38 and 26 percent, respectively) and courses of oral glucocorticoids (0.05 versus 0.3 and 0.25 courses/year, respectively), as well as a longer time to first severe exacerbation. Growth was also significantly better in the two groups of children on budesonide-formoterol versus the higher daily dose of budesonide (approximately 1 cm adjusted mean difference in growth). (See "Initiating asthma therapy and monitoring in adolescents and adults", section on 'Low-dose maintenance and reliever therapy (MART)' and "Initiating asthma therapy and monitoring in adolescents and adults", section on 'Preferred options' and "Ongoing monitoring and titration of asthma therapies in adolescents and adults", section on 'Increasing (stepping up) therapy, for persistent poor symptom control'.)

Acute exacerbations — The initial at-home approach to treatment of acute exacerbations is similar to that for isolated acute symptoms outlined above. Home management of more significant symptoms associated with an asthma exacerbation are reviewed in detail separately. The outpatient, emergency department (ED), and hospital management of acute asthma exacerbations in children are also discussed in detail elsewhere. (See "Acute asthma exacerbations in children younger than 12 years: Overview of home/office management and severity assessment" and "Acute asthma exacerbations in children younger than 12 years: Emergency department management" and "Acute asthma exacerbations in children younger than 12 years: Inpatient management" and "Acute severe asthma exacerbations in children younger than 12 years: Intensive care unit management".)

Prophylaxis — SABAs can be used preventively in patients with well-controlled asthma who have symptoms with exercise and/or allergen exposure. An alternative in adolescents and adults is a combination inhaled glucocorticoid and rapid-onset LABA, but this option has not been adequately studied in younger children. LABAs should not be used as monotherapy. Ipratropium is generally not used due to its slower onset of action. Prophylactic use of SABAs prior to anticipated triggers (eg, exercise, allergen exposure) is discussed in detail separately. (See "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Use in exercise-induced asthma' and "Exercise-induced bronchoconstriction", section on 'Pre-exercise treatments for EIB' and "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Allergen-induced asthma'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Asthma in children (The Basics)" and "Patient education: How to use your child's metered dose inhaler (The Basics)")

●Beyond the Basics topic (see "Patient education: Asthma treatment in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Roles and types of quick-relief asthma medications – Quick-relief medications are primarily taken to relieve the bronchoconstriction that occurs with acute asthma symptoms, although some agents may have additional effects. The most commonly used quick-relief agents are a short-acting beta agonist (SABA) alone, a SABA plus an inhaled glucocorticoid, and a rapid-onset long-acting beta agonist (LABA) in combination with an inhaled glucocorticoid. (See 'Introduction' above and 'Types of quick-relief medications' above.)

●Short-acting beta agonists – Inhaled SABAs are the mainstay of management of acute asthma symptoms and exacerbations (table 1). These drugs generally provide rapid relief of acute asthma symptoms (eg, coughing, wheezing, chest tightness, and shortness of breath). (See 'Short-acting beta agonists (SABAs)' above.)

●Combined glucocorticoids and beta agonists – Inhaled glucocorticoids and beta agonists work in a reciprocal manner, enhancing the response to the other drug when used concomitantly. (See 'Combination inhaled glucocorticoid and beta agonist' above.)

●Approach to quick-relief therapy – Our suggested approach to providing quick-relief (rescue) therapy for children with asthma is as follows:

•Moderate-to-severe persistent asthma – For children 4 to 11 years of age with moderate-to-severe persistent asthma on step 3 or step 4 therapy, we suggest an inhaled glucocorticoid combined with a rapid-onset LABA (eg, formoterol) for both daily and quick-relief therapy (single maintenance and reliever therapy [SMART]) rather than a SABA for quick-relief therapy (Grade 2C). For children 4 to 11 years of age with severe persistent asthma on step 5 or 6 therapy, we suggest a SABA for quick-relief therapy rather than SMART (Grade 2C). (See 'Acute symptoms in patients with persistent asthma' above.)

•Intermittent and mild persistent asthma – For most children with less severe asthma (step 1 or step 2) who require quick-relief (rescue) medication, we suggest treatment with a SABA alone rather than in combination with an inhaled glucocorticoid (Grade 2C). Taking a low-dose inhaled glucocorticoid whenever a SABA is used is an alternative to a SABA alone in children >5 years of age who are not on daily controller therapy. (See 'Acute symptoms in patients with persistent asthma' above and 'Acute symptoms in patients with intermittent asthma/wheezing' above.)

•Young children with intermittent virus-induced wheezing - In young children (≤4 years old) with intermittent virus-induced wheezing, a short course of a high-dose inhaled glucocorticoid may be used starting at the onset of a respiratory illness in addition to as-needed SABA. This is discussed separately. (See "Treatment of recurrent virus-induced wheezing in young children", section on 'Intermittent preventive therapy'.)