Asthma in Children

History

• Dyspnea with activity or caregiver notices any of the following: ^c1
  • Exercise intolerance ^c2
  • Self-imposed activity restrictions ^c3
  • Inability to take a deep breath ^c4
  • More fatigued from play; cannot keep up with peers ^c5
• Dyspnea at rest ^c6
• Nocturnal dyspnea ^c7
• Nocturnal awakening with any of the following:
  • Chest tightness ^c8
  • Dry cough ^c9
  • Poor or impaired sleep ^c10
• Cough may be a predominant symptom ^c11c12
  • However, in children, chronic cough (for more than 4 weeks) with no other symptoms is unlikely to represent asthma ^r17
• Recurrence of episodes with exposure to possible triggers ^c13
  • Respiratory infection
  • Inhaled allergens
  • Cold, dry weather
  • Transition from hot to cold environment
  • Passive (or active) tobacco smoke exposure
  • Hydrocarbon fumes (eg, in homes with gas stoves or kerosene heaters)
  • Exposure to other triggers (eg, food allergies, house dust, ozone air pollution, mold spores, cockroach frass, rodent scat)
  • Exacerbations most common in early September, least common in summer months ^r10
• For a patient with known diagnosis of asthma, assess previous disease control based on:
  • Level of adherence to treatment plans
  • Frequency of short-acting β₂-agonist use
  • Steroid use
  • Number and severity of exacerbations in the past year
  • Previous hospital admissions and admission course (especially the need for ICU level of care and intubation)
• Personal or family history of eczema, allergies, or asthma ^{c14c15c16c17c18c19}
• Inner-city residence ^c20

Physical examination

• Typically normal findings in patients with well-controlled asthma
• With exacerbation, findings are variable depending on severity of airflow obstruction and comorbidities
• General appearance
  • Anxiety or agitation ^c21c22
  • Drowsiness with impending respiratory failure ^c23
  • Ability to speak may be impaired ^c24
  • Struggling to breathe ^c25
  • Posture: upright versus lying down ^c26
• Vital signs
  • Tachypnea and tachycardia with severe exacerbation ^c27c28
  • Diminished oxygen saturation is variable with moderate to severe exacerbation ^c29
• Prolonged expiratory phase with exacerbation ^c30
  • Forced expiration precipitates bronchospasm as evidenced by a coughing spell
• Labored breathing, use of respiratory accessory muscles with intercostal recession, and nasal flaring ^c31c32c33
• Wheezing is usually present during exacerbation, but absence of wheezing does not rule out significant bronchospasm ^c34
  • Poor air movement is a sign of impending respiratory failure ^c35
• Cyanosis and diaphoresis with significant hypoxia ^c36c37
• Findings consistent with concomitant disease commonly found in children who also have asthma
  • Allergic rhinitis: increased nasal secretions, swollen turbinates, allergic shiners, and nasal polyps ^c38c39c40
  • Eczema: characteristic chronic dry skin with breakdown in typical eczema distribution ^c41

Causes

• Underlying cause is incompletely understood; may be environmental in combination with genetic interaction ^c42
  • Environmental insult may be allergen, infectious agent, or airborne irritant (eg, air pollution)
  • Parental asthma or allergy history may be the most important factor
• Exacerbation triggers ^c43
  • Aeroallergens (eg, pollen, pet dander, dust, dust mites, mold spores, cockroach frass) ^c44
  • Airborne irritants (eg, cigarette or wood smoke, air pollution, chemical compounds) ^c45
  • Respiratory infection ^c46
  • Drugs (eg, NSAIDs including aspirin, β-blockers) ^c47
  • Ingested substances (eg, foods, sulfites) ^c48
  • Psychological or emotional stress ^c49c50
  • Cold, dry air (eg, weather change) ^c51c52
  • Exercise ^c53

Risk factors and/or associations

Primary diagnostic tools

• New diagnosis
  • History and physical examination consistent with asthma (ie, episodic airflow obstruction and airway hyperresponsiveness) and documentation of reversible airway obstruction support the diagnosis ^r1r3c74
    • Documentation of reversible airway obstruction
      • Patients younger than 5 years ^r1
        • Diagnosis is challenging in this age group because objective measurements of lung function are difficult to obtain ^r1
          • Documentation of episodic clinical response to bronchodilator therapy is a good indicator of reversible airway obstruction
          • Spirometry may not be feasible owing to patient cooperation or comprehension ^c75
          • Broncho provocation can be assessed by a trained specialist, but is not commonly performed in young children ^c76
          • Impulse oscillometry, if available, measures respiratory impedance, requires little cooperation, and documents reversible obstruction ^c77
      • Patients aged 5 years or older ^r1
        • Obtain spirometry to show reversible airflow obstruction after trial of bronchodilator ^r17c78
        • Response to a therapeutic trial of inhaled corticosteroids supports the diagnosis in symptomatic children with abnormal spirometry and negative bronchodilator response; repeat spirometry after 4 to 8 weeks ^r17c79
        • Bronchoprovocation may be performed when asthma is suspected and spirometry results are within (or nearly within) the reference range ^c80
        • Measurement fraction of exhaled nitric oxide can be useful to support diagnosis of asthma ^r17c81
      • Exercise-induced asthma ^r1
        • Exercise provocation testing with FEV₁ or peak expiratory flow documentation ^c82
        • Diagnosis confirmed by a positive response to asthma medications ^c83
  • Consider and exclude alternative diagnoses ^c84
    • Important at time of initial diagnosis and if there is no clear response to therapy
    • Younger the child is at time of initial concern for asthma (eg, wheezing), the higher the possibility of alternative diagnosis (eg, gastrointestinal reflux, cystic fibrosis, aspiration syndrome, immune deficiency, congenital heart disease, bronchopulmonary dysplasia) ^r13
  • Imaging and additional diagnostic testing do not typically add to the initial diagnostic workup
    • Chest radiography ^r1c85
      • Indicated only to exclude or support presence of other conditions (eg, in a patient whose condition fails to respond to conventional therapy or in a patient with wheezing and atypical clinical presentation that suggests alternative diagnosis)
        • Atypical features include a history of symptoms starting at or shortly after birth, continuous wheezing, wheezing unresponsive to bronchodilators, failure to thrive, digital clubbing, and wheezing not associated with typical asthma triggers
    • CT scan (and sometimes bronchoscopy) ^c86c87
      • Performed in rare circumstances when response to conventional therapy is poor
    • Evaluation for atopic disease ^r3
      • Expert consensus recommends evaluating for atopy when there is suspicion or diagnosis of asthma, particularly for patients with persistent or increasingly severe asthma ^r1
      • Identification of specific allergic sensitizations can support diagnosis, can indicate avoidable disease triggers, and has prognostic significance
      • Both in vivo methods (eg, skin prick test) and in vitro methods (eg, specific IgE antibodies) can be used
• Acute exacerbation
  • Obtain peak expiratory flow measurement ^c88
  • Obtain pulse oximetry for noninvasive SaO₂ monitoring ^c89
    • Arterial blood gas tests are rarely indicated ^r1c90
  • Obtain chest radiograph if complicating chest infection suspected, hospitalization required, or diagnosis is uncertain ^r11c91
  • Laboratory testing adds little in most patients
    • CBC demonstrating elevated WBC count may suggest infection ^c92
  • Exacerbations in outpatient specialist setting ^r1
    • Consider the following:
      • Total serum IgE level, serum-specific IgE, or both to diagnose allergic rhinitis as a trigger ^c93
      • Fraction of exhaled nitric oxide ^c94
• Multiple resources are available to assist with the diagnostic process, including:
  • NAEPP (National Asthma Education and Prevention Program) guidelines and NIH Asthma Care Quick Reference ^r1r8r21
  • GINA (Global Initiative for Asthma) guidelines and resources ^r22
  • European Respiratory Society guidelines for diagnosis of asthma in children aged 5 to 16 years ^r17
  • European Respiratory Society Task Force evidence-based approach to assessment and treatment of wheezing in preschool children ^r23
  • Canadian Thoracic Society guidelines for preschoolers and for children and adults ^r24r25
  • National Institute for Health and Care Excellence asthma pathway and guidelines ^r9

Functional testing

• Spirometry (objective measure of FEV₁ in patients aged 5 years or older) ^r1c95
  • Obtain at initial assessment (to evaluate for objective signs of reversible airway obstruction), after treatment has started, and when symptoms and peak expiratory flow have stabilized
  • Measure during periods of prolonged loss of asthma control and at least every 1 to 2 years for a patient with stable disease
  • In children aged 5 to 16 years, a diagnosis of asthma diagnosis is supported by: ^r17
    • FEV₁/FVC ratio less than the lower reference limit or less than 80% predicted
    • FEV₁ less than the lower reference limit or less than 80% predicted
      • Indicates current obstruction and risk for future exacerbation
  • Normal spirometry result does not exclude asthma
  • Bronchodilator reversibility testing should be performed in children with FEV₁ and/or FEV₁/FVC findings supportive of asthma diagnosis; also consider if spirometry is normal but clinical history is highly suggestive ^r17
  • Reversibility is determined by an increase in FEV₁ of more than 200 mL or 12% or more from baseline measure, or 10% or more predicted after inhalation of short-acting β₂-agonist ^r1r17
    • A change of less than 12% from baseline does not exclude asthma
• Peak expiratory flow (objective measure of airway obstruction) ^r1c96
  • Measure at baseline
  • Determine personal best when asthma is stable
  • Monitor for worsening or improvement at home
• Bronchoprovocation testing ^r1c97
  • Performed with methacholine or exercise challenge (if exercise-induced asthma suspected); can be useful when asthma is suspected and spirometry results are within (or nearly within) the reference range ^r17
  • Performed by an asthma care specialist or other trained person (for safety reasons)
  • Positive test result is diagnostic for airway hyperresponsiveness, which is characteristic of asthma although not specific to it
  • Negative test result is helpful to exclude the diagnosis of asthma
• Fraction of exhaled nitric oxide ^r26c98
  • Simple, noninvasive test
  • A positive test suggests the presence of eosinophilic inflammation and supports an asthma diagnosis but is not conclusive ^r27
    • A negative test does not exclude asthma ^r17r27
  • Sensitivity is 79% and specificity is 81% for detection of asthma in children ^r28
  • European Respiratory Society recommends measurement of FeNO as part of the diagnostic workup for the diagnosis of asthma in children aged 5 to 16 years; has not been standardized in children younger than 4 years ^r17r23
    • FeNO value of 25 ppb or higher in a child with asthma symptoms is supportive of diagnosis of asthma
  • NAEPP recommends use as an adjunct to diagnosis in patients aged 5 years and older in whom diagnosis of asthma remains uncertain based on history, clinical findings, clinical course, and spirometry (or if spirometry cannot be performed), including bronchodilator responsiveness testing ^r21
  • British guidelines recommend offering this as a diagnostic test for all adults, with a level 40 parts per billion or higher, supporting diagnosis of asthma ^r27
  • American Thoracic Society recommends measuring the fraction of exhaled nitric oxide at time of diagnosis ^r26c99
  • 2021 GINA guidelines do not consider this test useful in the diagnosis of asthma ^r11
• Impulse oscillometry ^c100
  • Simple, noninvasive test; uses sound waves to measure respiratory mechanics
  • Test is performed easily in children younger than 5 years because testing requires minimal cooperation ^r29
  • Detects obstruction in large and small peripheral airways; measures airway hyperreactivity (eg, bronchodilator response, response to bronchoprovocation testing); may be useful to predict loss of asthma control ^r30
  • May be more sensitive than spirometry to detect subtle changes in airway function and detects distal changes in airway function when spirometry results are normal ^r30
  • Interpretation of results is less straightforward than with spirometry
  • Findings consistent with asthma include: ^r30
    • Elevated R5 (resistance at 5 Hz), AX (area of reactance), and Fres (resonant frequency) and more negative X5 (reactance at 5 Hz) indexes
    • Improvement in airway resistance after bronchodilator administration
    • Increase in R5, R20 (resistance at 20 Hz), and Fres with a decrease in X5 with bronchoprovocation testing
    • Abnormal peripheral airway impulse oscillometry indexes in children considered to have otherwise controlled asthma represent risk for losing asthma control

Most common

• Vocal cord dysfunction (paradoxical vocal cord motion disorder) ^r31c101c102
  • Vocal cord dysfunction is frequently misdiagnosed as asthma, which leads to mismanagement (eg, unnecessary intubation, use of continuous maintenance oral corticosteroids, otherwise preventable hospital admissions, emergency department visits) ^r32
  • Symptoms include episodic dyspnea that mimics an asthma exacerbation, anxiety, wheezing, and/or inspiratory or biphasic stridor
  • Paroxysmal episodes of vocal cord adduction primarily during inspiration, possibly expiration, can be triggered by exercise or stress, though they may occur spontaneously; inspiratory stridor favors an extrathoracic cause for dyspnea
  • Vocal cord dysfunction can coexist with asthma;^r32 consider vocal cord dysfunction in any patient with asthma that is difficult to treat or atypical and in athletes with exercise-related dyspnea unresponsive to bronchodilators ^r1
  • Spirometry can support the diagnosis with flattening of the inspiratory flow-volume loops when symptoms are present; there is no improvement with bronchodilators
  • Differentiated from asthma by history, physical examination, and lack of response to asthma medication
  • Diagnosis can be made by documenting abnormal vocal cord adduction by indirect or direct visualization during an acute episode ^r32
• Congenital malformation of airway (eg, laryngotracheomalacia, bronchomalacia, laryngeal web, tracheoesophageal fistula, vascular malformation) ^{c103c104c105c106c107c108c109}
  • Presents during infancy with history of cough, stridor, or wheezing (depending on anatomic location of anomaly); symptoms usually include chronic feeding difficulties
  • Symptom severity associated with a structural abnormality (eg, tracheomalacia) may change with activity or positional changes
    • Tracheomalacia may worsen with agitation or excitement and improve with prone positioning
  • Differentiated from asthma by fiberoptic bronchoscopy and by failure to respond to bronchodilators
• Foreign body aspiration ^c110
  • Typically affects toddlers; presentation includes acute onset of stridor, wheezing, or both after a choking, gagging, or coughing event
  • Physical signs can include stridor or unilateral wheezing on lung examination
  • Diagnosis can be aided by soft tissue neck and bilateral decubitus lung radiographs; fiberoptic laryngobronchoscopy is diagnostic
• Respiratory infection (eg, viral bronchiolitis, laryngotracheobronchitis, pneumonia) ^{c111c112c113c114}
  • Wheezing and increased work of breathing from a respiratory infection may be difficult to differentiate from a first-time asthmatic wheezing episode that is triggered by a respiratory infection ^d2
  • Nasal suctioning in younger children will improve work of breathing if bronchiolitis is a cause of respiratory distress ^d3
  • Bronchodilator trial will show reversibility of increased work of breathing or wheezing if caused by respiratory infection–induced asthma
• Bronchiectasis ^c115d4
  • Dilation of the intrathoracic airways with loss of structural integrity, usually secondary to chronic recurrent infection or inflammation owing to cystic fibrosis or primary immunodeficiency; bronchiectasis can develop with time as a complication of chronic severe persistent asthma
  • Similar to asthma, bronchiectasis presents with cough and wheezing
  • History of chronic cough, failure to thrive, and production of a large amount of purulent sputum predominate in children with bronchiectasis; pulmonary examination may find diffuse or localized crackles and digital clubbing
  • History and physical examination differentiate bronchiectasis from asthma; if the definitive diagnosis is in question, a chest CT scan will differentiate
• Cardiac causes for wheezing
  • Congestive heart failure can cause cough, fatigue, dyspnea on exertion, wheezing, and respiratory distress in children; infants classically present with diaphoresis and difficulty feeding ^c116d5
  • Onset is typically more insidious than that of asthma, and the patient has no family history or personal history of asthma
  • Bronchodilator trial will fail to reverse wheezing for cardiac causes
  • Cardiomegaly may be suggested by chest radiograph or EEG; diagnose by echocardiogram ^d6
  • Hepatomegaly and abnormal cardiac examination findings (eg, murmurs, rubs, gallops) differentiate cardiac causes of wheezing from asthma
• Mediastinal mass ^c117
  • Can present with insidious onset of cough, wheezing, orthopnea, and dysphagia; children often have history of failure to thrive
  • Physical examination sometimes shows signs of superior vena cava syndrome, pleural effusions, or both
  • Diagnosis is made by bronchodilator trial failure and chest radiography
• Gastroesophageal reflux ^r33c118
  • Can cause recurrent or chronic cough with or without wheezing; can result in chronic pulmonary disease
  • Symptoms are often worse at night; children often suffer from chronic hoarseness, laryngitis, and/or esophageal pain from reflux
  • Gastroesophageal reflux is suggested by the following: primarily nocturnal symptoms without other typical asthma triggers for symptoms, no family history of asthma, no personal history of eczema or allergic symptoms, lack of response to bronchodilators, and improved symptoms after treatment of gastroesophageal reflux
  • If the diagnosis is in question, an esophageal pH probe study is the most useful study to document temporal relationship between acid reflux and symptoms

Admission criteria

All age groups

• Admit if SaO₂ is lower than 92% to 94% on pulse oximetry 1 hour after treatments ^r1

Infants

• Lower threshold for admission of infants and very young children where objective measures of airway obstruction/improvement are not possible
• Admit if patient is in significant respiratory distress or continues to meet requirements for moderate to severe exacerbation 1 hour after third short-acting β₂-agonist treatment ^r1

Older children ^r1

• When FEV₁ or peak expiratory flow is at least 40% but lower than 69% after third short-acting β₂-agonist treatment, keep in observation unit (good likelihood of being able to discharge) or admit if no observation unit available
• Admit if FEV₁ or peak expiratory flow is lower than 40% after third short-acting β₂-agonist treatment
• Admit if dyspnea at rest interferes with conversation or the patient continues to meet requirements for moderate to severe exacerbation 1 hour after third short-acting β₂-agonist treatment

Recommendations for specialist referral

• Refer to an asthma specialist (usually a pulmonologist or an allergist) for the following patients: ^r1
  • Patient receiving step 4 or higher drug therapy
  • Patient younger than 4 years receiving step 3 drug therapy
  • Patient possibly requiring immunotherapy or omalizumab
  • Patient who has required more than 2 rounds of oral steroids in past year
  • Patient who has required hospitalization for asthma in past year
  • Patient in whom diagnosis is uncertain, whose symptoms are atypical, or for whom additional testing is indicated
• Refer to an allergist for allergy desensitization treatment ^r34c119

Drug therapy

• For acute asthma exacerbation
  • Short-acting β₂-agonists
    • Albuterol ^c120
      • Inhaler
        • Albuterol Pressurized inhalation, suspension; Infants, Children 1 to 5 years: 2 to 6 oral inhalations of 90 mcg/actuation (total: 180 to 540 mcg) every 20 minutes for first hour, then 2 to 3 oral inhalations (180 to 270 mcg) every hour as needed. Delivery should occur with a spacer and a mask. ^c121c122c123
        • Albuterol Pressurized inhalation, suspension; Children and Adolescents 6 to 17 years: 360 to 900 mcg (4 to 10 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes during the first hour for mild to moderate exacerbations. After the first hour, the dose required may vary from 360 to 900 mcg (4 to 10 actuations) every 3 to 4 hours up to 540 to 900 mcg (6 to 10 actuations) every 1 to 2 hours, or more often.
      • Nebulizer ^c124c125c126
        • Albuterol Sulfate Nebulizer solution; Infants† and Children† younger than 2 years: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that.
        • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that. Usual dose: 0.63 to 1.25 mg inhaled by nebulizer 3 to 4 times daily. If weight at least 15 kg: May give 2.5 mg inhaled by nebulizer 3 to 4 times daily, if needed.
        • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 2.5 mg every 3 to 4 hours up to 2.5 mg every 1 to 2 hours, or more often. Usual dose: 0.63 to 1.25 mg via nebulizer 3 to 4 times daily. If weight at least 15 kg: 2.5 mg may be given inhaled by nebulizer 3 to 4 times daily if needed and this dose may be more appropriate for acute exacerbation in children 6 years and older.
        • Albuterol Sulfate Nebulizer solution; Adolescents: 2.5 mg via inhaled by nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 2.5 mg every 3 to 4 hours up to 2.5 mg every 1 to 2 hours, or more often. Usual dose: 2.5 mg inhaled nebulizer 3 to 4 times daily.
    • Levalbuterol ^c127c128c129
      • Inhaler
        • Levalbuterol Tartrate Pressurized inhalation, suspension (45 mcg/puff); Infants and Children 0 to 12 years: 4 to 8 inhalations using a valved holding chamber and face mask every 20 minutes for 3 doses, then 4 to 8 puffs every 1 to 4 hours as needed ^r21
        • Levalbuterol Tartrate Pressurized inhalation, suspension (45 mcg/puff); Children and Adolescents 13 years and older: 4 to 8 inhalations every 20 minutes for up to 4 hours, then 4 to 8 puffs every 1 to 4 hours as needed ^r21
      • Nebulizer
        • Levalbuterol Hydrochloride Nebulizer solution; Infants† and Children† 5 years and younger: 1.25 mg via nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that.
        • Levalbuterol Hydrochloride Nebulizer solution; Children 6 to 11 years: 1.25 mg via nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that. Typical dose range: 0.31 mg to 0.63 mg via nebulizer 3 times daily, every 6 to 8 hours.
        • Levalbuterol Hydrochloride Nebulizer solution; Children and Adolescents 12 years and older: 1.25 mg via nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 1.25 mg every 3 to 4 hours and up to 1.25 mg every 1 to 2 hours, or more often. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3 times daily, every 6 to 8 hours.
  • Inhaled anticholinergics ^c130
    • Ipratropium
      • Ipratropium Bromide Pressurized inhalation, solution
        • Ipratropium Bromide Pressurized inhalation, solution; Infants and Children 5 years and younger: 160 mcg (approximately 9 actuations of 17 mcg/actuation) via oral inhalation every 20 minutes for up to 1 hour only, in conjunction with a SABA (e.g., albuterol) for moderate to severe asthma exacerbation in the emergency care setting if poor response to initial SABA alone.
        • Ipratropium Bromide Pressurized inhalation, solution; Children 6 to 12 years: 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) every 20 minutes as needed for up to 3 hours recommended for severe asthma exacerbation in the emergency care setting. Used in addition to SABA (e.g., albuterol).
        • Ipratropium Bromide Pressurized inhalation, solution; Adolescents: 136 mcg (8 actuations of 17 mcg/actuation) via oral inhalation every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting. Used in addition to SABA (e.g., albuterol).
    • Ipratropium Bromide Nebulizer solution ^c131
      • Ipratropium Bromide Nebulizer solution; Infants and Children 5 years and younger: 250 mcg via nebulizer every 20 minutes for up to 3 doses only (1 hour) has been recommended in conjunction with a SABA for moderate to severe asthma exacerbation in the emergency care setting in patients with poor response to initial SABA alone.
      • Ipratropium Bromide Nebulizer solution; Children 6 to 12 years: 250 to 500 mcg via nebulizer every 20 minutes for 3 doses, then as needed (for up to 3 hours) for initial management of severe asthma exacerbation in the emergency care setting. Used in addition to SABA (e.g., albuterol).
      • Ipratropium Bromide Nebulizer solution; Adolescents: 500 mcg via nebulizer every 20 minutes for 3 doses, then as needed (for up to 3 hours) has been recommended for severe asthma exacerbation in the emergency care setting. Used in addition to SABA (e.g., albuterol).
    • Ipratropium-albuterol combination product
      • Albuterol-ipratropium ^c132
        • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Infants and Children 0 to 5 years: 1.5 mL (0.25 mg ipratropium bromide; 1.25 mg albuterol) via nebulizer every 20 minutes for 3 doses only (up to 1 hour) has been recommended.
        • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 1.5 mL (0.25 mg ipratropium bromide; 1.25 mg albuterol) or 3 mL (0.5 mg ipratropium bromide; 2.5 mg albuterol) via nebulizer every 20 minutes for 3 doses, then as needed (usually every 4 to 6 hours) in the emergency care setting.
        • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Adolescents: 3 mL (0.5 mg ipratropium bromide; 2.5 mg albuterol per 3 mL) via nebulizer every 20 minutes for 3 doses, then as needed (usually every 4 to 6 hours).
  • Smooth muscle relaxant
    • Magnesium sulfate ^c133
      • Magnesium Sulfate Solution for injection; Infants, Children, and Adolescents: 25 to 75 mg/kg (Max: 2 g/dose) IV infusion as a single dose over 15 to 30 minutes.
      • Recommended option for severe exacerbation in children aged 2 years or older ^r11
  • Systemic β₂-agonists ^r1r42c134
    • Alternative to inhaled short-acting β₂-agonists for severe exacerbation if inhaled products unavailable; no proven advantage of systemic over inhaled therapy ^r1
    • Epinephrine (1 mg/mL) ^c135
      • Intramuscular
        • Epinephrine Hydrochloride Solution for injection; Infants and Children weighing less than 30 kg: 0.01 mg/kg/dose (Max: 0.3 mg/dose) IM every 5 to 15 minutes as needed for up to 3 injections.
        • Epinephrine Hydrochloride Solution for injection; Children and Adolescents weighing 30 kg or more: 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM every 5 to 15 minutes as needed for up to 3 injections.
      • Subcutaneous
        • Epinephrine Hydrochloride Solution for injection; Children 1 to 12 years: 0.01 mg/kg/dose (Max: 0.5 mg/dose) subcutaneously every 20 minutes for 3 doses may be given if an inhaled short-acting beta-agonist is not available.
        • Epinephrine Hydrochloride Solution for injection; Adolescents: 0.3 to 0.5 mg subcutaneously every 20 minutes for 3 doses.
    • Terbutaline (1 mg/mL) ^c136
      • Terbutaline Sulfate Solution for injection; Children 2 to 11 years†: 0.01 mg/kg/dose (Max: 0.25 mg) subcutaneously every 10 to 20 minutes for 3 doses or until IV infusion is initiated. May repeat intermittent injection every 2 to 6 hours as needed.
      • Terbutaline Sulfate Solution for injection; Children and Adolescents 12 to 17 years: 0.25 mg subcutaneously once; repeat in 15 to 30 minutes if no significant improvement. Max: 0.5 mg within a 4 hour period.
  • Systemic corticosteroids ^r1c137
    • Prednisone ^c138c139
      • Inpatient management
        • Prednisone Oral solution; Infants and Children 1 month to 11 years: 1 to 2 mg/kg/day PO in 1 or 2 divided doses until peak expiratory flow (PEF) is 70% of predicted or personal best. Total course of treatment may range from 3 to 10 days (usually 5 days). Max: 60 mg/day. Suggested age-based Max: 20 mg/day for less than 2 years of age; 30 mg/day for 3 to 5 years; 40 mg/day for 6 to 11 years.
        • Prednisone Oral tablet; Children and Adolescents 12 to 17 years: One recommendation is 40 mg/day or 1 mg/kg/day for 5 to 7 days; Max: 50 mg/day. Alternatively, 40 to 80 mg/day PO in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best; total course: 3 to 10 days.
      • Outpatient management
        • Prednisone Oral solution; Infants and Children less than 12 years: 1 to 2 mg/kg/day PO in 1 or 2 divided doses for 3 to 10 days (usually 5 days) or until patient achieves peak expiratory flow (PEF) of 80% of personal best or symptoms resolve. Max: 60 mg/day. Suggested age-based Max: 20 mg/day for less than 2 years of age; 30 mg/day for 3 to 5 years; 40 mg/day for 6 to 11 years.
        • Prednisone Oral tablet; Children and Adolescents 12 to 17 years: 40 to 60 mg/day PO given in 1 to 2 divided doses for 3 to 10 days or until patient achieves peak expiratory flow (PEF) of 80% of personal best or symptoms resolve. Another recommendation is 40 to 50 mg/day for 5 to 7 days (or 1 mg/kg/day); Max: 50 mg/day.
    • Methylprednisolone ^c140c141
      • Oral tablet
        • Methylprednisolone Oral tablet; Infants and Children 1 month to 11 years: 1 to 2 mg/kg/day PO in 1 to 2 divided doses for 3 to 10 days (usually 5 days). Max: 60 mg/day.
        • Methylprednisolone Oral tablet; Children and Adolescents 12 to 17 years: 40 to 80 mg/day PO in 1 to 2 divided doses for 3 to 10 days (usually 5 days).
      • Solution for injection (intravenous or Intramuscular)
        • Methylprednisolone Sodium Succinate Solution for injection; Infants and Children 1 month to 11 years: 1 to 2 mg/kg/day IV/IM in 2 divided doses until peak expiratory flow is 70% of predicted or personal best. Max: 60 mg/day. Alternatively, 1 mg/kg/dose every 6 hours for the first 24 hours.
        • Methylprednisolone Sodium Succinate Solution for injection; Children and Adolescents 12 to 17 years: 40 mg IV/IM once daily each morning for 5 to 7 days is adequate for most patients. Alternatively, 40 to 80 mg/day IV/IM in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best.
    • Dexamethasone ^c142c143
      • Oral
        • Dexamethasone Oral solution; Infants, Children, and Adolescents: 0.6 mg/kg/dose PO as a single dose or once daily for 2 days. Max: 16 mg/dose.
      • Solution for injection (intravenous or Intramuscular)
        • Dexamethasone Sodium Phosphate Solution for injection; Infants, Children, and Adolescents: 0.6 mg/kg/dose IV or IM as a single dose or once daily for 2 days. Max: 16 mg/dose.
• Chronic asthma
  • For relief of episodic wheezing (relievers)
    • Short-acting β₂-agonists
      • Albuterol ^c144c145
        • Inhaler ^c146c147
          • Albuterol Pressurized inhalation, suspension; Children and Adolescents 4 to 17 years: 180 mcg (2 actuations of 90 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. In some patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 1,080 mcg/day (12 actuations/day).
        • Nebulizer ^c148
          • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed. Those with more severe asthma may achieve a better initial response with the 1.25 mg dose. If weight at least 15 kg: may give up to 2.5 mg inhaled by nebulizer 3 to 4 times daily if needed.
          • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed. Those with more severe asthma, weight more than 40 kg, or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose. If weight at least 15 kg: May give up to 2.5 mg inhaled by nebulizer 3 to 4 times daily if needed.
          • Albuterol Sulfate Nebulizer solution; Adolescents: 2.5 mg inhaled by nebulizer 3 to 4 times daily as needed. Usual Max: 10 mg/day.
      • Levalbuterol (for patients intolerant of albuterol) ^c149c150
        • Inhaler
          • Levalbuterol Tartrate Pressurized inhalation, suspension; Children and Adolescents 4 years and older: 90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation every 4 to 6 hours as needed; in some patients 45 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (540 mcg/day).
        • Nebulizer
          • Levalbuterol Hydrochloride Nebulizer solution; Children 6 to 11 years: 0.31 to 0.63 mg via nebulizer 3 times daily as needed. Max: 3 doses/day.
          • Levalbuterol Hydrochloride Nebulizer solution; Children and Adolescents 12 to 17 years: 0.63 to 1.25 mg via nebulizer 3 times daily (every 6 to 8 hours) as needed. Max: 3 doses/day.
    • Combination inhaled corticosteroids plus fast-onset, long-acting β₂-agonist
      • Budesonide-formoterol combination product ^r21c151
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† 4 to 11 years: 1 or 2 oral inhalations twice daily (80 mcg budesonide/4.5 mcg formoterol per inhalation) as controller therapy, plus 1 to 2 additional inhalations/dose as needed for reliever therapy. NAEPP Max: 8 oral inhalations/day (max formoterol: 36 mcg/day).
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† and Adolescents† 12 to 17 years: 1 or 2 oral inhalations twice daily (80 to 160 mcg budesonide/4.5 mcg formoterol per inhalation) as controller therapy, plus 1 to 2 additional inhalations/dose as needed for reliever therapy. NAEPP Max: 12 oral inhalations/day (max formoterol: 54 mcg/day).
  • Maintenance treatment (controllers)
    • Inhaled corticosteroids ^c152
      • Multiple forms of inhaled corticosteroid preparations are available in low-, medium-, and high-dose strengths; a comprehensive list of all recommended asthma medications for use in children and low-/medium-/high-dose comparisons can be found in the NAEPP and GINA guidelines ^r1r11r21

        • Estimated comparative daily dosages: inhaled corticosteroids for long-term asthma control.

          *It is preferable to use a higher mcg/puff or mcg/inhalation formulation to achieve as low a number of puffs or inhalations as possible. DPI, dry powder inhaler (requires deep, fast inhalation); MDI, metered dose inhaler (releases a puff of medication); N/A, not applicable.

          From NIH: Asthma Care Quick Reference: Diagnosing and Managing Asthma. NIH Publication No. 12-5075. NIH website. Revised September 2012. Accessed June 23, 2021. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf

          Daily dose	Aged 0 to 4 years			Aged 5 to 11 years			Aged 12 years or older
          	Low	Medium*	High*	Low	Medium*	High*	Low	Medium*	High*
          Medication
          Beclomethasone MDI	N/A	N/A	N/A	80 to 160 mcg	Greater than 160 to 320 mcg	Greater than 320 mcg	80 to 240 mcg	Greater than 240 to 480 mcg	Greater than 480 mcg
          40 mcg/puff	N/A	N/A	N/A	1 to 2 puffs twice daily	3 to 4 puffs twice daily		1 to 3 puffs twice daily	4 to 6 puffs twice daily
          80 mcg/puff	N/A	N/A	N/A	1 puff twice daily	2 puffs twice daily	3 or more puffs twice daily	1 puff AM, 2 puffs PM	2 to 3 puffs twice daily	4 or more puffs twice daily
          Budesonide DPI	N/A	N/A	N/A	180 to 360 mcg	Greater than 360 to 720 mcg	Greater than 720 mcg	180 to 540 mcg	Greater than 540 to 1080 mcg	Greater than 1080 mcg
          90 mcg/inhalation	N/A	N/A	N/A	1 to 2 inhalations twice daily	3 to 4 inhalations twice daily		1 to 3 inhalations twice daily
          180 mcg/inhalation	N/A	N/A	N/A		2 inhalations twice daily	3 or more inhalations twice daily	1 inhalation AM, 2 inhalations PM	2 to 3 inhalations twice daily	4 or more inhalations twice daily
          Budesonide nebules	0.25 to 0.5 mg	Greater than 0.5 to 1 mg	Greater than 1 mg	0.5 mg	1 mg	2 mg	N/A	N/A	N/A
          0.25 mg	1 to 2 nebules/day			1 nebule twice daily			N/A	N/A	N/A
          0.5 mg	1 nebule/day	2 nebules/day	3 nebules/day	1 nebule/day	1 nebule twice daily		N/A	N/A	N/A
          1 mg		1 nebule/day	2 nebules/day		1 nebule/day	1 nebule twice daily	N/A	N/A	N/A
          Ciclesonide MDI	N/A	N/A	N/A	80 to 160 mcg	Greater than 160 to 320 mcg	Greater than 320 mcg	160 to 320 mcg	Greater than 320 to 640 mcg	Greater than 640 mcg
          80 mcg/puff	N/A	N/A	N/A	1 to 2 puffs/day	1 puff AM, 2 puffs PM to 2 puffs twice daily	3 or more puffs twice daily	1 to 2 puffs twice daily	3 to 4 puffs twice daily
          160 mcg/puff	N/A	N/A	N/A	1 puff/day	1 puff twice daily	2 or more puffs twice daily		2 puffs twice daily	3 or more puffs twice daily
          Flunisolide MDI	N/A	N/A	N/A	160 mcg	320 to 480 mcg	480 mcg or more	320 mcg	Greater than 320 to 640 mcg	Greater than 640 mcg
          80 mcg/puff	N/A	N/A	N/A	1 puff twice daily	2 to 3 puffs twice daily	4 or more puffs twice daily	2 puffs twice daily	3 to 4 puffs twice daily	5 or more puffs twice daily
          Fluticasone MDI	176 mcg	Greater than 176 to 352 mcg	Greater than 352 mcg	88 to 176 mcg	Greater than 175 to 352 mcg	Greater than 352 mcg	88 to 264 mcg	Greater than 264 to 440 mcg	Greater than 440 mcg
          44 mcg/puff	2 puffs twice daily	3 to 4 puffs twice daily		1 to 2 puffs twice daily	3 to 4 puffs twice daily		1 to 3 puffs twice daily
          110 mcg/puff		1 puff twice daily	2 or more puffs twice daily		1 puff twice daily	2 or more puffs twice daily		2 puffs twice daily	3 puffs twice daily
          220 mcg/puff								1 puff twice daily	2 or more puffs twice daily
          Fluticasone DPI	N/A	N/A	N/A	100 to 200 mcg	Greater than 200 to 400 mcg	Greater than 400 mcg	100 to 300 mcg	Greater than 300 to 500 mcg	Greater than 500 mcg
          50 mcg/inhalation	N/A	N/A	N/A	1 to 2 inhalations twice daily	3 to 4 inhalations twice daily		1 to 3 inhalations twice daily
          100 mcg/inhalation	N/A	N/A	N/A	1 inhalation twice daily	2 inhalations twice daily	More than 2 inhalations twice daily		2 inhalations twice daily	3 or more inhalations twice daily
          250 mcg/inhalation	N/A	N/A	N/A			1 inhalation twice daily		1 inhalation twice daily	2 or more inhalations twice daily
          Mometasone DPI	N/A	N/A	N/A	110 mcg	220 to 440 mcg	Greater than 440 mcg	110 to 220 mcg	Greater than 220 to 440 mcg	Greater than 440 mcg
          110 mcg/inhalation	N/A	N/A	N/A	1 inhalation/day	1 to 2 inhalations twice daily	3 or more inhalations twice daily	1 to 2 inhalations PM	3 to 4 inhalations PM or 2 inhalations twice daily	3 or more inhalations twice daily
          220 mcg/inhalation	N/A	N/A	N/A		1 to 2 inhalations/day	3 or more inhalations divided in 2 doses	1 inhalation PM	1 inhalation twice daily or 2 inhalations PM	3 or more inhalations divided in 2 doses

      • Fluticasone may be associated with less effect on growth in children than equivalent doses of beclomethasone and budesonide ^r58
      • Fluticasone
        • Fluticasone Propionate Pressurized inhalation, suspension; Children 1 to 3 years†: Not FDA-approved; 88 mcg (2 oral inhalations of 44 mcg/actuation) twice daily is the max dosage that has been used with a spacer device with mask. Use the lowest effective dose once stable.
        • Fluticasone Propionate Pressurized inhalation, suspension; Children 4 to 11 years: 88 mcg (2 oral inhalations of 44 mcg/actuation) twice daily is the recommended and max dose. Use the lowest effective dose once stable.
        • Fluticasone Propionate Pressurized inhalation, suspension; Children and Adolescents 12 years and older: 88 mcg (2 oral inhalations of 44 mcg/actuation) twice daily for patients not currently on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. Max: 4 oral inhalations of 220 mcg/actuation twice daily (880 mcg twice daily). Use the lowest effective dose once stable.
        • Fluticasone Propionate Inhalation powder; Children 4 to 11 years: 50 mcg (1 oral inhalation of 50 mcg/actuation) twice daily for patients not on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. Max: 2 oral inhalations of 50 mcg/actuation twice daily or 1 oral inhalation of 100 mcg/actuation twice daily (100 mcg twice daily). Titrate to lowest effective dose once stable.
        • Fluticasone Propionate Inhalation powder; Children and Adolescents 12 years and older: 100 mcg (1 oral inhalation of 100 mcg/actuation) twice daily for patients not on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. Max: 4 oral inhalations of 250 mcg twice daily (1,000 mcg twice daily). Titrate to lowest effective dose once stable.
      • Budesonide ^c153c154
        • Inhaler
          • Budesonide Inhalation powder; Children and Adolescents 6 years and older: 180 mcg (1 oral inhalation of 180 mcg/actuation or 2 oral inhalations of 90 mcg/actuation) twice daily is the recommended starting dosage; 360 mcg (2 oral inhalations of 180 mcg/actuation) twice daily may be appropriate for some patients. Max: 2 oral inhalations of 180 mcg/actuation twice daily (360 mcg twice daily). Titrate to lowest effective dose once stable.
        • Nebulizer ^c155c156c157
          • Budesonide Nebulizer suspension; Infants 3 months and older†: Use not established; not FDA-approved. In Europe, the usual maintenance dose is 0.25 to 0.5 mg via nebulizer twice daily.
          • Budesonide Nebulizer suspension; Children 1 to 8 years: Dosing based on previous therapies: PREVIOUSLY ON BRONCHODILATORS ALONE: Give 0.5 mg once daily or 0.25 mg twice daily via nebulizer. A dose of 0.25 mg once daily may be considered for some patients. Max: 0.5 mg/day. PREVIOUSLY ON INHALED CORTICOSTEROIDS (CS): Give 0.5 mg once daily or 0.25 mg twice daily via nebulizer; may give up to 0.5 mg twice daily. Max: 1 mg/day. PREVIOUSLY TAKING ORAL CS: Give 0.5 mg twice daily or 1 mg once daily via nebulizer. Max: 1 mg/day. Titrate to lowest effective dose once stable.
          • Budesonide Nebulizer suspension; Children 9 to 11 years†: Not FDA-approved in U.S. for this age group. European usual dose for severe asthma is 0.5 to 1 mg via nebulizer twice daily. Usual maintenance dose is 0.25 to 0.5 mg via nebulizer twice daily; may increase during exacerbations or severe asthma. Max: 1 mg/day. Titrate to lowest effective dose once stable.
          • Budesonide Nebulizer suspension; Children and Adolescents 12 years and older†: Not FDA-approved in U.S. in this age group. European usual dose for severe asthma is 1 to 2 mg via nebulizer twice daily. Usual maintenance dose is 0.5 to 1 mg via nebulizer twice daily; may increase during exacerbations or severe asthma. Max: 4 mg/day. Titrate to lowest effective dose once stable.
    • Inhaled corticosteroid plus long-acting β₂-agonists ^c158
      • ICS-LABA combinations (inhaled corticosteroid plus long-acting β₂-agonist) are a NAEPP-preferred^r21r50 therapy in step 4 and higher for children younger than 4 years and a preferred option in step 3 and higher for children aged 4 years or older; GINA does not recommend combination ICS-LABA in children aged 4 years or younger^r11
        • SMART with ICS-LABA combination inhaler ^r48
          • Same inhaler is used for both regular maintenance dosing and as needed to alleviate symptoms
          • Only use budesonide-formoterol as reliever when this combination is also used as maintenance therapy
          • Strongly recommended as the preferred therapy for children 4 years or older who are not well controlled on a low- or medium-dose daily inhaled corticosteroid alone ^r49
        • Budesonide-formoterol ^c159
          • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† 4 to 11 years: 1 or 2 oral inhalations twice daily (80 mcg budesonide/4.5 mcg formoterol per inhalation) as controller therapy, plus 1 to 2 additional inhalations/dose as needed for reliever therapy. NAEPP Max: 8 oral inhalations/day (Max formoterol: 36 mcg/day).
          • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† and Adolescents† 12 to 17 years: 1 or 2 oral inhalations twice daily (80 to 160 mcg budesonide/4.5 mcg formoterol per inhalation) as controller therapy, plus 1 to 2 additional inhalations/dose as needed for reliever therapy. NAEPP Max: 12 oral inhalations/day (Max formoterol: 54 mcg/day).
        • Fluticasone-salmeterol ^c160
          • Fluticasone Propionate, Salmeterol Inhalation powder; Children 4 to 11 years: 1 oral inhalation of 100/50 (100 mcg fluticasone and 50 mcg salmeterol per inhalation) twice daily is the recommended and max dosage. Only approved for children in this age group who are not controlled on an inhaled corticosteroid (ICS) alone.
          • Fluticasone Propionate, Salmeterol Inhalation powder; Children and Adolescents 12 years and older: 1 oral inhalation twice daily of either 100/50 (100 mcg fluticasone and 50 mcg salmeterol per inhalation), 250/50 (250 mcg fluticasone and 50 mcg salmeterol per inhalation), or 500/50 (500 mcg fluticasone and 50 mcg salmeterol per inhalation). Max: 1 oral inhalation of 500/50 twice daily (1,000 mcg fluticasone and 100 mcg salmeterol per day).
          • Fluticasone Propionate, Salmeterol Pressurized inhalation, suspension; Children and Adolescents 12 years and older: 2 oral inhalations twice daily, of either 45/21 (45 mcg fluticasone/21 mcg salmeterol per inhalation), 115/21 (115 mcg fluticasone/21 mcg salmeterol per inhalation), or 230/21 (230 mcg fluticasone/21 mcg salmeterol per inhalation). Max: 2 oral inhalations of 230/21 twice daily (920 mcg fluticasone with 84 mcg salmeterol per day).
    • Leukotriene receptor antagonists (second line) ^c161
      • Montelukast ^r8r59c162
        • Montelukast Sodium Oral granules; Children 1 to 5 years: 4 mg PO once daily in the evening. LIMIT OF USE: Montelukast is not indicated for treatment of an acute asthma attack.
        • Montelukast Sodium Chewable tablet; Adolescents and Children 6 to 14 years: 5 mg PO once daily in the evening. LIMIT OF USE: Montelukast is not indicated for treatment of an acute asthma attack.
        • Montelukast Sodium Oral tablet; Adolescents 15 to 17 years: 10 mg PO once daily in the evening. LIMIT OF USE: Montelukast is not indicated for treatment of an acute asthma attack.
        • Montelukast is associated with an increased risk for serious neuropsychiatric events (e.g., agitation, aggression, depression, sleep disturbances, suicidal thoughts and behaviors); montelukast products now carry a boxed warning recommending careful consideration of risks and benefits before prescribing ^r60r61
      • Zafirlukast ^r1r8c163
        • Zafirlukast Oral tablet; Children 5 to 11 years: 10 mg PO twice daily.
        • Zafirlukast Oral tablet; Children and Adolescents 12 to 17 years: 20 mg PO twice daily.
  • Maintenance therapy; add-on agents
    • Long-acting muscarinic antagonist
      • Daily ICS-LAMA (inhaled corticosteroid plus long-acting muscarinic antagonist) is an alternative therapy after SMART (preferred choice) and after daily ICS-LABA (secondary choice) for moderate persistent disease asthma in children aged 12 years or older ^r21r49c164
        • Approved for children aged 6 to 11 years; however, NAEPP recommendations for use apply only to children aged 12 years or older
      • Tiotropium ^r59r62c165
        • Tiotropium Respiratory spray, solution; Children and Adolescents 6 years and older: 2 oral inhalations (1.25 mcg/actuation) for a total dose of 2.5 mcg once daily, at the same time each day, is the usual and max dosage.
    • Mast cell stabilizer ^r1c166
      • Alternative for patients requiring step 2 care (mild persistent asthma), preventative treatment before exercise, and for unavoidable exposure to known allergens ^r1
        • Cromolyn ^c167
          • Nebulizer solution
            • Cromolyn Sodium Nebulizer solution; Children and Adolescents 2 years and older: 20 mg via nebulizer 4 times per day. Once stabilized, may be able to reduce to 3 times per day.
    • Methylxanthines ^r1c168
      • Theophylline ^c169
        • Least preferred alternative owing to significant interactions with other medications, narrow therapeutic index, wide interpatient variability in theophylline metabolic clearance, and need for monitoring of serum concentrations ^r1
        • Target serum concentration: 5 to 15 mcg/mL ^r1
          • Measure theophylline serum concentration 3 to 5 days after initiation. Repeat measurement occasionally to ensure dosage continues to be optimized, at least 2 days after any change expected to alter theophylline clearance, and if any signs or symptoms of toxicity develop (eg, headache, tachycardia, nausea/vomiting)
        • Theophylline oral solution ^r1
          • Theophylline, Anhydrous Oral solution; Children and Adolescents 5 years and older: Initially, 10 mg/kg/day (Max: 300 mg/day) PO. Divide daily dose every 4 to 6 hours for younger patients and every 6 to 8 hours for older children and adolescents. If tolerated, may increase dosage incrementally no more frequently than every 3 days to achieve desired effect/concentration. Usual maximum is 16 mg/kg/day; however, some patients may require higher daily dosages.
        • Theophylline extended-release oral tablet ^r1
          • Theophylline, Anhydrous Oral tablet, extended-release; Children and Adolescents 6 years and older: Initially, 10 mg/kg/day (Max: 300 mg/day) PO divided every 12 hours. If tolerated, may increase dosage incrementally no more frequently than every 3 days to achieve desired effect/concentration. Usual maximum is 16 mg/kg/day (Max: 800 mg/day); however, some patients may require higher daily dosages.
    • Oral corticosteroids
      • Prednisone ^c170c171c172
        • Prednisone Oral solution; Infants and Children less than 12 years: 0.25 to 2 mg/kg/day PO administered once daily in the morning or every other day as needed for symptom control; use lowest effective dose; alternate day therapy may produce less adrenal suppression. Max: 60 mg/day. Usual age-based Max: 20 mg/day for less than 2 years of age; 30 mg/day for 3 to 5 years; 40 mg/day for 6 to 11 years.
        • Prednisone Oral tablet; Children and Adolescents 12 to 17 years: 7.5 to 60 mg/day PO once daily in the morning or every other day as needed for symptom control; use lowest effective dose; alternate day therapy may produce less adrenal suppression.
      • Methylprednisolone ^c173c174c175
        • Methylprednisolone Oral tablet; Infants and Children less than 12 years: 0.25 to 2 mg/kg/day PO once daily in the morning or every other day as needed for symptom control. Use lowest effective dose. Max: 60 mg/day. Usual age-based Max: 20 mg/day for less than 2 years of age; 30 mg/day for 3 to 5 years; 40 mg/day for 6 to 11 years.
        • Methylprednisolone Oral tablet; Children and Adolescents 12 years and older: 7.5 to 60 mg PO administered once daily in the morning or as alternate-day therapy as needed for symptom control; use lowest effective dose.
      • Dexamethasone ^c176c177c178
        • Dexamethasone Oral solution; Infants, Children, and Adolescents: 0.4 mg/kg/dose PO once daily as an alternative for patients unable to tolerate other liquid preparations. Dexamethasone IV solution for oral use in the same dose for a given weight or dexamethasone tablets (whole or crushed) can also be substituted in the same dose for a given weight of patient is unable to tolerate other preparations.
          • NOTE: There is no absolute maximum dosage for dexamethasone maintenance therapy; however, most clinicians avoid exceeding adult maximum doses. Corticosteroids must be individualized and are highly variable depending on the nature/severity of the disease and patient's response.
    • Leukotriene synthesis inhibitor
      • Zileuton ^c179c180
        • Zileuton is an add-on option for adolescents aged 12 years and older ^r21
        • Immediate-release formulation
          • Zileuton Oral tablet; Children and Adolescents 12 years and older: 600 mg PO 4 times per day, taken with meals and at bedtime.
        • Extended-release formulation
          • Zileuton Oral tablet, biphasic release; Children and Adolescents 12 years and older: 1,200 mg PO twice daily, within one hour after morning and evening meals.
    • Biologic agents ^r1c181
      • Be prepared and equipped to identify and treat anaphylaxis. Although most cases occur within the first 3 doses, sporadic cases can occur with later doses. ^r63
      • Omalizumab (patients 6 years and older) ^c182
        • Adjunctive therapy for patients who have sensitivity to relevant allergens (eg, dust mites, cockroach frass, pet dander) and who require step 5 or 6 care (for severe persistent asthma) ^r1
        • Omalizumab (Hamster) Solution for injection; Children and Adolescents 6 years and older: Dosing is based on age, weight, and baseline serum IgE and ranges from 75 to 375 mg per dose. Doses are administered subcutaneously every 2 to 4 weeks depending on serum IgE. Adjust dosage for significant changes in weight.
      • Mepolizumab (patients 6 years and older) ^c183c184c185
        • Adjunctive therapy for patients with severe asthma (eosinophilic phenotype) ^r64r65
          • Mepolizumab Solution for injection; Children 6 to 11 years: 40 mg subcutaneously once every 4 weeks.
          • Mepolizumab Solution for injection; Children and Adolescents 12 to 17 years: 100 mg subcutaneously once every 4 weeks.
      • Benralizumab (patients 12 years and older) ^c186
        • Adjunctive therapy for patients with severe asthma (eosinophilic phenotype)
          • Benralizumab Solution for injection; Children and Adolescents 12 to 17 years: 30 mg subcutaneously once every 4 weeks for the first 3 doses, followed by 30 mg subcutaneously once every 8 weeks thereafter.
      • Dupilumab (patients 12 years and older) ^c187
        • Eosinophilic phenotype moderate to severe asthma
          • Dupilumab Solution for injection; Children and Adolescents 12 to 17 years: 400 mg subcutaneously initially (as two 200 mg injections), followed by 200 mg subcutaneously every other week OR 600 mg subcutaneously initially (as two 300 mg injections), followed by 300 mg subcutaneously every other week.
        • Oral corticosteroid–dependent moderate to severe asthma
          • Dupilumab Solution for injection; Children and Adolescents 12 to 17 years: 600 mg subcutaneously initially (as two 300 mg injections), followed by 300 mg subcutaneously every other week.

• Estimated comparative daily dosages: inhaled corticosteroids for long-term asthma control.

  *It is preferable to use a higher mcg/puff or mcg/inhalation formulation to achieve as low a number of puffs or inhalations as possible. DPI, dry powder inhaler (requires deep, fast inhalation); MDI, metered dose inhaler (releases a puff of medication); N/A, not applicable.

  From NIH: Asthma Care Quick Reference: Diagnosing and Managing Asthma. NIH Publication No. 12-5075. NIH website. Revised September 2012. Accessed June 23, 2021. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf

  Daily dose	Aged 0 to 4 years			Aged 5 to 11 years			Aged 12 years or older
  	Low	Medium*	High*	Low	Medium*	High*	Low	Medium*	High*
  Medication
  Beclomethasone MDI	N/A	N/A	N/A	80 to 160 mcg	Greater than 160 to 320 mcg	Greater than 320 mcg	80 to 240 mcg	Greater than 240 to 480 mcg	Greater than 480 mcg
  40 mcg/puff	N/A	N/A	N/A	1 to 2 puffs twice daily	3 to 4 puffs twice daily		1 to 3 puffs twice daily	4 to 6 puffs twice daily
  80 mcg/puff	N/A	N/A	N/A	1 puff twice daily	2 puffs twice daily	3 or more puffs twice daily	1 puff AM, 2 puffs PM	2 to 3 puffs twice daily	4 or more puffs twice daily
  Budesonide DPI	N/A	N/A	N/A	180 to 360 mcg	Greater than 360 to 720 mcg	Greater than 720 mcg	180 to 540 mcg	Greater than 540 to 1080 mcg	Greater than 1080 mcg
  90 mcg/inhalation	N/A	N/A	N/A	1 to 2 inhalations twice daily	3 to 4 inhalations twice daily		1 to 3 inhalations twice daily
  180 mcg/inhalation	N/A	N/A	N/A		2 inhalations twice daily	3 or more inhalations twice daily	1 inhalation AM, 2 inhalations PM	2 to 3 inhalations twice daily	4 or more inhalations twice daily
  Budesonide nebules	0.25 to 0.5 mg	Greater than 0.5 to 1 mg	Greater than 1 mg	0.5 mg	1 mg	2 mg	N/A	N/A	N/A
  0.25 mg	1 to 2 nebules/day			1 nebule twice daily			N/A	N/A	N/A
  0.5 mg	1 nebule/day	2 nebules/day	3 nebules/day	1 nebule/day	1 nebule twice daily		N/A	N/A	N/A
  1 mg		1 nebule/day	2 nebules/day		1 nebule/day	1 nebule twice daily	N/A	N/A	N/A
  Ciclesonide MDI	N/A	N/A	N/A	80 to 160 mcg	Greater than 160 to 320 mcg	Greater than 320 mcg	160 to 320 mcg	Greater than 320 to 640 mcg	Greater than 640 mcg
  80 mcg/puff	N/A	N/A	N/A	1 to 2 puffs/day	1 puff AM, 2 puffs PM to 2 puffs twice daily	3 or more puffs twice daily	1 to 2 puffs twice daily	3 to 4 puffs twice daily
  160 mcg/puff	N/A	N/A	N/A	1 puff/day	1 puff twice daily	2 or more puffs twice daily		2 puffs twice daily	3 or more puffs twice daily
  Flunisolide MDI	N/A	N/A	N/A	160 mcg	320 to 480 mcg	480 mcg or more	320 mcg	Greater than 320 to 640 mcg	Greater than 640 mcg
  80 mcg/puff	N/A	N/A	N/A	1 puff twice daily	2 to 3 puffs twice daily	4 or more puffs twice daily	2 puffs twice daily	3 to 4 puffs twice daily	5 or more puffs twice daily
  Fluticasone MDI	176 mcg	Greater than 176 to 352 mcg	Greater than 352 mcg	88 to 176 mcg	Greater than 175 to 352 mcg	Greater than 352 mcg	88 to 264 mcg	Greater than 264 to 440 mcg	Greater than 440 mcg
  44 mcg/puff	2 puffs twice daily	3 to 4 puffs twice daily		1 to 2 puffs twice daily	3 to 4 puffs twice daily		1 to 3 puffs twice daily
  110 mcg/puff		1 puff twice daily	2 or more puffs twice daily		1 puff twice daily	2 or more puffs twice daily		2 puffs twice daily	3 puffs twice daily
  220 mcg/puff								1 puff twice daily	2 or more puffs twice daily
  Fluticasone DPI	N/A	N/A	N/A	100 to 200 mcg	Greater than 200 to 400 mcg	Greater than 400 mcg	100 to 300 mcg	Greater than 300 to 500 mcg	Greater than 500 mcg
  50 mcg/inhalation	N/A	N/A	N/A	1 to 2 inhalations twice daily	3 to 4 inhalations twice daily		1 to 3 inhalations twice daily
  100 mcg/inhalation	N/A	N/A	N/A	1 inhalation twice daily	2 inhalations twice daily	More than 2 inhalations twice daily		2 inhalations twice daily	3 or more inhalations twice daily
  250 mcg/inhalation	N/A	N/A	N/A			1 inhalation twice daily		1 inhalation twice daily	2 or more inhalations twice daily
  Mometasone DPI	N/A	N/A	N/A	110 mcg	220 to 440 mcg	Greater than 440 mcg	110 to 220 mcg	Greater than 220 to 440 mcg	Greater than 440 mcg
  110 mcg/inhalation	N/A	N/A	N/A	1 inhalation/day	1 to 2 inhalations twice daily	3 or more inhalations twice daily	1 to 2 inhalations PM	3 to 4 inhalations PM or 2 inhalations twice daily	3 or more inhalations twice daily
  220 mcg/inhalation	N/A	N/A	N/A		1 to 2 inhalations/day	3 or more inhalations divided in 2 doses	1 inhalation PM	1 inhalation twice daily or 2 inhalations PM	3 or more inhalations divided in 2 doses

• Usual dosages for other long-term control medications.*

  *Dosages are provided for those products that have been approved by the FDA or have sufficient clinical trial safety and efficacy data in the appropriate age ranges to support their use. DPI, dry powder inhaler; IgE, immunoglobulin E; MDI, metered-dose inhaler; N/A, not available (not approved, no data available, or safety and efficacy not established for this age group).

  From NIH: Asthma Care Quick Reference: Diagnosing and Managing Asthma. NIH Publication No. 12-5075. NIH website. Revised September 2012. Accessed June 23, 2021. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf

  Medication	Aged 0 to 4 years	Aged 5 to 11 years	Aged 12 years or older
  Combined medication (inhaled corticosteroid + long-acting β₂-agonist)
  Fluticasone-salmeterol
  DPI: 100 mcg/50 mcg,  250 mcg/50 mcg,  or 500 mcg/50 mcg	N/A	1 inhalation twice daily; dose depends on level of severity or control	1 inhalation twice daily; dose depends on level of severity or control
  MDI: 45 mcg/21 mcg, 115 mcg/21 mcg, or 230 mcg/21 mcg	N/A	1 inhalation twice daily; dose depends on level of severity or control	1 inhalation twice daily; dose depends on level of severity or control
  Budesonide-formoterol
  MDI: 80 mcg/4.5 mcg  or  160 mcg/4.5 mcg	N/A	2 puffs twice daily; dose depends on level of severity or control	2 puffs twice daily; dose depends on level of severity or control
  Mometasone-formoterol
  MDI: 100 mcg/5 mcg	N/A	N/A	2 inhalations twice daily; dose depends on severity of asthma
  Leukotriene modifiers
  Leukotriene receptor antagonist: montelukast
  Leukotriene receptor antagonist: zafirlukast
  4- or 5-mg chewable tablet, 4-mg granule packets, 10-mg tablet	4 mg every night at bedtime (age 1 to 5 years)	5 mg every night at bedtime (age 6 to 14 years)	10 mg every night at bedtime
  10- or 20-mg tablet (Take at least 1 hour before or 2 hours after a meal. Monitor liver function.)	N/A	10 mg twice daily (age 7 to 11 years)	40 mg daily (20-mg tablet twice daily)
  5-lipoxygenase inhibitor: zileuton
  600-mg tablet (Monitor liver function.)	N/A	N/A	2400 mg daily (give 1 tablet 4 times daily)
  Immunomodulators
  Omalizumab (anti-IgE)
  Subcutaneous injection, 150 mg/1.2 mL after reconstitution with 1.4-mL sterile water for injection (Monitor patients after injections; be prepared to treat anaphylaxis that may occur.)	N/A	N/A	150- to 375-mg subcutaneous injection every 2 to 4 weeks, depending on body weight and pretreatment serum IgE level
  Cromolyn
  Cromolyn
  Nebulizer: 20 mg/ampule	1 ampule 4 times daily, N/A in children younger than 2 years	1 ampule 4 times daily	1 ampule 4 times daily
  Methylxanthines
  Theophylline
  Liquids, sustained-release tablets, and capsules (Monitor serum concentration levels.)	Starting dose 10 mg/kg/ day; usual maximum:	Starting dose 10 mg/ kg/day; usual maximum: 16 mg/kg/day	Starting dose 10 mg/kg/day up to 300 mg maximum; usual maximum: 800 mg/day
  	Infants younger than 1 year: 0.2 (age in weeks) + 5 = mg/kg/day
  	Infants or children aged 1 year or older: 16 mg/kg/day
  Inhaled long-acting β₂-agonists (used in conjunction with inhaled corticosteroids for long-term control; long-acting β₂-agonists are NOT to be used as monotherapy)
  Salmeterol
  DPI: 50 mcg/blister	N/A	1 blister every 12 hours	1 blister every 12 hours
  Oral systemic corticosteroids
  Methylprednisolone
  2-, 4-, 8-, 16-, 32-mg tablets	0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control	0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control	7.5 to 60 mg daily in single dose in AM or every other day as needed for control
  	Short course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 days	Short course "burst": 1 to 2 mg/kg/day; Max: 60 mg/day for 3 to 10 days	Short course "burst": to achieve control, 40 to 60 mg/day as single dose or 2 divided doses for 3 to 10 days
  Prednisone
  1-, 2.5-, 5-, 10-, 20-, 50-mg tablets; 5 mg/mL, 5 mg/5 mL	0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control	0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control	7.5 to 60 mg daily in single dose in AM or every other day as needed for control
  	Short course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 days	Short course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 days	Short course "burst": to achieve control, 40 to 60 mg/day as single dose or 2 divided doses for 3 to 10 days
  Prednisolone
  5-mg tablets; 5 mg/5 mL, 15 mg/5 mL	0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control	0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control	7.5 to 60 mg daily in single dose in AM or every other day as needed for control
  	Short course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 days	Short course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 days	Short course "burst": to achieve control, 40 to 60 mg/day as single dose or 2 divided doses for 3 to 10 days

Nondrug and supportive care

Asthma self-management (home management)

• Establishing a partnership with the patient and caregivers is a major component of care ^c188
• Educate caregivers about home management and monitoring, use of maintenance medications, and inhaler technique ^r66c189
• Use of control chart (sample available within the NAEPP guidelines) and written asthma action plan, emphasizing difference between controller and reliever medications (sample available within the NAEPP guidelines) ^r1c190
• Encourage caregivers to provide a copy of written asthma action plan to school, child care facility, or camp ^r1c191
• School-based asthma self-management interventions may reduce asthma symptoms, emergency department visits, and hospital admissions, particularly in younger children from socially disadvantaged populations ^r67c192
• Telephone-based peer coaching for caregivers of children with asthma may improve outpatient management, reduce emergency department visits, and minimize hospitalizations ^r68c193c194

Promote active participation in physical activities, exercise, and sports ^{r1c195c196c197}

Reduce exposure to allergen, irritant, and air pollution triggers ^c198

• Multicomponent allergen-specific intervention strategies are recommended over single-component interventions in patients who are known to be sensitized or become symptomatic on exposure to a specific allergen ^r48
  • For rodents and/or cockroaches, integrated pest management including measures to block infestation (eg, filling holes in walls) and abatement (eg, traps)
  • For dust mites, combination of dust mite–impermeable pillow and mattress covers, HEPA (high-efficiency particulate air) filter–equipped vacuum cleaner, carpet and curtain removal, and cleaning products
  • For mold, use of HEPA purifiers and mold abatement
• National Environmental Education Foundation provides guidelines for environmental management in pediatric asthma ^r69
• Consider subcutaneous allergen immunotherapy for patients with persistent asthma when (1) there is a clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive and (2) exposure reduction measures have failed

Avoid using β-blockers and NSAIDs (including aspirin) in patients with asthma because they have potential to exacerbate symptoms ^c199c200

Multidisciplinary case management may be needed for patients with severe, difficult-to-treat disease ^c201

Comorbidities

• Gastroesophageal reflux disease ^r1c203
  • Common, but may be unrecognized; prevalence of gastroesophageal reflux disease among patients with asthma is between 34% and 89% ^r33
  • Consider evaluation for gastroesophageal reflux disease (eg, 24-hour pH probe, endoscopic investigation)^r43 in patients who have poorly controlled asthma, especially with nighttime symptoms, even in the absence of symptoms suggestive of gastroesophageal reflux disease
  • Asthma symptom control (especially in those patients with frequent nighttime symptoms) may be improved by adding gastroesophageal reflux treatment in the subset of patients who complain of frequent heartburn
• Obesity ^c204d7
  • Increased prevalence of asthma in obese children; obesity also may be a predisposing factor for asthma, but causality is uncertain ^r70r71
  • Concomitant comorbidity (eg, obstructive sleep apnea, gastroesophageal reflux, diminished lung volumes) often renders management more difficult
  • Obesity makes asthma more difficult to manage and is associated with a diminished benefit of asthma medications ^r70
  • Weight loss of 5% to 10% often leads to significant improvement in asthma control ^r43
• Allergic bronchopulmonary aspergillosis ^r1c205d8
  • Consider in patients who have asthma and history of pulmonary infiltrates, IgE sensitization to aspergillus, or dependency on corticosteroids
  • Diagnostic criteria include:
    • Positive immediate skin test result
    • Elevated serum IgE and/or IgG level to aspergillus
    • Total serum IgE level greater than 417 units (1000 ng/mL)
    • Central bronchiectasis
  • Treat using prednisone with a gradual taper; adjunctive therapy with azole antifungal agents also may be helpful
• Obstructive sleep apnea ^r1c206d9
  • Consider in patients with poorly controlled asthma, particularly those who are obese or who report symptoms consistent with obstructive sleep apnea (eg, snoring, pauses in respiration while asleep, daytime fatigue)
  • Order a sleep study to confirm diagnosis; treat obstructive sleep apnea with nasal continuous positive airway pressure
  • Surgical intervention with adenotonsillectomy may be indicated ^r72
• Allergic rhinitis ^r1c207d9
  • Common; treatment may make asthma easier to manage
  • Treat using intranasal corticosteroids or antihistamine therapy; consider immunotherapy
• Infectious sinusitis ^r1c208d10
  • Can cause asthma exacerbation
  • Treat with intranasal corticosteroids and appropriate antibiotics (particularly infectious sinusitis); evidence is inconclusive regarding the effect of sinus surgery on asthma in patients who have chronic rhinosinusitis
• Psychological disorders (eg, anxiety disorders, depressive disorders) ^{r1c209c210c211}
  • Can complicate asthma management; often associated with low treatment adherence ^r43
  • Consider stress and depression in patients with poor asthma control ^c212c213
  • Outcomes may be improved by additional education to improve self-management and coping skills; consider referral to a psychologist for further diagnostic and treatment recommendations if initial management techniques are ineffective
• Vocal cord dysfunction ^c214
  • Comorbidity that can be misdiagnosed as asthma ^r1
  • Spirometry aids in the diagnosis of vocal cord dysfunction; direct vocal cord visualization is the gold standard to diagnose ^r32
  • Long-term therapy includes speech and behavioral treatment involving muscle relaxation techniques, controlled breathing exercises, anxiety reduction techniques, and pharmacologic adjuncts (eg, anxiolytics, anticholinergic inhalers) ^r32
• Food allergies (eg, tree nuts, peanuts) ^r43c215
  • Fatal reactions can result in people with asthma and food allergy exposed to allergen
  • Instruct patients with comorbid food allergies to always carry an epinephrine autoinjector
• COVID-19 infection ^c216
  • It is not known whether asthma confers an increased risk of COVID‐19 morbidity or whether COVID‐19 infection increases the risk of asthma exacerbations in children ^r73
    • Asthma does not appear significantly to increase the risk of contracting COVID-19 infection or of more severe disease or death in adult patients ^r74
  • Experts advise that children with asthma can go to school and participate in regular activities in keeping with public health guidance during the pandemic; increased shielding is not recommended ^r73
  • Regular asthma medications should be continued during the COVID-19 pandemic ^r11
    • Regular use of inhaled corticosteroids is considered unlikely to increase the risk of acquiring COVID-19 infection or increasing the severity of the infection ^r73
  • Nonsevere asthma exacerbations may be managed telehealth with a low threshold for face-to-face assessment ^r75
  • Usual guidelines for initiation of systemic corticosteroids for asthma exacerbations should be followed
  • If possible, patients with COVID-19 infection should be given inhaled asthma medications via inhaler rather than nebulizer to avoid aerosolizing the virus: nebulized medication should only be considered when no other option is available ^r11r73
  • Avoid spirometry in patients with known or suspected COVID-19 infection; if possible, postpone spirometry and peak frequency ratio measurements while community transmission rates are concerning

Special populations

• Infants
  • Objective measurements of airflow obstruction are not possible
  • Assessment depends on physical examination and oxygen saturation. Signs of severe obstruction include respiratory rate higher than 60 breaths per minute, use of accessory muscles, inspiratory and expiratory wheezing, paradoxical breathing, cyanosis, and SaO₂ less than 90%
  • Greater risk for respiratory failure; lack of response on physical examination or by objective measurements requires hospitalization
  • Use systemic corticosteroids early
• Patients aged 4 years and younger ^r1
  • Young children are at risk for severe exacerbations despite having a low level of impairment between episodes
    • Begin long-term daily therapy in a patient who has had 4 or more episodes of wheezing in the past year that affected sleep and lasted longer than 1 day, as well as a positive asthma risk profile, which includes either of the following: ^r1
      • 1 of the following factors: ^r1
        • Parental history of asthma
        • Physician diagnosis of atopic dermatitis
        • Evidence of sensitization to aeroallergens
      • 2 of the following factors: ^r1
        • Sensitization to foods
        • 4% or higher peripheral blood eosinophils ^r1
        • Wheezing apart from colds
    • Consider initiating long-term therapy in the following situations: ^r1
      • Consistent short-term bronchodilator use required more than 2 days per week for a period of more than 4 weeks
      • After 2 acute exacerbations requiring oral corticosteroids within 6 months
      • During seasonal exacerbations in young children who exhibit a pattern of seasonal asthma symptom exacerbation
  • Begin a trial of daily inhaled corticosteroids to prevent exacerbation in preschool children with recurrent wheezing (intermittent asthma or viral-triggered wheezing) ^r76
  • Few long-term control medications are FDA approved for this age group, including: ^r1
    • Budesonide nebulizer solution (patients aged 1-8 years)
    • Fluticasone dry power inhaler (patients older than 4 years)
    • Salmeterol dry power inhaler, alone or in combination with inhaled corticosteroid (patients older than 4 years)
    • Montelukast (chewable tablets, patients aged 2-6 years; granules, patients as young as 1 year)
  • Use a metered-dose inhaler plus valved holding chamber with face mask or nebulizer with face mask for children younger than age 5 years ^r13
  • Monitor therapy response closely in young children; treatment is often given in the form of a therapeutic trial ^r1
    • If there is no clear positive response within 4 to 6 weeks with adherence to plan and proper medication technique, stop treatment and consider alternate therapy and diagnosis ^r1
    • Patients in this age group have high rates of spontaneous symptom remission; consider treatment step-down if benefit is sustained for 3 months and reevaluate the need for continued daily therapy ^r1
• Children with exercise-induced bronchospasm ^r1
  • Anticipate in all patients with asthma; history of cough, dyspnea, chest pain or tightness, wheezing, or endurance problems with exercise are suggestive of exercise-induced bronchospasm
    • Establish the diagnosis with an exercise challenge in which a 15% decrease in peak expiratory flow or FEV₁ occurs (measured before and after exercise at 5-minute intervals for 20-30 minutes) ^r1
  • Treatment strategies
    • Pretreatment with short-acting β₂-agonists before exercise is effective in 80% of patients ^r1
      • Avoid frequent or chronic pretreatment use of long-acting β₂-agonist, which can disguise poorly controlled persistent asthma
      • Alternate pretreatment options include:
        • Leukotriene receptor antagonists have an onset of action hours after administration and will attenuate exercise-induced bronchospasm in 50% of patients ^r1
        • Cromolyn or nedocromil administration shortly before exercise
    • Long-term control therapy (eg, inhaled corticosteroids) may be appropriate in patients with frequent or severe exercise-induced bronchospasm ^r43
    • Encourage a gradual warm-up period before exercise and use of a mask or scarf over mouth during cold weather
• Children with cough variant asthma ^r1
  • Can be challenging to diagnose; determination of peak expiratory flow or bronchoprovocation may be helpful
  • Diagnosis can be confirmed by positive response to asthma medications after exclusion of alternate etiology for symptoms
  • Long-term management is similar to other asthmatics (ie, first line inhaled corticosteroids, second line leukotriene receptor antagonists) ^r77