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 (cough variant asthma) ^c11c12
  • One of the most common causes of chronic cough in children is asthma ^r32r33
  • Can present as the sole complaint ^r32r33
  • Typically dry and hacking, but wet cough with white sputum can occur ^r32r33
  • If persist more than 2 to 3 weeks, consider asthma as the differential diagnosis ^r32r33
  • However, in children, chronic cough (for more than 4 weeks) with no other symptoms is unlikely to represent asthma ^r34
• Recurrence of episodes with exposure to possible triggers ^c13
  • Respiratory infection
  • Inhaled allergens
  • Cold, dry^r35 or hot, humid^r36 air
  • Rain, thunderstorm, or wind ^r37
  • Passive (or active) tobacco smoke exposure
  • Hydrocarbon fumes (eg, in homes with gas stoves or kerosene heaters)
  • Exposure to other triggers (eg, house dust, ozone air pollution, mold spores, cockroaches, rodents)
  • Exacerbations most common in fall and winter months, least common in summer months ^r38r39
• For a patient with known diagnosis of asthma, assess previous disease control on the basis of:
  • 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 ^r1
  • Tachypnea and tachycardia with asthma exacerbation ^c27c28
    • Bradycardia occurs in life-threatening exacerbation
  • Diminished oxygen saturation is variable with moderate to severe exacerbation ^c29
  • Pulsus paradoxus occurs in moderate and severe exacerbation and disappears in life-threatening exacerbation due to respiratory muscle fatigue
• 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, leading to airway inflammation, hyperresponsiveness, airway obstruction, and disease chronicity ^c42
  • Environmental insult may be allergen, infectious agent, stress, or airborne irritant (eg, air pollution, smoke exposure) ^r1
  • Genetic factors lead to Th2 cytokine response profiles ^r1
    • Parental asthma or allergy history is an important factor
• Exacerbation triggers ^c43
  • Aeroallergens (eg, pollen, pet dander, dust, mold, cockroach and rodent droppings) ^c44
  • Airborne irritants (eg, cigarette or wood smoke, air pollution, chemical compounds) ^c45
  • Respiratory infection (eg, respiratory syncytial virus, rhinovirus) ^c46
  • Drugs (eg, NSAIDs including aspirin, β-blockers) ^c47
  • Ingested substances (eg, sulfites, alcohol) ^c48
  • Psychological or emotional stress ^c49c50
  • Cold, dry air or hot, humid air; change in temperature and humidity; thunderstorm ^r36r37
  • Exercise ^c51

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 ^r1r3c61
    • Documentation of reversible airway obstruction
      • Patients aged 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 ^c62
          • Broncho provocation can be assessed by a trained specialist, but is not commonly performed in young children ^c63
          • Impulse oscillometry, if available, measures respiratory impedance, requires little cooperation, and documents reversible obstruction ^c64
          • Understand wheezing phenotypes and utilize asthma predictive tools to help diagnose asthma in infants and children
      • Patients aged 5 to 11 years ^r1
        • Obtain spirometry to show reversible airflow obstruction after trial of bronchodilator ^r34c65
        • Response to a therapeutic trial of inhaled corticosteroids supports the diagnosis in symptomatic children with normal or near-normal spirometry results and negative bronchodilator response; repeat spirometry after 4 to 8 weeks ^r34c66
        • Bronchoprovocation may be performed when asthma is suspected, spirometry results are within (or nearly within) the reference range, and response to asthma medications is not significant ^c67
        • Measurement fraction of exhaled nitric oxide can be useful to support diagnosis of asthma ^r34c68
      • Exercise-induced bronchoconstriction ^r1
        • Previously termed "exercise-induced asthma" which is now not preferred as exercise does not cause asthma
        • Exercise-induced bronchoconstriction is a component of asthma and typically occurs in people with asthma but not all patients with asthma have exercise-induced bronchoconstriction
        • Characterized by clinical symptoms of cough, wheezing, or dyspnea associated with exercise as well as reversible airway obstruction in response to exercise or surrogate challenge
        • In patients with documented asthma, formal testing is not needed for diagnosis of exercise-induced bronchoconstriction
        • Evaluate using exercise challenge or surrogate provocation testing with FEV₁ or peak expiratory flow documentation ^c69
        • Confirm diagnosis by a positive response to asthma medications ^c70
  • Consider and exclude alternative diagnoses ^c71
    • Important at time of initial diagnosis and if there is no clear response to therapy
    • The 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) ^r29
  • Imaging and additional diagnostic testing do not typically add to the initial diagnostic workup
    • Chest radiography ^r1c72
      • 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
        • Chest radiography may reveal structural concerns such as vascular ring, findings suggestive of cystic fibrosis, or chronic lung disease
    • CT scan (and sometimes bronchoscopy) ^c73c74
      • Performed in rare circumstances when response to conventional therapy is poor or if other pulmonary disease is suspected. Referral to pulmonology may be necessary
    • 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 aeroallergen sensitization can support diagnosis, can indicate avoidable disease triggers, and has prognostic significance as indicated by the asthma predictive tools
      • Both in vivo methods (eg, skin prick test) and in vitro methods (eg, specific IgE antibodies) can be used
      • Food allergy testing is not helpful in the diagnosis of asthma. However, children with food allergy and asthma are at higher risk for fatal anaphylaxis and should be prescribed epinephrine ^r48
• Acute exacerbation
  • Obtain peak expiratory flow measurement ^c75
  • Obtain pulse oximetry for noninvasive SaO₂ (arterial oxygen saturation) monitoring ^c76
    • Arterial blood gas tests are rarely indicated ^r1c77
  • Obtain chest radiograph if complicating chest infection is suspected, hospitalization is required, or diagnosis is uncertain ^r7c78
  • Laboratory testing adds little in most patients
    • CBC demonstrating elevated WBC count may suggest infection ^c79
    • However, if systemic steroid was given, it can cause leukocytosis with neutrophilia
• Multiple resources are available to assist with the diagnostic process, including:
  • National Asthma Education and Prevention Program guidelines and NIH Asthma Care Quick Reference ^r1r9r49
  • Global Initiative for Asthma guidelines and resources ^r50
  • European Respiratory Society guidelines for diagnosis of asthma in children aged 5 to 16 years ^r34
  • European Respiratory Society Task Force evidence-based approach to assessment and treatment of wheezing in preschool children ^r27
  • Canadian Thoracic Society guidelines for preschoolers and for children and adults ^r51r52
  • National Institute for Health and Care Excellence asthma pathway and guidelines ^r12

Functional testing

• Spirometry (objective measure of FEV₁ in patients aged 5 to 11 years) ^r1c80
  • Evaluates for objective signs of reversible airway obstruction as well as severity of asthma
  • Obtain at initial assessment, 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
  • Normal spirometry result does not exclude asthma
  • Perform bronchodilator reversibility testing in children with FEV₁ and/or FEV₁/FVC findings supportive of asthma diagnosis; also consider if spirometry result is normal but clinical history is highly suggestive of asthma ^r34
    • Assess reversibility by performing spirometry before and after administration of bronchodilator using 1 of the following definitions
      • Global Initiative for Asthma: reversibility is defined by an increase in FEV₁ of 12% or greater from baseline with a minimum of 200 mL ^r7
        • A change of 12% from baseline is based on adult criteria; an increase in FEV₁ of 8% or greater is considered a more sensitive criteria for diagnosing asthma in children ^r53
      • European Respiratory Society/American Thoracic Society: reversibility is defined by a change of greater than 10% relative to the predicted value for FEV₁ or FVC ^r54
  • Use FEV₁ and FEV₁/FVC to classify severity per National Heart, Lung, and Blood Institute Expert Panel Report 3 guidelines
• Peak expiratory flow (objective measure of airway obstruction) ^r1c81
  • Limited role in diagnosis of asthma
  • Discuss and demonstrate technique at office visit
  • Determine personal best when asthma is stable
  • Measure at baseline
  • Monitor for worsening or improvement at home
  • Benefits: requires short expiratory burst, portable device, can be used at home
  • Limitations: effort dependent, imprecise, variation with each use
• Bronchoprovocation testing ^r1c82
  • Performed with methacholine, exercise, cold air challenge, and other triggers to assess airway hyperresponsiveness ^r34
  • Can be useful when asthma is suspected and spirometry results are within (or nearly within) the reference range
  • Exercise testing or eucapnic voluntary hyperpnea testing can be used for patients with concern for exercise-induced bronchoconstriction
  • Performed by an asthma care specialist or other trained person owing to possibility of severe bronchospasm
  • 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
• FeNO (fraction of exhaled nitric oxide) ^r55c83
  • Simple, noninvasive test that can be utilized when diagnosis of asthma is suspected and other diagnostic tests cannot be performed
  • FeNO levels are increased in patients with asthma due to presence of eosinophilic inflammation leading to airway epithelial cells to produce nitric oxide
    • FeNO less than 20 ppb in children younger than 12 years: absence of eosinophilic inflammation
      • Does not exclude asthma
      • Consider different diagnosis
      • Unlikely to benefit from inhaled corticosteroid
    • FeNO greater than 35 ppb in children younger than 12 years: eosinophilic inflammation; supportive in diagnosis of asthma but not conclusive ^r55
      • Likely to benefit from inhaled corticosteroid
    • FeNO 20 to 35 ppb in children younger than 12 years: evaluate in clinical context, monitor changes over time
    • Other factors can affect FeNO including smoking (associated with lower FeNO) and atopy (associated with higher FeNO)
  • Sensitivity is 79% and specificity is 81% for detection of asthma in children ^r56
  • 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 aged younger than 4 years ^r27r34
  • EPR-4 (National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group 4) 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 ^r49
    • Recommends incorporating FeNO for ongoing asthma monitoring and management strategy
    • Recommends against using FeNO in isolation to assess asthma control, predict exacerbations, or assess severity
    • Not recommended in children aged 4 years and younger with recurrent wheezing to predict development of asthma
  • British guidelines recommend measurement of FeNO (feasible from the age of 3-4 years) with level of 35 ppb or more regarded as a positive test in school-aged children ^r57
  • American Thoracic Society recommends measuring FeNO at time of asthma diagnosis ^r55c84
  • Global Initiative for Asthma guidelines suggest that FeNO is not useful for ruling in or ruling out asthma as FeNO can be higher in asthma (with Th2 inflammation) but can also be elevated in non-asthma conditions (eg, eosinophilic bronchitis, atopy, allergic rhinitis) and not elevated in neutrophilic asthma ^r7
    • Unclear whether FeNO-guided treatment is associated with fewer exacerbations, and further studies are needed before determining populations who would benefit from FeNO-guided therapy and monitoring frequency
    • Recommend using FeNO to characterize asthma phenotype and presence of type 2 inflammation (FeNO greater than or equal to 20 ppb) to guide treatment of patients with severe asthma
      • FeNO 20 ppb or greater predicts good response to anti-IgE therapy
      • FeNO 25 ppb or greater makes patients eligible for anti-IL4R therapy
      • Higher FeNO is associated with good response to anti-IL(interleukin)4R and anti-TSLP (thymic stromal lymphopoietin) therapies
• Impulse oscillometry ^c85
  • Simple, noninvasive test; uses sound waves to measure respiratory mechanics
  • Test is performed easily in children aged younger than 5 years because testing requires minimal cooperation ^r58
  • 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 ^r59
  • May be more sensitive than spirometry to detect subtle changes in airway function and distal changes in airway function when spirometry results are normal ^r59
  • Interpretation of results is less straightforward than with spirometry
  • Not readily available to most clinicians and specialists

Most common

• Vocal cord dysfunction (paradoxical vocal cord motion disorder, inducible laryngeal obstruction) ^r60c86c87
  • 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) ^r61
  • 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;^r61 consider vocal cord dysfunction in any patient with asthma that is difficult to treat or atypical, with absent symptoms during sleep, 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 with flexible laryngoscopy during an acute episode ^r61
• Congenital malformation or anomalies of airway (eg, laryngotracheomalacia, bronchomalacia, laryngeal web, tracheoesophageal fistula, vascular malformations including vascular rings or slings) ^{c88c89c90c91c92c93c94}
  • Presents during infancy with history of cough, stridor, or wheezing (depending on anatomic location of anomaly); symptoms usually include chronic feeding difficulties
    • Vascular rings and slings present with biphasic stridor due to compression and narrowing of large airways and can also have esophageal compression leading to feeding difficulty and vomiting
    • Tracheoesophageal fistula can present with chronic cough, recurrent pneumonia, and wheezing. Symptoms increase with feeding
  • 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 ^c95
  • Typically affects toddlers (aged 1-3 years); 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
  • Rigid bronchoscopy is used for removal of aspirated foreign bodies in most cases
• Respiratory infection (eg, viral bronchiolitis, laryngotracheobronchitis, pneumonia) ^c96c97c98c99
  • 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
  • Infections in children aged younger than 2 years is a common cause of wheezing
  • 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 ^c100d4
  • Dilation of the intrathoracic airways with loss of structural integrity and obstructive lung disease, usually secondary to chronic recurrent infection or inflammation due to cystic fibrosis or primary immunodeficiency; bronchiectasis can develop with time as a complication of chronic severe persistent asthma
  • Like 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
  • High-resolution CT findings include parallel lines, dilated bronchi, and signet ring sign
• Cardiac causes for wheezing
  • Conditions with left to right shunting leading to increased pulmonary blood flow, overcirculation, and pulmonary venous congestion can cause compression of large airways causing wheezing ^c101d5
  • This can present as tachypnea, cough, fatigue, dyspnea on exertion, wheezing, and respiratory distress in children; infants classically present with diaphoresis and difficulty feeding
  • 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, peripheral edema, splenomegaly, and abnormal cardiac examination findings (eg, murmurs, rubs, gallops) differentiate cardiac causes of wheezing from asthma
• Mediastinal mass ^c102
  • 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 ^r62c103
  • Motility disorder characterized by reflux of gastric contents into the esophagus or oral cavity with resulting symptoms or complications
  • Can coexist with asthma and can be a trigger for asthma
  • 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
  • Evaluation can include gastroenterology referral with endoscopy, esophageal pH and impedance monitoring, and esophageal contrast radiography
  • An empiric trial of acid suppression can be appropriate to exclude diagnosis

Admission criteria

Infants and young children

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

Infants

• Maintain lower threshold for admission for 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 less 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 the following to an asthma specialist (usually a pulmonologist or an allergist): ^r1
  • Patient receiving step 4 or higher drug therapy
  • Patient younger than 4 years receiving step 3 drug therapy
  • Patient possibly requiring immunotherapy or monoclonal antibody treatment
  • Patient who has required more than 2 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, with other conditions that complicate asthma, or for whom additional testing is indicated
  • Patient who requires additional education or has issues with adherence or allergen avoidance
  • History of life-threatening asthma exacerbation
• Refer to an allergist for allergy desensitization treatment ^r63c104

Drug therapy

• For acute asthma exacerbation
  • Short-acting β₂-agonists
    • Albuterol ^c106
      • Inhaler ^c107c108c109
        • Albuterol Pressurized inhalation, suspension; Children 1 to 5 years: 180 to 540 mcg (2 to 6 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes for the first hour, then 180 to 270 mcg (2 to 3 actuations of 90 mcg/actuation) every hour as needed. Delivery should occur with a spacer.
        • 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 for the first hour, then 360 to 900 mcg (4 to 10 actuations of 90 mcg/actuation) every 3 to 4 hours up to 540 to 900 mcg (6 to 10 actuations of 90 mcg/actuation) every 1 to 2 hours, or more often.
      • Nebulizer ^c110c111c112
        • Albuterol Sulfate Nebulizer solution; Infants† and Children† 1 year: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
        • Albuterol Sulfate Nebulizer solution; Children 2 to 12 years: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
        • Albuterol Sulfate Nebulizer solution; Adolescents: 2.5 to 5 mg inhaled by nebulizer every 20 minutes for the first hour, then 2.5 to 10 mg inhaled by nebulizer every 1 to 4 hours as needed.
    • Levalbuterol ^c113c114c115
      • Inhaler
        • Levalbuterol Tartrate Pressurized inhalation, suspension; Infants and Children: 180 to 360 mcg (4 to 8 actuations of 45 mcg/actuation) every 20 minutes for the first hour, then every 1 to 4 hours as needed. Delivery should occur with a spacer.
        • Levalbuterol Tartrate Pressurized inhalation, suspension; Adolescents: 180 to 360 mcg (4 to 8 actuations of 45 mcg/actuation) every 20 minutes for the first hour, then every 1 to 4 hours as needed.
      • Nebulizer
        • Levalbuterol Hydrochloride Nebulizer solution; Infants† and Children† 1 to 5 years: 1.25 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
        • Levalbuterol Hydrochloride Nebulizer solution; Children 6 to 12 years: 1.25 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
        • Levalbuterol Hydrochloride Nebulizer solution; Adolescents: 1.25 to 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 1.25 to 5 mg inhaled by nebulizer every 1 to 4 hours as needed.
  • Inhaled anticholinergics ^c116
    • Ipratropium
      • Inhaler
        • Ipratropium Bromide Pressurized inhalation, solution; Infants and Children 1 to 5 years: 160 mcg (approximately 9 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes for up to 1 hour, or alternately, 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) every 20 minutes as needed for up to 3 hours.
        • Ipratropium Bromide Pressurized inhalation, solution; Children 6 to 12 years: 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours.
        • Ipratropium Bromide Pressurized inhalation, solution; Adolescents: 136 mcg (8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours.
      • Nebulizer ^c117
        • Ipratropium Bromide Nebulizer solution; Infants and Children 1 to 5 years: 250 mcg inhaled by nebulizer every 20 minutes for up to 1 hour, or alternately, 250 to 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours.
        • Ipratropium Bromide Nebulizer solution; Children 6 to 12 years: 250 to 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours.
        • Ipratropium Bromide Nebulizer solution; Adolescents: 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours.
    • Ipratropium-albuterol ^c118
      • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Infants and Children 1 to 5 years: 0.25 mg ipratropium bromide/1.25 mg albuterol (1.5 mL) inhaled by nebulizer every 20 minutes for 3 doses.
      • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 0.25 mg ipratropium bromide/1.25 mg albuterol (1.5 mL) or 0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours.
      • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Adolescents: 0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours.
  • Smooth muscle relaxant
    • Magnesium sulfate ^c119
      • Magnesium Sulfate Solution for injection; Infants, Children, and Adolescents: 25 to 75 mg/kg/dose (Max: 2 g/dose) IV as a single dose over 15 to 30 minutes.
  • Systemic β₂-agonists ^r1r71c120
    • 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) ^c121
      • 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 doses.
        • 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 doses.
      • 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 as needed for up to 3 doses.
        • Epinephrine Hydrochloride Solution for injection; Adolescents: 0.3 to 0.5 mg subcutaneously every 20 minutes as needed for up to 3 doses.
    • Terbutaline ^c122
      • Terbutaline Sulfate Solution for injection; Children 1 to 11 years†: 0.01 mg/kg/dose (Max: 0.25 mg/dose) subcutaneously every 10 to 20 minutes for 3 doses then every 2 to 6 hours as needed.
      • Terbutaline Sulfate Solution for injection; Children and Adolescents 12 to 17 years: 0.01 mg/kg/dose (Max: 0.25 mg/dose) subcutaneously every 10 to 20 minutes for 3 doses then every 2 to 6 hours as needed.
  • Systemic corticosteroids ^r1c123
    • Dexamethasone ^c124c125
      • 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.
      • 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.
    • Prednisolone ^{r50r100r101r102c126c127}
      • Prednisolone Oral solution; Infants and Children 1 to 2 years: 1 to 2 mg/kg/day (Max: 20 mg/dose) PO in 1 to 2 divided doses for 3 to 10 days.
      • Prednisolone Oral solution; Children 3 to 5 years: 1 to 2 mg/kg/day (Max: 30 mg/dose) PO in 1 to 2 divided doses for 3 to 10 days.
      • Prednisolone Oral solution; Children 6 to 11 years: 1 to 2 mg/kg/day (Max: 40 mg/dose) PO in 1 to 2 divided doses for 3 to 10 days.
      • Prednisolone Oral solution; Children and Adolescents 12 to 17 years: 40 to 80 mg/day PO in 1 to 2 divided doses for 3 to 10 days. Usual Max: 60 mg/day. Max: 80 mg/day.
    • Methylprednisolone ^{r100r102c128c129}
      • Intravenous or intramuscular
        • Methylprednisolone Sodium Succinate Solution for injection; Infants and Children 1 to 5 years: 1 to 2 mg/kg/day (Max: 60 mg/day) IV/IM in 1 to 2 divided doses for 3 to 10 days. May consider 1 mg/kg/dose IV every 6 hours on day 1.
        • Methylprednisolone Sodium Succinate Solution for injection; Children 6 to 11 years: 1 to 2 mg/kg/day (Max: 60 mg/day) IV/IM in 1 to 2 divided doses for 3 to 10 days.
        • Methylprednisolone Sodium Succinate Solution for injection; Children and Adolescents 12 to 17 years: 40 to 80 mg/day IV/IM in 1 to 2 divided doses for 3 to 10 days.
• Chronic asthma
  • For relief of episodic wheezing (relievers)
    • Combination inhaled corticosteroids plus fast-onset, long-acting β₂-agonist (preferred)
      • Budesonide-formoterol ^r49c130
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† 4 to 11 years: 80 mcg budesonide/4.5 mcg formoterol (1 actuation of 80 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth once daily, with additional inhalations as needed. Max: 36 mcg formoterol/day.
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children and Adolescents 12 to 17 years: 160 mcg budesonide/9 mcg formoterol (2 actuations of 80 mcg budesonide/4.5 mcg formoterol/actuation) to 320 mcg budesonide/9 mcg formoterol (2 actuations of 160 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth as needed in addition to a daily maintenance dose; may repeat dose after 5 minutes if needed. Max: 54 mcg/day of formoterol (12 actuations/day of 4.5 mcg formoterol/actuation).
    • Short-acting β₂-agonists
      • Albuterol ^c131c132
        • Inhaler ^c133c134
          • Albuterol Pressurized inhalation, suspension; Children and Adolescents 4 to 17 years: 90 to 180 mcg (1 to 2 actuations of 90 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. Max: 1,080 mcg/day (12 actuations/day).
        • Nebulizer ^c135
          • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years weighing less than 15 kg: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed.
          • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years weighing 15 kg or more: 0.63 to 2.5 mg inhaled by nebulizer 3 or 4 times daily as needed.
          • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years weighing less than 15 kg: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed.
          • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years weighing 15 kg or more: 0.63 to 2.5 mg inhaled by nebulizer 3 or 4 times daily as 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) ^c136c137
        • Inhaler
          • Levalbuterol Tartrate Pressurized inhalation, suspension; Children and Adolescents 4 to 17 years: 45 to 90 mcg (1 to 2 actuations of 45 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. Max: 540 mcg/day (12 actuations/day).
        • Nebulizer
          • Levalbuterol Hydrochloride Nebulizer solution; Children 6 to 11 years: 0.31 or 0.63 mg inhaled by nebulizer 3 times daily as needed. Max: 1.89 mg/day.
          • Levalbuterol Hydrochloride Nebulizer solution; Children and Adolescents 12 to 17 years: 0.63 or 1.25 mg inhaled by nebulizer 3 times daily as needed. Max: 3.75 mg/day.
  • Maintenance treatment (controllers)
    • Inhaled corticosteroids ^c138
      • Fluticasone
        • Aerosol inhaler
          • Fluticasone Propionate Pressurized inhalation, suspension; Children 1 to 3 years†: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily. Use the lowest effective dose once stable.
          • Fluticasone Propionate Pressurized inhalation, suspension; Children 4 to 11 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily. Use the lowest effective dose once stable.
          • Fluticasone Propionate Pressurized inhalation, suspension; Children and Adolescents 12 to 17 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily. May increase the dose after 2 weeks if the response is not adequate. Max: 880 mcg (4 actuations of 220 mcg/actuation) twice daily. Use the lowest effective dose once stable.
        • Dry powder inhaler
          • Fluticasone Propionate Inhalation powder; Children 4 to 11 years: 50 mcg (1 actuation of 50 mcg/actuation) inhaled by mouth twice daily. May increase the dose after 2 weeks if the response is not adequate. Max: 100 mcg (2 actuations of 50 mcg/actuation or 1 actuation of 100 mcg/actuation) twice daily. Use the lowest effective dose once stable.
          • Fluticasone Propionate Inhalation powder; Children and Adolescents 12 to 17 years: 100 mcg (1 actuation of 100 mcg/actuation) inhaled by mouth twice daily. May increase the dose after 2 weeks if the response is not adequate. Max: 1,000 mcg (4 actuations of 250 mcg/actuation) twice daily. Use the lowest effective dose once stable.
      • Budesonide ^c139c140
        • Inhaler
          • Budesonide Inhalation powder; Children and Adolescents 6 to 17 years: 180 to 360 mcg (1 to 2 actuations of 180 mcg/actuation or 2 actuations of 90 mcg/actuation) inhaled by mouth twice daily. Max: 360 mcg (2 actuations of 180 mcg/actuation) twice daily. Use the lowest effective dose once stable.
        • Nebulizer ^c141c142c143
          • Budesonide Nebulizer suspension; Infants 3 to 11 months†: 0.5 to 1 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 2 mg/day. Limited data from small safety studies used 0.25 to 1 mg/day via nebulizer once daily or in 2 divided doses. Use the lowest effective dose once stable.
          • Budesonide Nebulizer suspension; Children 1 to 8 years: 0.25 to 1 mg inhaled by nebulizer once daily or 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 1 mg/day. Use the lowest effective dose once stable.
          • Budesonide Nebulizer suspension; Children 9 to 11 years†: 0.5 to 1 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 2 mg/day. Use the lowest effective dose once stable.
          • Budesonide Nebulizer suspension; Children and Adolescents 12 to 17 years†: 1 to 2 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.5 to 1 mg inhaled by nebulizer twice daily. Max: 4 mg/day. Use the lowest effective dose once stable.

      • 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. Published June 2002. Revised September 2012. Accessed September 19, 2023. 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
        Medication
        	Low	Medium*	High*	Low	Medium*	High*	Low	Medium*	High*
        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

    • Inhaled corticosteroid plus long-acting β₂-agonists ^c144
      • Budesonide-formoterol ^c145
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† 4 to 11 years: 80 mcg budesonide/4.5 mcg formoterol (1 actuation of 80 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth once daily, with additional inhalations as needed. Max: 36 mcg formoterol/day.
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children and Adolescents 12 to 17 years: 160 mcg budesonide/9 mcg formoterol (2 actuations of 80 mcg budesonide/4.5 mcg formoterol/actuation) or 320 mcg budesonide/9 mcg formoterol (2 actuations of 160 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth once or twice daily. Max: 54 mcg formoterol/day when used as both controller and reliever therapy.
      • Fluticasone-salmeterol ^c146
        • Fluticasone Propionate, Salmeterol Inhalation powder; Children 4 to 11 years: 100 mcg fluticasone/50 mcg salmeterol (1 actuation of 100 mcg fluticasone/50 mcg salmeterol/actuation) inhaled by mouth twice daily.
        • Fluticasone Propionate, Salmeterol Inhalation powder; Children and Adolescents 12 to 17 years: 100 mcg fluticasone/50 mcg salmeterol (1 actuation of 100 mcg fluticasone/50 mcg salmeterol) or 250 mcg fluticasone/50 mcg salmeterol (1 actuation of 250 mcg fluticasone/50 mcg salmeterol) or 500 mcg fluticasone/50 mcg salmeterol (1 actuation of 500 mcg fluticasone/50 mcg salmeterol) inhaled by mouth twice daily. Max: 1,000 mcg fluticasone/100 mcg salmeterol/day.
    • Leukotriene receptor antagonists (second line) ^c147
      • Montelukast ^r9r103c148
        • Montelukast Sodium Oral granules; Children 1 to 5 years: 4 mg PO once daily in the evening.
        • Montelukast Sodium Chewable tablet; Children and Adolescents 6 to 14 years: 5 mg PO once daily in the evening.
        • Montelukast Sodium Oral tablet; Adolescents 15 to 17 years: 10 mg PO once daily in the evening.
      • Zafirlukast ^r1r9c149
        • 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
      • Tiotropium ^r103r104c150
        • Tiotropium Respiratory spray, solution; Children 1 to 5 years†: 2.5 mcg (2 actuations of 1.25 mcg/actuation) inhaled by mouth once daily.
        • Tiotropium Respiratory spray, solution; Children and Adolescents 6 to 17 years: 2.5 mcg (2 actuations of 1.25 mcg/actuation) inhaled by mouth once daily.
    • Leukotriene synthesis inhibitor
      • Zileuton ^r49c151c152
        • Immediate release
          • Zileuton Oral tablet; Children and Adolescents 12 to 17 years: 600 mg PO 4 times daily.
        • Extended release
          • Zileuton Oral tablet, biphasic release; Children and Adolescents 12 to 17 years: 1,200 mg PO twice daily.
    • Mast cell stabilizer ^r1c153
      • Cromolyn
        • Cromolyn Sodium Nebulizer solution; Children and Adolescents 2 to 17 years: 20 mg inhaled by nebulizer 4 times daily. Usual maintenance dose: 20 mg inhaled by nebulizer 3 times daily.
    • Biologic agents ^r1c154
      • Benralizumab ^c155
        • Adjunctive therapy for patients with severe asthma (eosinophilic phenotype)
          • Benralizumab Solution for injection; Children and Adolescents 12 to 17 years: 30 mg subcutaneously every 4 weeks for 3 doses, then 30 mg subcutaneously every 8 weeks.
      • Dupilumab ^c156
        • Eosinophilic phenotype moderate to severe asthma
          • Dupilumab Solution for injection; Children 6 to 11 years weighing 15 to 29 kg: 300 mg subcutaneously every 4 weeks.
          • Dupilumab Solution for injection; Children 6 to 11 years weighing 30 kg or more: 200 mg subcutaneously every other week.
          • Dupilumab Solution for injection; Children and Adolescents 12 to 17 years: 400 mg subcutaneously as a single dose, then 200 mg subcutaneously every other week or 600 mg subcutaneously as a single dose, then 300 mg subcutaneously every other week.
        • Oral corticosteroid–dependent moderate to severe asthma
          • Dupilumab Solution for injection; Children 6 to 11 years weighing 15 to 29 kg: 300 mg subcutaneously every 4 weeks.
          • Dupilumab Solution for injection; Children 6 to 11 years weighing 30 kg or more: 200 mg subcutaneously every other week.
          • Dupilumab Solution for injection; Children and Adolescents 12 to 17 years: 600 mg subcutaneously as a single dose, then 300 mg subcutaneously every other week.
      • Mepolizumab ^c157c158c159
        • Adjunctive therapy for patients with severe asthma (eosinophilic phenotype) ^r105r106
          • Mepolizumab Solution for injection; Children 6 to 11 years: 40 mg subcutaneously every 4 weeks.
          • Mepolizumab Solution for injection; Children and Adolescents 12 to 17 years: 100 mg subcutaneously every 4 weeks.
      • Omalizumab ^c160
        • 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 to 17 years: 75 to 375 mg subcutaneously every 2 to 4 weeks. Dosing varies based on age, weight, and baseline serum IgE. Adjust dosage for significant changes in weight.
      • Tezepelumab
        • Add on maintenance for severe asthma
        • Tezepelumab Solution for injection; Children and Adolescents 12 to 17 years: 210 mg subcutaneously every 4 weeks.
    • Methylxanthines ^r1c161
      • Theophylline
        • Theophylline oral solution ^r1
          • Theophylline, Anhydrous Oral solution; Infants 4 to 25 weeks: 10 mg/kg/day PO divided every 8 hours, initially. Adjust dose based on serum theophylline concentrations.
          • Theophylline, Anhydrous Oral solution; Infants 26 to 51 weeks: 10 mg/kg/day PO divided every 6 hours, initially. Adjust dose based on serum theophylline concentrations.
          • Theophylline, Anhydrous Oral solution; Children 1 to 11 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 4 to 6 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 16 mg/kg/day.
          • Theophylline, Anhydrous Oral solution; Children 1 to 11 years weighing more than 45 kg: 300 mg/day PO divided every 6 to 8 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 16 mg/kg/day.
          • Theophylline, Anhydrous Oral solution; Children and Adolescents 12 to 15 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 4 to 6 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 800 mg/day.
          • Theophylline, Anhydrous Oral solution; Children and Adolescents 12 to 15 years weighing more than 45 kg: 300 mg/day PO divided every 6 to 8 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
          • Theophylline, Anhydrous Oral solution; Adolescents 16 to 17 years: 300 mg/day PO divided every 6 to 8 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
        • Theophylline extended-release oral tablet ^r1
          • Theophylline Oral tablet, extended-release; Children 6 to 11 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 16 mg/kg/day.
          • Theophylline Oral tablet, extended-release; Children 6 to 11 years weighing more than 45 kg: 300 mg/day PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 16 mg/kg/day.
          • Theophylline Oral tablet, extended-release; Children and Adolescents 12 to 15 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 800 mg/day.
          • Theophylline Oral tablet, extended-release; Children and Adolescents 12 to 15 years weighing more than 45 kg: 300 mg/day PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
          • Theophylline Oral tablet, extended-release; Adolescents 16 to 17 years: 300 mg/day PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
    • Oral corticosteroids
      • Prednisolone ^r101
        • Prednisolone Oral solution; Infants and Children 1 to 2 years: 0.25 to 2 mg/kg/dose (Usual Max: 20 mg/dose) PO once daily or every other day. Use the lowest effective dose.
        • Prednisolone Oral solution; Children 3 to 5 years: 0.25 to 2 mg/kg/dose (Usual Max: 30 mg/dose) PO once daily or every other day. Use the lowest effective dose.
        • Prednisolone Oral solution; Children 6 to 11 years: 0.25 to 2 mg/kg/dose (Usual Max: 40 mg/dose) PO once daily or every other day. Use the lowest effective dose.
        • Prednisolone Oral solution; Children and Adolescents 12 to 17 years: 7.5 to 60 mg PO once daily or every other day. Use the lowest effective dose.
      • Methylprednisolone ^c162c163c164
        • Methylprednisolone Oral tablet; Infants and Children 1 to 2 years: 0.25 to 2 mg/kg/dose (Usual Max: 20 mg/dose) PO once daily or every other day. Use the lowest effective dose.
        • Methylprednisolone Oral tablet; Children 3 to 5 years: 0.25 to 2 mg/kg/dose (Usual Max: 30 mg/dose) PO once daily or every other day. Use the lowest effective dose.
        • Methylprednisolone Oral tablet; Children 6 to 11 years: 0.25 to 2 mg/kg/dose (Usual Max: 40 mg/dose) PO once daily or every other day. Use the lowest effective dose.
        • Methylprednisolone Oral tablet; Children and Adolescents 12 to 17 years: 7.5 to 60 mg PO once daily or every other day. Use the lowest effective dose.
      • Dexamethasone ^c165c166c167
        • Alternative for patients unable to tolerate other liquid preparations
        • Dexamethasone Oral solution; Infants and Children 1 to 11 years: 0.4 mg/kg/dose PO once daily or every other day.

• 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. Published June 2002. Revised September 2012. Accessed September 19, 2023. 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
  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
  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
  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
  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
  Leukotriene receptor antagonist: zafirlukast
  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)
  Leukotriene synthesis inhibitor: zileuton
  600-mg tablet	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	N/A	N/A	150- to 375-mg subcutaneous injection every 2 to 4 weeks, depending on body weight and pretreatment serum IgE level
  Mast cell stabilizer
  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	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
  Formoterol
  DPI: 12 mcg/single-use capsule	N/A	1 capsule every 12 hours	1 capsule 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 ^c168
• Educate caregivers about home management and monitoring, use of maintenance medications, and inhaler technique ^r107c169
• Use control chart and written asthma action plan emphasizing difference between controller and reliever medications (sample available within the National Asthma Education and Prevention Program guidelines) ^r1c170
• Encourage caregivers to provide a copy of written asthma action plan to school, child care facility, or camp ^r1c171
• School-based asthma self-management interventions may reduce asthma symptoms, emergency department visits, and hospital admissions, particularly in younger children from socially disadvantaged populations ^r108c172
• Use of technology including telephone-based peer coaching in the past has been associated with improved asthma outcomes ^r109
• Electronic health (e-health) resources such as web-based asthma management systems, social media platforms, text message reminders, and mobile health applications can increase awareness of asthma, promote asthma self management, potentially increase adherence, and improve quality of life ^r110
• Inhaler trackers may improve asthma outcomes ^r110

Can utilize peak expiratory flow meters to monitor asthma control at home. Results are technique dependent; review at each visit

Promote active participation in physical activities, exercise, and sports ^{r1c173c174c175}

Reduce exposure to allergen, irritant, and air pollution triggers ^c176

• 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 per the National Asthma Education Prevention Program 2020 updates ^r74
  • 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

  • Examples of allergen mitigation interventions and their targeted allergens.

    SR, Systematic review.
    ++Primary target allergen(s) for the intervention.
    +Secondary target allergen(s) for the intervention.
    *Dander from rodents.

    Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC) et al: 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 146(6):1217-70, 2020

    Intervention assessed in studies in the SR	Animal dander	Dust mites	Cockroaches	Mold
    Acaricide		++
    Air filtration systems and air purifiers	++	+	+	++
    Carpet removal	++	++		+
    Cleaning products (eg, bleach)				++
    HEPA vacuum cleaners	++	+	+	++
    Impermeable pillow and mattress covers		++
    Integrated pest management	+*		++
    Mold mitigation				++
    Pet removal	++

• National Environmental Education Foundation provides guidelines for environmental management in pediatric asthma ^r111
• Subcutaneous allergen immunotherapy is indicated in patients with allergic asthma
  • It is efficacious in patients where there is there is clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive and exposure reduction measures have failed
  • Avoid in patients with severe asthma as they may be at risk for systemic allergic reactions during immunotherapy administration

Avoid using β-blockers and NSAIDs (including aspirin) in patients with asthma because they have potential to exacerbate symptoms ^c177c178

Multidisciplinary case management may be needed for patients with severe, difficult-to-treat disease ^c179

Comorbidities

• Gastroesophageal reflux disease ^r1c181
  • Common, but may be unrecognized; prevalence of gastroesophageal reflux disease among patients with asthma is between 34% and 89% ^r62
  • Consider evaluation for gastroesophageal reflux disease (eg, 24-hour pH probe, endoscopic investigation)^r72 in patients who have poorly controlled moderate to severe persistent asthma, especially with nighttime symptoms, even in the absence of symptoms suggestive of gastroesophageal reflux disease
    • Reflux can be a trigger for asthma and treatment can help improve symptoms ^r112
  • 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
  • Trial empiric therapy for proton pump inhibitors taken twice daily for 4 to 8 weeks in patients with gastroesophageal reflux disease symptoms
  • Refer to gastroenterology for any alarm signs or gastroesophageal reflux disease refractory to treatment
    • Alarm signs include unexplained weight loss, hematemesis, dysphagia, forceful vomiting
• Obesity ^c182d7
  • Increased prevalence of asthma in children who are obese; obesity also may be a predisposing risk factor for asthma, but causality is uncertain ^r113r114
  • Concomitant comorbidity (eg, obstructive sleep apnea, gastroesophageal reflux, diminished lung volumes) often renders management more difficult ^r115
  • Children who are obese children to have more severe asthma with increased exacerbations and poor asthma control ^r116
  • Children with asthma who are obese may have higher FEV₁ and FVC but lower FEV₁/FVC ratio on spirometry ^r117
    • Children with asthma who are obese have associated airway 'dysanapsis' or a "incongruence between the growth of the lungs and the airways", which is associated with increased morbidity and poor response to inhaled corticosteroids ^r118
  • Obesity makes asthma more difficult to manage and is associated with a diminished benefit of asthma medications ^r114
    • Adult patients with elevated BMI have decreased in vitro response to systemic steroids (dexamethasone) and inhaled corticosteroid ^r119r120
      • Unlike adults, preschool children who are obese respond to inhaled corticosteroid therapy and have decreased symptoms and exacerbations
    • Trials conducted in adults show omalizumab improves exacerbations, lung function, and symptoms across all BMI groups compared to placebo ^r121
      • Mepolizumab also has benefits regardless of weight and BMI in patients with severe eosinophilic asthma aged older than 12 years ^r122
  • Weight loss of 5% to 10% often leads to significant improvement in asthma control ^r72
• Allergic bronchopulmonary aspergillosis ^r1c183d8
  • Consider in patients with asthma with recurrent severe exacerbations despite appropriate therapy, productive brown mucus, fever, malaise, and weight loss
  • Chest radiography may reveal pulmonary parenchymal opacities and findings consistent with bronchiectasis such as "gloved finger shadows" or "tram lines"
  • Diagnostic criteria include:
    • Positive immediate skin test result
    • Elevated serum IgE and/or IgG level to aspergillus
    • Total serum IgE level greater than 417 kU/L (1000 ng/mL)
    • Central bronchiectasis
  • Treat using prednisone with a gradual taper; adjunctive therapy with azole antifungal agents also may be helpful
  • Monitor with serum IgE every 1 to 2 months to assess response to glucocorticoids
  • Refer to pulmonologist
• Eosinophilic granulomatosis with polyangiitis
  • Multi-organ vasculitis
  • Presents with allergic rhinitis, asthma, and paranasal sinus disease, leading to eosinophilic infiltration of multiple organs and then systemic vasculitis
  • Peripheral blood eosinophilia, perinuclear anti-neutrophil cytoplasmic antibodies–positive
  • Cardiac manifestations are a common cause of mortality
  • Treat with glucocorticoids, biologic therapies (mepolizumab), and immunosuppressants ^r123
• Obstructive sleep apnea ^r1c184d9
  • Consider in patients with poorly controlled asthma, particularly those who are obese and/or who report symptoms consistent with obstructive sleep apnea (eg, snoring, pauses in respiration while asleep, daytime fatigue)
  • Nocturnal dyspnea is a common symptom in both obstructive sleep apnea and asthma
  • Associated with more severe asthma in children ^r124
  • Order a sleep study to confirm diagnosis; refer to Ear, Nose, and Throat specialist or pulmonologist; treat obstructive sleep apnea with nasal CPAP
  • Surgical intervention with adenotonsillectomy may be indicated ^r125
• Allergic rhinitis ^r1c185d9
  • Common in patients with asthma
  • Rhinitis presents with sneezing, congestion, rhinorrhea, and itching of nose and/or eyes
  • Allergic rhinitis is triggered by allergens, although rhinitis can be triggered by irritants, infections, and medications (eg, aspirin), among others
  • One airway hypothesis
    • Upper and lower airways are not distinct and allergic rhinitis/rhinosinusitis impacts asthma
    • Sensitivity to aeroallergens in children at risk for atopy is associated with increased airway hyper responsiveness ^r126
    • Nasal provocation with allergen can increase bronchial responsiveness to methacholine ^r127
    • Suggest the importance of management of allergic rhinitis in the treatment of asthma ^r128
  • Treat using intranasal corticosteroids or intranasal and/or systemic or antihistamine therapy; consider immunotherapy
    • Treatment with intranasal corticosteroids for allergic rhinitis is associated with improvements in asthma outcomes including FEV₁, bronchial challenge, asthma symptom score, rescue medication use, emergency department visits, and hospitalizations
• Infectious sinusitis ^r1c186d10
  • Can trigger asthma exacerbation (one airway hypothesis)
  • Treat with appropriate antibiotics
    • Treating sinusitis has been found to increase the threshold for bronchial provocation by methacholine in children with asthma ^r129
  • Evidence is inconclusive regarding the effect of sinus surgery on asthma in patients who have chronic rhinosinusitis
• Psychological disorders (eg, anxiety disorders, depressive disorders) ^{r1c187c188c189}
  • Can complicate asthma management
    • Often associated with low treatment adherence, increased asthma- related emergency department use, and poor asthma control ^r72r130r131
    • Chronic psychiatric disorders and major psychosocial problems are risk factors for asthma death ^r1
  • 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 ^c190
  • Can be misdiagnosed as asthma but can be seen concomitantly with asthma ^r1
  • Spirometry aids in the diagnosis of vocal cord dysfunction; direct vocal cord visualization is the gold standard to diagnose ^r61
  • 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) ^r61
• Food allergies (eg, tree nuts, peanuts) ^r72c191
  • Asthma is a risk factor for food-induced fatal anaphylaxis in patients with food allergy ^r48
  • Instruct patients with comorbid food allergies to always carry an epinephrine autoinjector
• COVID-19 infection ^c192
  • 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 ^r132
    • Children with asthma have had improved asthma symptom control and outcomes during the COVID-19 pandemic owing to lockdown measures and concomitant decreased exposure to viruses ^r133
    • Allergen sensitization and asthma is associated with decreased ACE2 receptor expression. ACE2 receptors are utilized by SARS-COV-2 to enter airway epithelial cells. Asthma may be a protective factor for COVID-19 infection in children ^r134r135
    • Asthma does not appear to significantly to increase the risk of contracting COVID-19 infection or of more severe disease or death in adult patients ^r136
    • Asthma does not appear to be a risk factor for hospitalization or ICU admission due to COVID-19 infection in children, and children with asthma did not experience a higher severity of COVID-19 infection ^r137
    • Poorly controlled asthma increases the risk of COVID-19 hospitalization in children aged 12 years and older; rate of hospitalization of 375.3 (206.9–543.8) per 100,000 among children who had two or more courses of oral corticosteroids in the past year compared with 94.4 (90.8–98.0) for children without a diagnosis of asthma ^r138
  • Regular use of inhaled corticosteroids is considered unlikely to increase the risk of acquiring COVID-19 infection or increasing the severity of the infection ^r132
  • Patients treated with biologic therapies may have a reduced humoral immune response to COVID 19 vaccination, which may warrant more frequent booster vaccination ^r139
  • 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 ^r7r132
  • 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
  • Follow local and national public health measures to control spread of infection including use of personal protection equipment
  • Follow applicable national guidelines for COVID-19 vaccination (eg, CDC guidelines) ^r140

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 (arterial oxygen saturation) less than 90%
  • Greater risk for respiratory failure; lack of response on physical examination or by objective measurements requires hospitalization
  • Consider structural abnormalities (trachea/bronchomalacia, vascular rings), viral-induced wheezing (bronchiolitis), or foreign body aspiration in young children
• Patients aged 4 years and younger ^r1
  • Young children are at risk for severe exacerbations despite having a low level of impairment between episodes
    • In children younger than 4 years who have had 3 or more episodes of wheezing triggered by respiratory tract infections in their lifetime or two episodes in the past year and who are asymptomatic between the respiratory infections
      • Start 7 to 10 day course of inhaled corticosteroid daily with as-needed short-acting β₂-agonist at the onset of signs and symptoms indicating respiratory tract infections
    • 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
      • Nighttime symptoms occur more frequently than 1 night a month
      • 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
  • Few long-term control medications are FDA approved for this age group, including: ^r1
    • Budesonide nebulizer solution (patients aged 1-8 years)
    • Fluticasone propionate dry powder inhaler or aerosol inhaler (patients aged 4 years and older)
    • Salmeterol dry powder inhaler in combination with inhaled corticosteroid (patients aged 4 years and older)
    • 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 aged younger than 5 years ^r29
  • 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 bronchoconstriction ^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 bronchoconstriction
  • Bronchoconstriction peaks 10 to 15 minutes after exercise
    • 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 5 to 20 minutes 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:
        • Budesonide-formoterol on-demand therapy when compared to on-demand short-acting β₂-agonist therapy improves asthma control and reduces exercise-induced bronchospasm ^r141
        • Leukotriene receptor antagonists must be administered at least 2 hours before exercise and will attenuate exercise-induced bronchospasm in 50% of patients for 12 to 24 hours ^r1
        • Cromolyn should be administered shortly (15 minutes) before exercise (not widely available in the US)
    • Long-term control therapy (eg, inhaled corticosteroids) may be appropriate in patients with frequent or severe exercise-induced bronchospasm; offers protection in 1 to 3 weeks ^r72
    • Encourage a gradual warm-up period before exercise and use of a mask or scarf over mouth during cold weather
    • Avoid high salt, low antioxidant, and high omega-6 polyunsaturated fatty acids, which can leads to increased exercise-induced bronchospasm
• Children with cough variant asthma ^r1
  • Can be challenging to diagnose
  • Spirometry with reversible obstruction with bronchodilators and bronchoprovocation can be helpful but not diagnostic
  • Chronic cough that is triggered by exercise, cold air, allergens, or cough at night without typical wheezing or dyspnea is suggestive of cough variant asthma
    • Personal or family history of atopy, wheezing also supports diagnosis
  • Trial and assess response to asthma medications (bronchodilators, leukotriene antagonist, inhaled corticosteroids) after exclusion of alternate etiology for symptoms; supports diagnosis of cough variant asthma
  • Long-term management is similar to that for other patients with asthma ^r142