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Aug.09.2021

Asthma in Children

Synopsis

Key Points

  • Asthma is a chronic inflammatory airway disease causing episodic, acute airflow obstruction and/or increased airway reactivity that is totally or partially reversible (with or without therapy) in a patient who has normal laryngeal function and lacks an alternative diagnosis r1
  • Presents with episodic wheezing, chest tightness, difficulty breathing, and cough
  • Diagnosis is based on episodic nature of symptoms, physical examination, and documented reversibility of airflow obstruction via spirometry
  • Physical signs and symptoms alone are sometimes unreliable in estimating the severity of an exacerbation; use peak expiratory flow measurements to objectively assess the degree of airway obstruction in children aged 5 years and older
  • Treat acute symptoms with an inhaled short-acting β₂-agonist; add systemic steroids and inhaled anticholinergics if needed
  • Follow stepwise treatment for long-term management of disease based on asthma severity classification (ie, mild intermittent, mild persistent, moderate persistent, severe persistent disease)
  • Long-term management requires frequent monitoring to assess level of asthma control; adjust treatment to achieve minimum dose of long-term control medication required to maintain asthma control
  • Identify and reduce precipitating factors to improve asthma control and reduce frequency and severity of exacerbation; some triggers include environmental allergens and irritants (eg, dust mites, cockroach frass, pet dander, mold spores), pollutants, and tobacco smoke
  • Management of common comorbid disease improves overall asthma control (eg, gastroesophageal reflux, obesity, obstructive sleep apnea, allergic rhinitis, vocal cord dysfunction, any psychological issues)
  • Long-term complications include airway remodeling with diminished lung function; short-term complications from exacerbation include respiratory failure and death
  • Overall prognosis is good if adequate disease control is achieved and maintained in patients with asthma, minimizing risk for acute exacerbation

Urgent Action

  • In exacerbation, quickly assess any patient with respiratory distress (eg, vital signs, signs of tiring from work of breathing, lung examination, oxygen saturation, peak expiratory flow); supplement oxygen to maintain SaO₂ at least 90%
  • For acute exacerbations in the emergent setting, begin treatment with short-acting β₂-agonist via inhaler with spacer or nebulizer; give oral steroids if there is no improvement
  • Consider alternative diagnoses that would require other urgent action (eg, foreign body aspiration)
  • For impending respiratory arrest, consider adjunct measures in addition to short-acting inhaled β₂-agonist, ipratropium, and oxygen (eg, IV systemic corticosteroids, subcutaneous epinephrine, IV magnesium sulfate) while preparing for intubation and mechanical ventilation

Pitfalls

  • Physical examination may be an unreliable indicator of the severity of airflow obstruction; wheezing may not be heard with severe airway obstruction
  • Spirometry, peak expiratory flow, and fraction of exhaled nitric oxide may be difficult to obtain in an uncooperative or very young patient, resulting in a higher level of reliance on physical examination (which is itself unreliable) and history
  • In patients who present with wheezing and atypical features, consider 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
  • Intubation and mechanical ventilation with 100% oxygen are needed only for imminent or actual respiratory arrest; make every effort to avoid intubation, because airway manipulation can abruptly worsen an asthmatic crisis r2

Terminology

Clinical Clarification

  • Asthma is a chronic inflammatory airway disease causing episodic, acute airflow obstruction and/or increased airway reactivity that is totally or partially reversible (with or without therapy) in a patient who has normal laryngeal function and lacks an alternative diagnosis r1
  • Presents with recurrent episodes of wheeze, cough, dyspnea, and chest tightness r3
  • Asthma affects approximately 8.5% to 13% of children in the United States and is the leading cause of childhood hospitalization and school absenteeism r4r5
  • Asthma in adolescents aged 12 years and older is diagnosed and managed as for adults d1
    • However, patients aged 12 to 18 years (particularly when prepubertal) are at higher risk for some medication adverse effects such as growth suppression and should be monitored as for children r6

Classification

  • Classification of asthma severity r1
    • Based on asthma severity at initial evaluation in patients not currently using controller medication r1r7r8
      • Mild intermittent asthma r1
        • Current impairment
          • Symptoms occur 2 days per week or less
          • Symptoms do not interfere with normal activity
          • Nighttime awakenings
            • No nighttime awakening in patients younger than 5 years
            • 2 or fewer nighttime awakenings per week in patients aged 5 years or older
          • Use of short-acting β₂-agonist for symptom control 2 days per week or less
          • Lung function
            • FEV₁ (predicted within the reference range for patient between exacerbations) or peak expiratory flow (personal best) greater than 80%
            • FEV₁/FVC greater than 85% (within the reference range)
        • Risk for severe exacerbation
          • 1 or no exacerbation requiring oral systemic steroids in the past year
        • This severity classification corresponds to step 1 management strategy when asthma is well controlled (lowest level of treatment required to maintain asthma)
      • Mild persistent asthma r1
        • Current impairment
          • Symptoms occur more than 2 days per week, but not daily
          • Symptoms interfere minimally with normal activity
          • Nighttime awakenings
            • 1 to 2 nighttime awakenings per month in patients younger than 5 years
            • 3 to 4 nighttime awakenings per month in patients aged 5 years or older
          • Use of short-acting β₂-agonist for symptom control more than 2 days per week, but not daily
          • Lung function
            • FEV₁ (predicted within the reference range for patient between exacerbations) or peak expiratory flow (personal best) greater than 80%
            • FEV₁/FVC greater than 80% in patients aged 5 to 11 years; within the reference range in patients aged 12 years or older
        • Risk for severe exacerbation
          • 2 or more exacerbations requiring oral systemic steroids in the past year (relative annual risk may be related to FEV₁)
          • 4 or more wheezing episodes per year lasting more than 1 day in a patient younger than 5 years with risk factors for persistent asthma
        • This severity classification corresponds to step 2 management strategy when asthma is well controlled (lowest level of treatment required to maintain asthma)
      • Moderate persistent asthma r9
        • Current impairment
          • Symptoms occur daily
          • Symptoms cause limitation of normal activity
          • Nighttime awakenings
            • 3 to 4 nighttime awakenings per month in patients younger than 5 years
            • More than 1 nighttime awakening per week (but not nightly) in patients aged 5 years or older
          • Use of short-acting β₂-agonist for daily symptom control
          • Lung function
            • FEV₁ (predicted within the reference range for patients between exacerbations) or peak expiratory flow (personal best) 60% to 80%
            • FEV₁/FVC 75% to 80% in patients aged 5 to 11 years; 80% to 85% in patients aged 12 years or older
        • Risk for severe exacerbation
          • 2 or more exacerbations requiring oral systemic steroids in the past year (relative annual risk may be related to FEV₁)
          • 4 or more wheezing episodes per year lasting more than 1 day in a patient younger than 5 years with risk factors for persistent asthma
        • This severity classification corresponds to step 3 or 4 management strategy when asthma is well controlled (lowest level of treatment required to maintain asthma)
      • Severe persistent asthma r1
        • Current impairment
          • Symptoms occur throughout the day
          • Symptoms cause major limitation of normal activity
          • Nighttime awakenings
            • More than 1 nighttime awakening per week in patients younger than 5 years
            • Frequent nighttime awakenings (7 times per week) in patients aged 5 years or older
          • Use of short-acting β₂-agonist for symptom control multiple times per day
          • Lung function
            • FEV₁ (predicted within the reference range for patients between exacerbations) or peak expiratory flow (personal best) less than 60%
            • FEV₁/FVC less than 75% in patients aged 5 to 11 years; less than 80% in patients aged 12 years or older
        • Risk for severe exacerbation
          • 2 or more exacerbations requiring oral systemic steroids in the past year (relative annual risk may be related to FEV₁)
          • 4 or more wheezing episodes per year lasting more than 1 day in a patient younger than 5 years with risk factors for persistent asthma
        • This severity classification corresponds to step 5 or 6 management strategy when asthma is well controlled (lowest level of treatment required to maintain asthma)
  • Classification based on level of long-term asthma control r1
    • Used as a guide to adjust asthma therapy in patients on long-term controller medications
      • Well controlled
        • Current impairment
          • Symptoms occur 2 or fewer days per week but not more than once per day
          • Nighttime awakenings
            • 1 or fewer nighttime awakenings per month in patients younger than 12 years
            • 2 or fewer nighttime awakenings per month in patients aged 12 years or older
          • No interference with normal activity
          • Use of short-acting β₂-agonist for symptom control (not including exercise-induced bronchospasm) 2 or fewer days per week
          • Lung function
            • FEV₁ (predicted) or peak expiratory flow (personal best) greater than 80%
            • FEV₁/FVC greater than 80%
        • Risk for severe exacerbation
          • 1 or no exacerbation requiring oral systemic steroids in the past year
        • This level of control corresponds to maintaining current step in management with regular follow-up; consider treatment step-down if well-controlled status is maintained for at least 3 months
      • Not well controlled (partially controlled)
        • Current impairment
          • Symptoms on more than 2 days per week or multiple times on 2 or fewer days per week
          • Nighttime awakenings
            • More than 1 nighttime awakening per month in patients younger than 5 years
            • 2 or more nighttime awakenings per month in patients aged 5 to 11 years
            • 1 to 3 nighttime awakenings per week in patients aged 12 years or older
          • Some limitation in normal activity
          • Use of short-acting β₂-agonist for symptom control 2 or more days per week (not including exercise-induced bronchospasm)
          • Lung function
            • FEV₁ (predicted) or peak expiratory flow (personal best) 60% to 80%
            • FEV₁/FVC 75% to 80%
        • Risk for severe exacerbation
          • 2 to 3 exacerbations requiring oral systemic steroids in the past year in patients younger than 5 years
          • 2 or more exacerbations requiring oral systemic steroids in the past year in patients aged 5 years or older
        • This level of control corresponds to changing management by moving up at least 1 step and reevaluating in 2 to 6 weeks
      • Very poorly controlled (uncontrolled)
        • Current impairment
          • Symptoms throughout the day
          • Nighttime awakenings
            • 1 or more nighttime awakenings per week in patients younger than 5 years
            • 2 or more nighttime awakenings per week in patients aged 5 to 11 years
            • 4 or more nighttime awakenings per week in patients aged 12 years or older
          • Extremely limited activity
          • Use of short-acting β₂-agonist for symptom control several times per day (not including exercise-induced bronchospasm)
          • Lung function
            • FEV₁ (predicted) or peak expiratory flow (personal best) less than 60%
            • FEV₁/FVC less than 75%
        • Risk for severe exacerbation
          • 3 or more exacerbations requiring oral systemic steroids in the past year in patients younger than 5 years
          • 2 or more exacerbations requiring oral systemic steroids in the past year in patients aged 5 years or older
        • This level of control corresponds to changing management by moving up 1 to 2 steps and considering a short course of systemic corticosteroids, then reevaluating in 2 weeks
  • Phenotypic classifications r10
    • Some of these classifications do not appear to describe stable phenotypes and are of uncertain usefulness clinically r11
    • Based on age at onset and pattern of chronicity
      • Early transient preschool wheezing
        • Triggered by recurrent respiratory infections
        • Begins before age 3 years; does not persist beyond age 6 years
        • More than half of preschoolers who wheeze become asymptomatic by school age, irrespective of treatment r3
      • Late-onset wheezing
        • Wheezing episodes begin between ages 3 and 6 years and persist into later childhood or adulthood
      • Chronic asthma r10
        • Often triggered by allergy coupled with unknown factors
        • Early persistent wheezing
          • Wheezing episodes start before age 3 years and continue beyond age 6 years
            • Subtypes include: r12
              • Nonatopic persistent wheezing
                • Characterized by wheezing onset in first year of life, fewer symptoms into adolescence, and resolution of symptoms by adulthood
              • IgE-associated and/or atopic persistent wheezing phenotype
                • Characterized by wheezing onset in second year of life persisting into adolescence, with or without persistence into adulthood
    • Based on wheezing patterns r13r14
      • Cough variant asthma r1
        • Cough (without wheezing) responsive to bronchodilators
      • Transient wheezing
        • Occurs in first 2 years of life
      • Nonatopic wheezing
        • Triggered by viral infections early in life and remitting later in childhood
      • Persistent asthma
        • Characterized by atopy, eosinophilia, positive parental history, associated food allergy, and high indoor allergen exposure
      • Severe intermittent wheezing
        • Infrequent episodes with minimal morbidity between episodes but associated with atopic characteristics
    • Based on phenotypic cluster (ie, atopic burden, lung function and airway lability, exacerbation history) r15
      • Mild asthma with low atopy, obstruction, and exacerbation rate
        • No history of atopic dermatitis, low prevalence of hay fever and skin prick test reactivity, and lowest IgE levels
        • Preserved lung function (highest FEV₁/FVC ratio)
        • Lowest bronchodilator response, intermediate airway hyperresponsiveness
        • Lowest risk of exacerbation
      • Atopic asthma with low levels of obstruction and medium rates of exacerbation
        • History of atopic dermatitis with high prevalence of allergic rhinitis and skin test reactivity
        • Preserved lung function (highest FEV₁)
        • Intermediate bronchodilator response and airway hyperresponsiveness
        • Low to intermediate risk of exacerbations
      • Atopic asthma with high levels of obstruction and medium rates of exacerbation
        • Rare history of atopic dermatitis but high prevalence of allergic rhinitis and skin test reactivity
        • Marked reduction in lung function (lowest FEV₁ and FEV₁/FVC ratio)
        • High bronchodilator response and most severe airway hyperresponsiveness
        • Intermediate risk of exacerbation
      • Moderately atopic asthma with high levels of obstruction and high exacerbation rates
        • No history of atopic dermatitis, intermediate prevalence of hay fever, and lower IgE levels
        • Reduced lung function (low FEV₁/FVC ratio)
        • High bronchodilator response and high airway hyperresponsiveness
        • Intermediate to high risk of exacerbation
      • Highly atopic asthma with high levels of obstruction and high exacerbation rates
        • History of atopic dermatitis with highest prevalence of skin test reactivity, highest IgE levels, highest eosinophilia, and intermediate prevalence of allergic rhinitis
        • Reduced lung function (low FEV₁/FVC ratio)
        • Highest bronchodilator response and severe airway hyperresponsiveness
        • Highest risk of exacerbation
    • Based on apparent trigger r13r14
      • Virus-induced asthma
      • Exercise-induced asthma
        • Prevalence is estimated at up to 10% in school-aged children r16
        • Many children with persistent asthma also have exercise-induced symptoms
      • Obesity-related asthma
      • Allergen-induced asthma
      • Multiple trigger wheeze
        • Several apparent triggers are identified that vary over time, including irritant exposure r3
      • Unresolved
  • Classification of acute asthma exacerbation r1
    • Mild
      • Dyspnea only with activity
      • Able to lie flat
      • Speaks in full sentences
      • Peak expiratory flow of 70% or higher of predicted or personal best
      • This degree of acute exacerbation usually correlates with a clinical course of strictly home management; relief is prompt with inhaled short-acting β₂-agonist treatment, which may require addition of a short course of oral steroids
    • Moderate
      • Dyspnea limits usual activity
      • Would rather sit than lie down
      • Speaks in short phrases
      • Peak expiratory flow 40% to 69% of predicted or personal best
      • This degree of acute exacerbation usually requires an office or emergency department visit and correlates with a clinical course managed with relief from scheduled inhaled short-acting β₂-agonist treatment and oral systemic steroids; some symptoms persist for 1 to 2 days after acute treatment is initiated
    • Severe
      • Dyspnea at rest
      • Speaks in single words
      • Must sit upright
      • Peak expiratory flow lower than 40% of predicted or personal best r1
      • This degree of acute exacerbation usually requires an emergency department visit and hospitalization. The patient experiences partial relief from inhaled short-acting β₂-agonist treatment and oral steroids with some symptoms lasting more than 3 days after acute treatment has begun; adjunctive therapies are often helpful
    • Life-threatening
      • Cannot speak
      • Often drowsy or confused
      • Paradoxical thoracoabdominal movement
      • Peak expiratory flow lower than 25% of predicted or personal best
      • This degree of acute exacerbation usually requires an emergency department visit and ICU hospitalization. The patient experiences minimal or no relief from inhaled short-acting β₂-agonist treatment and may require IV corticosteroids; adjunctive therapies are helpful
    • Status asthmaticus
      • Continuous, severe asthma exacerbation that is resistant to treatment

Diagnosis

Clinical Presentation

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 and Risk Factors

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

Age
  • Recurrent early-onset wheezing increases risk of asthma development r10
    • Recurrent wheezing in first 3 years of life raises risk of developing asthma by 4.7-fold
    • Persistent wheezing through age 6 years raises risk of asthma to 15-fold higher than in general population
  • Asthma prevalence among children is as follows: r18
    • Birth to age 4 years: 3.8% c54
    • Age 5 and older: approximately 10% c55
Sex
  • Overall, more prevalent among boys (9.2%) than among girls (7.4%) r18c56c57
  • In first year of life, more common in boys than in girls r4c58
  • In adolescence, more common in girls than in boys r4c59
Genetics
  • Parental history of asthma is a major risk factor c60
  • A meta-analysis reported that use of a long-acting β₂-agonist as an add-on controller is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713 r19
Ethnicity/race
  • Prevalence is higher in non-Hispanic Black children (15.7%) and in children of Puerto Rican descent (12.9%) than among non-Hispanic White children (7.1%) r18c61c62
Other risk factors/associations
  • Risk factors for development of persistent asthma
    • Physician diagnosis of atopic disease (eg, atopic dermatitis, allergic rhinitis) r3c63
    • Greater than 4% peripheral eosinophilia r14c64
    • Wheezing apart from upper respiratory infection at young age r14c65
    • Allergen sensitization (eg, environmental, food) at young age c66
    • Abnormal pulmonary function in early childhood c67
    • Specific viral and bacterial respiratory infections in infancy (eg, respiratory syncytial virus infection, rhinovirus infections) c68c69
    • Exposure to tobacco smoke c70
    • Premature birth (ie, less than 37 weeks of gestation) c71
    • Low birth weight r20c72
    • Obesity may be a risk factor, but findings are inconsistent c73

Diagnostic Procedures

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) r14
    • 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

Differential Diagnosis

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

Treatment

Goals r1

  • Reduce current impairment
    • Prevent symptoms
    • Decrease need for short-acting β₂-agonist inhaler to 2 or fewer days per week
    • Maintain normal activity levels
    • Maintain near-normal pulmonary function (measured by FEV₁ or peak expiratory flow)
  • Reduce future risk
    • Prevent exacerbations
    • Prevent structural changes in airways and decline in pulmonary function
    • Minimize risks/adverse effects of therapy

Disposition

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
Criteria for ICU admission r1
  • Infants and younger children with obvious respiratory distress who have normal or rising PCO₂ (42 mm Hg or higher) on blood gas analysis (suggests impending respiratory arrest)
  • Older children with poor response (FEV₁ or peak expiratory flow lower than 40%) to prolonged therapy or respiratory fatigue

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

Treatment Options

Acute asthma exacerbation

  • Advise use of inhaled short-acting β₂-agonist if symptoms occur or if peak expiratory flow drops below 80% predicted or personal best at home r1
    • If peak expiratory flow is 50% to 79%, caregiver should monitor response and consider contacting physician
    • If peak expiratory flow is below 50%, caregiver should bring patient to urgent care facility or emergency department (emergency department if peak expiratory flow is lower than 40%; call 9-1-1 if patient appears in significant distress)
  • Emergent clinical setting r1
    • Use pediatric asthma scoring tools during initial assessment and to assess response to treatment r35
      • Mild to moderate exacerbation with FEV₁ or peak expiratory flow 40% or more of predicted or personal best r1
        • Give supplemental oxygen to achieve SaO₂ 90% or higher r1
        • Give inhaled short-acting β₂-agonist by nebulizer or metered-dose inhaler with valved holding chamber, up to 3 doses in the first hour
        • Give oral systemic steroids if no immediate response is achieved or patient has recently taken oral steroids
        • Give inhaled ipratropium plus short-acting β₂-agonist if patient requires more than 1 dose of inhaled short-acting β₂-agonist r36
          • Inhaled ipratropium plus short-acting β₂-agonist decreases risk of hospital admission r1r37
          • Do not use ipratropium alone without inhaled short-acting β₂-agonist r1
      • Severe exacerbation with FEV₁ or peak expiratory flow less than 40% of predicted or personal best r1
        • Give supplemental oxygen to achieve SaO₂ 90% or higher r1
        • Give high-dose inhaled short-acting β₂-agonist by nebulizer or metered-dose inhaler with valved holding chamber every 20 minutes or continuously for 1 hour
        • Give inhaled ipratropium with inhaled short-acting β₂-agonist for 3 doses
        • Give oral systemic steroids
        • Consider adjunctive medications for severe exacerbations unresponsive to initial treatment (eg, FEV₁ or peak expiratory flow less than 40% predicted or personal best after initial treatments)
          • IV magnesium sulfate infusion is appropriate as second line therapy in children with moderate to severe asthma exacerbation r35
      • Impending or actual respiratory arrest r1
        • Maximize asthma therapy
          • Give continuous nebulized short-acting β₂-agonist and inhaled ipratropium (for 3 doses)
          • Give IV corticosteroids
          • Consider adjunctive therapies
        • Start adjunct therapies
          • Magnesium sulfate infusion r1
            • In children who fail to respond to first line treatments, IV magnesium sulfate is associated with reduced risk of hospital admission and reduced hospital length of stay r37
          • Heliox
            • NAEPP guidelines suggest adjunctive administration of heliox in patients with life-threatening exacerbations or who are not responding to conventional therapy r1
          • Methylxanthines (eg, aminophylline)
            • Use in the treatment of acute exacerbation is controversial
              • Cochrane review recommends considering IV aminophylline in a patient with severe acute exacerbations of asthma where response to inhaled bronchodilators and glucocorticoids is poor r38
              • GINA and NAEPP 2007 guidelines do not recommend aminophylline for treatment of acute exacerbation owing to poor safety profile r1r39
              • British Thoracic Society guidelines along some children's hospitals in Australia and New Zealand recommend aminophylline as adjunct to treatment of life-threatening asthma r27r40r41
          • Epinephrine or terbutaline
            • Consider intramuscular dose of epinephrine or terbutaline for severe life-threatening exacerbations r42
        • Avoid intubation if at all possible, because airway manipulation can abruptly worsen an asthmatic crisis and is associated with a 10% to 20% mortality rate r2
        • Indications for intubation and mechanical ventilation with 100% oxygen include: r2r35
          • Poor response to maximum therapy
          • Hypercarbia (PCO₂ higher than 50 mm Hg)
          • Severe hypoxemia (PO₂ less than 60 mm Hg)
          • Worsening mental status
          • Impending respiratory arrest (indicated by respiratory depression or bradycardia)
          • Worsening metabolic acidosis
          • Cardiopulmonary arrest
          • Progressive severe fatigue or respiratory failure
        • Admit to ICU
    • Ongoing treatment and disposition are determined by response to initial round of respiratory treatments r36
    • Use caution during assessment and disposition of patients with risk factors for death from asthma, including: r43
      • History of previous ICU admission or intubation
      • Hospitalization or emergency department care for exacerbation in the past year
      • Current use of corticosteroids
      • Significant comorbid cardiovascular or chronic respiratory disease
    • If the patient is discharged after an acute exacerbation, management should include: r1
      • Review of inhaler technique, environmental control measures, and acute asthma exacerbation discharge action plan
      • Continued use of scheduled inhaled short-acting β₂-agonist r44
      • Initiation of inhaled corticosteroids in patients who are discharged from emergency department and who are not currently receiving inhaled corticosteroid therapy r1
        • Some guidelines recommend a step-up in controller treatment (eg, increase inhaled corticosteroid dose) for patients on long-term therapy r43
      • Oral steroids for 5 additional days if steroids are given in emergent setting r1
        • Alternative steroid regimen consists of a single intramuscular dose of dexamethasone or 2-day oral regimen if the patient is unable to tolerate other oral steroid formulations r45r46
      • Referral to outpatient primary care physician for follow-up care in office within 2 to 7 days r47

Chronic asthma

  • Long-term asthma treatment is based on severity level and control, and adjusted via a stepwise approach
  • Initial step is determined by disease severity classification (for newly diagnosed patients not on controller medications) or by disease control classification (for patients currently using controller medications) r1r48
    • Adjustments are based on ongoing level of control
    • Therapy can be both stepped-up and stepped-down; step-down can be considered after 3 months of good control
  • 3 types of medications may be used r11
    • Controllers
      • Inhaled corticosteroid–containing controller medications reduce airway inflammation and symptoms, reduce future exacerbations, and decline in lung function
      • SMART (Single Maintenance And Reliever Treatment) strategy using a combination of inhaled corticosteroid plus formoterol in a single inhaler therapy is the preferred treatment in children 4 years and older who are not well controlled on a low- or medium-dose daily inhaled corticosteroid alone r11r21r27r49
    • Relievers
      • Used as needed to alleviate breakthrough symptoms
      • Once a mainstay of asthma therapy, short-acting β-agonists are no longer recommended because the preferred reliever for symptomatic patients should not be used as monotherapy because of safety concerns and poor outcomes r47
      • A combined inhaled corticosteroid plus fast-onset, long-acting β-agonist (ie, formoterol) is the preferred reliever
      • Reduction or elimination in need for use is a major goal of asthma treatment
    • Add-on medications
      • A variety of agents may be considered when symptoms persist or exacerbations occur despite optimal therapy with controllers
  • Preferred treatments (see NAEPP and GINA guidelines for alternative medication options for each step) r11r21
    • Step 1 (intermittent asthma; infrequent symptoms less than twice per month and no risk factors for exacerbations)
      • Children aged 4 years and younger
        • As-needed short-acting β₂-agonist r21
        • In children with recurrent episodes of wheezing triggered by respiratory tract infections and no interval symptoms, consider commencing a short course (7-10 days) of daily inhaled corticosteroid with as-needed short-acting β₂-agonists at the onset of any respiratory tract infection r21r49
      • Children aged 5 r21or 6r11 to 11 years
        • As-needed short-acting β₂-agonist with or without low-dose inhaled corticosteroid used concomitantly r11r21
      • Children aged 12 years and older
        • Low-dose inhaled corticosteroid plus formoterol in a single inhaler, as required to alleviate symptoms r11
        • As-needed short-acting β₂-agonist with or without low-dose inhaled corticosteroid used concomitantly r6r11r21
          • GINA no longer recommends as-needed inhaled short-acting β₂-agonist monotherapy for such symptoms r47
            • Inhaled corticosteroid–containing reliever medications are superior to short-acting β₂-agonists reliever alone and significantly reduce risks of severe asthma exacerbation
    • Step 2 (asthma symptoms or need for reliever medication more than twice per month, but less than daily)
      • Children aged 4 years and younger
        • Daily low-dose inhaled corticosteroid plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms r21r50
      • Children aged 5 or 6r11 to 11 years
        • Low-dose inhaled corticosteroid maintenance therapy plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms r11r21
      • Children aged 12 years and older
        • Low-dose inhaled corticosteroid maintenance therapy plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms r6r21
        • As-needed short-acting β₂-agonist with low-dose inhaled corticosteroid used concomitantly r21
        • Low-dose inhaled corticosteroid plus formoterol in a single inhaler,r6r11 as needed to alleviate symptoms, particularly in patients with poor adherence to daily medicationr6
    • Step 3 (asthma symptoms most days or waking due to asthma symptom once per week or more)
      • Children aged 4 years and younger
        • Daily medium-dose inhaled corticosteroid plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms r21r50
      • Children aged 5 or 6 to 11 years
        • Low-dose inhaled corticosteroid plus formoterol in a single inhaler, as maintenance therapy and as needed to alleviate symptoms r21
        • Low-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, as maintenance therapy and as-needed inhaled short-acting β₂-agonist as reliever r11
        • Medium-dose inhaled corticosteroid plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms r11
        • Very-low-dose inhaled corticosteroid plus formoterol in a single inhaler, as maintenance therapy and as needed to alleviate symptoms r11
      • Children aged 12 years and older
        • Low-dose inhaled corticosteroid plus formoterol in a single inhaler, as maintenance therapy and as needed to alleviate symptoms (preferred by NAEPP) r11r21
        • Low-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, as maintenance therapy and as-needed inhaled short-acting β2 agonist as reliever r11
    • Step 4 (asthma symptoms most days or waking due to asthma symptoms once per week or more or low lung function)
      • Referral to an asthma specialist is recommended
      • Children aged 4 years and younger r21r50
        • Medium-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, as maintenance therapy with as-needed inhaled short-acting β₂-agonist to alleviate symptoms
      • Children aged 5 or 6 to 11 years
        • Medium-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, as maintenance therapy with as-needed inhaled short-acting β2 agonist to alleviate symptoms r11
        • Low-dose inhaled corticosteroid plus formoterol in a single inhaler, as maintenance therapy and as needed to alleviate symptoms r11
        • Medium-dose inhaled corticosteroid plus formoterol in a single inhaler, as maintenance therapy and as needed to alleviate symptoms r21
      • Children aged 12 years and older
        • Medium-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, as maintenance therapy with as-needed low-dose inhaled corticosteroid plus formoterol single inhaler (preferred by NAEPP) or inhaled short-acting β₂-agonist to alleviate symptoms r11r21
    • Step 5 (severe uncontrolled asthma)
      • Referral to an asthma specialist is recommended
      • Address any factors that may contribute to suboptimal control (eg, poor adherence to therapy, incorrect inhaler technique, comorbidities, modifiable risk factors)
      • Children aged 4 years and younger
        • High-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist with as-needed inhaled short-acting β₂-agonist to alleviate symptoms r21
        • Consider add-on oral corticosteroid r21
      • Children aged 5 or 6 to 11 years
        • High-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist with as-needed inhaled short-acting β₂-agonist to alleviate symptoms r11r21
        • Refer for assessment of asthma phenotype (for type 2 airway inflammation) to guide add-on therapy r11
        • Consider add-on oral corticosteroid or omalizumab r11r21
        • Add-on macrolide antibiotic (eg, azithromycin) is not generally recommended for children with refractory disease, oral corticosteroid dependence, noneosinophilic inflammation, or recurrent lower respiratory tract infections r51
      • Children aged 12 years and older
        • Medium-/high-dose corticosteroid plus inhaled long-acting β₂-agonist plus tiotropium bromide, a long-acting muscarinic antagonist with as-required inhaled short-acting β₂-agonist to alleviate symptoms r21
        • High-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist with as-needed low-dose inhaled corticosteroid plus formoterol single inhaler or inhaled short-acting β₂-agonist to alleviate symptoms r11
        • Refer for assessment of asthma phenotype (for type 2 airway inflammation) to guide add-on therapy r11r52
          • Type 2 airway inflammation is defined by the presence of 1 or more of the following:
            • Blood eosinophils 150/μL or higher
            • FeNO 20 ppb or higher
            • Sputum eosinophils 2% or more
            • Asthma that is clinically allergen driven
            • Oral corticosteroid dependent
          • If no evidence of type 2 inflammation, consider the following:
            • Add-on tiotropium bromide, a long-acting muscarinic antagonist
            • Course of low-dose oral corticosteroid
            • Add-on macrolide antibiotic (eg, azithromycin)
          • If evidence of type 2 airway inflammation, consider addition of biological agents (refer to local eligibility criteria and published guidelines for use) r11r53
            • Anti-interleukin (IL)-5/IL-5 receptor monoclonal antibodies (mepolizumab, benralizumab) for severe asthma with an eosinophilic phenotype, ascertained by either sputum or peripheral eosinophilia
              • Anti-IL-5 agents reduce exacerbations in patients with severe eosinophilic asthma r54
              • Mepolizumab and benralizumab are effective in reducing oral steroid doses in patients with corticosteroid-dependent asthma
              • Mepolizumab is approved for ages 6 years and older; benralizumab is approved for ages 12 years and older r51r52
              • A blood eosinophil count threshold of 150 /μL or higher can be used to guide initiation of anti-IL-5 agents r54
            • Omalizumab, an anti-IgE monoclonal antibody, for allergic asthma with documented sensitivity to a perennial aeroallergen and elevated total IgE level r52
              • A blood eosinophil threshold of 260/μL or higher in patients and an exhaled FeNO threshold of 19.5 ppb or higher to identify patients most likely to benefit from anti-IgE treatment r54
              • Approved for ages 6 years and older r51
            • Dupilumab, an anti-IL-4 receptor monoclonal antibody, for patients with severe eosinophilic asthma and those requiring maintenance oral corticosteroids regardless of eosinophil levels r54
              • Approved for ages 12 years and older; under review by FDA as treatment for children aged 6 to 11 years r52r55
          • Guidelines have been developed to aid evaluation and management of difficult-to-treat and severe asthma
  • Other aspects of long-term management
    • Educate patient and caregiver about self-management skills (eg, asthma action plan, peak expiratory flow measurements, correct inhaler technique)
    • Use appropriate inhalation medication delivery devices for age of child r3
      • Patients aged 0 to 5 years
        • Pressurized metered-dose inhaler with static-treated spacer and mask (or mouthpiece as soon as the child is capable of using)
      • Age 5 years and older: base choice on patient's ability to use and patient's preference
        • Pressurized metered-dose inhaler with static-treated spacer and mouthpiece
        • Dry powder inhaler
        • Breath-actuated pressurized metered-dose inhaler
      • Nebulizer
        • Second choice at any age
    • Address and treat comorbid conditions (eg, allergic bronchopulmonary aspergillosis, gastroesophageal reflux disease, obesity, obstructive sleep apnea, rhinitis, sinusitis, stress, depression) r1
    • Identify and reduce precipitating factors or triggers (eg, environmental allergens, irritants, or pollutants; tobacco smoke exposure)
      • Skin testing or in vitro allergen testing is indicated to assess sensitivity to perennial indoor allergens in patients with persistent asthma r1
      • Recommend reduced exposure to specific allergens, pollutants, or irritants (eg, dust mites, cockroach frass, pet dander, mold spores)
      • Complete checklist of known asthma allergen triggers can be found in Figure 9 of National Heart, Lung, and Blood Institute guidelines r1
      • Mitigation measures should be used only for patients who are either sensitized to or become symptomatic after exposure to a specific allergen r49
    • Immunotherapy r56
      • Allergen-specific immunotherapy involves administering increasing doses of allergen extracts to render persistent clinical tolerance in patients with allergen-induced symptoms r3
        • Greatest benefit occurs with administration of standardized, single-allergen extracts of dust mite, animal dander, grass, or tree pollen
        • Allergen therapy is usually administered for a length of 3 to 5 years r3
        • Minimum age for immunotherapy is not rigorously standardized;r3some guidelines suggest beginning intervention when child is older than 3 yearsr13
        • Administered only by an expert trained in immunotherapy in a controlled setting with available resources to manage potential systemic anaphylactic reactions r3
      • Subcutaneous allergen immunotherapy reduces long-term asthma medication use and may also improve asthma-related quality of life and FEV₁ r56
      • Consider subcutaneous allergen immunotherapy as an adjunct to pharmacotherapy in patients aged 5 years or older with mild to moderate allergic asthma for whom a potential decrease in long-term medication is important r21r49
        • There should be clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive
        • Allergen therapy is usually avoided in patients with severe asthma because of concern regarding greater risk for possible severe systemic reactions and lack of evidence supporting efficacy in this subgroup r3
      • Sublingual immunotherapy is not recommended in the treatment of asthma r49

Multiple resources are available to assist with treatment decisions including:

  • GINA guidelines and resources r22
  • NAEPP guidelines and NIH Asthma Care Quick Reference guide r1r8r21
  • Canadian Thoracic Society guidelines for preschoolers, children, and adults r24r25
  • National Institute for Health and Care Excellence asthma pathway and guidelines r9
  • Australian Asthma Handbook r57
  • European Respiratory Society Task Force evidence-based approach to assessment and treatment of wheezing in preschool children r23

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 years and older: 4 to 10 oral inhalations of 90 mcg/actuation (total: 360 to 900 mcg) every 20 minutes for the first hour for mild to moderate exacerbations. After the first hour, the dose required may vary from 4 to 10 oral inhalations (360 to 900 mcg) every 3 to 4 hours up to 6 to 10 oral inhalations (540 to 900 mcg) every 1 to 2 hours, or more often.
        • Nebulizer c124c125c126
          • Albuterol Sulfate Nebulizer solution; Infants† and Children† less than 2 years: 2.5 mg via 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 via nebulizer every 20 minutes for the first hour for acute exacerbation, with reassessment after that. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3 to 4 times daily. If weight at least 15 kg: May give 2.5 mg via nebulizer 3 to 4 times daily, if needed.
          • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 2.5 mg via 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. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3 to 4 times daily. If weight at least 15 kg: 2.5 mg may be given via 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 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. Typical dose: 2.5 mg via 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 years and older: 180 mcg (2 actuations of 90 mcg/actuation) via oral inhalation every 4 to 6 hours as needed. In some patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (1,080 mcg/day).
          • Nebulizer c148
            • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years: 0.63 mg or 1.25 mg via 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 via nebulizer 3 to 4 times daily if needed.
            • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 0.63 mg or 1.25 mg via 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 via nebulizer 3 to 4 times daily if needed.
            • Albuterol Sulfate Nebulizer solution; Adolescents: 2.5 mg via nebulizer 3 to 4 times daily as needed. Usual Max: 4 doses/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 doseAged 0 to 4 yearsAged 5 to 11 yearsAged 12 years or older
            LowMedium*High*LowMedium*High*LowMedium*High*
            Medication
            Beclomethasone MDIN/AN/AN/A80 to 160 mcgGreater than 160 to 320 mcgGreater than 320 mcg80 to 240 mcgGreater than 240 to 480 mcgGreater than 480 mcg
            40 mcg/puffN/AN/AN/A1 to 2 puffs twice daily3 to 4 puffs twice daily1 to 3 puffs twice daily4 to 6 puffs twice daily
            80 mcg/puffN/AN/AN/A1 puff twice daily2 puffs twice daily3 or more puffs twice daily1 puff AM, 2 puffs PM2 to 3 puffs twice daily4 or more puffs twice daily
            Budesonide DPIN/AN/AN/A180 to 360 mcgGreater than 360 to 720 mcgGreater than 720 mcg180 to 540 mcgGreater than 540 to 1080 mcgGreater than 1080 mcg
            90 mcg/inhalationN/AN/AN/A1 to 2 inhalations twice daily3 to 4 inhalations twice daily1 to 3 inhalations twice daily
            180 mcg/inhalationN/AN/AN/A2 inhalations twice daily3 or more inhalations twice daily1 inhalation AM, 2 inhalations PM2 to 3 inhalations twice daily4 or more inhalations twice daily
            Budesonide nebules0.25 to 0.5 mgGreater than 0.5 to 1 mgGreater than 1 mg0.5 mg1 mg2 mgN/AN/AN/A
            0.25 mg1 to 2 nebules/day1 nebule twice dailyN/AN/AN/A
            0.5 mg1 nebule/day2 nebules/day3 nebules/day1 nebule/day1 nebule twice dailyN/AN/AN/A
            1 mg1 nebule/day2 nebules/day1 nebule/day1 nebule twice dailyN/AN/AN/A
            Ciclesonide MDIN/AN/AN/A80 to 160 mcgGreater than 160 to 320 mcgGreater than 320 mcg160 to 320 mcgGreater than 320 to 640 mcgGreater than 640 mcg
            80 mcg/puffN/AN/AN/A1 to 2 puffs/day1 puff AM, 2 puffs PM to 2 puffs twice daily3 or more puffs twice daily1 to 2 puffs twice daily3 to 4 puffs twice daily
            160 mcg/puffN/AN/AN/A1 puff/day1 puff twice daily2 or more puffs twice daily2 puffs twice daily3 or more puffs twice daily
            Flunisolide MDIN/AN/AN/A160 mcg320 to 480 mcg480 mcg or more320 mcgGreater than 320 to 640 mcgGreater than 640 mcg
            80 mcg/puffN/AN/AN/A1 puff twice daily2 to 3 puffs twice daily4 or more puffs twice daily2 puffs twice daily3 to 4 puffs twice daily5 or more puffs twice daily
            Fluticasone MDI176 mcgGreater than 176 to 352 mcgGreater than 352 mcg88 to 176 mcgGreater than 175 to 352 mcgGreater than 352 mcg88 to 264 mcgGreater than 264 to 440 mcgGreater than 440 mcg
            44 mcg/puff2 puffs twice daily3 to 4 puffs twice daily1 to 2 puffs twice daily3 to 4 puffs twice daily1 to 3 puffs twice daily
            110 mcg/puff1 puff twice daily2 or more puffs twice daily1 puff twice daily2 or more puffs twice daily2 puffs twice daily3 puffs twice daily
            220 mcg/puff1 puff twice daily2 or more puffs twice daily
            Fluticasone DPIN/AN/AN/A100 to 200 mcgGreater than 200 to 400 mcgGreater than 400 mcg100 to 300 mcgGreater than 300 to 500 mcgGreater than 500 mcg
            50 mcg/inhalationN/AN/AN/A1 to 2 inhalations twice daily3 to 4 inhalations twice daily1 to 3 inhalations twice daily
            100 mcg/inhalationN/AN/AN/A1 inhalation twice daily2 inhalations twice dailyMore than 2 inhalations twice daily2 inhalations twice daily3 or more inhalations twice daily
            250 mcg/inhalationN/AN/AN/A1 inhalation twice daily1 inhalation twice daily2 or more inhalations twice daily
            Mometasone DPIN/AN/AN/A110 mcg220 to 440 mcgGreater than 440 mcg110 to 220 mcgGreater than 220 to 440 mcgGreater than 440 mcg
            110 mcg/inhalationN/AN/AN/A1 inhalation/day1 to 2 inhalations twice daily3 or more inhalations twice daily1 to 2 inhalations PM3 to 4 inhalations PM or 2 inhalations twice daily3 or more inhalations twice daily
            220 mcg/inhalationN/AN/AN/A1 to 2 inhalations/day3 or more inhalations divided in 2 doses1 inhalation PM1 inhalation twice daily or 2 inhalations PM3 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-preferredr21r50 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 youngerr11
          • 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 years and older: 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 years and older: 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 doseAged 0 to 4 yearsAged 5 to 11 yearsAged 12 years or older
    LowMedium*High*LowMedium*High*LowMedium*High*
    Medication
    Beclomethasone MDIN/AN/AN/A80 to 160 mcgGreater than 160 to 320 mcgGreater than 320 mcg80 to 240 mcgGreater than 240 to 480 mcgGreater than 480 mcg
    40 mcg/puffN/AN/AN/A1 to 2 puffs twice daily3 to 4 puffs twice daily1 to 3 puffs twice daily4 to 6 puffs twice daily
    80 mcg/puffN/AN/AN/A1 puff twice daily2 puffs twice daily3 or more puffs twice daily1 puff AM, 2 puffs PM2 to 3 puffs twice daily4 or more puffs twice daily
    Budesonide DPIN/AN/AN/A180 to 360 mcgGreater than 360 to 720 mcgGreater than 720 mcg180 to 540 mcgGreater than 540 to 1080 mcgGreater than 1080 mcg
    90 mcg/inhalationN/AN/AN/A1 to 2 inhalations twice daily3 to 4 inhalations twice daily1 to 3 inhalations twice daily
    180 mcg/inhalationN/AN/AN/A2 inhalations twice daily3 or more inhalations twice daily1 inhalation AM, 2 inhalations PM2 to 3 inhalations twice daily4 or more inhalations twice daily
    Budesonide nebules0.25 to 0.5 mgGreater than 0.5 to 1 mgGreater than 1 mg0.5 mg1 mg2 mgN/AN/AN/A
    0.25 mg1 to 2 nebules/day1 nebule twice dailyN/AN/AN/A
    0.5 mg1 nebule/day2 nebules/day3 nebules/day1 nebule/day1 nebule twice dailyN/AN/AN/A
    1 mg1 nebule/day2 nebules/day1 nebule/day1 nebule twice dailyN/AN/AN/A
    Ciclesonide MDIN/AN/AN/A80 to 160 mcgGreater than 160 to 320 mcgGreater than 320 mcg160 to 320 mcgGreater than 320 to 640 mcgGreater than 640 mcg
    80 mcg/puffN/AN/AN/A1 to 2 puffs/day1 puff AM, 2 puffs PM to 2 puffs twice daily3 or more puffs twice daily1 to 2 puffs twice daily3 to 4 puffs twice daily
    160 mcg/puffN/AN/AN/A1 puff/day1 puff twice daily2 or more puffs twice daily2 puffs twice daily3 or more puffs twice daily
    Flunisolide MDIN/AN/AN/A160 mcg320 to 480 mcg480 mcg or more320 mcgGreater than 320 to 640 mcgGreater than 640 mcg
    80 mcg/puffN/AN/AN/A1 puff twice daily2 to 3 puffs twice daily4 or more puffs twice daily2 puffs twice daily3 to 4 puffs twice daily5 or more puffs twice daily
    Fluticasone MDI176 mcgGreater than 176 to 352 mcgGreater than 352 mcg88 to 176 mcgGreater than 175 to 352 mcgGreater than 352 mcg88 to 264 mcgGreater than 264 to 440 mcgGreater than 440 mcg
    44 mcg/puff2 puffs twice daily3 to 4 puffs twice daily1 to 2 puffs twice daily3 to 4 puffs twice daily1 to 3 puffs twice daily
    110 mcg/puff1 puff twice daily2 or more puffs twice daily1 puff twice daily2 or more puffs twice daily2 puffs twice daily3 puffs twice daily
    220 mcg/puff1 puff twice daily2 or more puffs twice daily
    Fluticasone DPIN/AN/AN/A100 to 200 mcgGreater than 200 to 400 mcgGreater than 400 mcg100 to 300 mcgGreater than 300 to 500 mcgGreater than 500 mcg
    50 mcg/inhalationN/AN/AN/A1 to 2 inhalations twice daily3 to 4 inhalations twice daily1 to 3 inhalations twice daily
    100 mcg/inhalationN/AN/AN/A1 inhalation twice daily2 inhalations twice dailyMore than 2 inhalations twice daily2 inhalations twice daily3 or more inhalations twice daily
    250 mcg/inhalationN/AN/AN/A1 inhalation twice daily1 inhalation twice daily2 or more inhalations twice daily
    Mometasone DPIN/AN/AN/A110 mcg220 to 440 mcgGreater than 440 mcg110 to 220 mcgGreater than 220 to 440 mcgGreater than 440 mcg
    110 mcg/inhalationN/AN/AN/A1 inhalation/day1 to 2 inhalations twice daily3 or more inhalations twice daily1 to 2 inhalations PM3 to 4 inhalations PM or 2 inhalations twice daily3 or more inhalations twice daily
    220 mcg/inhalationN/AN/AN/A1 to 2 inhalations/day3 or more inhalations divided in 2 doses1 inhalation PM1 inhalation twice daily or 2 inhalations PM3 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
    MedicationAged 0 to 4 yearsAged 5 to 11 yearsAged 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 mcgN/A1 inhalation twice daily; dose depends on level of severity or control1 inhalation twice daily; dose depends on level of severity or control
    MDI: 45 mcg/21 mcg, 115 mcg/21 mcg, or 230 mcg/21 mcgN/A1 inhalation twice daily; dose depends on level of severity or control1 inhalation twice daily; dose depends on level of severity or control
    Budesonide-formoterol 
    MDI: 80 mcg/4.5 mcg  or  160 mcg/4.5 mcgN/A2 puffs twice daily; dose depends on level of severity or control2 puffs twice daily; dose depends on level of severity or control
    Mometasone-formoterol 
    MDI: 100 mcg/5 mcgN/AN/A2 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 tablet4 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/A10 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/AN/A2400 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/AN/A150- to 375-mg subcutaneous injection every 2 to 4 weeks, depending on body weight and pretreatment serum IgE level
    Cromolyn
    Cromolyn
    Nebulizer: 20 mg/ampule1 ampule 4 times daily, N/A in children younger than 2 years1 ampule 4 times daily1 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/blisterN/A1 blister every 12 hours1 blister every 12 hours
    Oral systemic corticosteroids
    Methylprednisolone
    2-, 4-, 8-, 16-, 32-mg tablets0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control7.5 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 daysShort course "burst": 1 to 2 mg/kg/day; Max: 60 mg/day for 3 to 10 daysShort 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 mL0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control7.5 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 daysShort course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 daysShort 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 mL0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control0.25 to 2 mg/kg daily in single dose in AM or every other day as needed for control7.5 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 daysShort course "burst": 1 to 2 mg/kg/day; max: 60 mg/day for 3 to 10 daysShort 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

Procedures
c202

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 r14
    • 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

Monitoring

  • Monitoring in the acute care setting after a significant asthma exacerbation
    • Reassess patient for response after each treatment is administered r1c217
    • Monitor patient for rebound respiratory distress or hypoxia c218
    • Patient can be safely discharged home with a close follow-up if all of the following clinical parameters are met:
      • 70% or higher predicted FEV₁ or peak expiratory flow is a goal for discharge from the emergency care setting (based on personal asthma action plan) r1c219
      • Patient does not have significant tachypnea or respiratory distress; does not have signs or symptoms of moderate or severe exacerbation after 1 to 2 hours of observation after initial treatment r1c220c221
      • Patient is not hypoxic; pulse oximetry measurement is higher than 92% to 94% just before discharge home r1c222
      • Patient is able to tolerate oral medication c223
      • Caregiver is comfortable managing patient at home c224
      • No barrier in transportation exists (eg, bad weather, long transport time to an acute facility) for emergent return visit if patient has decompensation at home c225
  • Periodic monitoring of asthma control to guide maintenance treatment r1
    • Home self-monitoring c226
      • Instruct all patients to monitor at home; symptom-based monitoring or peak flow monitoring is similarly beneficial
        • Several validated asthma control questionnaire assessment tools are available r78r79r80r81r82
      • For patients with moderate or severe persistent asthma, peak flow monitoring is preferred r1
    • Office monitoring c227c228
      • Assess asthma control, medication technique, asthma action plan, adherence, and patient concerns at every patient visit
      • Adjust drug therapy using stepwise approach (step-up or step-down) after initiating treatment or adjusting long-term control medication
        • Use of inhaled short-acting β₂-agonist more than 2 days per week for symptom relief (not for prevention of exercise-induced bronchospasm) indicates inadequate control and need for treatment step-up
        • Before treatment step-up:
          • Consider alternative diagnosis if no clear benefit is observed over 4 to 6 weeks in patients younger than 5 years
          • Assess patient adherence to medication, inhaler technique, and environmental control measures
        • Consider treatment step-up during seasonal periods for patients with asthma symptoms only related to certain seasons (eg, pollens, allergens, viral respiratory seasons)
        • Switch to an alternate treatment option if patient is experiencing significant adverse effects
      • Schedule follow-up office visit at 2- to 6-week intervals when starting a new or stepped-up therapy; perform spirometry when patient is stable after medication change r1c229c230
      • Follow-up at 1- to 6-month intervals, after asthma control is achieved r1c231
      • Follow-up at 3-month intervals, if step-down therapy is likely r1c232
      • Perform spirometry at least every 1 to 2 years for well-controlled asthma, more frequently for asthma that is not well controlled, and during periods of progressive or prolonged loss of asthma control r1c233
      • For children requiring high-dose inhaled corticosteroids r14
        • Regularly review dietary intake of calcium and vitamin D c234c235
        • Consider slitlamp ocular examination and bone densitometry c236c237

Complications and Prognosis

Complications

  • Complications of disease
    • Respiratory failure c238
    • Pneumothorax c239
    • Pneumomediastinum c240
    • Airway remodeling and decreased lung growth over time (due to persistent asthma or moderate to severe exacerbations) c241c242
    • Death c243
  • Complications during surgical procedures r1
    • Respiratory decompensation during or after surgical procedures c244
      • Assess asthma control before any surgery; if lung function is not well controlled, provide medications to improve lung function shortly before and after surgical procedure (short course of systemic corticosteroids may be necessary) r1
      • Alert an anesthesiologist if the patient has required oral corticosteroids during 6 months before the surgery or if the patient is on high-dose inhaled corticosteroids; consider steroid stress dosing r1
  • Complications of steroid pharmacotherapy
    • Inhaled corticosteroids
      • Slight reduction of growth, which is most pronounced in the first year of use r83c245
      • Oropharyngeal candidiasis c246
    • Long-term oral corticosteroid therapy
      • Growth inhibition c247
      • Increased infection risk c248
      • Increased risk of oral candidiasis, osteoporosis, cataracts, and hyperglycemia c249c250c251
      • Secondary hypocortisolism after withdrawal of drug c252
    • To reduce steroid complications: r1
      • Advise patient to use spacers with non–breath-activated metered-dose inhalers
      • Advise patient to rinse mouth (rinse and spit) after inhalation
      • Use lowest dose of inhaled or oral corticosteroid that maintains asthma control
      • Consider calcium and vitamin D supplementation

Prognosis

  • Progression of disease
    • More than half of preschoolers who wheeze become asymptomatic by school age, irrespective of treatment r3
      • Infants and young children commonly wheeze during viral respiratory infections; only some will experience asthma in childhood r4
      • Risk factors for recurrent wheezing after preschool age are variably reported; the Asthma Predictive Indexr84 has been used to help distinguish children at higher risk for continued wheezing after preschool age r4
      • Overall, mild and infrequent wheezing in infancy and preschool years does not usually persist into school years; in contrast, persistent asthma into school years is more likely to occur after more frequent and severe wheezing early in life r85
      • Other significant risk factors that may play a part in persistent asthma include exposure to tobacco smoke and continued exposure to other environmental triggers
    • Severity of chronic persistent asthma in children is often stable through adolescent years r85
      • Risk factors for persistent and severe childhood asthma include:
        • More severe and frequent wheezing episodes during preschool age
        • Onset during school age
        • Family history of asthma and allergy
        • Elevated serum IgE and early development of positive skin test results
        • Early development of bronchial hyperresponsiveness
        • Frequent respiratory infections
        • Parenting difficulties and greater childhood psychological risk
    • Presence of severe asthma in childhood is the primary risk factor for asthma persistence into adulthood r85
      • Continued exposure to tobacco smoke, environmental allergens, and presence of atopy may further increase risk
    • Use of controller medications and decreasing environmental exposures do not appear to modify progression of disease (eg, progression of asthma in childhood, development of persistent asthma) r4
  • Prognosis is good for patients with mild intermittent disease or persistent disease if well controlled
  • Patients with severe exacerbation may require hospital admission
    • Risk factors for asthma exacerbations include: r43
      • Uncontrolled symptoms
      • High short-acting bronchodilator use
      • Inadequate inhaled corticosteroid use (eg, inappropriate inhalation technique, noncompliance with treatment)
      • Low FEV₁ (especially less than 60% of predicted)
      • Serious psychosocial problems
      • Exposure to smoking or allergens (in those with coexisting allergy)
      • Sputum or blood eosinophilia
      • Pregnancy
      • Previous intubation or ICU admission for asthma
      • 1 or more serious exacerbation in previous 12 months
  • Death from asthma is rare c253
    • Mortality rate is 4 times higher in Black children with asthma than in other ethnic groups r86c254
    • Risk factors for asthma-related death include:
      • Current or recent use of oral corticosteroids r43
      • Poor compliance with treatment plan and lack of asthma action plan r43
      • Existing food allergy r43
      • Near-lethal episode requiring intubation with mechanical ventilation r43
      • Hospitalization or presentation to the emergency department for exacerbation in the past 1 year r43
      • Previous severe exacerbation requiring ICU care r1
      • Use of more than 2 canisters of short-acting bronchodilator per month r1
      • Difficulty perceiving airway obstruction or severity of worsening asthma r1
      • Low socioeconomic status or inner city residence r1
      • Illicit drug use r1
      • Major psychosocial problems or psychiatric disease r1
      • Comorbidity of chronic respiratory or cardiac disease r1

Screening and Prevention

Prevention

  • Primary prevention; the following measures may help reduce risk of child developing asthma: r11
    • Avoid exposure to tobacco smoke during pregnancy and first year of life c255c256
    • Encourage vaginal delivery c257
    • Encourage breastfeeding for overall health benefits c258
    • Avoid use of acetaminophen and broad-spectrum antibiotics in first year of life c259c260
    • Identify and treat maternal vitamin D deficiency prior to conception or during pregnancy c261
  • Secondary prevention: the following measures may reduce risk of exacerbations:
    • Avoid known triggers of exacerbation r1c262c263c264
    • Annual influenza vaccine to prevent influenza-induced exacerbation r1c265
    • Avoid known triggers of exacerbation (eg, exposure to cigarette smoke) c266c267c268
    • Education regarding the use of inhalers, peak flow meter, spacers, asthma action plan, and adherence to recommended treatments c269
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