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    Asthma in Children

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    Apr.19.2024

    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, response to asthma medication, 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/spirometry 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; provide asthma medication and asthma action plan education; consider referral to asthma specialist
    • Address factors contributing to poor control including adherence to medication, inhaler technique, comorbidities, and modifiable risk factors
    • Identify and reduce precipitating factors to improve asthma control and reduce frequency and severity of exacerbation; some triggers include environmental allergens and irritants (eg, pollens, dust mites, cockroach, pets, molds, 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 (arterial oxygen saturation) 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, epinephrine or terbutaline, 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 due to poor air entry
    • 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. However, intubation should not be delayed once it is deemed necessary 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 is one of the most common childhood illnesses, affecting more than 4.2 million US children r4
    • Asthma affects approximately 5.9% to 9.3% of children in the United Statesr4 and is the leading cause of childhood hospitalization and school absenteeism r5r6
    • National Heart, Lung, Blood Institute guidelines differentiate assessment and management of asthma in children based on the following age groups: those aged 0 to 4 years, 5 to 11 years, and 12 years and older r1
      • Global Initiative for Asthma guidelines similarly differentiate into those aged 0 to 5 years, 6 to 11 years, and 12 years and older r7
    • 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 r8

    Classification

    • Classification of asthma severity r1
      • Based on asthma severity at initial evaluation in patients not currently using controller medication r1r9r10
      • Components of severity include impairment domain and risk domain
        • Intermittent asthma r1
          • Impairment
            • Symptoms occur 2 days per week or fewer
            • Symptoms do not interfere with normal activity
            • Nighttime awakenings
              • No nighttime awakening in patients younger than 5 years
              • 0 to 2 nighttime awakenings per month in patients aged 5 years and older
            • Use of short-acting β₂-agonist for symptom control 2 days or fewer per week (not including use for prevention of exercise-induced bronchoconstriction)
            • Lung function
              • Normal FEV₁ between exacerbation (aged 5 years and older)
              • FEV₁ greater than 80% predicted (aged 5 years and older)
              • FEV₁/FVC greater than 85% (aged 5-11 years) and normal FEV₁/FVC in patients aged 12 years and older (greater than 85% in those aged 12-19 years)
          • Risk for exacerbation
            • 0 to 1 exacerbation requiring oral systemic steroids in the past year
              • Note that severe exacerbations occur in patients with any asthma severity
          • 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
          • 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 to 11 years
            • Use of short-acting β₂-agonist for symptom control more than 2 days per week, but not daily
            • Lung function
              • FEV₁ greater than 80% in patients aged 5 years and older
              • FEV₁/FVC greater than 85% in patients aged 5 to 11 years
              • FEV₁/FVC normal in patients aged 12 years and older (greater than 85% in patients aged 12 to 19 years)
          • Risk for exacerbation
            • 2 or more exacerbations requiring oral systemic steroids in the past year in patients aged 5 years and older
            • More than 2 exacerbations requiring oral systemic steroids in 6 months OR more than 4 wheezing episodes/1 year lasting longer than 1 day AND risk factors for persistent asthma in children aged younger than 5 years
          • This severity classification corresponds to step 2 management strategy when asthma is well controlled
          • Consider asthma specialist consultation for patients aged younger than 5 years r11
        • Moderate persistent asthma r12
          • Impairment
            • Symptoms occur daily
            • Symptoms cause some 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 to 11 years
            • Use of short-acting β₂-agonist for daily symptom control
            • Lung function
              • FEV₁ 60% to 80% predicted in patients aged 5 years and older
              • FEV₁/FVC 75% to 80% in patients aged 5 to 11 years
              • FEV₁/FVC reduced 5% in patients aged 12 years and older (normal FEV₁/FVC for those aged 12-19 years is 85%)
          • Risk for exacerbation
            • More than 2 exacerbations requiring oral systemic steroids in the past year in patients aged 5 years and older
            • More than 2 exacerbations requiring oral systemic steroids in 6 months OR more than 4 wheezing episodes/1 year lasting longer than 1 day AND risk factors for persistent asthma in children aged younger than 5 years
          • This severity classification corresponds to step 3 or 4 management strategy when asthma is well controlled (lowest level of treatment required to maintain asthma control)
          • Consult with asthma specialist if step 3 or higher is required for patients younger than 5 years r11
          • Consult with asthma specialist if step 4 or higher is required for patients aged 5 years and older. Consider consultation at step 3 r11
        • Severe persistent asthma r1
          • Impairment
            • Symptoms occur throughout the day
            • Symptoms cause extreme limitation of normal activity
            • Nighttime awakenings
              • More than 1 nighttime awakening per week in patients aged younger than 5 years
              • Frequent nighttime awakenings (often 7 times per week) in patients aged 5 to 11 years
            • Use of short-acting β₂-agonist for symptom control multiple times per day
            • Lung function
              • FEV₁ less than 60% predicted in patients aged 5 years and older
              • FEV₁/FVC less than 75% in patients aged 5 to 11 years; FEV₁/FVC reduced greater than 5% in patients aged 12 years and older (normal FEV₁/FVC for patients aged 12-19 years is 85%)
          • Risk for exacerbation
            • More than 2 exacerbations requiring oral systemic steroids in the past year for patients aged 5 years and older
            • More than 2 exacerbations requiring oral systemic steroids in 6 months OR more than 4 wheezing episodes/1 year lasting longer than 1 day AND risk factors for persistent asthma in children aged younger than 5 years
          • This severity classification corresponds to step 5 or 6 management strategy when asthma is well controlled (lowest level of treatment required to maintain asthma)
          • Consult with asthma specialist if step 3 or higher is required for patients younger than 5 years r11
          • Consult with asthma specialist if step 4 or higher is required for patients aged 5 years and older. Consider consultation at step 3 r11
    • 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
          • Impairment
            • Symptoms occur 2 or fewer days per week for patients of all ages but less than 1 time per day in patients aged 5 to 11 years
            • Nighttime awakenings
              • No more than 1 nighttime awakening per month in patients aged 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% for patients aged 5 to 11 years
              • FEV₁/FVC greater than 80% for patients aged 5 to 11 years
            • Validated questionnaires for patients 12 years and older
              • The Asthma Therapy Assessment Questionnaire score of 0 r13
              • Asthma Control Questionnaire score of 0.75 or less r14
              • Asthma Control Test score of 20 or greater r15
          • Risk for exacerbation
            • No more than 1 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)
          • Impairment
            • Symptoms on more than 2 days per week for patients of all ages or multiple times on 2 or fewer days per week for patients aged 5 to 11 years
            • Nighttime awakenings
              • More than 1 nighttime awakening per month in patients aged younger than 12 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% for patients aged 5 to 11 years
              • FEV₁/FVC 75% to 80% for patients aged 5 to 11 years
            • Validated questionnaires for patients 12 years and older
              • The Asthma Therapy Assessment Questionnaire score of 1 or 2 r13
              • Asthma Control Questionnaire score of 1.5 or higher r14
              • Asthma Control Test score of 16 through 19 r15
          • Risk for exacerbation
            • 2 to 3 exacerbations requiring oral systemic steroids in the past year in patients aged younger than 5 years
            • 2 or more exacerbations requiring oral systemic steroids in the past year in patients aged 5 to 11 years
          • This level of control corresponds to changing management by moving up at least 1 step and reevaluating in 2 to 6 weeks
          • Before stepping up, review adherence, inhaler technique, environmental factors, and comorbid diseases
        • Very poorly controlled (uncontrolled)
          • Impairment
            • Symptoms throughout the day
            • Nighttime awakenings
              • 2 or more nighttime awakenings per week in patients aged younger than 12 years
              • 4 or more nighttime awakenings per week in patients aged 12 years or older
            • Extremely limited normal 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% for patients aged 5 to 11 years
              • FEV₁/FVC less than 75% for patients aged 5 to 11 years
            • Validated questionnaires for patients aged 12 years and older
              • The Asthma Therapy Assessment Questionnaire score of 3 or 4 r13
              • Asthma Control Questionnaire: not applicable r14
              • Asthma Control Test score of 15 or higher r15
          • Risk for exacerbation
            • 3 exacerbations requiring oral systemic steroids in the past year in patients aged younger than 5 years
            • 2 or more exacerbations requiring oral systemic steroids in the past year in patients aged 5 to 11 years
          • 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 to 6 weeks
          • Before stepping up, review adherence, inhaler technique, environmental factors, and comorbid diseases
    • Phenotypic classifications r16
      • Based on epidemiologic phenotypes, which are limited by the retrospective nature of the birth cohorts
      • Some of these classifications do not appear to describe stable phenotypes, have different age cutoffs, and are of uncertain usefulness clinically in terms of the most effective treatment and intervention r7
        • Based on age of onset and pattern of chronicity r17r18
          • Early transient wheezers (approximately 20%)
            • Begins before age 3 years; does not persist beyond age 6 years
              • Transient wheezers in infancy
                • Wheezing in the first year of life, resolving by preschool age
                • Associated with maternal tobacco use, daycare attendance, having siblings, and decreased lung function
              • Non-atopic persistent wheezers
                • Wheezing in the first year of life, resolving by school age
                • Associated with no allergic sensitization and lack of methacholine hyperresponsiveness
          • Late-onset wheezers (approximately 15%)
            • Wheezing episodes begin between ages 3 and 6 years
            • At risk for persistent asthma in later childhood or adulthood
            • Some present with aeroallergen sensitization at 3 to 4 years, followed by high serum IgE levels, then asthma symptoms r19
            • High serum IgE level is associated with impaired lung function and increases asthma in later life r19
          • Persistent wheezers (approximately 14%)
            • Wheezing episodes start before 3 years and continue beyond 6 years
              • Atopic persistent wheezers (classic atopic asthma phenotype)
                • Wheezing can begin in the first year of life but increases with age
                • Associated with atopic diseases and family history of atopy, early-life bronchiolitis, ORMDL3 polymorphism r20
                • Unclear if this will persist into adulthood
                • Polysensitization is related with severe asthma, more persistent symptoms, and increased IgE levels r21
              • Early persistent wheezers r22
            • Certain interventions decreased the risk of persistent wheezing in school-aged children: avoidance of house dust mites, pet allergens, and environmental tobacco smoke exposure, and breastfeeding or use of a partially hydrolyzed formula r22
        • Based on early-life environmental exposures incorporated with allergic sensitization and lung function data r23r24
          • Low wheeze/low atopy
          • Transient wheeze/low atopy
            • Wheezing early in life and resolving by age 3 to 4 years
          • Moderate wheeze/low atopy
            • High wheezing during infancy but decreased through age 10 years
          • High wheeze/low atopy
            • Associated with decreased indoor allergen exposure
            • Associated with prenatal smoke exposure, maternal stress, and depression
            • Associated with female sex, abnormal chest radiograph findings, parental asthma, and wheezing despite high doses inhaled corticosteroid r25
            • Associated with increased frequency of asthma by age 7 years
          • Low wheeze/high atopy
            • High allergic sensitization with little or no wheezing
          • Moderate wheeze/high atopy
            • High allergic sensitization
            • High wheezing in infancy but decreased with time
          • High wheeze/high atopy
            • High allergic sensitization
            • High wheezing that persists through age 10 years
            • Associated with decreased indoor allergen exposure, decreased house dust microbial diversity, and elevated exposure to ergosterol in house dust
            • Low lung function with evidence of airway obstruction
            • Associated with increase in asthma burden and morbidity
        • Based on symptoms. Can be used prospectively and may be beneficial for treatment choice. Applies to children aged 1 to 6 years r26r27
          • Episodic wheeze
            • Wheezing only occurs with viral infection, no wheezing between episodes
            • Most have mild disease and symptoms are controlled without needing high-dose inhaled corticosteroid treatment r26
          • Unremitting wheeze
            • Wheezing with viral infection AND at least one wheezing episode without viral infection
          • Recurrent, unremitting wheeze
            • Wheezing with viral infection AND 2 or more years of wheezing episodes without viral infection
          • Frequent wheeze
            • Wheezing monthly for 1 or more years
          • Multi-trigger wheeze (applied to children aged 3 to 6 years)
            • Wheezing during exacerbation and between episodes of exacerbation
            • At least 2 of following triggers (cold, effort, dust, animals, grass, other) are reported to elicit wheeze
            • Associated with decreased lung function in puberty r25
            • Associated with male sex, eczema, elevated IgE levels, and abnormal chest radiography results r25
          • Asthma diagnosis
            • Physician diagnosis of asthma or recurrent diagnoses of spastic, obstructive, or asthmatic bronchitis by age 6 years
        • Based on phenotypic cluster (ie, atopic burden, degree of airway obstruction, and exacerbation history) r28
          • These clusters predict longitudinal asthma control (need of oral steroid and additional controller medication) to target treatment strategies
          • Appear to be consistent over time
          • Different inhaled corticosteroid had no significant effect on cluster membership
            • Mild asthma with low atopy, obstruction, and exacerbation rate (largest subgroup, approximately 29%)
              • 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
              • No previous admission, low emergency department visits
              • 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
              • No previous admission, low emergency department visits
              • 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
              • Few previous admissions, moderate emergency department visits
              • 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
              • Most reports of previous admissions
              • Intermediate to high risk of exacerbation
              • Decreased exacerbations with budesonide and nedocromil
            • Highly atopic asthma with high levels of obstruction and high exacerbation rates (smallest subgroup, approximately 9%)
              • 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
              • Most reports of previous admissions, highest emergency department visits
              • Highest risk of exacerbation
              • Poor response to budesonide and nedocromil
        • Based on apparent trigger; overlap between phenotypes is common r29r30
          • Virus-induced asthma
          • Exercise-induced asthma
            • Prevalence is estimated at up to 10% in school-aged children r31
            • Many children with persistent asthma also have exercise-induced symptoms
          • Allergen-induced asthma
          • Unresolved asthma
            • Consider different causes such as irritant and/or allergen exposure
        • Based on wheezing patterns r29r30
          • Transient wheezing
            • Wheezing during the first 2 to 3 years, resolving after 3 years
          • Nonatopic wheezing
            • Triggered by viral infections early in life and remitting later in childhood
          • Persistent asthma
            • Characterized by atopy, eosinophilia, positive parental history, associated atopy (eczema, food allergy, allergic rhinitis/conjunctivitis), and high indoor allergen exposure
          • Severe intermittent wheezing
            • Infrequent episodes with minimal morbidity between episodes but associated with atopic characteristics
    • Classification of acute asthma exacerbation r1
      • Mild
        • Dyspnea only with activity
        • Able to lie flat
        • Speaks in full sentences
        • Can be agitated
        • Moderate, frequently end expiratory, wheezing
        • Tachypnea with no use of accessory muscles or suprasternal retractions
        • Heart rate less than 100 beats per minute; no pulsus paradoxus
        • Oxygen saturation greater than 95%, PaO₂ within reference range, PaCO₂ (partial pressure of arterial carbon dioxide) less than 42 mm Hg
        • Peak expiratory flow at least 70% of predicted or personal best
        • 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
        • Young children can have softer, shorter cry, and difficulty in feeding
        • Would rather sit than lie down, usually agitated
        • Speaks in short phrases
        • Tachypnea and frequent use of accessory muscles or presence of suprasternal retractions
        • Loud wheezing throughout exhalation
        • Heart rate 100 to 120 beats per minute; pulsus paradoxus may be present
        • Peak expiratory flow 40% to 69% of predicted or personal best
        • Oxygen saturation 90% to 95%, PaO₂ 60 mm Hg or higher, PaCO₂ (partial pressure of arterial carbon dioxide) less than 42 mm Hg
        • Usually requires an office or emergency department visit and correlates with a clinical course managed with relief from scheduled, frequent 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, usually agitated
        • Loud wheezing both inspiratory and expiratory phases
        • Tachypnea with respiratory rate greater than 30 breaths per minute
        • Heart rate faster than 120 beats per minute; pulsus paradoxus often present
        • Oxygen saturation less than 90%, PaO₂ less than 60 mm Hg, PaCO₂ (partial pressure of arterial carbon dioxide) 42 mm Hg or higher
        • Cyanosis may present
        • Peak expiratory flow lower than 40% of predicted or personal best r1
        • Usually requires an emergency department visit and likely hospitalization. Patient experiences partial relief from frequent inhaled short-acting β₂-agonist treatment. Requires oral steroids with some symptoms lasting more than 3 days after acute treatment has begun; adjunctive therapies are often helpful
      • Life-threatening
        • Cannot speak
        • Perspiring
        • Often drowsy or confused
        • Bradycardia
        • Paradoxical thoracoabdominal movement
        • Wheezing can be absent and pulsus paradoxus can disappear due to respiratory muscle fatigue
        • Peak expiratory flow lower than 25% of predicted or personal best
        • Usually requires an emergency department visit, hospitalization, and possibly ICU. The patient experiences minimal or no relief from frequent inhaled short-acting β₂-agonist treatments and may require IV corticosteroids; adjunctive therapies are helpful

    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 (cough variant asthma) c11c12
      • One of the most common causes of chronic cough in children is asthma r32r33
      • Can present as the sole complaint r32r33
      • Typically dry and hacking, but wet cough with white sputum can occur r32r33
      • If persist more than 2 to 3 weeks, consider asthma as the differential diagnosis r32r33
      • However, in children, chronic cough (for more than 4 weeks) with no other symptoms is unlikely to represent asthma r34
    • Recurrence of episodes with exposure to possible triggers c13
      • Respiratory infection
      • Inhaled allergens
      • Cold, dryr35 or hot, humidr36 air
      • Rain, thunderstorm, or wind r37
      • Passive (or active) tobacco smoke exposure
      • Hydrocarbon fumes (eg, in homes with gas stoves or kerosene heaters)
      • Exposure to other triggers (eg, house dust, ozone air pollution, mold spores, cockroaches, rodents)
      • Exacerbations most common in fall and winter months, least common in summer months r38r39
    • For a patient with known diagnosis of asthma, assess previous disease control on the basis of:
      • Level of adherence to treatment plans
      • Frequency of short-acting β₂-agonist use
      • Steroid use
      • Number and severity of exacerbations in the past year
      • Previous hospital admissions and admission course (especially the need for ICU level of care and intubation)
    • Personal or family history of eczema, allergies, or asthma c14c15c16c17c18c19
    • Inner-city residence c20

    Physical examination

    • Typically normal findings in patients with well-controlled asthma
    • With exacerbation, findings are variable depending on severity of airflow obstruction and comorbidities
    • General appearance
      • Anxiety or agitation c21c22
      • Drowsiness with impending respiratory failure c23
      • Ability to speak may be impaired c24
      • Struggling to breathe c25
      • Posture: upright versus lying down c26
    • Vital signs r1
      • Tachypnea and tachycardia with asthma exacerbation c27c28
        • Bradycardia occurs in life-threatening exacerbation
      • Diminished oxygen saturation is variable with moderate to severe exacerbation c29
      • Pulsus paradoxus occurs in moderate and severe exacerbation and disappears in life-threatening exacerbation due to respiratory muscle fatigue
    • Prolonged expiratory phase with exacerbation c30
      • Forced expiration precipitates bronchospasm as evidenced by a coughing spell
    • Labored breathing, use of respiratory accessory muscles with intercostal recession, and nasal flaring c31c32c33
    • Wheezing is usually present during exacerbation, but absence of wheezing does not rule out significant bronchospasm c34
      • Poor air movement is a sign of impending respiratory failure c35
    • Cyanosis and diaphoresis with significant hypoxia c36c37
    • Findings consistent with concomitant disease commonly found in children who also have asthma
      • Allergic rhinitis: increased nasal secretions, swollen turbinates, allergic shiners, and nasal polyps c38c39c40
      • Eczema: characteristic chronic dry skin with breakdown in typical eczema distribution c41

    Causes and Risk Factors

    Causes

    • Underlying cause is incompletely understood; may be environmental in combination with genetic interaction, leading to airway inflammation, hyperresponsiveness, airway obstruction, and disease chronicity c42
      • Environmental insult may be allergen, infectious agent, stress, or airborne irritant (eg, air pollution, smoke exposure) r1
      • Genetic factors lead to Th2 cytokine response profiles r1
        • Parental asthma or allergy history is an important factor
    • Exacerbation triggers c43
      • Aeroallergens (eg, pollen, pet dander, dust, mold, cockroach and rodent droppings) c44
      • Airborne irritants (eg, cigarette or wood smoke, air pollution, chemical compounds) c45
      • Respiratory infection (eg, respiratory syncytial virus, rhinovirus) c46
      • Drugs (eg, NSAIDs including aspirin, β-blockers) c47
      • Ingested substances (eg, sulfites, alcohol) c48
      • Psychological or emotional stress c49c50
      • Cold, dry air or hot, humid air; change in temperature and humidity; thunderstorm r36r37
      • Exercise c51

    Risk factors and/or associations

    Age
    • Recurrent early-onset wheezing increases risk of asthma development r40
      • Recurrent wheezing in first 3 years of life increased the risk of having asthma in adolescents by 4.7-fold
      • Recurrent wheezing in children aged 4 to 6 years increased the risk of having asthma in adolescence by 15.4-fold
    • Asthma prevalence among children is as follows: r41
      • Birth to 4 years: 4% c52
      • 5 to 11 years: 8.8% c53
      • 12 to 17 years: 10.5%
    Sex
    • Overall, more prevalent among males (9.0%) than among females (7.1%) r42c54c55
    • In first year of life, more common in males than in females r6r43c56
    • In adolescence, more common in females than in males and remains more prevalent in females in adulthood r6r43c57
    Genetics
    • Parental history of asthma is a major risk factor c58
    • Gene markers and loci are associated with asthma susceptibility and atopic and childhood-onset asthma r44
      • Markers near ORMDL3/GSDMB genes were associated with childhood-onset asthma
      • Single nucleotide polymorphisms in IL-33 and IL-1RL1 were associated with atopic asthma
      • A TSLP single nucleotide polymorphism was protective against the risk to allergic asthma
    • Epigenetic factors can modify gene expression r45
      • Includes DNA methylation, modification of histone tails, and noncoding RNAs
      • Influenced by environmental exposures and genetic variation
      • Play roles in pathogenesis of asthma
      • Explain the link between environmental exposures and asthma susceptibility
    Ethnicity/race r42
    • Asthma prevalence was higher among Black people (10.7%) and persons of multiple races (13.1%) than among White people (8.0%) r41c59c60
    • Lower among Asian (4.5%) and Hispanic races (6.5%)
    • In Hispanic race, Puerto Rican people had the highest prevalence (14.0%), then Mexican people (5.4%), and other Hispanic individuals (6.3%)
    Other risk factors/associations
    • Risk factors for development of asthma using modified asthma predictive index in patients aged 3 years and younger r1
      • Sensitivity 17% and specificity 99%
      • Positive modified asthma predictive index is defined by 4 or more wheezing episodes per 12 months
        • AND one of the following:
          • Parental history of asthma
          • Diagnosis of atopic dermatitis
          • Sensitization to aeroallergens
        • OR two of the following:
          • Food allergy to milk, egg, or peanut
          • 4% or greater of peripheral blood eosinophilia
          • Wheezing apart from colds
      • Positive modified asthma predictive index has high predictive value
        • Positive likelihood ratio ranges from 4.9 to 5.5 for asthma development in patients aged 6, 8, and 11 years
    • Risk factors for development of asthma at age 7 years using PARS (Pediatric Asthma Risk Score) r46
      • Use in children aged 3 years and younger
      • Improves ability to predict asthma in children with mild to moderate asthma risk with 68% sensitivity and 77% specificity
      • Asthma risk of 3% to 79%
        • Parental asthma
        • Eczema
        • Early wheezing from birth to 3 years
        • Wheezing when healthy
        • Black/African ancestry
        • Allergic sensitization to 2 or more aeroallergens or foods
    • Abnormal pulmonary function in early childhood r3
    • Specific viral and bacterial respiratory infections in infancy may play roles in asthma development and severity (eg, respiratory syncytial virus infection, rhinovirus infections)
    • Exposure to tobacco smoke
    • Premature birth (ie, less than 37 weeks of gestation)
    • Low birth weight r47
    • Obesity may be a risk factor, but findings are inconsistent
    • Physician diagnosis of atopic disease (eg, atopic dermatitis, allergic rhinitis) r3
    • Greater than 4% peripheral eosinophilia r29

    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 r1r3c61
        • Documentation of reversible airway obstruction
          • Patients aged younger than 5 years r1
            • Diagnosis is challenging in this age group because objective measurements of lung function are difficult to obtain r1
              • Documentation of episodic clinical response to bronchodilator therapy is a good indicator of reversible airway obstruction
              • Spirometry may not be feasible owing to patient cooperation or comprehension c62
              • Broncho provocation can be assessed by a trained specialist, but is not commonly performed in young children c63
              • Impulse oscillometry, if available, measures respiratory impedance, requires little cooperation, and documents reversible obstruction c64
              • Understand wheezing phenotypes and utilize asthma predictive tools to help diagnose asthma in infants and children
          • Patients aged 5 to 11 years r1
            • Obtain spirometry to show reversible airflow obstruction after trial of bronchodilator r34c65
            • Response to a therapeutic trial of inhaled corticosteroids supports the diagnosis in symptomatic children with normal or near-normal spirometry results and negative bronchodilator response; repeat spirometry after 4 to 8 weeks r34c66
            • Bronchoprovocation may be performed when asthma is suspected, spirometry results are within (or nearly within) the reference range, and response to asthma medications is not significant c67
            • Measurement fraction of exhaled nitric oxide can be useful to support diagnosis of asthma r34c68
          • Exercise-induced bronchoconstriction r1
            • Previously termed "exercise-induced asthma" which is now not preferred as exercise does not cause asthma
            • Exercise-induced bronchoconstriction is a component of asthma and typically occurs in people with asthma but not all patients with asthma have exercise-induced bronchoconstriction
            • Characterized by clinical symptoms of cough, wheezing, or dyspnea associated with exercise as well as reversible airway obstruction in response to exercise or surrogate challenge
            • In patients with documented asthma, formal testing is not needed for diagnosis of exercise-induced bronchoconstriction
            • Evaluate using exercise challenge or surrogate provocation testing with FEV₁ or peak expiratory flow documentation c69
            • Confirm diagnosis by a positive response to asthma medications c70
      • Consider and exclude alternative diagnoses c71
        • Important at time of initial diagnosis and if there is no clear response to therapy
        • The younger the child is at time of initial concern for asthma (eg, wheezing), the higher the possibility of alternative diagnosis (eg, gastrointestinal reflux, cystic fibrosis, aspiration syndrome, immune deficiency, congenital heart disease, bronchopulmonary dysplasia) r29
      • Imaging and additional diagnostic testing do not typically add to the initial diagnostic workup
        • Chest radiography r1c72
          • Indicated only to exclude or support presence of other conditions (eg, in a patient whose condition fails to respond to conventional therapy or in a patient with wheezing and atypical clinical presentation that suggests alternative diagnosis)
            • Atypical features include a history of symptoms starting at or shortly after birth, continuous wheezing, wheezing unresponsive to bronchodilators, failure to thrive, digital clubbing, and wheezing not associated with typical asthma triggers
            • Chest radiography may reveal structural concerns such as vascular ring, findings suggestive of cystic fibrosis, or chronic lung disease
        • CT scan (and sometimes bronchoscopy) c73c74
          • Performed in rare circumstances when response to conventional therapy is poor or if other pulmonary disease is suspected. Referral to pulmonology may be necessary
        • Evaluation for atopic disease r3
          • Expert consensus recommends evaluating for atopy when there is suspicion or diagnosis of asthma, particularly for patients with persistent or increasingly severe asthma r1
          • Identification of specific aeroallergen sensitization can support diagnosis, can indicate avoidable disease triggers, and has prognostic significance as indicated by the asthma predictive tools
          • Both in vivo methods (eg, skin prick test) and in vitro methods (eg, specific IgE antibodies) can be used
          • Food allergy testing is not helpful in the diagnosis of asthma. However, children with food allergy and asthma are at higher risk for fatal anaphylaxis and should be prescribed epinephrine r48
    • Acute exacerbation
      • Obtain peak expiratory flow measurement c75
      • Obtain pulse oximetry for noninvasive SaO₂ (arterial oxygen saturation) monitoring c76
        • Arterial blood gas tests are rarely indicated r1c77
      • Obtain chest radiograph if complicating chest infection is suspected, hospitalization is required, or diagnosis is uncertain r7c78
      • Laboratory testing adds little in most patients
        • CBC demonstrating elevated WBC count may suggest infection c79
        • However, if systemic steroid was given, it can cause leukocytosis with neutrophilia
    • Multiple resources are available to assist with the diagnostic process, including:
      • National Asthma Education and Prevention Program guidelines and NIH Asthma Care Quick Reference r1r9r49
      • Global Initiative for Asthma guidelines and resources r50
      • European Respiratory Society guidelines for diagnosis of asthma in children aged 5 to 16 years r34
      • European Respiratory Society Task Force evidence-based approach to assessment and treatment of wheezing in preschool children r27
      • Canadian Thoracic Society guidelines for preschoolers and for children and adults r51r52
      • National Institute for Health and Care Excellence asthma pathway and guidelines r12

    Functional testing

    • Spirometry (objective measure of FEV₁ in patients aged 5 to 11 years) r1c80
      • Evaluates for objective signs of reversible airway obstruction as well as severity of asthma
      • Obtain at initial assessment, after treatment has started, and when symptoms and peak expiratory flow have stabilized
      • Measure during periods of prolonged loss of asthma control and at least every 1 to 2 years for a patient with stable disease
      • Normal spirometry result does not exclude asthma
      • Perform bronchodilator reversibility testing in children with FEV₁ and/or FEV₁/FVC findings supportive of asthma diagnosis; also consider if spirometry result is normal but clinical history is highly suggestive of asthma r34
        • Assess reversibility by performing spirometry before and after administration of bronchodilator using 1 of the following definitions
          • Global Initiative for Asthma: reversibility is defined by an increase in FEV₁ of 12% or greater from baseline with a minimum of 200 mL r7
            • A change of 12% from baseline is based on adult criteria; an increase in FEV₁ of 8% or greater is considered a more sensitive criteria for diagnosing asthma in children r53
          • European Respiratory Society/American Thoracic Society: reversibility is defined by a change of greater than 10% relative to the predicted value for FEV₁ or FVC r54
      • Use FEV₁ and FEV₁/FVC to classify severity per National Heart, Lung, and Blood Institute Expert Panel Report 3 guidelines
    • Peak expiratory flow (objective measure of airway obstruction) r1c81
      • Limited role in diagnosis of asthma
      • Discuss and demonstrate technique at office visit
      • Determine personal best when asthma is stable
      • Measure at baseline
      • Monitor for worsening or improvement at home
      • Benefits: requires short expiratory burst, portable device, can be used at home
      • Limitations: effort dependent, imprecise, variation with each use
    • Bronchoprovocation testing r1c82
      • Performed with methacholine, exercise, cold air challenge, and other triggers to assess airway hyperresponsiveness r34
      • Can be useful when asthma is suspected and spirometry results are within (or nearly within) the reference range
      • Exercise testing or eucapnic voluntary hyperpnea testing can be used for patients with concern for exercise-induced bronchoconstriction
      • Performed by an asthma care specialist or other trained person owing to possibility of severe bronchospasm
      • Positive test result is diagnostic for airway hyperresponsiveness, which is characteristic of asthma although not specific to it
      • Negative test result is helpful to exclude the diagnosis of asthma
    • FeNO (fraction of exhaled nitric oxide) r55c83
      • Simple, noninvasive test that can be utilized when diagnosis of asthma is suspected and other diagnostic tests cannot be performed
      • FeNO levels are increased in patients with asthma due to presence of eosinophilic inflammation leading to airway epithelial cells to produce nitric oxide
        • FeNO less than 20 ppb in children younger than 12 years: absence of eosinophilic inflammation
          • Does not exclude asthma
          • Consider different diagnosis
          • Unlikely to benefit from inhaled corticosteroid
        • FeNO greater than 35 ppb in children younger than 12 years: eosinophilic inflammation; supportive in diagnosis of asthma but not conclusive r55
          • Likely to benefit from inhaled corticosteroid
        • FeNO 20 to 35 ppb in children younger than 12 years: evaluate in clinical context, monitor changes over time
        • Other factors can affect FeNO including smoking (associated with lower FeNO) and atopy (associated with higher FeNO)
      • Sensitivity is 79% and specificity is 81% for detection of asthma in children r56
      • European Respiratory Society recommends measurement of FeNO as part of the diagnostic workup for the diagnosis of asthma in children aged 5 to 16 years; has not been standardized in children aged younger than 4 years r27r34
      • EPR-4 (National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group 4) recommends use as an adjunct to diagnosis in patients aged 5 years and older in whom diagnosis of asthma remains uncertain based on history, clinical findings, clinical course, and spirometry (or if spirometry cannot be performed), including bronchodilator responsiveness testing r49
        • Recommends incorporating FeNO for ongoing asthma monitoring and management strategy
        • Recommends against using FeNO in isolation to assess asthma control, predict exacerbations, or assess severity
        • Not recommended in children aged 4 years and younger with recurrent wheezing to predict development of asthma
      • British guidelines recommend measurement of FeNO (feasible from the age of 3-4 years) with level of 35 ppb or more regarded as a positive test in school-aged children r57
      • American Thoracic Society recommends measuring FeNO at time of asthma diagnosis r55c84
      • Global Initiative for Asthma guidelines suggest that FeNO is not useful for ruling in or ruling out asthma as FeNO can be higher in asthma (with Th2 inflammation) but can also be elevated in non-asthma conditions (eg, eosinophilic bronchitis, atopy, allergic rhinitis) and not elevated in neutrophilic asthma r7
        • Unclear whether FeNO-guided treatment is associated with fewer exacerbations, and further studies are needed before determining populations who would benefit from FeNO-guided therapy and monitoring frequency
        • Recommend using FeNO to characterize asthma phenotype and presence of type 2 inflammation (FeNO greater than or equal to 20 ppb) to guide treatment of patients with severe asthma
          • FeNO 20 ppb or greater predicts good response to anti-IgE therapy
          • FeNO 25 ppb or greater makes patients eligible for anti-IL4R therapy
          • Higher FeNO is associated with good response to anti-IL(interleukin)4R and anti-TSLP (thymic stromal lymphopoietin) therapies
    • Impulse oscillometry c85
      • Simple, noninvasive test; uses sound waves to measure respiratory mechanics
      • Test is performed easily in children aged younger than 5 years because testing requires minimal cooperation r58
      • Detects obstruction in large and small peripheral airways; measures airway hyperreactivity (eg, bronchodilator response, response to bronchoprovocation testing); may be useful to predict loss of asthma control r59
      • May be more sensitive than spirometry to detect subtle changes in airway function and distal changes in airway function when spirometry results are normal r59
      • Interpretation of results is less straightforward than with spirometry
      • Not readily available to most clinicians and specialists

    Differential Diagnosis

    Most common

    • Vocal cord dysfunction (paradoxical vocal cord motion disorder, inducible laryngeal obstruction) r60c86c87
      • Vocal cord dysfunction is frequently misdiagnosed as asthma, which leads to mismanagement (eg, unnecessary intubation, use of continuous maintenance oral corticosteroids, otherwise preventable hospital admissions, emergency department visits) r61
      • Symptoms include episodic dyspnea that mimics an asthma exacerbation, anxiety, wheezing, and/or inspiratory or biphasic stridor
      • Paroxysmal episodes of vocal cord adduction primarily during inspiration, possibly expiration, can be triggered by exercise or stress, though they may occur spontaneously; inspiratory stridor favors an extrathoracic cause for dyspnea
      • Vocal cord dysfunction can coexist with asthma;r61 consider vocal cord dysfunction in any patient with asthma that is difficult to treat or atypical, with absent symptoms during sleep, and in athletes with exercise-related dyspnea unresponsive to bronchodilators r1
      • Spirometry can support the diagnosis with flattening of the inspiratory flow-volume loops when symptoms are present; there is no improvement with bronchodilators
      • Differentiated from asthma by history, physical examination, and lack of response to asthma medication
      • Diagnosis can be made by documenting abnormal vocal cord adduction by indirect or direct visualization with flexible laryngoscopy during an acute episode r61
    • Congenital malformation or anomalies of airway (eg, laryngotracheomalacia, bronchomalacia, laryngeal web, tracheoesophageal fistula, vascular malformations including vascular rings or slings) c88c89c90c91c92c93c94
      • Presents during infancy with history of cough, stridor, or wheezing (depending on anatomic location of anomaly); symptoms usually include chronic feeding difficulties
        • Vascular rings and slings present with biphasic stridor due to compression and narrowing of large airways and can also have esophageal compression leading to feeding difficulty and vomiting
        • Tracheoesophageal fistula can present with chronic cough, recurrent pneumonia, and wheezing. Symptoms increase with feeding
      • Symptom severity associated with a structural abnormality (eg, tracheomalacia) may change with activity or positional changes
        • Tracheomalacia may worsen with agitation or excitement and improve with prone positioning
      • Differentiated from asthma by fiberoptic bronchoscopy and by failure to respond to bronchodilators
    • Foreign body aspiration c95
      • Typically affects toddlers (aged 1-3 years); presentation includes acute onset of stridor, wheezing, or both after a choking, gagging, or coughing event
      • Physical signs can include stridor or unilateral wheezing on lung examination
      • Diagnosis can be aided by soft tissue neck and bilateral decubitus lung radiographs
      • Rigid bronchoscopy is used for removal of aspirated foreign bodies in most cases
    • Respiratory infection (eg, viral bronchiolitis, laryngotracheobronchitis, pneumonia) c96c97c98c99
      • Wheezing and increased work of breathing from a respiratory infection may be difficult to differentiate from a first-time asthmatic wheezing episode that is triggered by a respiratory infection d2
      • Infections in children aged younger than 2 years is a common cause of wheezing
      • Nasal suctioning in younger children will improve work of breathing if bronchiolitis is a cause of respiratory distress d3
      • Bronchodilator trial will show reversibility of increased work of breathing or wheezing if caused by respiratory infection–induced asthma
    • Bronchiectasis c100d4
      • Dilation of the intrathoracic airways with loss of structural integrity and obstructive lung disease, usually secondary to chronic recurrent infection or inflammation due to cystic fibrosis or primary immunodeficiency; bronchiectasis can develop with time as a complication of chronic severe persistent asthma
      • Like asthma, bronchiectasis presents with cough and wheezing
      • History of chronic cough, failure to thrive, and production of a large amount of purulent sputum predominate in children with bronchiectasis; pulmonary examination may find diffuse or localized crackles and digital clubbing
      • History and physical examination differentiate bronchiectasis from asthma; if the definitive diagnosis is in question, a chest CT scan will differentiate
      • High-resolution CT findings include parallel lines, dilated bronchi, and signet ring sign
    • Cardiac causes for wheezing
      • Conditions with left to right shunting leading to increased pulmonary blood flow, overcirculation, and pulmonary venous congestion can cause compression of large airways causing wheezing c101d5
      • This can present as tachypnea, cough, fatigue, dyspnea on exertion, wheezing, and respiratory distress in children; infants classically present with diaphoresis and difficulty feeding
      • Onset is typically more insidious than that of asthma, and the patient has no family history or personal history of asthma
      • Bronchodilator trial will fail to reverse wheezing for cardiac causes
      • Cardiomegaly may be suggested by chest radiograph or EEG; diagnose by echocardiogram d6
      • Hepatomegaly, peripheral edema, splenomegaly, and abnormal cardiac examination findings (eg, murmurs, rubs, gallops) differentiate cardiac causes of wheezing from asthma
    • Mediastinal mass c102
      • Can present with insidious onset of cough, wheezing, orthopnea, and dysphagia; children often have history of failure to thrive
      • Physical examination sometimes shows signs of superior vena cava syndrome, pleural effusions, or both
      • Diagnosis is made by bronchodilator trial failure and chest radiography
    • Gastroesophageal reflux r62c103
      • Motility disorder characterized by reflux of gastric contents into the esophagus or oral cavity with resulting symptoms or complications
      • Can coexist with asthma and can be a trigger for asthma
      • Can cause recurrent or chronic cough with or without wheezing; can result in chronic pulmonary disease
      • Symptoms are often worse at night; children often suffer from chronic hoarseness, laryngitis, and/or esophageal pain from reflux
      • Gastroesophageal reflux is suggested by the following: primarily nocturnal symptoms without other typical asthma triggers for symptoms, no family history of asthma, no personal history of eczema or allergic symptoms, lack of response to bronchodilators, and improved symptoms after treatment of gastroesophageal reflux
      • Evaluation can include gastroenterology referral with endoscopy, esophageal pH and impedance monitoring, and esophageal contrast radiography
      • An empiric trial of acid suppression can be appropriate to exclude diagnosis

    Treatment

    Goals r1

    • Reduce current impairment
      • Prevent symptoms
      • Decrease need for short-acting β₂-agonist inhaler to 2 or fewer days per week (not including use to prevent exercise-induced bronchoconstriction)
      • Maintain normal activity levels
      • Maintain near-normal pulmonary function (measured by FEV₁ or peak expiratory flow)
      • Meet patients' satisfaction
    • Reduce future risk
      • Prevent exacerbations
      • Minimize risk for emergency department visit and hospitalization
      • Prevent structural changes in airways and decline in pulmonary function
      • Minimize risks/adverse effects of therapy

    Disposition

    Admission criteria

    Infants and young children

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

    Infants

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

    Older children r1

    • When FEV₁ or peak expiratory flow is at least 40% but lower than 69% after third short-acting β₂-agonist treatment, keep in observation unit (good likelihood of being able to discharge) or admit if no observation unit available
    • Admit if FEV₁ or peak expiratory flow is less than 40% after third short-acting β₂-agonist treatment
    • Admit if dyspnea at rest interferes with conversation or the patient continues to meet requirements for moderate to severe exacerbation 1 hour after third short-acting β₂-agonist treatment
    Criteria for ICU admission r1
    • Infants and younger children with obvious respiratory distress who have normal or rising PCO₂ (42 mm Hg or greater) on blood gas analysis (suggests impending respiratory arrest)
    • Older children with poor response (FEV₁ or peak expiratory flow less than 40%) to prolonged therapy or respiratory fatigue

    Recommendations for specialist referral

    • Refer the following to an asthma specialist (usually a pulmonologist or an allergist): r1
      • Patient receiving step 4 or higher drug therapy
      • Patient younger than 4 years receiving step 3 drug therapy
      • Patient possibly requiring immunotherapy or monoclonal antibody treatment
      • Patient who has required more than 2 oral steroids in past year
      • Patient who has required hospitalization for asthma in past year
      • Patient in whom diagnosis is uncertain, whose symptoms are atypical, with other conditions that complicate asthma, or for whom additional testing is indicated
      • Patient who requires additional education or has issues with adherence or allergen avoidance
      • History of life-threatening asthma exacerbation
    • Refer to an allergist for allergy desensitization treatment r63c104

    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 less than 50%, caregiver should bring patient to urgent care facility or emergency department (emergency department if peak expiratory flow is less 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 r64
        • Mild to moderate exacerbation with FEV₁ or peak expiratory flow equal to at least 40% of predicted or personal best r1
          • Give supplemental oxygen to achieve SaO₂ (arterial oxygen saturation) of 90% or greater 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 r65
            • Inhaled ipratropium plus short-acting β₂-agonist decreases risk of hospital admission r1r66
            • Do not use ipratropium alone without inhaled short-acting β₂-agonist. Continue treatment for 1 to 3 hours; make decision to admit within 4 hours r1
        • Severe exacerbation with FEV₁ or peak expiratory flow less than 40% of predicted or personal best r1
          • Give supplemental oxygen to achieve SaO₂ (arterial oxygen saturation) of at least 90% r1
          • Give high-dose inhaled short-acting β₂-agonist plus ipratropium by nebulizer or metered-dose inhaler with valved holding chamber every 20 minutes or continuously for 1 hour
          • Give oral systemic steroids
          • Continue nebulized short-acting β₂-agonist plus ipratropium, hourly or continuous
          • 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 r64
            • Consider heliox r1
        • Impending or actual respiratory arrest r1
          • Maximize asthma therapy
            • Give nebulized short-acting β₂-agonist and inhaled ipratropium, hourly or continuous
            • Give IV corticosteroids
            • Consider adjunctive therapies
          • Start adjunct therapies for patients with life-threatening exacerbations and those whose exacerbations remain severe after 1 hour of conventional therapy r1
            • Magnesium sulfate infusion r1
              • Reduce hospitalization rates in patients with severe exacerbations (peak expiratory flow less than 40%) 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 r66
            • Heliox
              • National Asthma Education and Prevention Program guidelines suggest adjunctive administration of heliox in patients with life-threatening exacerbations or those who are not responding to conventional therapy r1
              • May reduced hospitalizations in children who had moderate to severe exacerbations r1
            • Methylxanthines (eg, aminophylline)
              • Use in the treatment of acute exacerbation is controversial
                • Cochrane review recommends considering IV aminophylline in patients with severe acute exacerbations of asthma where response to inhaled bronchodilators and glucocorticoids is poor r67
                • Global Initiative for Asthma and National Asthma Education and Prevention Program guidelines do not recommend aminophylline for treatment of acute exacerbation owing to poor safety profile r1r68
                • British Thoracic Society guidelines along with some children's hospitals in Australia and New Zealand recommend aminophylline as adjunct to treatment of life-threatening asthma r57r69r70
            • Epinephrine or terbutaline
              • Consider intramuscular or subcutaneous dose of epinephrine or terbutaline for severe life-threatening exacerbations r71
          • 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
          • However, intubation should not be delayed once it is deemed necessary r1
          • Indications for intubation and mechanical ventilation with 100% oxygen include: r2r64
            • Poor response to maximum therapy
            • Hypercarbia (PCO₂ 42 mm Hg or greater)
            • Severe hypoxemia (PO₂ less than 60 mm Hg)
            • Worsening mental status or coma
            • Impending respiratory arrest (indicated by respiratory depression, apnea, or bradycardia)
            • Worsening metabolic acidosis
            • Cardiopulmonary arrest
            • Progressive severe fatigue, worsening airflow obstruction, or respiratory failure
          • Admit to ICU
      • Ongoing treatment and disposition are determined by response to initial round of respiratory treatments r65
      • Use caution during assessment and disposition of patients with risk factors for death from asthma, including: r72
        • History of previous severe exacerbation (ICU admission or intubation)
        • 2 or more hospitalizations or 3 or more emergency department visits for asthma in the past year
        • Using more than 2 canisters of short-acting β₂-agonist per month
        • Difficulty perceiving asthma symptoms or severity of exacerbations
        • Lack of asthma action plan
        • Sensitization to Alternaria spp.
        • Low socioeconomic status or inner-city patients
        • Illicit drug use
        • Major psychosocial problems
        • Significant comorbid cardiovascular or chronic respiratory disease, or chronic psychiatric disorders
      • If the patient is discharged after an acute exacerbation, management should include: r1
        • Review of inhaler technique and environmental control measures, and review or initiation of asthma action plan
        • Continued use of scheduled inhaled short-acting β₂-agonist r73
        • 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 for patients on long-term therapy r72
        • Oral steroids for 3 to 10 additional days if steroids are given in emergent setting r1
        • Schedule an outpatient follow-up appointment with primary provider and/or asthma specialist in 1 to 4 weeks r1

    Chronic asthma

    • Primary components of chronic asthma management
      • Measures to assess and monitor asthma severity and control
      • Patient education and partnership in asthma care
      • Control of environmental factors and asthma comorbidities
      • Pharmacologic treatment
    • Long-term asthma treatment is based on severity level and control, and adjusted via a stepwise approach
    • Determine initial step by disease severity classification (for newly diagnosed patients not on controller medications) or by disease control classification (for patients currently using controller medications) r1r74
      • Adjustments are based on ongoing level of control
      • Therapy can be both stepped up and stepped down; consider step down after 3 months of good control
      • Always address any factors that may contribute to suboptimal control (eg, poor adherence to therapy, incorrect inhaler technique, comorbidities, modifiable risk factors)
    • 3 types of medications may be used r7
      • Controllers
        • Inhaled corticosteroid–containing controller medications reduce airway inflammation and symptoms, future exacerbations, and decline in lung function
          • 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-, and high-dose comparisons can be found in the National Asthma Education and Prevention Program and Global Initiative for Asthma guidelines r1r7r49
            • Fluticasone may be associated with less effect on growth in children than equivalent doses of beclomethasone and budesonide r75
            • Estimated comparative daily dosages: inhaled corticosteroids for long-term asthma control.*It is preferable to use a higher mcg/puff or mcg/inhalation formulation to achieve as low a number of puffs or inhalations as possible. DPI, dry powder inhaler (requires deep, fast inhalation); MDI, metered dose inhaler (releases a puff of medication); N/A, not applicable.From NIH: Asthma Care Quick Reference: Diagnosing and Managing Asthma. NIH Publication No. 12-5075. NIH website. Published June 2002. Revised September 2012. Accessed September 19, 2023. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf
              Daily doseAged 0 to 4 yearsAged 5 to 11 yearsAged 12 years or older
              Medication
              LowMedium*High*LowMedium*High*LowMedium*High*
              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
        • SMART (Single Maintenance And Reliever Treatment) or MART (Maintenance And Reliever Treatment) using a combination of inhaled corticosteroid plus formoterol in a single inhaler is the preferred treatment in children aged 5 years and older who are not well controlled on a low- or medium-dose daily inhaled corticosteroid alone r7r11r49r57
      • Relievers
        • Used as needed to alleviate breakthrough symptoms
        • Once a mainstay of asthma therapy, short-acting β-agonists are no longer recommended as monotherapy owing to safety concerns and poor outcomes r76
        • A combined inhaled corticosteroid plus fast-onset, long-acting β-agonist (ie, formoterol) is the preferred reliever for step 3 and 4 treatment in children aged 5 years and older; this combination is referred to as an anti-inflammatory reliever
          • Can be used as needed at steps 1 and 2 without maintenance inhaled corticosteroids r7
        • 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
        • These include long-acting β₂-agonist, long-acting muscarinic antagonists, leukotriene receptor antagonist, leukotriene synthesis inhibitor, mast cell stabilizers, methylxanthines, and biologic agents
          • Long-acting muscarinic antagonist
            • Tiotropium is approved for use in children aged 6 years and older r7
              • However, National Asthma Education and Prevention Program recommendations for use apply only to children aged 12 years and older
            • Daily inhaled corticosteroid–long-acting muscarinic antagonist is an alternative therapy after SMART (Single Maintenance And Reliever Treatment; preferred choice) and after daily inhaled corticosteroid–long-acting β₂-agonist (secondary choice) for moderate persistent disease asthma in children aged 12 years and older r11r49c105
          • Leukotriene receptor antagonists
            • Zafirlukast and montelukast
            • Montelukast is associated with an increased risk for serious neuropsychiatric events (eg, 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 r77r78
          • Leukotriene synthesis inhibitor
            • Zileuton is an add-on option for adolescents aged 12 years and older r49
          • Biologic agents
            • Monoclonal antibodies (eg, anti-IgE, anti-IL[interleukin]-4/IL-13, anti-IL-5/IL-5R, and anti-TSLP[thymic stromal lymphopoietin])
            • Option for uncontrolled severe asthma despite maximal optimal therapy r7
          • Mast cell stabilizers
            • Cromolyn sodium and nedocromil sodium have now been discontinued worldwide r7
            • Previously used as an alternative for patients with mild persistent asthma and preventative treatment before exercise, and for unavoidable exposure to known allergens r1
          • Methylxanthines
            • Theophylline is the least preferred alternative and is rarely used r1
            • Significant interactions with other medications, narrow therapeutic index, wide interpatient variability in metabolic clearance, and need for monitoring of serum concentrations
    • Preferred treatments (see NAEPP EPR-4 [National Asthma Education and Prevention Program Expert Panel Report-4] 2020 focused updates to the asthma management guidelines and GINA [Global Initiative for Asthma] guidelines for alternative medication options for each step) r7r49
      • Step 1 (intermittent asthma)
        • Children aged 4 years and younger (EPR-4)r49 or 5 years (GINA) r7and younger
          • As-needed short-acting β₂-agonist r49
          • 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 r11r49
        • Children aged 5 to 11 (EPR-4) r49or 6 to 11 (GINA)r7 years
          • As-needed short-acting β₂-agonist alone (EPR-4) r49or with low-dose inhaled corticosteroid used concomitantly whenever short-acting β₂-agonist is taken (GINA-preferred treatment), or daily low-dose inhaled corticosteroid with short-acting β₂-agonist as needed (GINA-alternative treatment) r7
        • Children aged 12 years and older
          • As-needed low-dose inhaled corticosteroid plus formoterol in a single inhaler as required to alleviate symptoms (GINA-preferred treatment) r7
          • Low-lose inhaled corticosteroid taken whenever short-acting β₂-agonist is taken (GINA-alternative treatment) r7
          • As-needed short-acting β₂-agonist alone (EPR-4) r49
            • GINA no longer recommends as-needed inhaled short-acting β₂-agonist monotherapy r76
              • Inhaled corticosteroid–containing fast-acting reliever medications are superior to short-acting β₂-agonists reliever alone to reduce risks of severe asthma exacerbation r7r79
      • Step 2 (mild persistent asthma)
        • Children aged 4 (EPR-4)r49 or 5 (GINA) years and younger
          • Daily low-dose inhaled corticosteroid and as-needed short-acting β₂-agonist to alleviate symptoms (preferred treatment) r7r49
          • Alternative options
            • Daily montelukastr49r7 and as-needed short-acting β₂-agonist
            • Intermittent short course of daily inhaled corticosteroid at the onset of respiratory illness and as-needed short-acting β₂-agonist may be considered r7
        • Children aged 5 to 11 (EPR-4)r49 or 6 to 11 (GINA) yearsr7
          • Daily low-dose inhaled corticosteroid maintenance and as-needed inhaled short-acting β₂-agonist to alleviate symptoms (preferred treatment) r7r49
          • Low dose inhaled corticosteroid taken whenever short-acting β₂-agonist is used (alternative treatment) r7
          • Consider adjunct treatment with subcutaneous immunotherapy r49
        • Children aged 12 years and older
          • Low-dose inhaled corticosteroid plus formoterol in a single inhaler,r7r8 taken as needed to alleviate symptoms (preferred treatment for GINA); r8particularly useful in patients with poor adherence to daily medicationr8
          • Daily low-dose inhaled corticosteroid maintenance therapy plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms (alternative treatment for GINA)r8r49
          • As-needed short-acting β₂-agonist with low-dose inhaled corticosteroid used concomitantly (preferred treatment for EPR-4)r49r49
          • Consider adjunct treatment with subcutaneous immunotherapy r49
      • Step 3 (moderate persistent asthma) r1
        • Children aged 4 (EPR-4)r49 or 5 (GINA) years and younger
          • Daily medium-dose inhaled corticosteroid plus as-needed short-acting β₂-agonist to alleviate symptoms r7r49
          • Daily low-dose inhaled corticosteroid plus leukotriene receptor antagonist may be considered as an alternative r7
          • Consider asthma specialist referral if symptoms remain inadequately controlled or exacerbations persist after 3 months
          • According to EPR-4, children aged 4 years can use step 3 treatment for children aged 5 to 11 years r49
        • Children aged 5 to 11 (EPR-4)r49 or 6 to 11 (GINA)r7 years
          • Low-dose inhaled corticosteroidr49 or very low–dose inhaled corticosteroidr7 plus formoterol in a single inhaler, as maintenance therapy and reliever as needed to alleviate symptoms (preferred treatment for both EPR-4 and GINA)
          • Daily low-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist and as-needed inhaled short-acting β₂-agonist as reliever (preferred treatment for GINA, alternative treatment for EPR-4) r7r49
          • Medium-dose inhaled corticosteroid plus as-needed inhaled short-acting β₂-agonist to alleviate symptoms (preferred treatment for GINA, alternative treatment for EPR-4) r7r49
          • Consider adjunct treatment with subcutaneous immunotherapy r49
        • Children aged 12 years and older
          • Low-dose inhaled corticosteroid plus formoterol in a single inhaler, as both maintenance therapy and reliever as needed to alleviate symptoms (preferred treatment for both EPR-4 and GINA) r7r49
          • Daily low-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, and as-needed inhaled short-acting β₂ agonist as reliever (alternative treatment) r7r49
          • Another alternative is daily medium-dose inhaled corticosteroid and as-needed short-acting β₂-agonist as reliever r7r49
          • Daily low-dose inhaled corticosteroid plus leukotriene receptor antagonist or low-dose sustained-release theophylline (with as-needed short-acting β₂-agonist as reliever) is less effective than above options r7r49
          • Consider adjunct treatment with subcutaneous immunotherapy r49
      • Step 4 (severe persistent asthma) r1
        • Children aged 4 (EPR-4)r49 or 5 (GINA) years and younger
          • GINA recommends continuing step 3 treatment and referral to asthma specialist r7
            • Optimal treatment has not been established
            • Carefully assess inhaler technique and medication adherence
            • Possible treatment options include addition of a leukotriene receptor antagonist, increased inhaled corticosteroid dose, addition of a inhaled corticosteroid plus inhaled long-acting β₂-agonist, or added intermittent high-dose inhaled corticosteroid at onset of respiratory illness
          • EPR-4 recommends daily medium-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist, with as-needed inhaled short-acting β₂-agonist to alleviate symptoms (preferred treatment) r49
            • Alternatively, daily medium-dose inhaled corticosteroid plus leukotriene receptor antagonist and as-needed short-acting β₂-agonist as reliever
            • Referral to an asthma specialist is recommended r49
          • According to EPR-4, children aged 4 years can use step 4 treatment for children aged 5 to 11 years r49
        • Children 5 to 11 (EPR-4)r49 or 6 to 11 (GINA)r7 years
          • Low-dose (GINA)r7 or medium-dose inhaled corticosteroid (EPR-4)r49 plus formoterol in a single inhaler, as maintenance therapy and reliever as needed to alleviate symptoms (preferred treatment for both GINA and EPR-4) r7
          • Daily medium-dose inhaled corticosteroid plus long-acting β₂-agonist, with as-needed short-acting β₂-agonist to alleviate symptoms (preferred treatment for GINA, alternative treatment for EPR-4) r7
          • Other alternatives include daily medium-dose inhaled corticosteroid plus leukotriene receptor antagonistr49r7, or tiotropiumr7, AND as-needed short-acting β₂-agonist as reliever r7
          • Consider adjunct treatment with subcutaneous immunotherapy r49
        • Children aged 12 years and older
          • Daily medium-dose inhaled corticosteroid plus formoterol in a single inhaler, as both maintenance therapy and reliever as needed to alleviate symptoms (preferred treatment for EPR-4 and GINA) r49
          • Daily medium- or high-dose inhaled corticosteroid plus formoterol as maintenance therapy with as-needed short-acting β₂-agonist to alleviate symptoms (alternative treatment for GINA) r7
          • Other alternatives include medium- or high-dose inhaled corticosteroid plus add on long-acting muscarinic antagonistr7r49, leukotriene receptor antagonistr49r7, low-dose sustained release theophylline (withr49 as-needed short-acting β₂-agonist as reliever) r7
          • Consider adjunct treatment with subcutaneous immunotherapyr49
      • Step 5 (severe persistent asthma)
        • GINA recommendations for children and adolescents aged 6 years and older with persistent symptoms or exacerbations despite good adherence to step 4 treatment (GINA does not make recommendations for this step for children younger than 5) r7
          • Referral to an asthma specialist if available
          • As-needed inhaled short-acting β₂-agonist to alleviate symptoms
          • Daily medium- or high-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist
          • Daily medium- to high-dose corticosteroid plus inhaled long-acting β₂-agonist plus tiotropium bromide
          • Refer for assessment of asthma phenotype (for type 2 airway inflammation) to guide add-on therapy for patients aged 6 years and older who required step 5 treatment r7r80
            • Guidelines have been developed to aid evaluation and management of difficult to treat and severe asthma
            • Type 2 airway inflammation is defined by the presence of 1 or more of the following: r49r81
              • Blood eosinophil count 150/μL or greater
              • FeNO (fraction of exhaled nitric oxide) 20 ppb or greater
              • Sputum eosinophil count 2% or greater
              • Asthma that is clinically allergen driven
              • Oral corticosteroid dependent
            • Consider addition of biologic agents to optimized maximal therapy if there is evidence of type 2 airway inflammation (refer to local eligibility criteria and published guidelines for use) r7r81
              • Anti–interleukin 5 monoclonal antibodies (mepolizumab, reslizumab) and interleukin 5 receptor monoclonal antibodies (benralizumab) for severe asthma with an eosinophilic phenotype, ascertained by either sputum or peripheral eosinophilia
                • Anti–interleukin 5 agents reduce exacerbations in patients with severe eosinophilic asthma r82
                • A blood eosinophil count threshold of 150/μL or greater can be used to guide initiation of anti–interleukin 5 agents r82r83
                • Mepolizumab reduces exacerbation rates by 50% in those with eosinophil counts 150-300/µL or greaterr85, reduces systemic steroid use,r86 and may improve asthma control and quality of lifer85. Appears to be less effective in inner-city children and adolescentsr87r84
                • Benralizumab reduces exacerbation rates by approximately 50% in those with eosinophil counts 300/µL or greater and may improve FEV₁ and quality of life; approved for those aged 12 years and older r84r88r89
                • Predictors for good response to anti–interleukin 5 agents: higher blood eosinophil count, more exacerbations in the past year, presence of nasal polyp, and adult-onset asthma r7
              • Omalizumab, an anti-IgE monoclonal antibody for allergic, moderate-severe persistent asthma with documented sensitivity to a perennial aeroallergen and elevated total IgE level (300-700 IU/mL) r80
                • A blood eosinophil count of 260/μL or greater and an exhaled FeNO (fraction of exhaled nitric oxide) threshold of 19.5 ppb or greater, childhood onset asthma, and allergen-driven symptoms are predictors of patients most likely to benefit from anti-IgE treatment r7r82
                • Approved for patients aged 6 years and older r84
                • Reduces exacerbations, admissions, inhaled corticosteroid/oral steroid dose, asthma symptoms, and short-acting β₂-agonist use r90
              • Dupilumab, an anti–interleukin 4 receptor monoclonal antibody for patients with moderate to severe eosinophilic asthma (eosinophil count 150/µL or greater) r91
                • Reduces exacerbations by 60% to 70%, reduces oral steroid dose, and improves lung function r92r93
                • Approved for patients aged 6 years and older
                • Predictors for good response: higher blood eosinophil count, higher FeNO (fraction of exhaled nitric oxide) r7
              • Tezepelumab, an anti-TSLP (thymic stromal lymphopoietin)
                • Reduces exacerbations by 56% to 70%, reduces emergency department visits and hospitalization, provides small improvement in asthma symptoms and quality of life r94r95r96
                • Approved for patients aged 12 years and older with severe asthma r91
                • Peripheral blood eosinophil count or FeNO (fraction of exhaled nitric oxide) level is not required as these patients still have clinically significant clinical improvement, but higher blood eosinophil count and higher FeNO are predictors for better outcome r94
            • If no evidence of type 2 inflammation, consider the following: r7
              • Add-on tiotropium bromide, a long-acting muscarinic antagonist
              • Course of low-dose oral corticosteroid
              • Consider a trial of anti-TSLP (thymic stromal lymphopoietin) or anti–interleukin 4/anti–interleukin 13
          • Last resort is addition of low-dose oral corticosteroid
        • EPR-4 recommendations for children with severe persistent asthma not controlled by step 4 treatments r49
          • Referral to an asthma specialist is recommended for children of all ages
          • Children aged 4 (EPR-4) years and younger
            • Daily high-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist with as-needed inhaled short-acting β₂-agonist to alleviate symptoms (preferred treatment for EPR-4) r49
              • Alternatively, high-dose inhaled corticosteroid with montelukast and as-needed short-acting β₂-agonist
            • Consider add-on oral corticosteroid as a step up to step 6 treatment r49
          • Children aged 5 to 11 years
            • Daily high-dose inhaled corticosteroid plus inhaled long-acting β₂-agonist with as-needed inhaled short-acting β₂-agonist to alleviate symptoms (preferred treatment for EPR-4) r7r49
              • Alternatively, daily high-dose inhaled corticosteroid with leukotriene receptor antagonist or theophylline
          • Children aged 12 years and older
            • Daily medium- to high-dose corticosteroid plus inhaled long-acting β₂-agonist plus tiotropium bromide, with as-needed inhaled short-acting β₂-agonist to alleviate symptoms (preferred treatment for EPR-4) r49
              • Alternatively, daily medium- to high-dose inhaled corticosteroid with long-acting β₂-agonist and leukotriene receptor antagonist with as-needed short-acting β₂-agonist
              • Alternatively, daily high-dose inhaled corticosteroid and leukotriene receptor antagonist with as-needed short-acting β₂-agonist
          • Consider monoclonal antibody treatment in children aged 5 years and older (eg, anti-IgEr49r7, anti-IL[interleukin]-4/IL-13r49r7, anti-IL-5/IL-5R)r49r7
          • Consider add-on oral corticosteroid as a step up to step 6 treatment for all ages r7r49
    • 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 r1r3
        • Patients aged 0 to 5 years
          • Pressurized metered-dose inhaler with spacer or valved holding chamber and mask (or mouthpiece as soon as the child is capable of using)
        • Aged 5 years and older: base choice on patient's ability to use and patient's preference
          • Pressurized metered-dose inhaler
          • Dry powder inhaler (aged 4 years and older)
          • Breath-actuated pressurized metered-dose inhaler
        • Nebulizer
          • For patients of any age who cannot use metered-dose inhaler with valved holding chamber and face mask
      • 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, pet dander, molds)
        • Complete checklist of known asthma allergen triggers can be found in Figure 3-19 of National Asthma Education and Prevention Program 2007 guidelines r1
        • Mitigation measures should be used only for patients who are either sensitized to or become symptomatic after exposure to a specific allergen r11
        • Measures to control allergen exposures include: r1
          • Pet dander: remove or keep pet out of the patient's bedroom
          • Dust: encase mattress and pillow in an allergen impermeable cover, wash sheets and blankets in hot water weekly, remove carpet from the bedroom, avoid lying on upholstered furniture, reduce indoor humidity to less than or equal to 60%
          • Cockroach: use poison bait or traps and intensive cleaning, put food in sealed container, do not leave garbage exposed
          • Pollens and outdoor molds: stay indoors with window closed during peak allergen hours
          • Indoor molds: clean moldy surfaces, eliminate leaks, reduce indoor humidity to 60% or lower especially in the basement
      • Immunotherapy r97
        • 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 yearsr30
          • 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 r97r98
        • Consider subcutaneous allergen immunotherapy as an adjunct to pharmacotherapy in patients aged 5 years or older with mild to moderate allergic asthma (step 2-4 therapy) r11r49
          • For whom asthma is controlled at the initiation, build up, and maintenance phases of immunotherapy r49
            • 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
          • For whom a potential decrease in long-term medication is important r11r49
            • There should be clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive r1
        • Sublingual immunotherapy is not recommended in the treatment of asthma in children r7r11

    Multiple resources are available to assist with treatment decisions including:

    • Global Initiative for Asthma guidelines and resources r50
    • National Asthma Education and Prevention Program guidelines and NIH Asthma Care Quick Reference guide r1r9r49
    • Canadian Thoracic Society guidelines for preschoolers, children, and adults r51r52
    • National Institute for Health and Care Excellence asthma pathway and guidelines r12
    • Australian Asthma Handbook r99
    • European Respiratory Society Task Force evidence-based approach to assessment and treatment of wheezing in preschool children r27

    Drug therapy

    • For acute asthma exacerbation
      • Short-acting β₂-agonists
        • Albuterol c106
          • Inhaler c107c108c109
            • Albuterol Pressurized inhalation, suspension; Children 1 to 5 years: 180 to 540 mcg (2 to 6 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes for the first hour, then 180 to 270 mcg (2 to 3 actuations of 90 mcg/actuation) every hour as needed. Delivery should occur with a spacer.
            • Albuterol Pressurized inhalation, suspension; Children and Adolescents 6 to 17 years: 360 to 900 mcg (4 to 10 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes for the first hour, then 360 to 900 mcg (4 to 10 actuations of 90 mcg/actuation) every 3 to 4 hours up to 540 to 900 mcg (6 to 10 actuations of 90 mcg/actuation) every 1 to 2 hours, or more often.
          • Nebulizer c110c111c112
            • Albuterol Sulfate Nebulizer solution; Infants† and Children† 1 year: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
            • Albuterol Sulfate Nebulizer solution; Children 2 to 12 years: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
            • Albuterol Sulfate Nebulizer solution; Adolescents: 2.5 to 5 mg inhaled by nebulizer every 20 minutes for the first hour, then 2.5 to 10 mg inhaled by nebulizer every 1 to 4 hours as needed.
        • Levalbuterol c113c114c115
          • Inhaler
            • Levalbuterol Tartrate Pressurized inhalation, suspension; Infants and Children: 180 to 360 mcg (4 to 8 actuations of 45 mcg/actuation) every 20 minutes for the first hour, then every 1 to 4 hours as needed. Delivery should occur with a spacer.
            • Levalbuterol Tartrate Pressurized inhalation, suspension; Adolescents: 180 to 360 mcg (4 to 8 actuations of 45 mcg/actuation) every 20 minutes for the first hour, then every 1 to 4 hours as needed.
          • Nebulizer
            • Levalbuterol Hydrochloride Nebulizer solution; Infants† and Children† 1 to 5 years: 1.25 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
            • Levalbuterol Hydrochloride Nebulizer solution; Children 6 to 12 years: 1.25 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.075 to 0.15 mg/kg/dose (Max: 5 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
            • Levalbuterol Hydrochloride Nebulizer solution; Adolescents: 1.25 to 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 1.25 to 5 mg inhaled by nebulizer every 1 to 4 hours as needed.
      • Inhaled anticholinergics c116
        • Ipratropium
          • Inhaler
            • Ipratropium Bromide Pressurized inhalation, solution; Infants and Children 1 to 5 years: 160 mcg (approximately 9 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes for up to 1 hour, or alternately, 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) every 20 minutes as needed for up to 3 hours.
            • Ipratropium Bromide Pressurized inhalation, solution; Children 6 to 12 years: 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours.
            • Ipratropium Bromide Pressurized inhalation, solution; Adolescents: 136 mcg (8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours.
          • Nebulizer c117
            • Ipratropium Bromide Nebulizer solution; Infants and Children 1 to 5 years: 250 mcg inhaled by nebulizer every 20 minutes for up to 1 hour, or alternately, 250 to 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours.
            • Ipratropium Bromide Nebulizer solution; Children 6 to 12 years: 250 to 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours.
            • Ipratropium Bromide Nebulizer solution; Adolescents: 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours.
        • Ipratropium-albuterol c118
          • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Infants and Children 1 to 5 years: 0.25 mg ipratropium bromide/1.25 mg albuterol (1.5 mL) inhaled by nebulizer every 20 minutes for 3 doses.
          • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Children 6 to 12 years: 0.25 mg ipratropium bromide/1.25 mg albuterol (1.5 mL) or 0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours.
          • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Adolescents: 0.5 mg ipratropium bromide/2.5 mg albuterol (3 mL) inhaled by nebulizer every 20 minutes for 3 doses, then as needed, usually every 4 to 6 hours.
      • Smooth muscle relaxant
        • Magnesium sulfate c119
          • Magnesium Sulfate Solution for injection; Infants, Children, and Adolescents: 25 to 75 mg/kg/dose (Max: 2 g/dose) IV as a single dose over 15 to 30 minutes.
      • Systemic β₂-agonists r1r71c120
        • Alternative to inhaled short-acting β₂-agonists for severe exacerbation if inhaled products unavailable; no proven advantage of systemic over inhaled therapy r1
        • Epinephrine (1 mg/mL) c121
          • Intramuscular
            • Epinephrine Hydrochloride Solution for injection; Infants and Children weighing less than 30 kg: 0.01 mg/kg/dose (Max: 0.3 mg/dose) IM every 5 to 15 minutes as needed for up to 3 doses.
            • Epinephrine Hydrochloride Solution for injection; Children and Adolescents weighing 30 kg or more: 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM every 5 to 15 minutes as needed for up to 3 doses.
          • Subcutaneous
            • Epinephrine Hydrochloride Solution for injection; Children 1 to 12 years: 0.01 mg/kg/dose (Max: 0.5 mg/dose) subcutaneously every 20 minutes as needed for up to 3 doses.
            • Epinephrine Hydrochloride Solution for injection; Adolescents: 0.3 to 0.5 mg subcutaneously every 20 minutes as needed for up to 3 doses.
        • Terbutaline c122
          • Terbutaline Sulfate Solution for injection; Children 1 to 11 years†: 0.01 mg/kg/dose (Max: 0.25 mg/dose) subcutaneously every 10 to 20 minutes for 3 doses then every 2 to 6 hours as needed.
          • Terbutaline Sulfate Solution for injection; Children and Adolescents 12 to 17 years: 0.01 mg/kg/dose (Max: 0.25 mg/dose) subcutaneously every 10 to 20 minutes for 3 doses then every 2 to 6 hours as needed.
      • Systemic corticosteroids r1c123
        • Dexamethasone c124c125
          • Oral
            • Dexamethasone Oral solution; Infants, Children, and Adolescents: 0.6 mg/kg/dose PO as a single dose or once daily for 2 days. Max: 16 mg/dose.
          • Intravenous or intramuscular
            • Dexamethasone Sodium Phosphate Solution for injection; Infants, Children, and Adolescents: 0.6 mg/kg/dose IV or IM as a single dose or once daily for 2 days. Max: 16 mg/dose.
        • Prednisolone r50r100r101r102c126c127
          • Prednisolone Oral solution; Infants and Children 1 to 2 years: 1 to 2 mg/kg/day (Max: 20 mg/dose) PO in 1 to 2 divided doses for 3 to 10 days.
          • Prednisolone Oral solution; Children 3 to 5 years: 1 to 2 mg/kg/day (Max: 30 mg/dose) PO in 1 to 2 divided doses for 3 to 10 days.
          • Prednisolone Oral solution; Children 6 to 11 years: 1 to 2 mg/kg/day (Max: 40 mg/dose) PO in 1 to 2 divided doses for 3 to 10 days.
          • Prednisolone Oral solution; Children and Adolescents 12 to 17 years: 40 to 80 mg/day PO in 1 to 2 divided doses for 3 to 10 days. Usual Max: 60 mg/day. Max: 80 mg/day.
        • Methylprednisolone r100r102c128c129
          • Intravenous or intramuscular
            • Methylprednisolone Sodium Succinate Solution for injection; Infants and Children 1 to 5 years: 1 to 2 mg/kg/day (Max: 60 mg/day) IV/IM in 1 to 2 divided doses for 3 to 10 days. May consider 1 mg/kg/dose IV every 6 hours on day 1.
            • Methylprednisolone Sodium Succinate Solution for injection; Children 6 to 11 years: 1 to 2 mg/kg/day (Max: 60 mg/day) IV/IM in 1 to 2 divided doses for 3 to 10 days.
            • Methylprednisolone Sodium Succinate Solution for injection; Children and Adolescents 12 to 17 years: 40 to 80 mg/day IV/IM in 1 to 2 divided doses for 3 to 10 days.
    • Chronic asthma
      • For relief of episodic wheezing (relievers)
        • Combination inhaled corticosteroids plus fast-onset, long-acting β₂-agonist (preferred)
          • Budesonide-formoterol r49c130
            • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† 4 to 11 years: 80 mcg budesonide/4.5 mcg formoterol (1 actuation of 80 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth once daily, with additional inhalations as needed. Max: 36 mcg formoterol/day.
            • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children and Adolescents 12 to 17 years: 160 mcg budesonide/9 mcg formoterol (2 actuations of 80 mcg budesonide/4.5 mcg formoterol/actuation) to 320 mcg budesonide/9 mcg formoterol (2 actuations of 160 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth as needed in addition to a daily maintenance dose; may repeat dose after 5 minutes if needed. Max: 54 mcg/day of formoterol (12 actuations/day of 4.5 mcg formoterol/actuation).
        • Short-acting β₂-agonists
          • Albuterol c131c132
            • Inhaler c133c134
              • Albuterol Pressurized inhalation, suspension; Children and Adolescents 4 to 17 years: 90 to 180 mcg (1 to 2 actuations of 90 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. Max: 1,080 mcg/day (12 actuations/day).
            • Nebulizer c135
              • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years weighing less than 15 kg: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed.
              • Albuterol Sulfate Nebulizer solution; Children 2 to 5 years weighing 15 kg or more: 0.63 to 2.5 mg inhaled by nebulizer 3 or 4 times daily as needed.
              • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years weighing less than 15 kg: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed.
              • Albuterol Sulfate Nebulizer solution; Children 6 to 12 years weighing 15 kg or more: 0.63 to 2.5 mg inhaled by nebulizer 3 or 4 times daily as needed.
              • Albuterol Sulfate Nebulizer solution; Adolescents: 2.5 mg inhaled by nebulizer 3 to 4 times daily as needed. Usual Max: 10 mg/day.
          • Levalbuterol (for patients intolerant of albuterol) c136c137
            • Inhaler
              • Levalbuterol Tartrate Pressurized inhalation, suspension; Children and Adolescents 4 to 17 years: 45 to 90 mcg (1 to 2 actuations of 45 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. Max: 540 mcg/day (12 actuations/day).
            • Nebulizer
              • Levalbuterol Hydrochloride Nebulizer solution; Children 6 to 11 years: 0.31 or 0.63 mg inhaled by nebulizer 3 times daily as needed. Max: 1.89 mg/day.
              • Levalbuterol Hydrochloride Nebulizer solution; Children and Adolescents 12 to 17 years: 0.63 or 1.25 mg inhaled by nebulizer 3 times daily as needed. Max: 3.75 mg/day.
      • Maintenance treatment (controllers)
        • Inhaled corticosteroids c138
          • Fluticasone
            • Aerosol inhaler
              • Fluticasone Propionate Pressurized inhalation, suspension; Children 1 to 3 years†: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily. Use the lowest effective dose once stable.
              • Fluticasone Propionate Pressurized inhalation, suspension; Children 4 to 11 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily. Use the lowest effective dose once stable.
              • Fluticasone Propionate Pressurized inhalation, suspension; Children and Adolescents 12 to 17 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily. May increase the dose after 2 weeks if the response is not adequate. Max: 880 mcg (4 actuations of 220 mcg/actuation) twice daily. Use the lowest effective dose once stable.
            • Dry powder inhaler
              • Fluticasone Propionate Inhalation powder; Children 4 to 11 years: 50 mcg (1 actuation of 50 mcg/actuation) inhaled by mouth twice daily. May increase the dose after 2 weeks if the response is not adequate. Max: 100 mcg (2 actuations of 50 mcg/actuation or 1 actuation of 100 mcg/actuation) twice daily. Use the lowest effective dose once stable.
              • Fluticasone Propionate Inhalation powder; Children and Adolescents 12 to 17 years: 100 mcg (1 actuation of 100 mcg/actuation) inhaled by mouth twice daily. May increase the dose after 2 weeks if the response is not adequate. Max: 1,000 mcg (4 actuations of 250 mcg/actuation) twice daily. Use the lowest effective dose once stable.
          • Budesonide c139c140
            • Inhaler
              • Budesonide Inhalation powder; Children and Adolescents 6 to 17 years: 180 to 360 mcg (1 to 2 actuations of 180 mcg/actuation or 2 actuations of 90 mcg/actuation) inhaled by mouth twice daily. Max: 360 mcg (2 actuations of 180 mcg/actuation) twice daily. Use the lowest effective dose once stable.
            • Nebulizer c141c142c143
              • Budesonide Nebulizer suspension; Infants 3 to 11 months†: 0.5 to 1 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 2 mg/day. Limited data from small safety studies used 0.25 to 1 mg/day via nebulizer once daily or in 2 divided doses. Use the lowest effective dose once stable.
              • Budesonide Nebulizer suspension; Children 1 to 8 years: 0.25 to 1 mg inhaled by nebulizer once daily or 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 1 mg/day. Use the lowest effective dose once stable.
              • Budesonide Nebulizer suspension; Children 9 to 11 years†: 0.5 to 1 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 2 mg/day. Use the lowest effective dose once stable.
              • Budesonide Nebulizer suspension; Children and Adolescents 12 to 17 years†: 1 to 2 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.5 to 1 mg inhaled by nebulizer twice daily. Max: 4 mg/day. Use the lowest effective dose once stable.
          • Estimated comparative daily dosages: inhaled corticosteroids for long-term asthma control.*It is preferable to use a higher mcg/puff or mcg/inhalation formulation to achieve as low a number of puffs or inhalations as possible. DPI, dry powder inhaler (requires deep, fast inhalation); MDI, metered dose inhaler (releases a puff of medication); N/A, not applicable.From NIH: Asthma Care Quick Reference: Diagnosing and Managing Asthma. NIH Publication No. 12-5075. NIH website. Published June 2002. Revised September 2012. Accessed September 19, 2023. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf
            Daily doseAged 0 to 4 yearsAged 5 to 11 yearsAged 12 years or older
            Medication
            LowMedium*High*LowMedium*High*LowMedium*High*
            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
        • Inhaled corticosteroid plus long-acting β₂-agonists c144
          • Budesonide-formoterol c145
            • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children† 4 to 11 years: 80 mcg budesonide/4.5 mcg formoterol (1 actuation of 80 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth once daily, with additional inhalations as needed. Max: 36 mcg formoterol/day.
            • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Children and Adolescents 12 to 17 years: 160 mcg budesonide/9 mcg formoterol (2 actuations of 80 mcg budesonide/4.5 mcg formoterol/actuation) or 320 mcg budesonide/9 mcg formoterol (2 actuations of 160 mcg budesonide/4.5 mcg formoterol/actuation) inhaled by mouth once or twice daily. Max: 54 mcg formoterol/day when used as both controller and reliever therapy.
          • Fluticasone-salmeterol c146
            • Fluticasone Propionate, Salmeterol Inhalation powder; Children 4 to 11 years: 100 mcg fluticasone/50 mcg salmeterol (1 actuation of 100 mcg fluticasone/50 mcg salmeterol/actuation) inhaled by mouth twice daily.
            • Fluticasone Propionate, Salmeterol Inhalation powder; Children and Adolescents 12 to 17 years: 100 mcg fluticasone/50 mcg salmeterol (1 actuation of 100 mcg fluticasone/50 mcg salmeterol) or 250 mcg fluticasone/50 mcg salmeterol (1 actuation of 250 mcg fluticasone/50 mcg salmeterol) or 500 mcg fluticasone/50 mcg salmeterol (1 actuation of 500 mcg fluticasone/50 mcg salmeterol) inhaled by mouth twice daily. Max: 1,000 mcg fluticasone/100 mcg salmeterol/day.
        • Leukotriene receptor antagonists (second line) c147
          • Montelukast r9r103c148
            • Montelukast Sodium Oral granules; Children 1 to 5 years: 4 mg PO once daily in the evening.
            • Montelukast Sodium Chewable tablet; Children and Adolescents 6 to 14 years: 5 mg PO once daily in the evening.
            • Montelukast Sodium Oral tablet; Adolescents 15 to 17 years: 10 mg PO once daily in the evening.
          • Zafirlukast r1r9c149
            • Zafirlukast Oral tablet; Children 5 to 11 years: 10 mg PO twice daily.
            • Zafirlukast Oral tablet; Children and Adolescents 12 to 17 years: 20 mg PO twice daily.
      • Maintenance therapy; add-on agents
        • Long-acting muscarinic antagonist
          • Tiotropium r103r104c150
            • Tiotropium Respiratory spray, solution; Children 1 to 5 years†: 2.5 mcg (2 actuations of 1.25 mcg/actuation) inhaled by mouth once daily.
            • Tiotropium Respiratory spray, solution; Children and Adolescents 6 to 17 years: 2.5 mcg (2 actuations of 1.25 mcg/actuation) inhaled by mouth once daily.
        • Leukotriene synthesis inhibitor
          • Zileuton r49c151c152
            • Immediate release
              • Zileuton Oral tablet; Children and Adolescents 12 to 17 years: 600 mg PO 4 times daily.
            • Extended release
              • Zileuton Oral tablet, biphasic release; Children and Adolescents 12 to 17 years: 1,200 mg PO twice daily.
        • Mast cell stabilizer r1c153
          • Cromolyn
            • Cromolyn Sodium Nebulizer solution; Children and Adolescents 2 to 17 years: 20 mg inhaled by nebulizer 4 times daily. Usual maintenance dose: 20 mg inhaled by nebulizer 3 times daily.
        • Biologic agents r1c154
          • Benralizumab c155
            • Adjunctive therapy for patients with severe asthma (eosinophilic phenotype)
              • Benralizumab Solution for injection; Children and Adolescents 12 to 17 years: 30 mg subcutaneously every 4 weeks for 3 doses, then 30 mg subcutaneously every 8 weeks.
          • Dupilumab c156
            • Eosinophilic phenotype moderate to severe asthma
              • Dupilumab Solution for injection; Children 6 to 11 years weighing 15 to 29 kg: 300 mg subcutaneously every 4 weeks.
              • Dupilumab Solution for injection; Children 6 to 11 years weighing 30 kg or more: 200 mg subcutaneously every other week.
              • Dupilumab Solution for injection; Children and Adolescents 12 to 17 years: 400 mg subcutaneously as a single dose, then 200 mg subcutaneously every other week or 600 mg subcutaneously as a single dose, then 300 mg subcutaneously every other week.
            • Oral corticosteroid–dependent moderate to severe asthma
              • Dupilumab Solution for injection; Children 6 to 11 years weighing 15 to 29 kg: 300 mg subcutaneously every 4 weeks.
              • Dupilumab Solution for injection; Children 6 to 11 years weighing 30 kg or more: 200 mg subcutaneously every other week.
              • Dupilumab Solution for injection; Children and Adolescents 12 to 17 years: 600 mg subcutaneously as a single dose, then 300 mg subcutaneously every other week.
          • Mepolizumab c157c158c159
            • Adjunctive therapy for patients with severe asthma (eosinophilic phenotype) r105r106
              • Mepolizumab Solution for injection; Children 6 to 11 years: 40 mg subcutaneously every 4 weeks.
              • Mepolizumab Solution for injection; Children and Adolescents 12 to 17 years: 100 mg subcutaneously every 4 weeks.
          • Omalizumab c160
            • Adjunctive therapy for patients who have sensitivity to relevant allergens (eg, dust mites, cockroach frass, pet dander) and who require step 5 or 6 care (for severe persistent asthma) r1
            • Omalizumab (Hamster) Solution for injection; Children and Adolescents 6 to 17 years: 75 to 375 mg subcutaneously every 2 to 4 weeks. Dosing varies based on age, weight, and baseline serum IgE. Adjust dosage for significant changes in weight.
          • Tezepelumab
            • Add on maintenance for severe asthma
            • Tezepelumab Solution for injection; Children and Adolescents 12 to 17 years: 210 mg subcutaneously every 4 weeks.
        • Methylxanthines r1c161
          • Theophylline
            • Theophylline oral solution r1
              • Theophylline, Anhydrous Oral solution; Infants 4 to 25 weeks: 10 mg/kg/day PO divided every 8 hours, initially. Adjust dose based on serum theophylline concentrations.
              • Theophylline, Anhydrous Oral solution; Infants 26 to 51 weeks: 10 mg/kg/day PO divided every 6 hours, initially. Adjust dose based on serum theophylline concentrations.
              • Theophylline, Anhydrous Oral solution; Children 1 to 11 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 4 to 6 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 16 mg/kg/day.
              • Theophylline, Anhydrous Oral solution; Children 1 to 11 years weighing more than 45 kg: 300 mg/day PO divided every 6 to 8 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 16 mg/kg/day.
              • Theophylline, Anhydrous Oral solution; Children and Adolescents 12 to 15 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 4 to 6 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 800 mg/day.
              • Theophylline, Anhydrous Oral solution; Children and Adolescents 12 to 15 years weighing more than 45 kg: 300 mg/day PO divided every 6 to 8 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
              • Theophylline, Anhydrous Oral solution; Adolescents 16 to 17 years: 300 mg/day PO divided every 6 to 8 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
            • Theophylline extended-release oral tablet r1
              • Theophylline Oral tablet, extended-release; Children 6 to 11 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 16 mg/kg/day.
              • Theophylline Oral tablet, extended-release; Children 6 to 11 years weighing more than 45 kg: 300 mg/day PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 16 mg/kg/day.
              • Theophylline Oral tablet, extended-release; Children and Adolescents 12 to 15 years weighing 45 kg or less: 12 to 14 mg/kg/day (Max: 300 mg/day) PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 16 mg/kg/day (Max: 400 mg/day) and then 20 mg/kg/day (Max: 600 mg/day) if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations. Usual Max: 800 mg/day.
              • Theophylline Oral tablet, extended-release; Children and Adolescents 12 to 15 years weighing more than 45 kg: 300 mg/day PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
              • Theophylline Oral tablet, extended-release; Adolescents 16 to 17 years: 300 mg/day PO divided every 8 to 12 hours, initially. After 3 days, increase the dose to 400 mg/day and then 600 mg/day if tolerated. Alternately, 10 mg/kg/day (Max: 300 mg/day) PO, initially. Adjust dose based on serum theophylline concentrations; doses of 400 to 1,600 mg/day may be needed. Usual Max: 800 mg/day.
        • Oral corticosteroids
          • Prednisolone r101
            • Prednisolone Oral solution; Infants and Children 1 to 2 years: 0.25 to 2 mg/kg/dose (Usual Max: 20 mg/dose) PO once daily or every other day. Use the lowest effective dose.
            • Prednisolone Oral solution; Children 3 to 5 years: 0.25 to 2 mg/kg/dose (Usual Max: 30 mg/dose) PO once daily or every other day. Use the lowest effective dose.
            • Prednisolone Oral solution; Children 6 to 11 years: 0.25 to 2 mg/kg/dose (Usual Max: 40 mg/dose) PO once daily or every other day. Use the lowest effective dose.
            • Prednisolone Oral solution; Children and Adolescents 12 to 17 years: 7.5 to 60 mg PO once daily or every other day. Use the lowest effective dose.
          • Methylprednisolone c162c163c164
            • Methylprednisolone Oral tablet; Infants and Children 1 to 2 years: 0.25 to 2 mg/kg/dose (Usual Max: 20 mg/dose) PO once daily or every other day. Use the lowest effective dose.
            • Methylprednisolone Oral tablet; Children 3 to 5 years: 0.25 to 2 mg/kg/dose (Usual Max: 30 mg/dose) PO once daily or every other day. Use the lowest effective dose.
            • Methylprednisolone Oral tablet; Children 6 to 11 years: 0.25 to 2 mg/kg/dose (Usual Max: 40 mg/dose) PO once daily or every other day. Use the lowest effective dose.
            • Methylprednisolone Oral tablet; Children and Adolescents 12 to 17 years: 7.5 to 60 mg PO once daily or every other day. Use the lowest effective dose.
          • Dexamethasone c165c166c167
            • Alternative for patients unable to tolerate other liquid preparations
            • Dexamethasone Oral solution; Infants and Children 1 to 11 years: 0.4 mg/kg/dose PO once daily or every other day.
    • Usual dosages for other long-term control medications.**Dosages are provided for those products that have been approved by the FDA or have sufficient clinical trial safety and efficacy data in the appropriate age ranges to support their use. DPI, dry powder inhaler; IgE, immunoglobulin E; MDI, metered-dose inhaler; N/A, not available (not approved, no data available, or safety and efficacy not established for this age group).From NIH: Asthma Care Quick Reference: Diagnosing and Managing Asthma. NIH Publication No. 12-5075. NIH website. Published June 2002. Revised September 2012. Accessed September 19, 2023. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf
      MedicationAged 0 to 4 yearsAged 5 to 11 yearsAged 12 years or older
      Combined medication (inhaled corticosteroid + long-acting β₂-agonist)
      Fluticasone-salmeterol
      MDI: 45 mcg/21 mcg, 115 mcg/21 mcg, or 230 mcg/21 mcgN/A1 inhalation twice daily; dose depends on level of severity or control1 inhalation twice daily; dose depends on level of severity or control
      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
      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
      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
      Leukotriene receptor antagonist: zafirlukast
      10- or 20-mg tablet (Take at least 1 hour before or 2 hours after a meal. Monitor liver function.)N/A10 mg twice daily (age 7 to 11 years)40 mg daily (20-mg tablet twice daily)
      Leukotriene synthesis inhibitor: zileuton
      600-mg tabletN/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 N/AN/A150- to 375-mg subcutaneous injection every 2 to 4 weeks, depending on body weight and pretreatment serum IgE level
      Mast cell stabilizer
      Cromolyn
      Nebulizer: 20 mg/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 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
      Formoterol
      DPI: 12 mcg/single-use capsuleN/A1 capsule every 12 hours1 capsule 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 c168
    • Educate caregivers about home management and monitoring, use of maintenance medications, and inhaler technique r107c169
    • Use control chart and written asthma action plan emphasizing difference between controller and reliever medications (sample available within the National Asthma Education and Prevention Program guidelines) r1c170
    • Encourage caregivers to provide a copy of written asthma action plan to school, child care facility, or camp r1c171
    • School-based asthma self-management interventions may reduce asthma symptoms, emergency department visits, and hospital admissions, particularly in younger children from socially disadvantaged populations r108c172
    • Use of technology including telephone-based peer coaching in the past has been associated with improved asthma outcomes r109
    • Electronic health (e-health) resources such as web-based asthma management systems, social media platforms, text message reminders, and mobile health applications can increase awareness of asthma, promote asthma self management, potentially increase adherence, and improve quality of life r110
    • Inhaler trackers may improve asthma outcomes r110

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

    Promote active participation in physical activities, exercise, and sports r1c173c174c175

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

    • Multicomponent allergen-specific intervention strategies are recommended over single-component interventions in patients who are known to be sensitized or become symptomatic on exposure to a specific allergen per the National Asthma Education Prevention Program 2020 updates r74
      • For rodents and/or cockroaches, integrated pest management including measures to block infestation (eg, filling holes in walls) and abatement (eg, traps)
      • For dust mites, combination of dust mite–impermeable pillow and mattress covers, HEPA (high-efficiency particulate air) filter–equipped vacuum cleaner, carpet and curtain removal, and cleaning products
      • For mold, use of HEPA purifiers and mold abatement
      • Examples of allergen mitigation interventions and their targeted allergens.SR, Systematic review.
        ++Primary target allergen(s) for the intervention.
        +Secondary target allergen(s) for the intervention.
        *Dander from rodents.
        Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC) et al: 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 146(6):1217-70, 2020
        Intervention assessed in studies in the SRAnimal danderDust mitesCockroachesMold
        Acaricide++
        Air filtration systems and air purifiers++++++
        Carpet removal+++++
        Cleaning products (eg, bleach)++
        HEPA vacuum cleaners++++++
        Impermeable pillow and mattress covers++
        Integrated pest management+*++
        Mold mitigation++
        Pet removal++
    • National Environmental Education Foundation provides guidelines for environmental management in pediatric asthma r111
    • Subcutaneous allergen immunotherapy is indicated in patients with allergic asthma
      • It is efficacious in patients where there is there is clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive and exposure reduction measures have failed
      • Avoid in patients with severe asthma as they may be at risk for systemic allergic reactions during immunotherapy administration

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

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

    Procedures
    c180

    Comorbidities

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

    Special populations

    • Infants
      • Objective measurements of airflow obstruction are not possible
      • Assessment depends on physical examination and oxygen saturation. Signs of severe obstruction include respiratory rate higher than 60 breaths per minute, use of accessory muscles, inspiratory and expiratory wheezing, paradoxical breathing, cyanosis, and SaO₂ (arterial oxygen saturation) less than 90%
      • Greater risk for respiratory failure; lack of response on physical examination or by objective measurements requires hospitalization
      • Consider structural abnormalities (trachea/bronchomalacia, vascular rings), viral-induced wheezing (bronchiolitis), or foreign body aspiration in young children
    • Patients aged 4 years and younger r1
      • Young children are at risk for severe exacerbations despite having a low level of impairment between episodes
        • In children younger than 4 years who have had 3 or more episodes of wheezing triggered by respiratory tract infections in their lifetime or two episodes in the past year and who are asymptomatic between the respiratory infections
          • Start 7 to 10 day course of inhaled corticosteroid daily with as-needed short-acting β₂-agonist at the onset of signs and symptoms indicating respiratory tract infections
        • Consider initiating long-term therapy in the following situations: r1
          • Consistent short-term bronchodilator use required more than 2 days per week for a period of more than 4 weeks
          • Nighttime symptoms occur more frequently than 1 night a month
          • After 2 acute exacerbations requiring oral corticosteroids within 6 months
          • During seasonal exacerbations in young children who exhibit a pattern of seasonal asthma symptom exacerbation
      • Few long-term control medications are FDA approved for this age group, including: r1
        • Budesonide nebulizer solution (patients aged 1-8 years)
        • Fluticasone propionate dry powder inhaler or aerosol inhaler (patients aged 4 years and older)
        • Salmeterol dry powder inhaler in combination with inhaled corticosteroid (patients aged 4 years and older)
        • Montelukast (chewable tablets, patients aged 2-6 years; granules, patients as young as 1 year)
      • Use a metered-dose inhaler plus valved holding chamber with face mask or nebulizer with face mask for children aged younger than 5 years r29
      • Monitor therapy response closely in young children; treatment is often given in the form of a therapeutic trial r1
        • If there is no clear positive response within 4 to 6 weeks with adherence to plan and proper medication technique, stop treatment and consider alternate therapy and diagnosis r1
        • Patients in this age group have high rates of spontaneous symptom remission; consider treatment step-down if benefit is sustained for 3 months and reevaluate the need for continued daily therapy r1
    • Children with exercise-induced bronchoconstriction r1
      • Anticipate in all patients with asthma; history of cough, dyspnea, chest pain or tightness, wheezing, or endurance problems with exercise are suggestive of exercise-induced bronchoconstriction
      • Bronchoconstriction peaks 10 to 15 minutes after exercise
        • Establish the diagnosis with an exercise challenge in which a 15% decrease in peak expiratory flow or FEV₁ occurs (measured before and after exercise at 5-minute intervals for 20-30 minutes) r1
      • Treatment strategies
        • Pretreatment with short-acting β₂-agonists 5 to 20 minutes before exercise is effective in 80% of patients r1
          • Avoid frequent or chronic pretreatment use of long-acting β₂-agonist, which can disguise poorly controlled persistent asthma
          • Alternate pretreatment options:
            • Budesonide-formoterol on-demand therapy when compared to on-demand short-acting β₂-agonist therapy improves asthma control and reduces exercise-induced bronchospasm r141
            • Leukotriene receptor antagonists must be administered at least 2 hours before exercise and will attenuate exercise-induced bronchospasm in 50% of patients for 12 to 24 hours r1
            • Cromolyn should be administered shortly (15 minutes) before exercise (not widely available in the US)
        • Long-term control therapy (eg, inhaled corticosteroids) may be appropriate in patients with frequent or severe exercise-induced bronchospasm; offers protection in 1 to 3 weeks r72
        • Encourage a gradual warm-up period before exercise and use of a mask or scarf over mouth during cold weather
        • Avoid high salt, low antioxidant, and high omega-6 polyunsaturated fatty acids, which can leads to increased exercise-induced bronchospasm
    • Children with cough variant asthma r1
      • Can be challenging to diagnose
      • Spirometry with reversible obstruction with bronchodilators and bronchoprovocation can be helpful but not diagnostic
      • Chronic cough that is triggered by exercise, cold air, allergens, or cough at night without typical wheezing or dyspnea is suggestive of cough variant asthma
        • Personal or family history of atopy, wheezing also supports diagnosis
      • Trial and assess response to asthma medications (bronchodilators, leukotriene antagonist, inhaled corticosteroids) after exclusion of alternate etiology for symptoms; supports diagnosis of cough variant asthma
      • Long-term management is similar to that for other patients with asthma r142

    Monitoring

    • Monitoring in the acute care setting during a significant asthma exacerbation
      • Reassess patient for response before and after each treatment is administered r1c193
        • Assess respiratory rate, work of breathing, level of consciousness, lung sounds, and pulse oximetry
        • Patients receiving continuous inhaled β₂-agonist should be on continuous cardiopulmonary monitoring
        • Routine laboratory evaluation during an acute asthma exacerbation is not necessary
          • Obtain serum electrolytes in patients receiving continuous albuterol owing to risk for hypokalemia and other electrolyte abnormalities
          • Venous or capillary blood gas with normal or rising CO₂ in a patient with respiratory distress is concerning for respiratory failure and an indication for intubation
        • Consider imaging in patients who fail to improve with asthma therapy if there is concern for a complication (pneumothorax, pneumonia)
        • Consult pediatric ICU if there is concern for respiratory failure
      • Monitor patient for rebound respiratory distress or hypoxia c194
      • Wean albuterol therapy as symptoms improve and as assessment suggests improvement
      • 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) r1c195
        • 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 r1c196c197
        • Patient is not hypoxic and does not require supplemental oxygen; pulse oximetry measurement is higher than 92% to 94% just before discharge home r1c198
        • Patient is able to tolerate oral medication c199
        • Caregiver is comfortable managing patient at home and providing treatment regimen at home c200
        • 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 c201
        • Asthma education has been provided
    • Periodic monitoring of asthma control to guide maintenance treatment r1
      • Home self-monitoring c202
        • Instruct all patients to monitor at home; symptom-based monitoring or peak flow monitoring is similarly beneficial
          • Provide personalized asthma action plan with instructions on adjusting medications based on symptoms or lung function
          • Several validated asthma control questionnaire assessment tools are available r143r144r145r146r147
        • For patients with moderate or severe persistent asthma, peak flow monitoring is preferred r1
      • Office monitoring c203c204
        • Assess asthma control, medication technique, lung function, asthma action plan, adherence, and patient concerns at every patient visit
          • Various asthma control questionnaires can be used such as r148
            • ACT (asthma control test): validated in children aged 12 years or older
              • Asks 5 questions regarding shortness of breath, nighttime waking, interference with activity, rescue bronchodilator use, and patient rating of asthma control over the past month
              • Rated 1 to 5 for each, adding up to a total score of 5 to 25
              • Asthma is well controlled when score is 20 or higher and poorly controlled when score is 15 or less
              • C-ACT (childhood ACT) has been developed and validated for children aged 4 to 11 years r146
                • C-ACT has 4 child-reported symptoms including how bad asthma is today, symptoms with exertion, frequency of cough, nighttime symptoms; 3 parent questions asking daytime symptoms, nighttime symptoms, and wheeze frequency
                • A score of 19 or less is considered poorly controlled
          • Asthma control questionnaire: validated in children aged 6 to 16 years r148
            • Asks questions based on recall of 7 days prior of breathlessness, nighttime symptoms, symptoms on waking up, activity interference, wheeze, short-acting β₂-agonist use, and pre-bronchodilator FEV₁% of predicted
            • Scored from 0 to 6 and an average of the responses is taken
            • Score 0.75 or less is considered well controlled; score 1.5 or higher is considered poorly controlled
        • 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) is considered poorly controlled asthma and per National Heart, Lung, and Blood Institute guidelines, therapy should be stepped up by 1 step
          • Re-evaluate in 2 to 6 weeks to achieve control
            • NHLBI classified that asthma is not well controlled if:
              • Patients aged 0 to 4 years:
                • Symptoms more than 2 days per week
                • Nighttime awakening more than 1 time per month
                • Asthma exacerbations requiring oral systemic corticosteroids 2 to 3 times per year
              • Patients aged 5 to 11 years:
                • Symptoms more 2 days per week or multiple times on 2 or fewer days per week
                • Nighttime awakening 2 times per month or more
                • Asthma exacerbations requiring oral systemic corticosteroids 2 times per year or more
              • Patients aged older than 12 years:
                • Symptoms more than 2 days per week
                • Nighttime awakening 1 to 3 times per week
                • Asthma exacerbations requiring oral systemic corticosteroids 2 times per year or more
          • Use of short-acting β₂-agonist several times a day for symptom relief indicates very poorly controlled asthma. Per NHLBI (National Heart, Lung, and Blood Institute) guidelines, a short course of oral corticosteroids or step up in 1 to 2 steps of therapy is recommended
            • Re-evaluate in 2 weeks to achieve control
            • NHLBI classified that asthma is very poorly controlled if:
              • Patients aged 0 to 4 years:
                • Symptoms throughout the day
                • Nighttime awakening more than 1 time per week
                • Asthma exacerbations requiring oral systemic corticosteroids 3 times per year or more
              • Patients aged 5 to 11 years:
                • Symptoms throughout the day
                • Nighttime awakening 2 times per week or more
                • Asthma exacerbations requiring oral systemic corticosteroids 2 times per year or more
              • Patients aged older than 12 years:
                • Symptoms throughout the day
                • Nighttime awakening 4 times per week or more
                • Asthma exacerbations requiring oral systemic corticosteroids 2 times per year or more
          • Before treatment step-up:
            • Consider alternative diagnosis if no clear benefit is observed with asthma therapy over 4 to 6 weeks in patients aged 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 r1c205c206
        • Follow up at 1- to 6-month intervals, after asthma control is achieved r1c207
        • Follow up at 3-month intervals if step-down therapy is likely r1c208
        • Pulmonary function testing with spirometry
          • 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 r1c209
        • FeNO (fractional exhaled nitric oxide) can be used as an ongoing asthma monitoring and management strategy with frequent assessments (every 2-3 months). FeNO is a marker of Th2 inflammation r49
        • Patient's comorbid conditions (eg, allergic rhinitis, obstructive sleep apnea, food allergy, chronic rhinosinusitis, gastroesophageal reflux) should be optimally managed
    • Drug therapy monitoring
      • For children requiring high-dose inhaled corticosteroids r29
        • Regularly review dietary intake of calcium and vitamin D c210c211
        • Consider slitlamp ocular examination and bone densitometry c212c213
      • Biologic agents r149
        • Monitor closely for hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria) and be prepared with necessary supplies to treat anaphylaxis. Delayed onset reactions (ie, hours to days) are possible
      • Leukotriene receptor antagonist
        • Zafirlukast r150
          • Periodic liver function testing may detect early drug-induced injury or hepatic dysfunction
      • Leukotriene synthesis inhibitor
        • Zileuton r151
          • Assess liver enzymes prior to initiation, monthly for the first 3 months, every 2 to 3 months for the rest of the first year, and periodically thereafter
      • Methylxanthines
        • Theophylline
          • Measure 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)
            • Target serum concentration: 5 to 15 mcg/mL r1

    Complications and Prognosis

    Complications

    • Complications of disease
      • Respiratory failure requiring non-invasive positive pressure ventilation and intubation requiring mechanical ventilation c214
      • Pneumothorax c215
      • Pneumomediastinum c216
      • Airway remodeling due to persistent inflammation and airflow obstruction c217c218
      • Decreased lung growth over time r152
      • Increased rate of FEV₁ decline r152
      • Death c219
    • Complications during surgical procedures r1
      • Respiratory decompensation during or after surgical procedures c220
        • 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
        • Consult asthma specialist when considering surgery for a child with poorly controlled severe asthma
        • Intubation can trigger bronchospasm; laryngeal mask airway is preferred r153
        • Inhalation induction in pediatric patients is associated with increased risk for perioperative respiratory adverse events; induction with IV propofol is preferred r154r155
        • Early mobilization, pain control, and incentive spirometry is important for pulmonary management postoperatively
        • Children with severe wheezing should be extubated and managed in the ICU
    • Complications of steroid pharmacotherapy
      • Inhaled corticosteroids
        • Use of low- or medium-dose inhaled corticosteroid daily is associated with an average reduction in linear growth velocity of 0.48 cm per year and an overall change in 0.61 cm from baseline height, which is most pronounced in the first year of use based on a Cochrane review r156c221
          • Another study of 1041 children found a change in 1.1 cm of baseline height during course of trial (4-6 years), which was persistent into adulthood with a 1.2 cm lower adult height in inhaled corticosteroid group. Importantly, this decrease was not cumulative or progressive r157c222
          • Asthma itself, as a chronic disease, can affect growth with reduction in growth rate during the first 10 years of life and delay in puberty, but with child ultimately reaching growth potential r158
          • Degree of growth limitation is minimal and is outweighed by the risk of poorly controlled asthma needing frequent oral systemic steroid bursts with associated morbidity and mortality. This should be discussed with concerned parents
        • Oropharyngeal candidiasis
      • Long-term oral corticosteroid therapy
        • Growth inhibition c223
        • Obesity
        • Increased blood pressure
        • Glucose intolerance
        • Myopathy
        • Psychosis
        • Peptic ulcer disease
        • Avascular necrosis
        • Increased infection risk c224
        • Increased risk of oral candidiasis, osteoporosis, cataracts, and hyperglycemia c225c226c227
        • Adrenal insufficiency c228
      • 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
        • Advise patient on importance of asthma medication compliance to prevent exacerbations and further oral steroid therapy
        • Consider biologic therapy to minimize exacerbations and oral corticosteroid therapy

    Prognosis

    • Progression of disease
      • More than half of preschoolers who wheeze develop asthma by school age, irrespective of treatment r3
        • Infants and young children commonly wheeze during viral respiratory infections; only some will experience asthma in childhood r6
        • Risk factors for recurrent wheezing after preschool age are variably reported; the Asthma Predictive Indexr159 and Pediatric Asthma Risk Score has been used to help distinguish children at higher risk for continued wheezing after preschool age r6
        • Overall, mild and infrequent wheezing in infancy and preschool years (transient wheezers) does not usually persist into school years r160
        • In contrast, persistent asthma into school years is more likely to occur after more frequent, severe wheezing early in life and in patients with allergen sensitization, smoke exposure, genetic predisposition, and female sex r160
          • Late onset wheezers (between ages 3-6 years) are at risk for persistent asthma later in childhood or adulthood
          • Persistent wheezers (present before age 3 years) tend to be atopic and have family history of atopy
          • Children with persistent wheezing have decreased lung function at age 6 years when compared to those children who don't wheeze r18
        • 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 r160
        • 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
        • Children and adolescents with severe or difficult to treat asthma have higher health care utilization rates and loss of lung function with age r161
      • Presence of severe asthma in childhood is the primary risk factor for asthma persistence into adulthood r160
        • 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) r6
      • Childhood asthma is associated with long-term abnormalities of lung growth with reduced growth and/or early decline in FEV
    • Patients with severe exacerbation may require hospital admission
      • Racial and ethnic disparities exist in pediatric asthma. African American, Native American, and Hispanic children have higher hospitalization rates when compared to White children. This may be related to financial and social issues, access to health care, and health literacy r162
      • Risk factors for asthma exacerbations include: r72
        • 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
        • Poor perception of dyspnea r163r164
    • Death from asthma is rare c229
      • Mortality rate is 4 times higher in Black children with asthma than in other racial and ethnic groups r165c230
      • Risk factors for asthma-related death include:
        • Current or recent use of oral corticosteroids r72
        • Poor compliance with treatment plan and lack of asthma action plan r72
        • Existing food allergy r72
        • Near-lethal episode requiring intubation with mechanical ventilation r72
        • Hospitalization or presentation to the emergency department for exacerbation in the past 1 year r72
        • 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
        • Sensitivity to Alternaria r166
        • Poor perception of dyspnea r166

    Screening and Prevention

    Prevention

    • The following measures may help reduce risk of child developing asthma (primary prevention): r7
      • Avoid exposure to tobacco smoke during pregnancy and first year of life c231c232
      • Address stress, weight gain, and obesity during pregnancy
      • Encourage vaginal delivery c233
      • Encourage breastfeeding for overall health benefits c234
      • Avoid use of acetaminophen and broad-spectrum antibiotics in first year of life c235c236
      • Identify and treat maternal vitamin D deficiency before conception or during pregnancy c237
      • Encourage maternal intake of high-dose vitamin D during pregnancy as vitamin D is important in fetal lung growth, immune system activity, and inhibiting inflammatory responses associated with asthma
      • Early life exposure to allergens and organic plant/animal material in farms are associated with lower risk of asthma in children
      • Day care attendance in the first 6 months of life is protective for asthma in children r167
    • The following measures may reduce risk of exacerbations (secondary prevention):
      • Annual influenza vaccine to prevent influenza-induced exacerbation r1c238
      • Avoid known triggers of exacerbation (eg, exposure to cigarette smoke) c239c240c241
      • Education regarding the use of inhalers, peak flow meter, spacers, asthma action plan, and adherence to recommended treatments c242
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