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Jul.01.2021

Asthma in Adults

Synopsis

Key Points

  • Asthma in adults may be persistence of childhood-onset asthma (usually allergic) or may reflect new onset in adulthood (often nonallergic)
  • Presents with episodic wheezing, chest tightness, difficulty breathing, and cough; cough-variant asthma may present with coughing as primary symptom
  • Diagnosis is based on appropriate history plus clinical picture and documented reversibility of airflow obstruction (12% increase or more from baseline in FEV₁; minimum 200 mL) following treatment with an inhaled short-acting bronchodilator r1
  • Classify the asthma initially by frequency of symptoms (intermittent or persistent) and their effect on daily functioning (ie, mild, moderate, severe); initial pharmacotherapy is based on this classification
  • After starting pharmacotherapy, classify the asthma by level of control; pharmacotherapies are stepped up or down based on this level
  • Persistent asthma requires use of a daily controller medication, starting with a low-dose inhaled corticosteroid for mild persistent asthma. There is some evidence that starting inhaled corticosteroids may be beneficial even for mild intermittent asthma
  • Step-up to an inhaled long-acting β₂ agonist with increasing doses of inhaled corticosteroids as needed. Leukotriene inhibitors are alternative add-on drugs
  • Begin treatment of an acute exacerbation with an inhaled short-acting β₂ agonist; add systemic steroids and inhaled anticholinergics for exacerbations classified as severe. On discharge from emergency department, consider initiating corticosteroids in patients who have not previously used them
  • In emergency care setting, discharge goal is improvement to 70% or more of predicted FEV₁ or peak expiratory flow
  • Education, home monitoring with a peak flow meter, and asthma action plans are as important as medication
  • Smoking cessation is critical

Urgent Action

  • Quickly assess the following in any patient with respiratory distress: vital signs, signs of tiring from work of breathing, lung function, and oxygen saturation. Give supplemental oxygen to maintain SaO₂ of at least 90%
  • Consider alternative diagnoses, such as foreign body aspiration or congestive heart failure, that would require other urgent action
  • FEV₁ or peak expiratory flow measurement is helpful to assess severity of an exacerbation, but do not allow testing to delay treatment
  • Begin treatment of mild to moderate asthma exacerbation with short-acting β₂ agonist via inhaler with spacer or nebulizer; for severe asthma, continuous administration via nebulizer is recommended
  • Give inhaled ipratropium in addition to short-acting β₂ agonist for exacerbations classified as severe or life-threatening r1

Pitfalls

  • Physical examination is not a reliable indicator of the severity of airflow obstruction; wheezing may be inaudible in severe asthma exacerbation
  • Athletes and elderly patients may underreport symptoms or attribute them to other causes
  • Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge may be useful when asthma is suspected and spirometry results are within reference range or nearly so

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
  • Clinically presents as recurrent episodes of cough and wheezing
  • Reversibility is defined as 12% increase or more from baseline in FEV₁ (minimum 200 mL) following treatment with an inhaled short-acting bronchodilator r1

Classification

  • Classification of asthma severity (patients not currently using controller medication) r1
    • Intermittent asthma r1
      • Symptoms occur 2 or fewer days per week
      • No interference with normal activity
      • Nighttime awakenings 2 times per month or less
      • Use of short-acting β₂ agonist for symptom control 2 days per week or less
      • Lung function
        • FEV₁ (predicted within reference range for patient between exacerbations) greater than 80%
        • FEV₁/FVC within reference range
      • 1 or fewer exacerbations per year requiring systemic corticosteroids
        • If patient otherwise meets criteria for intermittent asthma but has at least 2 exacerbations per year that require systemic corticosteroids, this is considered persistent asthma
    • Mild persistent asthma r1
      • Symptoms occur more than 2 days per week, but not daily
      • Minor limitation to normal activity
      • Nighttime awakenings 3 to 4 times per month
      • Use of short-acting β₂ agonist for symptom control more than 2 days per week, but not daily and not more than 1 time on any day
      • Lung function
        • FEV₁ 80% predicted or higher
        • FEV₁/FVC within reference range
      • 2 or more exacerbations per year that require systemic corticosteroids
    • Moderate persistent asthma r1
      • Symptoms occur daily
      • Some limitation to normal activity
      • Nighttime awakenings more than once per week, but not nightly
      • Use of short-acting β₂ agonist for daily symptom control
      • Lung function
        • FEV₁ 60% to 80% predicted
        • FEV₁/FVC is reduced by 5%
      • 2 or more exacerbations per year that require systemic corticosteroids
    • Severe persistent asthma r1
      • Symptoms occur throughout the day on a daily basis
      • Extreme limitation of normal activity
      • Nightly awakenings
      • Use of short-acting β₂ agonist daily for symptom control multiple times per day
      • Lung function
        • FEV₁ less than 60% predicted
        • FEV₁/FVC reduced by more than 5%
      • 2 or more exacerbations per year that require systemic corticosteroids
  • Classification of asthma control (patients using controller medication)
    • Well controlled r1
      • Symptoms occur 2 or fewer days per week
      • No interference with normal activities
      • Nighttime awakenings 2 times per month or less
      • FEV₁ (predicted) or peak expiratory flow (personal best) greater than 80%
    • Not well controlled r1
      • Symptoms occur more than 2 days per week
      • Some limitation of normal activities
      • Nighttime awakenings 1 to 3 times per week
      • FEV₁ (predicted) or peak expiratory flow (personal best) 60% to 80%
    • Very poorly controlled r1
      • Symptoms occur throughout the day
      • Extreme limitation of normal activities
      • Nighttime awakenings 4 or more times per week
      • FEV₁ (predicted) or peak expiratory flow (personal best) less than 60%
  • Classification of acute exacerbations (worsening of baseline function)
    • Mild r1
      • Dyspnea only with activity
      • Peak expiratory flow of 70% or higher of predicted or personal best
    • Moderate r1
      • Dyspnea limits usual activity
      • Peak expiratory flow 40% to 69% of predicted or personal best
    • Severe r1
      • Dyspnea at rest
      • Peak expiratory flow lower than 40% predicted or personal best
    • Life threatening r1
      • Too dyspneic to speak
      • Peak expiratory flow lower than 25% of predicted or personal best
    • Status asthmaticus
      • Continuous, severe asthma exacerbation resistant to treatment
  • Classification by phenotype r2
    • Intrinsic (nonallergic) r1
      • Common phenotype in late/adult-onset asthma
      • Occurs in patients with no history of allergies
      • May be triggered by upper respiratory tract infection or other factors
    • Allergic asthma
      • Associated with elevated blood IgE
      • Early/childhood onset
    • Eosinophilic asthma
      • Late/adult onset
      • Associated with airway eosinophilia
      • Blood/sputum eosinophil count is a predictive biomarker for increased severity of asthma attacks
      • Agents targeting eosinophils (interleukin-5) may improve asthma control
    • Aspirin-exacerbated respiratory disease
      • Presents as allergy to NSAIDs
      • Late/adult onset
      • Often severe and may be accompanied by sinusitis and nasal polyposis
    • Neutrophilic asthma
      • Associated with airway neutrophils (interleukin-8)
      • Late/adult onset
      • Neutrophils in the airways are associated with reduced lung function and airway wall thickening
      • Usually occurs in patients treated with corticosteroids and presents challenge to management
    • Obesity-associated asthma
      • Late/adult onset
      • Poor response to corticosteroid therapy
      • Weight loss may improve symptoms
    • Exercise-induced asthma
      • Early onset
      • May occur in patients with or without underlying asthma r3
      • Presents intermittently with strenuous exercise
        • FEV₁ or peak expiratory flow decreases 10% to 15% soon after onset of vigorous activity (compared with measurement just before exercise) r1r3
        • May persist up to 30 minutes after exerciser3
    • Severe asthma phenotype
      • Subtype that is difficult to treat and control; estimated to affect approximately 5% to 10% of patients r2r4
      • 50% of patients with severe asthma have evidence of type 2 inflammation and may be candidates for treatment with type 2 targeting biologic agents r5
    • Cough variant asthma r6
      • Manifests with nonproductive cough, often without usual wheezing and shortness of breath associated with asthma

Diagnosis

Clinical Presentation

History

  • Episodic dyspnea is the most common symptom c1
    • Present on exertion in mild to moderate asthma c2
    • Present at rest in severe asthma c3
    • Athletes may report decreased exercise tolerance c4
    • Nocturnal dyspnea with awakenings is common c5
    • Inability to take a deep breath c6
  • Cough, especially nocturnal or in the early morning c7c8c9
    • Usually nonproductive; sometimes produces sputum c10
  • Chest tightness c11
  • Wheezing may be audible to patient c12
  • Breathlessness, cough, wheezing, and/or sputum production that begin shortly after onset of vigorous exercise are suggestive of exercise-induced asthma c13c14c15c16
  • Patient may report recent exposure to common allergic and nonallergic triggers c17
  • Baseline level of disease control may change owing to level of adherence to treatment plans
  • Level of short-acting β₂ agonist use, steroid use, and number/severity of exacerbations in the past year are indicative of disease control

Physical examination

  • Results are typically within reference range in a patient with well-controlled asthma
    • There may be evidence of associated diseases, such as nasal secretions and mucosal edema (allergic rhinitis) or rash (atopic eczema) c18c19c20
    • Nasal polyps may be present c21
  • During exacerbation
    • General appearance
      • May be anxious c22
      • Labored breathing c23
      • Diaphoresis with increased respiratory effort c24c25
      • Cyanosis with significant hypoxia c26
      • Drowsiness with impending respiratory failure c27
    • Vital signs
      • Tachypnea and tachycardia c28c29
      • With severe exacerbation:
        • Sustained tachypnea exceeding 30 breaths per minute and tachycardia exceeding 120 beats per minute c30c31
        • May eventually become apneic c32
        • Pulsus paradoxus (drop in systemic arterial pressure with inspiration higher than 10 mm Hg) is often higher than 18 mm Hg but may disappear with fatigue c33
    • Respiratory examination
      • Prolonged expiratory phase c34
      • Use of respiratory accessory muscles/intercostal muscle recession c35c36
      • Wheezing is usually present during exacerbation, but absence of wheezing does not rule out significant bronchospasm c37

Causes and Risk Factors

Causes

  • Underlying cause is incompletely understood; may be environmental in combination with genetic interaction c38c39
  • Exacerbation triggers
    • Aeroallergens (eg, pollen, pet dander, dust mites, mold) c40c41c42c43c44
    • Airborne irritants (eg, cigarette or wood smoke, air pollution, chemical compounds, grain dust) c45c46c47
    • Drugs (eg, aspirin, NSAIDs, β-blockers) c48c49c50
    • Ingested substances (eg, foods, sulfites) c51c52
    • Respiratory infection c53
    • Exercise c54
    • Cold air c55
    • Psychological stress c56

Risk factors and/or associations

Age
  • Asthma in adults may be either persistent childhood-onset asthma or new-onset asthma in adulthood c57
Sex
  • Higher prevalence in women c58c59
Genetics
  • Predisposed sensitivity to environmental allergens is strongest risk factor c60
Ethnicity/race
  • Higher prevalence in Hispanic and Black populations than in White population c61c62c63
Other risk factors/associations
  • In females, obesity or increased waist circumference c64c65
    • Large waist circumference (more than 88 cm) is associated with increased asthma prevalence, even among women with a BMI within reference range r7
  • Adjusted odds ratio for adult-onset asthma increases from 1.4 for overweight women to 3.3 for extremely obese women r7c66
  • Presence of the following risk factors increases risk for exacerbations, even if patients have few symptoms r4
    • Previous intubation or intensive care unit admission for asthma
    • One or more severe exacerbations in the past year
    • Low FEV₁ (especially if lower than 60% predicted)
    • Exposures
      • Smoking c67
      • Allergens, if sensitized c68
      • Air pollution c69
    • Comorbidities
      • Chronic rhinosinusitis c70
      • Obesity c71
      • Food allergy c72
      • Pregnancy c73
      • Gastroesophageal reflux disease c74
    • Medications
      • Frequent use of short-acting β agonists c75
      • Not prescribed or inadequate dose of inhaled corticosteroids
      • Poor adherence or inhaler technique c76

Diagnostic Procedures

Primary diagnostic tools

  • New diagnosis
    • History and physical examination suggest the diagnosis r1c77
    • Perform spirometry. Obstruction (FEV₁/FVC ratio of 70% or less) with reversibility after bronchodilator administration (12% increase or more from baseline in FEV₁; minimum 200 mL) strongly supports the diagnosis r1c78
      • However, in an asymptomatic patient, normal spirometry does not rule out an asthma diagnosis
    • Measurement of fractional nitric oxide concentration in exhaled breath (FeNO) may be helpful in the initial diagnosis of asthma as a surrogate marker of eosinophilic airway inflammation c79
      • 2017 NICE guidelinesr8 recommend that this be performed routinely in the diagnostic evaluation of adults
      • Other guidelines suggest utility in confirming asthma when symptoms and signs suggest asthma, but spirometry is not definitive r9
      • Measurement of fractional nitric oxide concentration in exhaled breath is also sometimes used as an alternative strategy for guiding therapy, but recent evidence is not supportive of this r4r10
    • Additional testing is not routinely necessary, but it may be helpful in some situations r1
      • Repeated peak flow measures over a period of weeks; variability above 20% within the measurement period supports the diagnosis of asthma r8c80
      • Bronchoprovocation when asthma is suspected and spirometry is within (or nearly within) reference range r1c81
      • Full pulmonary function testing to differentiate from chronic obstructive pulmonary disease in smokers r1c82
      • Skin testing or in vitro allergy testing to assess sensitivity to perennial indoor allergens for patients with persistent asthma r1c83
      • Peripheral blood eosinophil count to assess for eosinophilic phenotype, which may later guide therapy r11c84
      • Exercise-induced asthma, suggested by respiratory symptoms associated with vigorous exercise, may be confirmed by serial changes in lung function (FEV₁ preferred) after exercise or hyperpnea challenge r3
  • Acute exacerbation
    • History and physical examination suggest the diagnosis
    • Immediate FEV₁ or peak expiratory flow measurement to determine severity of exacerbation
      • A peak flow rate below 200 L/min generally indicates severe airway obstruction r1
    • Immediate assessment of oxygenation with pulse oximeter
    • Arterial blood gas measurement is not routine, but it may be helpful in staging exacerbation to guide treatment or if there is poor response to repeated treatments r1c85
    • Obtain chest radiograph if complicating chest infection suspected, hospitalization required, or diagnosis is uncertain r4c86

Laboratory

  • Arterial blood gas level r1c87
    • Rarely indicated; noninvasive SaO₂ monitoring is preferred for monitoring oxygenation in acute exacerbation
    • Can be used in staging severity of asthma exacerbation
      • Mild: decreased PaO₂ and PCO₂ with increased pH level
      • Moderate: decreased PaO₂ with PCO₂ and pH levels within reference range
      • Severe: markedly decreased PaO₂, increased PCO₂, and decreased pH level
      • Results do not correlate with pulmonary function tests or predict clinical outcome
    • Venous blood gas level may be preferable (less painful and lower risk of complication); if PCO₂ is within reference range, arterial hypercarbia is excluded r12
  • CBC and differential c88
    • Not required for diagnosis; however, eosinophilia may be a useful predictor of future risk of asthma exacerbations r13
    • Blood eosinophil count of 150/μL or more suggests type 2 inflammation r5
  • Other blood tests
    • C reactive protein, IgE, IgA, IgG, IgM, antineutrophil cytoplasmic autoantibody, or fungal precipitins may be considered in cases of difficult to treat or severe asthma r5c89c90c91c92c93c94c95

Imaging

  • Chest radiography or high-resolution CT c96
    • Imaging is not routinely required; only used to exclude/support the presence of other conditions or in evaluation of severe/difficult to treat asthma

Functional testing

  • Spirometry c97
    • Measures how an individual inhales or exhales volumes of air as a function of time; reported as either volume or flow
    • Obtain at initial assessment to evaluate for objective signs of reversible airway obstruction (before and after 2-4 inhalations of a short-acting bronchodilator) r1r9
    • Repeat after treatment has begun to assess response, 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 r1
    • Relevant measurements are FVC, FEV₁, and FEV₁/FVC ratio
      • Measured values are reported as percent predicted from a set of reference values
        • The 2005 American Thoracic Society and European Respiratory Society published recommendations prefer the third National Health and Nutrition Examination Survey datar15 as reference values for White Americans, African Americans, and Mexican Americans r14
      • Measured from a series of at least 3 forced expiratory curves
      • FVC: volume during an expiration made as forcefully and completely as possible starting from full inspiration
      • FEV₁: volume delivered in the first second of an FVC expiration
      • FEV₁/FVC reference range by age
        • 20 to 39 years: 80% r1
        • 40 to 59 years: 75% r1
        • 60 to 80 years: 70% r1
      • In general, a FEV₁/FVC of less than 70% is considered obstructive r1
      • 12% increase or more from baseline in FEV₁ with a minimum 200 mL increase is considered reversible r1
      • Greater than 400 mL increase in FEV₁ postbronchodilator is highly suggestive of asthma in adults r9
  • Peak expiratory flow c98
    • Maximum expiratory flow achieved from a maximum forced expiration, starting without hesitation from the point of maximal lung inflation r16
      • Teach patient to use a peak flow monitor at home to monitor for personal best and for worsening or improvement r1
      • Perform at baseline and when stable to determine personal best r1
      • Do not use for initial diagnosis of asthma because there is wide variability in meters and reference values r1
    • Measured value is in liters per second when part of spirometry, but it is often expressed in liters per minute when using a patient-administered handheld meter r16
  • Serial FEV₁ measurement with exercise (or induced-hyperpnea) challenge c99c100
    • Indicated to confirm exercise-induced asthma
    • Measure FEV₁ (at least 2 reproducible maneuvers) at baseline, before exercise challenge r3
    • Perform exercise challenge or stationary surrogate hyperpnea challenge r3
      • Exercise challenge or surrogate to achieve a high level of ventilation
        • Most protocols recommend breathing dry air with a nose clip in place while running or cycling
        • Heart rate is typically used as a surrogate for high ventilation; 80% to 90% of predicted maximum (predicted maximum heart rate is approximately 220 minus age in years) r3
        • Once this level of exercise is reached, continue exercise at high level for 4 to 6 minutes r3
      • Hyperpnea challenge
        • Protocols vary; include eucapnic voluntary hyperpnea or hyperventilation, inhalation of hyperosmolar aerosols (4.5% saline), and inhalation of dry powder mannitol r3
    • Measure FEV₁ at 5, 10, 15, and 30 minutes after exercise challenge r3
    • Response is expressed as the percentage fall in FEV₁ from the baseline (preexercise) value r3
    • Greater than 10% fall is diagnostic in some guidelines; many laboratories use a criterion of more than 15% decrease because of greater specificity r3
    • Severity grading, based on the percentage fall in FEV₁ from the preexercise level
      • Mild: 10% to 25% r3
      • Moderate: 25% to 50% r3
      • Severe: more than 50% r3
  • Fractional nitric oxide concentration in exhaled breath c101
    • Recommended use in diagnosis
      • A positive test result suggests presence of eosinophilic inflammation and supports an asthma diagnosis but is not conclusive r13
        • A negative test result does not exclude asthma r9
      • British guidelines recommend offering this as a diagnostic test to all adults, with a level of 40 ppb or higher supporting a diagnosis of asthma r8
      • National Asthma Education and Prevention Program recommends use as an adjunct to diagnosis only if asthma remains uncertain based on history, clinical findings, clinical course, and spirometry (or if spirometry cannot be performed), including bronchodilator responsiveness testing r17
      • 2020 Global Initiative for Asthma guidelines do not consider this test useful in the diagnosis of asthma r4
    • Recommendations for the use of this test as an alternative strategy for guiding therapy are mixed
      • American Thoracic Society guidelines recommend testing to determine if eosinophilic inflammation is present and to predict steroid responsiveness r10r18
        • Low level (less than 25 ppb) indicates that eosinophilic inflammation and responsiveness to corticosteroids are less likely r18
        • High level (greater than 50 ppb) indicates that eosinophilic inflammation and, in symptomatic patients, responsiveness to corticosteroids are likely r18
        • Mid-range levels (25-50 ppb) should be interpreted cautiously with reference to clinical context r18
      • A Cochrane review did not find a significant change in exacerbation rate when using therapy guided by fractional nitric oxide concentration in exhaled breath (as compared with standard guideline directed therapy) in adults r10
      • 2020 Global Initiative for Asthma guidelines do not recommend using a fractional nitric oxide concentration in exhaled breath-based treatment strategy in adults; can support decision to commence inhaled corticosteroids but should not be used to decide against treatment r4
      • National Asthma Education and Prevention Program recommends use in persistent allergic asthma with uncertainty in choosing, monitoring, or adjusting anti-inflammatory therapies based on history, clinical findings, and spirometry r17
        • Use as part of ongoing asthma monitoring and management strategy
  • Bronchoprovocation testing r1c102
    • Performed by an asthma care specialist or trained individual for safety reasons
    • Performed with methacholine, histamine, cold air, or exercise challenge; can be useful when:
      • Asthma is suspected and spirometry is within (or nearly within) reference range
      • There is obstructive spirometry without bronchodilator reversibility, and r8
        • Fractional nitric oxide concentration in exhaled breath level is midrange (not clearly low or elevated), and
        • There is less than 20% peak flow variability over 2 to 4 weeks
    • Positive test result is diagnostic for airway hyperresponsiveness, which is characteristic for asthma but can be present in other conditions as well
    • Negative test result is helpful to exclude asthma

Differential Diagnosis

Most common

  • Chronic obstructive pulmonary disease c103d1
    • Difficult to clinically distinguish
    • Perform pulmonary function tests with carbon monoxide–diffusing capacity
      • Airway obstruction is more severe with less reversibility in chronic obstructive pulmonary disease
      • Diffusing capacity is lower in chronic obstructive pulmonary disease
  • Congestive heart failure c104
    • History of coronary artery disease, congestive heart failure, or valvular disease
    • Physical examination may reveal wheezing, but other findings (eg, rales, dependent edema, cardiac gallop) suggest heart failure
    • Chest radiograph and ECG aid in diagnosis
  • Chronic cough due to other cause (eg, gastroesophageal reflux disease, rhinitis with postnasal drip, ACE inhibitor adverse effect) c105c106c107d2
    • History and physical examination may be suggestive
    • Discontinuing ACE inhibitor or initiating trial of medication for other conditions may eliminate symptoms
    • Bronchoprovocation testing may be helpful when cough-variant asthma versus alternative cause of cough is a consideration (result will be negative with nonasthma cause)
  • Pulmonary embolus c108d3
    • History is sometimes suggestive (eg, previous deep vein thrombosis or pulmonary embolus, recent immobilization due to travel or surgery)
    • D-dimer testing and/or appropriate imaging to diagnose
  • Mechanical obstruction of airway due to benign or malignant tumor c109
    • Suggestive history may include constitutional symptoms, weight loss, difficulty swallowing, and hemoptysis
    • Chest radiograph, CT scan, soft tissue radiograph of the neck, and/or endoscopic visualization to diagnose
  • Vocal cord dysfunction (paradoxical vocal cord motion disorder) c110
    • May mimic asthma, but will be unresponsive to bronchodilators
    • Consider in atypical asthma and in athletes who have exercise-related dyspnea that is unresponsive to asthma medication
    • Spirometry demonstrates extrathoracic airway obstruction on flow-volume loops (truncated inspiratory loop)
    • Laryngoscopy confirms abnormal adduction

Treatment

Goals r1

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

Disposition

Admission criteria

Base admission decisions on serial assessment of lung function (using FEV₁ or peak expiratory flow) after the patient receives 3 doses of an inhaled bronchodilator (at least 1 hour after initiation of treatment); use pulse oximetry if patient is unable to comply with FEV₁ or peak expiratory flow measurement

  • Criteria for discharge from urgent care/emergency department
    • Patient is not in distress, physical examination results are normal, and FEV₁ is at least 70% of personal best (or predicted value) r1
    • Response sustained at least 1 hour after last treatment r1
  • Criteria for keeping in observation unit (if available) or admitting to hospital ward (individualized decision)
    • After 1 to 3 hours of treatment with short-acting β₂ agonist treatments and oral corticosteroids, patient has mild to moderate symptoms and FEV₁ or peak expiratory flow is 40% to 69%
  • More severe disease requires ICU admission
Criteria for ICU admission
  • Impending (or actual) respiratory arrest
  • Drowsiness or confusion
  • FEV₁ or peak expiratory flow less than 25% before treatment often predicts need for ICU r1
  • FEV₁ or peak expiratory flow less than 40% after multiple or continuous nebulized albuterol-ipratropium treatments with oral corticosteroidsr1
  • PCO₂ of 42 mm Hg or higher on arterial blood gas after multiple treatmentsr1

Recommendations for specialist referral

  • Refer to asthma specialist (pulmonologist or allergist)
    • Severe, persistent asthma requiring step 4 care or higherr1
    • Poorly controlled asthma with frequent absence from school or work
    • Consideration of immunotherapy or omalizumab treatment
    • Patient has required more than 2 rounds of oral steroids or high-dose inhaled corticosteroids in past year r1
    • Patient required hospitalization in past year
    • Diagnosis is uncertain or symptoms are atypical

Treatment Options

Acute asthma exacerbation

  • Exacerbation with peak expiratory flow remaining at 50% or more of personal best can often be managed at home with use of inhaled short-acting β₂ agonist with or without a short course of oral corticosteroids r1
    • Patients may be advised to quadruple maintenance dose of inhaled corticosteroids at the onset of an asthma attack and for up to 14 days in order to reduce the risk of needing oral corticosteroids r13
  • Exacerbation with peak expiratory flow less than 50% of predicted or personal best requires immediate medical care in urgent care facility or emergency department; if peak expiratory flow is less than 40%, patient should go to emergency department r1
  • Emergent clinical setting
    • For mild-moderate exacerbation
      • Supplemental oxygen by nasal cannula or face mask if SaO₂ is lower than 90% r1
      • Immediately start treatment with inhaled short-acting β₂ agonist drug; start with repeated doses via metered dose inhaler r19
      • Give oral corticosteroids if there is no immediate response to inhaled short-acting β₂ agonist drug or if patient recently took oral corticosteroids r1
      • Reassess
        • Continue inhaled short-acting β₂ agonist drug treatments for 1 to 3 hours; make admission decision within 4 hours r1
    • For severe exacerbation
      • Provide supplemental oxygen by nasal cannula or face mask if SaO₂ is lower than 90% r1
      • Immediately start treatment with inhaled short-acting β₂ agonist drug; give continuous (instead of intermittent) nebulized short-acting β₂ agonist r20
        • Injected epinephrine or terbutaline is no more effective than inhaled short-acting β₂ agonist r1r21
      • Give ipratropium by nebulizer along with short-acting β₂ agonist r1
      • Give oral corticosteroids r1
      • Reassess
        • Repeat administration of inhaled short-acting β₂ agonist with ipratropium as necessary r1
        • Consider adjunctive therapies if FEV₁ remains lower than 40% r1
          • IV magnesium sulfate reduces hospital admissions and improves lung function in adults when inhaled short-acting medications and IV steroids have failed; not for routine use r22r23
    • For severe exacerbation with impending or actual respiratory arrest
      • Some authors advocate for noninvasive positive pressure ventilation for severe exacerbation when attempting to avoid intubation;r24r12however, evidence of benefit is limitedr25
      • Intubate and mechanically ventilate with 100% oxygen if respiratory arrest is occurring or impending, signaled by:
        • Paradoxical thoracoabdominal movement
        • Absence of wheeze
        • Peak expiratory flow lower than 25% r1
        • If arterial blood gas is obtained, PCO₂ of 42 mm Hg or higherr1
        • Cyanosis
        • Drowsiness
        • Bradycardia
      • Immediately start treatment with continuous inhaled short-acting β₂ agonist plus inhaled ipratropium r1
      • Give IV corticosteroids r1
      • Consider adjunctive therapies
        • Magnesium sulfate if FEV₁ remains less than 40% r1
          • Recent trials of nebulized inhaled magnesium sulfate have not shown significant benefit r26
    • For all patients before discharge from emergency department or hospital
      • Ensure that the patient will receive these critical components of asthma management as an outpatient: r1
        • Ongoing clinical assessment and home monitoring
        • Education and asthma action plan
        • Control of environmental factors and comorbid conditions
        • Ongoing controller medication

Chronic asthma

  • Pharmacotherapy is prescribed using stepwise approach;r17r1 initial step is determined by disease severity classification (for newly diagnosed patients not on controller medications) or by disease control classification (for patients currently using controller medications)
    • Adjustments are based on the ongoing level of control
    • Therapy can be both stepped up and stepped down; step-down can be considered after 3 months of good control
  • 3 types of medications may be used r4
    • Controllers
      • Inhaled corticosteroid-containing controller medications reduce airway inflammation and symptoms, reduce future exacerbations and decline in lung function
      • The Single Maintenance and Reliever Treatment (SMART) strategy using a combination of inhaled corticosteroid (ICS) plus formoterol in a single inhaler therapy is the preferred treatment of steps 3 and 4 r4r13r17
    • Relievers
      • Used as needed to alleviate breakthrough symptoms
      • Once a mainstay of asthma therapy, short-acting β agonists are no longer recommended as the preferred reliever for symptomatic patients and should not be used as monotherapy because of safety concerns and poor outcomes r27
        • A combined inhaled corticosteroid plus fast onset, long-acting β agonist (ie, formoterol) is the preferred reliever
      • Reduction or elimination of 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
  • Step 1 (Intermittent asthma; infrequent symptoms less than twice per month and no risk factors for exacerbations) r1
    • Global Initiative for Asthma and National Asthma Education and Prevention Program recommend using a low-dose inhaled corticosteroid plus the inhaled long-acting β₂ agonist, formoterol, in a single inhaler, as required to alleviate symptoms r4r17
      • Alternatively, give a dose of low-dose inhaled corticosteroid whenever inhaled short-acting β₂ agonist is used to relieve symptoms
      • Inhaled corticosteroid-containing reliever medications are superior to short-acting β₂ agonist reliever alone and significantly reduce risks of severe asthma exacerbation r28r29
      • Global Initiative for Asthma no longer recommends as-needed inhaled short-acting β₂ agonist monotherapy for such symptoms r30
    • British guidelines recommend use of an inhaled short-acting β₂ agonist as reliever therapy for patients with symptomatic asthma who have infrequent, short-lived wheeze and normal lung function r8r13
  • Step 2 (Asthma symptoms or need for reliever medication more than twice per month)
    • Global Initiative for Asthma recommends either: r4
      • As-needed low-dose inhaled corticosteroid plus formoterol in a single inhaler, to alleviate symptoms
      • Low-dose inhaled corticosteroid maintenance therapy plus as-needed inhaled short-acting β₂ agonist to alleviate symptoms
      • Alternatives
        • Daily leukotriene receptor antagonist
        • Dose of low-dose inhaled corticosteroid whenever inhaled short-acting β₂ agonist is used to relieve symptoms
    • British guidelines recommend low-dose inhaled corticosteroids as maintenance therapy for patients with asthma-related symptoms 3 times a week or more, or causing waking at night or asthma that is uncontrolled with a reliever alone r8r13
  • Step 3 (Asthma symptoms on most days or waking due to asthma symptom once per week or more)
    • Global Initiative for Asthma recommends either: r4
      • Low-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist as maintenance therapy and low-dose inhaled corticosteroid plus formoterol single inhaler as needed to alleviate symptoms (preferred by National Asthma Education and Prevention Program)r17
      • Low-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist as maintenance therapy and as-needed inhaled short-acting β₂ agonist as reliever
      • Alternatives:
        • Medium-dose inhaled corticosteroid plus as-needed inhaled short-acting β₂ agonist to alleviate symptoms
        • Low-dose inhaled corticosteroid maintenance therapy plus leukotriene receptor antagonist
        • Addition of house dust mite sublingual immunotherapy for sensitized patients with allergic rhinitis and FEV₁ greater than 70% predicted
        • Low-dose inhaled corticosteroid plus a long-acting muscarinic antagonist, tiotropium (National Asthma Education and Prevention Program recommended) r17
    • British guidelines recommend add-on therapy with inhaled long-acting β₂ agonist or a leukotriene receptor antagonist r8r13
      • If asthma control still remains suboptimal, then medium-dose inhaled corticosteroid or combined low-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist as maintenance therapy and low-dose inhaled corticosteroid plus formoterol single inhaler as needed to alleviate symptoms
  • Step 4 (Asthma symptoms on most days, or waking due to asthma symptoms once per week or more, or low lung function)
    • Global Initiative for Asthma recommends medium-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist as maintenance therapy with as-needed low-dose inhaled corticosteroid plus formoterol single inhaler (preferred by National Asthma Education and Prevention Program) r17or inhaled short-acting β₂ agonist to alleviate symptoms r4
      • Alternatives
        • High-dose inhaled corticosteroid
        • Add-on tiotropium bromide, a long-acting muscarinic antagonist r17
        • Add-on leukotriene receptor antagonist
        • Add-on house dust mite sublingual immunotherapy for sensitized patients with allergic rhinitis and FEV₁ greater than 70% predicted
    • British guidelines recommend 1 of the following if asthma control remains inadequate on medium-dose inhaled corticosteroid plus a long-acting β₂ agonist or a leukotriene receptor antagonist: r13
      • High-dose inhaled corticosteroids
      • Addition of a leukotriene receptor antagonist (if not already using)
      • Addition of tiotropium bromide, a long-acting muscarinic antagonist
      • Addition of a theophylline (rarely used nowadays)
  • Step 5 (severe uncontrolled asthma) r1
    • Referral to asthma specialist is recommended
    • Address any factors that may contribute to suboptimal control (eg, poor adherence to therapy, incorrect inhaler technique, comorbidities, modifiable risk factors such as smoking) r5
    • Use high-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist with as-needed low-dose inhaled corticosteroid plus formoterol single inhaler or inhaled short-acting β₂ agonist to alleviate symptoms
    • Assess asthma phenotype for type 2 airway inflammation during high-dose inhaled corticosteroid treatment r5
      • Type 2 airway inflammation is defined by the presence of 1 or more of the following:
        • Blood eosinophil count of 150/μL or more
        • Fractional nitric oxide concentration in exhaled breath of 20 ppb or more
        • Sputum eosinophil concentration of 2% or more
        • Asthma that is clinically allergen-driven
        • Oral corticosteroid dependent
      • If no evidence of type 2 inflammation, consider the following:
        • Add-on tiotropium bromide, a long-acting muscarinic antagonist r31
        • Add-on macrolide antibiotic (eg, azithromycin) r31
          • Consider in adults aged 50 to 70 years who have persistent symptoms despite more than 80% adherence to high-dose inhaled steroids (over 800 mcg/day) and 1 or more exacerbation requiring oral steroids in the past year r32
          • Treat for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations r32
        • Course of low-dose oral corticosteroid
        • Bronchial thermoplasty: may be considered for some patients with severe asthma despite optimal medical therapy r4r5r13
      • If there is evidence of type 2 airway inflammation, consider addition of biological agents (refer to local eligibility criteria and published guidelines for use) r5r33
        • Evaluate response to the biological agent after 4 months and, if favorable, continue treatment with reevaluation every 3 to 6 months; switch to a different agent if response to the initial agent is inadequate r33
        • Anti-interleukin-5/interleukin-5 receptor monoclonal antibodies (mepolizumab, benralizumab, reslizumab) for severe asthma with an eosinophilic phenotype, ascertained by either sputum or peripheral eosinophilia r34
          • Anti-interleukin-5 agents reduce exacerbations in patients with severe eosinophilic asthma r31r35
          • Mepolizumab and benralizumab are effective in reducing oral steroid doses in patients with corticosteroid-dependent asthma
          • A blood eosinophil count threshold of 150/μL or more can be used to guide initiation of anti-interleukin-5 agents r31
        • Omalizumab, an anti-IgE monoclonal antibody, for allergic asthma with documented sensitivity to a perennial aeroallergen and elevated total IgE level
          • A blood eosinophil count of 260/μL or more and fractional nitric oxide concentration in exhaled breath of 19.5 ppb or more identify patients most likely to benefit from anti-IgE treatment r31
        • Dupilumab, an anti-interleukin-4 receptor monoclonal antibody, for patients with severe eosinophilic asthma and those requiring maintenance oral corticosteroids regardless of blood eosinophil levels r31
    • Guidelines have been developed to aid evaluation and management of difficult-to-treat and severe asthma r5r31r33

Exercise-induced asthma r3

  • Use inhaled short-acting β₂ agonist 15 minutes before exercise r3r13
    • Combination low-dose inhaled corticosteroid plus formoterol used as required and before exercise is an alternative
  • Ensure training and warm up is sufficient r4
  • For patients who require an inhaled short-acting β₂ agonist daily or more frequently, add low-dose inhaled corticosteroids r4r13
  • Review and optimize asthma treatment for patients in whom exercise-induced asthma reflected overall poorly controlled asthma r13
  • If exercise remains a specific problem in patients who are otherwise well controlled on low-dose inhaled corticosteroids, consider adding 1 of the following therapies: r3r13
    • Daily leukotriene antagonist r3
    • Sodium cromoglicate (cromolyn) or nedocromil sodium before exercise
    • Long-acting β₂ agonists (only in conjunction with an inhaled corticosteroid)
    • Theophyllines
  • Use antihistamine only if there are definite allergies r3
  • Consider adding inhaled anticholinergic (weak evidence, but can be tried if other options are inadequate) r3

Cough variant asthma r6

  • Low-dose inhaled corticosteroids are considered first line treatment
  • If response is incomplete, inhaled corticosteroid dose may be increased and/or leukotriene antagonist added

Drug therapy

  • Chronic asthma
    • Relief of episodic wheezing (relievers)
      • Short-acting β₂ agonists
        • Albuterol c111
          • Albuterol Pressurized inhalation, suspension; Adults: 180 mcg (2 actuations of 90 mcg/actuation) via oral inhalation every 4 to 6 hours as needed. In some patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (1,080 mcg/day).
          • Albuterol Inhalation powder; Adults: 180 mcg (2 actuations of 90 mcg/actuation) via oral inhalation every 4 to 6 hours as needed. In some patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (1,080 mcg/day).
          • Albuterol Sulfate Nebulizer solution; Adults: 2.5 mg via nebulizer 3 to 4 times daily as needed. Usual Max: 4 doses/day.
          • Some guidelines recommend simultaneous administration of low-dose inhaled corticosteroids when albuterol is used to relieve symptoms
            • Fluticasone c112
              • Fluticasone Propionate Pressurized inhalation, suspension; Adults: GINA recommends 88 mcg (2 oral inhalations of 44 mcg/actuation) or 110 mcg to 220 mcg (1 to 2 oral inhalations of 110 mcg/actuation) or 220 mcg (1 oral inhalation of 220 mcg/actuation) as needed whenever short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed ICS/SABA as an option for patients with mild persistent asthma. FDA-approved Max: 1,760 mcg/day.
              • Fluticasone Furoate Inhalation powder; Adults: GINA recommends 100 mcg (1 oral inhalation of 100 mcg/actuation) as needed whenever short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed ICS/SABA as an option for patients with mild persistent asthma. FDA-approved Max: 200 mcg/day.
            • Budesonide c113
              • Budesonide Inhalation powder; Adults: GINA recommends 180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) as needed whenever short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed ICS/SABA as an option for patients with mild persistent asthma. FDA-approved Max: 1,440 mcg/day.
          • Inhaled corticosteroid plus fast onset, long-acting β₂ agonist
            • Budesonide-formoterol combination product c114
              • Budesonide, Formoterol Fumarate Pressurized inhalation, powder; Adults: 1 or 2 oral inhalations (total per dose = 160 to 320 mcg budesonide with 4.5 to 9 mcg formoterol) as needed in addition to daily maintenance dosing; may repeat after 5 minutes if needed. Max per National Asthma Education and Prevention Program: formoterol 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.
        • Levalbuterol (for patients intolerant of albuterol) c115
          • Levalbuterol Tartrate Pressurized inhalation, suspension; Adults: 90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation every 4 to 6 hours as needed; in some patients 45 mcg (1 actuation) every 4 hours may be sufficient. Max: 12 actuations/day (540 mcg/day).
          • Levalbuterol Hydrochloride Nebulizer solution; Adults: 0.63 to 1.25 mg via nebulizer 3 times daily (every 6 to 8 hours) as needed. Max: 3 doses/day.
    • Maintenance treatment (controllers)
      • Inhaled corticosteroids (preferred)
        • Fluticasone c116
          • Fluticasone Propionate Pressurized inhalation, suspension; Adults: 88 mcg (2 oral inhalations of 44 mcg/actuation) twice daily for patients not currently on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. Max: 4 oral inhalations of 220 mcg/actuation twice daily (880 mcg twice daily). Use the lowest effective dose once stable.
          • Fluticasone Propionate Inhalation powder; Adults: 55 mcg (1 oral inhalation of 55 mcg/actuation) twice daily is recommended for patients not on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. After 2 weeks, may increase to 113 mcg twice daily if not controlled. Max: 232 mcg (1 oral inhalation of 232 mcg/actuation) twice daily. Use lowest effective dose once stable.
        • Budesonide c117
          • Budesonide Inhalation powder; Adults: 360 mcg (2 oral inhalations of 180 mcg/actuation) twice daily is the recommended starting dosage; 180 mcg (1 actuation) twice daily may be appropriate for some patients. Max: 4 oral inhalations of 180 mcg/actuation twice daily (720 mcg twice daily). Titrate to lowest effective dose once stable.
          • Budesonide Nebulizer suspension; Adults†: Not FDA-approved in U.S. in adults. European usual dose for severe asthma is 1 to 2 mg via nebulizer twice daily. Usual maintenance dose is 0.5 to 1 mg via nebulizer twice daily; may increase during exacerbations or severe asthma. Max: 4 mg/day. Titrate to lowest effective dose once stable.
      • Inhaled corticosteroid plus long-acting β₂ agonists (preferred)
        • Budesonide-formoterol combination product c118
          • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Adults: 2 oral inhalations of either 80/4.5 (80 mcg budesonide with 4.5 mcg formoterol per actuation) or 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) twice daily. Choose dose based on asthma severity and previous therapy. Max: 2 oral inhalations of 160/4.5 twice daily (640 mcg budesonide with 18 mcg formoterol per day).
          • Single maintenance and reliever therapy (SMART); same inhaler is used for both regular maintenance dosing and as needed to alleviate symptoms.
            • Only use Budesonide-formoterol as reliever when this combination is also used as maintenance therapy. r17
        • Fluticasone-salmeterol combination product c119
          • Fluticasone Propionate, Salmeterol Pressurized inhalation, suspension; Adults: 2 oral inhalations twice daily, of either 45/21 (45 mcg fluticasone/21 mcg salmeterol per inhalation), 115/21 (115 mcg fluticasone/21 mcg salmeterol per inhalation), or 230/21 (230 mcg fluticasone/21 mcg salmeterol per inhalation). Max: 2 oral inhalations of 230/21 twice daily (920 mcg fluticasone with 84 mcg salmeterol per day).
          • Fluticasone Propionate, Salmeterol Inhalation powder; Adults: 1 oral inhalation twice daily of either 100/50 (100 mcg fluticasone and 50 mcg salmeterol per inhalation), 250/50 (250 mcg fluticasone and 50 mcg salmeterol per inhalation), or 500/50 (500 mcg fluticasone and 50 mcg salmeterol per inhalation). Max: 1 oral inhalation of 500/50 twice daily (1,000 mcg fluticasone and 100 mcg salmeterol per day).
          • Fluticasone Propionate, Salmeterol Inhalation powder; Adults: 1 oral inhalation of 55/14 (55 mcg fluticasone and 14 mcg salmeterol per inhalation) twice daily is the usual initial dose if not previously on inhaled corticosteroids (ICS). Do not use a spacer device or volume holding chamber. Use higher dosages in patients with more severe asthma, either 1 oral inhalation of 113/14 (113 mcg fluticasone and 14 mcg salmeterol per inhalation) or 232/14 (232 mcg fluticasone and 14 mcg salmeterol per inhalation) twice daily. SWITCHING FROM ANOTHER ICS PRODUCT: Select dose based on asthma severity and previous asthma therapy. Max: 1 oral inhalation of 232/14 twice daily (464 mcg fluticasone and 28 mcg salmeterol per day).
        • Fluticasone-vilanterol combination product c120
          • Fluticasone Furoate Inhalation powder, Vilanterol Inhalation powder; Adults: 1 oral inhalation of either 100/25 (100 mcg of fluticasone and 25 mcg of vilanterol per actuation) or 200/25 (200 mcg fluticasone and 25 mcg vilanterol per actuation) once daily. Choose dose based on asthma severity and previous therapy. Max: 200 mcg fluticasone with 25 mcg vilanterol per day.
      • Leukotriene receptor antagonists (second line)
        • Montelukast c121
          • Montelukast Sodium Oral tablet; Adults: 10 mg PO once daily in the evening. LIMIT OF USE: Montelukast is not indicated for treatment of an acute asthma attack.
          • FDA has issued warning regarding serious neuropsychiatric adverse effects. r4
        • Zafirlukast c122
          • Zafirlukast Oral tablet; Adults: 20 mg PO twice daily.
    • Maintenance therapy; add on agents for step 4 and 5
      • Long-acting muscarinic antagonist
        • Tiotropium c123
          • Tiotropium Respiratory spray, solution; Adults: 2 oral inhalations (1.25 mcg/actuation) for a total dose of 2.5 mcg once daily, at the same time each day, is the usual and max dosage.
      • Leukotriene synthesis inhibitor
        • Zileuton c124
          • Zileuton Oral tablet; Adults: 600 mg PO 4 times per day, taken with meals and at bedtime.
          • Zileuton Oral tablet, biphasic release; Adults: 1,200 mg PO twice daily, within one hour after morning and evening meals.
      • Macrolide antibiotic
        • Azithromycin c125
          • Azithromycin Oral tablet; Adults: 250 to 500 mg PO 3 days per week.
      • Biologic agents r33
        • Benralizumab c126
          • Benralizumab Solution for injection; Adults: 30 mg subcutaneously once every 4 weeks for the first 3 doses, followed by 30 mg subcutaneously once every 8 weeks thereafter.
        • Mepolizumab c127
          • Mepolizumab Solution for injection; Adults: 100 mg subcutaneously once every 4 weeks.
        • Omalizumab c128
          • Omalizumab (Hamster) Solution for injection; Adults: 150 to 375 mg subcutaneously every 2 weeks or every 4 weeks. Dosage and frequency determined by baseline IgE (units/mL) and weight (kg). Adjust doses for significant changes in body weight. Do not administer more than 150 mg per injection site.
            • Risk of serious hypersensitivity reactions or anaphylaxis, and omalizumab hypersensitivity may occur after any dose of omalizumab. Omalizumab is derived from Chinese hamster ovarian cells and may be inappropriate for use by patients with known hamster protein hypersensitivity. Omalizumab is contraindicated for use by patients who have experienced a severe omalizumab hypersensitivity reaction, including anaphylaxis or a history of angioedema with the drug. Administration of omalizumab requires a specialized care setting that is equipped and prepared to manage serious hypersensitivity reactions, including anaphylaxis that can be life-threatening.
        • Reslizumab c129
          • Reslizumab Solution for injection; Adults: 3 mg/kg IV infusion once every 4 weeks. Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis.
        • Dupilumab c130
          • For eosinophilic phenotype moderate-to-severe asthma
            • Dupilumab Solution for injection; Adults: 400 mg subcutaneously initially (as two 200 mg injections), followed by 200 mg subcutaneously every other week OR 600 mg subcutaneously initially (as two 300 mg injections), followed by 300 mg subcutaneously every other week.
          • For oral corticosteroid-dependent moderate-to-severe asthma
            • Dupilumab Solution for injection; Adults: 600 mg subcutaneously initially (as two 300 mg injections), followed by 300 mg subcutaneously every other week.
      • Oral corticosteroid
        • Prednisone c131
          • Prednisone Oral tablet; Adults: 7.5 to 60 mg/day PO once daily in the morning or every other day as needed for symptom control; use lowest effective dose; alternate day therapy may produce less adrenal suppression.
  • Acute exacerbation of asthma
    • Inhaled short-acting β₂ agonist
      • Albuterol c132
        • Albuterol Pressurized inhalation, suspension; Adults: 4 to 10 oral inhalations of 90 mcg/actuation (total: 360 to 900 mcg) every 20 minutes for the first hour for mild to moderate exacerbations. After the first hour, the dose required may vary from 4 to 10 oral inhalations (360 to 900 mcg) every 3 to 4 hours up to 6 to 10 oral inhalations (540 to 900 mcg) every 1 to 2 hours, or more often.
        • Albuterol Sulfate Nebulizer solution; Adults: 2.5 mg via nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 2.5 mg every 3 to 4 hours up to 2.5 mg every 1 to 2 hours, or more often. Typical dose: 2.5 mg via nebulizer 3 to 4 times daily.
      • Levalbuterol (for patients intolerant of albuterol) c133
        • Levalbuterol Hydrochloride Nebulizer solution; Adults: 1.25 mg via nebulizer every 20 minutes for the first hour for mild to moderate exacerbation. After the first hour, 1.25 mg every 3 to 4 hours and up to 1.25 mg every 1 to 2 hours, or more often. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3 times daily, every 6 to 8 hours.
    • Mast cell stabilizer
      • Cromolyn c134
        • Cromolyn Sodium Nebulizer solution; Adults: 20 mg via nebulizer 4 times per day. Once stabilized, may be able to reduce to 3 times per day.
    • Inhaled anticholinergics
      • Ipratropium c135
        • Ipratropium Bromide Pressurized inhalation, solution; Adults: 136 mcg (8 actuations of 17 mcg/actuation) via oral inhalation every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting. Used in addition to SABA (e.g., albuterol).
        • Ipratropium Bromide Nebulizer solution; Adults: 500 mcg via nebulizer every 20 minutes for 3 doses, then as needed (for up to 3 hours) has been recommended for severe asthma exacerbation in the emergency care setting. Used in addition to SABA (e.g., albuterol).
      • Ipratropium-albuterol combination product c136
        • Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Adults: 3 mL (containing 0.5 mg ipratropium bromide; 2.5 mg albuterol per 3 mL) via nebulizer every 20 minutes for 3 doses, then as needed (usually every 4 to 6 hours).
    • Smooth muscle relaxant
      • Magnesium sulfate c137
        • Magnesium Sulfate Solution for injection; Adults: 2 g IV once.
    • Systemic corticosteroids
      • Prednisone c138
        • For mild exacerbation (outpatient)
          • Prednisone Oral tablet; Adults: 40 to 60 mg/day PO in 1 to 2 divided doses for 3 to 10 days or until the patient achieves peak expiratory flow (PEF) of 80% of personal best or symptoms resolve. Another recommendation is 40 to 50 mg/day usually for 5 to 7 days (or 1 mg/kg/day); Max: 50 mg/day.
        • For moderate to severe exacerbation (emergency department or inpatient)
          • Prednisone Oral tablet; Adults: One recommendation is 40 mg/day or 1 mg/kg/day for 5 to 7 days; Max: 50 mg/day. Alternatively, 40 to 80 mg/day PO in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best; total course: 3 to 10 days.
      • Methylprednisolone c139
        • For mild exacerbation (outpatient)
          • Methylprednisolone Oral tablet; Adult: 40 to 60 mg/day PO in 1 to 2 divided doses for 5 to 10 days.
        • For moderate to severe exacerbation (emergency department or inpatient)
          • Methylprednisolone Oral tablet; Adults: 40 mg PO once daily in the morning for 5 to 7 days. Alternatively, 40 to 80 mg/day PO in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best; total course of treatment may range from 3 to 10 days.
          • Methylprednisolone Sodium Succinate Solution for injection; Adults: 40 mg IV/IM once daily each morning for 5 to 7 days is adequate for most patients. Alternatively, 40 to 80 mg/day IV/IM in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best. Change to oral therapy as soon as feasible.
  • Exercise-induced asthma
    • Take as required before exercise; maintenance low-dose inhaled corticosteroids may also be indicated
    • Inhaled short-acting β₂ agonist
      • Albuterol c140
        • Albuterol Pressurized inhalation, suspension; Adults: 180 mcg (2 actuations of 90 mcg/actuation) via oral inhalation 15 to 30 minutes before exercise.
        • Albuterol Inhalation powder; Adults: 180 mcg (2 actuations of 90 mcg/actuation) via oral inhalation 15 to 30 minutes before exercise.
      • Levalbuterol (for patients intolerant of albuterol)
        • Levalbuterol Tartrate Pressurized inhalation, suspension; Adults: 90 mcg (2 actuations of 45 mcg/actuation) via oral inhalation 15 minutes (range, 5 to 20 minutes) before exercise.
    • Inhaled corticosteroid plus long-acting β₂ agonists
      • Budesonide-formoterol combination product c141
        • Budesonide, Formoterol Fumarate Pressurized inhalation, suspension; Adults: 1 oral inhalation of 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) 5 to 20 minutes before exercise has been used and was efficacious in a clinical trial. FDA-approved Max: 2 oral inhalations of 160/4.5 twice daily.
    • Leukotriene receptor antagonists
      • Montelukast c142
        • Montelukast Sodium Oral tablet; Adults: 10 mg PO once, given at least 2 hours before exercise. Max: 10 mg/24 hours. Patients receiving daily montelukast for another indication should not take an additional dose to prevent EIB. Rescue medications (e.g., beta-agonists) should be available.
    • Mast cell stabilizer
      • Cromolyn c143
        • Cromolyn Sodium Nebulizer solution; Adults: Inhale 20 mg via nebulization not more than 1 hour before anticipated exercise or other precipitating factor. Effective prophylaxis lasts approximately 1 to 2 hours.

Nondrug and supportive care

Patient education about self-management establishes a partnership with the patient and is a major component of care c144

  • Self-monitoring symptoms and peak flow meter use
  • Use of control chart (sample available within the National Asthma Education and Prevention Program guidelinesr1) and written asthma action plan, emphasizing difference between controller and reliever medications (sample plan available from the National Heart, Lung, and Blood Institute)
  • Supported self-management involving at least 2 hours of scheduled follow-up with health providers significantly reduced healthcare use and improved quality of life compared to less intensive review r36
  • Multidisciplinary case management may be needed for patients with severe, difficult-to-treat disease

Reduce exposure to allergen, irritant, and air pollution triggers

  • 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 specific allergen r17
    • 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 (high-efficiency particulate air) purifiers and mold abatement

Breathing exercises c145

  • Breathing exercise programs can be considered as an adjuvant to pharmacological treatment r13

Smoking cessation c146

Weight-loss interventions c147

  • Weight loss may help overweight and obese patients to improve asthma control r13

Supplemental oxygen c148

  • Indicated for SaO₂ lower than 90%
  • Nasal cannula or Venturi mask (Ventimask) to maintain SaO₂ of at least 90%
  • Noninvasive positive pressure ventilation decreases admissions, but evidence base is not strong r25
Procedures
Bronchial thermoplasty r17c149
General explanation
  • Procedure using radiofrequency energy to reduce airway smooth muscle mass
  • Administered in 3 sessions as part of a bronchoscopy
  • Variable outcomes; no consistent improvement in asthma control or reduction in hospitalization, but improved quality of life and a small decrease in exacerbations
  • Moderate risk of adverse effects
  • National Asthma Education and Prevention Program recommends against its use in patients with persistent asthma; however, it remains an option for treatment of poorly controlled asthma

Comorbidities

  • Obesity c150
    • Associated with increased risk of asthma, worsening symptoms, and decreased responsiveness to therapies r37
    • Weight loss may improve asthma control and should be encouraged
  • Allergic rhinitis c151
    • Common comorbidity that is managed with intranasal corticosteroids, antihistamines, and/or immunotherapy r1
  • Chronic rhinosinusitis with nasal polyposis c152
    • In patients with this condition, better management of rhinosinusitis can decrease asthma exacerbation
    • Subset of these patients have aspirin sensitivity that can result in severe bronchospasm; referral to specialist is indicated
  • Gastroesophageal reflux disease c153
    • Unclear role in causing asthma; uncontrolled gastroesophageal reflux disease may worsen asthma symptoms, and management of the disease is important
  • Allergic bronchopulmonary aspergillosis r1c154
    • Consider in patients who have asthma and a history of pulmonary infiltrates, IgE sensitization to as­pergillus, and/or corticosteroid dependency
    • Treat with prednisone and azole antifungal agents
  • COVID-19 infection c155
    • Asthma does not appear to significantly increase the risk of contracting COVID-19 infection or of more severe disease or death in most patients r38r39r40
    • However, some studies have found higher rates of intubation and prolonged mechanical ventilation in patients with asthma r41
    • Regular asthma medications should be continued during the COVID-19 pandemic r4r42
    • Non-severe asthma exacerbations may be managed via telehealth with a low threshold for face-to-face assessment r42
    • 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 r4
    • Avoid spirometry in patients with known or suspected COVID-19 infection; if possible, postpone spirometry and peak flow measurements while community transmission rates are concerning r4

Special populations

  • Pregnant women
    • Asthma symptoms may change during pregnancy; can improve or worsen r43
    • Monthly monitoring is recommended due to the unpredictable course of asthma during pregnancy r43
    • Asthma is undertreated during pregnancy compared with prepregnancy treatment rates
    • Maternal asthma is associated with increased risk of low birthweight, preeclampsia, gestational diabetes, cesarean delivery, perinatal mortality, and neonatal hospitalization at birth r43
      • Uncontrolled asthma, in particular, is associated with poor perinatal outcomes
    • Use stepwise approach to therapy for chronic asthma r44
      • General principles
        • Inhaled medications should be continued; used for decades without demonstrated adverse effects on the fetus r43
          • Albuterol is classified as a pregnancy risk category C drug but has good safety profile r44
          • Guidelines recommend use of whichever inhaled corticosteroid formulation was effective prepregnancy r44
          • Budesonide has the most safety documentation
        • Monoclonal antibodies should be continued during pregnancy if required for asthma control r43
        • Minimal data exists on leukotriene receptor antagonists and long-acting β₂ agonists
      • Step 1 (mild intermittent asthma): short-acting β₂ agonist as needed r44
      • Step 2 (mild persistent asthma): low-dose inhaled corticosteroid r44
      • Step 3 (moderate persistent asthma): low-dose inhaled corticosteroid and a long-acting β₂ agonist or low-dose inhaled corticosteroid and either theophylline or leukotriene receptor antagonist r44
      • Step 4 (severe persistent asthma): high-dose inhaled corticosteroid and a long-acting β₂ agonist; if needed, add long-term oral corticosteroid or high-dose inhaled corticosteroid and sustained-release theophylline r44
    • Treat asthma exacerbations according to guidelines without modification;r45undertreatment with avoidance of oral corticosteroids results in increased return visits for exacerbationr46
  • Older adults (older than 65 years) r47
    • Asthma is associated with higher morbidity and mortality in this group; reasons for this are not clearly understood
    • May not be recognized if overlapping with chronic obstructive pulmonary disease (ie, asthma-chronic obstructive pulmonary disease overlap syndrome)
    • Diagnosis is the same as with younger adults
      • Use age-adjusted values when interpreting the FEV₁/FVC ratio to avoid overdiagnosing respiratory impairment
      • Frail patients usually cannot adequately complete spirometric maneuvers; alternative monitoring with effort-independent testing may be better (ie, forced oscillation testing, if available)
    • Treatment guidelines were developed based on studies of younger adults, with little data available on older patients
      • Carefully monitor inhaler technique as cognition and dexterity declines
      • Short-acting anticholinergic medications may be useful bronchodilators in elderly patients without the cardiac adverse effects of β₂ agonists, but there are other potential risks (eg, cognitive impairment, falls, symptomatic urinary outlet obstruction, closed-angle glaucoma)
      • Inhaled corticosteroids appear to be underused and should be used as directed by guidelines. Patients on higher doses should be monitored for cataracts and decreased bone density
      • There are no studies specifically focused on the safety of inhaled long-acting β₂ agonists in elderly patients
      • Pharmacologic treatment of comorbidities may worsen asthma (eg, β-blockers, aspirin and non-steroidal agents, cholinergic agents)

Monitoring

  • Periodic monitoring of asthma control guides decisions for maintaining or adjusting therapy
    • Home self-monitoring r1
      • Instruct all patients to monitor at home; symptom-based monitoring or peak flow monitoring are similarly beneficial c156c157
      • For patients with moderate or severe persistent asthma, peak flow monitoring is preferred r1
    • Office monitoring
      • Assess asthma control, medication technique, asthma action plan, adherence, and patient concerns at every patient visit c158c159
      • Schedule office visit at 2- to 6-week intervals when starting a new treatment or changing treatment; perform spirometry when patient is stable after medication change r1c160c161
      • Schedule office visit at 1- to 6-month intervals, after asthma control is achieved r1c162
      • Schedule office visit at 3-month intervals, if step-down therapy is likely r1c163
      • Review treatment of established stable patients regularly (eg, at least every 12 months) r30
      • Perform spirometry at least every 1 to 2 years r1c164
      • A Cochrane review suggests that adults with frequent exacerbations and severe asthma may benefit from sputum eosinophil monitoring to guide need for corticosteroid initiation or step-up therapy r48c165
  • Urgent asthma review is indicated in the following circumstances: r30
    • Patient's asthma symptoms worsen despite appropriate use of controller medications
    • Patient experiences an asthma exacerbation, especially if associated with emergency department visit or urgent care, hospitalization, nocturnal awakening, difficulty in speaking, or marked impairment in activities of daily living
    • Patient has not had a routine review in the last 12 months
    • Patient has been prescribed more than 1 short-acting β agonist inhaler in the last 4 months or 3 or more during the previous year
    • Patient has been prescribed a new course of oral corticosteroids (eg, in secondary care)
  • Consider periodic ophthalmologic monitoring for cataract and bone densitometry for patients treated with high-dose inhaled corticosteroids (longer than 1 year) and/or repeated courses of oral corticosteroids r1c166c167

Complications and Prognosis

Complications

  • Complications of disease
    • Respiratory failure c168
    • Pneumothorax c169
    • Pneumomediastinum c170
    • Airway remodeling over time with worsening airflow obstruction c171
    • Death c172
  • Complications during surgical procedures
    • Assess asthma control and maximize lung function before planned surgery
    • Make anesthesiologist aware of recent corticosteroid use
  • Complications of steroid pharmacotherapy
    • Inhaled corticosteroids
      • Increased incidence of pneumonia, especially at higher doses r49
      • May increase risk of cataracts and osteoporosis
      • Increased risk of oral candidiasis
    • Oral corticosteroids
      • Increased risk of oral candidiasis, osteoporosis, cataracts, and hyperglycemia
    • 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, especially for perimenopausal women

Prognosis

  • Good with mild intermittent disease or persistent disease (if well controlled)
  • Risk factors for death from asthma include: r1
    • Previous exacerbations requiring ICU admission and/or intubation
    • 3 or more emergency department visits for asthma and/or 2 or more hospitalizations for asthma in the past year r1
    • Hospitalization or emergency department visit in the past 30 days r1
    • Use of more than 2 canisters of short-acting β₂ agonist per month r1
    • Current use or recent use of systemic corticosteroids
    • Patient has difficulty perceiving severity of exacerbations

Screening and Prevention

Screening c173

At-risk populations

  • A 2007 American Thoracic Society report concluded that there was insufficient evidence to support the adoption of population-based asthma screening r50
  • No universally accepted screening guideline exists for exercise-induced asthma in athletes, although some sporting organizations have established screening programs for their internationally competitive athletes r3

Prevention

  • Avoid known triggers of exacerbation r1c174c175
  • Smoking cessation c176
  • Annual influenza vaccine to prevent influenza-induced exacerbation r1c177
  • Pneumococcal vaccination (PPSV23 unless patient has criteria for PCV13 as well) if not previously administered r51c178
  • Education regarding the use of inhalers, peak flow meter, spacers, asthma action plan, and adherence to recommended treatments c179
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