Asthma

Asthma is a chronic disease characterized by airway hyper-responsiveness, airway inflammation, and reversible airway obstruction.

Pathophysiology

Multiple inflammatory cell types and inflammatory mediators are implicated in the pathophysiology of asthma, as illustrated in the following figure:

(Source: Severe and Difficult-to-Treat Asthma in Adults. N Engl J Med 2017.)

Although the natural history of asthma is markedly variable, patterns of disease include transient early symptoms and late-onset persistent symptoms. Most children will experience significant improvement or resolution of asthma symptoms by early adulthood.

Risk Factors

Risk factors for increased severity and/or persistence of disease include:

• food allergy

• severe atopy

• elevated IgE level

• maternal history of asthma

• medication nonadherence

• overuse of short-acting bronchodilators

• increased utilization of emergency department (ED) or urgent care centers 

Diagnosis and Assessment

Initial evaluation consists of establishing the diagnosis of asthma. Symptoms of asthma include recurrent episodes of dry cough (often worse with exertion or at night), wheezing, and dyspnea.

Differential diagnosis of pediatric asthma includes:

• vocal cord dysfunction

• foreign body aspiration

• tracheobronchomalacia

• fixed-airway obstruction from external compression (e.g., vascular rings)

Identifying triggers: Identifying asthma triggers is a key component to management. The history helps identify exposures to triggers that stimulate airway inflammation including:

• upper-airway infections

• aeroallergens (e.g., pets, molds, dust mites)

• exercise

• smoke (tobacco exposure, including use of electronic cigarettes)

• cold air

• hot, humid air

• stress and emotion

Assessment of impairment and risk: The focus of follow-up visits is to evaluate the degree of asthma control and determine whether adjustments in medication are needed. The assessment of disease severity focuses on social and physical impairment (the frequency and intensity of symptoms and functional limitations) and risk (the likelihood of future exacerbations and progression of disease). The degree of impairment and risk help to guide medication choices.

Components of the history consistent with impairment from asthma include exertional or nocturnal cough, school absences, difficulty participating in physical activities, impaired sleep, and increased frequency of albuterol use.

Asthma risk is determined by the frequency of oral glucocorticoids, hospital admissions, and emergency visits for asthma exacerbations.

Supportive Diagnostic Tests

• spirometry

• • An obstructive pattern (as seen in asthma) shows reduced FEV₁/FVC (forced expiratory volume in one second/forced vital capacity) with either normal or decreased FEV₁, depending on severity of obstruction.

  • A positive response to bronchodilator consists of an increase in the FEV₁ of >12% or 200 mL — this signifies reversible airway obstruction and helps make the diagnosis of asthma.

  • Spirometry is generally obtainable starting at age 6 to 7 years; however, interpretation may be limited by reproducibility.

(Figure created by Mengdi Lu.)

• chest radiograph

• • hyperinflation, flattening of the diaphragms

  • bronchial-wall thickening

• other laboratory tests consistent with asthma in the appropriate clinical context:

• • elevated serum IgE and positive specific IgE

  • allergy skin testing

  • methacholine challenge

Management

The pharmacologic mainstays of asthma therapy are bronchodilators and glucocorticoids:

• Short-acting as-needed bronchodilators provide quick relief of symptoms and include beta-agonists (e.g., albuterol) and anticholinergics (e.g., ipratropium).

• Asthma controller medications are taken daily with the goal of reducing persistent asthma symptoms and preventing exacerbations; classes of controller medications include:

• • Inhaled glucocorticoids with or without a long-acting beta-agonist (LABA) are the mainstay of asthma maintenance through their anti-inflammatory effect. LABAs delivered in combination with inhaled glucocorticoids may improve asthma control, however they should not be used as monotherapy.

  • A leukotriene receptor antagonist (LTRA): may be a useful adjunct to inhaled glucocorticoids and represent a glucocorticoid-sparing agent. Montelukast, the most commonly used LTRA, is less effective compared to inhaled glucocorticoids as monotherapy. Potential side effects include nightmares or changes in behavior.

  • A long-acting muscarinic antagonist (LAMA): may be a useful adjunct to therapy in patients with asthma not well controlled on the above maintenance therapies. Tiotropium is approved in children >6 years old.

  • Methylxanthines: are rarely used but may be indicated in patients who cannot tolerate the above medications. Use is limited by the need for frequent serum levels to maintain a therapeutic window.

Management goals: The goal of management is full participation in all activities while minimizing the amount of medication required to control symptoms. Dosing of inhaled glucocorticoids and glucocorticoid/LABA combination therapies is guided by degree of asthma control.

Consider initiating or adjusting asthma controller therapy in the following circumstances:

• consistently requiring bronchodilator use more than two times per week

• evidence of functional impairment (e.g., frequent nighttime awakenings or physical activity limitations) due to asthma symptoms

• severe exacerbations requiring hospital admission

Short-term follow-up after initiation of controller therapy is recommended to monitor control. Selection of a controller therapy necessitates attention to the optimal mode of drug delivery (nebulizer vs. metered-dose inhaler with spacer), medication cost, potential adverse effects, and individual patient characteristics.

Delivery of medications: Most asthma medications are delivered via nebulizer machine or an inhaler with spacer device. The goal is to use the delivery method that is most effective for the family. It is acceptable to use an inhaler with spacer regardless of the child’s age if proper technique can be demonstrated. An inhaler with spacer delivers up to twice as much medication to the lower airways compared to delivery via nebulizer. When using an inhaler, a spacer must be used for optimal delivery, including by adolescents.

Medication adherence: Identifying and addressing factors associated with poor medication adherence is important, including parental health literacy, complex family schedules, and perceptions of asthma severity. Regular follow-up provides an opportunity to assess asthma control, address patient and parental concerns, and adjust spacer technique. Patient and family asthma education is a cornerstone of management, including provision of an asthma action plan.

Biologics: Subsets of children with difficult-to-treat severe asthma may benefit from biologic drugs. Three biologics are FDA-approved for use in pediatric patients: Omalizumab, an anti-IgE monoclonal antibody, is approved for use in moderate-to-severe asthma and perennial aeroallergen sensitization in children >6 years; mepolizumab, an anti-interleukin (IL)-5 monoclonal antibody, is approved for use in severe eosinophilic asthma in children >12 years; and dupilumab, an IL-4 receptor antagonist, is approved for use in moderate-to-severe asthma in children aged 12 years and older. Development of new drugs in the pipeline, including novel asthma biologics, is informed by an emerging understanding of airway inflammatory phenotypes.

Referral to a Pulmonologist

For many patients, asthma is managed by a primary care physician. Consider referral to a pulmonologist in the following circumstances:

• life-threatening asthma exacerbation

• asthma hospitalization

• atypical signs and/or symptoms (less-than-expected response to bronchodilators or glucocorticoids)

• requiring escalating doses of daily medications and/or frequent courses of oral glucocorticoids

• consideration for biologic therapies

• consideration for additional diagnostics (e.g., pulmonary-function tests, bronchoscopy)