Asthma

Asthma is a chronic lung disease characterized by airway inflammation that manifests as intermittent episodic coughing, wheezing, dyspnea, and chest tightness. The symptoms and severity of asthma are variable and often driven by hyperresponsiveness to environmental stimuli, including respiratory infections, allergens, exercise, weather, and emotions. Physiologically, the disease is characterized by variable expiratory airflow limitation that is usually reversible with appropriate therapy or preventable by avoiding triggers.

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

Assessment

Symptoms: The pretest probability for a diagnosis of asthma is increased in patients with typical episodic patterns of wheeze, dyspnea, and chest tightness following exposure to triggers (e.g., allergen, exercise, viral infection). Because asthma symptoms may be nonspecific, certain historical features reduce the likelihood of the diagnosis, including lack of improvement with asthma-directed therapy; onset after age 50 years; history of extensive cigarette smoking; or symptoms such as chest pain, syncope, or palpitations.

History: A personal or family history of atopy in a patient with characteristic symptoms further supports this diagnosis.

Physical exam: The utility of a physical exam for asthma is often limited.

• Wheezing is the most distinguishing feature, but it does not predict the severity of underlying disease (and can be absent outside of exacerbation). The asthmatic wheeze is described as polyphonic, high-pitched, and musical. It is typically worse on expiration and multifocal in location.

• Allergic rhinitis and nasal polyposis may coexist with asthma. For common exam findings in allergic rhinitis, please see the Allergy/Immunology rotation guide.

• Use of accessory muscles of ventilation, sternal retraction at the onset of a breath, >10 mm Hg of pulsus paradoxus are associated with more-severe cases.

Spirometry: Testing is necessary for diagnosis and to distinguish reversible airflow limitation characteristic of asthma versus other causes of dyspnea, such as chronic obstructive pulmonary disease (COPD). (See spirometry testing below.)

Classification of asthma: Asthma is typically categorized as intermittent or persistent based on an assessment of patient-reported symptoms and measured lung function. The determination of impairment and evaluation of risk for future exacerbations are used to guide asthma therapy.

Investigations

Spirometry: Spirometry testing is fundamental to both diagnosis and follow-up of asthma. Ideally, baseline spirometry is obtained prior to empiric initiation of bronchodilator therapy. When the patient is symptomatic, spirometry will show a reduced forced expiratory volume in one second (FEV₁) and evidence of airway obstruction (i.e., reduced FEV₁/forced vital capacity [FVC] ratio). After administration of a short-acting bronchodilator, an increase in FEV₁ or FVC >200 mL and ≥12% from baseline is diagnostic of a bronchodilator response and consistent with asthma. Diurnal variation of peak expiratory flow >10% or visit-to-visit variability of >200 mL and ≥12% can also be diagnostic.

Bronchoprovocation testing (the methacholine challenge): The diagnosis of asthma can also be made by demonstrating airway hyperresponsiveness via the methacholine challenge test.

Peak expiratory flow (PEF): PEF is measured during a brief, forceful exhalation using a simple meter. PEF can be measured to monitor a patient rather than as a diagnostic tool.

Blood testing: Routine blood testing is not necessary for a diagnosis of asthma but may be indicated to aid in treatment decisions if the patient has normal spirometry and no response to bronchodilator testing.

• Complete blood count (CBC) with differential and serum IgE can be used to evaluate candidacy for advanced therapies or to elucidate other diagnoses (e.g., eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis, or allergic bronchopulmonary aspergillosis).

• Allergen testing may be helpful to inform trigger avoidance in patients with an allergic component to their disease.

The fraction of nitric oxide in the exhaled air (FeNO) is associated with airway inflammation. Levels above 30 ppb (in a nonsmoker on no treatment) help confirm an asthma diagnosis.

Imaging: In the absence of comorbid illness, chest radiography is almost always normal.

Phenotypes: Identifiable clusters of clinical, demographic, and some pathophysiological features; phenotype-directed therapy is available for some phenotypes.

• Allergic asthma: Often begins in childhood and is associated with a history of atopy. Patients in this group usually respond well to inhaled glucocorticoids.

• Nonallergic asthma

• Adult-onset asthma: Some adults, particularly women, present with adult-onset asthma and often require higher-dose glucocorticoids or are refractory to glucocorticoid treatment; occupational asthma should be ruled out in this group of patients.

• Asthma with persistent airflow obstruction: Long-standing asthma can lead to persistent or incompletely reversed airway obstruction secondary to airway remodeling.

• Asthma with obesity

Treatment

Glucocorticoids: In contrast with primary use of bronchodilators in the treatment for COPD, the hallmark of treatment for asthma is inhaled glucocorticoids.

• Stepwise approach: The 2020 update of the U.S. National Asthma Education and Prevention Program (NAEPP) and the 2023 update of the Global Initiative for Asthma (GINA) guidelines recommend that treatment of asthma involve a continuous cycle of assessment, adjustment, and review and a stepwise approach to the number of medications and frequency of dosing with the objective of using the least amount of medication needed to control symptoms and reduce risk for exacerbations. The graphics below detail the stepwise approach of both groups.

• Treatment should begin with proper patient education, trigger avoidance, and management of comorbidities. Proper inhaler technique is fundamental to adequate medication delivery. See a brief video of multidose inhaler technique.

• Some debate exists about whether an as-needed short-acting beta-agonist (SABA) should be used alone or with an inhaled glucocorticoid. GINA advocates for starting therapy with as-needed budesonide-formoterol combination inhalers (inhaled glucocorticoids with a long-acting beta-agonist), whereas NAEPP continues to support the use of a short-acting bronchodilator (e.g., albuterol) alone as a first step, specifically for intermittent asthma. However, the subsequent step in the NAEPP guideline is as-needed budesonide-formoterol combination inhaler. An alternative is for patients to take low-dose inhaled glucocorticoids whenever short-acting bronchodilators are used.

• If the priority is symptom control (as opposed to prevention of exacerbation), daily low-dose inhaled glucocorticoids can be used instead of as-needed budesonide-formoterol.

• An alternative to the addition of a long-acting beta-agonist (LABA; e.g., formoterol) to a glucocorticoid inhaler is the addition of a leukotriene modifier or a long-acting antimuscarinic. These agents can also be added on to treatment with an inhaled glucocorticoid-LABA combination if additional controller medications are needed.

• If further control is needed, the patient should be referred to an asthma specialist to rule out other asthma-associated conditions and to consider biologic therapy.

(Source: ©2023 Global Initiative for Asthma, reprinted with permission. Available from https://ginasthma.org/2023-gina-main-report/)

(Source: 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 2020.)

Monoclonal antibodies: The introduction of monoclonal antibodies targeting inflammatory pathways central to asthma pathogenesis has transformed asthma therapy; these are usually used under the supervision of asthma care specialists. An algorithm for considering biologic therapy and targets of potential therapies is detailed in the figure below.

(Source: Biologic Therapies for Severe Asthma. N Engl J Med 2022.)

Asthma Exacerbation

Asthma exacerbation is common and potentially life-threatening if not managed emergently. The following approach can be used to manage an acute exacerbation.

Asthma action plan: Ideally, patients assess the severity of an attack by following an individualized “asthma action plan.” Asthma action plans are based on symptoms and peak expiratory flow (PEF) measurements and provide clear instructions on how to detect and respond to changes in these parameters. An example plan is available here.

(Source: Pocket Guide for Asthma Management and Prevention. ©2022 Global Initiative for Asthma, reprinted with permission.)

(Source: Emergency Treatment of Asthma. N Engl J Med 2010.)

(Source: Emergency Treatment of Asthma. N Engl J Med 2010.)