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Asthma

Last updated: July 27, 2021

Summarytoggle arrow icon

Asthma is a chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic acute asthma exacerbations, and reversible airflow obstruction. Allergic (extrinsic) asthma usually develops in childhood and is triggered by allergens such as pollen, dust mites, and certain foods. Nonallergic (environmental or intrinsic) asthma usually develops in patients over the age of forty and can have various triggers, such as cold air, medications (e.g., aspirin), exercise, and viral infections. The cardinal symptoms of asthma are intermittent dyspnea, cough, and high-pitched expiratory wheeze. Symptoms remit in response to antiasthmatic medications or resolve spontaneously upon removal of the trigger. In a patient with typical clinical features of asthma, diagnosis is confirmed by demonstrating reversible bronchial obstruction on pulmonary function tests. Additional tests may be required to evaluate for asthma triggers and comorbidities that increase the risk of acute exacerbations. Treatment regimens differ based on the severity of asthma but primarily consist of different combinations of beta-2 agonists and inhaled corticosteroids (ICS). Systemic corticosteroids are usually reserved for patients with severe persistent asthma. To achieve symptomatic control and minimize the risk of exacerbations, comorbidities should be managed and exposure to asthma triggers minimized Follow-ups are essential to monitor the response to therapy and to adjust treatment regimens in a stepwise manner.

Acute asthma exacerbations” are discussed in their own article.

  • Asthma: a chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic exacerbation (asthma attacks), and reversible airflow obstruction; manifests with reversible cough, wheezing, and dyspnea
  • Acute asthma exacerbation: a reversible worsening of the clinical features of asthma that develops over a short period of time and can progress to life-threatening asthma; may be the first manifestation of asthma in some patients
  • Allergic asthma: the most common type of asthma; begins with intermittent symptoms in childhood and is usually associated with atopy (e.g., eczema, rhinitis) and a good response to treatment
  • Nonallergic asthma: an uncommon type of asthma that is not related to atopy and is typically associated with a poor response to standard treatment (e.g., ICS)
  • See also “Subtypes and variants.”
  • Prevalence
    • 5–10% of the US population
    • More common in black than white patients
    • For unknown reasons, the prevalence of asthma has been increasing over the past 20 years. [1]
  • Sex: differs depending on age of onset
    • > in patients < 18 years
    • > in patients > 18 years
  • Age of onset

References:[2]

Epidemiological data refers to the US, unless otherwise specified.

Asthma triggers
Allergic asthma
(extrinsic asthma)
Nonallergic asthma
(intrinsic asthma)
  • Cardinal risk factor: atopy
  • Environmental allergens: pollen (seasonal), dust mites, domestic animals , mold spores
  • Allergic occupational asthma: from exposure to allergens in the workplace (e.g., flour dust)

Childhood exposure to second-hand smoke increases the risk of developing asthma!.

Common underlying pathophysiology

Asthma is an inflammatory disease driven by T-helper type 2 cells (Th2-cell) that manifests in individuals with a genetic predisposition. It consists of the following three pathophysiologic processes:

  1. Bronchial hyperresponsiveness
  2. Bronchial inflammation
  3. Endobronchial obstruction caused by:

Type-specific pathophysiology


Characteristic examination findings may not be present between episodes of asthma exacerbation!

  • Exercise-induced asthma: asthma in which bronchoconstriction is triggered by physical exertion; treated with inhaled SABAs shortly prior to exercise and reduction of potential environmental triggers (e.g., cold air, allergens) [3][6]
  • Adult-onset asthma: an uncommon phenotype in which patients present with symptoms for the first time in adulthood; more likely to be nonallergic and involves a poor response to standard treatment
  • Cough variant asthma: : a form of asthma in which the predominant symptom is chronic dry cough, without other characteristic symptoms of asthma (e.g., wheezes, congestion, dyspnea)

General principles [3][6][7]

Pulmonary function testing [3][6][7]

  • Characteristic findings (observable using any of the PFT modalities described below)
Diagnostic testing in asthma [6][7]
PFT modality Supportive findings Test characteristics
Peak flow meter (PFM)
  • Portable device
  • Allows rapid serial measurement of PEFR
  • Less accurate than spirometry
Spirometry
  • FEV1
  • FEV1/FVC ratio
  • Excessive variability of FEV1 or FEV1/FVC:
    • Between visits
    • In response to therapy
    • In response to physiological challenges
  • Greater accuracy than PFM
  • Can identify baseline parameters (“personal best”)
  • Difficult to perform compared to PFM
  • Greater logistical challenge
Bronchial reversibility tests
  • Added to spirometry or PFM as part of the first-line investigations to assess reversibility or responsiveness of airflow limitation to treatment
Bronchial provocation tests
  • Second-line test if bronchial reversibility testing is inconclusive

A normal FEV1 in a patient who is symptomatic at the time of testing makes a diagnosis of asthma less likely.

Asthma and COPD both cause an obstructive pattern on PFTs. Complete reversibility of bronchial obstruction after bronchodilator administration rules out COPD.

Adjunctive studies

Comparison of asthma and COPD

Asthma COPD
Age at diagnosis
  • Typically > 40 years old
Etiology
  • Allergic and nonallergic (see “Etiology” above)
  • Cigarette consumption (90% of cases)
Clinical presentation
  • Insidious onset
  • Chronic progression over years
Bronchial obstruction
  • Reversible
  • Persistent

Medication

Consider allergic bronchopulmonary aspergillosis if respiratory symptoms worsen and/or features of bronchiectasis develop despite asthma treatment.

The differential diagnoses listed here are not exhaustive.

General principles [3][6][7]

The key to long-term asthma management is a continuous cycle of clinical assessment and treatment adjustment.

Approach [3][6][7]

  1. Confirm diagnosis of asthma.
  2. Assess severity (see “Classification of asthma severity”).
  3. Initiate antiasthmatic medication based on severity.
  4. Manage comorbidities; reduce exposure to asthma triggers (see “Adjunctive therapy”).
  5. Monitor response to therapy.
  6. Adjust treatment (step up or step down) based on response to therapy.
  7. Schedule frequent follow-ups.

Long-term follow-up and reassessment of asthma symptom control are recommended every 1–6 months.

  • The National Asthma Education and Prevention Program (NAEPP) guidelines classify asthma severity as intermittent or persistent in individuals who have not yet been initiated on long-term therapy based on the following: [3][6]
    • Symptom severity
    • Degree of impairment in lung function
    • Frequency and risk of exacerbations
  • The 2020 Global Initiative for Asthma (GINA) guidelines classify severity into well-controlled, partly-controlled, and uncontrolled based on the minimum level of long-term treatment required to achieve symptom control (not detailed here). [3][7]

Classification of asthma severity in adults and children ≥ 12 years of age (NAEPP) [3][6]

The most severe category of any feature determines the severity.

Class Symptom severity Lung function Exacerbations requiring systemic corticosteroids
Intermittent asthma
  • Symptom frequency: ≤ 2/week
  • Waking up because of symptoms: ≤ 2/month
  • No interference with daily activities
  • Use of SABA ≤ 2 days/week
  • Normal between exacerbations
  • FEV1 > 80% predicted
  • Normal FEV1/FVC
  • ≤ 1/year
Mild persistent asthma
  • Symptom frequency: > 2/week (but not on the same day)
  • Waking up because of symptoms: 3–4/month
  • Use of SABA > 2 days/week
  • Minor limitation of daily activities
  • ≥ 2/year
Moderate persistent asthma
  • Symptom frequency: daily
  • Waking up because of symptoms: > 1/week (but not consecutively)
  • Some limitation of daily activities
  • Daily use of SABA
Severe persistent asthma
  • Daily symptoms throughout the day
  • Waking up because of symptoms: every night
  • Extreme limitation of daily activities
  • Use of SABA several times a day
  • Different combinations of daily and rescue therapies are given in a stepwise fashion until symptoms are controlled. [3][6]
  • In treatment-naive patients, the initial treatment regimen should be guided by the severity class of asthma, clinical judgment, and patient preference.
  • Consult asthma specialists for treatment of step 4 and higher; consider specialist consultation for step 3 treatment. [6]
  • The recommendations here are consistent with the 2020 NAEPP guidelines; in areas in which they differ, the 2020 GINA guideline recommendations are also discussed.
  • Treatment of patients ≥ 12 years is detailed here; regimens differ according to the patient's age (see “Tips & links” for guidance on management of asthma in infants and children < 12 years of age).

Stepwise pharmacological treatment of chronic asthma in adults and children ≥ 12 years old (NAEPP)
See “Overview of asthma medications” for dosages. [3][6][7]

Treatment steps

Daily therapy

Single inhalers are preferred for combination medications.

Rescue inhaler (as needed)

Step 1 (intermittent asthma)

  • None [10][11][12]

Step 2 (mild persistent asthma)

Preferred
Alternatives

Step 3 (moderate persistent asthma)

Preferred

Alternatives

Step 4 (moderate to severe persistent asthma)

Preferred
Alternatives

Step 5 (severe persistent asthma)

Preferred
Alternatives
  • Medium- to high-dose ICS-LABA
  • High-dose ICS, PLUS LTRA
  • Consider adding immunotherapy.

Step 6 (severe persistent asthma)

  • Assess response to therapy in 2–6 weeks
  • Good response for ≥ 3 consecutive months: Consider a gradual decrease in pharmacotherapy (step down).
  • Inadequate response
    • Assess treatment adherence, inhaler technique.
    • Manage comorbidities and environmental factors (see “Adjunctive therapy” below).
    • Consider advancing treatment to the next step (step up).

Any change in treatment regimen should be monitored closely with regular follow-ups.

General principles [3][6][7]

Commonly used medications [3][6][7]

Overview of commonly used asthma medications [3][6]

Dosages detailed here are for adults or children ≥ 12 years of age
(DPI: dry powdered inhaler; MDI: metered dose inhaler)

Class Examples Mechanism and uses Adverse effects Contraindications Interactions
Short-acting beta-2 agonists (SABA)
Long-acting beta-2 agonists (LABA)
Inhaled corticosteroids (ICS) [3]
Oral corticosteroids

ICS-LABA (combination inhaled corticosteroid and long-acting beta-2 agonist)

  • Combination of action of ICS plus bronchodilation
  • Dual use: long-term maintenance PLUS reliever for adolescents and adults
Leukotriene receptor antagonists (LTRAs)
  • Montelukast
  • Zafirlukast
  • Hypersensitivity
  • No major interactions
Long-acting muscarinic antagonists (LAMA)
Short-acting muscarinic antagonists (SAMA)

Inhaled corticosteroids do not take full effect until they have been used for approx. 1 week.

Additional medications

These medications are not commonly used in clinical practice. They are typically reserved for special cases under the guidance of a specialist.

Overview of additional asthma drugs
Agents Indications Mechanism of action Adverse effects Contraindications Interactions
Leukotriene pathway modifiers (e.g., zileuton) [13]
  • Hypersensitivity
  • Liver disease
Mast cell stabilizers (chromones; e.g., cromolyn sodium) [14]
  • Preventive treatment prior to exercise
  • Prevent release of inflammatory mediators from mast cells

  • Throat irritation, cough
  • Hypersensitivity
  • No data available
Methylxanthines (e.g., theophylline)
  • Limited use
  • Cardiotoxic
  • Neurotoxic
Biologics

Anti-IgE antibodies (omalizumab) [15]

  • Select cases of severe asthma
  • Binds to serum IgE↓ expression of high-affinity IgE receptors (FcεRI) on mast cells and basophils
  • Prevents binding of IgE to FcεRI↓ release of inflammatory mediators → asthma symptoms and exacerbations
  • Hypersensitivity
  • No data available
IL-5 antibodies (e.g., mepolizumab, reslizumab,benralizumab) [16]
  • Refractory severe eosinophilic asthma

Theophylline is no longer routinely prescribed due to the risk of toxicity. It is used solely as an adjunctive or alternative therapy.

The following drugs are not effective during an acute asthma attack: LABAs, leukotriene pathway modifiers, theophylline, mast-cell stabilizers, biological agents!

These measures should be optimized in all patients to reduce antiasthmatic medication requirements and decrease the frequency of acute asthma exacerbations. [3][6][7]

  • Reducing exposure to triggers or allergens
  • Managing comorbidities
  • Reducing the risk of infection-induced exacerbations
  • Lifestyle recommendations
    • Provide information and tools for self-monitoring and self-management (e.g., written action plan, peak flow meter).
    • Encourage physical activity, especially in younger patients.
    • Smoking cessation
  • Social interventions [17][18][19]
    • Screen for systemic barriers to care and socioeconomic/environmental risk factors contributing to poor outcomes.
    • Provide support to enhance access to care, treatment adherence, and sustainable functional improvement.

Controlling modifiable risk factors (e.g., smoking cessation) and comorbidities (e.g., GERD, sinusitis) can lead to better symptom control, often allowing for a step down in treatment.

  • Asthma in pregnancy
    • Asthma symptoms may be worse, better, or unchanged during pregnancy.
    • Same stepwise management as with other patients
    • Inhalation treatments preferred
    • Poorly managed asthma can increase the risk of pregnancy complications (e.g., preeclampsia, premature birth, congenital abnormalities).
    • Monthly monitoring of asthma is recommended.
  • Children under 5 years of age
    • Asthma in patients under 5 years of age is challenging to diagnose and is often underdiagnosed, as children in this age group are not typically able to adequately perform the spirometric maneuvers.
    • Regimens containing corticosteroids are preferred as initial therapy in infants and young children; see “Tips & links” for details on treatment regimens and dosages. [6]
    • Young children (< 5 years) may require nebulizers because of difficulty using inhalers. [3]
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