Summary
Asthma is a chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic exacerbations (asthma attacks), 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, medication (e.g., aspirin), exercise, and viral infection. The cardinal symptoms of asthma are intermittent dyspnea, coughing, and high-pitched expiratory wheezing. Symptoms remit in response to antiasthmatic medication or resolve spontaneously upon removal of the trigger. Confirmation of the diagnosis involves pulmonary function tests, allergy tests, and chest x-ray. First-line treatment consists of inhaled bronchodilators (e.g., short-acting beta-2 agonists) for acute exacerbations and inhaled corticosteroids (e.g., budesonide) for long-term asthma control. Patients should be taught the correct usage of inhalers for self-medication and measurement of peak expiratory flow (PEF) to self-monitor disease progression and severity. Severe asthma exacerbation can be life-threatening and may require emergency treatment and/or hospitalization.
Epidemiology
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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 at onset
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Age of onset
- Allergic asthma: typically in childhood
- Nonallergic asthma: typically > 40 years
References:[2][3]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
The exact etiology of asthma remains unknown. Known risk factors for asthma include the following:
- Family history of asthma
- Past history of allergies
- Atopic dermatitis
- Low socioeconomic status
Childhood exposure to second-hand smoke increases the risk of developing asthma!
The following factors can also act as initial triggers of asthma or exacerbate an existing condition:
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Allergic asthma (extrinsic 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)
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Nonallergic asthma (intrinsic asthma)
- Viral respiratory tract infections (one of the most common stimuli, especially in children) [1]
- Cold air
- Physical exertion (exercise-induced asthma)
- Gastroesophageal reflux disease (GERD): often exists concurrently with asthma
- Chronic sinusitis or rhinitis
- Medication: aspirin/NSAIDS (aspirin-induced asthma); , beta blockers
- Stress
- Irritant-induced asthma; (e.g., from exposure to solvents, ozone, tobacco or wood smoke, cleaning agents)
References:[2][3]
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:
- Bronchial hyperresponsiveness
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Bronchial inflammation
- Symptoms are primarily caused by inflammation of the terminal bronchioles, which are lined with smooth muscle but lack the cartilage found in larger airways.
- Overexpression of Th2-cells → inhalation of antigen results in production of cytokines (IL-3, IL-4, IL-5, IL-13) → activation of eosinophils and induction of cellular response (B-cell IgE production) → bronchial submucosal edema and smooth muscle contraction → bronchioles collapse [4][5]
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Endobronchial obstruction caused by:
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Increased parasympathetic tone
- Reversible bronchospasm
- Increased mucus production
- Mucosal edema
- Hypertrophy of smooth muscle cells
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Increased parasympathetic tone
Some forms of asthma have specific pathophysiologies:
- Allergic asthma: IgE-mediated type 1 hypersensitivity to a specific allergen; ; characterized by mast cell degranulation; and release of histamine after a prior phase of sensitization
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Nonallergic asthma
- Irritant asthma: irritant enters lung → ↑ release of neutrophils → submucosal edema → airway obstruction
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Aspirin-induced asthma (NSAID-exacerbated respiratory disease) is characterized by the Samter triad:
- Inhibition of COX-1 → ↓ PGE2 → ↑ leukotrienes and inflammation → submucosal edema → airway obstruction
- Chronic rhinosinusitis with nasal polyposis
- Asthma symptoms
References: [3]
Clinical features
Chronic/persistent signs and symptoms
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Mild to moderate signs and symptoms
- Persistent, dry cough that worsens at night, with exercise, or on exposure to triggers/irritants (e.g., cold air, allergens, smoke)
- End-expiratory wheezes
- Dyspnea
- Chest tightness
- Chronic allergic rhinitis with nasal congestion
- Severe signs and symptoms
- Cough variant asthma
Acute asthma attack
- Definition: acute, reversible episode of lower airway obstruction that may be life-threatening
Clinical features | Mild | Moderate | Severe |
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Symptoms | |||
Breathlessness | While walking | While at rest | At rest |
Position | Can lie down | Prefers sitting | Hunched over |
Ability to speak | Sentences | Phrases | Individual words |
Alertness | May be agitated | Usually agitated | Agitated |
Signs | |||
Respiratory rate | Increased | Increased | Often > 30/minute |
Wheezing | Moderate, often only end-expiratory | Loud; throughout exhalation | Throughout inhalation and exhalation; can also be absent |
Use of accessory muscles | Rarely | Commonly | Usually |
Pulse/minute | < 100 | 100–120 | > 120 |
Pulsus paradoxus | Absent | May be present | Often present |
PCO2 | < 42 mm Hg | > 42 mm Hg | ≥ 42 mm Hg |
SaO2 | > 95% | 90–95% | < 90% |
Clinical examination
- Auscultation (characteristic findings are usually only present during acute attacks)
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Percussion
- Hyperresonant sound
- Inferior displacement and poor movement of the diaphragm
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In severe attacks
- Altered level of consciousness
- Cyanosis
Characteristic examination findings may not be present between episodes of asthma exacerbation!
References: [5][8][2][9]
Differential diagnoses
- The differential diagnosis of chronic cough and the causes of dyspnea are both addressed in other articles.
- The other main obstructive lung disease is COPD, which is compared with asthma in the table below.
Comparison of asthma and COPD | ||
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Asthma | COPD | |
Age at diagnosis |
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Etiology |
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Clinical presentation |
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Obstruction |
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Medication |
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References:[2]
The differential diagnoses listed here are not exhaustive.
Diagnostics
A combination of clinical findings ; and objective measurement of pulmonary function (for adults and children ≥ 5 years of age) is needed to confirm the diagnosis and assess the severity of asthma.
Evaluation of pulmonary function
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Pulmonary function testing (spirometry)
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First-line diagnostic test for confirmation of the diagnosis in patients ≥ 5 years of age.
- Shows signs of obstructive lung disease with increased airway resistance → ↓ FEV1, ↓ Tiffeneau index (FEV1/FVC ratio)
- Obstruction is reversible with bronchodilators → diagnostic confirmation via post-bronchodilator test
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First-line diagnostic test for confirmation of the diagnosis in patients ≥ 5 years of age.
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Methacholine challenge test (bronchoprovocation test)
- Second-line diagnostic test if pulmonary function testing is nondiagnostic
- Evidence of bronchial hyperresponsiveness after inhalation of methacholine
- Positive if FEV1 reduced ≥ 20%
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Chest x-ray
- Usually only indicated in patients with severe asthma to exclude differential diagnoses (e.g., pneumonia, pneumothorax)
- Normal in mild cases
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Signs of pulmonary hyperinflation in cases of severe asthma
- Low, flattened diaphragm
- Wide intercostal spaces
- Barrel chest
Laboratory studies and further workup
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Pulse oximetry and blood gas analysis (ABG)
- Blood gas analysis should be performed if oxygen saturation (SpO2) is < 94%.
- Findings on ABG
- Initially: ↓ pCO2, ↑ pH, ↓ pO2 leading to type 1 respiratory failure
- Ultimately: severe respiratory distress: ↑ pCO2, ↓ pH, and ↓↓ pO2 leading to type 2 respiratory failure
Patients with acute asthma exacerbations initially have ↓ PCO2 and respiratory alkalosis (↑ pH) due to tachypnea. Rising PCO2 is a sign of respiratory fatigue and impending respiratory failure! ICU admission and intubation should be considered.
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In allergic asthma
- Antibody testing, total IgE (increased), allergen-specific IgE (increased)
- CBC: possibly eosinophilia
- Skin allergy tests: skin prick testing (SPT) or intradermal skin testing
- In asthma triggered by infection: elevated inflammatory markers
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Sputum sample
- Curschmann spirals (whorled mucous plug in sputum that is formed by shed bronchial epithelium)
- Charcot-Leyden crystals (histopathologic finding in patients with eosinophilic inflammation and/or proliferation)
- and/or Creola bodies (aggregate of desquamated epithelial cells) [6]
Classification of asthma severity at initial assessment for children ≥ 12 years and adults
The following table allows for classification of asthma severity in the initial assessment of patients who are not yet taking asthma control medication.
Classification of asthma severity | ||||
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Mild intermittent asthma | Mild persistent | Moderate persistent | Severe persistent | |
Symptoms (e.g., dyspnea, wheezing, cough) | ≤ 2 days/week | > 2 days/week | Daily | Throughout the day |
Nighttime symptoms (e.g., difficulty falling asleep because of symptoms, nighttime awakenings) | Rare | 3–4 times/month | 1–2 times/week | Often (most nights) |
FEV1 | > 80% | > 80% | 60–80% | < 60% |
References: [1][3][7]
Treatment
Causal
- Avoid triggers (see “Etiology” above).
- Allergen immunotherapy in allergic asthma
- Early treatment of infections in infection-triggered asthma
- If GERD is suspected: proton pump inhibitors
Symptomatic
Overview of asthma medication | ||||
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Class | Examples | Mechanism | Primary use | |
Beta-2 agonists |
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Inhaled corticosteroids (ICS) |
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Leukotriene pathway modifiers |
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Muscarinic antagonists |
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Biological agents | ||||
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Methylxanthines |
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Mast cell stabilizers |
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Oral corticosteroids |
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Acute management
- For mild symptoms: short-acting beta-2 agonist
- For exercise-induced asthma: short-acting beta-2 agonist prior to exercise
- For severe asthma exacerbations, see “Treatment” in status asthmaticus.
The following drugs are not effective during an acute asthma attack: LABA, leukotriene pathway modifiers, theophylline, mast-cell stabilizers, biological agents!
To remember the meds for asthma exacerbations, think ASTHMA: Albuterol, Steroids, Theophylline (rare), Humidified O2, Magnesium (severe exacerbations), Anticholinergics.
Long-term management
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General principles
- Reduce number of asthma attacks → Medical therapy is escalated or de-escalated depending on the patient's individual needs.
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Self-monitoring for patients: peak flow meter to measure peak expiratory flow rate (PEFR)
- Patients can avoid exacerbations with frequent PEFR measurements: PEFR decreases before symptoms appear → indicates insufficient medication regimen
- Influenza and pneumococcal vaccines are administered in all patients.
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Pharmaceutical management
- Reliever medications: provide relief of asthma symptoms and are taken as needed when symptoms are present
- Controller medications: control underlying inflammation of asthma
- Shift in treatment paradigm as of 2019 [13]
- Previously: As-needed SABA reliever inhaler was the mainstay of intermittent asthma treatment.
- New recommendation: ICS-containing controller inhaler for every adult and adolescent with asthma (no more SABA-only treatment)
- Reasoning: ICS addresses the underlying problem of airway inflammation → reduces both frequency of symptoms and risk of severe asthma exacerbations (SABAs only address symptoms)
- Note that many resources still list as-needed SABA reliever treatment as the only therapy necessary in intermittent asthma.
Pharmaceutical management of chronic asthma (adults and adolescents) | ||||
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Severity | ||||
Treatment | Mild intermittent | Mild persistent | Moderate persistent | Severe persistent |
Preferred reliever |
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Preferred controller |
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Alternative and add-on controllers |
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Inhaled corticosteroids do not take full effect until they have been used for approx. 1 week!
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Monitoring
- Routine follow-up every 1–6 months, depending on severity
- Purpose of follow-up: assessment of asthma symptom control
Asthma symptom control | |||
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Control questions | Well controlled | Partly controlled | Uncontrolled |
Limitation of activities due to asthma symptoms? |
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Reliever inhaler use more than twice weekly? | |||
Daytime asthma symptoms more than twice weekly? | |||
Awakening at night due to asthma symptoms? |
References: [5][8][4][14][13]
Acute management checklist
Mild to moderate asthma exacerbation
- Supplemental oxygen: target SpO2 > 90%
- Inhaled SABA MDI or SABA nebulizer
- Oral systemic corticosteroids
- Triage depends on the clinical course.
- Continuous pulse oximetry if the patient requires supplemental oxygen.
Severe asthma exacerbation
- Supplemental oxygen: target SpO2 > 90%
- Administer bronchodilators.
- SABA nebulizer with ipratropium nebulizer
- Or combination therapy with inhaled SABA and ipratropium nebulizer
- Oral systemic corticosteroids
- ICU transfer
- Continuous telemetry, continuous pulse oximetry
Impending respiratory arrest
- Consider intubation with mechanical ventilation (100% FiO2). [15]
- Administer combined inhaled SABA with ipratropium bromide.
- Administer intravenous corticosteroids.
- Administer IV magnesium.
- Consider heliox administration of albuterol.
- Transfer to ICU.
- Continuous telemetry, pulse oximetry
All patients with asthma exacerbation
- Identify and treat the underlying cause.
- Consider antibiotics if there are signs of bacterial infection.
- Avoid sedating medications.
- Avoid intubation if possible; trial NIPPV
Intubation of patients with acute asthma exacerbation can be dangerous and should only be performed by an experienced physician. Care should be taken to avoid post-intubation hyperinflation (e.g., low tidal volume, low PEEP, high inspiratory flow).
Complications
Status asthmaticus
- Definition: extreme asthma exacerbation that does not respond to initial treatment with bronchodilators
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Clinical features
- Initially: orthopnea, tachypnea, tachycardia, and cyanosis
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Signs of imminent respiratory arrest
- Drowsiness/confusion
- Paradoxical thoracoabdominal movement
- Bradycardia
- Absent wheezing
- Pulsus paradoxus
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Diagnosis
- The following diagnostic workups should be done in patients with status asthmaticus attacks:
- ABG (i.e., to identify hypercapnia and hypoxemia)
- CBC
- BMP
- Peak expiratory flow measurement
- Chest x-ray
- ECG (in older patients)
- The following diagnostic workups should be done in patients with status asthmaticus attacks:
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Management
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Hospitalization
- PEF or FEV1: 50–70% of the predicted value
- PEF or FEV1 < 50% of the predicted value → admitted in the ICU
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Medications
- Short-acting beta-2 agonist (SABA)
- Short-acting muscarinic antagonists (SAMA) like ipratropium bromide
- Oral corticosteroid
- Intravenous magnesium sulfate
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Oxygenation and ventilation
- Supplemental oxygen and/or helium-oxygen mixture (heliox)
- Noninvasive ventilation (NIV)
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Indications for intubation
- Use of accessory muscles
- Decreased oxygen saturation
- Inability to speak in full sentences
- Inadequate response to initial therapy
- Normalizing PCO2 or pH (see “Laboratory Studies” under “Diagnostics” above)
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Hospitalization
Status asthmaticus is a medical emergency, as it can be a life-threatening!
References: [16][17]
We list the most important complications. The selection is not exhaustive.
Special patient groups
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Pregnant women
- Asthma symptoms can 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.
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Children
- 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.
- Treatment similar to that for adults, with inhaled corticosteroids as the initial drug of choice
- Young children (< 5 years) may require nebulizers because of difficulty using inhalers. [4]
References: [2][18]