Severe Asthma Exacerbations: Foundational Concepts
Learning Objective
Recognize risk factors, pathophysiology, and clinical presentation of severe asthma exacerbations.
1.1 Risk Factors for Severe or Fatal Asthma Exacerbations
Recognizing and stratifying patient-, environment-, and system-level risk factors is essential to prevent life-threatening asthma events.
Patient-specific factors:
- Prior near-fatal exacerbation requiring ICU stay, intubation or mechanical ventilation
- Frequent short-acting beta₂-agonist (SABA) use (e.g., ≥3 × 200-dose canisters per year or ≥1 canister per month)
- Recent systemic corticosteroid courses (e.g., ≥2 per year)
- Poor adherence to inhaled corticosteroids or lack of an asthma action plan
- Comorbidities: psychiatric disorders, cardiovascular disease, obesity, GERD, chronic rhinosinusitis
Environmental triggers:
- Allergen exposure: dust mites, pollens, animal dander, molds
- Viral respiratory infections: rhinovirus, influenza, RSV
- Pharmacologic: NSAIDs, nonselective β-blockers (especially in patients with Aspirin Exacerbated Respiratory Disease)
- Extreme weather and air pollution, thunderstorm-related pollen or spore surges
Social determinants:
- Low health literacy, limited insurance or medication access
- Socioeconomic hardship, crowding, occupational irritants
Key Pearls
- History of near-fatal asthma (intubation) is the strongest predictor of asthma-related death.
- SABA overuse is both a marker and mediator of poor control; aim to limit use to less than 3 canisters per year.
- Address ICS adherence and patient education to reduce exacerbation risk.
1.2 Pathophysiology of Acute Severe Asthma
Acute exacerbations result from a vicious cycle of bronchospasm, inflammation, mucus plugging and dynamic hyperinflation leading to airflow obstruction and gas trapping.
Bronchospasm:
This involves mediator-induced smooth muscle contraction through both IgE-dependent and non-IgE pathways.
Airway inflammation:
- Eosinophilic and neutrophilic infiltration
- Cytokine cascade (e.g., IL-4, IL-5, IL-13), leading to mucosal edema
Mucus plugging:
- Goblet cell hyperplasia and increased mucin secretion
- Impaired mucociliary clearance, contributing to airway obstruction
Dynamic hyperinflation:
- Expiratory flow limitation leads to air trapping and auto-PEEP (Positive End-Expiratory Pressure).
- This results in increased work of breathing and potential respiratory muscle fatigue.
- Ventilation/perfusion (V/Q) mismatch and carbon dioxide retention can occur.
Key Pearls
- Autopsy and CT studies link high mucus burden to fatal asthma.
- Auto-PEEP worsens gas exchange and can precipitate hemodynamic compromise.
1.3 Clinical Presentation of Severe Asthma Exacerbations
Exacerbation severity ranges from mild/moderate to life-threatening. Early recognition of warning signs guides escalation to critical care.
Mild/Moderate:
- Wheezing, dyspnea with exertion
- Able to speak in full sentences
- Peak Expiratory Flow (PEF) or Forced Expiratory Volume in 1 second (FEV₁) 50–75% of predicted
- Respiratory Rate (RR) 20–30 breaths/min, Oxygen Saturation (SpO₂) ≥94% on room air
Severe:
- Tachypnea >30 breaths/min, tachycardia >120 beats per minute (bpm)
- Use of accessory muscles, inability to speak full sentences
- PEF or FEV₁ ≤50% of predicted
- Pulsus paradoxus >20 mmHg, SpO₂ <92% on room air
Impending respiratory failure:
- Rising partial pressure of carbon dioxide in arterial blood (PaCO₂) despite bronchodilator therapy
- “Silent chest” with minimal wheezing and poor air entry
- Altered mental status (agitation progressing to drowsiness), bradycardia, hypotension
Clinical Pearl
A “quiet chest” indicates minimal airflow and is a sign of imminent respiratory arrest.
References
- Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2025. GINA. Available from: ginasthma.org.
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