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

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.

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