Non-fully reversible airway obstruction in fatal asthma is often seen in association with profound structural changes of the bronchial wall, termed airway remodeling. Evidence suggests that heavy precipitation events can trigger epidemics of severe asthma. We present a case of fatal asthma in a young woman with no prior near-fatal exacerbations and postulate that the patient's extensive airway remodeling and puerperal state (susceptibility factors), in combination with a massive allergen challenge during a hurricane landfall (triggering factor), played a central role in her death. The autopsy revealed diffuse obstruction of proximal and distal bronchi by mucous plugs together with transmural chronic inflammation, tissue eosinophilia, extensive goblet cell hyperplasia with MUC-5 expression and airway smooth muscle (ASM) thickening. The observed distribution of airway remodeling was heterogeneous with sparing of the lingula, which exhibited hyperinflation and expansion of perivascular spaces indicative of dissecting air. The massive stagnation of mucus and significant inter-airway structural heterogeneity created an anatomical substrate for unequal airflow distribution facilitating the development of barotrauma. Although not considered conventional risk factors for fatal asthma, we believe that in this case, the patient's puerperal state in conjunction with an extreme environmental event dispersing aeroallergens were major contributors to the development of a fatal asthma attack. Our autopsy findings suggest that effective strategies to evacuate stagnated mucus and induce relaxation of thickened ASM are crucial in the management of life-threatening asthma exacerbations.