Hyma, Bruce A.

Abstract To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 μg/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic/therapeutic agents. Tryptase levels were normal (<10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured by pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis.

Abstract To determine the histologic differences in the airways of patients who died from sudden-onset asthma and the more common slow-onset asthma, we studied seven cases of fatal asthma. The numbers of eosinophilsand neutrophils, as well as extracellular deposition of their respective granule contents in the airway mucosa and submucosa, were determined and statistically analyzed. Four of the seven patients had slow-onset asthma attacks in which the time interval between onset of asthma and death was more than 2.5 h. In contrast, three patients had sudden-onset asthma in which the time interval between onset of asthma attack and death was less than 1 h. The four patients with slow-onset fatal asthma had more eosinophils (34.1 ± 6.3 in slow-onset; 9.7 ± 3.5 in sudden-onset; p = 0.002) and fewer neutrophils (4.8 ± 2.0 in slow-onset; 16.8 ± 5.4 in sudden-onset; p = 0.008) in the airway submucosa than did patients with sudden-onset fatal asthma. In addition, within the slow-onset fatal asthma group, eosinophils exceeded neutrophils in the airway submucosa (eosinophils > neutrophils, p = 0.002). By contrast, within the sudden-onset fatal asthma group, neutrophils exceeded eosinophils (neutrophils > eosinophils, p = 0.04). We suggest that sudden-onset fatal asthma is immunohistologically distinct from slow-onset fatal asthma and that it is characterized by a relative paucity of eosinophils in the face of an excess of neutrophils in the airway submucosa. These observations raise the possibility that the mechanism of airway inflammation as well as that of airway narrowing in sudden-onset fatal asthma may be quite distinct from those in slow-onset fatal asthma.