We have tested the hypothesis that airway infiltration by inflammatory cells reflects the severity of asthma by comparing the inflammatory cell infiltrates in fatal severe asthma and in subjects with mild to moderate asthma who died of unrelated causes. Sections of lung tissue from 25 fatal asthma cases and eight asthmatics who died of unrelated causes were immunostained by monoclonal antibodies (mAbs) using streptavidin-biotin peroxidase technique. The following cells were identified: mast cells (AA1:tryptase), eosinophils (EG1:stored cationic protein and EG2: secretory form of cationic protein), monocytes/macrophages (CD68), neutrophils (elastase), CD3+ and CD8+ T cells (CD3 polyclonal Ab and CD8+ mAb, respectively). Positive cells were counted in the epithelium and airway wall. The airways were divided into two groups: larger airways with internal perimeter (Pi) > 2 mm and smaller airways with Pi < 2 mm. All airways together were studied first, followed by larger and smaller airways examined separately. The numbers of intraepithelial CD3+ T cells were significantly lower in fatal asthma than in mild-moderate asthma both when all airways were considered (0.35 versus 0.86 cells/mm, p = 0.034) and in the larger airways alone (0.08 versus 1.05 cells/mm, p = 0.039). The numbers of EG1- and EG2-positive eosinophils infiltrating the airway wall of the larger airways were greater in fatal asthma than in mild-moderate asthma (78.2 versus 22.8 cells/mm2, p = 0.012 and 138.1 versus 31.7 cells/mm2, p = 0.022). In the smaller airways no significant difference was found between the two groups. We conclude that in fatal asthma there is a redistribution of CD3+ T cells away from the epithelium and proximal enhancement of the eosinophil inflammatory infiltrate. These findings have implications for the pathophysiology of asthma that results in death.

A hypothesis was postulated that the characteristic clinical course of fatal soybean asthma may be reflected by specific immunopathological findings. Seven cases of fatal soybean dust-induced asthma from Barcelona, Spain were compared with 25 fatal asthma cases from New Zealand. Sections of lung tissue were stained by monoclonal antibodies using standard streptavidin-biotin peroxidase technique. The following cell types were identified: mast cells, "activated" eosinophils, neutrophils, monocytes/macrophages, CD3+ T-cells and CD8+ T-cells. The positively staining cells were counted in the epithelium and the submucosa and their numbers expressed per mm and mm2, respectively. The airways were divided into larger (internal perimeter (Pi) > 2 mm) and smaller (Pi < 2 mm). Firstly, all airways were studied together; and subsequently, larger and smaller airways were studied separately. Differences in the numbers of mast cells, eosinophils, neutrophils and monocytes/macrophages between the two groups were not significant. The numbers of CD3+ and CD8+ T-cells were significantly reduced in fatal soybean asthma when all airways were taken together. In larger airways, the difference was not significant in the epithelium, but was significant in the submucosa for CD3+ cells. CD8+ cells were significantly reduced in fatal soybean asthma both in the epithelium and the submucosa. The cell counts in smaller airways were not significantly different either in the epithelium or in the submucosa for CD3+ cells. The numbers of CD8+ cells were not different in the epithelium, but were significantly reduced in the submucosa of fatal soybean asthma cases. We conclude that the numbers of CD3+ and CD8+ T-cells are substantially reduced in fatal soybean asthma. These data together with the clinical features of the fatal attack suggest a different mechanism(s) from that described for most asthma deaths, probably involving anaphylaxis.