Immunopathology of fatal soybean dust-induced asthma

Abstract

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.

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

“…These sudden fatal episodes may occur against a background of persistent airway inflammation and structural derangement; moreover, those with the most extreme structural changes, such as mucous gland hypetrophy, will have the most devastating response [50]. Patients with fatal soybean asthma have diminished numbers of CD3+ and CD8+ T-cells in the airway epithelium and submucosa compared with fatal asthma cases [51]. However, there were no differences in the numbers of mast cells, eosinophils and neutrophils in relation to basal asthma severity or to the pattern of fatal attack.…”

Pathogenesis of Small Airways in Asthma

“…Carroll et al [14] carefully examined the distribution of inflammatory cells throughout the bronchial tree of both fatal and nonfatal cases of asthma and showed increased numbers of lymphocytes and eosinophils uniformly distributed throughout the large and distal airways of mild and severe asthmatics when compared to control cases. Similar infiltration of T cells, macrophages, and eosinophils into the proximal and distal lung tissues has also been reported in rare cases of sudden asthma death (dying within 1 h after the onset of their symptoms) [15] and in soybean dust-induced asthma [20] .…”

“…Together with the recent applications of molecular pathological techniques, including immunocytochemistry and in situ hybridization to biopsies and bronchoalveolar lavage fluid, these technological advances have had a profound impact on our understanding of the pathogenesis of bronchial asthma [9,10] . Recent studies utilizing these approaches in surgically resected lung tissue [11][12][13] , postmortem lung specimens [14][15][16] , and transbronchial biopsies [17,18] have demonstrated that similar but more severe inflammatory and structural changes are also occurring in the distal lung [15,19,20] and extending into the lung parenchyma of asthmatic patients [17] .…”

Difficult/therapy-resistant asthma The need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies

“…Some studies have indicated that the eosinophilic inflammatory response is worse in the proximal airways, with a redistribution of T-lymphocytes away from the airway epithelium, and others emphasize the even distribution of inflammation in both small and large airways [52,53]. Submucosal vascular congestion may also be an important feature.…”