Lung immunopathology in cases of sudden asthma death

Abstract

The histopathology of airway inflammation in rare cases of sudden asphyxic asthma death (SAAD) is unclear. This study examines, for the first time, the relative disposition of lymphocyte and macrophage subsets and eosinophils in proximal and distal tissues of such cases. Multiple resection specimens from five cases of SAAD were studied. Tissue blocks were obtained at necroscopy and immediately frozen in liquid nitrogen within 18 hours of death (death occurring within 1 h of the onset of an unprovoked asphyxic asthma attack). After immunohistological staining, frozen sections underwent semi-quantitative analysis (cell counts per unit area) for T-cells, macrophages and eosinophils using computerized imaging systems. Subsets of T-cells and macrophages were estimated using double immunofluorescence techniques. Variability within samples, between samples and between cases was compared. These cases of fatal asthma showed infiltrates of T-cells, macrophages and eosinophils within peribronchial tissues. Distinct from stable asthma, a CD8+ T-cell dominance was found. A high proportion of eosinophils were activated (EG2+), whereas the relative proportion of antigen-presenting cells (RFD1+) did not seem to be abnormal, although numbers of these cells were high. These features were seen both in proximal and distal tissues. The variability of these parameters within an individual was 9.4-15.2%, however, the variability between individual cases was greater. Sudden asphyxic asthma is associated with inflammatory infiltrates both of proximal and distal lung tissues. In contrast to stable asthma, this infiltrate contains large numbers of CD8+ T-cells, suggesting distinct qualitative as well as quantitative characteristics in the immunopathology of sudden asthma death.