CELLULAR INFILTRATION OF THE AIRWAYS IN ASTHMA OF VARYING SEVERITY

We have tested the hypothesis that airway infiltration by inflammatory cells reflects the severity of asthma by comparing the inflammatory c ell infiltrates in fatal severe asthma and in subjects with mild to mo derate asthma who died of unrelated causes. Sections of lung tissue fr om 25 fatal asthma cases and eight asthmatics who died of unrelated ca uses were immunostained by monoclonal antibodies (mAbs) using streptav idin-biotin peroxidase technique. The following cells were identified: mast cells (AA1:tryptase), eosinophils (EG1:stored cationic protein a nd EG2: secretory form of cationic protein), monocytes/macrophages (CD 68), 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 intraep ithelial CD3(+) T cells were significantly lower in fatal asthma than in mild-moderate asthma both when all airways were considered (0.35 ve rsus 0.86 cells/mm, p = 0.034) and in the larger airways alone (0.08 v ersus 1.05 cells/mm, p = 0.039). The numbers of EG1- and EG2-positive eosinophils infiltrating the airway wall of the larger airways were gr eater in fatal asthma than in mild-moderate asthma (78.2 versus 22.8 c ells/mm(2), p = 0.012 and 138.1 versus 31.7 cells/mm(2), p = 0.022). I n 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 o f the eosinophil inflammatory infiltrate. These findings have implicat ions for the pathophysiology of asthma that results in death.