Effects of Treatment on Airway Inflammation and Thickening of Basement Membrane Reticular Collagen in Asthma: A Quantitative Light and Electron Microscopic Study

Abstract

Abstract We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 µg, two puffs four times daily; n = 5) or inhaled budesonide (200 µg, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine > 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p < 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p < 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p < 0.01) and eosinophils (p < 0.05) in Group A and of eosinophils (p < 0.01) and histiocytes (p < 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p < 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p < 0.05). But for the percentage of lymphocytes, which increased (p < 0.05), terbutaline was without effect. By electron microscopy budesonide reduced the number of mast cells (p < 0.05) and the frequency with which foci of free eosinophil granules were found (p < 0.05). Terbutaline had no statistically significant effect. Long-term corticosteroid treatment resulted in a low total cell infiltrate similar to that of the healthy control subjects. Neither short- nor long-term treatment reduced the thickening of the reticular basement membrane. We conclude in this relatively small study that in the treatment of mild atopic asthma budesonide reduces the numbers of mast cells, eosinophils, and foci of eosinophil degranulation in the bronchial mucosa, and it appears to be more effective in this respect than terbutaline.