Effect of chronic antigen and beta 2 agonist exposure on airway remodeling in guinea pigs

We recently reported that chronic exposure to fenoterol (FEN) in guinea pigs increases in vivo and in vitro airway responsiveness to a degree similar to that induced by chronic antigen (ovalbumin [OA]) exposure. We hypothesized that these changes were due to airway inflammation and airway remodeling. To trace newly recruited granulocytes as a marker of inflammation and to detect DNA replication in resident airway wall cells, the nucleotide 5'-bromo-2'-deoxyuridine (BrdU) was administered intermittently over the six-wk period of chronic FEN and/or OA exposure. Noncartilaginous airway dimensions were measured and the area fraction of BrdU-immunoreactive and total nuclei in adventitia, smooth muscle, and epithelium was determined by immunohistochemistry and point counting. The proliferation index was defined as the ratio of the two area fractions in each wall area. The adventitial areas of FEN- and OA-treated airways were respectively 62 and 88% greater than those of control airways (p < 0.05). The inner wall areas were not increased. The smooth muscle cell and epithelial cell proliferation index was increased after OA (smooth muscle index: control, 2.7 +/- 1.1% [SEM]; OA, 23.0 +/- 3.7%; p < 0.02) but not after FEN exposure, and there was an increased number of BrdU-immunoreactive granulocytes in the adventitia and epithelium after OA but not after FEN exposure. The increased in vivo airways responsiveness produced by chronic OA or FEN exposure may be attributable to adventitial thickening and increased in vitro muscle contractility, but the cellular mechanisms underlying these and other airway wall responses are different.(ABSTRACT TRUNCATED AT 250 WORDS)