Effect of Bronchodilators on Bronchial Gland Cell Proliferation After Inhalation and Burn Injury in Sheep

Abstract

The objective of this study is to measure the temporal changes in bronchial submucosal gland (SMG) cell proliferation in sheep after smoke inhalation and burn (S+B) injury, and to assess the effect of bronchodilators on the proliferative response. Archived main bronchial airways from sheep after S+B injury were immunostained for Ki67, and the percentage of ciliated duct and SMG cells expressing nuclear localization of Ki67 was determined for uninjured sheep and in sheep 24, 48, 72, and 96 hours after injury. A semiquantitative measure of lining epithelial exfoliation was made for each tissue. Bronchial tissues from sheep at 48 hours after S+B injury that had been nebulized with albuterol or tiotropium bromide (tiotropium) were examined to assess the effect of bronchodilators on the proliferative response. At 48 through 96 hours after injury, both ciliated duct and SMG cell proliferation were significantly increased compared with that of uninjured animals and animals 24 hours after injury, P <.05. A small increase in proliferation was seen in the SMG cells of albuterol-treated sheep compared with nebulized saline controls, P = .048. SMG cells of tiotropium-treated animals showed a significant increase in Ki67 nuclear staining compared with their study controls, P = .001. Extensive injury to the lining epithelium is associated with a proliferative response in both ciliated duct and SMG cells 24 hours after injury. The increase in proliferation in sheep treated with bronchodilators suggests that therapies for inhalation injury modify the glandular proliferative response. Further study to assess the ability of bronchodilators to enhance epithelial repair is warranted.