Prior exposure to aged and diluted sidestream cigarette smoke impairs bronchiolar injury and repair

The bronchiolar injury/repair response to naphthalene (NA) in mice includes acute distal airway epithelial injury that is followed by epithelial proli feration and redifferentiation, which result in repair of the epithelium wi thin 14 days. To test whether prior exposure to aged and diluted sidestream cigarette smoke (TS) would alter the injury/repair response of the airway epithelium, adult mice were exposed to either filtered air (FA) or smoke fo r 5 days before injection with either corn oil carrier (CO) or naphthalene. Mice were killed 1 and 14 days after naphthalene injury. Lung and lobar br onchus were examined and measured using high-resolution epoxyresin sections . The control group (FACOFA) that was exposed to filtered air/corn oil/filt ered air contained airway epithelium similar to untreated controls at all a irway levels. The group exposed to tobacco smoke/corn oil/filtered air (TSC OFA) contained some rounded cells in the small airways and some expansion o f the lateral intercellular space in the larger airways, Necrotic or vacuol ated cells were not observed, As expected, the epithelium in the group expo sed to filtered air/naphthalene/filtered air (FANAFA) contained many light- staining vacuolated Clara cells and squamated ciliated cells within distal bronchioles during the acute injury phase. Repair (including redifferentiat ion of epithelial cells and restoration of epithelial thickness) was nearly complete 14 days after injury. The extent of Clara cell injury, as assesse d in lobar bronchi, was not different between the four groups. Although the FANAFA group contained greater initial injury in the distal airways at 1 d ay, the group exposed to tobacco smoke/naphthalene/filtered air (TSNAFA) ha d the least amount of epithelial repair at 14 days after naphthalene treatm ent; many terminal bronchioles contained abundant squamated undifferentiate d epithelium. We conclude that tobacco smoke exposure prior to injury (1) d oes not change the target site or target cell type of naphthalene injury, s ince Clara cells in terminal bronchioles are still selectively injured; (2) results in slightly diminished acute injury from naphthalene in distal bro nchioles; and (3) delays bronchiolar epithelial repair.