Persistence of emphysema following cessation of cigarette smoke exposure requires a susceptibility factor.

Chronic obstructive pulmonary disease (COPD) is caused by cigarette smoke (CS) exposure but can often be progressive even in former smokers. Exposure of mice to CS for 22 wk causes emphysema, but whether emphysema persists after cessation of CS exposure is not clear. The purpose of this study was to determine whether emphysema persists in mice following a recovery period of 22 wk and whether a susceptibility factor, such as deficiency in the Bcl-2-interacting killer (Bik), is required for this persistence. Therefore, bik+/+ and bik-/- mice at 6-10 wk of age were exposed to 250 mg/m3 total particulate matter of CS or filtered air (FA) for 3 or 22 wk and were kept in FA for an additional 22 wk. Lungs were lavaged to quantify inflammatory cells, and sections were stained with hematoxylin and eosin to assess severity of emphysema. Exposure to CS for 3 wk increased the number of inflammatory cells in bik-/- mice compared with bik+/+ mice but not at 22 wk of exposure. At 22 wk of CS exposure, extent of emphysema was similar in bik+/+ and bik-/- mice. However, when mice were exposed to CS over the first 22 wk and were kept in FA for an additional 22 wk, emphysema remained similar in bik+/+ mice but was enhanced in bik-/- mice. These findings link increased inflammation with persistent emphysematous changes even after smoking cessation and demonstrate that a preexisting susceptibility condition is required to sustain enhanced emphysema that was initiated by long-term CS exposure.NEW & NOTEWORTHY Exposure of mice to cigarette smoke (CS) for 22 wk causes emphysema, but whether emphysema persists after an additional period of 6 mo after cessation of CS exposure has not been reported. In addition, the role of preexisting susceptibility in enhancing the persistence of CS-induced emphysema after exposure to CS has stopped has not been shown. The present study shows that a preexisting susceptibility must be present to enhance CS-induced emphysema after cessation of CS exposure.