Effect of smoking cessation on pulmonary and cardiovascular function and structure: analysis of guinea pig model

Abstract

To assess the pulmonary structural and functional effects of smoking cessation, we exposed groups of guinea pigs to cigarette smoke for 4 and 8 mo and included a group of animals in which smoke exposure was stopped at 4 mo (ex-smokers). We found that, compared with control nonsmokers, the smokers at both 4 and 8 mo showed airflow obstruction with alterations in lung volume and morphological evidence of emphysema with increased alveolar air space size and decreased alveolar surface area-to-volume ratio. There was an alteration in the pulmonary vascular structure, with increased numbers of muscularized arterioles, in the smokers at both time periods, and this was associated with significantly increased pulmonary arterial pressure at 8 mo. Cessation of smoke exposure appeared to halt, but not reverse, these structural changes. The smokers at 8 mo showed clear evidence for a "healthy smoker" effect, underscoring the necessity for longitudinal studies even when using an animal model. We conclude that cessation of exposure to cigarette smoke is associated with an apparent halt, but not a reversal, of emphysematous lung enlargement and pulmonary arteriolar muscularization. However, the magnitude of improvement in pulmonary function is not as great as the apparent structural differences would imply, and there is no clear effect on the pulmonary arterial pressure.

A longitudinal analysis of pulmonary function in rats during a 12 month cigarette smoke exposure

“…In the guinea-pig, there was significant interanimal variation in pulmonary function, even when accounting for animal age and weight [3]. Furthermore, we found that our cross-sectional studies were biased by a "healthy smoker" effect, whereby the animals that were most affected by cigarette smoke tended to die before the end of the experiment; the final results were, thus, derived from the animals with the least disease [2,4]. Finally, the use of a single pulmonary function end-point does not allow for analysis of the temporal profile of the development of abnormalities, or for analysis of results that might predict response to cigarette smoke.…”

“…Eur Respir J 1997; 10: 1115-1119. In our laboratory, we have previously developed a guinea-pig model of cigarette smoke-induced alterations in pulmonary function [1,2]. Although this model has proved successful in that we have been able to show clear evidence of airflow obstruction and emphysematous lung destruction in smoke-exposed animals, it has also illustrated the problems inherent in such kinds of cross-sectional studies.…”

Using guinea pigs in studies relevant to asthma and COPD

“…But the pathology of cigarette smoke exposure is similar in guinea pigs and humans. Features of the cigarette smoke-exposed lung of guinea pigs similar to that seen in COPD include an acute neutrophilia, a slowly developing but sustained recruitment of monocytes, alveolar destruction, mucus secretion, increased epithelial permeability, altered reflexes and pulmonary hypertension [209][210][211][212][213][214][215][216][217][218][219].…”

Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation

“…Several studies have shown that inflammation of the airway mucosa of COPD patients persist even after smoking cessation [24][25][26][27]. In addition, alveolar destruction, emphysematous lung enlargement, permeability coefficient and pulmonary arterial pressure are unchanged by cessation of cigarette smoking [28,29].…”