SMOKE-INDUCED EMPHYSEMA IN GUINEA-PIGS IS ASSOCIATED WITH MORPHOMETRIC EVIDENCE OF COLLAGEN BREAKDOWN AND REPAIR

We have previously shown that chronic cigarette smoke exposure produce s emphysema and airflow obstruction in the guinea pig. To further exam ine the changes in the connective tissue matrix associated with emphys ema in this model, we used ultrastructural morphometry to determine th e volume proportions of collagen and elastin in the alveolar walls of animals exposed to smoke or air (control) for 1, 3, 6, and 12 mo. Afte r 1 mo of smoke exposure, there was a statistically significant (P < 0 .001) decrease in the volume proportion of collagen in the smoke-expos ed animals, whereas by 6 and 12 mo of smoke exposure, the proportion o f collagen had significantly (P < 0.02, P < 0.03, respectively) increa sed. The volume proportion of elastin was increased in the smoke-expos ed animals at the 12-mo time period. While our results do not exclude reorganization of elastin within the alveolar wall, we conclude that, in this model, cigarette smoke-induced emphysema appears to be associa ted with collagen breakdown and repair. We suggest that the currently accepted proteolysis-antiproteolysis theory is too narrow in its focus on elastin destruction as the major contributor to emphysema and shou ld be broadened to the concept that smoke-induced emphysema reflects b reakdown and resynthesis (possibly overproduction in the form of scarr ing) of a variety of connective tissue proteins in addition to elastin .