Respiratory mechanics do not always mirror pulmonary histological changes in emphysema

OBJECTIVE : To verify the accordance of functional and morphometric parameters during the development of emphysema. METHODS : BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days. Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed. To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma. RESULTS : We only observed decreases in tissue elastance and tissue damping on the 28(th) day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema. However, only the mean linear intercept values remained increased until the 40(th) day. The volume proportion of collagen fibers was increased from the 15(th) day to the 40(th) day, whereas the volume proportion of elastic fibers was only increased on the 40(th) day. The number of macrophages increased beginning on the 1(st) day. The expression of metalloproteinase 12 was increased from the 3(rd) day until the 40(th) day. However, 8-isoprostane expression was only increased on the 1(st) and 3(rd) days. CONCLUSIONS : In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics. Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process.