No abstract

This study was designed to determine if aerosolized hyaluronan (HA) could prevent airspace enlargement and elastic fiber injury in a mouse model of cigarette smoke-induced pulmonary emphysema. Compared to untreated/smoked controls, HA-treated animals showed statistically significant reductions in mean linear intercept (54 versus 65 microm; P < .001) and elastic fiber breakdown products (desmosine and isodesmosine) in bronchoalveolar lavage fluid (0.3 versus 7.0 ng/mL; P < .05). As in previous studies, the aerosolized HA showed preferential binding to elastic fibers, suggesting that it may protect them from injury. These findings support further investigation of the potential use of HA as a treatment for pulmonary emphysema.

This laboratory has previously shown that an intratracheally instilled solution of hyaluronic acid (HA) protects the lung from elastase-induced airspace enlargement. In those studies, fluorescein-labeled HA was found to bind preferentially to lung elastic fibers, suggesting a mechanism for the protective effect. The current investigation extends these findings by examining the capacity of an aerosol preparation of HA to similarly inhibit elastase-induced lung injury. Syrian hamsters were exposed to aerosolized bovine tracheal HA (0.1% solution in water) for either 25 or 50 min, then immediately instilled intratracheally with 80 units of human neutrophil elastase. One week later the lungs were examined for airspace enlargement, using the mean linear intercept method. Animals exposed to HA for 50 min showed a significant decrease in airspace enlargement compared to controls exposed to aerosolized water alone (68.2 microm vs 85.9 microm; P < 0.05). The 25-min exposure to the HA aerosol also reduced the mean linear intercept compared to controls (73.7 microm vs 85.9 microm), but this decrease was not statistically significant. With regard to possible inflammatory effects of HA, there was no difference in the percentage of lavaged neutrophils between HA-treated and control lungs at 24 hr (1.4% vs 1.8%, respectively). As with earlier experiments using intratracheally instilled HA, aerosolized fluorescein-labeled HA was found to bind to lung elastic fibers. These results suggest that aerosolized HA may prevent elastase-mediated injury in pulmonary emphysema.