RELATIONSHIP OF ALVEOLAR MACROPHAGE PLASMINOGEN-ACTIVATOR AND ELASTASE ACTIVITIES TO LUNG-FUNCTION AND CT EVIDENCE OF EMPHYSEMA

Objective: To evaluate the relationship between alveolar macrophage (A M) elastase and plasminogen activator (PA) activities (considered to b e potential pathogenetic factors in emphysema) and the development of emphysema in smokers. Participants: Thirty-four healthy smokers >35 ye ars of age (mean+/-SD, 46+/-7 years), with a meant-SD of 33+/-10 pack- years of smoking, who were recruited as volunteers. Methods: Subjects had lung function testing and BAL to obtain AMs; limited high-resoluti on CT scans of the chest were obtained in 32 subjects to assess the pr esence of emphysema. Macrophage PA and elastase were determined using AM cultured on I-131-fibrin-coated plates and H-3-elastin-coated plate s, respectively. Results: The number of AMs recovered per milliliter o f BAL was significantly greater in the 16 subjects with CT evidence of mild emphysema than the 16 subjects without evidence of emphysema (66 9+/-301x10(3)/mL vs 414+/-268x10(3)/mL; p=0.01), There was no signific ant difference between AM elastase or PA activities in the 16 subjects with CT evidence of mild emphysema, when compared with the 16 subject s who had no CT evidence of emphysema (elastase, 2.72+/-1.35 mu g vs 2 .49+/-0.91 mu g elastin per 10(6) AMs per first 24 h; PA, 0.375+/-0.12 6 vs 0.344+/-0.096 urokinase units/10(6) AMs). There was no significan t correlation between levels of PA. or elastase activities and FEV1, F EV1/FVC, forced expiratory flow rate between 25% and 75% of the FVC; P A activity but not elastase activity had a significant negative correl ation (r=-0.47, p<0.01) with diffusion of carbon monoxide (DCO). The m acrophage count in BAL had a significant negative correlation with DCO percent predicted (r= -0.61, p<0.001). Conclusions: The findings sugg est that the number of AMs recovered per milliliter of BAL (presumably indicating the number in the alveolar spaces) is related to the devel opment of emphysema in smokers as indicated by CT scan of the chest an d DCO. The results also suggest that the level of PA enzyme activity i n AMs may be a pathogenetic factor in the decrease in DCO in smokers.