SHORT-TERM AND LONG-TERM EFFECTS OF SERIAL BRONCHOALVEOLAR LAVAGES IN A NONHUMAN PRIMATE MODEL

Bronchoalveolar lavage (BAL) has gained widespread use as a tool for investigating human lung diseases. In certain cases, it can be useful to obtain BAL material in a serial manner. There is convincing evidence from experimental and clinical studies that BAL can cause influx of neutrophils into the bronchoalveolar space. However, conflicting data have been reported on whether this side effect of BAL also affects previously nonlavaged lung areas. In addition, there is little information available on whether multiple repetitive BAL procedures cause damage to lung tissue. To reexamine the short-term effects of serial BAL procedures, the left lung of 10 cynomolgus monkeys was ravaged with five 20-ml aliquots of saline four times at 24-h intervals (Group A), 72 h after the initial BAL, the right lung was ravaged as a control. The percentage of neutrophils increased significantly (p < 0.05), with the greatest ef feet seen at 48 h (30.7 +/- 5.8 versus 0.8 +/- 0.3%, mean +/- SEM). No significant changes were observed in the control BAL of the right lung at 72 h. A multidisciplinary approach was used to assess the long-term effects of multiple BAL procedures. BAL was performed 14 times over 26 mo at 2-mo intervals (Group B, n = 5). The right lung was lavaged as a control 25 mo after the initial BAL. In addition to standard cellular BAL parameters, the concentrations of fibronectin, procollagen III amino-terminal peptide-related antigen, total phospholipids, and lactate dehydrogenase activity were measured. To assess possible damage to bronchoalveolar structures, quantitative high-resolution CT, qualitative histomorphology, and histomorphometric analyses were performed separately for left and right lung. Lung areas lavaged in an extensive repetitive fashion did not show significant differences with respect to cell numbers, biochemical factors, or structural parameters compared with baseline values or samples from previously nonlavaged lung areas. We conclude that each BAL procedure leads to an influx of neutrophils into the airspace that is restricted to the area of the lung where BAL was initially performed. However, extensive serial ravages performed over a prolonged period of time do not cause damage to bronchoalveolar structures in healthy experimental animals, although large numbers of neutrophils are induced repeatedly to extravasate from the pulmonary microvasculature into the bronchoalveolar space.