Changes in pulmonary surfactant composition following MACC chemotherapy for lung carcinoma

Many antineoplastic drugs can derange lung structures, cause necrosis of type I pneumocytes, abnormal proliferation of type II alveolar epithelial cells, and, occasionally, accumulation of inflammatory and immune effector cells. Since type II cells secrete lung surfactant, treatment may alter surfactant composition. In 8 patients with nonresectable lung cancer, we performed bronchoalveolar lavage before and after MACC polychemotherapy (methotrexate, doxorubicin HCl, cyclophosphamide and lomustine). Before treatment, cellular composition and the phospholipid and fatty acid constituents of lavage surfactant were similar to those found in control subjects. After MACC polychemotherapy there was, in all patients, a mild decrease in the number of immune effector cells, without changes in the relative proportion of cell types. In addition, MACC therapy resulted in a significant decrease of phosphatidylcholine levels, and increased levels of phosphatidylglycerol, whereas the levels of palmitic lavage surfactant were decreased. These MACC treatment abnormalities of the phospholipid and fatty acid composition of lung surfactant may reflect preclinical pulmonary toxicity. The decrease in the numbers of bronchoalveolar cells suggests that the changes in surfactant composition may be chemically induced rather than immune mediated.