Changes in Surfactant in Bronchoalveolar Lavage Fluid after Hemithorax Irradiation in Patients with Mesothelioma

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Abstract
Experimental studies have shown that the surfactant system of the lung is affected shortly after irradiation. It is unclear, however, whether surfactant plays a role in the pathogenesis of radiation pneumonitis. In the present study surfactant components (saturated phosphatidylcholine, surfactant protein A, phosphatidylglycerol, and phosphatidylinositol) and other phospholipids of bronchoalveolar lavage fluid (BAL) were studied in four patients with pleural mesothelioma before and during hemithorax irradiation (70 Gy) as well as zero, 1,2,3, and 4 months following irradiation. The concentrations of these same components and of soluble proteins were also estimated in the epithelial lining fluid (ELF) using urea as a marker of dilution. After radiotherapy, the concentrations of the surfactant components in ELF decreased to 12 to 55% of the control values before radiation, whereas the concentration of sphingomyelin in ELF increased ninefold. There were small changes in the other phospholipids. The concentration of soluble protein in ELF increased sevenfold. The minimum surface activity of crude BAL increased from 12 .+-. 4 to 32 .+-. 6 mN/m, and that of the sediment fraction of BAL increased from 7 .+-. 4 to 22 .+-. 6 mN/m, p < 0.001. The protein-rich supernatant fraction of BAL from irradiated lung had a inhibitory effect on normal surfactant. There were significant correlations between the increasing severity of the radiologic changes on the hand and, on the other, the saturated phosphatidylcholine/sphingomyelin ratio (p < 0.001), the concentrations of soluble protein (p < 0.001), and the concentrations of the surfactant components (p < 0.02-0.001) in ELF. There were also significant (p < 0.05) correlations between the deterioration of lung function on the one hand and the same changes in the lung effluent indices on the other. Our results show that hemithorax irradiation caused accumulation of proteins in the alveolar space, inactivation of surfactant, and a decrease in the concentration of surfactant components in ELF. These changes may play a role in the pathogenesis of radiation-induced lung injury.