Radiation-induced lung injury was first described in 1898, soon after the development of roentgenograms . The distinction between two separate types of radiation-induced lung injury, radiation pneumonitis and radiation fibrosis, was made in 1925 . Both types of lung injury are observed today in patients who have undergone thoracic irradiation for the treatment of lung, breast, or hematologic malignancies. Radiation-induced damage to normal lung parenchyma remains the dose-limiting factor in chest radiotherapy, and can involve other structures within the thorax in addition to the lungs (table 1).
A large body of literature describes the histopathologic, biochemical, kinetic, physiologic, and molecular responses of lung cells to ionizing radiation [3-7]. However, the clinical diagnosis of radiation-induced lung injury is often complicated by the presence of other conditions, including malignancy, infection, and cardiogenic pulmonary edema . Radiation-induced lung injury will be reviewed here. The cardiac effects of therapeutic radiation are discussed separately. (See "Cardiotoxicity of radiation therapy for malignancy".)
Ionizing radiation causes the localized release of sufficient energy to break strong chemical bonds and generate highly reactive free radical species. Cellular molecules including peptides, lipids, and DNA can be affected directly or indirectly via the interaction of the ionizing radiation with tissue water.
Overexpression of a transgene for manganese superoxide dismutase protects against the late fibrotic response in a murine model of radiation pneumonitis, and confirms the role of oxygen radicals in the pathogenesis of radiation-induced fibrosis . There have been preclinical studies of gene therapy combined with chest irradiation to increase tissue expression of manganese superoxide dismutase and limit radiation-induced pulmonary damage .
Radiation-induced lung injury results from the combination of direct cytotoxicity upon normal lung tissue and, perhaps more importantly, the development of fibrosis triggered by radiation-induced cellular signal transduction. The cytotoxic effect is largely a consequence of DNA damage that causes clonogenic death in normal lung epithelial cells, though apoptotic pathways are also induced by radiation. The development of fibrosis that can compromise lung function is mediated by a number of different cytokines, as discussed below.