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Radiation-induced lung injury

Kenneth R Olivier, MD
Tobias Peikert, MD
Section Editors
James R Jett, MD
Steven E Schild, MD
Deputy Editor
Helen Hollingsworth, MD


Radiation-induced lung injury (RILI) was first described in 1898, soon after the development of roentgenograms [1]. The distinction between two separate types of RILI, radiation pneumonitis and radiation fibrosis, was made in 1925 [2]. 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 RILI is often complicated by the presence of other conditions, including malignancy, infection, and cardiogenic pulmonary edema [8]. RILI will be reviewed here. The cardiac, esophageal, chest wall, and brachial plexus effects of therapeutic radiation to the chest are discussed separately. (See "Cardiotoxicity of radiation therapy for breast cancer and other malignancies" and "Overview of gastrointestinal toxicity of radiation therapy" and "Patterns of relapse and long-term complications of therapy in breast cancer survivors" and "Stereotactic body radiation therapy for primary and metastatic lung tumors".)


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.

RILI 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.

Genetic background – Animal and human studies suggest that there is a significant role for genetic susceptibility to irradiation injury [9-11]. Contemporary studies of patients receiving irradiation for breast cancer have shown suggestive associations between certain genetic factors and development of cutaneous telangiectasia [12] and/or fibrosis following irradiation [13,14]. Among 137 patients receiving irradiation for non-small cell or small cell lung cancer, presence of a single nucleotide polymorphism in the methylene tetrahydrofolate reductase gene (MTHFR; rs1801133) was associated with an increased risk of radiation pneumonitis [15]. In separate studies of lung cancer patients, polymorphisms of the ataxia telangiectasia mutated (ATM) gene were associated with an increased risk of radiation pneumonitis [16,17].

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Literature review current through: Oct 2017. | This topic last updated: Aug 16, 2017.
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