Drug-Induced Lung Toxicity

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Abstract
The number of blood-borne chemotherapeutic agents implicated in drug-induced lung toxicity continues to increase, although problems in detection remain. The initiation of drug-induced lung injury can have an immunologic or nonimmunologic basis. If endothelial cells are injured, interstitial pulmonary edema may result. Regardless of the source of injury, the progression of drug-induced lung toxicity is often quite similar, involving (1) parenchymal damage, (2) recruitment of inflammatory cells, and (3) progression of the inflammatory process. If the inflammatory reponse is sufficiently severe and disperse, increased collagen can be deposited in interstitial and intra-alveolar areas. The resulting attenuation of gas exchange can induce dyspnea and possibly death. Recent research suggests mediation of the fibrogenic process via cytokines such as transforming growth factor-β and tumor necrosis factor. Preliminary results demonstrating amelioration of cytokine mediated lung-induced fibrosis in animal models with appropriate antibodies suggest a possible future modality of therapy. Certain amphiphilic drugs are capable of eliciting a more specific form of lung toxicity. This class of drugs can interfere with phospholipid metabolism in pulmonary macrophages. In these cases, phospholipidosis results from phospholipid accumulation. The physiologic sequelae in human phospholipidosis is still uncertain.