Definition and Pathogenesis of Drug-Induced Lung Injury: What Is DLI?

Abstract

Drug-induced lung injury (DLI) results from the specific use of a drug, including prescription drugs, over-the-counter drugs, and supplements. A DLI is an adverse drug reaction that occurs in the pulmonary system including the lungs, bronchi, and pulmonary vessels. The following diagnostic criteria are generally used: (1) history of ingestion of a drug known to induce lung injury, (2) the clinical manifestation reported to be induced by a drug, (3) exclusion of other causes of the clinical manifestation, (4) improvement of the clinical manifestations after drug discontinuation, and (5) exacerbation of the clinical manifestations after resuming the drug. Pathogenetic mechanisms of DLI have not been precisely elucidated, but two possible mechanisms have been suggested. First, there are cytotoxic effects of drugs on alveolar type II and airway epithelial cells or vascular endothelial cells. The cytotoxic effects may be mediated by reactive oxygen species, proteases, and cytokines. Second, activation of immune cells may promote the development of DLI through acquisition of immunogenicity by binding of a drug or its metabolite to cytoplasmic proteins as a hapten. These two mechanisms may be involved in the pathogenesis of DLI independently or in combination, and they may be modified by a variety of host and environmental factors, such as genetic predisposition, age, underlying lung diseases, and interactions with concomitant drugs.