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Toxicol Appl Pharmacol. 2016 Aug 15;305:1-11. doi: 10.1016/j.taap.2016.05.014. Epub 2016 May 19.

Mustard vesicant-induced lung injury: Advances in therapy.

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Division of Neonatal and Perinatal Medicine, Hofstra Northwell School of Medicine, Cohen Children's Medical Center of New York, New Hyde Park, NY 11040, USA. Electronic address:
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Department of Environmental Health Science, New York Medical College, School of Public Health, Valhalla, NY 10595, USA.
Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ 08854, USA.


Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.


Fibrosis; Inflammatory mediators; Lung injury; Mustard gas; Therapeutic approaches; Vesicant

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