title: Mustard vesicant-induced lung injury: Advances in therapy.
abstract: 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.
authors.affiliation: 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: bweinberger@northwell.edu.
authors.forename: Barry
authors.initials: B
authors.lastname: Weinberger
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Rama
authors.initials: R
authors.lastname: Malaviya
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Vasanthi R
authors.initials: VR
authors.lastname: Sunil
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Venosa
authors.affiliation: Department of Environmental Health Science, New York Medical College, School of Public Health, Valhalla, NY 10595, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Heck
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000628:therapy*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells; D009151:Mustard Gas / Q000633:toxicity*; D022661:RNA, Untranslated; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002619:Chemical Warfare Agents; D007509:Irritants; D022661:RNA, Untranslated; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D050051:Transient Receptor Potential Channels; D014409:Tumor Necrosis Factor-alpha; D005337:Fibrin; D020782:Matrix Metalloproteinases; D009151:Mustard Gas
keywords: Fibrosis; Inflammatory mediators; Lung injury; Mustard gas; Therapeutic approaches; Vesicant