Possible Treatment Approaches of Sulfur Mustard-Induced Lung Disorders, Experimental and Clinical Evidence, an Updated Review

Sulfur mustard (SM) is one of the major potent chemical warfare that caused the death of victims in World War I and the Iraq-Iran conflict (1980–1988). The respiratory system is the main target of SM exposure and there are no definitive therapeutic modalities for SM-induced lung injury. The effects of the new pharmaceutical drugs on lung injury induced by SM exposure were summarized in this review. Literature review on PubMed, ScienceDirect, and Google Scholar databases was performed to find papers that reported new treatment approach on SM-exposure-induced injury in the respiratory system until October 2019. The search was restricted to sulfur mustard AND induced injury (in vitro studies, animal experiments, and clinical trials) AND respiratory system OR lung, AND treatment in all fields. Two hundred and eighty-three relevant articles were identified that 97 retrieved articles were eligible and were included in the review. Some new pharmaceutical drugs have shown therapeutic potential in controlling various characteristics of lung injury due to SM exposure. Recent studies showed therapeutic effects of mucolytic drugs, non-steroidal drugs, and antibiotics on reducing lung inflammation, oxidative stress responses, and modulating of the immune system as well as improving of respiratory symptoms and pulmonary function tests. Studies on the therapeutic effects of new agents with amelioration or treatment of SM-induced lung injury were reviewed and discussed.

• Publication year

  2022

• Venue

  Frontiers in Medicine

• Publication date

  2022-04-29

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.3389/fmed.2022.791914PMID 35572987PMCID 9106304
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Possible treatment with medicinal herbs and their ingredients of lung disorders induced by sulfur mustard exposures: a review

  2021cited by this paper
• N-Acetylcysteine as a treatment for sulphur mustard poisoning

  2020cited by this paper
• Functional Composites and Structures

  2019cited by this paper
• Long term effect of sulfur mustard exposure on hematologic and respiratory status, a case control study

  2019cited by this paper
• What is a NOT a Literature Review ?

  2018cited by this paper
• Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease

  2017cited by this paper
• Doxycycline improves clinical outcomes during cystic fibrosis exacerbations

  2017cited by this paper
• Comparison of doxycycline with azithromycin in treatment of pharyngeal chlamydia infection

  2016cited by this paper
• The effect of vitamin E on lung pathology in sulfur mustard-exposed guinea pigs

  2016cited by this paper
• Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human keratinocyte cell line.

  2016cited by this paper
• Airway tissue plasminogen activator prevents acute mortality due to lethal sulfur mustard inhalation.

  2015cited by this paper
• Respiratory effects of sulfur mustard exposure, similarities and differences with asthma and COPD

  2015cited by this paper
• IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway

  2014influential reference
• The role of N-acetylcysteine in the management of acute and chronic pulmonary complications of sulfur mustard: a literature review

  2014cited by this paper
• an update on

  2014cited by this paper
• Iraq-Iran chemical war: calendar, mortality and morbidity.

  2014cited by this paper
• Effect of recombinant human IFNγ in the treatment of chronic pulmonary complications due to sulfur mustard intoxication

  2014cited by this paper
• Inhibition of matrix metalloproteinase-9 with low-dose doxycycline reduces acute lung injury induced by cardiopulmonary bypass.

  2014cited by this paper
• Preventive measures against the mustard gas: a review

  2013cited by this paper
• N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine

  2013cited by this paper
• Study on Effectiveness of Low Dose Theophylline as Add-on to Inhaled Corticosteroid for Patients with Sulfur Mustard Induced Bronchiolitis

  2013cited by this paper
• Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction.

  2013cited by this paper
• Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation.

  2013influential reference
• Natural‐source d‐α‐tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo

  2012influential reference
• The effect of vitamin E on pathological changes in kidney and liver of sulphur mustard-exposed guinea pigs

  2012cited by this paper
• The Argatroban and tPA Stroke Study: final results of a pilot safety study

  2012cited by this paper
• Doxycycline treatment attenuates acute lung injury in mice infected with virulent influenza H3N2 virus: involvement of matrix metalloproteinases.

  2012cited by this paper
• Low-dose theophylline restores corticosteroid responsiveness in rats with smoke-induced airway inflammation.

  2012cited by this paper
• Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide

  2012cited by this paper
• Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

  2012cited by this paper
• The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study.

  2012cited by this paper
• The effect of vitamin E on tracheal responsiveness and lung inflammation in sulfur mustard exposed guinea pigs

  2011cited by this paper
• Macrolide antibiotics improve chemotactic and phagocytic capacity as well as reduce inflammation in sulfur mustard-exposed monocytes.

  2010cited by this paper
• Mechanisms mediating the vesicant actions of sulfur mustard after cutaneous exposure.

  2010cited by this paper
• Inflammatory effects of inhaled sulfur mustard in rat lung.

  2010cited by this paper
• Airway obstruction due to bronchial vascular injury after sulfur mustard analog inhalation.

  2010cited by this paper
• Potential Therapeutic Effects of Vitamin E and C on Placental Oxidative Stress Induced by Nicotine: An In Vitro Evidence

  2010cited by this paper
• Oxidants and antioxidants in sulfur mustard–induced injury

  2010cited by this paper
• Role of MAPK/AP-1 signaling pathway in the protection of CEES-induced lung injury by antioxidant liposome.

  2009cited by this paper
• Treatment with dexamethasone or liposome-encapsuled vitamin E provides beneficial effects after chemical-induced lung injury

  2009cited by this paper
• Mustard gas exposure and carcinogenesis of lung.

  2009cited by this paper
• Highly sensitive C-reactive protein levels in Iranian patients with pulmonary complication of sulfur mustard poisoning and its correlation with severity of airway diseases

  2009cited by this paper
• Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by sulfur mustard: Sardasht-Iran Cohort Study.

  2009cited by this paper
• Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study

  2009cited by this paper
• Protection of half sulfur mustard gas–induced lung injury in guinea pigs by antioxidant liposomes

  2009cited by this paper
• Effect of theophylline plus beclometasone on lung function in smokers with asthma-a pilot study

  2009influential reference
• Serum soluble Fas ligand and nitric oxide in long-term pulmonary complications induced by sulfur mustard: Sardasht-Iran Cohort Study.

  2009cited by this paper
• N-acetylcysteine improves the clinical conditions of mustard gas-exposed patients with normal pulmonary function test.

  2008cited by this paper
• A Novel Role for Tissue Factor Pathway Inhibitor-2 in the Therapy of Human Esophageal Carcinoma

  2008cited by this paper
• Comparative evaluation of some flavonoids and tocopherol acetate against the systemic toxicity induced by sulphur mustard

  2008cited by this paper
• Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: evaluating clinical aspect in patients with impaired pulmonary function test.

  2008cited by this paper
• Effectiveness of liposomal-N-acetylcysteine against LPS-induced lung injuries in rodents.

  2008cited by this paper
• Doxycycline attenuated lung injury by its biological effect apart from its antimicrobial function.

  2007influential reference
• Inhaled Corticosteroids and Long-Acting β2-Agonists in Treatment of Patients with Chronic Bronchiolitis Following Exposure to Sulfur Mustard

  2007cited by this paper
• Effects of theophylline on chronic inflammatory lung injury induced by LPS exposure in guinea pigs.

  2007influential reference
• Effect of gamma interferon on lung function of mustard gas exposed patients, after 15 years.

  2006cited by this paper
• Tissue factor pathway inhibitor: structure, biology and involvement in disease

  2006cited by this paper
• Anti-fibrotic effects of theophylline on lung fibroblasts.

  2006influential reference
• Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice

  2006cited by this paper
• Diagnostic and therapeutic value of short-term corticosteroid therapy in exacerbation of mustard gas-induced chronic bronchitis.

  2005cited by this paper
• Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life.

  2005cited by this paper
• Effect of doxycycline on sulfur mustard-induced respiratory lesions in guinea pigs.

  2005cited by this paper
• Histone Deacetylation: An Important Mechanism in Inflammatory Lung Diseases

  2005cited by this paper
• Late Respiratory Complications of Sulfur Mustard Poisoning in Iranian Veterans

  2005cited by this paper
• Medical aspects of sulphur mustard poisoning.

  2005cited by this paper
• Bronchiolitis obliterans: an update

  2004cited by this paper
• Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard.

  2004cited by this paper
• Protective effects of ascorbic acid, dl-α-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

  2004cited by this paper
• Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial

  2004cited by this paper
• Regular review: Chemical weapons

  2002cited by this paper
• Tissue Factor Pathway Inhibitor Reduces Experimental Lung Metastasis of B16 Melanoma

  2002cited by this paper
• [Mucolytics in acute and chronic respiratory tract disorders. I. Pathophysiology and mechanisms of action].

  2002cited by this paper
• [Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties].

  2002cited by this paper
• Cytotoxicity in ciprofloxacin-treated human fibroblast cells and protection by vitamin E

  2002cited by this paper
• Effect of N-acetyl-L-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis.

  2002cited by this paper
• Protection from half‐mustard‐gas‐induced acute lung injury in the rat

  2002cited by this paper
• The use of N-acetylcysteine in intensive care.

  2002cited by this paper
• Immunological consequence of sulfur mustard exposure.

  2002cited by this paper
• Human Neutrophil Oxidative Bursts and their in vitro Modulation by Different N-Acetylcysteine Concentrations

  2002cited by this paper
• Il-13 and IFN-gamma: interactions in lung inflammation.

  2001cited by this paper
• IL-13 and IFN-γ: Interactions in Lung Inflammation1

  2001cited by this paper
• Anti-inflammatory effects of macrolide antibiotics.

  2001cited by this paper
• Nuclear dependence of sulfur mustard-mediated cell death.

  2001cited by this paper
• N‐acetyl‐L‐cysteine inhibits bleomycin‐induced interleukin‐8 secretion by bronchial epithelial cells

  2000cited by this paper
• N‐acetylcysteine and endothelial cell injury by sulfur mustard

  2000cited by this paper
• Treatment of sulfur mustard (HD)‐induced lung injury †

  2000cited by this paper
• Recombinant tissue factor pathway inhibitor reduces lipopolysaccharide-induced pulmonary vascular injury by inhibiting leukocyte activation.

  2000influential reference
• Sulfur mustard toxicity in macrophages: effect of dexamethasone

  2000cited by this paper
• A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis.

  1999cited by this paper
• Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.

  1999cited by this paper
• Activation of poly [ADP-Ribose] polymerase in endothelial cells and keratinocytes: role in an in vitro model of sulfur mustard-mediated vesication.

  1999cited by this paper
• Dietary factors and pulmonary function: a cross sectional study in middle aged men from three European countries

  1999cited by this paper
• Characterization of the protective effects of L-nitroarginine methyl ester (L-NAME) against the toxicity of sulphur mustard in vitro.

  1998cited by this paper
• Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats.

  1998cited by this paper
• Clinical Investigations: Worms and GasThe Diversity of the Effects of Sulfur Mustard Gas Inhalation on Respiratory System 10 Years After a Single, Heavy Exposure: Analysis of 197 Cases

  1997cited by this paper
• Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study.

  1997cited by this paper
• Does dietary intake of vitamins C and E influence lung function in older people?

  1996cited by this paper
• Doxycycline inhibition of aneurysmal degeneration in an elastase-induced rat model of abdominal aortic aneurysm: preservation of aortic elastin associated with suppressed production of 92 kD gelatinase.

  1996cited by this paper
• Anti‐inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy

  1996cited by this paper
• Pathologic Changes in Rat Lungs Following Acute Sulfur Mustard Inhalation

  1996cited by this paper

• Mustard lung with a unique oxidative stress profile as an independent pulmonary disease.

  2025cites this paper
• Zataria multiflora Hydroalcoholic Extract: A Triple-Blind Randomized Controlled Trial on Immune Genes, Inflammation, and Ulcerative Colitis Symptoms.

  2025cites this paper
• Proteomic profiling and bioinformatics insights into lung tissue damage following whole-body exposure to sulfur mustard vapor.

  2025cites this paper
• Repurposing the anesthetic dexmedetomidine: a novel antidote for sulfur mustard analog-induced acute lung injury via multi-mechanism modulation.

  2025cites this paper
• Oxidative stress reactions in rats with pulmonary injuries induced by sulfur mustard (1 LD50)

  2024cites this paper
• HMSCs exosome‐derived miR‐199a‐5p attenuates sulfur mustard‐associated oxidative stress via the CAV1/NRF2 signalling pathway

  2023cites this paper