Sulfur mustard and respiratory diseases

Abstract

Victims exposed to sulfur mustard (HD) in World War I and Iran–Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran–Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO⁻), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.

Keywords::

• Sulfur mustard
• pulmonary diseases
• World War I
• Iran–Iraq war
• molecular mechanism
• drug targets

Acknowledgements

We thank Chang May Ling Joyce, Sew Wen Hui Tracey and Seow Josefina for preparation of the rat model of intratracheal spray of sulfur mustard for pathological study of the lung.

Declaration of interest

The author’s affiliation is as shown on the cover page. The authors have sole responsibility for the writing and content of the paper. The paper was prepared during the normal course of our employment and, thus, the costs were borne by our employer.