Open Access

Pirfenidone; can it be a new horizon for the treatment of pulmonary fibrosis in mustard gas-intoxicated patients?

DARU Journal of Pharmaceutical Sciences201321:13

DOI: 10.1186/2008-2231-21-13

Received: 16 November 2012

Accepted: 7 February 2013

Published: 18 February 2013

Abstract

Sulfur mustard is an alkylating substance still regarded as a threat in chemical warfare and terrorism. Lung parenchymal damage occurs in the most severe inhalational exposures. It accompanies an increased risk of respiratory tract carcinomas and chronic respiratory sequelae including chronic bronchitis, bronchiectasis, pulmonary fibrosis, interstitial lung disease, emphysema, and bronchiolitis obliterans. Pirfenidone is an antifibrotic with anti-inflammatory and anti hydroxyl radical activities which stabilizes pulmonary function in idiopathic pulmonary fibrosis patients. It can be suggested in chronically exposed soldiers or workers with signs and symptoms of pulmonary fibrosis to improve their quality of life and even prognosis.

Keywords

Pirfenidone Mustard gas Pulmonary fibrosis

Introduction

Sulfur mustard (SM) is an alkylating substance still regarded as a significant threat in chemical warfare and terrorism. The organs that are most commonly affected by mustard are the eyes, skin, and respiratory tract. Even decades after exposure, severe long-term effects such as chronic obstructive lung disease, lung fibrosis, eye problems, abnormal pigmentation of the skin, and various forms of cancer have been diagnosed in these individuals. Mustard undergoes intramolecular cyclization to form a highly reactive sulfonium ion that alkylates sulfhydryl (−SH) and amino (−NH2) groups. Hoarseness, cough, sore throat, and chest pressure are common initial complaints, but lung parenchymal damage only occurs in the most severe inhalational exposures. Factory workers chronically exposed to mustard as well as soldiers exposed to it during chemical wars have been reported to have an increased risk of respiratory tract carcinomas as well as chronic respiratory sequelae including chronic bronchitis, bronchiectasis, pulmonary fibrosis, interstitial lung disease, emphysema, and bronchiolitis obliterans [1].

During world war I, airway injury had been reported in 75% of those exposed to it [1]. Many Iranian soldiers (about 40000 to 50000 during the war between Iran and Iraq in 1980–88) are also of those currently injured and have chronic respiratory diseases due to mustard gas [2]. In different studies, the late onset of lung injuries among Iranian soldiers with wartime exposure to SM has been reported to be between 42.5% and 95% [1, 2]. In a review performed by Mansour Razavi and colleagues, the prevalence of chronic pulmonary complications has been mentioned to be between 45.8% to 100% in civilian populations, 42.5% to 95% in veterans, and almost 100% in the children [3]. The late complications of SM in 600 patients evaluated 19 years after exposure has been reported 80.7% in another study [4]. In a review done by Poursaleh and associates, respiratory problems have been mentioned to be the greatest cause of long-term disability among the people with combat exposure to SM [5]. In this study, honeycomb lung pathology as fibrosis and slightly increased tendency for development of lung cancer with a latency of 20 years have been mentioned as two potential chronic complications of SM.

Mild, severe, and focal fibrosis were present in 4.8%, 1.6%, and 4.8% of the patients [6]. The most common alleged mechanism of such injuries is damaging the epithelial layer of the lung and airways with subsequent release of inflammatory mediators [7].

On the other hand, pirfenidone (5-methyl-1-phenyl H-pyridin-2-one) is a newly discovered antifibrotic with anti-inflammatory and anti hydroxyl radical activities [8]. Its probable mechanism of act is inhibition of transforming Growth Factor Beta production. Its anti-inflammatory effect is probably due to the amelioration of the effect of Tumor Necrosis Factor Alpha. It has been shown that pirfenidone stabilizes pulmonary function in idiopathic pulmonary fibrosis patients [8].

It can be suggested that in the sulfur mustard-exposed soldiers or the workers who are chronically exposed to this hazardous material and show signs and symptoms of pulmonary fibrosis, administration of this medication can improve their quality of life and even prognosis. This approach, however, should be reserved for those with confirmed pulmonary fibrosis and not as a routine approach for all who have confronted SM. Besides, prospective case–control studies in this regard are warranted. Thank you.

Declarations

Authors’ Affiliations

(1)
Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences

References

  1. Suchard JR: Chemical weapons. Goldfrank's Toxicologic Emergencies. Edited by: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS. 2006, New York: McGraw-Hill, 1775-71. 8Google Scholar
  2. Mustard agents.http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/mustard-agents,
  3. Mansour Razavi S, Salamati P, Saghafinia M, Abdollahi M: A review on delayed toxic effects of sulfur mustard in Iranian veterans. Daru. 2012, 20: 51-PubMed CentralView ArticlePubMedGoogle Scholar
  4. Ghassemi-Broumand M, Aslani J, Emadi SN: Delayed ocular, pulmonary, and cutaneous complications of mustards in patients in the city of Sardasht. Iran. Cutan Ocul Toxicol. 2008, 27: 295-305. 10.1080/15569520802327807.View ArticlePubMedGoogle Scholar
  5. Poursaleh Z, Harandi AA, Vahedi E, Ghanei M: Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase. Daru. 2012, 20: 27-PubMed CentralView ArticlePubMedGoogle Scholar
  6. Bakhtavar K, Sedighi N, Sheikhvatan M: Inspiratory and expiratory high-resolution CT findings and chronic pulmonary effects of mustard gas exposure. Research Journal of Biological Science. 2009, 4: 453-7.Google Scholar
  7. Bijani K, Moghadamnia AA: Long-term effects of chemical weapons on respiratory tract in Iraq-Iran war victims living in Babol (North of Iran). Ecotoxicol Environ Saf. 2002, 53: 422-4. 10.1016/S0147-6513(02)00034-9.View ArticlePubMedGoogle Scholar
  8. Azuma A: Pirfenidone treatment of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2012, 6: 107-14. 10.1177/1753465812436663.View ArticlePubMedGoogle Scholar

Copyright

© Zamani; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement