Complications and Carcinogenic Effects of Mustard Gas - a Systematic Review and Meta-Analysis in Iran

Abstract

Background: Catastrophic effects of mustard gas as a chemical warfare agent have always been a major problem for those exposed to this agent. In this meta-analysis it was tried to evaluate carcinogenesis, ocular, cutaneous and respiratory complications of mustard gas exposure among Iranians who had been exposed to this agent during the Iran-Iraq war. Materials and Methods: In this meta-analysis, the required data were collected using keywords "mustard gas", "sulfur mustard", "cancer", "neoplasm", "respiratory complications", "ocular complications" , "lung disease", "chronic complication", "eye", "skin", "cutaneous complication", "carcinogenesis" and their combination with keywords "Iran", "Iranian", "prevalence", "mortality" and their Farsi equivalent terms from the databases of SID, Iranmedex, Magiran, Pubmed, Science Direct, Google Search engine, Gray Literature and Reference of References. To determine the prevalence of each complication and perform meta-analysis, CMA: 2 (Comprehensive Meta-Analysis) software with a randomized model was used. Results: Of the 542 articles found, 7 national articles, consistent with the aims of this study were selected. Metaanalysis of seven papers revealed that cancer risk, especially cancer of the respiratory system was elevated, so that the relative risk (RR) of cancer role of mustard gas was inconsistent from 2/1 to 4 in this survey. Also prevalence of delayed skin disorders due to sulfur mustard was 94.6%, pulmonary complications 94.5% and ocular complications 89.9%. The incidence of various cancers in victims exposed to mustard gas was 1.7% worldwide where the rate was 2.2% in Iranian victims of the Iraq-Iran war. Conclusions: Based on present study the prevalence of delayed mustard gas related cutaneous, pulmonary and ocular complications is above 90% and risk of carcinogenesis is higher in comparison to worldwide statistics. This may suggest need for long-term and persistent follow-up and rehabilitation procedures for populations exposed to this agent.

Clinical practice guidelines for prevention, diagnosis and management of early and delayed-onset ocular injuries due to mustard gas exposure

“…[21415] Because of the wet and mucosal surface of the cornea and conjunctiva and the high volume of interactions and metabolic activities of corneal epithelial cells, eye is the most sensitive tissue to SM. [16171819] The delayed-onset MG injuries have been reported one to forty years after the initial exposure.…”

Sulfur mustard inhalation: mechanisms of injury, alteration of coagulation, and fibrinolytic therapy

“…A meta‐analysis of studies of formerly exposed individuals determined a 94.6% prevalence of delayed skin disorders, a 94.5% prevalence of pulmonary complications, and an 89.9% prevalence of ocular complications . The incidence of various cancers varied, but was in the range 1.7–2.2%.…”

“…Among those exposed in the Iran–Iraq conflict, 75% of survivors were noted to develop tracheal and/or bronchial deformities or strictures, BO, and/or pulmonary fibrosis. Additional airway complications, including chronic bronchitis, recurrent pneumonia, bronchiectasis, and tracheobronchomalacia, have also been reported . A number of patients have had constrictive bronchiolitis on lung biopsy, even with normal pulmonary function tests and chest high‐resolution computed tomography scans …”

“…For example, chronic complications in the skin can include hyperpigmentation, hypertrophic scarring, and/or secondary joint deformity. Within the eyes, latent onset of ulcerative keratitis after a decade‐long asymptomatic period was described in World War I veterans and in Iranian veterans exposed during the 1980s . These lesions recur even after corneal transplant and may lead to late‐onset blindness.…”

TGF‐β and Th17 cells related injuries in patients with sulfur mustard exposure

“…Approximately, 80% of the SM exposed individuals exhibit chronic symptoms even after 20 years of exposure such as sputum production, cough, shallow breathing, and chest pain (Ghanei, Poursaleh, Harandi, Emadi, & Emadi, ). The complications of eyes, skin, genitourinary system, and cancers in both acute and chronic exposure have been reported (Ghabili, Agutter, Ghanei, Ansarin, & Shoja, ; Panahi et al, , ). Oxidative stress and chronic inflammation following SM gas inhalation cause tissue damage and immune cell stimulation and recruitment (Ghanei & Harandi, ; Mansour Razavi, Salamati, Saghafinia, & Abdollahi, ; Tahmasbpour, Ghanei, Qazvini, Vahedi, & Panahi, ; Tahmasbpour Marzony, Ghanei, & Panahi, ), which eventuate in overexpression of profibrotic mediators (Murray et al, ; Wynn, ) and pro‐inflammatory cytokines (Li et al, ; Wang et al, ).…”