UNASSIGNED: The primary objective of this study was to analyze the long-term survival of 48,067 chemical warfare survivors who suffered from pulmonary, cutaneous, and ocular lesions in the decades following the Iran-Iraq war.
UNASSIGNED: The data for this study were obtained from the Veterans and Martyr Affair Foundation (VMAF) database. The survivors were divided into two groups based on whether they were evacuated/admitted (EA) to a hospital or not evacuated/admitted (NEA) to a hospital. The proportional hazard (PH) assumption for age categories, gender, exposure statuses, and eye severity was not satisfied. Therefore, we used a Generalized Gamma (GG) distribution with an Accelerated Failure Time (AFT) model for analysis.
UNASSIGNED: The study included a total of 48,067 observations, and among them, 4342 (9.03 %) died during the study period. The mean (SD) age of the survivors was 55.99 (7.9) years. The mortality rate increased with age, and higher rates were observed in males. Survival probabilities differed significantly among age categories, provinces, lung severity, and eye severity based on log-rank tests (p-value<0.05 for all). The GG model results showed that higher age and being male were associated with a shorter time to death. The study also found that the mortality rate was significantly higher in the EA group compared to the NEA group.
UNASSIGNED: The present study showed no significant difference in survival time between the EA and NEA groups. The findings suggest that pulmonary lesions caused by mustard gas are more likely to be fatal compared to skin and eye lesions. The results also indicate a potential association between survival time and the severity of lung damage.

UNASSIGNED: In 1988, the Iraqi government used a range of chemical weapons (CWs) against the Iraqi Kurds of Halabja. Here, we aim to investigate the long-term health consequences in exposed survivors as they are not sufficiently studied.
UNASSIGNED: This was a retrospective study conducted from November 2019 to May 2020 assessing the health status of all exposed Halabja chemical attack survivors compared to non-exposed people from the same area.
UNASSIGNED: Two hundred thirty survivors and 240 non-exposed participants were enrolled in this study, with control participants matched to age, gender, and occupation. Among the survivors, females were more prevalent. The respiratory system was the most common single exposure route (83, 36.1%), with 138 (60%) of the survivors being exposed by multiple routes. The vast majority (88.7%) of survivors had activities of daily living (ADL) impairment. There was female predominance in mild and moderate cases, with more males in severe cases (p < 0.01). Respiratory and cardiac diseases were significantly more common in the survivors compared to the controls (p < 0.001). Survivors with multiple CW exposure routes had significantly higher rates of ADL impairment (p < 0.001) and cardiac disease, respiratory diseases, and miscarriage (p < 0.01), than those with a single exposure route.
UNASSIGNED: In this study comparing CW survivors with a local control population, a single, high-dose exposure to CWs was associated with significant increases in chronic respiratory and cardiac conditions, in addition to high rates of ADL impairment. Similar studies are needed in other, more recent CW survivor cohorts.

BACKGROUND: Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the eight-year Iran-Iraq conflict and permanently injured while the socioeconomic imbalance in their healthcare utilization (HCU) and health expenditures remains. This study aims to describe the HCU of SM-exposed survivors in Iran from 2018 to 2021; identify high-risk areas; and apply an inequality analysis of utilization regarding the socioeconomic groups to reduce the gap by controlling crucial determinants.
METHODS: From Oct 2018 to June 2021, the Veterans and Martyrs Affairs Foundation (VMAF) recorded 58,888 living war survivors with eye, lung, and skin ailments. After cleaning the dataset and removing junk codes, we defined 11 HCU-related variables and predicted the HCU for the upcoming years using Bayesian spatio-temporal models. We explored the association of individual-level HCU and determinants using a Zero-inflated Poisson (ZIP) model and also investigated the provincial hotspots using Local Moran\'s I.
RESULTS: With ≥ 90% confidence, we discovered eleven HCU clusters in Iran. We discovered that the expected number of HCU 1) rises with increasing age, severity of complications in survivors\' eyes and lungs, wealth index (WI), life expectancy (LE), and hospital beds ratio; and 2) decreases with growing skin complications, years of schooling (YOS), urbanization, number of hospital beds, length of stay (LOS) in bed, and bed occupancy rate (BOR). The concentration index (CInd) of HCU and associated costs in age and wealth groups were all positive, however, the signs of CInd values for HCU and total cost in YOS, urbanization, LOS, and Hospital beds ratio groups were not identical.
CONCLUSIONS: We observed a tendency of pro-rich inequity and also higher HCU and expenditures for the elderly population. Finally, health policies should tackle potential socioeconomic inequities to reduce HCU gaps in the SM-exposed population. Also, policymakers should allocate the resources according to the hotspots of HCU.

OBJECTIVE: This study aims to assess the prognosis of inpatients with COVID-19 infection who have a history of sulfur mustard exposure.
METHODS: We started a cohort study in October 2020 and ended in May 2021 on inpatients with COVID-19 infection who had been admitted to university healthcare centers. The analytic sample included 960 inpatients having COVID-19 infection (192 with; and 768 without sulfur mustard exposure). The exposed patients were male war veterans, and the unexposed patients were male individually age-matched people. All patients had a positive RT-PCR test and a positive chest CT for COVID-19. The outcome was death within 28 days of admission, and the predictors were clinical features recorded at patients\' bedsides.
RESULTS: There was a significantly higher prevalence for asthma (p = 0.026) and pulmonary disease other than asthma (p < 0.001) in patients with the exposure. Sulfur mustard exposure was associated with increased risk for mortality of COVID-19 [hazard ratio (95% CI) = 1.92 (1.14,3.24), p = 0.013]. Early intubation signified a poor prognosis [hazard = 7.34 (4.65,11.58), p < 0.001]. However, individuals with higher PaO2 [hazard = 0.97 (0.95,0.98), p < 0.001], or people undergoing O2 therapy early upon admission [hazard = 0.58 (0.38,0.89), p = 0.011] showed lower risks for mortality. Individuals with asthma were at higher risk for mortality [hazard = 3.76 (1.69,8.36), p = 0.001].
CONCLUSIONS: Individuals with COVID-19 infection and sulfur mustard exposure should be considered high-risk patients and that, healthcare settings should be ready to provide critical care for them, including O2 therapy. They are more likely to have asthma or other pulmonary diseases.

Sulfur Mustard (SM) induces cell injury via exerting oxidative stress, protease-anti protease imbalance, and inflammation. Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1), and Interleukin-1β (IL-1β)  genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to up-regulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1 (~4 fold) genes (p<0.0001). However, the NF-ĸB gene expression level did not alter following CEES exposure. Even though low doses of curcumin (20, 40, and 80 mM) were able to down-regulate the studied genes, it was found that the treatment of cells with 160 mM of curcumin for 48 h was able to normalize the expression level of all genes. The present study concludes that curcumin as an anti-inflammatory agent may have beneficial immunomodulatory effects following CEES exposure.

This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model.
Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer\'s tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.
TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer\'s test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer\'s test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.
The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.
TED is effective against MGK.

BACKGROUND: Zataria multiflora (Z. multiflora) belongs to the Lamiaceae family and has several traditional uses owing to its antiseptic, aesthetic, antispasmodic, analgesic, and antidiarrheal properties.
OBJECTIVE: We aimed to investigate the effect of Z. multiflora on serum cytokine levels and pulmonary function tests (PFT) in patients exposed to sulfur mustard (SM) for a long term (27-30 years).
METHODS: Thirty-five patients were randomly assigned to the placebo group (P) and two experimental groups treated with Z. multiflora extracts, i.e., 5 and 10 mg/kg/day (Z5 and Z10). Serum levels of cytokines including IL (2, 4, 6, 8, and 10) and IFN-γ as well as PFT indices such as maximum mid-expiratory flow (MMEF) and maximum expiratory flow at 25, 50, and 75% of vital capacity (VC) (MEF25, 50, and 75) were assessed at the beginning (phase 0) and at the end of 4 and 8 weeks (phases I and II, respectively) after starting the treatment.
RESULTS: Serum levels of IL-2, IL-6, and IL-8 were significantly decreased, while serum levels of IL-10 and IFN-γ were significantly increased in the Z5 and Z10 treatment groups in phases I and II as compared to those in phase 0 (p < 0.05 to p < 0.001). MMEF and MEF25, 50, and 75 values were significantly increased in the Z5 group in phase II and in the Z10 group in phases I and II compared to those in phase 0 (p < 0.05 to p < 0.001). The percent change in serum cytokine levels and the change in MEF25, 50, and 75 during the two-month treatment period were significantly higher in the treatment groups than in the placebo group.
CONCLUSIONS: Two months of treatment with Z. multiflora reduced inflammation, while it enhanced anti-inflammatory cytokines and improved PFT indices in SM-exposed patients.

Sulfur mustard (SM) is a destructive and harmful chemical agent for the eyes, skin and lungs that causes short-term and long-term lesions and was widely used in Iraq war against Iran (1980-1988). SM causes DNA damages, oxidative stress, and Inflammation. Considering the similarities between SM and COPD (Chronic Obstructive Pulmonary Disease) pathogens and limited available treatments, a novel therapeutic approach is not developed. Gene therapy is a novel therapeutic approach that uses genetic engineering science in treatment of most diseases including chronic obstructive pulmonary disease. In this review, attempts to presenting a comprehensive study of mustard lung and introducing the genes therapy involved in chronic obstructive pulmonary disease and emphasizing the pathways and genes involved in the pathology and pathogenesis of sulfur Mustard. It seems that, given the high potential of gene therapy and the fact that this experimental technique is a candidate for the treatment of pulmonary diseases, further study of genes, vectors and gene transfer systems can draw a very positive perspective of gene therapy in near future.

Oxidative stress is the major mechanism impairing cell homeostasis, inducing cell death and tissue damage in sulfur mustard (SM)-exposed individuals. The aim of the present study was to evaluate time course changes of oxidative stress in the mice exposed with 2‑chloroethyl ethyl sulfide (CEES) as SM analog. For this purpose, male BALB/c mice were divided into control groups and experimental groups that received CEES (10 mg/kg) through intraperitoneal injection. In both groups, animals were euthanized at three periods: short (12, 24 h and 1 week), medium (1, 2 and 3 months) and long-term (5 and 6 months) after CEES exposure. Oxidative stress indices and the antioxidant defense systems were evaluated in lung and liver tissues. The time course findings in both tissues showed a significant increase in oxidative damage markers such as malondialdehyde (lung P < 0.001, liver P < 0.001), protein carbonyl (lung P < 0.0001), and 8-hydroxy-deoxyguanosine (lung P < 0.0001, Liver P < 0.0001) and also a significant reduction in the antioxidant defense system including reduced glutathione level (lung P < 0.001, Liver P < 0.001,), activities of catalase (lung P < 0.01 and liver P < 0.05), superoxide dismutase (lung P < 0.05), glutathione S‑transferase (lung P < 0.05, liver P < 0.01), glutathione peroxidase (lung, P < 0.05, Liver P < 0.05) and glutathione reductase (lung P < 0.001, liver P < 0.01) in the long-term. However, these changes occur with less intensity in the short-term and return to the normal status in the medium-term. Moreover, there was a positive time course correlation between oxidative damage indices and the percent of histopathological damage in both tissues (P < 0.05). This correlation finding confirms and supports the fact that time course oxidative-antioxidant imbalance plays an important role in the development of SM-induced acute and delayed injuries.

The aim of this study was to evaluate the effect of carvacrol on serum level of inflammatory mediators and respiratory symptoms in the veterans exposed to sulfur mustard (SM).
Twenty-one patients who were exposed to SM more than two decades\' ago were divided to placebo and carvacrol (1.2 mg/kg/day) treated groups. Serum levels of Tumor Necrosis Factor-α (TNF-α), Monocyte chemotactic protein-1 (MCP-1), Vascular endothelial growth factor (VEGF), Epidermal growth factor (EGF), forced expiratory volume-one second (FEV1) and respiratory symptoms including; Chest wheeze (CW), night wheeze (NW), night cough (NC) and cough and wheeze during exercise (ECW) were assessed at the baseline (step 0), one and two months after starting treatment (step I and II, respectively).
FEV1 value was significantly increased in carvacrol treated group in step II compared to step 0 (p < 0.001) and also increased in step II compared to step I (p < 0.05). The respiratory symptoms including; CW and NW was significant decreased in carvacrol treated group in step I and II compared to step 0 (p < 0.01 to p < 0.001), NC and ECW were significantly decreased only in step II compared to step 0 (p < 0.01, for both cases). The serum levels of TNF-α, EGF and VEGF were decrease in carvacrol treated group in step I and II compared to step 0 (p < 0.05 to p < 0.001). The serum level of MCP-1 was decrease in carvacrol treated group only in the step II compared to step 0 (p < 0.05).
Two months\' treatment with carvacrol reduced inflammatory cytokine and chemokine while increased anti-inflammatory cytokines and improved respiratory symptom and FEV1 value in SM exposed patients.
This trial was registered under IRCT2014031617020N1 at http://www.irct.ir/.