Altered levels of GST activity, Vit C, TPX and Cu in individuals with long-term sulfur mustard-induced lung complications.

CONTEXT: Sulfur mustard (SM) as a cytotoxic and blistering agent can alkylate a variety of cellular components, causing the incidence of ongoing oxidative stress. OBJECTIVE: The present study was conducted to assess oxidative stress index (OSI) in SM-exposed veterans with long-term pulmonary complications. METHODS: Participants consisted of 289 SM-exposed individuals with pulmonary complications (classified into three groups: mild, moderate and severe) and 66 healthy individuals as the control group. Enzymatic and non-enzymatic antioxidant and also trace elements were measured in the study groups. Moreover, some of oxidative stress indicators consist of malondialdehyde (MDA), protein carbonyl (CO), total antioxidant (TA) and total peroxide (TPX) were measured and then OSI was calculated. RESULTS: Glutathione-S-transferase (GST) activity and vitamin C (Vit C) were significantly decreased in SM-exposed patients as compared with controls. Besides, Cu level and Cu/Zn ratio in SM-exposed veterans showed a significant correlation with the severity of the diseases. Serum TPX was significantly increased in SM-exposed individuals, as a result of which the OSI was slightly higher in them than controls. This can be considered as an indicative for oxidative stress in SM-exposed patients. CONCLUSION: This study suggests a particular role for TPX, Cu, Vit C and GST in SM-induced pulmonary complications. Therefore, a special attention should be paid to these factors in designing therapeutic protocols, which can reduce the progression risk of the disease.

A clinicopathological approach to sulfur mustard-induced organ complications: a major review.

CONTEXT: Sulfur mustard (SM), with an old manufacturing history still remains as potential threat due to easy production and extensive effects. OBJECTIVES: Increasing studies on SM indicates the interest of researchers to this subject. Almost all human body organs are at risk for complications of SM. This study offers organ-by-organ information on the effects of SM in animals and humans. METHODS: The data sources were literature reviews since 1919 as well as our studies during the Iraq-Iran war. The search items were SM and its all other nomenclatures in relation to, in vivo, in vitro, humans, animals, eye, ocular, ophthalmic, lungs, pulmonary, skin, cutaneous, organs and systemic. Amongst more than 1890 SM-related articles, 257 more relevant clinicopathologic papers were selected for this review. RESULTS: SM induces a vast range of damages in nearly all organs. Acute SM intoxication warrants immediate approach. Among chronic lesions, delayed keratitis and blindness, bronchiolitis obliterans and respiratory distress, skin pruritus, dryness and cancers are the most commonly observed clinical sequelae. CONCLUSION: Ocular involvements in a number of patients progress toward a severe, rapid onset form of keratitis. Progressive deterioration of respiratory tract leads to "mustard lung". Skin problems continue as chronic frustrating pruritus on old scars with susceptibility to skin cancers. Due to the multiple acute and chronic morbidities created by SM exposure, uses of multiple drugs by several routes of administrations are warranted.

Effect of turbinoplasty in concha bullosa induced rhinogenic headache, a randomized clinical trial.

BACKGROUND: Rhinogenic origin is an important source for headache, which may be treated by medical or endoscopic intervention. An aim of this study was to clarify whether the surgical or medical intervention is superior. MATERIALS AND METHODS: In this randomized double blind clinical trial study, 44 patients (19 male and 25 female) with periorbital or frontal pain were enrolled. Patients were divided into 2 groups of surgical or medical intervention randomly. Medical group received 3 courses of 1.5 months 125 µg per puff, fluticason nasal spray (2 puffs Q 24 hours in each side), and oral Pseudoephedrin 30 mg Q 8 hours with 2 weeks intervals. Surgical group underwent turbinoplasty with functional endoscopic sinus surgery approach. Duration (per hour), frequency (per week) and severities of the headaches were measured by Visual Analog Scale (VAS) before treatment, and at 1.5, 3 and 6 months after institution of treatment by an examiner, who was unaware of the patients' treatment plan. RESULTS: Before treatment, chronicity (P = 0.980), severity (P = 0.742), frequency (P = 0.730), and duration (P = 0.603) of the headaches were not significantly different. The severities of the headaches in surgical group were significantly lower at 1.5, 3 and 6 months (P < 0.001), also the frequencies and the durations of the headaches were significantly lower at 6 months after an institution of treatment compared to medical group (P = 0.027, P = 0.008, respectively). CONCLUSION: Turbinoplasty in chonca bullusa patients is an acceptable and a simple procedure for relieving pain in rhinogenic headaches, compared with medical treatment.

Alteration in inflammatory mediators in seriously eye-injured war veterans, long-term after sulfur mustard exposure.

BACKGROUND: Sulfur mustard (SM) exposure produces extensive systemic and ocular adverse effects on the victims. One of the most important effects is immunological insults that can lead to other organ damages, including the eyes. METHODS: In this descriptive study, 128 SM-exposed veterans with severe eye injury were compared with 31 healthy controls. Tear levels of tumor necrosis factor (TNF)-α and serum concentrations of interleukin (IL)-1α, IL-1ß, IL1Ra, IL-6, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and Fas Ligand (FasL) were compared between the two groups. RESULTS: Meibomian gland dysfunction (MGD); tear breakup time (TBUT < 10″); and conjunctival, limbal, and corneal abnormalities were more frequent among the cases (MS-exposed veterans) than the controls. Ocular involvement was mild in 14.8%, moderate in 24.2%, and severe in 60.9% of the cases. Serum levels of IL-1α and FasL were significantly higher among the cases than among the controls (P < 0.001 and P = 0.037, respectively). Also, a significant decrease was observed in serum and tear levels of TNF-α in the cases as compared with controls (P < 0.001, P < 0.001, respectively). Serum levels of FasL were significantly higher in cases with severe ocular involvement than in the controls (P = 0.03). Nonetheless, serum levels of IL-1ß, IL-1Ra, IL-1α/IL-1Ra, and IL-6 were not significantly different between the two groups. CONCLUSION: Serum levels of IL-1α and FasL may cause different ocular surface abnormalities in SM-exposed patients. Lower tear TNF-α concentration may be due to lower serum levels of this cytokine in these patients.

Sardasht-Iran cohort study of chemical warfare victims: design and methods.

BACKGROUND: Insights into long-term clinical consequences of sulfur mustard have emerged from some investigations but less is known about the basic and molecular mechanisms of these complications. Sardasht-Iran Cohort Study is a comprehensive historical cohort study on Sardasht chemical victims' population which was designed to find out the long-term complications of sulfur mustard exposure and the basic mechanisms underlying clinical manifestations. This paper describes the design and methodology of Sardasht-Iran Cohort Study. METHODS: In Sardasht-Iran Cohort Study, 500 individuals including 372 subjects from Sardasht, as the exposed group, and 128 subjects from Rabat, as the unexposed age-matched control group were evaluated. The exposed group was divided into two groups based on the severity of clinical complications at the time of exposure. Different samples including blood, sputum, saliva, tear, urine, and semen were collected for immunologic, hematologic, biochemical, and other laboratory analysis. Data were gathered from medical records, clinical examinations, laboratory tests, and questionnaires for psychological and lifestyle situations. CONCLUSION: The important distinctions setting this study apart from the previous ones are discussed. The Sardasht-Iran Cohort Study provides important information on various aspects of long-term consequences of sulfur mustard exposure. This database will provide a better position to suggest guidelines for the diagnosis, treatment, and prevention of delayed complications in the patients exposed to sulfur mustard.

Serum and sputum levels of IL-17, IL-21, TNFα and mRNA expression of IL-17 in sulfur mustard lung tissue with long term pulmonary complications (28 years after sulfur mustard exposure).

BACKGROUND: Iranian veterans who had exposed to Sulfur Mustard (SM) suffer from long term complications such as Chronic Obstructive Pulmonary Disease (COPD) and bronchiolitis obliterate (BO). Th17 cells product IL-17A, IL-17F, IL-21, and IL-22. They have important roles in chronic inflammatory diseases. Also, TNFα has a major part in pathobiological processes of COPD. In this study, we evaluate the serum and sputum levels of IL-17, IL-21, TNF-α, and mRNA expression of IL-17 in the lung tissue of the patients 28 years after SM exposure. MATERIAL AND METHOD: The cytokine levels of IL-17, IL-21 and TNFα were measured by ELISA method in serum and sputum of 455 SM-exposed and 123 unexposed people participated in Sardasht-Iran Cohort Study (SICS) of chemical victims. The mRNA expression of IL-17 was evaluated with qRT-PCR in lung biopsies (SM-exposed =52, control =33). Analyses of all data were accomplished with the SPSS software with P value ≤05. RESULT: The results show the sputum level of IL-17 in the exposed group decreased significantly compared to control group (P = 0.007) and Veterans and Martyrs Affair Foundation (VMAF) assessment was significantly lower in abnormal/exposed than normal/exposed group (P = 0.042). There were no significant differences between control and exposed groups in serum level of IL-17; also serum and sputum levels of IL-21, TNF-α, and IL-17 mRNA expression. CONCLUSION: Conclusively, The IL-17 level decreased in the exposed group. This decline could cause by mutation on transcription factors like Signal transducer and activator of transcription 3 gene (STAT3) or CCL20 as a chemokine.

Long-term ocular complications of sulfur mustard in the civilian victims of Sardasht, Iran.

Eyes are very sensitive to sulfur mustard (SM) gas because they have wet surfaces. The severity of ocular damage is related to the dose and duration of exposure to SM, and recovery may take up to several years after the exposure. We conducted a large cohort study to evaluate the ocular signs and symptoms of 367 chemical war victims in Sardasht City, Iran, 20 years after their exposure to mustard gas. The results of these chemical war victims (i.e., the cases) were compared with the results for 128 unaffected civilians (i.e., the controls). Photophobia was the most significant symptom in the cases (36.8%) (compared with 20.3% in the controls) (p < or = .001). Ocular surface discomfort (burning, itching, and redness) was the second most significant symptom in the cases (29.2%) (compared with 19.5% in the controls) (p = .034). Other symptoms such as foreign-body sensation, tearing, pain, blurring of vision, and dry eye sensation were not significantly different between the 2 groups. In the slit-lamp findings, bulbar conjunctival abnormality was the most significant sign in the cases (9.3%) (compared with 1.6% in the controls) (p = .004). Limbal tissue changes were the second most significant sign in the cases (3.0%) (compared with 0.0% in the controls) (p = .048). Other slit-lamp findings related to tearing and abnormalities in the lids and cornea were not significantly different between the 2 groups. Our findings in the present study showed that photophobia and ocular surface discomfort (burning, itching, and redness) were the most significant symptoms. In addition, bulbar conjunctival abnormalities and limbal tissue changes were the most significant signs among the sulfur mustard chemical war victims.

Evaluation of Association Between the Serum Levels of MMP-9 and MMP-9/TIMPs With Soluble Forms of Selectins and Itching Induced by Sulfur Mustard.

BACKGROUND & OBJECTIVE: Pruritus is the most frequent chronic dermal complication of sulfur mustard (SM), which negatively influences the quality of life. Exact pathophysiology of SM-induced itching is unknown. The current study aimed at evaluating the possible association between SM-induced itching and the serum levels of matrix metalloproteinase (MMP)-9 and their endogenous inhibitors, and serum levels of soluble forms of selectins (sL-, sP-, and sE-selectins) as adhesion molecules involved in the development of different inflammatory reactions. METHODS: Serum levels of MMP-9, MMP-9/ tissue inhibitors of metalloproteinases (TIMPs), and selectins were measured by the enzyme-linked immunosorbent assay (ELISA), and compared between the groups (n=368) with and without itching, and matched control groups (n=126). RESULTS: Serum levels of MMP-9 were significantly higher in the SM exposed group with itching, compared with that of the group without itching (medians: 894 and 624 pg/mL respectively; P-value =0.034). There was no relationship between the serum levels of MMP-9/TIMP-1, MMP-9/TIMP-2, MMP-9/TIMP-4, and itching in the patients exposed to SM. Median serum levels of sE- and sL-selectins in the exposed group with itching were higher than those of the exposed group without itching. These differences were statistically insignificant (P-values =0.084 and 0.095, respectively). CONCLUSION: According to the results of the current study, the increased serum levels of MMP-9 and selectins 20 years after exposure may play role in the pathogenesis and persistence of SM-induced itching in the exposed individuals.

Correlation between MMP-9 and MMP-9/ TIMPs Complex with Pulmonary Function in Sulfur Mustard Exposed Civilians: Sardasht-Iran Cohort Study.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure. METHODS: Totally, 372 male volunteers with a history of SM- exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique. RESULTS: Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ± 2.836 vs. 1.546 ± 2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P = 0.013 respectively). CONCLUSION: High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM-exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors.

Association of Macrophage Activating Syndrome with Castleman's Syndrome in Systemic Lupus Erythematosus.

Macrophage Activating Syndrome (MAS) is a life-threatening disease seen in autoimmune diseases including lupus erythematosus, rheumatoid arthritis, Still's disease, polyarteritis nodosa. It is characterized by fever, pancytopenia, liver failure, coagulopathy, and neurologic symptoms and high serum ferritin. A 27 yr. old female patient was admitted in shahid Mostafa Khomeini Hospital (Tehran-Iran) in May 2011 because of lower extremities edema and ascites and fever from 1.5 month ago. In physical examinations she had generalized lymphadenopathy, splenomegaly and pleural effusion. In laboratory tests she had pancytopenia, positive ANA and Anti DNA (ds), hypocomplementemia, hypertriglyceridemia and high ferritin level. Gradually she had signs of RPGN and ARDS. The patient had no skin and musculoskeletal signs of SLE and no liver failure nor coagulopathy of MAS. Her lymph node biopsy was reported as Castleman syndrome. Unlike other studies, the patient showed MAS before treatment with cytotoxic for lupus nephritis.

Fibrinogen and inflammatory cytokines in spontaneous sputum of sulfur-mustard-exposed civilians--Sardasht-Iran Cohort Study.

Sulfur mustard (SM) causes late complications in respiratory system of exposed individuals. In this preliminary study, the levels of IL-1α and ß, TNF, IL-1Ra, IL-6 and fibrinogen in the spontaneous sputum of SM-exposed individuals were examined 20 years after exposure and the correlation with pulmonary function was tested. The participants were categorized into two major subgroups (hospitalized and non-hospitalized) based on the severity of the clinical complications immediately after exposure. Every participant was visited by a physician; the respiratory functions were checked using spirometry and were categorized as normal, mild, moderate or severe pulmonary complications. The levels of cytokines in the sputum and serum samples were measured using ELISA method. The mean values of TNF, IL-1α and IL-1ß were 524.15, 115.15, 1951.33 pg/ml respectively, and the mean levels of IL-1Ra and IL-6 were 6410.52 and 124.44 pg/ml respectively; fibrinogen was 71.59 ng/ml and index of IL-Ra/IL-1ß was 7.78. There was more TNF-α and IL-1ß and less IL-1Ra and fibrinogen in the sputum of the hospitalized subgroup. The level of TNF-α and IL-1ß also increased in moderate and severe pulmonary status comparing with the group with mild disorders, while fibrinogen was lower or decreased significantly in problematic patients. IL-1ß and TNF showed positive correlation (r=0.5, and r=0.59, respectively); fibrinogen and IL1Ra/IL-1ß have negative correlation with lung function according to the GOLD classification (r=-0.4, and r=-0.61, respectively). It is concluded that sputum cytokines and fibrinogen, reflect the degree of the severity of airway inflammation and the cytokine levels in the sputum might be completely different from the serum fluctuations.

Are serum levels of immunoglobulin classes and IgG subclasses involved in delayed pulmonary complications induced by sulfur mustard? Sardasht-Iran Cohort Study.

Respiratory complications are the foremost long term debilitating effects after sulfur mustard toxicity. The underlying immunological mechanisms of sulfur mustard induced lung damage are still poorly understood. The question of the involvement of immunoglobulin classes and subclasses in delayed pulmonary complications induced by SM was addressed in this study as a part of Sardasht-Iran Cohort Study (SICS).In SICS, 372 male participants who were exposed to SM 20 years earlier were compared with 128 unexposed age-matched controls. At the time of study (2007), the clinical evaluations and spirometry was performed for all subjects according to the American Thoracic Society Criteria, and at the same time, the sera were isolated, labeled and aliquots were kept frozen in -80°C. Serum immunoglobulin (Ig) levels including IgM, IgA, IgE, IgG, and IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were measured using quantitative Elisa method. It was found that among immunoglobulin classes and IgG subclasses only IgM and IgG4 were significantly decreased in the peripheral blood of exposed cases. IgM level also positively correlated with FEV1 only in the SM exposed group. These results indicated a weak but significant role for IgA in control of the delayed pulmonary complications. There were no strong correlations between other immunoglobulin classes or IgG subclasses with pulmonary disease severity in sulfur mustard intoxicated subjects. The authors proposed that systemic levels of immunoglobulins do not exert essential roles in severity of delayed pulmonary complications following SM toxicity. However, more studies on local and systemic levels of immunoglobulins in more severe groups are suggested.

Chemokines, MMP-9 and PMN elastase in spontaneous sputum of sulfur mustard exposed civilians: Sardasht-Iran Cohort Study.

Chemokines play an important role in acute and chronic pulmonary diseases. The aim of this study was to evaluate the levels of chemokines, MMP-9, and PMN elastase in spontaneous sputum and serum of patients 20 years after SM exposure. In context of Sardasht-Iran Cohort Study (SICS) 40 male volunteers with a history of SM exposure in June 1987 and complain of excessive sputum were recruited. The volunteers were clinically examined and their history was collected by internists. Sputum and serum levels of IL-8, fractalkine, MCP-1, RANTES, MMP-9, and PMN elastase were measured using ELISA kits (R&D System). Spirometries were performed on all the participants. Sputum level of fractalkine was significantly lower in the hospitalized group (N=16, Median=1.05; IQR=0.41-2.62) than non-hospitalized group (N=18, 4.031; IQR=0.947-8.203) (p=0.042). However, serum levels of fractalkine were higher in the hospitalized group (Mean±SD=2.08±5.09) than in the non-hospitalized (Mean±SD=0.53±0.87) group (T-test, p=0.03). Serum levels of PMN-elastase were also higher in the hospitalized group (Mean±SD; 64,794.43±26,820.08) than in the non-hospitalized group (Mean±SD=44,049.33±17,675.85) (p=0.017). There was no relationship between the cytokines and the studied factors in sputum and the GOLD classification, but the serum levels of fractalkine and MMP-9 were significantly higher in the more severe (grades 3-4) group. There was no significant correlation between sputum and serum levels of measured inflammatory mediators and pulmonary complications in the patients who were exposed to SM 20 years earlier. Pathophysiologic process involved in SM induced pulmonary problems might be different from those in other chronic pulmonary diseases such as COPD and asthma.

Salivary levels of secretary IgA, C5a and alpha 1-antitrypsin in sulfur mustard exposed patients 20 years after the exposure, Sardasht-Iran Cohort Study (SICS).

Sulfur mustard (SM) is a strong toxic agent that causes acute and chronic health effects on a myriad of organs following exposure. Although the primary targets of inhaled mustard gas are the epithelia of the upper respiratory tract, the lower respiratory tract is the focus of the current study, and upper tract complications remain obscure. To our knowledge there is no study addressing the secretory IgA (S-IgA), C5a, alpha 1 antitrypsin (A1AT) in the saliva of SM-exposed victims. In this study, as many as 500 volunteers, including 372 SM-exposed cases and 128 control volunteers were recruited. A 3 ml sample of saliva was collected from each volunteer, and the level of secretory IgA, C5a, and alpha 1 antitrypsin in the samples were compared between the two groups. The SM-exposed group showed a significantly higher amount of salivary alpha 1 antitrypsin and secretary IgA compared to the control group (p<.006 and p<.018 respectively). The two groups showed no significant difference (p=0.192) in the level of C5a. The results also showed that the level of salivary A1AT is more than that of IgA in severely injured cases. The findings presented here provide valuable insight for both researchers and practitioners dealing with victims of the chemical warfare agent, sulfur mustard. This research indicates that certain branches of the inflammatory processes mandate serious attention in therapeutic interventions.

Evaluation of pre lumbar puncture position on post lumbar puncture headache.

BACKGROUND: The most common complication of lumbar puncture (LP) occurring in over thirty percent of patients is headache. The position after lumbar puncture, needle type and size, and volume of the extracted cerebrospinal fluid (CSF) have been evaluated as contributory factors in occurrence of post lumbar puncture headache (PLPH), but the position before lumbar puncture has not been evaluated. METHODS: The occurrence of post lumbar puncture headache was evaluated in 125 patients undergoing lumbar puncture, divided randomly into sitting and lateral decubitus groups in the following five days. Chi-square test was used for statistical analysis. RESULTS: Thirty eight patients (30.4%) reported headache after lumbar puncture in the two groups, and post lumbar puncture headache was significantly lower in the lateral decubitus position (p = 0.001). There was no significant difference between genders in the post lumbar puncture headache occurrence (p = 0.767). CONCLUSIONS: Lumbar puncture in sitting position could produce more post lumbar puncture headache in comparison with lateral decubitus position.

Evaluation of relationship between the serum levels of inflammatory mediators and ocular injuries induced by sulfur mustard: Sardasht-Iran Cohort Study.

Ocular damages induced by sulfur mustard (SM) are the important problems in exposed patients. The damaging mechanisms are not clearly understood. In the present study the relationship between the serum levels of inflammatory mediators and ocular injuries induced by SM was evaluated. Bulbar conjunctiva and limbal tissue abnormalities were significantly more frequent in the expose versus control group (P=0.004 and 0.048 respectively). The serum levels of IL-1alpha and TNF-alpha in the exposed group with and without Slit lamp findings were significantly lower than their counterpart in the control group. The serum levels of IL-1beta in the exposed group with Slit lamp findings were significantly lower than their counterpart in the control group. The serum levels of IL-1beta in the controls with Slit lamp findings were significantly higher than the controls without Slit lamp findings. The serum levels of IL-1Ra and MMP-9 in the exposed group with and without Slit lamp findings do not display any significant differences as compared to the similar controls. The serum levels of IL-6 in the exposed group with or without Slit lamp findings were significantly lower than their counterpart in the control group (P=0.048 and 0.008 respectively). The serum titers of the CRP and RF in the exposed group without Slit lamp findings were significantly elevated versus their counterpart in the control group (P=0.004 and 0.011 respectively). The serum levels of these inflammatory cytokines except for IL-1Ra and MMP-9, decreased in SM exposed subject independent of ocular problems. More local studies on the eyes are needed to clarify the exact role of this cytokines in ocular problems of chemical.

Serum levels of GM-CSF 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study.

Sulfur mustard (SM) is highly toxic for various organs. The eyes, skin, respiratory tract, as well hematopoietic and immune systems are the main organs affected by SM. Granulocyte-macrophage colony stimulating factor (GM-CSF) is a potent cytokine that plays an important role in the hematopoietic and immune system. The aim of this study was to determine the serum levels of GM-CSF and its relation to blood cell count and other inflammatory cytokines 20 years after SM exposure. The association of GM-CSF with the clinical severity of pulmonary, ophthalmic and dermatologic complications has also been studied. In this historical cohort study named as Sardasht-Iran Cohort Study (SICS), 369 SM exposed male participants and 125 unexposed volunteers were studied. The serum concentrations of cytokines were measured by ELISA technique. The severity of clinical complications was graded according to the criteria verified by the Medical Committee of the Foundation of Martyr and Veterans Affairs. The serum levels of GM-CSF in the SM exposed group did not display any significant differences with the control group. Median of GM-CSF was 7.33 and 9.39 pg/ml in the SM exposed group and the controls respectively. There was a positive correlation between the serum levels of GM-CSF and the percent of eosinophils only in the exposed group. Moreover, positive correlations were found between circulating levels of GM-CSF with IL-1alpha, IL-1beta, TNF-alpha and IL-6. This correlation was not observed between GM-CSF and IL-8 in both study groups. The serum levels of GM-CSF did not show any significant association with clinical complications.

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

Sulfur mustard (SM) has short- and long-term toxicity against various organs including the respiratory system. However, the basic and molecular mechanisms of SM long-term toxicity have not clearly been defined. Thus, the aim of this study was to evaluate the association of soluble Fas ligand (sFasL) as well as nitric oxide (NO) serum levels with long-term pulmonary complications in a SM exposed population 20 years after SM exposure. In this historical cohort study 372 male SM exposed subjects and 128 age-matched unexposed controls were studied. Clinical evaluation and pulmonary function tests were carried out for all participants and serum concentrations of sFasL and NO measured. According to our results, the serum levels of sFasL and NO were not significantly different between the exposed and control groups. However, the serum levels of sFasL in the exposed group with pulmonary problems were significantly higher than their corresponding in the control group (116.711+/-81.166 vs 86.027+/-30.199 and p=0.028). Furthermore a significant elevation in sFasL levels was found in the exposed subjects with pulmonary problems compared to those exposed participants without pulmonary problems (116.711+/-81.166 vs 90.692+/-57.853 and p=0.004). Based on Global Initiative for chronic Obstructive Lung Disease (GOLD) classification analysis a positive correlation was observed between sFasL levels and pulmonary problems. There was also a significant negative correlation between sFasL and the white blood cell (WBC) count in the SM exposed cohort, but not in the control group. No significant association was shown between NO and pulmonary impairment in the SM exposed subjects. Thus, our results indicate that elevated serum levels of sFasL may be associated with progression of pulmonary diseases in the SM exposed subjects.

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

Sulfur mustard (SM) is a blistering chemical agent which has short and long term toxicity against many organs. The respiratory tract is one of the main targets, and is the most disabling long term complication of SM. Inflammatory mediators especially IL-8 and IL-6 play the primary role in the various chronic pulmonary diseases. Sardasht-Iran Cohort Study (SICS) was designed to evaluate immunological and molecular parameters in SM exposed people 20 years after exposure. In the present study, the association of the serum levels of IL-8, IL-6, C reactive protein (CRP) and rheumatoid factor (RF) with long term pulmonary involvement was evaluated. There were 348 exposed and 120 control participants. The clinical evaluations were done for all subjects and Spirometry was performed according to American Thoracic Society Criteria. Severity of pulmonary involvement was assessed by Global Initiative for chronic Obstructive Lung Disease (GOLD) classification. The serum levels of IL-8, IL-6 and RF were assessed by ELISA assay. CRP was assessed by photometric method. The serum levels of IL-8 and IL-6 significantly decreased in the SM exposed participants compared to the control group. There were no significant associations between the serum levels of IL-8 and pulmonary symptoms (chronic cough, sputum, hemoptysis, and dyspnea), pulmonary findings (crackles, rales, and wheezing) as well as spirometry parameters. IL-6 was associated with wheezing and CRP was associated with wheezing and rales in SM exposed group. We concluded the serum levels of these inflammatory mediators probably do not have any major role in pathogenesis and persistence of pulmonary complications and do not reflect the degree of severity of pulmonary involvement following SM exposure.