Adipose-derived mesenchymal stem cells for treatment of airway injuries in a patient after long-term exposure to sulfur mustard

Objective: Sulfur mustard [SM] is a potent mutagenic agent that targets several organs, particularly lung tissue. Changes in morphological structure of the airway system are associated with chronic obstructive pulmonary deficiency following exposure to SM. Although numerous studies have demonstrated pathological effects of SM on respiratory organs, unfortunately there is no effective treatment to inhibit further respiratory injuries or induce repair in these patients. Due to the extensive progress and achievements in stem cell therapy, we have aimed to evaluate safety and potential efficacy of systemic mesenchymal stem cell [MSC] administration on a SM-exposed patient with chronic lung injuries

Materials and Methods: In this clinical trial study, our patient received 100x106 cells every 20 days for 4 injections over a 2-month period. After each injection we evaluated the safety, pulmonary function tests [PFT], chronic obstructive pulmonary disease [COPD] Assessment Test [CAT], St. George's Respiratory Questionnaire [SGRQ], Borg Scale Dyspnea Assessment [BSDA], and 6 Minute Walk Test [6MWT]. One-way ANOVA test was used in this study which was not significant [P>0.05]

Results: There were no infusion toxicities or serious adverse events caused by MSC administration. Although there was no significant difference in PFTs, we found a significant improvement for 6MWT, as well as BSDA, SGRQ, and CAT scores after each injection

Conclusion: Systemic MSC administration appears to be safe in SM-exposed patients with moderate to severe injuries and provides a basis for subsequent cell therapy investigations in other patients with this disorder

[Comparison between therapeutic effects of doxepine and hydroxyzine on resistant pruritic lesions due to sulfur mustard]

Chronic pruritus is one of the major complaints in chemically-injured patients. It may cause many psychological problems and consequently, decrease the patient's quality of life. The aim of this study is to compare the safety and efficacy of Doxepin and Hydroxyzine in treatment of chronic pruritus due to Sulfur Mustard. This randomized, double-blind clinical trial was carried out in Baqiyatallah hospital on 50 chemically-injured patients for a period of 4 weeks. Patients randomly divided into 2 groups, first group [mean age of 42.3 +/- 5.4 years old] received Doxepin capsules [10 mg/day] and the second group [mean age of 41.1 +/- 6.2 years old] received Hydroxyzine capsules [25 mg/day]. Pruritus score was measured by a standard questionnaire and Visual Analogue Scale [VAS]. The mean before and after-treatment puritus scores of Hydroxyzine, were 34.6 +/- 3.4 and 25.9 +/- 3.1, respectively [P<0.001] and those of Doxepin were 33.8 +/- 4.4 and 24.5 +/- 4.1, respectively [P<0.001]. Both drugs decreased pruritus, similarly [P = 0.245]. 18 patients in the hydroxyzine-received group and 11 patients in the Doxepin-received group were complaining from sedation as a side-effect [P=0.035]. Both drugs are of significant effectiveness in decreasing pruritus. However, considering its fewer side effects, Doxepin seems to be more useful in these conditions

Pulmonary function test trend in adult bronchiolitis obliterans

Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical entity, such as respiratory bronchiolitis caused by cigarette smoking and toxic fumes i.e. sulfur mustard [SM]. The aim of this study was to determine the trend of pulmonary function indices in SM-exposed patients with the diagnosis of bronchiolitis obliterans. In this retrospective cohort study, 407 cases were evaluated. Patients were divided into 4 groups according to the time period from performing PFT: 1-3, 4-6, 7-10 and more than 10 years. The amounts of these changes amongst four PFT interval groups were compared by analysis of variance test. In addition, we used linear regression analysis to create a linear model of changes for each PFT index. The following equations imply a correlation between decrease in PFT indices and interval between the two tests plus index value of baseline PFT. 1: [FVC%]= -2.23 - [0.76 T]-[0.23 FVC1%], 2: [FEV1%]= -1.43 - [0.95 T]-[0.10 FEV11%], 3: [PEF%]= -0.91 - [1.07 T]-[0.14 PEF1%]. Better understanding of the nature of bronchiolitis obliterans, helps improve the treatment of this disease. Our study suggests a pattern of decline in pulmonary function indices directly proportional to the percentage of each index in the baseline PFT which was apparent during a 10-year observation period

Multiple large cherry angiomas after exposure to sulfur mustard gas in Iranian veterans in Iraq-Iran war: a historical cohort study

Sulfur mustard [SM] is a blistering agent which has been used as a chemical warfare agent in many wars since 1917. It has been used several times by Iraqi forces during Iraq Iran war [1980-88]. Lungs, skin and eyes are the three major targets affected by SM. We had observed an increased number of cherry angiomas, benign vascular tumors, in Iranian veterans after exposure to SM, so we decided to assess number and size of cherry angiomas in Iranian veterans several years after exposure to SM. In this historical cohort study, 99 veterans exposed to SM were compared to 52 non-exposed individuals. Participants were examined for number and maximum size of cheny angiomas and the findings were compared between the two groups. All participants were male. The age range in case group was from 30 to 60 years [mean +/- SD: 42.7 +/- 7.6] and in control group was from 30 to 65 years [mean +/- SD: 39.9 +/- 9.9]. In case group, number of angiomas and maximum size of them were significantly greater than those in control group [P=0.001 and P=0.0001; respectively]. There was a direct correlation between number of angiomas and maximum size of them in case group [P=0.0001]. Most of lesions were located in trunk and upper extremities. SM seemed to be responsible for the presence of multiple cherry angiomas in veterans several years after exposure. Maximum size of angiomas in veterans was significantly greater than those were observed in non-exposed individuals

study of the prevalence of skin tumors in chemically injured patients in comparison with the general population

During Iran-Iraq war between the years 1980-1988, several chemical warefare agents were used which the most common was Mustard gas [SM]. The side effects of mutation and tumor-formation of sulfur mustard in humanbeings and animals are well described. The aim of current study is to determine the late-onset complications in Iranian veterans exposed by SM in formation of skin tumors. During this retrospective descriptive-analytic study, 9605 chemically injured patients who were examined by dermatologists and their characteristics were studied. Sixty-two out of 9605 of chemically injured patients exposed to sulfur mustard after 10-15 years from exposure had skin tumors. Four of them were malignant and diagnosed as BCC and the others were benign.Lipoma and Becker nevus where the most common benign lesions. The results showed that no significant difference between prevalence of BCC in the chemically injured patients and the general population based on previous reports and as far as the age range and frequency of exposure was considered [P>0.05]

Comparison of serum magnesium values among sulfur mustard induced asthma with non- chemical asthmatic in Iranian war victims

Sulfur mustard as a chemical weapon was used during imposed war against I.R. Iran. We investigate the comparison of serum magnesium values between sulfur mustard asthmatic victims and non-chemical asthmatic patients and magnesium status evaluates between the two groups. Seventy-five consecutive and volunteers Patients with sulfur mustard -induced asthma were enrolled in the study. Confirmations of chemical exposure with sulfur mustard and involvement to asthma were documented by a definite criterion. Normal serum Mg value was 1.8-2.6 mg/dl. Seventy- five patients as mustard exposure were selected with mean age [46.78 +/- 10.15]. Mean Mg value was [1/96 +/- 0.19]. Magnesium deficiency was found in 15% of the patients. the significant difference was found between the two groups. [P<0.05]. Mg ion has significant role in management and therapeutic of asthma disease. Reducing Mg level may cause increased rate of hospitalization and morbidity. Considering Mg deficiency and diagnosis in MS induced asthma conduct to better results from management

Skin lesions in 800 Iranian victims of mustard gas, 14-20 years after exposure

Mustard gas is a disabling chemical weapon and was widely used in First World War and Iraq-Iran war. Its toxic effects could be acute or chronic and they could particularly affect lungs, eyes and skin.To study the frequency of chronic complications of sulfur mustard gas in Iranian victims 14 to 20 years after exposure. This descriptive cross-sectional study was performed on 800 patients that were randomly selected from different provinces of Iran, who had been exposed to sulfur mustard gas during 1983 to 1988. These patients were clinically re-evaluated in 2002-2003 and laboratory tests were performed if necessary. The mean age of the patients at the time of study was 39.3 [ +/- 9.8] years. Three types of skin lesions were observed. Non-specific lesions including 39.6% xerosis, 19% pigmentary disorders, 17.4% cherry angioma, 12.7% seborrheic dermatitis, 12.2% eczema [dermatitis], 11.6% acneiform lesions, 7% tinea versicolor, 5.1% urticaria,, 3.6% vitiligo, 2.5% alopecia areata, 2% psoriasis, and 1.3% aphthous stomatitis. Specific skin lesion called mustard scar was defined according to morphology, location, history and observed in 44 [5.5%] patients. Malignant neoplasms including basal cell carcinoma, Bowen's disease, squamous cell carcinoma, mycosis fungoides and dermatofibrosarcoma protuberans occurred in 9 victims [1.1%]. Mustard gas can cause acute and late-onset skin lesions. Specific lesion of mustard gas called mustard scar is the most important finding of this study

Long-term pulmonary complications of sulphur mustard gas exposure in Iranian chemical war victims

Sulphur Mustard [SM] is a major threat around the world not only on the battle field but also to civilian population. It has been used by Iraqi troops against Iranian veterans and resulted in severe inhalation injury and pulmonary complications in Iranian soldiers. To determine the long-term pulmonary sequelae of SM gas exposure on Iranian veterans of Iraqi -Iran conflict, chemical victims of Babol, who have been referred for follow up examination to Shaheed Beheshti Hospital clinic [were studied]. A total of 220 male chemical exposed victims and 92 age matched healthy controls were studied. Diagnosis of SM-related disease was confirmed on the basis of prior history of SM gas exposure and excluding other unrelated diseases. The results were regarded positive if the FEVI% or FVC% or absolute FEVI volume increased by 15%, 20% or 180 ml respectively compared with baseline value. In statistical analysis, the frequency of respiratory signs and symptoms, radiographic changes of chest radiographs, and the proportion of persons with abnormal PFT results were determined and compared with age matched controls. Emphysema in 2%, cor pulmonale in 4% and severe respiratory disease requiring permanent supportive treatment in 4.5% of patients. Abnormal radiographic findings were detectable in 64% of chest radiographs which were remarkable in only 13%. Obstructive airway disease was detected in 110 [50%] patients and 11 [5.4%] controls [P<0.0001]. The degree of obstruction was mild, moderate or severe in 13.5%,73% and 13.5% of patients and 80%, 20% and 0% of controls respectively. Restrictive airway disease was observed in 22 [10%] patients and 11 [12%] controls [P=NS]. Normal PFT was seen in 40% of patients and 83% of controls [P<0.0001]. Only 30% of patients with obstructive airway disease were responsive to bronchodilator test. The findings of the present study show that, a remarkable number of Iranian veterans are suffering from chronic lung diseases several years after exposure to SM gas

Pulmonary complications of chemical warfare 15 years after exposure

Chemical weapons, [mainly mustard gas-MG] were heavily used by Iraq against Iranian soldiers between 1984-1986. It has acute effects on respiratory tract in the form of tracheobronchitis and ARDS, whereas chronic respiratory complications include chronic bronchitis, bronchiectasis, asthma and pulmonary fibrosis. There are few reports about human victims. Some of them describe acute effects while our purpose is to define chronic sequelae and their microbiologic, radiologic and physiologic behavior. Fourty four chemical weapon injured patients with moderate to severe disability were selected by AMA criteria [1]. All of them underwent history taking and physical examination, ABG, spirometry, CXR, HRCT, bronchoscopy and BAL for cytology and quantitative culture. Of fourty four patients; 29[66%] had diagnosis of chronic bronchitis by ATS criteria [2], 8 [18%] and 7 [16%] had diagnosis of bronchiectasis and asthma respectively. The most common HRCT finding was ground glass appearance. In one-fourth of patients BAL culture was positive and revealed unusual organisms [S.aureus, S.coagulase negative, E.coli]., BAL neutrophils were increased in bronchiectatic group [258 136 hpf] vs. [96 49 hpf], [148 133 hpf] [p<0.01 p]. Bronchiectatic patients were younger than the other groups [35.5 6.1 yr] vs. [43.5 5.2 yr], and [42.3 5.2 yr] [p<0.01]. The most common respiratory complication of MG is chronic bronchitis. Unusual microorganisms should be considered in the treatment of pulmonary infections. Persons who are exposed to mustard gas at younger age maybe more prone to development of bronchiectasis