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PubMed2003

High-resolution CT in chronic pulmonary changes after mustard gas exposure.

PURPOSE: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. MATERIAL AND METHODS: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. RESULTS: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. CONCLUSION: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury.

Adult↗
PubMedDate not supplied

Protection from half-mustard-gas-induced acute lung injury in the rat.

The chemical warfare agent analog, 2-chloroethyl ethyl sulfide, known as 'half-mustard gas' (HMG), is less toxic and less of an environmental hazard than the full molecule and has been shown to produce an acute lung injury in rats when instilled via intrapulmonary injection. This injury is characterized by massive, localized hemorrhage and edema into the alveolar compartment and can be quantitated by measuring extravasation of (125)I-bovine serum albumin into the extravascular compartment. Employing this rat model of HMG-induced lung injury, we observed significant attenuation of the pulmonary injury when experimental animals were complement or neutrophil depleted prior to HMG challenge. Significant protection also was provided by the use of antioxidants such as catalase, dimethyl sulfoxide, dimethyl thiourea, resveratrol and N-acetyl-L-cysteine (NAC). The last compound showed protection from lung injury as high as 70% and was still effective even when given up to 90 min after exposure of the lungs to HMG. These data suggest that acute lung injury caused by exposure to HMG may be related partially to complement mediated pathways and the generation by neutrophils of toxic oxygen species The data indicate that NAC is an effective antidote against HMG-induced acute lung injury in the rat.

Animals↗
PubMed1985

[Early cancer and related changes in the bronchial epithelium of former mustard gas workers].

The bronchial epithelium taken in stepwise transverse sections was examined histologically in 66 autopsy cases, composed of groups consisting of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. An additional 5 surgical lung cancer specimens removed from MG ex-workers were also examined. From these groups, foci of moderate or severe atypia including cellular atypia, dysplasia and carcinoma in situ (CIS), detected in the total number of slides for each autopsy group, were counted as 146 out of 3,485, 72 out of 2,226, 70 out of 3,797, and 18 out of 4,611, respectively. Seven CIS lesions were detected from among all MG-exposed cases and 1 CIS lesion was found in a non-MG lung cancer case. Six of these occurred with dysplasia and 4 were associated with early invasion. Among 62 autopsy cases with known smoking histories, multivariate analysis revealed a significant correlation between the incidence rate of atypia and MG exposure only in non-lung cancer cases: the incidence rate of atypia was also influenced significantly by smoking and age. Among lung cancer cases, the incidence rate of atypia was significantly higher (p less than 0.01) in cases of squamous cell carcinoma than those of small cell carcinoma.

Aged↗
PubMed1986

Early cancer and related lesions in the bronchial epithelium in former workers of mustard gas factory.

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2,226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.

Adenocarcinoma↗
PubMed1997

Toxicity of mustard gas skin lesions.

Although the exact pathogenesis of mustard gas-induced dermal toxicity remains elusive, morphopathological data gathered in controlled animal and in vitro investigations is providing important clues as to approximate mechanisms. Our laboratory has been studying dermal effects of the chemical warfare agent, sulfur mustard, in a variety of animal models, cultured isolated human cells, and in vitro organotypic skin models. Published anatomical, pathological, and ultrastructural results of these studies have documented consistent cellular and basement membrane zone effects irrespective of the model. Cellular effects include the early targeting of basal cells of the stratum basale to the exclusion of other epidermal cells, with nuclear and cytoplasmic indications of cell injury and cell death. Effects on the basement membrane zone include the formation of characteristic microvesicles in the lamina lucida of those models which possessed structural components of a true basement membrane. We are now investigating effects on proteins of the basement membrane microenvironment and correlate in the present paper the morphopathology of sulfur mustard dermal lesions with immunohistochemical study of bullous pemphigoid antigen, laminin, type IV collagen, and type VII collagen.

Animals↗
PubMed2004

A recent exposure to mustard gas in the United States: clinical findings of a cohort (n = 247) 6 years after exposure.

OBJECTIVE: To describe the acute and long-term effects of mustard gas (MG) and propose a screening protocol to prevent complications. METHODS: Follow-up of (n = 247) workers exposed to MG with a standard protocol. RESULTS: Healing of burns varied according to natural pigmentation of skin, not reported elsewhere. Multiple and chronic skin infections developed on burns. Liver functions and cardiac conduction were temporarily altered in burn cases without other complications. No fatalities were noted. Months after exposure, bronchitis and posttraumatic stress disorder became prevalent regardless of initial presentation. Other symptoms did not lead to any organ pathology except one case of Barrett's esophagus and another of oral metaplasia. Two infants conceived after exposure appeared healthy. Although the screening protocol administered became an effective screening tool, follow-up of cases was severely flawed by a lack of cooperation between providers and noncompliance by patients after settlement of lawsuits. CONCLUSION: Research of findings attributable to MG needs close follow-up of this group of patients due to latent carcinogenic, hematologic, pulmonary, and infertility effects. Therefore, annual follow-up screens, instruction on the effects of MG, and prevention, including immunization and autopsy in all cases of death, are strongly suggested.

Adult↗
PubMed2004

Photooxidation of a mustard gas simulant over TiO2-SiO2 mixed-oxide photocatalyst: site poisoning by oxidation products and reactivation.

The photooxidation of 2-chloroethyl ethyl sulfide (2-CEES), a simulant for mustard gas, was studied using transmission IR spectroscopy on a mixed-oxide TiO2-SiO2 photocatalyst. Ultraviolet irradiation in the photon energy range from 2.1 to 5 eV was employed at a catalyst temperature of 200 K. Rapid photooxidation was observed by the loss of infrared intensity in the v(CHx) stretching region, and concomitant infrared features of adsorbed oxidation products were observed to develop. The oxidation products, captured on the photocatalyst at 200 K, were found to block 2-CEES readsorption. Upon heating the poisoned photocatalyst to about 300 K, infrared measurements indicate that the adsorbed CO2 oxidation product was desorbed. The capability for full readsorption of 2-CEES was achieved upon heating the poisoned photocatalyst to 397 K, and continued rapid photooxidation of the 2-CEES was then possible at about 1/3 the rate found for the fresh catalyst. Thus thermal treatment at 397 K of oxidation-product-poisoned TiO2-SiO2 material is able to partially restore the TiO2-SiO2 photooxidation activity.

Catalysis↗
PubMed1991

The role of bronchoscopy in pulmonary complications due to mustard gas inhalation.

Over the last five years we have repetitively treated a group of 21 Iranian soldiers who developed pulmonary complications as a result of severe inhalation injury due to mustard gas during the Iran-Iraq war. Early respiratory manifestations included hemorrhagic inflammation of the tracheobronchial tree accompanied by severe erosions. Secondary complications consisted of chronic infections, suppurative bronchitis, and extensive stenotic process of the entire tracheobronchial tree with life-threatening sequelae. After a delay of up to 15 months, scars, ulcers, and strictures developed in the central airways. Progressive deterioration of gas exchange was common. At this point, bronchoscopy, both diagnostic and therapeutic, was invaluable in evaluating the conditions in these patients since many required multiple therapeutic bronchoscopies. Repeated bougienage of the stenotic tracheobronchial lesions and laser photoresection of scarring tissue was life-saving. The recurrence rate of stenosis was very high, with intervals of less than six months on the average. One pneumonectomy was necessary, with the excised lung showing bronchiectasis and chronic pneumonia. To this date we have performed 146 therapeutic bronchoscopies. In four patients, silicone stents had to be implanted. One patient received brachytherapy and external beam radiation therapy in an effort to prevent continued scarring and life-threatening stenoses of the tracheobronchial tree. Our experience demonstrates the extreme usefulness of bronchoscopy in the diagnosis and treatment of pulmonary complications due to inhalation of poisonous gases.

Bronchoscopy↗
PubMed2006

Inhibition of inducible Nitric Oxide Synthase by a mustard gas analog in murine macrophages.

BACKGROUND: 2-Chloroethyl ethyl sulphide (CEES) is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2'-dichlorodiethyl sulphide, or sulphur mustard gas (HD). Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS) enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO) production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS) activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing. RESULTS: We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours) in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA) or dichlorofluorescin diacetate (DCFH-DA). Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEES in vitro did not inhibit its enzymatic activity CONCLUSION: CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-kappaB) signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS-stimulated macrophages could elevate oxidative stress. Since macrophage generated NO is known to play a key role in cutaneous wound healing, it is possible that this work has physiological relevance with respect to the healing of HD induced skin blisters.

Animals↗
PubMed2006

Distal esophagitis in patients with mustard-gas induced chronic cough.

Although confounded by some factors such as medications or surgical complications, the relationship between esophageal pathology and pulmonary disorders has been the subject of many studies. The present study sought to investigate the said relationship in patients inflicted by respiratory disorders induced by mustard gas (MG). A case group of patients complaining of respiratory complications and chronic coughs following MG exposure, and a control group of patients with chronic coughs but without a history of MG exposure were studied. All the case and control subjects had symptoms of gastro-esophageal reflux disease. Chest high resolution tomography (HRCT) was performed to evaluate the existence of pulmonary disorders. Endoscopy and histological studies were carried out to determine the severity of esophagitis in both groups presenting with gastroesophageal reflux. Ninety male patients, who had met our criteria, along with 40 male control cases underwent the diagnostic procedures. The frequency of endoscopic esophagitis findings in the chemically exposed group was significantly higher than that in the control group (70.0%vs. 42.5%). A pathological evaluation revealed that the frequency of esophagitis in the cases was more than that in the controls (32.3%vs. 14.2%). Chest HRCT evaluation demonstrated that half the case group had more than 25% air trapping in expiratory films, mostly compatible with bronchiolitis obliterans (BO). In addition, they were suffering from asthma, chronic bronchitis and bronchiectasis. Bronchiolitis obliterans, along with other lung disorders, can be considered as contributors in the pathogenesis of esophagitis in MG exposed patients.

Adult↗
PubMed1999

Effect of mustard gas on supraoxide dismutase activity and the level of malonyl dialdehyde: in vitro studies.

The investigation aimed at evaluating free supraoxide radicals generations and the degree of blood platelets cell membrane lipids peroxidation on the basis of supraoxide dismutase activity and the level of malonyl dialdehyde (MDA) after a 30-min exposure to mustard gas in vitro. The obtained results showed that blood platelets supraoxide dismutase activity and the MDA level are higher in comparison with the control groups.

Animals↗