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Bronchiolitis has been known as one of the pathological features of lung injuries in mustard gas exposed patients
The purpose of this research was to evaluate the efficacy of interferon gamma-1b on the lung function in mustard gas exposed patients with bronchiolitis. In multicenter research interferon gamma-1b was effective in pulmonary fibrosis w...
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Citations
... In 2004, a placebo-controlled randomized trial showed that aerosolized IFN-γ failed to both improve FEV and reduce sputum bacterial density in patients with cystic fibrosis lung disease and caused an exacerbation of pulmonary symptoms at higher dosages [72]. However, combined treatment with IFN-γ and prednisolone successfully ameliorated respiratory symptoms in patients suffering from bronchiolitis obliterans resulting from exposure to mustard gas in the 1980-1988 Iran-Iraq war [73]. After six months of treatment, the IFN-γ/prednisolone group showed significant improvement in FEV1 and reduction in dyspnea and hospitalization compared to the prednisolone-only control group. ...
The term “fibrosis” refers to a spectrum of connective tissue disorders characterized by the excessive accumulation of extracellular matrix leading to organ dysfunction and, ultimately, failure. Fibrosis affects millions of patients worldwide and often manifests itself as a late-stage pathological condition associated with poor prognostic outcome. Although the aetiology and clinical course vary widely depending on the affected organ, fibrotic degeneration of different tissues is underpinned by similar molecular and cellular mechanisms, most notably the persistence and dysregulated activity of myofibroblasts. A systematic search of clinical trials was conducted using PubMed and Cochrane to qualitatively evaluate the effectiveness of different therapeutic approaches to the pharmacological targeting of myofibroblasts in patients affected by fibrotic disorders. The systematic search and screening returned 54 eligible clinical trials, 38 of which reported an improvement of the patients’ symptoms following treatment. The majority of the eligible articles focused on fibrotic degeneration of the respiratory system, skin, liver, and kidneys. The evaluation of clinical data unearthed commonalities between strategies that successfully ameliorated symptoms in patients affected by the same fibrotic disorder. However, none of the treatments evaluated in this study could improve symptoms across a range of fibrotic pathologies. These results indicate that, although no “one size fits all” treatment for fibrosis has yet been identified, the systematic analysis of clinical data can be used to inform the development of therapeutical strategies tailored to suit the diverse aetiology of each fibrotic condition.
... As level of TGF-ß increased, IFN-γ may be effective in pathologic situation. Interferon gamma-1b (200 µg) three times per week subcutaneously and low dose prednisolone (7.5 mg) once a day orally for six months could improve dyspnea indices and pulmonary function tests, a decrease in hospitalization time, an increase in arterial oxygenation of sulfur mustard exposed with severe delayed lung complications (88,90,105,106). ...
Among the blistering (vesicant) chemical warfare agents (CWA), sulfur mustard is the most important since it is known as the "King of chemical warfare agents". The use of sulfur mustard has caused serious damages in several organs, especially the eyes, skin, respiratory, central and peripheral nervous systems after short and long term exposure, incapacitating and even killing people and troops. In this review, chemical properties, mechanism of actions and their effects on each organ, clinical manifestations, diagnostic evaluation of the actions triage, and treatment of injuries have been described.
... Anticholinergic drugs insert their therapeutic effects by blocking muscarinic cholinergic receptors (M_1) and thereby prevent the acetylcholine function [26]. In addition to oxygen therapy [22], antibiotics, suppressant agent, prednisolone [20], membrane stabilizers, antioxidants [27], macrolides, and interferons [28] are the other drugs which are used in chemical injuries. ...
Sulfur mustard (SM) is a toxic agent which causes severe abnormalities in an airway system such as necrosis and inflammation, oxidative stress, chronic bronchitis, shortness of breath, and chronic obstructive pulmonary disease. Although possible mechanisms of SM toxicity have been extensively considered, there is still need to find an appropriate clinical treatment to decrease chronic lung injuries caused by SM. Due to extensive progresses and achievement in tissue repairing through stem cells therapy, the importance of cell therapy for the treatment of lung injuries has been increased.
However, several factors such as types of stem cells, necessary conditions for growth and proliferation of stem cells, and their homing into the target tissues are considered as the most important problems in this issue. Mesenchymal stem cells (MSCs) are a class of multipotent stem cells with proliferative and self-renewal capacity which are able to differentiate into different cell lines such as lung epithelial cells. They have a potential repairing and immune modulatory properties which make them as a good candidate for the regeneration of bronchioles tract in SM-exposed patients. Unlike chemical drugs, the
differentiation and high-level safety properties of MSCs can be considered as a new strategy for the treatment of SM-injured patients with pulmonary complications. This review aims to consider the therapeutic effects of MSCs in the treatment of SM-induced pulmonary injuries in both animals and humans.
... 1 Ghanei et al. 25 (2008) treated 144 DRCS patients with NAC (1,200 mg daily) or placebo for 4 months (table 3). 19,21,[25][26][27][28][29][30][31][32][33] All patients had SM-induced bronchiolitis obliterans. The NAC treated group showed a significant improvement in dyspnea, wake-up dyspnea, cough, spirometric components, and reduced sputum compared to the control group. ...
The present study aimed to review and discuss the recommended and recently suggested protocols by Iranian researchers for a long-term treatment of delayed complications of sulfur mustard (DCSM) in veterans. As indicated clinically, patients who suffer from delayed ocular complications of sulfur mustard (DOCS) benefit from treatments for dry eyes, therapeutic contact lenses, amniotic membrane transplantation; blepharorrhaphy, tarsorrhaphy, limbal stem cell transplantation; corneal transplantation, topical steroids, and immunosuppressive. In spite of penetrating keratoplasty, lamellar keratoplasty and keratolimbal allograft had a good long-term survival.
Delayed respiratory complications (DRCS) are the most common effects and life-threatening in Iranian veterans. The recommended treatment protocols include regular clinical evaluations, respiratory physiotherapy and rehabilitation, N-acetyl cysteine; warm humidified air, long-acting 2-agonists, and inhaled corticosteroids. Azithromycin has also been effective in improving clinical conditions, pulmonary function tests, inflammatory indexes, and life quality of the veterans. Interferon gamma (IFN-γ) and helium: oxygen combination were also used in severe DRCS with good results. Some of the delayed cutaneous complications (DCCS) such as itching affects the quality of life of victims. Regular but not frequent showering and bathing, applying sunscreen compounds, topical corticosteroids, and systemic antihistamines reduce the problems of DCCS patients. Several compounds such as capsaicin cream, pimecrolimus, IFN-γ, phenol-menthol; Aloe vera/olive oil cream, cetirizine, doxepine, and hydroxyzine were evaluated in DCCS patients with some benefits. The physicians in charge of veterans emphasize the importance of a healthy lifestyle, appropriate financial/social/cultural supports, and a degree of reassurance and supportive care on the clinical improvement of patients.
... Pulmonary function tests indicate that chronic obstructions are the most common abnormal patterns, and half of the obstruction cases are reversible after use of inhaled bronchioles. Spirometry findings increase in disruptive factors over time [7][8][9]. One of the best pathways of medicine is Thiotropium bromide, which is a long-acting anticholinergic agent and can improve lung function and exercise tolerance. ...
Abstract
Justification: At present, lung cancer has been diagnosed with about 1.6 million people in the world and each
year there are 1.3 million cancer-related deaths worldwide, which is a major health threat that increases treatment
and health costs. It is also one of the deadly causes of functional biological mustard, namely, sulfur mustard (SM), in
various wars since First World War, and more than 80% of all recorded losses of chemical gases. It should be noted
that when treating patients with possible injury to the respiratory tract, you will be aware of the relevant risk factors.
This includes closed-air fire, carbon smoke; increased carbon monoxide levels (CO) and severe coughs and,
eventually, burns. Acute respiratory conditions are usually highly responsive to the invasive severity, and this event
is performed in all malignant respiratory diseases.
Methodology: This article is a descriptive study, all data and scientific information calculated via high value
scientific resources according to final achievements of pulmonary rehabilitation on malignant respiratory patients.
Also, methodology on this article to be bibliographic and descriptive. Some scientific sites for extract newest articles
include: PubMed, web of science, EBSCO host, Science direct, Elsevier, Google scholar and Scopus. In this study
with style of Theoretical basic research and data calculate of digital resources (PubMed, Science direct, and
Scopus) and, Guidelines of ERS/ATS with Bibliographic method.
Discussion: Accordingly, the efficacy of pulmonary rehabilitation in patients with COPD, obstructive sleep apnea,
asthma, metastatic lung cancer, and in patients requiring one or two lung transplants are observed. Pulmonary
rehabilitation planners have been somewhat effective in terms of family and community conditions to improve
functional capacity, and assessment by 6MWT and quality of life questionnaires. Pulmonary rehabilitation is leading
to significant improvement in the quality of life, exercise capacity and shortness of breath. Other effects of pulmonary
rehabilitation are the reduction of the number of days in the hospital after the successful completion of this program
compared with the previous year for these patients. Further study of the biological causes of COPD, lung cancer,
inhalation injury caused by smoking and, lastly, chemical damage, indicates that patients with COPD or other types
of patients exhibit appropriate screening for pulmonary radiography?
... Unlike IL-17, interferon (IFN)-γ represses the recruitment of neutrophils and monocytes. Therefore, interferon therapy has been effective in amelioration of the complications in patients with SM exposure Panahi et al., 2005;Panahi et al., 2012). There is increased infiltration of IL-17A positive cells to the injured lung tissue. ...
Sulfur mustard (SM) is a vesicating agent that has been employed as a chemical warfare agent. High-dose exposure to sulfur mustard may lead to the damage of rapidly proliferating cells of bone marrow and, therefore, suppression of the immune system. This may be continued as dysfunction of the immune system, and ultimately result in secondary immune disorders. Studies have suggested a role for T cells in SM-induced lung injury. Moreover, observations from animal studies indicate a delayed-type hypersensitivity (DTH) response after skin exposure to SM, providing an understanding that SM can stimulate specific T cell-mediated immune responses. On the other hand, T helper (Th) 17 cells, which are a subset of CD4+ T cells, have recently been reported to be involved in a number of inflammatory, autoimmune, and chronic fibrotic lung diseases. Furthermore, a strong association has been established between the overproduction of profibrotic cytokines like transforming growth factor (TGF)-β and Th17 cell number. In this review, we aimed to go through the new findings about the involvement and interactions of TGF-β and Th17 in SM-related injuries. This article is protected by copyright. All rights reserved.
... Current strategies for treatment of respiratory disorders among these patients include bronchodilators, N-acetyl cysteine and antibiotics ( Poursaleh et al. 2012). Oxygen therapy ( ), antibiotics, prednisolone ( Ghanei et al. 2005), membrane stabilizers, antioxidants, macrolides and interferons ( Panahi et al. 2005) are other popular drugs that used in these patients. These current therapies are not suitable for SMexposed patients because airway structure is destroyed and they need a regeneration method for repairment. ...
Oxidative stress and inflammation are one of the main pathological consequences of sulfur mustard on human lungs. Unfortunately, there is no effective treatment to mitigate pathological effects of sulfur mustard in mustard lungs. Here, we aimed to evaluate potential efficacy of systemic mesenchymal stem cells administration on expression of oxidative stress- and inflammation-related genes in sulfur mustard-exposed patients. Our patient received 100 million cells per injection, which was continued for four injections within 2 months. Sputum samples were provided after each injection. Oxidative stress was evaluated by determining sputum levels of malondialdehyde and glutathione. Furthermore, changes in expression of several oxidative stress- (metallothionein 3, glutathione reductase, oxidative stress responsive 1, glutathione peroxidase 2, lacto peroxidase, forkhead box M1) and inflammation-related genes (matrix metallopeptidase 2, matrix metallopeptidase 9, transforming growth factor-β1, vascular endothelial growth factor, metallopeptidase inhibitor 1, metallopeptidase inhibitor 2) were also evaluated using real-time PCR after treatments. Two-lung epithelial-specific proteins including Clara cell protein 16 and Mucin-1 protein levels were measured using enzyme immunoassay method. No significant differences were found between serum levels of Clara cell protein 16 and serum Mucin-1 protein in patient before and after cell therapy. Most of the oxidative stress responsive genes, particularly oxidative stress responsive 1, were overexpressed after treatments. Expressions of antioxidants genes such as metallothionein 3, glutathione reductase and glutathione peroxidase 2 were increased after cell therapy. Upon comparison of inflammation-related genes, we observed upregulation of vascular endothelial growth factor and matrix metallopeptidase 9 after mesenchymal stem cells therapy. Additionally, a trend for increased value of glutathione and decreased levels of malondialdehyde was observed from baseline to final evaluation times. Mesenchymal stem cells administration mitigates oxidative stress and inflammation in sulfur mustard-exposed patients.
... Acute toxic effects are manifested in a dose-dependent manner as laryngitis and tracheobronchitis [5], airway epithelial cell death [6,7] and respiratory distress syndrome [5]. The delayed long-term pathological changes observed after examination of lung biopsies are reported to be similar to chronic bronchiolitis [8,9], parenchymal lung fibrosis and obliterative bronchiolitis [10][11][12][13][14]. But, the collective histopathological lung parenchymal and airway epithelial changes cannot be exactly defined by any of these three histopathological conditions. Although many studies have been conducted to determine the cellular and molecular mechanisms of acute SM-induced injuries in different organs [2,15], little has been done to understand the mechanisms governing the delayed pathological changes in the respiratory system. ...
... Several reports of the pathological examination of lung tissue in SM-exposed patients, who suffered from the delayed respiratory complications, identified a collective parenchymal and airway epithelial changes, which conformed to two pathologies of obliterative bronchiolitis (OB) and parenchymal lung fibrosis [9][10][11][12]. The former has been shown to be the major feature not only in patients underwent open lung biopsy, but also in those who were studied with high-resolution CT scanning and broncho-alveoar lavage (BAL) [12]. ...
Purpose
In patients with short-term exposure to the sulfur mustard gas, the delayed cellular effects on lungs have not been well understood yet. The lung pathology shows a dominant feature consistent with obliterative bronchiolitis, in which fibroblasts play a central role. This study aims to characterize alterations to lung fibroblasts, at the cellular level, in patients with delayed respiratory complications after short-term exposure to the sulfur mustard gas.
Methods
Fibroblasts were isolated from the transbronchial biopsies of patients with documented history of exposure to single high-dose sulfur mustard during 1985–7 and compared with the fibroblasts of control subjects.
Results
Compared with controls, patients’ fibroblasts were thinner and shorter, and showed a higher population doubling level, migration capacity and number of filopodia. Sulfur mustard decreased the in vitro viability of fibroblasts and increased their sensitivity to induction of apoptosis, but did not change the rate of spontaneous apoptosis. In addition, higher expression of alpha smooth muscle actin showed that the lung's microenvironment in these patients is permissive for myofibroblastic differentiation.
Conclusions
These findings suggest that in patients under the study, the delayed pulmonary complications of sulfur mustard should be considered as a unique pathology, which might need a specific management by manipulation of cellular components.
... corticosteroids and b2 agonists), are also warranted to confirm the protective effects of NAC itself, as well as to specify its optimal dose, treatment duration and mechanism of action in mitigating clinical and paraclinical long-term pulmonary complications of SM. Two preliminary clinical studies have demonstrated the efficacy of interferon gamma-1b plus prednisolone (Panahi et al., 2005) and helium–oxygen mixture (Ghanei et al., 2011) in improving clinical and pulmonary functions finding of SM-exposed patients with delayed lung complications. Various costbenefit aspects of these agents in combination with NAC, including clinical effectiveness, direct costs, plausible adverse reactions and drug interactions, should be further assessed by well-designed clinical trials, before advocating these combinations for the management of SM-induced long-term pulmonary toxicity. ...
Context:
Sulfur mustard exposure, as the most widely used chemical weapon, can lead to acute and long-term pulmonary complications via various pathways, such as triggering an imbalance between the oxidant and antioxidant system. Currently, there is no validated antidote, chemoprophylaxis and curative modality for pulmonary toxicities secondary to sulfur mustard exposure.
Objective:
The aim of this literature review is to collect available experimental and clinical data on the efficacy of N-acetylcysteine (NAC), as a prominent antioxidant agent, in the prevention and/or treatment of sulfur mustard-induced acute and chronic pulmonary toxicities.
Methods:
A literature search was performed by the relevant keywords like "N-acetyl cysteine", "Sulfur mustard" and "Lung injury" in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. No time limitation was considered. Nineteen articles were selected for review.
Results:
A number of in vitro and experimental studies concluded that oral, intravenous, intraperitoneal and intra-tracheal administration of NAC is effective in the management of sulfur mustard-induced acute lung injury, in a time-dependent manner, via direct scavenging, inhibition of oxidative stress, inflammatory responses and apoptosis. In addition, oral NAC alone (1200 or 1800 mg/day for 4 months) or at a dose 600 mg/day for 6 months in combination with clarithromycin (500 mg/day) have led to improvements of clinical and paraclinical pulmonary parameters of patients with bronchiolitis obliterans due to sulfur mustard, through undetermined mechanisms.
Conclusion:
Despite limitations of relevant experimental and clinical studies, NAC can be considered as a candidate agent for prevention and/or treatment of sulfur mustard-induced acute lung injuries, as well as its long-term pulmonary toxicities, especially bronchiolitis obliterans.
... [20] Although, TGF-beta regulating medication such as gamma interferon was effectively used in these patients and other anti-inflammatory treatment such as anti cytokines and TNF-alpha antagonist theorically may be effective but we need medications which impress the main pathogenesis pathway. [21] Another therapeutic option such as vitamin E and proanthocyanidin was sporadically used on patients with SM injury but more study is needed to approve their results. [22,23] On the other hand, using other ways to administrate routine medications e.g. ...
Treatment of sulfur mustard (SM) injured patient with pulmonary involvement remains as a challenging issue and almost all of used medications, such as corticosteroid, are conservative treatments. Also, we would like to recommend some medications which it theoretically can be effective on patients with SM lung injuries.
