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Annals of the New York Academy of... Nov 2020Acute respiratory distress syndrome (ARDS) is a highly morbid lung pathology induced by exposure to chemical warfare agents, including vesicants, phosgene, chlorine, and... (Review)
Review
Acute respiratory distress syndrome (ARDS) is a highly morbid lung pathology induced by exposure to chemical warfare agents, including vesicants, phosgene, chlorine, and ricin. In this review, we describe the pathology associated with the development of ARDS in humans and experimental models of acute lung injury following animal exposure to these high-priority threat agents. Potential future approaches to disease-modifying treatment used in preclinical animal studies, including antioxidants, anti-inflammatories, biologics, and mesenchymal stem cells, are also described. As respiratory pathologies, including ARDS, are the major cause of morbidity and mortality following exposure to chemical threat agents, understanding mechanisms of disease pathogenesis is key to the development of efficacious therapeutics beyond the primary intervention principle, which remains mechanical ventilation.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chemical Warfare Agents; Humans; Respiration, Artificial; Respiratory Distress Syndrome
PubMed: 32726497
DOI: 10.1111/nyas.14438 -
Clinical and Translational Medicine Dec 2017Phosgene (carbonyl dichloride) gas is an indispensable chemical inter-mediate used in numerous industrial processes. There is no clear consensus as to its time- and... (Review)
Review
BACKGROUND
Phosgene (carbonyl dichloride) gas is an indispensable chemical inter-mediate used in numerous industrial processes. There is no clear consensus as to its time- and inhaled-dose-dependent etiopathologies and associated preventive or therapeutic treatment strategies.
METHODS
Cardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight. Noninvasive diagnostic and prognostic endpoints in exhaled breath (carbon dioxide and nitric oxide) were used to detect the clinically occult stage of pulmonary edema.
RESULTS
The first event observed in rats following high but sublethal acute exposure to phosgene was the stimulation of alveolar nociceptive vagal receptors. This afferent stimulation resulted in dramatic changes in cardiopulmonary functions, ventilation: perfusion imbalances, and progressive pulmonary edema and phospholipoproteinosis. Hematology revealed hemoconcentration to be an early marker of pulmonary edema and fibrin as a discriminating endpoint that was positive for the airway irritant chlorine and negative for the alveolar irritant phosgene.
CONCLUSIONS
The application of each gas produced typical ALI/ARDS (acute lung injury/acute respiratory distress syndrome) characteristics. Phosgene-induced ALI showed evidence of persistent apnea periods, bradycardia, and shifts of vascular fluid from the peripheral to the pulmonary circulation. Carbon dioxide in expired gas was suggestive of increased ventilation dead space and appeared to be a harbinger of progressively developing lung edema. Treatment with the iNOS inhibitor aminoguanidine aerosol by inhalation reduced the severity of phosgene-induced ALI when applied at low dose-rates. Symptomatic treatment regimens were considered inferior to causal modes of treatment.
PubMed: 28577109
DOI: 10.1186/s40169-017-0149-2 -
Materials (Basel, Switzerland) Jun 2021Polyurethanes (PUs) are a significant group of polymeric materials that, due to their outstanding mechanical, chemical, and physical properties, are used in a wide range... (Review)
Review
Polyurethanes (PUs) are a significant group of polymeric materials that, due to their outstanding mechanical, chemical, and physical properties, are used in a wide range of applications. Conventionally, PUs are obtained in polyaddition reactions between diisocyanates and polyols. Due to the toxicity of isocyanate raw materials and their synthesis method utilizing phosgene, new cleaner synthetic routes for polyurethanes without using isocyanates have attracted increasing attention in recent years. Among different attempts to replace the conventional process, polyaddition of cyclic carbonates (CCs) and polyfunctional amines seems to be the most promising way to obtain non-isocyanate polyurethanes (NIPUs) or, more precisely, polyhydroxyurethanes (PHUs), while primary and secondary -OH groups are being formed alongside urethane linkages. Such an approach eliminates hazardous chemical compounds from the synthesis and leads to the fabrication of polymeric materials with unique and tunable properties. The main advantages include better chemical, mechanical, and thermal resistance, and the process itself is invulnerable to moisture, which is an essential technological feature. NIPUs can be modified via copolymerization or used as matrices to fabricate polymer composites with different additives, similar to their conventional counterparts. Hence, non-isocyanate polyurethanes are a new class of environmentally friendly polymeric materials. Many papers on the matter above have been published, including both original research and extensive reviews. However, they do not provide collected information on NIPU composites fabrication and processing. Hence, this review describes the latest progress in non-isocyanate polyurethane synthesis, modification, and finally processing. While focusing primarily on the carbonate/amine route, methods of obtaining NIPU are described, and their properties are presented. Ways of incorporating various compounds into NIPU matrices are characterized by the role of PHU materials in copolymeric materials or as an additive. Finally, diverse processing methods of non-isocyanate polyurethanes are presented, including electrospinning or 3D printing.
PubMed: 34201649
DOI: 10.3390/ma14133497 -
BMJ (Clinical Research Ed.) Feb 2002
Review
Topics: Chemical Warfare Agents; Decontamination; Humans; Mustard Gas; Organophosphate Poisoning; Phosgene; Poisoning
PubMed: 11834561
DOI: 10.1136/bmj.324.7333.332 -
Indian Journal of Occupational and... 2022Phosgene is a highly toxic gas causing irritation of the airways and eyes though at high dose exposure. The effect on airways can be assessed by peak expiratory flow...
INTRODUCTION
Phosgene is a highly toxic gas causing irritation of the airways and eyes though at high dose exposure. The effect on airways can be assessed by peak expiratory flow rate (PEFR) which is a cheaper, simple, and easy to perform test under field conditions and routine monitoring. Thus, this study is undertaken to understand the effect of chronic low-dose phosgene exposure on PEFR and the associated factors.
METHODS
This study included 287 workers of phosgene production and captive units. After recording the demographic, occupational, and clinical history on a questionnaire, every participant was subjected to clinical examination, chest radiography, and measurement of PEFR using Spirovit SP-10.
RESULTS
The mean age and mean duration of the job of participants was 42.8 ± 10.4 years and 18.9 ± 9.6 years, respectively. The PEFR was significantly reduced with increasing age, increasing duration in the job, and those having direct exposure.
CONCLUSION
PEFR is affected by chronic low-dose exposure to phosgene.
PubMed: 36408435
DOI: 10.4103/ijoem.ijoem_417_20 -
Cell Journal Feb 2024Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dry and burning throat, vomiting, coughing, the...
Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dry and burning throat, vomiting, coughing, the production of foamy sputum, difficulty in breathing, and chest pain. This systematic review aims to provide a comprehensive overview of the clinical manifestations and treatment of phosgene toxicity by systematically analyzing available literature. The search was carried out on various scientific online databases to include related studies based on inclusion and exclusion criteria with the use of PRISMA guidelines. The quality of the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Thirteen articles were included in this study after the screening process. Inhalation was found to be the primary health problem of phosgene exposure with respiratory symptoms such as coughing and dyspnea. Chest pain and pulmonary oedema were also observed in some cases. Furthermore, pulmonary crackle was the most common reported physical examination. Beyond respiratory tract health issues, other organs involvements such as cardiac, skin, eye, and renal were also reported in some studies. The symptoms can occur within minutes to hours after exposure, and the severity of symptoms depends on the amount of inhaled phosgene. The findings showed that bronchodilators can alleviate symptoms of bronchoconstriction caused by phosgene. Oxygen therapy is essential for restoring oxygen levels and improving respiratory function in cases of hypoxemia. In severe cases, endotracheal intubation and invasive mechanical ventilation are used for artificial respiration, along with the removal of tracheal secretions and pulmonary oedema fluid through suctioning as crucial components of supportive therapy.
PubMed: 38459726
DOI: 10.22074/cellj.2024.2011864.1405 -
Journal of Cellular and Molecular... May 2022Phosgene gas leakage can cause life-threatening acute lung injury (ALI), which is characterized by inflammation, increased vascular permeability, pulmonary oedema and...
Phosgene gas leakage can cause life-threatening acute lung injury (ALI), which is characterized by inflammation, increased vascular permeability, pulmonary oedema and oxidative stress. Although the downregulation of neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) is known to be associated with inflammation and oxidative damage, its functions in phosgene-induced ALI remain unclear. In this study, rats with phosgene-induced ALI were intravenously injected with NEDD4-overexpressing lentiviruses to determine the functions of NEDD4 in this inflammatory condition. NEDD4 expression was decreased in the lung parenchyma of phosgene-exposed control rats, whereas its expression level was high in the NEDD4-overexpressing rats. Phosgene exposure increased the wet-to-dry lung weight ratio, but NEDD4 abrogated this effect. NEDD4 overexpression attenuated phosgene-induced lung inflammation, lowering the high lung injury score (based on total protein, inflammatory cells and inflammatory factors in bronchoalveolar lavage fluid) and also reduced phosgene-induced oxidative stress and cell apoptosis. Finally, NEDD4 was found to interact with Notch1, enhancing its ubiquitination and thereby its degradation, thus attenuating the inflammatory responses to ALI. Therefore, we demonstrated that NEDD4 plays a protective role in alleviating phosgene-induced ALI, suggesting that enhancing the effect of NEDD4 may be a new approach for treating phosgene-induced ALI.
Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Inflammation; Lung; Nedd4 Ubiquitin Protein Ligases; Phosgene; Rats; Rats, Sprague-Dawley; Receptor, Notch1
PubMed: 35355403
DOI: 10.1111/jcmm.17296 -
Frontiers in Immunology 2022Phosgene (COCl) gas is a chemical intermediate of high-volume production with numerous industrial applications worldwide. Due to its high toxicity, accidental exposure...
Phosgene (COCl) gas is a chemical intermediate of high-volume production with numerous industrial applications worldwide. Due to its high toxicity, accidental exposure to phosgene leads to various chemical injuries, primarily resulting in chemical-induced lung injury due to inhalation. Initially, the illness is mild and presents as coughing, chest tightness, and wheezing; however, within a few hours, symptoms progress to chronic respiratory depression, refractory pulmonary edema, dyspnea, and hypoxemia, which may contribute to acute respiratory distress syndrome or even death in severe cases. Despite rapid advances in medicine, effective treatments for phosgene-inhaled poisoning are lacking. Elucidating the pathophysiology and pathogenesis of acute inhalation toxicity caused by phosgene is necessary for the development of appropriate therapeutics. In this review, we discuss extant literature on relevant mechanisms and therapeutic strategies to highlight novel ideas for the treatment of phosgene-induced acute lung injury.
Topics: Acute Lung Injury; Humans; Lung; Phosgene; Pulmonary Edema; Respiratory Distress Syndrome
PubMed: 35983054
DOI: 10.3389/fimmu.2022.917395 -
Toxicology Letters Sep 2019Phosgene (Carbonyl Chloride, COCl) remains an important chemical intermediate in many industrial processes such as combustion of chlorinated hydrocarbons and synthesis...
Phosgene (Carbonyl Chloride, COCl) remains an important chemical intermediate in many industrial processes such as combustion of chlorinated hydrocarbons and synthesis of solvents (degreasers, cleaners). It is a sweet smelling gas, and therefore does not prompt escape by the victim upon exposure. Supplemental oxygen and ventilation are the only available management strategies. This study was aimed to delineate the pathogenesis and identify novel biomarkers of acute lung injury post exposure to COCl gas. Adult male and female C57BL/6 mice (20-25 g), exposed to COCl gas (10 or 20 ppm) for 10 min in environmental chambers, had a dose dependent reduction in PO and an increase in PCO, 1 day post exposure. However, mortality increased only in mice exposed to 20 ppm of COCl for 10 min. Correspondingly, these mice (20 ppm) also had severe acute lung injury as indicated by an increase in lung wet to dry weight ratio, extravasation of plasma proteins and neutrophils into the bronchoalveolar lavage fluid, and an increase in total lung resistance. The increase in acute lung injury parameters in COCl (20 ppm, 10 min) exposed mice correlated with simultaneous increase in oxidation of red blood cells (RBC) membrane, RBC fragility, and plasma levels of cell-free heme. In addition, these mice had decreased plasmalogen levels (plasmenylethanolamine) and elevated levels of their breakdown product, polyunsaturated lysophosphatidylethanolamine, in the circulation suggesting damage to cellular plasma membranes. This study highlights the importance of free heme in the pathogenesis of COCl lung injury and identifies plasma membrane breakdown product as potential biomarkers of COCl toxicity.
Topics: Acute Lung Injury; Administration, Inhalation; Animals; Chemical Warfare Agents; Female; Hemolysis; Male; Mice; Mice, Inbred C57BL; Phosgene
PubMed: 31047999
DOI: 10.1016/j.toxlet.2019.04.019 -
ACS Applied Materials & Interfaces Feb 2018Polycarbonates are widely used in food packages, drink bottles, and various healthcare products such as dental sealants and tooth coatings. However, bisphenol A (BPA)...
Polycarbonates are widely used in food packages, drink bottles, and various healthcare products such as dental sealants and tooth coatings. However, bisphenol A (BPA) and phosgene used in the production of commercial polycarbonates pose major concerns to public health safety. Here, we report a green pathway to prepare BPA-free polycarbonates (BFPs) by thermal ring-opening polymerization and photopolymerization. Polycarbonates prepared from two cyclic carbonates in different mole ratios demonstrated tunable mechanical stiffness, excellent thermal stability, and high optical transparency. Three-dimensional (3D) printing of the new BFPs was demonstrated using a two-photon laser direct writing system and a rapid 3D optical projection printer to produce structures possessing complex high-resolution geometries. Seeded C3H10T1/2 cells also showed over 95% viability with potential applications in biological studies. By combining biocompatible BFPs with 3D printing, novel safe and high-performance biomedical devices and healthcare products could be developed with broad long-term benefits to society.
Topics: Benzhydryl Compounds; Phenols; Polycarboxylate Cement; Printing, Three-Dimensional
PubMed: 29345455
DOI: 10.1021/acsami.7b18312