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Proceedings of the American Thoracic... Jul 2010The inhalation of reactive gases and vapors can lead to severe damage of the airways and lung, compromising the function of the respiratory system. Exposures to... (Review)
Review
The inhalation of reactive gases and vapors can lead to severe damage of the airways and lung, compromising the function of the respiratory system. Exposures to oxidizing, electrophilic, acidic, or basic gases frequently occur in occupational and ambient environments. Corrosive gases and vapors such as chlorine, phosgene, and chloropicrin were used as warfare agents and in terrorist acts. Chemical airway exposures are detected by the olfactory, gustatory, and nociceptive sensory systems that initiate protective physiological and behavioral responses. This review focuses on the role of airway nociceptive sensory neurons in chemical sensing and discusses the recent discovery of neuronal receptors for reactive chemicals. Using physiological, imaging, and genetic approaches, Transient Receptor Potential (TRP) ion channels in sensory neurons were shown to respond to a wide range of noxious chemical stimuli, initiating pain, respiratory depression, cough, glandular secretions, and other protective responses. TRPA1, a TRP ion channel expressed in chemosensory C-fibers, is activated by almost all oxidizing and electrophilic chemicals, including chlorine, acrolein, tear gas agents, and methyl isocyanate, the highly noxious chemical released in the Bhopal disaster. Chemicals likely activate TRPA1 through covalent protein modification. Animal studies using TRPA1 antagonists or TRPA1-deficient mice confirmed the role of TRPA1 in chemically induced respiratory reflexes, pain, and inflammation in vivo. New research shows that sensory neurons are not merely passive sensors of chemical exposures. Sensory channels such as TRPA1 are essential for maintenance of airway inflammation in asthma and may contribute to the progression of airway injury following high-level chemical exposures.
Topics: Acids; Animals; Chemical Warfare Agents; Chemoreceptor Cells; Environmental Exposure; Gases; Humans; Inhalation Exposure; Irritants; Mice; Nociceptors; Occupational Exposure; Respiratory System; Sensory Receptor Cells; Transient Receptor Potential Channels
PubMed: 20601631
DOI: 10.1513/pats.201001-004SM -
Cureus Jul 2023Phosgene is a chemical used in the manufacture of plastics and pesticides. Phosgene remains one of the most dangerous of today's high-volume chemicals, as evidenced by...
BACKGROUND
Phosgene is a chemical used in the manufacture of plastics and pesticides. Phosgene remains one of the most dangerous of today's high-volume chemicals, as evidenced by the deaths and widespread evacuations caused by its release in industrial accidents. The respiratory system is most severely harmed by exposure to phosgene.
CASE PRESENTATION
A 39-year-old male patient arrived feeling short of breath, nauseous, and tachypnoeic after being exposed to triphosgene gas at work. Upon examination, the patient's oxygen saturation (spo2) was 72% without oxygen, 95% on 15 L of oxygen (o2), hemodynamically unstable, and transferred to the intensive care unit (ICU) for additional care. A ventilator was started in non-invasive mode, and antibiotics were administered based on an initial CT scan of the chest that revealed bilateral fluffy alveolar deposits. The same course of treatment was continued on day two. Chest X-ray shadows improved starting on day three. Saturation is 95% after weaning off Niv support and placing 5 L of o2. He was discharged with oral medications once he was hemodynamically stable.
CONCLUSION
An incidental phosgene poisoning is described in detail here, along with its clinical symptoms and treatment. It is critical to suspect phosgene gas exposure and monitor such patients to save lives.
PubMed: 37575869
DOI: 10.7759/cureus.41679 -
Emergency Medicine Journal : EMJ Jun 2006There is no specific antidote for the treatment of casualties exposed to chlorine, phosgene, or mustards; therefore, management is largely supportive. Corticosteroid... (Review)
Review
There is no specific antidote for the treatment of casualties exposed to chlorine, phosgene, or mustards; therefore, management is largely supportive. Corticosteroid treatment has been given to casualties accidentally exposed to chlorine. Clinical data on efficacy are inconclusive as the numbers given steroids have been small and the indications for administration unclear. There have been no clinical controlled studies. There is a stronger evidence base from animal studies, particularly from porcine and rodent models. Lung injury induced by phosgene and mustard appears to be mediated by glutathione depletion, lipid peroxidation, free radical generation, and subsequent cellular toxicity. There is limited evidence to suggest that repletion of glutathione reduces and/or prevents lung damage by these agents. This may provide an opportunity for therapeutic intervention.
Topics: Animals; Bronchodilator Agents; Chemical Warfare Agents; Humans; Inhalation Exposure; Lung Diseases; Mustard Compounds; Phosgene; Porphyrins; Rats; Swine
PubMed: 16714497
DOI: 10.1136/emj.2003.011775 -
The Hospital Jul 1899
PubMed: 29820080
DOI: No ID Found -
Supporting discovery and development of medical countermeasures for chemical injury to eye and skin.Experimental Eye Research Aug 2022Vesicants, from vesica (Latin for blister), can cause local and systemic toxicity. They include the chemotherapy drug nitrogen mustard and chemical warfare agents sulfur...
Vesicants, from vesica (Latin for blister), can cause local and systemic toxicity. They include the chemotherapy drug nitrogen mustard and chemical warfare agents sulfur mustard, Lewisite, and phosgene oxime. These agents are commonly released in vapor form and consequently, eyes and skin are the most vulnerable. The ocular and cutaneous injuries can be acute, subacute, or chronic, and can predispose casualties to secondary deleterious effects. Underlying these broad organ responses are shared and tissue-specific cellular and molecular biological cascades that attempt to counteract such chemical injuries. Depending on the severity of the chemical insult, biological responses often lead to inadequate wound healing and result in long-term pathology instead. Exposure to other toxic industrial chemicals such as acrolein, chloropicrin, and hydrogen fluoride, can also cause prominent eye and skin damage. There are currently no FDA-approved drugs to counteract these injuries. Hence, the possibility of a mass casualty emergency involving these chemicals is a major public health concern. Recognizing this critical challenge, the United States Department of Health and Human Services (HHS) is committed to the development of medical countermeasures to advance national health and medical preparedness against these highly toxic chemicals. Here, we provide an overview of various HHS funding and scientific opportunities available in this space, emphasizing parallels between eye and skin response to chemical injury. We also discuss a main limitation of existing data and suggest ways to overcome it.
Topics: Burns, Chemical; Chemical Warfare Agents; Humans; Mechlorethamine; Medical Countermeasures; Mustard Gas; Skin; United States
PubMed: 35716762
DOI: 10.1016/j.exer.2022.109156 -
Chemical Society Reviews Aug 2016The positron-emitting radionuclide carbon-11 ((11)C, t1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or... (Review)
Review
The positron-emitting radionuclide carbon-11 ((11)C, t1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [(11)C]methyl iodide or [(11)C]methyl triflate (generated from [(11)C]carbon dioxide or [(11)C]methane). Consequently, small molecules that lack an easily substituted (11)C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [(11)C]Carbon dioxide itself, [(11)C]carbon monoxide, [(11)C]cyanide, and [(11)C]phosgene represent alternative reactants to enable (11)C-carbonylation. Methodologies developed for preparation of (11)C-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. (11)C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry.
Topics: Carbon Radioisotopes; Dacarbazine; Humans; Molecular Structure; Oxygen; Positron-Emission Tomography; Radiopharmaceuticals; Temozolomide
PubMed: 27276357
DOI: 10.1039/c6cs00310a -
Polymers Nov 2022Polyurethanes (PUs) are versatile and widespread, particularly as flexible and rigid foams. To avoid isocyanates and other toxic reagents required for synthesis, such as...
Polyurethanes (PUs) are versatile and widespread, particularly as flexible and rigid foams. To avoid isocyanates and other toxic reagents required for synthesis, such as phosgene, alternative synthetic routes have been utilized to produce non-isocyanate polyurethanes (NIPUs). A thermally and flame-resistant rigid NIPU was produced from environmentally benign and bio-sourced ingredients, requiring no catalyst or solvents. A foamed structure was obtained by the addition of glutaraldehyde and four different carboxylic acids: malic acid, maleic acid, citric acid, and aconitic acid. The resulting morphology, thermal degradation, and flame resistance of each foam were compared. The properties vary with each carboxylic acid used, but in each case, peak thermal degradation and peak heat release are postponed by >100 °C compared to commercial rigid PU foam. Furthermore, in a butane torch test, NIPU foams exhibit an 80% higher remaining mass and a 75% reduction in afterburn time, compared to commercial polyurethane. This bio-based polyurethane eliminates the hazards of traditional PUs, while imparting inherent thermal stability and flame resistance uncharacteristic of conventional foams.
PubMed: 36433146
DOI: 10.3390/polym14225019 -
Journal of Inflammation Research 2023Chemically induced acute lung injury (CALI) has become a serious health concern in our industrialized world, and abnormal functional alterations of immune cells...
PURPOSE
Chemically induced acute lung injury (CALI) has become a serious health concern in our industrialized world, and abnormal functional alterations of immune cells crucially contribute to severe clinical symptoms. However, the cell heterogeneity and functional phenotypes of respiratory immune characteristics related to CALI remain unclear.
METHODS
We performed scRNA sequencing on bronchoalveolar lavage fluid (BALF) samples obtained from phosgene-induced CALI rat models and healthy controls. Transcriptional data and TotalSeq technology were used to confirm cell surface markers identifying immune cells in BALF. The landscape of immune cells could elucidate the metabolic remodeling mechanism involved in the progression of acute respiratory distress syndrome and cytokine storms. We used pseudotime inference to build macrophage trajectories and the corresponding model gene expression changes, and identified and characterized alveolar cells and immune subsets that may contribute to CALI pathophysiology based on gene expression profiles at single-cell resolution.
RESULTS
The immune environment of cells, including dendritic cells and specific macrophage subclusters, exhibited increased function during the early stage of pulmonary tissue damage. Nine different subpopulations were identified that perform multiple functional roles, including immune responses, pulmonary tissue repair, cellular metabolic cycle, and cholesterol metabolism. Additionally, we found that individual macrophage subpopulations dominate the cell-cell communication landscape. Moreover, pseudo-time trajectory analysis suggested that proliferating macrophage clusters exerted multiple functional roles.
CONCLUSION
Our findings demonstrate that the bronchoalveolar immune microenvironment is a fundamental aspect of the immune response dynamics involved in the pathogenesis and recovery of CALI.
PubMed: 37220504
DOI: 10.2147/JIR.S407580 -
BMJ Case Reports Apr 2012Phosgene is a highly toxic gas to which accidental exposure may occur in occupational workers. This case report describes the clinical presentation and management of...
Phosgene is a highly toxic gas to which accidental exposure may occur in occupational workers. This case report describes the clinical presentation and management of accidental phosgene poisoning happened after the leakage of phosgene gas from nearby pipeline. The need to suspect phosgene gas exposure and observe such patients is crucial for life saving, especially in view of the delay in clinical deterioration observed in some patients who subsequently develop adult respiratory distress syndrome.
Topics: Humans; Male; Phosgene; Poisoning; Respiration, Artificial; Vasoconstrictor Agents; Young Adult
PubMed: 22602834
DOI: 10.1136/bcr.11.2011.5233 -
Toxicological Sciences : An Official... Jul 2015Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption...
Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption of epithelial tight junctions, surfactant dysfunction, and oxidative stress. There are no targeted treatments for phosgene-induced ALI. Previous studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of phosgene-induced ALI remains unknown. We previously demonstrated that NOS-2 expression in lung epithelium exacerbates inhaled endotoxin-induced ALI in mice, mediated partially through downregulation of surfactant protein B (SP-B) expression. Therefore, we hypothesized that a selective NOS-2 inhibitor delivered to the lung epithelium by inhalation would mitigate phosgene-induced ALI. Inhaled phosgene produced increases in bronchoalveolar lavage fluid protein, histologic lung injury, and lung NOS-2 expression at 24 h. Administration of the selective NOS-2 inhibitor 1400 W via inhalation, but not via systemic delivery, significantly attenuated phosgene-induced ALI and preserved epithelial barrier integrity. Furthermore, aerosolized 1400 W augmented expression of SP-B and prevented downregulation of tight junction protein zonula occludens 1 (ZO-1), both critical for maintenance of normal lung physiology and barrier integrity. We also demonstrate for the first time that NOS-2-derived nitric oxide downregulates the ZO-1 expression at the transcriptional level in human lung epithelial cells, providing a novel target for ameliorating vascular leak in ALI. Our data demonstrate that lung NOS-2 plays a critical role in the development of phosgene-induced ALI and suggest that aerosolized NOS-2 inhibitors offer a novel therapeutic strategy for its treatment.
Topics: Acute Lung Injury; Animals; Chemical Warfare Agents; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Phosgene
PubMed: 25870319
DOI: 10.1093/toxsci/kfv072