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The Journal of Pharmacology and... Jan 2024Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical... (Review)
Review
Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
Topics: Humans; Lung; Chlorine; Chemical Warfare Agents; Phosgene; Acute Lung Injury; Irritants
PubMed: 37863486
DOI: 10.1124/jpet.123.001822 -
Immunity, Inflammation and Disease Nov 2023Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic... (Review)
Review
AIM
Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic agents of responsible for RD. Among these, proteomics emerges as a valuable diagnostic method for pinpointing the specific proteins involved in RD pathogenesis. Therefore, in this study, for the first time, we examined the protein markers involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, bronchiolitis obliterans (BO), and chemical warfare victims exposed to mustard gas, using the proteomics method as a systematic study.
MATERIALS AND METHODS
A systematic search was performed up to September 2023 on several databases, including PubMed, Scopus, ISI Web of Science, and Cochrane. In total, selected 4246 articles were for evaluation according to the criteria. Finally, 119 studies were selected for this systematic review.
RESULTS
A total of 13,806 proteins were identified, 6471 in COPD, 1603 in Asthma, 5638 in IPF, three in BO, and 91 in mustard gas exposed victims. Alterations in the expression of these proteins were observed in the respective diseases. After evaluation, the results showed that 31 proteins were found to be shared among all five diseases.
CONCLUSION
Although these 31 proteins regulate different factors and molecular pathways in all five diseases, they ultimately lead to the regulation of inflammatory pathways. In other words, the expression of some proteins in COPD and mustard-exposed patients increases inflammatory reactions, while in IPF, they cause lung fibrosis. Asthma, causes allergic reactions due to T-cell differentiation toward Th2.
Topics: Humans; Lung; Mustard Gas; Proteomics; Pulmonary Disease, Chronic Obstructive; Asthma; Biomarkers
PubMed: 38018577
DOI: 10.1002/iid3.1090 -
IScience Jun 2024Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is...
Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.
PubMed: 38883811
DOI: 10.1016/j.isci.2024.110042 -
Journal of Cellular and Molecular... Aug 2023Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress...
Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress is considered to be vital processes for the SM toxicity mechanism. We previously proved the therapeutic effect of exosomes derived from bone marrow mesenchymal stromal cells in promoting the repair of alveolar epithelial barrier and inhibiting apoptosis. However, the key functional components in exosomes and the underlying mechanisms have not been fully elaborated. This research shed light on the function of the key components of human umbilical cord mesenchymal stem cell-derived exosomes (HMSCs-Ex). We noted that HMSCs-Ex-derived miR-199a-5p played a vital role in reducing pneumonocyte oxidative stress and apoptosis by reducing reactive oxygen species, lipid peroxidation products and increasing the activities of antioxidant enzymes in BEAS-2B cells and mouse models after exposure to SM for 24 h. Furthermore, we demonstrated that the overexpression of miR-199a-5p in HMSCs-Ex treatment induced a further decrease of Caveolin1 and the activation of the mRNA and protein level of NRF2, HO1 and NQO1, compared with HMSCs-Ex administration. In summary, miR-199a-5p was one of the key molecules in HMSCs-Ex that attenuated SM-associated oxidative stress via regulating CAV1/NRF2 signalling pathway.
Topics: Animals; Humans; Mice; Exosomes; Mesenchymal Stem Cells; MicroRNAs; Mustard Gas; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 37386746
DOI: 10.1111/jcmm.17803 -
Polymers Feb 2024There have been many studies on surface acoustic wave (SAW) sensors for detecting sulfur-containing toxic or harmful gases. This paper aims to give an overview of the... (Review)
Review
There have been many studies on surface acoustic wave (SAW) sensors for detecting sulfur-containing toxic or harmful gases. This paper aims to give an overview of the current state of polymer films used in SAW sensors for detecting deleterious gases. By covering most of the important polymer materials, the structures and types of polymers are summarized, and a variety of devices with different frequencies, such as delay lines and array sensors for detecting mustard gas, hydrogen sulfide, and sulfur dioxide, are introduced. The preparation method of polymer films, the sensitivity of the SAW gas sensor, the limit of detection, the influence of temperature and humidity, and the anti-interference ability are discussed in detail. The advantages and disadvantages of the films are analyzed, and the potential application of polymer films in the future is also forecasted.
PubMed: 38399835
DOI: 10.3390/polym16040457 -
BMJ Open May 2024People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition.
DESIGN
An assessor-blind, two-armed, parallel-design randomised controlled clinical trial.
SETTING
Secondary care clinics in Iran.
PARTICIPANTS
60 men with breathlessness due to respiratory disease caused by documented mustard gas exposure, mean (SD) age 52.7 (4.36) years, MRC dyspnoea score 3.5 (0.7), St. George's Respiratory Questionnaire (SGRQ) 72.3 (15.2).
INTERVENTIONS
Participants were allocated either to a 6-week course of thrice-weekly PR (n=31) or to usual care (n=29), with 6-week data for 28 and 26, respectively.
OUTCOME MEASURES
Primary endpoint was change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Secondary endpoints included 6 min walk distance, quadriceps strength and bulk, body composition and health status. For logistical reasons, blood tests that had been originally planned were not performed and 12-month follow-up was available for only a small proportion.
RESULTS
At 6 weeks, cycle endurance time increased from 377 (140) s to 787 (343) s with PR vs 495 (171) s to 479 (159) s for usual care, effect size +383 (231) s (p<0.001). PR also improved 6 min walk distance+103.2 m (63.6-142.9) (p<0.001), MRC dyspnoea score -0.36 (-0.65 to -0.07) (p=0.016) and quality of life; SGRQ -8.43 (-13.38 to -3.48) p<0.001, as well as quadriceps strength+9.28 Nm (1.89 to 16.66) p=0.015.
CONCLUSION
These data suggest that PR can improve exercise capacity and quality of life in people with breathlessness due to mustard gas lung disease and support the wider provision of this form of care.
TRIAL REGISTRATION NUMBER
IRCT2016051127848N1.
Topics: Humans; Male; Iran; Mustard Gas; Middle Aged; Exercise Tolerance; Quality of Life; Dyspnea; Lung Diseases; Adult; Outpatients; Treatment Outcome; Chemical Warfare Agents
PubMed: 38806414
DOI: 10.1136/bmjopen-2023-083085 -
Iranian Journal of Allergy, Asthma, and... Sep 2023Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA...
Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA (miR) transcript levels are found in pulmonary diseases and even inflammation. Therefore, we evaluated the expression levels of miR-20a-5p, miR-21-5p, and two target transcripts (transforming growth factor-beta [TGF-β1] and TGF-β receptor 2 [TGFR2]) in lung, serum, and skin samples from patients exposed to SM. Total RNA was extracted from lung, serum, and skin samples of patients with moderate (n=10) and high (n=10) SM exposure, as well as 10 healthy subjects. Following the synthesis of complementary deoxyribonucleic acid using real-time polymerase chain reaction, we determined the expression levels of miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 transcripts. Furthermore, we evaluated the sensitivity and specificity of the chosen miRs by employing receiver operating characteristic (ROC) curves and calculating the area under the ROC curve. The results showed that miR-20a-5p and miR-21-5p expressions in the groups with moderate and high SM exposure were significantly lower than the normal controls. The expression analysis demonstrated that TGFR2 was significantly less expressed in skin samples exposed to SM in both groups of patients compared with healthy controls. Furthermore, the TGF-β1 expression in the skin samples of the group with moderate SM exposure was lower than that of the normal control group. Our findings suggest that miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 expressions could be used as potential biomarkers for discriminating SM-exposed patients from healthy individuals.
PubMed: 37767679
DOI: 10.18502/ijaai.v22i4.13609 -
RSC Advances Sep 2023Methyl-diethanolamine (CAS: 105-59-9), ethyl-diethanolamine (CAS: 139-87-7), and triethanolamine (CAS: 102-71-6) were identified as the degradation products and...
Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine gas chromatography tandem mass spectrometry.
Methyl-diethanolamine (CAS: 105-59-9), ethyl-diethanolamine (CAS: 139-87-7), and triethanolamine (CAS: 102-71-6) were identified as the degradation products and bio-markers of nitrogen mustard exposure. Sensitive and convenient detection methods for amino alcohol are of great importance to identify nitrogen mustard exposure in forensic analysis. Herein, analytical methods including gas chromatography-tandem mass spectrometry combined with heptafluorobutyryl derivatization and solid phase extraction were established for retrospective detection of the biomarkers in human plasma and urine samples. The efficiency of the method was improved by optimizing the conditions for sample preparation and the GC-MS/MS method. The optimization included the derivatization temperature, reaction time, reagent dosage and solid phase extraction cartridges, eluent and pH of the loading sample. The results indicated that the SCX cartridge resulted in better enrichment and purification effects, and the best recovery could be obtained with pH = 3-4 for the loading samples and an eluent of 2 mL 10% NHOH/MeOH. The GC-MS/MS parameters were also optimized for better specificity and sensitivity. The established method was fully validated for each analyte both in plasma and urine matrixes. The linear range of analytes in plasma was 1.0-1000 ng mL with a correlation parameter () of ≥0.994, intra-day/inter-day accuracy of 93.7-117%, and relative standard deviation (RSD) of ≤6.5%. Meanwhile the results in urine were 1.0-1000 ng mL with of ≥0.996, intra-day/inter-day accuracy of 94.3-122%, and RSD of ≤6.6%. The detection limit of the analytes was 1.0 ng mL. The method was applied for the detection and identification of trace amino alcohols present in urine samples dispatched by the Organization for the Prohibition of Chemical Weapons (OPCW) and the results were confirmed to be correct.
PubMed: 37720833
DOI: 10.1039/d3ra04697d -
Disaster Medicine and Public Health... Oct 2023To summarize presentations and discussions from the 2022 trans-agency workshop titled "Overlapping science in radiation and sulfur mustard (SM) exposures of skin and...
Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin.
PURPOSE
To summarize presentations and discussions from the 2022 trans-agency workshop titled "Overlapping science in radiation and sulfur mustard (SM) exposures of skin and lung: Consideration of models, mechanisms, organ systems, and medical countermeasures."
METHODS
Summary on topics includes: (1) an overview of the radiation and chemical countermeasure development programs and missions; (2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses.
RESULTS
There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, US Government program officials, and regulators to discuss lung-, and skin- specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries.
CONCLUSIONS
Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall US Government emergency preparedness.
Topics: Animals; Humans; Mustard Gas; Lung; Skin; Burns, Chemical; Biomarkers
PubMed: 37852927
DOI: 10.1017/dmp.2023.176 -
BMC Health Services Research Dec 2023Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the...
BACKGROUND
Sulfur Mustard (SM) is a chemical warfare agent that has serious short-term and long-term effects on health. Thousands of Iranians were exposed to SM during the eight-year Iran-Iraq conflict and permanently injured while the socioeconomic imbalance in their healthcare utilization (HCU) and health expenditures remains. This study aims to describe the HCU of SM-exposed survivors in Iran from 2018 to 2021; identify high-risk areas; and apply an inequality analysis of utilization regarding the socioeconomic groups to reduce the gap by controlling crucial determinants.
METHODS
From Oct 2018 to June 2021, the Veterans and Martyrs Affairs Foundation (VMAF) recorded 58,888 living war survivors with eye, lung, and skin ailments. After cleaning the dataset and removing junk codes, we defined 11 HCU-related variables and predicted the HCU for the upcoming years using Bayesian spatio-temporal models. We explored the association of individual-level HCU and determinants using a Zero-inflated Poisson (ZIP) model and also investigated the provincial hotspots using Local Moran's I.
RESULTS
With ≥ 90% confidence, we discovered eleven HCU clusters in Iran. We discovered that the expected number of HCU 1) rises with increasing age, severity of complications in survivors' eyes and lungs, wealth index (WI), life expectancy (LE), and hospital beds ratio; and 2) decreases with growing skin complications, years of schooling (YOS), urbanization, number of hospital beds, length of stay (LOS) in bed, and bed occupancy rate (BOR). The concentration index (CInd) of HCU and associated costs in age and wealth groups were all positive, however, the signs of CInd values for HCU and total cost in YOS, urbanization, LOS, and Hospital beds ratio groups were not identical.
CONCLUSIONS
We observed a tendency of pro-rich inequity and also higher HCU and expenditures for the elderly population. Finally, health policies should tackle potential socioeconomic inequities to reduce HCU gaps in the SM-exposed population. Also, policymakers should allocate the resources according to the hotspots of HCU.
Topics: Humans; Bayes Theorem; Health Expenditures; Health Services Accessibility; Iran; Mustard Gas; Spatio-Temporal Analysis; Healthcare Disparities; Socioeconomic Factors
PubMed: 38093322
DOI: 10.1186/s12913-023-10352-7