Phosgene is not only a dangerous asphyxiating chemical warfare agent, but also an important chemical raw material, which is widely used in chemical production. According to statistics, there are more than 1 000 phosgene production enterprises in China, with an annual production volume of more than 3 million tons and hundreds of thousands of employees. Therefore, once the leakage accident occurs during production, storage and transportation, it often causes a large number of casualties. In the past 20 years, phosgene poisoning accidents in China have occurred from time to time, and due to the weak irritation, high density, and high concentration of phosgene at the scene of the accident, it often results in acute high-concentration inhalation of the exposed, triggering acute lung injury (ALI), and is very likely to progress to acute respiratory distress syndrome (ARDS), with a mortality rate up to 40%-50%. In view of the characteristics of sudden, mass, concealed, rapid and highly fatal phosgene, and the mechanism of its toxicity and pathogenicity is still not clear, there is no effective treatment and standardized guidance for the sudden group phosgene poisoning. In order to improve the efficiency of clinical treatment and reduce the mortality, this paper has summarized the pathophysiological mechanism of phosgene poisoning, clinical manifestations, on-site treatment, research progress, and innovative clinical therapies by combining the extensive basic research on phosgene over the years with the abundant experience in the on-site treatment of sudden mass phosgene poisoning. This consensus aims to provide guidance for the clinical rescue and treatment of patients with sudden mass phosgene poisoning, and to improve the level of treatment.
Humans ; Phosgene ; Chemical Warfare Agents ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome/therapy* ; Treatment Outcome

BACKGROUNDOrganophosphate poisoning is an important health problem in developing countries which causes death mainly by inducing acute lung injury. In this study, we examined the effects of penehyclidine hydrochloride (PHC), a selective M-receptor inhibitor, on dichlorvos-induced acute lung injury in swine.

METHODSTwenty-two female swines were randomly divided into control (n = 5), dichlorvos (n = 6), atropine (n = 6), and PHC (n = 5) groups. Hemodynamic data, extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) were monitored; blood gas analysis and acetylcholinesterase (AchE) levels were measured. PaO2/FiO2, cardiac index (CI), and pulmonary vascular resistance indices (PVRI) were calculated. At termination of the study, pulmonary tissue was collected for ATPase activity determination and wet to dry weight ratio (W/D) testing 6 hours post-poisoning. TUNEL assay, and Bax, Bcl-2, and caspase-3 expression were applied to pulmonary tissue, and histopathology was observed.

RESULTSAfter poisoning, PHC markedly decreased PVRI, increased CI more effectively than atropine. Anticholinergic treatment reduced W/D, apoptosis index (AI), and mitigated injury to the structure of lung; however, PHC reduced AI and caspase-3 expression and improved Bcl-2/Bax more effectively than atropine. Atropine and PHC improved ATPase activities; a significant difference between groups was observed in Ca(2+)-ATPase activity, but not Na(+)-K(+)-ATPase activity.

CONCLUSIONSThe PHC group showed mild impairment in pathology, less apoptotic cells, and little impact on cardiac function compared with the atropine group in dichlorvos-induced acute lung injury.

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Dichlorvos ; toxicity ; Female ; Quinuclidines ; therapeutic use ; Swine

Traditional remedies, especially the extract of elm bark, are frequently used in Korea. But the exact efficacy and adverse effects are not known. Cancer patients are frequently recommended various traditional remedies by family members. However such remedies may lead to life-threatening complications. We observed two cases of severe hepatic and renal toxicities that developed after ingestion of elm extract. One patient was a 67-year-old man diagnosed with stage IV non-small cell lung cancer (NSCLC). He ingested the bark extract of elm for 2 weeks during routine work-up prior to chemotherapy. He abruptly showed acute toxic hepatitis with cardiac tamponade. The other patient was a 57-year-old woman diagnosed with extensive disease-small cell lung cancer (ED-SCLC). She consumed the extract of root bark of elm for 5 months during complete remission status and developed acute renal failure. These cases suggest that use of the extract of elm bark in cancer patients must be more careful.
Acute Kidney Injury ; Aged ; Carcinoma, Non-Small-Cell Lung ; Cardiac Tamponade ; Drug Therapy ; Drug-Induced Liver Injury* ; Eating* ; Female ; Humans ; Korea ; Lung Neoplasms* ; Lung* ; Middle Aged ; Renal Insufficiency*

Acute Lung Injury ; drug therapy ; therapy ; Fluid Therapy ; Glucocorticoids ; therapeutic use ; Humans ; Inflammation ; drug therapy ; therapy ; Respiratory Distress Syndrome, Adult ; drug therapy ; therapy

BACKGROUNDLow potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.

METHODSTwelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n = 6) pretreated with normal saline and the LPD group (n = 6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.

RESULTSAll animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0 ± 12.6) mmHg vs. (284.3 ± 11.3) mmHg at 6 hours after ALI, P < 0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0 ± 0.6) and (2.50 ± 0.08) folds in placebo group; and (2.5 ± 0.5) and (1.40 ± 0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P < 0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg×ml(-1)×g(-1) protein) was significantly lower (P < 0.01) than that in placebo group ((67.2 ± 25.3) pg×ml(-1)×g(-1) protein).

CONCLUSIONThese findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.

Acute Kidney Injury ; prevention & control ; Acute Lung Injury ; drug therapy ; physiopathology ; Animals ; Dextrans ; therapeutic use ; Disease Models, Animal ; Hemodynamics ; Interleukin-6 ; blood ; Kidney ; pathology ; Oleic Acid ; toxicity ; Swine

OBJECTIVETo observe the effect of inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine on the hemodynamics and histopathology in a porcine model of acute lung injury.

METHODSNormal adult pigs were subjected to saline lavage of the bilateral lungs to induce acute lung injury and randomized subsequently into 3 groups for treatment with inhalation of perfluorocarbon, combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP, CVP and PAWP were recorded at different time points following the lung injury, and the lung tissues were sampled for histological observations.

RESULTSThe MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon inhalation significantly improved these indices as compared with inhalation of tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology was the mildest in the combined inhalation group, and the most severe in tetramethylpyrazine group.

CONCLUSIONCombined inhalation of perfluorocarbon and tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

Acute Lung Injury ; drug therapy ; etiology ; pathology ; Administration, Inhalation ; Animals ; Drug Therapy, Combination ; Fluorocarbons ; administration & dosage ; Hemodynamics ; drug effects ; Lung ; pathology ; Phytotherapy ; Pyrazines ; administration & dosage ; Swine

OBJECTIVETo observe the protective effect of the proteasome inhibitor MG-132 in rats with severe acute pancreatitis (SAP) and the associated lung injury.

METHODSIn rat models of the SAP established with injection of 5% sodium taurocholate into the biliary-pancreatic duct, the changes of the serum amylase and myeloperoxidase (MPO) activity in the pancreatic and lung tissues were evaluated. The pathological changes of the pancreatic and lung tissues were also observed.

RESULTSMG-132 significantly decreased serum amylase, pancreatic weight/body weight ratio, and pancreatic and pulmonary myeloperoxidase activity (P<0.05). Histopathological examinations revealed milder edema, cellular damage, and inflammation in the pancreatic and lung tissues of rats pretreated with the peptide (P<0.05).

CONCLUSIONMG-132 ameliorates SAP and the associated lung injury in rats.

Acute Disease ; Amylases ; blood ; Animals ; Cysteine Proteinase Inhibitors ; pharmacology ; Leupeptins ; pharmacology ; Lung ; pathology ; Lung Injury ; drug therapy ; Pancreas ; pathology ; Pancreatitis ; drug therapy ; Peroxidase ; blood ; Rats ; Rats, Sprague-Dawley

Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Acute Kidney Injury

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Endotoxins ; Glycoproteins ; therapeutic use ; Male ; Propofol ; therapeutic use ; Rats ; Rats, Sprague-Dawley

ObjectiveExposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.

Data SourcesThis review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."

Study SelectionThe original articles and reviews including the topics were the primary references.

ResultsBased on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.

ConclusionsAt present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.

Acute Lung Injury ; chemically induced ; Animals ; Chlorine ; toxicity ; Halogens ; toxicity ; Humans ; Lung ; drug effects ; pathology ; Respiratory Distress Syndrome, Adult ; drug therapy