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

BACKGROUNDAn acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (JNK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model.

METHODSThirty-six rats were randomized into three groups: control, LPS, and LPS + JNK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups.

RESULTSMPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 ± 0.15 U in LPS vs. 0.77 ± 0.27 U in control, P < 0.05). Inhibiting JNK attenuated LPS-induced MPO activity upregulation (0.52 ± 0.12 U in LPS + JNK inhibitor vs. 1.26 ± 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting JNK attenuated LPS-induced neutrophils increase in BALF (255.0 ± 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 ± 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 ± 4.82 vs. 7.00 ± 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + JNK inhibitor group.

CONCLUSIONSInhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.

Animals ; Anthracenes ; therapeutic use ; Collagen ; metabolism ; JNK Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism ; Lipopolysaccharides ; toxicity ; Lung ; drug effects ; metabolism ; pathology ; Male ; Rats ; Respiratory Distress Syndrome, Adult ; chemically induced ; drug therapy ; Signal Transduction ; drug effects

Acute respiratory distress syndrome (ARDS) is a medical emergency that threatens life. To this day, ARDS is very rarely reported by iodine contrast media, and there is no reported case of ARDS induced by gadolinium contrast media. Here, we present a case with ARDS after the use of gadobutrol (Gadovist) as a magnetic resonance imaging (MRI) contrast medium. A 26 years old female without any medical history, including allergic diseases and without current use of drugs, visited the emergency room for abdominal pain. Her abdominopelvic computed tomography with iodine contrast media showed a right ovarian cyst and possible infective colitis. Eighty-three hours later, she underwent pelvis MRI after injection of 7.5 mL (0.1 mL/kg body weight) of gadobutrol (Gadovist) to evaluate the ovarian cyst. She soon presented respiratory difficulty, edema of the lips, nausea, and vomiting, and we could hear wheezing upon auscultation. She was treated with dexamethasone, epinephrine, and norepinephrine. Her chest X-ray showed bilateral central bat-wing consolidative appearance. Managed with mechanical ventilation, she was extubated 3 days later and discharged without complications.
Adult ; Animals ; Contrast Media/administration & dosage/*adverse effects ; Female ; Gadolinium ; Humans ; Magnetic Resonance Imaging/*methods ; *Organometallic Compounds/adverse effects ; Respiratory Distress Syndrome, Adult/*chemically induced ; Tomography, X-Ray Computed

OBJECTIVETo investigate the effect of melatonin (MT) on p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with phosgene-induced lung injury.

METHODSFifty specific pathogen-free male Sprague-Dawley rats were randomly divided into phosgene inhalation group, air control group, saline control group, MT treatment group, and SB203580 (specific inhibitor of p38 MAPK) group, with 10 mice in each group. All groups except the air control group were exposed to phosgene, and the animals were sacrificed 6 h later. Lung wet/dry weight (W/D) ratio and the content of malondialdehyde (MDA) and nitric oxide (NO) and activity of myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) were measured. The qualitative and quantitative expression of p38 MAPK and phospho-p38 MAPK (p-p38) was measured by immunohistochemistry (IHC) and Western blot, respectively. Inducible nitric oxide synthase (iNOS) level in lung tissue was determined by Western blot.

RESULTSCompared with the air control group, the phosgene inhalation group had significantly increased lung W/D ratio and neutrophil count in BALF (P < 0.01); the MT treatment group had significantly lower neutrophil count and lung W/D ratio than the phosgene inhalation group (P < 0.05). IHC demonstrated that the air control group had relatively weak expression of p-p38 in lung tissue; the expression of p-p38 was significantly up-regulated after phosgene inhalation, and it was mainly distributed in infiltrating inflammatory cells and vascular endothelial cells, positive in the cytoplasm and nucleus of many cells. The distribution of p-p38-positive cells in the MT treatment and SB203580 groups was similar to that in the phosgene inhalation group, but the MT treatment and SB203580 groups had a significantly reduced number of cells with p-p38-positive nuclei and a significantly reduced intensity of p-p38 expression signals. The phosgene inhalation group had significantly increased content of MDA and NO and activity of MPO compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had significantly reduced content of MDA and NO and activity of MPO compared with the phosgene inhalation group (P < 0.05), but had higher content of MDA and NO and activity of MPO than the air control group. The Western blot showed that the phosgene inhalation group had significantly increased expression of iNOS and p-p38 compared with the air control group (P < 0.01); the MT treatment and SB203580 groups had lower expression of iNOS and p-p38 than the phosgene inhalation group (P < 0.05).

CONCLUSIONMT and SB203580 have a significant protective effect in rats with phosgene-induced lung injury, and the mechanism may be associated with scavenging free radicals and inhibiting activation of p38 MAPK and expression of iNOS.

Animals ; Bronchoalveolar Lavage Fluid ; Chemical Warfare Agents ; toxicity ; Imidazoles ; Lung ; drug effects ; Lung Injury ; chemically induced ; Male ; Malondialdehyde ; adverse effects ; Melatonin ; physiology ; Mice ; Nitric Oxide ; adverse effects ; Nitric Oxide Synthase Type II ; metabolism ; Phosgene ; toxicity ; Pyridines ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism

Antithymocyte globulin (ATG) has long been used for immune-induction and anti-rejection treatments for solid organ transplantations. To date, few cases of ATG-induced acute respiratory distress syndrome (ARDS) have been published. Here, we present a case of ARDS caused by a single low-dose of ATG in a renal transplant recipient and the subsequent treatments administered. Although the patient suffered from ARDS and delayed graft function, he was successfully treated. We emphasize that the presence of such complications should be considered when unexplained respiratory distress occurs. Early use of corticosteroids, adjustment of immunosuppressive regimens, and conservative fluid management, as well as empiric antimicrobial therapies, may be effective strategies for the treatment of ARDS caused by ATG.
Adrenal Cortex Hormones ; therapeutic use ; Adult ; Antilymphocyte Serum ; adverse effects ; Humans ; Kidney Transplantation ; Male ; Respiratory Distress Syndrome, Adult ; chemically induced ; drug therapy

OBJECTIVETo investigate the effect of dexamethasone (Dx) combined with modified Dachengqi Decoction (DCQD), a Chinese herbal decoction for purgation, on patients with severe acute on patients with severe acute, a Chinese herbal decoction for purgation, on patients with severe acute pancreatitis (SAP) accompanied with systematic inflammatory response syndrome (SIRS).

METHODSA total of 81 patients diagnosed as SAP were randomly assigned to a control group or treatment group according to a random number table generated from an SPSS software. The patients in the control group (38 cases) received standard treatment and Chinese herbal decoction for purgation; those in the treatment group (43 cases) received additional 1 mg/(kg·d) dexamethasone (Dx) treatment for three days based on the above treatment. The mortality rate, acute respiratory distress syndrome (ARDS), renal failure, hemorrhage, sepsis, pancreatic pseudocyst, pancreatic abscess, operability, and days of hospitalization were compared between the two groups.

RESULTSThree patients in the control group and eight patients in the treatment group dropped out from the study with a drop-out rate of 7.8% and 18.6%, respectively, and no statistics difference was shown between the two groups (P>0.05). Dx treatment significantly reduced ARDS rate and shortened the length of hospitalization compared to those in the control group (7/35, 20.0% versus 15/35, 42.9%, P=0.0394; 32.5±13.2 days versus 40.2±17.5 days, P=0.0344). Other parameters including the mortality rate were not significant different between the two groups.

CONCLUSIONDx combined with DCQD could decrease the risk of developing ARDS in SAP patients with SIRS and shorten their length of hospitalization.

Acute Disease ; Adult ; Aged ; Anti-Inflammatory Agents ; administration & dosage ; adverse effects ; Cathartics ; administration & dosage ; adverse effects ; Dexamethasone ; administration & dosage ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Humans ; Length of Stay ; statistics & numerical data ; Male ; Middle Aged ; Observation ; Pancreatitis ; complications ; drug therapy ; mortality ; Plant Extracts ; administration & dosage ; adverse effects ; Respiratory Distress Syndrome, Adult ; chemically induced ; epidemiology ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo analysis clinical characteristics of the multiple organ dysfunction syndrome (MODS) caused by acute paraquat poisoning (APP).

METHODClinical data of 68 APP cases from Jan 2006 to Jun 2009, including age, gender, poisoning time and dosage, and MODS time, were compared in two groups, i.e. the death (37 cases) and survived (31cases) groups. It was less than 24 hours from poisoning to rescue in all cases.

RESULTSAmong the 68 cases, the incident rate of ARDS was 51.47% (35 cases). The rate of acute lung injure was 97.1% (66 cases). The mortality was 54.4% (37 cases). There was no significant difference in age and gender between both groups (P > 0.05). The dosages and times from poisoning to rescue were significant different between two groups (P < 0.05, P < 0.01). In the death group, proportion of amounts (> 3) of organs related with MODS was 70.29%, which was significantly higher than that (38.71%) in survived group (P < 0.01). MODS and ALI/ARDS occurred in death group earlier than those in survival group (P < 0.05). On the other hand, cardiac, hepatic and renal damage occurred earlier than the lung injure.

CONCLUSIONMODS in APP patients occurred earlier, were more sever, and caused higher mortality. The poisoning dosage and time were important prognostic factors.

Adult ; Female ; Humans ; Male ; Middle Aged ; Multiple Organ Failure ; chemically induced ; diagnosis ; Paraquat ; poisoning ; Prognosis ; Respiratory Distress Syndrome, Adult ; chemically induced ; diagnosis ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the relationship between aquaporin 4 (AQP4) in alveolar type II (AT-II) cells and MAPK signaling pathway in rats with early-stage oleic acid-induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

METHODSThree groups of rats, namely the normal control, ALI and U0126 treatment group were used in this study. After oleic acid-induced ALI in the latter two groups, the rats in the treatment group received 100 micromol/L U0126 treatment at the dose of 10 micro, and dimethyl sulfoxide (DMSO) were given in the normal control and ALI groups. Arterial blood gas and the extravascular lung water (EVLW) content were measured after the treatments, and pathological changes in the lung tissues were observed microscopically. ATII cells were isolated from the lung tissues and identified using tannic acid staining and alkaline phosphatase (APK) staining. The expression of AQP-4 mRNA in the cells was detected with RT-PCR.

RESULTSBlood gas analysis, HE staining and EVLW content measurement revealed severer injury of the lung tissues in ALI group than in the normal control group, but the severity was comparable between the treatment and ALI groups. RT-PCR demonstrated significantly increased AQP-4 mRNA expression in ALI group as compared with that in the normal control group, and U0126 treatment resulted in obvious reduction in AQP-4 mRNA expression in the U0126 treatment group.

CONCLUSIONOleic acid-induced ALI results in the activation of MAPK signaling pathway and up-regulation of AQP-4 mRNA expression in the ATII cells of rats.

Acute Lung Injury ; chemically induced ; metabolism ; pathology ; Animals ; Aquaporin 4 ; genetics ; Butadienes ; pharmacology ; Extravascular Lung Water ; metabolism ; Gene Expression Regulation ; drug effects ; MAP Kinase Signaling System ; drug effects ; Male ; Nitriles ; pharmacology ; Oleic Acid ; pharmacology ; Pulmonary Alveoli ; enzymology ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; chemically induced ; metabolism ; pathology

AIMTo study preventive and therapeutic effect of anisodamine on acute respiratory distress syndrome(ARDS) induced by oleic acid and their mechanism of action.

METHODSModel of ARDS was made in rabbits by oleic acid (OA). The effect of anisodamine on the malondialdehyde (MDA), fibronectin (FN), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in plasma, and superoxide dismutase (SOD) in erythrocyte and MDA, SOD and pulmonary surfactant (PS) in lung tissues homogenate and pathological examination of lung were observed.

RESULTSThe administration of anisodamine before and after 30 minutes of injection OA decreased MDA, LDH and ACP, prevented the reduction of SOD, FN and PS. Compared with ARDS group, there was marked difference between the two, and alleviated lung injury.

CONCLUSIONAnisodamine possesses preventive and therapeutic effects on ARDS by inhibiting lipid peroxidation and stabilizing membranes.

Animals ; Disease Models, Animal ; Female ; Free Radical Scavengers ; therapeutic use ; Lipid Peroxidation ; drug effects ; Male ; Oleic Acid ; Rabbits ; Random Allocation ; Respiratory Distress Syndrome, Adult ; chemically induced ; drug therapy ; prevention & control ; Solanaceous Alkaloids ; therapeutic use

OBJECTIVEAlveolar type II (AT II) cells play a crucial role in the maintenance of pulmonary surfactant homeostasis and pulmonary immunity. The effects of dexamethasone (Dex) on the ultrastructure of AT II cells after acute lung injury remain unknown. This study focused on the ultrastructural changes caused by acute lung injury and on the effects of Dex administration on these ultrastructural changes in young rats.

METHODSSeventy-two 21-day-old Sprague-Dawley rats were randomly divided into control, acute lung injury and Dex-treated groups. Rats in the lung injury group were intraperitoneally injected with 4 mg/kg lipopolysaccharide (LPS) in order to induce acute lung injury, while the control rats were injected with the same amount of normal saline (NS). The Dex-treated group was injected first with LPS followed 1 hr later by Dex (5 mg/kg) injection. Eight rats in each group were sacrificed 24, 48 and 72 hrs after LPS or NS injection. Lung samples were obtained from the lower parts of left lungs and fixed with 2.5% glutaraldehyde for transmission electron microscope examination.

RESULTSMicrovilli of AT II cells disappeared and the number of lamellar bodies (LBs) increased in the lung injury group 24 hrs after LPS injection. The ring-like arrangement of LBs around nuclei was present until 48 hrs after LPS injection. By 48 hrs after LPS injection, giant LBs with vacuole-like abnormalities appeared. The shape of nuclei became irregular and the border of the nuclei became blurred. By 72 hrs after LPS injection, the number of LBs was obviously reduced; nucleoli disappeared; and karyolysis occurred in some of the nuclei. In contrast, in the Dex-treated group, LBs crowded on one side of AT II cells and exocytosis appeared on the same side by 24 hrs after LPS injection. By 48 hrs, the number of LBs was reduced. The number of mitochondria increased, and some of them became swollen and enlarged. However, by 72 hrs, the number of LBs increased and the ring-like arrangement of LBs around the nucleus again appeared.

CONCLUSIONSUltrastructural changes of AT II cells following lung injury induced by LPS were time-dependent in young rats. Dex may ameliorate AT II cell injury and promote functional restoration of AT II cells in LPS-induced acute lung injury.

Animals ; Dexamethasone ; pharmacology ; therapeutic use ; Lipopolysaccharides ; toxicity ; Pulmonary Alveoli ; drug effects ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; chemically induced ; drug therapy ; pathology