The role of routine pulmonary imaging before hyperbaric oxygen treatment.

Respiratory injury during or following hyperbaric oxygen treatment (HBOT) is rare, but associated pressure changes can cause iatrogenic pulmonary barotrauma with potentially severe sequelae such as pneumothoraces. Pulmonary blebs, bullae, and other emphysematous airspace abnormalities increase the risk of respiratory complications and are prevalent in otherwise healthy adults. HBOT providers may elect to use chest X-ray routinely as a pre-treatment screening tool to identify these anomalies, particularly if a history of preceding pulmonary disease is identified, but this approach has a low sensitivity and frequently provides false negative results. Computed tomography scans offer greater sensitivity for airspace lesions, but given the high prevalence of incidental and insignificant pulmonary findings among healthy individuals, would lead to a high false positive rate because most lesions are unlikely to pose a hazard during HBOT. Post-mortem and imaging studies of airspace lesion prevalence show that a significant proportion of patients who undergo HBOT likely have pulmonary abnormalities such as blebs and bullae. Nevertheless, pulmonary barotrauma is rare, and occurs mainly in those with known underlying lung pathology. Consequently, routinely using chest X-ray or computed tomography scans as screening tools prior to HBOT for low-risk patients without a pertinent medical history or lack of clinical symptoms of cardiorespiratory disease is of low value. This review outlines published cases of patients experiencing pulmonary barotrauma while undergoing pressurised treatment/testing in a hyperbaric chamber and analyses the relationship between barotrauma and pulmonary findings on imaging prior to or following exposure. A checklist and clinical decision-making tool based on suggested low-risk and high-risk features are offered to guide the use of targeted baseline thoracic imaging prior to HBOT.

Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury and Pulmonary Fibrosis in Mice.

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as indices of lung function and bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for biomarkers of fibrosis. Mice on phytoestrogen-free diet demonstrated increased mortality and stronger signs of chronic lung injury and pulmonary fibrosis, as reflected in the expression of collagen, extracellular matrix deposition, histology, and lung mechanics, compared to mice on regular diet. We conclude that dietary phytoestrogens play an important role in the pathogenesis of pulmonary fibrosis and suggest that phytoestrogens (e.g., genistein) may be useful as part of a therapeutic regimen against hydrochloric acid-induced lung fibrosis and chronic lung dysfunction.

Proteomic analysis of therapeutic effects of Qingyi pellet on rodent severe acute pancreatitis-associated lung injury.

Severe acute pancreatitis (SAP) is a common acute clinical abdomen syndrome which is characterized by pancreatic self-digestion. As one of the major complication of SAP, acute lung injury is the main reason of high mortality. The traditional Chinese medicine Qingyi pellet (QYT) has been widely used for SAP in clinic. In our study, we constructed the severe acute pancreatitis-associated lung injury (SAP-ALI) rat model and treated with QYT, then characterized the protein from the lung tissue by using a mass spectrometry-based proteomic strategy. Our results showed that, in the SAP group, 9 proteins exhibited obvious changes according to the proteomic analysis. Among the 9 proteins, 7 proteins (alpha-2-macroglobulin, Cathepsin S, ras-related protein RAP-1A, integrin beta, protein phosphatase 2A, Intercellular adhesion molecule 1 and p38) were up-regulated, and 2 proteins (adapter molecule Crk and stathmin) were down-regulated. Interestingly, the data of the QYT group showed that adapter molecule Crk and stathmin were up-regulated, but the other 7 proteins were down-regulated. The kyoto encyclopedia of genes shows that the proteins act on PI3K-AKT, chemokine signaling pathways, apoptosis, leukocyte transendothelial migration and focal adhesion. Therefore, the therapeutic effects of QYT on SAP-ALI are potentially through the additive and/or synergistic interactions of numerous components.

Protective effect of hydroxysafflor yellow A on bleomycin- induced pulmonary inflammation and fibrosis in rats.

OBJECTIVE: To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats. METHODS: Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone (DXM) group. Three doses of HSYA (35.6, 53.3, and 80.0 mg•kg-1•day-1) were intraperitoneally (i.p.) injected in rats for 3 weeks after BLM administration and DXM was used as the positive control (n=8 or 12). Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin (α-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. RESULTS: On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure (PaO2) increased (HSYA 80.0 mg•kg-1, P<0.01) and CO2 partial pressure (PaCO2) decreased (HSYA 53.3, 80.0 mg•kg-1, P<0.05). Moreover, the mRNA expression of TNF-α, IL-1ß, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg•kg-1 groups than those in the model group (all P<0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 (HSYA 53.3, 80.0 mg•kg-1, P<0.01), and decreased PaCO2 (53.3 and 80.0 mg•kg-1, P<0.05). Further, the mRNA expression of TGF-ß1, α-SMA, and collagen I as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes (53.3, 80.0 mg•kg-1, P<0.05). Hematoxylin and eosin and Masson's trichrome staining indicated that the fibrosis and collagen deposition were ameliorated in HSYA groups (53.3, 80.0 mg•kg-1, P<0.05). CONCLUSION: HSYA could alleviate acute lung inflflammation and chronic pulmonary fibrosis induced by BLM in rats.

Xuebijing Injection () and Resolvin D1 Synergize Regulate Leukocyte Adhesion and Improve Survival Rate in Mice with Sepsis-Induced Lung Injury.

OBJECTIVE: To investigate the effect of combined application of Xuebijing Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. METHODS: The cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 µL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule 1 (ICAM-1). RESULTS: Compared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01). CONCLUSIONS: XBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.

Radiation mitigating properties of the lignan component in flaxseed.

BACKGROUND: Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. METHODS: We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. RESULTS: FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60-73.3% survival in mice fed 10%-20% FLC initiated 24-72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. CONCLUSIONS: Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy.

Effect of safflor yellow injection on inhibiting lipopolysaccharide-induced pulmonary inflammatory injury in mice.

OBJECTIVE: To observe the effect of Safflor Yellow (SY) Injection on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. METHODS: Seventy-two mice were divided into six groups: control (saline + saline); LPS (LPS + saline); SY Injection [LPS + SY (10, 20 or 40 mg/kg, intravenously)] and anisodamine (AD) (LPS + AD). Thirty minutes after SY or AD administration, 15 mg/kg LPS was given intraperitoneally. All animals were sacrificed 4 h after LPS injection. Arterial blood gas and lung water content index (LWCI) were measured. Lung tissue myeloperoxidase (MPO) activity was assayed. mRNA expression of inflammatory cytokines was assayed by reverse-transcription polymerase chain reaction. Lung morphological and nuclear factor (NF)-κB p65-positive cell changes were observed by HE and immunohistochemical staining. p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed by Western blotting. RESULTS: After LPS administration, all animals displayed increased arterial carbon dioxide partial pressure (PaCO2) and decreased arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SO2), HCO3 (-) concentration and pH, and increased LWCI, MPO activity, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α mRNA expression, NF-κB p65-positive staining and p38 MAPK activation compared with normal controls (all P<0.01). SY Injection significantly mitigated the LPS-induced increase in arterial PaCO and the decreases in arterial PaO2, SO2 and pH, and attenuated increases in LWCI and lung tissue MPO activity (all P<0.01). Moreover, SY Injection inhibited the increases in NF-κB p65 staining and in TNF-α, IL-1ß and IL-6 mRNA expression (all P<0.01), and promoted the expression of the antiinflammatory cytokine IL-10 (P<0.05) following LPS injection. LPS-induced pulmonary p38 MAPK phosphorylation was suppressed by pretreatment with SY Injection (P<0.01). CONCLUSION: SY Injection ameliorates inflammatory ALI induced by LPS in mice.

[Pulmonary resection and ECMO: A salvage therapy for penetrating lung trauma]. / Lobectomie d'hémostase et ECMO : une association salvatrice après plaie pénétrante du thorax.

The majority of chest penetrating trauma patients are successfully managed with tube thoracostomy and general supportive measures. Pulmonary resection for hemorrhagic shock is rarely required after trauma to control bleeding. Both pulmonary injury and massive blood transfusion can lead to acute respiratory distress syndrome (ARDS). The mortality rate in these patients reaches up to 40% despite advanced ventilatory treatment. The use of extracorporeal membrane oxygenation (ECMO) can be started as rescue therapy. We report a case of 24-year-old man with major hemorrhagic shock with cardiac arrest and ARDS after traumatic penetrating lung injury that was successfully treated with pulmonary resection and ECMO.

Death receptors mediate the adverse effects of febrile-range hyperthermia on the outcome of lipopolysaccharide-induced lung injury.

We have shown that febrile-range hyperthermia enhances lung injury and mortality in mice exposed to inhaled LPS and is associated with increased TNF-α receptor activity, suppression of NF-κB activity in vitro, and increased apoptosis of alveolar epithelial cells in vivo. We hypothesized that hyperthermia enhances lung injury and mortality in vivo by a mechanism dependent on TNF receptor signaling. To test this, we exposed mice lacking the TNF-receptor family members TNFR1/R2 or Fas (TNFR1/R2(-/-) and lpr) to inhaled LPS with or without febrile-range hyperthermia. For comparison, we studied mice lacking IL-1 receptor activity (IL-1R(-/-)) to determine the role of inflammation on the effect of hyperthermia in vivo. TNFR1/R2(-/-) and lpr mice were protected from augmented alveolar permeability and mortality associated with hyperthermia, whereas IL-1R(-/-) mice were susceptible to augmented alveolar permeability but protected from mortality associated with hyperthermia. Hyperthermia decreased pulmonary concentrations of TNF-α and keratinocyte-derived chemokine after LPS in C57BL/6 mice and did not affect pulmonary inflammation but enhanced circulating markers of oxidative injury and nitric oxide metabolites. The data suggest that hyperthermia enhances lung injury by a mechanism that requires death receptor activity and is not directly associated with changes in inflammation mediated by hyperthermia. In addition, hyperthermia appears to enhance mortality by generating a systemic inflammatory response and not by a mechanism directly associated with respiratory failure. Finally, we observed that exposure to febrile-range hyperthermia converts a modest, survivable model of lung injury into a fatal syndrome associated with oxidative and nitrosative stress, similar to the systemic inflammatory response syndrome.

Ozone therapy and hyperbaric oxygen treatment in lung injury in septic rats.

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1ß and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1ß, lung GSH-Px and histologic outcome.

Riboflavin supplementation does not attenuate hyperoxic lung injury in transgenic (spc-mt)hGR mice.

The aims of this study were to test the hypothesis that mice expressing mitochondrially targeted human glutathione reductase (GR) driven by a surfactant protein C promoter ((spc-mt)hGR) are functionally riboflavin deficient and that this deficiency exacerbates hyperoxic lung injury. The authors further hypothesized that dietary supplementation with riboflavin (FADH) will improve the bioactivity of GR, thus enhancing resistance to hyperoxic lung injury. Transgenic (mt-spc)hGR mice and their nontransgenic littermates were fed control or riboflavin-supplemented diets upon weaning. At 6 weeks of age the mice were exposed to either room air (RA) or >95% O(2) for up to 84 hours. GR activities (with and without exogenous FADH) and GR protein levels were measured in lung tissue homogenates. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were assayed to identify changes in GR activity in vivo. Lung injury was assessed by right lung to body weight ratios and bronchoalveolar lavage protein concentrations. The data showed that enhanced GR activity in the mitochondria of lung type II cells does not protect adult mice from hyperoxic lung injury. Furthermore, the addition of riboflavin to the diets of (spc-mt)hGR mice neither enhances GR activities nor offers protection from hyperoxic lung injury. The results indicated that modulation of mitochondrial GR activity in lung type II cells is not an effective therapy to minimize hyperoxic lung injury.

Brainstem response amplitudes in neonatal chronic lung disease and differences from perinatal asphyxia.

OBJECTIVE: To examine neuronal function of the auditory brainstem in neonatal chronic lung disease (CLD) and detect any differences from perinatal asphyxia. METHODS: Infants with CLD and infants after perinatal asphyxia were studied at term (37-42 weeks postconceptional age). Wave amplitudes of maximum length sequence brainstem auditory evoked response (MLS BAER) were recorded and compared between CLD and asphyxia. RESULTS: The amplitudes of waves I, III and V, and V/I and V/III amplitude ratios in CLD infants did not differ from those in normal term controls at all click rates 21-910/s. The slopes of amplitude-rate functions were all similar to those in the controls. In infants after asphyxia, however, wave III and V amplitudes were smaller than those in both the controls and CLD infants, particularly at high-rate stimulation. The intercepts of amplitude-rate functions for waves III and V were smaller than in both the controls and CLD infants, although there were no significant differences in the slopes of these functions. CONCLUSIONS: No abnormalities in MLS BAER amplitudes were found in CLD infants but the amplitudes were significantly reduced in asphyxiated infants, resulting in major differences between CLD and perinatal asphyxia. SIGNIFICANCE: There is no major neuronal impairment in the auditory brainstem in CLD but there is in perinatal asphyxia. This difference may be, at least partly, related to the difference in the nature of hypoxia associated with the two problems; the hypoxia is chronic and sublethal in CLD, but is often acute, lethal and associated with ischaemia in perinatal asphyxia.