ObjectiveTo discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with severe pneumonia.MethodsData of 80 patients with severe pneumonia admitted in our ICU were analyzed retrospectively, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, weight, Acute Physiology and Chronic Health EvaluationⅡscore, lactate, PSI score and LIPS score, etc. were collected. Statistical significance results were evaluated by multivariate logistic regression analysis after univariate analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS after severe pneumonia.ResultsForty patients with severe pneumonia progressed to ARDS, there were 4 moderate cases and 36 severe cases according to diagnostic criteria. Univariate analysis showed that procalcitonin (t=4.08, P<0.001), PSI score (t=10.67, P<0.001), LIPS score (t=5.14, P<0.001), shock (χ2=11.11, P<0.001), albumin level (t=3.34, P=0.001) were related to ARDS. Multivariate logistic regression analysis showed that LIPS ［odds ratio (OR) 0.226, 95%CI=4.62-5.53, P=0.013］ and PSI (OR=0.854, 95%CI=132.2-145.5, P=0.014) were independent risk factors for ARDS. The predictive value of LIPS and PSI in ARDS occurrence was significant. The area under ROC curve (AUC) of LIPS was 0.901, the cut-off value was 7.2, when LIPS ≥7.2, the sensitivity and specificity were both 85.0%. AUC of PSI was 0.947, the cut-off value was 150.5, when PSI score ≥150.5, the sensitivity and specificity were 87.5% and 90.0% respectively.ConclusionsPSI and LIPS are independent risk factors of ARDS in patients with severe pneumonia, which may be references for guiding clinicians to make an early diagnosis and treatment plan.
ObjectiveTo investigate the effects of esophageal cooling (EC) on lung injury and systemic inflammatory response after cardiopulmonary resuscitation in swine.MethodsThirty-two domestic male white pigs were randomly divided into sham group (S group, n=5), normothermia group (NT group, n=9), surface cooling group (SC group, n=9), and EC group (n=9). The animals in the S group only experienced the animal preparation. The animal model was established by 8 min of ventricular fibrillation and then 5 min of cardiopulmonary resuscitation in the other three groups. A normal temperature of (38.0±0.5)℃ was maintained by surface blanket throughout the experiment in the S and NT groups. At 5 min after resuscitation, therapeutic hypothermia was implemented via surface blanket or EC catheter to reach a target temperature of 33℃, and then maintained until 24 h post resuscitation, and followed by a rewarming rate of 1℃/h for 5 h in the SC and EC groups. At 1, 6, 12, 24 and 30 h after resuscitation, the values of extra-vascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were measured, and meanwhile arterial blood samples were collected to measure the values of oxygenation index (OI) and venous blood samples were collected to measure the serum levels of tumor necrosis factor-α (TNF-α) and inerleukin-6 (IL-6). At 30 h after resuscitation, the animals were euthanized, and then the lung tissue contents of TNF-α, IL-6 and malondialdehyde, and the activities of superoxide dismutase (SOD) were detected.ResultsAfter resuscitation, the induction of hypothermia was significantly faster in the EC group than that in the SC group (2.8 vs. 1.5℃/h, P<0.05), and then its maintenance and rewarming were equally achieved in the two groups. The values of ELWI and PVPI significantly decreased and the values of OI significantly increased from 6 h after resuscitation in the EC group and from 12 h after resuscitation in the SC group compared with the NT group (all P<0.05). Additionally, the values of ELWI and PVPI were significantly lower and the values of OI were significantly higher from 12 h after resuscitation in the EC group than those in the SC group [ELWI: (13.4±3.1) vs. (16.8±2.7) mL/kg at 12 h, (12.4±3.0) vs. (16.0±3.6) mL/kg at 24 h, (11.1±2.4) vs. (13.9±1.9) mL/kg at 30 h; PVPI: 3.7±0.9 vs. 5.0±1.1 at 12 h, 3.4±0.8 vs. 4.6±1.0 at 24 h, 3.1±0.7 vs. 4.2±0.7 at 30 h; OI: (470±41) vs. (417±42) mm Hg (1 mm Hg=0.133 kPa) at 12 h, (462±39) vs. (407±36) mm Hg at 24 h, (438±60) vs. (380±33) mm Hg at 30 h; all P<0.05]. The serum levels of TNF-α and IL-6 significantly decreased from 6 h after resuscitation in the SC and EC groups compared with the NT group (all P<0.05). Additionally, the serum levels of IL-6 from 6 h after resuscitation and the serum levels of TNF-α from 12 h after resuscitation were significantly lower in the EC group than those in the SC group [IL-6: (299±23) vs. (329±30) pg/mL at 6 h, (336±35) vs. (375±30) pg/mL at 12 h, (297±29) vs. (339±36) pg/mL at 24 h, (255±20) vs. (297±33) pg/mL at 30 h; TNF-α: (519±46) vs. (572±49) pg/mL at 12 h, (477±77) vs. (570±64) pg/mL at 24 h, (436±49) vs. (509±51) pg/mL at 30 h; all P<0.05]. The contents of TNF-α, IL-6, and malondialdehyde significantly decreased and the activities of SOD significantly increased in the SC and EC groups compared with the NT group (all P<0.05). Additionally, lung inflammation and oxidative stress were further significantly alleviated in the EC group compared with the SC group [TNF-α: (557±155) vs. (782±154) pg/mg prot; IL-6: (616±134) vs. (868±143) pg/mg prot; malondialdehyde: (4.95±1.53) vs. (7.53±1.77) nmol/mg prot; SOD: (3.18±0.74) vs. (2.14±1.00) U/mg prot; all P<0.05].ConclusionTherapeutic hypothermia could be rapidly induced by EC after resuscitation, and further significantly alleviated post-resuscitation lung injury and systemic inflammatory response compared with conventional surface cooling.
Objective To explore the migration and differentiation of bone marrow mesenchymal stem cells（MSCs） in lung . Methods MSCs were harvested from a male Wister rat. Sixty female Wister rats were randomly divided into four groups. The pulmonary fibrosis model was established by intratracheal instillation of bleomycin in group A-D. Immediately and 7 days after bleomycin administration respectively，the rats in group B and C received infusion with 5-bromodeoxynridine （BrdU） labeled MSCs via tail vein. And the rats in group D were infused MSCs without BrdU labeling serving as a negative control. The sry gene of Y chromosome was detected by polymerase chain reaction （PCR）. Double immunofluorescence staining was used to detected BrdU and surfactant associated protein-C （SP-C） expression in lung tissue，fresh bone marrow，and the 5th generation MSCs. Reverse transcriptipon-PCR was used to detect the expressions of SP-C mRNA and AQP-5 mRNA. Results The sry gene was detected in bleomycin induced lung injury tissues of the rats after MSCs infusion immediately and on the 7th day The MSCs in lung tissue could transformed into cells with ACEⅡ morphological features and molecular phenotype. The transformation rate was higher in the rats received MSCs infusion immediately than the rats received on 7th day. The 5th generation MSCs and fresh bone marrow expressed SP-C mRNA，without AQP-5 mRNA and SP-C expression. Conclusions Exogenous MSCs can be transplanted into injured lung tissues and transform into AECⅡ，especially in early stage of lung injury. The differentiation potential of MSCs can be activated in injury micro-environment.
【Abstract】Objective To investigate the role of interleukin-10（IL-10） and interleukin-18 （IL-18） in the pathogenesis of acute lung injury in experimental severe acute pancreatitis.Methods Forty-eight SD rats were divided into control group and SAP group by the random data table. The model of experimental severe acute pancreatitis was established by injection of 3.5% sodium taurocholate into the bili-pancreatic duct. Lung wet weight index, ascities and level of serum amylase, IL-10 and IL-18 were quantitatively measured in different time. Intrapulmonary expressions of IL-10 mRNA and IL-18 mRNA were detected by semiquantitative RTPCR. The histopathology of pancreas and lung were observed under the light microscope.Results Lung wet weight index, ascities, level of serum amylase, IL-10 and IL-18, intrapulmonary expressions of IL-10 mRNA and IL-18 mRNA were significantly increased in SAP group (P＜0.01). The level of serum IL-18 and intrapulmonary expression of IL-18mRNA are positively correlated with lung wet weight index （r=0.68,P＜0.01; r=0.72,P＜0.01） and lung injury score （r=0.74,P＜0.01; r=0.79,P＜0.01) respectively, whereas the level of serum IL-10 and intrapulmonary expression of IL-10 mRNA are negatively correlated with lung wet weight index（r=-0.62,P＜0.01; r=-0.69,P＜0.01） and lung injury score（r=-0.66,P＜0.01; r=-0.60,P＜0.01）. Conclusion IL-18 may play a key role in the pathogenesis of acute lung injury in experimental severe acute pancreatitis, and IL-10 exerts the protection role in this process.
Objective To improve the knowledge of lung injury induced by rituximab. Methods Clinical data of 5 lymphoma patients with lung injury caused by rituximab chemotherapy were analyzed. Results Five patients received chemotherapy including rituximab, and had fever, cough and dyspnea after 3 to 5 chemotherapy cycles. Chest CT showed bilateral diffuse interstitial infiltrates. All 5 cases experienced hypoxemia or respiratory failure. Clinical symptoms were improved 3 to 5 days after the treatment of glucocorticoids, and pulmonary lesions were significantly alleviated 1 to 2 weeks after the treatment. According to the literature, the incidence rate of lung injury caused by rituximab was 0. 03% to 4. 9%, which has increased recently. Conclusions With the comprehensive application of rituximab, lung injury caused by this drug is not rare. The good prognosis depends on early diagnosis and treatment by further recognition of the side effect of rituximab.
Objective To establish a stable and reliable lung injury model caused by severe acute pancreatitis（SAP）in rats， which is helpful to study the acute lung injury （ALI）and acute respiratory distress syndrome （ARDS） induced by SAP.Methods Sixty Sprague-Dawley rats were randomized into ligature group （n=20）， traditional group （n=20），and sham operation group （n=20）. SAP model was established through retrograde injection of 5% taurocholic acid. After injection， the pancreatic duct of rats was ligated in ligature group， but not in traditional group. The lung damage and edema at 24 h after operaton and natural course of rats were observed.Results The ALI model of rats induced by SAP was established successfully in ligature group. The rats died of acute respiratory failure within 48 h in ligature group， the mortality was significantly higher than that in traditional group （100% vs.20%），P＜0.05. Pleural effusion occurred in four rats in ligature group， while no pleural effusion was found in rats in other two groups. The volume of ascites of rats in ligature group was （21.15±5.33） ml， which was more than that in traditional group 〔（7.75±2.66） ml〕，P＜0.05， while no ascites was found in rats in sham operation group. The level of serum amylase of rats in ligature group was （2 470.70±399.73） U/L，which was significantly higher than that in traditional group 〔（1 528.40±289.54） U/L〕 and sham operation group 〔（831.10±93.26） U/L〕，P＜0.001. The level of serum albumin of rats in ligature group was （6.90±1.66）g/L， which was significantly lower than that in traditional group 〔（13.10±0.99） g/L〕 and sham operation group 〔（16.20±0.92） g/L〕，P＜0.001.The lung wet-to-dry weight ratio （W/D） of rats in ligature group was 6.50±0.23， which was greater than that in traditional group （4.92±0.18） and sham operation group （4.61±0.16）， P＜0.001. The score of lung histopathologic of rats in ligature group was 29.25±1.07， which was significantly higher than that in traditional group （12.65±1.98） and sham operation group （0），P＜0.001. The score of pancreas histopathologic of rats in ligature group was 15.95±0.15，which was significantly higher than that in traditional group （13.75±0.66） and sham operation group （0.13±0.29），P＜0.001. Under transmission electron microscope， basement membrane of pulmonary capillary of rats in ligation group was destructive， the nuclei was dissolved， endothelial pinocytotic vesicles was functional active， and tight junctions between capillary endothelial cells were blurred and even ruptured. Moreover， tight junctions between alveolar epithelial cells were destructive. Pathological changes of lung ultrastructure of rats in ligation group were more severe than that in traditional group， while no pathological change of lung ultrastructure was observed in rats in sham operation group. Conclusions Injury process and pathogenesis of ALI or ARDS clinically caused by acute gallstone pancreatitis can be reproduced in this animal model， which is suitable to explore the related mechanisms of ALI caused by SAP and provides good animal model for the study of ALI caused by SAP.
ObjectiveTo explore the effects of inhibition of paxillin phosphorylation on ventilation associated lung injury. MethodsSixty healthy male SD rats were randomly divided into four groups, namely a control group, a protective ventilation group, a high tidal volume ventilation group, and an inhibitor group. The rats in the control group received only tracheotomy and breathe naturally. The rats in the protective ventilation group received protective ventilation for 2 hours. The rats in the high tidal volume ventilation group and the inhibitor group received high tidal volume ventilation for 2 hours. The rats in the inhibitor group additionally received intraperitoneal injection of tyrosine protein kinase inhibitor PP2 before ventilation. All rats were sacrificed and the specimens of lung tissue were collected. The pathological changes of lungs were observed under light microscope and estimated by the diffuse alveolar damage (DAD) score system. The activity of myeloperoxidase (MPO) and the lungs wet/dry (W/D) weight ratio were measured. The expression of tumor necrosis factor-α(TNF-α) in BALF was detected by ELISA. Evans blue (EB) method was used to detect the pulmonary vascular permeability. The expression levels of phosphorylated paxillin (p-paxillin) and paxillin in lung tissue were measured by Western blot. Apoptosis in situ was detected by TUNEL. ResultsThere were significant differences in the W/D ratio, the EB extravasation, DAD score, the MPO activity and the TNF-αexpression in BALF between the high tidal volume ventilation group and the inhibitor group (P < 0.05). The apoptosis rate of each group was sorted from high to low as the high tidal volume ventilation group, the inhibitor group, the protective ventilation group, and the control group. The expression level of p-paxillin was the highest in the high tidal volume ventilation group which was significantly different from other groups (all P < 0.05). There was no significant difference in the expression of paxillin in the protective ventilation group, the high tidal volume ventilation group and the inhibitor group (P > 0.05). ConclusionInhibition of paxillin phosphorylation can significantly alleviate mechanical ventilation associated lung injury.
Objective To explore the role of chronic ethanol ingestion in pulmonary fibrosis. Methods Twenty SD rats were randomly divided into a control group (n=10) and an ethanol group ( n=10) , and fed with quantitative non-ethanol and ethanol Lieber-DeCarli liquid diet every day respectively. All rats were sacrificed after 8 weeks. The morphological changes and collagen deposition of lung tissue were observed under light microscope by HE and Masson staining. Levels of glutathione (GSH) and hydroxyproline (HYP) in lung tissues were measured by colorimetric method. The content of connective tissue growth factor (CTGF) in lung tissue was detected by ELISA. Results Compared with the control group, varied degrees of alveolar and alveolar septal infiltration of inflammatory cells can be shown in the ethanol group, and also some alveolar wall damage or collapse.Masson staining showed that the ethanol group has more significant deposition of collagen fibers in alveolar interstitumthan the control group. The content of GSH in rat lung tissue reduced, but the contents of HYP and CTGF increased in the ethanol group compared with the control group [ GSH( mg/g) :0.08±0.04 vs. 0.22±0.14, HYP(mg/g) : 0.57±0.15 vs. 0.40 ± 0.09, CTGF(ng/mL) :306.57±46.86 vs. 134.02±79.82, Plt;0.05] . Conclusions Lieber-DeCarli ethanol liquid diet can establish a rat model of chronic ethanol ingestion. Lung injury and pulmonary fibrosis in rats can be induced by chronic ethanol ingestion. Ethanol may be one of the causes of the pulmonary fibrosis.
Objective To study the effects of hyperoxia on ventilator-induced lung injury（VILI） in rats.Methods 48 healthy male SD rats were randomly divided into four groups：Group A received conventional mechanical ventilation（VT=8 mL/kg） with room air，Group B received the same tidal volume as group A with 100% O2，Group C received large tidal volume（VT=40 mL/kg） with room air，group D received the same tidal volume as group C with 100% O2.Arterial blood gases were measured every one hour and oxygenation index（PaO2/FiO2） was calculated.The changes of lung histopathology were assessed by HE staining and observed under light microscope.Wet-to-dry weight ratio（W/D） of left lung，neutrophils and white blood cell（WBC） counts in BALF were measured.TNF-α，IL-1β，and MIP-2 levels in BALF，malondialdehyde（MDA），myeloperoxidase（MPO），and superoxide dismutase（SOD） levels in the lung were assayed，respectively.Results Compared with the Group C，the Group D demonstrated more infiltrating neutrophils in the lung and more destructive changes in the alveolar wall.Meanwhile，the oxygenation index decreased，the WBC and neutrophils counts in BALF increased，and the W/D of left lung was higher in the Group D with significant differences compared with the Group C.Moreover，the BALF levels of TNF-α，IL-1β and MIP-2，the lung levels of MDA increased，and the lung levels of SOD decreased significantly in the Group D compared with those in the Group C.There were no statistical significant differences between the Group B and Group A in all parameters except that MDA levels increased and SOD levels decreased significantly in the Group B.Conclusion Hyperoxia can increase lung injury induced in large tidal volume ventilation in rats，but has mininmal effects in conventional mechanical ventilation.