Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome

ObjectiveIt has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.MethodsEighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP_SB) and abdominal muscle paralysis group (BIPAP_AP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH₂O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO₂ of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.ResultsFor the comparable ventilator setting, as compared with BIPAP_SB group, the BIPAP_AP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP_AP group (22.5±2.0 vs. 25.2±2.1).ConclusionAbdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.     

机械通气与乌司他丁治疗急性呼吸窘迫综合症的疗效观察

目的:观察机械通气与乌司他丁治疗急性呼吸窘迫综合症的临床疗效。方法:回顾性分析60例急性呼吸窘迫综合症患者的资料,治疗组(30例)采取机械通气与乌司他丁治疗,对照组(30例)采取机械通气治疗,观察两组的的呼吸频率、PaO2、PaO2/FiO2、PCO2、APACHEII评分、胸片变化、VAP发生率及病死率。结果:治疗组的呼吸频率、PaO2、PaO2/FiO2、PCO2指标均优于对照组(t=6.39,6.27,24.07,9.82,P0.05);治疗组的VAP发生率20.0%明显小于对照组的36.7%(X2=5.84,P=0.0160.05);治疗组的病死率3.3%明显小于对照组的16.7%(X2=5.71,P=0.0170.05)。两组之间的APACHEII评分及胸片变化均有明显差异(t=7.14,6.33,P0.05)。结论:机械通气与乌司他丁治疗急性呼吸窘迫综合症的临床疗效较好,能够较好地改善肺功能,缓解ARDS患者症状,提高安全可靠性,控制死亡率。     

机械通气与乌司他丁治疗急性呼吸窘迫综合症的疗效观察

目的：观察机械通气与乌司他丁治疗急性呼吸窘迫综合症的临床疗效。方法：回顾性分析60例急性呼吸窘迫综合症患者的资料,治疗组（30例）采取机械通气与乌司他丁治疗,对照组（30例）采取机械通气治疗,观察两组的的呼吸频率、PaO2、PaO2／FiO2、PCO2、APACHEII评分、胸片变化、VAP发生率及病死率。结果：治疗组的呼吸频率、Pa02、PaO2/FiO2、PCO2指标均优于对照组（t=-6．39,6．27,24．07,9．82,P〈0．05）;治疗组的VAP发生率20．0％明显小于对照组的36．7％（x^2=5．84,P=0．016〈0．05）;治疗组的病死率3.3％明显小于对照组的16．7％（x^2=5．71,P=0．017〈0．05）。两组之间的APACHEII评分及胸片变化均有明显差异（t=7．14,6．33,P〈0．05）。结论：机械通气与乌司他丁治疗急性呼吸窘迫综合症的临床疗效较好,能够较好地改善肺功能,缓解ARDS患者症状,提高安全可靠性,控制死亡率。     

高频振荡呼吸机治疗呼吸窘迫综合征致呼吸机相关性肺损伤的疗效观察

目的:观察高频振荡呼吸机在治疗呼吸窘迫综合征(NRDS)致呼吸机相关性肺损伤(VALI)患儿的临床疗效。方法:选择我院2012年6月~2014年10月收治的NRDS致VALI患儿83例为研究对象,采用随机数字表法将患者随机分为研究组(45例)和对照组(38例)。两组均进行一般治疗,在此基础上对照组采用常规机械通气,研究组采用高频振荡呼吸机行高频通气。观察两组患者治疗24 h后p H值、二氧化碳分压(Pa CO2)、氧分压(Pa O2)、血压(BP)、心率(HR)及并发症情况。结果:两组患者治疗24 h后p H值、Pa CO2、Pa O2及BP比较,差异均无统计学意义(P0.05),研究组HR心率低于对照组,差异存在统计学意义(P0.05);研究组纵膈气肿、肺损伤、间质气肿及气胸的发生率均低于对照组,差异有统计学意义(P0.05)。结论:高频振荡呼吸机治疗NRDS致VALI患儿能够明显改善其症状及减少并发症的发生率,是治疗NRDS致VALI的有效的方式。     

低容量负荷对创伤后ARDS肺功能的保护作用研究

目的：观察低容量负荷对创伤后急性呼吸窘迫综合征(ARDS)肺功能的保护作用。方法：165 例创伤后ARDS患者随机分为 液体控制组和对照组,用脉搏指示连续心输出量监测(PiCCO)指导液体控制,观察中心静脉压(CVP)、肺动脉楔压(PAWP)、氧合指 数(PaO2/FiO2)、肺泡- 肺动脉氧分压差,测定肺泡灌洗液中白细胞介素6(IL-6)水平、血清的肺泡表面活性蛋白D(SP-D)水平的变 化,检测呼吸机脱机时间,评估两组患者肺功能的恢复情况。结果：液体控制组血管外肺水肿指数(EVLWI)、CVP、PWAP、IL-6、 SP-D 以及肺泡-动脉氧分压差均较对照组明显下降(P<0.05),动脉血气氧分压、氧合指数较均对照组明显升高(P<0.05),机械通气 支持时间较对照组明显缩短(P<0.05)。结论：严格的液体控制可有效降低人体的容量负荷,有效促进创伤后ARDS 肺损伤和肺功 能的恢复,这可能与低容量负荷能够降低炎症反应、促进肺泡复张和改善氧合效率有关。     

Aspiration-Related Acute Respiratory Distress Syndrome in Acute Stroke Patient

Background

Aspiration of oral or gastric contents into the larynx and lower respiratory tract is a common problem in acute stroke patients, which significantly increases the incidence of acute respiratory distress syndrome (ARDS). However, little is known about the clinical characteristics of aspiration-related ARDS in acute stroke patients.

Methods

Over 17-month period a retrospective cohort study was done on 1495 consecutive patients with acute stroke. The data including demographic characteristics, clinical manifestations, laboratory examinations, chest imaging, and hospital discharge status were collected to analysis.

Results

Aspiration-related ARDS was diagnosed in 54 patients (3.6%). The most common presenting symptom was tachypnea (respiratory rate ≥25 breaths/min) in 50 cases. Computed tomography (CT) images usually demonstrated diffuse ground-glass opacities (GGOs) and inhomogeneous patchy consolidations involving the low lobes. Age, NIHSS score, GCS score, dysphagia, dysarthria, hemoglobin concentration, serum aspertate aminotransferase (AST), serum albumin, serum sodium, and admission glucose level were independently associated with aspiration-related ARDS (odds ratio (OR) 1.05, 95% confidence interval (CI) (1.04–1.07); OR 2.87, (2.68–3.63); OR 4.21, (3.57–5.09); OR 2.18, (1.23–3.86); OR 1.67, (1.31–2.14); OR 2.31, (1.11–4.84); OR 1.68, (1.01–2.80); OR 2.15, (1.19–3.90); OR 1.92, (1.10–3.36) and OR 1.14, (1.06–1.21) respectively).

Conclusions

Aspiration-related ARDS frequently occurs in acute stroke patient with impairment consciousness. It is advisable that performing chest CT timely may identify disease early and prompt treatment to rescue patients.     

机械通气治疗急性呼吸窘迫综合征的肺复张策略研究

目的:探讨机械通气治疗急性呼吸窘迫综合征(Acute respiratory distress syndrome,ARDS)的肺复张策略的作用。方法:选择2012年1月~2012年12月我院收治的采用机械通气并进行肺复张治疗的ARDS患者94例,根据肺复张方法不同,将所有患者分为对照组和实验组,并比较两组患者的不同时点的氧合指数、肺顺应性及两组出现的并发症。结果:对照组肺复张成功率为72.34%,实验组肺复张成功率为95.75%,X2=38.928,P0.05,两组患者肺复张成功率差异具有统计学意义。两组患者氧合指数、肺顺应性和PaCO2在肺复张实施前比较,差异无统计学意义。肺复张策略实施后24h、48h和72h的氧合指数和PaCO2比较,这三个时点的氧合指数和PaCO2差异具有统计学意义。两组患者肺顺应性在肺复张策略实施后1h、2h和6h比较,t分别=4.939,5.391和5.999,P0.05,此三个时点的肺顺应性差异同样具有统计学意义。对照组气压伤发生率为82.98%,实验组气压伤发生率为59.57%,两组患者气压伤发生率差异具有统计学意义。结论:ARDS的患者在机械通气治疗的过程中上采用肺复张策略,不但可以提高肺复张成功率,改善肺部通气效果,且安全性好,适合临床使用。     

Altered Lipid Composition of Surfactant and Lung Tissue in Murine Experimental Malaria-Associated Acute Respiratory Distress Syndrome

Malaria-associated acute lung injury (MA-ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) are common, often fatal complications of severe malaria infections. However, little is known about their pathogenesis. In this study, biochemical alterations of the lipid composition of the lungs were investigated as possible contributing factors to the severity of murine MA-ALI/ARDS. C57BL/6J mice were infected with Plasmodium berghei NK65 to induce lethal MA-ARDS, or with Plasmodium chabaudi AS, a parasite strain that does not induce lung pathology. The lipid profile of the lung tissue from mice infected with Plasmodium berghei NK65 developing MA-ALI/ARDS, but not that from mice without lung pathology or controls, was characterized by high levels of phospholipids -mainly phosphatidylcholine- and esterified cholesterol. The high levels of polyunsaturated fatty acids and the linoleic/oleic fatty acid ratio of the latter reflect the fatty acid composition of plasma cholesterol esters. In spite of the increased total polyunsaturated fatty acid pool, which augments the relative oxidability of the lung membranes, and the presence of hemozoin, a known pro-oxidant, no excess oxidative stress was detected in the lungs of Plasmodium berghei NK65 infected mice. The bronchoalveolar lavage (BAL) fluid of Plasmodium berghei NK65 infected mice was characterized by high levels of plasma proteins. The phospholipid profile of BAL large and small aggregate fractions was also different from uninfected controls, with a significant increase in the amounts of sphingomyelin and lysophosphatidylcholine and the decrease in phosphatidylglycerol. Both the increase of proteins and lysophosphatidylcholine are known to decrease the intrinsic surface activity of surfactant. Together, these data indicate that an altered lipid composition of lung tissue and BAL fluid, partially ascribed to oedema and lipoprotein infiltration, is a characteristic feature of murine MA-ALI/ARDS and possibly contribute to lung dysfunction.     

细胞因子在ARDS发病机制中的作用

细胞因子是由多种细胞产生的多肽或低分子糖蛋白,在人体内含量极微,在pg水平就发挥作用。作为特异性免疫反应和非特异性免疫反应的蛋白质,细胞因子以自分泌、旁分泌、或内分泌方式产生,与相应的细胞表面受体结合,在局部或全身发挥复杂的生物学效应,它们的代谢异常和疾病的发生、发展有着密切的关系。有些细胞因子已应用于临床的生物学治疗,具有深远的临床应用价值,故对细胞因子的研究将是一个越来越重要的课题。急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)发病机制错综复杂,大量临床和实验室研究证明多种效应细胞释放的炎症介质是造成ARDS的"中心环节",其中TNF-α、IL-1、IL-8、IL-10、CXC趋化因子等细胞因子在ARDS发病中的作用尤为重要。本文就细胞因子在ARDS发病机制中的作用做一综述。     

Serum biomarkers in Acute Respiratory Distress Syndrome an ailing prognosticator

Background

T cells play a dominant role in the pathogenesis of asthma. Costimulation of T cells is necessary to fully activate them. An inducible costimulator (ICOS) of T cells is predominantly expressed on Th2 cells. Therefore, interference of signaling pathways precipitated by ICOS may present new therapeutic options for Th2 dominated diseases such as asthma. However, these signaling pathways are poorly characterized in vitro and in vivo.

Methods

Human primary CD4⁺ T cells from blood were activated by beads with defined combinations of surface receptor stimulating antibodies and costimulatory receptor ligands. Real-time RT-PCR was used for measuring the production of cytokines from activated T cells. Activation of mitogen activated protein kinase (MAPK) signaling pathways leading to cytokine synthesis were investigated by western blot analysis and by specific inhibitors. The effect of inhibitors in vivo was tested in a murine asthma model of late phase eosinophilia. Lung inflammation was assessed by differential cell count of the bronchoalveolar lavage, determination of serum IgE and lung histology.

Results

We showed in vitro that ICOS and CD28 are stimulatory members of an expanding family of co-receptors, whereas PD1 ligands failed to co-stimulate T cells. ICOS and CD28 activated different MAPK signaling cascades necessary for cytokine activation. By means of specific inhibitors we showed that p38 and ERK act downstream of CD28 and that ERK and JNK act downstream of ICOS leading to the induction of various T cell derived cytokines. Using a murine asthma model of late phase eosinophilia, we demonstrated that the ERK inhibitor U0126 and the JNK inhibitor SP600125 inhibited lung inflammation in vivo. This inhibition correlated with the inhibition of Th2 cytokines in the BAL fluid. Despite acting on different signaling cascades, we could not detect synergistic action of any combination of MAPK inhibitors. In contrast, we found that the p38 inhibitor SB203580 antagonizes the action of the ERK inhibitor U0126 in vitro and in vivo.

Conclusion

These results demonstrate that the MAPKs ERK and JNK may be suitable targets for anti-inflammatory therapy of asthma, whereas inhibition of p38 seems to be an unlikely target.     

Proteomic Profiles in Acute Respiratory Distress Syndrome Differentiates Survivors from Non-Survivors

Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS.     

Predictors of Acute Respiratory Distress Syndrome in Patients with Paraquat Intoxication

Introduction

Paraquat poisoning is characterized by acute lung injury, pulmonary fibrosis, respiratory failure, and multi-organ failure, resulting in a high rate of mortality and morbidity. The objectives of this study were to identify predictors of acute respiratory distress syndrome (ARDS) in cases of paraquat poisoning and determine the association between these parameters.

Materials and Methods

In total, 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and Acute Kidney Injury Network (AKIN) scores were collected, and predictors of ARDS were analyzed.

Results

The overall mortality rate for the entire population was 54% (101/187). Furthermore, the mortality rate was higher in the ARDS patients than in the non-ARDS patients (80% vs. 43.80%, P<0.001). Additionally, the ARDS patients not only had higher AKIN_48-h scores (P<0.009), SOFA_48-h scores (P<0.001), and time to ARDS/nadir PaO₂ (P=0.008) but also suffered from lower nadir PaO₂ (P<0.001), nadir AaDO₂ (P<0.001), and nadir eGFR (P=0.001) compared to those in the non-ARDS patients. Moreover, pneumomediastinum episodes were more frequent in the ARDS patients than in the non-ARDS patients (P<0.001). A multivariate Cox regression model revealed that blood paraquat concentrations (P<0.001), SOFA_48-h scores (P=0.001), and steroid and cyclophosphamide pulse therapies (P=0.024) were significant predictors of ARDS. The cumulative survival rates differed significantly (P<0.001) between patients with SOFA_48-h scores <3 and SOFA_48-h scores ≥3, with a sensitivity of 95.8%, specificity of 58.4%, and overall correctness of 67.6%. Finally, the area under the receiver operating characteristic (AUROC) analysis showed that SOFA_48-h scores (P<0.001) had a better discriminatory power than blood paraquat concentrations (P=0.01) for predicting ARDS.

Conclusions

The analytical results indicate that SOFA_48-h scores, blood paraquat concentrations, and steroid and cyclophosphamide pulse therapies are significantly associated with ARDS complications after paraquat intoxication.     

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.     

黄磷及其化合物急性吸入致大鼠急性肺损伤或急性呼吸窘迫综合征模型的制作

目的建立黄磷及其化合物急性吸入致大鼠急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）的模型。方法健康SD大鼠48只随机分为对照组以及实验组（0、4、12、24、48 h时间点处死）。采用自制染毒装置,间歇染毒形成ALI/ARDS模型。观察ALI/ARDS大鼠动脉血气分析以及肺系数和肺组织病理变化。结果肺损伤后大鼠动脉血气分析以及肺组织病理改变明显恶化,肺系数较对照组明显增大。结论成功地建立了黄磷及其化合物急性吸入致大鼠ALI/ARDS的模型,为黄磷及其化合物吸入中毒的防治研究提供良好实验基础,同时也适用于其他气体吸入致ARDS的实验研究。