Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

CRRT at early stageon in patients with severe acute pancreatitis applied to preventing acute lung injury in patients with severe acute pancreatitis / 中国基层医药

Objective To investigate the effects of early continuous renal replacement thempy(CRRT)on acute lung injury and prognosis in severe acute pancreatitis (SAP)patients.Methods 46 SAP patients were divided into the two groups randomly:the control group and CRRT treatment group.The levels of IL-1β,IL-6,TNF-α,the APACHEⅡscore,oxygenation index,the incidence of acute lung injury(ALI)/acute respiratory distress syndrome (ARDS),ICU stay were compared between the two groups.Results The level of interleukin-6(IL-6)in the con-trol group was significantly higher than that in CRRT group in day 1(t=2.265,P0.05).Conclusion Early CRRT therapy can eliminate the IL-1β,IL-6 and TNF-αin SAP patients,which can improve the oxygenation index and reduce the incidences of ALI/ARDS,may provide more clinical benefits in the early phase of SAP.

The impact of relevant factors in mechanical ventilation on intra-abdominal pressure in patients with ALI/ARDS / 中华急诊医学杂志

Objective To investigate the impact of relevant factors in mechanical ventilation on intraabdominal pressure in patients with ALI/ARDS by continuous monitoring of intra-abdominal pressure.Methods A total of 116 ALI/ARDS patients treated with mechanical ventilation in ICU were enrolled in this study.Intra-abdominal pressure (IAP) was recorded continuously.Meanwhile ventilator parameters, arterial blood gas analysis, hemodynamic variables, and as well as the levels of IL-4, IL-8 and TNF-α in blood and bronchial alveolar lavage fluid (BALF) were determined and recorded.The detection of risk factors for intra-abdomen hypertension (IAH) were carried out using multivariate stepwise logistic regression.ROC curve analysis used to estimate the diagnostic performance of these parameters for IAH.Results The oxygenation index (PaO2/FiO2) in patients with IAH after 2 hours' mechanical ventilation was significantly lower than that in patients with normal intra-abdomen pressure (IAP) (P ＜ 0.01);PEEP and RR in mechanical ventilation were higher in IAH group (P ＜ 0.01 or P =0.001);Mean artery pressure (MAP), ejection time percent (ET), stroke volume (SV), cardiac index (CI) were lower in IAH group than those in normal IAP group (P ＜ 0.01);the levels of IL-4, IL-8 and TNF-α in blood and bronchial alveolar lavage fluid were higher in IAH group than those in normal IAP group (P ＜ 0.01);IAH patients have a higher mortality on 28 d (Log rank test, P =0.023).Poor oxygenation index (PaO2/ FiO2) after 2 hours' ventilation, high PEEP setting, low MAP, ET, SV, CI and elevated IL-4 in the BALF were resulted in increasing risk of IAH for ARDS patients under mechanical ventilation support.Conclusions The monitoring of intra-abdominal pressure should be emphasized for ALI/ARDS patients when mechanical ventilation was employed.PaO2/FiO2, SV and IL-4 in BALF might be the independent risk factors of IAH.

The clinical effect of traditional Chinese medicine dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury/acute respiratory distress syndrome undergoing mechanical ventilation / 中国中西医结合急救杂志

Objective To explore the clinical effect of traditional Chinese medicine (TCM) dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury / acute respiratory distress syndrome(ALI/ARDS)undergoing mechanical ventilation. Methods A prospective,randomized controlled trial was conducted. Ninety-six ALI/ARDS patients admitted in intensive care unit(ICU)and treated with mechanical ventilation in Tianjin First Central Hospital were chosen and randomly divided into traditional Chinese medicine(TCM) group and conventional therapy group using a random number table,48 patients in each group. Conventional therapy alone was used in conventional therapy group,and TCM therapy of primarily using Dachengqi decoction combined with conventional therapy was applied in TCM group〔Dachengqi decoction was composed of mongolian milkvetch root 15 g, pilose asiabell toot 15 g,Chinese angelica 10 g,officinal magnolia bark 10 g,tangerine peel 10 g,immature tangerine fruit 10 g,peach seed 10 g,white peony root 12 g,red peony root 12 g,immature bitter orange 6 g,mongolian dandelion herb 30 g,radish seed(stir-fried)30 g,foxtail millet sprout 20 g,barley sprout 20 g,glauber salt 9 g (with water),rhubarb 10 g(added in water at last)〕,one dose orally taken daily for 28 days. The intra-abdominal pressure(IAP),gastrointestinal diseases in TCM symptom score and the incidence of gastrointestinal dysfunction were compared between the two groups before treatment and on the 3rd,6th and 8th day after treatment. Results There were no statistical significant differences in IAP and TCM symptom scores between the two groups before treatment (both P>0.05),but after treatment with the prolongation of therapeutic time the IAP and TCM symptom scores were decreased gradually compared with those before treatment,having reached the valley value on the 18th day and the changes in TCM group were more remarkable〔IAP(mmHg,1 mmHg=0.133 kPa):0.91±0.69 vs. 2.08±0.92, TCM symptom score:48.33±10.41 vs. 88.33±20.21,both P<0.05〕. In the TCM group,the incidences of the untoward symptoms and signs of gastrointestinal dysfunction such as bleeding of stress ulcer,toxic intestinal paralysis, abdominal distension,diarrhea and so on were lower than those in conventional therapy group〔stress ulcer bleeding:16.7%(8/48)vs. 39.6%(19/48),toxic intestinal paralysis:16.7%(8/48)vs. 43.8%(21/48),abdominal distension:10.4%(5/48)vs. 37.5%(18/48),diarrhea:6.3%(3/48)vs. 33.3%(16/48),all P<0.05〕. Conclusion Addition of TCM Dachengqi decoction on conventional treatment can effectively lower the incidence of gastrointestinal dysfunction in treatment of patients with ALI/ARDS undergoing mechanical ventilation.

The clinical significance of nitric oxide and endothelin-1 in exhaled breath condensate and serum of patients with acute lung injury/acute respiratory distress syndrome / 实用医学杂志

Objective To observe the level of the nitric oxide (NO) and endothelin-1 (ET-1) in the exhaled breath condensate(EBC)and serum of the patients with ALI /ARDS, and investigate its clinical significance. Methods The study group included 52 mechanical ventilation patients with ALI/ARDS in ICU , which were divided into the survival and death group, while 30 healthy volunteers were recruited as healthy control. EBC samples of the healthy control and the study group on the 1st day and 5st day were collected by EcoScreen condenser with the synchronous collection of the venous blood. The concentrations of NO and ET-1 in the EBC and serum were measured by EIA. Results The levels of NO and ET-1 in EBC and serum of the patients with ALI /ARDS were all significantly higher than those of the healthy control. After treatment , the levels of NO and ET-1 in EBC and serum of the patients all decreased significantly compared with before treatment. After treatment , The levels of NO in EBC and serum of the survival group were significantly lower than those of the death group. After treatment , the levels of ET-1 in serum of the survival group was significantly lower than that of the death group. Conclusions Detecting the levels of NO and ET-1 in the EBC and serum can reflect oxidative stress , inflammatory reaction and endothelial injury in lung of patients with ALI/ARDS.

Application of nitric oxide in the therapy of respiratory diseases / 中国小儿急救医学

Nitric oxide (NO) played an important role in the pathogenesis of many diseases. It selectively dilates the pulmonary vasculare, combats pulmonary hypertension associated with hypoxemia, improves oxygen. At the same time, it could relaxe bronchial smooth muscle, kill pathogens and have anti-inflammatory effect,etc. Inhaled nitric oxide has important significance in the treatment of respiratory diseases.

The effect of EVLW in fluid managemeent on sepsis ALI/ARDS / 中华急诊医学杂志

Objective The management of fluid infusion is crucial in severe sepsis/septic shock patients.The correlation of extravascular lung water index(EVLWI) versus oxygenation index ( PaO2/FiO2 ) and EVLWI versus intrathoracic blood volume index(ITBVI) were analysed in this present study. Method Totally 24 patients,admitted to the Intensive Care Unit of Second Affiliated Hospital of Zhejiang University, College of Medicine and diagnosed as severe sepsis/septic shock with acute lung injury and/or acute respiratory distress syndrome,were enrolled. ITBVI and EVLWI were detected with PiCCO technique. Correlation of EVLWI and PaO2/FiO2, ITBVI and EVLWI were analysed,respectively. Simple correlation and simple linear regression were used for statistical analysis. Results Significant negative correlation was found of EVLWI and PaO2/FiO2 ( r = - 0. 45, P ＜ 0.01).EVLWT = 14 mL/kg was defined as the cutoff value for the subgroup analysis. No correlation was found between EVLWI and PaO2/FiO2 in the subgroup with EVLWI≤ 14 mL/kg ( r = 0. 12, P = 0.243), but in the subgroup with EVLWI ＞ 14 mL/kg, significant negative correlation was found ( r = - 0. 47, P ＜ 0. 01 ). When EVLWI was higher than 14 mL/kg,EVLW should be decreased to improve oxygenation and other aspects should be taken into account. No significant correlation was found between ITBVI and EVLWI. A ITBVI value 1000 mL/m2 was also defined as the cutoff value for the subgroup analysis. No significant correlation was found in the subgroup with ITBVI≤ 1000 mL/m2( r = 0.13, P = 0.17), while significant positive correlation was found in the subgroup with ITBVI ＞ 1000 mL/m2. This result suggested that in patients of severe sepsis/septic shock with ALI/ARDS, when the blood volume is high, ITBV should be decreased to improve the oxygenation,however,it is not useful in the situation of high pulmonary vascular permeability. Conclusions Extravascular lung water has a important role in the fluid management in patients of severe sepsis/septic shock with ALI/ARDS.

Interleukin-4 decreases expression of epithelial sodium channel ?-subunit in A549 cells / 第三军医大学学报

Objective To observe the effects of IL-4 on the expression of epithelial sodium channel(ENaC) ?-subunit.Methods A549 cells were cultured with IL-4 at the concentration of 0,0.1,1 and 10 ng/ml for 12 h or with 1 ng/ml IL-4 for 3,6,12,24 and 48 h.Then ?-ENaC protein and mRNA expressions were detected by Western blotting and RT-PCR respectively.Results IL-4 decreased the expression of ?-ENaC in A549 cells in a time-and dose-dependent manner,via gene transformation.When A549 cells were cultured with IL-4 at the concentration of 1 ng/ml for 3,6,12,24 and 48 h,the expression of ?-ENaC protein and mRNA were decreased in a time-dependent manner.Statistical analysis showed culture for 6 h had a significant difference compared with other time points(P