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.     

Is Endocan a Novel Diagnostic Marker for the Severity of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants?

IntroductionEndocan levels were found to be associated with severity and mortality of the respiratory system diseases.ObjectiveWe aimed to figure out whether endocan was an important marker for the diagnosis, severity and follow-up of bronchopulmonary dysplasia (BPD).Materials and methodsInfants with moderate/severe BPD, and who required hydrocortisone treatment were included in the study group. Infants without BPD were allocated in the control group. Endocan levels were compared between the control group and the study group, and before and after the treatment in the study group.ResultsA total of 148 infants, 74 infants in the control group and 74 infants in the BPD group, were included. The endocan level was higher in the BPD group than in the control group (P = .001). Endocan levels before treatment in the BPD group was found to be higher than endocan level after treatment (P = .021).ConclusionOur study found that endocan levels increased in moderate/severe BPD. Serum endocan levels may be a safe and novel indicator for the follow-up of response to treatment and the prognosis of the severity of the disease.     

Young convalescent COVID‐19 pneumonia with extensive pneumomediastinum emphysema: Case report

The development of the SARS‐CoV‐2 pandemic caused a common appearance of severe pulmonary complications, rarely seen as a result of the other infections. These are pneumothorax, pneumomediastinum, emphysematous bullae, cavitary lung lesions, or subcutaneous emphysema. Their formation is influenced by both—the natural course of the disease and the treatment strategy adopted.     

N-乙酰半胱氨酸在呼吸系统疾病中的应用

目的:评价N-乙酰半胱氨酸(NAC)在呼吸系统疾病中的应用。方法:通过查阅国外近期相关文献进行综述。结果:(1)NAC能减少COPD患者急性发作的发生率,改善临床症状,可能有助于肺功能的改善;(2)初步临床试验结果表明,长时间大剂量的NAC治疗有助于肺间质纤维化患者肺功能的改善;(3)NAC可以通过抗氧化作用,保护急性肺损伤及ARDS肺组织免受氧化作用损伤,从而减轻临床症状,改善氧合。结论:NAC是一种具有广泛前景的治疗急性和慢性呼吸道疾病的药物。     

肺表面活性物质-呼气末正压治疗血浆诱导的急性呼吸窘迫综合征

目的研究在急性呼吸窘迫综合征(ARDS)时,联合应用肺表面活性物质(PS)和呼气末正压(PEEP)治疗的效果,并探讨两者之间的关系。方法45只健康SD大鼠,体重为200~312g,麻醉后进行机械通气,气管内滴注血浆至PaO2<200mmHg,将实验动物随机分为PEEP4.0(4 cmH2O)和PEEP7.5(7.5 cmH2O)条件下对照组、PS100(100mg/kg)组和PS200(200mg/kg)组共6组,分别在滴注血浆前、急性肺损伤制成后、给药后30、60、90、120、150和180分钟测定大鼠血气分析、静态比胸肺顺应性(Cst)。实验后取左肺用于病理检查和计算肺指数(LI)。结果经过血浆滴注后,各组实验动物PaO2和Cst分别下降到79.8±19.8mmHg和0.42±0.07m l/(cmH2O.kg)。PEEP7.5PS200组和PS100组的PaO2回升至383±57mmHg和398±51mmHg,明显高于其他4组(P<0.01),此两组比较,PaO2无显著差别。PEEP7.5水平下的3个组,PaO2和LI均显著高于PEEP4.0各对应组(P<0.05)。PEEP7.5PS 100组和PS200组大鼠肺透明膜形成显著少于其他四组(P<0.05),PEEP7.5PS100组肺透明膜形成显著少于PEEP4.0PS200组(P<0.05)。结论在滴注血浆诱导的大鼠ARDS时,高剂量PS较低剂量PS能更有效对抗血浆蛋白的抑制作用;使用合适的较高PEEP与低剂量PS联合治疗能有效改善肺氧合功能和胸肺顺应性,并节省PS用量。     

人工肾与呼吸机治疗急性呼吸窘迫综合征临床对比研究

目的探讨人工肾(代替人工肺)治疗急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的临床疗效,并论证在ARDS早期其替代呼吸机的可行性。方法24例ARDS患者,随机分为两组:人工肾(代替人工肺)治疗研究组(n=12)和呼吸机治疗对照组(n=12),两组均持续治疗6h,观察治疗前后临床症状、全胸片、血气分析、血常规、凝血四项、电解质及中心静脉压(CVP)的变化,判断疗效。结果研究组治疗前后动脉血氧分压PaO2和CVP差异有显著性(P<0.01),而对照组治疗前后动脉血氧分压PaO2和CVP差异无显著性(P>0.05),研究组与对照组治疗后动脉血氧分压PaO2、CVP比较差异有显著性(P<0.01)。结论人工肾(代替人工肺)显著纠正了ARDS患者的低氧血症和心功能衰竭,可减轻肺水肿、缓解肺部和全身炎症反应,提高疗效,在早期可完全替代呼吸机。     

Cardiac Beriberi (Shoshin Beriberi) Caused by Excessive Intake of Isotonic Drink

A 21 month old female had voluntarily ingested 0.5–1.51 of isotonic sports drink daily from 10 months of age. She developed hyponatremia and beriberi heart disease, which resulted in metabolic acidosis and cardiogenic shock (shoshin beriberi). Mechanical ventilation was applied for pulmonary edema. Right heart failure was improved after administering vitamin Bi. However, 5 days after the shock, hypoxemia and diffuse radiographic infiltrates progressed, and a diagnosis of adult respiratory distress syndrome (ARDS) was made. After the occurrence of an air leak, the patient died of respiratory failure. The cardiogenic shock and pulmonary edema due to cardiac beriberi may have triggered the ARDS.     

Chronic ethanol ingestion increases expression of the angiotensin II type 2 (AT2) receptor and enhances tumor necrosis factor-alpha- and angiotensin II-induced cytotoxicity via AT2 signaling in rat alveolar epithelial cells

BACKGROUND: Alcohol abuse increases the risk of acute lung injury in critically ill patients. We have shown that alveolar epithelial cell (AEC) apoptosis in response to inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), parallels endotoxin-mediated acute lung injury in ethanol-fed rats. Although angiotensin II mediates TNF-alpha-induced apoptosis of AECs in vitro, its role in ethanol-mediated susceptibility to AEC apoptosis is unknown. METHODS: Adult male rats were fed the Lieber-DeCarli diet for 6 weeks. AECs were isolated, and TNF-alpha- and angiotensin II-induced cytotoxicity (by terminal transferase-mediated dUTP nick end labeling staining) was determined with or without the addition of the angiotensin-converting enzyme inhibitor (lisinopril) or a selective blocker of the angiotensin II type 1 receptor (AT(1)) or type 2 receptor (AT(2)). Finally, the relative expression of the AT(1) and AT(2) receptors in AECs was determined by Western blot analysis. RESULTS: TNF-alpha-induced cytotoxicity, but not angiotensin II-induced cytotoxicity, was prevented by lisinopril, indicating that de novo angiotensin II synthesis is required for TNF-alpha-induced apoptosis in these cells. Both TNF-alpha- and angiotensin II-induced cytotoxicity in AECs from control-fed and ethanol-fed rats were inhibited by the selective AT(2) blocker, PD123319, but not by the selective AT(1) blocker, losartan. In parallel, ethanol ingestion doubled AT(2) expression in AECs (by Western blot) but had no significant effect on AT(1) receptor expression. CONCLUSIONS: Chronic ethanol ingestion increases AT(2) expression in the alveolar epithelium and enhances TNF-alpha- and angiotensin II-induced cytotoxicity, both of which act via AT(2). Together, these findings suggest that selective AT(2) receptor inhibition could limit the development of acute lung injury in alcoholic patients.