Fusu mixture alleviates inflammatory reactions in lipopolysaccharide-induced acute respiratory distress syndrome mice via regulation of surfactant-associated protein C, aquaporin 5, and Notch1
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Abstract:
Acute respiratory distress syndrome (ARDS) is a common life-threatening critical illness with high mortality. Fusu mixture (FSM) can improve the mechanical ventilation in ARDS patients. However, the detailed pharmacological mechanisms and active substances of FSM are still unclear. This study aimed to explore the potential pharmacological mechanisms of FSM for treating ARDS and its chemical compositions.A lipopolysaccharide (LPS)-induced ARDS mouse model was established, and the mice subsequently received FSM (50 mg/kg) orally for 5 days. Then, the blood samples and lung tissues were collected. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum, and histopathology examinations were applied to analyze the inflammatory response of lung tissues in ARDS mice. In addition, protein expressions of aquaporin 5 (AQP-5), surfactant-associated protein C (SP-C), and Notch1 were detected by western blot assays and immunohistochemical (IHC) examination. In addition, the chemical compositions of FSM were analyzed by high performance liquid chromatography (HPLC), using standard reference agents.After LPS induction, the serum levels of IL-6 and TNF-α in ARDS mice were significantly increased (P<0.01, vs. Control), and FSM significantly reduced these 2 pro-inflammatory cytokines (IL-6 and TNF-α) compared to the model mice (P<0.01). Histopathology examinations showed FSM significantly attenuated the inflammatory responses in lung tissues. Furthermore, after FSM treatment, the SP-C and AQP-5 were significantly increased, compared to the Model mice (P<0.01), and FSM also up-regulated the Notch1 expressions in lung tissues of ARDS mice (P<0.001, vs. Model).Collectively, it is suggested that FSM alleviates inflammatory reactions and promotes the proliferation of alveolar epithelial cells in LPS-induced ARDS mice via regulation of SP-C, AQP-5, and Notch1 in lung tissues.Keywords:
Histopathology
Proinflammatory cytokine
2019-20 coronavirus outbreak
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Fifteen years have passed since lung protective strategy to the patients with acute respiratory distress syndrome (ARDS) established. Recently, the new Berlin Definition of ARDS has been developed and this classified ARDS into three stages (mild, moderate, and severe ARDS), depending on the PaO2/FiO2. After this new definition of ARDS, each treatment to the patients with ARDS should be considered, depending on the severity of lung injury, such as prone position to the patients with severe ARDS, muscle paralysis to the patients with severe ARDS. In this review article, we review the history of lung protective strategy and ARDS definition, discuss the novel physiological approaches to minimizing ventilator-induced lung injury, and highlight a numbers of experimental/clinical studies to support these concepts.
Prone position
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Objective The influence of pulmonary and extra-pulmonary factors on the prognosis of acute respiratory distress syndrome (ARDS) were analyzed.Methods Clinical data of patients with ARDS in ICU of our hospital from March 2000 to December 2001 were collected, and they were divided into pulmonary (ARDS P) and extra-pulmonary (ARDS EXP-) groups according to the inducing factors. The significances on the prognosis were evaluated by t-test and χ 2.Results There were 15 cases with ARDS P and 29 with ARDS EXP- including male/female 4/11 and 14/15, age ( 59.0- ±18.5-) and ( 52.7- ±21.9-) years old, respectively. There were no significant differences between the two groups on the following items as age, underlying diseases, nutritional condition, PaO 2/FiO 2, Q S/Q T, APACHE-Ⅱ score, PEEP level, time of ventilation support, septic shock and multiple organic dysfunction syndrome (MODS, P 0.05-).The oxygenation of ARDS EXP- was improved more significantly than ARDS P by ventilation support (P 0.05-). Also, there were no significant differences on the incidence of indefinite pathogen and mixed infection between the two groups (P 0.05-) but the antibiotic effect in ARDS P was lower than that in ARDS EXP- (P 0.05-). The mortality rate was higher in ARDS P group than that in ARDS EXP- ( 93.3%- vs 44.8%-, P 0.01-).Conclusion The mortality rate in ARDS P is significant higher than that in ARDS EXP- due to the uncontrollable pulmonary infection.
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Objective To explore the clinical value of serum Ang-1,Ang-2 and IL-8 in ARDS prediction.Methods Totally 283 critically ill patients admitted in EICU of the Hunan Provincial People's Hospital from January 2012 to July 2013 were enrolled in this study and divided into the non-ARDS group (n =251) and ARDS group (n =32) depending on the development of ARDS.According to the occurrence of death in the following 60 days,the non-ARDS group and the ARDS group were further subdivided into the non-ARDS survival group,the non-ARDS death group,thc ARDS survival group and the ARDS death group.The differences in serum Ang-1,Ang-2 and IL-8 concentrations between these four groups measured by ELISA on admission were analyzed by statistical methods and ROC curve.Results The EICU stays,duration of mechanical ventilation,APACHE Ⅱ score、serum Ang-2 and IL-8 levels in the ARDS group were significantly higher than those in the non-ARDS group,while the Ang-1 level in the ARDS group was significantly lower than that in the non-ARDS group.The serum Ang-2 and IL-8 concentrations in the ARDS death group were significantly higher than those in the non-ARDS survival group and the non-ARDS death group,and the serum Ang-2 concentrations in the ARDS death group were also significantly higher than those in the ARDS survival group.Further ROC curve analysis showed that the area under the curve of Ang-2 for ARDS diagnosis and ARDS death prediction were 0.907 and 0.899 respectively and their diagnostic sensitivity and specificity were 0.969 and 0.725,0.907 and 0.882 respectively,illustrating that Ang-2 possess the best diagnostic efficiency.Conclusions Ang-2 functions as a valuable biomarker for early diagnosis and prognosis of ARDS.
Key words:
Acute respiratory distress syndrome; Angiopoietin-1; Angiopoietin-2; Interleukin-8
Angiopoietin 2
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Acute respiratory distress syndrome (ARDS) is one the leading causes of mortality and morbidity in patients with COVID-19 and Influenza, with only small number of studies comparing these two viral illnesses in the setting of ARDS. Given the pathogenic differences in the two viruses, this study shows trends in national hospitalization and outcomes associated with COVID-19- and Influenza-related ARDS. To evaluate and compare the risk factors and rates of the adverse clinical outcomes in patients with COVID-19 associated ARDS (C-ARDS) relative to Influenza-related ARDS (I-ARDS), we utilized the National Inpatient Sample (NIS) database 2020. Our sample includes 106,720 patients hospitalized with either C-ARDS or I-ARDS between January and December 2020, of which 103,845 (97.3%) had C-ARDS and 2875 (2.7%) had I-ARDS. Propensity-matched analysis demonstrated a significantly higher in-hospital mortality (aOR 3.2, 95% CI 2.5–4.2, p < 0.001), longer mean length of stay (18.7 days vs. 14.5 days, p < 0.001), higher likelihood of requiring vasopressors (aOR 1.7, 95% CI 2.5–4.2) and invasive mechanical ventilation (IMV) (aOR 1.6, 95% CI 1.3–2.1) in C-ARDS patients. Our study shows that COVID-19-related ARDS patients had a higher rate of complications, including higher in-hospital mortality and a higher need for vasopressors and invasive mechanical ventilation relative to Influenza-related ARDS; however, it also showed an increased utilization of mechanical circulatory support and non-invasive ventilation in Influenza-related ARDS. It emphasizes the need for early detection and management of COVID-19.
2019-20 coronavirus outbreak
Betacoronavirus
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Introduction: It is uncertain whether ventilation management in patients with COVID-19 ARDS differs from that in patients with ARDS from another origin. Aim: To compare ventilation management in published cohorts of COVID-19 patients vs patients with ARDS from another origin. Methods: Two literature searches in PubMed were performed to identify observational studies reporting on ventilation management–one for COVID-19 ARDS, and one for ARDS from another origin. Results: The two searches identified 14 studies in COVID–19 ARDS patients, and 8 studies in patients with ARDS from another origin. In patients with COVID-19 ARDS, ventilation with a lower VT (median from 5.8 to 7.0 ml/kg PBW) was applied more rigorously than in patients with ARDS from another origin (median from 6.7 to 8.4 ml/kg PBW), albeit that Pplat was comparable between patients with COVID-19 ARDS (median from 24 to 27 cm H2O) and patients with ARDS from another origin (median from 19 to 26 cm H2O). PEEP and FiO2 were higher in patients with COVID-19 ARDS (median from 10 to 15 cm H2O, and from 60 to 80%) than in patients with ARDS from another origin (median from 7.5 to 10 cm H2O, and from 45 to 50%). Prone positioning was used more often in patients with COVID-19 ARDS (17 to 76%) than in patients with ARDS from another origin (1%, 6% and 16% in mild, moderate and severe ARDS). Conclusions: Remarkable differences exist in ventilation management of patients with COVID-19 ARDS vs patients with ARDS from another origin. Differences may, at least in part originate from disparities in oxygenation problems, that are more severe in COVID-19 ARDS patients.
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Abstract Background: Prone positioning is recommended for patients with moderate-to-severe acute respiratory distress syndrome (ARDS) receiving mechanical ventilation. While the debate continues as to whether COVID-19 ARDS is clinically different from non-COVID ARDS, there is little data on whether the physiological effects of prone positioning differ between the two conditions. We aimed to compare the physiological effect of prone positioning between patients with COVID-19 ARDS and those with non-COVID ARDS. Methods: We retrospectively compared 23 patients with COVID-19 ARDS and 145 patients with non-COVID ARDS treated using prone positioning while on mechanical ventilation. Changes in PaO 2 /FiO 2 ratio and static respiratory system compliance (Crs) after the first session of prone positioning were compared between the two groups: first, using all patients with non-COVID ARDS, and second, using subgroups of patients with non-COVID ARDS matched 1:1 with patients with COVID-19 ARDS for baseline PaO 2 /FiO 2 ratio and static Crs. We also evaluated whether the response to the first prone positioning session was associated with the clinical outcome. Results: When compared with the entire group of patients with non-COVID ARDS, patients with COVID-19 ARDS showed more pronounced improvement in the PaO 2 /FiO 2 ratio (adjusted difference 39.3 [95% CI 5.2–73.5] mmHg) and static Crs (adjusted difference 3.4 [95% CI 1.1–5.6] mL/cmH 2 O). However, these between-group differences were not significant when the matched samples (either PaO 2 /FiO 2 -matched or compliance-matched) were analyzed. The improvements in PaO 2 /FiO 2 ratio (subdistribution hazard ratio 1.19, 95% CI 1.08–1.30) and static Crs (subdistribution hazard ratio 1.57, 95% CI 1.29–1.91) after the first prone positioning session were associated with successful discontinuation of mechanical ventilation in patients with COVID-19 ARDS. Conclusions: In patients with COVID-19 ARDS, prone positioning was as effective in improving respiratory physiology as in patients with non-COVID ARDS. Thus, it should be actively considered as a therapeutic option. The physiological response to the first session of prone positioning was predictive of the clinical outcome of patients with COVID-19 ARDS.
Prone position
Pulmonary compliance
Respiratory physiology
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前言：一氧化氮(nitric oxide，NO)是選擇性肺血管擴張劑，具有抗發炎性質，用於急性呼吸窘迫症候群(acute respiratory distress syndrome，ARDS)，能改善血氧和臨床症狀。然而，使用吸入一氧化氮(inhaled nitric oxide，iNO)治療ARDS是本院的標準醫療程序，但似乎過度使用，對於重度末期的ARDS病人，仍積極以NO治療，即使病人預後不佳或高死亡風險。目前已有多篇隨機分派臨床試驗(randomized clinical trials , RCTs)指出iNO無法降低ARDS病人死亡率，亦會增加腎衰竭風險。故而，為避免無效醫療， 並考量iNO的高成本費用， 增加醫療人員工作負荷， 本研究針對重度ARDS(PaO2/FiO2 ratio＜100 mmHg)使用NO治療的病人，進行統合分析，探究iNO是否能降低重度ARDS病人的死亡率，以提供醫療團隊和病人家屬，謹慎評估iNO治療重度ARDS之必要性。研究方法：我們篩選成人或兒童ARDS病人使用iNO機械通氣治療實驗組和沒有iNO控制組比較之RCTs，執行系統性文獻回顧及統合分析。檢索策略：搜尋PubMed、Cochrane Library、Ovid Medline、UpToDate 2001至2017年的RCTs。納入標準：採取最新ARDS柏林定義，研究對象為成人或兒童重度ARDS(PaO2/FiO2 ratio＜100 mmHg)、輕度中度ARDS(PaO2/FiO2 ratio＞100 mmHg)的病人；比較措施是iNO與無iNO；結果指標為死亡率。統計工具：使用Review Manager 5.3 版，以二分類變項，計算風險比，選擇隨機效應模式，繪製森林圖。結果：ARDS病人使用iNO治療和控制組比較之死亡率無顯著差異P=0.62＞0.05，低度異質性P＝0.95＞0.1，I2=0 (圖一)；重度ARDS病人(PaO2/FiO2 ratio＜100 mmHg)實驗組和控制組的死亡率無顯著差異P=0.99，低度異質性P＝0.99＞0.1，I2=0%(圖二)；輕度與中度ARDS病人(PaO2/FiO2 ratio＞100mmHg)，實驗組和控制組的死亡率亦無顯著差異P=0.82，低度異質性P＝ 0.67＞0.1，I2=0%(圖三)。但因RCTs之間研究樣本數差異大，必須小心解讀。結論：iNO無法降低重度ARDS病人的死亡率，且不因低血氧的程度而有所不同，因此，不管ARDS病人的預後與嚴重度，都常規使用NO治療ARDS的醫療策略，應依據臨床效益，重新評估檢討。此外，尚須收集更多應用iNO於重度ARDS病人的隨機分派臨床試驗之最新數據，納入統計分析，以提供更有力的證據。
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