scholarly journals Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 431
Author(s):  
Matthias Otto ◽  
Jörg Krebs ◽  
Peter Welker ◽  
René Holm ◽  
Manfred Thiel ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Lung Mechanics ◽  
Systemic Absorption ◽  
Control Group ◽  
Pharmacokinetic Data ◽  
Tnf Α ◽  
Semifluorinated Alkanes

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

scholarly journals Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

2020 ◽  
Author(s):  
Rongyuan Zhang ◽  
Xu Wang ◽  
Shoujun Li ◽  
Jun Yan
Keyword(s):  
Cardiac Surgery ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Standard Therapy ◽  
Low Dose ◽  
Distress Syndrome ◽  
Exogenous Surfactant ◽  
Control Group ◽  
Surfactant Treatment

Abstract Background: To evaluate the effect of low-dose exogenous surfactant therapy on infants suffering acute respiratory distress syndrome (ARDS) after cardiac surgery. Methods: We conducted a retrospective case-control study of infants diagnosed with moderate-severe ARDS after cardiac surgery. A case was defined as a patient that received surfactant and standard therapy, while a control was defined as a patient that underwent standard therapy. The primary endpoint was the improvement in oxygenation index (OI) after 24-hour of surfactant treatment; and secondary endpoints were the ventilator time and PICU time. Results: 22 infants treated with surfactant were matched with 22 controls. Early low-dose (20mg/kg) surfactant treatment was associated with improved outcomes. After surfactant administration for 24-hour, the surfactant group was much better compared with the control group at the 24-hour in OI (difference in average change from baseline, -6.7 [95% CI, -9.3 to -4.1]) (P < 0.01) and VI (mean difference, -11.9 [95% CI, -18.1 to -5.7]) (P < 0.01). Ventilation time and PICU time were significantly shorter in the surfactant group compared with the control group (133.6h±27.2 vs 218.4h±28.7, P < 0.01 ; 10.7d±5.1 vs 17.5d±6.8, P < 0.01). Infants in the surfactant group under 3 months benefit more from OI and VI than the infants over 3 months in a preliminary exploratory analysis.Conclusions: In infants with moderate-severe ARDS after cardiac surgery, early low-dose exogenous surfactant treatment could prominently improve oxygenation and reduce mechanical ventilation time and PICU time. Infants younger than 3 months may get more benefit of oxygenation than the older ones.

scholarly journals Mesenchymal Stromal Cells Attenuate Infection-Induced Acute Respiratory Distress Syndrome in Animal Experiments: A Meta-Analysis

2020 ◽  
Vol 29 ◽  
pp. 096368972096918
Author(s):  
Wang Fengyun ◽  
Zhou LiXin ◽  
Qiang Xinhua ◽  
Fang Bin
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Meta Analysis ◽  
Weight Ratio ◽  
Lung Injury Score ◽  
Control Group ◽  
Inflammatory Factor

Mesenchymal stromal cell (MSC) therapy is a potential therapy for treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which was widely studied in the last decade. The purpose of our meta-analysis was to investigate the efficacy of MSCs for simulated infection-induced ALI/ARDS in animal trials. PubMed and EMBASE were searched to screen relevant preclinical trials with a prespecified search strategy. 57 studies met the inclusion criteria and were included in our study. Our meta-analysis showed that MSCs can reduce the lung injury score of ALI caused by lipopolysaccharide or bacteria (standardized mean difference (SMD) = −2.97, 95% CI [−3.64 to −2.30], P < 0.00001) and improve the animals’ survival (odds ratio = 3.64, 95% CI [2.55 to 5.19], P < 0.00001). Our study discovered that MSCs can reduce the wet weight to dry weight ratio of the lung (SMD = −2.58, 95% CI [−3.24 to −1.91], P < 0.00001). The proportion of the alveolar sac in the MSC group was higher than that in the control group (SMD = 1.68, 95% CI [1.22 to 2.13], P < 0.00001). Moreover, our study detected that MSCs can downregulate the levels of proinflammatory factors such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung and it can upregulate the level of anti-inflammatory factor IL-10. MSCs were also found to reduce the level of neutrophils and total protein in bronchoalveolar lavage fluid, decrease myeloperoxidase (MPO) activity in the lung, and improve lung compliance. MSC therapy may be a promising treatment for ALI/ARDS since it may mitigate the severity of lung injury, modulate the immune balance, and ameliorate the permeability of lung vessels in ALI/ARDS, thus facilitating lung regeneration and repair.

scholarly journals C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

2008 ◽  
Vol 180 (11) ◽  
pp. 7368-7375 ◽  
Author(s):  
Konstantinos Kambas ◽  
Maciej M. Markiewski ◽  
Ioannis A. Pneumatikos ◽  
Stavros S. Rafail ◽  
Vassiliki Theodorou ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Tissue Factor ◽  
Distress Syndrome ◽  
Tnf Α

scholarly journals Silencing of long noncoding RNA H19 alleviates pulmonary injury, inflammation and fibrosis in acute respiratory distress syndrome rats through regulating MicroRNA-423-5p

2020 ◽  
Author(s):  
Xianyu Mu ◽  
Hongrong Wang ◽  
Haiyong Li
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Distress Syndrome ◽  
Luciferase Reporter ◽  
Pulmonary Injury ◽  
Tnf Α ◽  
Histology Score

Abstract Background: This study aimed to explore the function of long noncoding RNA H19 (H19) on pulmonary injury, inflammation and fibrosis in lipoproteins (LPS)-induced acute respiratory distress syndrome (ARDS) rats. Methods: The LPS-induced ARDS rat model was established by intratracheal instillation with 2 mg/kg LPS. QRT-PCR was performed to detect the expression of H19, miR-423-5p, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6,, monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF). Histology score was detected by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of proinflammatory cytokines and the concentration of VEGF in bronchoalveolar lavage fluid (BALF). The protein expression of fiber factors was measured by western blot. The degree of fibrosis was observed by masson-trichrome staining. Dual-luciferase reporter assay was used to determine the binding site between miR-423-5p and H19.Results: The expression of H19 was significantly increased, while miR-423-5p was decreased in LPS-induced ARDS rats. Silencing of H19 decreased the mRNA expression of TNF-α, IL-1β, IL-6, MCP-1 and VEGF in LPS-induced ARDS rats, and decreased the levels of TNF-α, IL-1β, IL-6and the concentration of VEGF in BALF, histology score of LPS-induced ARDS rats. H19 inhibition also decreased the fibrosis score and the proteins expression of fiber factors of LPS-induced ARDS rats. Furthermore, miR-423-5p eliminated the effect of H19 on LPS-induced MH-S cells.Conclusions: Silencing of H19 ameliorated the pulmonary injury, inflammation and fibrosis of LPS-induced ARDS through regulating miR-423-5p, which may be a promising therapeutic strategy to treat ARDS.

scholarly journals Expression Level, Correlation, and Diagnostic Value of Serum miR-127 in Patients with Acute Respiratory Distress Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Hui Lin ◽  
Lingxiang Jiang ◽  
Yiqun Ren ◽  
Fen Sheng ◽  
Luxi Wang ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Molecular Marker ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Pearson Correlation ◽  
Diagnostic Value ◽  
Control Group ◽  
Observation Group ◽  
Severe Group

Objective. To analyze the expression of miR-127 in the serum of patients with acute respiratory distress syndrome (ARDS) and to explore its correlation with the severity of ARDS patients and its value as a molecular marker for diagnosis of ARDS. Methods. 70 patients with ARDS admitted to our hospital from September 2017 to September 2019 were selected as the observation group, and 60 healthy persons with physical examination were collected as the control group. RT-PCR was used to detect the serum miR-127 levels of all subjects, and the serum miR-127 levels of the observation group and control group were compared. The oxygenation index (PaO2/FiO2) of ARDS patients was recorded and divided into three subgroups: mild group, moderate group, and severe group. Serum miR-127 levels of patients in the mild group, moderate group, and severe group were compared. Pearson correlation was used to analyze the relationship between serum miR-127 levels and the severity of ARDS patients. The receiver operating characteristic curve (ROC) was drawn, and the area under the ROC curve (AUC) was used to evaluate the diagnostic value of miR-127 in patients with ARDS. Results. The serum level of miR-127 (10.15 ± 1.03) in the observation group was significantly higher than that in the control group (3.09 ± 0.62). And in the three subgroups of mild, moderate, and severe, the serum miR-127 level in the moderate group (10.43 ± 0.71) and the severe group miR-127 level (11.05 ± 1.26) were significantly higher than those in the mild group level (9.38 ± 1.24). Pearson correlation analysis showed that the serum miR-127 level was negatively correlated with PaO2/FiO2 (r = −0.715, P < 0.05 ), that is, the serum miR-127 level was positively correlated with the severity of ARDS patients. The area under the curve (AUC) of the diagnostic value of serum miR-127 for ARDS was 0.732 (95% CI 0.607–0.858). When the optimal cutoff value was 0.380, the sensitivity was 59.1% and the specificity was 78.6%, which suggested that miR-127 can be used as a marker for ARDS diagnosis. Conclusion. There is an increase in miR-127 levels in the serum of ARDS patients. The serum miR-127 level is positively correlated with the severity of ARDS. The higher the level of miR-127, the worse the condition of ARDS, which is positively correlated with the severity of the condition. It suggests that the serum miR-127 level is an important indicator for evaluating the severity of ARDS patients. It can be used as a molecular marker for clinical diagnosis of ARDS.

scholarly journals Monitoring Expired CO2 Kinetics to Individualize Lung-Protective Ventilation in Patients With the Acute Respiratory Distress Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernando Suárez-Sipmann ◽  
Jesús Villar ◽  
Carlos Ferrando ◽  
Juan A. Sánchez-Giralt ◽  
Gerardo Tusman
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Gas Exchange ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Lung Volume ◽  
Cyclic Deformation ◽  
Distress Syndrome ◽  
Pulmonary Ventilation ◽  
Lung Mechanics

Mechanical ventilation (MV) is a lifesaving supportive intervention in the management of acute respiratory distress syndrome (ARDS), buying time while the primary precipitating cause is being corrected. However, MV can contribute to a worsening of the primary lung injury, known as ventilation-induced lung injury (VILI), which could have an important impact on outcome. The ARDS lung is characterized by diffuse and heterogeneous lung damage and is particularly prone to suffer the consequences of an excessive mechanical stress imposed by higher airway pressures and volumes during MV. Of major concern is cyclic overdistension, affecting those lung segments receiving a proportionally higher tidal volume in an overall reduced lung volume. Theoretically, healthier lung regions are submitted to a larger stress and cyclic deformation and thus at high risk for developing VILI. Clinicians have difficulties in detecting VILI, particularly cyclic overdistension at the bedside, since routine monitoring of gas exchange and lung mechanics are relatively insensitive to this mechanism of VILI. Expired CO2 kinetics integrates relevant pathophysiological information of high interest for monitoring. CO2 is produced by cell metabolism in large daily quantities. After diffusing to tissue capillaries, CO2 is transported first by the venous and then by pulmonary circulation to the lung. Thereafter diffusing from capillaries to lung alveoli, it is finally convectively transported by lung ventilation for its elimination to the atmosphere. Modern readily clinically available sensor technology integrates information related to pulmonary ventilation, perfusion, and gas exchange from the single analysis of expired CO2 kinetics measured at the airway opening. Current volumetric capnography (VCap), the representation of the volume of expired CO2 in one single breath, informs about pulmonary perfusion, end-expiratory lung volume, dead space, and pulmonary ventilation inhomogeneities, all intimately related to cyclic overdistension during MV. Additionally, the recently described capnodynamic method provides the possibility to continuously measure the end-expiratory lung volume and effective pulmonary blood flow. All this information is accessed non-invasively and breath-by-breath helping clinicians to personalize ventilatory settings at the bedside and minimize overdistension and cyclic deformation of lung tissue.

Pulmonary Edema II: Noncardiogenic Pulmonary Edema

2017 ◽  
Author(s):  
Annette Esper ◽  
Greg S Martin ◽  
Gerald W. Staton Jr
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pulmonary Edema ◽  
Distress Syndrome ◽  
Diffuse Alveolar Damage ◽  
Lung Resection ◽  
Upper Airway ◽  
Experimental Models ◽  
Lung Mechanics

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome [ARDS]). This review focuses on noncardiogenic pulmonary edema and describes the general approach to patients with suspected pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of noncardiogenic pulmonary edema are reviewed. Miscellaneous causes of pulmonary edema are discussed, including neurologic insults, exposure to high altitude, reexpansion of a collapsed lung, lung transplantation, upper airway obstruction, drugs, and lung resection. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with noncardiogenic pulmonary edema, the definition of ARDS, causes of ARDS, and treatments for ARDS that do not involve ventilation. This review contains 3 figures, 9 tables, and 55 references. Key words: acute respiratory distress syndrome, diffuse alveolar damage, noncardiogenic pulmonary edema, pulmonary edema

Pulmonary Edema II: Noncardiogenic Pulmonary Edema

2017 ◽  
Author(s):  
Annette Esper ◽  
Greg S Martin ◽  
Gerald W. Staton Jr
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pulmonary Edema ◽  
Distress Syndrome ◽  
Diffuse Alveolar Damage ◽  
Lung Resection ◽  
Upper Airway ◽  
Experimental Models ◽  
Lung Mechanics

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome [ARDS]). This review focuses on noncardiogenic pulmonary edema and describes the general approach to patients with suspected pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of noncardiogenic pulmonary edema are reviewed. Miscellaneous causes of pulmonary edema are discussed, including neurologic insults, exposure to high altitude, reexpansion of a collapsed lung, lung transplantation, upper airway obstruction, drugs, and lung resection. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with noncardiogenic pulmonary edema, the definition of ARDS, causes of ARDS, and treatments for ARDS that do not involve ventilation. This review contains 3 figures, 9 tables, and 55 references. Key words: acute respiratory distress syndrome, diffuse alveolar damage, noncardiogenic pulmonary edema, pulmonary edema

scholarly journals Corticosteroid treatment for early acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Yohei Hirano ◽  
Shunsuke Madokoro ◽  
Yutaka Kondo ◽  
Ken Okamoto ◽  
Hiroshi Tanaka
Keyword(s):  
Systematic Review ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Meta Analysis ◽  
Corticosteroid Treatment ◽  
Control Group ◽  
Controlled Trials ◽  
Secondary Outcomes

Abstract Background The effect of corticosteroid treatment on survival outcome in early acute respiratory distress syndrome (ARDS) is still debated. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of prolonged corticosteroid therapy in early ARDS. Methods We assessed the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception to August 1, 2020. We included RCTs that compared prolonged corticosteroid therapy with control treatment wherein the intervention was started within 72 h of ARDS diagnosis. Two investigators independently screened the citations and conducted the data extraction. The primary outcomes were all-cause 28- or 30-day mortality and 60-day mortality. Several endpoints such as ventilator-free days and adverse events were set as the secondary outcomes. DerSimonian-Laird random-effects models were used to report pooled odds ratios (ORs). Results Among the 4 RCTs included, all referred to the all-cause 28- or 30-day mortality. In the corticosteroid group, 108 of 385 patients (28.1%) died, while 139 of 357 (38.9%) died in the control group (pooled OR, 0.61; 95% confidence interval [CI], 0.44–0.85). Three RCTs mentioned the all-cause 60-day mortality. In the corticosteroid group, 78 of 300 patients (26.0%) died, while 101 of 265 (38.1%) died in the control group (pooled OR, 0.57; 95% CI, 0.40–0.83). For secondary outcomes, corticosteroid treatment versus control significantly prolonged the ventilator-free days (4 RCTs: mean difference, 3.74; 95% CI, 1.53–5.95) but caused hyperglycemia (3 RCTs: pooled OR, 1.52; 95% CI, 1.04–2.21). Conclusions Prolonged corticosteroid treatment in early ARDS improved the survival outcomes. Trial registration PROSPERO, CRD42020195969

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