scholarly journals The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology

2015 ◽  
Vol 36 (4) ◽  
pp. 1644-1658 ◽  
Author(s):  
Gisele P. Oliveira ◽  
Johnatas D. Silva ◽  
Patricia S. Marques ◽  
Cassiano F. Gonçalves-de-Albuquerque ◽  
Heloísa L. Santos ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Transforming Growth Factor ◽  
Diffuse Alveolar Damage ◽  
Lung Mechanics ◽  
Dose Monitoring

Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required.

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 Molecular and Immune Biomarkers in Acute Respiratory Distress Syndrome: A Perspective From Members of the Pulmonary Pathology Society

2017 ◽  
Vol 141 (12) ◽  
pp. 1719-1727 ◽  
Author(s):  
Vera Luiza Capelozzi ◽  
Timothy Craig Allen ◽  
Mary Beth Beasley ◽  
Philip T. Cagle ◽  
Don Guinee ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Diffuse Alveolar Damage ◽  
Response To Therapy ◽  
Lung Mechanics ◽  
High Morbidity ◽  
Therapeutic Approaches ◽  
Immune Biomarkers

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the greatest risk of developing ARDS, to evaluate response to therapy, to predict outcome, and to improve clinical trials. The ARDS pathogenesis is presented in this article, as well as concepts and information on biomarkers that are currently used clinically or are available for laboratory use by academic and practicing pathologists and the developing and validating of new assays, focusing on the assays' major biologic roles in lung injury and/or repair and to ultimately suggest innovative, therapeutic approaches.

scholarly journals Transforming Growth Factor-β1 in predicting early lung fibroproliferation in patients with acute respiratory distress syndrome

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206105 ◽  
Author(s):  
Jean-Marie Forel ◽  
Christophe Guervilly ◽  
Catherine Farnarier ◽  
Stéphane-Yannis Donati ◽  
Sami Hraiech ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Growth Factor ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1

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.

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