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

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

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Pulmonary Edema II: Noncardiogenic Pulmonary Edema

10.2310/fm.1372 ◽

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

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

Cellular Physiology and Biochemistry ◽

10.1159/000430325 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1644-1658 ◽

Cited By ~ 13

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.

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A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome

Disease Markers ◽

10.1155/2016/3501373 ◽

2016 ◽

Vol 2016 ◽

pp. 1-20 ◽

Cited By ~ 53

Author(s):

Raiko Blondonnet ◽

Jean-Michel Constantin ◽

Vincent Sapin ◽

Matthieu Jabaudon

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Diffuse Alveolar Damage ◽

Response To Therapy ◽

Lung Edema ◽

Ongoing Research ◽

Therapeutic Implications

Acute respiratory distress syndrome (ARDS) is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS-associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care.

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

Pharmaceutics ◽

10.3390/pharmaceutics13030431 ◽

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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Fatal acute respiratory distress syndrome with diffuse alveolar damage: donor lymphocyte infusion imputability?

European Respiratory Journal ◽

10.1183/13993003.01130-2016 ◽

2016 ◽

Vol 48 (6) ◽

pp. 1794-1796 ◽

Cited By ~ 1

Author(s):

Colombe Saillard ◽

Magali Bisbal ◽

Antoine Sannini ◽

Laurent Chow-Chine ◽

Jean-Paul Brun ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Diffuse Alveolar Damage ◽

Donor Lymphocyte Infusion

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Respiratory Reovirus 1/L Induction of Diffuse Alveolar Damage: Pulmonary Fibrosis Is Not Modulated by Corticosteroids in Acute Respiratory Distress Syndrome in Mice

Clinical Immunology ◽

10.1006/clim.2002.5214 ◽

2002 ◽

Vol 103 (3) ◽

pp. 284-295 ◽

Cited By ~ 17

Author(s):

Lucille London ◽

Elizabeth I. Majeski ◽

Sanja Altman-Hamamdzic ◽

Candace Enockson ◽

Manjeet K. Paintlia ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Pulmonary Fibrosis ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Diffuse Alveolar Damage

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Mesenchymal Stem/Stromal Cells Therapy for Sepsis and Acute Respiratory Distress Syndrome

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0040-1713422 ◽

2020 ◽

Cited By ~ 1

Author(s):

Declan Byrnes ◽

Claire H. Masterson ◽

Antonio Artigas ◽

John G. Laffey

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Stromal Cells ◽

Distress Syndrome ◽

Immune Cell ◽

Therapeutic Potential ◽

Phase Iii ◽

High Morbidity ◽

Lung Dysfunction

AbstractSepsis and acute respiratory distress syndrome (ARDS) constitute devastating conditions with high morbidity and mortality. Sepsis results from abnormal host immune response, with evidence for both pro- and anti-inflammatory activation present from the earliest phases. The “proinflammatory” response predominates initially causing host injury, with later-phase sepsis characterized by immune cell hypofunction and opportunistic superinfection. ARDS is characterized by inflammation and disruption of the alveolar-capillary membrane leading to injury and lung dysfunction. Sepsis is the most common cause of ARDS. Approximately 20% of deaths worldwide in 2017 were due to sepsis, while ARDS occurs in over 10% of all intensive care unit patients and results in a mortality of 30 to 45%. Given the fact that sepsis and ARDS share some—but not all—underlying pathophysiologic injury mechanisms, the lack of specific therapies, and their frequent coexistence in the critically ill, it makes sense to consider therapies for both conditions together. In this article, we will focus on the therapeutic potential of mesenchymal stem/stromal cells (MSCs). MSCs are available from several tissues, including bone marrow, umbilical cord, and adipose tissue. Allogeneic administration is feasible, an important advantage for acute conditions like sepsis or ARDS. They possess diverse mechanisms of action of relevance to sepsis and ARDS, including direct and indirect antibacterial actions, potent effects on the innate and adaptive response, and pro-reparative effects. MSCs can be preactivated thereby potentiating their effects, while the use of their extracellular vesicles can avoid whole cell administration. While early-phase clinical trials suggest safety, considerable challenges exist in moving forward to phase III efficacy studies, and to implementation as a therapy should they prove effective.

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