Biological subphenotypes of acute respiratory distress syndrome may not reflect differences in alveolar inflammation

Heijnen, Nanon F. L.; Hagens, Laura A.; Smit, Marry R.; Schultz, Marcus J.; Poll, Tom van der; Schnabel, Ronny M.; Horst, Iwan C. C. van der; Dickson, Robert P.; Bergmans, Dennis C. J. J.; Bos, Lieuwe D. J.

doi:10.14814/phy2.14693

Cited by 25 publications

(22 citation statements)

References 27 publications

(40 reference statements)

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“…Therefore, we initially postulated that the decreased AM efferocytosis in ARDS may be due to the polarization of AMs to a proinflammatory phenotype, which is associated with reduced efferocytosis ( 17 ). The concentrations of inflammatory cytokines within our pooled ARDS BAL are in keeping with those reported in previous studies ( 35 , 36 ). We then undertook experiments using the in vitro model of ARDS to investigate the association between AM phenotype and function.…”

Section: Discussionsupporting

confidence: 89%

Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome

et al. 2021

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Background: Impaired alveolar macrophage (AM) efferocytosis may contribute to acute respiratory distress syndrome (ARDS) pathogenesis; however, studies are limited by the difficulty in obtaining primary AMs from patients with ARDS. Our objective was to determine whether an in vitro model of ARDS can recapitulate the same AM functional defect observed in vivo and be used to further investigate pathophysiological mechanisms.Methods: AMs were isolated from the lung tissue of patients undergoing lobectomy and then treated with pooled bronchoalveolar lavage (BAL) fluid previously collected from patients with ARDS. AM phenotype and effector functions (efferocytosis and phagocytosis) were assessed by flow cytometry. Rac1 gene expression was assessed using quantitative real-time PCR.Results: ARDS BAL treatment of AMs decreased efferocytosis (p = 0.0006) and Rac1 gene expression (p = 0.016); however, bacterial phagocytosis was preserved. Expression of AM efferocytosis receptors MerTK (p = 0.015) and CD206 (p = 0.006) increased, whereas expression of the antiefferocytosis receptor SIRPα decreased following ARDS BAL treatment (p = 0.036). Rho-associated kinase (ROCK) inhibition partially restored AM efferocytosis in an in vitro model of ARDS (p = 0.009).Conclusions: Treatment of lung resection tissue AMs with ARDS BAL fluid induces impairment in efferocytosis similar to that observed in patients with ARDS. However, AM phagocytosis is preserved following ARDS BAL treatment. This specific impairment in AM efferocytosis can be partially restored by inhibition of ROCK. This in vitro model of ARDS is a useful tool to investigate the mechanisms by which the inflammatory alveolar microenvironment of ARDS induces AM dysfunction.

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Section: Discussionsupporting

confidence: 89%

Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome

et al. 2021

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“…Descriptions of ARDS cases by Ashbaugh and colleagues [ 142 ] and later in several other reports of ALI/ARDS cases [ 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 ] are strikingly similar to those clinical and autoptic descriptions by Petersdorf [ 42 ].…”

Section: Respiratory Distress Syndrome Pulmonary Hyaline Membrane Dis...supporting

confidence: 73%

SARS-CoV-2-Infection (COVID-19): Clinical Course, Viral Acute Respiratory Distress Syndrome (ARDS) and Cause(s) of Death

Ramadori

2022

Medical Sciences

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SARS-CoV-2-infected symptomatic patients often suffer from high fever and loss of appetite which are responsible for the deficit of fluids and of protein intake. Many patients admitted to the emergency room are, therefore, hypovolemic and hypoproteinemic and often suffer from respiratory distress accompanied by ground glass opacities in the CT scan of the lungs. Ischemic damage in the lung capillaries is responsible for the microscopic hallmark, diffuse alveolar damage (DAD) characterized by hyaline membrane formation, fluid invasion of the alveoli, and progressive arrest of blood flow in the pulmonary vessels. The consequences are progressive congestion, increase in lung weight, and progressive hypoxia (progressive severity of ARDS). Sequestration of blood in the lungs worsens hypovolemia and ischemia in different organs. This is most probably responsible for the recruitment of inflammatory cells into the ischemic peripheral tissues, the release of acute-phase mediators, and for the persistence of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autopsy studies have been performed mostly in patients who died in the ICU after SARS-CoV-2 infection because of progressive acute respiratory distress syndrome (ARDS). In the death certification charts, after respiratory insufficiency, hypovolemic heart failure should be mentioned as the main cause of death.

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“…106,107 The differences in systemic inflammatory response that drive the distinction between the hypoinflammatory and hyperinflammatory subphenotypes in ARDS are not necessarily mirrored in the alveolar host response; discordant levels of bronchoalveolar lavage and systemic proinflammatory cytokines have been observed. 108 Therefore, inflammatory heterogeneity in ARDS is at least two-dimensional; with subphenotypes in systemic and alveolar inflammation (figure 4). We need to better understand the heterogeneity in alveolar host response, how it relates to subphenotypes that are based on underlying cause, and its potential for use in predictive enrichment.…”

Section: Biological Subphenotypesmentioning

confidence: 99%

Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes

2022

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Biological subphenotypes of acute respiratory distress syndrome may not reflect differences in alveolar inflammation

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 25 publications

References 27 publications

Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome

Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome

SARS-CoV-2-Infection (COVID-19): Clinical Course, Viral Acute Respiratory Distress Syndrome (ARDS) and Cause(s) of Death

Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes

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