An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome

Fan, Eddy; Sorbo, Lorenzo Del; Goligher, Ewan C.; Hodgson, Carol; Munshi, Laveena; Walkey, Allan J.; Adhikari, Neill K. J.; Amato, Marcelo B. P.; Branson, Richard D.; Brower, Roy G.; Ferguson, Niall D.; Gajic, Ognjen; Gattinoni, Luciano; Hess, Dean; Mancebo, Jordi; Meade, Maureen O.; McAuley, Daniel F.; Pesenti, Antonio; Ranieri, V. Marco; Rubenfeld, Gordon D.; Rubin, Eileen; Seckel, Maureen A.; Slutsky, Arthur S.; Talmor, Daniel; Thompson, Bruce; Wunsch, Hannah; Uleryk, Elizabeth; Brožek, Jan; Brochard, Laurent

doi:10.1164/rccm.201703-0548st

Cited by 1,186 publications

(1,066 citation statements)

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“…Although mortality rates have fallen with modifications in mechanical ventilation, they remain as high as 25 to 40%, and no effective pharmacological treatments are available (1)(2)(3). ARDS results from multiple causes, pneumonia and sepsis being the most common and most devastating.…”

mentioning

confidence: 99%

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

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543

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Rationale: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs' effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer.Objectives: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects.Methods: Human monocyte-derived macrophages (MDMs) were studied in noncontact coculture with human MSCs when stimulated with LPS or bronchoalveolar lavage fluid (BALF) from patients with ARDS. Murine alveolar macrophages (AMs) were cultured ex vivo with/without human MSC-derived EVs before adoptive transfer to LPS-injured mice.Measurements and Main Results: MSCs suppressed cytokine production, increased M2 macrophage marker expression, and augmented phagocytic capacity of human MDMs stimulated with LPS or ARDS BALF. These effects were partially mediated by CD44-expressing EVs. Adoptive transfer of AMs pretreated with MSCderived EVs reduced inflammation and lung injury in LPS-injured mice. Inhibition of oxidative phosphorylation in MDMs prevented the modulatory effects of MSCs. Generating dysfunctional mitochondria in MSCs using rhodamine 6G pretreatment also abrogated these effects.Conclusions: In the ARDS environment, MSCs promote an antiinflammatory and highly phagocytic macrophage phenotype through EV-mediated mitochondrial transfer. MSC-induced changes in macrophage phenotype critically depend on enhancement of macrophage oxidative phosphorylation. AMs treated with MSCderived EVs ameliorate lung injury in vivo.

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confidence: 99%

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

Self Cite

543

490

View full text Add to dashboard Cite

show abstract

“…Because ARDS-related mortality is high, also in patients who underwent cardiac surgery, it is important to diagnose ARDS as soon as possible. This allows implementing low tidal-volume ventilation and other evidence-based recommendations previously associated with improved outcomes [10], as for example using higher PEEP and prolonged prone position in severe ARDS. It is important to note that although it is known that protective ventilation improves ARDS patients’ survival, evidence-based recommendations are poorly applied in ARDS patients.…”

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confidence: 99%

ARDS after Cardiac Surgery: Is It a Problem, a Problem of Definition, or Both?

Piquilloud¹

2019

Respiration

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“…Although there is still an area of uncertainty for the latter, experts recently recommended lower tidal volume for ARDS and prone positioning for the severe category (22). Overall, only 63% of intubated patients received protective ventilation (with no difference between geo-economic groups), while less than 10% received prone positioning (contrasting with 41% to 52% of patients with a PaO 2 /FiO 2 <150 mmHg), and 5% to 20% of patients had neuromuscular blocking agents, with variability among the 3 groups.…”

Section: Discussion Of the Resultsmentioning

confidence: 99%