Therapeutic strategies for severe acute lung injury

Dı́az, Janet; Brower, Roy G.; Calfee, Carolyn S.; Matthay, Michael A.

doi:10.1097/ccm.0b013e3181e795ee

Cited by 156 publications

(129 citation statements)

References 59 publications

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“…Lungprotective ventilation strategies seek to prevent ventilatorassociated lung injury by using low tidal volume (V T ) to avoid overdistention, and PEEP to prevent repetitive alveolar collapse and reopening. [2][3][4] SEE THE RELATED EDITORIAL ON PAGE 1552…”

Section: Introductionmentioning

confidence: 99%

Individualized PEEP Setting in Subjects With ARDS: A Randomized Controlled Pilot Study

et al. 2013

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BACKGROUND: Low-tidal-volume ventilation may be associated with repetitive opening and closing of terminal airways. The use of PEEP is intended to keep the alveoli open. No method of adjusting the optimal PEEP has shown to be superior or to improve clinical outcomes. We conducted a pilot study to evaluate the effect of setting an individualized level of PEEP at the highest compliance on oxygenation, multiple-organ-dysfunction, and survival in subjects with ARDS. METHODS: Subjects with ARDS ventilated with low tidal volumes and limitation of airway pressure to 30 cm H 2 O were randomized to either a compliance-guided PEEP group or an F IO 2 -guided group. RESULTS: Of the 159 patients with ARDS admitted during the study period, 70 met the inclusion criteria. Subjects in the compliance-guided group showed nonsignificant improvements in P aO 2 /F IO 2 during the first 14 days, and in 28-day mortality (20.6% vs. 38.9%, P ‫؍‬ .12). Multipleorgan-dysfunction-free days (median 6 vs 20.5 d, P ‫؍‬ .02), respiratory-failure-free days (median 7.5 vs 14.5 d, P ‫؍‬ .03), and hemodynamic-failure-free days (median 16 vs 22 d, P ‫؍‬ .04) at 28 days were significantly lower in subjects with compliance-guided setting of PEEP. CONCLUSIONS: In ARDS subjects, protective mechanical ventilation with PEEP application according to the highest compliance was associated with less organ dysfunction and a strong nonsignificant trend toward lower mortality. ClinicalTrials.gov Number NCT01119872.

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Section: Introductionmentioning

confidence: 99%

Individualized PEEP Setting in Subjects With ARDS: A Randomized Controlled Pilot Study

et al. 2013

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“…In patients suffering sepsis, acute lung injury (ALI) is characterized by higher lung vascular permeability, and severe lung infection and inflammation that typically lead to a gradual decline of lung function (Diaz et al, 2010). Lipopolysaccharides (LPSs) are bacterial cell wall toxins that are contributing agents implicated in ALI and the disease pathogenesis (Dellinger et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

Jayakumar

Samanta

Rajasingh

et al. 2015

Journal of Cell Science

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Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema, and respiratory failure. Here, we examined the efficacy of DNA methyl transferase (DNMT) inhibitor Aza (5-Aza 2-deoxycytidine), histone deacetylase (HDAC) inhibitor TSA (Trichostatin A), and combination therapy (Aza+TSA) in protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed a substantial attenuation of adverse lung histopathological changes, and inflammations. Importantly, these protective effects were due to significant macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK-HuR-TNF and activation of STAT3-Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI. This finding gives further evidence that the epigenetic treatment has a therapeutic potential for patients with sepsis.

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“…Matthay, 2006). Despite the improvement in these strategies, recent data indicate that the mortality of ALI/ARDS is still as high as 30 to 50% (Rubenfeld et al, 2005;Diaz et al, 2010). Thus, there is a need for innovative therapies to further improve clinical outcomes of ALI/ARDS.…”

Section: Issn: 2319-7706 Volume 7 Number 06 (2018)mentioning

confidence: 99%

Impact of Mesenchymal Stem Cells on Lipopolysaccharide-Induced Apoptosis in Acute Lung Injury Rat Model

Mansour¹,

Soliman²,

Hasan³

et al. 2018

Int.J.Curr.Microbiol.App.Sci

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Therapeutic strategies for severe acute lung injury

Cited by 156 publications

References 59 publications

Individualized PEEP Setting in Subjects With ARDS: A Randomized Controlled Pilot Study

Individualized PEEP Setting in Subjects With ARDS: A Randomized Controlled Pilot Study

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

Impact of Mesenchymal Stem Cells on Lipopolysaccharide-Induced Apoptosis in Acute Lung Injury Rat Model

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