Emerging therapies for the prevention of acute respiratory distress syndrome

Ruthman, Carl; Festić, Emir

doi:10.1177/1753465815585716

Cited by 28 publications

(22 citation statements)

References 101 publications

(113 reference statements)

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“…As such, the opportunity for ARDS prevention is constrained in a small window of time [31]. Some observational studies and experimental data suggested a potential preventive role of antiplatelet therapy in patients at high risk of ARDS [32][33][34].…”

Section: Preventionmentioning

confidence: 99%

Acute respiratory distress syndrome

2017

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Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in atrisk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care. Definition and epidemiologySince its first description by ASHBAUGH et al. [1] in 1967, the acute respiratory distress syndrome (ARDS) has been widely recognised as a major clinical problem worldwide, carrying a high morbidity and mortality burden [2][3][4]. Although the recent Berlin definition [5] is probably much better than previous ones, there is still a high variability in both epidemiology and clinical outcomes in diverse healthcare settings [4]. In fact, the incidence of ARDS ranges from 1.5 cases per 100 000 [2] to nearly 79 cases per 100 000 [3], with European countries reporting a lower incidence than USA [6]. Moreover, studies from Brazil reported incidence rates ranging from 1.8 to 31 per 100 000 [7,8].Although the overall survival rate is improving [9,10], there is a notable difference when considering in-hospital mortality over several observational studies [2][3][4][8][9][10][11]. This may be explained by differences in risk factors, availability of diagnostics, ability to recognise ARDS and some selection biases affecting clinical trials [12]. Recently, a large international observational study (the LUNG SAFE trial) evaluated the incidence of ARDS across 459 intensive care units (ICUs) in 50 countries [13]. To assess the clinical recognition of ARDS according to the latest definition, any patient inclusion into the trial was made through a computer algorithm following the Berlin criteria [5], and then compared to the diagnosis made by the attending physicians. Among 4499 patients who developed acute hypoxaemic respiratory failure, ARDS occurred in 1...

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Section: Preventionmentioning

confidence: 99%

Acute respiratory distress syndrome

2017

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“…The pathophysiological mechanisms of ALI are related to overwhelming innate immune response, leading to acute organ failure including the lungs . There are no specific pharmacological therapies for ALI and other therapeutic approaches are extremely limited so far …”

Section: Introductionmentioning

confidence: 99%

25‐Hydroxycholesterol protects against acute lung injury via targeting MD‐2

Ouyang

Zhou

Liu

et al. 2018

J Cellular Molecular Medi

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Acute lung injury (ALI) is mainly caused by uncontrolled inflammatory response, and it remains without effective therapeutic options. 25‐hydroxycholesterol (25HC) has been reported to be a potent regulator of inflammation. The aim of this study was to investigate the effects of 25HC on lipopolysaccharide (LPS)‐induced ALI. C57BL/6 mice were pretreated with 25HC intraperitoneally before intratracheal exposure to LPS. Our results showed that 25HC pretreatment improved survival rate, attenuated the pathological changes of the lung and decreased the release of inflammatory cytokines in mice. Consistently, 25HC reduced expression of Toll‐like receptor (TLR4)‐mediated inflammatory cytokines in vitro. These effects of 25HC were obtained by preventing LPS binding to TLR4 via interaction with myeloid differentiation protein 2 (MD‐2). Crystal structure analysis suggested that 25HC could bind MD‐2 with high affinity into its hydrophobic pocket. Furthermore, LPS‐induced activation of Akt/NF‐κB pathway was partially down‐regulated by 25HC pretreatment. In summary, this study demonstrates that 25HC could inhibit the overwhelming inflammatory response through MD‐2 interaction, which suppresses Akt/NF‐κB signalling pathway. These findings suggest 25HC may be a promising candidate for ALI prevention.

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“…Because most cases develop within 2 to 5 days of hospitalization, 3 efforts to develop molecular-based therapies that interrupt the progression of ALI to ARDS is an attractive endeavor. 4 This article reviews ALI/ARDS, including current research in the molecular aspects and pathogenesis of ALI/ARDS.…”

mentioning

confidence: 99%

Acute Lung Injury: A Clinical and Molecular Review

Butt¹,

Kurdowska²,

Allen

2016

Archives of Pathology &Amp; Laboratory Medicine

702

447

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ARDS is primarily a clinicoradiologic diagnosis; however, lung biopsy plays an important diagnostic role in certain cases. A significant amount of progress has been made in the elucidation of ARDS pathophysiology and in predicting patient response, however, currently there is no viable predictive molecular biomarkers for predicting the severity of ARDS, or molecular-based ARDS therapies. The proinflammatory cytokines TNF-α (tumor necrosis factor α), interleukin (IL)-1β, IL-6, IL-8, and IL-18 are among the most promising as biomarkers for predicting morbidity and mortality.

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Emerging therapies for the prevention of acute respiratory distress syndrome

Cited by 28 publications

References 101 publications

Acute respiratory distress syndrome

Acute respiratory distress syndrome

25‐Hydroxycholesterol protects against acute lung injury via targeting MD‐2

Acute Lung Injury: A Clinical and Molecular Review

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