Cell therapy for acute respiratory distress syndrome patients: the START study.
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ABSTRACT:
SUBMITTER: Cruz FF
PROVIDER: S-EPMC6560575 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
Cell therapy for acute respiratory distress syndrome patients: the START study.
Cruz Fernanda Ferreira FF Rocco Patricia Rieken Macedo PRM
Journal of thoracic disease 20190501 Suppl 9
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Project description:Acute respiratory distress syndrome (ARDS) is driven by a severe pro-inflammatory response resulting in lung damage, impaired gas exchange and severe respiratory failure. There is no specific treatment that effectively improves outcome in ARDS. However, in recent years, cell therapy has shown great promise in preclinical ARDS studies. A wide range of cells have been identified as potential candidates for use, among these are mesenchymal stromal cells (MSCs), which are adult multi-lineage cells that can modulate the immune response and enhance repair of damaged tissue. The therapeutic potential of MSC therapy for sepsis and ARDS has been demonstrated in multiple in vivo models. The therapeutic effect of these cells seems to be due to two different mechanisms; direct cellular interaction, and paracrine release of different soluble products such as extracellular vesicles (EVs)/exosomes. Different approaches have also been studied to enhance the therapeutic effect of these cells, such as the over-expression of anti-inflammatory or pro-reparative molecules. Several clinical trials (phase I and II) have already shown safety of MSCs in ARDS and other diseases. However, several translational issues still need to be addressed, such as the large-scale production of cells, and their potentiality and variability, before the therapeutic potential of stem cells therapies can be realized.
| S-EPMC6196176 | biostudies-literature
Project description:Prone position has been used in acute respiratory distress syndrome (ARDS) patients for more than 40 years in ICU. After having demonstrated its capability to significantly improve oxygenation in a large number of patients, sometimes dramatically, this procedure has been found to prevent ventilator-induced lung injury, the primary concern for the intensivists managing ARDS patients. Over the time, several trials have been done, which regularly improved and refined from each other. At the end, significant improvement in survival has been demonstrated in the most severe ARDS patients, at a threshold of 100-150 mmHg PaO2/FiO2 ratio. The effect of proning on survival cannot be predicted and seems unrelated with both severity of oxygenation impairment and oxygenation response to proning. The rate of complication is declining with the increase in centers expertise. The pressure sores are more frequent in prone and require a special attention. Prone position is a key component of lung protective mechanical ventilation and should be used as a first line therapy in association with low tidal volume and neuromuscular blocking agents in patients with severe ARDS.
| S-EPMC5537107 | biostudies-other
Project description: Not available
| S-EPMC3576439 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.
| S-EPMC8801611 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is a devastating hypoxemic respiratory failure, characterized by disruption of the alveolar-capillary membrane barrier. Current management for ARDS remains supportive, including lung-protective ventilation and a conservative fluid strategy. Mesenchymal stem cells (MSCs) have emerged as a potentially attractive candidate for the management of ARDS through facilitating lung tissue regeneration and repair by releasing paracrine soluble factors. Over the last decade, a variety of strategies have emerged to optimize MSC-based therapy. Among these, the strategy using genetically modified MSCs has received increased attention recently due to its distinct advantage, in conferring incremental migratory capacity and, enhancing the anti-inflammatory, immunomodulatory, angiogenic, and antifibrotic effects of these cells in numerous preclinical ARDS models, which may in turn provide additional benefits in the management of ARDS. Here, we provide an overview of recent studies testing the efficacy of genetically modified MSCs using preclinical models of ARDS.
| S-EPMC6915956 | biostudies-literature
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| S-EPMC7490973 | biostudies-literature
Project description:BackgroundMany patients confront physical, cognitive, and emotional problems after acute respiratory distress syndrome (ARDS). No proven therapies for these problems exist, and many patients manage new disability and recovery with little formal support. Eliciting patients' adaptations to these problems after hospitalization may identify opportunities to improve recovery.ObjectivesTo explore how patients adapt to physical, cognitive, and emotional changes related to hospitalization for ARDS.MethodsSemistructured interviews were conducted after hospitalization in patients with ARDS who had received mechanical ventilation. This was an ancillary study to a multicenter randomized controlled trial. Consecutive surviving patients who spoke English, consented to follow-up, and had been randomized between November 12, 2017, and April 5, 2018 were interviewed 9 to 16 months after that.ResultsForty-six of 79 eligible patients (58%) participated (mean [range] age, 55 [20-84] years). All patients reported using strategies to address physical, emotional, or cognitive problems after hospitalization. For physical and cognitive problems, patients reported accommodative strategies for adapting to new disabilities and recuperative strategies for recovering previous ability. For emotional issues, no clear distinction between accommodative and recuperative strategies emerged. Social support and previous familiarity with the health care system helped patients generate and use many strategies. Thirty-one of 46 patients reported at least 1 persistent problem for which they had no acceptable adaptation.ConclusionsPatients employed various strategies to manage problems after ARDS. More work is needed to identify and disseminate effective strategies to patients and their families.
| S-EPMC9214834 | biostudies-literature
Project description:Sepsis and acute respiratory distress syndrome (ARDS) are life threating diseases with high mortality and morbidity in all the critical care units around the world. After decades of research, and numerous pre-clinical and clinical trials, sepsis and ARDS remain without a specific and effective pharmacotherapy and essentially the management remains supportive. In the last years cell therapies gained potential as a therapeutic treatment for ARDS and sepsis. Based on numerous pre-clinical studies, there is a growing evidence of the potential benefits of cell based therapies for the treatment of sepsis and ARDS. Several cell types are used in the last years for the treatment of both syndromes showing high efficiency. Embryonic stem cells (ESC), multipotent stem (or stromal) cells (MSC) and epithelial progenitors cells (EpPC) have been used for both diseases. Nowadays, the major part of the pre-clinical studies are using MSC, however other relevant groups are also using induced pluripotent stem cells (iPSC) for the treatment of both syndromes and alveolar type II cells for ARDS treatment. Numerous questions need further study including: determining the best source for the progenitor cells isolation, their large scale production and cryopreservation. Also, the heterogeneity of patients with sepsis and ARDS is massive, and establish a target population or the stratification of the patients will help us to determine better the therapeutic effect of these cell therapies. In this review we are going to describe briefly the different cell types, their potential sources and characteristics and mechanism of action. Here, also we elucidate the results of several pre-clicinical and clinical studies in ARDS and in sepsis and the future directions of these studies.
| S-EPMC5721220 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is a heterogeneous form of acute, diffuse lung injury that is characterized by dysregulated inflammation, increased alveolar-capillary interface permeability, and non-cardiogenic pulmonary edema. In the general population, the incidence and mortality associated with ARDS over the last two decades have steadily declined in parallel with optimized approaches to pneumonia and other underlying causes of ARDS as well as increased utilization of multimodal treatment strategies that include lung-protective ventilation. In the cancer settings, significant declines in the incidence and mortality of ARDS over the past two decades have also been reported, although these rates remain significantly higher than those in the general population. Epidemiologic studies identify infection, including disseminated fungal pneumonias, as a major underlying cause of ARDS in the cancer setting. More than half of cancer patients who develop ARDS will not survive to hospital discharge. Those who do survive often face a protracted and often incomplete recovery, resulting in significant long-term physical, psychological, and cognitive sequelae. The residual organ dysfunction and poor functional status after ARDS may delay or preclude subsequent cancer treatments. As such, close collaboration between the critical care physicians and oncology team is essential in identifying and reversing the underlying causes and optimizing treatments for cancer patients with ARDS. This chapter reviews the diagnosis and common causes of ARDS in cancer and gives an update on the general management principles for cancer patients with ARDS in the ICU.
| S-EPMC7123590 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS), a fatal critical disease, is induced by various insults. ARDS represents a major global public health burden, and the management of ARDS continues to challenge healthcare systems globally, especially during the pandemic of the coronavirus disease 2019 (COVID-19). There remains no confirmed specific pharmacotherapy for ARDS, despite advances in understanding its pathophysiology. Debate continues about the potential role of glucocorticoids (GCs) as a promising ARDS clinical therapy. Questions regarding GC agent, dose, and duration in patients with ARDS need to be answered, because of substantial variations in GC administration regimens across studies. ARDS heterogeneity likely affects the therapeutic actions of exogenous GCs. This review includes progress in determining the GC mechanisms of action and clinical applications in ARDS, especially during the COVID-19 pandemic.
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