In Pursuit of Microbiome-based Therapies for Acute Respiratory Failure.
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ABSTRACT:
SUBMITTER: Ali F
PROVIDER: S-EPMC7737586 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The defining features of acute respiratory distress syndrome (ARDS) are an excessive inflammatory respiratory response associated with high morbidity and mortality. Treatment consists mainly of measures to avoid worsening lung injury and cannot reverse the underlying pathophysiological process. New pharmacological agents have shown promising results in preclinical studies; however, they have not been successfully translated to patients with ARDS. The lack of effective therapeutic interventions has resulted in a recent interest in strategies to prevent ARDS with treatments delivering medications directly to the lungs by inhalation and nebulization, hopefully minimizing systemic adverse events. We analyzed the effect of different aerosolized drugs such as bronchodilators, corticosteroids, pulmonary vasodilators, anticoagulants, mucolytics and surfactant. New therapeutic strategies and ongoing trials using carbon monoxide (CO) and AP301 peptide are also briefly reviewed.
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Project description:BackgroundThe recent pandemic highlights the essential nature of optimizing the use of invasive mechanical ventilation (IMV) in complex critical care settings. This review of reviews maps evidence-based practices (EBPs) that are associated with better outcomes among adult patients with acute respiratory failure or ARDS on the continuum of care, from intubation to liberation.Research questionWhat EPBs are recommended to reduce the duration of IMV and mortality rate among patients with acute respiratory failure/ARDS?Study design and methodsWe identified an initial set of reports that links EBPs to mortality rates and/or duration of IMV. We conducted a review of reviews, focusing on preappraised guidelines, meta-analyses, and systematic reviews. We searched Scopus, CINAHL, and PubMed from January 2016 to January 2019 for additional evidence that has not yet been incorporated into current guidelines.ResultsOur initial search produced 61 publications that contained 42 EBPs. We excluded 42 manuscripts during the data extraction process, primarily because they were not associated with improved patient outcomes. The remaining 19 preappraised guidelines, meta-analyses, and systematic reviews met our full inclusion criteria and spanned the continuum of IMV care from intubation to liberation. These contained 20 EBPs, a majority of which were supported with moderate levels of evidence. Of these, six EBPs focused on intubation and escalation of care, such as ventilator management and synchrony; ten EBPs reduced complications associated with IMV, which included spontaneous awakening and breathing trials and early mobility protocols; and four EBPs promoted timely extubation and postextubation recovery.InterpretationThis review describes EBPs that are associated with fewer ventilator days and/or lower mortality rates among patients who received IMV for acute respiratory failure/ARDS. Many of these EBPs are connected across the care continuum, which indicates the need to promote and assess effective implementation jointly, rather than individually.
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Project description:As the number of confirmed cases and resulting death toll of the COVID-19 pandemic continue to increase around the globe - especially with the emergence of new mutations of the SARS-CoV-2 virus in addition to the known alpha, beta, gamma, delta and omicron variants - tremendous efforts continue to be dedicated to the development of interventive therapeutics to mitigate infective symptoms or post-viral sequelae in individuals for which vaccines are not accessible, viable or effective in the prevention of illness. Many of these investigations aim to target the associated acute respiratory distress syndrome, or ARDS, which induces damage to lung epithelia and other physiologic systems and is associated with progression in severe cases. Recently, stem cell-based therapies have demonstrated preliminary efficacy against ARDS based on a number of preclinical and preliminary human safety studies, and based on promising outcomes are now being evaluated in phase II clinical trials for ARDS. A number of candidate stem cell therapies have been found to exhibit low immunogenicity, coupled with inherent tropism to injury sites. In recent studies, these have demonstrated the ability to modulate suppression of pro-inflammatory cytokine signals such as those characterizing COVID-19-associated ARDS. Present translational studies are aiming to optimize the safety, efficacy and delivery to fully validate stem cell-based strategies targeting COVID-19 associated ARDS for viable clinical application.
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Project description:We performed single cell RNAseq of liver cells in acute liver failure model in mice with different microbiome states to unravel cellular changes in the disease and the impact of gut microbiota on the physiology in this disease.
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Project description:Acute respiratory failure occurs in up to half of patients with haematological malignancies and 15% of those with solid tumours or solid organ transplantation. Mortality remains high. Factors associated with mortality include a need for invasive mechanical ventilation, organ dysfunction, older age, frailty or poor performance status, delayed intensive care unit admission, and acute respiratory failure due to an invasive fungal infection or unknown cause. In addition to appropriate antibacterial therapy, initial clinical management aims to restore oxygenation and predict the most probable cause based on variables related to the underlying disease, acute respiratory failure characteristics, and radiographic findings. The cause of acute respiratory failure must then be confirmed using the most efficient, least invasive, and safest diagnostic tests. In patients with acute respiratory failure of undetermined cause, a standardised diagnostic investigation should be done immediately at admission before deciding whether to perform more invasive diagnostic procedures or to start empirical treatments. Collaborative and multidisciplinary clinical and research networks are crucial to improve our understanding of disease pathogenesis and causation and to develop less invasive diagnostic strategies and more targeted treatment options.
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Project description:Acute hypoxic respiratory failure (AHRF) is associated with significant acute mortality. It is unclear whether later mortality is predominantly driven by pre-existing comorbid disease, the acute inciting event or is the result of AHRF itself.Observational cohort study of elderly US Health and Retirement Study (HRS) participants in fee-for-service Medicare (1998-2012). Patients hospitalised with AHRF were matched 1:1 to otherwise similar adults who were not currently hospitalised and separately to patients hospitalised with acute inciting events (pneumonia, non-pulmonary infection, aspiration, trauma, pancreatitis) that may result in AHRF, here termed at-risk hospitalisations. The primary outcome was late mortality-death in the 31 days to 2 years following hospital admission.Among 15?075?HRS participants, we identified 1268 AHRF and 13?117 at-risk hospitalisations. AHRF hospitalisations were matched to 1157 non-hospitalised adults and 1017 at-risk hospitalisations. Among patients who survived at least 30 days, AHRF was associated with a 24.4% (95%CI 19.9% to 28.9%, p<0.001) absolute increase in late mortality relative to adults not currently hospitalised and a 6.7% (95%CI 1.7% to 11.7%, p=0.01) increase relative to adults hospitalised with acute inciting event(s) alone. At-risk hospitalisation explained 71.2% of the increased odds of late mortality, whereas the development of AHRF itself explained 28.8%. Risk for death was equivalent to at-risk hospitalisation beyond 90?days, but remained elevated for more than 1?year compared with non-hospitalised controls.In this national sample of older Americans, approximately one in four survivors with AHRF had a late death not explained by pre-AHRF health status. More than 70% of this increased risk was associated with hospitalisation for acute inciting events, while 30% was associated with hypoxemic respiratory failure.
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Project description:The use of extracorporeal membrane oxygenation (ECMO) to support children with acute respiratory failure has steadily increased over the past several decades, with major advancements having been made in the care of these children. There are, however, many controversies regarding indications for initiating ECMO in this setting and the appropriate management strategies thereafter. Broad indications for ECMO include hypoxia, hypercarbia, and severe air leak syndrome, with hypoxia being the most common. There are many disease-specific considerations when evaluating children for ECMO, but there are currently very few, if any, absolute contraindications. Venovenous rather than veno-arterial ECMO cannulation is the preferred configuration for ECMO support of acute respiratory failure due to its superior side-effect profile. The approach to lung management on ECMO is variable and should be individualized to the patient, with the main goal of reducing the risk of VILI. ECMO is a relatively rare intervention, and there are likely a minimum number of cases per year at a given center to maintain competency. Patients who have prolonged ECMO runs (i.e., greater than 21 days) are less likely to survive, though no absolute duration of ECMO that would mandate withdrawal of ECMO support can be currently recommended.
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