Browsing by Subject "Respiratory Distress Syndrome"

Now showing 1 - 5 of 5
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    Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome.
    (Journal of translational medicine, 2020-11) Norton, Dustin L; Ceppe, Agathe; Tune, Miriya K; McCravy, Matthew; Devlin, Thomas; Drummond, M Bradley; Carson, Shannon S; Vincent, Benjamin G; Hagan, Robert S; Dang, Hong; Doerschuk, Claire M; Mock, Jason R

    Background

    Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples.

    Methods

    We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs.

    Results

    The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood.

    Conclusion

    Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.
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    Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome.
    (Stem cells translational medicine, 2020-09) Qu, Wenchun; Wang, Zhen; Hare, Joshua M; Bu, Guojun; Mallea, Jorge M; Pascual, Jorge M; Caplan, Arnold I; Kurtzberg, Joanne; Zubair, Abba C; Kubrova, Eva; Engelberg-Cook, Erica; Nayfeh, Tarek; Shah, Vishal P; Hill, James C; Wolf, Michael E; Prokop, Larry J; Murad, M Hassan; Sanfilippo, Fred P
    Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2 /FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.
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    Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.
    (Stem cells translational medicine, 2022-07) Qu, Wenchun; Wang, Zhen; Engelberg-Cook, Erica; Yan, Dan; Siddik, Abu Bakar; Bu, Guojun; Allickson, Julie G; Kubrova, Eva; Caplan, Arnold I; Hare, Joshua M; Ricordi, Camillo; Pepine, Carl J; Kurtzberg, Joanne; Pascual, Jorge M; Mallea, Jorge M; Rodriguez, Ricardo L; Nayfeh, Tarek; Saadi, Samer; Durvasula, Ravindra V; Richards, Elaine M; March, Keith; Sanfilippo, Fred P
    MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I  2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I  2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.
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    Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms.
    (Critical care (London, England), 2019-11) Sasannejad, Cina; Ely, E Wesley; Lahiri, Shouri
    Acute respiratory distress syndrome (ARDS) survivors experience a high prevalence of cognitive impairment with concomitantly impaired functional status and quality of life, often persisting months after hospital discharge. In this review, we explore the pathophysiological mechanisms underlying cognitive impairment following ARDS, the interrelations between mechanisms and risk factors, and interventions that may mitigate the risk of cognitive impairment. Risk factors for cognitive decline following ARDS include pre-existing cognitive impairment, neurological injury, delirium, mechanical ventilation, prolonged exposure to sedating medications, sepsis, systemic inflammation, and environmental factors in the intensive care unit, which can co-occur synergistically in various combinations. Detection and characterization of pre-existing cognitive impairment imparts challenges in clinical management and longitudinal outcome study enrollment. Patients with brain injury who experience ARDS constitute a distinct population with a particular combination of risk factors and pathophysiological mechanisms: considerations raised by brain injury include neurogenic pulmonary edema, differences in sympathetic activation and cholinergic transmission, effects of positive end-expiratory pressure on cerebral microcirculation and intracranial pressure, and sensitivity to vasopressor use and volume status. The blood-brain barrier represents a physiological interface at which multiple mechanisms of cognitive impairment interact, as acute blood-brain barrier weakening from mechanical ventilation and systemic inflammation can compound existing chronic blood-brain barrier dysfunction from Alzheimer's-type pathophysiology, rendering the brain vulnerable to both amyloid-beta accumulation and cytokine-mediated hippocampal damage. Although some contributory elements, such as the presenting brain injury or pre-existing cognitive impairment, may be irreversible, interventions such as minimizing mechanical ventilation tidal volume, minimizing duration of exposure to sedating medications, maintaining hemodynamic stability, optimizing fluid balance, and implementing bundles to enhance patient care help dramatically to reduce duration of delirium and may help prevent acquisition of long-term cognitive impairment.
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    Utilization of Brain Tissue Oxygenation Monitoring and Association with Mortality Following Severe Traumatic Brain Injury.
    (Neurocritical care, 2022-04) Komisarow, Jordan M; Toro, Camilo; Curley, Jonathan; Mills, Brianna; Cho, Christopher; Simo, Georges Motchoffo; Vavilala, Monica S; Laskowitz, Daniel T; James, Michael L; Mathew, Joseph P; Hernandez, Adrian; Sampson, John; Ohnuma, Tetsu; Krishnamoorthy, Vijay

    Background

    The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity.

    Methods

    We conducted a retrospective cohort study of patients from United States trauma centers participating in the American College of Surgeons National Trauma Databank between 2008 and 2016. We examined patients with severe TBI (defined by admission Glasgow Coma Scale score ≤ 8) over the age of 18 years who survived more than 24 h from admission and required intracranial pressure (ICP) monitoring. The primary exposure was PbtO2 monitor placement. The primary outcome was hospital mortality, defined as death during the hospitalization or discharge to hospice. Secondary outcomes were examined to determine the association of PbtO2 monitoring with health care use and pulmonary toxicity and included the following: (1) intensive care unit length of stay, (2) hospital length of stay, and (3) development of acute respiratory distress syndrome (ARDS). Regression analysis was used to assess differences in outcomes between patients exposed to PbtO2 monitor placement and those without exposure by using propensity weighting to address selection bias due to the nonrandom allocation of treatment groups and patient dropout.

    Results

    A total of 35,501 patients underwent placement of an ICP monitor. There were 1,346 (3.8%) patients who also underwent PbtO2 monitor placement, with significant variation regarding calendar year and hospital. Patients who underwent placement of a PbtO2 monitor had a crude in-hospital mortality of 31.1%, compared with 33.5% in patients who only underwent placement of an ICP monitor (adjusted risk ratio 0.84, 95% confidence interval 0.76-0.93). The development of the ARDS was comparable between patients who underwent placement of a PbtO2 monitor and patients who only underwent placement of an ICP monitor (9.2% vs. 9.8%, adjusted risk ratio 0.89, 95% confidence interval 0.73-1.09).

    Conclusions

    PbtO2 monitor utilization varied widely throughout the study period by calendar year and hospital. PbtO2 monitoring in addition to ICP monitoring, compared with ICP monitoring alone, was associated with a decreased in-hospital mortality, a longer length of stay, and a similar risk of ARDS. These findings provide further guidance for clinicians caring for patients with severe TBI while awaiting completion of further randomized controlled trials.