Browsing by Author "Ceppe, Agathe"

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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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    Posttraumatic Stress Disorder Symptom Clusters in Surrogate Decision Makers of Patients Experiencing Chronic Critical Illness.
    (Critical care explorations, 2022-03) Wendlandt, Blair; Ceppe, Agathe; Gaynes, Bradley N; Cox, Christopher E; Hanson, Laura C; Nelson, Judith E; Carson, Shannon S
    Symptoms of posttraumatic stress disorder (PTSD) are common among surrogate decision makers of patients with chronic critical illness (CCI). PTSD symptoms can be categorized into clusters including intrusion, avoidance, and hyperarousal, each of which has been associated with distinct outcomes and treatment responses. Our objective was to determine which symptom cluster was predominant among surrogates of patients with CCI.

    Design

    Secondary analysis of data from a clinical trial of a communication intervention.

    Setting

    The original trial was conducted in medical intensive care units at three tertiary-care centers and one community hospital.

    Patients

    Patients with CCI (≥7 d of mechanical ventilation and not expected to die or to be weaned from the ventilator in the subsequent 72 hr) and their surrogates.

    Interventions

    None.

    Measurements and main results

    Surrogate PTSD symptoms were measured 90 days after onset of patient CCI using the Impact of Events Scale-Revised (IES-R). The IES-R includes a total score (range, 0-88, higher scores indicate severe symptoms) as well as three subscales that assess intrusion, avoidance, and hyperarousal (range of intrusion and avoidance scores 0-32 and range of hyperarousal score 0-24). Intrusion symptoms were most severe (mean score, 10.3; 95% CI, 9.3-11.2), followed by avoidance (mean score, 8.0; 95% CI, 7.2-8.8). Hyperarousal symptoms were lowest (mean score, 5.1; 95% CI, 4.5-5.7). In a multivariable linear regression model, we found that surrogates of patients who died had higher odds of intrusion (β, 5.52; p < 0.0001) and avoidance (β, 3.29; p = 0.001) symptoms than surrogates of patients who lived, even after adjusting for baseline symptoms of anxiety and depression. Patient death was not associated with hyperarousal symptoms.

    Conclusions

    Intrusive thoughts are the most severe PTSD symptom in surrogates of patients experiencing CCI, with intensified symptoms among surrogates of patients who died. These results have the potential to inform tailored treatment strategies to reduce PTSD symptoms in this population.