Noel Britton

Introduction: Previous work has described impaired long-term functional recovery in survivors of acute hypoxemic respiratory failure (AHRF) including patients who were managed on ECMO. Aims: We sought to determine whether the functional recovery of patients with AHRF managed with veno-venous ECMO (VV-ECMO) differs from patients who did not receive ECMO. Methods: We conducted a multi-center retrospective cohort study of adults cannulated for VV-ECMO or admitted to the ICU for AHRF. Enrolled patients presented to ICU follow-up clinic between April 2020 and January 2023. Hospital Anxiety and Depression Scale (HADS), PCL-5, and Montreal Cognitive Assessment (MoCA), PFTs, and 6-minute walk test (6MWT) were obtained at follow-up. Results: Sixty-four patients were included in this analysis, 34 received VV-ECMO and 30 did not (non-ECMO). ECMO patients were younger (35 v. 50 years, p<0.01), had a higher SOFA score (6 v. 4, p<0.01) and were less likely to have COVID-19 (58 v. 90%, p<0.01). ECMO patients had a significantly longer median duration of hospitalization (46 v. 22 days, p<0.01), ICU stay (29 v. 14 days, p<0.01), and mechanical ventilation (21 v. 12 days, p <0.04). At follow-up, there was no difference in HADS, PCL-5, or MOCA between the ECMO and non-ECMO group. There were no significant differences in pulmonary function tests or 6MWT when comparing the ECMO to non-ECMO patients after adjusting for potential confounders. This remained true in a subgroup analysis of patients with COVID-19. Conclusion: Potentially relevant to resource allocation and prognostication, we found no difference in functional recovery when comparing AHRF patients managed with and without VV-ECMO.

Background: Isolation of Pseudomonas aeruginosa ( PsA ) is associated with increased BAL (bronchoalveolar lavage) inflammation and lung allograft injury in lung transplant recipients (LTR). However, the effect of PsA on macrophage responses in this population is incompletely understood. We examined human alveolar macrophage (AM) responses to PsA and Pseudomonas dominant microbiome in healthy lung transplant recipients (LTR). Methods: We stimulated THP-1 derived macrophages (THP-1M) and human AM from LTR with different bacteria and LTR BAL derived microbiome characterized as Pseudomonas-dominant. Macrophage responses were assessed by high dimensional flow cytometry, including their intracellular production of cytokines (TNF-α, IL-6, IL-8, IL-1β, IL-10, IL-1RA, and TGF-β). Pharmacological inhibitors were utilized to evaluate the role of the inflammasome in PsA -macrophages interaction. Results: We observed upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-1β) following stimulation by PsA compared to other bacteria ( Staphylococcus aureus, Prevotella melaninogenica, Streptococcus pneumoniae ) in both THP-1 derived and LTR AM, predominated by IL-1β. IL-1β production from THP-1 was sustained after PsA stimulation for up to 96 hours and 48 hours in LTR AM. Treatment with the inflammasome inhibitor BAY11-7082 abrogated macrophage IL-1β and IL-18 production after PsA exposure. BAL Pseudom onas-dominant microbiota elicited an increased IL-1β, similar to PsA , an effect abrogated by the addition of antibiotics. Conclusion: PsA and PsA -dominant lung microbiota induce sustained IL-1β production in LTR AM. Pharmacological targeting of the inflammasome reduces PsA -macrophage-IL1β responses, underscoring their use in lung transplant recipients.