Abstract Rationale ARDS survivors frequently experience long-term disability from ICU-acquired weakness (ICUAW). Prior studies implicate monocyte-driven inflammation in severe and prolonged ARDS, but post-discharge immune trajectories and their relationship to physical recovery remain unclear. Methods We conducted a nested case-control study within an ongoing prospective multicenter study of ARDS survivors. Sixteen ARDS survivors with ICUAW at hospital discharge were sampled 1:1 based on 3-month physical recovery status, defined as no new disability relative to pre-hospitalization activities of daily living (ADLs), instrumental ADLs, and mobility. Matching was performed on demographics, comorbidity burden, and ARDS severity. Six-minute walk distance (6MWD), short physical performance battery (SPPB), and hand-grip strength were measured at hospital discharge and 3 months. Plasma cytokines were quantified at both time points using a 71-plex immunoassay. We evaluated cross-sectional and longitudinal associations of cytokines with recovery status, defining statistical significance as p 0.05 (exploratory; no multiple-comparison correction). Results Non-recovered and recovered groups had non-significant differences in age (median IQR 63 40-66 vs. 50 32-66 years, p = 0.60), Charlson comorbidity burden (0.5 0-2 vs. 1 0.5-2, p = 0.60), initial ARDS severity (PaO2/FiO2 147 74-199 vs. 139 78-203, p = 0.87; SOFA 13 8-17 vs. 12 11-13, p = 0.71), and hospital length of stay (21 10-29 vs. 20 18-32 days, p = 0.60). At hospital discharge, most patients had difficulty standing; non-recovered vs. recovered groups had low percent-predicted 6MWD (0 0-13 vs. 59 0-88, p = 0.12), SPPB (1 0-6 vs. 3 1-7, p = 0.45), and weak grip (100% vs. 75%, p = 0.47). At 3 months, non-recovered survivors had worse performance than recovered survivors: lower percent-predicted 6MWD (8 0-49 vs. 65 60-75, p 0.01), lower SPPB (5 1-7 vs. 11 9-12, p 0.01), and a higher prevalence of weak grip (75% vs. 12.5%, p = 0.04). Thirteen cytokines were significantly higher in non-recovered survivors at hospital discharge and seven at 3-month follow-up; none were statistically significantly lower. At hospital discharge, elevations predominantly reflected monocyte/neutrophil activation (IL-1α, MIP-1α, IL-17A, G-CSF). By 3 months, these differences were no longer significant, but other inflammatory cytokines associated with monocyte activation were significantly higher in non-recovered survivors (IL-6, MIP-1δ, IL-1RA, CXCL1). Conclusions Among ARDS survivors with ICU-acquired weakness at hospital discharge, impaired 3-month physical recovery is associated with persistent inflammation, particularly via monocyte- and neutrophil-linked pathways. These exploratory findings support the evaluation of immunomodulatory strategies targeting these pathways to improve long-term physical recovery after ARDS. This abstract is funded by: NHLBI R01 HL 164777
Paul et al. (Fri,) studied this question.