Abstract Rationale Acute respiratory failure is highly heterogeneous and better understanding this heterogeneity through protein biomarkers can help predict clinical outcomes. Heat moisture exchange (HME) filter fluid (HMEF) has been shown to accurately represent airspace proteins, presenting a non-invasive alternative to bronchoalveolar lavage. Urine biospecimens provide another accessible and non-invasive means to evaluate systemic protein biomarker expression that may be more strongly associated with multi-organ failure free days (OFFD). We sought to understand the associations between urine and HMEF/urine biomarker ratios with OFFDs in individuals with acute respiratory failure. Methods HME filters were placed in-line for 4 (±1) hours and were collected from 53 patients who had been mechanically ventilated for less than 72 hours. Urine biospecimens were collected at the end of the HME filter dwell period in patients with an indwelling urinary catheter. Ella™, a multi-analyte immunoassay platform, was used to measure interleukin-8 (IL-8) and tumor necrosis factor receptor-1 (TNFR1) in HME and urine and angiopoietin-2 (ANG-2) and interleukin-6 (IL-6) in urine. Total protein was determined by bicinchoninic acid assay. EHR data were used to determine OFFD, defined as days without advanced cardiovascular, renal, or respiratory support. OFFD were grouped into 3 categories. Study participants were categorized as acute respiratory distress syndrome (ARDS) (n = 24), Pneumonia (n = 16), other ARDS risk factors (Other) (n = 10), or Control (n = 3). Biomarker concentrations were compared between ARDS, Pneumonia, and Other using Mann-Whitney Test. Unadjusted associations of log-transformed urine biomarker and HMEF/urine biomarker ratios with OFFD category were evaluated by ordinal logistic regression. Results We report demographic data, clinical outcomes, and biomarker concentrations in Table 1. Median P/F ratio was lower in ARDS than Pneumonia and Other cohort subgroups. There were no significant differences in urine biomarker expression of IL-8, TNFR-1, ANG-2, or IL-6 between cohort subgroups (ARDS and Pneumonia or ARDS and Other). Higher urine TNFR-1 was significantly associated with worse OFFD category (OR 1.63, 95% CI 1.08-2.55, p = 0.023). HMEF/urine biomarker ratios were not found to have statistically significant differences between cohort subgroups and were not associated with OFFD. Conclusions HMEF and urine biospecimens are useful in identifying inflammatory biomarkers. Although urine TNFR-1 appears to be associated with OFFD category, a larger cohort is needed to better delineate a potential predictive role for TNFR-1 and other urine and HMEF biomarkers. The value of biomarker expression trajectory in HMEF and urine was not assessed in this study but may provide additional insight into clinical trajectories. This abstract is funded by: University of Colorado
Murphy et al. (2026) studied this question.