Distinct profiles of host responses between plasma and lower respiratory tract during acute respiratory failure

Abstract

Current plasma-based subphenotyping approaches in acute respiratory failure represent host responses at a systemic level but do not capture important differences in lower respiratory tract biology https://bit.ly/40kTdDG.

FIGURE 1

Lower respiratory tract biomarker levels discriminate types of acute respiratory failure (ARF) and constitute distinct host-response profiles compared to plasma biomarkers. a) Plasma and endotracheal aspirate (ETA) soluble receptor for advanced glycation end-products (sRAGE) discriminate ARF clinical categories (acute respiratory distress syndrome (ARDS), at-risk for ARDS, congestive heart failure (CHF) or airway controls (patients intubated for airway protection)). CHF and airway controls were included as a control group with expected low levels of lower respiratory tract inflammation compared to subjects with lung injury (ARDS and at-risk for ARDS). b and c) Depicted correlograms represent pairwise correlations of plasma and ETA biomarkers (raw) with Pearson's correlation test, adjusted for multiple comparisons with the Benjamini–Hochberg method. Significant correlations (positive in red and negative in blue) are shown. Results were similar when we analysed total protein and urea-normalised ETA biomarker values. d) Comparison of log₂ differences in ETA-plasma biomarker ratios (estimated by the following equation: biomarker ratio=log₂(biomarker_ETA/urea_ETA)/(biomarker_plasma/urea_plasma)). Pentraxin-3, interleukin (IL)-8 and IL-6 were significantly enriched in ETA samples, whereas procalcitonin, angiotensin (Ang)-2 and soluble suppressor of tumorigenicity (sST)2 were enriched in plasma samples. We did not obtain analysable urea values in coronavirus disease 2019 (COVID-19) subjects due to interference of the DNA/RNA Shield solution with the colorimetric urea assays. sTNFR: soluble tumour necrosis factor receptor.