Peripheral blood leukocyte PGLYRP1 mRNA as a candidate marker of subsequent acute respiratory distress syndrome in sepsis: a retrospective cohort study

Neutrophil-related host responses are prominent in sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether peripheral blood leukocyte peptidoglycan recognition protein 1 (PGLYRP1) mRNA, sampled within 2 h of intensive care unit (ICU) admission, was associated with subsequent ARDS and added discrimination to admission clinical variables. This single-center retrospective cohort study included 202 adults with sepsis who had no ARDS at admission sampling. PGLYRP1 mRNA expression was measured by reverse-transcription quantitative PCR in peripheral blood leukocytes from samples collected within 2 h of ICU admission. Multivariable logistic regression assessed the association between log₂-transformed PGLYRP1 expression and ARDS documented during the ICU stay, adjusting for age, sex, pulmonary infection, septic shock and admission Sequential Organ Failure Assessment (SOFA) score. Discrimination, calibration, Brier scores and decision curves were assessed. Internal validation used 1000 bootstrap resamples and 10-fold cross-validation repeated ten times. During the ICU stay, 86 patients developed ARDS. Median PGLYRP1 mRNA expression was 18.91 (interquartile range, 12.16–32.16) in patients who developed ARDS and 10.57 (7.63–15.24) in those who did not (P < 0.001). Each doubling of PGLYRP1 expression was associated with higher odds of subsequent ARDS (adjusted odds ratio, 3.572; 95% confidence interval, 2.179–5.854; P < 0.001). Apparent areas under the receiver operating characteristic curve (AUCs) were 0.792 for PGLYRP1, 0.719 for the clinical model and 0.818 for the combined model. The combined model had a higher apparent AUC than the clinical model (ΔAUC = 0.0989; P < 0.001), while its difference from PGLYRP1 alone was not statistically significant (ΔAUC = 0.0265; P = 0.122). The combined model’s bootstrap optimism-corrected and mean cross-validated AUCs were 0.797 and 0.790, respectively. PGLYRP1 mRNA expression in peripheral blood leukocytes was associated with subsequent ARDS after adjustment for admission SOFA and the other selected clinical covariates. Adding PGLYRP1 improved apparent discrimination compared with the selected clinical model, while the combined model did not significantly outperform PGLYRP1 alone. These exploratory findings warrant prospective multicenter validation and evaluation of clinical impact. Not applicable.