Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery

Ahmed Asfari; Erica A Doyle; Gregory D Jay; Natalia Aristizabal; Ananya Manchikalapati; A K M Fazlur Rahman; Kristal M Hock; Santiago Borasino; Namasivayam Ambalavanan; Tannin A Schmidt; Leslie A Rhodes

doi:10.21037/tp-23-194

Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery

Transl Pediatr. 2023 Sep 18;12(9):1668-1675. doi: 10.21037/tp-23-194. Epub 2023 Sep 11.

Affiliations

¹ Section of Cardiac Critical Care, Division of Cardiology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
² Biomedical Engineering Department, School of Dental Medicine, UConn Health, Farmington, CT, USA.
³ Department of Emergency Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
⁴ School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁵ Division of Critical Care, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
⁷ Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Abstract

Background: Identification of biological molecules related to post cardiopulmonary bypass (CPB) lung injury could help diagnose, predict and potentially impact patient's clinical course after cardiac surgery. Proteoglycan 4 (PRG4) initially identified as potential biomarker for patients with prolonged mechanical ventilation following CPB in a prior study. To further validate these findings, we sought to understand the association of lower plasma PRG4 with prolonged mechanical ventilation and worse lung compliance in a larger cohort of pediatric patients post CPB.

Methods: Retrospective chart review study. Pediatric Cardiac Intensive Care Unit, Tertiary Hospital. Infants <1 year old with tetralogy of Fallot, ventricular septal defect, or atrioventricular septal defect who underwent surgical repair 2012-2020 and had stored plasma samples in our biorepository were screened for inclusion. Patients with mechanical ventilation before surgery were excluded. Patients were divided into quartiles based on postoperative duration of mechanical ventilation (control <25^th percentile, study >75^th percentile). Preoperative and 48-hour postoperative samples for each cohort (20 patients each) were tested for PRG4 level using enzyme-linked immunosorbent assay (ELISA) technique.

Results: Study group had lower lung compliance, higher mean airway pressure and higher oxygen need postoperative when compared to control group. Plasma PRG4 levels before surgery and 48 hours postoperative were lower in study group compared to control group (P=0.0232 preoperative; P=0.0016 postoperative). Plasma PRG4 levels were compared preoperative to PRG4 levels postoperative in both group, there was no statistically significant difference (study group: P=0.0869; control group: P=0.6500).

Conclusions: Lower levels of plasma PRG4 is associated with longer duration of mechanical ventilation, worse ventilator compliance and higher oxygen requirement after cardiac surgery in our patient population. Further validation of this finding in a larger and more diverse patient population is necessary prior to its application at the bedside.

Keywords: Acute lung injury (ALI); biomarkers; infants; pediatric cardiac surgery; proteoglycan 4 (PRG4).