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Biomarkers for Adverse Lung Injury Following Pediatric Cardiopulmonary Bypass
Ahmed Asfari1, Kristal M Hock1, Jonathan W Byrnes1
1Department of Pediatric Cardiology, Section of Cardiac Critical Care, University of Alabama at Birmingham, Birmingham, AL.
Insights
Proteomic analysis identified serum protein biomarkers associated with lung injury after cardiac surgery. These biomarkers may help predict respiratory complications and understand their underlying mechanisms.
Area of Science:
- Biomarker discovery
- Proteomics
- Cardiac surgery outcomes
Background:
- Cardiopulmonary bypass (CPB) can cause systemic inflammation and lung injury, often necessitating prolonged mechanical ventilation.
- Predictive biomarkers are needed to identify patients at risk for these CPB-related complications.
- This study aimed to identify serum protein biomarkers for predicting lung injury severity post-cardiac surgery.
Observation:
- A retrospective chart review and unbiased proteomic analysis using mass spectrometry were conducted on plasma samples from infants undergoing complex cardiac surgery.
- Patients were divided into two groups: prolonged mechanical ventilation (>48 hours) and shorter ventilation (<48 hours), matched for age, weight, and CPB duration.
- Proteomic analysis identified hundreds of proteins, with significant differences noted at pre-CPB, 0-hour, and 48-hour post-CPB time points.
Findings:
- Several proteins, including tenascin, hemoglobin beta, and proteoglycan 4, were significantly elevated or decreased at different time points relative to ventilation duration.
- Pathway analysis revealed cytoskeleton remodeling, immune response, and blood coagulation as key affected biological processes.
- Proteoglycan 4 was validated as a potential biomarker using enzyme-linked immunosorbent assay (ELISA).
Implications:
- Proteomic biomarkers identified pre-CPB may indicate pre-existing risk factors, such as coagulation abnormalities.
- Biomarkers found at 0 and 48 hours post-CPB could reflect the ongoing mechanisms of lung injury.
- These findings suggest potential for novel diagnostic tools to manage respiratory complications after cardiac surgery.
Abstract:
Cardiopulmonary bypass triggers systemic inflammation, resulting in lung injury, and frequently leads to prolonged mechanical ventilation. Biomarkers of systemic inflammation are required to predict the risk of such complications. We hypothesize that specific serum proteins can be used as biomarkers to predict the severity of lung injury following cardiac surgery.
Design:
Retrospective chart review study.
Setting:
Clinical variables were collected and used in conjuncture with unbiased proteomic analysis using mass spectrometry that was performed on frozen plasma samples from a study group (patients with mechanical ventilation > 48 hr post surgery) and a control group (patients with mechanical ventilation < 48 hr post surgery).
Subjects:
Subjects included were infants who underwent cardiac surgery with similar complexity (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery 3 or 4) using cardiopulmonary bypass. Patients in both groups were matched for their weight, age, and duration of cardiopulmonary bypass.
Intervention:
None.
Measurements And Main Results:
Four-hundred eighty-three proteins were identified (99% minimum confidence and two peptides minimum, protein false discovery rate 0.1%) on proteomic analysis of four control and four study patients at precardiopulmonary bypass, 0, and 48 hours postcardiopulmonary bypass samples. Thirty-six of 178 proteins were significantly different (≥ 1.5-fold; p < 0.05) at precardiopulmonary bypass (top increased: tenascin; top decreased: tetranectin), 18 of 140 proteins at 0 hour (top increased: hemoglobin beta; top decreased: C8 beta), and 25 of 166 proteins at 48 hours post surgery (top increased: proteoglycan 4; top decreased: galectin-3-binding protein). The top pathway involved cytoskeleton remodeling. Other pathways involved immune response and blood coagulation. Proteoglycan 4 was validated by enzyme-linked immunosorbent assay in a different set of samples (n = 20/group; mean ± sd: 128 ± 67 vs 195 ± 160 ng/mL) (p = 0.037).
Conclusions:
Multiple proteomic biomarkers were associated with worse respiratory outcomes. Precardiopulmonary bypass biomarkers might indicate risk factors (e.g., abnormalities of coagulation), whereas those identified at 0 hour and post cardiopulmonary bypass may reflect mechanisms of ongoing pathobiology.
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