230 - Plasma ASC, Caspase-1, and IL-18 Levels are Elevated in Preterm Infants Developing Bronchopulmonary Dysplasia

Publication Number: 230.6430

Natalie Starke, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Naga Venkata Divya Challa, University of Alabama School of Medicine, Pike Road, AL, United States; Huijun Yuan, University of Miami Medical Center, MIAMI, FL, United States; Shaoyi Chen, University of Miami, Miller school of Medicine, Miami, FL, United States; Matthew Duncan, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Erika de la Rosa Mistica Cabrera Ranaldi, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Juan Pablo de Rivero Vaccari, University of Miami, Miami, FL, United States; Alini Schott, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Ana Cecilia. Aguilar, University of Miami, Miami, FL, United States; Merline Benny, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Augusto Schmidt, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Karen C. Young, Division of Neonatology, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United States; Nelson Claure, University of Miami Leonard M. Miller School of Medicine, Miami, FL, United States; Shu Wu, University of Miami School of Medicine, Miami, FL, United States

Background: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm infants. Inflammasomes are multi-protein complexes that activate caspase-1, which results in proteolytic cleavage of gasdermin D. This leads to pyroptosis and cellular release of active IL-1beta and active IL-18, causing inflammation. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly and activation of caspase-1.

Objective: Our objective was to determine if earlier elevation of inflammasomes is associated with subsequent development of BPD in preterm infants.

Design/Methods: We prospectively enrolled 48 preterm infants born between 23-29 weeks gestational age. BPD was diagnosed at 36 weeks postmenstrual age (PMA) with the NICHD definitions. BPD was defined as the need for FiO2 at 36 weeks PMA and subdivided into mild BPD (FiO2=21%), moderate BPD (21%< FiO2 < 30%), and severe BPD (FiO2≥30% and/or positive pressure support). We included moderate and severe BPD infants in the BPD group and mild BPD and others in the non (n) BPD group. We assessed expression profiles of plasma ASC, caspase-1, IL-18, and IL-1beta using Ella Simple Plex in these infants on the day of life 7. We also performed receiver operating characteristic curve (ROC) analysis to determine the predictive potentials of these factors as biomarkers for BPD. Data are presented as mean ± SD and analyzed by t-test. P< 0.05 is considered significant.

Results: There were 28 infants in the nBPD group and 20 infants in the BPD group. The BPD infants were born earlier, had lower birth weights, and required longer oxygen therapy (Table 1). The BPD infants had higher ASC compared to nBPD infants (2125.5 ± 1044 vs.1342.2 ± 582, P=0.0052). The ASC’s potential as a BPD biomarker had an AUC of 0.8 (95% CI, 0.64 to 0.95, P=0.004). The caspase-1 levels were higher in the BPD infants than nBPD infants (42.2 ± 46.9 vs. 17.9 ± 14.4, P=0.029). The caspase-1’s potential as a BPD marker had an AUC of 0.68 (95% CI, 0.51-0.85, P=0.048). The IL-18 levels were also higher in BPD infants (241.9 ± 128.7 vs. 160.4 ± 93.8, P=0.024). The IL-18’s potential as a BPD marker had an AUC of 0.72 (95% CI, 0.55-0.88, P=0.016). There was no difference in IL-1beta levels between BPD and nBPD infants.

Conclusion(s): To the best of our knowledge, we are the first to show that BPD infants have higher levels of ASC, caspase-1, and IL-18 in their plasma compared to nBPD infants at day of life 7. We also found that these three factors have the potential to serve as biomarkers for BPD development.

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