383 - Grade 3 Bronchopulmonary Dysplasia Mechanical Ventilation Weaning Classifications

Publication Number: 1367.383

Matthew Kielt, Nationwide Children's Hospital, Columbus, OH, United States; Jonathan L. Slaughter, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, United States; Yi Jin, Nationwide Children's Hospital, Columbus, OH, United States; Khushboo Gupta, Nationwide Children's Hospital, Dublin, OH, United States; Erik Jensen, Stanford University School of Medicine, Palo Alto, CA, United States; Leif D. Nelin, Nationwide Children's Hospital, Columbus, OH, United States

Background: Ventilator-dependent infants with bronchopulmonary dysplasia (grade 3 BPD) demonstrate marked variability in the time required to wean from mechanical ventilation (MV). MV weaning classifications that discriminate high- versus low-risk infants with grade 3 BPD are not well characterized.

Objective: Primary: To characterize clinical MV weaning classifications in infants with grade 3 BPD. Secondary: To identify exploratory biomarkers that correlate with time-to-wean from MV in infants with grade 3 BPD.

Design/Methods: This is a retrospective cohort study of infants born < 32 weeks' GA with grade 3 BPD admitted to our BPD unit from 1/2010-9/2022. Successful weaning was defined as liberation from MV with no subsequent reintubations outside of elective surgical procedures. Cumulative incidence analysis was used, with censoring performed for the competing risk of death, to classify subjects who were simple- versus difficult-to-wean from MV. An exploratory analysis was performed to evaluate the Pearson correlation of tracheal and plasma levels of inflammatory cytokines with duration of MV in a subset of the cohort (N=9) who had available specimens biobanked at 36 weeks' PMA.

Results: A total of 180 subjects were included. Among subjects who successfully weaned from MV, time-to-wean ranged from 36 to 144 weeks PMA (Fig 1), with 75% of the cohort successfully weaning by 48 weeks PMA. Infants who were difficult-to-wean from MV had higher rates of death, higher rates of tracheostomy, and longer lengths of stay as compared to subjects who were simple-to-wean from MV (Table). In our exploratory analysis (N=9), tracheal and plasma pro-inflammatory cytokine expression at 36 weeks PMA was highly variable between subjects. (Fig 2) Interleukin-8 (IL-8) was the most abundantly expressed cytokine in tracheal aspirate supernatants and plasma of analyzed subjects (Fig 2, Panel A, Panel B). Tracheal and plasma IL-8 expression correlated with days spent on MV after 36 weeks PMA, Pearson correlation coefficient of 0.39 and 0.63, respectively. (Fig 2, Panel C, Panel D)

Conclusion(s): In this study, we found that a timepoint of 48 weeks PMA discriminates ventilator-dependent infants with grade 3 BPD who are and are not difficult-to-wean from MV. Future research is needed to identify biomarkers that predict successful weaning from MV. We speculate that such biomarkers can be integrated into the design of clinical trials of precision therapeutics that accelerate the time-to-wean from MV for infants with grade 3 BPD.

Figure 1
Weaning classifications in grade 3 BPD. Panel A - Weaning by 48 weeks' PMA differentiates grade 3 BPD infants who are and are not difficult-to-wean. Panel B - RSS (MAP x FiO2) at 36 weeks' PMA is elevated in infants who are difficult-to-wean as compared to infants who are simple-to-wean.

Table.
Hospital outcomes of cohort stratified by weaning classification.

Figure 2.
Heterogeneous expression of pro-inflammatory biomarkers, measured at 36 weeks PMA (N=9). IL-8 was the most abundantly expressed biomarker in tracheal aspirate supernatant (Panel A) and plasma (Panel B). Tracheal (Panel C) and plasma (Panel D) IL-8 expression at 36 weeks' PMA correlates with days spent on MV after 36 weeks' PMA (N=9), Pearson correlation coefficient 0.39 and 0.63, respectively.