748 - Chorioamnionitis-associated lung inflammation correlates with respiratory illness severity in extremely premature infants

Publication Number: 2729.748

Timothy Boly, University of Iowa, Iowa City, IA, United States; Jennifer Bermick, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States

Background: Infants born < 25 weeks' GA have an increased risk of developing bronchopulmonary dysplasia (BPD). Chorioamnionitis (CA) exposure further increases this risk. Previous studies have assessed the relationship of serum or tracheal aspirate (TA) cytokines in the first postnatal week to the development of BPD, but few have assessed both serum and tracheal aspirates concurrently.

Objective: To evaluate the relationship of serum and TA cytokines to the development of BPD in extremely premature infants following CA exposure. A secondary objective was to assess the relationship of cytokines to markers of respiratory illness severity.

Design/Methods: Infants born 21 0/7-24 6/7 weeks' GA were included. Respiratory data were collected by review of EHR. Weekly TAs were collected during routine endotracheal tube suctioning for 8 weeks or until extubation. Residual clinical serum samples were collected from the day of suctioning +/- 2 days. A multi-plex protein assay was performed on the collected samples to assess concentrations of IFNy, IL-1b, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1a, TNF. Mann-Whitney tests were performed to assess differences in TA and serum cytokines each week. Samples were then divided by CA exposure and serially assessed by Mann-Whitney tests. Relationship of cytokine concentrations to clinical respiratory markers were assessed by Pearson correlation.

Results: TA and serum samples were collected from 19 infants, of which 13 (68%) had histopathologic evidence of CA. TA levels of IFNy, IL-1b, IL-6, IL-8, MCP-1 and MIP-1a were significantly elevated compared to serum (Figure 1). CA-exposure resulted in significant elevation of IL-1b, IL-6, IL-8, MCP-1, MIP-1a and TNF compared to unexposed in the first week TA samples, with no significant difference in cytokines at any timepoint in the serum samples. First week cytokine concentrations were not associated with the incidence of moderate-severe BPD, but there were significant correlations with time to first extubation, FiO2 on DOL 14, paCO2 on DOL 7, and total surfactant doses (Table 1).

Conclusion(s): CA exposure results in lung-specific inflammation that is not reflected in serum concentrations in the first postnatal week. The degree of inflammation is associated with respiratory outcomes outside of this initial time period, suggesting early inflammation has long-lasting consequences. BPD was not associated with TA cytokines, which may be related to local practice as 94% of included infants had moderate-severe BPD. Better understanding of tissue-specific inflammation in this population can help drive future research and identify new therapeutic targets.

Figure 1
Mean cytokine concentrations by postnatal week from tracheal aspirate (blue circles) and serum (black squares). *p < 0.05, **p < 0.01, ***p < 0.001, ***p < 0.0001.

Figure 2
Mean cytokine concentrations from tracheal aspirate (blue circles) and serum (black squares) stratified by chorioamnionitis exposure (dark color) vs unexposed (light color). *p < 0.05

Table 1
Results of Pearson correlation of first week tracheal aspirate cytokine concentrations to respiratory outcomes. Values shown are Pearson r value. Significance is demonstrated by bolding of the value and *p < 0.05, **p < 0.01. BPD: bronchopulmonary dysplasia, DOL: day of life; PPV: positive pressure ventilation; FiO2: fraction of inspired oxygen; paCO2: partial pressure of arterial carbon dioxide; MAP: mean airway pressure.