Pro-inflammatory and matricellular protein expression patterns associated with bronchopulmonary dysplasia severity.

Abstract

Background: Pulmonary inflammation and dysregulated repair have been linked to the development of bronchopulmonary dysplasia (BPD), but disease severity varies widely, and the mechanisms leading to BPD heterogeneity remain unclear. We hypothesized that levels of pro-inflammatory and matricellular proteins in preterm infants airways in the first week of life are associated with BPD severity.

Methods: We collected tracheal aspirates from preterm infants, born ≤32 weeks gestational age, receiving mechanical ventilation in the first week of life. Protein levels were measured in the supernatants. BPD severity categories were defined by the Jensen classification.

Results: We observed three distinct expression patterns, including (i) proteins increased in any BPD severity, most significantly pro-inflammatory interleukin (IL)-17A and IL-23, (ii) proteins elevated only in grade 1 BPD (IL-12 isoforms, the matricellular protein periostin), and (iii) proteins decreased in grade 2/3 BPD, notably the matricellular protein thrombospondin 1 (THBS1). Low THBS1 discriminated grade 2/3 BPD, whereas high periostin levels discriminated grade 1 BPD, adjusting for sex and birth weight.

Conclusions: Tracheal aspirate levels of select pro-inflammatory and matricellular proteins show distinct patterns associated with BPD severity categories. THBS1 and periostin, tissue repair, immune, and angiogenesis regulators, display differential expression and potential roles as biomarkers and therapeutic targets in the pathogenesis of BPD severity categories.

Impact: We identify differential patterns and relationships between pro-inflammatory cytokine and matricellular protein expression levels in preterm infant airways by bronchopulmonary dysplasia (BPD) severity. Particularly, low levels of the matricellular protein thrombospondin 1 discriminated grade 2/3 BPD from grade 1 and 0, whereas high levels of the matricellular protein periostin discriminated grade 1 BPD, all after adjusting for sex and birth weight. Quantifying pro-inflammatory and tissue repair signals in preterm infant airways provides novel insights into early mechanisms that may impact BPD severity. Early biomarkers of BPD severity can provide crucial information for diagnosis, prognosis, and potential future treatment selection.