Early alterations of growth factor patterns in bronchoalveolar lavage fluid from preterm infants developing bronchopulmonary dysplasia

Chronic lung disease of prematurity (bronchopulmonary dysplasia; BPD) is characterized by an arrest in lung development. We hypothesized that early alterations in pulmonary expression of growth factors important for normal lung development would precede development of BPD. Bronchoalveolar lavage fluid (BALF) was obtained from ventilated preterm infants (n = 62) on postnatal d 0, 1, 3, and 7 and analyzed for total phospholipids (PL), VEGF, PDGF-BB, TGF-α and-β1, granulocyte macrophage colony stimulating factor (GM-CSF), and keratinocyte growth factor (KGF). Levels (Ln transformed) were compared between infants developing BPD and BPD-free survivors, adjusted for potential confounders. BPD was associated with higher overall GM-CSF (β (95% CI) = 0.69 (0.13;1.25); p < 0.05), lower overall latent TGF-β1 (β (95% CI) =-1.19 (-1.87,-0.39); p < 0.01) and total PL (β (95% CI) =-0.64 (-1.23,-0.05); p < 0.05), and lower d 0 and 3 levels of VEGF (mean difference (95% CI) =-1.75 (-2.72,-0.77), p < 0.001; and-1.18 (-2.30,-0.06), p < 0.05, respectively) and TGF-α (mean difference (95% CI) =-0.73 (-1.42,-0.04), p < 0.05; and-1.01 (-1.64,-0.38), p < 0.01, respectively). Day 0 VEGF levels had the highest predictive value for BPD (area under receiver operating characteristic curve = 0.87; p < 0.01). In conclusion, substantial alterations in BALF growth factor levels are present in infants developing BPD. An early imbalance in pulmonary growth factors may contribute to the developmental arrest of the lung seen in BPD.