Since parathyroid hormone-related protein (PTHrP) secreted by pulmonary alveolar type II cells is a key physiologic paracrine factor in maintaining alveolar homeostasis, we hypothesized that its levels in the tracheal aspirates (TA) of ventilated very low birth weight infants (VLBWI) would correlate with the development of bronchopulmonary dysplasia (BPD). Therefore, we examined whether TA PTHrP content during the first week of life correlates with the later development of BPD. Forty VLBWI [birth weight, 943 +/- 302 g (mean +/- SD); gestational age, 27 +/- 2 wk; 21 males and 19 females], who were ventilated for respiratory distress syndrome, were studied. The TA were collected once daily until the infants were extubated and immediately frozen at -70 degrees C for subsequent assays for PTHrP and matrix metalloproteinase-8 (MMP-8), a previously described, nonspecific TA biomarker for BPD. The levels of these proteins were correlated with the later development of BPD. PTHrP in the TA during the first week of life was significantly lower in those infants who developed BPD (12/40) than among those who did not (28/40). The PTHrP levels also correlated with the duration of mechanical ventilation needed in these infants. In contrast, MMP-8 levels did not correlate with BPD. We conclude that lower TA PTHrP content during the first week of life in ventilated VLBWI inversely correlates with prolonged ventilation and the later development of BPD.