Urinary bombesin‐like peptide levels in infants and children with bronchopulmonary dysplasia and cystic fibrosis

Abstract

Summary. Compared to normal infants and children, there are increased numbers of neuroendocrine cells with bombesin-like peptide (BLP) immunostaining in the lungs of infants and children with bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF). However, there are no data documenting levels of urinary BLP in normal infants and children, or in children with lung disease. We therefore determined the normal developmental pattern for urinary BLP excretion in healthy infants and children, and in infants and children with BPD and CF, and correlated these findings with the subjects' clinical course. We measured urinary BLP levels in 110 subjects: 54 controls, 33 with BPD, and 23 with CF.An age-dependent decline in urinary bombesin levels was evident in the control and BPD subjects, but not in those with CF. There were no statistically significant differences in BLP levels between normal infants and those with BPD. Mean BLP levels were higher in the more immature preterm infants with BPD who required increased ventilatory support. The highest mean BLP levels were documented in BPD infants under age 3 months (882 fmol/mg creatinine), in controls between 3 and 12 months of age (625 fmol/mg creatinine), and in 12-60-month-old CF subjects (486 fmol/mg creatinine). Thus there is an age-dependent decline in BLP levels in controls and BPD, but not in CF. We speculate that the elevated urinary BLP levels in infants and children with BPD and CF may reflect increased pulmonary neuroendocrine cell activity in these conditions, due to the epithelial regenerative response to airway damage and repair. Pediatr Pulmonol. 1998; 26:326-331.

Pulmonary Neuroendocrine Cells, Airway Innervation, and Smooth Muscle Are Altered in Cftr Null Mice

“…In earlier studies, hyperplasia of PNEC in lungs of patients with CF with chronic severe lung disease has been reported (18), as have increased urine levels of bombesin (19), a secretory product of PNEC/NEB. The hyperplastic response of PNEC/ NEB in this setting was interpreted as secondary to the effects of chronic hypoxia/hypercapnia due to airway obstruction characteristic of late-stage CF lung disease.…”

Urine gastrin‐releasing peptide in the first week correlates with bronchopulmonary dysplasia and post‐prematurity respiratory disease

“…Pulmonary neuroendocrine cell density and GRP concentrations are increased following oxygen therapy, 20 smoking, 18,32 ozone exposure, 33 and chronic lung diseases such as cystic fibrosis. 32,34 Oxidation of proteins, DNA, and lipids generate biomarkers that indicate ROS exposure. We demonstrate that urinary GRP was positively associated with urinary allantoin and 8-OHdG, both established markers of oxidative stress in preterm infants.…”

Expression of CFTR and Cl−conductances in cells of pulmonary neuroepithelial bodies

“…The potential involvement of PNECs in CF lung disease processes is still not understood. However, reports of PNEC hyperplasia in lungs of CF patients (30) and detection of significant amounts of BN-like peptide (BLP) in urine from CF patients (46) suggest an overactive neuroendocrine cell system. In contrast to the age-dependent decrease of BLP in urine of normal humans, BLP levels in urine from CF patients were found to be elevated for up to 5 yr of age (46).…”