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Am. J. Respir. Crit. Care Med., Volume 165, Number 8, April 2002, 1093-1097

Urine Bombesin-like Peptide Elevation Precedes Clinical Evidence of Bronchopulmonary Dysplasia

Anne Cullen, Linda J. Van Marter, Elizabeth N. Allred, Marianne Moore, Richard B. Parad, and Mary E. Sunday

Children's Hospital, Departments of Pathology and Medicine, Division of Neonatology, and Brigham and Women's Hospital, Department of Newborn Medicine, Boston, Massachusetts

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of very low birth weight infants, associated with oxygen therapy, barotrauma, and/or infections. Improved medical care has led to a paradoxically increased incidence of BPD due to greater infant survival. Early prediction of BPD has proven challenging. Increased pulmonary neuroendocrine cells containing bombesin-like peptide immunoreactivity occur in infants with BPD. We hypothesized that elevated urine bombesin-like peptide levels precede BPD. One hundred thirty-two infants, 28-weeks gestation or less, were studied. Urine bombesin-like peptide levels, determined by radioimmunoassay, were normalized for creatinine. BPD was defined as oxygen dependence at 36 weeks postmenstrual age. A first urine bombesin-like peptide level greater than 20,000 pg/mg creatinine (12,500 fmol/mg) between postnatal days 1-4 occurred among 54% of the infants who later developed BPD (p =< 0.001), versus 10% among non-BPD infants (specificity 90%). Multivariable logistic regression analyses revealed that elevated urine bombesin-like peptide levels are associated with BPD (odds ratio 9.9, 95% confidence interval: 3.4, 29) (p =< 0.001) after adjusting for all confounding factors. Thus, elevated bombesin-like peptide levels in these infants at 1-4 days after birth are associated with a 10-fold increased risk of developing BPD. Utilizing urine bombesin-like peptide for screening might permit early therapeutic interventions to reduce disease progression and could provide a target for new preventive therapies.




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