Pepsin, a marker of gastric contents, is increased in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia.
OBJECTIVE
The objective of this study was to study the association between pepsin in tracheal aspirate samples and the development of bronchopulmonary dysplasia in preterm infants.


METHODS
Serial tracheal aspirate samples were collected during the first 28 days from mechanically ventilated preterm neonates. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen at 36 weeks' postmenstrual age. An enzymatic assay with a fluorescent substrate was used to detect pepsin. Total protein was measured by the Bradford assay to correct for the dilution during lavage. Immunohistochemistry using antibody against human pepsinogen was performed in 10 lung tissue samples from preterm infants.


RESULTS
A total of 256 tracheal aspirate samples were collected from 59 preterm neonates. Pepsin was detected in 234 (91.4%) of 256 of the tracheal aspirate samples. Twelve infants had no bronchopulmonary dysplasia, 31 infants developed bronchopulmonary dysplasia, and 16 infants died before 36 weeks' postmenstrual age. The mean pepsin concentration was significantly lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks' postmenstrual age. Moreover, the mean pepsin level was significantly higher in infants with severe bronchopulmonary dysplasia compared with moderate bronchopulmonary dysplasia. The mean pepsin level in tracheal aspirate samples from the first 7 days was also lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks' postmenstrual age. Pepsinogen was not localized in the lung tissues by immunohistochemistry.


CONCLUSIONS
The concentration of pepsin was increased in the tracheal aspirate of preterm infants who developed bronchopulmonary dysplasia or died before 36 weeks' postmenstrual age. Recovery of pepsin in tracheal aspirate samples is secondary to gastric aspiration, not by hematogenous spread or local synthesis in the lungs. Chronic aspiration of gastric contents may contribute in the pathogenesis of bronchopulmonary dysplasia.
Farhath
Sabeena
S
Division of Gastroenterology and Nutrition and Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA.
He
Zhaoping
Z
Nakhla
Tarek
T
Saslow
Judy
J
Soundar
Sam
S
Camacho
Jeanette
J
Stahl
Gary
G
Shaffer
Stephen
S
Mehta
Devendra I
DI
Aghai
Zubair H
ZH
D015415:Biomarkers / Q000032:analysis; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005750:Gastric Juice / Q000201:enzymology; D005766:Gastrointestinal Contents / Q000201:enzymology; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D010434:Pepsin A / Q000032:analysis*; D012121:Respiration, Artificial; D053120:Respiratory Aspiration / Q000150:complications* / Q000175:diagnosis; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications / Q000628:therapy; D018709:Statistics, Nonparametric; D014132:Trachea / Q000201:enzymology*
D015415:Biomarkers; D010434:Pepsin A