Early increase in endothelin-1 in tracheal aspirates of preterm infants: Correlation with bronchopulmonary dysplasia,☆☆,

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Abstract

Objectives: To determine whether endothelin-1 (ET-1) in tracheal aspirates (TA) is a specific marker for acute lung injury in preterm infants with respiratory distress syndrome (RDS) who progress to bronchopulmonary dysplasia (BPD); and to investigate the relationship between TA ET-1 and the proinflammatory cytokines, interleukin-6 (IL-6) and IL-8, as early mediators of BPD. Study design: We measured TA ET-1, IL-6, and IL-8 levels in preterm infants whose lungs were mechanically ventilated for RDS, categorized into two groups, BPD or non-BPD, on the basis of oxygen requirement at 36 weeks' postconceptional age. Results: A total of 106 TA samples were obtained from 34 infants with gestational ages ranging from 24 to 28 weeks on days 1, 3, 5, and 7 of life. There was a wide range of ET-1 concentration. TA ET-1 levels were significantly elevated on days 1, 3, and 7 in infants in whom BPD developed, in comparison with the non-BPD group (Mann-Whitney U test: p < 0.01). TA IL-8 levels were elevated on days 1, 3, 5, and 7 in the BPD group (p < 0.01); TA IL-6 levels were elevated (p < 0.05) only on day 5. There was a similarity in pattern of increase of TA ET-1 and TA IL-8 levels in the BPD group, with both being elevated in the first 24 hours of life and through the first week. There was no correlation between ET-1 and IL-8 values. Conclusion: Early significant increase in the TA ET-1 and IL-8 concentrations in preterm infants with acute lung injury correlates with subsequent progression to BPD. (J Pediatr 1998;132:965-70.)

Section snippets

Patient Groups

Preterm infants born at 28 weeks of gestation or sooner who required mechanical ventilation for RDS and who had been admitted to the neonatal intensive care unit at the University Medical Center at Stony Brook were recruited for this study. Excluded from the study were infants with sepsis verified by positive blood culture results at birth, with perinatal asphyxia, with severe persistent pulmonary hypertension, and with major congenital anomalies. Infants who remained oxygen dependent at 36

Results

Thirty-four infants born at 28 weeks' gestation or sooner and with RDS were entered into the study; BPD developed in half of them. Clinical characteristics of the two groups (non-BPD and BPD) were similar for gestational age, birth weight, maternal antenatal steroid therapy, duration of rupture of membranes or histologic evidence of chorioamnionitis or both, rate of cesarean delivery, and surfactant replacement therapy. There were significantly more boys (59% vs 18%) and a higher mean initial

Discussion

Most mammalian cells and tissues express ET-1; however, they are present in the largest amounts in the lungs, particularly in the trachea, bronchiolar smooth muscle and epithelia, pulmonary tissues, bronchoalveolar space, and pulmonary circulation. In adults, ET-1 has been implicated as a mechanism of injury in diseases involving abnormal vascular reactivity and hypoxia-ischemia, such as hypertension, myocardial and cerebral infarction, sepsis syndromes, and other vasculopathies.19 A role for

Acknowledgements

We thank the nurses in the neonatal unit for their continuing support. A special thank-you is extended to Dr. Leonard I. Kleinman for his assistance with statistics and his critical review of the manuscript.

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      CT-proET-1, however, was not predictive of BPD after adjusting for GA. An early increase in endothelin-1 was a prognostic factor for BPD when endothelin-1 in tracheal aspirate was measured on day 7 of life.9 In our study, plasma CT-proET-1 concentrations were measured on day 3 of life, which may reduce prognostic power compared with measurement on day 7.

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    From the Department of Pediatrics (Division of Neonatal Medicine), State University of New York at Stony Brook, and St. Mary's Hospital, Leonardtown, Maryland.

    ☆☆

    Reprint requests: Lance A. Parton, MD, Department of Pediatrics, State University of New York at Stony Brook, Stony Brook, NY 11794-8111.

    0022-3476/98/$5.00 + 0 9/21/88985

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