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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.