Association of Pulmonary Inflammation and Increased Microvascular Permeability During the Development of Bronchopulmonary Dysplasia: A Sequential Analysis of Inflammatory Mediators in Respiratory Fluids of High-Risk Preterm Neonates
1 Department of Pediatrics, Childrens' Hospital of the City of Cologne
2 Department of Pediatrics, University of Göttingen, Göttingen, Germany
3 Department of Immunology, University of Göttingen, Göttingen, Germany
4 Department of Medical Microbiology, University of Göttingern, Göttingen, Germany
Objectives. Bronchopulmonary dysplasia (BPD) of preterm neonates is associated with an increased recruitment of inflammatory cells into the airways. To evaluate further the role of inflammation in the pathogenesis of BPD, tracheobronchial aspirate fluid of neonates with birth weight <1200 g (n = 59) was sequentially analyzed in a prospective study.
Methods. Tracheobronchial aspirate fluid was assessed for chemotactic activity, neutrophil cell count, concentrations of elastase-
1-proteinase inhibitor and activity of free elastase, concentrations of chemoattractants (complement component C5-derived anaphylatoxin, leukotrien B4, interleukin-8), and albumin concentrations as well as 1-proteinase inhibitor activity. The secretory component for immunoglobulin A was used as reference protein. Only specimens without evidence of microbiological colonization were studied.
Results. In neonates with prolonged respiratory disease (BPD-risk neonates, n = 24, fraction of inspired oxygen 
0.3 and/or peak inspiratory pressure 16 cm H2O at day 10 postnatal age, birth weight 892 ± 36 g, gestational age 27.2 ± 0.3 weeks) chemotactic activity, cell count, concentrations of the chemoattractants complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8, as well as levels of elastase-1-proteinase inhibitor were significantly higher at day 10 and/or day 15 of postnatal age compared with neonates without chronic pulmonary disease (total n = 35; day 10, n = 11; day 15, n = 8). There was no difference in free elastolytic activity. Concentrations of albumin as well as 1-proteinase inhibitor activity were higher in BPD-risk patients on day 15, indicating an increased pulmonary leak.
Conclusion. We conclude that preterm neonates at risk for the development of BPD show an enhanced inflammatory reaction in the lungs and an associated increase in pulmonary microvascular permeability. We speculate that inflammation may play an important role in the pathogenesis of BPD.
Submitted on August 2, 1993Accepted on December 30, 1993
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