Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity,☆☆,,★★

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Abstract

OBJECTIVE: Pulmonary fibrosis is a prominent feature of chronic lung disease of prematurity (CLD). We sought to determine the influence of the potent profibrotic cytokine transforming growth factor beta-1 (TGF-β1) on the development of CLD. METHODS: We determined the concentration of active and total TGF-β1 in bronchoalveolar lavage fluid obtained from 18 infants who subsequently had CLD (mean gestation, 25.7 weeks; birth weight, 816 gm), 15 (29.8 weeks, 1493 gm) who recovered from the respiratory distress syndrome, and 7 (35.1 weeks, 2441 gm) control infants. RESULTS: The concentration of both active and total TGF-β1 was increased in the infants with CLD when compared with the respiratory distress syndrome and control groups. The increase in active and total TGF-β1 was greatest on day 4 of age, when infants who eventually had CLD were compared with those who did not progress to CLD (active TGF-β1, 39.5 vs 4.6 ng/ml; total TGF-β1, 43.8 vs 13.8 ng/ml). In addition, immunocytochemistry studies localized pan-TGF-β to alveolar macrophages obtained by bronchoalveolar lavage. CONCLUSIONS: These observations indicate that TGF-β1 may contribute to the fibrotic response that is observed in the lungs of infants who have CLD. (J PEDIATR 1996;128:464-9)

Section snippets

Patient groups

Infants supported by mechanical ventilation and admitted to the regional neonatal intensive care unit at Hammersmith Hospital were recruited for the study. Three groups of infants were studied: (1) the CLD group, consisting of infants who required mechanical ventilation for RDS, who subsequently had CLD, whose diagnosis was made on the basis of oxygen dependency at 28 days of age, and who had radiologic changes of CLD,17 (2) the RDS group, consisting of infants who received mechanical

Patient characteristics

One hundred twenty-six bronchoalveolar lavage procedures were performed in 40 infants requiring mechanical ventilation (Table). Of 33 infants with respiratory failure, 18 subsequently had CLD and 15 recovered from RDS. Seven control infants received mechanical ventilation for nonrespiratory reasons, including one for magnetic resonance imaging, two for congenital muscular dystrophy, three perioperatively, and one for prematurity (requiring respiratory support in air for poor respiratory

DISCUSSION

In this study, we demonstrated that both active and total TGF-β1 concentrations were increased in the bronchoalveolar lavage fluid obtained from infants who subsequently had CLD compared with values for those who recovered from RDS and for infants who received mechanical ventilation for nonrespiratory reasons. This increase in both active and total TGF-β1 in the CLD group was most marked on day 4 of age. Both active and total TGF-β1 appeared to decrease gradually during a 4-week period. In

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    From the Department of Paediatrics, Royal Postgraduate Medical School, London and the Department of Respiratory Medicine, St. Mary's Hospital Medical School, London, United Kingdom

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    Supported in part by a Training Fellowship from the Medical Research Council (Dr. Kotecha).

    Reprint requests: Sailesh Kotecha, MRCP, Department of Child Health, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, PO Box 65, Leicester LE2 7LX, England.

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