Abstract 1867

The pathogenesis for the development of Bronchopulmonary Dysplasia (BPD) probably involves acute lung inflammatory responses in the first days of postnatal life. Clara cells are non-ciliated, secretory cells that line the bronchiolar epithelium of the lung that secrete a protein, Clara cell secreted protein (CCSP), that has potent anti-inflammatory activity in vitro. Animal studies have shown that CCSP provides a protective effect during exposure to hyperoxia. Recently, we have reported that prematurely born infants that go on to develop BPD have higher levels of oxidized CCSP in their tracheal aspirate fluids in the first week of life. Therefore, this study was designed to test the hypothesis that infants that develop BPD will have lower levels of CCSP in the tracheal lining fluid in the first week of life than in infants that do not develop BPD. Infants less than or equal to 29 weeks gestation, admitted to Texas Children's Hospital on the first day of life were studied. Tracheal aspirate samples were collected on days of life 1, 3, and 6 in all infants. Samples were assayed for total protein content followed by Western blotting with an antibody that detects CCSP. The infants were evaluated at 28 days of life, to determine whether they met the criteria for the diagnosis of BPD as defined by a persistent oxygen requirement and abnormal radiographic findings consistent with BPD. Infants that developed BPD had higher tracheal aspirate protein concentrations than those that did not develop BPD (1.55 ± 0.34 vs. 0.73 ± 0.30 on day of life 6, P<0.05). By Western blotting in which equal volumes of samples were loaded, infants that did not develop BPD had an increase in CCSP that was more than four times greater than baseline expression, while infants that developed BPD or died in the first month of life had only a 66% increase in CCSP expression over baseline (p < 0.05 BPD vs. no BPD). These findings suggest that decreased protein expression of CCSP in the tracheal lining fluid in the first week of life may contribute to the uncontrolled inflammatory process involved in the early evolution of BPD. These findings coupled with our observation of greater CCSP protein oxidation in tracheal aspirate samples of infants that develop BPD suggests that the function of the Clara cell and the CCSP may be critical for the normal homeostatic balance modulating pulmonary inflammation, and that therapies directed at preserving CCSP expression and/or function may be beneficial in therapies directed at preventing the development of BPD.

Supported in part by a resident/fellow research grant by the Southern Medical Association.