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Title: Inflammatory mediators in the lungs of preterm infants and their role in the development of chronic lung disease
Author: McColm, Janet R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The clinical pilot study enrolled 26 infants and measured IL-8, TNF-α and inflammatory cells in bronchoalveolar lavage samples. The results demonstrated that it may be possible to predict a group of babies at extremely high risk for developing chronic lung disease by early measurement of IL-8 in tracheal secretions. To further investigate the role of the genital mycoplasmas, Ureaplasma urealyticum and Mycoplasma hominis, a randomised study using an effective antibiotic, erythromycin, was carried out. A low grade untreated infection could persistently stimulate an in vivo inflammatory response, but we also wished to investigate the reported anti-inflammatory properties of erythromycin. The infection rate in the study was lower than expected (12% compared to 30% in a pilot study) and did not correlate with outcome. There was also no correlation between outcome and treatment and the inflammatory response, as measured by IL-8, did not correlate with outcome as it had in our pilot study. As part of a randomised trial of a natural and synthetic surfactant taking place on our unit, bronchoalveolar lavage samples both pre and post surfactant were analysed for cytokines and cells. Our results showed that Curosurf produced a significantly lower inflammatory response compared to Exosurf 24 hours after administration but there was no correlation between surfactant type and development of chronic lung disease. The cell population present in the lung effluent has been an area of controversy. Standard cytospin smears of bronchoalveolar lavage samples were compared using a differential stain and an immunocytochemical stain which relies on monoclonal antibodies to identify specific cell surface markers. Our results confirm that the differential stain identifies neutrophils but it significantly under-estimates cells of the monocyte/macrophage lineage. Laboratory investigations were carried out to further elucidate and quantify the response of A549 human lung epithelial cells to Ureaplasma urealyticum, and other genital isolates, a Gram-positive (Staphylococcus albus) and a Gram-negative (Eschericia coli). The cells were stimulated in the presence of TNF-α and high oxygen concentrations, and with used in the clinical management of these infants, including surfactants, antibodies and steroids.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available