The respiratory distress syndrome (RDS) is an acute self-limited disease due to surfactant deficiency and is the most common respiratory disease in premature human infants. Supportive 02 treatment allows most infants to survive until surfactant activity becomes normal but some require long-term 02 support and develop chronic lung disease (CLD) presumably due to 02 toxicity. The reason that some premature infants require an increased duration of 02 remains obscure. We have recently shown Ureaplasma urealyticum to be the most common microbial isolate from the lower respiratory tract of infants within the first 24 hrs of life. Furthermore, we have shown these infants to be 3 times greater risk for development of CLD than infected infants of similar birth weight or infected infants greater than 1100 gms. However in the absence of 02 therapy, there is no evidence that U. urealyticum induces chronic respiratory disease. Exposure of newborn mice infected with U. urealyticum to 80% oxygen greatly potentiates development of respiratory disease and death compared to infection or oxygen exposure alone. The data indicate that there is an decrease in the number of U. urealyticum present in lungs of mice exposed to 80% 02. Thus it seems likely that increased lesions and death following hyperoxia are not related to a decrease in pulmonary clearance of the organism but rather to exacerbations of pulmonary damage related to hyper- reactivity of some host response(s). The purpose of the proposed experiments are to more fully characterize the synergism between hyperoxia and U. urealyticum pneumonia using the newborn mouse model and to identify the host response that most likely is response for increased pulmonary damage. This will be accomplished by competing the following specific aims: i) The model of U. urealyticum pneumonia and potentiation by 02 will be further characterized by determining the dose response curve for potentiation, quantitation of upper and lower tract lesions by morphometry, and quantitative culture. ii) The inflammatory response in newborn mice reared under both normoxic and hyperoxic conditions and following U. urealyticum exposure will be characterized at various time points within the first 7 days following infection and correlated with biochemical evidence of free radical production in the lung. Specifically, the amount of edema, hemorrhage, and cellular influx will be quantitated. In addition, the numbers of macrophages, neutrophils, T cells, B cells and NK cells in the cellular influx will be determined.
| Crouse, D T; Odrezin, G T; Cutter, G R et al. (1993) Radiographic changes associated with tracheal isolation of Ureaplasma urealyticum from neonates. Clin Infect Dis 17 Suppl 1:S122-30 |
