Meter-Dosed, Inhaled Beclomethasone Attenuates Bronchoalveolar Oxyradical Inflammation in Premature Infants at Risk for Bronchopulmonary Dysplasia

ABSTRACT

The object of this study was to examine the hypothesis that meter-dosed, inhaled beclomethasone administered to premature infants beginning at birth in a tapering dosage schedule over the first 12 days of life attenuates bronchoalveolar lining fluid oxyradical inflammation concomitant with modulation of bronchopulmonary dyspla-sia. The design of this study was an unblinded, uncontrolled phase I, pilot investigation of inhaled beclomethasone primarily examining safety and administration. The setting was a tertiary care neonatal intensive care unit. Intubated, premature infants were studied longitudinally to 36 weeks corrected gestational age. Meter-dosed, inhaled beclomethasone was administered in a tapering dosage schedule over the first 12 days of life. Endotracheal tube aspirates were collected on Days 2, 4, and 6 of life and assayed for various markers of bronchoalveolar lining fluid oxyradical stress. Infants were also assessed with regards to a number of relevant clinical variables and presence or absence of bronchopulmonary dysplasia at 36 weeks corrected gestational age. Although no differences in clinical outcome were apparent in comparing nine control infants with nine beclomethasone-treated infants, bronchoalveolar lining fluid from control infants exhibited evidence of apparent phospholipid peroxidation (enhanced polyunsatu-rated fatty acid consumption) on Day 2 of life compared to beclomethasone-treated infants. Significant differences were noted for percent arachidonic acid, total polyunsat-urated fatty acids and ratio of polyunsaturated fatty acids, to saturated fatty acids. The ratio of monohydroxyl linolenic acid to native linoleic acid (a more specific marker of lipid peroxidation) as well as myeloperoxidase activity (a marker of neutrophil oxyradical stress) tended to be higher in the control group but did not achieve statistical significance for this small subject number study. No adverse reactions related to meter-dosed, inhaled beclomethasone were noted in the treatment group; most specifically no evidence of hypothalamic-pituitary-adrenal axis suppression was noted in either control or beclomethasone-treated infants. Meter-dosed, inhaled beclomethasone in the dosage schedule utilized was safe and appeared to moderate bronchoalveolar lining fluid phospholipid peroxidation. Small numbers of infants entered into the present investigation preclude comments on clinical efficacy because of the likelihood of a statistical type 2 error. However, additional investigations of inhaled beclomethasone initiated at birth in premature infants at risk for bronchopulmonary dysplasia, enrolling larger number of subjects and perhaps a higher dosage of beclomethasone, are warranted.

Keywords

Bronchopulmonary dysplasia - beclomethasone - oxyradicals - prematurity - lipid peroxidation - myeloperoxidase