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
