Effects of natural surfactant combined with beclomethasone on oxidative stress: a pilot study in preterm lambs with RDS

Inflammation and oxidative stress play a central role in the etiology of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD).
In fact, RDS and mechanical ventilation with oxygen are associated with increased recruitment of inflammatory cells within lung tissues, with the production of oxygen radicals. The resulting oxidative stress damages the lung by increasing collagenase activity, by causing disruption of the extracellular matrix, and by inducing, at least partly, the typical fibrotic process of BPD. In addition, inflammation and oxidative stress contribute to surfactant inactivation.
Natural surfactant can modulate the pulmonary inflammatory cascade by the inhibition of macrophage-mediated neutrophil chemotaxis, nitric oxide (NO) production, oxidative burst activity, and secretion of pro-inflammatory cytokines from alveolar macrophages. In addition, glucocorticoids have been shown to decrease oxidative stress in inflamed lungs, to accelerate antioxidant enzyme activity and to decrease the synthesis of reactive oxygen species in fetal lambs with pulmonary hypertension. Therefore, the treatment of neonatal RDS with surfactant combined with a glucocorticoid, such as beclomethasone, could reduce pulmonary oxidative damages and the risk of developing BPD in preterm infants.
Dani and colleagues have recently conducted an experimental randomized study in preterm lambs with RDS, to compare the effects on the oxidative stress in lung tissues following treatment either with porcine natural surfactant 200 mg/kg plus beclomethasone (400 or 800 mg/kg [n=6 in both groups]) or with natural surfactant alone (n=6). Lung tissue oxidation was studied by measuring total hydroperoxide (TH), advanced oxidation protein products (AOPP), and non-protein bound iron (NPBI) in bronchial aspirate samples. In addition, lung mechanics was evaluated.
Overall, TH was lower in the surfactant + beclomethasone groups than in the surfactant alone group (n=6); AOPP was lower in the group treated with surfactant plus 800 mg/kg of beclomethasone than in the other groups; NPBI was similar in all groups. Surfactant treatment was followed by a sustained improvement of tidal volume (TV) and airway resistance, while dynamic compliance did not vary. However, the mean airway pressure needed to obtain similar values of TV was lower in the surfactant + beclomethasone 800 mg/kg group than in other groups.
These results show that natural porcine surfactant combined with beclomethasone at 800 mg/kg effectively reduced the oxidative lung stress and improves the respiratory function in preterm lambs with RDS. These findings may support the opportunity of planning large randomized control trials in preterm infants with RDS to evaluate the hypothesis that the intratracheal administration of natural surfactant combined with a corticosteroid may decrease the occurrence of BPD without relevant adverse effects, with particular consideration to the neurodevelopmental outcome.

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