NITRIC OXIDE AND SURFACTANT

NITRIC OXIDE AND SURFACTANT

Ballard PL, Merrill JD, Truog WE, et al. Surfactant function and composition in premature infants treated with inhaled nitric oxide. Pediatrics 2007;120:346-353. [Full text] [PDF]

Objectives. We hypothesized that inhaled nitric oxide treatment of premature infants at risk for bronchopulmonary dysplasia would not adversely affect endogenous surfactant function or composition.

Methods. As part of the Nitric Oxide Chronic Lung Disease Trial of inhaled nitric oxide, we examined surfactant in a subpopulation of enrolled infants. Tracheal aspirate fluid was collected at specified intervals from 99 infants with birth weights <1250 g who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Large-aggregate surfactant was analyzed for surface activity with a pulsating bubble surfactometer and for surfactant protein contents with an immunoassay.

Results. At baseline, before administration of study gas, surfactant function and composition were comparable in the 2 groups, and there was a positive correlation between minimum surface tension and severity of lung disease for all infants. Over the first 4 days of treatment, minimum surface tension increased in placebo-treated infants and decreased in inhaled nitric oxide-treated infants. There were no significant differences between groups in recovery of large-aggregate surfactant or contents of surfactant protein A, surfactant protein B, surfactant protein C, or total protein, normalized to phospholipid.

Conclusions. We conclude that inhaled nitric oxide treatment for premature infants at risk of bronchopulmonary dysplasia does not alter surfactant recovery or protein composition and may improve surfactant function transiently.

Comments. Previous studies with lung cells in vitro as well as animal studies have demonstrated an inhibitory effect of iNO on surfactant composition and function. The results of this study suggest that iNO as used in the Nitric Oxide CLD Trial (see 7-030 for details) has no short term adverse effect on the surfactant system of preterm infants. The observed transient improvement of surface tension properties in iNO exposed infants was unexpected and the mechanisms that might be responsible for this effect are unclear. Although not reaching statistical significance (possibly due to insufficient sample size), decreases in minimum surface tension between day 4 and 7 of study gas application was associated with better outcomes, i.e. survival without BPD. While these results may be reassuring, the precise role of iNO in preterm infants with respiratory distress syndrome remains to be determined. TMB.

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