Neonatal respiratory distress syndrome: An inflammatory disease?

Surfactant substitution has represented a major breakthrough in the treatment of neonatal respiratory distress syndrome (RDS), which is primarily caused by a lack of pulmonary surfactant. Surfactant substitution reduces the risk of mortality and acute pulmonary morbidity in most preterm infants. However, some very immature infants present a poor response to surfactant replacement or an early relapse.
In this short review, the hypothesis that neonatal RDS may have a more complex pathogenesis in some preterm infants is discussed. In particular, besides primary surfactant deficiency, the pathogenesis of RDS may be characterized by an injurious inflammatory sequence in the immature lung which may subsequently affect surfactant function, synthesis and metabolism.
Fetal exposure to chorioamnionitis has been shown to initiate an inflammatory reaction beginning in utero, and may be associated with severe RDS requiring excessive ventilatory support with high inspiratory oxygen concentrations. In contrast, a 'low-grade' inflammatory stimulus in utero may 'prime' the fetal lung for accelerated maturation of the surfactant system, especially in conjunction with the administration of prenatal steroids, and may protect the preterm infant from developing moderate to severe RDS. Depending on the severity of inflammatory injury to the alveolar-capillary unit, however, serum proteins will leak into the airways and induce surfactant inactivation. Following this intrauterine 'first hit', the immature infant may develop severe RDS and have a poor response to surfactant substitution. In addition, secondary insults such as traumatic stabilization techniques, oxygen toxicity, initiation of mechanical ventilation and others injure the immature lung immediately after birth, thus perpetuating and worsening the inflammatory process and increasing the risk of developing RDS.
The above-described concepts are supported by a number of observational studies in preterm infants and extensive data collected from animal experiments.
In short, the multiple-hit theory which is widely accepted to explain the pathogenesis of BPD could also hold true for RDS. Clearly, it has broad implications for the prevention and treatment of RDS. The administration of prenatal steroids and early surfactant treatment in all immature preterm infants with signs of respiratory distress may help to minimize the effects of the postnatal injurious events which have been shown to aggravate or perpetuate the pulmonary inflammatory reaction. In addition, whenever surfactant inactivation is suspected, the administration of a higher dose or repetitive doses of natural surfactant may help to overcome inactivation and to restore lung function. Since natural surfactant preparations contain a number of anti-inflammatory factors and properties, early surfactant replacement may also mitigate the inflammatory pathway associated with RDS.

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