title: Neonatal respiratory distress syndrome: an inflammatory disease?
abstract: Surfactant substitution has been a major breakthrough in the treatment of neonatal respiratory distress syndrome (RDS), primarily caused by a lack of pulmonary surfactant; it has significantly reduced mortality and acute pulmonary morbidity in preterm infants. Some very immature infants, however, have a poor response to surfactant replacement or an early relapse. This brief article is based on the hypothesis that neonatal RDS has a complex and multifactorial pathogenesis characterized by an injurious inflammatory sequence in the immature lung. Fetal exposure to chorioamnionitis has been shown to initiate an inflammatory reaction beginning in utero. A 'low-grade' inflammatory stimulus in utero may 'prime' the fetal lung for accelerated maturation of the surfactant system, especially in conjunction with 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. Secondary insults such as traumatic stabilization techniques, oxygen toxicity, initiation of mechanical ventilation and others injure the immature lung immediately after birth and perpetuate and may aggravate the inflammatory process. Observational studies in preterm infants and animal experiments support this concept. Whenever surfactant inactivation is suspected, higher or repetitive doses of natural surfactant may help to overcome surfactant inactivation and to restore lung function.
authors.affiliation: University Children's Hospital, Würzburg, Germany. speer_c@klinik.uni-wuerzburg.de
authors.forename: Christian P
authors.initials: CP
authors.lastname: Speer
mesh_terms: D000818:Animals; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000150:complications*; D011663:Pulmonary Surfactants / Q000627:therapeutic use; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D013501:Surface-Active Agents / Q000627:therapeutic use
chemical_list: D011663:Pulmonary Surfactants; D013501:Surface-Active Agents