Does surfactant type cause a differential proinflammatory response in preterm infants with respiratory distress syndrome?

INTRODUCTION: The objective of this study was to compare the pulmonary inflammatory response of premature infants with respiratory distress following instillation of one of two commonly available surfactant preparations. METHODS: This was a prospective, randomized investigation of preterm infants who were less than 30 weeks of gestational age, weighed less than 1 kg at birth, and who qualified to receive surfactant. Infants with multiple congenital anomalies or whose mothers were taking anti-inflammatory medications were ineligible. Tracheal aspirates (TAs) were collected on days 1, 3, 5, and 7 and airway cytokines from TAs were assayed for interleukin (IL)-8 and IL-6. RESULTS: Infants were evenly matched by gestation (26+/-2 days and 26+/-1 days [mean+/-SD], Surfactant A and B, respectively) and birth weight (730+/-141 g and 732+/-167 g). TA cytokine levels were not different between or within groups. Ventilator requirements and clinical outcomes were similar between the two groups. CONCLUSION: The postnatal airway inflammatory response observed in preterm infants is not altered by the instillation of either surfactant preparation.

Single nucleotide polymorphisms of tumor necrosis factor-alpha and the susceptibility to bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. A "New" BPD has been characterized in preterm infants that may begin in utero, and then progress post-natally, resulting in arrested lung development and alveolar hypoplasia. Foundations for this "New" BPD may be derived from pro-inflammatory genes including tumor necrosis factor-alpha (TNFalpha). The hypothesis of the current study is that single nucleotide polymorphisms (SNPs) of the pro-inflammatory TNFalpha gene place preterm infants at increased risk for BPD. Preterm infants (105 in number) with birthweights

The genetic basis for bronchopulmonary dysplasia.

While the 'original' bronchopulmonary dysplasia (BPD) was attributed to the iatrogenic effects of oxygen and barotrauma on the preterm lung, analyses of the 'new' BPD suggests that these environmental effects may contribute to arrested pulmonary development, and that there may also be genetic foundations for the susceptibility to BPD. Twinning, family and population studies implicate heritable factors in the evolution of BPD. The candidate genes examined for their potential role in BPD include surfactant apoprotein and inflammatory genes. With the identification and mapping of single nucleotide polymorphisms (SNPs), an explosion of testing for these genetic components that may contribute to a number of complex, multigenic disease conditions-including BPD-have been initiated. Sophisticated multiplex analyses are now available to link candidate SNPs to conditions such as BPD. However, there continues to be wide variation in the expression of BPD throughout neonatal units. Differentiating the effects caused by environmental and environmental-genetic interactions from isolated genetic etiologies is still problematic and will require carefully designed genetic analyses of preterm infant groups and their families.

Polymorphism of Fas and Fas ligand in preterm premature rupture of membranes in singleton pregnancies.

OBJECTIVE: Fetal inflammatory response has been previously shown to be involved in the pathogenesis of preterm premature rupture of membranes. We investigated the association between polymorphisms at position -670 in the Fas gene and position -124 in the Fas ligand gene demonstrated in neonatal oral mucosa cells and preterm premature rupture of membranes. STUDY DESIGN: Thirty-six singleton pregnancies were studied. Eighteen pregnancies were complicated by preterm premature rupture of membranes, and 18 were delivered at term without preterm premature rupture of membranes. Buccal swabs were obtained from each neonate, and extracted deoxyribonucleic acid was analyzed by polymerase chain reaction-based restriction fragment length polymorphism for an adenine (A) to guanine (G) substitution at position -670 in the Fas promoter gene and at position -124 in the Fas ligand gene. chi2 and Fisher's exact tests were used for statistical analysis. RESULTS: There was no difference with respect to race, maternal age, and parity between the 2 groups. Frequencies of Fas -670 AG, -AA, and -GG genotypes in preterm premature rupture of membranes group were significantly different from those in the control group (P = .004). The frequency of the heterozygous AG genotype was significantly higher in preterm premature rupture of membranes group as compared with controls (83.3% versus 33.3%, P = .003). Fas -670 AA genotype was not observed among patients with preterm premature rupture of membranes. Similarly, the difference of frequencies of the Fas ligand -124 AG, -AA, and -GG genotypes among preterm premature rupture of membranes group and controls was observed but did not reach statistical significance. Neither of the groups demonstrated homozygous GG genotype at position -124 of the Fas ligand gene. CONCLUSION: Our data indicate an association between preterm premature rupture of membranes and increased prevalence of neonatal AG genotype at -670 Fas promoter gene. Genetically predetermined regulation of the Fas/Fas ligand system appears to play an important role in the pathogenesis of the preterm premature rupture of membranes.