Surfactant protein-A gene locus associated with recurrent otitis media.

Surfactant protein-A, which plays a role in innate host defense in the lung, is also expressed in the Eustachian tube. We report that the frequency of specific surfactant protein-A haplotypes and genotypes differs between children with recurrent otitis media compared with a control population.

Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure.

We prospectively analyzed airway specimens from 24 newborn infants. Inhaled nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the concentrations of the lipid peroxidation product, the surface activity, or the cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of life in the two infants requiring prolonged ventilation, suggesting toxicity of endogenous nitric oxide.

Increased incidence of bronchopulmonary dysplasia after antenatal administration of indomethacin to prevent preterm labor.

The aim of this randomized study was to compare the neonatal outcome in infants who have been exposed in utero to indomethacin with that in infants exposed to a beta-adrenergic agonist, nylidrin hydrochloride. Eighty pregnant women threatened with preterm labor between 24 and 34 weeks of gestation were enrolled in the study. An intravenous infusion of nylidrin or enterally administered indomethacin was given for a maximum of 72 hours. If preterm labor recurred, all parturient patients were treated with nylidrin. Indomethacin prolonged gestation significantly more than the beta-adrenergic agonist (6.6 weeks vs 4.5 weeks; p = 0.04). Ten of the forty-two infants exposed to indomethacin and 2 of the 45 infants exposed to nylidrin had bronchopulmonary dysplasia (24% vs 5%; p = 0.02). Among the 28 infants delivered within 120 hours after the start of treatment, the incidences of respiratory distress syndrome (82% vs 29%; p = 0.02), bronchopulmonary dysplasia (73% vs 6%; p = 0.0006), and necrotizing enterocolitis or focal intestinal perforation (27% vs 0%; p = 0.03) were higher among those exposed to indomethacin than among those exposed to nylidrin. We infer that administration of indomethacin to pregnant women threatened with premature labor is associated with an increased risk of bronchopulmonary dysplasia in their infants if delivery occurs early.

Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: a randomized, placebo-controlled trial of human surfactant.

We compared the neurodevelopmental outcome of extremely premature, surfactant-deficient infants who received either prophylactic surfactant at birth, "rescue" surfactant after the clinical diagnosis of respiratory distress syndrome was established, or placebo. Infants studied were participants in a randomized, bicenter (San Diego, Calif., and Helsinki, Finland), controlled trial of human surfactant therapy. One hundred fifty infants (prophylaxis group, 63 infants; rescue group, 57; placebo group, 30) were prospectively enrolled at 38 weeks of gestational age. There were no neonatal intergroup differences in the incidence or severity of sonographic central nervous system abnormality or retinopathy. One hundred forty-five infants were alive at 1 year of adjusted age, at which time growth, neurosensory, and neurologic outcome were similar in all three treatment groups at both centers. Cerebral palsy occurred in 20% overall. Five infants (3.5%) were functionally blind. However, infants treated at birth had lower mean mental and motor scores on the Bayley Scales of Infant Development compared with those of infants rescued with surfactant after the onset of respiratory distress syndrome (Mental Development Index: 78 vs 96, p = 0.02; Psychomotor Development Index: 73 vs 87, p = 0.04). Chronic lung disease occurred more frequently in the prophylactically treated group and contributed to the subjects' neurologic and developmental morbidity. Because prophylactic surfactant treatment offered no neurodevelopmental advantage and may contribute to poorer outcome, we currently recommend early surfactant replacement only for those infants who have postnatal evidence of respiratory distress syndrome.

Randomized, placebo-controlled trial of human surfactant given at birth versus rescue administration in very low birth weight infants with lung immaturity.

A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (1) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full treatment protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was less than or equal to 2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of greater than 0.5, and mean airway pressure was greater than or equal to 7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic- and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.18) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p = 0.0001). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants.

Lipid peroxidation was measured in 19 very low birth weight infants with respiratory distress syndrome by quantitating ethane and pentane in expired air during the first 5 days postnatally. Despite high levels of inspiratory oxygen, the ethane and pentane output was low within the first 24 hours; thereafter it increased up to 100 and 30 fold, respectively. On days 1 to 3 there was no detectable correlation between lipid peroxidation and fractional inspiratory oxygen. However, on days 4 and 5, lipid peroxidation and fractional inspiratory oxygen showed a significant correlation. Maximal amounts of expired ethane and pentane were significantly higher for patients with a poor outcome (five deaths, six cases of bronchopulmonary dysplasia) than for those with good outcome (eight infants surviving intact) (p less than 0.01). The results imply a role for free oxygen radicals in the pathogenesis of life-threatening complications in the very low birth weight infant.

Inositol supplementation in respiratory distress syndrome: relationship between serum concentration, renal excretion, and lung effluent phospholipids.

Inositol or placebo was given to 48 small preterm infants with respiratory distress syndrome (mean birth weight 1365 g, gestational age 30.1 weeks) between 48 hours and 10 days of age. The dose of inositol, 40 mg/kg every 6 hours, was at least as high as amounts received in full preterm human milk feedings. Serum inositol concentration increased between days 2 and 3 from a mean of 566 mumol/L to 823 mumol/L in the infants given supplement and fell from 451 mumol/L to 292 mumol/L in the controls. On day 16, serum inositol values remained higher in the infants given supplement than in those given placebo (mean 334 mumol/L vs 146 mumol/L, P = 0.014). The infants who developed bronchopulmonary dysplasia had significantly higher renal inositol clearance, lower inositol intake, and lower serum inositol concentrations. Inositol supplementation increased the saturated phosphatidylcholine/sphingomyelin ratio in tracheal aspirates. According to these results, supplementation with inositol in preterm infants leads to a rise in serum inositol concentration and improvement in the surfactant phospholipids. Inositol deserves further study as a dietary supplement for immature preterm infants who do not receive full human milk feeds.

Human surfactant treatment of severe respiratory distress syndrome: pulmonary effluent indicators of lung inflammation.

Pulmonary effluent from infants who received exogenous human surfactant for severe respiratory distress syndrome was evaluated for inflammatory changes previously identified with lung injury during the first 2 weeks after birth. The number of pulmonary effluent inflammatory cells was higher only on day 1 in infants given surfactant. No other evidence of enhanced inflammation was detected in cytologic assessment of tracheal secretions. The classical pathway of complement was not activated in infants given surfactant or in control infants 2 weeks after birth. Albumin content of airway secretions was higher on the first day but not significantly altered on subsequent days. Human surfactant treatment was not associated with increased proteolytic activity, measured as neutrophilic elastase per milligram of albumin in lung effluent, but was associated with significantly higher alpha 1-proteinase inhibitor levels than in control infants from days 2 to 7 after birth. These findings provide evidence that exogenous human surfactant instilled into the lungs of preterm infants with severe respiratory distress syndrome is not associated with enhanced lung inflammation, compared with conventional mechanical ventilation alone. These data support additional clinical trials using human surfactant.

Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial.

We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome.