Plasma nitrite/nitrate and endothelin-1 concentrations in neonatal sepsis

Aim: To determine the changes in plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) concentrations during neonatal sepsis. Methods: In a prospective study, 60 consecutive newborns meeting the criteria for sepsis and without receiving exogenous nitric oxide (25 haemoculture-positive [HC+] and 35 haemoculture-negative [HC-]) were compared with 68 healthy newborns (46 full-term and 22 preterm). NOx and ET-1 concentrations were measured in each newborn within 48 h of diagnosis of sepsis and then every third day up to three determinations. SNAP-II and SNAPPE-II severity scores were performed at the moment of highest clinical severity. Results: At the beginning of the sepsis period, controls and septicaemic newborns had similar NOx and ET-1 levels, with the exception of infants with severe HC+ sepsis. Throughout the sepsis period, NOx increased in moderate HC+ sepsis and decreased in HC- sepsis, reaching a significant difference at the end of the study period (59.9 ± 72.7 vs 33.9 ± 15.3 μmol/L; p = 0.036). Meanwhile, ET-1 in newborns with severe HC+ sepsis remained higher than that in the moderate HC+ sepsis group and HC- group, reaching significant differences in all the periods. The highest ET-1 value was positively correlated with SNAP-II and SNAPPE-II scores.

Conclusion: NOx concentrations increased throughout the neonatal HC+ sepsis period, reaching significant differences after 7-9 d. The highest ET-1 levels in neonatal HC+ sepsis emerged before the NOx peak, at 3-5 d, and later decreased. Only newborns with severe HC+ sepsis presented a significant increase in ET-1 concentrations from the beginning of the septicaemic process.     

Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia

Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants <32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants <28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD <28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.     

Ureaplasma and bronchopulmonary dysplasia

Advances in neonatal intensive care have greatly improved survival rates for children born in a very early stage of lung development (i.e. less than 26 weeks of gestation). In these premature babies, even low levels of oxygen and methods of minimally invasive ventilation may disrupt the growth of the distal airways, a condition described as “new” bronchopulmonary dysplasia (BPD).Ureaplasma infection can occur in utero or in the perinatal period in premature infants, in some of which the infection with these organisms triggers an important lung pro-inflammatory and pro-fibrotic response, and may increase the risk of developing BPD. The inflammation may be worsened by exposure to oxygen and mechanical ventilation. At present, clinical studies have not clarified the role of Ureaplasma in the pathogenesis of BPD and there is insufficient evidence to determine whether antibiotic treatment of Ureaplasma has influence on the development of BPD and its comorbidities.Future research in the context of well-designed and controlled clinical trials of adequate statistical power should focus on how to determine whether the treatment of Ureaplasma decreases lung inflammation, reduces rates of BPD, and improves long-term neurodevelopment.     

支气管肺发育不良研究的新进展

支气管肺发育不良(bmnchopulmonary dysplasia,BPD)是常发生于早产儿长期应用高浓度氧气和辅助机械通气后的一种慢性肺疾病。随着新生儿重症监护技术的迅速发展,越来越多的早产儿和极低体重儿得以存活,但BPD的发病率并未随之显著降低甚或有增高趋势,是新生儿重症监护的重要并发症和婴幼儿时期最常见的慢性呼吸系统疾病。     

Plasma 3-nitrotyrosine is elevated in premature infants who develop bronchopulmonary dysplasia

OBJECTIVE: Premature infants are susceptible to bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy that appears to be caused in part by oxidative stress from hyperoxia. To investigate the possible role of nitric oxide-derived oxidants such as peroxynitrite in the etiology of BPD, we measured levels of plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with proteins. PATIENTS AND METHODS: Ten premature infants who developed BPD, defined as requiring supplemental oxygen beyond 36 weeks' postmenstrual age, were identified retrospectively from a group of subjects enrolled in a clinical trial of antenatal therapy. Serial plasma samples had been collected on these infants during the first month of life as part of the trial. Sixteen comparison premature infants were identified from the same population: 5 had no lung disease, 6 had respiratory distress syndrome that resolved, and 5 had residual lung disease at 28 days of life that resolved by 36 weeks' postmenstrual age. Plasma 3-nitrotyrosine levels were measured using a solid phase immunoradiochemical method. RESULTS: All 3-nitrotyrosine values in infants without BPD were <0.25 ng/mg protein, and levels did not change with postnatal age. Plasma 3-nitrotyrosine concentrations were significantly higher in infants with BPD, increasing approximately fourfold during the first month of life. For the 20 infants who had blood samples available at 28 days of life, plasma 3-nitrotyrosine levels correlated with the fraction of inspired oxygen that the infant was receiving (r = 0.7). CONCLUSION: Plasma 3-nitrotyrosine content is increased during the first month of life in infants who develop BPD. This suggests that peroxynitrite-mediated oxidant stress may contribute to the development of this disease in premature infants and that 3-nitrotyrosine may be useful as an early plasma indicator of infants at risk for developing BPD.     

Pathogenic factors in bronchopulmonary dysplasia

Serum factors related to oxygen exposure were studied in 56 full-term cord blood samples and in 69 newborn infants of varying gestational age (GA). Serum malondialdehyde (MDA), which reflects membrane lipid peroxidation, was elevated during the first 2 d of life and rose to a peak at 3-5 d of life. This peak value was unrelated to GA or to assisted ventilation. The serum antioxidant, vitamin E, showed a significant rise by 6-10 d, and came into the adult range after d 11. Vitamin E levels did not correlate with GA, assisted ventilation, or the development of bronchopulmonary dysplasia (BPD). Serum ceruloplasmin, another antioxidant, was measured both by activity assay and by protein concentration assay. Little activity was found in cord blood. Ceruloplasmin activity increased during the first 48 h of life, and both activity and protein concentration correlated with GA at that time. Infants who subsequently developed BPD had a less active protein than infants on ventilators who did not develop BPD. In addition, activity and protein levels on 3-5 d were lower in infants on ventilators than in those not requiring assisted ventilation. Serum levels of alpha-1-AP activity and protein concentration were also correlated with GA during the first 48 h of life. The less mature infants had levels of activity and protein which were significantly less than the more mature infants and significantly less than the full-term cord values. The proportion of active protein correlated with GA at 3-5 d, indicating that the less mature infants had a lower proportion of active protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutrition and bronchopulmonary dysplasia]

Bronchopulmonary dysplasia remains a frequent complication of extreme prematurity. In preterm neonates catch-up and pulmonary alveolar growth occur during the first two years of life. However 10 to 25% of preterm infants with bronchopulmonary dysplasia are under-nourished after two years of age, and 30 to 60% of them also suffer from persistent airway obstruction, hyperinflation and bronchial hyperreactivity. Recommendations on nutritional requirements in this population are not yet clearly defined, but an adequate nutritional status in prenatal and early postnatal period can have long-term consequences on brain and lung development. There are a few randomised trial of nutrition for preterm infants with bronchopulmonary dysplasia after discharge. Caloric and protein requirements in this population are probably higher than in full-term infants. Moreover there are potential benefits in using specific nutrients: supplementation with long chain polyunsaturated fatty acids could decrease lung inflammation injuries, glutamine is the main source of energy of pneumocyte, vitamin A is essential for lung development, inositol is necessary for surfactant synthesis, vitamin E and selenium have anti-oxidant effects. Controlled nutritional trial are needed with a long term follow-up in late childhood in order to test their effects on growth and pulmonary status.     

Dexamethasone therapy in bronchopulmonary dysplasia

Dexamethasone has recently been introduced for the treatment of bronchopulmonary dysplasia (BPD). Whereas the short-term effect of dexamethasone has been documented in previous publications, studies on the long-term effect do not appear to exist in the literature. The aim of this retrospective study was to investigate the influence of dexamethasone on respiratory parameters, the long-term efficacy, and the side-effects. Dexamethasone was given to premature babies with BPD who could not be weaned from the respirator. Twelve infants were included in this study. The gestational ages ranged from 26 to 30 weeks and the birth weights ranged from 640 to 1410 g. Dexamethasone treatment was initiated at the age of 14 to 44 days. After 6 days of dexamethasone therapy, ventilation rates and FiO2 values improved significantly. All infants were successfully weaned from mechanical ventilation and extubated at 2 to 40 days after the start of dexamethasone therapy. The follow-up for the estimation of the long-term efficacy ranged from 3 to 18 months. Ten out of twelve patients had been weaned permanently from the ventilator; one 12-months-old infant is still respirator-dependent. One patient died at 8 months from BPD. In 5 out of 12 infants we observed a leukocytosis with neither clinical signs nor microbiological signs of an infection. Septicaemia developed in one case and one patient suffered from pneumonia. Arterial hypertension was observed in one infant during dexamethasone therapy. The results suggest that dexamethasone facilitates the weaning of preterm infants with BPD from the ventilator. This treatment may prevent some infants from long-term ventilation.     

氧化应激与支气管肺发育不良研究进展

支气管肺发育不良( bronchopulmonary dysplasia,BPD)是早产儿重要疾病.BPD的病因及发病机制复杂,高浓度吸氧引起的BPD与机体氧化和抗氧化失衡有关.氧化应激与炎症反应过程关系密切,二者相互影响并在BPD的发生发展中起重要作用.活性氧作为第二信使调节大量与细胞增殖、凋亡和炎症反应相关的核转录因子活性,这可能是氧化应激从基因水平促进BPD发生发展的重要机制.目前BPD的防治仍处于探索阶段.该文探讨高浓度氧疗引起的氧化应激和炎症反应与BPD的内在联系及BPD的抗氧化防治措施.     

Plasma lipid metabolites are associated with gestational age but not bronchopulmonary dysplasia

Aim: To test the hypothesis that plasma lipid metabolite levels in premature infants are associated with the development of bronchopulmonary dysplasia (BPD). The studies also tested a secondary hypothesis that plasma lipid metabolite levels were correlated with gestational age. Methods: Infants born <32 weeks’ gestation were enrolled during the first 72 h of life. Plasma samples were obtained and lipid levels were measured by LC‐MS/MS. Clinical data were collected to determine infant outcomes and BPD diagnosis. Results: Following adjustment for confounders, lipid levels were not associated with BPD; however, levels of specific lipid metabolites were correlated with gestational age. Conclusion: Immature lipid metabolism pathways in premature infants may contribute to the pathogenesis of BPD and other diseases.     

Dexamethasone therapy in severe bronchopulmonary dysplasia

Seven ventilator-dependent infants with severe bronchopulmonary dysplasia were treated with dexamethasone. Six of the seven infants were extubated within 12 days of commencing the dexamethasone, whilst the remaining infant continued to need respiratory support for apnoea, despite significant improvement in the pulmonary disease. All infants survived; although only two were neurologically intact. Of the other five survivors, two had mild developmental delay, two were blind (secondary to retinopathy of prematurity) and the other had a spastic quadriplegia (secondary to bilateral periventricular leukomalacia).     

Wnt信号通路与支气管肺发育不良

Wnt信号通路是一条在进化上保守的信号传导途径,主要由经典的Wnt/β-catenin途径和非经典的Wnt/平面细胞极性途径及Wnt/Ca2+途径组成,该通路从多个水平参与肺发育及多种肺部疾病过程.支气管肺发育不良(bronchopulmonary dysplasia,BPD)是在肺发育不成熟基础上由于炎症损伤及损伤后肺纤维化异常修复所导致的慢性肺疾病.该文就Wnt信号通路与肺发育、肺部炎症和肺纤维化的关系作一综述,以期揭示Wnt信号通路与BPD之间的可能联系,为BPD的防治提供新的切入点.     

早产儿支气管肺发育不良的病因及发病机制新进展

支气管肺发育不良是一种与早产相关的慢性肺部疾病,有较高的病死率和再入院率,目前尚缺乏有效的预防和治疗方法.它的病因尚不明确,目前认为是在遗传易患性的基础上,肺发育不成熟、肺损伤和损伤后的异常修复引起.肺部町见明显的炎症细胞及炎症因子的浸润,存在细胞的坏死和凋亡,同时在蛋白质水平及基因水平均有所改变.