Interleukin-10 -1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

IL-10 is an anti-inflammatory cytokine that may have a protective role in acute lung injury. IL-10 expression is affected by a single-nucleotide polymorphism (SNP) located at position -1082 (G to A). The A allele is associated with lower IL-10 production. Low IL-10 production has been linked to the development of BPD. Thus, the IL-10 -1082 SNP may be a genetic risk factor for the development of BPD in the premature newborn. The IL-10 -1082 SNP was determined in 294 (235 African American, 56 Caucasian, and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants and compared to outcome (death and/or development of BPD). Differences in groups were analyzed using ANOVA (continuous variables) or chi square (proportions). The frequency of the A allele in our population was 0.62. Thirty-nine (13.3%) infants were homozygous GG, 146 (49.7%) were heterozygous GA, and 109 (37.0%) were homozygous AA. There were no significant differences between genotype groups with respect to ethnic origin, gender, need for surfactant replacement therapy, and isolation of Ureaplasma urealyticum or Mycoplasma hominis from tracheal aspirates at birth. However, AA infants were slightly more mature and of greater birth weight than GA infants (26.9 +/- 0.2 weeks vs. 26.3 +/- 0.2 weeks, P < 0.05, and 940 +/- 22 g vs. 882 +/- 18 g, P < 0.05, respectively). There was no significant effect of the IL-10 -1082 SNP on mortality or the development of BPD (O2 on 28 days or 36 weeks postconceptional age). However, when considered together, the IL-10 -1082 AA/GA genotypes (lower IL-10 production) were associated with a trend toward reduction in risk for the combined outcome of BPD or death (18/39 vs. 80/255, respectively; P = 0.068). The incidence of other complications of prematurity (retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia) was not different between groups. In conclusion, the IL-10 -1082 G/A SNP does not have a major influence on mortality or the development of BPD in ventilated VLBW infants.     

早产儿支气管肺发育不良的高危因素及防治对策

目的研究早产儿支气管肺发育不良的高危因素及防治对策。方法统计2010年1月~2013年12月在我院妇产科出生的早产儿498例的胎龄,出生体重,机械通气参数,是否发生宫内感染,产前或产后是否使用肺泡表面活性物质、肾上腺皮质激素等药物,是否输血,是否发生败血症、动脉导管未关闭以及肺透明膜病等合并症,分析上述指标与早产儿支气管肺发育不良之间的关系。结果早产儿支气管肺发育不良发生率为7.23%。低胎龄、低出生体重、宫内感染、吸入氧气浓度40%、机械通气吸气峰压20 cm H2O、机械通气潮气量6 ml/kg、应用呼吸机3 d、胎龄≤32周且未用使用肾上腺皮质激素及肺泡表面活性物质、输血、未早期喂养、合并症、胎膜早破等为早产儿支气管肺发育不良的高危因素。结论预防感染与早产,使用肾上腺皮质激素及肺泡表面活性物质,早期喂养,于低吸气峰压、低潮气量以及低浓度氧气的前提下机械通气,尽量降低输血量及液体入量,降低并发症发生率等是防治早产儿支气管肺发育不良的对策。     

Lung function following very preterm birth in the era of ‘new’ bronchopulmonary dysplasia

One of the most significant complications of preterm birth is bronchopulmonary dysplasia (BPD). The pathophysiology of BPD has changed in recent years as advances in neonatal care have led to increased survival of smaller, more preterm, infants who display alterations to alveolar and pulmonary microvascular development. It is becoming clear that infants with ‘new’ BPD experience lung disease that persists into later childhood, however, the oldest of these children are just now entering young adulthood and therefore the longer term pulmonary implications remain unknown. The role of lung function testing in the identification and subsequent management of patients with lung disease resulting from a neonatal classification of BPD is reviewed based on the underlying pathophysiology of the disease.     

Diffusing capacity of the lung in school-aged children born very preterm,with and without bronchopulmonary dysplasia

The aim of this study was to determine the extent to which bronchopulmonary dysplasia (BPD) affects the diffusing properties of lung tissue in childhood. Pulmonary function in 31 prematurely born children (BW. < 1250 g) was examined at ages 7–11 years. Twenty out of 31 prematurely born children met the criteria for BPD. The remaining 11 children had milder forms of neonatal lung disease. Twenty healthy children of the same age and born at term served as a control group. The diffusing capacity of the lung for carbon monoxide (D_LCO) was measured by the single breath method. Lung volumes were determined in a body plethysmograph and expiratory flow rates with a flow/volume spirometer. D_LCO values of children with histories of BPD did not differ significantly from those of the prematurely born children without BPD. However, D_LCO values in both prematurely born study groups were significantly lower than those in controls born at term. Thoracic gas volumes measured with a body plethysmograph were similar in all groups. Spirometry demonstrated reduced flow rates in both BPD and non-BPD prematurely born children. The results suggest that some structural changes in lung tissues and airways persist for years in children who are born very preterm regardless of whether they develop BPD or not. Pediatr Pulmonol. 1996; 21:353–360. © 1996 Wiley-Liss, Inc.     

CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants

Bronchopulmonary dysplasia (BPD) remains a major complication and accounts for high morbidity and mortality of preterm infants. The present study aimed to identify the key genes in the development of BPD and to provide some new insights into the pathogenesis of BPD. The {"type":"entrez-geo","attrs":{"text":"GSE108754","term_id":"108754"}}GSE108754 dataset was downloaded from Gene Expression Omnibus database containing 5 samples of BPD patients and 6 of non-BPD infants. The differentially expressed genes (DEGs) between BPD and non-BPD patients were identified by R software. The pathway and function enrichment analyses were performed through Database for Annotation Visualization and Integrated Discovery website. The protein-protein interaction network for DEGs was established by Cytoscape software and the most highly connected module was selected through MCODE plugin. Furthermore, the clinical sample verification among 25 BPD patients and 10 non-BPD infants was carried out in our center. Finally, based on the results above, the gene set enrichment analysis focusing on CD74 upregulated status was employed. Totally, 189 DEGs including 147 upregulated genes and 42 downregulated genes between BPD and non-BPD patients were screened out. The pathway and function enrichments revealed these DEGs were mainly enriched in asthma, intestinal immune network for IgA production, antigen processing and presentation and immune response. Thirteen DEGs (CD74, HLA-DMA, HLA-DRA, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DRB5, HLA-DPA1, HLA-DOA, HLA-DPB1, HLA-DQB2, HLA-DQA2, and HLA-DQB1) were determined as hub genes. The mRNA expression levels of the 13 hub genes were tested by quantitative real-time polymerase chain reaction among our clinical samples. Eventually, CD74 was confirmed to be the most significant highly expressed in BPD samples (P < .001) and its expression level was negatively correlated with gestational age (r = –0.653) and birth weight (r = –0.675). The gene set enrichment analysis results showed the gene sets associated with lupus erythematosus, viral myocarditis, immune network for IgA production, graft versus host disease, cell adhesion molecules and so no were differentially enriched with the phenotype of high-expression CD74. In conclusion, CD74 may serve to predict the BPD development and provide a new therapeutic target for BPD.     

Early versus late identification of infants at high risk of developing moderate to severe bronchopulmonary dysplasia

We developed a simple method to identify neonates at high risk of bronchopulmonary dysplasia (BPD) and determined whether early (8 hours) and late (14 days) risk assessment is equally useful. A retrospective cohort design was utilized of subjects enrolled in multi-dose surfactant trials to develop each risk identification model. Prospective testing of the late 14-day model was done to determine accuracy. The primary outcome variable (moderate to severe BPD) was defined as the need for oxygen and mechanical ventilation beyond 28 days of life and significant chest X-ray changes. Variables were screened for inclusion in the models by univariate and multiple regression analysis of data available at 14 days or 8 hours of life, converted to yes-no variables by the use of receiver-operator curves; the final model was based on those variables that gave the highest sensitivity and specificity for identifying BPD risk. Thirty-eight out of 116 of the 14-day model subjects developed BPD. The 14-day model [F₁O₂ ≥ 0.30 and ventilation index (defined as 10,000/peak pressure × rate × PCO₂) < 0.510 (or < 0.800 if previously septic)] had a sensitivity of 82% and specificity of 89%. It accurately identified 83% of cases (51/61) during a 1-year prospective test. The positive predictive value was 81% and negative predictive value 88%. Forty-four of the 698 early 8-hour model subjects developed BPD. The 8-hour model [gestational age < 31 weeks, 5-minute Apgar < 9, ventilator rate > 23 breaths/min, and ventilation index < 0.895] had a sensitivity of 73%, specificity of 83%, negative predictive value of 98% but positive predictive value of only 22%. These observation indicated that clinical data can create an accurate and simple model to classify infants into high- or low-risk groups for BPD. Using such models very early in life (e.g., at 8 hours) may lead to a high number of false-positive identifications. Pediatr Pulmonol. 1996; 21:345–352. © 1996 Wiley-Liss, Inc.     

Spontaneous desaturations in intubated very low birth weight infants with acute and chronic lung disease.

Patients with chronic lung disease (CLD) have frequent episodes of spontaneous desaturations. Utilizing computerized pulse oximetry (CPO) we quantified the frequency and severity of spontaneous desaturations in very low birth weight (VLBW) infants with CLD. Thirty-four studies by CPO were performed in intubated infants for 4 hours; 17 patients (birth weight, 550-980 g; postnatal age 28-85 days) had CLD, and 17 (birth weight, 520-980 g; postnatal age, 1-7 days) had acute lung disease. Oxygen saturation (SaO2) was measured with the Nellcor N-200 oximeter, its serial output (updated once a second) captured by a computer. Pulse rate, pulse amplitude, and heart rate were also monitored continuously. We measured respiratory system mechanics in 23 patients. Tidal volume (VT), respiratory system compliance (Crs), and resistance (Rrs) were obtained by the PeDS system. Spontaneous desaturation to SaO2 less than 90% occurred for 4.5% of the time in acute patients vs. 27.1% of the time in chronic patients (P less than 0.0001); to SaO2 less than 85%, 0.7% vs. 7.6% of the time in acute vs. chronic patients (P less than 0.002); and to SaO2 less than 80%, 0.4% vs. 2.6% of the time in acute vs. CLD patients (P less than 0.05). Rrs was significantly higher in the ventilated patients with CLD (174 cmH2O/L/s) than in the ventilated patients with acute lung disease (94 cmH2O/L/s, P less than 0.0001). The mean Crs values of the two groups were comparable. Our preliminary data indicate that VLBW infants with CLD receiving assisted ventilation have a greater number of spontaneous desaturation episodes, as compared to patients with acute lung disease.     

巨细胞病毒感染与早产儿支气管肺发育不良的相关性探讨

目的 探讨临床巨细胞病毒（CMV）感染与早产儿支气管肺发育不良（BPD）的关系.方法 选取我院收治的42例支气管肺发育不良的早产儿作为观察组,另选取在我院生产的42例非支气管肺发育不良的早产儿作为对照组,通过酶联免疫吸附测定实验（ELISA）检查两组早产儿血清中的CMV-IgM及CMV-IgG抗体情况,比较两组早产儿发生巨细胞病毒感染情况.结果 检测结果显示观察组早产儿巨细胞感染率显著高于对照组,（P〈0.01）;而临床症状感染率观察组较对照组明显升高（P〈0.05）,有统计学意义.结论 CMV感染,尤其是症状性感染是引起早产儿BPD的重要因素之一.     

Frontiers in pulmonary hypertension in infants and children with bronchopulmonary dysplasia

Pulmonary hypertension (PH) is an increasingly recognized complication of premature birth and bronchopulmonary dysplasia (BPD), and is associated with increased morbidity and mortality. Extreme phenotypic variability exists among preterm infants of similar gestational ages, making it difficult to predict which infants are at increased risk for developing PH. Intrauterine growth retardation or drug exposures, postnatal therapy with prolonged positive pressure ventilation, cardiovascular shunts, poor postnatal lung and somatic growth, and genetic or epigenetic factors may all contribute to the development of PH in preterm infants with BPD. In addition to the variability of severity of PH, there is also qualitative variability seen in PH, such as the variable responses to vasoactive medications. To reduce the morbidity and mortality associated with PH, a multi‐pronged approach is needed. First, improved screening for and increased recognition of PH may allow for earlier treatment and better clinical outcomes. Second, identification of both prenatal and postnatal risk factors for the development of PH may allow targeting of therapy and resources for those at highest risk. Third, understanding the pathophysiology of the preterm pulmonary vascular bed may help improve outcomes through recognizing pathways that are dysregulated in PH, identifying novel biomarkers, and testing novel treatments. Finally, the recognition of conditions and exposures that may exacerbate or lead to recurrent PH is needed to help with developing treatment guidelines and preventative strategies that can be used to reduce the burden of disease. Pediatr Pulmonol. 2012. 47:1042–1053. © 2012 Wiley Periodicals, Inc.