Eosinophil activation in preterm infants with lung disease

AIM: We investigated the role of eosinophils in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Fifteen preterm infants with BPD were compared to 13 preterms with respiratory distress syndrome (RDS) and to 16 healthy preterms. We assessed total eosinophil and neutrophil counts in venous blood samples and the levels of the eosinophilic activity markers eosinophilic cationic protein (ECP) and the cellular surface antigen (CD9). RESULTS: The eosinophil count was greater in BPD compared with RDS and healthy infants (1414 vs. 797 and 471 cells per microlitre, respectively, p = 0.03). ECP levels were elevated (34 vs. 12.8 and 9.8 microg/L, respectively, p = 0.002) and CD9 levels reduced (75 vs. 94 and 86 mean fluorescence intensity units, respectively, p = 0.01) in BPD compared with RDS and healthy infants, suggesting eosinophilic activation in BPD. These findings were not solely explained by differences between gestational age or birth weight of the different groups. ECP levels were positively correlated with the duration of oxygen supplementation in the BPD group. The eosinophil count fell promptly after steroid treatment was commenced in the BPD group. CONCLUSION: The findings suggest that BPD is linked to eosinophil activation, which might contribute to the pathogenesis.     

Occurrence and severity of bronchopulmonary dysplasia and respiratory distress syndrome after a preterm birth

BACKGROUND:

Despite notable advances in neonatal care, bronchopulmonary dysplasia (BPD) remains an important complication of preterm birth, frequently resulting in prolonged hospital stay and long-term morbidity.

METHODS:

A historical cohort study of all preterm infants (gestational age younger than 37 weeks) admitted to the Montreal Children’s Hospital (Montreal, Quebec) between January 1, 1980, and December 31, 1992, was conducted. Information collected included demographic data, maternal and perinatal history, and main neonatal outcomes. Independent risk factors associated with BPD were identified by univariate analysis using one-way ANOVA, t tests or Mantel-Haenszel χ² testing. Severity of disease was studied using an ordinal multinomial logistic regression model.

RESULTS:

In total, 1192 preterm infants were admitted, of whom 551 developed respiratory distress syndrome and 322 developed BPD. For each additional week of prematurity, the risk of developing BPD increased by 54% (adjusted OR 1.54/week [95% CI 1.45 to 1.64]). For each point subtracted on the 1 min Apgar score, the risk of developing BPD was increased by 16% (OR 1.16 [95% CI 1.1 to 1.3]). BPD was also associated with the presence of patent ductus arteriosus (OR 3.5 [95% CI 2.1 to 6.0]), pneumothorax in the first 48 h (OR 9.4 [95% CI 3.6 to 24.8]) or neonatal pneumonia/sepsis in the neonatal period (OR 1.9 [95% CI 1.1 to 3.2]). Severity of BPD was associated with gestational age, 1 min Apgar score, very low birth weight and the presence of neonatal pneumonia/sepsis.

CONCLUSION:

Factors associated with BPD following a preterm birth were the degree of prematurity, birth weight, Apgar score at 1 min, and the presence of patent ductus arteriosus, pneumothorax or neonatal pneumonia/sepsis.     

呼吸窘迫综合征并发支气管肺发育不良危险因素分析

目的：探讨呼吸窘迫综合征（RDS）患儿支气管肺发育不良（BPD）的危险因素。方法：对该院2000年1月至2005年8月应用呼吸机治疗并住院28 d以上的呼吸窘迫综合征患儿进行回顾性分析,比较并综合分析20余种高危因素与BPD的关系。结果：72例呼吸机治疗、住院＞28 d呼吸窘迫综合征患儿BPD发生率为23.6%（17/72）,BPD 组 FiO2,PIP,PEEP,MAP,上机日龄、产前应用地塞米松促肺成熟、生后应用肺表面活性物质（PS）等与对照组差异无显著性（P＞0.05）,而胎龄≤30周、出生体重≤1 250 g、上机次数≥2次、合并肺炎、肺出血、上机天数≥5 d、痰培养阳性2次以上等与对照组差异有显著性（P<0.05）;多因素Logistic回归显示：出生体重≤1 250 g、机械通气≥10 d,痰培养阳性3次以上为发生BPD的独立危险因素。结论：避免低体重早产儿、缩短应用机械通气时间、防止及减少肺部感染,尤其是严重感染是预防RDS发生BPD的重要措施。［中国当代儿科杂志,2007,9（1）：15-18］     

早产儿支气管肺发育不良的防治

随着围生医学的发展,早产儿存活率上升,支气管肺发育不良(bronchopulmonary dysplasia,BPD)发病率也逐年增高.BPD是一种由多因素引发的慢性肺疾病,其病因及发病机制复杂,早期病死率高,晚期伴有呼吸系统,甚至神经系统的不良结局,严重影响早产儿存活率及生活质量.该文就BPD的防治进展作一综述.     

Outcomes of extremely low birth weight infants with bronchopulmonary dysplasia: impact of the physiologic definition

Aims

We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.

Study design

ELBW (birth weights < 1000 g) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n = 1189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18–22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score < 70).

Results

BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO₂ > 30% and 66 who failed the room air challenge. Infants on room air (n = 505) and those who passed the room air challenge (n = 51) were classified as “no BPD” (n = 556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores < 70 (24.2 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40–4.13) with cognitive impairment.

Conclusions

Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention.     

支气管肺发育不良患儿血清白细胞介素33的水平变化及临床意义

目的 探讨白细胞介素33（IL-33）在早产儿支气管肺发育不良（BPD）发生、发展中的作用及意义。方法 本研究采用前瞻性队列研究,选取胎龄≤32周和/或出生体重≤1 500 g的早产儿128例,根据病情分为非BPD组50例,轻度BPD组32例,中度BPD组30例,重度BPD组16例,收集所有早产儿母亲产前因素（母亲产前使用激素、母亲绒毛膜羊膜炎）、患儿产时因素（性别、胎龄、出生体重、分娩方式、出生窒息）、生后治疗情况（肺表面活性物质、有创通气时间、无创通气时间、肠外营养时间、总住院时间）;对各组早产儿分别于生后第1天、第14天、第28天采用酶联免疫吸附试验（ELISA）法检测血清IL-33水平,比较不同组别生后不同时间血清IL-33水平差异;对中重度BPD患儿确诊后采用传统激素治疗（DART方案）,检测治疗前后两组间血清IL-33水平变化。结果 BPD早产儿在母亲感染绒毛膜羊膜炎、胎龄、出生体重、出生窒息、有创通气时间、无创通气时间、肠外营养时间、总住院时间等方面,与非BPD早产儿比较,差异均有统计学意义（P < 0.05）,且上述指标在不同病情严重程度BPD早产儿组间比较差异有统计学意义（P < 0.05）。早产儿生后第1天、第14天、第28天,BPD组患儿血清IL-33水平高于非BPD组,且BPD病情程度越重,IL-33水平越高;随着生后时间的推移,BPD患儿血清IL-33水平有升高趋势（P < 0.05）。中重度BPD早产儿采用DART方案治疗后血清IL-33水平较治疗前均降低（P < 0.05）。结论 血清IL-33与BPD发生及病情严重程度密切相关,DART方案抗炎治疗可降低BPD患儿血清IL-33水平。     

早产儿支气管肺发育不良严重程度的影响因素

目的 探讨早产儿支气管肺发育不良（BPD）严重程度的影响因素。方法 收集2011 年1 月至2013 年12 月住院28 d 以上的明确诊断为BPD 的早产儿110 例,根据临床分度标准分为轻度BPD（52 例）、中度BPD（44 例）、重度BPD（14 例）,探讨不同分度BPD 与出生胎龄、出生体重、窒息、吸氧、母亲妊娠并发症、宫内感染性肺炎及机械通气等因素的关系。结果 不同分度BPD 与出生胎龄、出生体重、母亲产前感染、吸氧浓度>40% 的持续时间、是否机械通气、机械通气参数、机械通气时间、持续气道正压通气（CPAP）时间、是否采用INSURE 模式及是否合并解脲脲原体感染、宫内感染性肺炎及动脉导管未闭有关。有序logistic 回归分析显示机械通气参数中的吸气峰压（OR=1.260,95%CI：1.096~1.448）、机械通气时间（OR=1.010,95%CI：1.005~1.016）为BPD 严重程度的独立危险因素,采用INSURE 模式为保护因素（OR=0.208,95%CI：0.060~0.923）。结论 早产儿BPD 严重程度与多种因素有关;避免低出生体重早产儿出生、缩短应用机械通气时间、防止和减少肺部感染以及尽量采用INSURE 技术是预防BPD 进展的重要措施。     

Reduction in the risk of bronchopulmonary dysplasia from 1980–1990: Results of a multivariate logistic regression analysis

A retrospective analysis (1980–1990) of normally formed low birthweight (<2500g) infants surviving to at least 28 days following intermittent positive pressure ventilation (IPPV) for longer than 12h was performed. Bronchopulmonary dysplasia (BPD) was defined as oxygen dependency at 28 days with characteristic radiographic findings. Logistic regression analysis of risk factors, before and after the initiation of IPPV was performed on 412 infants. Decreasing birth weight (BW) and gestational age (GA) were associate with an increased risk of BPD. When controlled for these variables, predictive factors prior to IPPV were gender, age at IPPV, respiratory diagnosis, and year of birth. Following IPPV, duration of peak inspiratory pressure >25cm H₂O, duration of fraction of inspired oxygen (FiO₂)>0.60 (DO₂), maximum peak inspiratory pressure (MPIP), maximum FiO₂, patent ductus arteriosus, bacteraemia and either pneumothorax or pulmonary interstitial emphysema were associated with an increased risk of BPD Adjusting for BW and GA, there was a significant reduction in BPD risk from 1980–1990 (relative odds of 0.88 for each year compared to the previous year). This trend could belargely accounted for by decreases in MPIP and DO₂ during the study period. Surfactant treatment was not independently associated with a significant change in the risk of BPD. Based on this analysis, we developed a scoring system for predicting the risk of BPDL in the neonatal period which we evaluated in a random sampleof infants. This predicted infants at risk of BPD with a sensitivity of 65% and a specificity of 88%. Use of this score would allow prediction of BPD at a tim when earlier preventive treatment could be started.     

支气管肺发育不良早产儿振幅整合脑电图的临床意义分析

目的 了解支气管肺发育不良(BPD)早产儿振幅整合脑电图(aEEG)的变化特点及临床意义.方法 回顾性纳入出生胎龄≤32+6周符合BPD诊断的早产儿156例为BPD组,选择同期住院的非BPD早产儿156例为对照组,应用早产儿aEEG评分系统比较两组患儿住院期间的aEEG结果 ,并按检查时间(纠正胎龄≤28+6周、29～...     

支气管肺发育不良早产儿婴儿期预后研究

目的 探讨支气管肺发育不良（BPD）患儿婴儿期体格发育、呼吸系统常见疾病发生情况以及运动发育情况。方法 回顾性分析2012年1月至2015年12月入住新生儿重症监护室的BPD早产儿的临床特征和婴儿期结局，并与同期住院胎龄及出生体重相近但未发生BPD的早产儿进行比较，比较两组早产儿婴儿期生长发育和运动发育情况、住院次数以及肺炎、喘息等疾病的发生情况。结果 与非BPD组患儿相比，BPD组患儿出院时更容易发生宫外发育迟缓（48% vs 41%），且生后更容易发生肺炎、喘息、湿疹、鼻炎，因呼吸道感染再次住院次数增加，差异均具有统计学意义（P < 0.05）。矫正3月龄、6月龄及12月龄时BPD组患儿头围小于非BPD组（P < 0.05）。矫正6月龄及9月龄时BPD组患儿粗大运动、精细运动以及总发育商均落后于非BPD组患儿（P < 0.05）。结论 BPD患儿出院时容易发生宫外发育迟缓，头围增长相对缓慢，婴儿期易发生肺炎及喘息，而且矫正6月龄及9月龄运动发育落后于非BPD早产儿。     

支气管肺发育不良早产儿体积描记肺功能的动态观察

目的 探讨支气管肺发育不良（BPD）对早产儿肺功能的影响。方法 根据是否发生BPD及BPD程度将72名早产儿分为3组：非BPD组（n=44）、轻度BPD组（n=15）、中度BPD组（n=13）,采用体积描记术测定各组生后7 d、14 d及28 d的肺功能。结果 3组早产儿公斤体重潮气量（TV/kg）、功能残气量（FRC）、达峰时间比（% T-PF）、达峰容积比（% V-PF）在生后7 d、14 d及28 d均逐渐升高,而公斤体重气道阻力（Reff/kg）及呼吸频率（RR）则逐渐下降（P < 0.05）;轻度及中度BPD组在生后7 d、14 d、28 d的TV/kg、FRC、% T-PF、% V-PF均低于非BPD组,而Reff/kg及RR则高于非BPD组（P < 0.05）;中度BPD组在生后7 d的气道阻力（Reff）、Reff/kg、公斤体重功能残气量（FRC/kg）高于轻度BPD组（P < 0.05）。结论 BPD患儿存在一定程度的肺功能受损;体积描记肺功能监测有助于评估BPD患儿在新生儿期的肺发育。     

早产儿支气管肺发育不良的危险因素研究进展

随着医疗技术水平的快速发展,早产儿的存活率逐步提高,支气管肺发育不良的发生率也随之增加。本文对早产儿支气管肺发育不良的危险因素进行分析阐述。早产、机械通气及吸氧、新生儿呼吸窘迫综合征、感染、动脉导管未闭、贫血及输血是支气管肺发育不良的主要病因和危险因素。     

Early repair of inguinal hernia in preterm infants with oxygen-dependent bronchopulmonary dysplasia

Despite inguinal hernia being both common and problematic in a significant proportion of preterm infants with bronchopulmonary dysplasia (BPD), there has been a reluctance to intervene surgically for fear of exacerbating the underlying lung disease. We report our experience of early operation in 12 consecutive infants with varying degrees of oxygen-dependent BPD and investigate the effect of general anaesthesia and herniotomy on pulmonary function by measuring oxygen requirements prior to and following operation. Two infants who required oxygen in a concentration in excess of 95% failed to improve and died from the pulmonary disease 6 and 8 weeks following their operation. The remaining infants all showed a reduction in mean oxygen requirements in the weeks following operation. We conclude that, in the short term, hernia repair performed under general anaesthesia in infants with BPD of varying severity had no adverse effects on respiratory function, as determined by oxygen requirements. We suggest that in certain infants early repair may have been beneficial-potential mechanisms are explored.     

Incidence and prediction of bronchopulmonary dysplasia in a cohort of premature infants

Farstad T, Bratlid D. Incidence and prediction of bronchopulmonary dysplasia in a cohort of premature infants. Acta Pzdiatr 1994;83:19–24. Stockholm. ISSN 0803–5253
A prospective study on the incidence of bronchopulmonary dysplasia (BPD) in premature infants is reported. A cohort of premature infants with gestational ages 32 weeks, treated during 1989, was followed for one year. Of a total study population of 117 infants, 23 (19.6%) developed BPD, defined as oxygen dependence at 28 postnatal days. However, only 15 infants (12.8%) needed supplementary oxygen at the age of 36 gestational weeks and 5 infants (4.2%) needed supplementary oxygen periodically at one year of age. BPD was found to account for a significant part of both the total and late mortality in the cohort. Measurements of pulmonary mechanics were performed at 3 ± 1 and 12(13) ± 1 days of life in a subgroup of 26 infants with RDS who required assisted ventilation for 4 days or longer. No significant difference in lung compliance or resistance could be found during the first examination between infants who later devleoped BPD and infants with RDS only. At the second examination, infants who later developed BPD had significantly lower lung compliance (0.48 ± 0.23 ml/cmH₂O) than infants in the RDS group (1.50 ± 0.72 ml/cmH₂O) (p<0.001). Measurements of pulmonary mechanics could be of importance for early prediction of infants at risk of BPD.     

Increase of interleukin-6 in tracheal aspirate at birth: a predictor of subsequent bronchopulmonary dysplasia in preterm infants

Aim: We tested whether interleukin-6 (IL-6) in tracheal aspirate (TA) at birth, as a marker of fetal pulmonary inflammation, can be a predictor of bronchopulmonary dysplasia (BPD) in preterm infants. Methods: A total of 75 preterm (≤32 wk) infants who were intubated in the delivery room were prospectively enrolled. Multivariate logistic regression analysis was done to determine whether IL-6 in TA at birth is an independent risk factor for BPD, and a receiver-operating characteristic curve was constructed to determine the accuracy of IL-6 in TA for predicting the risk of BPD. Results: IL-6 in TA at birth was an independent risk factor for BPD. Fetal pulmonary inflammation defined as IL-6 in TA at birth ≥316 pg/ml together with patent ductus arteriosus (PDA) additively predicted the risk of BPD. The sensitivity, specificity, and positive and negative predictive values of fetal pulmonary inflammation for the identification of BPD were 73%, 71%, 58% and 83%, respectively.

Conclusion: IL-6 in TA at birth can be used as a predictor of BPD in combination with the presence of PDA.     

早产儿支气管肺发育不良营养管理专家共识

早产儿出生早期营养供给不足是支气管肺发育不良（BPD）发生的重要影响因素,并与其发生发展和最终临床结局密切相关。优化营养支持对降低BPD发生率和严重程度,促进患儿肺发育和神经系统预后至关重要。现基于国内外相关研究,采用证据推荐分级的评价方法（GRADE）,制定BPD营养管理专家共识,从营养在BPD中的重要性、液体量、能量、肠内营养、肠外营养、出院后营养、营养监测和评估等7个方面进行阐述,旨在为临床医师提供BPD高危儿和确诊患儿的营养管理建议,以期减少BPD的发生及改善BPD患儿的近远期预后。     

不同程度支气管肺发育不良早产儿的临床特征及预后分析

目的 探讨不同程度支气管肺发育不良（BPD）早产儿的临床特点及预后。方法 收集2014年3月至2016年3月入住NICU诊断为BPD且胎龄 < 32周的144例早产儿的临床资料,其中轻度组81例,中重度组63例,对轻度组与中重度组围生期高危因素及治疗情况、合并症及并发症、呼吸系统预后等情况进行比较和分析。结果 中重度组胎龄大于轻度组（P < 0.05）,但小于胎龄儿比例高于轻度组（P < 0.05）。中重度组重度子癎前期比例高于轻度组（P < 0.05）,先兆早产比例低于轻度组（P < 0.05）。中重度组生后2周仍需机械通气比例、机械通气时间、总氧疗时间、住院时间、肺炎及胆汁淤积综合症发生率高于轻度组（均P < 0.05）,枸橼酸咖啡因应用率低于轻度组（P < 0.05）。多因素logistic回归分析显示,小于胎龄儿（OR=5.974）、肺炎（OR=2.590）、出生2周仍需机械通气（OR=4.632）是BPD程度较重的危险因素（P < 0.05）。纠正胎龄40周肺功能检测中,中重度组达峰时间比（TPTEF/TE%）、达峰容积比（VPEF/VE%）及25%潮气量时呼吸流速（TEF25%）均低于轻度组（P < 0.05）。随访至纠正胎龄1岁,中重度组因肺炎反复入院率及喘息发作率均高于轻度组（P < 0.05）。结论 小于胎龄儿、肺炎、机械通气时间较长与BPD的严重程度相关,可加重BPD程度。中重度BPD患儿肺功能较差,易出现反复感染、喘息等并发症,应关注其远期预后。     

Cord blood Clara cell protein CC16 predicts the development of bronchopulmonary dysplasia

Clara cell protein (CC16) is an anti-inflammatory protein and a biomarker of pulmonary epithelial cells and alveolocapillary membrane injury in adults. We investigated whether low cord blood concentrations of CC16 are associated with the development of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants and the relationship between CC16 and its pro-inflammatory counterpart, the secretory phospholipase A₂ (sPLA₂) enzyme. CC16 concentration, sPLA₂ activity and IL-6 concentration were measured in cord blood plasma from 79 preterm infants (25 controls, 37 infants who developed RDS and 17 infants who developed BPD). After adjustment for gestational age and Apgar score at 5 min, the CC16 concentration was lower in BPD infants than in preterm controls (p<0.01). sPLA₂ activity was similar in all groups and the IL-6 concentrations were increased in both RDS and BPD infants (p<0.01 and p<0.05, respectively, vs. controls). We conclude that low cord blood CC16 concentrations in preterm infants independently predict the development of BPD. Low CC16 levels may reflect early lung injury, which contributes to the severity of RDS and progress towards BPD. Future studies are needed to assess whether the early administration of recombinant human CC16 in preterm infants with low cord blood CC16 prevents the development of BPD. This study was supported by grant 920-03-083 from the Netherlands Organisation for Scientific Research (NWO).