Lung function at term reflects severity of bronchopulmonary dysplasia

OBJECTIVE: To test whether infants with bronchopulmonary dysplasia (BPD) express the same functional impairments at term as healthy, preterm infants, and whether clinical severity of BPD is qualitatively or quantitatively related. STUDY DESIGN: Prospective measurements on a consecutive sample of 50 infants with BPD and 19 healthy preterm controls in a university hospital. BPD infants were classified as "severe," "moderate," or "mild," according to their need for oxygen. A multiple-breath nitrogen wash-out method was used to assess functional residual capacity (FRC) and gas mixing efficiency. Mechanical variables were estimated by the occlusion test. RESULTS: Infants with severe BPD had lower FRC, less efficient gas mixing, and higher specific conductance than those with mild and moderate BPD, and the preterm controls. Mild and moderate BPD did not differ in any property from each other but differed from controls in the same variables. The elastic properties of the respiratory system appeared unaffected by BPD. CONCLUSIONS: The ventilatory impairments in BPD were of the same nature as in healthy preterm infants when compared with term infants, but their magnitude was related to the clinical severity of the BPD. Gas mixing efficiency together with FRC appears to be useful to assess lung development in BPD.     

Increased lung water and tissue damage in bronchopulmonary dysplasia

OBJECTIVES: To test the hypothesis that high and asymmetrical water content persists in infants with bronchopulmonary dysplasia (BPD) and that this is associated with nonuniform lung damage. STUDY DESIGN: Magnetic resonance imaging was used to assess lung water content in 20 infants and tissue injury in 35 infants of 23 to 33 weeks' gestational age (15 with severe BPD, 13 with mild BPD, and 7 without BPD). Relative proton density provided an index of water content and distribution. The location and extent of focal densities and cyst-like appearances indicating lung damage were defined. RESULTS: Proton density was significantly higher in dependent regions. Average proton density, proton density gradient, and severity of lung damage were greater in infants with severe BPD. Indicators of damage were greatest in dorsal lung regions. BPD was associated with a higher lung water burden and gravity-dependent atelectasis and/or alveolar flooding. Lesions were more common in dorsal lung regions in infants with severe lung damage. CONCLUSIONS: Infants with BPD have increased lung water and are susceptible to gravity-induced collapse and/or alveolar flooding in the dependent lung. Focal tissue damage appears to be distributed inhomogenously.     

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.     

小胎龄早产儿支气管肺发育不良发生率和危险因素分析

目的探讨小胎龄早产儿支气管肺发育不良(BPD)的发生率和高危因素。方法回顾性分析2008年5月至2011年12月我院新生儿科收治、胎龄≤32周、且存活28天以上的早产儿临床资料,发生BPD的早产儿为BPD组,按1∶2的比例随机选取未发生BPD的早产儿为对照组。结果共纳入197例早产儿,BPD组28例,BPD发生率14.2%,早产儿随胎龄和出生体重降低BPD发生率明显增加,各胎龄段和体重组差异均有统计学意义(χ2=32.269,30.244,P=0.000)。通过对23个单因素的分析发现,BPD组和对照组胎龄、出生体重、吸氧时间、最高吸入氧浓度、住院时间、气管插管机械通气、应用肺表面活性物质治疗、贫血、使用美罗培南、第10天体重/出生体重比值、氧合指数<300和生后第1次血气评分值12个单因素差异有统计学意义(P均<0.05);多因素Logistic回归分析发现,出生体重低(OR=0.996)、吸氧浓度高(OR=0.898)、第10天体重/出生体重比值小(OR=1.069)为发生BPD的高危因素(P均<0.05)。中重度BPD组与轻度BPD组相比,窒息和使用利尿剂比例高、吸氧时间长、生后第1次血气评分低,差异有统计学意义(P均<0.05)。结论出生体重低、吸入高浓度氧、第10天体重/出生体重比值低为小胎龄早产儿发生BPD的高危因素。     

早产儿支气管肺发育不良发生率及高危因素的多中心回顾调查分析

目的 了解国内早产儿支气管肺发育不良(BPD)的发生率,探讨影响其发病及其严重程度的因素,为早期预防BPD提供指导意见。方法 回顾性收集国内10家NICU2006年1月1日至2008年12月31日收治的胎龄＜37周且存活≥28 d早产儿临床资料,根据患儿出生后28 d是否用氧(＞21％)分为BPD组和非BPD组。生后28 d未用氧为非BPD组;生后持续用氧≥28 d为BPD组。计算各个胎龄BPD发病率;从数字表中随机选取360例非BPD早产儿做为对照组进行对比研究,对两组患儿临床资料进行对比研究;并对两组患儿生后10d内的总液体量、热卡摄入以及体重下降的百分比进行了组间比较。同时根据出生时胎龄在生后不同日龄进行评估疾病严重程度,即如胎龄＜32周,在校正胎龄36周或出院时进行评估;如胎龄≥32周,在生后56 d或出院时评估：①轻度：未用氧;②中度：FiO2＜ 30％;（③重度：FiO2≥30％或需机械通气。比较轻度BPD和中重度BPD两组患儿的临床资料。临床资料结果采用计量或计数资料描述,计量资料采取非参数检验法,计数资料采用卡方检验（fisher精确概率法）比较两组资料的差异;Logistic回归分析逐步向前引入法找出BPD发病及其病情程度的主要影响因素。结果 10家医院胎龄＜37周早产儿共12 351例,其中符合BPD诊断的156例,BPD发生率为1.26％。其中GA≤28、28～、30～、32～、34～、＜37周BPD发生率分别为19.3％、13.11％、5.62％、0.95％和0.09％,BPD发生率随胎龄增加明显降低。多因素逐步Logistic回归分析结果显示,体重低于1.5 kg、动脉导管未闭、早产儿贫血、肺透明膜病、巨细胞病毒感染、机械通气、呼吸机持续时间≥7d及PaO2/FiO2＜ 300这8个因素为支气管肺发育不良患儿的高危因素。BPD组与非BPD组患儿生后5d内液体量摄入组间比较无差异,而BPD组患儿生后10d内热卡摄入以及生后前3d内体重下降的百分比明显减少(P＜0.01)。 156例BPD中,20份因资料丢失过多剔除,剩余136例病例中轻度支气管肺发育不良71例,中重度65例。住院天数、用氧时间及氧浓度大于0.3持续时间、院内感染、巨细胞病毒感染、羊水污染、生后是否使用CPAP、呼吸机持续时间≥7 d、生后第一次血气CO2共9个因素组间差异有统计学意义;多因素逐步Logistic回归分析结果显示,合并院内感染、巨细胞病毒感染、呼吸机持续时间≥7 d这三个因素为中重度支气管肺发育不良患儿的高危因素。结论国内10家医院早产儿BPD发生率为1.26％,发病率随胎龄增加而明显降低。极低生体重、动脉导管未闭、贫血、肺透明膜病、巨细胞病毒感染、机械通气、PaO2/FiO2＜ 300等是其高危因素,BPD组生后10 d内热卡摄入明显低于非BPD组。预防院内感染、巨细胞病毒感染及减少机械通气持续时间可降低BPD严重程度。     

Eosinophil cationic protein in tracheal aspirates of preterm infants with bronchopulmonary dysplasia

Eosinophil cationic protein was elevated during the first week of life in tracheal aspirates from 11 preterm infants in whom bronchopulmonary dysplasia subsequently developed compared with 8 preterm and 8 term infants without bronchopulmonary dysplasia. Eosinophil cationic protein levels increased progressively with continued intubation in the infants with bronchopulmonary dysplasia but remained low in a comparison group of term infants. We suggest that eosinophils participate in the inflammatory process in bronchopulmonary dysplasia and may contribute to lung injury. (J Pediatr 1997;130:944-7)     

Behaviour and quality of life at school age of children who had bronchopulmonary dysplasia

BACKGROUND: There is little information available concerning behavioural and functional health problems in children who had bronchopulmonary dysplasia (BPD). AIM: To compare behavioural problems and quality of life in a cohort of children at school age who had BPD with preterm and term controls. METHODS: The cohort of 78 BPD children of 26 to 33 weeks' gestation was matched for birth weight with preterm controls. At school age follow-up, information was available for 66 BPD children and 60 preterm controls. (Three children with severe cerebral palsy were excluded). Parents completed the Child Behaviour Checklist (CBCL) and the Child Health Questionnaire (CHQ). The child's teacher completed the Teacher Report Form (TRF) of the CBCL, with the teachers of the BPD children completing a TRF on a classroom control. Parents completed a questionnaire on their levels of anxiety and depression. RESULTS: The mean total problem score on the CBCL for the BPD children was similar to the controls, with the BPD children displaying more internalising behaviours. Little variation was seen between the BPD and preterm children on the TRF. Significant differences between classroom controls and the BPD children were found for the total problem scores (p=0.001), internalising behaviours (p=0.01) and social (p=0.047), attention (p=0.0001) and thought problems (0.047). Results from the CHQ showed no difference between the groups in their physical health or the impact of health problems on family life. CONCLUSION: BPD children at school age display more internalising behaviour than preterm controls, with marked differences on comparison with classroom controls. Quality of life, however, does not seem to be adversely affected compared to the preterm controls.     

早产儿机械通气治疗后支气管肺发育不良危险因素分析

目的探讨早产儿支气管肺发育不良（BPD）的危险因素及预防对策。方法回顾性分析本院2000年1月至2005年8月应用呼吸机治疗并住院28d以上的早产儿，比较并综合分析20余种高危因素与BPD发生的关系。结果106例呼吸机治疗、住院〉28d早产儿BPD发生率为30．19％（32／106），占所有住院28d以上早产儿的13．91％（32／230），占住院28d以上、应用机械通气治疗、出生体重≤1500g早产儿的18．52％（25／135）。BPD组FiO2、PIP、PEEP、MAP、上机时日龄与对照组无显著性差异（P〉0．05）。多因素Logistic回归分析显示：出生体重≤1250g、机械通气≥10d、痰培养阳性2次以上为发生BPD的独立危险因素。结论避免低出生体重早产儿、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早产儿发生BPD的重要措施。     

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.     

Respiratory and systemic effects of inhaled dexamethasone on ventilator dependant preterm infants at risk for bronchopulmonary dysplasia

Short term inhaled dexamethasone therapy was evaluated in a double blind placebo controlled trial in 36 ventilator dependent preterm neonates (BW<1500 gm, postnatal age>7 days) who were at risk for bronchopulmonary dysplasia. Pulmonary and systemic effects were compared at early (day 3), late (7–10 days) and post (14 days after initiation) phases of therapy. Airflow mechanics improved as demonstrated by a net 101% improvement in pulmonary resistance (a decrease from 139 to 101 cm H₂O/L/s in the dexamethasone treated infants as compared to an increase from 153 to 267 cm H₂O/L/s in the placebo treated infants during the early phase of therapy); this was associated with a 45% increase in inspiratory airflow (1.29±0.43 to 1.87±0.978 L/min; p<0.01), and 37% increase in expiratory airflow. These changes resulted in a significant reduction in the work of breathing such that the mean tidal driving pressure significantly decreased from 13.6 cmH₂O to 9.4 cm H₂O with inhaled steroid administration. Though the brief duration of therapy did not result in cessation of ventilatory support, the level of support was significantly reduced (decreased values of oxygen supplementation, mean airway pressure and oxygenation index and increased ventilatory efficiency index). The inhaled dexamethasone therapy was also associated with systemic absorption of the drug as evidenced by transient but apparently reversible reduction in serum cortisol levels. No systemic side effects of hypertension, hyperglycemia or nosocomial sepsis were observed. These data demonstrate beneficial effects of short term inhaled dexamethasone on the resistive airflow properties of preterm infants at risk for BPD and may provide adjunctive means to facilitate weaning in the ventilator dependent neonates.     

Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002

OBJECTIVE: To examine temporal trends in the rates of severe bronchopulmonary dysplasia (BPD) between 1994 and 2002. STUDY DESIGN: In a retrospective cohort study, all infants with a gestational age (GA) <33 weeks in a large managed care organization were identified. Annual rates of BPD (defined as an oxygen requirement at 36 weeks corrected GA), severe BPD (defined as respiratory support at 36 weeks corrected GA), and death before 36 weeks corrected GA were examined. RESULTS: Of the 5115 infants in the study cohort, 603 (12%) had BPD, including 246 (4.9%) who had severe BPD. There were 481 (9.5%) deaths before 36 weeks corrected GA. Although the decline in BPD in this period was not significant, the rates of severe BPD declined from 9.7% in 1994 to 3.7% in 2002. Controlling for gestational age, the odds ratio (95% CI) for annual rate of decline in severe BPD was 0.890 (0.841-0.941). Controlling for gestational age, deaths before 36 weeks corrected GA also declined, with the odds ratio (CI) for the annual decline being 0.944 (0.896-0.996). CONCLUSIONS: In this study population, the odds of having of BPD remained constant after controlling for GA. However, the odds of having severe BPD declined on average 11% per year between 1994 and 2002.     

早产儿支气管肺发育不良危险因素及2岁时随访结局

目的探讨早产儿发生支气管肺发育不良（BPD）的危险因素及远期随访结局。方法 以2012年1月至2013年12月在复旦大学附属儿科医院新生儿科病房住院的胎龄≤32周、出生体重≤1 500 g及生后7 d内入院的BPD早产儿为BPD组,同期入住我院的非BPD早产儿中选取与BPD组等同样本量的病例为对照组。采集与BPD发生的母亲和新生儿因素行单因素分析和多因素分析。同时统计BPD早产儿生后1岁内和~2岁的支气管炎、肺炎、喘息发作次数和住院次数等指标。结果 BPD组和对照组均纳入了156例早产儿。单因素分析显示,BPD组母亲年龄（P=0.046）、先兆子（P=0.025）和阴道产（P<0.001）比例显著高于对照组;BPD组出生胎龄、出生体重显著低于对照组 (P均<0.001 )。BPD组1 和5 min Apgar 评分,败血症 ≥72 h、动脉导管未闭（PDA）、早产儿视网膜病变、应用肺表面活性物质、呼吸机相关性肺炎、机械通气≥7 d的比例均与对照组差异有统计学意义。多因素Logistic回归分析显示胎龄(OR= 0.46,95%CI:0.37~0.58)、机械通气≥7 d(OR=9.47,95%CI：3.70~24.27)、PDA(OR=2.21,95%CI：1.18~4.12)、先兆子(OR=4.91,95%CI：1.26~19.15 )是发生BPD的危险因素。BPD组1岁以内支气管炎、喘息的发生率高于对照组,再入院率两组差异无统计学意义;BPD组生后~2岁较生后1岁以内肺炎的发生率显著下降,支气管炎、喘息的发生率及再入院率差异无统计学意义。结论 低出生胎龄、机械通气≥7 d、PDA、先兆子是发生BPD的危险因素;BPD早产儿在生后1年以内下呼吸道感染的发生率增高。     

Association between fluid intake and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants

OBJECTIVE: To demonstrate the association between fluid intake and weight loss during the first 10 days of life and the risk of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. STUDY DESIGN: A retrospective analysis of data from a cohort of ELBW infants enrolled in the Neonatal Research; 1,382 infants with birth weight between 401 and 1,000 g were randomized. The daily fluid intake and weight loss during the first 10 days of life were compared between the infants who survived without BPD and those who either died or developed BPD. Demographic and clinical neonatal variables were also compared. Multivariate logistic regression was used to analyze the effect of fluid intake and weight loss on death or BPD, controlling for demographic and clinical factors that are significantly associated with BPD by univariate analysis. RESULTS: 585 infants survived without BPD and 797 infants either died or developed BPD. Univariate analysis showed that the daily fluid intakes were higher (day 2-10) and weight loss less (day 6-9) in the group of infants who either died or developed BPD. In addition, lower birth weight, lower gestational age, male gender, lower 1 and 5-minute Apgar Scores, higher oxygen requirement at 24 hours of age, longer duration of assisted ventilation, use of postnatal steroids for BPD and presence of severe intraventricular hemorrhage, proven necrotizing enterocolitis, patent ductus arteriosus, and late onset sepsis, were associated with higher incidence of death or BPD. The adjusted risk of higher fluid intake and less weight loss during the first 10 days of life remained significantly related to death or BPD. CONCLUSION: In this cohort of ELBW infants treated during the post surfactant era, higher fluid intake and less weight loss during the first 10 days of life were associated with an increased risk of BPD. The finding suggests that careful attention to fluid balance might be an important means to reduce the incidence of BPD.     

Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia

OBJECTIVE: To describe rates and identify risk factors for rehospitalization during the first year of life among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a retrospective cohort study of infants born at a gestational age (GA) <33 weeks, between 1995 and 1999. BPD was defined as requirement of supplemental oxygen and/or mechanical ventilation at 36 weeks' corrected GA. The outcome was rehospitalization for any reason before first birthday. RESULTS: In the first year of life, 118 of 238 (49%) infants with BPD were rehospitalized, more than twice the rate of rehospitalization of the non-BPD population, which was 309 of 1359 (23%) (P=<.0001). No measured factor discriminated between those infants with BPD who were and were not rehospitalized, even when only rehospitalizations for respiratory diagnoses were considered. CONCLUSIONS: Among premature infants, BPD substantially increases the risk of rehospitalization during the first year of life. Neither demographic nor physiologic factors predicted rehospitalization among the infants with BPD. Other factors, such as air quality of home environment, passive smoking exposure, respiratory syncytial virus prophylaxis, breast-feeding status, and/or parenting and primary care management styles, should be examined in future studies.     

CD105在高氧肺损伤小鼠肺内表达水平及意义

目的探讨吸入中浓度氧新生小鼠血清和肺部血管内皮细胞膜抗原CD105表达水平及意义,寻求高氧肺损伤新生小鼠肺微血管发育可能的机制。方法清洁级4日龄昆明小鼠50只,随机分为观察组、对照组各25只。观察组置于氧箱中(FiO2:0.6),对照组置于空气中(FiO2:0.21),建立高氧肺损伤小鼠模型,每组分别于实验第0(实验开始时)、7、14、21、28天时随机选取5只小鼠留取血标本及肺组织,HE染色观察肺组织病理形态,酶联免疫吸附法检测血中CD105含量,免疫组化染色法检测肺组织CD105表达水平,并分析血清CD105浓度与肺组织CD105表达量的相关性。结果观察组HE染色下正常肺泡结构消失、肺泡融合、肺泡间隔增厚,肺泡炎和肺组织纤维化增加,放射状肺泡计数较对照组明显减少(P<0.01),随着吸氧时间延长,CD105的表达水平呈逐渐增高趋势,实验第7、14、21、28天观察组血清CD105浓度和肺组织CD105表达水平均高于对照组,血清(ng/L):[7天:(346.4±14.7)比(265.7±2.0),14天:(400.2±20.1)比(266.3±3.2),21天:(505.1±6.1)比(267.1±5.8),28天:(451.9±10.0)比(268.6±4.5),P<0.01];肺组织累积光密度值:[7天:(2.24±0.15)比(1.19±0.14),14天:(3.42±0.20)比(1.20±0.11),21天:(4.35±0.18)比(1.16±0.18),28天:(4.04±0.12)比(1.17±0.14),P<0.01],且观察组CD105在血清中与肺组织中的表达水平呈正相关(r=0.973,P<0.001)。结论 CD105可能代替传统的血管内皮生长因子和血管生成素-1,成为氧疗通气诱导血管重塑的重要血管生长因子。     

Substrate utilization and kinetics of surfactant metabolism in evolving bronchopulmonary dysplasia

OBJECTIVES: To use stable isotopically labeled precursors of pulmonary surfactant phospholipids to measure precursor utilization and surfactant turnover in premature infants who required mechanical ventilation at birth, 2 weeks, and >4 weeks of age. STUDY DESIGN: Infants of < or =28 weeks' gestation received simultaneous 24-hour intravenous infusions of [1,2,3,4-13C4] palmitate and [1-13C1] acetate at birth, 2 weeks, and > or =4 weeks of life. Disaturated phospholipids were extracted from sequential tracheal aspirate samples obtained over a period of 2 weeks. Fractional catabolic rate (a measure of total turnover) and the fractional synthetic rates from plasma palmitate and de novo synthesis (acetate) were measured. RESULTS: The fractional catabolic rate increased from 25.3% +/- 7.0% per day at birth to 53.8% +/- 14.4% per day at 4 weeks (P=.001). The combined contribution from plasma palmitate and de novo synthesis to total synthesis increased from 44.2% +/- 19.8% at birth to 85.2% +/- 32.8% at 4 weeks (P=.03). CONCLUSIONS: Total surfactant turnover increased in premature infants with evolving bronchopulmonary dysplasia. The increasing contributions from acetate and plasma palmitate suggest a decrease in surfactant phospholipid recycling.