Interstitial lung disease in infancy: A general approach

Childhood Interstitial lung disease (chILD) is an umbrella term used to define a broad range of rare, diffuse pulmonary disorders with altered interstitial structure that leads to abnormal gas exchange. Presentation of chILD in infancy can be difficult to differentiate from other common causes of diffuse lung disease. This article aimed at paediatricians provides an overview of interstitial lung disease presenting in infancy and includes key clinical features, a suggested approach to investigation and a summary of management. An overview of three clinical cases has been included to demonstrate the diagnostic approach, characteristic investigation findings and varied clinical outcomes.     

Chronic lung disease in newborns

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) occurs in preterm infants who require respiratory support in the first few days of birth. Apart from prematurity, oxygen therapy and assisted ventilation, factors like intrauterine/postnatal infections, patent ductus arteriosus, and genetic polymorphisms also contribute to its pathogenesis. The severe form of BPD with extensive inflammatory changes is rarely seen nowadays; instead, a milder form characterized by decreased alveolar septation due to arrest in lung development is more common. A multitude of strategies, mainly pharmacological and ventilatory, have been employed for prevention and treatment of BPD. Unfortunately, most of them have not been proved to be beneficial. A comprehensive protocol for management of BPD based on the current evidence is discussed here.     

高氧致慢性肺疾病新生大鼠肺泡损伤及肺泡上皮细胞的变化

目的 探讨高浓度氧致新生鼠肺损伤时肺泡形态学变化和肺泡上皮细胞动态变化.方法 通过吸入85%～90%高浓度氧气建立新生鼠慢性肺疾病组织模型.80只新生鼠分为实验组和对照组,实验组(n=40)吸人85%～90%氧气,对照组(n=40)吸入空气.分别留取1、3、7、14、21 d的肺组织,应用放射状肺泡计数(RAC)并且测量肺泡间隔厚度以判定肺泡发育情况,应用免疫组化及RT-PCR技术测定肺组织表面活性蛋白C(SPC)、水通道蛋白-5(AQP5)蛋白及mRNA表达.结果 在生后1 d和3 d,两组RAC和肺泡间隔厚度差异无显著性(P>0.05).在7 d和14 d,实验组的RAC明显低于对照组(P<0.01),肺泡间隔厚度高于对照组(P<0.01),21 d时肺泡间隔厚度升至最高,与对照组间比较差异有显著性(10.62±5.01 vs 3.62±0.88,P<0.001),RAC降至最低,与对照组间比较差异有显著性(3.57±1.24 vs10.47±0.88,P<0.001).高氧肺损伤实验组SPC 3 d时表达明显减少,7d后开始增多,14 d、21d明显高于对照组;而AQP5随着肺损伤的加重表达进行性下降.结论 高氧肺损伤可导致肺泡发育停滞,明显损伤肺泡上皮细胞,肺泡上皮细胞特异性标志物SPC、AQP5表达结果提示I型肺泡上皮细胞损伤严重,Ⅱ型肺泡上皮细胞虽然数量有所增加但其分化与转化能力明显下降.     

Interstitial lung disease in infancy

Objective To describe the clinical profile of interstitial lung disease in infancy. Methods A retrospective analysis of cases diagnosed to have ILD was carried out in Kanchi Kamakoti CHILDS Trust hospital over a period of 2 yr. Infants aged 1 month to 1 yr of age were included if they had (1) respiratory symptoms (Cough, tachypnea or crepitations) for at least 1 month (2) diffuse infiltrates on chest radiography (3) Hypoxemia as defined by oxygen saturation less than 90% by pulse oximetry and (4) High Resolution Computed Tomography (HRCT) of the chest revealing findings of interstitial infiltrates of ground glass pattern. Their case records were analyzed for clinical data, treatment and follow up details. Results Of the 9 children, who were diagnosed to have ILD, 5 were boys and 4 were girls. The male: female ratio was 1.25: 1. The median age of onset of symptoms was 5 month. The common clinical features observed were tachypnea associated with chest indrawing (100%), cough (100%), hypoxia (100%), failure to thrive and fever (55%) each. The following radiographic patterns were observed in the chest skiagrams: reticulo-nodular pattern in 6(67%) and ground glass pattern in 3(33%). HRCT showed interstitial infiltrates in 6 (67%) and ground glass pattern in 3(33%). Evidence for cyto megalo virus (CMV) infection was detected in 5(56%), Adenovirus in 1 (11%) and Pneumocystis carinii (PCP) in 1(11%) infant. Open lung biopsy was performed in 2 infants, which detected CMV in 1 and PCP in the other. All children received oxygen therapy and systemic corticosteroids (oral/IV) in addition to specific therapy for infection and 3 of these infants succumbed to respiratory failure. Conclusion CMV Infection was the commonest cause of ILD in infancy in our study. However, the consequences on long term follow up in these infants need to be ascertained.     

Histopathological features of open lung biopsies in children treated with extracorporeal membrane oxygenation (ECMO)

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established treatment for severe respiratory distress in a range of pediatric conditions. This study describes the histopathological features in a series of 22 children receiving ECMO therapy in whom open lung biopsy was carried out. AIMS: To describe the histopathological features of open lung biopsies in children receiving ECMO therapy. STUDY DESIGN: Retrospective review of clinical material. SUBJECTS: Children receiving ECMO therapy in whom open lung biopsy was carried out. RESULTS: In those investigated in infancy, open lung biopsy allowed a definite diagnosis to be made of the underlying condition in more than 90% of cases. In older children, the histopathological changes were more non-specific and, although providing useful clinical information, a definitive diagnosis could often not be made. In about a quarter of cases, there are additional pathological features, which may be related to ECMO treatment, such as significant intra-alveolar haemorrhage, but ECMO does not in itself impair the diagnostic usefulness of open lung biopsy in these selected patients. CONCLUSION: Open lung biopsy provides clinically useful information in infants receiving ECMO therapy. The histopathological changes may be complex and represent both the effects of ECMO and progression of the underlying disease.     

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目的探讨新生儿常见肺部疾病支气管肺泡灌洗液肺表面活性蛋白A(BALSPA)水平及其与临床的关系。方法收集2000年1月至2003年2月在广州市儿童医院新生儿重症监护室住院的需行机械通气治疗的新生儿重症肺炎、胎粪吸入综合征(MAS)、急性呼吸窘迫综合征(ARDS)以及新生儿呼吸窘迫综合征(RDS)患儿共57例。测定其BALSPA水平,监测血气、PaO2/FiO2水平。结果重症肺炎组与MAS组患儿BALSPA水平无明显差异,但MAS组患儿PaO2、PaCO2及PaO2/FiO2水平较重症肺炎组明显降低(P值<0.01,<0.05,<0.05);ARDS及RDS组患儿BALSPA水平均较上述两组低(P值均<0.001),而RDS组患儿BALSPA水平较ARDS组低(P<0.001),但ARDS组患儿PaO2水平较RDS组患儿低(P<0.05)。PS治疗组患儿的病死率较非PS治疗组明显降低(P=0.049),其PaO2/FiO2与BALSPA水平密切相关(r=0.741,P=0.000)。结论与重症肺炎患儿比较胎粪吸入综合征患儿BALSPA水平无明显降低;ARDS及RDS患儿BALSPA水平明显降低;BALSPA水平能反映新生儿肺损伤的严重程度,对于新生儿肺部疾病预后的判断有一定意义。     

MicroRNA在肺部疾病中的研究进展

已知MicroRNA是调控细胞分化代谢、机体生长发育的关键。近年来,针对肺发育和肺部疾病的发生发展机制以及诊断和治疗肺部疾病如肺癌、慢性阻塞性肺疾病等方面有关MicroRNA的研究取得了较多进展,该文就MicroRNA在肺部疾病的最新研究情况作一综述。     

儿童特发性间质性肺疾病与肺表面活性物质-B基因多态性的相关性研究

目的 探讨肺表面活性物质(surfactant protein,SP)-B外显子4(T131I)位点的基因多态性与儿童特发性间质性肺疾病的相关性.方法 收集2013年10月至2016年9月在深圳市儿童医院和广西医科大学附属第一医院住院诊断为特发性间质性肺疾病的患儿共67例为病例组,选择同期与特发性间质性肺疾病无关的因呼吸道感染在深圳市儿童医院住院的102例患儿为对照组,采用SP-B全外显子和侧翼区高通量测序法对所有病例采集的标本进行检测,分析外显子4(T131I)位点的基因型和等位基因分布.结果 病例组和对照组SP-B基因外显子 4(T131I)位点的基因型均可检出3 种,CC、CT及TT型,病例组所占比例分别为67.16%、25.37%、7.46%,对照组分别为56.86%、35.29%、7.84%,两组基因型分布的差异无统计学意义(χ2=1.981,P=0.371);病例组C等位基因频率为79.85%,对照组为74.51%,差异无统计学意义(χ2=1.288,P=0.256).对照组SP-B基因外显子 4(T131I)位点的基因突变频率为43.14%(44/102),与人类基因组千人人群数据库基因突变频率平均值52.00%比较,差异无统计学意义(P>0.05);与欧洲千人人群数据库基因突变频率53.88%、南亚千人人群数据库基因突变频率45.50%和美洲整体人群数据库基因突变频率41.93%比较,差异无统计学意义(P>0.05),而与东亚千人人群数据库基因突变频率26.39%和非洲千人人群数据库基因突变频率80.18%比较,差异有统计学意义(P<0.05).结论 SP-B 基因外显子4(T131I)位点的基因多态性与儿童特发性间质性肺疾病易感性不存在相关性,外显子4(T131I)位点的基因突变频率与种族人群和地域具有一定的差异性.     

硫酸羟氯喹治疗肺表面活性蛋白C基因突变致婴儿间质性肺病1例并文献复习

目的：报道硫酸羟氯喹治疗肺表面活性蛋白C基因（SFTPC）突变致婴儿间质性肺病的疗效,提高对该病诊断和治疗的认识。方法：总结分析1例SFTPC突变致婴儿间质性肺病的临床特点、诊断过程和硫酸羟氯喹的疗效,并进行文献复习。结果：患儿女,2月龄,因“生后反复咳嗽伴气促2个月”于2015年9月9日就诊。患儿在新生儿期即发生呼吸窘迫,持续无法离氧。影像学示肺部渗出,病原学检查均阴性,常规抗感染治疗无效,否认肺部疾病家族史。基因检测发现SFTPC基因外显子4有1个杂合错义突变位点（c.T337C:p.Y113H）,目前尚无报道。患儿13月龄时开始硫酸羟氯喹治疗,治疗6个月后,呼吸窘迫、生长发育情况和胸部CT影像学表现明显改善。在PubMed、Web of Science、中国知网、维普数据库和万方数据库中检索SFTPC基因突变的间质性肺病,检索时间均从建库至2016年12月1日,共检索到相关文献12篇,均为英文文献。总结包括本文1例患儿在内的51例SFTPC基因突变致间质性肺病病例使用硫酸羟氯喹的治疗情况,随访0.3~15.8年,其中单用硫酸羟氯喹治疗的有12例,均取得良好疗效,未提及或未发现药物不良反应;全身糖皮质激素合用硫酸羟氯喹治疗39例,33例（84.6%）有效,2例（5.1%）无改善,4例（10.3%）恶化（1例死亡）。结论：对于SFTPC基因突变的婴儿间质性肺病,早期发现和早期诊断很重要,及早使用硫酸羟氯喹治疗可以改善临床症状、体征和生长发育情况,减少终末肺的发生。     

microRNA 调控肺发育的研究进展

微小 RNA(miRNA)是一类长约22个核苷酸的内源性非编码 RNA,它在转录后水平通过翻译抑制或介导靶 mRNA 的降解来调节基因的表达。近年来研究发现,miRNA 参与调节细胞分化、增殖、组织发育及脂质代谢等,与多种疾病的发生密切相关。该文对 miRNA 生物学作用及其对胎肺、出生后不同阶段肺发育的调控进行综述。     

先天性巨结肠Cajal间质细胞的研究

目的　本研究通过观察Cajal间质细胞 (interstitialcellofCajal,ICC)在先天性巨结肠患者狭窄段、移行段、扩张段中的分布情况 ,探讨ICC在先天性巨结肠发病中的作用。方法　收集我院1999～ 2 0 0 2年 2 6例先天性巨结肠患儿标本。短段型 2 4例 ,长段型 2例。于手术中分别选取扩张段 ,移行段及狭窄段肠壁的全层组织。采用SP法 (过氧化物酶标记的链霉卵白素法 )免疫组织化学技术 ,对 2 6例先天性巨结肠的狭窄段、移行段及扩张段标本分别进行c kit免疫组织化学反应 ,观察Ca jal间质细胞分布情况。 结果　发现ICC的密度从扩张段→移行段→狭窄段是逐渐减低的。ICC与肌间神经丛关系密切 ,在扩张段ICC分布在神经丛的周边部和内部 ,且数量相对较多 ,在狭窄段ICC偶见于神经丛的周边部 ,在神经丛内部未见该细胞。光学显微镜下比较同一例患者扩张段和狭窄段神经丛中Cajal间质细胞的数目不同 (t=2 3.0 4 ,P <0 .0 5 ) ,有统计学显著性差异。结论　ICC的分布异常与先天性巨结肠的发生有密切关系。我们推测胚胎基质的某种缺陷不仅损害了神经嵴细胞的移行 ,也影响ICC的分化和成熟。我们可以推论 ,与HD肠壁神经节缺失一样 ,ICC分布异常导致HD病变肠管慢波节律和兴奋传导异常 ,从而引起或加重HD的发病。     

Growth factors gene expression in the developing lung

AIM: This is the first systematic study using quantitative real-time PCR to analyze and compare the expression profiles for critical members of the epidermal growth factor (EGF), transforming growth factor beta (TGFbeta), and vascular endothelial growth factor (VEGF) families in developing rat lungs. METHODS: mRNA expression was quantified at embryonic (E) day 15, 17, 19, 21, and postnatal age 1 day, 2 weeks, 12 weeks. RESULTS: EGF and EGFR increased during gestation and development, then decreased in adulthood, whereas TGFalpha was highest at birth and remained unchanged afterwards. All TGFbeta isoforms increased slightly during pregnancy, reached highest expression during development, and returned to neonatal levels in adulthood. TGFbetaRI and TGFbetaRII patterns were similar to TGFbeta2 and TGFbeta1 respectively, whereas TGFbetaRIII expression was lowest at the postnatal time points. VEGF(164) and VEGF(120) showed a steady increase up to 2 weeks and declined at 12 weeks, whereas highest VEGF(188) expression occurred at 12 weeks. VEGF-A receptors expression paralleled the summation of all three isoforms, increasing steadily with age. CONCLUSION: Expression of growth factors in the developing lung is characterized by highly regulated distinctive patterns that may be critical to understand the early origin and progression of pulmonary diseases in childhood as well as in adulthood. Quantitative real-time PCR analysis revealed several differences compared to previously reported expression patterns defined with older methodologies.     

Spectrum of chronic lung disease in a population of newborns with extremely low gestational age

Aims: To determine how the ability to oxygenate the blood develops after birth in infants of extremely low gestational age (ELGANs) and to find risk factors for chronic lung disease. Method: A prospective, population‐based, cohort study was undertaken in one tertiary‐care centre. The alveolar–arterial oxygen pressure difference (AaDO₂) was monitored. Results: Of 41 survivors, 21 had a period of normal lung function in the first week of life, after which oxygenation deteriorated. Low gestational age and low Apgar score at 5 min were found to be strong and independent predictors of AaDO₂ in the first month of life. Mechanical ventilation did not appear as a risk factor. Lung function at 36 weeks of gestation and duration of oxygen treatment could be better predicted by the severity of lung disease in the first month than by gestational age at birth. Conclusions: Difficulty in oxygenation was a general observation in ELGANs and not only a particular subset. Gestational age and Apgar score were independent predictors of the degree of difficulty over the first month of life. As oxygenation failure often developed after a few days, the process may be possible to treat or prevent once the pathogenesis is known.     

高氧诱导早产鼠慢性肺疾病肺超微结构变化及氧化应激反应的研究

目的　慢性肺疾病 (CLD)是早产儿吸入高浓度氧治疗后最常见的并发症 ,目前认为肺部氧化应激反应与CLD的发生密切相关。该文探讨高氧致早产鼠CLD发生中肺组织超微结构及氧化应激反应的动态变化。方法　高浓度氧致早产鼠CLD模型 (实验组 )和正常对照组各 4 0例为研究对象 ,应用分光光度计比色法在实验后1 ,3,7,1 4 ,2 1d动态测定肺组织超氧化物岐化酶 (SOD)活性及脂质过氧化产物丙二醛 (MDA)的含量 ,并同步观察肺组织超微结构的变化。结果　吸高氧后初期 (1～ 3d) ,Ⅱ型肺泡上皮细胞 (AEC Ⅱ )即出现线粒体、板层小体等细胞器的损伤 ;7d后 ,除细胞器结构破坏外 ,开始出现细胞核的异常 ,且随吸氧时间的延长上述改变逐渐加重。实验组肺组织SOD的活性虽逐渐增高 ,但与对照组比较 ,其差异无显著性 (P >0 .0 5 ) ;实验组MDA水平从吸高氧第3天起即明显高于对照组 (5 5 .9± 5 .5nmol/mgvs 2 2 .5± 4 .4nmol/mg) (P <0 .0 1 ) ,7d达高峰 94 .3± 1 2 .4nmol/mg ,持续 1周后逐渐下降 ,2 1d时仍高于对照组 (4 8.0± 7.5nmol/mgvs2 3.6± 5 .7nmol/mg) (P <0 .0 1 )。结论　AEC Ⅱ损伤是高氧诱导CLD的早期特征 ;肺部氧化应激反应与AEC Ⅱ损伤密切相关。     

Early protein oxidation in the neonatal lung is related to development of chronic lung disease

Free radical-mediated oxidation of proteins may impair their function and cause cellular damage. We studied pulmonary protein oxidation and its association with the development of chronic lung disease in 61 newborn infants (mean gestational age 31.1 ± 4.0, range 24-41 weeks) requiring intensive care with oxygen therapy. Protein oxidation was quantified as protein carbonylation in tracheal aspirates recovered daily during the first week of life. Mean carbonyl concentration was 3.5 ± 1.6 μmol/mg protein. Negative correlations existed between protein carbonylation during days 2-4 and gestational age (day 2: r = -0.37, p = 0.01; day 3: r = -0.48, p = 0.001; and day 4: r = -0.33, p = 0.03). Patients who developed bronchopulmonary dysplasia showed significantly higher protein carbonylation on days 1-6 (all p < 0.05). In multiple regression analysis explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on days 1-3 and protein carbonylation on day 3 as independent variables, only protein carbonylation remained significant. We conclude that immaturity is the most important factor explaining free radical-mediated pulmonary protein oxidation in newborn infants and that oxidation of proteins is related to the development of chronic lung disease.     

A common mutation in the surfactant protein C gene associated with lung disease

OBJECTIVE: To determine the contribution of the surfactant protein C (SP-C) I73T mutation to lung disease. STUDY DESIGN: Genomic DNA was obtained from 116 children with interstitial lung disease (ILD) or chronic lung disease of unclear cause and from 166 control subjects and was screened for the I73T mutation using an allele-specific polymerase chain reaction assay. RESULTS: The I73T mutation was found on 7 of 232 SP-C alleles from 7 unrelated children with ILD but was not found on 332 control SP-C alleles ( P < .01, Fisher exact test). The I73T mutation segregated with lung disease in one kindred with familial ILD. The I73T mutation was found in an asymptomatic parent from two different families with affected children consistent with variable penetrance, but it was not found in either asymptomatic parent of two other unrelated affected children consistent with a de novo mutation. Analysis of single nucleotide polymorphisms indicated diverse genetic backgrounds of the I73T alleles. Immunohistochemical analysis of lung tissue from an infant with the I73T mutation demonstrated normal staining patterns for proSP-B, SP-B, and proSP-C. CONCLUSIONS: These findings support the hypothesis that the I73T mutation predisposes to or causes lung disease.     

Management of infants with chronic lung disease of prematurity in China

With improved survival of very low birth weight infants in China over the last decade, chronic lung disease of prematurity (CLD) is only now becoming prevalent. As a result the management of CLD in China is only now beginning. In this paper, we describe the practice of managing these infants with as much evidence base as possible but often the management is based on other published papers in China and elsewhere and other people's personal experience. It appears that oxygen therapy is important to the survival of CLD infants but blood oxygen concentrations must be monitored closely in infants needing oxygen supplementation. We aim for a target range for oxygen saturation range of between 90%-95% to prevent retinopathy of prematurity. Although dexamethasone is effective in the treatment of CLD particularly extubation of preterm infants from mechanical ventilation, we restrict its use in severe infant due to their side effects. We have little experience of home oxygen and are only now setting up management protocols for oxygen use for CLD in both hospital and at home. We hope that the survival and outlook for these infants with CLD will improve over the next few years.     

Ascorbate acid concentration in airways lining fluid from infants who develop chronic lung disease of prematurity

Chronic lung disease of prematurity (CLD) remains a common cause of morbidity and mortality in preterm infants. Oxygen toxicity remains a major risk factor for the development of CLD and as a consequence the antioxidant status of CLD babies is a major focus of interest. In the present study, we determined whether ascorbate, urate, and total glutathione concentrations were decreased in infants who developed CLD when compared to those who did not. From 34 preterm infants, 141 serial bronchoalveolar lavage fluid (BALF) and plasma samples were collected: 12 developed CLD (median gestation 26 weeks, range 23–28 weeks, median birth weight 780 g, range 630–1070 g), 16 developed and recovered from respiratory distress syndrome (RDS) (median gestation 31 weeks, range 26–39 weeks, median birth weight 1820 g, range 840–4160 g), and six were ventilated for non-respiratory reasons, (median gestation 35 weeks, range 32–38 weeks, median birth weight 2180 g, range 1100–2860 g). Following birth, the concentration of BALF ascorbate, urate and glutathione decreased over the 1st week in all three groups. Thereafter, BALF ascorbate increased in RDS and control infants during the 2nd week but this increase was delayed by 2 weeks in the CLD infants. No differences were noted between the RDS and CLD groups for urate and total glutathione in BALF or urate in plasma. BALF protein concentration was similar in all three groups except for a rise at day 7 in the CLD group but this did not reach statistical significance. Conclusion A delayed increase in bronchoalveolar lavage fluid ascorbate concentration might be associated with an increased risk of developing chronic lung disease of prematurity. Received: 3 May 2000 / Accepted: 17 October 2000     

高氧致慢性肺疾病早产鼠肺组织CDK4 p21的表达及意义

目的：早产儿慢性肺疾病（CLD）的发病机制目前研究还不十分清楚,但CLD的最终病理变化与肺细胞增殖有关。该文采用高氧诱导早产鼠CLD模型为对象,探讨CDK4和p21基因动态表达与肺细胞增殖调控的关系。方法：高浓度氧致早产鼠CLD模型（实验组）和正常对照组各40例为研究对象,每组分别于实验后的1,3,7,14和21 d随机选取8只大鼠处死, 取出肺组织,常规制成5 μm切片。检测观察：①肺组织形态学;②肺组织纤维化评分;③采用免疫组化检测肺组织内PCNA表达;④采用原位杂交检测肺组织CDK4 mRNA和p21 mRNA的表达。结果：两组肺组织细胞PCNA指数：与对照组比较,实验组1 d,3 d PCNA表达均减弱（P﹤0.05）,7 d开始表达增强（P＜0.01）, 14 d和21 d明显高于对照组（P＜0.01）。两组肺组织细胞CDK4 mRNA表达强度： 从7 d开始实验组高于对照组（P﹤0.05）, 14 d,21 d明显高于对照组（P﹤0.01）。两组肺组织细胞p21 mRNA表达强度：实验组1 d,3 d表达明显高于对照组（P﹤0.01）, 7 d 后持续下降, 但也高于对照组（P﹤0.05）。7~21 d肺组织细胞CDK4 mRNA,p21 mRNA 表达分别与PCNA呈显著正、负相关（r分别为0.83和-0.81,P﹤0.05）。结论：高氧可诱导早产鼠肺细胞增殖。肺组织细胞CDK4基因的过度表达、p21基因的表达下降,可能是高氧诱导肺细胞增殖的机制之一。［中国当代儿科杂志,2007,9（6）：595-600］     

Pentoxyfylline in and prevention and treatment of chronic lung disease

The anti-inflammatory effects of pentoxfylline are associated with a number of clinical benefits. These include reduction in mortality in patients who have undergone bone marrow transplants or suffer peritonitis. In infants with sepsis, a reduction in mortality has also been associated with pentoxyfylline administration. The anti-inflammatory effects of pentoxyfylline, as well as its bronchodilator, diuretic and respiratory muscle stimulant effects suggest it may have a useful role in BPD. Interim analysis of a prophylactic trial suggests pentoxyfylline may reduce treatment requirements after the neonatal period and that, in established BPD, pentoxyfylline and dexamethasone may be of similar efficacy.