Exhaled nitric oxide levels in infants with chronic lung disease

Chronic lung disease (CLD) is an inflammatory disorder; in patients with other inflammatory disorders exhaled nitric oxide (NO) levels are elevated. The aim of this study was to test the hypothesis that prematurely born infants with CLD would have elevated exhaled NO levels compared to those without CLD and healthy term-born infants. Ten infants with CLD (median gestational age 26 weeks; CLD group), ten infants without CLD (median gestational age 32 weeks; non-CLD group) and ten term-born infants (term group) were examined at post-conceptional ages between 36 and 45 weeks. NO levels were measured during spontaneous tidal breathing. A facemask was positioned over the infants nose and mouth and a sampling catheter was inserted through a small leak-free valve into the facemask. To measure nasal NO, the tip of the sampling catheter was placed in the nasal space and to measure facemask NO, the catheter tip was positioned inside the facemask at the infants lips. Nasal compared to facemask NO levels were higher in all three groups (CLD; non-CLD; term: P =0.017, P =0.012 and P =0.017, respectively). The CLD group had higher peak nasal and facemask NO levels than the non-CLD ( P =0.011 and P =0.034 respectively) and the term ( P =0.005 and P =0.01 respectively) infants. Regression analysis demonstrated that facemask NO levels were significantly related to CLD, independent of gestational, post-natal and post-conceptional age ( P =0.006). Conclusion:our results suggest that exhaled nitric oxide levels are elevated in chronic lung disease infants. Facemask measurement of nitric oxide levels might be a potentially useful method to monitor infants with chronic lung disease.Abbreviations CLD chronic lung disease - NO nitric oxide     

Anti-interleukin-8 autoantibody in the tracheobronchial aspirate of infants with chronic lung disease

BACKGROUND: A high concentration of interleukin (IL)-8 has been observed in the tracheobronchial aspirate of infants with chronic lung disease (CLD), although the pattern varies depending on the type of CLD. Alveolar fluid from patients with adult respiratory distress syndrome (ARDS) also contains an elevated level of IL-8. Recently, the presence of anti-IL-8 autoantibody was demonstrated in the alveolar fluid from patients with ARDS. METHODS AND RESULTS: The concentration of anti-IL-8 autoantibody in the tracheobronchial aspirate of infants with CLD was measured in order to discover whether there was any correlation with the concentration of IL-8. Similar to IL-8 concentration, the anti-IL-8 IgM antibody concentration in all infants with CLD following intrauterine infection was already high during the first 48 h. However, the concentration in infants with CLD following respiratory distress syndrome began to increase after 11 days of life, in contrast with the rise in IL-8 between 48 h after birth and day 5. CONCLUSIONS: The presence of anti-IL-8 autoantibody may provide a mechanism that limits the bioavailability of free IL-8 in the lungs. In addition, the time lag between the increase in IL-8 and anti-IL-8 IgM autoantibody demonstrated in the present study could be used to estimate the time when the inflammation begins, even if the IL-8 concentration is already high.     

Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of early-onset infection in premature infants

BACKGROUND: Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection. PATIENTS AND METHODS: Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns. RESULTS: Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml, and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226-514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). CONCLUSION: In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.     

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目的观察川崎病(KD)患儿血清降钙素原(PCT)、白介素-6(IL-6)水平的变化,探讨其与KD并发症间的关系。方法研究对象为2003-10—2005-12在首都儿科研究所附属儿童医院住院的88例KD患儿,测定其血清PCT、IL-6水平;正常对照为同期33例健康儿童,进行同样检测。结果(1)71例急性期患儿PCT水平与14例亚急性期患儿、33例正常对照儿童PCT水平相比,其差异均有统计学意义(P<0.05和<0.01)。(2)急性期24例其他系统并发症患儿PCT水平显著高于47例无其他系统并发症患儿,且差异有统计学意义(P<0.01);当PCT≤0.5ng/mL时,其他系统并发症发生率16.3%;当PCT>0.5时,其他系统并发症发生率41.0%,两者差异有统计学意义(P<0.05)。(3)56例急性期患儿IL-6水平与11例亚急性期患儿、14例正常对照儿童IL-6水平相比,其差异均有统计学意义(P值均<0.01)。(4)急性期17例其他系统并发症患儿IL-6水平显著高于39例无其他系统并发症患儿IL-6水平,二者差异有统计学意义(P<0.01)。结论(1)KD患儿急性期血清PCT、IL-6水平增高,亚急性期下降,PCT增高维持时间较IL-6稍长。(2)血清PCT、IL-6水平在发生其他系统并发症患儿中是显著升高的,对其检测有助于KD的病情评价。     

热休克蛋白47的表达与胆道闭锁肝纤维化及预后的相关性研究

目的 研究热休克蛋白47的表达与胆道闭锁患儿肝脏纤维化程度及预后的相关性.方法 选择30例胆道闭锁、10例胆汁淤积症和10例胆总管囊肿患儿入组,分别取肝脏组织以及外周血,通过RT-PCR、Western-blot、ELISA以及病理切片来评估不同水平HSP47的表达情况及其与肝脏纤维化相关性.结果 三组HSP47在mRNA水平(0.915±0.730比0.066±0.037比0.314±0.150,P＜0.05)、蛋白水平(3.061 81±0.504 763比1.358 018±0.373 174比1.23649±0.350 173,P＜0.05)以及血清水平(63.38±17.11比57.87±14.83比45.78±11.23,P＜0.05)的表达胆道闭锁组均比胆汁淤积组以及胆总管囊肿组高,差异有统计学意义,且不同水平表达具有一致性(mRNA比蛋白水平:r=0.836,P＜0.05;蛋白水平比血清水平:r=0.989,P＜0.01;mRNA比血清水平:r=0.883,P＜0.05).胆道闭锁血清HSP47的表达与肝脏组织光镜下纤维化程度呈正相关关系(r=0.669,P＜0.01).结论 肝脏组织HSP47的表达与血清HSP47的表达水平具有一致性,能够评估肝脏纤维化程度;血清HSP47的高表达可能作为胆道闭锁预后不良的一个监测指标.     

白细胞介素4受体Q576R基因多态性与支气管哮喘病人IgE的相关性

目的：白细胞介素4(IL-4)是哮喘发病机制中重要的细胞因子。该文探讨了白细胞介素4受体(IL-4R)基因Q576R多态性与儿童支气管哮喘及IgE水平的相关性。方法：用聚合酶链反应/限制性片段长度多态性分析方法(PCR/RFLP)，检测94例哮喘儿童和68例正常对照儿童IL-4R Q576R的多态性,并用酶联免疫吸附法(ELISA)检测两组儿童血浆总IgE的水平，然后进行χ2检验及成组t检验。结果：IL-4R杂合突变基因型Q576R、突变等位基因R576的分布频率在哮喘儿童及正常对照儿童中分布频率分别为41%，16%及26%,16%,差异有显著性(P<0.01，<0.05)；哮喘儿童中杂合突变基因型Q576R携带者与野生型Q576Q携带者比较，血浆总IgE水平分别为225.78±51.43 IU/mL、163.24±31.32 IU/mL，差异无显著性。结论：IL-4R突变等位基因R576可能是儿童易感哮喘的一个候选基因；未发现IL-4R等位基因R576对哮喘儿童血浆总IgE水平升高有明显影响；白细胞介素4受体Q576R基因多态性与支气管哮喘有相关性。     

Plasmatic levels of interleukin-1beta and interleukin-6 in newborn infants with fever

OBJECTIVE: To study plasma levels of IL-1beta and IL-6 in order to distinguish the presence of bacterial infection in newborn infants with fever. METHODS: A cohort of 117 newborn infants with postnatal age equal to or less than 5 days, with no previous use of antibiotic therapy, and with clinical suspicion of bacterial infection was studied from July 1995 through August 1996. Those with definite criteria for sepsis were considered infected. Fever was defined as axillar temperature > 37.5 degrees C in three independent measurements. The patients were classified in four different groups: Group 1: infected with fever; Group 2: infected without fever; Group 3: not infected with fever; Group 4: not infected without fever. Complete blood count, platelet count, blood or other fluid cultures, and plasmatic levels of IL-1beta and IL-6 were collected before the beginning of antibiotic therapy. RESULTS: Of the 117 newborn infants studied were 66 infected and 51 not infected. Fever was present in 45 (38.46%). The median values of IL-1beta and IL-6 were significantly higher in newborn infants with fever than in those with no fever. There were significant differences between groups 1 and 2, 1 and 4, and 2 and 3 for IL-1beta. There were no significant differences between groups 2 and 4, and 1 and 3 for IL-1beta. Eight (72%) newborn infants with no infection and no fever had environment heating, and 3 had dehydration. There were no differences in median IL-6 levels between groups 1 and 2, and 3 and 4. There were significant differences in the median IL-6 levels between groups 1 and 3, and 1 and 4. CONCLUSIONS: IL- 6 is a marker of early neonatal sepsis. IL-1beta is related to neonatal fever response independently of the presence of bacterial infection.     

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。     

慢性肝炎患儿四项血清肝纤维化标志物的检测及其临床意义

目的为了解慢性肝炎患儿血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PcⅢ)和Ⅳ型胶原(cⅣ)的水平及诊断价值.方法用放射免疫法(RIA)分5个年龄组测定459名1～15岁健康儿童和180名慢性肝炎患儿的4项肝纤维化标志物.结果4项标志物检测结果(x±s)如下HA(58±16)μg/L,LN(115±17)μg/L,PC(146±27)μg/L,cⅣ(51±16)μg/L.这4种标志物的正常参考值以95%的上限x+1.645s计算,分别为HA85(58+16)μg/L,LN142(115+16.6)μg/L,PC190(146+27)μg/L,cIV77(51+16)μg/L.HA、cⅣ与年龄不相关(r=-0.022,P＞0.05;r=0.070,P＞0.05),然而LN与年龄显著相关(r=0.1282,P＜0.01),PC与年龄呈负相关(r=-0.669,P＜0.01).慢性表面抗原携带者与同龄对照组差异无显著性.轻度慢性肝炎患儿除HA显著性高于对照组(P＜0.05)外,其他3项均无差异.中度、重度及肝硬化儿童的4种血清标志物浓度均高于正常对照组(P＜0.01).在中度、重度和肝硬化患儿中,有2种或2种以上的标志物显著性增加.结论4项标志物在儿童期有其年龄特征.它们可反映慢性肝炎患儿肝纤维化的严重程度.因此,对慢性肝炎和早期肝硬化的诊断有临床应用价值.     

慢性乙型肝炎病毒感染患儿肝纤维化血清标志检测及分析

目的探讨儿童乙型肝炎病毒感染者血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ     

Decreased interleukin-10 in tracheal aspirates from preterm infants developing chronic lung disease

The inability to balance pulmonary injury with healing may predispose preterm infants to chronic lung disease (CLD). It is postulated that the production of interleukin (IL)-10, an anti-inflammatory cytokine, is gestationally influenced and that CLD-prone infants may have a reduced ability to produce IL-10. METHODS: Tracheal fluid (TF) was collected at least twice weekly from 48 mechanically ventilated infants within the first 7 d of life while intubated. RESULTS: A total of 87 TF specimens were obtained. None of the 11 CLD infants (24-31 wk of gestation) had TF IL-10 levels above 4 pg/ml (0/20 TF specimens), while 14 (70%) of the 20 non-CLD preterm infants (27-36 wk of gestation) had IL-10 levels above 5 pg/ml in one or more of their TF specimens (18/48 TF specimens, p < 0.001). Only the 5 term infants who were ventilated for severe lung disease had raised IL-10 levels (17 infants, 5/19 TF specimens). IL-10 levels, if detected, (range 6-938 pg/ml) tended to be higher with increasing gestation (Spearman's rho coefficient = 0.43; p = 0.003). TF IL-10 detection was not associated with hyaline membrane disease, antenatal steroids or influenced by TF sample volume. Overall IL-8 levels were wide ranging but towards the end of week 1 the levels were significantly higher in CLD infants (CLD: median 34 184 ng/ml, preterm non-CLD: median 699 ng/ml, p < 0.001, term: 2961 ng/ml, p = 0.028). CONCLUSION: A gestationally influenced low IL-10 may predispose preterm infants to persistent pulmonary inflammation of CLD.     

胆道闭锁肝纤维化与自体肝生存关系的研究进展

胆道闭锁是婴儿期最严重的肝胆系统疾病之一。肝门-空肠吻合术(Kasai手术)是治疗胆道闭锁的主要手段,但术后自体肝长期生存效果不佳,大部分患儿需要通过肝移植来挽救生命。肝纤维化是影响胆道闭锁患儿自体肝生存的重要因素之一,其发生机制复杂,涉及多种信号通路及细胞因子的调控。Kasai手术后胆汁引流不畅、胆管炎发作都会导致肝纤维化进展,进而发生肝硬化。在完善早期诊断、早期手术、通畅引流胆汁及控制胆管炎的同时,还应积极应对患儿肝纤维化的持续进展,以期达到自体肝的长期生存。     

A case of incomplete Kawasaki disease with extremely high serum ferritin and interleukin-18 levels

Background

The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (sJIA) occasionally overlap. Therefore, serum levels of cytokine and ferritin are used as markers to distinguish between KD and sJIA. KD patients have a high level of interleukin (IL)-6, low level of IL-18, and no elevation of the level of serum ferritin. Conversely, sJIA patients have a low level of IL-6 and high levels of IL-18 and ferritin in the serum. However, to the best of our knowledge, no case report of KD with a low serum level of IL-6 and extremely high levels of IL-18 and ferritin is found.

Case presentation

A 6-year-old boy presented with a history of fever for 9?days and a rash that appeared 7?days from the onset. He was diagnosed with incomplete KD because of fever, skin rash, oral cavity erythematous changes, and erythema and edema of the hands with laboratory findings of serum albumin level?<?3.0?g/dL, elevated alanine aminotransferase level and leukocyturia. Intravenous immunoglobulin and prednisolone and oral aspirin were introduced on the 10th day. Fever subsided 1?day after initiating the treatment, but arthritis of both knees appeared in addition to hepatosplenomegaly. We suspected sJIA, as the serum level of ferritin was 19,740?ng/mL, IL-6 was <?3?pg/mL, and IL-18 was 132,000?pg/mL. Skin desquamation of the fingertips was observed 18?days from the onset; thus, he was finally diagnosed with incomplete KD with arthritis. At 32?days from the onset, we stopped the prednisolone therapy and no symptoms of relapse were observed afterwards. In the follow-up at 16?months from the onset, he had neither signs of active joint or skin involvement, nor cardiac involvement.

Conclusions

Although patients with sJIA generally have high serum levels of IL-18 and ferritin, this was a case of incomplete KD with extremely high serum levels of IL-18 and ferritin. Serum cytokine and ferritin are often used for the differential diagnosis of KD and sJIA. We need to recognize the existence of KD with high serum levels of IL-18 and ferritin.

     

Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients

A total of 203 paediatric cancer treatment survivors were tested for serum antibodies against hepatitis-C virus (anti-HCV). Anti-HCV was detected in 41 patients (20.2%) with first generation anti-HCV ELISA. Positive results were confirmed in all samples retested with a second generation ELISA (n=35) and in all but two cases re-analysed by immunoblotting (n=23). Anti-HCV positive children had received significantly more blood product transfusions compared to seronegative patients. In 75 children (32%) chronic liver disease was found. It was defined as an elevation of serum alanine aminotransferase values to a least 2.5 times the upper limit of normal persisting for 6 months or longer. Hepatitis A was never detected, and in 58 children the chronic hepatopathy was unexplained by hepatitits B (non-A non-B chronic liver disease). Of these patients 29 (50%) were seropositive for anti-HCV. Surprisingly, non-A/non-B chronic liver disease was associated with anti-HCV in 14 of 19 solid tumour patients (78.9%), but in no more than 14 of 39 leukaemia and lymphoma patients (35.9%). This phenomenon was not explained by different rates of cytomegalovirus disease and drug toxicity related hepatopathies between the two groups. It may be related to differences of leukaemia/lymphoma compared to solid tumour therapy schedules (differential immuno-suppression and liver toxicity).     

Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants

There is growing evidence that sepsis-related complications in neonates are crucially mediated by the action of proinflammatory cytokines. It has previously been demonstrated that elevated IL-6 and IL-8 levels can predict brain damage and chronic lung disease in preterm infants. However, it is the current view that neonates have a reduced capability to produce proinflammatory cytokines. To clarify this issue, we analyzed the inflammatory response in term and preterm infants directly at the single cell level by flow cytometry. Endotoxin challenge was performed under defined conditions on monocytes obtained from 50 healthy adults and 119 neonates, which consist of 45 term infants, 63 preterm infants (26.1-36.7 wk of gestational age), and 11 preterm infants with proven infection (24.6-29.9 wk). Our results challenge the existing view of an immature inflammatory response by demonstrating that term infants and preterm infants display a higher percentage of IL-6- and IL-8-positive cells than adults. After preincubation with dexamethasone the number of cytokine-positive cells decreased in all groups, but the number of IL-8-positive cells remained higher in term and preterm infants >32 wk compared with adults. These observations demonstrate not only a well-developed but also an enhanced inflammatory response in term and preterm infants. Under consideration of several detrimental effects of IL-6 and IL-8, our data may have major implications on the pathophysiology of inflammatory-triggered neonatal diseases.