Serum eosinophil cationic protein and interleukin-5 in children with bronchial asthma and acute bronchiolitis

The aim of our study was to evaluate the clinical applicability of serum eosinophil cationic protein (ECP), interleukin-5 (IL-5) and total eosinophil counts in childhood asthma and bronchiolitis. These parameters were measured in 44 children aged 12-84 months with moderate and mild asthma during symptomatic and asymptomatic phases of disease. Fifteen of the patients were included at the time of admission to hospital due to an acute asthmatic attack, and ten of these were also examined one month after discharge. None of the patients were treated with glucocorticoids or cromoglycate at any time during the study. Serum ECP was significantly increased in the children with acute asthma compared to children with stable moderate asthma, stable mild asthma, as well as to controls. There was no difference between the groups with stable asthma or between stable asthma and controls, and there was large overlap between all groups of asthmatics and controls. Detectable levels of circulating IL-5 were demonstrated in eight of 15 children with acute asthma, with significantly higher levels in atopic children, whereas all samples from children with stable asthma and controls were negative. The results suggest that even though serum ECP and IL-5 increases during acute asthmatic attacks, these parameters cannot alone be used to discriminate between different groups of young children with stable asthma, nor between asthmatics and healthy controls. In addition, the same parameters of eosinophil inflammation were examined in serum samples from 25 children aged 1-17 months undergoing their first episode of acute bronchiolitis. Children with acute respiratory syncytial virus (RS V) bronchiolitis had significantly higher levels of serum ECP than those with RSV negative disease, whereas the total eosinophil counts were significantly decreased in all patients with acute bronchiolitis. Serum IL-5 was only detected in two children with acute bronchiolitis. The results suggest that the inflammation in RSV bronchiolitis differs from that induced by other viruses.     

哮喘患儿Clara细胞分泌蛋白的临床意义

目的探讨Clara细胞分泌蛋白(CCSP)检测在儿童哮喘中的临床意义。方法采用酶联免疫吸附法检测50例哮喘急性发作期患儿血清CCSP水平,其中22例患儿经治疗后于缓解期采血复查,另设20例健康儿童作对照。结果哮喘急性发作期、缓解期患儿血清CCSP水平均较健康对照组显著降低(P<0.001,0.01)。中重度发作哮喘患儿,血清CCSP浓度显著低于轻度发作的哮喘患儿(P<0.001)。病程长的哮喘患儿CCSP水平显著低于病程短者(P<0.05)。结论CCSP具有抗感染作用,CCSP的减少可诱导或加重哮喘儿童的呼吸道炎症。检测血清CCSP是反映小呼吸道Clara细胞受损的一种非侵入性方法;CCSP可作为判断哮喘病情、治疗效果及预后的指标之一。     

Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma

Vascular endothelial growth factor (VEGF) induces angiogenesis and increases vascular permeability participating in narrowing of the airway lumen that follows lung injury. We sought to investigate the expression of VEGF in induced sputum during and after recovery from acute episodes of bronchial asthma in children. Eighteen asthmatic children with acute attacks of varying severity were subjected to VEGF estimation by an enzymatic immunoassay in induced sputum. They were followed up till complete remission of symptoms and signs and were then retested. VEGF was also estimated in sputum induced from age 34 and sex-matched healthy children enrolled as a control group. The sputum VEGF levels during acute asthma [median = 71 ng/ml; mean (s.d.) = 114.6 (121.8) ng/ml] were significantly higher than the levels estimated during remission [median = 50 ng/ml; mean (s.d.) = 45.7 (24.2) ng/ml] and both were higher than the corresponding levels of the control group [median = 36 ng/ml; mean (s.d.) = 31.3 (17.2) ng/ml]. VEGF levels during asthmatic episodes correlated positively to the recovery levels (r = 0.6, p = 0.009). The patients' VEGF expression did not vary with asthma severity, serum total IgE concentration, peripheral blood eosinophil count, or erythrocyte sedimentation rate of patients. Children on corticosteroids inhalation therapy at enrollment had sputum VEGF levels that were comparable to those on other therapies. The increased expression of sputum VEGF in asthmatic children reinforces the concept that it might have a pathogenetic role in bronchial asthma and may represent a biomarker of airway inflammation.     

Serum levels of eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lipid peroxidation products, interleukin (IL)-5 and interferon (IFN)-gamma in children with bronchial asthma at acute asthma attack and remission

We determined serum levels of myeloperoxidase (MPO), eosinophilic cationic protein (ECP), reactive oxygen species measured as thiobarbituric acid reactive substances (TBARS), interleukin (IL)-5, and interferon (IFN)-gamma in 14 asthmatic children during an asthma attack and remission. Twelve healthy children served as controls. In atopic asthmatics, asthma attack resulted insignificant elevations of ECP, MPO, and TBARS compared to remission. TBARS levels were also higher at remission compared to controls. However, there was a great deal of overlap in the values of asthmatics and controls. IL-5 and IFN-gamma were detectable at low levels and only in a few patients. These results provide further evidence for participation of eosinophils, neutrophils and reactive oxygen species in the pathogenesis of acute asthma, and suggest that their products may be used in monitoring asthma attack. Serum IL-5 and IFN-gamma levels are not appropriate for use in the follow-up of asthmatic children.     

Eosinophil cationic protein, myeloperoxidase and tryptase in children with asthma and atopic dermatitis

Serum levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, total IgE and differential blood cell counts were studied in atopic children with: 1) moderate to severe asthma using inhaled steroids and symptom-free for the last 3 weeks (n= 13), 2) mild asthma with sporadic symptoms, using only inhaled β₂-agonists < 3 times/week (n= 15), 3) acute asthmatic attacks admitted to hospital (n= 12), 4) mild to moderate atopic dermatitis (n= 14). Fifteen children without any history of atopy served as controls. ECP, MPO, tryptase and IgE were measured in serum by radioimmunoassays (RIA). The symptom-free children with inhaled steroids had similar median ECP and MPO values as the controls, 8.0 and 360 μg/l, vs. 9.0 and 310 μg/l, while both ECP and MPO were significantly (p < 0.001) increased in the symptom-free children without anti-inflammatory treatment, 32 and 887 μg/l and in those with acute asthma, 28 and 860 μg/l. The children with atopic dermatitis had increased ECP but normal MPO levels, 16.0 and 455 μg/l. Tryptase in serum was not measurable in any patient. All groups except the control group had significantly elevated total IgE levels. The results indicate that in atopic children serum ECP is a good marker of ongoing asthma or atopic dermatitis. The normal levels of ECP and MPO in the children with asthma using inhaled steroids seem to reflect successful anti-inflammatory treatment. The increased levels of ECP and MPO in the children with mild asthma and no anti-inflammatory treatment may indirectly reflect airway inflammation.     

Serum total and free carnitine levels in children with asthma

Background  Serum carnitine is decreased in recurrent pulmonary infections. We aimed to evaluate serum carnitine levels in asthmatic children. Methods  Study group consisted of children with stable asthma and those with acute asthma attacks, while control group included healthy children. Attack severity was determined by the pulmonary score system. Total and free carnitine levels were studied in one blood sample from the control group and stable asthmatics and in two samples from children with acute asthma exacerbation during and after the attack. Results  All the 40 patients in the study group had moderate asthma including 30 with acute attack (13 mild and 17 moderate) and 10 with stable asthma. Carnitine levels were significantly lower in acute attack asthmatics than in the stable asthmatics and controls, while there was no significant difference between the latter two groups. Carnitine levels were not different between asthmatics with mild and moderate attack, and were similar during and after an acute attack. Conclusions  Serum carnitine levels decrease in children with moderate asthma during exacerbation of asthma and shortly thereafter. Further studies are needed to evaluate the effect of carnitine treatment on serum carnitine level.     

Circadian variation of exhaled nitric oxide and urinary eosinophil protein X in asthmatic and healthy children.

Asthmatic symptoms and the frequency of admissions to hospital because of acute asthma tend to increase in the early morning hours, and it is therefore possible that airway inflammation increases during the night. To elucidate the hypothetical circadian variation of airway inflammation, we measured concentrations of exhaled nitric oxide (FeNo), urinary eosinophil protein X excretion (EPX), and forced expiratory volume in the first second (FEV1) in 20 asthmatic and 6 nonatopic nonasthmatic children every 3 h during a 21-h period. Compared with control subjects, asthmatic subjects had higher FeNo (median, 22.7 versus 10.3 ppb, p = 0.016) and lower FEV1 % predicted (median, 91.0 versus 101.9%, p = 0.045), but did not differ significantly in EPX (median, 153.8 versus 148.7 microg/mmol creatinine, p = 0.83) at 7 AM. However, differences in gender and age do not allow direct comparisons between asthmatic and control children. FeNo and EPX demonstrated a cosinelike circadian rhythm (log FeNo, p = 0.0001; log EPX, p = 0.0001) with lowest levels at 7 PM and highest at 7 AM. This was also the case for FEV1 % (p = 0.01). No difference in the amplitude of circadian rhythm was observed between asthmatic and healthy control children for log FeNo (p = 0.35), log EPX (p = 0.57), and FEV1 % (p = 0.17). A stratified analysis showed a significant circadian rhythm in the control group for log FeNo (p = 0.014) and log EPX (p = 0.0001). Our results therefore suggest a circadian rhythm of inflammatory markers, which peaks in the early morning. Rhythmicity of EPX excretion and FeNo in healthy children suggests a physiologic mechanism; however, pathologic effects during the night might occur under conditions of asthma-specific inflammation.     

神经激肽A在哮喘患儿血浆含量变化的动态研究

目的　动态研究哮喘患儿血浆神经激肽A(NKA)含量变化规律 ,探讨NKA与小儿哮喘的关系。方法　用酶联免疫方法 ,动态测定 35例不同严重程度哮喘小儿血浆NKA在哮喘发作期及其临床症状缓解期的含量变化。结果　 (1 )小儿哮喘发作期血浆NKA含量 [(2 56± 1 53)ng/L]高于自身症状缓解期 [(70± 66)ng/L]及正常对照组 [(38± 6)ng/L] ,差异有非常显著意义 (q分别为9 497、8 599,P均 <0 0 1 ) ;哮喘症状缓解期血浆NKA含量较正常对照组差异无显著意义 (q =1 2 4 5 ,P >0 0 5)。 (2 )哮喘小儿病情加重 ,血浆NKA含量亦随之增高 ,重度哮喘发作时血浆NKA含量 [(2 96± 1 70 )ng/L]明显高于轻、中度哮喘发作时含量 [(1 90± 99)ng/L] ,差异有显著意义 (q =3 77,P <0 0 5)。结论　小儿哮喘发作期血中NKA含量明显增高 ,病情愈重增高越明显 ,随哮喘症状缓解血中NKA含量下降至正常水平 ;血中NKA含量的变化与小儿哮喘的发作及缓解关系密切     

儿童哮喘急性发作与肺炎衣原体感染的临床研究

目的：对儿童哮喘急性发作病例与肺炎衣原体(CP)感染相关性进行临床研究。方法：采用固相酶联免疫吸附(ELISA)方法,检测120例儿童哮喘急性发作期的肺炎衣原体血清特异性CP-IgM,CP-IgG抗体,探讨哮喘患儿急性发作及临床控制与肺炎衣原体感染的关系。以健康体检者作为对照。结果：120例儿童哮喘急性发作病例中,检测出CP-IgM阳性22例,阳性率18.3%,CP-IgG阳性32例,阳性率26.7%,与健康对照组比较差异有显著性(P<0.01)。CP感染的32例哮喘病人中有15例(46.9%)单纯给予吸入治疗获良好哮喘控制;有17例(53.1%)给予阿奇霉素足疗程治疗,配合吸入治疗,哮喘急性发作方得以完全控制。结论：儿童哮喘急性发作与肺炎衣原体感染有关,应作肺炎衣原体相关特异性抗体检测,并须配合大环内酯类药物治疗及规范吸入激素治疗,以早日达到哮喘的完全控制。     

哮喘儿童外周血可溶性干细胞因子的测定和临床意义

目的 探讨可溶性干细胞因子（solublestem cell factor，sSCF）在哮喘发病中的作用。方法 使用酶联免疫吸附法对90例哮喘患儿发作期和缓解期外周血血清sSCF的水平进行了检测。结果 哮喘发作期sSCF水平较缓解期和正常对照组明显降低（P均〈0．05）；缓解期水平有明显升高，但仍然低于正常对照组。结论 sSCF参与了儿童支气管哮喘的发病，检测患儿外周血sSCF水平可作为判断病情严重程度的重要指标。     

哮喘儿童外周血可溶性干细胞因子的测定和临床意义

目的探讨可溶性干细胞因子(soluble stem cell factor,sSCF)在哮喘发病中的作用。方法使用酶联免疫吸附法对90例哮喘患儿发作期和缓解期外周血血清sSCF的水平进行了检测。结果哮喘发作期sSCF水平较缓解期和正常对照组明显降低(P均<0.05);缓解期水平有明显升高,但仍然低于正常对照组。结论sSCF参与了儿童支气管哮喘的发病,检测患儿外周血sSCF水平可作为判断病情严重程度的重要指标。     

Cough, airway inflammation, and mild asthma exacerbation.

BACKGROUND: Prospective data on the temporal relation between cough, asthma symptoms, and airway inflammation in childhood asthma is unavailable. AIMS AND METHODS: Using several clinical (diary, quality of life), lung function (FEV(1), FEV(1) variability, airway hyperresponsiveness), cough (diary, cough receptor sensitivity (CRS)), and inflammatory markers (sputum interleukin 8, eosinophilic cationic protein (ECP), myeloperoxidase; and serum ECP) of asthma severity, we prospectively described the course of these markers in children with asthma during a non-acute, acute, and resolution phase. A total of 21 children with asthma underwent these baseline tests; 11 were retested during days 1, 3, 7, and 28 of an exacerbation. RESULTS: Asthma exacerbations were characterised by increased asthma and cough symptoms and eosinophilic inflammation. Sputum ECP showed the largest increase and peaked later than clinical scores. Asthma scores consistently related to cough score only early in the exacerbation. Neither CRS nor cough scores related to any inflammatory marker. CONCLUSION: In mild asthma exacerbations, eosinophilic inflammation is dominant. In asthmatic children who cough as a dominant symptom, cough heralds the onset of an exacerbation and increased eosinophilic inflammation, but cough scores and CRS do not reflect eosinophilic airway inflammation.     

超敏C-反应蛋白对支气管哮喘严重度分级的临床价值

目的 评估不同严重程度及控制水平的支气管哮喘(哮喘)患儿血清超敏C-反应蛋白(hs-CRP)水平,探讨其临床价值.方法 选取本院儿科门诊和住院的儿童哮喘患者80例,分为2组:40例为非激素治疗组(非激素组),40例为吸入性激素治疗组(激素组).测定患儿hs-CRP水平和经校正年龄和性别的第1秒用力呼气量(FEV1)％的预计值,并进行诱导痰细胞学检查.同时纳入80例年龄和性别匹配的健康儿童作为健康对照组.结果 哮喘患儿血清hs-CRP水平显著高于健康对照组,非激素组血清hs-CRP水平显著高于激素组.激素组与非激素组患儿血清hs-CRP水平均与FEV1％预计值呈负相关.结论 尽管肺功能检查和临床分类作为哮喘分级的金标准,但hs-CRP可作为评估哮喘严重程度及控制水平的新指标,其可在哮喘患儿中用来间接监测呼吸道炎症、疾病严重性和对激素的治疗反应.     

Cough, airway inflammation, and mild asthma exacerbation

Background: Prospective data on the temporal relation between cough, asthma symptoms, and airway inflammation in childhood asthma is unavailable. Aims and methods: Using several clinical (diary, quality of life), lung function (FEV₁, FEV₁ variability, airway hyperresponsiveness), cough (diary, cough receptor sensitivity (CRS)), and inflammatory markers (sputum interleukin 8, eosinophilic cationic protein (ECP), myeloperoxidase; and serum ECP) of asthma severity, we prospectively described the course of these markers in children with asthma during a non-acute, acute, and resolution phase. A total of 21 children with asthma underwent these baseline tests; 11 were retested during days 1, 3, 7, and 28 of an exacerbation. Results: Asthma exacerbations were characterised by increased asthma and cough symptoms and eosinophilic inflammation. Sputum ECP showed the largest increase and peaked later than clinical scores. Asthma scores consistently related to cough score only early in the exacerbation. Neither CRS nor cough scores related to any inflammatory marker. Conclusion: In mild asthma exacerbations, eosinophilic inflammation is dominant. In asthmatic children who cough as a dominant symptom, cough heralds the onset of an exacerbation and increased eosinophilic inflammation, but cough scores and CRS do not reflect eosinophilic airway inflammation.     

Genetic association study between mbl2 and asthma phenotypes in Chinese children

Mannose-binding lectin (MBL), a member of the innate immune system, initiates complement deposition on microbial surfaces. MBL deficiency is associated with severe respiratory infections. Polymorphisms in the MBL gene (mbl2) were associated with the susceptibility and severity of autoimmune diseases. This study investigated whether mbl2 polymorphisms at positions -550 and -221 and at codon-54 are associated with asthma phenotypes in Chinese children. Asthmatics aged 5-18 yr and non-allergic controls were eligible, and their plasma total and allergen-specific immunoglobulin E (IgE) concentrations were measured by micro-particle immunoassay and fluorescent enzyme immunoassay. mbl2 polymorphisms were genotyped by restriction fragment length polymorphism. Three hundred and seventeen asthmatic children and 140 controls were recruited, with their mean (s.d.) log-transformed plasma total IgE being 2.61 (0.61) and 1.77 (0.77), respectively (p < 0.0001). Polymorphisms at -550 and codon-54 (p < 0.0001 for both) but not at -221 (p = 0.534) of mbl2 were significantly associated with plasma MBL concentrations. mbl2 genotypes were not associated with asthma, atopy, sensitization to individual aeroallergens or spirometric variable. Subjects with LYB haplotype had the lowest plasma MBL concentrations (p < 0.0001), but two- and three-loci mbl2 haplotypes were also not associated with asthma diagnosis. However, patients with LY and LYB haplotypes were less likely to be atopic (p = 0.006 and 0.031). Subjects with LY and LYA were also less likely to be sensitized to cockroach (p = 0.035 and 0.047). The latter three associations became insignificant when adjusted for multiple comparisons. Despite the importance of MBL in innate immunity, our mbl2 polymorphisms only show weak association with asthma and atopy in children.     

儿童哮喘急性发作时血清C-反应蛋白浓度变化及临床意义

目的探讨血清C-反应蛋白(CRP)在儿童哮喘急性发作时的浓度变化及其临床意义。方法检测182例支气管哮喘急性发作患儿和50例非感染患儿的血清CRP和总IgE浓度,根据发病诱因,将哮喘急性发作患儿分为过敏诱发组、病毒感染诱发组和细菌感染诱发组,检测哮喘患儿血清过敏原特异性IgE,分析各组患儿及正常儿童的血清CRP变化。结果在哮喘急性发作时,细菌感染诱发组患儿的血清CRP水平最高(19.55±17.61)mg/L,过敏诱发组(5.45±4.32)mg/L、病毒感染诱发组(8.61±8.03)mg/L轻度升高,与正常对照组(1.61±1.25)mg/L相比,差异均有统计学意义(P均<0.001)。正常对照组、过敏诱发组、病毒感染诱发组、细菌感染诱发组儿童所对应的血清CRP水平分别为0～2 mg/L、2～10 mg/L、5～16 mg/L、≥16 mg/L,当CRP≥16 mg/L时应考虑发作诱因为细菌感染的可能性大。血清CRP、总IgE及食物呼吸过敏原之间没有显著性关系。结论过敏诱发、病毒感染诱发哮喘急性发作血清CRP浓度范围一般为2～10 mg/L、5～16 mg/L,哮喘急性发作时血清CRP≥16 mg/L时注意细菌感染及合并肺炎。     

血清Clara 细胞分泌蛋白、总IgE与嗜酸性粒细胞阳离子蛋白在儿童哮喘检测中的临床意义

目的探讨血清Clara细胞分泌蛋白（CC16）、总IgE和嗜酸性粒细胞阳离子蛋白（ECP）检测在哮喘儿童中的意义。方法采用酶联免疫吸附法（ELISA）测定59例哮喘患儿急性发作期血清CC16水平,同时应用UniCAP100变态反应检测仪检测血清总IgE、ECP;另设30例健康儿童作为健康对照组。结果与健康对照组比较,哮喘组血清CC16水平显著降低、血清总IgE、ECP水平显著增高（t=2.93,2.72,4.52Pa〈0.01）;中重度哮喘发作患儿血清CC16水平显著低于轻度发作患儿（t=5.26P〈0.05）,中重度哮喘发作患儿血清总IgE显著高于轻度发作患儿（t=3.89P〈0.05）,血清ECP水平在哮喘轻度发作组与中重度发作组比较无统计学差异（t=1.57P〉0.05）;哮喘组血清CC16与总IgE呈显著负相关（r=-0.602P〈0.05）,血清CC16与ECP（r=0.153P〉0.05）及总IgE与ECP（r=0.290P〉0.05）无相关。结论血清CC16降低与总IgE、ECP水平增高在儿童哮喘发病过程中发挥重要作用;血清总IgE、CC16可反映哮喘发作严重程度;血清ECP水平高低并不能反映呼吸道炎症严重程度。     

miR-98在哮喘患儿外周血单个核细胞中的表达及意义

目的 探讨支气管哮喘患儿外周血单个核细胞(PBMCs)中miR-98的表达及其临床意义.方法 收集43例发作期和缓解期哮喘患儿,30例健康儿童(对照组)的外周血标本,分离PBMCs,采用实时定量PCR法检测PBMCs中miR-98及IL-13、IL-4 mRNA的相对表达量.结果 miR-98在哮喘发作期患儿PBMCs中的表达低于缓解期和对照组儿童,而IL-13、IL-4在哮喘发作期患儿PBMCs中的mRNA水平均高于缓解期和对照组,差异有统计学意义(P均<0.01);缓解期患儿和对照组间miR-98、IL-4 mRNA和IL-13 mRNA水平差异无统计学意义(P均>0.05).哮喘患儿发作期,miR-98水平与IL-4、IL-13 mRNA相对表达量均呈负相关(r=-0.794、-0.804,P均<0.001),IL-4和IL-13 mRNA相对表达量呈正相关(r=0.853,P<0.001).结论 miR-98在哮喘发作期患儿PBMCs中表达降低,可能与小儿哮喘的发作相关.     

支气管哮喘儿童尿白三烯E_4检测的临床意义

目的半胱氨酰白三烯(CysLTs)是参与哮喘气道炎症与重塑的重要介质,通过检测尿白三烯E4(LTE4)可以反映人体CysLTs的水平。该研究旨在探讨尿LTE4测定在儿童支气管哮喘中的临床意义。方法将60例哮喘急性发作儿童随机分成孟鲁司特治疗组和常规治疗组,每组各30例。采用竞争性酶联免疫吸附试验技术(ELISA)检测急性期和缓解期患儿尿LTE4水平,并测定气道阻力值(Rint)。同时选择20例健康儿童作为对照组。结果哮喘儿童急性期、缓解期尿LTE4水平均明显高于对照组儿童,差异有显著性(均P<0.01)。缓解期哮喘儿童尿LTE4较急性期下降,差异有显著性(P<0.01),且孟鲁司特治疗组儿童尿LTE4下降值明显高于常规治疗组,差异有显著性(P<0.01)。急性期哮喘儿童尿LTE4水平与Rint无相关性(P>0.05)。结论急性期哮喘儿童尿LTE4水平明显升高;检测哮喘儿童尿中LTE4水平可以为哮喘的临床诊断和治疗监测提供依据。