毛细支气管炎患儿血清25-(OH)-D3水平及维生素D3干预后尿LTE_4的变化
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摘要
第一部分毛细支气管炎患儿血清25-(OH)-D3水平及与喂养关系的探讨
     目的:
     通过检测毛细支气管炎患儿血清25-羟维生素D3(25-(OH)-D3)的水平,探讨血清25-(OH)-D3水平与毛细支气管炎的关系,并探讨不同的喂养方式对血清25-(OH)-D3水平和病程的影响。
     方法:
     选择我院呼吸科病房住院的毛细支气管炎患儿作为毛细支气管炎组,共63例,根据四个月内的喂养方式分为纯母乳喂养、部分母乳喂养和人工喂养三种。选择同期在我院外科住院的非感染性小儿作为对照组,共50例,既往无喘息史、过敏性疾病史和过敏家族史,无活动性佝偻病史。所有入选对象于入院当日治疗前抽取空腹静脉血2ml,利用竞争性酶联免疫吸附试验技术(ELISA)检测血清25-(OH)-D3的水平。采用SPSS17.0统计软件完成数据的统计、分析。
     结果:
     1.毛细支气管炎组与对照组血清25-(OH)-D3水平比较
     毛细支气管炎组血清25-(OH)-D3水平为(55.18±18.87)nmol/L,明显低于对照组(67.75±28.44)nmol/L,两者比较有显著统计学差异,t值为-2.69,P=0.009,<0.01。
     2.毛细支气管炎组与对照组血清25-(OH)-D3水平缺乏者(<50nmol/L)、不足者(50-75nmol/L)与良好者(>75nmol/L)分别所占的比率
     (1)毛细支气管炎组血清25-(OH)-D3水平缺乏者18例,占28.57%;不足者36例,占57.14%;良好者9例,占14.28%;
     (2)对照组血清25-(OH)-D3水平缺乏者13例,占26%;不足者13例,占26%;良好者24例,占48%;
     (3)两组血清25-(OH)-D3水平缺乏者、不足者和良好者比率经统计学检验,Χ2=17.15,P<0.01,有显著统计学差异。
     3.毛细支气管炎组中血清25-(OH)-D3水平缺乏者、不足者与良好者的病程长短比较
     (1)血清25-(OH)-D3水平良好者的病程为(6.89±1.45)天,较缺乏者(9.11±1.74)天和不足者(8.67±1.58)天均明显缩短,t值分别为-3.28、-3.05,P均<0.01,有显著统计学差异。
     (2)血清25-(OH)-D3水平缺乏者与不足者病程比较,t值为0.93,P=0.35,>0.05,差异无统计学意义。
     4.毛细支气管炎组中纯母乳喂养儿、部分母乳喂养儿与人工喂养儿血清25-(OH)-D3水平的比较
     (1)纯母乳喂养儿血清25-(OH)-D3水平为(48.13±23.35)nmol/L,低于部分母乳喂养儿(58.92±11.41)nmol/L和人工喂养儿(64.43±12.70)nmol/L,t值分别为-2.18、-3.15,P值分别为0.03、0.003,均<0.05,差异有统计学意义;
     (2)部分母乳喂养儿与人工喂养儿血清25-(OH)-D3水平比较,t值为-1.31,P=0.199,>0.05,差异无统计学意义。
     5.毛细支气管炎组中纯母乳喂养儿、部分母乳喂养儿与人工喂养儿血清25-(OH)-D3水平缺乏者(<50nmol/L)、不足者(50-75nmol/L)与良好者(>75nmol/L)分别所占的比率
     (1)纯母乳喂养儿共30例,血清25-(OH)-D3水平缺乏者13例,占43.33%;不足者13例,占43.33%;良好者4例,占13.33%;
     (2)部分母乳喂养儿共17例,血清25-(OH)-D3水平缺乏者6例,占35.29%;不足者10例,占58.82%;良好者1例,占5.88%;
     (3)人工喂养儿共16例,血清25-(OH)-D3水平缺乏者1例,占6.25%;不足者11例,占68.75%;良好者4例,占25%;
     (4)毛细支气管炎组三种喂养方式中血清25-(OH)-D3水平缺乏者、不足者和良好者比率经统计学检验,Χ2=8.10,P=0.08,>0.05,差异无统计学意义。
     6.毛细支气管炎组中纯母乳喂养儿、部分母乳喂养儿与人工喂养儿的病程长短比较
     (1)毛细支气管炎组中纯母乳喂养儿的病程为(7.90±1.37)天,较部分母乳喂养儿(8.88±1.78)天和人工喂养儿(9.35±1.93)天短,t值分别为-2.064、-2.99,P值分别为0.045、0.004,<0.05,差异有统计学意义。
     (2)部分母乳喂养儿病程与人工喂养儿比较,t值为-0.736,P值为0.46,>0.05,差异无统计学意义。
     结论:
     1.毛细支气管炎组血清25-(OH)-D3水平明显低于对照组。
     2.毛细支气管炎组血清25-(OH)-D3水平缺乏者、不足者的病程较良好者长。
     3.毛细支气管炎组中纯母乳喂养儿血清25-(OH)-D3水平低于部分母乳喂养儿,明显低于人工喂养儿。
     4.毛细支气管炎组中纯母乳喂养儿的病程短于部分母乳喂养儿和人工喂养儿。
     第二部分毛细支气管炎患儿维生素D3干预后尿白三烯E4水平的变化及意义
     目的:
     1.通过检测毛细支气管炎患儿尿白三烯E4的水平证实尿白三烯E4可作为毛细支气管炎的一个炎性指标。
     2.通过检测维生素D3干预后尿白三烯E4水平的变化探讨维生素D3对哮喘二级预防的作用。
     方法:
     选择我院呼吸科病房住院的毛细支气管炎患儿作为毛细支气管炎组,共90例,所有患儿均为特应性体质(有湿疹或特应性皮炎史)。所有患儿应用常规治疗(布地奈德、复方异丙托溴铵氧喷平喘,孟鲁斯特抗白三烯,抗病毒及对症治疗等),症状、体征控制后(缓解期)随机分成两组:维生素D3干预组予以维生素D3滴剂口服(400IU/天),空白对照组不予干预,随访六个月。选择同期在我院外科住院的非感染性小儿作为对照组,共56例,既往无喘息史、过敏性疾病史和过敏性家族史。毛细支气管炎组分别在喘息急性期(入院当日)、缓解期(维生素D3干预前)、维生素D3干预后留取晨尿10mL,其中2ml于-70℃冰箱保存,待测尿LTE4(pg/ml),8ml测定尿肌酐(μmol/L)。对照组于入院当日留取晨尿10mL,其中2ml于-70℃冰箱保存,待测尿LTE4,8ml测定尿肌酐。终结果以尿LTE4浓度/尿肌酐浓度(×103pg/μmol)表示。采用SPSS17.0统计软件完成数据的统计、分析。
     结果:
     1.毛细支气管炎组喘息急性期、缓解期与对照组尿LTE4水平比较
     (1)毛细支气管炎组喘息急性期尿LTE4水平为(6.18±1.26)×103pg/μmol,较对照组(3.31±0.60)×103pg/μmol高,t=15.938,P<0.01,有显著统计学差异;
     (2)喘息缓解期尿LTE4水平为(3.66±0.77)×103pg/μmol,较急性期下降,t=-16.198,P<0.01,有显著统计学差异;
     (3)喘息缓解期尿LTE4水平较对照组高,t=2.877,P=0.005,<0.01,有显著统计学差异。
     2.维生素D3干预组与空白对照组尿LTE4水平比较
     (1)两组干预前尿LTE4水平比较,t=1.87,P=0.065,>0.05,差异无统计学意义,有可比性。
     (2)维生素D3干预组干预后尿LTE4水平为(3.36±0.61)×103pg/μmol,较干预前下降,t=-2.815,P=0.006,<0.01,有显著统计学差异。
     (3)空白对照组随访六个月后尿LTE4水平为(3.27±0.39)×103pg/μmol,较六月前下降,t=-2.11,P=0.037,<0.05,差异有统计学意义。
     (4)维生素D3干预组干预后尿LTE4水平与空白对照组比较,t=0.83, P=0.408,>0.05,差异无统计学意义。
     3.维生素D3干预组与空白对照组六个月内喘息再次发作的人数比较
     维生素D3干预组六个月内喘息再次发作者3例,空白对照组六个月内喘息再次发作者5例,两组比较,Χ2=0.549,P=0.459,>0.05,差异无统计学意义。
     结论:
     1.毛细支气管炎患儿尿LTE4水平较对照组显著升高,喘息急性期尿LTE4水平升高尤为明显。喘息缓解期尿LTE4水平较急性期下降,但仍高于对照组。
     2.维生素D3干预组干预后尿LTE4较干预前下降,但与空白对照组比较无统计学差异,表明维生素D3对尿LTE4无下调作用。
     3.维生素D3对哮喘二级预防的作用尚需更多的证据。
PART Ⅰ Serum25-hydroxy VitaminD3levels in infants with bronchiolitisand the relationship with feeding
     Objective:
     To explore the relationship between serum25-hydroxy VitaminD3Level andbronchiolitis by detecting the serum25-hydroxy VitaminD3Level in infants withbronchiolitis,and to discuss the influence of different feeding ways to serum25-hydroxyVitaminD3Level and the course of disease.
     Methods:
     Chooseing63cases of infants with bronchiolitis in respiration ward as bronchiolitisgroup.The bronchiolitis group were divided into breast-feeding,the part of thebreastfeeding and artificial feeding according to different feeding ways within fourmonths.Chooseing50noninfectious infants in surgical ward in our hospital in the sameperiod as control group.The infants of the control group had no wheezeing history,noallergic disease history and no allergic family history,also had no active rickets history.Allof them were taken hollow venous blood2ml the day they hospitalized beforetreatment.Detecting the serum25-hydroxy VitaminD3Level by Enzyme-linkedimmunoadsordent assay.Collate and analyse the above data by statistical softwareSPSS17.0and got conclusions.
     Results:
     1. Bronchiolitis group serum25-hydroxy VitaminD3levels compared with the controlgroup
     The serum25-hydroxy VitaminD3levels of bronchiolitis group(55.18±18.87)nmol/L were significantly lower than the control group(67.75±28.44)nmol/L.There was significant difference in statistics,t value was-2.69,P value was0.009,<0.01.
     2. The proportion of the lack of serum25-hydroxy VitaminD3(<50nmol/L),vitaminD3deficiency(50-75nmol/L) and normal (>75nmol/L) in bronchiolitis group and controlgroup
     (1)In bronchiolitis group,there were18cases with the lack of serum25-hydroxyVitaminD3,accounted for28.57%.36cases of the serum25-hydroxy VitaminD3deficiency,accounted for57.14%.9cases were normal,accounted for14.28%.
     (2)In control group,there were13cases with the lack of serum25-hydroxyVitaminD3,accounted for26%.13cases of the serum25-hydroxy VitaminD3deficiency,accounted for26%.24cases were normal,accounted for48%.
     (3)There was significant difference in statistics of the proportion between thebronchiolitis group and the control group,the chi-square value was17.15,P<0.01.
     3. In bronchiolitis group,the comparison of the course of disease among the lack ofserum25-hydroxy VitaminD3,vitamin D3deficiency and normal
     (1)The course of serum25-hydroxy VitaminD3normal group(6.89±1.45days)was shorter than the lack of serum25-hydroxy VitaminD3group(9.11±1.74days)andvitamin D3deficiency group(8.67±1.58days),there was significant difference instatistics,t value was-3.28and-3.05,P<0.01.
     (2)There was no significant difference in statistics of the course between the lack ofserum25-hydroxy VitaminD3group and the vitamin D3deficiency group, t value was0.93,P value was0.35,>0.05.
     4.In bronchiolitis group,the serum25-hydroxy VitaminD3levels of breast-feedinginfants, the part of the breastfeeding infants and artificial feeding infants
     (1)The serum25-hydroxy VitaminD3levels of breast-feeding infants(48.13±23.35)nmol/L were lower than the part of the breastfeeding infants(58.92±11.41)nmol/Land artificial feeding infants(64.43±12.70)nmol/L.There was difference in statistics,tvalue were-2.18and-3.15,P value were0.03and0.003,<0.05.
     (2)There was no difference in statistics between the part of the breastfeeding infantsand artificial feeding infants,t value was-1.31,P value was0.199,P>0.05.
     5. In bronchiolitis group,the proportion of the lack of serum25-hydroxy VitaminD3(<50nmol/L),vitamin D3deficiency(50-75nmol/L) and normal (>75nmol/L) inbreast-feeding infants,the part of the breastfeeding infants and artificial feeding infants
     (1)Breast-feeding infants included30cases, there were13cases with the lack of serum25-hydroxy VitaminD3,accounted for43.33%.13cases of the serum25-hydroxyVitaminD3deficiency,accounted for43.33%.4cases normal,accounted for13.33%.
     (2)The part of the breastfeeding infants included17cases,there were6cases withthe lack of serum25-hydroxy VitaminD3,accounted for35.29%.10cases of the serum25-hydroxy VitaminD3deficiency accounted for58.82%.1case was normal,accounted for5.88%.
     (3)Artificial feeding infants included16cases,there was1case with the lack ofserum25-hydroxy VitaminD3,accounted for6.25%.11cases of the serum25-hydroxyVitaminD3deficiency accounted for68.75%.4cases were normal,accounted for25%.
     (4)There was no significant difference in statistics of the proportion among the threefeeding ways,the chi-square value was8.10,P value was0.08,>0.05.
     6. The comparison of the course of disease among breast-feeding group,the part of thebreastfeeding group and artificial feeding group
     (1)The course of breast-feeding group(7.90±1.37days)was shorter than the othertwo groups(8.88±1.78and9.35±1.93days),t value were-2.064and-2.99,P value were0.045and0.004,there was difference in statistics.
     (2)There was no significant difference in statistics of the course of the part of thebreastfeeding group and artificial feeding group, t value was-0.736,P value was0.46,>0.05.
     Conclusion:
     1.The serum25-hydroxy VitaminD3levels of bronchiolitis group were significantlylower than the control group.
     2. In the bronchiolitis group,the course of disease in the lack of serum25-hydroxyVitaminD3and vitamin D3deficiency infants were longer than the normal infants.
     3.In the bronchiolitis group,the serum25-hydroxy VitaminD3levels of breast-feedinginfants were significantly lower than the artificial feeding infants,were lower than the partof the breastfeeding infants.
     4.The course of disease in breast-feeding group were shorter than the other twogroups.
     PART Ⅱ The study of urine leukotriene E4levels in infants with bronchiolitisafter VitaminD3intervention
     Objective:
     1.To confirm the urine leukotriene E4is an inflammatory mediator of bronchiolitis bydetecting the urine leukotriene E4level in infants with bronchiolitis.
     2.To discuss the effect of VitaminD3to the secondary prevention of asthma bydetecting the urine leukotriene E4levels in infants with bronchiolitis after VitaminD3intervention.
     Methods:
     Chooseing90infants diagnosed bronchiolitis in respiration ward as bronchiolitisgroup.All of them were atopic constitution (had eczema or atopic dermatitis) and weregiven conventional treatment (inhaled Budesonide and Compound Ipratropium BromideSolution,Montelukast,antiviral therapy,symptomatic treatment and so on).The90caseswere randomly divided into two groups after clinical symptom remission.VitaminD3(400IU per day)was given to the VitaminD3intervention group.The black control groupwas given no intervention.Follow-up six months. Chooseing56infants in surgical in ourhospital with noninfectious in the same period as control group.The infants of the controlgroup had no wheezing history,no allergic disease history and no allergic familyhistory.The bronchiolitis group were taken morning urine10ml respectively in the acutewheezeing stage(the day they were hospitalized),the remission stage(before VitaminD3intervention) and after VitaminD3intervention.Put2ml in-70℃refrigerator storage todetect the urine leukotriene E4(pg/ml),8ml to detect urine creatinine(μmol/L).The controlgroup were taken morning urine10ml the day they were hospitalized.Put2ml in-70℃refrigerator storage to detect the urine leukotriene E4,8ml to detect urine creatinine.Thefinally result was the urine leukotriene E4divided by the urine creatinine(×103pg/μmol).Collate and analyse the above data by statistical software SPSS17.0andgot conclusions.
     Results:
     1.Bronchiolitis group urine leukotriene E4levels in the acute wheezeing stage and the remission stage compared with the control group
     (1)There was significant difference in statistics of the urine leukotriene E4levelsbetween the acute wheezeing stage of bronchiolitis group(6.18±1.26)×103pg/μmol andthe control group(3.31±0.60)×103pg/μmol,t value was15.938,P <0.01.
     (2)The urine leukotriene E4levels in the remission stage(3.66±0.77)×103pg/μmolwere lower than the acute wheezeing stage,there was significant difference,t value was-16.198,P<0.01.
     (3)There was significant difference of the urine leukotriene E4levels between theremission stage of bronchiolitis group and the control group,t value was2.877,P value was0.005,<0.01.
     2.The urine leukotriene E4levels of VitaminD3intervention group and the blankcontrol group
     (1)The two groups are comparable before intervention and has no statisticaldifference,t value was1.87,P value was0.065,>0.05.
     (2)In the VitaminD3intervention group,the urine leukotriene E4levels afterVitaminD3intervention (3.36±0.61)×103pg/μmol were lower than beforeintervention,there was significant statistical difference,t value was–2.815,P value was0.006,<0.01.
     (3)In the blank control group,the urine leukotriene E4levels after six months(3.27±0.39)×103pg/μmol were descend, there was statistical difference,t value was–2.11,Pvalue was0.037,<0.05.
     (4)There was no statistical difference of the urine leukotriene E4levels betweenVitaminD3intervention group and the blank control group after VitaminD3intervention,tvalue was0.83,P value was0.408,>0.05.
     3.The comparison of the cases of wheezeing recurrence within six months betweenVitaminD3intervention group and the blank control group.
     VitaminD3intervention group had three cases and the blank control group had fivecases of wheezeing recurrence.There was no statistical difference of the cases ofwheezeing recurrence between the two groups,the chi-square value was0.549,P value was0.459,>0.05.
     Conclusion:
     1.The urine leukotriene E4levels of bronchiolitis group were significantlyincreased,especially in the acute wheezeing stage.The urine leukotriene E4levels inremission stage were lower than in acute wheezeing stage,but higher than the controlgroup.
     2.The urine leukotriene E4levels in VitaminD3intervention group after interventionwere lower than before intervention,but there was no statistical difference between theVitaminD3intervention group and the black control group.So,the VitaminD3can notdecrease the urine leukotriene E4.
     3.The effect of VitaminD3on the secondary prevention of asthma still need moreevidence.
引文
[1]胡亚美,江载芳.诸福棠实用儿科学[M]:第7版.北京:人民教育出版社,2002:1199-1200.
    [2] EderW,Ege M.Ivon Mutius E.The asthma epidemic[J].N Engl J Med,2006,355(21):2226-2235.
    [3] The global burden of asthma [J].Chest,2006,130(l):4-12.
    [4]陈育智.中国儿童哮喘防治近况.中华儿科杂志,2004,42(2):8l-82.
    [5] Sib SR.MohuaM,Samir B,et al.A new cell secreting insulin[J].Endocrinology,2003,144(4):1585-1593.
    [6] Michae1F Holiek,M.D.Ph.D.VitaminD Deficiency [J].NEJM,Volume357:266-28lJuly19,2007Number3.
    [7] MARY M. Functional genomics: vitamin D and disease [J].Nat Rev Genet,2010,11:670.
    [8]郗文政,袁刚.人乳的组成及其功能.国外医学妇幼保健分册,2002,13(6):243.
    [9]朱圣陶,0-6个月婴儿完全母乳喂养的营养适应性.国外医学卫生学分册,2005,32(3):187.
    [10] Dent G,Ruhlmann E,Bodtake K,et al.Up-regulation of human eosinophil leukotrieneC4generation through contact with bronchial epithelial cells[J].Inflamm.ReS,2000,49(5):236-239.
    [11] Rabinovitch N.Uninary leukotriene E4[J].Immunol Allergy Clin North Am,2007,27(4):651-654.
    [1]胡亚美,江载芳.诸福棠实用儿科学[M]:第7版.北京:人民教育出版社,2002:1199-1200.
    [2] Smith JM.The prevalence of asthma and wheezing in children.Br J DisChest,1976,70(2):73-77.
    [3] Brehm J M,Celedon J C,Soto-Quiros M E et al.Serum vitamin D levels and markersof severity of childhood asthma in Costa Rica.Am J Respir Crit Care Med2009,179(9):765-771.
    [4] Black PN,Scragg R.Relationship between serum25-hydroxyvitamin D and pulmonaryfunction in the third national health and nutrition examination survey. Chest2005,128:3792-3798.
    [5] Holick M.Vitamin D deficiency.The New England Journal of Medicine2007,357:266-281.
    [6] Hypponen E,Sovio U,Mjst M,et al.Infant vitamin D supplementation and allergiccondition in adulthood:northern Finland birth cohort1966.Ann N Y AcadSci,2004,1037:84-95.
    [7]陈荣光,孙慧,冯海燕,等.维生素AD治疗婴幼儿支气管哮喘37例.医药导报.2009,28(12),1581-1582.
    [8]林岚,关智平.维生素D对免疫功能调节作用的初步研究.中华儿科杂志.1999,37(2),119-120.
    [9] Mansbach Ji,Camargo CA Jr.Bronchiolitis:lingering questions about its definition andthe potential role of vitamin D[J].Pediattics,2008,122(4):177-179.
    [10] Janssen R,Bont L,Siezen CL,et a1.Genetic susceptibility to respiratory syncytialvirus bronchiolitis is predominantly associated with innate immune genes [J].J InfectDis,2007,196(6):826-834.
    [11]杜秋影,于立君,范慧子,等.维生素D缺乏与小婴儿毛细支气管炎发病的关系.实用儿科杂志,2011,26(4):304-305.
    [12]向伟.维生素D缺乏和维生素D缺乏性佝偻病防治进展[J].中华儿科杂志,2008,46(3):195.
    [13] SREERAM V R,ANDREAS H,ANTONIO J,et al.AChIP-seq defined genome-widemap of vitamin D receptor [J].Genome Res,2010,24:published online August.
    [14] ROBERT P H,FACN R L,DIANE M C,et al.Vitamin D3distribution and status in thebody[J].J Am Coll Nut,2009,28,3:252-256.
    [15] Veldman CM,C antorna MT,DeLuca HF.Expression of1,25-dihydroxyvitamin D(3)receptor in the immune system.Arch Biochem Biophys,2000,374:334-338.
    [16] Weaver CM,Fleet JC,Vitamin D requirements:current and future Am J ClinNutr,2004,80Suppl:S1735-l739.
    [17] Holick MF.Chen TC. Vitamin D deficiency:a worldwide problem with healthconsequences.Am J Clin Nutr,2008,87Supp1:Sl080-1086.
    [18] Carol LW,Frank RG.The section on breastfeeding and committee on nutrition.Prevention of rickets and vitamin D deficiency in infants, children andadolescents.Pediatrics.2008;122(5):1142-1152.
    [19] Nassef M,Temparano J,Frieri M et al. Should Fracture Risk Influence Our DecisionMaking in Asthma Care?.Ann Allergy Asthma Immunol2010,In press.
    [20] Gartner LM,Morton J,Lawrence RA,et a1.Breastfeeding and the use of humanmilk.Pediatrics,2005,115(2):496-506.
    [21] Jackson KM,Nazar A M.Breastfeeding,the immune response and long-term health. JAm Osteopath Assoc.2006.106(4):203-207.
    [22]朱圣陶.0~6个月婴儿完全母乳喂养的营养适宜性.国外医学卫生学分册,2005,32(3):187-191.
    [23]郗文政,袁刚.人乳的组成及其功能.国外医学妇幼保健分册,2002,13(6):243.
    [24] Greer FR.Issues in establishing vitamin D recommendations for infants andchildren.Am J Clin Nutr,2004,80(6suppl):1759S-1762S.
    [25] Perrine CG,Sharma AJ,Jeferds ME,et a1.Adherence to Vitamin D recommendationsamong US infants[J].Pediatrics,2010,125(4):627-632.
    [26]李昌崇,郑吉善.毛细支气管炎发展为哮喘的影响因素[J].中国实用儿科杂志,2006,21(4):245-248.
    [27] Brandtzae KP.ucosal immunity:ntegration bctweol mother and the breast-fed infantVaccine,003,1(24):382.
    [28] Roine I,Ernandez JA,Vasquez A,et al.Breastfeeding reduces immune activation inprimary respiratory syncytial virus infection [J].Eur Cytokine Netw,2005,16(3):206-210.
    [29] Dioxn DL,Griggs KM,Forsyth KD,et al.Lower interleukin-8levels in airway aspiratesfrom breastfed infants with acute bronchiolitis[J].Pediatr Allergy Immunol,2010,21(4):691-696.
    [30] Friedman NJ,Eiger RS.The role of breast-feeding in the development of allergies andasthma. Allergy Clin Immunol,2005,15:238-1248.
    [31]徐进,刘筱娴,邹商群,等.毛细支气管炎发展为哮喘的危险因素研究[J].中国社会医学杂志,2008,25(5):319-321.
    [32]刘艳云.6个月内喂养方式与毛细支气管炎发病的相关性调查分析.中外医学研究,2009,7(14):16-17.
    [33] Duncan JM,Sears MR.Breastfeeding and allergies:time for a change in paradigm[J].Current Opinion in Allergy and Clinical Immunology,2008,8(5):398-405.
    [1]胡亚美,江载芳.诸福棠实用儿科学[M]:第7版.北京:人民教育出版社,2002:1199-1200.
    [2]沈丽萍,张英,王跃进.毛细支气管炎患儿IL-12和INF-γ的检测及分析[J].中国实用儿科杂志,2005,20(8):498-499.
    [3] Walter MJ,Morton JD,Kajiwara N,et a1.Viral induction of a chronic asthmaphenotype and genetic segregation from the acute response.J Clin Invest.2002Jul;110(2):165-75.
    [4] Piipposavolainen E,Remes S,Kannisto S,et a1.Asthma and lung function20yearsafter wheezing in infancy:results from a prospective follow up study[J].ArchPediatr,2004,158(11):1070-1076.
    [5]陈坤华.毛细支气管炎后吸入激素干预治疗与哮喘相关研究[J].临床儿科杂志,2003,21(8):506-507.
    [6] Sigurs N,Gustafsson PM,Bjarnason R,et al.Severe respiratory syncytial virusbronchiolitis in infancy and asthma and allergy at age13[J].Am J Respir Crit CareMed,2005,171(2):137-141.
    [7] Sigurs N,Bjainason R,Sigurbergsson F,et al.Respiratory syncytial virus bronchiolitisin infancy is an important risk factor for asthma and allergy at age7.Am J Respir CritCare Med,2000,161:1501-1507.
    [8] Lazzaw T,Hogg G,Barnett P.Respiratory syncytial virus infection and recurrentwheeze/asthma in children under five years:an epidemiological survey.J PaediatrChild Heath,2007,43:29-33.
    [9] Lorena Cifuentes,Solange Canssade.Risk factors for recurrent wheezing followingacute bronchiolitis:a12-month follow-up.Pediatric Pulmonology.2003,36(3):316-321.
    [10] Mita H,Turikisawa N,Yamada T,Taniguchi M.Quantification of leukotriene B4glucuronide in human urine [J].Prostaglandins Other Lipid Mediators,2007,83(1):42-49.
    [11] Rabinovitch N.Uninary leukotriene E4[J].Immunol Allergy Clin North Am,2007,27(4):651-654.
    [12] TagerAM,Luster AD.BLT1and BLT2:the leukotriene B4receptors.ProstaglandinsLeukot Essent Fatty Acids,2003,69:123-134.
    [13] Hashimoto A,Endo H,Hayashi I,et al.Differential expression of leukotriene B4receptor subtypes(BLT1and BLT2)in human synovial tissues and synovial fluidleukoeytes of patients with rheumatoid arthritis.J Rheumatol,2003,30:81712-81718.
    [14]陶哲,喻书彻,杨谊平,等.支气管哮喘患儿尿白三烯的测定及其临床意义.中国实用儿科杂志,2004,19(1):22-24.
    [15] DentG,Uhlmann E,Bodtake K,et al.Up-regulation of human eosinophil leukotriene C4generation through contact with bronchial epithelial cells[J].Inflamm. ReS,2000,49(5):236-239.
    [16] Yokomizo T,Lzumi T.Co-expression of LTB4receptors in human mononuclearcells.Life Sci,2001,68(19-20):2207-2212.
    [17] Mellis C.Leukotriene receptor antagonists in virus-induced wheezing:evidence todate.Treat Respir Med,2006,5(6):407-417.
    [18] Da Dalt L,Callegaro,et al.Nasal Lavage Leukotrienes in infants with RSVbronchiolitis[J].Pediatr Allergy Immunol.2007Mar;18(2):100-4.
    [19] Piedimonte G,Renzetti G,Anais A,et al.Leukotriene synthesis during respiratorysyncytial virus bronehiolitis:influence of age and atopy.Pediatr Pulmonology,2005,40(4):285-291.
    [20] Kim CK,Koh JY,Han TH,Kim do K,Kim BI,Koh YY.Increased levels of BALcysteinyl leukotrienes in acute corrected RSV bronchiolitis[J].Acta Paediatr.2006Apr;95(4):479-85.
    [21]李兰,王智斌等.毛细支气管炎血中半胱氨酰白三烯的测定及意义[J].四川大学学报(医学版),2005,36(2):297-300.
    [22]项红霞,赵德育.呼吸道合胞病毒毛细支气管炎患儿尿白三烯测定及临床意义[J].临床儿科杂志,2008,26(1):33-35.
    [23]纪经智等,白三烯受体拮抗剂对呼吸道合胞病毒肺炎血清Th1/Th2细胞因子水平影响的研究[J].中华实验和临床病毒学杂志,2007,21(2):132-134.
    [24]张国秀,陈小文,张亦楠.布地奈德悬液与盐酸特布他林雾化液联合治疗儿童哮喘急性发作[J].实用儿科临床杂志,2006,21(16):1099-1100.
    [25] Allen DB.Effects of inhaled steroids on growth,bone metabolism and adrenal function[J].Adv Pediatr,2006,53:101-110.
    [26]翁俊良,郑义珊,马琼凤.小剂量布地奈德粉吸入剂治疗轻度支气管哮喘患者的远期疗效[J].中华结核和呼吸杂志,2005,28(2):88-92.
    [27] Munger KL,Levin LI,Hollis BW,et al.Serum25-hydroxyvitamin D levels and risk ofmultiple sclerosis.JAMA,2006,296:2832-2838.
    [28] Mural A,et a1.Comparision study between the mechanisms of allergic asthmaamelioration by a cysteiny-leukotrience type1receptor antagonist montelukast andmethylpredinisolom [J].J Pharmacol Exp Ther,2005,312(2):432-440.
    [29] Kearm GL,Lu s,Maganti L,et a1.Pharmaeokineties and safety of montelukast oralgranules in children1to3months of age with bronchiolitis.J CIin Pharmaeol,2008,48(4):510-511.
    [30] Hypponen E,Hartikainen AL,Sovio U,et al.Does vitamin D supplementation ininfancy reduce the risk of pre-eclampsia?.Eur J Clin Nutr,2007,61:1136-1139.
    [31] Chambers ES,et al.Curr Allergy Asthma Rep.2011,11:29-36.
    [32] Litonjua AA,Weiss ST.Is vitamin D deficiency to blame for the asthma epidemic?.JAllergy Clin Immunol,2007,120:1031-1035.
    [33] KARATEKIN G,KAYA A,BALCI H.et a1.Association of subclinical vitamin Ddeficiency in newborns with acute lower respiratory infection and their mothers[J].Eur J Cli Nutr t,2009,63(4):1473-477.
    [34] BREHM J M,CELEDON J C,SOTO-QUIROS M E,et a1.Serum vitamin D levels andmakers of severity of childhood asthma in Costa Rica[J].Am J Respir Crit CareMed,2009,179(9):1765-771.
    [35]王晓芳,洪建国,周小健.维生素D对大鼠哮嗤模型气道炎症的影响[J].上海医学,2008.31(1):27-29.
    [36]刘向荣.纪明慧.小儿反复呼吸道感染相关因素分析[J].齐牛医学杂志,2003,18(4):442.
    [37] Hypponen E,Sovio U,Wjst M,et a1.Infant vitamin D supplementation and allergicconditions in adulthood:northern Finland birth cohort1966.Sci2004,1037:84-95.
    [38] Back O,Blomquist HK,Hemell O,et a1.Does vitamin D intake during infancy promotethe development of atopic allergy.Acts Derm Venereol,2009,89(1):28-32
    [39] Erkkola M,Kaila M,Nwam BI,et a1.Matemal vitamin D intake during pregnancy isinversely associated with asthma and allergic rhinitis in5-year old children.Clin ExpAllergy,2009,39(6):875-882.
    [40] Gale CR,Robinson SM,Harvey NC,et al.Matemal vitamin I)status during pregnancyand child outcomes.Princess Anne Hospital Study Group.Eur J Clin Nutr.2008,62(1):68-77.
    [41] Harvey L,Burne TH,Me Grath JJ,et a1.Developmental vitamin D3deficiency inducesalterations in immune organ morphology and function in adult offspring.J SteroidBiehem Mol Biol,2010,121(1·2):239-242.
    [42]中国营养学会.中国居民膳食营养素参考摄入量.第一版,北京:中国轻工业出版社,2006,280-288.
    [43] Wagner CL,Hulsey TC,Fanning D,et a1.High dose vitamin D3supplementation in acohort of breast feeding mothers and their infants:a six-month follow-up pilotstudy.Breastfeed Med,2006,1(2):59-70.
    [44] Raiakumar K,Thomas SB.Reemerging nutritional tickets:a historical perspective.ArchPediatr Adolese Med,2005,159(4):335-341.
    [1] Matthew Masoli,Denise Fabian,et al.The report of Global Burden of Asthma[J].Allergy,2004,59(5):469-78.
    [2] Dougherty RH,Fahy J V.Acute exacerbations of asthma:epidemiology,biology and theexacerbation-prone phenotype[J].Clin Exp Allergy,2009,39(2):193-202.
    [3] Gillam GL,Mc Nichol KN,Williams HE.Chest Deformity,residual airways obstructionand hyperinflation,and growth in children with asthma[J].Arch Dis Child,2008,45(244):789-799.
    [4] Panettieri RA Jr,Covar R,et al.The natural history of asthma: persistence versusprogession-does the beginning predict the end?[J].Allergy Clic Immunol,2008,121(3):607-613.
    [5] Sib SR,MohuaM,Samir B,et al.A new cell secreting insulin [J].Endocrinology,2003,144(4):1585-1593.
    [6] Michae1F Holiek,M.D.Ph.D.VitaminD Deficiency [J].NEJM,Volume357:266-28lJuly19,2007Number3.
    [7] MARY M.Functional genomics:vitamin D and disease[J].Nat Rev Genet,2010,11:670.
    [8]俞银芳,刘兆鹏.活性维生素D类药物研究概况[J].中国药物化学,2006,16:311-315.
    [9] Goltzman D,Miao D S,Panda D K,et a1.Effect of calcium and the vitamin D systemon skeletal and calcium homeostasis:lessons from genetic modelsE[J].J SteroidBiochem Mol Biol,2004,89/90:485-489.
    [10] SREERAM V R,ANDREAS H,ANTONIO J,et al.AChIP-seq defined genome-widemap of vitamin D receptor [J].Genome Res,2010,24:published online August.
    [11] ROBERT P H,FACN R L,DIANE M C,et al.Vitamin D3distribution and status in thebody[J].J Am Coll Nut,2009,28,3:252-256.
    [12] Veldman CM,C antorna M T,DeLuca HF.Expression of1,25-dihydroxyvitamin D3receptor in the immune systam.Arch Biochem Biophys,2000,374:334-338.
    [13]宋亮年.1,25-(OH)2D3的免疫调节作用[J].生理科学进展,1994,25:8385.
    [14]肖玲莉.Th1/Th2免疫应答失衡及其影响因素[J].国际儿科学杂志,2006,33(6):399-402.
    [15] Taback SP,Simons FE.Anaphylaxis and vitamin D:a role for the sunshine hormone7.JAllergy Clin Immunol,2007,120:128-130.
    [16] Staeva2Vieira TP,Freedman LP.l,252dihydroxyvitaminD3inhibits IFN2gamma andIL-24levels during in vitro Polarization of Primary murine CD4+T cells.JImmunol,2002,168:1181-1189.
    [17] Topil ski Flaishonl L,Naveh Y et al.The anti2inflammatory effeets of1,25-dihydroxyvitaminD3on Th2cells in vivo are due in part to the control of integrin-mediated Tlymphocyte homing.EurJ Immunol,2004,34:1068-1076.
    [18] Mathcu V,Back O,Mondoc E,et al.Dual effects of vitamin D-induced alteration ofTH1/TH2cytokine expression;enhanceing IgE production and decreasing airwaycosinophilia in murine allergic airway disease.J Allergy Clin Immunol,2003,112:585-592.
    [19] Cippitelli M,Fionda C,Di Bona D,et a1. Negative regulation of CD95ligand geneexpression by vitamin D3in T lymphocytes.J Immunol2002:168(3):1154-1166.
    [20] CAI Q,CHANDLER J S,WASSERMAN R H,et a1.Vitamin D and adaptation todietary calcium and phosphate deficiencies increase intestinal plasma mambranecalcium pump gene expression[J].Proc Natl Acad Sci US1993,90(4):1345.
    [21] Adorini L,Penna G,Giarratana N,et a1.Dendritic cells as key targets forimmunomodulation by vitamin D receptor ligands [J].J Steroid Bio MoleBio,2004,89-90(1-5):437-441.
    [22] Van Halteren AG,van Etten E,de Jong EC,et a1.Redirection of human autoreactiveT-cells Upon interaction with dendritic cells modulated by TX527,an analog ofl,25-dihydroxy vitamin D3.Diabetes2002;51(7):2119-2125.
    [23]刘甜甜.CD4+CD25+调节性T细胞与支气管哮喘.国际内科学杂志,2008,35(1):37-40.
    [24] Xystrakis E,Kusumakar S,Boswell S,et a1.Reversing the defective in duction ofIL-10-secreting regulatory T cells in glucocortieoid-resistant asthma patients.J ClinInvest,2006,116(1):146-155.
    [25] Jouuleit BH,Schmitt F,Schuler G,et a1.Induction of interleukin10producing,Nonproliferating CD4+T cells with regulatory properties by repetitive stimulationwith allogeneic immature human dendritic cells[J].J Exp Med.2000,192(9):1213-1222.
    [26] Liu PT, Stenger S,Li H,et al.Toll like receptor triggering of a vitamin D mediatedhumanant imicrobial response.Science,2006,311:1770-1773.
    [27] Boss6Y,Maghni K Hudson TJ.1alpha,25dihydroxy vitamin D3stimulation ofbronchia1smooth muscle cells induces autocrine,contractility,and remodelingprocesses.Physiol Genomics,2007,29:161-168.
    [28] Lee HC,Kim SJ,Kim KS,e t al.R emission in models of type1diabetes bygenetherapy using a s inglechain insulin an alogue [J]. Nature,2000,408(6811):483 488.
    [29]宋颖芳,柏长青,戚好文,等.1,25-二羟维生素D3对哮喘小鼠气道重塑及基质金属蛋白酶-9表达的影响[J].细胞与分子免疫学杂志.2008,24(5):527-531.
    [30] Matheu V,Back O,Mondoc E,et al.Dual effects of vitamin D-induced alteration ofTH1/TH2cytokine expression: enhancing IgE production and decreasing airwayeosinophilia in murine allergic airway disease.J Allergy Clin Immunol,2003,112:585-592.
    [31] Lemire JM.Immunomodulatory role of1,25-dihydroxyvitamin D3.J Cell Biochem1992,49:26-31.
    [32] LitonjuaAA.Childhood asthma may be a consequence of vitamin D deficiency [J].Current Opinion in Allergy and Clinical Immunology.2009Jun:9(3):202-7.
    [33] Harvey L,Burne TH.McGrath JJ,et a1.Developmental vitamin D3deficiency inducesalterations in immune organ morphology and function in adult of spring.J SteroidBiochem Mol Biol,2010,121(1-2):239-242.
    [34] Nguyen TM,Guillozo H,Marin L,et a1.Evidence for a vitamin D paracrine systemregulating maturation of developing rat lung epithelium.Am J Physiol,1996,271(3Pt1):L392-L399.
    [35] Edelson J D,Chan S,Jassal D,et a1.Vitamin D stimulates DNA synthesis in alveolartype-1T cells.Biolchim Biophys Acta,1994,1221:159-l66.
    [36] Nguyen M,Trubert CI,Rizk-Rabin M,et al.1,25-Dihydroxy vitamin D3and fetal lungmaturation:immunogold detection of VDR expression in pneumocytes type II cellsand effect on fructose1,6bisphosphatase.J Steroid Binchem Molbiol,2004,89-90:93-97.

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