Clara细胞分泌蛋白10基因G38A多态性与5岁以下喘息患儿的相关性

目的探讨5岁以下喘息患儿Clara细胞分泌蛋白10(CC10)基因G38A位点多态性与喘息发病机制的关系。方法随机选取于本院就诊的5岁以下反复喘息患儿120例,分为有特应质高危因素的喘息Ⅰ组(n=67)(湿疹45例,父母或父母一方有哮喘病史13例,变应性鼻炎5例,变应性皮炎4例)和无特应质高危因素的喘息Ⅱ组(n=53);对照组为本院外科近期无感染疾病史、择期进行手术的术前患儿(n=55)。采用PCR-限制性片段长度多态性分析对喘息组和对照组患儿CC10 G38A位点基因型频率和等位基因频率进行检测,比较3组间CC10 G38A位点基因型频率和等位基因频率。结果喘息Ⅰ组、喘息Ⅱ组和对照组3种基因型AA、GA、GG分布频率分别为20.9%、44.8%、34.3%,9.4%、32.1%、58.5%、9.1%、31.0%、60.0%;喘息Ⅰ组和喘息Ⅱ组CC10基因G38A位点基因型频率比较差异有统计学意义(P<0.05);喘息Ⅰ组和对照组CC10基因G38A位点基因型频率比较差异亦具有统计学意义(P<0.05)。喘息Ⅰ组、喘息Ⅱ组和对照组38A和38G等位基因频率分别为43.3%、56.7%,25.5%、74.5%,24.5%、75.5%;喘息Ⅰ组和喘息Ⅱ组、喘息Ⅰ组和对照组比较差异均有统计学意义(Pa<0.05)。结论喘息患儿与哮喘存在相同的基因分布频率,发生哮喘的危险性高;对于CC10基因具有A等位基因的喘息患儿应密切关注。     

Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection

Respiratory syncytial virus (RSV) infection is an important cause of recurrent wheezing in infants. Nevertheless, the link between RSV infection and wheezing has yet to be elucidated at the molecular level. Here, we present a preliminary study on the evolution of the immune response in the respiratory tract at long‐term after RSV infection. Twenty‐seven immune mediators were profiled in nasopharyngeal aspirates (NPAs) obtained from 20 children hospitalized due to a severe infection by RSV at discharge from hospital and again 1 yr later. The same mediators were profiled in parallel in NPAs from 12 healthy controls. In the year following discharge, 85% (17/20) of children of the RSV group suffered at least one episode of wheezing documented by the pediatrician. On the contrary, wheezing episodes were observed only in 25% (3/12) of children in the control group. While most of the mediators profiled returned to normal levels by 1 yr after discharge from hospital, RSV children showed a persistent nasal hyper‐secretion of VEGF, G‐CSF, IL‐10, IL‐6, IFN‐γ, IL‐7 and IL‐13. In previous works VEGF, IL‐10 and IFN‐γ have been put in relation with the pathogenesis of post‐virus induced asthma. G‐CSF, IL‐6, IL‐7 and IL‐13 are increased in respiratory and plasma samples of asthmatic patients. Here, we evidence for the first time a persistent elevation of these mediators as late as 1 yr after severe RSV disease resolution, reinforcing their possible implication in the pathogenesis of wheezing.     

Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.     

Respiratory syncytial virus infection in lower respiratory tract and asthma attack in hospitalized children in North Hokkaido,Japan

Respiratory syncytial virus (RSV) infection is severe and life-threatening in some infants. To investigate the epidemiology of RSV infection in hospitalized children in North Hokkaido, Japan, we tried to detect RSV antigen in nasopharyngeal aspirates (NPA) from those children with lower respiratory tract infection (LRTI) and asthma attack. From April 1991 to March 1992, 317 patients were hospitalized in our pediatric ward for the treatment of LRTI and asthma attack. The presence of RSV antigen in NPA taken from 283 patients (89.3%) were examined by enzyme immunoassay. RSV antigen was detected in 88 patients (31.1%). RSV LRTI were noted throughout the year, and the epidemic peak was observed in November and December. There was no significant correlation between the RSV antigen positive rate and mean temperature. RSV played an important role in LTRI in children in North Hokkaido, Japan. RSV LRTI in North Hokkaido was not rare in summer, indicating that RSV was transmitted commonly among children throughout the year.     

Immunoglobulin heavy G2 chain (IGHG2) gene restriction in the development of severe respiratory syncytial virus infection

AIM: Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 y of age. It is assumed that host factors influence the severity of disease presentation, and thus the need for hospitalization. The variation of IGHG genes from chromosome 14q32 are linked to serum IgG subclass levels but also to the variations in IgG responses to pneumococcal, meningococcal and Haemophilus influenzae antigens. The aim of this investigation was to clarify whether IGHG genes are involved in the development of severe RSV lower respiratory tract infection (LRTI). METHODS: The alternative expressions of IGHG3(b) and (g), IGHG1(f) and (a), and IGHG2(n) and (-n) genes were studied in a cohort of 49 previously healthy children hospitalized for RSV LRTI. The gene frequencies were compared to a population of healthy individuals. RESULTS: The homozygous IGHG2(-n/-n) genotypes dominated in hospitalized children with severe RSV infection: 55.1%, compared with 34.2% in the healthy population (OR 2.3; p = 0.004). The IGHG2 genotypes containing (n/n) and (n/-n) were significantly decreased. The IGHG(bf-n) alleles were significantly increased (OR 1.7; p = 0.025) and the IGHG(bfn) alleles significantly decreased (OR 0.5; p = 0.005). CONCLUSION: The IGHG(bf-n) allele and homozygous IGHG2(-n/-n) genotypes are associated with the development of severe RSV LRTI.     

呼吸道合胞病毒毛细支气管炎与白细胞介素-10-592A/C基因多态性的相关性研究

目的 探讨白细胞介素-10-592A/C基因多态性与呼吸道合胞病毒(RSV)毛细支气管炎易感性、病情的关联和对血清白细胞介素(IL)-10的影响.方法 采用聚合酶链反应-限制性片段长度多态性检测100例汉族RSV毛细支气管炎患儿(病例组)和100例健康儿童(对照组)IL-10-592A/C位点单核苷酸多态性;应用ELISA法检测病例组血清IL-10水平.结果 病例组IL-10-592A/C位点基因型频率分别为AA 44%、AC 38%、CC 18%,等位基因频率分别为A 63%、C 37%;对照组基因型频率分别为AA 41%、AC 42%、CC 17%,等位基因频率分别为A 64%、C 36%;两组基因型及等位基因频率比较差异均无显著性(χ2=0.33,P>0.05;χ2=0.43,P>0.05).病例组IL-10-592A/C位点不同基因型患儿血清IL-10水平比较差异无显著性(F=0.87,P>0.05).IL-10-592A/C位点基因型频率在轻度和中重度患儿之间的差异无显著性(χ2=2.67,P>0.05).结论 IL-10-592A/C位点基因多态性与RSV毛细支气管炎不存在关联.     

乌鲁木齐地区维、 汉族儿童哮喘与ADAM33 基因多态性的相关性

目的探讨乌鲁木齐地区维、汉族儿童支气管哮喘与ADAM33基因多态性的相关性。方法选取同期3~15岁于乌鲁木齐地区生活的86例维族和111例汉族哮喘患儿,同时纳入64例汉族、56例维族健康儿童为对照组;采用聚合酶链反应对ADAM33基因V4、T2位点进行单核苷酸多态性(SNP)分型,并对其中部分进行基因检测验证。结果哮喘组和对照组之间,ADAM33基因V4、T2位点三种基因型的分布差异有统计学意义(P均0.01);V4位点哮喘组CC基因型频率较高,与G等位基因个体比较,C等位基因携带者儿童发生哮喘的风险增加1.51倍(95%CI:1.10~2.09);T 2位点哮喘组AA基因型频率较高,与G等位基因个体比较,A等位基因携带者儿童发生哮喘的风险增加1.96倍(95%CI:1.32~2.91)。汉族儿童中,哮喘组和对照组之间ADAM 33基因V 4、T 2位点三种基因型分布的差异无统计学意义(P均0.05);而维族儿童中,V 4、T 2位点三种基因型分布的差异有统计学意义(P均0.05)。结论 ADAM 33基因V 4、T 2位点与乌鲁木齐地区维族儿童哮喘发病相关。     

Respiratory syncytial virus infection and chronic respiratory morbidity – is there a functional or genetic predisposition?

A systematic literature review has been undertaken. Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infancy is associated with chronic respiratory morbidity. Premorbid abnormal lung function may predispose to RVS LRTI in prematurely born infants. Conclusion: Single‐nucleotide polymorphisms in genes coding for IL‐8, IL‐19, IL‐20, IL‐13 mannose‐binding lectin, IFNG and a RANTES polymorphism have been associated with subsequent wheeze following RSV LRTI in term‐born infants.     

IL10 family member genes IL19 and IL20 are associated with recurrent wheeze after respiratory syncytial virus bronchiolitis

Mechanisms underlying the increased risk of recurrent wheeze after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are unclear. Specifically, information about genetic determinants of recurrent wheeze after RSV LRTI is limited. We performed a candidate gene association study to identify genetic determinants of recurrent wheeze after RSV LRTI. We investigated 346 single nucleotide polymorphisms (SNPs) in 220 candidate genes in 166 Dutch infants hospitalized for RSV LRTI. Logistic regression analysis was used to study associations between genotypes and haplotypes and recurrent wheeze after RSV LRTI. We found associations with recurrent wheeze for SNPs in IL19, IL20, MUC5AC, TNFRSF1B, C3, CTLA4, CXCL9, IL4R, and IL7 genes. Haplotype analysis of the combined IL19/IL20 genotyped polymorphisms demonstrated an inverse association between the TGG haplotype and recurrent wheeze after RSV LRTI. IL19 and IL20 genes were notably associated with recurrent wheeze in infants without asthmatic parents. The association of IL20 SNP rs2981573 with recurrent wheeze was confirmed in a healthy birth cohort. We concluded that genetic variation in adaptive immunity genes and particularly in IL19/IL20 genes associates with the development of recurrent wheeze after RSV LRTI, suggesting a role for these IL10 family members in the etiology of airway disease during infancy.     

川崎病患儿FCGR2A基因单核苷酸多态性的研究

目的：探讨中国汉族儿童FCGR2A基因 rs1801274位点单核苷酸多态性（SNP）与川崎病（KD）易感性及静脉注射免疫球蛋白(IVIG)治疗KD疗效的关系。方法：应用聚合酶链反应（PCR）联合直接基因测序技术对35例KD患儿和25例健康儿童的FCGR2A基因SNP rs1801274位点进行检测和分析,并将KD患儿根据IVIG治疗后有无并发冠脉损害（CAL）分为CAL和无CAL（NCAL）两个亚组。结果：在研究对象中均检测到FCGR2A基因rs1801274位点,该位点存在3种基因型(AA、AG、GG)。该SNP位点的基因型分布及等位基因频率在KD组与对照组及CAL组与NCAL组之间比较差异均有统计学意义（P<0.05）。其中携带A等位基因或AA基因型者发生KD的危险性大(分别OR=3.39,95%CI:1.53~7.50;OR=4.93,95%CI：1.61~15.1);携带基因型AG或G等位基因使KD患儿发生CAL的危险性增高（分别OR=5.43,95%CI:1.06~27.8;OR=4.88,95%CI: 1.44~16.5）。结论：FCGR2A基因rs1801274位点SNP可能是影响中国汉族儿童KD易感性以及IVIG治疗KD疗效的一个重要因素。     

Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (+/-2 wk) and gestational age at birth (+/-2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p = 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders, i.e. smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p = 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection.     

RANTES启动子-28C/G基因多态性与呼吸道合胞病毒致细支气管炎易感性的关联

目的 探讨正常T淋巴细胞表达和分泌的活性调节蛋白RANTES的启动子-28C/G基因多态性与呼吸道合胞病毒(RSV)致细支气管炎(既往称毛细支气管炎)易感的关联性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测238例RSV细支气管炎患儿及288例正常对照者的RANTES-28C/G多态性,ELISA法检测血清总IgE浓度,全自动血细胞计数仪计数嗜酸性粒细胞,并搜集受检者的特应性体质史、特应性家族史及临床相关资料.结果 RANTES-28C/G基因型分布在RSV细支气管炎组和对照组均符合Hardy-Weinberg平衡.与对照组比较,RANTES-28C/G基因型及等位基因频率在RSV细支气管炎组中的分布差异均有统计学意义(G=10.22,P＜0.01;x2=9.708,P＜0.01);与CC基因型个体相比,携带G等位基因的个体发生RSV细支气管炎的风险增加了2.09倍(OR:2.09,95% CI=1.32～3.30,P＜0.01).在RSV细支气管炎组,携带G等位基因个体具有特应性体质和特应性家族史的风险分别比CC基因型个体增加了1.85倍(OR=1.85,95% CI=1.01～3.38,P＜0.05)和1.91倍(OR=1.91,95% CI=1.03～3.54,P＜0.05),其嗜酸性粒细胞计数亦显著升高(Z=-2.303,P＜0.05).结论 RANTES启动子-28C/G基因多态性与RSV细支气管炎易感性相关联,并且-28G等位基因与RSV细支气管炎患儿的特应性体质及特应性家族史相关联.     

Clara细胞分泌蛋白10在5岁以下喘息儿童外周血中的表达

目的：探讨外周血中Clara细胞分泌蛋白10（CC10）和血清总IgE浓度在5岁以下喘息儿童中的表达。方法：随机选取5岁以下反复喘息患儿59例,分为有特应质高危因素的喘息Ⅰ组（n=33）和无特应质高危因素的喘息Ⅱ组（n=26）,对照组为近期无感染疾病史的外科术前患儿(n=23)。采用固相夹心酶免疫吸附实验（ELISA）测定3组患儿外周血CC10与IgE水平。结果：喘息Ⅰ组、Ⅱ组CC10水平(3.95±1.26, 5.41±1.64 ng/mL)均低于对照组(8.72±2.23 ng/mL),差异有统计学意义(P<0.01);喘息Ⅰ组CC10水平低于喘息Ⅱ组(P＜0.05)。喘息Ⅰ组IgE水平高于喘息Ⅱ组和对照组,差异有统计学意义（P＜0.05）,喘息Ⅱ组和对照组之间差异无统计学意义（P＞0.05）。喘息Ⅰ组血清CC10与IgE呈负相关（r=-0.912, P＜0.01）。结论：外周血CC10水平在5岁以下患儿喘息发作期显著降低,有特应质高危因素的患儿降低更为明显,并与外周血IgE水平呈负相关。     

Long-term consequences of respiratory syncytial virus (RSV) bronchiolitis

Despite differences in study design, follow-up studies consistently show that approximately half of the infants with respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) go on to have recurrent wheezing episodes during childhood. Respiratory symptoms are associated with abnormal lung function, including bronchial hyper-responsiveness. Wheezing symptoms following RSV LRTI gradually decrease, and it appears that during school age airway morbidity is no longer related to RSV LRTI during infancy. Mechanisms underlying the association between RSV LRTI and long-term airway morbidity are poorly understood. On the one hand, abnormal airway function that is congenitally present or acquired before RSV LRTI occurs could be the cause of both RSV LRTI and subsequent recurrent wheezing. On the other hand, it is possible that RSV LRTI causes changes in the lower airways or the immune system that result in long-term airway morbidity. Animal models suggest that RSV infection can promote the development of allergic sensitization, but most studies in humans do not indicate a role for atopy in the development of recurrent wheezing following RSV LRTI.     

Maturation of gastric electrical activity, gastric emptying and intestinal permeability in preterm newborns during the first month of life

Objectives

Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTI) in young children worldwide. We evaluate the epidemiological and clinical patterns of RSV infection in infants hospitalized for LRTI in in Palermo, South Italy, Sicily.

Methods

We collected the demographic details of infants hospitalized to G. Di Cristina Children's Hospital in Palermo for LRTI between November 2005 and May 2006. We also included all cases occurred in newborns hospitalized in the Neonatal Intensive Care Unit (NICU) Of Palermo.

Results

During the studied period, 335/705 hospitalized infants for LRTI were enrolled in the study. The trend of hospitalization started in late winter and lasting until May 2006 with an epidemic peak in spring. 178/335 infants tested for viral infection showed RSV disease. Three cases occurred in preterm newborns hospitalized from birth in NICU. The likelihood to be RSV+, rather than RSV negative (RSV-) was higher for infants < 6 months and lower for infants with history of breast feeding (P < 0.05). RSV infection was associated with a higher likelihood to be admitted to intensive care unit and to a longer hospitalization and oxygen therapy.

Conclusion

The study shows that, in Sicily, RSV is an important cause of LRTI in infants. The seasonal distribution shows that both LRTI and RSV infections peak in late spring, in contrast to Northern Italy. Our data could help to define the regional appropriate start of prophylactic interventions.     

IL-13基因多态性与RSV感染后婴幼儿喘息及哮喘关系的研究

目的 探讨IL-13基因Arg110Gln多态性在RSV感染后婴幼儿喘息发生和哮喘发病中的作用.方法 哮喘患儿和止常儿童各96例,RSV感染后喘息婴幼儿112例,取其颊黏膜细胞,提取DNA,用实时PCR法对IL-13 Arg110Gln位点进行基因分型.结果 IL-13 Arg110Gln位点的基因型和等位基因频率分布在哮喘组和对照组间差异有高度统计学意义(P<0.01);哮喘组的A等位基因和A/A纯合子基因型频率明显高于对照组(分别为68.2%和47.4%,46.9%和29.2%,P<0.01).IL-13 Arg110Gln位点的基因型和等位基因频率分布在哮喘组和RSV感染后喘息组间差异无统计学意义(P>0.05).结论 IL-13 Arg110Gln位点G→A变异与RSV感染后婴幼儿喘息发生和哮喘发病相关,两者在该位点上可能存在相似的遗传基础.     

Lower respiratory tract infections associated with influenza A and B viruses in an area with a high prevalence of pediatric human immunodeficiency type 1 infection

BACKGROUND: Despite the high burden of pediatric HIV-1 infection in developing countries, there are few data on the clinical course of influenza virus-associated lower respiratory tract infection (LRTI) in these children. OBJECTIVE: To define and compare the clinical course of HIV-1-infected and -uninfected African children hospitalized with influenza virus associated severe LRTI. METHODS: Children with severe LRTI were prospectively recruited between March, 1997, and March, 1999, as part of a broader study evaluating the etiology and outcome of this condition in hospitalized HIV-1-infected and -uninfected children. The results of children in whom influenza A or B virus was identified by immunofluorescent antibody staining after shell vial culture are reported. Viruses isolated were typed by hemagglutination inhibition assays. RESULTS: Twenty-five (21.6%) of the 116 children hospitalized with severe LRTI in whom influenza A or B virus was identified were HIV-1-infected. HIV-1-infected children were older than uninfected children (mean age +/- SD 17.4 +/- 10.8 months vs. 10.2 +/- 8.9 months; P = 0.002). HIV-1-infected children were more likely to have an underlying medical illness (in addition to HIV-1 infection) predisposing them to more severe LRTI (32.0% vs. 13.2%; P = 0.03). HIV-infected children were also more likely to have indirect evidence of bacterial coinfection, including chest radiographic evidence of confluent alveolar consolidation (78.9% vs. 35.1%, P = 0.006), and were less likely be wheezing (8.0% vs. 31.9%, P = 0.01). However, there was no difference in the clinical outcome of HIV-1-infected and -uninfected children. The duration of hospitalization [median (range) 5 (2 to 33) days vs. 4 (0 to 21) days, P = 0.08] and the mortality rates (8.0% vs. 2.2%, P = 0.20) were similar between HWV-1-infected and -uninfected children. CONCLUSION: HIV-1-infected children hospitalized with severe LRTI associated with influenza virus have an outcome similar to that of HIV-1-uninfected children even in the absence of antiretroviral or anti-influenza virus treatment.     

IL-12 p40 3''''非翻译区rs3212227单核苷酸多态性与呼吸道合胞病毒感染后喘息发生的关系研究

目的 探讨IL-12 p40基因3'非翻译区(3'URT)单核苷酸多态性位点(rs3212227)与呼吸道合胞病毒(RSV)感染后病情严重度的关系.方法 对2004-2006年儿内呼吸科收治的呼吸道感染患儿用直接免疫荧光法进行鼻咽部分泌物呼吸道病原抗原检测,选取RSV阳性患儿共175例,按临床表现分为喘息组(112例)和非喘息组(63例),用Taqman探针检测法对两组患儿行IL-12 p40rs3212227位点单核苷酸多态性分析.两组患儿血清总IgE定量采用Unicap体外检测系统测定.结果 RSV感染后喘息组rs3212227位点等位基因A和C的发生频率分别为48.2%、51.8%,非喘息组分别为29.4%、70.6%,两组等位基因频率差异有统计学意义.喘息组A/A纯合子、C/C纯合子和A/C杂合子基因型频率分别为21.4%、25.0%和53.6%,非喘息组A/A纯合子、C/C纯合子和A/C杂合子基因型频率分别为9.5%、50.8%和39.7%,两组基因型频率差异有统计学意义.尽管喘息组患儿血清总IgE水平显著高于非喘息组患儿(P＜0.05),但喘息组rs3212227位点A/A纯合子、C/C纯合子和A/C杂合子患儿之间的血清总IgE水平差异无统计学意义(P＞0.05).结论 IL-12 p40rs3212227位点单核苷酸多态性与RSV感染后喘息的发生有关,但与血清总IgE水平无关.