呼吸道合胞病毒毛细支气管炎与支气管哮喘的相关性研究

目的探讨呼吸道合胞病毒(RSV)毛细支气管炎(毛支)与支气管哮喘两者发病机制的相关性。方法采用ELISA法检测31例RSV毛支患儿、25例支气管哮喘患儿、27例非RSV肺炎患儿和24例健康儿童外周血IFN-γ、IL-4、IL-10、TGF-β、IL-17水平,并进行比较分析。结果 RSV毛支患儿和哮喘患儿的IL-10、TGF-β水平显著低于非RSV肺炎患儿和健康对照儿童,而IL-4、IL-17水平则显著高于非RSV肺炎患儿和健康对照儿童(P均<0.05)。RSV毛支患儿和哮喘患儿的IFN-γ/IL-4、IL-10/IL-17比例显著低于非RSV肺炎患儿和健康对照儿童(P均<0.05),哮喘患儿的TGF-β/IL-17显著低于非RSV肺炎患儿与健康对照儿童(P均<0.05)。RSV毛支患儿与哮喘患儿之间、非RSV肺炎患儿与健康对照儿童之间IFN-γ、IL-4、IL-10、TGF-β、IL-17水平及其比值IFN-γ/IL-4、IL-10/IL-17、TGF-β/IL-17的差异均无统计学意义(P均>0.05)。结论 RSV毛支患儿与哮喘患儿存在相同的外周血细胞因子IFN-γ、IL-4、IL-10、TGF-β、IL-17水平的改变,这可能是其共同的发病机制之一。     

Association of MBL2 polymorphism with asthma after bronchiolitis in infancy

Background: Mannose‐binding lectin (MBL) is a component of innate immunity and has been linked with the pathogenesis of asthma. The aim of the present study was to evaluate the association of MBL genotypes with preschool asthma and allergy in children with bronchiolitis in early infancy. Methods: In all, 205 infants were hospitalized for bronchiolitis at <6 months of age. Asthma and allergy were studied from a total of 166 children at 6.4 years (mean). A total of 141 (85%) frozen whole blood samples were available for MBL genotyping and MBL2 gene mutations were determined on pyrosequencing for detection of three single‐nucleotide polymorphisms. Results: Ninety‐five children (67.4%) had the wild‐type MBL genotype A/A and 46 had A/O or O/O genotypes. Asthma was present in 16 children (11.3%) at 5–7 years of age. Nine children (19.6%) with non‐AA genotype had asthma (vs 7.4% of those with genotype AA, P= 0.03). The result remained significant after adjustment for age, gender and atopy. There were no significant associations between MBL genotypes and asthma at any age before the study. Atopic dermatitis, allergic rhinitis or paternal and/or maternal asthma had no significant associations with MBL genotypes. Conclusions: The variant non‐A/A MBL genotype is associated with asthma after bronchiolitis in infancy, but not earlier than at 5–7 years of age.     

Gender analysis in acute bronchiolitis due to respiratory syncytial virus

It is reasonable to compare immune reactions between boys and girls because many infections in the early stages are predominant in males. A relationship between immunomodulatory effects of sex hormone surge in boys at early months and infectious diseases is still unclear. We compared clinical features between boys and girls who suffered from wheezing that was initially triggered by acute respiratory syncytial virus (RSV) bronchiolitis. For systemic immune response evaluation, white blood cell (WBC) count, blood eosinophil count, and serum C-reactive protein (CRP) were measured. For local inflammation evaluation, scores for eosinophils and neutrophils in sputum were evaluated microscopically. Patients consisted of 90 boys and 51 girls. Most children were under 6 months of age. WBC counts and serum CRP levels were significantly increased in girls compared with boys. Blood eosinophilia at the acute stage was rarely observed in children after 6 months of age. For local response evaluation, sputum specimens obtained from 42 boys and 29 girls were microscopically examined. Sputum eosinophil score of 2+ and more was observed in boys (6/42) exclusively. In contrast, sputum neutrophilia was commonly observed in boys and girls. From a follow-up study, we confirmed that 28 children with RSV bronchiolitis showed wheezing episodes afterwards. However, their blood and sputum eosinophilia during RSV bronchiolitis did not reflect their subsequent wheezing. We speculated that gender-specific responses to RSV infection might account for male susceptibility. Differences in RSV pathogenicity between boys and girls should be further investigated in terms of asthma progression.     

孟鲁司特钠治疗呼吸道合胞病毒毛细支气管炎的临床观察

目的 观察孟鲁司特钠对呼吸道合胞病毒毛细支气管炎患儿临床症状及预后的影响.方法 选择年龄6～12个月的毛细支气管炎患儿,均为首次发病,采用鼻咽分泌物定性检测呼吸道合胞病毒(RSV)抗原,阳性者作为研究对象,共80例,随机分为观察组和对照组各40例.两组患儿均采用相同的综合治疗,观察组加用孟鲁司特钠4 mg每晚1次口服.观察各组患儿临床症状恢复情况及住院天数;检测两组患儿入院第2天、第6天晨尿中的白三烯E4的含量;对所有病例随访3个月(观察组孟鲁司特钠持续应用3个月),观察各组患儿在此期间再次出现喘息的情况.结果 观察组达到喘息缓解所需时间及住院天数与对照组相比差异有统计学意义(P<0.01);两组患儿入院第2天、第6天晨尿中的白三烯E4的含量比较,治疗组在治疗前后及与对照组比较差异无统计学意义;随访3个月后,治疗组有3例出现再次喘息,而对照组有11例出现再次喘息.结论 呼吸道合胞病毒毛细支气管炎加用孟鲁司特钠可有效改善临床症状并缩短住院时间,降低病毒感染后喘息的复发率;两组尿白三烯含量差异无统计学意义,提示并非所有RSV感染的毛细支气管炎患儿喘息均与白三烯有关.     

嗜酸性粒细胞趋化因子在呼吸道合胞病毒性毛细支气管炎中的作用和意义

目的探讨呼吸道合胞病毒(RSV)毛细支气管炎(毛支)患儿血、痰中嗜酸性粒细胞趋化因子(Eotaxin)的临床意义。方法对象为轻、中度毛支患儿22例和重度毛支患儿11例,选择无喘息病毒性肺炎12例作为对照组。采用双抗体夹心酶联免疫吸附试验(ELISA)测定各组患儿血清和痰中Eotaxin水平,并进行比较。结果急性期轻、中度毛支组和重度毛支组血清、痰Eotaxin水平高于对照组(P<0.01)。恢复期轻、中度毛支组和重度毛支组血清Eotaxin水平高于对照组。轻、中度毛支组和重度毛支组比较差异无统计学意义。结论 RSV毛支患儿血和痰液中Eotaxin增高,Eotaxin在毛支的发病机制中起重要作用。     

呼吸道合胞病毒毛细支气管炎特应性与血清IL-10及病情恢复的关系

为探讨呼吸道合胞病毒(RSV)毛纫支气管炎患儿特应性与血清白介素10(IL-10)水平及病情恢复的关系，应用酶联免疫吸附法分别检测17例年龄50天--12月，特应性体质的RSV毛细支气管炎患儿急性期与恢复期血清IL-l0水平，并以24例非特应性患儿及37例正常儿为对照组。结果显示，急性期待应性组IL—10水平与正常对照组相比，差异无显著性(P＞0．05)，但明显低于无特应性组(P＜0．001)；特应性组喘憋和肺部体征消失均较非特应性组慢，住院时间延长(P＜0．05)；恢复期两组IL-l0差异无显著意义。提示特应性体质患儿RSV感染后不能上调IL-l0产生，结果可导致病变恢复缓慢。     

Lower levels of plasmacytoid dendritic cells in peripheral blood are associated with a diagnosis of asthma 6 yr after severe respiratory syncytial virus bronchiolitis

Plasmacytoid dendritic cells (pDC) play a crucial role in antiviral immunity and promoting Th1 polarization, possibly protecting against development of allergic disease. Examination of the relationship between peripheral blood plasmacytoid DC levels and manifestations of asthma and atopy early in life. We have isolated peripheral blood mononuclear cells (PBMC) from 73 children (mean age ± SD: 6.6 ± 0.5 yr old) participating in the RSV Bronchiolitis in Early Life (RBEL) study. Flow cytometry was performed on PBMC detecting DC surface-markers: Blood Dendritic Cell Antigens (BDCA) 1, 3, and 2 which identify myeloid type 1, type 2, and plasmacytoid cells, respectively. Total serum IgE, peripheral eosinophil count, and allergy skin tests were documented. About 45% (n = 33) of study participants had physician-diagnosed asthma by 6 yr of age. These children had significantly lower quantities (mean ± SD) of plasmacytoid DC than their non-asthmatic counterparts (1020 ± 921 vs. 1952 ± 1170 cells per 10⁶ PBMC, p = 0.003). We found significantly lower numbers of myeloid dendritic cells in children with asthma (3836 ± 2472 cells per 10⁶ PBMC) compared with those without asthma (4768 ± 2224 cells per 10⁶ PBMC, p = 0.02); however, this divergence was not significant after adjusting for covariates of age, gender, race, skin test reactivity, smoke exposure, and daycare attendance. We did not identify any direct association between DC levels and markers of atopy: skin test reactivity, peripheral eosinophilia, and IgE level. Children who are diagnosed with asthma after severe RSV bronchiolitis appear to have a relative deficiency of plasmacytoid DC in peripheral blood.     

Wheezing illness caused by respiratory syncytial virus and other agents

Background: Respiratory syncytial virus (RSV) and other pathogenic agents cause lower respiratory infection with wheezing in infants (wheezing illness in infancy). Wheezing illness in infancy due to RSV can be life-threatening and can induce recurrent wheezing; but these events can also be produced by infection by other pathogenic agents. Thus, whether RSV induces more severe wheezing illness in infancy remains poorly understood.
Methods: Infants with an initial wheezing illness were divided into an RSV-positive group and an RSV-negative group and the differences in disease severity, intensity of acute symptoms, and susceptibility to recurrent wheezing, between these two groups, were investigated.
Results: The RSV-positive group accounted for 57.4% of the infants. The infants in the RSV-positive group were significantly younger than those in the RSV-negative group. Other background parameters, gender and family history, were not significantly different. There were no significant differences in indicators of severity (hospitalization periods, periods of persistent wheezing and requirement of oxygen supplementation) between the two groups.
Conclusion: Wheezing illness in infancy caused by RSV is more common in younger infants, but it is not more severe than that caused by other pathogenic agents.     

Ribavirin for respiratory syncytial virus bronchiolitis reduced the risk of asthma and allergen sensitization

Respiratory syncytial virus (RSV) bronchiolitis in early life is a risk factor for later development of asthma and atopy. Ribavirin is the only effective drug currently available against acute RSV bronchiolitis. However, the long-term effects of ribavirin remain unclear. We investigated a cohort of children hospitalized with RSV bronchiolitis from when they were under 2 yr old until they reached a mean age of 6.2 yr. In total, we enrolled 175 children in this study. Both the group treated with ribavirin and the group not treated with ribavirin included high-risk young children with congenital heart disease or chronic lung disease. Their respective age-matched controls, that we labeled groups A and B, both without ribavirin treatment, consisted of previously healthy subjects. Wheezing was either verified by physicians or estimated by a questionnaire. Allergen sensitization was judged by serum allergen-specific IgE levels. The cumulative incidence of physician-diagnosed asthma or recurrent wheezing in the ribavirin group (15%) was significantly lower than its incidence in the non-ribavirin-treated group (34%, p = 0.049), and in the control A group (43%, p = 0.005). Allergen sensitization was also least frequent in the ribavirin group. Ribavirin therapy was an independent factor in reducing the risk of developing asthma, asthma/recurrent wheezing, and sensitization to D. pteronyssinus / D. farinae. The long-term value of ribavirin for acute RSV bronchiolitis and its underlying mechanisms deserves further research.     

Teenage asthma after severe infantile bronchiolitis or pneumonia

OBJECTIVE: The purpose of the study was to evaluate asthma at >13 y of age in children with infantile bronchiolitis or pneumonia. METHODS: In 1981-1982, 127 children at <2 y of age were hospitalized for bronchiolitis (n = 81) or pneumonia (n = 46). Respiratory syncytial virus (RSV) infection, eosinophilia and markers of atopy were assessed and recorded on admission. At a median age of 14.9 y, atopic and asthmatic symptoms were screened by a written questionnaire in 98/127 (77%) study subjects. RESULTS: Asthma was present, according to two definitions, in 14% to 23% in the original bronchiolitis and in 12% to 15% in the original pneumonia group. The figures were 8% to 17% in the RSV infection and 16% to 23% in the non-RSV infection group. Early asthma-predictive factors were repeated wheezing, atopic dermatitis and elevated blood eosinophils. All but one of the teenage asthmatics had allergic rhinitis. CONCLUSION: An increased risk for asthma persists until the teenage period after bronchiolitis and pneumonia in infancy. Both early and later atopy were significant risk factors. The present study was unable to demonstrate the association between early RSV infection and teenage asthma.     

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

目的 探讨呼吸道合胞病毒(RSV)毛细支气管炎(毛支)患儿尿白三烯E4(LTE4)的临床意义.方法 采用竞争性酶联免疫吸附试验技术检测20例健康婴儿和30例RSV毛支患儿急性期和恢复期的尿LTE4水平;采用潮气分析测定急性期患儿呼吸频率(RR)、达峰时间比(tPTEF/tE)及达峰容积比(vPTEF/vE),分析其与尿LTE4水平的相关性.结果 RSV毛支患儿急性期的尿LTE4比恢复期、正常健康组明显增高(P＜0.01),恢复期与正常健康组相比差异无统计学意义(P＞0.05);急性期毛支患儿潮气肺功能中RR增快、tPTEF/tE和vPTEF/vE下降,与正常健康组比较,差异有统计学意义(P＜0.0001);急性期尿LTE4浓度与RR呈正相关(r=0.4376,P=0.0126),与tPTEF/tE和vPTEF/vE呈负相关(r=-0.6895,-0.6636,P均＜0.001).结论 RSV毛支患儿尿LTE4增高,与肺功能指标呈负相关;尿LTE4浓度可作为RSV毛支临床诊治的非创伤性炎性指标.     

Bronchiectasis and bronchiolitis obliterans post respiratory syncytial virus infection: think again

Respiratory syncytial virus (RSV) lower respiratory tract infections are common, yet long-term sequelae in previously healthy infants and children are rarely reported. We report a child who developed bronchiectasis and bronchiolitis obliterans following an RSV lower respiratory tract infection but in whom adenovirus was detected on stored serum. Co-infection with adenovirus is the likely cause for the bronchiectasis and bronchiolitis obliterans.     

Risk of respiratory syncytial virus in survivors with severe congenital diaphragmatic hernia

Background: During the follow-up period in surviving patients with severe congenital diaphragmatic hernia (CDH), respiratory complications, such as recurrence of CDH or chronic lung disease, have been reported to occur as a late complication. Although some risk factors for deterioration of respiratory condition have been reported in CDH, the risk of respiratory syncytial virus (RSV) in postoperative CDH patients has not as yet been reported upon.
Methods: In 21 survivors with severe CDH, which had been detected antenatally, and whose lung:thoracic ratio was <0.2, the risk of RSV infection in those patients was investigated.
Results: Five survivors with severe CDH had RSV infection and three patients needed hospitalization due to bronchiolitis during the follow-up period. In two patients the recurrence of CDH after the infection resulted in the need to perform a re-operation for CDH. All patients often suffered from chronic wheezing requiring medication after the first RSV infection.
Conclusion: RSV infection is a risk for deterioration of postoperative respiratory condition in severe CDH survivors. Considering the presence of pulmonary hypoplasia in severe CDH, the routine use of monoclonal antibody for RSV (palivizumab) might be effective for patients with severe CDH in the high season of RSV, similar to the patients with chronic lung disease, although further large multicenter studies are needed to clarify this hypothesis.     

Nasal lavage leukotrienes in infants with RSV bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis is a very common infection in infants and, after the acute phase, a number of patients develop a reactive airway disease that lasts for years. Although the pathogenesis of the lung damage after RSV bronchiolitis is still largely unknown, previous studies suggest that leukotrienes may play an active part in it. The aim of this study was to measure leukotriene levels in the nasal lavage fluid (NLF) collected in infants during RSV bronchiolitis and 1 month later. Cysteinyl leukotrienes (Cys-LTs) and leukotriene B(4) (LTB(4)) were measured in the NLF of 22 infants with their first episode of RSV bronchiolitis and 16 healthy infants. A second NLF sample was collected to measure leukotriene levels 1 month after the acute disease. NLF Cys-LT levels were significantly higher in infants with RSV bronchiolitis than in healthy controls [950 pg/ml (285.5-2155.9) vs. 110.5 pg/ml (66.5-451.3), p = 0.01], and they remained so a month after the acute infection (p = 0.02). A subanalysis showed no difference in Cys-LTs concentrations, either between bronchiolitis infants with and without a family history of atopy, or between those with and without passive exposure to cigarette smoke. No significant difference was found between the LTB(4) levels measured in the bronchiolitis cases and the control children. Cys-LTs are significantly increased in the NLF of infants with acute RSV bronchiolitis, and remain so at 1-month follow-up, suggesting a possible role of these eicosanoids in the pathogenesis of the disease.     

Eosinophil cationic protein in nasal secretion and in serum and myeloperoxidase in serum in respiratory syncytial virus bronchiolitis: relation to asthma and atopy

Eosinophil cationic protein (ECP) in nasal secretions was determined in 34 infants with respiratory syncytial virus (RSV) bronchiolitis during the acute infection stage and one and six months later. ECP in serum was determined in 19 of these children at the same time. Myeloperoxidase (MPO) was determined in the same 19 children at the acute infection stage and after one month. All children were followed prospectively for two years after the infection with regard to the development of bronchial obstructive symptoms. Asthma, defined as three or more episodes of bronchial obstruction verified by a physician, developed in 18% of children and less severe obstructive symptoms in 29%. A screening test for food IgE antibodies in serum was performed six months and a skin prick test two years after the acute infection. Nasal ECP/albumin ratios after six months were significantly higher than during the acute RSV infection. MPO, but not ECP, levels in serum were significantly elevated at the time of acute infection compared with levels after one month. Nasal ECP/albumin ratios at the acute infection were compared to a control group of 27 infants with non-RSV upper respiratory tract infections and did not differ. It was not possible to predict, either from ECP/albumin ratios in nasal secretion or from ECP and MPO in serum, which children would develop asthma, other bronchial obstructive symptoms or positive IgE tests.