Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar

Records of 70 infants admitted to Hamad General Hospital with RSV bronchiolitis and a similar number of controls were retrospectively reviewed. Two years after admission, 44% of the infants with RSV bronchiolitis developed recurrent wheezing compared with only 12.9% of controls (P=0.001). A family history of atopy appeared not to be a significant predisposing factor for the occurrence of recurrent wheezing in post RSV bronchiolitis patients. These results are similar to those from similar studies in industrialized countries.     

Peripheral blood T and B lymphocyte subpopulations in infants with acute respiratory syncytial virus brochiolitis

Most data concerning immunopathogenetic mechanisms involved in respiratory syncytial virus (RSV) infection are derived from animal studies. In infants with RSV bronchiolitis the target organ i. e. the airway is hard to explore. We looked for specific alterations in peripheral blood lymphocyte subpopulations in infants hospitalized for RSV bronchiolitis. Flow cytometric analysis with a large panel of monoclonals was performed on peripheral blood lymphocytes in thirty-two infants (mean age: 4. 9 months) admitted for RSV bronchiolitis. Data collected on admission were compared with age-matched control values and also with results obtained at the end of the first week of hospitalization. Differences between age-groups (older or younger than 4 months) and between clinical subgroups (clinical severity score more or less than 6) were looked for. In the group of infants as a whole, regardless of age and clinical score the number of CD4+ cells on admission was significantly elevated compared to normal values for age (p < 0.001) including a high fraction of the naive suppressor-inducer subpopulation (CD4+/CD45RA+) and a low fraction of the reciprocal memory helper-inducer subpopulation (CD4+/CD29+). Within the CD8+ cell population the number of T cells with cytotoxic activity (CD8+/S6F1+) was significantly elevated (p < 0.001) as were other types of cytotoxic cells. A significant decrease (p < 0.0001) in the proportion of the precursor/suppressor-effector subpopulation (CD8+/S6F1-) was seen. Absolute numbers and percentages of CD 19+ B cells were significantly elevated (p < 0.001) with a significant increase in the CD5+ subfraction (p < 0.001) as well as in the CD 10+ subfraction (p < 0.001). In the older age group immunophenotypic cytotoxicity was more pronounced with increased clinical score. During recovery the CD45RA+: CD29+ ratio tended to normalize within the CD4+ T cells. Within the B lymphocyte subsets significant increase in the CD19+/ CD5+ fraction (p < 0.5) was seen. We conclude that there are significant changes in the number of peripheral blood lymphocyte subsets in infants with RSV bronchiolitis as compared to age-related controls. We hope that present data could be useful in further exploration of RSV immunology in humans. A possible link between RSV bronchiolitis and the subsequent development of atopy is mentioned.     

The role of respiratory syncytial virus in acute bronchiolitis in small children in northern Japan

Respiratory syncytial virus (RSV) plays an important role in acute bronchiolitis, which is life threatening in some infants. We investigated the epidemiology of RSV acute bronchiolitis in children less than 3 years old in northern Japan. From April 1991 to March 1993, 162 infants with acute bronchiolitis were hospitalized in our pediatric wards. The diagnosis of RSV acute bronchiolitis was based on the typical clinical manifestations and the presence of RSV antigen in their nasopharyngeal specimens or the rise of the RSV antibody titer. 124 out of 162 patients (76.5%) were diagnosed as having RSV acute bronchiolitis. 43.5% of patients with RSV acute bronchiolitis were 6 months old or less. The epidemic of RSV acute bronchiolitis commenced in October, peaked in December and ended in summer. RSV is quite prevalent in infants with acute bronchiolitis in northern Japan.     

Prevention of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infection in young children, with significant numbers of premature infants and those with other risk factors requiring hospitalization in Canada each year. Palivizumab, an RSV-specific monoclonal antibody, can reduce the hospitalization rate and severity of illness for a small group of high-risk or premature infants during their first RSV season. The present statement reviews the published literature and provides recommendations regarding its use in premature and other at-risk infants, for Canadian physicians.     

Treatment and prevention of respiratory syncytial virus infection

This review discusses the current knowledge on treatment and prevention of respiratory synctial virus (RSV) infections in children. Unfortunately, an effective therapy is not yet available. The efficacy of corticosteroids and bronchodilators has not yet been adequately documented and the use of ribavirin is only indicated in a highly selected group of high risk patients with T-cell immunodeficiency. The results of studies on the efficacy of vitamin A, interferon and antibiotics showed disappointing results. Vaccination research has produced candidate vaccines such as the recombinant vaccine BBG2Na, a subunit vaccine PFP-2 and cold-passaged-temperature sensitive vaccines. However, phase III efficacy trials in infants, young children and the elderly are still lacking. Passive protection against infections by RSV can be conferred by the use of RSV hyperimmune globulin or by the administration of palivizumab, a monoclonal antibody. However, large costs are involved. In addition, major differences have been reported in the prevalence of RSV lower respiratory tract infections in different countries, regions and even within well-known high-risk populations. Conclusion We suggest the development of local and regional guidelines based on hospitalisation rates in high-risk infants and cost-benefit analysis studies. Received: 29 October 1999 and in revised form 28 December 1999 / Accepted: 30 December 1999     

吸入糖皮质激素预防呼吸道合胞病毒毛细支气管炎后反复喘息的临床观察

目的 观察吸入糖皮质激素能否预防呼吸道合胞病毒(RSV)毛细支气管炎(简称毛支)后反复喘息的发生.方法 选择2003年7月-2004年12月住院的RSV毛支患儿200例,入院后查外周血嗜酸性粒细胞、血清总IgE,血TH1/TH2水平及肺功能.毛支治愈后随机分为治疗组(100例)和对照组(100例),治疗组吸入布地奈德气雾剂3个月,对照组未给予治疗.3个月后随访,复查肺功能.停止治疗后继续观察2年,了解吸入激素3个月对患儿反复喘息发生的影响.结果 ①毛支治愈后的3个月内,治疗组无症状天数为(78.92±8.03)d,对照组为(74.83±9.54)d,两组比较差异有统计学意义(P＜0.01).②3个月后治疗组肺功能各项指标均比对照组明显好转(P＜0.05).③治疗组按吸入激素疗效分为毛支后喘息组和未再喘息组,这两组患儿入院时外周血嗜酸性粒细胞、血清总IgE、血Th1/Th2差异均有统计学意义(P＜0.05),而肺功能差异无统计学意义(P＞0.05).④停止治疗后2年两组患儿喘息再发比例差异无统计学意义(P＞0.05).结论 RSV毛支患儿治愈后吸入布地奈德气雾剂3个月,可改善肺功能.外周血嗜酸性粒细胞增多、血清总IgE升高、Th2功能亢进者,治疗期间可以减少毛支后喘息再发.吸入激素3个月不能减少停药后2年内喘息的发生.     

丙种球蛋白治疗RSV毛细支气管炎的临床及免疫学研究

为评估静脉注射丙种球蛋白(IVIG)治疗呼吸道合胞病毒毛细支气管炎(RSV毛支)的临床疗效及免疫学机理,比较26例IVIG治疗组和30例常规治疗组患儿症状体征消失时间及住院天数,同时检测治疗前后血清白介素6(IL-6)、白介素8(IL-8)及肿瘤坏死因子-α(TNF-α)水平。结果:与常规治疗组相比,IVIG治疗组喘憋和肺部体征消失时间明显缩短(4.0天±1.1天比5.2天±1.4天,5.4天±1.5天比6.5天±1.8天,P分别<0.001和<0.05),而住院天数则无显著差异(9.0天±2.2天比10.3天±3.1天,P>0.05)。治疗前两组患儿血清IL-6、IL-8及TNF-α水平均高于正常对照组;IVIG治疗后3种细胞因子水平明显降低.但与常规治疗组相比无显著差异。结论:细胞因子参与了RSV毛支的发病过程。IVIG治疗有较确切的临床疗效,但单剂(0.25g/kg)对血清细胞因子的抑制作用不明显。     

Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review

One of the major questions regarding long-term side effects of bronchiolitis by respiratory syncytial virus (RSV) is whether or not it induces asthma in later life. In this quantitative review, the data of 10 controlled studies are analysed. METHODS: Follow-up studies of RSV bronchiolitis published between January 1978 and December 1998 were identified through a MEDLINE search. Studies were selected if (i) postnatal age at the time of the initial illness was below 12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the diagnosis RSV was virologically confirmed in all cases, and (iv) a control group was used. RESULTS: Six studies met all selection criteria. Up to 5 y of follow-up after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared to only 11% in the control group (p <0.001). Between 5 and 10 y of follow-up 22% of the bronchiolitis group reported wheezing against 10% of the control group (p = 0.19). The incidence of recurrent wheezing as defined by three or more wheezing episodes also decreased with increasing years of follow-up: at 5 or more years of follow-up the difference between the RSV group and the control group was no longer significant. Furthermore, the presence of either a personal and/or a family history of either atopy and/or asthma did not differ between the two groups. CONCLUSIONS: Wheezing is common after RSV bronchiolitis in infancy. It may persist for > or = 5 y of follow-up. However, no significant difference between the RSV bronchiolitis and the control group was observed regarding recurrent wheezing by 5 y of follow-up. No significant difference between the RSV bronchiolitis and the control group were found regarding a personal history of atopy, a family history of atopy and/or asthma. Therefore it seems unlikely that RSV bronchiolitis is a cause of atopic asthma in later life.     

Vitamin A status of children with a history of respiratory syncytial virus infection in infancy

Abstract In order to extend our earlier observation that children who experience frequent respiratory episodes may benefit from Vitamin A supplementation, 206 children aged 2-7 years who had been hospitalized for bronchiolitis during infancy were randomized into a controlled trial of Vitamin A supplementation. Of these, 149 met the criteria of protocol compliance after 12 months of follow-up. Mean plasma retinol at baseline was 39.2 μg/100 ml (s.e.m. = 1.0) and did not increase after 12 months (mean = 36.0 μg/100 ml, s.e.m. =0.7) despite the older age of the cohort. The range observed (11.7–73.9 μg/100 ml) included some children at risk of marginal Vitamin A deficiency. Mean plasma retinol levels were 20% lower than those of children experiencing frequent respiratory episodes recorded earlier. Oral supplementation did not change plasma retinol levels, nor did it affect respiratory morbidity.     

Epidemiology and clinical characteristics of respiratory syncytial virus infections in Jordan

This study was carried out to determine the prevalence, seasonal distribution of RSV, the signs and symptoms associated with it in Jordan. A total of 200 nasopharyngeal aspirates were obtained from hospitalized children (below 2 years old). RSV was detected in 12.5% of patients using direct immunofluorescence technique. Most infections were associated with bronchilolitis, and higher rates of hypoxemia, retractions, tachypnea, hyperinflation and interstitial infiltrates in 1 to 3 months old children. RSV showed a clear temporal periodicity. The epidemic began in December and disappeared in March with a peak of incidence during February 2003 and January 2004. The seasonal distribution showed a significant correlation with temperature, rainfall and relative humidity. This study provides further information on RSV epidemiology which could help in planning of prevention and control programs in Jordan, distinguishing RSV infections on the basis of the clinical picture and considering RSV between December and March each year.     

呼吸道合胞病毒感染防治进展

呼吸道合胞病毒(RSV)是引起婴幼儿毛细支气管炎、肺炎的重要病原.RSV感染引起的毛细支气管炎诊断并不困难,但关于感染后喘息、发生哮喘的机制并不明确.目前尚没有防治RSV感染的疫苗与特效药.随着对RSV感染预防控制及治疗方法的深入研究,为临床面对RSV挑战提供了新思路与前景.     

Eleven consecutive years of respiratory syncytial virus outbreaks in Croatia

Background:  Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infections (LRTI) in infants. The aim of the present study was to analyze the epidemiologic characteristics of RSV outbreaks in Croatian children.
Methods:  Over a period of 11 consecutive years (1994–2005), 3435 inpatients with acute respiratory infections (ARI) aged from birth to 10 years and were residing in Zagreb County were tested for infection with RSV and other respiratory viruses at the Virology Department, Croatian National Institute of Public Health. RSV was identified in nasopharyngeal secretions by isolation on cell culture and/or detection with monoclonal antibodies using a direct fluorescence assay.
Results:  RSV was the most common causative agent of ARI (42.2%; 658/1559) for the infants 0–6 months of age. It was also the etiologic agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those with pneumonia in this age group.
Conclusion:  The overall prevalence of RSV infection in Croatian children with acute respiratory illness, and its occurrence in various age groups, has remained stable over the past decade. RSV was found to be the most common cause of bronchiolitis occurring throughout childhood (52.7%; 482/913).     

小儿呼吸道合胞病毒感染流行特点分析

目的探讨小儿呼吸道合胞感染病毒感染的流行特点及影响RSV流行的气候因素。方法对2001年1月至2006年12月因下呼吸道感染在浙江大学医学院附属儿童医院住院的39597例患儿取鼻咽分泌物标本进行呼吸道合胞病毒(RSV)抗原检测。结果39597例患儿中RSV检测阳性患儿共8657例(21.86%),<1岁者6804例(30.99%),1～3岁者1576例(14.84%),～13岁者277例(3.95%),各年龄组间检出率有统计学意义(P<0.01)。男性5783例(22.76%)高于女性2873例(20.24%),有统计学意义(P<0.01)。RSV检出率与气温之间存在直线负相关,气温每升高1℃,下呼吸道感染患儿中RSV的检出率下降1.8%。冬季是RSV流行高峰,其次是春季和秋季,夏季RSV感染率最低,全年都有RSV的散发流行。结论RSV是冬春季节引起小儿下呼吸道感染的主要病毒,年龄越小RSV感染率越高,男性较女性易感RSV。气温越低,RSV的检出率越高,低气温是杭州地区RSV流行的重要因素之一。     

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.     

Phenotype of acute respiratory syncytial virus induced lower respiratory tract illness in infancy and subsequent morbidity

The objective of this study was to investigate the association hypothesis that outcome following respiratory syncytial virus (RSV) induced bronchiolitis (RSVB) and RSV induced wheeze (RSVW) are different. At 3 years respiratory symptoms were more common in those with RSV infection than the control group but there was no increase in allergic sensitisation (11% vs 10%). Those with RSVW were more likely to have evidence of allergic sensitisation when compared with RSVB subjects (22% vs 7%), and have increased symptoms and increased use of inhaled steroids. Conclusion: The data argue that RSV infection during infancy does not induce allergic asthma and that host factors rather than the virus determine long-term outcomes.     

Association of TNF-α with severe respiratory syncytial virus infection and bronchial asthma

Tumor necrosis factor (TNF-)α is a proinflammatory cytokine that is important in the innate host defence and thus in the defence of infectious agents. However, in excess it provokes the development of chronic inflammatory diseases. The aim of this study was to test association of TNF with severe RSV bronchiolitis as example of an infectious disease and asthma as representative for a chronic inflammatory condition. The following study populations were genotyped for 4 polymorphisms within TNF-β (rs909253) and TNF-α (rs1799964, rs1799724, rs1800629): 322 asthmatic children, 151 children with severe respiratory syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF-α levels were measured by a FlowCytomix Assay. Asthma showed association with two TNF-α polymorphisms as well as with TNF haplotpyes (p = 0.0050). In contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but not with any single polymorphism. In addition, TNF-α serum levels correlated with rs1799724 (p = 0.034). A genetically mediated up-regulation of TNF-α expression might provoke a pronounced inflammation of the airways and thus a more severe course of RSV infection as well as the onset of asthma. It remains to be elucidated whether severe RSV bronchiolitis starts TNF-α upregulation and is one first step in the direction to asthma later in life, or whether both dieases are independent from each other and supported by TNF-α upregulation.     

Cost of hospitalization for respiratory syncytial virus chest infection and implications for passive immunization strategies in a developing nation

Respiratory syncytial virus (RSV) chest infection is a common cause of hospitalization in the very young child. The aim of this study was to determine the direct cost of resource utilization in the treatment of children hospitalized with RSV chest infection and the potential cost-savings with passive immunization for high-risk infants. An audit of the hospital resource consumption and its costs was performed for 216 children aged < 24 mo admitted with RSV chest infection between 1995 and 1997. The cost-saving potential of passive immunization using monoclonal RSV antibodies during the RSV season was determined by assuming an 0.55 efficacy in hospitalization reduction when administered to "high-risk" infants according to the guidelines outlined by the American Academy of Pediatrics (AAP). The hospital treatment cost of 1064 bed-days amounted to USD 64 277.70. Each child occupied a median of 4.0 bed-days at a median cost of USD 169.99 (IQ1 128.08, IQ3 248.47). Children, who were ex-premature or with an underlying illness were more likely to have a longer hospital stay, higher treatment costs and need for intensive care. Ten (42%) of 24 ex-premature infants fulfilled the recommended criteria for passive immunization. Its use resulted in an incremental cost of USD 31.39 to a potential cost saving of USD 0.91 per infant for each hospital day saved. CONCLUSION: Ex-prematurity and the presence of an underlying illness results in escalation of the direct treatment cost of RSV chest infection. Current guidelines for use of passive RSV immunization do not appear to be cost-effective if adopted for Malaysian infants.     

Aerosolized ribavirin treatment of respiratory syncytial virus infection in infants hospitalized during an epidemic

Thirty-three infants with predisposing conditions and/or severely symptomatic with respiratory syncytial virus (RSV) infection were treated with aerosolized ribavirin during a 12-week period at Oklahoma Children's Memorial Hospital. These patients were compared with 97 untreated patients with RSV infection hospitalized during the same epidemic. Despite preconditions which selected for a more seriously ill treatment group, patients who received ribavirin showed prompter resolution of the illness than did untreated controls. Greatest clinical improvement in treated patients occurred between the first and second days of ribavirin therapy; mean ribavirin treatment duration was 4.5 days. Ten of 22 ribavirin-treated patients continued to excrete RSV after conclusion of antiviral therapy. No adverse hematologic, renal or metabolic effects occurred with ribavirin therapy. Our experience with ribavirin therapy during a major epidemic confirms and extends the results of previous controlled evaluations demonstrating this treatment safe and effective in high risk and seriously ill infants with RSV bronchiolitis and bronchopneumonia.