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.     

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。     

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.     

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.     

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。     

Adult asthma after non-respiratory syncytial virus bronchiolitis in infancy: Subgroup analysis of the 20-year prospective follow-up study

BACKGROUND: Recent studies have stressed the influence of other viruses than respiratory syncytial virus (RSV) in the development of asthma in later childhood after bronchiolitis in infancy. However, the virus-specific prognosis until adulthood has remained obscure, due to lack of sufficiently long follow-up studies. The aim of the present study was to evaluate adult respiratory morbidity after bronchiolitis in infancy, focused on cases not caused by RSV. METHODS: A total of 54 children hospitalized for bronchiolitis at age <2 years were re-studied at median age 19 years; 22 with RSV bronchiolitis and 22 with non-RSV bronchiolitis outside RSV epidemic were included. RSV etiology was studied by antigen and antibody assays on admission. Adult asthma was defined by two ways, based on written questionnaire, clinical examination and home peak expiratory flow monitoring. Lung function was evaluated by flow-volume spirometry (FVS), bronchial reactivity by methacholine inhalation challenge (MIC), and atopy by skin prick tests (SPT). RESULTS: In the non-RSV group, asthma by two definitions was present in 41-50% (vs 18-27% in RSV group). In logistic regression, adjusted for gender, age on admission, current atopy and smoking, non-RSV etiology of bronchiolitis, compared with RSV etiology, increased asthma risk by both strict (odds ratio [OR], 8.34; 95% confidence interval [CI], 1.18-58.69) and less strict (OR, 7.93; 95% CI, 1.14-55.41) criteria. An abnormal result in FVS was present in 32-41% and in MIC in 48-52% of cases in non-RSV and RSV groups, respectively. CONCLUSIONS: Infants with non-RSV bronchiolitis requiring treatment in hospital are at an increased risk for subsequent asthma in adulthood.     

Correlation between respiratory syncytial virus (RSV) test data and hospitalization of children for RSV lower respiratory tract illness in Florida

BACKGROUND: Florida experiences year-round outbreaks of respiratory syncytial virus (RSV), but it is unknown if there is a correlation between RSV virology data and disease-related hospitalizations. We analyzed RSV surveillance and hospitalization data for the state of Florida to determine if there is an association between seasonal virology data and the incidence of International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM) coded hospitalizations for RSV lower respiratory tract illness. METHODS: We conducted a retrospective analysis for each of 5 regions of Florida for 4 years (2001-2004) of monthly RSV surveillance data presented on the Florida Department of Health website and hospitalization data provided by the Agency for Health Care Administration. RSV was considered present when > or =10% of laboratory tests were positive in a given month and the duration of seasons was determined by the number of consecutive months threshold values were exceeded. Hospitalizations in children 24 months of age and younger were defined as RSV related if any of the following RSV-specific ICD-9-CM codes appeared on the discharge summary: 079.6 RSV; 466.11 acute bronchiolitis caused by RSV; and 480.1 pneumonia caused by RSV. RESULTS: RSV circulated year-round statewide and seasons ranged from 7-8 months in the southwest, northwest, and north regions of Florida to 11-12 months in the central and southeast regions, respectively. More than 23,000 children younger than 24 months of age were hospitalized throughout the state for an RSV-related illness during the 4-year period, with almost 20,000 (86%) of the admissions in infants less than 12 months of age. There were 23 hospitalizations yearly per 1000 births and more than 90% of discharges occurred during the defined RSV seasons. CONCLUSIONS: To our knowledge, this is the first study to demonstrate a positive correlation between RSV test data and hospitalizations both statewide and for individual regions within Florida. It would be prudent for clinicians to obtain results of local RSV virology data to guide decisions on timing of prophylaxis to prevent RSV hospitalizations.     

Bronchial responsiveness to methacholine and adenosine 5'-monophosphate (AMP) in young children with post-infectious bronchiolitis obliterans

Aim: Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, but it is also frequently demonstrated by children and adults with chronic obstructive lung diseases. BHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in young children with post-infectious bronchiolitis obliterans (BO). Methods: Methacholine and adenosine 5'-monophosphate (AMP) bronchial challenges were performed on preschool children with post-infectious BO (n=18), those with asthma (n=23) and in controls (n=20), using a modified auscultation method. The endpoint was defined as the appearance of wheezing and/or oxygen desaturation. Results: A positive response to methacholine (an endpoint concentration ≤8 mg/ml) was observed in 88.9% (16/18) of the patients with post-infectious BO, but a positive response to AMP (an endpoint concentration ≤200 mg/ml) was observed in only 22.2% (4/18). All patients with asthma responded positively to methacholine, and most (21/23, 91.3%) of them also responded positively to AMP. The majority of the controls were insensitive to both challenges.

Conclusion: BHR to methacholine is a frequent, but by no means universal, finding in young children with post-infectious BO, but is usually not accompanied by BHR to AMP.     

Severe respiratory syncytial virus (RSV) infection in infants with neuromuscular diseases and immune deficiency syndromes

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection (LRTI) in infants and children. There is growing evidence of severe RSV disease in infants with neuromuscular diseases and immune deficiency syndromes. Factors predisposing to a more severe course of RSV disease in neuromuscular diseases include the impaired ability to clear secretions from the airways due to ineffective cough, respiratory muscle weakness, high prevalence of gastro-oesophageal reflux and swallowing dysfunction which leads to aspiration. Similarly, pulmonary disease is a common presenting feature and complication of T-cell immunodeficiency. Infants with severe congenital and acquired immune deficiency syndromes may demonstrate prolonged viral shedding in RSV LRTI and are reported to have increased morbidity and mortality associated with RSV infection. Although not indicated in most guideline statements, palivizumab prophylaxis for these uncommon underlying conditions is under consideration by clinicians. Prospective studies are needed to determine the burden of RSV disease in these children.     

Respiratory syncytial virus (RSV) immune globulin intravenous therapy for RSV lower respiratory tract infection in infants and young children at high risk for severe RSV infections: Respiratory Syncytial Virus Immune Globulin Study Group

OBJECTIVES: To evaluate the efficacy of high-titer intravenous respiratory syncytial virus immune globulin (RSVIG) in the treatment of children at high risk for severe RSV infection who were hospitalized with proven RSV. METHODS: Infants and young children younger than 2 years with bronchopulmonary dysplasia, chronic lung disease, congenital heart disease, or prematurity (<32 weeks' gestational age), hospitalized with a history of lower respiratory tract infection (LRI) of less than 4 days, were enrolled in this study. Patients were randomized in a blinded fashion to receive either 1500 mg/kg RSVIG or placebo in equal volumes. They were evaluated daily for safety and respiratory scores and for RSV nasal shedding. RESULTS: One hundred seven high-risk children were randomized--54 in the RSVIG group and 53 in the placebo group. Of these children, 51 in each group were considered evaluable. Children with pulmonary disease, congenital heart disease, or prematurity were equally distributed between the two treatment groups. However, two important differences were found in baseline variables between the two groups: there were more patients in the placebo group who had histories of previous LRI and there was a trend toward more severe disease at study entry in the RSVIG group. This was manifested by a higher entry respiratory score in the RSVIG group than in the placebo group (3.4 +/- 0.2 vs 3.1 +/- .01). A higher proportion of children in the RSVIG group (47%) than in the placebo group (28%) required intensive care at entry and mechanical ventilation at study entry (31% RSVIG-treated vs 18% placebo-treated patients). No significant difference was found between groups in the mean unadjusted duration of hospitalization (RSVIG group, 9.10 +/- 1.18 days; control group, 8.17 +/- 1.08 days). When the mean was adjusted for entry respiratory score, likewise, no difference was observed between each group (8.41 +/- 0.97 vs 8.89 +/- .99 days). The lack of efficacy observed in the study primary endpoint was observed in all diagnostic groups. No differences between the RSVIG and placebo groups were observed in the following secondary endpoints: duration of intensive care unit stay, duration of intensive care unit stay for RSV, mechanical ventilation, or supplemental oxygen. No significant differences in adverse events were reported in the RSVIG group (16 children) when compared with the control group (10 children). CONCLUSION: RSVIG treatment was safe but not efficacious in the treatment of children with bronchopulmonary dysplasia, congenital heart disease, or premature gestation who were hospitalized with RSV LRI.     

Hospitalization for respiratory syncytial virus among California infants: disparities related to race, insurance, and geography

OBJECTIVES: To evaluate population-based rates of Respiratory Syncytial Virus (RSV)-associated infant hospitalizations related to race/ethnicity, payer source, and geography in California. STUDY DESIGN: Retrospective analysis of RSV-coded infant hospitalizations were performed using the California patient discharge data for 1999 to 2003. All discharge records for infants younger than 1 year of age with an ICD-9-CM code for any RSV-related illness (466.11, 480.1, or 079.6) among any of the diagnosis fields were selected for analysis (n = 45,330). Rates were expressed as the number of RSV-associated hospitalizations per 1000 live births in the same calendar year. RESULTS: Infants enrolled in MediCal (California's version of the United States' national Medicaid program) had a relative risk of 2.03 (95% CI, 1.99 to 2.06) compared with non-MediCal payers (24.3 vs 12.0/1000 live births, respectively). The 1999 to 2003 rates per 1000 live births of RSV-associated hospitalizations for MediCal payers by race/ethnicity were: non-Hispanic white (34.9), African-American (27.9), Hispanic (21.8), Asian/Pacific Islander (12.5), and American Indian/Alaska Native (12.2). CONCLUSIONS: RSV was the leading cause of infant hospitalizations in California between 1999 and 2003. RSV hospitalization rates were highest among non-Hispanic white MediCal insured infants.     

Concentrations of LTB4, LTC4, LTD4 and LTE4 in bronchiolitis due to respiratory syncytial virus

Fifty-five infants with bronchiolitis due to respiratory syncytial virus were evaluated for the presence of leukotriene B₄, C₄, D₄ and E₄ in nasopharyngeal secretions. An attempt was made to correlate concentrations of leukotrienes to arterial oxygen tension. Forty participants received conventional therapy consisting primarily of aerosolized albuterol and occasional aminophylline therapy. The other 15 individuals received ribavirin therapy in addition to conventional therapy, and leukotriene concentrations were compared among individuals in these groups. RSV infection was documented by standard methods, and leukotrienes were measured by reverse-phase high pressure liquid chromatography. The leukotriene detected most commonly was LTC₄ (up to 83% of subjects); LTD₄ and LTB₄ were present in approximately 30% of individuals. The mean partial pressure of oxygen was found to be lower in those individuals with detectable LTB₄ than in those without detectable LTB₄ (p < 0.025), and an overall inverse correlation of LTB₄ concentrations with initial pO₂ values was observed (r = 0.318, p < 0.05). The presence and quantity of other leukotrienes did not correlate with the severity of illness. During the first week of illness, the concentration of leukotrienes declined sharply in ribavirin recipients. Individuals receiving conventional therapy during the same time interval exhibited stable or increasing leukotriene concentrations. These observations suggest that LTB₄ may be important in the pathogenesis of bronchiolitis, and that ribavirin therapy may inhibit leukotriene release in the respiratory tract.     

Prophylaxis of respiratory syncytial virus (RSV) in preterm infants with/without bronchopulmonary dysplasia: hyperimmune globulin (RSV-IGIV) and palivizumab (MEDI-493)

Respiratory syncytial virus (RSV) causes seasonal epidemics between December and March (April) and remains the main agent that causes severe lower respiratory tract infections in young infants. Children with bronchopulmonary dysplasia up to 24 months of age and preterm infants with a gestational age of 32 weeks and below, who are less than six months of age, are at highest risk for severe RSV infection. RSV-IGIV has been demonstrated to reduce significantly RSV associated hospitalizations, RSV associated hospital days and the incidence of severe RSV lower respiratory tract infections. Monthly infusions during RSV season were safe and well tolerated. Adverse events related to the hyperimmune globulin infusion were generally mild (< 3%) including fluid overload, decreased oxygen saturation and fever. Palivizumab, an intramuscularly administered humanized monoclonal antibody (RSV-glycoprotein-F antibody), will be preferable for the future because of ease of administration and comparable reduction in the risk of hospitalization. RSV-IGIV and palivizumab are both cost expansive and prophylaxis should be limited to high-risk infants.     

哮喘儿童呼吸道合胞病毒感染后血清抗F和抗G蛋白特异性IgG抗体的变化

目的探讨血清抗呼吸道合胞病毒（ＲＳＶ）抗Ｆ和抗Ｇ蛋白ＩｇＧ抗体水平与哮喘儿童ＲＳＶ感染及感染后病情轻重的关系。方法以ＲＳＶ（Ｌｏｎｇ株）及表达ＲＳＶＦ和Ｇ蛋白的重组痘苗病毒为抗原，采用酶联免疫吸附试验，检测了６６例６岁以下哮喘患儿ＲＳＶ流行期间双份血清中抗ＲＳＶＦ和Ｇ蛋白特异性ＩｇＧ抗体水平。结果（１）本组哮喘患儿ＲＳＶ感染率为３５％；（２）ＲＳＶ感染组哮喘患儿血清抗Ｆ和Ｇ蛋白ＩｇＧ抗体滴度明显低于非ＲＳＶ感染组；（３）ＲＳＶ感染后哮喘中～重度发作组血清抗Ｆ蛋白ＩｇＧ抗体滴度明显低于轻度发作组；（４）哮喘患儿ＲＳＶ感染后恢复期较急性期血清抗Ｆ和Ｇ蛋白抗体滴度均有明显升高，其升高程度在不同年龄组及两种蛋白间差异均无显著意义。结论血清抗Ｆ和抗Ｇ蛋白特异性ＩｇＧ抗体对哮喘患儿ＲＳＶ感染有一定保护作用；ＲＳＶ感染后抗Ｆ和抗Ｇ蛋白特异性ＩｇＧ抗体滴度的高低亦反映哮喘急性发作的轻重程度