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.     

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。     

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.     

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。     

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.     

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。     

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.     

Respiratory syncytial virus immunoprophylaxis in high-risk infants with heart disease

Aim: Passive immunisation with palivizumab is recommended in many countries for children with haemodynamically significant cardiac disease. We trialled respiratory syncytial virus (RSV) immunoprophylaxis in such infants during 2008–2009. Methods: We identified all RSV admissions between 2005–2009 and examined all patients with significant cardiac disease who received palivizumab in 2008–2009. Results: Infants with symptomatic cardiac disease had a more complicated course of RSV bronchiolitis with longer hospital stay, more frequent intensive care admission, longer intensive care stay and were more likely to receive respiratory support (all P < 0.05). One hundred seventeen infants with symptomatic cardiac disease received palivizumab. Of these, two (1.7%) required admission for RSV bronchiolitis. Overall, there was a reduction in admission of infants with symptomatic cardiac disease with RSV bronchiolitis in 2008–2009 (2% per year) compared with 2005–2007 (5–9% per year; P < 0.03). The number of patients with symptomatic cardiac disease who required intensive care for RSV bronchiolitis in the same period was unchanged, as a number presented to our service with RSV infection prior to commencing immunoprophylaxis or having had their cardiac diagnosis made in other centres. Conclusions: Compared with other infants, those with haemodynamically significant cardiac disease have a more complicated course of illness with RSV bronchiolitis. In these infants, palivizumab reduced the number of hospitalisations because of RSV. Cohorting patients for maximal palivizumab use reduced overall cost. To significantly impact on intensive care admissions overall, immunoprophylaxis should be considered at a regional level.     

毛细支气管炎患婴肺功能检测及评价

目的观察婴儿毛细支气管炎(毛支)的肺功能动态变化情况以及呼吸道合胞病毒(RSV)感染对其的影响并探讨其临床意义。方法对42例毛支婴儿(其中RSV感染22例)急性期、恢复期及16例正常组婴儿进行肺功能检查。结果毛支急性期呼吸频率(RR)增高、每千克体重潮气量(Vt/kg)、达峰时间比(tPTEF/tE)及达峰容积时间比(vPTEF/vE)均下降,与正常组比较差异有统计学意义;其中RR、tPTEF/tE及vPTEF/vE与恢复期比较差异有统计学意义。而恢复期与正常组比较各项指标差异均无统计学意义。在急性期RSV感染毛支患儿tPTEF/tE、vPTEF/vE下降更明显,与非RSV感染患儿比较差异有统计学意义;在恢复期RSV感染患儿与非RSV感染患儿比较,各项指标差异均无统计学意义。结论毛支急性期,肺功能呈现小气道阻力增高、阻塞性通气障碍改变,恢复期小气道功能好转,说明小气道功能异常能在较短时间内恢复。同时在急性期RSV感染比非RSV感染引起更强的下呼吸道阻塞的肺功能表现。婴儿肺功能检查是判断病情、评估疗效、推断预后的实用和可靠的方法。     

Peripheral blood eosinophil counts and eosinophil cationic protein content of respiratory secretions in bronchiolitis: relationship to severity of disease

Infants and young children with acute viral respiratory illness were studied to determine the association of peripheral blood eosinophil counts and concentrations of eosinophil cationic protein (ECP) in nasopharyngeal secretions with the development and severity of bronchiolitis. Subjects included those with upper respiratory illness (URI) alone, pneumonia or bronchiolitis. Controls consisted of healthy infants, and those hospitalized with non-respiratory illnesses. While peripheral blood eosinophil counts were suppressed in all infected infants greater than two months of age, eosinophil counts in patients with bronchiolitis were significantly greater than in those with URI alone. ECP concentrations were significantly greater among individuals with bronchiolitis than other infected infants. For bronchiolitis cases with detectable peripheral blood eosinophils, eosinophil counts correlated weakly and inversely with oxygen saturations. In contrast, ECP concentrations were strongly inversely correlated with initial oxygen saturation. ECP concentrations were also significantly correlated with peripheral blood eosinophil counts. Viral infections suppress peripheral blood eosinophil counts in infants greater than two months of age, although the effect is somewhat overcome in patients with bronchiolitis. The form and severity of bronchiolitis is much more strongly related to degranulation of eosinophils in the respiratory tract than to peripheral blood eosinophil counts.     

Immunomodulatory constituents of human milk change in response to infant bronchiolitis

Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p < or = 0.001). Further, the cells obtained from the mothers of infants hospitalized with bronchiolitis were found to produce a skewed cytokine profile ex vivo in response to stimulation by live RSV but not when cultured with a non-specific mitogen (concanavalin A). This study provides preliminary evidence for an immunological link between mothers and their breast-fed infants during severe respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.     

Neutrophil-mediated inflammation in respiratory syncytial viral bronchiolitis

BACKGROUND: The involvement of neutrophil-mediated inflammation may play an important role in the pathogenesis of acute respiratory syncytial virus bronchiolitis. However, no measurable marker is sensitive enough to assess neutrophil-mediated inflammation in the airways. Released neutrophil elastase (NE) in intraluminal airways has been reported to induce pulmonary inflammation. The aim of this study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by NE, reflects the degree of airway inflammation in children with respiratory syncytial viral (RSV) bronchiolitis and whether the severity of inflammation is evaluated. The pre-alpha-/inter-alpha-trypsin inhibitor is assumed to be precursors of the UTI. When NE degrades these inhibitors, UTI is liberated. METHODS: Serum UTI concentrations in infants admitted with RSV bronchiolitis, other viral infections, bacterial pneumonia and control subjects were measured by means of one-step sandwich-type enzyme immunoassay. RESULTS: Serum UTI concentrations in 25 patients on admission were significantly higher than the 15 infantile control values (mean +/- SEM, 22.126 +/- 2.317 and 6.701 +/- 0.719 U/mL, respectively; P < 0.0001). The elevated levels returned to baseline values with improvement in the respiratory symptoms. Higher levels of serum UTI with RSV infection were consistently associated with clinical symptoms and artificial ventilation. Serum NE concentrations of patients were elevated in some patients but not significantly different from controls in the patients who showed only upper respiratory symptoms with RSV infections. CONCLUSION: The findings strongly suggested that neutrophil-mediated events are involved in the pathogenesis of RSV bronchiolitis, and the monitoring of UTI concentrations might be useful for evaluating the neutrophil-mediated airway inflammation.     

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.     

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.     

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.     

Time course of severe respiratory syncytial virus infection in mechanically ventilated infants

The time course of intensive care for severe respiratory syncytial virus (RSV) lower respiratory tract illness may be predicted by the severity of gas exchange during the first 48 h of mechanical ventilation. To test this hypothesis, two studies were undertaken in RSV-positive mechanically ventilated patients who did not have chronic lung disease, congenital heart disease or immunodeficiency. First, a retrospective criteria-generating review of 45 infants was carried out. In these infants, more severe lower airway disease, as demonstrated by four-quadrant consolidation on chest X-ray, was associated with 'best' alveolar arterial oxygen gradients (AaDO₂, torr) and mean airway pressure (MAP, cm H₂O) values as follows: first 24 h, AaDO₂ > 400 and MAP > 10 (positive and negative predictive values 100% and 97%, respectively); second 24 h, AaDO₂