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。     

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。     

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.     

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.     

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.     

白介素-4基因C-33T多态性与呼吸道合胞病毒毛细支气管炎的相关性

目的 研究白介素-4(IL-4)基因C-33T与呼吸道合胞病毒(RSV)毛细支气管炎的易感性、病情严重程度的关系及对血清总IgE和鼻咽分泌物(NPS)IL-4水平的影响.方法 采用聚合酶链-限制性片段长度多态法(PCR-RFLP)检测130例RSV毛细支气管炎患儿和108例对照组儿童IL-4/C-33T位点多态性,分别用化学发光法和酶联免疫分析法,检测RSV毛细支气管炎患儿血清总IgE和NPs中IL-4水平.结果 两组IL-4启动子区C-33T位点均可见TT、CT和CC 3种基因型,其中病例组,TT、CT和CC基因型频率分别为66.9%、26.9%和6.2%,对照组分别为69.4%、26.9%和3.7%,两组差异无统计学意义(X2=0.758,P>0.05);病例组T、C等位基因频率分别为80.3%、19.7%,对照组分别为82.9%、17.1%,两组差异亦无统计学意义(X2=0.073,P>0.05;OR=0.847,P>0.05).病例组三种基因型间NPS中IL-4及血清总IgE水平差异均无统计学意义(H=0.103,F=0.529,P均>0.05);三种基因型频率在轻度组和中重度组间的差异亦无统计学意义(X2=0.825,P>0.05).结论 温州地区儿童存在IL-4/C-33T位点的多态性,但未发现其与RSV毛细支气管炎存在关联.     

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.     

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.     

Quantifying pulmonary hypertension in ventilated infants with bronchiolitis: a pilot study

OBJECTIVE: To determine whether previously well infants ventilated for bronchiolitis have sufficiently elevated pulmonary artery pressures (PAP) to warrant a trial of inhaled nitric oxide (iNO) therapy. METHODS: Consecutive infants mechanically ventilated for bronchiolitis were offered Doppler echocardiography between 24 and 72 h after intubation. Patients were divided into those with normal PAP, mild, moderate or severe pulmonary hypertension. Patients with at least moderate pulmonary hypertension (systolic PAP > 30 mmHg and > 50% of systemic systolic arterial pressure) were offered a 60 min trial of iNO therapy at a concentration of 20 ppm and repeat echocardiography. RESULTS: Six infants (four preterm, two term) were studied at a mean corrected age of 13 weeks (4, 24). Respiratory syncytial virus was confirmed on immunofluorescence of nasal secretions in five of six subjects (84%). Echocardiography was performed (mean, 5.5 days) (95%CI 3.8-7.3) after the onset of symptoms. All patients had structurally normal hearts. Four patients had mild pulmonary artery hypertension and two had normal pulmonary artery pressures. None of the patients qualified for iNO therapy. The mean (range) duration of intubation was 14 days (9-19) and the duration of hospitalization was 28 days (14-42). All patients recovered. CONCLUSION: Significant pulmonary hypertension should not be presumed in previously well preterm and term infants ventilated for bronchiolitis.     

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.     

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.     

Allergic sensitization is associated with rhinovirus‐, but not other virus‐, induced wheezing in children

Jartti T, Kuusipalo H, Vuorinen T, Söderlund‐Venermo M, Allander T, Waris M, Hartiala J, Ruuskanen O. Allergic sensitization is associated with rhinovirus‐, but not other virus‐, induced wheezing in children.
Pediatr Allergy Immunol 2010: 21: 1008–1014.
© 2010 John Wiley & Sons A/S Background: Data on the link between atopy and viral wheeze are limited. Aim: To evaluate the association between IgE sensitization and viral infection in wheezing children. Methods: This is an observational study in hospitalized wheezing children (n = 247; median age 1.6 ; interquartile range 1.1, 2.9). Eighteen respiratory viral infections were studied using all available methods. A specific immunoglobulin E (IgE) sensitization for common food and aeroallergens and other atopy‐related variables including total IgE, blood and nasal eosinophils, exhaled nitric oxide, eczema and atopic eczema, parental allergy and asthma, number of wheezing episodes, positive asthma predictive index or asthma and use of inhaled corticosteroid were correlated with specific viral etiology. Results: Atopy was closely associated with sole rhinovirus etiology (n = 58) but not with sole respiratory syncytial virus, sole enterovirus, sole human bocavirus, sole other virus, mixed viral, or virus negative etiology. The number of sensitizations was particularly associated with sole rhinovirus etiology (odds ratio 4.59; 95% confidence interval 1.78, 11.8; adjusted to age and sex), followed by aeroallergen sensitization (respectively; 4.18; 2.00, 8.72), total IgE level (2.06; 1.32, 3.21), food allergen sensitization (2.02; 1.08, 3.78), and nasal eosinophil count (1.52; 1.08, 2.13). Conclusions: According to our data, allergic sensitization is positively linked to rhinovirus‐, but not other virus‐, associated wheezing and calls attention for studies to test rhinovirus‐associated wheezing as a part of asthma risk indices.     

Apnoea and bronchiolitis due to respiratory syncytial virus

ABSTRACT. A study was made of 146 children admitted to hospital with bronchiolitis due to respiratory syncytial virus. Fifteen subjects (10%) had apnoea. Six of the 16 infants (38%) less than two months of age had apnoea, compared with nine of 130 children (6.9%) over two months old (P<0.001). Nine of the 28 infants (32%) who were preterm had apnoea compared with six of 118 children (5.1%) over 37 weeks gestation (P<0.001).
Both early chronological age and prematurity are risk factors for the development of apnoea in children with RSV bronchiolitis.