A hypothesis: antenatal sensitisation to respiratory syncytial virus in viral bronchiolitis.

Aim: To investigate the possibility of antenatal sensitisation to respiratory syncytial virus (RSV). METHODS: A total of 36 cord blood specimens were obtained from newborn infants; serum IgA was measured to exclude maternal blood contamination. Cord peripheral blood mononuclear cells were separated and cultured in the presence of either uninfected negative control cells or cells containing ultraviolet (UV) inactivated RSV. Proliferation was assessed by tritiated thymidine incorporation. Supernatant cytokine concentrations were measured using ELISA. RESULTS: Significantly higher proliferative response rates to UV inactivated RSV were shown in those infants exposed in utero to the RSV epidemic after 22 weeks gestation. UV inactivated RSV stimulation induced significantly higher interferon gamma production from specimens with a positive proliferative response (sensitised) than from those with a negative response (not sensitised). CONCLUSIONS: Antenatal sensitisation to RSV occurs in one third of infants exposed to an RSV epidemic at the appropriate time of gestation. This sensitisation is associated with increased interferon gamma production, suggesting a type 1 memory response. We hypothesise that priming of fetal T cells to RSV results in a reduced severity of subsequent RSV disease in these individuals and that this will explain much of the clinical diversity of RSV disease.     

A hypothesis: antenatal sensitisation to respiratory syncytial virus in viral bronchiolitis

Aim: To investigate the possibility of antenatal sensitisation to respiratory syncytial virus (RSV). Methods: A total of 36 cord blood specimens were obtained from newborn infants; serum IgA was measured to exclude maternal blood contamination. Cord peripheral blood mononuclear cells were separated and cultured in the presence of either uninfected negative control cells or cells containing ultraviolet (UV) inactivated RSV. Proliferation was assessed by tritiated thymidine incorporation. Supernatant cytokine concentrations were measured using ELISA. Results: Significantly higher proliferative response rates to UV inactivated RSV were shown in those infants exposed in utero to the RSV epidemic after 22 weeks gestation. UV inactivated RSV stimulation induced significantly higher interferon γ production from specimens with a positive proliferative response (sensitised) than from those with a negative response (not sensitised). Conclusions: Antenatal sensitisation to RSV occurs in one third of infants exposed to an RSV epidemic at the appropriate time of gestation. This sensitisation is associated with increased interferon γ production, suggesting a type 1 memory response. We hypothesise that priming of fetal T cells to RSV results in a reduced severity of subsequent RSV disease in these individuals and that this will explain much of the clinical diversity of RSV disease.     

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.     

Airway eicosanoids in acute severe respiratory syncytial virus bronchiolitis

We prospectively studied the levels of eicosanoids in intubated patients with severe bronchiolitis and compared them to electively intubated non-infected infants. LeukotrieneE(4) (LTE(4)), leukotrieneB(4) (LTB(4)), and prostaglandinE(2) (PGE(2)) levels were significantly increased (P <.01) from endotracheal (ET) aspirates of infants with bronchiolitis compared with controls, as were urinary LTE(4) levels (P <.001). We conclude that eicosanoids are increased in the tracheal aspirates and urine of children with bronchiolitis.     

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.     

Production of interferon in respiratory syncytial virus bronchiolitis.

Production of interferon alfa in vitro was significantly reduced during acute respiratory syncytial virus bronchiolitis but subsequently returned to normal. Nasopharyngeal and endotracheal interferon alfa were detected intermittently and in low concentrations. The degree of impairment of in vitro production and poor in vivo production of interferon alfa suggest the need for a therapeutic trial of nebulised or systemic interferon in acute bronchiolitis.     

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。     

Lung function after acute bronchiolitis.

We performed 211 lung function measurements on 93 children in the first year after they had been admitted with acute bronchiolitis. During the convalescent phase of the illness, 77% of the infants were hyperinflated with a thoracic gas volume greater than 40 ml/kg and 3 months later 43% were hyperinflated. Twelve months after the initial illness, 17% still had lung function abnormalities and most of these children have had lower respiratory tract symptoms. For the group as a whole about 60% have had at least one episode of wheezing. Specific conductances were significantly lower in children from atopic families, indicating worse lung function, but the significance of this finding is unclear.     

Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis.

Aim: To examine over time, the cellular response within the lungs of infants ventilated with respiratory syncytial virus (RSV) bronchiolitis and to compare this response in infants born at term with those born preterm. METHODS: Non-bronchoscopic bronchoalveolar lavage (BAL) samples were taken from 47 infants (24 born at term and 23 born preterm) who were ventilated for RSV positive bronchiolitis and 10 control infants. BAL cellularity and differential cell counts were calculated using standard techniques. RESULTS: Total cellularity in BAL over the first four days of ventilation in infants with RSV bronchiolitis was greater in term infants (median 2.2 (IQR 4.27) x 10(6) cells/ml) compared with preterm infants (0.58 (1.28) x 10(6) cells/ml). The magnitude of the cellular response in preterm infants with bronchiolitis was similar to that in the control group measured on day 1 (0.62 (0.77) x 10(6) cells/ml). BAL cellularity decreased progressively from the time of intubation in term infants, but remained relatively constant in preterm infants up to seven days after intubation. CONCLUSIONS: There are differences in the magnitude and type of pulmonary cellular response in term and preterm infants ventilated with RSV bronchiolitis. The cellular response in term infants with bronchiolitis differs from that in a control group of infants. These differences may reflect variations in cellular recruitment in the lung and/or variations in airway calibre.     

Long-term consequences of respiratory syncytial virus (RSV) bronchiolitis

Despite differences in study design, follow-up studies consistently show that approximately half of the infants with respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) go on to have recurrent wheezing episodes during childhood. Respiratory symptoms are associated with abnormal lung function, including bronchial hyper-responsiveness. Wheezing symptoms following RSV LRTI gradually decrease, and it appears that during school age airway morbidity is no longer related to RSV LRTI during infancy. Mechanisms underlying the association between RSV LRTI and long-term airway morbidity are poorly understood. On the one hand, abnormal airway function that is congenitally present or acquired before RSV LRTI occurs could be the cause of both RSV LRTI and subsequent recurrent wheezing. On the other hand, it is possible that RSV LRTI causes changes in the lower airways or the immune system that result in long-term airway morbidity. Animal models suggest that RSV infection can promote the development of allergic sensitization, but most studies in humans do not indicate a role for atopy in the development of recurrent wheezing following RSV LRTI.     

Severe bronchiolitis and respiratory syncytial virus among young children in Hawaii

BACKGROUND: Lower respiratory tract infections are a leading cause of hospitalization and mortality among children worldwide. Our objective was to describe the incidence and epidemiology of severe bronchiolitis, respiratory syncytial virus (RSV), and pneumonia among children in Hawaii. METHODS: Retrospective analysis of the patient-linked hospital discharge data associated with bronchiolitis, RSV, and pneumonia among Hawaii residents younger than 5 years of age during 1997 through 2004 using the Hawaii State Inpatient Database. RESULTS: During 1997 through 2004, the average annual incidence rates for bronchiolitis, RSV, and pneumonia were 3.8, 2.7, and 6.8 per 1000 children younger than 5 years, respectively. The incidence of each condition was higher for infants younger than 1 year (15.1, 9.8, and 15.9 per 1000 infants, respectively) than the incidence for children 1-4 years of age, and higher for boys compared with girls. The incidence of each condition was highest among Native Hawaiian and other Pacific Islander children compared with children of other race groups living in Hawaii. Most hospitalizations occurred during the months of October through February. Estimated median hospital charges were $4806 (bronchiolitis), $5465 (RSV) and $5240 (pneumonia), with overall average annual charges of $11.5 million. CONCLUSION: The incidence and hospitalization rates for bronchiolitis, RSV, and pneumonia among children younger than 5 years of age in Hawaii were low; the corresponding hospitalization rates were lower than those for the general U.S. population. However, the hospitalization rates for each condition among Hawaiian and other Pacific Islander children were much higher than those for other race groups or for the U.S. population.     

呼吸道合胞病毒毛细支气管炎患儿炎症递质的变化

目的研究气道炎症递质鼻咽分泌物嗜酸粒细胞阳离子蛋白(NPS-ECP)和尿白三烯E4(LTE4)在呼吸道合胞病毒(RSV)毛细支气管炎患儿体内的变化。方法 120例RSV检测阳性毛细支气管炎住院患儿,分为特应性组和非特应性组;同时选取30名健康体检儿童作为对照组。以酶联免疫吸附试验(ELISA)检测尿LTE4浓度,UniCAP100变态反应检测仪检测患儿鼻咽分泌物中ECP浓度,比较各组间的差异。结果特应性组尿LTE4水平为(172.21±67.29)pg/ml,高于非特应性组的(78.21±28.78)pg/ml和正常对照组的(44.22±16.14)pg/ml,三组间差异有统计学意义(F=97.33,P0.01);两两比较差异也均有统计学意义(P均0.01)。RSV毛细支气管炎患儿尿LTE4与血浆IgE、鼻咽分泌物ECP水平均呈显著正相关(r=0.57、0.49,P均0.01)。结论尿LTE4和鼻咽分泌物ECP可为RSV毛细支气管患儿的治疗和预后提供参考。     

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.     

Echocardiographic assessment of cardiac function during respiratory syncytial virus infection

Respiratory syncytial virus infection has been associated with increased morbidity and mortality in infants with underlying cardiac and pulmonary disease. To understand better the cardiopulmonary interaction in patients with acute respiratory syncytial virus bronchiolitis, we performed M-mode echocardiograms and pulsed Doppler assessment of pulmonary arterial flow in 19 patients with structurally normal hearts during acute illness. Studies were repeated in 11 of these patients following complete recovery. Based on severity of respiratory compromise, patients were grouped into those with severe illness (ten patients) or mild illness (nine patients). Left ventricular dimensions and shortening fraction were used to assess left ventricular function. Right ventricular systolic time intervals and specific Doppler flow velocity measurements were used to assess right ventricular function and elevation of pulmonary artery pressure. Comparisons were made between patients with severe and mild illness and between acute and follow-up studies. No statistically significant differences in left ventricular function, right ventricular systolic time intervals, or Doppler flow measurements were observed. We conclude that in patients with structurally normal hearts, respiratory syncytial virus bronchiolitis is not associated with significant depression of cardiac performance or elevation in pulmonary resistance.     

Epidemiological and genetic characteristics associated with the severity of acute viral bronchiolitis by respiratory syncytial virus

Objectiveto assess the epidemiological and genetic factors associated with severity of acute viral bronchiolitis (AVB) by respiratory syncytial virus (RSV).Data sourcethe key words “bronchiolitis”, “risk factor”, “genetics” and “respiratory syncytial virus”, and all combinations among them were used to perform a search in the PubMed, SciELO, and Lilacs databases, of articles published after the year 2000 that included individuals younger than 2 years of age.Data synthesisa total of 1,259 articles were found, and their respective summaries were read. Of these, 81 were selected, which assessed risk factors for the severity of AVB, and were read in full; the 60 most relevant studies were included. The epidemiologic factors associated with AVB severity by RSV were prematurity, passive smoking, young age, lack of breastfeeding, chronic lung disease, congenital heart disease, male gender, ethnicity, viral coinfection, low weight at admission, maternal smoking during pregnancy, atopic dermatitis, mechanical ventilation in the neonatal period, maternal history of atopy and/or asthma during pregnancy, season of birth, low socioeconomic status, Down syndrome, environmental pollution, living at an altitude > 2,500 meters above sea level, and cesarean section birth. Conversely, some children with severe AVB did not present any of these risk factors. In this regard, recent studies have verified the influence of genetic factors on the severity of AVB by RSV. Polymorphisms of the TLRs, RANTES, JUN, IFNA5, NOS2, CX3CR1, ILs, and VDR genes have been shown to be associated with more severe evolution of AVB by RSV.Conclusionthe severity of AVB by RSV is a phenomenon that depends on the varying degrees of interaction among epidemiological, environmental, and genetic variables.     

Clinical and physiological manifestations of bronchiolitis and pneumonia. Outcome of respiratory syncytial virus.

The physiological abnormalities and clinical correlates of 32 infants consecutively hospitalized with lower respiratory tract disease from respiratory syncytial virus (RSV) were studied in an attempt to characterized the infant most at risk for the acute and long-term complications of RSV infection. Arterial oxygen saturation (Sao2) determinations were obtained daily by means of an ear oximeter. On admission all infants were hypoxemic with a mean Sao2 of 87% (range, 74% to 95%). The mean of the lowest Soa2 recorded during their hospitalization was 85.5% (range, 53% to 96%). The hypoxemia improved little during hospitalization but showed improvement three to seven weeks later. The severity of the hypoxemia correlated significantly with the duration of viral shedding, occurrence of apnea, respiratory rate, age, and percentage of immature neutrophils. Clinical severity did not correlate with the degree of hypoxemia.     

Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis

Aim: To examine over time, the cellular response within the lungs of infants ventilated with respiratory syncytial virus (RSV) bronchiolitis and to compare this response in infants born at term with those born preterm. Methods: Non-bronchoscopic bronchoalveolar lavage (BAL) samples were taken from 47 infants (24 born at term and 23 born preterm) who were ventilated for RSV positive bronchiolitis and 10 control infants. BAL cellularity and differential cell counts were calculated using standard techniques. Results: Total cellularity in BAL over the first four days of ventilation in infants with RSV bronchiolitis was greater in term infants (median 2.2 (IQR 4.27) x 10⁶ cells/ml) compared with preterm infants (0.58 (1.28) x 10⁶ cells/ml). The magnitude of the cellular response in preterm infants with bronchiolitis was similar to that in the control group measured on day 1 (0.62 (0.77) x 10⁶ cells/ml). BAL cellularity decreased progressively from the time of intubation in term infants, but remained relatively constant in preterm infants up to seven days after intubation. Conclusions: There are differences in the magnitude and type of pulmonary cellular response in term and preterm infants ventilated with RSV bronchiolitis. The cellular response in term infants with bronchiolitis differs from that in a control group of infants. These differences may reflect variations in cellular recruitment in the lung and/or variations in airway calibre.