Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants.

BACKGROUND: Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants. AIMS: To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants. METHODS: Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23-31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C(rs) and R(rs)) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture. RESULTS: The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R(rs) and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R(rs) was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R(rs) and a symptomatic RSV LRTI, and for wheeze were a high R(rs). CONCLUSION: Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.     

Clinical predictors of respiratory syncytial virus infection in children

Aim: The aim of this study was to develop a clinical prediction model that identifies respiratory syncytial virus (RSV) infection in infants and young children.
Methods: Children ≤ 36 months of age with respiratory illness, who were suspected of having RSV infection, were enrolled in this prospective cohort study during the study period between January and February 2002. RSV testing was performed on all patients.
Results: Of the 197 patients enrolled in the study, 126 (64%) were positive for RSV and 71 (36%) patients were either negative for RSV or had a positive culture for viruses other than RSV. The mean age of patients was 5 months and 57% were male. Backwards stepwise logistic regression analysis identified cough (p = 0.000), wheezing (p = 0.002), and retractions (p = 0.008) as independent variables predictive of RSV infection. The prediction model had a sensitivity of 80% (95% CI, 71–87%), specificity of 68% (95% CI, 54–79%), positive predictive value 82% (95% CI, 74–89%), negative predictive value 66% (95% CI, 52–77), positive likelihood ratio 2.5 (95% CI, 1.8–3.7) and post-test probability of 82%.
Conclusion: The combination of cough, wheezing and retractions predicts RSV infection in infants and young children.     

Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants

Background

Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants.

Aims

To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants.

Methods

Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23–31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C_rs and R_rs) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture.

Results

The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R_rs and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R_rs was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R_rs and a symptomatic RSV LRTI, and for wheeze were a high R_rs.

Conclusion

Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.     

Asthma and protracted bronchitis: Who fares better during an acute respiratory infection?

Aim:   Acute respiratory infections (ARI) are common in children, and symptoms range from days to weeks. The aim of this study was to determine if children with asthma have more severe ARI episodes compared with children with protracted bronchitis and controls.
Methods:   Parents prospectively scored their child's next ARI using the Canadian acute respiratory illness and flu scale (CARIFS) and a validated cough diary (on days 1–7, 10 and 14 of illness). Children were age- and season-matched.
Results:   On days 10 and 14 of illness, children with protracted bronchitis had significantly higher median CARIFS when compared with children with asthma and healthy controls. On day 14, the median CARIFS were: asthma = 4.1 (interquartile range (IQR) 4.0), protracted bronchitis = 19.6 (IQR 25.8) and controls = 4.1 (IQR 5.25). The median cough score was significantly different between groups on days 1, 7, 10 and 14 ( P  < 0.001). A significantly higher proportion of children with protracted bronchitis (63%) were still coughing at day 14 in comparison with children with asthma (24%) and healthy controls (26%).
Conclusion:   Children with protracted bronchitis had the most severe ARI symptoms and higher percentage of respiratory morbidity at day 14 in comparison with children with asthma and healthy controls.     

Viral aetiology of lower respiratory tract infection in young Malaysian children

OBJECTIVE: To study the viral aetiology of lower respiratory tract infection (LRTI) in young Malaysian children. METHODOLOGY: A retrospective review was performed of LRTI patients aged less than 24 months who were admitted to the University Malaya Medical Centre between 1982 and 1997. Respiratory viruses in their nasopharyngeal secretion were identified by indirect immunofluorescence, viral culture, or both. RESULTS: A total of 5691 children were included in the study. The mean age was 8.6 +/- 6.6 months and the M:F ratio was 1.6:1. The most common diagnosis was pneumonia (52%) followed by bronchiolitis (45%) and croup (2%). Positive viral isolation rate was 22.0%. Respiratory syncytial virus (RSV) was the commonest virus isolated (84%), followed by parainfluenza virus (8%), influenza virus (6%) and adenovirus (2%). Patients with positive virus isolation were younger (7.8 +/- 6.2 vs 8.7 +/- 6.7 months, P = 0.0001) and were more likely to have bronchiolitis. CONCLUSION: Young Malaysian children admitted with LRTI had a 22% viral isolation rate and RSV was the commonest virus isolated.     

Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitis

Aim:  To evaluate the long-term effect of montelukast on symptoms of cough and wheeze following RSV bronchiolitis.
Methods:  Fifty eight patients (aged ≤ 24 months) hospitalized with a first episode of RSV bronchiolitis were enrolled in this double blind prospective randomized trial comparing montelukast (n = 31) vs placebo (n = 27).
Results:  During the 3-month treatment period, there were no statistical significant differences between the two groups for symptom-free days and nights (48.5 [interquartile range 33.0.0–66.0] for montelukast vs 57.0 [29.0–71.0] for placebo p = 0.415) nor disease-free days and nights (44.5 days [26.0–54.0] vs 53.0 [22.3–71.0]; p = 0.266). During the 1 year follow-up, there were 41 exacerbations in the montelukast group vs 54 exacerbations in the placebo group (p = 0.57). Time to first exacerbation was not different. Number of unscheduled visits and need to start inhaled steroids were comparable in the two groups.
Conclusion:  Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment.     

呼吸道合胞病毒毛细支气管炎患儿T细胞亚群检测的临床价值

目的：呼吸道合胞病毒(RSV)感染所致的毛细支气管炎日后发展为哮喘的机率很高,由于哮喘患儿机体存在明显的免疫功能紊乱,而RSV毛细支气管炎在这方面的研究不多,为此该研究探讨毛细支气管炎患儿T细胞亚群的变化及其临床意义。方法：采用流式细胞术对21例RSV毛细支气管炎患儿及20例正常儿童T细胞亚群进行检测。结果：RSV毛细支气管炎组与对照组外周血T细胞亚群CD4,CD8差异无显著性(P>0.05),CD4/CD8比值RSV毛细支气管炎组高于对照组,差异有显著性(P<0.05)。结论：RSV毛细支气管炎患儿存在与哮喘相似的T细胞亚群变化相关的免疫功能紊乱,提示两者在发病机制上存在一定的联系。     

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.     

Risk Factors for Hospitalization due to Lower Respiratory Tract Infection in Preterm Infants on Palivizumab Prophylaxis

Objective

To determine the risk factors associated with lower respiratory tract infections (LRTI) related hospitalizations in preterm infants receiving palivizumab throughout the high season for respiratory syncytial virus (RSV) infection.

Methods

Premature infants who were commenced on palivizumab prophylaxis during the RSV season were included in the study following parental consent. Information on demographic, social, prenatal and postnatal clinical characteristics was recorded and risk factors associated with hospitalization were evaluated for each patient.

Findings

While 234 participants (Group 1, 92.8%) did not require hospitalization during the study period, 18 patients (Group 2, 7.2%) were hospitalized at least once for LRTI during the RSV season. The rate of moderate-severe bronchopulmonary dysplasia (BPD) was significantly higher in group 2 compared to group 1 (38.9% vs 16.2%; P=0.016). Of the 18 infants who were hospitalized, 6 (33.3%) tested positive for RSV while the remaining 12 patients (66.7%) were negative for RSV. Odds ratio (OR) analysis of several risk factors revealed the presence of BPD (OR: 3.28; 95%CI: 1.19-9), being from a family with low socioeconomic status (OR: 3.64; 95%CI 1.08-12.3) to be associated with a higher likelihood of LRTI-related hospitalization.

Conclusion

Our data demonstrated that RSV is an important LRTI agent and cause of hospitalization especially in preterm infants with additional risks such as BPD, gestational age of <28 weeks and low socioeconomic status. We suggest that improving care conditions and decreased BPD with prematurity would help in prevention of LRTI hospitalization.     

Respiratory syncytial virus prophylaxis: a survey of pediatric solid organ transplant centers

Abstract:  RSV can cause respiratory illness after SOT, yet preventive recommendations are lacking for this population. To ascertain current preventive practices against RSV disease in pediatric SOT candidates and recipients, a survey was developed. The survey was mailed to 108 SOT programs in the United States (liver, 42; heart, 28; lung, 11; intestinal, 25; and heart-lung, 2). Results were tabulated and analyzed using standard methods. Sixty-two percent (67/108) of surveys were completed. Forty-nine percent (33/67) of programs reported using RSV prophylaxis; palivizumab was used at 97% (32/33) of centers with 26 giving palivizumab to candidates and 27 to recipients. Prophylaxis was provided to infants aged 0–12 months by 27/29 (93%) of responding centers; 23/29 of centers extended its use to infants aged 0–24 months. Three centers gave prophylaxis to children between ages two and four yr and two centers for those over four yr. RSV prophylactic strategies, and in particular the use of palivizumab, are employed by almost 50% of responding pediatric SOT centers. Strategies varied at centers based on age and organ type. Data on RSV hospitalization and outcome are needed to refine approaches to RSV immunoprophylaxis in these high-risk patients.     

Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.     

Epidemiology and clinical presentation of respiratory syncytial virus infection in a rural area of southern Mozambique

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in infants throughout most of the world, but little is known about RSV infection in Africa where LRTI are among the leading causes of infant and childhood death. METHODS: The study took place in a rural district hospital in southern Mozambique between October, 1998, and May, 2000. From all children (n = 5635) <1 year of age presenting to an outpatient department with cough or nasal secretion and all children (n = 1307) <5 years of age admitted to hospital with a LRTI, a nasopharyngeal aspirate was collected and tested for RSV by enzyme-linked immunosorbent assay (Abbott). RESULTS: RSV infection was found in 8.6% of study infants in the outpatient department and 10.6% of admitted children with LRTI. Cases presented in predictable yearly outbreaks during the warm and rainy season. Lower respiratory tract involvement was frequent (59.7%). Cough, chest indrawing and increased respiratory rate were all independently related to RSV infection. Wheezing was infrequent. Bacterial coinfection (4.6%) and the case-fatality rate (3.4%) were low. CONCLUSIONS: There is a substantial burden of disease attributable to RSV infection in this rural African setting, with the highest incidence and severity occurring in young infants.     

苏州地区急性呼吸道感染住院患儿病毒病原学分析

目的：了解苏州地区急性呼吸道感染（ARI）住院患儿的病毒病原学情况。方法：采集1 668例7岁以下ARI住院患儿鼻咽分泌物,直接免疫荧光法检测呼吸道合胞病毒（RSV）,流感病毒A,B型（IV A,B）,副流感病毒1,2,3型（PIV 1,2,3）及腺病毒A(ADA)等7种常见呼吸道病毒,用RT-PCR法检测人类偏肺病毒（hMPV）N基因。结果：① 1 668例患儿中,病毒检测阳性597例（35.8%）。单项病毒感染561例（33.6%）,其中7种常见呼吸道病毒检出率为23.1%,以RSV为主（17.6%）,好发于冬春季,主要见于1岁以下婴幼儿;② hMPV阳性率为10.6%,3~5月份为检出高峰期。③ 36例混合感染中,22例为RSV合并hMPV感染,主要见于1岁以下婴幼儿。结论：RSV是该地区ARI的主要病毒病原,RSV感染好发于冬春季,多见于1岁以下婴幼儿,hMPV是3~5月份ARI患儿的主要病毒病原,混合感染多见于1岁以下婴幼儿。［中国当代儿科杂志,2009,11（7）：529-531］     

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。     

Respiratory syncytial virus infection in lower respiratory tract and asthma attack in hospitalized children in North Hokkaido,Japan

Respiratory syncytial virus (RSV) infection is severe and life-threatening in some infants. To investigate the epidemiology of RSV infection in hospitalized children in North Hokkaido, Japan, we tried to detect RSV antigen in nasopharyngeal aspirates (NPA) from those children with lower respiratory tract infection (LRTI) and asthma attack. From April 1991 to March 1992, 317 patients were hospitalized in our pediatric ward for the treatment of LRTI and asthma attack. The presence of RSV antigen in NPA taken from 283 patients (89.3%) were examined by enzyme immunoassay. RSV antigen was detected in 88 patients (31.1%). RSV LRTI were noted throughout the year, and the epidemic peak was observed in November and December. There was no significant correlation between the RSV antigen positive rate and mean temperature. RSV played an important role in LTRI in children in North Hokkaido, Japan. RSV LRTI in North Hokkaido was not rare in summer, indicating that RSV was transmitted commonly among children throughout the year.     

Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study

INTRODUCTION: Although acute respiratory illnesses (ARI) are major causes of morbidity and mortality in early childhood worldwide, little progress has been made in their control and prophylaxis. Most studies have focused on hospitalized children or children from closed populations. It is essential that the viral etiology of these clinical diseases be accurately defined in the development of antiviral drugs. OBJECTIVE: To investigate the role of all common respiratory viruses as upper and lower respiratory tract pathogens in the first year of life. STUDY DESIGN: This community-based birth cohort study prospectively collected detailed information on all ARI contracted by 263 infants from birth until 1 year of age. Nasopharyngeal aspirates were collected for each ARI episode, and all common respiratory viruses were detected by polymerase chain reaction. Episodes were classified as upper respiratory illnesses or lower respiratory illnesses (LRI), with or without wheeze. RESULTS: The majority reported 2-5 episodes of ARI in the first year (range, 0-11 episodes; mean, 4.1). One-third were LRI, and 29% of these were associated with wheeze. Viruses were detected in 69% of ARI; most common were rhinoviruses (48.5%) and respiratory syncytial virus (RSV) (10.9%). Compared with RSV, >10 times the number of upper respiratory illnesses and >3 times the number of both LRI and wheezing LRI were attributed to rhinoviruses. CONCLUSION: Rhinoviruses are the major upper and lower respiratory pathogens in the first year of life. Although RSV is strongly associated with severe LRI requiring hospitalization, the role of rhinoviruses as the major lower respiratory pathogens in infants has not previously been recognized.     

Lower respiratory tract illness and RSV prophylaxis in very premature infants.

AIMS: To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis. METHODS: Multicentre prospective longitudinal cohort study of 2813 infants, born between April 2000 and December 2000 at less than 33 weeks of gestational age, and followed until the end of the epidemic season. RESULTS: Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were readmitted at least once for any reason during the epidemic season; 15.1% and 7.2% were readmitted at least once for any LRTI and RSV related LRTI, respectively. Children born at less than 31 weeks' gestation, having an intrauterine growth restriction, or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI. Of the 376 children submitted to prophylaxis, 28.2% were readmitted at least once for any LRTI and 6.1% for RSV related LRTI. CONCLUSION: One out of four children who had received no prophylaxis, was born very prematurely, and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was readmitted at least once for any reason. Roughly 50% and 20% of these readmissions were related to a LRTI and an RSV infection, respectively. Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population.     

Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis

Aim: To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants <12 months of age experiencing their first episode of bronchiolitis. Methods: Epidemiological, clinical and virological data were prospectively collected. Severity was assessed by the need for ventilatory support. Results: Of the 310 infants enrolled, 16 (5.1%) presented with severe bronchiolitis requiring ventilatory support (11 since admission). Compared with infants with less severe bronchiolitis, infants with severe disease presented with lower birth weight, gestational age, postnatal weight and postnatal age, and were more likely to be born by cesarian section. C‐reactive protein positive results (>0.8 mg/dL) and pulmonary consolidation on chest X‐ray were more common among infants with severe disease. Severity was independently associated with younger age on admission <30 days, respiratory syncytial virus (RSV) infection and lymphocyte counts <3200/μL. No significant differences were found between epidemiologic variables. Conclusions: Severe bronchiolitis is uncommon in previously healthy term infants <12 months of age and when present develops soon after disease onset. Severity is predicted by young age and RSV carriage, whereas epidemiologic variables seem less likely to intervene.     

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.