Respiratory Syncytial Virus Lower Respiratory Tract Infection Research Articles

Toward primary prevention of asthma. Reviewing the evidence for early-life respiratory viral infections as modifiable risk factors to prevent childhood asthma.

A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts.

Risk factors associated with death in patients with severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. This retrospective study describes the clinical characteristics of severe RSV infection and determines the risk factors for death. Patients were identified through a review of all patients discharged with a diagnosis of RSV lower respiratory tract infection and admitted to hospital in the pediatric intensive care unit (PICU) of a tertiary medical center between July 1, 2001 and June 30, 2010. The medical and demographic variables were recorded and analyzed. The 186 RSV-positive patients admitted to the PICU had a median age of 5.3 months (interquartile range 2.3-12.4 months) and included 129 boys and 57 girls. Among them, 134 had at least one underlying disease: prematurity in 92, neurological disease in 57, bronchopulmonary dysplasia in 40, congenital heart disease in 26, hematological malignancies in 11, and Down's syndrome in nine patients. The 10 patients who died from RSV-related causes had a median age of 20.8 months (interquartile range 6.6-89.2 months) and all had a comorbidity. In multivariate analysis, the risk factors for death in severe RSV infection were Down's syndrome (odds ratio 7.20, 95% confidence interval 1.13-45.76; p=0.036) and nosocomial RSV infection (odds ratio 4.46, 95% confidence interval 1.09-18.27; p=0.038). Down's syndrome and nosocomial RSV infection are significantly associated with death in severe RSV infections. Clinicians should be alert to these conditions.

Safety and Effectiveness of Palivizumab in Children at High Risk of Serious Disease Due to Respiratory Syncytial Virus Infection: A Systematic Review.

IntroductionLower respiratory tract infection (LRTI) is the leading cause of infant mortality globally in post-neonatal infants (i.e., 28–364 days of age). Respiratory syncytial virus (RSV) is the most commonly identified pathogen for infant LRTI and is the second most important cause of death in post-neonatal infants. Despite 50 years of RSV vaccine research, there is still no approved vaccine. Therefore, passive immunity with the monoclonal antibody palivizumab is the sole regulatory-approved option for the prevention of serious LRTI caused by RSV in pediatric patients at high risk of RSV disease.MethodsWe conducted a comprehensive systematic literature review of randomized controlled trials (RCTs), open-label non-comparative clinical trials, and prospective observational studies/registries, and summarized the evidence related to the safety, efficacy, and effectiveness of palivizumab.ResultsThe efficacy of palivizumab, as measured by the relative reduction in RSV-related hospitalization rate compared with placebo ranged from 39% to 78% (P < 0.05) in the 2 pivotal RCTs. A meta-analysis of the RSV-related hospitalization rate from 5 randomized placebo-controlled trials yielded an overall odds ratio of 0.41 (95% CI, 0.31–0.55) in favor of palivizumab prophylaxis over placebo (P < 0.00001). Low rates of RSV-related hospitalizations were observed in palivizumab recipients consistently over time in more than 42,000 pediatric subjects across 7 RCTs, 4 open-label non-comparative trials, and 8 observational studies/registries conducted in 34 countries. In addition, among palivizumab-prophylaxed subjects with breakthrough RSV LRTI, rates of intensive care unit admission and mechanical ventilation from RSV hospitalization also were low and consistent across studies. With respect to safety, no differences were observed between palivizumab and placebo in the blinded RCTs.ConclusionRates of RSV hospitalizations and RSV hospitalization-related endpoints in pediatric subjects who received prophylaxis with palivizumab were low and constant over time and across RCTs, open-label non-comparative trials, and observational studies/registries.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-014-0046-6) contains supplementary material, which is available to authorized users.

Viral lower respiratory tract infections and preterm infants' healthcare utilisation.

The aim of this study was to determine whether respiratory syncytial virus (RSV) and other viral lower respiratory tract infections (LRTI) in prematurely born infants were associated with similar effects on healthcare utilisation and related cost of care in the second compared to the first year after birth. Thirteen infants who had RSV LRTIs (RSV), 21 who had other viral LRTIs (other viral) and 25 had no viral LRTIs (no LRTI) were prospectively followed. Nasopharyngeal aspirates were collected whenever an infant had an LRTI regardless of whether it was in the hospital or in the community. Healthcare utilisation and the health-related cost of care were determined. Only the RSV group compared to the no LRTI group had higher overall respiratory costs in both year 1 (mean, £3,917 versus £24; p < 0.041) and year 2 (mean, £1,164 versus £61; p = 0.012). Only the RSV group required respiratory admissions; the RSV admission rate in year 2 was 3.4 % (number needed to treat 59). RSV LRTIs are associated with increased healthcare utilisation and cost of care in the first and second year; nevertheless, if prophylaxis is to be cost-effective in the second year, a high risk group needs to be identified.

Motavizumab Treatment of Infants Hospitalized With Respiratory Syncytial Virus Infection Does Not Decrease Viral Load or Severity of Illness

This study was conducted to determine whether treatment with motavizumab, an anti-respiratory syncytial virus (RSV) monoclonal antibody, would decrease viral load and improve clinical outcomes in previously healthy term infants hospitalized with RSV lower respiratory tract infection. Infants hospitalized with lower respiratory tract infection and a positive RSV test performed locally were randomized to receive 1 intravenous dose of motavizumab (30 or 100 mg/kg) or placebo. Nasal wash samples were tested by real-time reverse transcriptase polymerase chain reaction at a central laboratory to determine viral load. Clinical data were collected during RSV hospitalization and at 12-month follow up. Of 118 infants, 112 were confirmed RSV positive by real-time reverse transcriptase polymerase chain reaction. In each study group, median (range) RSV load (log10 copies/mL) decreased at a similar rate from baseline to study day 7 [motavizumab 30 mg/kg: 8.35 (2.5-9.5) to 5.03 (2.5-6.8); motavizumab 100 mg/kg: 8.22 (5.5-9.7) to 4.25 (2.5-8.0); placebo: 8.02 (6.7-9.8) to 5.17 (2.5-7.3)]. Median (range) duration of hospitalization was 3.05 (0.8-16.0), 2.99 (1.0-25.0) and 2.88 (0.8-11.7) days for the motavizumab 30 mg/kg, motavizumab 100 mg/kg and placebo groups, respectively. Six (8%) motavizumab and 0 placebo recipients were admitted to the intensive care unit and 4 required mechanical ventilation. The incidence of wheezing episodes during the 12-month follow up was comparable for all 3 groups. Motavizumab had no appreciable effect on RSV viral load measured in the upper respiratory tract of children hospitalized for RSV lower respiratory tract infection. No differences were observed for duration of hospitalization, severity of illness measures or wheezing episodes during 12-month follow up in children treated with motavizumab or placebo.

Malnutrition

Longitudinal information examining the effect of poor infant growth on respiratory syncytial virus (RSV) severity is limited. Children hospitalized with RSV lower respiratory infection represent those at the severe end of the disease spectrum. We followed up a cohort of 12,191 infants enrolled in a previous pneumococcal vaccine trial in Bohol, Philippines. Exposure measures were weight for age z-score at the first vaccination visit (median age 1.8 months) as well as the growth (the difference in weight for age z-score) between the first and third vaccination visits. The outcome was hospitalization with RSV lower respiratory infection. Children with a weight for age z-score ≤ -2 at their first vaccination visit had the highest rate of hospitalization with RSV lower respiratory infection, but this association was only evident in children whose mothers had >10 years of education (hazard ratio: 3.38; 95% confidence interval: 1.63-6.98). Children who had lower than median growth between their first and third vaccinations had a higher rate of RSV-associated hospitalization than those with growth above the median (hazard ratio: 1.34; 95% confidence interval: 1.02-1.76). Poor infant growth increases the risk for severe RSV infection leading to hospitalization.

Respiratory outcome of prematurely born infants following human rhinovirus A and C infections

Human rhinoviruses (HRVs) are a common cause of lower respiratory tract infections (LRTIs) and are associated with chronic respiratory morbidity. Our aim was to determine whether HRV species A or C were associated with chronic respiratory morbidity and increased health care utilisation in prematurely born infants. A number of 153 infants with a median gestational age of 34 (range 23-35) weeks were prospectively followed. Nasopharyngeal aspirates were collected whenever the infants had LRTIs regardless of hospitalisation status. Parents completed a respiratory diary card and health questionnaire about their infant when they were 11 and 12 months corrected age, respectively. The health-related cost of care during infancy was calculated from the medical records using the National Health Service (NHS) reference costing scheme and the British National Formulary for children. There were 32 infants that developed 40 HRV LRTIs; samples were available from 23 of the 32 infants for subtyping. Nine infants had HRV-A LRTIs, 13 HRV-C LRTIs, and one infant had a HRV-B LRTI. Exclusion of infants who also had RSV LRTIs revealed that the infants who had a HRV-C LRTI were more likely to wheeze (p < 0.0005) and use respiratory medications (p < 0.0005) and had more days of wheeze (p = 0.01) and used an inhaler (p = 0.02) than the no LRTI group. In addition, the respiratory cost of care was greater for the HRV-C LRTI than the no LRTI group (p < 0.0005). Our results suggest HRV-C is associated with chronic respiratory morbidity during infancy in prematurely born infants.

Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants

The aim of this study was to assess whether prematurely born infants have a genetic predisposition to respiratory syncytial virus (RSV) infection-related respiratory morbidity. One hundred and forty-six infants born at less than 36 weeks of gestation were prospectively followed. Nasopharygeal aspirates were obtained on every occasion the infants had a lower respiratory tract infection (LRTI) regardless of need for admission. DNA was tested for 11 single-nucleotide polymorphisms (SNPs). Chronic respiratory morbidity was assessed using respiratory health-related questionnaires, parent-completed diary cards at a corrected age of 1 year and review of hospital notes. Lung function was measured at a post menstrual age (PMA) of 36 weeks and corrected age of 1 year. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36-week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (interleukin 10 (IL10), nitric oxide synthase 2A (NOS2A), surfactant protein C (SFTPC), matrix metalloproteinase 16 (MMP16) and vitamin D receptor (VDR)) and reduced lung function at 1 year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs. Our results suggest that prematurely born infants may have a genetic predisposition to RSV LRTIs and subsequent respiratory morbidity which is independent of premorbid lung function.

Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity. This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary.

RSV Immunoprophylaxis: Does the Benefit Justify the Cost?

* Abbreviations: RSV — : respiratory syncytial virus Respiratory syncytial virus (RSV) is among the last viruses to cause major, predictable worldwide outbreaks of disease and for which no vaccine or broadly effective antiviral drug is available. Annually in the United States, RSV accounts for ∼125 000 hospitalizations, 2.1 million outpatient visits to a pediatrician’s office or an emergency department, and 250 deaths among children in the first years of life.1 In addition to the burden of acute disease caused by RSV, severe lower respiratory tract infection early in life is associated with recurrent wheezing during the first decade of life.2,3 The unresolved issue of the association between severe viral respiratory illness early in life and subsequent wheezing remains one of the more perplexing issues in pediatrics. Numerous studies have documented that infants hospitalized with viral lower airway disease (especially after rhinovirus or RSV infection) are more likely to experience recurrent wheezing in contrast to infants who do not experience severe bronchiolitis.3–5 Association of a susceptibility locus on chromosome 17q21, rhinovirus infection in early childhood, and wheezing indicates the existence of a complex interaction between a genetic predisposition and environmental factors.4 The unresolved question is whether a severe viral respiratory infection early in life alters normal lung development in a way that predisposes to subsequent wheezing or whether certain infants have a preexisting aberration of the immune response or of airway function that predisposes to both severe bronchiolitis and recurrent wheezing.6 If viral lower respiratory tract infections have a causal association with recurrent wheezing, prevention of infection should reduce the incidence of wheezing. If severe bronchiolitis simply identifies an infant who is predisposed to recurrent wheezing from a number of causes, prevention of RSV infection will have little or no impact on subsequent wheezing. An industry-sponsored report by Yoshihara et … Address correspondence to H. Cody Meissner, MD, Tufts Medical Center, 800 Washington St, Boston, MA 02111. E-mail: cmeissner{at}tuftsmedicalcenter.org

Respiratory syncytial virus and asthma

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Furthermore, epidemiological evidence has been accumulating that RSV lower respiratory tract infection in infants may be linked to subsequent development of recurrent wheezing and asthma in childhood. This article reviews the epidemiological evidence linking RSV and asthma and some new hypotheses of the cellular and molecular mechanisms of postviral airway inflammation and hyperreactivity that have been proposed to explain the epidemiological link. New epidemiological studies have suggested that viral pathogens other than RSV, especially human rhinoviruses (HRV), may play an important role in the inception of atopic asthma. Also, recent experimental evidence is challenging the widely accepted axiom that RSV is cleared from immunocompetent hosts within weeks from the onset of the infection. In particular, bone marrow stromal cells may be a frequent target of human RSV infection, develop structural and functional changes when infected, participate actively in the pathogenesis of the acute disease, and harbor the virus chronically, allowing persistence of the infection. RSV - and possibly other common respiratory pathogens - play an important role not only in the exacerbation, but also in the inception of asthma. The latter effect may involve the persistence of latent virus in extrapulmonary tissues, similar to what has been recently found for some bacterial species. The most immediate consequence of these discoveries is that future prophylactic and therapeutic strategies for common infections caused by viral or bacterial pathogens may have to address the coverage of remote sites of latent persistence or replication, in order to avoid chronic sequelae-recurrent wheezing and asthma.

Infectious Burden of Respiratory Syncytial Virus in Relation to Time of Birth Modifies the Risk of Lower Respiratory Tract Infection in Infancy

The risk of respiratory syncytial virus (RSV) infection according to calendar month of birth has previously been demonstrated. We hypothesize that the real-time infectious burden (IB) of RSV, in relation to time and county of birth, modifies the risk of lower respiratory tract infection (LRTI) in infants, an association that has not been investigated previously, and may be used as an alternative measure of RSV risk when drafting RSV immunoprophylaxis guidelines. Thirty thousand eighty-seven pregnancies were included from July 1, 2003, to July 31, 2006. IB was defined by month and county as the number of RSV detections per inhabitant. IB for 5 periods ante- and postnatally was calculated for each child. Outcome variables were maternally reported hospitalization for LRTI before age 6 months and LRTI before age 12 months. Logistic regression was used to estimate associations between IB and LRTI. The odds of hospitalization for LRTI rise with increased IB the first 3 months after birth. Low IB: odds ratio (OR) 1.17 (95% confidence interval [CI]: 0.98-1.39); medium IB: OR 1.42 (95% CI: 1.21-1.68); high IB: OR 2.51 (95% CI: 2.15-2.94). High IB 3-0 months before birth confers a lower odds of hospitalization for LRTI the first 6 months of life, OR 0.51 (95% CI: 0.43-0.61). Similar results were seen for maternally reported LRTI the first 12 months of life. We find an association between real-time RSV infectious burden and LRTI in infancy: high burden before birth is protective and high burden after birth increases the risk.

Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections

Respiratory syncytial virus (RSV) infections are well recognized as a significant cause of morbidity and mortality in allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients. We evaluated the spectrum of clinical manifestations, management (including ribavirin-based antiviral therapy) and outcomes of RSV infections and determined the risk factors associated with RSV lower respiratory tract infection (LRTI) and all-cause mortality. In this retrospective study, we analysed clinical data from all laboratory-confirmed RSV infections in allo-HSCT recipients (n = 280) who presented at our institution from January 1996 to May 2009. Of the 280 patients, 80 (29%) developed LRTI within 20 days (median 1 day, range 0-19 days) and 44 (16%) died within 90 days (median 26 days, range 1-82 days) from RSV diagnosis. Multivariable logistic regression analyses identified several significant risk factors associated with RSV LRTI and all-cause mortality, including age, male sex, neutropenia, lymphocytopenia and lack of ribavirin-based antiviral therapy at the upper respiratory tract infection (URTI) stage. Aerosolized ribavirin-based therapy at the URTI stage was the single most significant factor in reducing the risk of RSV LRTI (83%), all-cause mortality (57%) and RSV-associated mortality (87%) in these patients (P < 0.05), irrespective of the year of RSV diagnosis. Our results demonstrate that RSV infections are a significant cause of morbidity and mortality in high-risk allo-HSCT recipients and ribavirin-based antiviral therapy at the URTI stage had a positive impact on both outcomes in this vulnerable population with multiple risk factors.

Rhinovirus infection and healthcare utilisation in prematurely born infants

Our aim was to determine whether rhinovirus (RV) lower respiratory tract infections (LRTIs) in prematurely born infants increase health-related cost of care during infancy. 153 infants born at <36 weeks of gestation were prospectively followed to 1 year. Cost of care was calculated from the National Health Service reference costing scheme and healthcare utilisation determined by examining hospital/general practitioner records. 20 infants developed RV LRTIs (RV group), 17 respiratory syncytial virus (RSV) LRTIs (RSV group), 12 both RV and RSV LRTIs (RV/RSV group) and 74 had no LRTI (no LRTI group). Compared with the no LRTI group, the RV/RSV LRTI group had the greatest increase in adjusted mean cost (difference GBP 5769), followed by the RV LRTI group (difference GBP 278) and, finally, the RSV LRTI group (difference GBP 172) (p=0.045). The RV group had more outpatient (p<0.05) and respiratory-related general practitioner (p<0.05) attendances, more wheezed at follow-up (p<0.001) than the no LRTI group and more had respiratory-related outpatient attendances than the RSV LRTI group (p<0.05). We conclude that RV LRTIs were associated with increased health-related cost of care during infancy; our results suggest that the RV group compared with the RSV group suffered greater chronic respiratory morbidity.

Should respiratory care in preterm infants include prophylaxis against respiratory syncytial virus infection? The case in favour

Respiratory syncytial virus (RSV) is the most significant cause of acute respiratory tract infections (RTI) in infants and young children throughout the world. Preterm infants are at increased risk for severe RSV lower respiratory tract infection due to small lung volumes, a reduced lung surface area, small airways and an increased air space wall thickness. Additionally, the airways of preterm infants have been ventilated mechanically and suctioned and potentially damaged by many microtraumas with disruption of endothelial surfaces enabling pathogens to invade more easily. The immune system of preterm infants is immature resulting in low antibody titers (incomplete transplacental transfer of maternal antibodies) and a reduced cellular immunity with reduced viral clearance. Rehospitalization rates of preterm compared to term infants due to RSV infection are increased as are total morbidity and mortality associated with RSV disease. Palivizumab effectively reduces RSV related rehospitalisation in this high-risk population.

The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the leading cause of childhood morbidity. Although also an important cause of childhood mortality worldwide, the impact of key risk factors has not been established. A systematic review of 34 articles reporting case fatality rates in young children hospitalized for severe RSV LRTI, according to the presence of underlying RSV risk factors, was conducted. The weighted mean case fatality rate was 1.2% (range, 0-8.3%; median, 0%; n = 10) among preterm infants; 5.2% (range, 2.0-37.0%; median, 5.9%; n = 7) among children with CHD; and 4.1% (range, 0-10.5%; median, 7.0%; n = 6) among children with BPD. Case fatality estimates among children not at high risk (n = 6) ranged from 0% to 1.5% (weighted mean, 0.2%; median, 0.0%). Fatality during hospitalization for severe RSV LRTI is rare among children not at high risk, but occurs more commonly among children at higher risk of RSV LRTI.

The Use of Intravenous Palivizumab for Treatment of Persistent RSV Infection in Children With Leukemia

Palivizumab is a humanized monoclonal antibody used to decrease the threat of respiratory syncytial virus (RSV) infection among children at high risk. There are no standard guidelines due to conflicting data on palivizumab's use in the treatment of RSV lower respiratory tract infections. Intravenous (IV) palivizumab was shown to be well tolerated and associated with decreased mortality in high-risk children who have RSV disease. However, it did not prevent lower respiratory tract infections and did not affect the survival rate of allogeneic stem cell transplant recipients who had RSV infection. We present 2 children with acute lymphocytic leukemia (ALL) and persistent RSV infection while receiving chemotherapy. Patient A is a 4-year-old male with Down syndrome, ALL, and persistent RSV infection for at least 3 months. Patient B is a 3-year-old female with pre-B cell ALL whose chemotherapy intensification phase was delayed due to a month-long RSV infection. RSV infections were determined by using real-time polymerase chain reaction assays from nasopharyngeal swabs before IV palivizumab therapy; patient A was positive for RSV at 36 cycles and patient B was positive for RSV at 29 cycles. RSV infection was cleared in both patients within 72 hours after receiving IV palivizumab (patient A: 16 mg/kg; patient B: 15 mg/kg). IV palivizumab may be a treatment option for persistent RSV infection among immunocompromised patients.

Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity. Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity. Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-α, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-α and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001). Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization.

846 Respiratory Syncytial Virus as Cause of Lower Respiratory Tract Infection in Young Children in Central and Eastern Europe

BackgroundRespiratory Syncytial virus (RSV) infection can cause severe morbidity leading to hospitalization and admission to paediatric intensive care unit (ICU). Limited epidemiological data exist about RSV as cause of lower...

Respiratory syncytial virus infection and chronic respiratory morbidity – is there a functional or genetic predisposition?

A systematic literature review has been undertaken. Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infancy is associated with chronic respiratory morbidity. Premorbid abnormal lung function may predispose to RVS LRTI in prematurely born infants. Single-nucleotide polymorphisms in genes coding for IL-8, IL-19, IL-20, IL-13 mannose-binding lectin, IFNG and a RANTES polymorphism have been associated with subsequent wheeze following RSV LRTI in term-born infants.