Respiratory Syncytial Virus Lower Respiratory Tract Infection Research Articles

An Adaptive Randomized Trial of an Intermittent Dosing Schedule of Aerosolized Ribavirin in Patients With Cancer and Respiratory Syncytial Virus Infection

A continuous dosing schedule of aerosolized ribavirin has been used for respiratory syncytial virus (RSV) upper respiratory tract infection and lower respiratory tract infection (LRTI) but is associated with high cost and inconvenient administration. We conducted an adaptive randomized trial to evaluate the effectiveness of an intermittent dosing schedule of ribavirin versus that of a continuous dosing schedule of ribavirin in preventing RSV LRTIs in 50 hematopoietic stem cell transplant recipients or patients with hematologic malignancies. LRTI occurred in 3 patients (9%) receiving the intermittent schedule and in 4 (22%) receiving the continuous schedule, with a 0.889 posterior probability. Because the intermittent schedule is easy to administer and has a higher efficacy than the continuous schedule, we recommend the intermittent schedule for patients who are at risk for RSV LRTI. Clinical Trials Registration. NCT00500578.

The Epidemiology of Respiratory Syncytial Virus Lower Respiratory Tract Infection on Young Children

Reply: We thank Cooper and colleagues for their comments on our article and that by Simões and co-workers.1,2 They bring up the highly interesting question what incidence should be considered substantial. Simões found that the incidence of respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) in patients with age 0–2 months, 3–5 months and 6–8 months is 0, 50 and 198, respectively, per 1000 child-years.1 These numbers are in-line with the accumulated cohort data from the Utrecht RSV Research group.2 These studies allow for the conclusion that RSV bronchiolitis is relatively rare during the first months of life, but when it occurs, the course of disease is severe. It seems obvious that both incidence and severity of RSV LRI during infancy determine the burden of disease. Thus, we agree with Cooper and colleagues that the burden of RSV LRI in children 3–6 months is quite substantial despite the consistent observation that incidence is lower than in children 7–12 months. Louis Bont, MD, PhD Michiel L. Houben, MD Department of Pediatrics,Utrecht RSV Research Group, University Medical Center Utrecht, Utrecht, The Netherlands

Ethical considerations and rationale of the MAKI trial: A multicenter double-blind randomized placebo-controlled trial into the preventive effect of palivizumab on recurrent wheezing associated with respiratory syncytial virus infection in children with a gestational age of 33–35 weeks

BackgroundRespiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the most frequent cause of bronchiolitis during infancy. Long-term airway morbidity with recurrent post bronchiolitis wheezing (PBW) episodes, which are probably associated with respiratory infections, occurs in 30 to 70% of infants that were hospitalised with RSV LRTI. MethodsWe set up a multicenter, placebo-controlled double-blind randomized clinical trial in healthy preterm infants born between 33 and 35weeks gestational age (WGA). The children received either one-monthly intramuscular palivizumab or placebo injection during the RSV season with a minimum of 2 injections. ResultsThe primary objective was to determine the preventive effect of RSV immunoprophylaxis (palivizumab) on the development of recurrent wheezing during the first year of life. The primary outcome measure was the number of wheezing days during the first year of life as obtained by daily logs. As a secondary outcome nasal swabs were taken for viral analysis in case of respiratory symptoms. We will also examine wheezing at age 1, 3 and 6years both reported by the parents and the general practitioner and quality of life as secondary outcomes. This trial is possible because RSV immunoprophylaxis, although effective in this population, is not completely used in the Netherlands due to its high costs. ConclusionThe Institutional review board (IRB) concluded the study has high clinical relevance because the benefit of 50% chance of protection by palivizumab outweighs the risk of side adverse events due to intramuscular administration of placebo.

Overview of respiratory syncytial virus disease in young children

Correspondence: J Michael Hoopes MedImmune, LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA Tel +1 301 398 5520 Fax +1 301 398 8520 Email hoopesm@medimmune.com Abstract: Respiratory tract illnesses associated with respiratory syncytial virus (RSV) were first reported more than 160 years ago and gained acceptance as a major respiratory pathogen in the late 1950s. Annual epidemics show a seasonal pattern typically beginning in the late fall and ending in early spring, averaging 5 months in length, and varying in time of onset, offset, and duration depending on geographic location. Manifestations of RSV illness primarily involve the upper respiratory tract but can spread to the lower airways and lead to bronchiolitis and/or pneumonia. Initial infection occurs in approximately two-thirds of children during the first year of life; nearly all children are infected at least once by 2 years of age. Reinfection is common throughout life, but initial illness during infancy generally presents with the most severe symptoms. Medical risk conditions that consistently predispose young children to serious lower respiratory tract infection (LRTI) include congenital heart disease, chronic lung disease, and premature birth. Serious LRTI due to RSV is the leading cause of hospitalization in infants and young children worldwide and annual mean hospital expenses have been estimated to exceed 1 billion dollars in the United States. Young children incur more inpatient and outpatient visits for RSV LRTI than for influenza. RSV has a greater impact than influenza on hospitalization in infants with respect to length of stay, severity/course of disease, and resultant needs for ancillary treatments. Unlike many other childhood illnesses, a vaccine is not currently available for preventing RSV disease.

Residential crowding and severe respiratory syncytial virus disease among infants and young children: A systematic literature review

BackgroundThe objective of this literature review was to determine whether crowding in the home is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in children younger than 5 years.MethodsA computerized literature search of PubMed and EMBASE was conducted on residential crowding as a risk factor for laboratory-confirmed RSV illness in children younger than 5 years. Study populations were stratified by high-risk populations, defined by prematurity, chronic lung disease of prematurity, hemodynamically significant congenital heart disease, or specific at-risk ethnicity (i.e. Alaska Native, Inuit), and mixed-risk populations, including general populations of mostly healthy children. The search was conducted for articles published from January 1, 1985, to October 8, 2009, and was limited to studies reported in English. To avoid indexing bias in the computerized databases, the search included terms for multivariate analysis and risk factors to identify studies in which residential crowding was evaluated but was not significant. Methodological quality of included studies was assessed using a Cochrane risk of bias tool.ResultsThe search identified 20 relevant studies that were conducted in geographically diverse locations. Among studies of patients in high-risk populations, 7 of 9 found a statistically significant association with a crowding variable; in studies in mixed-risk populations, 9 of 11 found a significant association with a crowding variable. In studies of high-risk children, residential crowding significantly increased the odds of laboratory-confirmed RSV hospitalization (i.e. odds ratio ranged from 1.45 to 2.85). In studies of mixed-risk populations, the adjusted odds ratios ranged from 1.23 to 9.1. The findings on the effect of residential crowding on outpatient RSV lower respiratory tract infection were inconsistent.ConclusionsResidential crowding was associated with an increased risk of laboratory-confirmed RSV hospitalization among high-risk infants and young children. This association was consistent despite differences in definitions of residential crowding, populations, or geographic locations.

Analysis of 75 cases lower respiratory tract infection by respiratory syncytial virus

Objective To summarize the clinical features of neonatal lower respiratory tract infection of respiratory syncytial virus (RSV). Methods Data of newborns admitted into Deparrment of Neonatology of Yuying Children Hospital of Wenzhou Medical College from January to December 2010 with RSV lower respiratory tract infection were retrospectively analyzed. The characteristics of clinical manifestation,examination,treatment and prognosis were studied.Factors affecting the duration of hospitalization were analyzed with x2 test. Results Of 354 cases of neonatal lower respiratory tract infection,75 (21.2％) were RSV positive,whose attack time was from 5 to 25 days with an average of 13.2 days; and there were two preterm infants (2.7％).The chief clinical manifestations were cough (100.0％,75/75),followed by shortness of breath (56.0％,42/75),spittle (52.0％,39/75) and fever with temperature ≥38.0 ℃ (25.3％,19/75).The white blood cell count of one newborn was higher than 20.0× 109/L; 52 cases (69.3％) had higher blood lymphocyte percentage (＞ 0.48) ; eight cases (10.7％) had higher level of C-reactive protein (≥ 8 mg/L).Among the 58 patients who underwent blood gas analysis,28 (48.3％) had carbon dioxide retention (partial pressure of carbon dioxide≥ 45 mm Hg). Chest X-ray results within 48 hours after hospitalization suggested that 52.0％ patients (n =39) had pneumonia and 20.0％ (n=15) had bronchitis.Among 69 patients who had sputum cultures,20 cases were positive.And for the 11 cases who had blood cultures,three were positive for Staphylococcus epidermidis.Finally,73 cases were cured,two were improved and no death was reported.The duration of hospitalization was from 3 to 17 days with an average of 8.4 days.Neonates with RSV lower respiratory tract infection who had higher C-reactive protein (≥8 mg/L),carbon dioxide retention,nasal oxygen catheter or assisted ventilation had higher percentage of longer hospital stay (≥7 days). Conclusions Compared with infants,the clinical characteristics of RSV lower respiratory tract infections in neonates are atypical,which are mainly menifested by cough,shortness of breath,spittle,but rare wheezing.There are no effective interventions against RSV infection except for supportive therapy. Key words: Respiratory syncytial virus infections ; Respiratory tract infections; Infant, newborn

Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus Infection in High-risk Children, Based on Long-term Epidemiologic Data From Austria

To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria. A decision-tree model was used, and the analysis was based on a lifetime follow-up investigating cost-effectiveness of palivizumab versus no RSV infection prevention. The primary perspective of the study was that of the healthcare system, the second that of society. Cost and effects were discounted by 5%. The base case analysis included only direct medical costs, and a scenario analysis included various indirect costs. Analyses were based on epidemiologic data on a total of 1579 children hospitalized because of RSV lower respiratory tract infection during 16 seasons. The incremental cost-effectiveness ratio for the first outcome measure (life years gained) amounted to discounted costs of €34,956 (for all preterm infants), €35,056 (for < 33 weeks' gestational age [wGA] infants), €35,233 (for 33-35 wGA infants), €35,611 (for infants with bronchopulmonary dysplasia), and €8956 (for infants with congenital heart disease). Use of palivizumab compared with no prophylaxis had an incremental cost-utility ratio of €26,212, €26,292, €24,392, €24,654, and €8484, respectively, per quality-adjusted life years. Results from the society perspective were more cost-effective in all study populations. An additional scenario analysis with 7 injections for the 33 to 35 wGA group revealed cost-effectiveness as well. Our results based on nationwide long-term epidemiologic data suggest that palivizumab is cost-effective in prevention of RSV disease in high-risk infants.

Burden of respiratory syncytial virus infection in young children.

Respiratory syncytial virus (RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants (below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-risk infants, lowers the burden of RSV infection in certain carefully selected patient groups.

Decreased Innate Immune Cytokine Responses Correlate With Disease Severity in Children With Respiratory Syncytial Virus and Human Rhinovirus Bronchiolitis

The immunopathogenesis of respiratory syncytial virus (RSV) and human rhinovirus lower respiratory tract infections in children remains to be defined. We measured nasal wash concentrations of 29 cytokines in infants with RSV or human rhinovirus lower respiratory tract infections. Concentrations of interferon-γ in RSV and innate immunity cytokines in both infections inversely correlated with disease severity.

Down Syndrome and Hospitalizations due to Respiratory Syncytial Virus: A Population-Based Study

To assess the risk estimates for respiratory syncytial virus (RSV) hospitalization in children with Down syndrome (DS) and the clinical features and severity of RSV lower respiratory tract infection (LRTI) in hospitalized children. Statewide hospitalization data for children with DS for 1995 through 2006 from the Colorado Health and Hospital Association database were combined with birth data from the Colorado Department of Public Health and Environment to obtain population-based estimates of RSV LRTI hospitalization for children with DS in the first 2years of life. RSV hospitalization data for children with DS at the Children's Hospital Colorado for 2000 through 2006 were used to compare the course and severity of hospitalization of DS LRTI admissions with those of matched control subjects. There were 85 RSV LRTI hospitalizations in 630 children born with DS in Colorado, with 50 having no concurrent underlying conditions identified. Children with DS had a significantly higher risk than did those without DS for being hospitalized with RSV LRTI (OR, 5.99; 95% CI, 6.68-5.38), even in the absence of other underlying conditions (OR 3.5; 95% CI, 3.10-4.12). In the case-control study, children with DS hospitalized for RSV presented more frequently with fever (P = .005), had consolidation reported more often on chest radiography (P = .003), and were given bronchodilator therapy more often during the hospital stay (P = .002). Children with DS have a higher risk of being hospitalized with RSV LRTI even in the absence of coexisting risk factors. They present more often with fever and more often have radiographic consolidation detected on chest radiography.

Relationship between Lower Respiratory Tract Infections Caused by Respiratory Syncytial Virus and Subsequent Development of Asthma in Japanese Children

Several studies in Western countries have found that lower respiratory tract infections (LRTIs) caused by the respiratory syncytial virus (RSV) in infancy may subsequently trigger the development of asthma. In this study, we enrolled 262 infants under the age of 3 who had been admitted to our hospital with LRTI between September 2002 and August 2003. RSV infection was diagnosed in these patients using an RSV rapid diagnostic kit and by measuring antibody titers in paired serum samples. In March 2009, we sent questionnaires on post-discharge allergic conditions to the families of the 249 patients, excluding 13 who had a prior history of asthma. A total of 133 responses were received (response rate, 53.4%); RSV was detected in 36 patients of the RSV group and 97 patients of the non-RSV group. Wheezing was experienced post-discharge by 10 patients in the RSV group (27.8%) and 32 in the non-RSV group (33.0%) (P = 0.57). Four patients in the RSV group (11.1%) and 6 in the non-RSV group (6.2%) (P = 0.34) were treated for asthma. This study revealed that RSV LRTI in infancy does not predispose children to subsequent development of asthma at the age of 7 years and 7 months. We believe that this is the first Japanese survey that has examined the relationship between RSV LRTI in infancy and the subsequent development of asthma.

RelA Ser276 phosphorylation-coupled Lys310 acetylation controls transcriptional elongation of inflammatory cytokines in respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a negative-sense single-stranded RNA virus responsible for lower respiratory tract infections (LRTIs) in humans. In experimental models of RSV LRTI, the actions of the nuclear factor κB (NF-κB) transcription factor mediate inflammation and pathology. We have shown that RSV replication induces a mitogen-and-stress-related kinase 1 (MSK-1) pathway that activates NF-κB RelA transcriptional activity by a process involving serine phosphorylation at serine (Ser) residue 276. In this study, we examined the mechanism by which phospho-Ser276 RelA mediates expression of the NF-κB-dependent gene network. RelA-deficient mouse embryonic fibroblasts (MEFs) complemented with the RelA Ser276Ala mutant are deficient in CXCL2/Groβ, KC, and interleukin-6 (IL-6) expression, but NFKBIA/IκBα is preserved. We show that RSV-induced RelA Ser276 phosphorylation is required for acetylation at Lys310, an event required for transcriptional activity and stable association of RelA with the activated positive transcriptional elongation factor (PTEF-b) complex proteins, bromodomain 4 (Brd4), and cyclin-dependent kinase 9 (CDK9). In contrast to gene loading pattern of PTEF-b proteins produced by tumor necrosis factor (TNF) stimulation, RSV induces their initial clearance followed by partial reaccumulation coincident with RelA recruitment. The RSV-induced binding patterns of the CDK9 substrate, phospho-Ser2 RNA polymerase (Pol) II, follows a similar pattern of clearance and downstream gene reaccumulation. The functional role of CDK9 was examined using CDK9 small interfering RNA (siRNA) and CDK inhibitors, where RSV-induced NF-κB-dependent gene expression was significantly inhibited. Finally, although RSV induces a transition from short transcripts to fully spliced mRNA in wild-type RelA (RelA WT)-expressing cells, this transition is not seen in cells expressing RelA Ser276Ala. We conclude that RelA Ser276 phosphorylation mediates RelA acetylation, Brd4/CDK9 association, and activation of downstream inflammatory genes by transcriptional elongation in RSV infection.

The Epidemiology of Respiratory Syncytial Virus Lower Respiratory Tract Infections in Children Less than 5 Years of Age in Indonesia

Although the epidemiology of respiratory syncytial virus (RSV) lower respiratory tract infections (LRI) is well known in industrialized countries, the burden in developing Asian countries is not well studied. To define the burden of RSV disease in children <5 years of age in rural and urban Indonesia, infants and children were enrolled from peri-urban and rural subdistricts, in the following 2 cohorts: (a) a cross-sectional cohort of approximately 100 children from each of 2 subdistricts in the following 5 age groups: 3 to 5, 6 to 8, 9 to 11, 12 to 23, and 24 to 48 months; (b) a birth cohort of all newborns in both subdistricts during the 28 months of the study. All subjects were visited weekly at home. Children with World Health Organization-defined LRI or wheezing had a nasal wash for detection of RSV using an enzyme immunoassay and polymerase chain reaction. Of the 2014 children studied, 1074 were in the cross-sectional and 940 in the newborn cohorts. Of the 802 episodes of LRI, 163 were caused by RSV. The RSV LRI incidence per 1000 child-years (C-Y) was higher in rural areas (57.25 vs. 38.54), P < 0.05. No RSV LRI occurred in the first 2 months of life and the peak incidence was in the 6- to 8-month-old infants (103/1000 C-Y). The rates were lowest in those <6 months, 16.5 per 1000 C-Y, compared with 83.1 per 1000 C-Y in those 6 to 11 months of age (P < 0.001), 66.99 in those 12 to 23 months of age, and 28.1 in 2- to 5-year-olds. In Indonesia, the incidence of RSV LRI in the first 6 months of life is relatively low with most disease occurring in older children.

Clara cell protein 10 polymorphism is not associated with severe respiratory syncytial virus infection*

To investigate a possible correlation between severe respiratory syncytial virus (RSV) infection and single-nucleotide polymorphism (SNP) in the Clara cell protein 10 (CC10) gene (A38G). Children hospitalized with severe RSV lower respiratory tract (LRTI) infection at Karolinska University Hospital, Stockholm, during three subsequent RSV seasons were selected and genotyped. Age-matched controls were used. The two groups were compared regarding SNP in the CC10 gene (A38G) and regarding later development of wheezing. No correlation was found between the genotype CC10 +38AA and severe RSV infection or wheezing during follow-up. Wheezing (p = 0.022), frequent wheezing (≥3 episodes) (p =0.042) as well as ever wheezing (p = 0.0022) occurred significantly more often after discharge in children hospitalized for RSV compared with the control group. Single-nucleotide polymorphism in the CC10 gene (A38G) does not seem to be involved in the severity of RSV infection or wheezing. In agreement with other studies, we found that children with severe RSV are at increased risk of future wheezing. The latter finding implies that the studied population represented children with severe LRTI, which supports that a correlation between the genotype CC10 +38AA and severe RSV is less likely.

Genetic Determinants of Severe Respiratory Syncytial Virus Infection and Post-Bronchiolitis Wheeze: A Systematic Review

Severity of respiratory syncytial virus (RSV) infection is subject to individual variation, and, accordingly, genetic determinants play a role in the risk of developing RSV lower respiratory tract infection (LRTI) in previously healthy infants. A twin study showed that 22% of the individual susceptibility to RSV LRTI is attributable to genetic factors. About half of the infants with RSV LRTI will develop post-bronchiolitis wheeze (PBW). It is unknown whether RSV LRTI and PBW have similar etiology. This systematic review aims to provide insight into the genetic factors influencing susceptibility to RSV LRTI and PBW. Published genetic associations of RSV LRTI with both single nucleotide polymorphisms (SNPs) and haplotypes are shown. Particularly SNPs in innate immunity genes are associated with the pathogenesis of RSV LRTI. However, no genetic variants associated with RSV LRTI have been exactly replicated in other cohorts. A limited number of studies have reported associations between SNPs and PBW, especially in chemokine and Th2 related genes. In conclusion, although RSV LRTI and PBW show similarities in clinical presentation, different genetic factors are important for the development of these diseases in young children. Keywords: Respiratory syncytial virus, post-bronchiolitis wheeze, single nucleotide polymorphism, haplotype, genetic association, lower respiratory tract infection, etiology, SNPs, upper respiratory tract infection, Genetic determinants, Postbronchiolitis wheeze

Cord Blood Vitamin D Deficiency Is Associated With Respiratory Syncytial Virus Bronchiolitis

Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI. To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI. A prospective birth cohort study was performed in healthy term neonates. Concentrations of 25-hydroxyvitamin D (25-OHD) in cord blood plasma were related to RSV LRTI in the first year of life, defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen. The study population included 156 neonates. Eighteen (12%) developed RSV LRTI. The mean plasma 25-OHD concentration was 82 nmol/L. Overall, 27% of neonates had 25-OHD concentrations < 50 nmol/L, 27% had 50-74 nmol/L and only 46% had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy. Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not (65 nmol/L versus 84 nmol/L, P = .009). Neonates born with 25-OHD concentrations <50 nmol/L had a sixfold (95% confidence interval: 1.6-24.9; P = .01) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥ 75 nmol/L. Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life. Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy.

Does RSV Infection Alter the Course of Chronic Lung Disease in Prematurely Born Infants?

Very premature birth frequently results in chronic respiratory morbidity, particularly if complicated by the development of chronic lung disease, bronchopulmonary dysplasia (BPD). Affected infants may remain oxygen dependent for many months and require hospital readmission in the first two years after birth. Troublesome, recurrent respiratory symptoms requiring treatment are common. The worst affected may remain symptomatic with evidence of airways obstruction even as adults. Infant who are born prematurely and develop BPD are at increased risk of severe respiratory syncytial virus (RSV) infection. RSV infection in prematurely born infants is associated with excess chronic respiratory morbidity, as evidenced by greater frequency of respiratory symptoms, lung function abnormalities and healthcare utilisation. There is some evidence to suggest that prematurely born infants, as those born at term, may be predisposed to symptomatic RSV lower respiratory tract infections by pre-morbid abnormal lung function. Longitudinal studies assessing lung function before and after RSV infection are required to determine whether RSV infection does alter the course of chronic lung disease in prematurely born infants.

HOSPITALIZATIONS DUE TO RESPIRATORY SYNCYTIAL VIRUS IN CHILDREN WITH CONGENITAL MALFORMATIONS

Statewide respiratory syncytial virus (RSV) lower respiratory tract infection hospitalization data of Colorado children with congenital malformations was used to estimate the population-based risk and severity of disease of RSV hospitalizations. Spina bifida without anencephaly, cleft palate, lung agenesis or dysgenesis, and biliary atresia were associated with a higher risk of being hospitalized with RSV lower respiratory tract infection and an increased severity of disease when hospitalized.

Comparison of risk factors between preterm and term infants hospitalized for severe respiratory syncytial virus in the Russian Federation

BackgroundRespiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants. Preterm birth, in addition to several demographic and environmental factors, increases the risk for development of severe RSV infection. The purpose of this study was to describe differences in risk factors and protective factors between preterm birth (up to 35 weeks’ gestational age) and term infants hospitalized for RSV lower respiratory tract infection in the Russian Federation during the 2008–2009 RSV season.MethodsInfants up to two years of age hospitalized for a lower respiratory tract infection in Moscow, St Petersburg, and Tomsk were tested for RSV. Patient data, including risk factors and protective factors for RSV, were captured at admission. Differences in these factors were compared between preterm and term patients.ResultsA total of 519 infants hospitalized for lower respiratory tract infection were included in the study. Of these, 197 infants (182 term and 15 preterm) tested positive for RSV. Of all hospitalizations, 51.7% (15/29) of preterm infants versus 37.1% (182/490) of term infants had confirmed RSV (P = 0.118). Among the RSV-positive patients, preterm infants were more likely to have a lower weight at admission (P = 0.050), be of multiple gestation (P < 0.001), have more siblings (P = 0.013), and have more siblings under the age of eight years (P < 0.007) compared with term patients. The preterm infants were less likely to be breastfed (P < 0.001) and more likely to have older mothers (P = 0.050).ConclusionCompared with term infants, RSV was a more prevalent cause of hospitalization for lower respiratory tract infection in preterm infants. Of infants hospitalized for RSV, preterm infants were more likely to have additional risk factors for severe RSV. These findings suggest that preterm infants may be exposed to a combination of more strongly interrelated risk factors for severe RSV than term infants.

Uteroglobulin‐related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.