Respiratory Syncytial Virus Bronchiolitis In Infancy Research Articles

Serum bilirubin is associated with a reduced risk of subsequent recurrent wheezing following acute respiratory syncytial virus bronchiolitis.

Bilirubin is a potent antioxidant and anti-inflammatory molecule that has been shown to ameliorate airway inflammation. We aimed to study whether serum bilirubin is protective and can predict the development of subsequent recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis. The medical records of 188 infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were retrospectively reviewed. Our main outcome of interest was the development of subsequent recurrent wheezing by the age of 3years. Each infant's serum bilirubin concentration was extracted from their blood biochemical results. Seventy-one (37.8%) infants developed recurrent wheezing by the age of 3 and 117 (62.2%) did not. The serum total bilirubin, unconjugated bilirubin, and conjugated bilirubin levels at hospital admission were lower in infants who developed recurrent wheezing as compared to those who did not (p ＜ 0.001). The area under the receiver-operating characteristic curve of serum total bilirubin, unconjugated bilirubin, and conjugated bilirubin for the prediction of subsequent recurrent wheezing were 0.71 (95% confidence interval [CI], 0.64-0.78), 0.70 (95% CI, 0.63-0.78), and 0.67 (95% CI, 0.59-0.75), respectively. Higher admission serum total bilirubin levels were independently associated with a lower risk of development of subsequent recurrent wheezing (adjusted OR 0.17, p ＜ 0.001). During the first episode of severe RSV bronchiolitis in infants <6 months of age, moderately higher levels of serum bilirubin are associated with a reduced risk of developing subsequent recurrent wheezing by 3 years of age.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. 55% of the study cohort (N=122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P<.0001) FVC (P<.0001) and FEV1 /FVC (P<.0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28mg/mL at 7years to 0.53mg/mL at 12years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P=.0003). Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis

Early interactions between respiratory viruses and microbiota might modulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis. Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6months of age or less were included and followed up until the age of 3years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively. Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P=.003), CXCL8 (P=.004), CCL5 (P=.029), IL-6 (P=.004), and IL-13 (P<.001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r=0.246, P=.037) level, and that of Moraxella was associated with IL-6 level (r=0.236, P=.046) and IL-10 level (r=0.266, P=.024). Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood.

Reduced PRF1 enhancer methylation in children with a history of severe RSV bronchiolitis in infancy: an association study

BackgroundAcute lower respiratory tract infection is the commonest disease affecting children under five worldwide. Respiratory syncytial virus (RSV) is among the most common causative pathogens. Epidemiological data suggest an association between severe viral respiratory infections in infancy and increased incidence of childhood wheeze and asthma. DNA methylation is involved in immune cell differentiation and identity. It provides an avenue for environmental influences on the genome and therefore has potential as a marker for sustained effects of infectious insults. In this study we investigated the association between DNA methylation patterns in the perforin gene (PRF1) in childhood and a history of hospitalisation for severe RSV disease in the first two years of life.MethodsIn this retrospective study, we explored patterns of whole blood DNA methylation at a methylation sensitive region of the proximal PRF1 enhancer in a group of children with a record of hospitalisation for severe RSV disease during infancy (n = 43) compared to healthy controls matched for age and sex with no similar hospitalisation history, no allergy and no persistent wheeze (n = 43). Univariate and bivariate conditional logistic regression analyses were conducted to test the association between PRF1 enhancer methylation and record of hospitalisation for RSV disease.ResultsChildren with a record of hospitalisation for severe RSV bronchiolitis demonstrated markedly lower levels of DNA methylation at two cytosine-phosphate-guanine dinucleotide (CpG) loci of the PRF1 proximal enhancer, corresponding to a signal transducer and activator of transcription 5 (STAT5) responsive element, compared to controls, adjusted odds ratios of 0.82 (95% confidence interval [CI] 0.71, 0.94) and 0.73 (95% CI 0.58, 0.92) for each 1% increase in DNA methylation. Smoking in the household showed a significant influence on DNA methylation at the assayed positions.ConclusionsOur findings support an association between childhood DNA methylation patterns in PRF1 and a record of severe RSV infection in infancy. Longitudinal studies are required to establish the utility of PRF1 methylation as a marker of severe RSV disease.

Best practice in the prevention and management of paediatric respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is ubiquitous with almost all infants having been infected by 2 years of age and lifelong repeated infections common. It is the second largest cause of mortality, after malaria, in infants outside the neonatal period and causes up to 200,000 deaths per year worldwide. RSV results in clinical syndromes that include upper respiratory tract infections, otitis media, bronchiolitis (up to 80% of cases) and lower respiratory tract disease including pneumonia and exacerbations of asthma or viral-induced wheeze. For the purposes of this review we will focus on RSV bronchiolitis in infants in whom the greatest disease burden lies. For infants requiring hospital admission, the identification of the causative respiratory virus is used to direct cohorting or isolation and infection control procedures to minimize nosocomial transmission. Nosocomial RSV infections are associated with poorer clinical outcomes, including increased mortality, the need for mechanical ventilation and longer length of hospital stay. Numerous clinical guidelines for the management of infants with bronchiolitis have been published, although none are specific for RSV bronchiolitis. Ribavirin is the only licensed drug for the specific treatment of RSV infection but due to drug toxicity and minimal clinical benefit it has not been recommended for routine clinical use. There is currently no licensed vaccine to prevent RSV infection but passive immunoprophylaxis using a monoclonal antibody, palivizumab, reduces the risk of hospitalization due to RSV infection by 39-78% in various high-risk infants predisposed to developing severe RSV disease. The current management of RSV bronchiolitis is purely supportive, with feeding support and oxygen supplementation until the infant immune system mounts a response capable of controlling the disease. The development of a successful treatment or prophylactic agent has the potential to revolutionize the care and outcome for severe RSV infections in the world's most vulnerable infants.

Pooled Sequencing of Candidate Genes Implicates Rare Variants in the Development of Asthma Following Severe RSV Bronchiolitis in Infancy.

Severe infection with respiratory syncytial virus (RSV) during infancy is strongly associated with the development of asthma. To identify genetic variation that contributes to asthma following severe RSV bronchiolitis during infancy, we sequenced the coding exons of 131 asthma candidate genes in 182 European and African American children with severe RSV bronchiolitis in infancy using anonymous pools for variant discovery, and then directly genotyped a set of 190 nonsynonymous variants. Association testing was performed for physician-diagnosed asthma before the 7th birthday (asthma) using genotypes from 6,500 individuals from the Exome Sequencing Project (ESP) as controls to gain statistical power. In addition, among patients with severe RSV bronchiolitis during infancy, we examined genetic associations with asthma, active asthma, persistent wheeze, and bronchial hyperreactivity (methacholine PC20) at age 6 years. We identified four rare nonsynonymous variants that were significantly associated with asthma following severe RSV bronchiolitis, including single variants in ADRB2, FLG and NCAM1 in European Americans (p = 4.6x10-4, 1.9x10-13 and 5.0x10-5, respectively), and NOS1 in African Americans (p = 2.3x10-11). One of the variants was a highly functional nonsynonymous variant in ADRB2 (rs1800888), which was also nominally associated with asthma (p = 0.027) and active asthma (p = 0.013) among European Americans with severe RSV bronchiolitis without including the ESP. Our results suggest that rare nonsynonymous variants contribute to the development of asthma following severe RSV bronchiolitis in infancy, notably in ADRB2. Additional studies are required to explore the role of rare variants in the etiology of asthma and asthma-related traits following severe RSV bronchiolitis.

Perinatal respiratory infections and long term consequences

Respiratory syncytial virus (RSV) is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis), activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis). The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11 th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy) · October 26 th -31 st , 2015 · From the womb to the adult Guest Editors: Vassilios Fanos (Cagliari, Italy), Michele Mussap (Genoa, Italy), Antonio Del Vecchio (Bari, Italy), Bo Sun (Shanghai, China), Dorret I. Boomsma (Amsterdam, the Netherlands), Gavino Faa (Cagliari, Italy), Antonio Giordano (Philadelphia, USA)

Respiratory syncytial virus infection and bronchiolitis.

1. Giovanni Piedimonte, MD*,† 2. Miriam K. Perez, MD*,‡ 1. *Cleveland Clinic Pediatric Institute, Cleveland, OH. 2. †Cleveland Clinic Children’s Hospital for Rehabilitation, The Cleveland Clinic, Cleveland, OH. 3. ‡Department of Community Pediatrics, Independence Family Health Center, Independence, OH. * Abbreviations: AAP: : American Academy of Pediatrics DBPC: : double-blind, placebo-controlled FDA: : Food and Drug Administration LRTI: : lower respiratory tract infection RSV: : respiratory syncytial virus 1. Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Although the most effective management of this infection remains supportive care, many patients continue to be managed with therapies that lack the support of scientific evidence. 2. Although the quest for a safe and effective vaccine remains unsuccessful, the more vulnerable patients can be protected with passive prophylaxis. Because of limited clinical benefits and high costs, RSV prophylaxis should be limited to high-risk infants as directed by the most current evidence-based guidelines that, however, are not consistently followed. 3. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. The phenotype of post-RSV wheezing is different from atopic asthma, yet it is usually managed using the same pharmacologic therapy with often ineffective results. After reading this article, readers should be able to: 1. Understand the microbiology, epidemiology, pathophysiology, and clinical manifestations of RSV bronchiolitis in infants and children. 2. Know the scientific evidence relevant to prophylactic and therapeutic strategies currently available and recognize the lack of evidence concerning several pharmacologic agents commonly used in the management of bronchiolitis. 3. Be aware of alternative pharmacologic strategies currently being evaluated. 4. Learn the epidemiologic and experimental information suggesting the existence of a link between early-life infection with RSV and the subsequent development of recurrent wheezing and asthma in childhood and adolescence. Human respiratory syncytial virus (RSV) is a single-stranded RNA virus of the …

Does cesarean section pose a risk of respiratory syncytial virus bronchiolitis in infants and children?

ObjectiveTo determine the risk of acquiring acute respiratory syncytial virus (RSV) bronchiolitis in infants and children delivered by the mode of cesarean section (C-section). MethodsA retrospective and descriptive study was conducted at Hamad Medical Corporation. Patients with ages 0 to 36 months hospitalized with acute bronchiolitis were included in the study. ResultsThe risk of RSV bronchiolitis was observed to be higher among C-section delivery compared to normal spontaneous vaginal delivery [odds ratio=1.10; 95% confidence interval (0.57, 1.80); P=0.965]; however, it was not statistically significant. Gestational age ≤35 weeks was significantly associated with increased risk of RSV bronchiolitis compared to gestational age >35 weeks [odds ratio=3.12; 95% confidence interval (1.53, 6.38); P=0.002]. ConclusionsDelivery by C-section does not appear to increase the risk of RSV bronchiolitis in infants compared with normal spontaneous vaginal delivery.

Vitamin D‐binding protein haplotype is associated with hospitalization for RSV bronchiolitis

Between 75000 and 125000 U.S. infants are hospitalized for respiratory syncytial virus (RSV) bronchiolitis every year. Up to half will be diagnosed with asthma in later childhood. Vitamin D deficiency has been associated with susceptibility to asthma and respiratory infections. Measured vitamin D is largely bound to vitamin D-binding protein (VDBP); VDBP levels are influenced by its gene (GC) haplotype. We assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma. We retrospectively recruited 198 otherwise healthy children (93% White) hospitalized for severe RSV bronchiolitis in Boston and 333 parents into a follow-up study to assess asthma diagnosis. Data were analysed using family-based genetic association tests. We independently validated our results in 465 White children hospitalized with RSV bronchiolitis and 930 White population controls from the Netherlands. The rs7041_C allele (denoting haplotype GC1s) was overtransmitted (P=0.02, additive model) in the entire Boston cohort, in Whites (P=0.03), and especially in children subsequently diagnosed with asthma (P=0.006). The GC1f haplotype was undertransmitted in the asthma subgroups (all races and White, both P<0.05). The rs7041_C allele was also more frequent in the RSV bronchiolitis group compared with controls (OR 1.12, 95% CI 1.02, 1.4, P=0.03) in the Netherlands, especially in mechanically ventilated patients (P=0.009). GC1s haplotype carriage may increase the risk of RSV bronchiolitis in infancy and subsequent asthma development. The GC1s haplotype is associated with higher VDBP levels, resulting in less freely available vitamin D. Vitamin D-binding protein (VDBP) haplotypes influence free vitamin D levels. We report an association between a VDBP haplotype and hospitalization for RSV bronchiolitis in infancy in two independent cohorts.

Global Gene Expression Profiling in Infants With Acute Respiratory Syncytial Virus Broncholitis Demonstrates Systemic Activation of Interferon Signaling Networks

Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to better understand the systemic host response to acute RSV bronchiolitis in infants and young children. Patients (age ≤ 24 months) who were clinically diagnosed with acute bronchiolitis and who had a positive rapid test for RSV assay were recruited from the Texas Children's Hospital emergency department. Global gene expression of peripheral whole blood cells were analyzed in 21 cases and 37 age-matched healthy controls. Transcripts exhibiting significant upregulation and downregulation as a result of RSV infection were identified and confirmed in a subset of samples using RNA sequencing. The potential pathways affected were analyzed. Blood was obtained from patients with acute RSV bronchiolitis (mean age 6 months). Of these, 43% were admitted to the hospital, 52% were given intravenous fluids and 24% received oxygen. Highly significant expression differences were detected in a discovery cohort of White infants (N = 33) and validated in an independent group of African-American infants (N = 19). Individuals with mild disease (N = 15) could not be distinguished from subjects with clinically moderate disease (N = 5). Pathway enrichment analyses of the differentially expressed genes demonstrated extensive activation of the innate immune response, particularly the interferon signaling network. There was a significant downregulation of transcripts corresponding to antigen presentation.

Rhinovirus‐induced bronchiolitis and asthma development

Human rhinovirus (HRV) and respiratory syncytial virus (RSV) are commonly associated with bronchiolitis. The breaking point in the dominance is approximately 12 months--rhinovirus dominates in the older children. Predisposition may markedly increase the prevalence of HRV bronchiolitis. Especially, low interferon responses and atopy-related factors have been associated with HRV bronchiolitis. The former has been considered as a sign of poor antiviral defense, and the latter could be associated with atopic airway inflammation in wheezing children. Although recurrent wheezing is common after both RSV and HRV bronchiolitis, HRV bronchiolitis carries a markedly higher risk of persistent wheezing until 6 years of age and for childhood asthma. This association has been independent from atopy at 7.2 (median) years of age. The increased risk of asthma in adulthood after non-RSV bronchiolitis vs. RSV bronchiolitis in infancy (at the time when PCR was not available for HRV diagnosis) offers indirect evidence for the association between HRV bronchiolitis and chronic asthma.

Causal Direction Between Respiratory Syncytial Virus Bronchiolitis and Asthma Studied in Monozygotic Twins

Respiratory syncytial virus (RSV) bronchiolitis has been associated with later development of asthma, wheezing, abnormal pulmonary function, and sensitization. Our aim was to determine the differential effect within monozygotic (MZ) twin pairs discordant for severe RSV bronchiolitis in infancy on the subsequent development of asthma, pulmonary function, and allergy. Thirty-seven MZ twin pairs discordant for RSV hospitalization in infancy (mean age 10.6 months) were compared at the mean age of 7.6 years for lung function, bronchial responsiveness, fractional exhaled nitric oxide (Feno), asthma diagnosis, use of asthma medication, and skin prick test to common inhalant allergens. There were no differences within MZ twin pairs discordant for RSV hospitalization in infancy with respect to pulmonary function, Feno, asthma prevalence, asthma medication use, or sensitization (P > .1 for all comparisons). We found no differential effect from severity of RSV infection on the development of asthma and allergy in MZ twin pairs discordant for RSV hospitalization in infancy. This argues against a specific effect of severe RSV infection in the development of asthma and allergy. Because of the small sample size, this study must be considered as a hypothesis-generating study.

Toll‐like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics

The respiratory syncytial virus (RSV) antigen serves as ligand for Toll-like receptor (TLR) 4 that is a transmembrane signaling receptor in macrophages and dendritic cells. According to current evidence single nucleotide polymorphism involving amino acid 299 influences the susceptibility to severe RSV infections. The Asp299Gly allele has been shown to influence the TLR4-mediated signaling causing conformational change in the extracellular domain that recognizes pathogen-associated molecular patterns. The aim was to study the association between the TLR4 Asp299Gly polymorphism and the susceptibility to severe RSV bronchiolitis in infants. Altogether 312 cases and 356 controls, selected on the basis place of residence, date of birth, gender, and gestation at birth, were studied. When adjusted for multiple dependent variables, no allele or genotype frequency difference was found between the cases and the controls. Post hoc analysis revealed that during the year 2000 epidemics, the Gly299Gly genotype associated with protection against severe RSV and during 2004 epidemics Gly299Gly genotype and 299Gly allele associated with severe RSV. To conclude, we could not confirm the association of the Gly299 allele with severe RSV. This is consistent with the evidence that the susceptibility to severe RSV infection is principally dependent on environmental and constitutional factors. We propose that the risk of severe RSV infection may additionally depend on the interaction between individual TLR4 genotype and the particular RSV group causing bronchiolitis.

Respiratory Syncytial Virus Bronchiolitis and Asthma – Insights from Recent Studies and Implications for Therapy

Infection with respiratory syncytial virus (RSV) is a leading cause of upper and lower respiratory tract infection in infants. It is accompanied by a considerably disease burden and a hospitalisation rate of up to 3% in infected infants. Besides, it is still a matter of intensive discussion whether severe RSV infection in early infancy causes the development of asthma later in live or whether RSV bronchiolitis just chronologically precedes asthma in children who are susceptible to asthma. The latter could be due to a common genetic background of both diseases predisposing to an exaggerated inflammatory response of the lungs to allergens and pathogens. Genetic studies might help to elucidate the mechanisms leading to both diseases and to highlight common as well as diverse pathways. The results of such investigations will influence the current understanding of the diseases and might even change our therapeutical approaches to both disorders. This review summarizes current findings in the genetics of bronchial asthma and severe RSV bronchiolitis. The question whether a relationship exists between severe RSV bronchiolitis in infancy and childhood asthma will also be discussed by taking recent epidemiological studies in account. A special focus is laid on the implications of these findings for a targeted drug therapy of both diseases.

Genetic association study for RSV bronchiolitis in infancy at the 5q31 cytokine cluster

Background:The pathophysiological basis of severe respiratory syncytial virus (RSV) bronchiolitis in infancy is poorly understood and has hindered vaccine development. Studies implicate the cell-mediated immune response in the pathogenesis of...

Asthma, lung function and sensitization in school children with a history of bronchiolitis

The purpose of the present retrospective study was to investigate the association of school-age asthma with acute-bronchiolitis and examine the influence of potential risk factors. One hundred and eighty-nine children aged 7.5 +/- 2.2 years consecutively hospitalized for respiratory syncytial virus (RSV)-positive acute bronchiolitis during infancy were evaluated by clinical examination and measurement of peak expiratory flow (PEFR), spirometry, IgE and skin-prick testing. Their pulmonary function was compared with that of 60 non-asthmatic matched controls. Of the entire cohort 57.1% were diagnosed as asthmatic. PEFR, the 1-second forced expiratory volume and forced expiratory flow of 50% vital capacity of children with a history of acute bronchiolitis were statistically significantly lower than in the control group (all P < 0.001). All the aforementioned measurements of children with/without asthma were also significantly lower than controls, while values of asthmatics were significantly lower than those of non-asthmatics. The incidence of asthma in childhood was independently associated with breast-feeding <3 months (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI]: 3.1-22.4), at least one positive skin prick test (aOR, 7.1; 95%CI: 2.8-18.1), male gender (aOR, 5.0; 95%CI: 2.2-11.5), evidence of moisture in the home environment (aOR, 2.9; 95%CI: 1.3-6.3) and presence of more than one house-resident smoking indoors (aOR, 4.9; 95%CI: 1.8-9.2). Children with a history of RSV-bronchiolitis during infancy have an increased risk for developing asthma in childhood, which was independently associated with male gender, breast-feeding <3 months, living in a home environment with moisture damage and/or tobacco smoke by two or more residents and sensitization to at least one aeroallergen. Children with a history of RSV bronchiolitis in infancy had lower spirometry in comparison to matched control group. The difference was more marked for asthmatic ones but remained significant even for non-asthmatic children.

Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy.

Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing asthma and recurrent wheezing. It is not known whether severe RSV infection itself causes persistent effects or is a marker of a "wheezy" predisposition. To determine the long-term immunological correlates of infantile bronchiolitis, interleukin (IL)-4 and interferon (IFN)-gamma responses to a panel of antigens were studied in a well-characterised cohort of 7-8-yr-old children with a history of severe RSV bronchiolitis in infancy. Peripheral blood lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in infancy and from 69 age-, sex- and location-matched controls were stimulated in vitro with RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN-gamma and IL-4 production were measured. IL-4 producing T-cells responding to RSV and cat antigens were significantly more frequent in exbronchiolitics. Other responses (including the IFN-gamma response to RSV) were equally strong in exbronchiolitics and controls. Respiratory syncytial virus infection primes memory T-cells that make interferon-gamma, but virus and aeroallergen-specific and interleukin-4 producing T-cells are also frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in infancy may increase the risk of allergic sensitisation by providing a local interleukin-4-rich environment, in which airborne allergens are first encountered.

Introduction. RSV and RAD: possibilities for prevention? The link between respiratory syncytial virus and reactive airway disease.

Introduction. RSV and RAD: possibilities for prevention? The link between respiratory syncytial virus and reactive airway disease.

Clinical perspectives on the association between respiratory syncytial virus and reactive airway disease.

Asthma is a leading cause of morbidity and mortality among children worldwide, as is respiratory syncytial virus (RSV). This report reviews controlled retrospective and prospective studies conducted to investigate whether there is an association between RSV bronchiolitis in infancy and subsequent development of reactive airway disease or allergic sensitization. Findings indicate that such a link to bronchial obstructive symptoms does exist and is strongest for children who experienced severe RSV illness that requires hospitalization. However, it is not yet clear what roles genetic predisposition and environmental or other risk factors may play in the interaction between RSV bronchiolitis and reactive airway disease or allergic sensitization. Randomized, prospective studies utilizing an intervention against RSV, such as a passive immunoprophylactic agent, may determine whether preventing RSV bronchiolitis reduces the incidence of asthma.