Viral Bronchiolitis In Infants Research Articles

Low peripheral blood chemokine (C-C motif) ligand 5 and tumor necrosis factor α gene expression is associated with unfavorable progression of respiratory syncytial virus bronchiolitis in infants

ObjectivesWe aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants’ peripheral blood is associated with bronchiolitis progression. MethodsWe conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room. ResultsInfants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007). ConclusionsAn inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis.

CQ Glucocorticoids for acute viral bronchiolitis in infants and young children

CQ Glucocorticoids for acute viral bronchiolitis in infants and young children

Toll-interacting protein polymorphisms in viral bronchiolitis outcomes.

Toll-interacting protein is a key factor in regulating innate immunity responses via gatekeeping Toll-like receptors. Genetic variance in innate immunity has been linked with susceptibility to infections. Children with viral bronchiolitis in infancy are at increased risk of later asthma. The aim was to evaluate the role of toll-interacting protein gene point mutations in severity of bronchiolitis and subsequent risk of asthma. Infants less than 6 months old were recruited during hospitalization due to bronchiolitis. In all, 166 children were prospectively followed up to age of 1.5, 6, and 11years. Clinical data on viral etiology and severity markers, and further post-bronchiolitis asthma and lung function outcomes were compared with genetic differences in two single-nucleotide point mutations rs116938768 and rs5743854 in the toll-interacting protein gene. Toll-interacting protein rs116938768 or rs5743854 did not show significant associations with severity markers or viral etiology of bronchiolitis. Follow-up data on current asthma or lung function at 6 or 11years of age after bronchiolitis were not associated with the investigated mutations. Toll-interacting protein gene point mutations in rs116938768 or rs5743854 were not involved with the clinical course of viral bronchiolitis in early infancy, and did not predict post-bronchiolitis asthma or lung function reduction by the age of 11years.

Respiratory Syncytial Virus Bronchiolitis in Infancy: The Acute Hospitalization Cost.

Introduction: Respiratory syncytial virus (RSV) bronchiolitis is among the leading causes of hospitalization in infants. Prophylaxis with palivizumab may reduce RSV infection, but its prescription is restricted to high-risk groups. The aim of the study is to retrospectively determine acute hospitalization costs of bronchiolitis.Materials and methods: Infants aged 1 month−1 year, admitted to Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of bronchiolitis from January 1 till December 31, 2017, were included in the study.Results: A total of 531 patients were enrolled in the study, and the mean age was 78.75 days. The main etiologic agent causing bronchiolitis was RSV, accounting for 58.38% of infections. The total cost of bronchiolitis hospitalization was 2,958,786 euros. The mean cost per patient was significantly higher in the case of RSV (5,753.43 ± 2,041.62 euros) compared to other etiology (5,395.15 ± 2,040.87 euros) (p = 0.04).Discussion: The study confirms the high hospitalization cost associated with bronchiolitis. In detail, in the case of RSV etiology, the cost was higher compared to other etiology, which is likely due to the longer hospitalization and the more frequent admission to the intensive cure department.Conclusion: This study highlights that bronchiolitis is an important cost item even in a tertiary hospital and that cost-effective interventions targeting RSV are increasingly urgent.

The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis.

Acute viral bronchiolitis causes significant mortality in the developing world, is the number one cause of infant hospitalisation in the developed world, and is associated with the later development of chronic lung diseases such as asthma. A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. However, much remains unknown about the underlying pathogenic mechanisms. Neutrophilic inflammation is the predominant phenotype observed in infants with both mild and severe disease, however, a clear understanding of the beneficial and deleterious effects of neutrophils is lacking. In this review, we describe the multifaceted roles of neutrophils in host defence and antiviral immunity, consider their contribution to bronchiolitis pathogenesis, and discuss whether new approaches that target neutrophil effector functions will be suitable for treating severe RSV bronchiolitis.

Long-lived regulatory T cells generated during severe bronchiolitis in infancy influence later progression to asthma.

The type-2 inflammatory response that promotes asthma pathophysiology occurs in the absence of sufficient immunoregulation. Impaired regulatory T cell (Treg) function also predisposes to severe viral bronchiolitis in infancy, a major risk factor for asthma. Hence, we hypothesized that long-lived, aberrantly programmed Tregs causally link viral bronchiolitis with later asthma. Here we found that transient plasmacytoid dendritic cell (pDC) depletion during viral infection in early-life, which causes the expansion of aberrant Tregs, predisposes to allergen-induced or virus-induced asthma in later-life, and is associated with altered airway epithelial cell (AEC) responses and the expansion of impaired, long-lived Tregs. Critically, the adoptive transfer of aberrant Tregs (unlike healthy Tregs) to asthma-susceptible mice failed to prevent the development of viral-induced or allergen-induced asthma. Lack of protection was associated with increased airway epithelial cytoplasmic-HMGB1 (high-mobility group box 1), a pro-type-2 inflammatory alarmin, and granulocytic inflammation. Aberrant Tregs expressed lower levels of CD39, an ectonucleotidase that hydrolyzes extracellular ATP, a known inducer of alarmin release. Using cultured mouse AECs, we identify that healthy Tregs suppress allergen-induced HMGB1 translocation whereas this ability is markedly impaired in aberrant Tregs. Thus, defective Treg programming in infancy has durable consequences that underlie the association between bronchiolitis and subsequent asthma.

Impact of Rhinovirus Infections in Children

Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection’s epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.

Relationships Between Adipokine Profiles, Physique Index, and Severity of Bronchiolitis in Infancy

ABSTRACTIntroduction: Relationships between adipokines, adiposity and severity of acute viral bronchiolitis in infancy have not been elucidated. Materials and Methods: We investigated the relationships between three serum adipokines (leptin, adiponectin and TNF-α), physique index (Kaup index) and clinical severity in 13 bronchiolitis infants. Seven healthy infants were enrolled as the control group. We used Modified Pulmonary Index Score (MPIS) to evaluate bronchiolitis severity. Results: No significant differences in adipokine levels were found between groups. In bronchiolitis infants, Kaup index negatively correlated with MPIS (r = −0.614, p = 0.03). A positive correlation was observed between the serum leptin/adiponectin ratio and MPIS (r = 0.618, p = 0.03), although correlations were not observed between respective serum adipokines levels and MPIS. Serum leptin and adiponectin had significantly negative correlations with age (r = 0.815, p = 0.001 and r = 0.566, p = 0.04, respectively), but not Kaup index. Conclusion: The severity of viral bronchiolitis in infancy may be related to the adipokine profile, but not adiposity.

Etiology and clinical features of viral bronchiolitis in infancy.

BackgroundBronchiolitis is a common lower respiratory tract infection in infancy. The aim of this review is to present the clinical profile of viral bronchiolitis, the different culprit viruses and the disease severity in relation to the viral etiology.Data sourcesDatabases including PubMed and Google Scholar were searched for articles about the clinical features of bronchiolitis and its viral etiology. The most relevant articles to the scope of this review were analyzed.ResultsCurrently there are two main definitions for bronchiolitis which are not identical, the European definition and the American one. The most common viral pathogen that causes bronchiolitis is respiratory syncytial virus which was identified in 1955; now many other viruses have been implicated in the etiology of bronchiolitis such as rhinovirus, adenovirus, metapneumovirus, and bocavirus. Several studies have attempted to investigate the correlation of bronchiolitis severity with the type of detected virus or viruses. However, the results were not consitent.ConclusionsFor the time being, the diagnosis of bronchiolitis remains clinical. The isolation of the responsible respiratory pathogens does not seem to confer to the prognosis of the disease severity.

Gene Polymorphism of Toll-Like Receptors and Lung Function at Five to Seven Years of Age after Infant Bronchiolitis.

AimToll-like receptors (TLR) play a crucial role in innate immunity, protecting the host from pathogens such as viruses. Genetic variations in TLRs have been associated with the severity of viral bronchiolitis in infancy and with the later occurrence of post-bronchiolitis asthma. The aim of the present study was to evaluate if there are any exploratory associations between TLR gene polymorphisms and lung function at 5 to 7 years of age in former bronchiolitis patients.MethodsWe performed impulse oscillometry (IOS) at the median age of 6.3 years for 103 children who had been hospitalized for bronchiolitis at less than six months of age. The main parameters evaluated were airway resistance and reactance at 5Hz in baseline and post-exercise measurements. Data on single nucleotide polymorphisms (SNP) of TLR1 rs5743618, TLR2 rs5743708, TLR6 rs5743810 and TLR10 rs4129009 (TLR2 subfamily) and TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992 and TLR 9 rs187084 were available for analyses.ResultsThe TLR4 rs4986790 wild genotype A/A was associated with a greater Rrs5 response (0.72 vs. -0.42, p = 0.03) to exercise. In TLR6 rs5743810, the minor allele T was associated with greater Rrs5 response (0.80 vs. -0.03, p = 0.04) to exercise. In TLR7 rs179008, the major allele A was associated with baseline decline in dRrs/df (-1.03 vs 0.61, p = 0.01) and increased Fres (2.28 vs. 0.89, p = 0.01) in girls.ConclusionAmong the nine studied TLRs, only TLR7 rs179008 showed some exploratory associations with post-bronchiolitis lung function deficiency, and polymorphisms of TLR4 rs4986790, and TLR6 rs5743810 in particular, with airway reactivity. These findings call for further confirmatory studies.

Interleukin-15 is associated with disease severity in viral bronchiolitis

Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.

Palivizumab epitope-displaying virus-like particles protect rodents from RSV challenge.

Respiratory syncytial virus (RSV) is the most common cause of serious viral bronchiolitis in infants, young children, and the elderly. Currently, there is not an FDA-approved vaccine available for RSV, though the mAb palivizumab is licensed to reduce the incidence of RSV disease in premature or at-risk infants. The palivizumab epitope is a well-characterized, approximately 24-aa helix-loop-helix structure on the RSV fusion (F) protein (F254-277). Here, we genetically inserted this epitope and multiple site variants of this epitope within a versatile woodchuck hepadnavirus core-based virus-like particle (WHcAg-VLP) to generate hybrid VLPs that each bears 240 copies of the RSV epitope in a highly immunogenic arrayed format. A challenge of such an epitope-focused approach is that to be effective, the conformational F254-277 epitope must elicit antibodies that recognize the intact virus. A number of hybrid VLPs containing RSV F254-277 were recognized by palivizumab in vitro and elicited high-titer and protective neutralizing antibody in rodents. Together, the results from this proof-of-principle study suggest that the WHcAg-VLP technology may be an applicable approach to eliciting a response to other structural epitopes.

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.

Lung function by impulse oscillometry at age 5–7 years after bronchiolitis at age 0–6 months

Viral bronchiolitis in infancy has been associated with increased bronchial reactivity and reduced lung function in later childhood and even in adulthood. However, lung function at preschool age is less studied, mainly due to technical difficulties. The purpose of the study was to evaluate lung function and bronchial reactivity at preschool age in children who were hospitalized for bronchiolitis in early infancy. Airway resistance and reactance, and bronchial reactivity to exercise were studied with impulse oscillometry (IOS) at the mean age of 6.3 years in 103 children hospitalized for bronchiolitis at less than 6 months of age. In baseline lung-function measurement, resistance (n = 8; 7.8%) or reactance (19; 18.4%) at 5 Hz were pathological in 20% of children compared to Finnish population-based height-adjusted reference values. Increased bronchial reactivity by exercise challenge (5; 4.9%) or bronchodilatation (11; 10.7%) tests was present in 16%. Irreversible changes were revealed in only one case. Though reduced lung function and increased airway reactivity were rather common, evidence for persistent lung function reduction was rare, less than 1%, at preschool age in children hospitalized for bronchiolitis caused mainly by respiratory syncytial virus at age less than 6 months.

Glucocorticoids for Acute Viral Bronchiolitis in Infants and Young Children

Are glucocorticoids, alone or combined with bronchodilators, associated with reduced admission rates, length of stay, or improvements in clinical severity scores without increased adverse effects in infants and young children with acute viral bronchiolitis? There is no consistent clinically relevant association of single therapy with systemic or inhaled glucocorticoids and improved outcomes in either outpatient or inpatient settings. Exploratory evidence suggests that combined glucocorticoids and nebulized epinephrine may be associated with lower hospitalization rates in outpatients, but these findings must be interpreted cautiously.

Neonatal Bronchial Hyperresponsiveness Precedes Acute Severe Viral Bronchiolitis in Infants

BL Chawes, P Poorisrisak, SL Johnston, H Bisgaard. J Allergy Clin Immunol. 2012;130(2):354–361, e3 To determine if host factors in neonates expressed as bronchial hyperresponsiveness precede later development of acute severe bronchiolitis. Previous studies showed that abnormal neonatal pulmonary function was associated with asthma by age 7 years. This study was nested in the Copenhagen Prospective Studies on Asthma in Childhood, a prospective study of a birth cohort of 411 neonates born to mothers with a history of asthma. Infants were enrolled at 1 month of age. Exclusion criteria included symptoms of lower …

Glucocorticoids for acute viral bronchiolitis in infants and young children.

Previous systematic reviews have not shown clear benefit of glucocorticoids for acute viral bronchiolitis, but their use remains considerable. Recent large trials add substantially to current evidence and suggest novel glucocorticoid-including treatment approaches. To review the efficacy and safety of systemic and inhaled glucocorticoids in children with acute viral bronchiolitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 12), MEDLINE (1950 to January week 2, 2013), EMBASE (1980 to January 2013), LILACS (1982 to January 2013), Scopus® (1823 to January 2013) and IRAN MedEx (1998 to November 2009). Randomised controlled trials (RCTs) comparing short-term systemic or inhaled glucocorticoids versus placebo or another intervention in children under 24 months with acute bronchiolitis (first episode with wheezing). Our primary outcomes were: admissions by days 1 and 7 for outpatient studies; and length of stay (LOS) for inpatient studies. Secondary outcomes included clinical severity parameters, healthcare use, pulmonary function, symptoms, quality of life and harms. Two authors independently extracted data on study and participant characteristics, interventions and outcomes. We assessed risk of bias and graded strength of evidence. We meta-analysed inpatient and outpatient results separately using random-effects models. We pre-specified subgroup analyses, including the combined use of bronchodilators used in a protocol. We included 17 trials (2596 participants); three had low overall risk of bias. Baseline severity, glucocorticoid schemes, comparators and outcomes were heterogeneous. Glucocorticoids did not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo (pooled risk ratios (RRs) 0.92; 95% confidence interval (CI) 0.78 to 1.08 and 0.86; 95% CI 0.7 to 1.06, respectively). There was no benefit in LOS for inpatients (mean difference -0.18 days; 95% CI -0.39 to 0.04). Unadjusted results from a large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes. Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy.

Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants

BackgroundRespiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors reflected in pre-existing increased bronchial responsiveness.ObjectiveWe sought to compare bronchial responsiveness and lung function in 1-month-old neonates who later develop acute severe bronchiolitis with those who do not.MethodsWe measured infant lung function (n = 402) and bronchial responsiveness to methacholine (n = 363) using the raised-volume rapid thoracoabdominal compression technique before any respiratory symptoms in 1-month-old neonates from the Copenhagen Prospective Study of Asthma in Childhood birth cohort born to mothers with asthma. The children were prospectively monitored for respiratory symptoms and given a diagnosis of acute severe bronchiolitis according to a fixed algorithm.ResultsThirty-four (8.5%) infants had acute severe bronchiolitis before 2 years of age, 21 (62%) were hospitalized, and 23 (67%) of the cases were associated with respiratory syncytial virus. Children who later had acute severe bronchiolitis irrespective of viral species had a 2.5-fold increased responsiveness to methacholine (provocative dose of methacholine producing a 15% decrease in transcutaneous oxygen pressure [PD15]) at age 1 month compared with control subjects (median PD15 in cases vs control subjects, 0.13 vs 0.33 μmol; P = .01), whereas differences in baseline airflow were not significant for forced expiratory volume at 0.5 seconds (mean z score for cases vs control subjects, −0.18 vs −0.01; P = .36) and forced expiratory flow at 50% of forced vital capacity (mean z score for cases vs control subjects, −0.37 vs −0.09; P = .13).ConclusionBronchial hyperresponsiveness in at-risk neonates precedes acute severe bronchiolitis in response to infections with respiratory tract virus.

Risk of Childhood Asthma Following Infant Bronchiolitis During RSV Season

To the Editor: The etiology of asthma remains unclear but is thought to include non-modifiable risk factors such as family history and genetic predisposition, as well as potentially modifiable risk factors including viral bronchiolitis in infancy(1;2). During the winter months, the predominant virus detected in infants with viral bronchiolitis is respiratory syncytial virus (RSV)(3). By 1 year of age approximately 70% of children have been infected with RSV, and this increases to almost 100% by 2 years of age(4). Infant RSV bronchiolitis is associated with recurrent wheeze or asthma throughout childhood and even into early adulthood(5;6), with a dose-response relationship identified between the severity of the bronchiolitis and the risk of developing asthma(7), and evidence for a causal relationship(8). The aim of our study was to determine what proportion of childhood asthma is associated with infant bronchiolitis during RSV season. We analyzed cohort data of children born from 1996–2003 cared for at Northern California Kaiser Permanente (KPNC), an integrated healthcare delivery system, and children born from 1995–2003 enrolled in Tennessee Medicaid (TennCare). KPNC and TennCare provide health insurance for approximately one-third of Northern California residents and approximately one-half of infants born in Tennessee, respectively. Eligible infants had a minimum gestation age of 32 weeks, no chronic lung disease, and were continuously enrolled in either TennCare or KPNC during the first year of life. The main predictor variable was infant bronchiolitis during RSV season defined by ICD-9 codes for bronchiolitis and limited to the RSV season, October through March, during the first year of life. The main outcome variable was early childhood asthma determined using an algorithm of ICD-9 codes for asthma and asthma-specific medication utilization between ages 4.5–6 years. The Vanderbilt University Institutional Review Board and the KPNC Institutional Board for the Protection of Human Subjects approved the study. The Bureau of TennCare approved use of Tennessee Medicaid data. To ascertain the proportion of childhood asthma in the TennCare or KPNC population that is associated with bronchiolitis exposure during RSV season, we calculated both the attributable risk of infants with a bronchiolitis event during infancy, and the population attributable risk. We estimated the attributable fraction of bronchiolitis from adjusted risk ratios that were calculated from multivariable Poisson regression models with a robust error variance for the early childhood asthma outcome. Adjustment covariates included gender, race, gestational age, birthweight, siblings, maternal age, and maternal smoking. Statistical analyses were performed with R version 2.12.1 software. A total of 264,010 infant births (KPNC 81,550, TennCare 182,460) were included in this study and followed until 6 years of age. Table I highlights key characteristics of the two cohorts. Compared to the TennCare population, the KPNC population had more Hispanic and Asian participants, less African American participants, higher rates of maternal education beyond high school, and lower rates of maternal smoking. Overall, 15% of infants had bronchiolitis during RSV season. The proportion of children diagnosed with asthma among the KPNC and TennCare cohorts was 8% and 12%, respectively, for those without a history of infant bronchiolitis during RSV season, and 16% and 23%, respectively, for those with a history of infant bronchiolitis during RSV season. The population attributable risk for asthma contributed by infant bronchiolitis during RSV season was 10% for the KPNC cohort, and among the subset of children with infant bronchiolitis during RSV season, the attributable risk was 49% (95% CI:47%,52%); in TennCare, it was 13% and 47% (95% CI:45%,48%), respectively (See Fig 1). The unadjusted risk ratio of childhood asthma following infant bronchiolitis during RSV seaso100 n for KPNC was 1.97 (95% CI:1.87,2.09) and the multivariate adjusted risk ratio of childhood asthma following infant bronchiolitis during RSV season was 1.94 (95% CI:1.84,2.05); for TennCare it was 1.87 (95% CI:1.82,1.92) and 1.81 (95% CI:1.77,1.86), respectively. In our analysis restricting to term infants (gestational age ≥37 weeks), results remain unchanged (data not shown). FIG 1 Attributable risk of asthma due to infant bronchiolitis during RSV season. *Multivariable Poisson regression analyses were used to calculate risk ratios within the KPNC and TennCare populations. In both the KPNC and TennCare cohorts, the proportion of children who developed asthma was almost two times higher in children with a history of infant bronchiolitis during RSV season as compared to the children who did not have a history of infant bronchiolitis during RSV season. The almost identical attributable risk and population attributable risk findings are notable given the significant differences between the two populations. Adjustment of risk ratios for potential confounders did not change the results. Despite the strengths of our large population-based study, several limitations deserve mention. This study relied on existing electronic data; however, the use of electronic data has been previously validated as both sensitive and specific(9). Secondly, the study was unable to detect infants with asymptomatic or mild bronchiolitis during RSV season as well as those who did not seek treatment. In addition, we were unable to confirm the diagnosis of RSV as the etiology of bronchiolitis events although prior studies support that the majority of infant bronchiolitis events during RSV season are attributable to RSV(3). In a retrospective study by Stemple et al. in which bronchiolitis was defined by ICD-9 codes for bronchiolitis, RSV was detected in the nasal wash samples of 77% of children under 2 years of age collected between October and April(10). By limiting our study to bronchiolitis episodes during the winter months, RSV is likely to be the associated viral pathogen. Lastly, while human rhinovirus (RV) infection has also been implicated in asthma inception, infant RV bronchiolitis is far less common than infant RSV bronchiolitis, and occurs in older infants, those born to parents with asthma, or those who have already been allergically sensitized, suggesting that rather than being causal, that RV bronchiolitis is a clinical biomarker of future asthma risk(11–13). In summary, in two representative US populations with significantly varying baseline characteristics, there were consistent findings that nearly 50% of asthma cases in children with a history of infant bronchiolitis during RSV season were associated with bronchiolitis. On a population level, 13% of asthma was associated with infant bronchiolitis during RSV season. The mechanism to explain how infant RSV infection results in the subsequent development of asthma remains unclear, but if truly causal in nature as supported by observational(8) and mechanistic(14) studies, our findings indicate up to 13% of asthma cases could be prevented by eliminating infant bronchiolitis during RSV season. Thus, next steps are to determine if preventing or altering host response to infant RSV infections decreases both the incidence and severity of childhood asthma as a primary asthma prevention strategy.

Evaluation of an Alternative Chest Physiotherapy Method in Infants With Respiratory Syncytial Virus Bronchiolitis

We proposed a new chest physiotherapy (CPT) secretion clearance method to treat respiratory syncytial virus bronchiolitis in infants. Our new CPT method consists of 15 prolonged slow expirations, then 5 provoked cough maneuvers. We randomized 20 infants (mean age 4.2 months) into 2 groups: 8 patients received 27 sessions of nebulization of hypertonic saline; 12 patients received 31 sessions of nebulization of hypertonic saline followed by our new CPT method. We used the Wang clinical severity scoring system (which assesses wheezing, respiratory rate, retractions, and general condition) and measured S(pO(2)) and heart rate before each CPT session (T0), immediately after the 30-min session (T30), and 120 min after the session (T150). Within the groups: in the first group, Wang score was significantly lower at T150 than at T0: 4.6 vs 5.0 (P = .008). In the new-method-CPT group, Wang score was significantly lower at T30 (3.6 vs 4.3, P = .001) and at T150 (3.7 vs 4.3, P = .002). Wheezing score was significantly lower at T150 than at T0 (1.1 vs 1.2, P = .02) in the first group, and in the new-method-CPT group at T30 than at T0 (0.8 vs 1.3, P = .001) and at T150 than at T0 (0.9 vs 1.3, P = .001). Between the groups: at T30 the improvement was significantly better in the new-method-CPT group for overall Wang score (P = .02), retractions (P = .05), respiratory rate (P = .001), and heart rate (P < .001). At T150 the Wang score was not significantly different between the groups. At T30 (versus T0) the difference in percent gain between the groups was significant for Wang score (P = .004), wheezing (P = .001), and heart rate (P = .02). Over 5-hospital days, the daily baseline (T0) Wang score decreased significantly in the new-method-CPT group (P = .002), whereas it did not in the first group. There were no adverse events. Average hospital stay was not significantly different between the groups. Our new CPT method showed short-term benefits to some respiratory symptoms of bronchial obstruction in infants with acute respiratory syncytial virus bronchiolitis.