Bronchiolitis In Young Children Research Articles

Disease Burden of RSV Infections and Bronchiolitis in Young Children (< 5 Years) in Primary Care and Emergency Departments: A Systematic Literature Review.

Respiratory syncytial virus (RSV) is the most common cause of acute respiratory infections in young children. Limited data are available on RSV disease burden in primary care and emergency departments (EDs). This review synthesizes the evidence on population-based incidence rates of RSV infections in young children (< 5 years) in primary care and EDs. A systematic literature review was performed in PubMed and Embase. Studies reporting yearly population-based RSV incidence rates in primary care and EDs were included. A total of 4244 records were screened and 32 studies were included, conducted between 1993 and 2019. Studies were mainly performed in high-income countries (n = 27), with 15 studies in North America and 10 studies in Europe. There was significant variability in study methodology and setting among studies, resulting in considerable variability in reported incidence rates. Incidence rates were higher in primary care-ranging from 0.8 to 330 (median = 109) per 1000 population-compared to EDs (7.5-144.0, median = 48). The highest incidence rates were reported in infants. Additionally, incidence rates were higher in high-income countries and in studies using laboratory-confirmed RSV cases compared to studies using bronchiolitis ICD-codes (non-laboratory confirmed). Our study found that a substantial number of children under 5 years of age attend primary care settings and EDs, every year for RSV infections. Due to the considerable heterogeneity in study methodology, it was impossible to draw definitive conclusions regarding factors explaining differences in reported incidence rates. Additionally, more studies in low- and middle-income countries are recommended.

Prevalence, Symptoms, and Treatment of Bronchiolitis and Pneumonia in Pediatric Patients

Background: Pediatric respiratory diseases, particularly pneumonia and bronchiolitis, pose significant health challenges worldwide. Understanding their prevalence, symptomatology, and effective treatment is crucial for improving pediatric health outcomes. Objective: This study aimed to investigate the occurrence, symptoms, and treatment outcomes of pneumonia and bronchiolitis in children under five years of age at the GKMC Swabi Department of Pediatrics. Methods: The study design was retrospective study, conducted from January 2022 to January 2023, at GKMC Swabi Department of Paediatrics included 100 pediatric patients diagnosed with either pneumonia (n=40) or bronchiolitis (n=60). Patients aged 0 to 10 years with respiratory symptoms indicative of these diseases were selected, excluding those with severe comorbidities or chronic respiratory disorders. Data on demographic characteristics, clinical symptoms, diagnostic test results, and treatment outcomes were collected from medical records. Diagnosis was based on clinical examination, chest Xrays, blood tests, and other relevant procedures. Descriptive statistics were used for data analysis, utilizing SPSS version 25. Results: The mean age of patients was 3.2 years (±0.5). Gender distribution was equal, with a 50/50 maletofemale ratio. Bronchiolitis and pneumonia accounted for 60% and 40% of cases, respectively. Common symptoms included cough (88%), fever (80%), and difficulty in breathing (65%). The positive treatment response was observed in 77.5% of cases, with 32.5% requiring hospitalization. The average duration of hospital stay was 5.0 days (±1.3). Secondary symptoms like wheezing (35%), chest pain (17.5%), runny nose (32.5%), and vomiting (17.5%) were also noted. Conclusion: The study highlights the significant burden of pneumonia and bronchiolitis in young children and the effectiveness of current treatment modalities. The findings emphasize the need for early recognition and treatment of these diseases, along with continued research into preventive measures and longterm outcomes. Keywords: Pediatric Respiratory Diseases, Pneumonia, Bronchiolitis, Child Health, Hospitalization, Treatment Outcomes.

Clinical course and complications of RSV versus non-RSV bronchiolitis in hospitalised children

Introduction and objective: Bronchiolitis in young children often requires hospitalisation. It is mostly caused by respiratory syncytial virus (RSV) and aetiological factors may be associated with clinical presentation and prognosis. We aimed to compare the epidemiology, clinical features, severity and management of RSV and non-RSV bronchiolitis. Materials and methods: This cross-sectional retrospective study included hospitalised children under 2 years of age. Children with a positive rapid antigen diagnostic test and/or molecular study were included in the RSV group, while those with a negative result were classified as non-RSV bronchiolitis. We compared patient history, clinical presentation, disease severity including passive oxygen therapy, intensive care unit transfer, death, length of hospital stay, presence of complications, oxygen saturation &lt;92%, acidosis, hypercapnia and treatment used. Results: The study included 524 patients (median age 2 months): 462 (88%) RSV and 62 (12%) non-RSV cases. A 7-fold increase in the number of cases was observed between 2010–2011 and 2017–2018. A univariate regression model showed lower odds of family history of atopy (odds ratio, OR = 0.46), higher odds of cough (OR = 4.74), apathy (OR = 2.61), feeding difficulties (OR = 2.03) and vomiting (OR = 3.34) in the RSV group. RSV patients required oxygen therapy (OR = 3.78) and antibiotics (OR = 2.82) more frequently, received inhaled steroid therapy for longer (9 vs. 8 days) and had a higher likelihood of complications (OR = 4.24). A multivariate model showed statistical significance for cough (OR = 6.22), oxygen therapy (OR = 4.43) and complications (OR = 15.95). Conclusions: We observed an increasing trend in bronchiolitis hospitalisations, including RSV bronchiolitis, which was associated with a more severe disease course. No significant clinical features were identified to replace laboratory tests.

Role of the cAMP-PKA-NF-κB pathway in Mucin1 over-expression in A549 cells during Respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.

Значення васкулярної молекули клітинної адгезії-1 та білка CC16 при бронхіоліті в дітей раннього віку

Given the severity of the course of bronchiolitis in young children, especially with a burdened allergic history, the search for biomarkers for early diagnosis and prognosis of the disease is urgent. Purpose - to substantiate the expediency of determining the levels of VCAM-1 and CC16 in blood serum in bronchiolitis in young children. Material and methods. The main group consisted of 34 children with bronchiolitis without a serious allergic history. The comparison group included 33 children who suffered from bronchiolitis and had a severe allergic history. The control group consisted of 25 conditionally healthy children. The clinical and laboratory examination consisted in determining the levels of VCAM-1 and CC16 in blood serum using the immunoenzymatic method. Results. The level of VCAM-1 in blood serum was established (55.5±1.12 ng/ml) in the children of the main group, while in the children of the comparison group the average value (164.9±1.1 ng/ml) of this indicator was 3 times higher, (AOR=3; 95% CI: 1.48-6.12; p&lt;0.05). In children of the control group, the average level of VCAM-1 in blood serum was (41.6±1.32 ng/ml). Analysis of the average level of CC16 protein in blood serum revealed its significant increase in children of the main group (41.2±1.24 ng/ml) compared to the indicator of children with bronchiolitis with a severe allergic history (22.8±1.64 ng/ml ml), (AOR=1.6; 95% CI: 0.8-3.2; p&lt;0.05). In children of the control group, the average value of the CC16 protein was within the reference values (16.2±2.43 ng/ml). Conclusions. In young children with bronchiolitis, it is advisable to determine the level of CC16 and VCAM-1 protein in blood serum. It was found that the level of SS16 protein in blood serum was significantly lower in children with a severe allergic history compared to children without a severe allergic history. On the other hand, regarding the level of VCAM-1 in blood serum, its value was significantly increased in the majority of children with severe allergic history. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Respiratory Syncytial Virus is the Most Common Causative Agent of Viral Bronchiolitis in Young Children: An Updated Review.

Viral bronchiolitis is a common condition and a leading cause of hospitalization in young children. This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV. A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR "respiratory syncytial virus infection". The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article. Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young children. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagnosis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effective. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramuscularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood. Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.

A mechanism for transcriptional regulation of innate immune response genes by RSV NS1 protein.

Human Respiratory syncytial virus (RSV) is a main cause of bronchiolitis in young children and a still unmet target for pediatric vaccines and antiviral drugs. RSV has evolved a unique strategy to evade host immune response by coding for two non-structural proteins NS1 and NS2, identified as interferon antagonists. Recently it was suggested that NS1 modulates host gene transcription via interactions with chromatin and the Mediator complex. Moreover, the C-terminal RSV NS1 α-helix, α3, was reported to be involved in modulation of host response and gene expression. Here, after identifying the MED25 Mediator subunit as an NS1 interactor in a yeast two-hybrid screen, we demonstrated that NS1 directly interacts with MED25 in cells and in vitro. We assigned this interaction to the MED25-ACID domain, a target of viral transcriptional activators, such as Herpes simplex virus VP16. We showed that NS1 α3 primarily targets the VP16 transactivation domain (TAD) binding site of MED25-ACID. In particular, we found out that NS1 could compete with the TAD of ATF6α, a master regulator of ER stress response activated upon viral infection, for MED25-ACID binding. The affinity for MED25-ACID determined using an NS1-α3 peptide was surprisingly low, as compared to that of full-length NS1. Although this can be partly explained by the unfolded state of the isolated peptide, it suggests the presence of a second binding site. We indeed observed that the NS1Δα3 deletion mutant was able to bind to MED25-ACID. Altogether our findings suggest a mechanism for transcription modulation of specific genes by RSV NS1, and hence for modulation of the host immune response, where NS1 competes with cellular TADs for recruitment of the Mediator MED25 subunit.

Trends in the global burden of lower respiratory infections: the knowns and the unknowns

Lower respiratory infections (LRIs) are a major killer globally, especially at the extremes of age—bronchiolitis in young children and pneumonia in all ages are the main contributors to LRI mortality. In The Lancet Infectious Diseases,1 the GBD 2019 LRI Collaborators provide updated modelled estimates of the global burden of LRIs by age and sex.

Susceptibility to Rhinovirus-induced Early Wheezing as a Risk Factor for Subsequent Asthma Development

Abstract: Rhinovirus is one of the two most common viral agents that cause bronchiolitis in young children. During the first 12 months, it is second to the respiratory syncytial virus, but after 12 months, it begins dominating the statistics. Wheezing and dry cough are typical clinical symptoms indicative of rhinovirus-induced bronchiolitis, although overlap of symptoms with other virus infections is common. Several studies have shown that atopic predisposition and reduced interferon responses increase susceptibility to rhinovirus-induced wheezing. More recent studies have found that certain genetic variations at strong asthma loci also increase susceptibility. Rhinovirus-induced wheezing in the early years of life is known to increase the risk of subsequent asthma development and may be associated with airway remodeling. This risk is increased by aeroallergen sensitization. Currently, there are no clinically approved preventive treatments for asthma. However, studies show promising results indicating that children with rhinovirus-affected first-time wheezing respond to bronchodilators in terms of less short-term symptoms and that controlling airway inflammatory responses with anti-inflammatory medication may markedly decrease asthma development. Also, enhancing resistance to respiratory viruses has been a topic of discussion. Primary and secondary prevention strategies are being developed with the aim of decreasing the incidence of asthma. Here, we review the current knowledge on rhinovirus-induced early wheezing as a risk factor for subsequent asthma development and related asthma-prevention strategies.

Polysaccharides from Platycodonis Radix ameliorated respiratory syncytial virus-induced epithelial cell apoptosis and inflammation through activation of miR-181a-mediated Hippo and SIRT1 pathways

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in young children, but there are few safe and effective treatments for this disease. Platycodonis Radix is widely used as an antitussive and expectorant drug for preventing various diseases in lower respiratory tract, in which the polysaccharides are one of the main bioactivity constituents. In this study, the protective effects of the P. Radix polysaccharides (PRP) against RSV-induced bronchiolitis in juvenile mice and RSV-induced apoptosis of epithelial HEp-2 cells were investigated. The results showed that PRP obviously decreased the levels of IL-1β, IL-4, IL-6, TNF-α, IFN-γ and TSLP in lung tissues, and reduced the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) of RSV-infected mice. Furthermore, it reduced the apoptosis of RSV-infected HEp-2 cells and remarkably inhibited the mRNA expressions of RSV L gene, which indicated that PRP affected transcription and replication of RSV in host cells. Compared with that in RSV-infected group, miR-181a-5p in the PRP-treated group presented the highest relative abundance and its expression was violently reduced by approximately 30%. Mechanistically, PRP had the similar effects as miR-181a-5p antagomir on RSV-induced apoptosis and inflammation in HEp-2 cells via upregulating BCL2, MLL3 and SIRT1, which could be reversed by miR-181a-5p mimic. Therefore, it demonstrated that PRP not only protected against RSV-induced lung inflammation in mice but also inhibited apoptosis of RSV-infected HEp-2 cells via suppressing miR-181a-5p and transcriptionally activating Hippo and SIRT1 pathways.

Role of age and birth month in infants hospitalized with RSV-confirmed disease in the Valencia Region, Spain.

BackgroundRSV is the leading cause of hospital admissions in infants and the principal cause of bronchiolitis in young children. There is a lack of granular data on RSV‐associated hospitalization per season using laboratory confirmed results. Our current study addresses this issue and intends to fill this gap.MethodsThe study was conducted from 2014 through 2018, in 4 to 10 hospitals in the Valencia Region, Spain. Infants included in this study were admitted in hospital through the Emergency Department with a respiratory complaint and tested by RT‐PCR for RSV in a central laboratory.ResultsIncidence rates of RSV‐associated hospitalization varied by season and hospital. Overall, the highest incidence rates were observed in 2017/2018. RSV‐associated hospitalization was highest in infants below 3 months of age and in those born before or at the beginning of the RSV season. Almost 54% of total infants hospitalized with laboratory confirmed RSV were found to be born outside the season, from April to October. The RSV positivity rate by ICD‐10 discharged codes varied by season and age with results from 48% to 57% among LRI (J09‐J22).ConclusionThe study was instrumental in bringing forth the time unpredictability of RSV epidemics, the critical impact of age, and the comparable distribution of RSV‐associated hospitalization in infants born on either side of the RSV season. These data could help in better characterization of the population that drives the healthcare burden and is crucial for the development of future immunization strategies, especially with upcoming vaccines in against RSV.

Rapid weight gain in early life is associated with severity of respiratory syncytial virus (RSV) bronchiolitis in children.

This study aimed to investigate whether rapid weight gain in early life was associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children. We retrospectively reviewed 190 patients (1-24 months) hospitalized for RSV bronchiolitis. Parameters of bronchiolitis severity were compared between rapid (change in weight z-score from birth >0.67, n = 65) and normal weight gain groups (n = 125). We assessed for correlations between bronchiolitis severity and weight gain. Linear regression was performed to predict for bronchiolitis severity based on weight gain, controlling for covariates. SPSS was used for statistical analyses. The rapid weight gain group had longer mean durations of tachypnea (2.3±2.0 vs. 1.7±1.8 days, P = 0.027), wheezing (3.2±2.5 vs. 1.6±1.8 days, P < 0.001), and chest retractions (1.5±2.2 vs. 0.6±1.3 days, P = 0.007). Correlations of weight gain with tachypnea (r = 0.146), wheezing (r = 0.279), and chest retractions (r = 0.179) were statistically significant. Weight gain predicted for tachypnea (B = 0.485, P = 0.013) and wheezing (B = 0.846, P = 0.001) durations after adjusting for covariates of severity (age, sex, current weight, RSV type, coinfection, recurrent bronchiolitis, hospital stay, fever, oxygen supplementation, maximal respiratory and heart rates, and laboratory indices). Our findings suggest an association between weight gain and severity of RSV bronchiolitis in young children. Weight gain was significantly associated with the durations of tachypnea and wheezing. The trajectory of weight gain in early life may play a significant role in the clinical course of RSV bronchiolitis.

Longitudinal plasma cytokine concentrations and recurrent wheezing after RSV bronchiolitis

BackgroundRespiratory syncytial virus (RSV) bronchiolitis in young children has been associated with increased risk for developing recurrent wheezing, but the underlying mechanisms, are not completely defined. We hypothesized that RSV induces a disregulated immune response defined by a distinct cytokine profile in infants at increased risk for developing recurrent wheezing. MethodsPreviously healthy infants less than 12 months of age hospitalized with a first episode of RSV bronchiolitis were enrolled and blood samples and clinical and epidemiological data collected. A group of healthy non-infected controls were enrolled in parallel. Children were followed longitudinally and subsequent blood samples collected in RSV-infected infants at one month and at one year after hospital discharge to measure longitudinal plasma concentrations of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17 and IL1-β. Risk of post-RSV wheezing was assessed by Poisson modelling. ResultsFrom October 2008 to March 2012 we enrolled 37 infants hospitalized with RSV bronchiolitis and 9 healthy age-matched controls. Within the RSV cohort, 17 (46%) children developed recurrent wheezing within the following 12 months. Plasma cytokine profiles measured during the acute infection were similar in children who developed recurrent wheezing versus those who did not, but lower in healthy controls vs RSV infants who subsequently developed wheezing. At one month and 12 months post-acute RSV infection, infants who developed recurrent wheezing had higher IFN-γ plasma concentrations versus those with no-wheezing (p < 0.05). Moreover, IFN-γ concentrations were identified as independent predictor of post-RSV wheezing. ConclusionsChildren with RSV-associated recurrent wheezing had persistently elevated plasma concentrations of IFN-γ for a year after acute infection, suggesting that this cytokine could be used as a biomarker for risk of recurrent wheezing and possibly plays a role in the pathogenesis of this condition.

Is multiple viral infection a predictor of severity in children with acute bronchiolitis?

Background:Acute bronchiolitis is a common cause of pediatric emergency department admissions in children younger than 2.Objectives:The study aimed to compare the outcomes and the severity of bronchiolitis in young children with multiple simultaneous respiratory virus infections to those with single virus infection and no virus identified group.Methods:Patients with moderate and severe bronchiolitis who visited our emergency department between November 2016 and May 2017 had nasopharyngeal swab samples results tested by multiplex polymerase chain reaction were included in the study. Patients’ characteristics, clinical severity of illness, and outcome (pediatric emergency department discharge, admission to ward or pediatric intensive care unit) were compared with the detected viral agents.Results:A total of 241 patients were included in the study. The mean age was 7.8 ± 2.6 months and 147 (61%) were male. Respiratory syncytial virus was the most common detected viral agent in 108 (39%) cases followed by human rhinoviruses in 67 (24%). Respiratory syncytial virus was found more frequently in February and March (p = 0.002). Leukocytosis and pneumonia were more likely observed in patients with only human rhinoviruses (+) subjects (p = 0.010 and p = 0.015, respectively). Intensive care hospitalization rate (16%) was higher in patients with multiple viral agents (p = 0.004).Conclusions:Respiratory syncytial virus remains the most common detected viral agent in acute bronchiolitis patients. While the pathogens detected were seasonally different, there was a significant relationship between leukocytosis, bacterial pneumonia, and detected viral agents. The disease was more severe in patients with multiple viral agents.

Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through PAD-4 and necroptosis pathways activation

Respiratory syncytial virus (RSV) is a major cause of diseases of the respiratory tract in young children and babies, being mainly associated with bronchiolitis. RSV infection occurs primarily in pulmonary epithelial cells and, once infection is established, an immune response is triggered and neutrophils are recruited. In this study, we investigated the mechanisms underlying NET production induced by RSV. We show that RSV induced the classical ROS-dependent NETosis in human neutrophils and that RSV was trapped in DNA lattices coated with NE and MPO. NETosis induction by RSV was dependent on signaling by PI3K/AKT, ERK and p38 MAPK and required histone citrullination by PAD-4. In addition, RIPK1, RIPK3 and MLKL were essential to RSV-induced NETosis. MLKL was also necessary to neutrophil necrosis triggered by the virus, likely promoting membrane-disrupting pores, leading to neutrophil lysis and NET extrusion. Finally, we found that RSV infection of alveolar epithelial cells or lung fibroblasts triggers NET-DNA release by neutrophils, indicating that neutrophils can identify RSV-infected cells and respond to them by releasing NETs. The identification of the mechanisms responsible to mediate RSV-induced NETosis may prove valuable to the design of new therapeutic approaches to treat the inflammatory consequences of RSV bronchiolitis in young children.

Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein

Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus–cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural and immunological studies. Here, we engineer a pre-fusion-stabilized hMPV F ectodomain and determine its crystal structure to 2.6 Å resolution. This structure reveals molecular determinants of strain-dependent acid-induced fusion, as well as insights into refolding from pre- to post-fusion conformations. A dense glycan shield at the apex of pre-fusion hMPV F suggests that antibodies against this site may not be elicited by host immune responses, which is confirmed by depletion studies of human immunoglobulins and by mouse immunizations. This is a major difference with pre-fusion F from human respiratory syncytial virus (hRSV), and collectively our results should facilitate development of effective hMPV vaccine candidates.

Serum YKL-40 levels may help distinguish exacerbation of post-infectious bronchiolitis obliterans from acute bronchiolitis in young children.

Children with post-infectious bronchiolitis obliterans (PIBO) are frequently hospitalized with acute exacerbation, but clinical differentiation of PIBO exacerbation from acute bronchiolitis is often challenging, which may result in treatment delay and chronic lung function impairment. We aimed to examine whether serum YKL-40 and growth factors could be markers for PIBO exacerbation. Thirty-seven children admitted with acute exacerbation of PIBO were enrolled and studied retrospectively. Diagnosis of PIBO was based on clinical history of acute respiratory infection followed by persistent airway obstruction and characteristic findings in high-resolution computed tomography. Serum levels of YKL-40, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and platelet-derived growth factor (PDGF)-BB were measured on admission. The biomarkers were also examined in children admitted with acute bronchiolitis serving as positive controls (N = 30) and in age-matched controls (N = 20). Only YKL-40 levels were found to be significantly higher in PIBO patients with exacerbation compared with that in bronchiolitis patients and showed a positive correlation with the severity of disease before diagnosis of PIBO. Conclusion: Our results suggest that measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from acute bronchiolitis in young children. What is Known: • The children with post-infectious BO (PIBO) usually have recurrent wheezing and need frequent hospitalization due to acute exacerbation during the first disease years. • Clinical differentiation of PIBO exacerbation from acute bronchiolitis in young children is often challenging, which may result in treatment delay and chronic lung function impairment. What is New: • Measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from acute bronchiolitis in young children.

P244 Serum YKL-40 levels may help distinguish exacerbation of post-infectious bronchiolitis obliterans from acute bronchiolitis in young children

Introduction: The children with post-infectious bronchiolitis obliterans (PIBO) are frequently hospitalized with acute exacerbation, but clinical differentiation of PIBO exacerbation from ordinary bronchiolitis is often challenging, which may result in treatment delay and chronic lung function impairment. We aimed to examine whether serum YKL-40 and growth factors could be markers for PIBO exacerbation. Methods: Thirty-seven children admitted with acute exacerbation of PIBO were enrolled. Diagnosis of PIBO was based on clinical history of acute respiratory infection followed by persistent airway obstruction and characteristic findings in high-resolution computed tomography. Serum levels of YKL-40, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1 and platelet derived growth factor (PDGF)-BB were measured. The mediators were also examined in the children admitted with acute bronchiolitis serving as positive controls (N=30) and in age-matched controls (N=20). Results: Only YKL-40 levels were found to be significantly higher in PIBO patients with exacerbation compared with bronchiolitis patients and showed a positive correlation with the severity of disease before diagnosis of PIBO. Conclusion: Our results suggest that YKL-40 might be involved in the pathogenesis of PIBO and measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from ordinary acute bronchiolitis in young children.

Molecular mechanism of respiratory syncytial virus fusion inhibitors.

Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis in young children and the elderly. Therapeutic small molecules have been developed that bind the RSV F glycoprotein and inhibit membrane fusion, yet their binding sites and molecular mechanisms of action remain largely unknown. Here we show that these inhibitors bind to a three-fold-symmetric pocket within the central cavity of the metastable prefusion conformation of RSV F. Inhibitor binding stabilizes this conformation by tethering two regions that must undergo a structural rearrangement to facilitate membrane fusion. Inhibitor-escape mutations occur in residues that directly contact the inhibitors or are involved in the conformational rearrangements required to accommodate inhibitor binding. Resistant viruses do not propagate as well as wild-type RSV in vitro, indicating a fitness cost for inhibitor escape. Collectively, these findings provide new insight into class I viral fusion proteins and should facilitate development of optimal RSV fusion inhibitors.

Efeitos da vitamina D na prevenção da bronquiolite viral aguda: revisão sistemática

Aims : Published evidence suggests that supplementation may have a protective effect on infectious disease of the lower respiratory tract. The objective of this review was to critically appraise the effects of vitamin intake in the prevention of acute bronchiolitis in children. Methods: We searched the databases MEDLINE, EMBASE, Web of Science, LILACS, and Cochrane Central Register of Controlled Trials, until December 2014. Keywords: Vitamin D OR cholecalciferol OR ergocalciferol AND bronchiolitis, viral OR bronchiolitides, OR bronchiolitides viral. Eligibility Criteria: We included studies evaluating the effect of vitamin intake in the prevention of acute bronchiolitis in young children. Studies with less than two weeks of intervention and review articles were excluded. Results: The search identified 241 articles; twenty were selected for full reading but only two were included in the systematic review, comprising 296 children. No study measured serum vitamin D. One of them was a clinical trial, where the number of episodes of acute bronchiolitis was significantly lower in children supplemented with vitamin (Group I: mean: 0.6 ± 0.7 Group II: mean: 1.4 ± 0.9; p = 0.001). The other, a case-control study, did not find a significant relationship between the occurrence of acute bronchiolitis cases and the intake of vitamin (OR 1.7 95% CI 0.7 to 4.0). Conclusions: Current scientific evidence is insufficient to prove clinical benefits of vitamin in preventing acute bronchiolitis.