Severe Bronchiolitis Research Articles

Contribution of Cytokines to Tissue Damage During Human Respiratory Syncytial Virus Infection.

The human respiratory syncytial virus (hRSV) remains one of the leading pathogens causing acute respiratory tract infections (ARTIs) in children younger than 2 years old, worldwide. Hospitalizations during the winter season due to hRSV-induced bronchiolitis and pneumonia increase every year. Despite this, there are no available vaccines to mitigate the health and economic burden caused by hRSV infection. The pathology caused by hRSV induces significant damage to the pulmonary epithelium, due to an excessive inflammatory response at the airways. Cytokines are considered essential players for the establishment and modulation of the immune and inflammatory responses, which can either be beneficial or harmful for the host. The deleterious effect observed upon hRSV infection is mainly due to tissue damage caused by immune cells recruited to the site of infection. This cellular recruitment takes place due to an altered profile of cytokines secreted by epithelial cells. As a result of inflammatory cell recruitment, the amounts of cytokines, such as IL-1, IL-6, IL-10, and CCL5 are further increased, while IL-10 and IFN-γ are decreased. However, additional studies are required to elicit the mediators directly associated with hRSV damage entirely. In addition to the detrimental induction of inflammatory mediators in the respiratory tract caused by hRSV, reports indicating alterations in the central nervous system (CNS) have been published. Indeed, elevated levels of IL-6, IL-8 (CXCL8), CCL2, and CCL4 have been reported in cerebrospinal fluid from patients with severe bronchiolitis and hRSV-associated encephalopathy. In this review article, we provide an in-depth analysis of the role of cytokines secreted upon hRSV infection and their potentially harmful contribution to tissue damage of the respiratory tract and the CNS.

A pilot study of heated and humidified low flow oxygen therapy: An assessment in infants with mild and moderate bronchiolitis (HHOT AIR study).

Heated and humidified high flow nasal cannula oxygen therapy has been used in children with severe bronchiolitis. No data exists in children with mild to moderate bronchiolitis requiring lower flows of heated and humidified oxygen therapy. We conducted a prospective, randomized pilot study of standard dry oxygen (control) versus heated and humidified low flow nasal cannula (HHLFNC), <4 liters per minute (LPM) oxygen, (treatment) in healthy children ≤24 months old with bronchiolitis. Clinical assessments were made using Respiratory Distress Assessment Instrument (RDAI), respiratory rate (RR), and oxygen saturation. Thirty-two children were enrolled (16 participants in each group). There was no significant difference in mean RDAI over time between groups. There was a significant difference in mean RDAI over time within control group, at hour 12, and treatment group, at hour 1, compared to baseline. RDAI in the treatment group was overall lower over time compared to control group. There was no significant difference in mean RR over time between or within groups, between mean length of stay and duration of oxygen requirement. Subgroup analyses showed lower RDAI in subjects that had RSV infection, male gender, and non-black race. The use of HHLFNC oxygen therapy may provide more comfort and may result in more rapid improvements in RDAI compared to standard dry oxygen therapy over time. HHFLNC is safe and well tolerated compared to standard dry oxygen. Larger studies are needed to assess the clinical efficacy of HHLFNC oxygen therapy.

Prenatal exposure to acid-suppressant medications and the risk of recurrent wheeze at 3 years of age in children with a history of severe bronchiolitis

Asthma, one of the most common chronic diseases of childhood, develops through complex interactions between genetic susceptibilities and environmental exposures.1,2 In the United States, acid-suppressant medications (ASMs) are available widely, either by prescription or over-the-counter purchase, and are commonly used throughout the lifespan, including during pregnancy.3,4 Recent evidence from outside the United States suggests that prenatal exposure to ASMs may be associated with an increased risk of asthma in children.

Association of Fluid Overload With Clinical Outcomes in Critically Ill Children With Bronchiolitis: Bronquiolitis en la Unidad de Cuidados Intensivos Pediátricos (BRUCIP) Study.

Increasing evidence supports the association of fluid overload with adverse outcomes in different diseases. To our knowledge, few studies have examined the impact of fluid balance on clinical outcome in severe bronchiolitis. Our aim was to determine whether fluid overload was associated with adverse clinical outcomes in critically ill children with severe bronchiolitis. Descriptive, prospective, multicenter study. Sixteen Spanish PICUs. Severe acute bronchiolitis who required admission from October 2014 to May 2015 were included. None. Total fluid intake and output were prospectively recorded during PICU assistance. Fluid balance was measured at 24, 48, and 72 hours after PICU admission. A total of 262 patients were enrolled; 54.6% were male. Median age was 1 month (interquartile range, 1-3 mo). Patients had a positive fluid balance during the first 4 days of PICU admission, reaching a neutral balance on day 4. A positive balance at 24 hours in patients admitted to the PICU with severe bronchiolitis was related with longer stay in PICU (p < 0.001), longer hospital stay (p < 0.001), longer duration of mechanical ventilation (p = 0.016), and longer duration of noninvasive ventilation (p = 0.0029). Critically ill patients with severe acute bronchiolitis who present a positive balance in the first 24 hours of PICU admission have poorer clinical outcomes with longer PICU and hospital length of stay and duration of invasive and noninvasive mechanical ventilation.

Rhinovirus Species in Children With Severe Bronchiolitis: Multicenter Cohort Studies in the United States and Finland.

In this analysis of 2 prospective multicenter, multi-year cohorts of children hospitalized for bronchiolitis in the United States and Finland, 306 rhinovirus infections were genotyped. Rhinovirus-A and -C species were predominant in the US study, while rhinovirus-C species was predominant in the Finland study. In both cohorts, there were no significant between-species differences in clinical characteristics, including acute severity measures.

High-flow Nasal Cannula Flow Rates, Severe Bronchiolitis

High-flow Nasal Cannula Flow Rates, Severe Bronchiolitis

High-flow nasal cannula use for bronchiolitis treatment in French intensive care units: A transversal study

Over the past 10 years, continuous positive airway pressure (CPAP) has revolutionized the prognosis and management of bronchiolitis patients hospitalized in pediatric intensive care units (PICUs). High-flow nasal cannula (HFNC) is emerging as an alternative to CPAP. Despite encouraging results of several clinical and physiological studies, HFNC use remains controversial and its indications heterogeneous. To better define the place of HFNC in severe bronchiolitis respiratory support, we investigated the different ventilation assistance techniques used for severe bronchiolitis over 3 days at the peak of a bronchiolitis epidemic in December 2015. We conducted an observational cross-sectional study in 27 French university hospital PICUs. Fifty-nine patients were included. The results show that HFNC already accounts for nearly half of the respiratory support techniques used for severe bronchiolitis in French PICUs with no significant difference between the CPAP group and the HFNC group of patients.

Successful Use of Quality Improvement Methodology to Reduce Inpatient Length of Stay in Bronchiolitis Through Judicious Use of Intermittent Pulse Oximetry

The American Academy of Pediatrics 2014 bronchiolitis guidelines recommend against the routine use of continuous pulse oximetry (CPO) because it has been implicated in prolonging the length of stay (LOS). At our institution, infants admitted with bronchiolitis were monitored by using CPO during the entire hospital stay and intermittent desaturations <90% appeared to delay discharge. This quality improvement initiative was designed to reduce the LOS by decreasing the use of CPO in stable infants with nonsevere bronchiolitis. The quality improvement project was implemented on the inpatient units of 2 community hospitals during the 2016 and 2017 bronchiolitis seasons. In cycle 1 (January 2016 to April 2016), the bronchiolitis pathway from the associated quaternary children's hospital was used to (1) limit the use of CPO to patients with severe bronchiolitis and those at high risk for apnea or severe disease, (2) discontinue CPO as patients improved and stabilized, and (3) standardize discharge criteria. In cycle 2 (November 2016 to April 2017), the clinical pathway was adopted. The main outcome measure was LOS, measured from the time of the admission order to the time of the discharge order. Process measures included compliance with the interventions. The project included 373 patients, 180 preintervention and 193 postintervention. The average LOS decreased by 20 hours, from 53 hours at baseline to 33 hours in cycle 2. No adverse events were noted, and there was no significant change in the number of emergency department revisits and readmissions within 7 days. In our study, LOS was successfully reduced in bronchiolitis patients by using a clinical pathway that limited CPO to patients with severe bronchiolitis and those at risk for severe disease or apnea.

Prenatal exposure to acid suppressant medications and the risk of recurrent wheeze at 3 years of age in children with a history of severe bronchiolitis

Infants diagnosed with severe bronchiolitis are at higher risk for developing recurrent wheeze and asthma. Prior studies from outside the United States (U.S.) suggest that prenatal exposure to acid suppressant medications (ASM), such as proton pump inhibitors and histamine-2 receptor antagonists, may increase the risk of developing asthma. We tested the hypothesis that prenatal exposure to ASM increases the risk of recurrent wheeze among a high-risk population of children with a history of severe bronchiolitis. We enrolled 921 infants hospitalized for bronchiolitis from 2011-2014 in a multi-center, U.S.-based prospective cohort. ASM use during pregnancy was ascertained by parent report. Children were followed for the development of recurrent wheeze by age 3 years (defined by 2007 NIH guidelines). Time-to-event analysis was performed using multivariable Cox-proportional hazards models stratified by age and adjusted for sex, race/ethnicity, income, maternal history of atopy, maternal smoking during pregnancy, use of antibiotics during pregnancy, gestational age at birth, multiple gestation and mode of delivery. Of the 921 infants enrolled in the longitudinal cohort, 900 children with complete data were included in this analysis. Prenatal exposure to ASM occurred in 16% (144/900) of children. Recurrent wheeze developed in 31% (233/756) of unexposed children as compared to 39% (56/144) of exposed children (unadjusted HR 1.38;95%CI, 1.03-1.85). The finding did not change after adjustment (adjusted HR 1.40;95%CI, 1.02 -1.91). In this high-risk cohort of U.S. children with a history of severe bronchiolitis, prenatal exposure to ASM further increased the risk of developing recurrent wheeze by 3 years of age.

Characterization of Gut Microbiome in Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Characterization of Gut Microbiome in Infants with Severe Respiratory Syncytial Virus Bronchiolitis

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.

Association between rhinovirus species and nasopharyngeal microbiota in infants with severe bronchiolitis

Bronchiolitis is the leading cause of hospitalization in US infants.1 Rhinovirus (RV) is the second most common cause of severe bronchiolitis (ie, bronchiolitis requiring hospitalization) following respiratory syncytial virus (RSV).1 RVs are RNA viruses consisting of more than 160 genotypes that are classified into 3 species (RV-A, RV-B, and RV-C).2 RV-A and RV-C are more frequently found than RV-B in children with acute respiratory infections (ARIs) and wheezing illnesses.3,4 Emerging evidence suggests a complex interplay between viral infection, airway microbes, and host immune response in the pathobiology of ARI.

Serum Metabolome Is Associated With the Nasopharyngeal Microbiota and Disease Severity Among Infants With Bronchiolitis.

Emerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis. In 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites. Serum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV. Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.

Nebulised hypertonic saline in children with bronchiolitis admitted to the paediatric intensive care unit: A retrospective study

Bronchiolitis is one of the most common lower respiratory tract infections in young children, associated with significant morbidity, but limited therapeutic options. Nebulised hypertonic saline (HS) has been a supportive treatment until current guidelines advised against its routine use. Accordingly, the University Hospital of Antwerp recently changed their policies to stop using it, allowing us to evaluate retrospectively if HS influences the duration of respiratory support. Because, to our knowledge, the effect of HS on children with severe bronchiolitis admitted to a paediatric intensive care unit (PICU) has not been studied yet, we aimed to investigate the effect in this specific patient group. Retrospective study including children up to the age of 2, admitted to the PICU with bronchiolitis from October 2013 until March 2016. The primary end point is the duration of respiratory support, including high flow nasal cannula, continuous positive airway pressure and invasive ventilation. A total of 104 children admitted to the PICU with bronchiolitis were included, with an average age of 3.4 months. In respiratory syncytial virus (RSV) positive patients, the use of nebulised HS was correlated with a decrease in the duration of respiratory support and the length of stay by factors 0.72 (P = 0.01) and 0.81 (P = 0.04), respectively. A significant correlation was found between the use of HS and a decreased duration of respiratory support and admission in the PICU in patients with RSV bronchiolitis. This finding may warrant new prospective studies investigating HS specifically in children with severe bronchiolitis.

New therapies for acute RSV infections: where are we?

Respiratory syncytial virus (RSV) infection is one of the main causes of infant hospitalization and mortality. The single-stranded RNA virus codes for 11 proteins of which the F protein, a surface epitope responsible for RSV fusion, is the most targeted for developing antiviral medicines and vaccines. The peak of symptoms occurs around day 4 to 6 of illness and the airway obstruction is merely caused by the host immune inflammatory response. Risk factors for severe bronchiolitis are prematurity, comorbidity, and/or being immunocompromised. At present, there are no curative therapies available for RSV infections and treatment is supportive only. Development of new antiviral medicines is however promising. The aim of this review is to give a summary of the most important new antiviral therapies in clinical development for RSV infection and to explain their mode of action. We therefore performed a literature search on this topic.Conclusion: There are currently at least eight antivirals being investigated in clinical trials. They all use different approaches to either focus on preventing viral fusion with host cells or inhibiting virus replication. Some target RSV surface epitopes like the F protein to halt fusion, others aim for RNA chain termination, while small interfering RNAs downregulate viral protein production. What is known: • RSV bronchiolitis is a very important pediatric disease as it is one of the main causes of infant hospitalization and mortality. By the age of 2years, 95% of all the infants worldwide will have been infected. • The only recommended therapy is supportive since there are no existing curative therapies yet. What this study adds: • This review gives an overview of the current progress in the research field of RSV antivirals with background information on their mode of action.

Efficacy and Safety of High-Flow Nasal Cannula Oxygen Therapy in Moderate and Severe Bronchiolitis

Efficacy and Safety of High-Flow Nasal Cannula Oxygen Therapy in Moderate and Severe Bronchiolitis

Vitamin D supplementation for acute bronchiolitis: a double-blind randomized controlled trial

Background Vitamin D deficiency has been declared as a risk factor for acute bronchiolitis. Objective The aim was to delineate the therapeutic effect of vitamin D supplementation on the clinical course of acute bronchiolitis and to investigate the relationship between vitamin D status and the severity of acute bronchiolitis. Materials and methods A randomized double-blind controlled trial was conducted including 60 infants who required hospital-based care for acute bronchiolitis. The included infants were randomly assigned to either vitamin D3 treatment (100 IU/kg/day) (vitamin D group) or placebo (placebo group) all through the period of admission. The primary outcome was the length of hospital stay in days, and the secondary outcome measures were as follows: time to resolution of tachypnea, chest retractions, hypoxia, inability to feed/lethargy, and any adverse events. Modified Tal score was used for severity assessment. Basal serum vitamin D level was evaluated in all patients before enrollment in the randomized trial. Results The vitamin D group had significantly shorter length of hospital stay, rapid resolution of signs of respiratory distress, and shorter need for oxygen therapy. Further, patients with severe disease showed significant low basal serum vitamin D level compared with milder cases. Moreover, patients with exclusive breastfeeding and those with daily outdoor exposure for less than 1 h were found to have significantly lower serum vitamin D. Conclusion Vitamin D supplementation at a dose of 100 IU/kg/day could have a significant beneficial effect in infants with acute bronchiolitis.

Effectiveness of 7% versus 3% hypertonic saline nebulization in infants with acute bronchiolitis : A randomized controlled trail

Background and objective: Acute bronchiolitis, the most common lower respiratory tract infection,is the leading cause of hospitalization among infants. The objective of the study is to compare the effect of 7% hypertonic saline (HS) with 3% HS among infants with acute bronchiolitis. Methods: A total of 96 infants between the age group of 2 to 24 months with acute bronchiolitis and Bronchitis Severity Score (BSS)> 4 were included in this double-blinded, randomized controlled trial. The infants were grouped based on the therapy administered: group A (7% HS with L-adrenaline, n=48) and group B (3% HS with L-adrenaline, n=48).The prime outcome measure was Length of Hospital Stay (LHS). Whereas, the secondary outcome measures included BSS, heart rate, oxygen saturation, need and durationof supplemental oxygen, and adverse events. Statistical analysis was performed using SPSS 21 software. Results and Conclusion: Patient’s baseline characteristics were alike in both the groups. The length of the hospital stay was 4.34 ± 1.01 days in 7% HS group and 4.59 ± 1.10 days in 3% HS group (P > 0.05). Treatment with 7% HS and 3% HS with adrenaline were associated with a decreased BSS and reduced length of hospital stay without any adverse effects among infants with acute bronchiolitis.

Lung Ultrasound Findings and Bronchiolitis Ultrasound Score for Predicting Hospital Admission in Children With Acute Bronchiolitis.

The purposes of this study were to determine the benefit of the bronchiolitis ultrasound score (BUS) in predicting hospital admission in children with acute bronchiolitis and to characterize lung sonography findings. This prospective observational study was performed in an academic pediatric emergency department. Children younger than 24 months presenting to the emergency department, diagnosed with acute bronchiolitis by 2 independent pediatricians were included in the study. Lung ultrasound was performed by a single sonographer, who was blinded to as much clinical information as possible. In addition, the treating physicians were blinded to the lung ultrasound findings. Logistic regression analysis models were used to identify admission predictors. Receiver operating characteristic analysis was used to evaluate the predictive value for effects of the BUS and the modified Bronchiolitis Severity Score on admission. The median age of the 76 patients diagnosed with acute bronchiolitis was 6 months (interquartile range, 3.6-10 months). Forty-two (55.3%) of the 76 patients enrolled were admitted. Lung ultrasound was compatible with acute bronchiolitis in 74 patients (97%). A significant correlation was determined between modified Bronchiolitis Severity Score and BUS in children with acute bronchiolitis (r = 0.698, P < 0.001). The most effective parameter in determining admission on logistic regression analysis, independently of other variables, was BUS (P = 0.044; adjusted odds ratio, 1.859; 95% confidence interval, 1.016-3.404). Bronchiolitis ultrasound score values of 3 or greater exhibited 73.81% sensitivity and 73.53% specificity, whereas BUS values of 4 or greater exhibited 50% sensitivity and 91.18% specificity. Point-of-care lung ultrasound can accurately detect pulmonary anomalies in children with acute bronchiolitis, has a close correlation with clinical findings, and is a useful tool in predicting hospital admission.

Severe bronchiolitis profiles and the risk of developing recurrent wheezing by age 3 years

Severe bronchiolitis profiles and the risk of developing recurrent wheezing by age 3 years