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Objective: To investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations, utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations., Study Design: We analyzed data from 2 multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam, and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (forced expiratory volume in the first second (FEV1) z-score ≤ -1.645) as per 2022 American Thoracic Society (ATS) guidelines., Results: Compared with the race-specific GLI, the race-neutral equation yielded increases in the median forced expiratory volume in the first second and forced vital capacity (FVC) percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21%, and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; P < .001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; P = .001). Results were similar across both cohorts., Conclusions: As there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children., Competing Interests: Declaration of Competing Interest The study was supported by NIH grants U01 AI087881, R01 AI114552, R01 AI127507, and UH3 OD023253. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Our aim was to evaluate the impact of the initial high flow nasal cannula (HFNC) flow rate on clinical outcomes in children with bronchiolitis., Methods: This secondary analysis of retrospective data included children <2 years who required HFNC for bronchiolitis between 10/01/2018-04/20/2019, and following implementation of a revised institutional bronchiolitis pathway between 10/01/2021-04/30/2022. The new pathway recommended weight-based initiation of HFNC at 1.5-2 L/kg/min. We evaluated the effect of low (<1.0 L/kg/min), medium (1-1.5 L/kg/min) and high (>1.5 L/kg/min) HFNC flow rates on need for positive pressure ventilation (PPV), intensive care unit (ICU) transfer, HFNC treatment time, and hospital length of stay (LOS)., Results: The majority of the 885 included children had low initial flow rates (low [n = 450, 50.8%], medium [n = 332, 37.5%] and high [n = 103, 11.7%]). There were no significant differences in PPV (high: 7.8% vs. medium: 9.3% vs. low: 8.2%, p = 0.8) or ICU transfers (high: 4.9% vs. medium: 6.0% vs. low: 3.8%, p = 0.3). The low flow group had a significantly longer median HFNC treatment time (High: 29 [18, 45] vs. medium: 29 [16, 50] vs. low: 39 [25, 63], p < .001) and hospital LOS (High: 41 [27, 59] vs. medium: 42 [29, 66] vs. low: 50 (39, 75), p < .001). Logistic and linear regression models did not demonstrate any associations between HFNC flow rates and PPV or hospital LOS., Conclusions: Initial HFNC flow rates were not associated with significant changes in clinical outcomes in children in children with bronchiolitis., (© 2024 Wiley Periodicals LLC.)

In a prospective, multicenter cohort of infants hospitalized with bronchiolitis, we found infants born late pre-term (ie, gestational age of 34-36.9 weeks) had 35% higher odds of having asthma by age 5 years compared with infants born at full-term., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: It has been speculated that the SARS-CoV-2 was already widespread in western countries before February 2020., Methods: We gauged this hypothesis by analysing the nasal swab of infants with either bronchiolitis or a non-infectious disease admitted to the Ospedale Maggiore, Milan (one of the first epicentres of SARS-CoV-2 outbreak in Europe) from November 2019., Results: The SARS-CoV-2 RNA was never detected in 218 infants with bronchiolitis (95 females, median age 4.9 months) and 49 infants (22 females, median age 5.6 months) with a non-infectious disease between November 2019 and February 2020. On the contrary, two infants hospitalised for bronchiolitis between March and April 2020 tested positive for SARS-CoV-2., Conclusions: This study does not support the hypothesis that SARS-CoV-2 was already circulating among infants before the official outbreak of SARS-CoV-2 infection. However, it shows for the first time that SARS-CoV-2 might cause bronchiolitis requiring hospitalisation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increasing evidence shows that environmental factors in childhood play a role in development of irreversible airway obstruction. We evaluated early-life and preschool-age risk factors for irreversible airway obstruction in adolescence after bronchiolitis in infancy., Methods: This study is a secondary analysis of data collected during prospective long-term follow-up of our post-bronchiolitis cohort. Risk factor data were collected during hospitalisation and on follow-up visits at 5-7 and 10-13 years of ages. Lung function was measured from 103 participants with impulse oscillometry at 5-7 years of age and from 89 participants with flow-volume spirometry at 10-13 years of age., Results: Asthma diagnosis at <12 months of age showed a significant association with irreversible airway obstruction at 10-13 years of age independently from current asthma. Irreversible airway obstruction was less frequent in children with variant than wild genotype of the Toll-like receptor 4(TLR4) rs4986790, but the significance was lost in logistic regression adjusted for current asthma and weight status. Higher post-bronchodilator respiratory system resistance at 5 Hz and lower baseline and post-bronchodilator reactance at 5 Hz by impulse oscillometry at 5-7 years of age were associated with irreversible airway obstruction at 10-13 years of age., Conclusion: Asthma diagnosis during the first living year and worse lung function at preschool age increased the risk for irreversible airway obstruction at 10-13 years of age after bronchiolitis. TLR4 rs4986790 polymorphism may be protective for development of irreversible airway obstruction after bronchiolitis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: acute bronchiolitis is the leading cause of hospitalization in infants worldwide. However, little is known about the real impact of on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years (DALYs) for acute bronchiolitis in infants in Colombia., Methods: data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to acute bronchiolitis in Colombia. A bootstrapped method with 10,000 iterations was used to estimate each statistical parameter using the package DALYs calculator in R., Results: in 2019, 447,434 years of life (confidence interval 95% 397,647- 512,759) were lost due to acute bronchiolitis in Colombian infants. The estimated rate was 34 DALYs/1000 person-year (95% confidence interval 30-39)., Conclusion: our paper shows the high burden of disease associated with bronchiolitis in Colombia. Prevention strategies, such as acute bronchiolitis vaccination, to reduce morbidity associated with acute bronchiolitis should be encouraged in our country., Competing Interests: The authors declare no competing interests., (Copyright: Jefferson Antonio Buendía et al.)

Objectives: To explore the predictive ability of capillary blood gas (CBG) pCO 2 for respiratory decompensation in infants aged ≤6 months with bronchiolitis admitted from the emergency department; to determine whether end-tidal CO 2 (etCO 2 ) capnography can serve as a less invasive substitute for CBG pCO 2 ., Study Design: This was a prospective cohort study of previously healthy infants aged ≤6 months admitted for bronchiolitis from the emergency department (ED). Initial CBG pCO 2 and etCO 2 capnography were obtained in the ED prior to inpatient admission. Simple logistic regression modeling was used to examine the associations of CBG pCO 2 and etCO 2 capnography with respiratory decompensation. Pearson's correlation measured the relationship between CBG pCO 2 and etCO 2 capnography., Results: Of 134 patients, 61 had respiratory decompensation. There was a significant association between CBG pCO 2 and respiratory decompensation (OR = 1.07, p = 0.003), even after outlying values were excluded (OR = 1.06, p = 0.005). End tidal CO 2 capnography was not significantly associated with decompensation (OR = 1.02, p = 0.17), even after outlying values were excluded (OR = 1.02, p = 0.24). There was a moderate correlation between etCO 2 capnography and CBG pCO 2 (r = 0.39, p < 0.001)., Conclusion: In infants with bronchiolitis, CBG pCO 2 provides an objective measure for predicting respiratory decompensation, and a single etCO 2 measurement should not replace its use., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: There is low level of evidence and substantial practice variation regarding the use of intermittent or continuous monitoring in infants hospitalized with bronchiolitis., Objective: To compare the effect of intermittent vs continuous pulse oximetry on clinical outcomes., Design, Setting, and Participants: This multicenter, pragmatic randomized clinical trial included infants 4 weeks to 24 months of age who were hospitalized with bronchiolitis from November 1, 2016, to May 31, 2019, with or without supplemental oxygen after stabilization at community and children's hospitals in Ontario, Canada., Interventions: Intermittent (every 4 hours, n = 114) or continuous (n = 115) pulse oximetry, using an oxygen saturation target of 90% or higher., Main Outcomes and Measures: The primary outcome was length of hospital stay from randomization to discharge. Secondary outcomes included length of stay from inpatient unit admission to discharge and outcomes measured from randomization: medical interventions, safety (intensive care unit transfer and revisits), parent anxiety and workdays missed, and nursing satisfaction., Results: Among 229 infants enrolled (median [IQR] age, 4.0 [2.2-8.5] months; 136 [59.4%] male; 101 [44.1%] from community hospital sites), the median length of hospital stay from randomization to discharge was 27.6 hours (interquartile range [IQR], 18.8-49.6 hours) in the intermittent group and 25.4 hours (IQR, 18.3-47.6 hours) in the continuous group (difference of medians, 2.2 hours; 95% CI, -1.9 to 6.3 hours; P = .17). No significant differences were observed between the intermittent and continuous groups in the median length of stay from inpatient unit admission to discharge: 49.1 (IQR, 37.2-87.0) hours vs 46.0 (IQR, 32.5-73.8) hours (P = .13) or in frequencies or durations of hospital interventions, such as oxygen supplementation initiation: 4 of 114 (3.5%) vs. 9 of 115 (7.8%) (P = .16) and median duration of oxygen supplementation: 20.6 (IQR, 7.6-46.1) hours vs. 21.4 (11.6-52.9) hours (P = .66). Similarly, there were no significant differences in frequencies of intensive care unit transfer: 1 of 114 (0.9%) vs 2 of 115 (2.7%) (P = .76); readmission to hospital: 3 of 114 (2.6%) in the intermittent group vs 4 of 115 (3.5%) in the continuous group (P > .99); parent anxiety: mean (SD) parent anxiety score, 2.9 (0.9) in the intermittent group vs 2.8 (0.9) in the continuous group (P = .40); or parent workdays missed: median workdays missed, 1.5 (IQR, 0.5-3.0) vs 1.5 (IQR, 0.5-2.5) (P = .36). Mean (SD) nursing satisfaction with monitoring was significantly greater in the intermittent group: 8.6 (1.7) vs 7.1 (2.8) of 10 workdays; the mean difference was 1.5 (95% CI, 0.9-2.2; P < .001)., Conclusions and Relevance: In this randomized clinical trial, among infants hospitalized with stabilized bronchiolitis with and without hypoxia and managed using an oxygen saturation target of 90% or higher, clinical outcomes, including length of hospital stay and safety, were similar with intermittent vs continuous pulse oximetry. Nursing satisfaction was greater with intermittent monitoring. Given that other important clinical practice considerations favor less intense monitoring, these findings support the standard use of intermittent pulse oximetry in stable infants hospitalized with bronchiolitis., Trial Registration: ClinicalTrials.gov Identifier: NCT02947204.

Background: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing., Methods: Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments., Results: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3-24.9; P = 0.023)., Conclusion: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

Background: Children with a history of rhinovirus (RV) positive bronchiolitis have a high risk of developing subsequent asthma. Maternal asthma might also increase this risk. The aim of this study was to investigate the combined effects of hospitalization for RV positive bronchiolitis in infancy and a history of maternal asthma on the development of asthma at preschool age., Methods: This is a prospective cohort study of 139 preschool-aged children, with a history of hospital admission for bronchiolitis in infancy, followed-up to ascertain asthma and asthma-like symptoms, skin prick allergy test positivity, and lung function measured pre- and post-bronchodilator using impulse oscillometry., Results: Children with a past hospitalization for RV positive bronchiolitis (42.4% of all) and a history of maternal asthma (36.7% of all) had the greatest prevalence and risk ratio (RR) for doctor-diagnosed asthma (prevalence 81.8% and RR 2.10, 95% confidence interval [CI] 1.37-3.19, p = .001), use of inhaled corticosteroids (68.2% and RR 2.17, 95% CI 1.19-3.99, p = .001) and short-acting β-agonists in the last 12 months (95.2% and RR 1.49, 95% CI 1.17-1.89, p = .001), as compared to those with RV negative bronchiolitis and no maternal asthma history. More children in this group had an abnormal airway resistance (33.3% and adjusted risk ratio [aRR] 3.11, 95% CI 1.03-9.47, p = .045) and reactance (27.8% and aRR 2.11, 95% CI 1.06-4.26, p = .035) at 5 Hz, as compared to those with RV negative bronchiolitis and no maternal asthma history., Conclusion: Hospitalization for RV positive bronchiolitis in early life combined with a history of maternal asthma identifies a subgroup of children with a high asthma burden while participants with only one of the two risk factors had intermediate risk for asthma., (© 2020 Wiley Periodicals LLC.)

Importance: Little is known about the natural course of oxygen desaturation in acute bronchiolitis. Information on risk factors associated with desaturation as well as the time to desaturation in infants with bronchiolitis could help physicians better treat these infants before deciding whether to hospitalize them., Objective: To prospectively determine the frequency of desaturation in infants with bronchiolitis, along with the time to desaturation and risk factors associated with desaturation, and to compare infants who were hospitalized with those discharged home and evaluate risk factors for rehospitalization., Design, Setting, and Participants: This cohort study was conducted during the 2017 to 2018 and 2018 to 2019 respiratory syncytial virus seasons in a tertiary care pediatric emergency department in Switzerland. Included individuals were 239 otherwise-healthy infants aged younger than 1 year, diagnosed with acute bronchiolitis and oxygen saturation of 90% or more on arrival. Data were analyzed from July 2019 to October 2020., Exposures: After receiving triage care, study participants admitted to the emergency department were equipped with a pulse oximeter to continuously record oxygen saturation (Spo2 levels), regardless of subsequent hospitalization or discharge home., Main Outcomes and Measures: The primary outcome was desaturation (ie, Spo2 < 90%) during the first 36 hours., Results: Of 239 infants enrolled, with a median (interquartile range [IQR]) age of 3.9 (1.5-6.5) months, 116 (48.5%) were boys and desaturation occurred in 165 infants (69.0%). Median (IQR) time to desaturation was 3.6 (1.8-9.4) hours. The rate of desaturation was similar between infants hospitalized and those discharged home (137 of 200 infants [68.5%] vs 28 of 39 infants [71.8%]; difference, -3.3%; 95% CI, -18.8% to 12.2%; P = .85). A more severe initial clinical presentation with moderate or severe retractions was the only independent risk factor associated with desaturation (odds ratio, 2.73; 95% CI, 1.49 to 5.02; P = .001). Of 39 infants discharged home, 22 infants (56.4%) experienced major desaturations. However, infants with desaturations, including those with major desaturations, had rates of rehospitalization similar to those of infants without desaturations (8 of 28 infants [28.5%] vs 3 of 11 infants [27.3%]; difference, 1.2%; 95% CI, -29.9% to 32.5; P > .99)., Conclusions and Relevance: These findings suggest that rates of desaturation in infants with acute bronchiolitis were high and similar between infants who were hospitalized and those discharged home. A more severe initial clinical presentation was the only risk factor associated with desaturation. However, for infants discharged home, desaturation was not a risk factor associated with rehospitalization.

Background: Bronchiolitis is the most common cause for hospitalization in infants. While the use of high flow nasal cannula (HFNC) has increased, it has not uniformly reduced intubation rates., Objective: We identified factors associated with respiratory failure in children with bronchiolitis on HFNC., Methods: We conducted a retrospective study of previously healthy children <24 months of age with bronchiolitis, who were treated with HFNC in two pediatric emergency departments from 1/2014-1/2018. The primary outcome was the identification of demographic and clinical factors that are associated with intubation after an antecedent trial of HFNC. A multivariable logistic regression model was constructed to identify predictors of respiratory failure., Results: Of 2657 children on HFNC, the median age was 7 months, while the median age of the intubated cohort was 3 months. Ten percent (271) progressed to mechanical ventilation within 48 h of PED presentation. Of the 301 patients that needed escalation to CPAP and/or BiPAP, 91 required intubation. Factors associated with intubation were young age and a high respiratory tool score; factors associated with no progression to intubation were a reduction in tachycardia after initiation of HFNC and presentation after day 5 of illness. A secondary analysis also revealed decreased rate of intubation with the use of bronchodilators. We identified demographic, clinical, and therapeutic factors that are associated with requiring intubation., Conclusion: Given the high burden of bronchiolitis in pediatric emergency departments, these factors can be considered upon presentation of children with bronchiolitis to selectively identify children at higher risk for respiratory failure., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Published by Elsevier Inc.)

Objective: Lung ultrasound (LUS) is an emerging tool that may be used in the diagnosis and follow-up of children with viral bronchiolitis. In this study, we describe LUS abnormalities in children receiving invasive mechanical ventilation (IMV) for severe bronchiolitis in the pediatric intensive care unit (PICU). Our aim was to semiquantify the loss of aeration and examine the association between serial LUS scores and oxygenation anomaly, as a marker of disease severity., Design: Prospective, observational study in a single-center PICU., Methods: LUS was performed by multiple observers using two different LUS scoring systems (counting B-lines and aeration score) in 17 patients in the PICU, generating 320 images. Oxygen saturation index (OSI) was the primary outcome marker to describe the severity of oxygenation anomaly., Results: Pulmonary aeration was moderately impaired with a homogeneous anterolateral pattern. LUS scores worsened after 24 hours, to improve in subsequent days. Both LUS scores were positively correlated with OSI on the first day of IMV (counting B-lines P = .034, r = .52 and LUS aeration score P = .017, r = .57), but not thereafter. There was considerable variability in the LUS scores despite moderate to high agreement between the observers., Conclusions: In children receiving IMV for severe bronchiolitis, pulmonary aeration is moderately impaired. LUS scores positively correlate with severity of oxygenation anomaly only in the acute phase of disease. We speculate that with the progression of disease other factors affect LUS patterns (eg, fluid overload, atelectasis), which may complicate the interpretation of LUS in follow-up of this specific cohort in the PICU., (© 2020 Wiley Periodicals LLC.)

We aimed to develop machine learning models to accurately predict bronchiolitis severity, and to compare their predictive performance with a conventional scoring (reference) model. In a 17-center prospective study of infants (aged < 1 year) hospitalized for bronchiolitis, by using routinely-available pre-hospitalization data as predictors, we developed four machine learning models: Lasso regression, elastic net regression, random forest, and gradient boosted decision tree. We compared their predictive performance-e.g., area-under-the-curve (AUC), sensitivity, specificity, and net benefit (decision curves)-using a cross-validation method, with that of the reference model. The outcomes were positive pressure ventilation use and intensive treatment (admission to intensive care unit and/or positive pressure ventilation use). Of 1,016 infants, 5.4% underwent positive pressure ventilation and 16.0% had intensive treatment. For the positive pressure ventilation outcome, machine learning models outperformed reference model (e.g., AUC 0.88 [95% CI 0.84-0.93] in gradient boosted decision tree vs 0.62 [95% CI 0.53-0.70] in reference model), with higher sensitivity (0.89 [95% CI 0.80-0.96] vs. 0.62 [95% CI 0.49-0.75]) and specificity (0.77 [95% CI 0.75-0.80] vs. 0.57 [95% CI 0.54-0.60]). The machine learning models also achieved a greater net benefit over ranges of clinical thresholds. Machine learning models consistently demonstrated a superior ability to predict acute severity and achieved greater net benefit.

Background and Objectives: Recent literature suggests that lung ultrasound might have a role in the diagnosis and management of bronchiolitis. The aim of the study is to evaluate the relationship between an ultrasound score and the clinical progression of bronchiolitis: need for supplemental oxygen, duration of oxygen therapy and hospital stay. Materials and Methods: This was a prospective observational single-center study, conducted in a pediatric unit during the 2017-2018 epidemic periods. All consecutive patients admitted with clinical signs of acute bronchiolitis, but without the need for supplemental oxygen, underwent a lung ultrasound in the first 24 h of hospital care. The lung involvement was graded based on the ultrasound score. During clinical progression, need for supplemental oxygen, duration of oxygen therapy and duration of hospital stay were recorded. Results: The final analysis included 83 patients, with a mean age of 4.5 ± 4.1 months. The lung ultrasound score in patients that required supplemental oxygen during hospitalization was 4.5 ± 1.7 (range: 2.0-8.0), different from the one of the not supplemented infants (2.5 ± 1.8; range: 0.0-6.0; p < 0.001). Ultrasound score was associated with the need for supplemental oxygen (OR = 2.2; 95% CI = 1.5-3.3; p < 0.0001). Duration of oxygen therapy was not associated with LUS score ( p > 0.05). Length of hospital stay (coef. = 0.5; 95% CI = 0.2-0.7; p < 0.0001) correlates with LUS score. Conclusion: Lung ultrasound score correlates with the need of supplemental oxygen and length of hospital stay in infants with acute bronchiolitis.

Background: A study of respiratory syncytial virus-A (RSV A) genotype ON1 genetic variability and clinical severity in infants hospitalized with bronchiolitis over 6 epidemic seasons (2012-2013 to 2017-2018) was carried out., Methods: From prospectively enrolled term infants hospitalized for bronchiolitis, samples positive for RSV A ON1 (N = 139) were sequenced in the second half of the G gene. Patients' clinical data were obtained from medical files and each infant was assigned a clinical severity score. ANOVA comparison and adjusted multinomial logistic regression were used to evaluate clinical severity score and clinical parameters., Results: The phylogenetic analysis of 54 strains showed 3 distinct clades; sequences in the last 2 seasons differed from previous seasons. The most divergent and numerous cluster of 2017-2018 strains was characterized by a novel pattern of amino acid changes, some in antigenic sites. Several amino acid changes altered predicted glycosylation sites, with acquisition of around 10 new O-glycosylation sites. Clinical severity of bronchiolitis increased in 2016-2017 and 2017-2018 and changed according to the epidemic seasons only., Conclusions: Amino acid changes in the hypervariable part of G protein may have altered functions and/or changed its immunogenicity, leading to an impact on disease severity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To assess cardiac function in infants with bronchiolitis and the association with disease severity and outcomes., Working Hypothesis: Cardiac function may be impaired in bronchiolitis and represent an early predictor of disease severity., Study Design: A prospective cohort study., Patient Selection: Infants with suspected bronchiolitis were included., Methodology: All cases received antigen detection and viral genome detection from nasal lavage or swabs and echocardiography within 24 hours from admission. Systolic and diastolic function in left ventricle (LV) and right ventricle (RV) were assessed using longitudinal strain (LS), a measure of myocardial deformation. Pulmonary artery pressures were estimated using tricuspid regurgitation jet (TR), when present, and end-systolic eccentricity index (EI ES). Main outcomes (duration of respiratory support, length of stay [LOS], and type of respiratory support) were collected. Data were compared to normative existing data, and a group of healthy infants, matched in age., Results: Twenty-eight infants with bronchiolitis and 10 healthy comparators were included. Cases with bronchiolitis showed significantly lower values of RV LS and LV LS compared to healthy comparators (LV: p0.04 and RV: P < .001). Ten infants (36%) had a normal biventricular function, nine (32%) had LV impairment, and nine (32%) had a biventricular impairment. No significant differences were found in TR and EI ES. Infants with biventricular impairment demonstrated a significant increase in LOS (p0.04) and higher levels of respiratory support compared to the healthy comparators (P = .03)., Conclusions: Bronchiolitis is associated with myocardial impairment. Cardiac function is related to disease severity and outcome., (© 2020 Wiley Periodicals, Inc.)

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) causes significant morbidity and mortality among young infants worldwide. It is currently widely accepted that neutrophil influx into the airways is a hallmark of the pathophysiology. However, the exact mechanism of neutrophil migration from the vasculature into the alveolar space in RSV LRTI has received little attention. Data shows that endothelial cells become activated upon RSV infection, driving a 'pro-adhesive state' for circulating neutrophils with upregulation of endothelial intercellular adhesion molecule-1 (ICAM-1). During RSV LRTI different subsets of immature and mature neutrophils are present in the bloodstream, that upregulate integrins lymphocyte-function associated antigen (LFA)-1 and macrophage (Mac)-1, serving as ICAM-1 ligands. An alveolar gradient of interleukin-8 may serve as a potent chemoattractant for circulating neutrophils. Neutrophils from lung aspirates of RSV-infected infants show further signs of inflammatory and migratory activation, while soluble endothelial cell adhesion molecules (sCAMs), such as sICAM-1, have become measurable in the systemic circulation. Whether these mechanisms are solely responsible for neutrophil migration into the alveolar space remains under debate. However, data indicate that the currently postulated neutrophil influx into the lungs should rather be regarded as a neutrophil efflux from the vasculature, involving substantial neutrophil-endothelial interactions. Molecular patterns of these interactions may be clinically useful to predict outcomes of RSV LRTI and deserve further study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Despite advances in medical knowledge, the treatment of viral bronchiolitis is mainly supportive. Antiviral therapies are being investigated in clinical trials. Identifying population-attributable risk factors for RSV hospitalization may help prioritizing targeted treatment., Aim: To utilize MDClone, a data acquisition tool, to examine factors associated with the risk of hospitalization and length of stay (LOS) in bronchiolitis., Methods: A single tertiary medical center retrospective study. Infants discharged with a diagnosis of bronchiolitis between January 2001 and March 2019 were included. Demographic, clinical, laboratory, microbiologic parameters and co-morbidities were collected. Correlations with the risk of hospitalization and LOS were examined., Results: A total of 4793 infants with bronchiolitis, 3851 (80.3%) previously healthy, were seen; 975 visited emergency room only; 3311 were hospitalized in pediatric wards and 507 required pediatric intensive care unit. O 2 saturation, age and fever correlated with the risk of hospitalization (OR = 0.703, p < 0.0001, OR = 0.4, p = 0.024 and OR = 2.388, p < 0.0001, respectively). Saturation, fever, gestational age and birth weight correlated with LOS (r = -0.283, p = 0.000; r = 0.16, p = 0.000; r = -0.12, p = 0.00; and r = -0.117, p = 0.00, respectively). Rates of hospitalization were higher (81.1% vs. 75.6%, p = 0.0008) and LOS was longer (median 2.97 vs. 2.73 days, p < 0.001) in Arabs than in Jews. In a multivariate model, saturation, fever, gestational age and age predicted LOS. Saturation and ethnicity predicted LOS for previously healthy infants. Prematurity and cardiac anomalies increased LOS (p = 0.016 and p < 0.0001, respectively)., Conclusions: Population-based data may enable predicting disease severity and LOS in bronchiolitis. Focusing on children at greatest risk may aid targeting new therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We examined the clinical and physiological benefits of heated humidified high-flow nasal cannula (HHHFNC) in treating pediatric bronchiolitis in a general pediatric ward. Children aged 0 to 2 years, hospitalized with moderate to severe bronchiolitis, were connected to HHHFNC. Each child was evaluated at 4- to 10-hour intervals, both on and off the device, using the Wang et al Bronchiolitis Severity score and transcutaneous CO 2 monitor. Sixteen children were included in the final analysis. The Bronchiolitis Severity score improved by 3 points during the first and second intervals ( P = .001). Transcutaneous CO 2 values were reduced by an average 8.7 mm Hg ( P = .001). No adverse effects were noted in children connected to the device. The HHHFNC device used in a general pediatric ward setting served as a safe and efficacious tool in treating moderate to severe bronchiolitis. Immediate clinical and physiological improvement was observed and maintained 1 to 4 hours after disconnection from the device.

Bronchiolitis is one of the most frequent reasons for Pediatric Intensive Care Unit (PICU) admission in children less than 1 year of age. It causes a wide spectrum of clinical scenarios from mild to severe respiratory failure and supportive therapy range from high flow nasal cannula (HFNC) to nonconventional ventilation and extra corporeal membrane oxygenation (ECMO) in the most severe forms. Aim of this article is to review the available ventilation mode in children with bronchiolitis and the scientific evidence. The main medical databases were explored to search for clinical trials that address management strategies for respiratory support of infants with respiratory syncytial virus (RSV) infection. HFNC use is increasing and it seems to be useful as first line therapy in the emergency room and in the pediatric ward to prevent PICU admission but it is not clear yet if it is equivalent to noninvasive ventilation (NIV). NIV use in bronchiolitis is well established, mainly in continuous positive airway pressure mode in moderate and severe bronchiolitis. A mild evidence towards use of NIV to prevent endotracheal intubation is raising from few studies. Finally, for patients who failed a NIV trial, endotracheal intubation should be considered as the best option to support ventilation with conventional, nonconventional mode and ECMO in the most severe acute respiratory distress syndromes. There is a lack of quality studies for the use of any of the proposed ventilatory support in infants with bronchiolitis, especially in the severe forms. Nevertheless, in the last two decades daily use of noninvasive positive pressure supports have reached a large consensus based on clinical judgement and weak published evidence. We need specific and clear guidelines on which is the optimal management of these patients, and more robust randomized clinical trials to best evaluate timing and efficacy of HFNC and NIV use.

Bronchiolitis is the most common acute lower respiratory tract infection in infants and the first cause of hospitalization in this age group. Despite it has been studied for over 70 years, its management remains controversial and nowadays the treatment is only supportive. Pediatricians should be well acquainted with the clinical course of the disease. In particular, they should know that the severity of respiratory symptoms peaks between days 3-7 of the disease and dehydration is a key sign to consider for the management. In this review, we will discuss the most controversial points in the management of bronchiolitis according to six evidence-based guidelines, six clinical practice guidelines and five consensus-based reviews.

A fit, 36-year-old man with a history of Crohn's disease previously treated with azathioprine, presented acutely with progressive shortness of breath on exertion and pleuritic chest pain. At the time of presentation, his Crohn's disease was quiescent, supported by a normal faecal calprotectin. The initial chest CT suggested the presence of a diffuse inflammatory disorder and he was subsequently started on high dose oral steroids. Despite 4 months of steroid therapy, there was minimal improvement. Following discussion at the inflammatory bowel disease multidisciplinary team meeting, a decision was made to commence infliximab. Subsequently, he made a dramatic clinical and physiological recovery. His forced expiratory volume in 1 s improved from 2.22 L/min (50% predicted) to 3.65 L/min (93% predicted) and he returned to baseline levels of exercise., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bronchiolitis is an acute lower respiratory infection which predominantly affects young children. Treatment for bronchiolitis is limited to supportive therapy. Nasal oxygen therapy is part of routine care, and delivery now incorporates varying levels of non-invasive continuous positive airway pressure and/or high-flow nasal cannula oxygen therapy. Despite wide clinical use, there remains a lack of evidence on the comparative effectiveness and safety of these interventions. Furthermore, research in this field is hampered by the use of multiple outcome measures in current clinical trials., Methods/design: This mixed methods study includes a systematic review of outcome measures, telephone interviews with parents, focus group workshops and a Delphi survey with healthcare professionals and parents. These methods will be used to identify and prioritise outcomes for inclusion in a core outcome set and to explore issues pertinent to the design of a future randomised controlled trial comparing different modes of oxygen therapy for bronchiolitis. UK hospitals will also be contacted and asked to complete a survey to provide an overview of current practice to enable assessment of capability and capacity to run a future clinical trial., Discussion: This study will facilitate the design of a future clinical trial of non-invasive ventilation in children with bronchiolitis which is acceptable to important stakeholders. Furthermore, core outcome set development will improve standardisation, measurement and reporting of clinically important outcomes in bronchiolitis., Trial Registration: ISRCTN Registry, ISRCTN75766048. Registered on 18 December 2017. This study was retrospectively registered in the ISRCTN Registry and on the Core Outcome Measures in Effectiveness Trials (COMET) Initiative database (15 September 2017).

Background and Objectives: Bronchiolitis is a leading cause of pediatric hospitalizations in the United States. Although the American Academy of Pediatrics recommends against routine use of bronchodilators in bronchiolitis management, racemic epinephrine was persistently used for this purpose at Le Bonheur Children's Hospital. Our aim was to decrease racemic epinephrine use for bronchiolitis by 50% within 8 months., Methods: Our multidisciplinary team used the Institute for Healthcare Improvement's Model for Improvement to develop an aim statement, choose metrics, and perform plan-do-study-act cycles to reduce racemic epinephrine use. We used focused education through in-person and online methods and provided direct feedback to residents, respiratory therapists, and nurses primarily caring for these children. The percentage of all patients admitted for bronchiolitis receiving at least 1 dose of racemic epinephrine was collected from the medical record and recorded on statistical process control charts for distribution to their work areas. Albuterol use and length of stay were collected as balancing measures. We used statistical process control charts to establish special cause variation and identify statistically significant differences in our measures., Results: During our intervention period, the percentage of bronchiolitis patients receiving at least 1 dose of racemic epinephrine to treat bronchiolitis decreased from an average of 26% to 5%, and similarly, albuterol use decreased from an average of 48% to 34%. There was no clinically significant difference in length of stay., Conclusions: Using a multidisciplinary approach and focused education techniques may be an effective way to reduce racemic epinephrine use for children with bronchiolitis., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

The frequency of Chlamydia trachomatis infection among young infants admitted with acute bronchiolitis was analysed to determine whether the former affects the clinical course of the latter. A total of 92 infants aged <6 months admitted with acute bronchiolitis were tested for C. trachomatis by a cell culture technique, obtaining nasal smears from each infant's nostrils. A second nasal sampling was taken for respiratory viruses from the study group and tested with real-time polymerase chain reaction. Clinical characteristics of C. trachomatis-positive and -negative cases were compared. C. trachomatis was detected in 22.8% of the infants, mostly as coinfection with respiratory viral agents. Infection with C. trachomatis affected the clinical outcome in acute bronchiolitis and such infants tended to have severe bronchiolitis.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Follicular bronchiolitis (FB) is a rare interstitial lung disease (ILD) and has been reported in diverse clinical contexts. Six FB patients demonstrated by surgical lung biopsy (SLB) were reviewed between 2009 and 2017 from Nanjing Drum Tower Hospital in China. The average age of subjects was 42 years old (range: 31-55 years). The clinical symptoms were very mild. The laboratory findings showed elevated Erythrocyte sedimentation rate (ESR) and serum globulin and anemia. Pulmonary function tests were normal in four cases. Five cases had underlying diseases, such as, Sjo¨gren's syndrome, multi-centric castlemans' disease, idiopathic pneumonia with autoimmune features and abscess. Five cases presented as interstitial lung disease (ILD) on chest imaging with centrilobular or peribronchiolar nodules, ground glass opacities, interlobular septal thickening, cysts and bronchiectasis. Isolated mass was in one patient. The histopathology suggested the changes of FB in all subjects. Prednisone and/or cyclophosphamide were used in four cases, one did the surgery and the other was clinically monitored. All cases were alive at the end of follow up. The adult patients of FB usually have mild symptoms, ILD and underlying diseases. The definite diagnosis needs SLB. The prognosis is depended on their underlying conditions.

Introduction: Bronchiolitis is an acute small airways inflammation mainly caused by a viral infection. It is frequent in children under two years of age, particularly under 12 months. The use of systemic corticosteroids has been proposed for bronchiolitis, especially for severely ill patients. However, its efficacy is still controversial., Methods: To answer this question we gathered information using Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data from primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified four systematic reviews, including 20 randomized trials overall. We concluded the use of systemic corticosteroids has no benefit for the treatment of bronchiolitis, even for patients with mechanical ventilation.

Background: The transition from early childhood wheezing to persistent asthma is linked to lung function impairment over time. Little is known how the methods used to study lung function at different ages correlate longitudinally., Methods: Sixty-four children with a history of hospitalization for bronchiolitis before 6 months of age were prospectively studied with impulse oscillometry (IOS) at the mean age of 6.3 years and these preschool IOS results were compared with flow-volume spirometry (FVS) measurements at mean age of 11.4 years., Results: The baseline respiratory system resistance at 5 Hz (Rrs5) showed a modest statistically significant correlation with all baseline FVS parameters except FVC. The post-bronchodilator (post-BD) Rrs5 showed a modest statistically significant correlation with post-BD FEV 1 and FEV 1 /FVC. The bronchodilator-induced decrease in Rrs5 showed a modest statistically significant correlation with the percent increase in FEV 1 . Baseline and post-BD respiratory reactance at 5 Hz (Xrs5) showed a modest statistically significant correlation with baseline and post-BD FVS parameters except post-BD FEV 1 /FVC, respectively, and post-BD Xrs5 showed a strong correlation with post-BD FVC (ρ = 0.61) and post-BD FEV 1 (ρ = 0.59). In adjusted linear regression, preschool Xrs5 remained as a statistically significant independent predictor of FVS parameters in adolescence; the one-unit decrease in the Z-score of preschool post-BD Xrs5 predicted 9.6% lower post-BD FEV 1 , 9.3% lower post-BD FVC, and 9.7% lower post-BD MEF 50 when expressed as %-predicted parameters., Conclusion: Persistent post-BD small airway impairment in children with a history of bronchiolitis detected with IOS at preschool age predicted FVS results measured in early adolescence., (© 2018 Wiley Periodicals, Inc.)

Introduction: Bronchiolitis consists of an acute small airways inflammation secondary to a viral infection and is a frequent pathology among children under 2 years. The use of inhaled corticosteroids during bronchiolitis has been proposed to reduce recurrent wheeze or asthma, however there is controversy about it., Methods: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified three systematic reviews including 11 randomized trials. We concluded that inhaled corticosteroids do not reduce recurrent wheeze or asthma in patients with bronchiolitis.

BackgroundAlthough rhinovirus infection is associated with increased risks of acute and chronic respiratory outcomes during childhood compared with respiratory syncytial virus (RSV), the underlying mechanisms remain unclear. We aimed to determine the differences in nasal airway microRNA profiles and their downstream effects between infants with rhinovirus and RSV bronchiolitis.MethodsAs part of a multicenter cohort study of infants hospitalized for bronchiolitis, we examined nasal samples obtained from 16 infants with rhinovirus and 16 infants with RSV. We tested nasal airway samples using microarrays to profile global microRNA expression and determine the predicted regulation of targeted transcripts. We also measured gene expression and cytokines for NFκB pathway components.ResultsBetween the virus groups, 386 microRNAs were differentially expressed (false discovery rate (FDR)<0.05). In infants with rhinovirus, the NFκB pathway was highly ranked as a predicted target for these differentially expressed microRNAs compared with RSV. Pathway analysis using measured mRNA expression data validated that rhinovirus infection had upregulation of NFκB family (RelA and NFκB2) and downregulation of inhibitor κB family. Infants with rhinovirus had higher levels of NFκB-induced type-2 cytokines (IL-10 and IL-13; FDR<0.01).ConclusionIn infants with bronchiolitis, rhinovirus and RSV infections had different nasal airway microRNA profiles associated with NFκB signaling.

The most common delayed complication of sulfur mustard (SM) poisoning has been observed in the respiratory tracts. It was thus aimed to investigate the delayed respiratory complications in SM-exposed patients around 25 years before the study. Forty-three veterans with more than 25% disability of due to SM poisoning were investigated. Clinical examinations as well as pulmonary function test (PFT) were performed. High-resolution computed tomography (HRCT) of the lungs was done as clinically indicated. Triad of chronic cough, dyspnea, and expectoration were the most common symptoms that were recorded in 88.2%, 88.2%, and 64.7% of the patients, respectively. PFT abnormalities were detected in 44.18% of the patients. Restrictive pattern was the most common (41.86%), while pure obstructive pattern did not detect at all. Mixed pattern was significantly correlated with higher disability percentages among the veterans ( p < 0.001). Significant reverse correlation between the disability percentages and forced expiratory volume in 1 s/forced vital capacity ratio was obtained ( p = 0.010, r = -0.389). Air trapping was the most common abnormality in HRCTs (50%). Bronchiectasis (25%), pulmonary fibrosis (25%), and ground-glass attenuation (16.66%) were other common HRCT findings. Comparing with the previous studies on these patients, more restrictive and mixed pattern were observed. Moreover, bronchiolitis, bronchiectasis, and lung fibrosis were the main pathological findings in these patients.

Objective: To evaluate the efficacy of nasal continuous positive airway pressure (nCPAP) in decreasing respiratory distress in bronchiolitis., Design: Randomized controlled trial., Setting: Tertiary-care hospital in New Delhi, India. Participants: 72 infants (age <1y) hospitalized with a clinical diagnosis of bronchiolitis were randomized to receive standard care, or nCPAP in addition to standard care, in the first hour after admission. 23 parents refused to give consent for participation. 2 infants did not tolerate nCPAP., Participants: 72 infants (age <1y) hospitalized with a clinical diagnosis of bronchiolitis were randomized to receive standard care, or nCPAP in addition to standard care, in the first hour after admission. 23 parents refused to give consent for participation. 2 infants did not tolerate nCPAP., Intervention: The outcome was assessed after 60 minutes. If nCPAP was not tolerated or the distress increased, the infant was switched to standard care. Analysis was done on intention-to-treat basis., Main Outcome Measures: Change in respiratory rate, Silverman-Anderson score and a Modified Pediatric Society of New Zealand Severity Score., Results: 14 out of 32 in nCPAP group and 5 out of 35 in standard care group had change in respiratory rate ≥10 (P=0.008). The mean (SD) change in respiratory rate [8.0 (5.8) vs 5.1 (4.0), P=0.02] in Silverman-Anderson score [0.78 (0.87) vs 0.39 (0.73), P=0.029] and in Modified Pediatric Society of New Zealand Severity Score [2.5 (3.01) vs. 1.08 (1.3), P=0.012] were significantly different in the nCPAP and standard care groups, respectively., Conclusions: nCPAP helped reduce respiratory distress significantly compared to standard care.

Objective: No recent studies have performed a systematic review of all available instruments aimed at evaluating the severity of bronchiolitis. The objective of the present study was to perform a systematic review of instruments aimed at evaluating the severity of bronchiolitis and to evaluate their measurement properties., Methods: A systematic search of the literature was performed in order to identify studies in which an instrument for evaluating the severity of bronchiolitis was described. Instruments were evaluated based on their reliability, validity, utility, endorsement frequency, restrictions in range, comprehension, and lack of ambiguity., Results: A total of 77 articles, describing a total of 32 different instruments were included in the review. The number of items included in the instruments ranged from 2 to 26. Upon analyzing their content, respiratory rate turned out to be the most frequently used item (in 26/32, 81.3% of the instruments), followed by wheezing (in 25/32, 78.1% of the instruments). In 18 (56.3%) instruments, there was a report of at least one of their measurement properties, mainly reliability and utility. Taking into consideration the information contained in the instruments, as well as their measurement properties, one was considered to be the best one available., Conclusions: Among the 32 instruments aimed at evaluating the severity of bronchiolitis that were identified and systematically examined, one was considered to be the best one available. However, there is an urgent need to develop better instruments and to validate them in a more comprehensive and proper way., (Copyright © 2017. Published by Elsevier Ltd.)

Objectives: Neurologic and functional morbidity occurs in ~30% of PICU survivors, and young children may be at particular risk. Bronchiolitis is a common indication for PICU admission among children less than 2 years old. Two single-center studies suggest that greater than 10-25% of critical bronchiolitis survivors have neurologic and functional morbidity but those estimates are 20 years old. We aimed to estimate the burden of neurologic and functional morbidity among more recent bronchiolitis patients using two large, multicenter databases., Design: Analysis of the Pediatric Health Information System and the Virtual Pediatric databases., Setting: Forty-eight U.S. children's hospitals (Pediatric Health Information System) and 40 international (mostly United States) children's hospitals (Virtual Pediatric Systems)., Patients: Previously healthy PICU patients less than 2 years old admitted with bronchiolitis between 2009 and 2015 who survived and did not require extracorporeal membrane oxygenation or cardiopulmonary resuscitation., Interventions: None. Neurologic and functional morbidity was defined as a Pediatric Overall Performance Category greater than 1 at PICU discharge (Virtual Pediatric Systems subjects), or a subsequent hospital encounter involving developmental delay, feeding tubes, MRI of the brain, neurologist evaluation, or rehabilitation services (Pediatric Health Information System subjects)., Measurements and Main Results: Among 3,751 Virtual Pediatric Systems subjects and 9,516 Pediatric Health Information System subjects, ~20% of patients received mechanical ventilation. Evidence of neurologic and functional morbidity was present at PICU discharge in 707 Virtual Pediatric Systems subjects (18.6%) and more chronically in 1,104 Pediatric Health Information System subjects (11.6%). In both cohorts, neurologic and functional morbidity was more common in subjects receiving mechanical ventilation (27.5% vs 16.5% in Virtual Pediatric Systems; 14.5% vs 11.1% in Pediatric Health Information System; both p < 0.001). In multivariate models also including demographics, use of mechanical ventilation was the only variable that was associated with increased neurologic and functional morbidity in both cohorts., Conclusions: In two large, multicenter databases, neurologic and functional morbidity was common among previously healthy children admitted to the PICU with bronchiolitis. Prospective studies are needed to measure neurologic and functional outcomes using more precise metrics. Identification of modifiable risk factors may subsequently lead to improved outcomes from this common PICU condition.

Objective: Hospital-based data reveal that children who have secondhand smoke exposure (SHSe) experience severe respiratory illnesses and greater resource utilization. Our objective was to assess the relationship between SHSe and illness severity/resource utilization among children presenting to the pediatric emergency department (PED) with three common respiratory conditions-asthma, bronchiolitis, and pneumonia., Methods: A retrospective review of a yearlong consecutive sample of PED patients with SHSe status documentation and asthma, bronchiolitis, or pneumonia diagnoses was performed. PED illness severity/resource utilization variables included triage categorization, initial oxygen saturation, evaluation/testing (influenza A & B, respiratory syncytial virus, chest X-ray), procedures/interventions performed (supplemental oxygen, suctioning, intubation), medications administered, and disposition. Logistic and linear regression models were conducted to determine differences in each diagnosis group while controlling for sociodemographics, medical history, seasonality, and insurance type., Results: There were 3,229 children with documentation of SHSe status and an asthma (41%), bronchiolitis (36%), or pneumonia (23%) diagnosis. Across diagnosis groups, approximately 1/4 had positive documentation of SHSe. Asthmatic children with SHSe were more likely to receive corticosteroids (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.19, 2.44) and/or magnesium sulfate (OR = 1.66, 95% CI = 1.14, 2.40). Children with SHSe and bronchiolitis were more likely to receive racemic epinephrine (OR = 2.48, 95% CI = 1.21, 5.08), have a chest X-ray (OR = 1.36, 95% CI = 1.00, 1.85), and/or be admitted (OR = 1.46, 95% CI = 1.09, 1.95). No differences in illness severity/resource utilization were identified for children with pneumonia., Conclusions: SHS-exposed children with asthma or bronchiolitis have greater illness severity/resource utilization. Our findings highlight the importance of SHSe assessment, cessation, and research efforts in the PED setting.

In this analysis of a prospective, multicenter study of children hospitalized with bronchiolitis, 925 had respiratory syncytial virus (RSV)-A and 649 had RSV-B. Overall, bronchiolitis severity did not differ by RSV subtype. However, among children with RSV-only bronchiolitis, those children with RSV-A had higher risk of intensive care treatment (odds ratio, 1.31; 95% confidence interval, 1.00-1.71; P = 0.048) when compared with those having RSV-B.

Background: The goal of this study was to determine if IV magnesium, useful for severe pediatric asthma, reduces time to medical readiness for discharge in patients with bronchiolitis when added to supportive care., Methods: We compared a single dose of 100 mg/kg of IV magnesium sulfate vs placebo for acute bronchiolitis. Patients received bronchodilator therapy, nebulized hypertonic saline, and 5 days of dexamethasone if there was eczema and/or a family history of asthma. Time to medical readiness for discharge was the primary efficacy outcome. Bronchiolitis severity scores and need for infirmary or hospital admission and for clinic revisits within 2 weeks were secondary outcomes. Cardiorespiratory instability onset was the safety outcome., Results: A total of 162 previously healthy infants diagnosed with bronchiolitis aged 22 days to 17.6 months (median, 3.7 months) were enrolled. Approximately one-half of patients had eczema and/or a family history of asthma; 86.4% had positive findings on nasopharyngeal virus swabs. Geometric mean time until medical readiness for discharge was 24.1 h (95% CI, 20.0-29.1) for the 78 magnesium-treated patients and 25.3 h (95% CI, 20.3-31.5) for the 82 patients receiving placebo (ratio, 0.95 [95% CI, 0.52-1.80]; P = .91). Mean bronchiolitis severity scores over time were similar for the two groups. The frequency of clinic visits in the subsequent 2 weeks (33.8% and 27.2%, respectively) was also similar. Fifteen magnesium recipients (19.5%) vs five placebo recipients (6.2%) were readmitted to the infirmary or hospital within 2 weeks (P = .016). No acute cardiorespiratory side effects were reported., Conclusions: IV magnesium did not provide benefit for patients with acute bronchiolitis and may be harmful., Trial Registry: ClinicalTrials.gov; No.: NCT02145520; URL: www.clinicaltrials.gov., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs).We assessed changes in admission rate, respiratory support, and outcomes of infants <24 months with bronchiolitis admitted to ICU between 2002 and 2014 in Australia and New Zealand.During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11-15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27-0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (p<0.001). We observed considerable variability in practice between units, with six-fold differences in risk-adjusted intubation rates that were not explained by ICU type, size, or major patient factors. Annual direct hospitalisation costs due to severe bronchiolitis increased to over USD30 million in 2014.We observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

The National Institute for Health and Care Excellence (NICE) ( 2015 ) defines bronchiolitis as a lower respiratory tract infection affecting children under two years, peaking between three and six months. It affects about one in three infants in the first year of life, making it the most common respiratory infection in infants ( NICE 2015 , 2016 ). Of these infants, 2-3% will require admission to hospital ( NICE 2016 ). Respiratory syncytial virus (RSV) is the most common organism detected in the nasopharyngeal aspirate in hospitalised infants, although other viruses such as rhinovirus, parainfluenza virus, influenza virus, adenovirus and human metapneumovirus are increasingly being recognised ( Paul et al 2016 ). As most infants with bronchiolitis are managed at home, the data available from the literature is not reflective of the true incidence and may represent only the 'tip of the iceberg'.

Background: Acute bronchiolitis in infancy is considered a risk factor for recurrent wheezing episodes in childhood. The present study assessed prevalence, clinical manifestations and risk factors for recurrent wheezing events during the first 3 years of life and persistent wheezing events beyond this age in children hospitalized as young infants with acute bronchiolitis., Methods: Two groups of children aged 6 years were included. The study group comprised 150 children with a history of hospitalization for bronchiolitis, with the first event at <6 months of age. The control group comprised 66 age- and sex-matched children with no history of bronchiolitis before 6 months of age. Children in both groups had been followed until 6 years of age by their pediatricians; data were obtained retrospectively by reviewing ambulatory records during children's visits in pediatricians' clinics. The data included epidemiological parameters, prevalence, age at onset, number of and treatments given for episodes of wheezing events prior to 6 years of age, pathogens detected, and severity of acute bronchiolitis in the study group., Results: Overall, 58% and 27% of children in the study and control groups, respectively (P=0.001) had recurrent wheezing episodes prior to the age of 3 years. Children in the study group had earlier onset of recurrent wheezing, had more episodes of wheezing, and required more bronchodilator and systemic steroids treatments compared to the control group., Conclusion: Hospitalization within the first six months of life for acute bronchiolitis is an independent risk factor for recurrent wheezing episodes during the first 3 years of life.

Background: Surgical lung biopsy (SLB) is invasive and not possible in all patients with undiagnosed interstitial lung disease (ILD). We hypothesized that transbronchial biopsy (TBB) findings combined with clinical and high-resolution CT (HRCT) data leads to a confident diagnosis congruent to SLB and therefore avoids the need for SLB in some patients., Methods: We evaluated 33 patients being investigated for suspected ILD who underwent HRCT, TBB, and SLB. First, clinicians, radiologists, and a pathologist reviewed the clinical information and HRCT and TBB findings. Clinicians were asked to provide a diagnosis and were also asked if SLB was needed for a more confident diagnosis. Subsequently, the clinical, HRCT, and SLB data were reviewed, and the same participants were asked to provide a final diagnosis. Clinician consensus and overall agreement between TBB- and SLB-based diagnoses were calculated., Results: Four patients had definite usual interstitial pneumonia (UIP) on HRCT and would not be considered for biopsy using current guidelines. Of the 29 patients without a definitive HRCT diagnosis, the clinicians felt confident of the diagnosis (ie, would not recommend SLB) in six cases. In these cases, there was 100% agreement between TBB and SLB diagnoses. UIP was the most common diagnosis (n = 3) and was associated with an HRCT diagnosis of possible UIP/nonspecific interstitial pneumonia-like. Agreement was poor (33%) between TBB and SLB diagnoses when confidence in the TBB diagnosis was low., Conclusions: Information from TBB, when combined with clinical and HRCT data, may provide enough information to make a confident and accurate diagnosis in approximately 20% to 30% of patients with ILD., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Bronchiolitis is a prevalent disease in children under two years of age, which carries significant morbidity and mortality. However, there is controversy regarding the optimal therapeutic management. Leukotriene inhibitors have been proposed as an alternative, although its efficacy is not clear yet. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified two systematic reviews comprising six trials addressing the question of this article. We extracted data, combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded leukotriene inhibitors might not decrease mortality levels on bronchiolitis patients and it is not clear whether they decrease length of hospital stay. They might reduce recurrent wheezing, but the certainty of the evidence is low, and they increase adverse effects.

Aim: The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months., Methods: This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test., Results: Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT., Conclusion: This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)