Fisiología respiratoria: fisiopatología de las enfermedades obstructivas / Pathophysiology of obstructive diseases

Las enfermedades obstructivas de la vía aérea pediátrica son muy frecuentes debido a los fenómenos mecánicos que están involucrados. En los niños más pequeños, la marcada resistencia de las vías aéreas pequeñas, determinada por la falta de tejido elástico y una caja torácica aún no bien desarrollada; tanto su estructura como la musculatura, facilitarán que cuadros infecciosos, mecánicos (cuerpo extraño) y compresivos, determinen que los flujos de aire se vean limitados y con ello la ventilación alveolar. La respuesta fisiológica con aumento del trabajo respiratorio es limitada y por lo tanto la fatiga muscular determinará hipoventilación con las consecuencias de hipoxemia e hipercapnia.

Obstructive diseases of the pediatric airway are very frequent due to the mechanical phenomena that are involved. The marked resistance of the small airways, such as the lack of elastic tissue and a thoracic cage that is not yet well developed, both in its structure and in the musculature, will make it easier for infectious, mechanical (foreign body), compressive and other conditions to determine that the flows of air are limited and with it the alveolar ventilation. The physiological response with increased work of breathing is limited and therefore muscle fatigue will determine hypoventilation, with the consequences of hypoxemia and hypercapnia.

Late Pre-term Infants with Severe Bronchiolitis and Risk of Asthma by Age 5 Years.

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.

Disability-adjusted life years for acute bronchiolitis in infants in Colombia.

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.

Risk factors for irreversible airway obstruction after infant bronchiolitis.

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.

Capillary blood gas in infants with bronchiolitis: Can end-tidal capnography replace it?

OBJECTIVES: To explore the predictive ability of capillary blood gas (CBG) pCO2 for respiratory decompensation in infants aged ≤6 months with bronchiolitis admitted from the emergency department; to determine whether end-tidal CO2 (etCO2) capnography can serve as a less invasive substitute for CBG pCO2. 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 pCO2 and etCO2 capnography were obtained in the ED prior to inpatient admission. Simple logistic regression modeling was used to examine the associations of CBG pCO2 and etCO2 capnography with respiratory decompensation. Pearson's correlation measured the relationship between CBG pCO2 and etCO2 capnography. RESULTS: Of 134 patients, 61 had respiratory decompensation. There was a significant association between CBG pCO2 and respiratory decompensation (OR = 1.07, p = 0.003), even after outlying values were excluded (OR = 1.06, p = 0.005). End tidal CO2 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 etCO2 capnography and CBG pCO2 (r = 0.39, p < 0.001). CONCLUSION: In infants with bronchiolitis, CBG pCO2 provides an objective measure for predicting respiratory decompensation, and a single etCO2 measurement should not replace its use.

Bronchiolitis and SARS-CoV-2.

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.

Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China.

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.

Intermittent vs Continuous Pulse Oximetry in Hospitalized Infants With Stabilized Bronchiolitis: A Randomized Clinical Trial.

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.

Rhinovirus bronchiolitis, maternal asthma, and the development of asthma and lung function impairments.

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 ß-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.

Actualización de la bronquiolitis aguda / Acute bronchiolitis update

La bronquiolitis aguda es una condición respiratoria frecuente en los niños menores de 2 años. Representa la principal causa de hospitalización infantil y se caracteriza por la presencia de sibilancias asociada a signos de una infección respiratoria alta. El agente etiológico más común es el virus respiratorio sincicial. Existe una falta de consenso con respecto a su definición clínica; y por ello, su tratamiento varía en todo el mundo. El diagnóstico es clínico, sin necesidad de emplear laboratorio o imágenes en forma rutinaria. Diversas revisiones han demostrado que los broncodilatadores, adrenalina, corticoides y antibióticos, entre otros, carecen de eficacia por lo que no se sugiere su empleo. El tratamiento sigue siendo de soporte, mediante la administración de oxígeno y manteniendo una adecuada hidratación. Cuando no se logra disminuir el trabajo respiratorio o corregir la hipoxemia se puede utilizar la presión positiva en la vía aérea para prevenir y controlar la insuficiencia respiratoria. Este artículo desarrolla una breve revisión de las principales características clínicas, epidemiológicas, radiológicas, así como algunos de los diferentes tratamientos publicados en las últimas dos décadas.

Acute bronchiolitis is a common respiratory condition in children under 2 years old. It represents the main cause of childhood hospitalization characterized by the presence of wheezing associated with signs of an upper respiratory infection. The most common etiologic agent is respiratory syncytial virus. There is a lack of consensus regarding its clinical definition; and therefore, its treatment varies around the world. Diagnosis is clinical, without the need for routine laboratory or imaging. Various reviews have shown that bronchodilators, epinephrine, corticosteroids, and antibiotics, among others, lack efficacy, so their use is not suggested. Treatment continues to be supportive, by administering oxygen and maintaining adequate hydration. When it is not possible to reduce the work of breathing or correct the hypoxemia, positive airway pressure can be used to prevent and control respiratory failure. This article develops a brief review of the main clinical, epidemiological, and radiological characteristics, as well as some of the different treatments published in the last two decades.

Frequency, Timing, Risk Factors, and Outcomes of Desaturation in Infants With Acute Bronchiolitis and Initially Normal Oxygen Saturation.

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.

Beta-2 agonists for the treatment of bronchiolitis. / Beta-2 agonistas para el tratamiento de bronquiolitis.

INTRODUCCIÓN: La bronquiolitis es la inflamación aguda de las vías aéreas de pequeño calibre, teniendo como causa principal las infecciones virales. Es altamente frecuente en menores de dos años, sobretodo en menores de 12 meses. Existe gran controversia sobre el manejo de esta patología, siendo especialmente cuestionable el uso de beta-2 agonistas de corta acción tanto en el ámbito ambulatorio como hospitalario. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos siete revisiones sistemáticas que en conjunto incluyen 47 estudios primarios, de los cuales 44 corresponden a ensayos aleatorizados. Concluimos que el uso de beta-2 agonistas podría no tener ningún beneficio en el manejo de la bronquiolitis, en términos de necesidad de hospitalización y/o duración de la misma. Por otra parte, podría aumentar efectos adversos como arritmias, sin embargo, la certeza de esta evidencia es baja.

Lung ultrasound scoring in invasive mechanically ventilated children with severe bronchiolitis.

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.

Machine learning-based prediction of acute severity in infants hospitalized for bronchiolitis: a multicenter prospective study.

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.

Lung Ultrasound and Clinical Progression of Acute Bronchiolitis: A Prospective Observational Single-Center Study.

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.

Myocardial strain on admission predicts disease severity in infants hospitalized for bronchiolitis.

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.

Novel Variants of Respiratory Syncytial Virus A ON1 Associated With Increased Clinical Severity of 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.

Neutrophil-endothelial interactions in respiratory syncytial virus bronchiolitis: An understudied aspect with a potential for prediction of severity of disease.

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.

Clinical factors associated with intubation in the high flow nasal cannula era.

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.

Pulmonary Manifestations of Inflammatory Bowel Disease.

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.