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Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respiratory tract infection and hospitalization in children < 5 years of age worldwide. While there are known clinical risk factors for severe RSV infection, the majority of those hospitalized are previously healthy infants. There is consequently an unmet need to identify biomarkers that predict host response, disease severity, and sequelae. The primary objective is to identify biomarkers of severe RSV acute respiratory tract infection (ARTI) in infants. Secondary objectives include establishing biomarkers associated with respiratory sequelae following RSV infection and characterizing the viral load, RSV whole-genome sequencing, host immune response, and transcriptomic, proteomic, metabolomic and epigenetic signatures associated with RSV disease severity. Six hundred thirty infants will be recruited across 3 European countries: the Netherlands, Spain, and the United Kingdom. Participants will be recruited into 2 groups: (1) infants with confirmed RSV ARTI (includes upper and lower respiratory tract infections), 500 without and 50 with comorbidities; and (2) 80 healthy controls. At baseline, participants will have nasopharyngeal, blood, buccal, stool, and urine samples collected, plus complete a questionnaire and 14-day symptom diary. At convalescence (7 weeks ± 1 week post-ARTI), specimen collection will be repeated. Laboratory measures will be correlated with symptom severity scores to identify corresponding biomarkers of disease severity., Clinical Trials Registration: NCT03756766., (© 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.)

Objectives: To apply metabolomic analysis of amniotic fluid in a discovery cohort to see whether a specific biochemical-metabolic profile at birth is associated with the subsequent onset of wheezing over the first year of life., Study Design: This prospective exploratory study was conducted in a healthy term-born Dutch cohort recruited at 2 hospitals in Utrecht (UMCU, Utrecht, and Diakonessenhuis, Utrecht), The Netherlands. A metabolomic approach based on mass spectrometry was applied to analyze 142 amniotic fluid samples collected at birth. The infants were followed up during their first year of life with recording any respiratory symptoms daily, and they were classified according to the onset of wheezing., Results: Orthogonally constrained projection to latent structures discriminant analysis was used to investigate differences in the metabolic profiles of the infants with (n = 86) and without (n = 56) wheezing. A search of the available databases for amniotic fluid metabolites identified by stability selection, combined with pathway analysis, highlighted the possible metabolic perturbations involved in this condition. The model built using 16 relevant variables with plausible biological significance, showed an area under the curve of 0.82 (P < .001) and an area under the curve calculated by 7-fold full cross-validation of 0.72 (P = .003), with the steroid hormone biosynthesis and the 2-phenylalanine metabolism emerging as probably perturbed pathways., Conclusions: Infants who will or will not experience wheezing in their first year of life have distinct amniotic fluid metabolomic profiles at birth. Changes occurring in biochemical-metabolic pathways in late intrauterine life may have a pathogenic role in early-onset wheezing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home., Objectives: We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma., Methods: Children with atopic asthma (n = 151) were randomly assigned to two groups: FeNO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FeNO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks., Measurements and Main Results: Telemonitoring was feasible with reliable FeNO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FeNO0.05 group., Conclusions: Thirty weeks of daily FeNO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FeNO0.05 monitoring compared with daily symptom monitoring only.