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Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

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INTRODUCTION: Reactance inversion (RI) has been associated with impaired peripheral airway function in persistent asthma. However, there is little to no data about the difference between asthmatic children with and without RI. This study aimed to detect clinical and lung function differences in moderate-severe asthmatic children with and without RI. METHODS: This study was conducted between 2021 and 2022 in asthmatic school-age children. Impulse oscillometry (IOS) and spirometry were performed according to ATS/ERS standards. RESULTS: A total of 62 patients, with a mean age of 8.4 years, 54.8% were males and were divided into three groups: group 1 (32.3%) with no RI, group 2 (27.4%) with RI but disappearing after bronchodilator test and group 3 (40.3%) with persistent RI after bronchodilator test. Children in groups 2 and 3 had significantly lower birth weights than in group 1. Group 2 had lower gestational age compared to group 1. FEV1 and FEF25-75 of forced vital capacity were significantly lower in groups 2 and 3. In group 3, R5, AX, R5-20, and R5-R20/R5 ratios were significantly higher. Bronchodilator responses (BDR) in X5c, AX, and R5-R20 were significantly different between groups and lower in group 3. CONCLUSION: RI is frequently found in children with moderate-severe persistent asthma, particularly in those with a history of prematurity or low birth weight. In some patients, RI disappears after the bronchodilator test; however, it, persists in those with the worst pulmonary function. RI could be a small airway dysfunction marker.

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RATIONALE: Experimental studies and epidemiological data in adults suggest that somatomedin-C (insulin-like growth factor-1, IGF-1) may play a role in asthma by modulating airway inflammation, bronchial hyperreactivity, and airway smooth muscle hyperplasia. However, its role in children with asthma is not well understood. METHODS: We established a birth cohort with 339 Chilean pregnant mothers enrolled at the time of delivery from December 2014 to January 2016. We obtained cord blood at birth and followed the offspring every 6 months until 30 months of age, recording data on atopy, wheezing, and other respiratory illnesses. We measured IGF-1 in cord blood and determined the Asthma Predictive Index (API) at 30 months. The cohort was divided according to the API. RESULTS: Complete data were available for 307/339 (91%) dyads, including 44 preschoolers with API+ and 263 with API-. Demographic characteristics were similar between groups, but mothers of API+ children had a higher prevalence of obesity, previous use of oral contraceptives, and higher education than those of API- children. API+ children had higher birth weight and significantly higher IGF-1 in cord blood (37.4 ± 13.2 in API+ vs. 30.5 ± 13.0 ng/ml in API-, p = .01). In the multivariable analysis, IGF-1 in cord blood remained independently associated with a higher risk of asthma (adjusted OR for API+ per ng/ml higher IGF-1 = 1.03 [1.0-1.06], p = .015). CONCLUSIONS: Higher insulin-like growth factor-1 in cord blood is associated with asthma risk in the preschool years.

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In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (ß2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.

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Asthma is a widespread disease affecting approximately 300-million people globally. This condition leads to significant morbidity, mortality, and economic strain worldwide. Recent clinical and laboratory research advancements have illuminated the immunological factors contributing to asthma. As of now, asthma is understood to be a heterogeneous disease. Personalized medicine involves categorizing asthma by its endotypes, linking observable characteristics to specific immunological mechanisms. Identifying these endotypic mechanisms is paramount in accurately profiling patients and tailoring therapeutic approaches using innovative biological agents targeting distinct immune pathways. This article presents a synopsis of the key immunological mechanisms implicated in the pathogenesis and manifestation of the disease's phenotypic traits and individualized treatments for severe asthma subtypes.

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The clinical manifestations of asthma in children are highly variable, are associated with different molecular and cellular mechanisms, and are characterized by common symptoms that may diversify in frequency and intensity throughout life. It is a disease that generally begins in the first five years of life, and it is essential to promptly identify patients at high risk of developing asthma by using different prediction models. The aim of this review regarding the early prediction of asthma is to summarize predictive factors for the course of asthma, including lung function, allergic comorbidity, and relevant data from the patient's medical history, among other factors. This review also highlights the epigenetic factors that are involved, such as DNA methylation and asthma risk, microRNA expression, and histone modification. The different tools that have been developed in recent years for use in asthma prediction, including machine learning approaches, are presented and compared. In this review, emphasis is placed on molecular mechanisms and biomarkers that can be used as predictors of asthma in children.

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Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNß-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 µg subcutaneous pegylated IFNß-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNß-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNß-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNß-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNß-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.

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BACKGROUND AND OBJECTIVES: Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults. METHODS: A double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. RESULTS: Exposure to inhaled IFN-α2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-α concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons). CONCLUSIONS: Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. CLINICAL TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.

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BACKGROUND: Lung function in children with persistent asthma may be impaired during preschool and school ages. The aim of this study was to describe if some preschool impulse oscillometry (IOS) parameters are related to spirometry alterations on reaching school age. METHODS: In 66 diagnosed with persistent asthma, an IOS was performed at entrance and followed-up to school age where a spirometry was done. RESULTS: The mean age was 4.9 years at the first evaluation and 7.9 years at the second evaluation, and 59.1% were male. During preschool, R5, R20, Fres, AX, and D5-20 were found to have diagnostic accuracy (area under the curve > 0.7) for predicting abnormal spirometry during school age (defined as FEV1 and/or FEV/FVC and/or FVC values below the lower limit of normality according to Quanjer predictive values). AX, D5-20, and R5 had the best LR+ to increase the probability of abnormal spirometry (50, 10, and 7.1, respectively). R20, R5, and AX was the best IOS parameters for discriminating bronchodilator response (BDR) in schoolchildren (LR+ = 3.4, 2.9, and 2.8, respectively). CONCLUSION: The findings of this study indicate that some IOS parameters between 3 and 5 years of age are useful for predicting abnormal spirometry and BDR at school age.

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BACKGROUND: Observational studies suggest that asthma/wheezing improves after adenotonsillectomy (AT). However, there is a paucity of randomized clinical trial (RCT) specifically studying the effects of AT in asthma/wheezing. Therefore, we conducted a post-hoc analysis of the Childhood Adenotonsillectomy Trial (CHAT), the largest RCT of AT in children with obstructive sleep apnea (OSA) to test the hypothesis that AT would result in fewer wheezing episodes. METHODS: In the CHAT study, 464 children with OSA, aged 5-9 years, were randomized to early AT (n = 226) or watchful waiting with supportive care (WWSC) (n = 227). For this post-hoc analysis, children were categorized as having "any wheezing" versus "no wheezing" at baseline and at 7 months of follow-up. A multivariate analysis was conducted to evaluate the association between "any wheezing" at follow-up and treatment group after controlling for several potential confounders. RESULTS: Children in the "any wheezing" group were predominantly black, had more allergic rhinitis, eczema, second-hand smoke exposure, body mass index, apnea-hypopnea index (AHI), and had lower maternal education and family income than those in the "no wheezing group." In the AT arm, the prevalence of wheezing significantly decreased from baseline to follow-up (at 7 months of the intervention) (47% vs. 21.6%, p < 0.001); while in the WWSC arms did not change (45.2% vs. 43.1%, p = 0.67). In the multivariate analysis, second-hand smoke exposure, wheezing at baseline, and belong to WWSC arm (odds ratio: 3.65 [2.16-6.19]) increase the risk of wheezing at follow-up. CONCLUSION: This study demonstrated that AT decreased the risk of wheezing at 7 months of follow-up.

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