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Carlos E Rodríguez-Martínez,1,2 Monica P Sossa-Briceño,3 Jose A Castro-Rodriguez4 1Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia; 2Department of Pediatric Pulmonology and Pediatric Critical Care Medicine, School of Medicine, Universidad El Bosque, Bogota, Colombia; 3Department of Internal Medicine, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia; 4Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Background: For the early identification of persistent asthma symptoms among young children with recurrent wheezing, it would be helpful to identify all available studies that have identified at least one factor for predicting the persistence of early wheezing. The objective of the present study was to perform a systematic review of all studies that have identified factors that predict the persistence of symptoms among young patients with recurring wheezing. Methods: A systematic review of relevant studies was conducted through searching in MEDLINE, EMBASE, CINHAL, and SCOPUS databases up to June 2016. Studies that identified predictors of persistence of wheezing illness among young children with recurrent wheezing were retrieved. Two independent reviewers screened the literature and extracted relevant data. Results: The literature search returned 649 references, 619 of which were excluded due to their irrelevance. Five additional studies were identified from reference lists, and 35 studies were finally included in the review. Among all the identified predictors, the most frequently identified ones were the following: family asthma or atopy; personal history of atopic diseases; allergic sensitization early in life; and frequency, clinical pattern, or severity of wheezing/symptoms. Conclusion: Parental asthma (especially maternal), parental allergy, eczema, allergic rhinitis, persistent wheezing, wheeze without colds, exercise-induced wheeze, severe wheezing episodes, allergic sensitization (especially polysensitization), eosinophils (blood or eosinophil cationic protein in nasal sample), and fraction of exhaled nitric oxide were risk factors predicting persistence of early wheezing through school age. All of them are included in conventional algorithms, for example, Asthma Predictive Index and its modifications, for predicting future asthma. Keywords: birth cohort, infantile asthma, longitudinal studies, persistence, continuance, prognosis

Omalizumab is a humanized monoclonal anti-IgE for the treatment of severe allergic asthma. Because omalizumab targets an immune system molecule, there has been particular interest in the drug's safety. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the efficacy of inhaled corticosteroids (ICS) versus montelukast (MONT) in schoolchildren and adolescents with mild-moderate persistent asthma. METHODS: Randomised, prospective, controlled trials published January 1996 to November 2009 with a minimum of 4 weeks of ICS versus MONT and of ICS versus MONT+ICS were retrieved through Medline, Embase and Central databases. The primary outcome was asthma exacerbations requiring systemic corticosteroids (AEX); secondary outcomes were pulmonary function, withdrawal/hospitalisation due to AEX, change in symptoms score, rescue-medication-free days, albuterol use, adverse effects and adherence. RESULTS: Of 124 studies identified, 18 studies (n=3757 patients) met criteria for inclusion (13 compared ICS vs MONT, 3 ICS vs MONT+ICS and 2 ICS vs MONT vs ICS+MONT). Patients receiving ICS showed a significantly lower risk for AEX than those with MONT (RR=0.83, 95% CI 0.72 to 0.96, p=0.01); post-hoc analysis suggests this effect was independent of quality, sponsorship and study duration. Children treated with ICS had a significant higher pulmonary function (final FEV1 % predicted, change from baseline FEV1 %, final morning peak expiratory flow (PEF)) and better clinical parameters (albuterol use, symptom score, rescue-medication-free days, withdrawals due to AEX) versus MONT. No significant difference in primary or secondary outcomes was found when MONT was added on to ICS versus ICS alone; however, these analyses were based on only two studies. CONCLUSIONS: Schoolchildren and adolescents with mild-moderate persistent asthma treated with ICS had less AEX and better lung function and asthma control than with MONT. There are insufficient data to determine whether the addition of MONT to ICS improves outcome. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend the use of inhaled corticosteroids (ICSs) added to long-acting beta(2)-agonists (LABAs) for treatment of symptomatic patients with severe and very severe COPD. However, the evidence has been inconclusive. The aim of this review was to assess the safety and efficacy of LABAs/ICSs compared with LABA monotherapy for patients with moderate-to-very severe COPD.Methods: Systematic searches were conducted on MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the trial registers of manufacturers, without language restriction. Primary outcomes were COPD exacerbations and mortality. Secondary outcomes included lung function, health-related quality of life, and adverse effects.Results: Eighteen randomized controlled trials (12,446 participants) were selected. Therapy with LABAs/ICSs did not decrease the number of severe exacerbations (relative risk [RR], 0.91; 95% CI, 0.82 to 1.01; I(2) = 1%), or all-cause mortality (RR, 0.90; 95% CI, 0.76 to 1.06; I(2) = 0%), respiratory mortality (RR, 0.80; 95% CI, 0.61 to 1.05; I(2) = 0%), and cardiovascular mortality (RR, 1.22; 95% CI, 0.88 to 1.71; I(2) = 0%). To the contrary, the number of moderate exacerbations (RR, 0.84; 95% CI, 0.74 to 0.96; I(2) = 50%) and the St. George respiratory questionnaire total score (weighted mean difference, -1.88; 95% CI, -2.44 to -1.33; I(2) = 29%) were significantly reduced with LABA/ICS therapy. Although therapy with LABAs/ICSs increases FEV(1) significantly (0.06 and 0.04 L, respectively), they were associated with an increased risk of pneumonia (RR, 1.63; 95% CI, 1.35 to 1.98; I(2) = 20%).Conclusions: Compared with LABA monotherapy, the magnitude of the benefits of LABA/ICS therapy did not reach that of the criteria for predefined clinically important effects and were associated with serious adverse effects. [ABSTRACT FROM AUTHOR]

Trinidad Sánchez,1 José A Castro-Rodríguez,2 Pablo E Brockmann2,3 1Division of Pediatrics, School of Medicine, 2Department of Pediatric Cardiology and Pulmonology, Division of Pediatrics, School of Medicine, 3Sleep Medicine Center, Department of Neurology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Background: The objective was to perform a systematic review in order to describe the relationship between asthma and sleep-disordered breathing (SDB) in children, especially regarding the impact of treatment and management. Methods: We performed an electronic search in MEDLINE, EMBASE, and LILACS database. Study inclusion criteria were the following: 1) studies that examined the relationship between asthma/wheezing and SDB/obstructive sleep apnea (OSA); and 2) studies conducted in children

OBJECTIVE: To compare the efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing or asthma. METHODS: Randomized, prospective, controlled trials published January 1996 to March 2008 with a minimum of 4 weeks of inhaled corticosteroids versus placebo were retrieved through Medline, Embase, and Central databases. The primary outcome was wheezing/asthma exacerbations; secondary outcomes were withdrawal caused by wheezing/asthma exacerbations, changes in symptoms score, pulmonary function (peak expiratory flow and forced expiratory volume in 1 second), or albuterol use. RESULTS: Of eighty-nine studies identified, 29 (N = 3592 subjects) met the criteria for inclusion. Patients who received inhaled corticosteroids had significantly less wheezing/asthma exacerbations than those on placebo (18.0% vs 32.1%); posthoc subgroup analysis suggests that this effect was higher in those with a diagnosis of asthma than wheeze but was independent of age (infants versus preschoolers), atopic condition, type of inhaled corticosteroid (budesonide metered-dose inhaler versus fluticasone metered-dose inhaler), mode of delivery (metered-dose inhaler versus nebulizer), and study quality (Jadad score: <4 vs >/=4) and duration (<12 vs >/=12 weeks). In addition, children treated with inhaled corticosteroids had significantly fewer withdrawals caused by wheezing/asthma exacerbations, less albuterol use, and more clinical and functional improvement than those on placebo. CONCLUSIONS: Infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations and improve their symptoms and lung function during treatment with inhaled corticosteroids. [ABSTRACT FROM AUTHOR]

Objectives: A significant percentage of patients with asthma appear to benefit from the addition of long-acting β2-agonists (LABAs) to ICS to achieve better control of their disease. The aim of the present study was to determine the cost-utility of single inhaler combination inhaled ICS/LABAs as both maintenance and reliever (SMART) versus remaining at the same treatment step with fixed-dose ICS-LABA maintenance with a short-acting β2-agonist (SABA) as reliever in patients aged 12 years or more with uncontrolled asthma., Methods: A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The effectiveness data and transition probabilities were obtained from a recent meta-analysis. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The main outcome was the variable "quality-adjusted life-years" (QALYs)., Results: The base-case analysis showed that compared with remaining at the same GINA treatment step with ICS/LABA maintenance plus SABA reliever, ICS/LABAs as SMART was associated with lower costs, US$2,906.92 versus $4,462.02 average cost per patient, and the greatest gain in QALYs, 0.8540 versus 0.8258 QALYs on average per patient, thus leading to dominance., Conclusions: Compared with remaining at the same GINA treatment step with ICS/LABA maintenance plus SABA reliever, ICS/LABAs as SMART is more cost-effective in patients aged 12 years or more with uncontrolled asthma. This is because ICS/LABAs as SMART showed a greater gain in QALYs at lower total treatment costs., (© 2024 Wiley Periodicals LLC.)

Inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are essential in asthma management, but the guidelines for treatment in preschool children remain heterogeneous worldwide. This systematic review evaluates the efficacy and safety of LABA + ICS therapy in asthmatic children under six years. We searched four databases, identifying six eligible studies (n = 1415 preschoolers), and in all the LABA used was salmeterol. Due to high heterogeneity, quantitative analysis was not feasible. Three before-and-after studies demonstrated significant reductions in unscheduled visits and hospitalizations due to asthma exacerbations with LABA + ICS. One RCT showed fewer exacerbations in the LABA + ICS group compared to ICS alone. Night-time awakenings decreased significantly in two studies but not in one RCT. Improvements in lung function using impulse oscillometry and FeNO levels were noted with LABA+ICS in one RCT. No significant adverse effects were reported. Despite positive findings, high-quality trials are needed to confirm these results, particularly using formoterol as LABA, aligning with the recommendations. Further research is imperative to optimize asthma management in preschool children., 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 © 2024 Elsevier Ltd. All rights reserved.)

Objective: The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting β2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting β2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia., Methods: A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ''quality-adjusted life-years'' (QALYs)., Results: The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs. $4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance., Conclusions: In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.

Objective: To review the recent evidence in the literature of various aspects of recurrent/severe wheezing in children under 3 in low-middle income countries [LMICS]., Sources: A non-systematic review including articles in English. We mainly selected publications from the last 5 years. Studies on epidemiology, aetiology, diagnosis, treatment, and prevention were included in the search. We reviewed differential diagnoses of wheezing that focused on LMICS. We also reviewed aspects of prevention., Summary of the Findings: Many epidemiological studies have shown a variable but significant number of wheezy infants [WI] cases in LMICS when compared to other countries. The differential diagnosis of causes of wheezing in this age group is mandatory, taking into account local facilities. Few treatment options have been well studied for this age group. In LMICS, a pragmatic approach could be considered, as described in the article. It is difficult to study primary prevention for WI and secondary prevention (mainly environmental) may have some impact. A schematic approach for recurrent wheezers is presented, which takes into account settings with limited resources., Conclusion: Severely or recurrently wheezy children under 3 is a common clinical issue in LMICS. Studies on this age group are needed to reduce the significant morbidity. It may be possible to lower the high burden of wheezing in this age group by selecting the phenotype which may respond to inhaled steroids., 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 © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features., Methods: Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated., Results: RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined., Conclusions: Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Asthma is the most prevalent chronic disease in children and constitutes a significant healthcare burden. First-line therapy for acute asthma exacerbations is well established. However, secondary treatments, including intravenous magnesium sulfate (IV-MgSO4), remain variable due to scarcity of data on its efficacy and safety., Objective: To assess the effectiveness and safety of IV-MgSO4 as a second line of treatment in managing children with asthma exacerbations., Methods: We searched five databases from inception until April 2023 on randomized clinical trials of IV-MgSO4 in children with acute asthma exacerbations. The primary outcomes were hospitalization rate and length, and change in the severity score. Secondary outcomes included percentage increase in peak expiratory flow rate (PEFR), hospital re-admission rate, need and length for pediatric intensive care unit (PICU) treatment, and adverse effects. Meta-analysis was performed for three outcomes with estimated odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs)., Results: Eleven studies met the final criteria. In comparison to control, administration of IV-MgSO4 was associated with a reduced hospitalization risk (OR 0.15; 95%CI: 0.03, 0.73) in four studies, and improvement of lung function (MD 26.77% PEFR; 95%CI: 18.41, 54.79) in two studies. There were no significant differences in the length of stay between groups. Due to heterogeneity, a narrative synthesis of other outcomes was performed., Conclusion: The use of IV-MgSO4 demonstrated a reduction in the hospitalization rate and PEFR improvement in children with asthma exacerbations. Adverse effects were rare. Further well-designed studies are needed to better determine the efficacy and safety profile of IV-MgSO4., 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 © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2023 Wiley Periodicals LLC.)

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-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., Competing Interests: Elsy M. Navarrete-Rodriguez receives speaking support and advice from Sanofi, AstraZeneca, GSK, Pfizer. Blanca E. del-Rio-Navarro receives speaking support and advice from Sanofi, Grunenthal. D&eacute;sir&eacute;e Larenas Linnemann receives speaking support and advice from Allakos, Armstrong, AstraZeneca, DBV Technologies, Grunenthal, GSK, Mylan, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer; and research grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, TEVA, Purina Institute. D&eacute;sir&eacute;e E.S. Larenas-Linnemann reports personal fees from ALK, AstraZeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GSK national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot, grants from Abbvie, Bayer, Lilly, Sanofi, AstraZeneca, Pfizer, Novartis, Circassia, UCB, GSK., outside the submitted work. She is coordinator of the immunotherapy committee of CMICA and general coordinator of ten national guidelines in the field of allergy, asthma, and immunotherapy. Jose A. Castro-Rodriguez receives speaking support and advice from AstraZeneca, Cassar&aacute;, Europharma, GSK, and Sanofi.

Introduction: Maternal obesity alters the immune function in the offspring. We hypothesize that maternal obesity and pro-inflammatory pathways induce leptin-related genes in neonatal monocytes, whereby high leptin levels enhance their inflammatory response., Methods: Transcriptional profiles of cord blood leukocytes (CBL) in basal and pro-inflammatory conditions were studied to determine differentially expressed genes (DEG). The DNA methylation profile of CB monocytes (CBM) of neonates born to control BMI mothers and women with obesity was assayed to identify differentially methylated probes (DMP). CBM-derived macrophages were cultured with or without leptin (10-100 ng/ml) and then stimulated with lipopolysaccharide (LPS, 100 ng/ml) and interferon-gamma (20 ng/ml) to assess the induction of TNF-α and IL-10 transcripts., Results: CBL from pregnancies with obesity (CBL-Ob) showed 12,183 DEG, affecting 49 out of 78 from the leptin pathway. Control CBM exposed to LPS showed 45 leptin-related DEG, an effect prevented by the co-exposure to LPS and IL-10. Conversely, CBM-Ob showed 5279 DMP enriched in insulin- and leptin-related genes, and Lasso regression of leptin-related DMP showed high predictive value for plasma leptin levels (r 2  = 0.9897) and maternal BMI categories (AUC = 1). Chronic exposure to leptin increased TNF-α and decreased IL-10 levels in control BMI samples but not in Ob-CBM. Enhanced TNF-α induction after proinflammatory stimulation was observed in leptin-treated control BMI samples., Discussion: Obesity in pregnancy is associated with a distinctive expression and DNA methylation profile of leptin-related genes in cord blood monocytes, meanwhile, leptin enhances the expression of pro-inflammatory cytokines upon stimulation with M1-skewing agents., 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 © 2023 Elsevier Ltd. All rights reserved.)

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.

Background: To characterize the use of sacubitril/valsartan in a group of patients with heart failure in Colombia., Research Design and Methods: Follow-up study of patients with heart failure who started sacubitril/valsartan and were affiliated with the Colombian health system between 2019 and 2021. Sociodemographic, clinical, and pharmacological variables and adherence and persistence of use were identified., Results: A total of 514 patients were identified, with a mean age of 65.7 years, 73.7% of whom started sacubitril/valsartan at low doses, and only 12.5% reached the maximum dose. Adherence was 78.2% and persistence was 56.8% at 1 year of follow-up. The increase in systolic blood pressure (odds ratio (OR): 1.01; 95% CI: 1.00-1.03) and the use of β-blockers (OR: 2.63; 95% CI: 1.42-4.85) were correlated with a greater persistence, while receiving furosemide (OR: 0.59; 95% CI: 0.39-0.89) and not having received renin - angiotensin - aldosterone system inhibitors in the 3 months before starting sacubitril/valsartan (OR: 0.48; 95% CI: 0.31-0.76) were associated with lower persistence., Conclusions: The persistence of treatment 1 year after starting sacubitril/valsartan was not high, and a small proportion of patients reached the target dose of the drug. Nontitration of the drug dose was common.

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.

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 IFNβ-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 IFNβ-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 IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-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 IFNβ-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, IFNβ-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., Competing Interests: Authors Castro-Rodriguez, Kollman, and Stick received funding from BHP Holdings Pty Ltd and Biogen Pty Ltd to conduct this study. Balshaw was paid consulting fees to advise on this study. Castro-Rodriguez received honoraria from AstraZeneca and GlaxoSmithKline to speak at symposia and Eurofarma for participation on advisory board. Kollmann has received research funding from NIH, Medical Research Future Fund, and Bill and Melinda Gates Foundation, honoraria from the Human Immunome Project to attend a conference, and holds two patents unrelated to this study. Montgomery received funding from NHMRC and TSANZ to present findings from this study at conferences. Authors Aniba, Borzutzky, Chen, Fish, Garcia-Huidobro, Gigi-Yunge, Hancock, Hartnell, Ho, Iturriaga, Karpievitch, Othman, Perret, Shannon, Tebbutt, and Urzua have no declared conflicts of interest., (© 2023 The Author(s).)

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., (© 2023 Wiley Periodicals LLC.)

Introduction: High altitude pulmonary edema (HAPE) is a form of acute noncardiogenic pulmonary edema caused by altitude-related hypoxia seen in children as well as in adults. In this systematic review we focus in HAPE occurring in children and adolescents., Methods: A systematic review was conducted including publications in children 0-18 years of age from three databases up to June 2022., Results: Thirty-five studies representing 210 cases were found. The mean age was 9.8 ± 3.6 years with a male/female ratio of 2.6. The peak age incidence was seen in children between 6 and 10 years old. Only two children (0.9%) were ≤2 years old. The mean altitude in 166 cases was 2861 masl. Only 17 cases (8.1%) occurred at altitudes below 2500 masl. Regarding the different HAPE subtypes there was a predominance of re-entry HAPE (R-HAPE) with 58%, followed by classic HAPE (C-HAPE) with 37.6%. The mean time between arrival and onset of symptoms was 16.5 h. The mortality rate was 1.4%. In 10/28 (36%) of C-HAPE cases there was a structural cardiac/pulmonary anomaly compared to 1/19 (5%) in R-HAPE (p < 0.01). HAPE recurrence was found in 46 cases (21.9%). The involvement in the chest X-rays was seen predominantly in the apices and in the right lung., Conclusions: R-HAPE was the most common HAPE subtype; HAPE peak age was found between 6 and 10 years of age; HAPE was more frequent in males and was rare in children under 2 years old; associated HAPE structural abnormalities were more common in C-HAPE than in R-HAPE., (© 2022 Wiley Periodicals LLC.)

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., (© 2022 Wiley Periodicals LLC.)

Background: Small airway dysfunction (SAD) in asthma can be measured by impulse oscillometry (IOS). Usually, the reactance should decrease with decreases in frequency oscillation. Sometimes an upward shift of the curve at low frequencies can be observed together with lower than expected reactance values. The actual value of the reactance at 5 Hz (X5) is calculated by the Sentry Suite application of the Jaeger Master screen iOS system™, providing the corrected X5 parameter (CX5). Our hypothesis is that correction of X5 is common in persistent asthma and it correlates better than X5 with the IOS parameters for evaluating SAD., Methods: In this transversal study, we evaluated 507 children (3-18 years old) using IOS-spirometry (Sentry Suite, Vyntus®). Resistance of all airways (R5), reactance area (AX), resonant frequency (Fres), X5, CX5, difference between R5 and R20 (D5-20), and spirometry parameters were analyzed. Reactance inversion and CX5 prevalence by age range was determined. The mean IOS-Spyrometry values in children with and without CX5 were compared, and correlations with each IOS-spirometry parameter in the age groups were performed., Results: CX5 was found in 83.5% of preschool children, 66.2% of schoolchildren, and 43.3% of adolescents ( p  < 0.001). The means of R5, AX, and D5-20 were significantly higher and FEV1 was significantly lower in children with CX5 ( p  < 0.05). In all ages, CX5 correlated better than X5 with IOS-spirometry parameters., Conclusion: Reactance inversion and CX5 are frequent in asthmatic children, decrease with age, and correlate more closely than X5 with other IOS-spirometry parameters for evaluating SAD.

Asthma affects a large number of people living in the Americas, a vast and diverse geographic region comprising 35 nations in the Caribbean and North, Central, and South America. The marked variability in the prevalence, morbidity, and mortality from asthma across and within nations in the Americas offers a unique opportunity to improve our understanding of the risk factors and management of asthma phenotypes and endotypes in children and adults. Moreover, a better assessment of the causes and treatment of asthma in less economically developed regions in the Americas would help diagnose and treat individuals migrating from those areas to Canada and the United States. In this focused review, we first assess the epidemiology of asthma, review known and potential risk factors, and examine commonalities and differences in asthma management across the Americas. We then discuss future directions in research and health policies to improve the prevention, diagnosis, and management of pediatric and adult asthma in the Americas, including standardized and periodic assessment of asthma burden across the region; large-scale longitudinal studies including omics and comprehensive environmental data on racially and ethnically diverse populations; and dissemination and implementation of guidelines for asthma management across the spectrum of disease severity. New initiatives should recognize differences in socioeconomic development and health care systems across the region while paying particular attention to novel or more impactful risk factors for asthma in the Americas, including indoor pollutants such as biomass fuel, tobacco use, infectious agents and the microbiome, and psychosocial stressor and chronic stress.

Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. RSV-induced bronchiolitis has been associated with preschool wheeze and asthma in cohort studies where the comparison groups consist of healthy infants. However, recent studies identify rhinovirus (RV)-induced bronchiolitis as a potentially stronger risk factor for recurrent wheeze and asthma., Aim: This systematic review and meta-analysis aimed to compare the associations of RSV- and RV-induced bronchiolitis with the development of preschool wheeze and childhood asthma., Methods: We performed a systematic search of the published literature in five databases by using a MeSH term-based algorithm. Cohort studies that enrolled infants with bronchiolitis were included. The primary outcomes were recurrent wheeze and asthma diagnosis. Wald risk ratios and odds ratios (ORs) were estimated, along with their 95% confidence intervals (CIs). Individual and summary ORs were visualized with forest plots., Results: There were 38 studies included in the meta-analysis. Meta-analysis of eight studies that had data on the association between infant bronchiolitis and recurrent wheeze showed that the RV-bronchiolitis group were more likely to develop recurrent wheeze than the RSV-bronchiolitis group (OR 4.11; 95% CI 2.24-7.56). Similarly, meta-analysis of the nine studies that had data on asthma development showed that the RV-bronchiolitis group were more likely to develop asthma (OR 2.72; 95% CI 1.48-4.99)., Conclusion: This is the first meta-analysis that directly compares between-virus differences in the magnitude of virus-recurrent wheeze and virus-childhood asthma outcomes. RV-induced bronchiolitis was more strongly associated with the risk of developing wheeze and childhood asthma., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The heterogeneity of bronchiolitis may imply or reflect a different predisposition to respiratory sequelae., Objective: Our aim was to investigate whether, among infants hospitalized with bronchiolitis, different clinical profiles extracted by latent class analysis (LCA) are associated with different risks of wheezing., Methods: Over 15 consecutive epidemic seasons (2004-2019), we prospectively enrolled infants <1 year hospitalized for the first episode of bronchiolitis in a single tertiary hospital. A detailed clinical questionnaire was filled for each infant. LCA was applied to differentiate bronchiolitis phenotypes, and after hospital discharge, a phone interview was performed annually to record the presence of wheezing episodes. Adjusted multivariate regression analyses were run to investigate the risk of wheezing during 7 years follow-up according to clinical phenotypes., Results: LCA performed on 1312 infants resulted in a three-class model. Profile 1 (65.5%): moderate bronchiolitis; Profile 2 (6.1%): severe bronchiolitis; and Profile 3(28.4%): bronchiolitis infants with high eosinophils blood count. At 1 year of follow up, about 50% of children presented wheezing in each profile. Compared to Profile 1, the adjusted odds ratio (OR) of having wheezing episodes was significantly higher in Profile 2 at 2, 3, and 4 years of follow-up. At 7 years, Profile 3 had an adjusted OR = 2.58, higher than Profile 2 (adjusted OR = 2.29)., Conclusions: LCA clearly identified a "moderate", "severe," and "high eosinophils blood count" bronchiolitis. During the first 4 years after bronchiolitis, the "severe" profile showed the higher risk of wheezing, but after 7 years this risk seems higher in the "high eosinophils blood count" group., (© 2021 Wiley Periodicals LLC.)

Over the past decade, "omics" approaches have advanced our understanding of the molecular programming of the airways in humans. Several studies have identified potential molecular mechanisms that contribute to early life epigenetic reprogramming, including DNA methylation, histone modifications, microRNAs, and the homeostasis of the respiratory mucosa (epithelial function and microbiota). Current evidence supports the notion that early infancy is characterized by heightened susceptibility to airway genetic reprogramming in response to the first exposures in life, some of which can have life-long consequences. Here, we summarize and analyze the latest insights from studies that support a novel epigenetic paradigm centered on human maturational and developmental programs including three cardinal elements: genes, environment, and developmental timing. The combination of these factors is likely responsible for the functional trajectory of the respiratory system at the molecular, functional, and clinical levels., (© 2021 Wiley Periodicals LLC.)

Obstructive sleep apnea syndrome affects 1%-4% of all children worldwide. Currently, diagnosis of obstructive sleep apnea is based on sea-level guidelines, without taking into account the altitude at which the populations live. It has been shown that at 3,200 m of altitude there is an increase in obstructive events in healthy children aged 7 to 16 years; on the other hand, it is known that SpO 2 dispersion between individuals becomes wider as altitude increases, a phenomenon that is more marked during sleep. About 17 million Colombians live in regions between 2,500 m and 2,700 m, as do significant populations in other Latin American countries. This research aimed to characterize respiratory polygraphy sleep parameters in healthy, non-snoring children aged 4-9 years living at 2,560 m. We carried out home respiratory polygraphy in 32 children with a mean age of 6.2 years (range 4-9 years). The average recorded sleep time was 7.8 h, the median apnea-hypopnea index was 9.2/h, the obstructive apnea-hypopnea index had a median of 8.8/h (p5 4.2 to p95 17.9) and central apnea a median of 0.4/h. The median SpO 2 was 93% (p5 90.5 to p95 94) and transcutaneous CO 2 had a median of 39.4 mmHg (p531.7 to p95 42.3). The median oxygen desaturation index ≥ 3% was 11.2 and median oxygen desaturation index ≥ 4% was 3.9. Normal measurements for respiratory polygraphy obtained at sea level do not apply to children at altitude. If such guidelines are used, obstructive sleep apnea will be over-diagnosed, resulting in unnecessary adenotonsillectomies, among other interventions., (© 2021 European Sleep Research Society.)

Diagnosing asthma in preschool children remains an unsolved challenge, at a time when early identification would allow for better education and treatment to prevent morbidity and lung function deterioration., Objective: To evaluate if the asthma predictive index (API) can be used as surrogate for asthma diagnosis in preschoolers., Methods: Birth cohort of 339 pregnant women enrolled at delivery and their offspring, who were followed for atopy, wheezing, and other respiratory illnesses through 30 months of age. The API was determined at 30 months of age by the researchers; and examined its association with physician-diagnosed asthma during the first 30 months, made independently by the primary care physician not involved in the study., Results: Among 307 offspring with complete follow-up, 44 (14.3%) were API+. Maternal body mass index, maternal education, past oral contraceptive use, birthweight, placenta weight, age of daycare at 12 m, gastroesophageal reflux disease at 12 m, acute otitis media at 18 m, bronchiolitis, croup and pneumonia, cord blood adiponectin were all associated with API+. In the multivariable analysis, API+ was associated with almost sixfold odds of asthma diagnosis (adjusted OR = 5.7, 95% CI [2.6-12.3]), after adjusting for the relevant covariates above including respiratory infections like bronchiolitis and pneumonia. The API sensitivity was 48%, specificity 92%, 61% PPV, 88% NPV, 6.4 LR+, 0.56 LR-, 0.84 diagnosis accuracy. The adjusted odds for asthma was 11.4., Conclusions: This longitudinal birth cohort suggests, for first time, that API (a structured definition for asthma), could be used as a diagnostic tool, not only as a prognostic tool, in toddlers and preschoolers., (© 2021 Wiley Periodicals LLC.)

Objectives: Although several randomized clinical trials performed in children 6 years and older with Omalizumab as add-on therapy have reported improvements in diverse clinical outcomes, the evidence regarding its cost effectiveness is not sufficient, especially in less-affluent countries, where the clinical and economic burden of the disease is the greatest. The aim of the present study was to perform a cost-utility analysis of adding omalizumab to standard treatment for treating pediatric patients with uncontrolled severe allergic asthma in Colombia, a middle-income country (MIC)., Methods: A Markov-type model was developed to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 5-year period. The effectiveness data and transition probabilities were obtained from various sources, including systematic reviews with meta-analysis. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome was the variable ''quality-adjusted life-years'' (QALYs)., Results: For the base-case analysis, the cost-utility analysis showed that compared with the standard treatment strategy, the omalizumab strategy involved higher costs (US$72,142.3 vs. $20,243.4 average cost per patient) and greater gain in QALYs (0.8718 vs. 0.8222 QALYs on average per patient). The incremental cost-utility ratio (ICUR) of omalizumab compared with standard treatment was US$82,748.1 per QALY CONCLUSIONS: This study shows that in Colombia, an MIC, compared with standard treatment, omalizumab is not a cost-effective strategy for treating pediatric patients with uncontrolled severe allergic asthma., (© 2021 Wiley Periodicals LLC.)

Background: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment., Methods: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 μg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29., Discussion: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection., Trial Registration: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020., (© 2021. The Author(s).)

Background: Deleterious long-term effects in the offspring from women with pregravid obesity have been described; however, the evidence supporting early metabolic and inflammatory markers in the offspring at birth and gender differences are conflicting., Objective: The present study aimed to compare cord blood adipokines and cytokines concentrations and anthropometric characteristics of the offspring of women with maternal obesity (MO) and normal-weight mothers (NWM). Also, maternal and neonatal variables on the association of maternal body mass index (BMI) with cord blood adipokines were evaluated., Methods: A cross-sectional analysis of a subsample of mother-child dyads participating in a cohort study (n = 221) was assessed. Anthropometrics, cord blood adipokines (leptin and adiponectin) and cytokines (interleukin [IL]-1β, IL-4, IL-10, IL-12 p40, IL-12p70, IL-13, and tumor necrosis factor α) concentrations in the offspring of normal-weight women (BMI >18.5 and <24.9 kg/m2) and women with pregravid obesity (BMI > 30 kg/m2) without comorbidities was performed., Results: Offspring from mothers with obesity had higher birth weight, a higher proportion of large for gestational age, higher ponderal index, and heavier placentae than offspring from normal-weight mothers (P < 0.05). Within the offspring from women with obesity, males had significantly higher weight, length, the proportion of large-for-gestational-age newborns, higher weight for length ratio. Males had more efficient placentas than females (P < 0.05). Higher adiponectin and leptin in both sexes and higher leptin in female offspring of mothers with obesity after adjusting for birth size (P < 0.05) were found. Higher IL-12p40 in the offspring of women with MO with no other differences in other cytokines among groups were evidenced., Conclusions: Maternal obesity associates with a higher concentration of adiponectin and leptin in their offspring at birth. There is a relevant effect on anthropometrics in male offspring and on leptin in female newborn. Further studies need to evaluate the extension of these effects in postnatal life., Trail Identification Number: NCT02903134., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted., Methods and Analysis: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence., Ethics and Dissemination: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank., Prospero Registration Numbers: CRD42020132990, CRD42020171624., Competing Interests: Competing interests: AGM reports grants from Boehringer Ingelheim outside the submitted work. AC reports personal fees from Novartis, Regeneron / Sanofi, Thermo Fisher Scientific, Boehringer Ingelheim and Philips, outside the submitted work. LB reports personal fees from Aerocrine, GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura and Circassia outside the submitted work. TC reports grants and personal fees CSL Behring, Dyax, Takeda, BioCryst, Pharming, personal fees from Grifols, grants and non-financial support from GSK, Regeneron, Novartis/Genetech outside the submitted work. AD reports grants and personal fees from Stallergenes Greer, personal fees from Novartis, ALK, TEVA, GSK, MEDA-MYLAN, CHIESI, AImmune, DBV technologies and Astra Zeneca, outside the submitted work. ZD reports personal fees from academic affiliations, ZD acts as Executive and Scientific Medical Director at a phase I/II pharmacological unit (QPS-NL), which performs clinical studies for pharmaceutical companies. ZD reports personal fees from Astrazeneca, ALK, Aquilon, Boehringer Ingelheim, CSL, HAL Allergy, MSD, and Sanofi-Genzyme outside the submitted work. FMD reports grants from Thorasys; personal fees from Jean-Coutu Pharmaceuticals, unrestricted research funds from Novartis Canada, Teva and Trudell Medical, research grants from GlaxoSmithKline and MEDteq in partnership with Thorasys; honorarium for consultancy work from Covis Pharma and Teva; and honorarium as invited speaker from Covis Pharma, Pharmacy Brunet, outside the submitted work. JEG reports grants from NIH/NIAID, personal fees from Regeneron, Ena Theraputics and MedImmune outside the submitted work; personal fees and stock options from Meissa Vaccines Inc outside the submitted work. JG reports personal fees from GSK, Vifor Pharmaceuticals, Novartis, BV Pharma and AstraZeneca outside the submitted work. AK reports personal fees Astra Zeneca, Behring, Boehringer Ingelheim, Covis, GSK, NovoNordisk, Novartis, Griffols, Pfizer, Sanofi, Teva and Trudel, outside the submitted work. RFL reports grants from NIH, non-financial support from GlaxoSmithKline, Boehringer-Ingelheim, Merck, TEVA, American Academy of Allergy, Asthma and Immunology, grants from Clinical and Translational Science Award (NIH), Childhood Origins of ASThma (COAST) grant, AsthmaNet, personal fees from LSU, Elsevier, UpToDate, the University of Kentucky, ThermoFischer, and Food Allergy Research and Education (FARE) Network, outside the submitted work. CM reports personal fees from Novartis, GSK, Astra Zeneca, Thermo Fisher and Boehringer Ingelheim outside the submitted work. NGP reports personal fees from ALK, Novartis, Nutricia, HAL, Menarini/FAES Farma, Sanofi, Mylan/MEDA, Biomay, AstraZeneca, GSK, MSD, ASIT BIOTECH and Boehringer Ingelheim; grants from Gerolymatos International SA and Capricare outside the submitted work. WP reports grants from NIH; grants and personal fees from Genentech/Novartis, Sanofi/Rgeneron; personal fees GSK; non-financial support from Thermo Fisher, Lincoln Diagnostics, Alk Abello, and Monaghen, outside the submitted work. PP reports grants from Astra Zeneca, Chiesi and TEVA; personal fees from Astra Zeneca, TEVA, Novartis, Mundipharma, S&D Pharma, and GlaxoSmithKline outside the submitted work. DP reports grants from AKL Research and Development, British Lung Foundation, Respiratory Effectiveness Group and the UK National Health Service; grants and personal fees from Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Napp, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, TEVA, Theravance and Zentiva (Sanofi Generics); personal fees from Cipla, GlaxoSmithKline, Kyorin and Merck; non-financial support from Efficacy and Mechanism Evaluation programme, Health Technology Assessment, outside the submitted work; DP also reports stock/stock options from AKL Research and Development which produces phytopharmaceuticals; and owns 74% of the social enterprise Optimum Patient Care (Australia and UK) and 74% of Observational and Pragmatic Research Institute (Singapore), outside the submitted work. GR reports personal fees from ALK, Allergen Therapeutics, Meda Plus, Merck; and a patent for the use of sublingual immunotherapy to prevent the development of allergy in at-risk infants, outside the submitted work. IT reports personal fees from Novartis, GSK, Boehringer Ingelheim and Astra Zeneca; grants from GSK Hellas, outside the submitted work. PX reports personal fees from Nutricia, Nestle, Friesland, Uriach, Novartis Pharma AG, and GlaxoSmithkline outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)