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Objectives:  This study aimed to evaluate implementation of a digital remote symptom monitoring intervention that delivered weekly symptom questionnaires and included the option to receive nurse callbacks via a mobile app for asthma patients in primary care., Methods:  Research questions were structured by the NASSS (Nonadoption, Abandonment, Scale-up Spread, and Sustainability) framework. Quantitative and qualitative methods assessed scalability of the electronic health record (EHR)-integrated app intervention implemented in a 12-month randomized controlled trial. Data sources included patient asthma control questionnaires; app usage logs; EHRs; and interviews and discussions with patients, primary care providers (PCPs), and nurses., Results:  We included app usage data from 190 patients and interview data from 21 patients and several clinician participants. Among 190 patients, average questionnaire completion rate was 72.3% and retention was 78.9% (i.e., 150 patients continued to use the app at the end of the trial period). App use was lower among Hispanic and younger patients and those with fewer years of education. Of 1,185 nurse callback requests offered to patients. Thirty-three (2.8%) were requested. Of 84 PCP participants, 14 (16.7%) accessed the patient-reported data in the EHR. Analyses showed that the intervention was appropriate for all levels of asthma control; had no major technical barriers; was desirable and useful for patient treatment; involved achievable tasks for patients; required modest role changes for clinicians; and was a minimal burden on the organization., Conclusion:  A clinically integrated symptom monitoring intervention has strong potential for sustained adoption. Inequitable adoption remains a concern. PCP use of patient-reported data during visits could improve intervention adoption but may not be required for patient benefits., Competing Interests: D.W.B. reports grants and personal fees from EarlySense, personal fees from CDI Negev, equity from ValeraHealth, equity from Clew, equity from MDClone, personal fees and equity from AESOP, personal fees and equity from Feelbetter, equity from Guided Clinical Solutions, and grants from IBM Watson Health, outside the submitted work., (Thieme. 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.)

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.)

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.)

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.)

Objective: To determine user and electronic health records (EHR) integration requirements for a scalable remote symptom monitoring intervention for asthma patients and their providers., Methods: Guided by the Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework, we conducted a user-centered design process involving English- and Spanish-speaking patients and providers affiliated with an academic medical center. We conducted a secondary analysis of interview transcripts from our prior study, new design sessions with patients and primary care providers (PCPs), and a survey of PCPs. We determined EHR integration requirements as part of the asthma app design and development process., Results: Analysis of 26 transcripts (21 patients, 5 providers) from the prior study, 21 new design sessions (15 patients, 6 providers), and survey responses from 55 PCPs (71% of 78) identified requirements. Patient-facing requirements included: 1- or 5-item symptom questionnaires each week, depending on asthma control; option to request a callback; ability to enter notes, triggers, and peak flows; and tips pushed via the app prior to a clinic visit. PCP-facing requirements included a clinician-facing dashboard accessible from the EHR and an EHR inbox message preceding the visit. PCP preferences diverged regarding graphical presentations of patient-reported outcomes (PROs). Nurse-facing requirements included callback requests sent as an EHR inbox message. Requirements were consistent for English- and Spanish-speaking patients. EHR integration required use of custom application programming interfaces (APIs)., Conclusion: Using the NASSS framework to guide our user-centered design process, we identified patient and provider requirements for scaling an EHR-integrated remote symptom monitoring intervention in primary care. These requirements met the needs of patients and providers. Additional standards for PRO displays and EHR inbox APIs are needed to facilitate spread., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

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.)

Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes., Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control., Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV 1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged., Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Rationale: Maternal obesity is associated with asthma in the offspring. Whether cord blood leptin is associated with risk of asthma in offspring is unclear. Objectives: To assess whether cord blood leptin from women with pregestational obesity predict preschool asthma. Methods: In this birth cohort study, we divided pregnant women into three weight categories during the first obstetric visit: normal (NL), overweight (OW), and obese (OB). Results: We followed the offspring recording atopy, wheezing, and other respiratory illnesses through 30 months of age. Cord blood and peripheral blood at 30 months of age were taken to measure cytokines, adipokines, metabolic biomarkers, and specific immunoglobulin E. Adjusted regression models were used to evaluate the association between maternal obesity and offspring asthma risk, defined by a positive Asthma Predictive Index. Three hundred thirty-nine mothers were recruited; 140 offspring were born from NL, 80 from OW, and 119 from OB mothers. OB women were older and less educated and had higher parity and higher C-section frequency. Offspring from OB women had higher birthweight, head circumference, and placental weight compared with other groups. The proportion of Asthma Predictive Index positive at 30 months of age was 12.2% in the NL, 14.7% in the OW, and 16.8% in the OB group ( P  = 0.18). Offspring from OB women had higher leptin, leptin/adiponectin ratio, interleukin-10, and insulin than the OW group and higher leptin than the NL group. In the adjusted analysis, offspring from OB mothers with high cord blood leptin had increased risk of asthma (adjusted odds ratio, 1.30; 95% confidence interval, 1.1-1.55; P  = 0.003). Conclusions: Offspring from obese mothers with high cord blood leptin have 30% higher asthma risk at age 3.Clinical trial registered with ClinicalTrials.gov (NCT02903134).

International guidelines have recommended the use of inhaled beta-2 agonists and systemic corticosteroids (SCs) as the first-line treatment for acute asthma., Objective: To evaluate the evidence for the efficacy of inhaled corticosteroids (ICSs) in addition to SCs compared to SCs alone in children with acute asthma in the emergency department (ED) or during hospitalization., Data Sources: Five electronic databases were searched., Study Selection: All randomized clinical trials that compared ICS (via nebulizer or metered dose inhaler) plus SC (oral or parenteral) with placebo (or standard care) plus SC were included without language restriction., Data Extraction: Two reviewers independently reviewed all the studies. The primary outcomes were hospital admission and hospital length of stay (LOS), and secondary outcomes were readmissions during follow-up, ED-LOS, lung function, asthma clinical score, oxygen saturation, and heart and respiratory rates., Results: Nine studies (n = 1473) met the inclusion criteria. In all the studies, the ICS was budesonide. Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreased hospital LOS by more than 1 day (MD = -29.08 hours [-39.9 to -18.3]; I 2  = 0%, P = < .00001). Moreover, adding budesonide significantly improved the acute asthma severity score among patients at ED., Conclusions: Compared to SC alone, adding budesonide to SC does not affect the hospitalization rate, but decreases the LOS and improves the acute asthma score in children in an ED setting., (© 2020 Wiley Periodicals LLC.)

Rationale: Whether asthma constitutes a risk factor for coronavirus disease-2019 (COVID-19) is unclear. Here, we aimed to assess whether asthma, the most common chronic disease in children, is associated with higher COVID-19 risk or severity in pediatric populations., Methods: We performed a systematic literature search in three stages: first, we reviewed PubMed, EMBASE, and CINAHL for systematic reviews of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 in pediatric populations, and reviewed their primary articles; second, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; third, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma., Results: In the first search, eight systematic reviews were found, of which five were done in pediatric populations; none of the 67 primary studies included data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 34 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 25 pre-prints in MedRxiv included data on asthma, but none on children. We found one report by the US Centers for Disease Control and Prevention stating that 40/345 (~11.5%) children with data on chronic conditions had "chronic lung diseases including asthma," and one from a tertiary hospital in New York that reported asthma in 11/46 (~23.9%) children hospitalized for COVID-19., Conclusion: There is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range., (© 2020 Wiley Periodicals LLC.)

Objective: Although the efficacy of systemic corticosteroids (SCs) in acute asthma exacerbations is well established, the fact that many children still require admission to hospital and that SCs have a slow onset of action are cause of concern. For this reason, the use of inhaled corticosteroids (ICS) as a therapy added to SCs has been explored, with no clarity about its cost-effectiveness. The aim of the present study was to evaluate the cost-effectiveness of ICS in addition to SCs (ICS + SCs) compared to standard therapy with SCs for treating pediatric asthma exacerbations. Methods: A decision-analysis model was developed to estimate the cost-effectiveness of SCs compared to ICS + SCs for treating pediatric patients with acute asthma exacerbations. Effectiveness parameters were obtained from a systematic review of the literature. Cost data obtained from hospital bills and from the national manual of drug prices. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission. Results: For the base-case analysis, the model showed that compared to SCs, therapy with ICS + SCs was associated with lower total costs (US$88.76 vs.US$97.71 average cost per patient) and a lower probability of hospital admission (0.9060 vs. 0.9000), thus showing dominance. Conclusions: This study shows that compared with standard therapy with SCs, ICS + SCs for treating pediatric patients with acute asthma exacerbations is the preferred strategy because it was associated with a lower probability of hospital admission, at lower total treatment costs.

Background: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic., Objective: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients., Methods: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma., Results: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts., Conclusions: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Although a short course (ie, 3 to 5 days) of orally administered prednisolone is a common and widely accepted practice among clinicians for administering systemic corticosteroids in pediatric acute asthma, oral dexamethasone for 1 to 2 days is an attractive alternative to prednisolone due to its better palatability and compliance. However, a cost-effectiveness analysis regarding the use of dexamethasone compared to prednisolone is not sufficient, especially in lower- and middle-income countries. The objective of this study was to analyze the cost-effectiveness of prednisolone vs oral dexamethasone for treating pediatric asthma exacerbations., Methods: Using a decision-analysis model, we analyzed the cost-effectiveness of prednisolone vs oral dexamethasone for treating acute pediatric asthma. Effectiveness parameters were derived from a systematic review of the published literature. Data for costs were acquired from hospital accounts and from an official national database, the national manual of drug prices in Colombia. The study was carried out from a Colombian third-party payer perspective. The principal outcome of the model was the avoidance of hospitalization., Results: The base-case analysis showed that compared to dexamethasone, administering prednisolone was associated with lower overall treatment costs (US$93.97 vs US$104.91 mean cost per patient) without a significant difference in the probability of hospitalization avoided (.9108 vs .9108)., Conclusions: The present study shows that in Colombia, a middle-income country, compared with oral dexamethasone, the use of prednisolone for treating acute pediatric asthma is cost-effective, yielding a similar probability of hospitalization at lesser overall costs., (© 2020 Wiley Periodicals LLC.)

Introduction and Objectives: Wheezing (RW) infants with a positive asthma predictive index (API+) have a lower lung function as measured by forced expiratory techniques. Tidal flow-volume loops (TFVL) are easy to perform in infants, and sedation is not necessary., Materials and Methods: A total of 216 wheezing infants were successfully measured, and 183 of them were followed for over a year. TFVL loops were classified into one of three categories depending of their geometric shape (symmetric, convex, and concave). Respiratory rate (Rr), presence of API+, and the number of exacerbations during the following year were also recorded., Results: Children with concave loops had more exacerbations in the following year (OR = 6.8 [IC95% 3.33;13.91]). Infants API + were also significantly more related to concave loops (OR = 10.02 [IC 95% 4.53; 22.15]). Rr was higher in infants with concave loops (44+/-15.5 vs. 36.6 +/-12.6; p < 0.01)., Conclusion: Infants with a concave TFVL have a higher probability of experiencing exacerbations in the following year, and are at a higher risk of suffering asthma., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Pediatric asthma remains a public health challenge with enormous impact worldwide., Objective: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities., Methods: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared., Results: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations., Conclusions: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: There has been no systematic review of studies aimed to predict differential responses to medication regimens for asthma controller therapies in pediatric patients. The aim of the present study was to summarize those identifying biomarkers for the different asthma controller therapies., Methods: Studies published by June 2019 that report phenotypic or genotypic characteristics or biomarkers that could potentially serve as response predictors to asthma controller therapies in pediatric patients were included. The quality of studies was assessed using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale tool., Results: Of 385 trials identified, 30 studies were included. Children with asthma and a positive family history of asthma, with more severe disease, of the white race, with allergy biomarkers, nonobese, with lower lung function, high bronchial hyperresponsiveness to methacholine, or having variants in the FCER2 and CRHR1 gene respond better to inhaled corticosteroids (ICS). Younger age (<10 years), short disease duration (<4 years), high cotinine and urinary leukotriene E4 (LTE4) levels, and 5/5 ALOX5 were associated with a better response to leukotriene receptor antagonist (LTRA). For patients that remain symptomatic, white Hispanics were more likely to respond to LTRA, blacks to ICS, white non-Hispanics to LTRA or LABA, and children without a history of eczema, regardless of race or ethnicity to LABA set-up therapy. In severe persistent asthma, those with atopy and body mass index greater than or equal 25 were more likely to benefit from omalizumab., Conclusion: Several phenotypic characteristics, biomarkers, or pharmacogenomics markers could be useful for predicting the best drug for asthma treatment., (© 2020 Wiley Periodicals, Inc.)

Introduction: The role of macrolides for treatment of children with acute asthma or wheezing exacerbations is unclear., Objective: The aim of this systematic review was to evaluate the effectiveness of macrolides in children with recurrent wheezing presenting with acute asthma or wheezing exacerbation., Methods: We conducted an electronic search in MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and ClinicalTrials.gov., Study Selection Criteria: Randomized controlled trials of macrolides (any macrolide) compared with placebo or standard treatment in children up to 18 years with recurrent wheezing/asthma presenting with an acute exacerbation., Outcomes: Primary outcomes were need for hospitalization and/or time of acute asthma/wheezing symptoms resolution; secondary outcomes were duration of stay in the emergency department (ED)/clinic, severity of symptoms of the index episode, use of additional systemic corticosteroids or short active β-2 agonists, changes in lung function measures, ED visit/hospitalization during first week after index episode, time to next exacerbation, or adverse effects (AEs)., Results: Only three studies met the inclusion criteria (n = 334 children, 410 treated episodes); two studies included recurrent wheezers and the third included asthmatic children. There was no difference in hospitalization between groups, but children treated with macrolides had a significantly lower time to symptoms resolution than controls, although the magnitude of benefit remains to be quantified due to no normal distribution data presented. There was no difference in time to next episode of exacerbation (HR 0.96; 95% CI 0.71-1.28; I 2  = 0%; p = 0.77). In one study, children receiving macrolides had a significant decrease in the severity of symptoms, decrease use of salbutamol, and another study showed improved lung function. No study evaluated antibiotic resistance development., Conclusions: Limited evidence support that a macrolide trial could be considered in children with acute asthma or recurrent wheezing exacerbation.

Objectives: Although the benefits of albuterol delivered via metered-dose inhalers with a spacer (MDI+S) have been increasingly recognized, the evidence regarding the cost-effectiveness of MDI+S compared to nebulization (NEB) 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 evaluate the cost-effectiveness of MDI+S vs NEB for delivering albuterol for the treatment of pediatric asthma exacerbations., Methods: A decision-analysis model was developed to estimate the cost-effectiveness of MDI+S vs NEB for delivering albuterol for the treatment of pediatric asthma exacerbations. Effectiveness parameters were obtained from a systematic review of the literature. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia, a middle-income country (MIC). The main outcome of the model was the avoidance of hospital admission., Results: For the base-case analysis, the model showed that compared to NEB, using MDI+S for the delivery of albuterol was associated with lower total costs (US$96.68 vs US$121.41 average cost per patient) and a higher probability of hospital admission avoided (0.9219 vs 0.8900), thus leading to dominance., Conclusions: This study shows that in Colombia, an MIC, compared with NEB, the use of MDI+S for delivering albuterol for the treatment of pediatric asthma exacerbations is the preferred strategy because it is associated with a lower probability of hospital admission at lower total treatment costs., (© 2020 Wiley Periodicals, Inc.)

Introduction and Objectives: With the aim of making informed decisions on resource allocation, there is a critical need for studies that provide accurate information on hospital costs for treating pediatric asthma exacerbations, mainly in middle-income countries (MICs). The aim of the present study was to evaluate the direct medical costs associated with pediatric asthma exacerbations requiring hospital attendance in Bogota, Colombia., Patients and Methods: We reviewed the available electronic medical records (EMRs) for all pediatric patients who were admitted to the Fundacion Hospital de La Misericordia with a discharge principal diagnosis pediatric asthma exacerbation over a 24-month period from January 2016 to December 2017. Direct medical costs of pediatric asthma exacerbations were retrospectively collected by dividing the patients into four groups: those admitted to the emergency department (ED) only; those admitted to the pediatric ward (PW); those admitted to the pediatric intermediate care unit (PIMC); and those admitted to the pediatric intensive care unit (PICU)., Results: A total of 252 patients with a median (IQR) age of 5.0 (3.0-7.0) years were analyzed, of whom 142 (56.3%) were males. Overall, the median (IQR) cost of patients treated in the ED, PW, PIMC, and PICU was US$38.8 (21.1-64.1) vs. US$260.5 (113.7-567.4) vs. 1212.4 (717.6-1609.6) vs. 2501.8 (1771.6-3405.0), respectively: this difference was statistically significant (p<0.001)., Conclusions: The present study helps to further our understanding of the economic burden of pediatric asthma exacerbations requiring hospital attendance among pediatric patients in a MIC., (Copyright © 2019 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The lack of effective, consistent, reproducible and efficient asthma ascertainment methods results in inconsistent asthma cohorts and study results for clinical trials or other studies. We aimed to assess whether application of expert artificial intelligence (AI)-based natural language processing (NLP) algorithms for two existing asthma criteria to electronic health records of a paediatric population systematically identifies childhood asthma and its subgroups with distinctive characteristics., Methods: Using the 1997-2007 Olmsted County Birth Cohort, we applied validated NLP algorithms for Predetermined Asthma Criteria (NLP-PAC) as well as Asthma Predictive Index (NLP-API). We categorised subjects into four groups (both criteria positive (NLP-PAC + /NLP-API + ); PAC positive only (NLP-PAC + only); API positive only (NLP-API + only); and both criteria negative (NLP-PAC - /NLP-API - )) and characterised them. Results were replicated in unsupervised cluster analysis for asthmatics and a random sample of 300 children using laboratory and pulmonary function tests (PFTs)., Results: Of the 8196 subjects (51% male, 80% white), we identified 1614 (20%), NLP-PAC + /NLP-API + ; 954 (12%), NLP-PAC + only; 105 (1%), NLP-API + only; and 5523 (67%), NLP-PAC - /NLP-API - . Asthmatic children classified as NLP-PAC + /NLP-API + showed earlier onset asthma, more Th2-high profile, poorer lung function, higher asthma exacerbation and higher risk of asthma-associated comorbidities compared with other groups. These results were consistent with those based on unsupervised cluster analysis and lab and PFT data of a random sample of study subjects., Conclusion: Expert AI-based NLP algorithms for two asthma criteria systematically identify childhood asthma with distinctive characteristics. This approach may improve precision, reproducibility, consistency and efficiency of large-scale clinical studies for asthma and enable population management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Invasive pneumococcal disease (IPD) and pneumonia are a leading cause of morbidity and mortality throughout the world, and asthma is the most common chronic disease of childhood., Objective: To evaluate the risk of IPD or pneumonia among children with asthma after the introduction of pneumococcal conjugate vaccines (PCVs)., Data Sources: Four electronic databases were searched., Study Selection: We selected all cohorts or case-control studies of IPD and pneumonia in populations who already received PCV (largely 7-valent pneumococcal conjugate vaccine), but not 23-valent pneumococcal polysaccharide, in which authors reported data for children with asthma and in which healthy controls were included, without language restriction., Data Extraction: Two reviewers independently reviewed all studies. Primary outcomes were occurrence of IPD and pneumonia. Secondary outcomes included mortality, hospital admissions, hospital length of stay, ICU admission, respiratory support, costs, and additional medication use., Results: Five studies met inclusion criteria; of those, 3 retrospective cohorts (∼26 million person-years) and 1 case-control study ( N = 3294 children) qualified for the meta-analysis. Children with asthma had 90% higher odds of IPD than healthy controls (odds ratio = 1.90; 95% confidence interval = 1.63-2.11; I 2 = 1.7%). Pneumonia was also more frequent among children with asthma than among controls, and 1 study reported that pneumonia-associated costs increased by asthma severity., Limitations: None of the identified studies had information of asthma therapy or compliance., Conclusions: Despite PCV vaccination, children with asthma continue to have a higher risk of IPD than children without asthma. Further research is needed to assess the need for supplemental 23-valent pneumococcal polysaccharide vaccination in children with asthma, regardless of their use of oral steroids., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Introduction: In moderate-severe asthma exacerbation, salbutamol by inhaler (MDI) is superior to salbutamol delivered by nebulizer (NEB); however, to our knowledge, no studies in children with exclusively severe exacerbations were performed., Objective: To compare the efficacy of salbutamol and ipratropium bromide by MDI versus by NEB in severe asthma exacerbations., Methods: We performed a clinical trial enrolling 103 children (2-14 years of age) with severe asthma exacerbations (defined by the Pulmonary Score ≥ 7) seen at the emergency room in Asuncion, Paraguay. One group received salbutamol and ipratropium (two puff every 10 min for 2 h and then every 30 min for 2 h more) by MDI with a valved-holding chamber and mask along with oxygen by a cannula separately (MDI-SIB); and the other received nebulization with oxygen (NEB-SIB) of salbutamol and ipratropium (1 every 20 min for 2 h and then every 30 min for 2 h more). Primary outcome was the rate of hospitalization (Pulmonary Score ≥ 7) after 4 h and secondary outcome was oxygen saturation., Results: Fifty two children received MDI-SIB and 51 NEB-SIB. After the 4th hour, children on MDI-SIB had significantly (P = 0.003) lower rate of hospital admission than on NEB-SIB (5.8% vs 27.5%, RR: 0.21 [0.06-0.69], respectively). Similarly, a significant improved clinical score after 60 min and increase in oxygen saturation after 90 min of treatment was observed in MDI-SIB versus NEB-SIB group (4.46 ± 0.7 vs 5.76 ± 0.65, P < 0.00001; and 90.5 ± 1.7 vs 88.43 1 ± 1, P < 0.00001, respectively)., Conclusion: Even in severe asthma exacerbations administration of salbutamol and ipratropium by MDI with valved-holding chamber and mask along with oxygen by a cannula separately was more effective than by a nebulizer., (© 2019 Wiley Periodicals, Inc.)

Objectives: To assess the impact of asthma and its treatment (inhaled corticosteroids and other control medications) on growth., Data Sources: The authors searched PubMed (up to August 24, 2018) and screened the reference lists of retrieved articles. Systematic reviews and meta-analysis were selected. If there was no such article, the authors selected either randomized clinical trials or observational studies., Data Synthesis: A total of 37 articles were included in this review. The findings from 21 studies suggest that asthma per se, especially more severe and/or uncontrolled cases, can transitorily impair child's growth. Two Cochrane reviews of randomized clinical trials showed a small mean reduction in linear growth (-0.91cm/year for beclomethasone, -0.59cm/year for budesonide, and -0.39cm/year for fluticasone) in the first year of treatment with inhaled corticosteroids in prepubertal children with persistent asthma. The effects were likely to be molecule- and dose-dependent. A recent review showed that most of "real-life" observational studies had not found significant effects of inhaled corticosteroids on growth in asthmatic children. Fifteen studies showed that the maintenance systemic corticosteroids could cause a dose-dependent growth suppression in children with severe asthma, but other controllers (cromones, montelukast, salmeterol, and theophylline) had no significant adverse effects no growth., Conclusions: Severe and/or uncontrolled asthma can transitorily impair child's growth. Regular use of inhaled corticosteroids may cause a small reduction in linear growth in children with asthma, but the well-established benefits of inhaled corticosteroids in controlling asthma outweigh the potential adverse effects on growth. Use of the minimally effective dose of inhaled corticosteroids and regular monitoring of child's height during inhaled corticosteroids therapy are recommended., (Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Most international asthma guidelines recommend that children ≤5 years with asthma or recurrent wheezing be treated with daily low- moderate dose inhaled corticosteroids (ICS) as the preferred controller and leukotriene receptor antagonists (LTRA) as alternative therapy. There is no systematic review comparing the efficacy of ICS versus LTRA monotherapy in this age group., Objective: To compare the efficacy of daily ICS versus LTRA in preschoolers with asthma or recurrent wheezing., Methods: Randomized, prospective, controlled trials published by December 2017, with a minimum of 3-month therapy with daily ICS versus LTRA were identified. The co-primary outcomes were the number of wheezing episodes and daily symptom score. Secondary outcomes included unscheduled emergency visits, need of rescue systemic corticosteroids (SC), hospitalization for exacerbations, lung function, and adverse effects., Results: Of 29 trials identified, six studies (n = 3204 patients, 62% males, age range: 6-54 months) met the inclusion criteria; two were at low risk of bias. Five pertained to children with asthma; one to those with recurrent wheezing. No outcomes were similarly reported in the six studies, preventing meta-analysis. Based on trials at lowest risk of bias and the largest open-labelled studies, ICS was associated with better control of symptoms and less exacerbations than LTRA. And also less need for rescue SC. Insufficient data of high quality prevented firm conclusions on other secondary outcomes., Conclusions: In preschoolers with asthma or recurrent wheezing, daily ICS appears more effective than daily LTRA for improving symptom control and decreasing exacerbations, particularly those requiring rescue SC, although the magnitude of benefit remains to be quantified., (© 2018 Wiley Periodicals, Inc.)

Objective: The objective of this article was to summarize the findings of all the available studies on alternative pharmacological treatments for asthma and assess their methodological quality, as well as to identify the main drivers of the cost effectiveness of pharmacological treatments for the disease., Methods: A systematic review of the literature in seven electronic databases was conducted in order to identify all the available health economic evidence on alternative pharmacological treatments for asthma published up to April 2017. The reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement., Results: A total of 72 studies were included in the review, classified as follows: medications for acute asthma treatment (n = 5, 6.9%); inhaled corticosteroids (ICS) administered alone or in conjunction with long-acting β-agonists (LABA) or tiotropium for chronic asthma treatment (n = 38, 52.8%); direct comparisons between different combinations of ICS, ICS/LABA, leukotriene receptor antagonists (LTRA), and sodium cromoglycate for chronic asthma treatment (n = 14, 19.4%); and omalizumab for chronic asthma treatment (n = 15, 20.8%). ICS were reported to be cost effective when compared with LTRA for the management of persistent asthma. In patients with inadequately controlled asthma taking ICS, the addition of long-acting β-agonist (LABA) preparations has been demonstrated to be cost effective, especially when combinations of ICS/LABA containing formoterol are used for both maintenance and reliever therapy. In patients with uncontrolled severe persistent allergic asthma, omalizumab therapy could be cost effective in a carefully selected subgroup of patients with the more severe forms of the disease. The quality of reporting in the studies, according to the CHEERS checklist, was very uneven. The main cost-effectiveness drivers identified were the cost or rate of asthma exacerbations, the cost or rate of the use of asthma medications, the asthma mortality risk, and the rate of utilization of health services for asthma., Conclusions: The present findings are in line with the pharmacological recommendations for stepwise management of asthma given in the most recent evidence-based clinical practice guidelines for the disease. The identified reporting quality of the available health economic evidence is useful for identifying aspects where there is room for improvement in future asthma cost-effectiveness studies.

Background: Low levels of serum CC16 were reported in asthmatic adults, but the studies on children were scarce and conflicting. The aim of this study was to compare serum CC16 levels in pre-school children with recurrent wheezing assessed using an asthma predictive index (API)., Methods: We performed a case-control study based on API, with all enrolled pre-school children who had recurrent wheezing episodes (>3 episodes/last year confirmed by a physician) and had presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative., Results: In a one-year period, 60 pre-schoolers were enrolled. After excluding 12, 48 pre-schoolers remained (27 males, age range from 24 to 71 months) and completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum CC16 levels for pre-schoolers with a positive API and negative API were (median 9.2 [7.1-11.5] and 9.4 [5.5-10], p=0.26, respectively). The area under the curve for the serum CC16 levels to predict a positive API was 0.6, 95% CI [0.43-0.77], p=0.3. A correlation between serum CC16 levels and age was found (r=0.36 [0.07-0.59], p=0.01], but not between serum CC16 levels and peripheral eosinophils blood., Conclusion: There was no evidence that serum CC16 levels played a role in recurrent wheezing and a positive API in pre-school children. More studies are needed to confirm this finding., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Frequent wheezing in original asthma predictive index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent wheezing in children, particularly aged over 3 years, has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records., Methods: Among children who participated in a previous study (n = 427), all wheezing episodes documented in medical records were collected for children who had ≥2 wheezing episodes PLUS met one major criterion or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1 year) compared to those with longer interval (1 to 3 years)., Results: A total of 62 children met API at median age of 2.3 years. During follow-up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1-year interval (n = 40) vs 1- to 3-year interval (n = 13) appeared to be similar in regard to the known risk factors for asthma., Conclusions: Our exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (<3 years) need to be considered to be determined as asthma cases when API is applied to retrospective medical records. Prospective studies with a larger sample size need to replicate this finding., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objectives: We aimed to perform a systematic review of all studies with direct measurements of both airway inflammation and remodeling in the subgroup of children with repeated wheezing and/or persistent asthma severe enough to warrant bronchoscopy, to address whether airway inflammation precedes remodeling or is a parallel process, and also to assess the impact of remodeling on lung function., Methods: Four databases were searched up to June 2017. Two independent reviewers screened the literature and extracted relevant data., Results: We found 526 references, and 39 studies (2390 children under 18 years old) were included. Airway inflammation (eosinophilic/neutrophilic) and remodeling were not present in wheezers at a mean age of 12 months, but in older pre-school children (mean 2.5 years), remodeling (mainly increased reticular basement membrane [RBM] thickness and increased area of airway smooth muscle) and also airway eosinophilia was reported. This was worse in school-age children. RBM thickness was similar in atopic and non-atopic preschool wheezers. Airway remodeling was correlated with lung function in seven studies, with FeNO in three, and with HRCT-scan in one. Eosinophilic inflammation was not seen in patients without remodeling. There were no invasive longitudinal or intervention studies., Conclusion: The relationship between inflammation and remodeling in children cannot be determined. Failure to demonstrate eosinophilic inflammation in the absence of remodeling is contrary to the hypothesis that inflammation causes these changes. We need reliable, non-invasive markers of remodeling in particular if this is to be addressed., (© 2018 Wiley Periodicals, Inc.)

Objective: Asthma educational interventions have been shown to improve several clinically and economically important outcomes. However, these interventions are costly in themselves and could lead to even higher disease costs. A cost-effectiveness threshold analysis would be helpful in determining the threshold value of the cost of educational interventions, leading to these interventions being cost-effective. The aim of the present study was to perform a cost-effectiveness threshold analysis to determine the level at which the cost of a pediatric asthma educational intervention would be cost-effective and cost-saving., Methods: A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a single uncontrolled before-and-after study performed with Colombian asthmatic children. 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: A deterministic threshold sensitivity analysis showed that the asthma educational intervention will be cost-saving to the health system if its cost is under US$513.20. Additionally, the analysis showed that the cost of the intervention would have to be below US$967.40 in order to be cost-effective., Conclusions: This study identified the level at which the cost of a pediatric asthma educational intervention will be cost-effective and cost-saving for the health system in Colombia. Our findings could be a useful aid for decision makers in efficiently allocating limited resources when planning asthma educational interventions for pediatric patients.

Background: In contrast to adult asthmatic patients, studies on the role of serum periostin levels in schoolchildren with asthma are still conflictive, and very few studies have been performed in pre-schoolers. The aim of this study was to compare serum periostin levels in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition., Methods: We performed a case-control study enrolling pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative., Results: In a one-year period, 60 pre-schoolers were enrolled. After excluding 12 (due to not fulfilment of inclusion criteria or refusal of blood sample extraction), 48 remaining pre-schoolers (27 males, age range from 24 to 71 months) completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum periostin levels for pre-schoolers with positive API and negative API were (median 46.7 [25.5-83.1] and 67.5 [20.5-131.8], p=0.9, respectively). The area under the curve for the serum periostin levels for predict positive API was 0.5, 95% CI [0.29-0.70], p=0.9. No significant correlation between serum periostin levels and peripheral blood eosinophils was found., Conclusion: Serum periostin levels were no significantly different between wheezer pre-schoolers with positive and negative API. More studies are needed to confirm this finding., (Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Thus far, no algorithms have been developed to automatically extract patients who meet Asthma Predictive Index (API) criteria from the Electronic health records (EHR) yet. Our objective is to develop and validate a natural language processing (NLP) algorithm to identify patients that meet API criteria., Methods: This is a cross-sectional study nested in a birth cohort study in Olmsted County, MN. Asthma status ascertained by manual chart review based on API criteria served as gold standard. NLP-API was developed on a training cohort (n = 87) and validated on a test cohort (n = 427). Criterion validity was measured by sensitivity, specificity, positive predictive value and negative predictive value of the NLP algorithm against manual chart review for asthma status. Construct validity was determined by associations of asthma status defined by NLP-API with known risk factors for asthma., Results: Among the eligible 427 subjects of the test cohort, 48% were males and 74% were White. Median age was 5.3 years (interquartile range 3.6-6.8). 35 (8%) had a history of asthma by NLP-API vs. 36 (8%) by abstractor with 31 by both approaches. NLP-API predicted asthma status with sensitivity 86%, specificity 98%, positive predictive value 88%, negative predictive value 98%. Asthma status by both NLP and manual chart review were significantly associated with the known asthma risk factors, such as history of allergic rhinitis, eczema, family history of asthma, and maternal history of smoking during pregnancy (p value < 0.05). Maternal smoking [odds ratio: 4.4, 95% confidence interval 1.8-10.7] was associated with asthma status determined by NLP-API and abstractor, and the effect sizes were similar between the reviews with 4.4 vs 4.2 respectively., Conclusion: NLP-API was able to ascertain asthma status in children mining from EHR and has a potential to enhance asthma care and research through population management and large-scale studies when identifying children who meet API criteria.

Caregiver's or maternal depression has been associated with increased asthma morbidity in children from prosperous nations, but little is known about this link in low and middle-income countries., Objective: To examine if caregiver's depressive symptoms are associated with poor asthma control and abnormal immune responses in school-aged children., Methods: Case-control study of 87 asthmatic children (aged 4-11 years) attending a primary care clinic in an underserved area of Santiago (Chile). Cases were children with poor asthma control (Child Asthma Control Test [cACT] <20 points) and controls were children with adequate asthma control (cACT ≥20 points). The Beck Depression Inventory-II (BDI) and a locally validated family health vulnerability test (SALUFAM) were used to assess caregivers' depression and family health vulnerability. Serum from participating children was assayed for IFN-γ, IL-4, IL-13, TGF-β, cortisol, and total IgE., Results: The mean (SD) age of study participants was 8.23 (2.15 years), and 55.2% were females. Use of inhaled corticosteroids (ICS), family health vulnerability, and caregiver's depressive symptoms were significantly more common in cases than in controls (65.4% vs. 34.6%, p = 0.003; 41.3% vs. 24.8%, p = 0.07; and 39.1% vs. 19.5%, p = 0.04, respectively). There was no significant difference in the level of any serum biomarkers between groups. In a multivariate analysis, only ICS use was significantly associated with better asthma control (OR = 3.56 [1.34-9.48], p = 0.01)., Conclusions: Presence of caregiver's depressive symptoms is associated with poor asthma control among children from an underserved community, but this association was no longer significant after accounting for ICS use.

Over the last few decades, asthma and sleep disordered breathing (SDB) in children have experienced similar increases in prevalence, and have both been shown to have airway inflammation, leading investigators to postulate an association between asthma and SDB. However, whether this relationship is causal or not needs to be proven. In this manuscript, we use the most widely accepted epidemiologic criteria for causality, the Bradford Hill criteria, to test step-by-step whether the relation between asthma and SBD in children is causal or not. We found studies supporting 8 of the 9 criteria (strength, consistency, specificity, biological gradient, coherence and biological plausibility, experiment, and analogy) for association between asthma and SDB. However, we did not find any study showing temporality or directionality between asthma and SDB. Therefore, establishing a causal association between asthma and SDB is not yet possible., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: To measure lung function by impulse oscillometry (IOS) and spirometry in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition., Methods: We performed a case-control study enrolling all pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) who presented at a paediatric pulmonology clinic. The population was divided according to stringent API criteria into positive or negative., Results: In the nine-month period, 109 pre-schoolers were enrolled. After excluding one patient (due to lung function technique problems) 108 pre-schoolers (56 males, age range from 24 to 72 months) completed the study; 50 belong to positive API and 58 to negative API group. There were no differences in demographics between groups. More use of ICS was found in those with positive API than with negative API (62% vs. 12%, respectively, p=0.001). No differences in basal lung function and post-bronchodilator response to salbutamol (by IOS or spirometry) were found between positive and negative API pre-schoolers. However, those positive API pre-schoolers with ICS had significantly higher central basal airway resistance (RA at 20Hz) and higher post-BD response (% change in FEF 25-75 and in FEV 0.5 ) than those positive API without ICS., Conclusion: Recurrent wheezer pre-schoolers with positive API and ICS used may have airway dysfunction. More studies are needed to confirm this finding., (Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

To summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR. A total of 227 studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the Assess Systematic Reviews tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke, and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild-to-moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe respiratory syncytial virus infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Systemic corticosteroids (SCS) are used for treat preschoolers with acute asthma or wheezing exacerbations, with conflicting results., Objective: To evaluate the effectiveness of oral corticosteroids (OCS) compared to placebo in preschoolers presenting with acute asthma/wheezing exacerbations., Methods: Five electronic databases were searched for all placebo-controlled, randomized clinical trials of OCS in children <6 years of age presenting with recurrent wheezing/asthma exacerbations of any severity. Primary outcomes were hospitalizations, unscheduled emergency department (ED) visits in following month, need of additional OCS courses, and length of stay (ED or hospital)., Results: Eleven studies met inclusion criteria (n = 1,733); four were conducted on an outpatient basis, five in inpatients, and two in the ED. Significant heterogeneity was found when pooling all studies, and thus analysis was stratified by trial setting. Among the outpatient studies, children who received OCS had a higher hospitalization rate (RR: 2.15 [95%CI = 1.08-4.29], I(2)  = 0%) compared to those to received placebo. Among the ED studies, children who received OCS had a lower risk of hospitalization (RR: 0.58 [0.37-0.92], I(2)  = 0%). Among the inpatient studies, children who received OCS needed fewer additional OCS courses than those on placebo (RR: 0.57 [0.40-0.81], I(2)  = 0%)., Conclusions: Treatment with OCS in the ED or hospital may be beneficial in toddlers and preschoolers with frequent asthma/wheezing exacerbations. However, more studies are needed before OCS can be broadly recommended for this age group. Future trials should be carefully designed to avoid bias and according to our findings regarding administration setting. Pediatr Pulmonol. 2016;51:868-876. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Suboptimal adherence to inhaled corticosteroids (ICs) is an important cause of poor asthma control in pediatric patients. Among the factors that can be most easily changed for enhancing adherence to ICs is a reduction in the dosing frequency, from twice-daily dosing to once-daily dosing. However, no previous studies have reported an economic evaluation comparing once-daily versus twice-daily IC dosing for pediatric asthma. The aim of this study was to compare the cost-effectiveness of once-daily versus twice-daily IC dosing for maintenance treatment of asthma in pediatric patients., Methods: A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a systematic review of the literature. 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: For the base-case analysis, the model showed that compared with twice-daily dosing, once-daily dosing strategy involved lower costs (US$1529.3 versus $1709.1 average cost per patient over 12 months) and the greatest gain in QALYs (0.8284 versus 0.8084 QALYs on average per patient over 12 months), resulting in once-daily dosing strategy being considered dominant., Conclusions: This study shows that compared with twice-daily dosing, once-daily IC dosing for treating pediatric patients with persistent asthma is the dominant strategy because it involves a greater gain in QALYs at lower total treatment cost.

Three concomitant phenomena occur in the later years of childhood: increases in the incidence of asthma, obesity and early menarche. This article is an overview of the current epidemiologic, basic, genetic and epigenetic evidence about this relationship. As a consequence we propose that obese girls who have an early menarche (≤ 11 years of age) constitute a new asthma phenotype in childhood. Future studies need to be carried out in order to find the best control and treatment of this new asthma phenotype., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Urinary leukotriene (LTE4) is an important marker of airway inflammation presence. A relationship between single nucleotide polymorphism in the glucocorticoid receptor (GCR) gene promoter (Bcl I polymorphism), development of asthma and sensitivity to glucocorticoids has been hypothesised., Objective: To explore the possible association between the Bcl I polymorphism and baseline levels of urinary LTE4 in preschoolers with recurrent wheezing episodes. We prospectively enrolled and classified 86 preschoolers based on the risk of developing asthma (by the Asthma Predictive Index [API])., Methods: At admission standardised questionnaires for demographics and respiratory illness characteristics were completed. The Bcl I polymorphism of the GCR was determined by a PCR-RFLP assay from blood samples, and urinary leukotriene was assessed from urine samples by an enzyme immunoassay., Results: We enrolled 86 preschoolers (46 with positive API and 40 with negative API). There were no statistical differences in demographic, respiratory illnesses and wheezing episodes characteristics between both groups. Also, the prevalence of Bcl I polymorphism was similar between positive vs. negative API groups (34.8% vs. 38.9% for homozygote GG, 56.5% vs. 52.8% for heterozygote GC, 8.7% vs. 8.3% for homozygote CC, respectively, p=0.94). However, urinary LTE4 (median [IQR]) was higher in preschoolers with positive than negative API (7.18 [5.57-8.96pg/ml] vs. 6.42 [3.96-8.07pg/ml], p=0.02, respectively)., Conclusions: In our population, wheezing preschoolers with positive API exhibit higher levels of urinary LTE4 than those with negative API; but there were no differences in Bcl I polymorphism of the GCR., (Copyright © 2015 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: Epidemiologic studies suggest a relationship between maternal nutrition during pregnancy and the occurrence of asthma and atopic conditions during childhood. However, individual study results are conflicting. The objective of this meta-analysis was to critically examine the current evidence for an association between nutrition (dietary patterns, food groups, vitamins, or oligo-elements) ingestion during pregnancy and asthma, wheeze, or atopic conditions in childhood., Methods: The inclusion criteria were as follows: (i) systematic recording of diet during the gestational period and (ii) documentation of asthma, wheezing, eczema, or other atopic disease in the offspring. The primary outcomes were prevalence of asthma or wheeze among the offspring during childhood; and secondary outcomes were prevalence of eczema, allergic rhinitis, or other atopic conditions., Results: We found 120 titles, abstracts, and citations, and 32 studies (29 cohorts) were included in this analysis. Data on vitamins, oligo-elements, food groups, and dietary patterns during pregnancy were collected. A meta-analysis revealed that higher maternal intake of vitamin D [odds ratio (OR) = 0.58, 95% confidence interval (CI) = 0.38-0.88], vitamin E (OR = 0.6, 95% CI = 0.46-0.78), and zinc (OR = 0.62, 95% CI = 0.40-0.97) was associated with lower odds of wheeze during childhood. However, none of these or other nutrients was consistently associated with asthma per se or other atopic conditions., Conclusions: Current evidence suggests a protective effect of maternal intake of each of three vitamins or nutrients (vitamin D, vitamin E, and zinc) against childhood wheeze but is inconclusive for an effect on asthma or other atopic conditions., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Consistent with the diversity of Latin America, there is profound variability in asthma burden among and within countries in this region. Regional variation in asthma prevalence is likely multifactorial and due to genetics, perinatal exposures, diet, obesity, tobacco use, indoor and outdoor pollutants, psychosocial stress and microbial or parasitic infections. Similarly, non-uniform progress in asthma management leads to regional variability in disease morbidity. Future studies of distinct asthma phenotypes should follow-up well-characterised Latin American subgroups and examine risk factors that are unique or common in Latin America (eg, stress and violence, parasitic infections and use of biomass fuels for cooking). Because most Latin American countries share the same barriers to asthma management, concerted and multifaceted public health and research efforts are needed, including approaches to curtail tobacco use, campaigns to improve asthma treatment, broadening access to care and clinical trials of non-pharmacological interventions (eg, replacing biomass fuels with gas or electric stoves)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Vitamin D deficiency and single nucleotide polymorphisms (SNP) in the gene encoding vitamin D receptor (VDR) have been associated with asthma., Objective: To compare 25-hydroxyvitamin D (25OHD) levels and the frequency of 3 SNPs in the VDR gene between asthmatic and healthy children., Methods: In persistent asthmatic and healthy control children, the 25OHD levels were measured using radioimmunoassay and SNPs (FokI, ApaI, and TaqI) were analyzed by a PCR-RFLP assay. Relevant medical history was collected., Results: About 75 asthmatic (median age: 9.1 years) and 227 healthy children (10.3 years) were studied. In the whole population, the proportion of sufficient, insufficient, and deficient levels of 25OHD were 14.9%, 44%, and 41.1%, respectively. 25OHD sufficiency status was similar in asthmatic and healthy children (p = 0.57). However, the proportion of 25OHD sufficient levels among asthmatics according to the Global Initiative for Asthma treatment steps 2, 3, and 4 was significantly different (8.6%, 16.6%, and 43.7%, respectively, p = 0.046). All patients on step 4 of the treatment (16/16) were heterozygous for the C allele (FokI VDR SNP). There was a lower presence of the C allele among asthmatics in step 2 (30/33), step 3 (16/24), and controls (45/50), p = 0.007, but this significance did not persist after logistic regression. No significant differences in ApaI and TaqI were found., Conclusions: We found a possible association of vitamin D sufficiency status and FokI C allele with higher requirement of therapy to reach asthma control, suggesting that it may be involved in treatment response. Variations in VDR might also play a role in the 25OHD levels., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Despite the many benefits that have been demonstrated by the continuous administration of inhaled corticosteroids (ICS) in persistent asthma, a new strategy for mild-asthma is emerging, consisting of using intermittent or as-needed ICS treatment in conjunction with short-acting beta2 agonists in response to symptoms. However, no previous studies have reported an economic evaluation comparing these two therapeutic strategies., Methods: A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a systematic review of the literature. 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: For the base-case analysis, the model showed that compared to intermittent ICS, daily therapy with ICS had lower costs (US$437.02 vs. 585.03 and US$704.62 vs. 749.81 average cost per patient over 12 months for school children and preschoolers, respectively), and the greatest gain in QALYs (0.9629 vs. 0.9392 QALYs and 0.9238 vs. 0.9130 QALYS for school children and preschoolers, respectively), resulting in daily therapy being considered dominant., Conclusions: The present analysis shows that compared to intermittent therapy, daily therapy with ICS for treating pediatric patients with recurrent wheezing and mild persistent asthma is a dominant strategy (more cost effective), because it showed a greater gain in QALYs with lower total treatment costs., (© 2014 Wiley Periodicals, Inc.)

Objective: The Childhood Asthma Control Test (c-ACT) is a validated tool for determining pediatric asthma control. However, it is not validated in the Spanish language in Spain. We evaluated the psychometric properties of the Spanish version of the Childhood Asthma Control Test (Sc-ACT) for assessing asthma control in children ages 4 to11., Methods: This national, multicentre, prospective study was conducted in Spain with asthmatic children and their caregivers. Patients were assessed at 3 visits (Baseline, 2 Weeks, and 4 Months). Clinical variables included: symptoms, exacerbations, FEV1, asthma classification, PAQLQ and PACQLQ questionnaire scores, and asthma control as perceived by physicians, patients and caregivers. The Sc-ACT feasibility, validity, reliability, and sensitivity to change were assessed., Results: A total of 394 children were included; mean (SD) time to complete the Sc-ACT was 5.3 (4.4) minutes. Sc-ACT score was correlated with asthma control as perceived by physician (-0.52), patient (-0.53), and caregiver (-0.51) and with the PAQLQ (0.56) and PACQLQ (0.55) scores. Sc-ACT was found to be significantly related to intensity and frequency of asthma symptoms. Cronbach alpha coefficient α was 0.81 and intraclass correlation coefficient was ≥0.85 for all of the items. The global effect size of Sc-ACT was 0.55. The cutoff point scores of 21 or higher indicated a good asthma control and their MCID was 4 points., Conclusion: The Spanish version of the c-ACT was found to be a reliable and valid questionnaire for evaluating asthma control in Spanish-speaking children ages 4 to 11 in Spain., (Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)