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Introduction: We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroid-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma. Methods: Participants (6-14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort-a prospective, multicenter, observational study (NCT04480242)-were followed for a period from 6 months to 5 years via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey-Asthma (MIS-A) was administered to assess the implementation stage of adherence, and the Inhalation Technique Questionnaire (InTeQ) was used to assess the five key steps when using an inhaler. Symptom control was measured with the Asthma Control Questionnaire (ACQ), and HRQL was measured with the EQ-5D and the Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as the dependent variables. Results: Of the 360 participants enrolled, 303 (1,203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (617) in the PROMIS-PAIS. Around 60% of participants were male subjects, and most of them underwent maintenance treatment with inhaled corticosteroids plus long-acting β-agonists in a fixed dose (73.3%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D, and 49.1% for PROMIS-PAIS. At the within-person level, patients with higher adherence had better symptom control ( p = 0.002) and HRQoL over time ( p = 0.016). Patients with a better inhalation technique reported worse HRQoL simultaneously ( p = 0.012), but they showed better HRQoL in future assessments ( p = 0.012). The frequency of reliever use was associated with symptom control ( p < 0.001), exacerbation occurrence ( p < 0.001), and HRQoL ( p = 0.042); and boys were more likely to present better symptom control and HRQoL than girls. Conclusion: Our results confirm longitudinal associations at the within-person level of the two indicators of quality use of inhalers: for adherence to maintenance treatment with symptom control and HRQoL, and for the inhalation technique with HRQoL. Although treatment adherence was shown to be excellent, a third of the participants reported a suboptimal inhalation technique, highlighting the need for actions for improving asthma management of the pediatric population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lizano-Barrantes, Garin, Mayoral, Dima, Pont, Caballero-Rabasco, Praena-Crespo, Valdesoiro-Navarrete, Guerra, Bercedo-Sanz and Ferrer.)

Asthma, the most prevalent chronic disease in pediatric age, continues to pose challenges in its management and treatment. National and international guidelines emphasize the importance of therapeutic education (TE) to achieve disease control. TE involves imparting knowledge and skills to the patient and their family, enhancing medication adherence, rectifying errors in inhalation technique, and tailoring treatment based on individual patient characteristics. It is essential for TE to be progressive, gradual, and personalized, spanning all levels of care. Training healthcare professionals in TE is crucial, particularly for pediatricians, who must also be aware of the extensive variability of available meds and inhalers and their respective age-specific indications. Addressing this need, the REGAP Group extensively reviewed inhalers currently available in Spain for pediatric asthma treatment. The review encompassed different inhalation systems and inhaled drugs used for pediatric asthma treatment. This review will be updated annually, providing information on medications, devices, inhalation chambers, indications, and financiation. The REGAP Group hopes that these tables will be a valuable help for pediatricians in their daily clinical practice and serve as an effective TE tool., (Copyright © 2023 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo., Methods: Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model., Results: Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36)., Conclusions: The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: Studies on the prevalence of asthma and allergies often lack representation of the pediatric population, and their impact has not been examined using children without these diseases as a reference group. This study aimed to determine the prevalence of asthma and allergies in children under 14 years old in Spain and their impact on health-related quality of life, activities, healthcare utilization, and environmental and household exposure risk factors., Methods: Data came from a Spanish population-based representative survey of children aged <14 years (N=6297). A sample of controls (1:4) from the same survey was matched using propensity score matching. Logistic regression models and population-attributable fractions were calculated to determine the impact of asthma and allergy., Results: The population prevalence of asthma was 5.7% (95% CI: 5.0%, 6.4%), and of allergy was 11.4% (95% CI: 10.5%, 12.4. In children with lower percentiles of health-related quality of life (≤20th), 32.3% (95% CI, 13.6%, 47.0%) was attributed to asthma and 27.7% (95% CI: 13.0%, 40.0%) to allergy. Forty-four percent of restrictions in usual activity were attributed to asthma (OR: 2.0, p-value: <0.001), and 47.9% to allergy (OR: 2.1, p-value: <0.001). 62.3% of all hospital admissions were attributed to asthma (OR: 2.8, p-value: <0.001), and 36.8% (OR: 2.5, p-value: <0.001) of all specialist consults to allergy., Conclusions: The high prevalence of atopic disease and its impact on daily life and healthcare utilization call for an integrated healthcare system focused on children and caregivers' needs with continuity of care across education and healthcare settings., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective., Methods: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab., Results: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively., Conclusion: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Cow's milk protein allergy (CMPA) is the most frequent food allergy in the first year of life. There is no clear consensus regarding its prevention. A recommendation to avoid CMP in the first week of life as a preventive measure in all infants, regardless of their atopic risk, has recently been published. The purpose of this document is to issue a recommendation on the use of extensively hydrolyzed CMP formulas in the first week of life for the primary prevention of CMPA., Methods: A group of experts was formed with members proposed by the Spanish Association of Pediatrics (AEP), the Spanish Society of Clinical Immunology and Allergology and Pediatric Asthma (SEICAAP), the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) and the Spanish Society of Neonatology (SENEO). The group conducted a critical review of the evidence on the subject published in the last 10 years., Results: The search yielded 72 studies, of which 66 were rejected for not meeting the inclusion criteria. The final review included 6 documents: 3 clinical trials and 3 systematic reviews, 2 of them with meta-analysis. There was no evidence of a statistically significant reduction in the incidence of CMPA in the infants who received hypoallergenic formulae or exclusive breastfeeding., Conclusion: Based on the current evidence, it is not possible to draw clear conclusions about the effect of avoiding CMP in the first week of life for prevention of CMPA. Although there are data that suggest a certain beneficial effect of avoiding CMPA in atopic risk infants, these results are not conclusive enough to extend the recommendation to the general population., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Oral immunotherapy (OIT) is a promising approach to cow's milk and egg allergies, but reactions are frequent and some patients cannot be desensitized., Objective: To evaluate long-term OIT outcomes with omalizumab (OMZ) in paediatric patients with severe egg and/or milk allergies., Methods: This retrospective real-life study analysed findings in children with Immunoglobulin E-mediated allergy to cow's milk and/or hen eggs refractory to conventional OIT, who underwent OIT with OMZ in our department between 1 January 2010 and 31 December 2015., Results: In all, 41 patients were included (median age: 7 years; interquartile range [IQR]: 5.5-9.5); 26/41 (63.4%) underwent OIT for milk, 8/41 (19.5%) for egg and 7/41 (17.1%) for both. The median time between initiation of OMZ and OIT was 27 weeks (IQR: 22-33). Forty (97.56%) patients reached the maintenance phase (200 mL of cow's milk and 30 mL of raw egg or 1 cooked egg) in a median time of 27 weeks (IQR: 18-37). The median total time with OMZ was 117 weeks (IQR: 88-144). During the OMZ period, 2.44% (1/41) of patients presented anaphylaxis. After discontinuation of OMZ, 29.3% (12/41) presented anaphylaxis, 50% of them had a poor adherence to daily ingestion. One patient (2.44%) was diagnosed with eosinophilic esophagitis after 2 years of discontinuation of OMZ. Currently, after a median time of 9 years (IQR: 7-10) since the initiation of OMZ, 75.6% (31/41) are desensitized (27/31 without OMZ)., Conclusions: Omalizumab allows desensitisation of children with severe allergies to cow's milk and/or egg without developing severe reactions while receiving this treatment. However, discontinuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.

Background: Asthma impacts children's physical, emotional, and psychosocial Health-Related Quality of Life (HRQL). The EQ-5D-Y is a generic econometric instrument developed to measure HRQL in children., Objective: Evaluation of feasibility, validity, reliability, and responsiveness of EQ-5D-Y descriptive system and utility index to allow the assessment of HRQL in children with asthma, aged 8-11 years (self-response version) or under 8 years old (proxy-response version)., Methods: We used data from baseline to 10 months of follow-up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018-2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ-5D-Y is composed of a 5-dimension descriptive system, a utility index ranging from 1 to - 0.5392, and a general health visual analogue scale (EQ-VAS). The Pediatric Asthma Impact Scale (PROMIS-PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evaluated following two approaches, multitrait-multimethod matrix and known groups' comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ-VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time., Results: The EQ-5D-Y was completed at baseline for 119 children (81 self-responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ-5D-Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait-multimethod matrix confirmed the associations previously hypothesized for the EQ-5D-Y utility index [moderate with PROMIS-PAIS (0.38) and weak with ACQ (0.28)], and for the EQ-5D-Y dimension "problems doing usual activities" [moderate with the ACQ item (0.35) and weak with the PROMIS-PAIS item (0.17)]. Statistically significant differences were found in the EQ-5D-Y between groups defined by asthma control, reliever inhalers use, and second-hand smoke exposure, with mostly moderate effect sizes (0.45-0.75). The ICC of the EQ-5D-Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance., Conclusions: These results support the use of the EQ-5D-Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ-5D-Y in this population., (© 2022. The Author(s).)

Background: In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated., Objective: This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM)., Methods: A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines)., Results: The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions., Conclusion: In this population-based study in children with severe asthma, the combined treatment with OM plus AIT was safe and effective. This strategy allows these pediatric patients to be safely treated with AIT.

Asthma is one of the main chronic diseases in childhood, due to its high prevalence and its social and health costs. This document is a summary of a consensus guideline approved by 6 Spanish pediatric societies related to asthma and endorsed by the Spanish Pediatric Association. Asthma is easily identifiable by clinical criteria in most patients. Spirometry and other tests are helpful for diagnosis, especially in atypical cases. Asthma exacerbation is a frequent manifestation of the disease and must be identified and treated promptly. When asthma symptoms are frequent and the quality of life is affected, maintenance treatment must be instituted to achieve control of the disease. Low-dose inhaled corticosteroids are effective and safe for long-term use. Education of the patient with asthma is essential for good control. The main reason for poor asthma control is non-compliance with treatment, either due to its erratic and insufficient administration, or due to poor application technique of inhaled drugs. If control is not obtained despite adequate treatment, the diagnosis must be reconsidered, as well as the factors or comorbidities that make control difficult. Other drugs can be added to avoid high doses of inhaled corticosteroids, notably montelukast or long-acting β2 adrenergic agonists. Severe or difficult-to-control asthma, which does not respond to the usual treatments, should be managed in specialized units., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date., Methods: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period., Results: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution., Conclusion: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Cat-scratch disease is caused by a Gram-negative bacillus known as Bartonella henselae. This disease is usually benign and causes regional adenitis that does not require treatment. However, some patients develop more serious atypical forms of the disease including prolonged systemic illness with hepatic and splenic abscesses.A 14-year-old girl was admitted to hospital with a 12-day history of persistent high fever and abdominal pain. Ultrasonography and computerized tomography of the abdomen revealed splenic abscesses. These findings, together with an antecedent of cat exposure, led to the suspicion of cat-scratch disease, which was confirmed by serology. The girl was treated with intramuscular ceftriaxone and clinical evolution was favorable. Splenic cat-scratch disease is infrequent. Cat-scratch disease sometimes presents as fever of unknown origin and consequently this disease should be considered in the differential diagnosis of prolonged fever. Although evolution is usually favorable, antibiotic therapy is recommended in systemic manifestations of cat-scratch disease.