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Introduction Viral infections are associated with pulmonary exacerbations in children with Cystic Fibrosis (cwCF), but after 3 years of SARS-CoV-2 pandemic, whether cwCF are at higher risk of developing COVID-19 or its adverse consequences remains controversial. Methods We conducted an observational, multicenter, cross-sectional study of cwCF infected by SARS-CoV-2 between March 2020 and June 2022, (1 to 6 COVID-19 pandemic waves) in Spain. The study aimed to describe patients’ basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. Results During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (6 wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). No multisystem inflammatory syndrome (MIS-C), persisting symptoms, long-term sequelae or deaths were reported. Conclusions Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients’ basal characteristics, clinical courses and outcomes were detected across waves. While the pandemic continues, and new SARS-CoV-2 variants are being identified, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

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 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 of health encounters and drug consumption before and up to six years after the beginning of the treatment with omalizumab. RESULTS The ICER per avoided MSE was \euro2,107 after one year, and it consistently decreased to \euro656 in those followed up to six years. Similarly, the ICER for the Minimally Important Difference in control tests showed a decrease from \euro2,059 to \euro380 per each 0.5 points of improvement in ACQ5, and from \euro3,141 to \euro2,322 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, mainly those who have frequent exacerbations, showing progressively reduced costs in successive years of treatment.

The receptor for advanced glycation end products (RAGE) has been studied in several respiratory diseases described as an important inflammatory mediator. The RAGE-axis is activated by multiple endogenous ligands related to pro-inflammatory states, upregulate the RAGE expression. The function of soluble RAGE (sRAGE) is not completely understood, it has been hypothesized an anti-inflamatory role as RAGE decoy receptor. Few studies have explored the RAGE-axis in Cystic Fibrosis (CF) with contradictory results. Based on previously, we present this pilot study with the aim of describe the plasma sRAGE levels in children with cystic CF (CFp), compare with the sRAGE levels in a healthy cohort and study its possible correlation with CFp clinical features. We conducted a single-center, cross-sectional observational study. We included 35 clinically stable CF patients (aged < 18 years). The median plasma sRAGE level in CFp was 1494,75 pg/ml [interquartile range (IQR) 708,75pg/ml], compared with 714,20 pg/ml (IQR 490,50 pg/ml)) in the historical cohort of healthy controls (p < 0,001). A positive correlation was found between plasma sRAGE level and forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) (p 0,004) and forced expiratory flow between 25% and 75% (FEF25%-75%) (p 0,032). In this preliminary study, the plasma sRAGE level were higher in CFp than in healthy controls. Also, we described a positive correlation between FEV1/FVC and FEF25%-75% and plasma sRAGE. To our knowledge, our study is the largest to describe plasma sRAGE values ​​in CFp and the only one carried out in pediatric CF population.

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

Background The most common cystic fibrosis (CF)-causing mutation is deltaF508 (F508del), which is present in 28% of CF Spanish patients. While the literature based on real-life studies on CF patients homozygous F508del treated with lumacaftor/ivacaftor is limited, it demonstrates the need for better strategies to prevent related adverse events (AEs) as well as the development of newer drugs. Methods We conducted a multicenter, retrospective, observational study to describe the effects of lumacaftor/ivacaftor treatment in real-life in Spain. 20 CF patients were included, all aged 6 and upwards and presented with ppFEV1 Results The mean age was 26.65 (range of 10–45), while the mean ppFEV1 before the treatment was 32.4% and mean BMI was 19.9 kg/m2. We analysed the changes in ppFEV1 and BMI from baseline during the treatment with lumacaftor/ivacaftor, but no differences were found. However, a moderate association between days of intravenous antibiotic needed and the use of lumacaftor/ivacaftor (p = 0.001) was established. Indeed, under the lumacaftor/ivacaftor, patients required 5.8 days of intravenous antibiotic treatment compared to 14.9 days prior to study. Also, severe pulmonary exacerbations requiring hospitalisation were statistically fewer under lumacaftor/ivacaftor treatment (p = 0.003). Finally, 75% of the sample presented with AEs, which led 35% of the subjects to discontinue the treatment. Conclusions While treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found.

Background Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation. Methods This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1β, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1β, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV1, pulmonary exacerbations, antibiotic use, nutritional status and quality of life). Results Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups. Conclusion In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613)

The evaluation of the benefits of omega-3 fatty acid supplementation in humans requires the identification and characterization of suitable biomarkers of its incorporation in the body. The reference method for the evaluation of omega-3, gas chromatography, is difficult to apply in clinical practice because of its low throughput and does not provide information about the incorporation of specific fatty acids in lipid species and the potential effects of supplementation on lipid classes. We used a quantitative lipidomic approach to follow the incorporation of omega-3 fatty acids into plasma lipids in cystic fibrosis patients (n=50) from a randomized controlled clinical trial after the supplementation of seaweed oil enriched with docosahexaenoic acid (DHA). Lipidomic analysis accurately showed the distribution of fatty acids in different lipid classes after omega-3 supplementation, and the performance in determining the compliance to supplementation was similar to that of gas chromatography coupled to mass spectrometry. Twelve months after fatty acid supplementation, DHA was predominantly incorporated into highly unsaturated cholesteryl esters (110.9±16.2 vs. 278.6±32.6 μM, mean±S.E.M.) and phosphatidylcholine (142.4±11.9 vs. 272.9±21.4 μM) and, to a lesser extent, into phosphatidylethanolamine (9.4±0.8 vs. 15.5±1.5 μM) and triglycerides (0.4±0.04 vs. 1.1±0.12 μM). In addition, a technique was developed for the fast measurement of the DHA/arachidonic acid ratio to simplify the follow-up of nutritional intervention with DHA-enriched foods. We conclude that lipidomics is a suitable approach for monitoring the incorporation of omega-3 fatty acids in nutritional studies.

Introduction. Pulmonary function tests allow an objective assessment of the degree of bronchial obstruction in collaborative subjects. The measurement of airway resistance using passive methods is very helpful in non-collaborative subjects. The objective of this study was to assess the applicability of measuring airway resistance by the interrupter technique (Rint) in pediatric subjects, determining its reproducibility, reliability and accuracy versus other techniques to measure airway resistance. Material and Methods. Cross-sectional study in healthy children and in children with an obstructive airway disease, all aged 2-18 years old. The Rint was measured using a portable device and results were compared to airway resistance measured by oscillometry and plethysmography. The reproducibility of measurements and the influence of the different outcome measures (use of mask or mouthpiece, cheek support, or nose clip) were assessed. Results. Valid measurements were obtained in 82.6% of 460 children (47.6% younger than 7 years old). Reproducibility was very good (ICC= 0.9412; p

Pulmonary function tests allow an objective assessment of the degree of bronchial obstruction in collaborative subjects. The measurement of airway resistance using passive methods is very helpful in non-collaborative subjects. The objective of this study was to assess the applicability of measuring airway resistance by the interrupter technique (Rint) in pediatric subjects, determining its reproducibility, reliability and accuracy versus other techniques to measure airway resistance.Cross-sectional study in healthy children and in children with an obstructive airway disease, all aged 2-18 years old. The Rint was measured using a portable device and results were compared to airway resistance measured by oscillometry and plethysmography. The reproducibility of measurements and the infuence of the different outcome measures (use of mask or mouthpiece, cheek support, or nose clip) were assessed.Valid measurements were obtained in 82.6% of 460 children (47.6% younger than 7 years old). Reproducibility was very good (ICC= 0.9412; p0.00001), and no differences were found among the measurements obtained at separate time intervals (0.75 ± 0.3 versus 0.74 ± 0.28; p= 0.435). None of the factors indicated before had an effect on the reproducibility of measurements. Resistance values obtained by plethysmography and oscillometry were higher than those obtained using the Rint, with a positive correlation between them. The higher the degree of airway obstruction, the worse the correlation with plethysmography.The Rint measurement is a plausible and reproducible technique, and has an adequate correlation with the resistance measurements obtained using oscillometry or plethysmography, thus making it useful for non-collaborative patients. In patients with airway obstruction, this technique could underestimate resistance, so it would be a hurdle to use it to follow-up subjects with a moderate to severe obstructive disease or in bronchial challenge tests.