Search

Objectives: To assess the degree of consensus among a multidisciplinary expert panel on the transition of adolescents with severe asthma from pediatric to adult care., Methods: A 61-item survey was developed based on guidelines for other chronic diseases, covering transition planning, preparation, effective transfer, and follow-up. A 2-round Delphi process assessed the degree of consensus among 98 experts (49 pediatricians, 24 allergists, and 25 pulmonologists). Consensus was established with ≥70% agreement., Results: Consensus was reached for 42 items (70%). Panelists were unable to agree on an age range for initiation of transition. The main goal during the transition identified by the experts is for adolescents to gain autonomy in managing severe asthma and prescribed treatments. The panelists agreed on the importance of developing an individualized plan, promoting patient autonomy, and identifying factors associated with the home environment. They agreed that the adult health care team should have expertise in severe asthma, biologics, and management of adolescent patients. Pediatric and adult health care teams should share clinical information, agree on the criteria for maintaining biological therapy, and have an on-site joint visit with the patient before the effective transfer. Adult health care professionals should closely follow the patient after the effective transfer to ensure correct inhaler technique, adherence, and attendance at health care appointments., Conclusion: This consensus document provides the first roadmap for Spanish pediatric and adult teams to ensure that key aspects of the transition process in severe asthma are covered. The implementation of these recommendations will improve the quality of care offered to the patient.

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: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size., Aim: To assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period., Methods: This observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks' gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V'maxFRC and FEF 25-75 , respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age., Results: Lung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V'maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV 0.5 and forced expiratory flows was seen in preterm infants., Conclusion: When compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: Post-infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post-transcriptional gene regulation in order to characterise PiBO., Methods: A total of 39 patients with well-defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next-generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein-protein interaction network analysis respectively., Results: Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL-1β, IL-6, IL-8 and TGF-β compared to controls.Next-generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for P adj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR-335-5p, miR-186-5p, miR-30b-5p and miR-30c-5p were further validated using qRT-PCR. Interestingly, these miRNAs are functionally implicated in cytokine-cytokine receptor interaction, TGF-β signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1)., Conclusion: Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics., Competing Interests: Dr Duecker reports grants from Starke Lunge Foundation, during the conduct of the study. Dr de Mir Messa reports grants from Starke Lunge Foundation, during the conduct of the study; personal fees from GSK, other from Novartis and other from Aldo Union, outside the submitted work. Dr Moreno‐Galdó reports grants from Starke Lunge Foundation, during the conduct of the study; personal fees from AbbVie, personal fees from AbbVie, personal fees from Sanofi, other from Novartis, other from AbbVie and other from Actelion outside the submitted work. Dr Rosewich reports grants from Starke Lunge Foundation, during the conduct of the study; other from Engelhard Arzneimittel, other from GSK Arzneimittel GmbH and other from Bencard GmbH, outside the submitted work. Dr Zielen reports grants and personal fees from bene‐Arzneimittel GmbH, grants and personal fees from Biotest GmbH, grants from Vifor Pharma Deutschland GmbH, grants from ALK Arzneimittel, personal fees from Novartis GmbH, grants and personal fees from Böhringer Ingelheim, personal fees from Lofarma GmbH, personal fees from IMS HEALTH GmbH & Co. OHG, personal fees from GSK, personal fees from Stallergen, personal fees from Procter and Gamble, personal fees from Allergopharma GmbH, personal fees from Engelhard Arzneimittel GmbH, personal fees from AstraZeneca, personal fees from Sanofi‐Aventis GmbH, personal fees from Allergy Therapeutics and personal fees from Aimmune Therapeutics, outside the submitted work. Dr Schubert reports grants from Starke Lunge Foundation, during the conduct of the study. All other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Background: Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain., Methods: Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019., Results: A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28-10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81-51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2-18 years of age compared with children 0-2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47)., Conclusions: We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients., Methods: This was a multicenter cross-sectional study of patients with a high suspicion of PCD, according to European Respiratory Society criteria, designed around a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD., Results: We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature., Conclusions: The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspicion of PCD. Sixty-eight (91.9%) patients were evaluable for all tested antibodies. Thirty-three cases (44.6%) presented an absence or mislocation of protein in the ciliary axoneme (15 absent and 3 proximal distribution of DNAH5 in the ciliary axoneme, 3 absent DNAH5 and DNALI1, 7 absent DNALI1 and cytoplasmatic localization of GAS8, 1 absent GAS8, 3 absent RSPH9 and 1 absent RSPH4A). Fifteen patients had confirmed or highly likely PCD but normal immunofluorescence results (68.8% sensitivity and 100% specificity). In conclusion, immunofluorescence analysis is a quick, available, low-cost and reliable diagnostic test for PCD, although it cannot be used as a standalone test.

Introduction: Recent publication of multi-ethnic spirometry reference equations for subjects aged from 3-95 years aim to avoid age-related discontinuities and provide a worldwide standard for interpreting spirometric test results., Objectives: To assess the agreement of the Global Lung Function Initiative (GLI-2012) and All ages (FEV 0.5 ) reference equations with the Spanish preschool lung function data. To verify the appropriateness of these reference values for clinical use in Spanish preschool children., Methods: Spirometric measurements were obtained from children aged 3 to 6 years attending 10 randomly selected schools in Barcelona (Spain). Stanojevic's quality control criteria were applied. Z-scores were calculated for the spirometry outcomes based on the GLI equations. If the z-score (mean) of each parameter was close to 0, with a maximum variance of ± 0.5 from the mean and a standard deviation of 1, the GLI-2012 equations would be applicable in our population., Results: Of 543 children recruited, 405 (74.6%) were 'healthy', and of these, 380 were Caucasians. Of these 380, 81.6% (169 females, 141 males) performed technically acceptable and reproducible maneuvers to assess FEVt, and 69.5% achieved a clear end-expiratory plateau. Z-scores for FVC, FEV 1 , FEV 1 /FVC, FEV 0.75 , FEV 0.75 /FVC, FEV 0.5 , FEF 75 and FEF 25-75 all fell within ± 0.5, except for FEV 1 /FVC (0.53 z-scores)., Conclusions: GLI equations are appropriate for Spanish preschool children. These data provide further evidence to support widespread application of the GLI reference equations., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Pulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality., Material and Methods: A retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data., Results: A total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good., Conclusions: High neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management., (Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Pulmonary hypertension (PH) in children is a serious disorder, for which the major goal of treatment is to prevent progressive vascular remodeling, and improve clinical status and survival. Iloprost is approved for the treatment of PH in adults; however, few studies have evaluated its effects in children. The objective of this study is to analyze the long-term effects of inhaled iloprost treatment in children with PH. A retrospective study was conducted in patients treated with iloprost between 2000 and 2012. Patients with left-right cardiac shunt and persistent PH of the newborn were excluded. The cohort comprised 22 patients (15 females) with a median age of 2.6 years. Twelve patients had pulmonary arterial hypertension including idiopathic (n = 6), hereditary (n = 2) and associated (congenital heart disease [n = 3], and schistosomiasis [n = 1]). One patient had pulmonary veno-occlusive disease, six patients had PH secondary to lung disease and three had multifactorial PH. Median mean pulmonary arterial pressure was 55 mmHg and median pulmonary vascular resistance was 15.5 Wood units. Good tolerability was observed, with the exception of one case of recurring abdominal pain. PH resolved in two patients, with functional capacity improvement in 10 patients and stabilization in three patients. The clinical condition of six patients deteriorated; two died, and two received lung transplants. In conclusion, the results of this uncontrolled study showed that iloprost was effective and well tolerated in children. However, further research is needed to support this study, as PH is a serious condition that can require organ transplantation or result in death., (© 2014 Wiley Periodicals, Inc.)

Sputum eosinophils and exhaled fractional nitric oxide (FENO) are markers of airway inflammation in asthma. Cytokines, cysteinyl-leukotrienes and leukotriene B4 (LTB4) are responsible for this inflammation. The aim of this study is to determine the usefulness of these markers in monitoring asthma treatment in children. FENO, sputum eosinophils, and LTB4 in induced sputum were performed in 10 children (9-15 years old). These determinations were repeated four months later, after the beginning or an increase in the treatment. FENO values tended to decrease (P=.15), pulmonary function tended to improve (P=.10), and sputum eosinophils decreased (P=.003) compared to the first determination. There were no differences in LTB4 concentrations (P=.88). Sputum eosinophils seem to be more precise than FENO in the monitoring of inflammation in asthmatic children., (Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Objective: To evaluate bronchial hyperresponsiveness in children under 4 years of age with recurrent wheezing bronchitis, and to determine if its presence or absence can predict the subsequent progression to a transient or persistent wheezing bronchitis phenotype., Population and Methods: A bronchial challenge test was performed with methacholine using a modified tidal volume method, without sedation in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥ 5% or an increase in respiration rate of >50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress., Results: A total of 63 patients and 16 controls were studied (mean age 23.9 vs. 25.2 months). The PCw was lower than the control group (≤ 4 mg/ml) in 43 (68%) children from the bronchitis group (P<0.001). No significant adverse effects were observed on performing the test. After a mean follow up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent and frequent wheezing (P=0.63)., Conclusions: A high percentage of children under 4 years of age affected by wheezing bronchitis had a bronchial hyperresponse. The subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness., (Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objective: To compare low and high flow nebulizers performance (total of samples) and its side effects on sputum induction in asthmatic children., Patients and Methods: Sputum induction was performed by inhalation of a hypertonic saline solution at increasing concentrations (3%, 4% and 5%) using low flow (OMRON NE-U07; flow rate 1ml/min), or high flow (OMRON NE-U12; flow rate 3ml/min, and DeVilbiss Ultraneb 3000; flow rate 2.5ml/min) ultrasonic nebulizers., Results: We performed 49 inductions in 49 patients from 7 to 15 years old (in 15 children we used a low flow nebulizer (Omron NE-U07) and in 34 children a high flow nebulizer (OMRON NEU12, 6 patients, and DeVilbiss Ultraneb 3000, 28 patients). We obtained 37 samples of which 36 had less than 20% of squamous cells, and 26 had a viability > or =60%. The test performance was higher with high-flow nebulizers, obtaining 85.3% of samples compared to 53% (p=0.04). A total of 69% of samples obtained with the high flow nebulizer were valid, compared to 62.5% (p=0.7) with the low flow nebulizers. With high flow rate nebulizers the incidence of cough (17.6%, p=0.08) and itchy eyes (0%, p=0.02) decreased with the low flow nebulizer (47% and 20% respectively), but bad taste (82.3%, p <0.001) and salivation (14.7%, p=0.3) increased., Conclusions: With high flow rate ultrasonic nebulizers we obtain a higher performance of the technique without an increase in significant side effects., (2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background: The objective of the study was to assess bronchial inflammation in preschool children with recurrent bronchitis by measuring exhaled nitric oxide., Patients and Methods: The study included patients under 4 years of age with at least 3 episodes of wheezing in the past year (n=63) and a control group (n=30). Exhaled nitric oxide was measured in samples collected offline during spontaneous tidal breathing with a face mask and stored in Mylar balloons., Results: The fractional exhaled nitric oxide concentration (FE(NO)) was higher in the group with bronchitis (mean [SD], 5.3 [1.3] parts per billion [ppb]) than in the control group (4.6 [1.1]ppb) (P=.02). There was a significant difference between the control group and children in the bronchitis group not treated with inhaled corticosteroids (P<.05), but not between controls and corticosteroid-treated patients. A relationship with eosinophil count was observed in that those with higher counts (>400 microL) had higher FE(NO) levels (P<.01). No relationship was observed between FE(NO) and a positive methacholine challenge test. Follow-up lasted at least 20 months. The initial FE(NO) level did not differ significantly according to whether patients were subsequently transient, infrequent, or frequent wheezers (5.2 [0.98]ppb, 5.6 [1.5]ppb, and 4.8 [1.34]ppb, respectively; P=.36)., Conclusions: In children under 4 years of age with recurrent wheezing bronchitis who were asymptomatic at study entry, a small increase in FE(NO) was observed although there was a good deal of overlap with the control group.

Objective: To assess the safety of the tracheal auscultation method for measuring bronchial hyperresponsiveness in healthy unsedated children aged less than 4 years and to establish a range of normal bronchial hyperresponsiveness values., Population and Methods: The study population consisted of healthy children aged between 6 months and 4 years. A methacholine bronchial provocation test was administered to unsedated children, using the tidal volume breathing technique and applying an abbreviated protocol. The test was considered positive when wheezing was heard in the trachea, arterial oxygen saturation (SaO2) fell by 5% or more, or respiratory rate increased by 50% or more., Results: A total of 16 children were studied. Ages ranged from 8 to 47 months, with a mean (SD) of 23.5 (12.2) months. There was no response to the methacholine in 11 children. In the other 5 children, there was a positive response at a concentration of 8 mg/mL. Response to the test was considered positive on the basis of tracheal wheezing in 3 cases, tracheal wheezing and a fall in SaO2 in 1 case, and a fall of SaO2 of 5% or more in 1 case. SaO2 never fell below 93%., Conclusions: As a means for assessing bronchial hyperresponsiveness, the tracheal auscultation method is appropriate, is simple to apply, and can be safely administered to unsedated children aged less than 4 years. The lowest concentration at which a response to methacholine occurs in healthy children of this age group is 8 mg/mL.