Search

Background/Objectives : The objective of this study was to provide real-world data on prognostic factors in children with severe eosinophilic asthma and to assess biomarkers of outcome. Methods : Fifty-nine children (aged 6-17 years) were included in a prospective cohort attended in a Severe Asthma Unit of a tertiary care teaching hospital in Badalona (Barcelona, Spain) and visited at baseline and at 1-year follow-up. Study variables included asthma control using the Asthma Control Test (ACT), forced expiratory volume in one second (FEV 1 ), exacerbation episodes, fractional exhaled nitric oxide (FeNO), and inflammatory biomarkers (blood tests, sputum cells, immunoallergic tests, and levels of cytokines and effector cells in blood and sputum). Results : There were 36 boys and 23 girls, with a mean (SD) age of 11.9 (2.8) years. Uncontrolled severe asthma was diagnosed in 83.1% of cases, with poor symptom control (ACT score < 20) in 52.5%, obstructive pattern (FEV 1 < 80% predicted) in 35.6%, and more than one exacerbation in the previous year in 30.5%. The mean duration of asthma was 9.2 (3.6) years. Positive prick tests were recorded in 55 patients, with polysensitization in 6. The mean percentage of sputum eosinophils was 2.5% (3.1%), and the mean eosinophil blood count 543.4 (427.7) cells/µL. Ten patients (32%) showed sputum eosinophilia (>3% eosinophils). Sputum eosinophils did not correlate with blood eosinophils, FeNO, and serum periostin. At 12 months, 13 (22%) children had uncontrolled asthma and 46 (78%) had controlled asthma. Variables significantly associated with uncontrolled asthma were duration of asthma (OR = 1.23, 95% CI 1.01-1.49, p = 0.04) and an ACT score < 20 (OR = 0.80, 95% CI 0.69-0.93, p = 0.004). Lower serum levels of IL-9 appeared to be related with uncontrolled asthma, but statistical significance was not reached. Conclusions : Pediatric severe eosinophilic asthma showed a predominant allergic phenotype with symptomatic disease as a main contributor of uncontrolled asthma at 1 year. Predictive biomarkers of outcome were not identified. Further studies are needed to confirm the present findings especially considering additional variables for a better phenotypic characterization of severe eosinophilic asthma in children and to study in-depth the role of inflammatory biomarkers.

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.