77fc0afac746cc9b90b1a93446f4ec11 jcm-13-07202.pdf 62aa0872006600d0bedcdedb7af0d9beb3860ae3 jcm-13-07202.pdf 23902b9a88f3cc8e4a67de08c7f44d5ae4951c4312e01d972b3d107bb48fd3c4 jcm-13-07202.pdf Title: Prognostic Factors in Severe Eosinophilic Asthma in a Pediatric Population: A Prospective Cohort Study in Spain Subject: 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 (FEV1), 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 (FEV1 < 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/L. 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. Keywords: eosinophilic asthma; severe asthma; pediatric asthma; induced sputum; biomarkers; cohort study Author: Clara Padró-Casas, María Basagaña, María del Mar Martínez-Colls, Ignasi García-Olivé, Carlos Pollan Guisasola, Aina Teniente-Serra, Eva Martínez-Cáceres, José Tomás Navarro and Carlos Martínez-Rivera Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Nov 27 10:31:46 2024 CET ModDate: Mon Dec 16 12:41:11 2024 CET Custom Metadata: no Metadata Stream: yes Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 954067 bytes Optimized: yes PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 335 0 ZXDKIP+EURM10 Type 1 Builtin yes yes yes 338 0 QPUIZM+URWPalladioL-Bold Type 1 Custom yes yes yes 342 0 XWLATX+URWPalladioL-Roma Type 1 Custom yes yes yes 345 0 JJHYFE+URWPalladioL-Ital Type 1 Custom yes yes yes 348 0 RAFMMA+VnURWPalladioL Type 1 Custom yes yes yes 351 0 LJEZBI+CMSY10 Type 1 Builtin yes yes yes 246 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 251 0 MBNHJK+CambriaMath CID TrueType Identity-H yes yes yes 127 0 MBNELA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 129 0 MBNELB+PalatinoLinotype CID TrueType Identity-H yes yes yes 132 0 MBNELC+PalatinoLinotype TrueType WinAnsi yes yes no 134 0 MBNEPC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 136 0 MBNFFB+PalatinoLinotype TrueType MacRoman yes yes no 138 0 MBNELA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 148 0 MBNELB+PalatinoLinotype CID TrueType Identity-H yes yes yes 151 0 MBNELC+PalatinoLinotype TrueType WinAnsi yes yes no 153 0 MBNEPC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 155 0 MBNFFB+PalatinoLinotype TrueType MacRoman yes yes no 157 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-12-17 02:58:04 CET RepresentationInformation: jcm-13-07202.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-12-16 12:41:57 CET Size: 954067 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design and Participants Destination: subsection.2.1 Item: Title: Study Procedures Destination: subsection.2.2 Item: Title: Study Outcomes Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Characteristics of the Study Population Destination: subsection.3.1 Item: Title: Sputum and Peripheral Blood Eosinophils Destination: subsection.3.2 Item: Title: Inflammatory and Immune-Related Variables Destination: subsection.3.3 Item: Title: Asthma Control at 12 Months of Follow-Up Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Children: Item: Title: Characteristics of Patients Destination: subsection.4.1 Item: Title: Inflammatory and Immune-Related Parameters Destination: subsection.4.2 Item: Title: Asthma Control at Follow-Up Destination: subsection.4.3 Item: Title: Limitations and Strengths of the Study Destination: subsection.4.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. 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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 (FEV1), 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 (FEV1 < 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/L. 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. 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