I Agache1, D S Strasser2, A Klenk3, C Agache4,5, H Farine2, C Ciobanu4, P M A Groenen2, C A Akdis5,6. 1. Transylvania University Brasov, Brasov, Romania. 2. Department of Translational Science, Actelion Pharmaceuticals Ltd., Davos, Switzerland. 3. Information Management Drug Discovery, Actelion Pharmaceuticals Ltd., Davos, Switzerland. 4. Theramed Medical Center, Brasov, Romania. 5. Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. 6. Swiss Institute for Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Abstract
BACKGROUND: Molecular biomarkers that identify the phenotype of blood eosinophilia were evaluated in adult asthmatics, and their relationship with clinically significant asthma outcomes was assessed. Patients were clustered based on their molecular fingerprint. METHODS: At inclusion, 64 patients were evaluated for phenotypic traits, sputum and blood eosinophilia, exhaled NO, serum cytokines and chemokines, total serum IgE, lung function (LF), and airway hyper-responsiveness (AHR). Within-patient changes were evaluated in 44 patients 6 weeks later. RESULTS: Lung function, asthma control, and monocyte chemotactic protein-1 (MCP-1) were identified as the most important distinguisher and blood eosinophilia as second most important identifier in principal component analysis. A robust relationship was observed between blood eosinophilia and IL-5, IL-13, and eosinophil-derived neurotoxin (EDN), which stayed consistent after 6 weeks. Serum IL-5 and IL-13 were the two best, followed by EDN as separators of high vs low blood eosinophilia. Periostin did not identify blood or sputum eosinophilia, even after stratification for total IgE, and did not correlate with IL-5, IL-13, eotaxin, or EDN. IL-5 and IL-13 showed strong correlations with AHR and monocyte chemoattractant protein (MCP)-1 with asthma severity and fast LF decline. The presence of high or low expression of MCP-1, eotaxin, and IL-8 identified two separate blood eosinophilia patient clusters linked to asthma severity. CONCLUSION: Serum IL-5 and IL-13 are reliable biomarkers for the blood eosinophilia asthma phenotype. High or low expression of MCP-1, eotaxin, and IL-8 discriminates between eosinophilic asthma severity clusters.
BACKGROUND: Molecular biomarkers that identify the phenotype of blood eosinophilia were evaluated in adult asthmatics, and their relationship with clinically significant asthma outcomes was assessed. Patients were clustered based on their molecular fingerprint. METHODS: At inclusion, 64 patients were evaluated for phenotypic traits, sputum and blood eosinophilia, exhaled NO, serum cytokines and chemokines, total serum IgE, lung function (LF), and airway hyper-responsiveness (AHR). Within-patient changes were evaluated in 44 patients 6 weeks later. RESULTS: Lung function, asthma control, and monocyte chemotactic protein-1 (MCP-1) were identified as the most important distinguisher and blood eosinophilia as second most important identifier in principal component analysis. A robust relationship was observed between blood eosinophilia and IL-5, IL-13, and eosinophil-derived neurotoxin (EDN), which stayed consistent after 6 weeks. Serum IL-5 and IL-13 were the two best, followed by EDN as separators of high vs low blood eosinophilia. Periostin did not identify blood or sputum eosinophilia, even after stratification for total IgE, and did not correlate with IL-5, IL-13, eotaxin, or EDN. IL-5 and IL-13 showed strong correlations with AHR and monocyte chemoattractant protein (MCP)-1 with asthma severity and fast LF decline. The presence of high or low expression of MCP-1, eotaxin, and IL-8 identified two separate blood eosinophiliapatient clusters linked to asthma severity. CONCLUSION: Serum IL-5 and IL-13 are reliable biomarkers for the blood eosinophilia asthma phenotype. High or low expression of MCP-1, eotaxin, and IL-8 discriminates between eosinophilic asthma severity clusters.
Authors: K R Brown; R Z Krouse; A Calatroni; C M Visness; U Sivaprasad; C M Kercsmar; E C Matsui; J B West; M M Makhija; M A Gill; H Kim; M Kattan; D Pillai; J E Gern; W W Busse; A Togias; A H Liu; G K Khurana Hershey Journal: PLoS One Date: 2017-07-07 Impact factor: 3.240
Authors: Luis Pérez de Llano; Borja G Cosío; Amanda Iglesias; Natividad de Las Cuevas; Juan Jose Soler-Cataluña; Jose Luis Izquierdo; Jose Luis López-Campos; Carmen Calero; Vicente Plaza; Marc Miravitlles; Alfons Torrego; Eva Martinez-Moragon; Joan B Soriano; Antolin Lopez Viña; Irina Bobolea Journal: Int J Chron Obstruct Pulmon Dis Date: 2018-02-12
Authors: Heimo Breiteneder; Zuzana Diamant; Thomas Eiwegger; Wytske J Fokkens; Claudia Traidl-Hoffmann; Kari Nadeau; Robyn E O'Hehir; Liam O'Mahony; Oliver Pfaar; Maria J Torres; De Yun Wang; Luo Zhang; Cezmi A Akdis Journal: Allergy Date: 2019-06-04 Impact factor: 13.146