Differential serum protein markers and the clinical severity of asthma

Abstract

Norbert Meyer,1,2 Sarah Janine Nuss,1 Thomas Rothe,1 Alexander Siebenhüner,1 Cezmi A Akdis,2 Günter Menz11Hochgebirgsklinik Davos, Davos-Wolfgang, Switzerland; 2Swiss Institute of Allergy and Asthma Research (SIAF), Davos Platz, SwitzerlandBackground: Asthma is a heterogeneous disease characterized by different clinical phenotypes and the involvement of multiple inflammatory pathways. During airway inflammation, many cytokines and chemokines are released and some are detectable in the sera.Objective: Serum chemokines and cytokines, involved in airway inflammation in asthma patients, were investigated.Methods: A total of 191 asthma patients were classified by hierarchical cluster analysis, including the following parameters: forced expiratory volume in 1 second (FEV1), eosinophil cationic protein (ECP) serum levels, blood eosinophils, Junipers asthma symptom score, and the change in FEV1, ECP serum levels, and blood eosinophils after 3 weeks of asthma therapy. Serum proteins were measured by multiplex analysis. Receiver operating characteristic (ROC) curves were used to evaluate the validity of serum proteins for discriminating between asthma clusters.Results: Classification of asthma patients identified one cluster with high ECP serum levels, increased blood eosinophils, low FEV1 values, and good FEV1 improvement in response to asthma therapy (n=60) and one cluster with low ECP serum levels, low numbers of blood eosinophils, higher FEV1 values, and no FEV1 improvement in response to asthma therapy (n=131). Serum interleukin (IL)-8, eotaxin, vascular endothelial growth factor (VEGF), cutaneous T-cell-attracting chemokine (CTACK), growth-related oncogene (GRO)-α, and hepatocyte growth factor (HGF) were significantly different between the two clusters of asthma patients. ROC analysis for serum proteins calculated a sensitivity of 55.9% and specificity of 75.8% for discriminating between them.Conclusion: Serum cytokine and chemokine levels might be predictors for the severity of asthmatic inflammation, asthma control, and response to therapy, and therefore might be useful for treatment optimization.Keywords: asthma, cluster, phenotype, serum cytokines