Severe Asthma by Yong Chul Lee So Ri Kim & Seong Ho Cho

Author:Yong Chul Lee, So Ri Kim & Seong Ho Cho
Language: eng
Format: epub
Publisher: Springer Singapore, Singapore

4.3.4 Other Biomarkers

Patil et al. measured serum levels of cytokines, chemokines, growth factors , adhesion molecules , and cytokine receptors in chronic asthmatics and analyzed their association with asthma control and quality of life. Results demonstrated that many cytokines and growth factors (excluding IFN-γ) were expressed at significantly higher levels in asthmatics as compared to non-asthmatic controls. Particularly, IL-3, IL-18, fibroblast growth factor, hepatocyte growth factor, and stem cell growth factor-β levels were elevated significantly in poorly controlled asthmatics as compared to those that were well controlled [287]. In another study, RANTES, a key chemotactic factor in allergic airway inflammation, was significantly increased in patients with severe asthma, and increased RANTES levels were positively associated with eosinophil count and total serum IgE level but negatively correlated to FEV1[288]. Recently, Chambers et al. found the existence of IL-17Ahigh and IFN-γhigh immunophenotypes in patients with corticosteroid-resistant asthma [289]. Ciprandi et al. showed that serum levels of IL-23 were increased among asthmatic children and negatively correlated with pulmonary function [290].

Galectins are a family of animal lectins with variable cellular and extracellular localization affecting a variety of cellular processes and biological activities. Of these, galectin-9 and galectin-3 were found to be relevant to asthma. Galectin-9 promotes recruitment of eosinophils and promotes Th2 dominance [291], but galectin-9 also binds IgE, thus promoting antiallergic effects and may prevent acute asthma exacerbations [292, 293]. Galectin-3 promotes multiple cellular activities including adhesion, growth, chemoattraction, differentiation, apoptosis, and cell cycle regulation. Galectin 3 may also have IgE binding activities [294–296]. Mauri et al. suggested that galectin-3 could be considered as a reliable biomarker to predict response to omalizumab therapy in severe asthmatics [297].

Other serum markers have been found to be elevated in the blood of asthmatics. These markers include C3 and C4 complement [298], chitinase-like proteinYKL-40 [299, 300] and OX40, and its ligands [301]. Serum leptin levels and body mass index have also been associated with the severity of airway inflammation in childhood asthma [302].

In recent years, research has focused on new avenues of exploration including proteomics , genomics , and metabolomics in an attempt to identify relevant biomarkers in severe asthma. The goal of identifying new biomarkers is to help improve the diagnosis, phenotyping, and management of this chronic and sometimes debilitating disease. Among these biomarkers, attractive candidates include C7 complement protein, alpha-1-antitrypsin [303], gamma fibrinogen and its isoforms, C3 complement fragments [304], fibronectin [305], arginase, and syntaxin [306]. In addition, Verrills et al. identified another series of candidate biomarkers that includes a panel of four acute-phase proteins (ceruloplasmin, haptoglobin, hemopexin, and α2-macroglobulin) that may be able to discriminate among asthma, COPD, and normal controls [307]. However, further investigation is needed to clarify the relevance of these systemic biomarkers in various aspects of asthma.

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