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Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics
Author(s) -
Kasaian M. T.,
Lee J.,
Brennan A.,
Danto S. I.,
Black K. E.,
Fitz L.,
Dixon A. E.
Publication year - 2018
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13151
Subject(s) - sputum , medicine , asthma , exacerbation , immunology , cohort , pathology , tuberculosis
Summary Background A major goal of asthma therapy is to achieve disease control, with maintenance of lung function, reduced need for rescue medication, and prevention of exacerbation. Despite current standard of care, up to 70% of patients with asthma remain poorly controlled. Analysis of serum and sputum biomarkers could offer insights into parameters associated with poor asthma control. Objective To identify signatures as determinants of asthma disease control, we performed proteomics using Olink proximity extension analysis. Methods Up to 3 longitudinal serum samples were collected from 23 controlled and 25 poorly controlled asthmatics. Nine of the controlled and 8 of the poorly controlled subjects also provided 2 longitudinal sputum samples. The study included an additional cohort of 9 subjects whose serum was collected within 48 hours of asthma exacerbation. Two separate pre‐defined Proseek Multiplex panels ( INF and CVDIII ) were run to quantify 181 separate protein analytes in serum and sputum. Results Panels consisting of 9 markers in serum ( CCL 19, CCL 25, CDCP 1, CCL 11, FGF 21, FGF 23, Flt3L, IL ‐10Rβ, IL ‐6) and 16 markers in sputum ( tPA , KLK 6, RETN , ADA , MMP 9, Chit1, GRN , PGLYRP 1, MPO , HGF , PRTN 3, DNER , PI 3, Chi3L1, AZU 1, and OPG ) distinguished controlled and poorly controlled asthmatics. The sputum analytes were consistent with a pattern of neutrophil activation associated with poor asthma control. The serum analyte profile of the exacerbation cohort resembled that of the controlled group rather than that of the poorly controlled asthmatics, possibly reflecting a therapeutic response to systemic corticosteroids. Conclusions and Clinical Relevance Proteomic profiles in serum and sputum distinguished controlled and poorly controlled asthmatics, and were maintained over time. Findings support a link between sputum neutrophil markers and loss of asthma control.