title: Characterization of sputum biomarkers for asthma-COPD overlap syndrome.
abstract: Asthma-COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease. However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized. To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected. This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma. The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS. Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135). The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves. Only sputum NGAL levels could differentiate ACOS from asthma (P<0.001 andP<0.001) and COPD (P<0.05 andP=0.002) in the discovery and replication cohorts, respectively. Sputum NGAL levels were independently correlated with the percentage of pre-bronchodilator forced expiratory volume in 1 second predicted in multivariate analysis in the discovery and replication cohorts (P=0.001 andP=0.002, respectively). In conclusion, sputum biomarkers reflecting both airway inflammation and remodeling of the tissue show potential in differentiation between asthma, COPD, and ACOS.
authors.affiliation: Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Clinical Research Unit of Pulmonary Diseases and Division of Pulmonology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital.
authors.forename: Jukka
authors.initials: J
authors.lastname: Koskela
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Hiroshima Cosmopolitan University, Hiroshima, Japan.
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.affiliation: Department of Pulmonary Diseases and Clinical Allergology, Turku University Hospital, University of Turku, Turku, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
authors.affiliation: Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.affiliation: Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D000071451:Chitinase-3-Like Protein 1 / Q000032:analysis; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005387:Finland; D005541:Forced Expiratory Volume; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D018793:Interleukin-13 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007564:Japan; D000071068:Lipocalin-2 / Q000032:analysis; D008168:Lung / Q000737:chemistry* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009195:Peroxidase / Q000032:analysis; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D012372:ROC Curve; D015203:Reproducibility of Results; D013183:Sputum / Q000737:chemistry*; D013577:Syndrome; D014797:Vital Capacity
chemical_list: D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; C508600:IL6 protein, human; D018836:Inflammation Mediators; D018793:Interleukin-13; D015850:Interleukin-6; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D009195:Peroxidase
keywords: ACOS; COPD pathology; asthma