title: Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study.
abstract: A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing fold-containing protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n = 31), smokers (n = 169), and patients with COPD (n = 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smoking-related lung diseases.
authors.affiliation: HUCH Heart and Lung Center, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.affiliation: Proteomics Core Facility, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland;
authors.forename: S
authors.initials: S
authors.lastname: Ohlmeier
authors.affiliation: Medical Informatics and Statistics Group, University of Oulu, Oulu, Finland;
authors.forename: P
authors.initials: P
authors.lastname: Nieminen
authors.affiliation: Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland;
authors.forename: T
authors.initials: T
authors.lastname: Toljamo
authors.affiliation: Medix Biochemica, Kauniainen, Finland;
authors.forename: S
authors.initials: S
authors.lastname: Tiitinen
authors.affiliation: HUCH Heart and Lung Center, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;
authors.forename: T
authors.initials: T
authors.lastname: Kanerva
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK; and.
authors.forename: L
authors.initials: L
authors.lastname: Bingle
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK; and.
authors.forename: B
authors.initials: B
authors.lastname: Araujo
authors.affiliation: HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Rönty
authors.affiliation: Medix Biochemica, Kauniainen, Finland;
authors.forename: M
authors.initials: M
authors.lastname: Höyhtyä
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK; and.
authors.forename: C D
authors.initials: CD
authors.lastname: Bingle
authors.affiliation: HUCH Heart and Lung Center, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;
authors.forename: W
authors.initials: W
authors.lastname: Mazur
authors.affiliation: HUCH Heart and Lung Center, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; ville.pulkkinen@helsinki.fi.
authors.forename: V
authors.initials: V
authors.lastname: Pulkkinen
mesh_terms: D001324:Autoantigens / Q000096:biosynthesis / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005541:Forced Expiratory Volume; D006023:Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D013183:Sputum / Q000737:chemistry*
chemical_list: D001324:Autoantigens; C485599:BPIFA1 protein, human; C568077:BPIFB1 protein, human; D050556:Fatty Acid-Binding Proteins; D006023:Glycoproteins; D010750:Phosphoproteins; D011506:Proteins
keywords: COPD; biomarkers; smoking