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.
Subject(s)
Autoantigens/metabolism , Proteins/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Smoking/adverse effects , Sputum/chemistry , Autoantigens/biosynthesis , Fatty Acid-Binding Proteins , Female , Forced Expiratory Volume , Glycoproteins/biosynthesis , Glycoproteins/metabolism , Goblet Cells/metabolism , Humans , Longitudinal Studies , Lung/metabolism , Male , Middle Aged , Phosphoproteins/biosynthesis , Phosphoproteins/metabolismABSTRACT
Serum surfactant protein (SP)-A has been postulated to associate with pulmonary fibrosis, but its role in cigarette smoking-related lung diseases is undefined. SP-A levels in plasma and induced sputum in nonsmokers, smokers with respiratory symptoms (cough and/or phlegm) and symptom-free smokers were assessed using a validated EIA method. A total of 474 current smokers without any diseases or medications were enrolled and followed for 2 yrs with 111 of them succeeding in stopping. Plasma SP-A level was detectable in all subjects and elevated in smokers independently of the symptoms compared to nonsmokers (p = 0.001). After 2 yrs of follow-up, the SP-A level was higher in those who continued smoking compared to the quitters (p<0.001). Plasma SP-A levels were associated with age, smoking history and lung function. Sputum (n = 109) SP-A was nondetectable in most nonsmokers, whereas smoking and symptoms increased sputum SP-A highly significantly (p = 0.001). In conclusion, SP-A may be involved in pathogenesis of cigarette smoking-related lung diseases. Further studies are needed to elucidate the role of SP-A in chronic obstructive pulmonary disease.
