Elevated sputum BPIFB1 levels correlate with progression of chronic obstructive pulmonary disease

Background: Bactericidal/permeability-increasing (BPI) fold-containing protein BPIFB1 (formerly known as L PLUNC1 ) was one of the proteins elevated in induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) in our previous proteomic screening. Aim: To further evaluate the association of sputum BPIFB1 levels with smoking and changes of lung function during the progression of COPD. Methods: Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 and BPIFA1 (SPLUNC1) in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels in induced sputum from non-smokers (n=31), smokers (n=169) and patients with COPD (n=52) were assessed with an ELISA-based method, and repeated for a subset of samples (n=74) after a 4-year follow-up. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. Results: Secreted and glycosylated BPIFB1 was significantly elevated in sputum of patients with COPD when compared with that of smokers and non-smokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by FEV 1 % predicted and FEV 1 /FVC 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 smokers with COPD. Conclusions Higher sputum concentrations of BPIFB1 were associated with greater progression of airflow limitation over time, especially in smokers with COPD. BPIFB1 may be involved in the pathogenesis of smoking-related lung diseases.