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 foldcontaining 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 ϭ 31), smokers (n ϭ 169), and patients with COPD (n ϭ 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 (FEV 1) % 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 smokingrelated lung diseases.

Identification of trans Protein QTL for Secreted Airway Mucins in Mice and a Causal Role for Bpifb1

“…Bpifb1 is a member of the BPI (bactericidal/permeabilityincreasing protein)/LBP (lipopolysaccharide-binding protein) family of lipid-transfer proteins, and was previously known as Lplunc1 for long palate lung and nasal epithelia clone (Bingle et al 2011). Previous studies in humans documented expression of BPIFB1 in goblet cells of the respiratory epithelium (Bingle et al 2010), secretion into the airways (Bingle et al 2010;Gao et al 2015), and upregulation in CF (Bingle et al 2012) and COPD (Gao et al 2015;Titz et al 2015). In contrast, BPIFA1 is down-regulated in asthma models (Chu et al 2007;Wu et al 2017).…”

“…Previous studies have provided evidence that BPIFB1 is involved in human airway diseases in which MUC5B is upregulated, including CF (Scheetz et al 2004;Bingle et al 2012) and COPD (Gao et al 2015;Titz et al 2015), as well as IPF (Yang et al 2013;Gao et al 2015). Data for the role of BPIFB1 in asthma are more sparse, but upregulation has been observed in a study involving segmental allergen challenge (Wu et al 2005).…”

Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs

“…Normal mouse lungs rarely express the gel-forming Muc5ac mucin, but this was dramatically induced together with Muc5b after elastase exposure, and other proteins -like Bpifb1, Chi3l1, Chi3l3, and Chi3l4 -were highly increased after elastase exposure. Bpifb1, also called Lplunc1, has been shown to be increased in sputum of COPD, as well as in CF patients, compared with nonsmokers (23,24).…”

COPD lungs show an attached stratified mucus layer resembling the protective colonic mucus

“…Also other proteins, like Bpifb1, Chi3l1, Chi3l3, and Chi3l4 were highly increased. Bpifb1, also called SPLUNC1, has been shown to be increased in sputum of COPD as well as in CF patients compared to non-smokers (Bingle et al, 2012;Gao et al, 2015).…”