Abstract

Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study (n = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air–liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly (p < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3–2.4) and TS-COPD (1.8; 1.4–2.5) subjects compared to TS-CONTROL (3.3; 2.9–3.5) and healthy controls (5.1; 4.5–7.2). The levels of SCGB1A1 were positively correlated (r = 0.7–0.8; p < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly (p < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly (p < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts.

Highlights

  • Secretoglobin family 1A member 1 (SCGB1A1), alternatively known as club cell protein 16 or 10 (CC16 or CC10), is a protective pneumo-protein present in normal airway secretions [1]

  • Sputum, and bronchoalveolar lavage fluid SCGB1A1 levels have been associated with increased tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD) severity and accelerated lung function decline [2]

  • We detected a similar reduction of serum SCGB1A1 concentrations in subjects with tobacco smoke induced COPD and biomass smoke induced COPD

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Summary

Introduction

Secretoglobin family 1A member 1 (SCGB1A1), alternatively known as club cell protein 16 or 10 (CC16 or CC10), is a protective pneumo-protein present in normal airway secretions [1]. The expression of SCGB1A1 is restricted to the airway club cells (formerly known as Clara cells) and has several functions including anti-inflammation, inhibition of phospholipase A2, and the sequestering of hydrophobic ligands [1]. Sputum, and bronchoalveolar lavage fluid SCGB1A1 levels have been associated with increased tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD) severity and accelerated lung function decline [2]. The global burden of disease study listed COPD as the 8th most common causes of disability in the world [3]. 3 billion people globally, mainly in low and lower-middle income countries, are exposed to biomass smoke (BMS) during cooking and heating in contrast to about 1 billion tobacco smokers [4].

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