BPI-ANCA in chronic obstructive pulmonary disease with pulmonary Pseudomonas aeruginosa colonisation: a novel indicator of poor prognosis

Bactericidal/permeability-increasing protein (BPI) is one of the target antigens of anti-neutrophil cytoplasmic antibodies (ANCA), which have clinical and laboratory significance in systemic and rheumatoid vasculitides. The detection rate of BPI-ANCA in pulmonary disease has increased in recent years: pulmonary inflammation of BPI-ANCA(+) in patients with cystic fibrosis and chronic pulmonary infection is linked to declining lung function [1]. Pseudomonas aeruginosa is one of the most common pathogens of respiratory infections in patients with chronic obstructive pulmonary disease (COPD), which significantly increases the chances of lower respiratory tract infections and acute exacerbation of COPD, resulting in increased hospitalisation. Although there is literature on BPI-ANCA in lung disease such as cystic fibrosis and pulmonary tuberculosis [1–3], there is none on its presence in COPD or links with clinical manifestations, hospitalisations and prognosis. We hypothesised that BPI-ANCA status is linked to lung function and a physiological test of general health (the six-minute walking time) and predicts poor outcome in patients with COPD. To test our hypothesis, we recruited 126 patients with chronic COPD and P. aeruginosa colonisation from the Second Affiliated Hospital of Nanchang University from June 2014 to August 2016. The diagnostic criteria for inclusion and acute exacerbations met the 2014 GOLD Global Initiative for Chronic Obstructive Pulmonary Disease [4]. Isolation of P. aeruginosa in three or more consecutive sputum cultures, taken at least one month apart during a 6-month period, was considered as chronic colonisation. Exclusion criteria were respiratory, cardiovascular, haematological or immune system diseases and severe metabolism abnormalities. The study was in accordance with the 1964 Helsinki declaration and approved by ethics committee of the Second Affiliated Hospital of Nanchang University with written informed consents obtained from all participants. Lung function tests (predicted% forced expiratory volume in 1 min (FEV1%pred) and forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC)), COPD assessment test (CAT) and the 6min walking test (6MWT) were conducted for each patient during a clinically stable period at entry and at 6, 12 and 18 months. Hospital readmissions for acute exacerbations and days of hospitalisation were noted. CAT consisted of eight items covering the most burdensome symptoms and limitations of COPD; each item had a score of 0–5 points and a total score of 0– 40 points [5]. Pulmonary function tests were performed using a German-born Master Screen Diffusion Pulmonary Function Tester. Lung ventilation function tests were performed in strict accordance with the quality control standards of the American Thoracic Society [6]. Lung volume measurements and flow rate capacity curves were performed to evaluate patients’ pulmonary function. Each item was conducted three times repeatedly, and the best value of FEV1%pred and FEV1/FVC(%) was taken as the result [5]. 6MWD was the best of two walks [7]. Five millilitre fasting blood was collected, and serum were obtained after a centrifugation at 1026 g for 10 min. Serum IgG-BPI-ANCA was detected by ELISA (Catalogue number E180104AH: EuroImmun Medical Diagnostics, Beijing, China). At the termination of antigen–antibody reaction, optical density (OD) was detected by a Multiskan Mk3 Plate Reader (ThermoFisher Scientific, Shanghai, China), with a cut-off value of 0.2× ODcalibration. BPI-ANCA considered positive (BPI-ANCA(+)) when ratio (ODsample to cut-off) >1 and negative (BPI-ANCA(−)) otherwise. SPSS23.0 software was used for statistical analysis. K-S test and Levene’s test were used to analyse the normality and variance homogeneity of measurements. Data are presented as mean with