Neutrophil gelatinase-associated lipocalin as a complementary biomarker for the asthma-chronic obstructive pulmonary disease overlap

Abstract

Background: There is no standardized definition of the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). Although the blood eosinophil count is regarded as a biomarker for identifying ACO, it has no distinct value. This study aimed to measure plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), a potential biomarker for distinguishing between ACO and non-ACO COPD. Methods: We used the Korean cohort in the COPD in dusty area (CODA) study which included 137 subjects with COPD confirmed by spirometry. We defined ACO by a positive bronchodilator response (forced expiratory volume in 1 s, FEV1 >12% and >200 mL from baseline) or based on a previous history of asthma. Plasma levels of NGAL were determined by enzyme immunoassay. Results: Among the 137 subjects, 77 were ACO and 60 were non-ACO COPD. Overall, the plasma NGAL levels were 15.9±7.9 and 15.6±6.6 ng/mL for non-ACO and ACO subjects respectively, and not significantly different. However, NGAL levels were significantly higher in female subjects with ACO (17.0±6.4 vs. 11.1±4.5, P=0.01). In female subjects, NGAL levels showed a good predictive ability to discriminate between ACO and non-ACO COPD [area under the receiver operating characteristic curve (AUROC), 0.77]; the predictive ability was similar to that of the blood eosinophil count (AUROC, 0.79). There was a higher probability of discriminating ACO from non-ACO among subjects in the highest tertile of NGAL levels (odds ratio, 1.72; 95% confidence interval, 0.69–4.28; P for trend =0.01). Conclusions: NGAL levels were significantly higher in ACO compared to non-ACO COPD in female subjects. After adjusting for gender as a confounding factor, the ability to distinguish ACO was better at higher levels of NGAL.