Differential DAMP release was observed in the sputum of COPD, asthma and asthma-COPD overlap (ACO) patients

Xiaolin Huang,Qinghua Huang,Dongming Qu,Xiaoyu Tan,Changchun Hou,Mengze Li,Yue Liang

doi:10.1038/s41598-019-55502-2

Abstract

Asthma-COPD overlap (ACO) has been under intensive focus; however, the levels of damage-associated molecular patterns (DAMPs) that can activate the innate and adaptive immune responses of ACO are unknown. The present study aimed to examine the levels of some DAMPs in asthma, COPD, and ACO and to identify the associations between clinical characteristics and DAMPs in ACO. Sputum from subjects with asthma (n = 87) or COPD (n = 73) and ACO (n = 68) or from smokers (n = 62) and never-smokers (n = 62) was analyzed for high mobility group protein B1 (HMGB1), heat shock protein 70 (HSP70), LL-37, S100A8, and galectin-3 (Gal-3). The concentration of HMGB1, HSP70, LL-37, and S100A8 proteins in sputum from ACO patients was significantly elevated, whereas that of Gal-3 was reduced, compared to that of smokers and never-smokers. The levels of HMGB1 and Gal-3 proteins in ACO patients were elevated compared to those in asthma patients. The sputum from ACO patients showed an increase in the levels of LL-37 and S100A8 proteins compared to that of asthma patients, whereas the levels decreased compared to those of COPD patients. The concentrations of HMGB1, HSP70, LL-37, and S100A8 proteins in the sputum of 352 participants were negatively correlated, whereas the levels of Gal-3 were positively correlated, with FEV1, FEV1%pred, and FEV1/FVC. Sputum HMGB1 had a high AUC of the ROC curve while distinguishing ACO patients from asthma patients. Meanwhile, sputum LL-37 had a high AUC of the ROC curve in differentiating asthma and COPD. The release of sputum DAMPs in ACO may be involved in chronic airway inflammation in ACO; the sputum HMGB1 level might serve as a valuable biomarker for distinguishing ACO from asthma, and the sputum LL-37 level might be a biomarker for differentiating asthma and COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic lung diseases worldwide, and obstructive airway diseases are characterized by airflow limitation and chronic airway inflammation[1,2]
Several studies have focused on the symptoms and clinical characteristics of Asthma-COPD overlap (ACO), the pathophysiology of this disease has been poorly investigated
The levels of sputum high mobility group protein B1 (HMGB1), heat shock protein 70 (HSP70), S100A8, and LL-37 were elevated, while those of sputum Gal-3 were decreased, in patients with ACO compared to healthy controls

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic lung diseases worldwide, and obstructive airway diseases are characterized by airflow limitation and chronic airway inflammation[1,2]. Some patients, especially elderly patients, may present several features associated with asthma and COPD, thereby complicating the diagnosis[3] These patients have been termed asthma-COPD overlap (ACO) by international guidelines, which define ACO as a persistent airflow limitation along with high airflow reversibility[1,2]. Chronic airway inflammation in asthma and COPD is characterized by activation of the innate and adaptive immune systems[5]. Pouwels et al postulated that DAMPs play a vital role in the initiation of chronic airway inflammation in COPD8. Increased levels of several DAMPs, including HMGB1, HSPs, and S100A8, have been observed in induced sputum and serum of asthma and COPD patients in our and other previous studies[9,10,11] that are implicated in the pathogenesis of asthma and COPD. The levels of five DAMPs in the sputum of patients with asthma, COPD, and ACO were examined, followed by an analysis of the correlations between the concentrations of these DAMPs and different clinical variables

Methods

Results

Conclusion