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Chronic obstructive pulmonary disease (COPD) is one of the major causes of death worldwide today, and its related morbidity has been predicted to show an increase in subsequent years. Recent studies have shown that Danshen, a Chinese herbal medicine, is a potential drug in the treatment of inflammation‑related lung diseases. COPD was induced in this study using cigarette smoke (CS) exposure plus intranasal inhalation of lipopolysaccharide to ascertain whether the main pharmacological component from Danshen, tanshinone IIA (TIIA), and its water soluble form, sodium tanshinone IIA sulfonate (STS), protect against the development of COPD. The weight, lung function, hematoxylin and eosin staining, and Masson Trichrome determinations revealed that TIIA inhalation attenuated lung dysfunction in COPD mice induced by cigarette smoke and lipopolysaccharide exposure. In addition, exosomes derived from TIIA‑treated COPD mice exerted similar protective effects against COPD, suggesting that TIIA may protect against COPD through exosome‑shuttled signals. miR‑486‑5p was found to be a key molecule in mediating the protective effects of exosomes derived from TIIA‑treated COPD mice using miRNA sequencing and cellular screening. Treatment of COPD mice with an agomiR of miR‑486‑5p protected lung function in COPD mice, and treatment of COPD mice with an antagomir of miR‑486‑5p abolished the protective effects of TIIA. Moreover, luciferase activity reporter assay, RT‑qPCR, and western blot analyses showed that miR‑486‑5p exerted protective effects against COPD via targeting phosphoinositide‑3‑kinase regulatory subunit 1 (

Matrix metalloproteinase-12 (MMP-12) and Tissue inhibitor of metalloproteinase-4 (TIMP-4) play important roles in the pathophysiology of chronic obstructive pulmonary disease (COPD). Subjects of many previous studies were patients with severe and very severe COPD. However, there are comparatively few studies on patients with mild-to-moderate COPD. Our aim was to measure MMP-12 and TIMP-4 levels and to compare its levels in various materials in patients with mild-to-moderate acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We also compared which of the two materials of these biomarkers was better correlated with disease severity and DODE index. A total of 39 patients with AECOPD and 25 control subjects were enrolled in our study. MMP-12 and TIMP-4 in different respiratory samples were detected by ELISA. Expression levels of MMP-12 in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) and TIMP-4 in BALF were significantly higher in AECOPD patients than that in healthy subjects (P

Objective: We sought to explore the relationships between multiple chemokines with spirometry, inflammatory mediators and CT findings of emphysema, small airways disease and bronchial wall thickness. Methods: All patients with COPD (n = 65) and healthy control subjects (n = 23) underwent high-resolution CT, with image analysis determining the low attenuation area (LAA), ratio of mean lung attenuation on expiratory and inspiratory scans (E/I MLD) and bronchial wall thickness of inner perimeter of a 10-mm diameter airway (Pi10). At enrollment, subjects underwent pulmonary function studies, chemokines and inflammatory mediators measurements. Results: Multiple chemokines (CCL2, CCL3, CCL5, CX3CL1, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12) and inflammatory mediators (MMP-9, MMP-12, IL-18 and neutrophil count) were markedly increased in the serum of COPD patients compared with healthy controls. There were associations between small airway disease (E/I MLD) and CCL11, CXCL8, CXCL10, CXCL11, CXCL12 and CX3CL1. Especially CXCL8 and CX3CL1 are strongly associated with E/I MLD (r = 0.74, p < 0.001; r = 0.76, p < 0.001, respectively). CXCL8, CXCL12 and CX3CL1 were moderately positively correlated with emphysema (%LAA) (r = 0.49, p < 0.05; r = 0.51, p < 0.05; r = 0.54, p < 0.01, respectively). Bronchial wall thickness (Pi10）showed no significant differences between the COPD and healthy controls,，but there was an association between Pi10 and FEV1% in COPD patients (r=−0.420, p = 0.048). Our statistical results showed that there were not any associations between airway wall thickness (Pi10) and chemokines. Conclusion: Pulmonary chemokines levels are closely associated with the extent of gas trapping, small airways disease and emphysema identified on high-resolution chest CT scan. Advances in knowledge: This study combines quantitative CT analysis with multiplex chemokines and inflammatory mediators to identify a new role of pathological changes in COPD.

The purpose of this study was to investigate the relationship between serum fractalkine (CX3CL1/FKN) level and the multi-slice spiral computed tomography (MSCT) emphysema index in Chinese patients with chronic obstructive pulmonary disease (COPD). We detected chemokine CX3CL1 in serum from 95 Chinese patients with COPD by using an enzyme-linked immunosorbent assay. According to the MSCT emphysema index, the selected cases were divided into an emphysema-dominant group (n = 25) and a non-emphysema-dominant group (n = 70). There were significant differences in body mass index and lung function between the two groups. The serum level of CX3CL1 in the emphysema-dominant group was significantly higher than that in the non-emphysema-dominant group. Through multivariate logistic regression analysis, it was found that high serum CX3CL1 levels were independently associated with emphysema, with a relative risk of 2.617 (95% CI 1.018–6.121; P = 0.029). The percentage of frequent acute exacerbations during the first year of follow-up was significantly higher in the high-level serum CX3CL1 group (P = 0.039). After 3 years of follow-up, there was no significant difference in the CT emphysema index between the high and low serum CX3CL1 groups (P = 0.503). Our results suggest that the serum level of CX3CL1 is related to the MSCT emphysema index. Chemokine CX3CL1 might be a useful predictor for identifying frequent exacerbation and emphysema severity in patients with COPD.

Objective: The aim of this work was to compare matrix metalloproteinase-9 and -12, tissue inhibitor of metalloproteinase-1 and -4, and neutrophil elastase in exhaled breath condensate (EBC) and peripheral blood of patients with COPD. Methods: Peripheral blood and EBC samples from COPD patients and healthy donors were collected. In serum and EBC, MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 proteins were detected by ELISA. The mRNA expression levels of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by qRT-PCR. Results: The protein levels of MMP-9 (p=.034) and MMP-12 (p=.041) in the EBC of COPD smokers were higher than those of COPD never-smokers. The concentrations of TIMP-1 (p=.072) and TIMP-4 (p=.084) in the EBC of COPD smokers were higher than those of COPD never-smokers; however, the difference was not statistically significant. MMP-9 (r=-0.78, p

Objective The present study was designed to investigate the biomarkers levels of fractalkine (FKN), neutrophil elastase (NE) and matrix metalloproteinase-12 (MMP-12) in chronic obstructive pulmonary disease (COPD) with ‘exacerbator with emphysema phenotype’ and to evaluate the associations between the biomarkers levels and the severity of disease by spirometric measurements. Methods A total of 84 COPD patients and 49 healthy controls were enrolled in our study. ELISA were utilised to detect the FKN, MMP-12 and NE in serum from all subjects. Results FKN (p Conclusion Serum FKN, MMP-12 and NE concentrations in COPD patients are directly associated with the severity of COPD with ‘exacerbator with emphysema phenotype’. This finding suggests that FKN, MMP-12 and NE might play an important role in the pathophysiology of COPD.

Objective. The purpose of this study was to compare matrix metalloproteinase-12 (MMP-12), neutrophil elastase (NE), and tissue inhibitor of metalloproteinase-4 (TIMP-4) in peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and controls. At the same time, MMP-12, NE, and TIMP-4 in exhaled breath condensate (EBC) were also evaluated. Methods. Peripheral blood and EBC samples from COPD patients and healthy controls were collected. In serum and EBC, MMP-12, NE, and TIMP-4 proteins were detected by enzyme-linked immunoassays. The mRNA expression levels of MMP-12, NE, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results. The concentration of TIMP-4 protein in EBC was lower in patients with COPD (P<0.001). MMP-12 (P=0.046), NE (P=0.027), and TIMP-4 (P=0.005) proteins in serum of patients with COPD showed higher levels of concentration. The mRNA of MMP-12 (P=0.0067), NE (P=0.0058), and TIMP-4 (P=0.0006) in PBMCs of COPD patients showed higher expression levels. Compared with stable patients, mRNA expression level of NE (P=0.033) in PBMCs of patients with acute exacerbation of COPD was increased. There were differences in the ratio of MMP-12/TIMP-4 in PBMC (P=0.0055), serum (P=0.0427), and EBC (P=0.0035) samples between COPD patients and healthy controls. The mRNA expression of MMP-12 (r=−0.3958, P=0.0186) and NE (r=−0.3694, P=0.0290) in COPD patients was negatively correlated with pulmonary function. However, the mRNA expression of TIMP-4 (r=0.2871, P=0.0945) in PBMCs was not correlated with the FEV1 of the pulmonary function. Serum MMP-12 level was positively correlated with the MMP-12 level in EBC (P=0.0387). The level of TIMP-4 in serum was not correlated with the level in the EBC sample (P=0.4332). Conclusion. The expression levels of MMP-12, NE, and TIMP-4 in PBMCs and serum were elevated in COPD patients. In PBMCs of COPD patients, the mRNA expression level of NE may predict acute exacerbation, and MMP-12 mRNA expression level may be used to reflect the severity of airflow limitation. However, to better assess their diagnostic or prognostic value, larger studies are necessary.

To investigate the concentration of CX3CL1 in serum of patients with chronic obstructive pulmonary disease (COPD), and to evaluate the associations between the CX3CL1 level and systemic inflammation, small airway obstruction, and COPD assessment test (CAT) scores in COPD patients.Enzyme-linked immunosorbent assay were utilized to detect the CX3CL1 protein in serum separately from 64 patients with COPD and 53 healthy controls.Compared with healthy non-smokers, healthy smokers and COPD non-smokers, serum CX3CL1 protein levels were significantly elevated in COPD smokers (258.33 ± 56.27 pg/mL versus 177.32 ± 43.21 pg/mL, 185.64 ± 47.03 pg/mL, and 226.55 ± 51.79 pg/mL, P 0.05). Correlation analysis indicated that serum CX3CL1 in COPD smokers was negatively correlated with FEVThe results demonstrated that elevated circulating CX3CL1 level is associated with the systemic inflammation, small airway obstruction, and CAT scores in COPD patients, suggesting that CX3CL1 may play crucial roles in the pathogenesis of COPD. Blocking CX3CL1 might prevent the progression of chronic obstructive pulmonary disease.