Severity of chronic obstructive pulmonary disease with ‘exacerbator with emphysema phenotype’ is associated with potential biomarkers

Abstract

ObjectiveThe 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.MethodsA 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.ResultsFKN (p<0.001), NE (p=0.039) and MMP-12 (p<0.001) in serum of COPD patients showed higher levels than that of healthy control subjects. Serum FKN (p<0.001), MMP-12 (p<0.001) and NE (p=0.043) levels were significantly higher in severe and very severe COPD patients than that in mild and moderate COPD patients. Circulating FKN, MMP-12 and NE expression levels were significantly elevated (p<0.001) in COPD smokers compared with COPD non-smokers. The smoke pack years were negatively correlated with FEV1%pred (r=−0.5036), FEV1/FVC ratio (r=−0.2847) (FEV, forced expiratory volume; FVC, forced vital capacity). Similarly, we observed a strong positive correlation between the smoke pack years and serum levels of FKN (r=0.4971), MMP-12 (r=0.4315) and NE (r=0.2754). FEV1%pred was strongly negatively correlated with cytokine levels of FKN (r=−0.4367), MMP-12 (r=−0.3295) and NE (r=−0.2684). Likewise, FEV1/FVC ratio was negatively correlated with mediators of inflammation levels of FKN (r=−0.3867), MMP-12 (r=−0.2941) and NE (r=−0.2153).ConclusionSerum 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.

Clinical significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute exacerbations of COPD: present and future

“…However, at the same time, there is evidence that MPO can favour the initiation of oxidative tissue damage and alterations in cellular homeostasis and increase the response of lung epithelial cells to pro-inflammatory stimuli [ 50 , 51 ]. Neutrophil elastase can stimulate the production and secretion of mucin, leading to excessive mucus secretion and airway obstruction [ 52 ]. Furthermore, MMP can degrade extracellular matrices, leading to structural damage and airway remodelling in COPD patients [ 52 ].…”

“…Neutrophil elastase can stimulate the production and secretion of mucin, leading to excessive mucus secretion and airway obstruction [ 52 ]. Furthermore, MMP can degrade extracellular matrices, leading to structural damage and airway remodelling in COPD patients [ 52 ]. Platelets also play a key role in the modulation of inflammation and immune responses.…”

Comparison of the Predictive Value of Inflammatory Biomarkers for the Risk of Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke

“…39,40 The respiratory epithelial cell structure may change as a result of neutrophil elastase, and increased local mucin secretion and other factors may also contribute to airway obstruction. 41,42 Decreased neutrophil counts can result in reduced immunity. 28 A rapid decrease in the number of lymphocytes can lead to the downregulation of the immune response, thereby increasing the risk of SAP.…”

The association between systemic immune-inflammation index and chronic obstructive pulmonary disease in adults aged 40 years and above in the United States: a cross-sectional study based on the NHANES 2013–2020

“…Their activation can release specific inflammatory mediators, leading to irreversible airway damage, such as neutrophil elastase, matrix metalloproteinase-9 (MMP-9), tissue protease G, Matrix metalloproteinases-48 (MMP-48), and myeloperoxidase (MPO), which can promote the pathological and physiological mechanisms of COPD (22). Neutrophil elastase can stimulate the production and secretion of mucin, leading to excessive mucus secretion and airway obstruction (23), while MPO can promote oxidative tissue damage and initiate cell homeostasis changes, and increase the response of lung epithelial cells to pro-inflammatory stimuli (24). Lymphocytes can cause alveolar destruction in COPD patients (25), among which CD8 cells produce pro-inflammatory cytokines, including IL-2, interferon-γ, and TNFα, which increase in COPD patients and recruit other inflammatory cells (26,27).…”