Inflammation mechanism and research progress of COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible progressive airflow limitation, often manifested by persistent cough, sputum production and other respiratory symptoms that pose a serious threat to human health and affect the quality of life of patients. The disease is associated with chronic inflammation, which is associated with the onset and progression of COPD, but anti-inflammatory therapy is not first-line treatment. Inflammation has multiple manifestations and phenotypes, and this heterogeneity reveals different patterns of inflammation, making treatment difficult. This paper aims to explore the direction of more effective anti-inflammatory treatment by analyzing the nature of inflammation and the molecular mechanism of disease occurrence and development in COPD patients, and to provide new ideas for the treatment of COPD patients.

Keywords: chronic inflammation; chronic obstructive pulmonary disease; inflammatory cells; oxidative stress; systemic inflammation.

Figure 1

COPD is mainly associated with cigarette/biomass smoke. Cigarette/biomass smoke can cause inflammation of the lung parenchyma and airways, activating macrophages, neutrophil, lymphocyte, eosinophils, and dendritic cells in response to toxic particles in the smoke. Various inflammatory factors can lead to tissue destruction and then to emphysema, impairing the defence and repair function of the airways and ultimately leading to small airway fibrosis and progressive irreversible airflow limitation.

Figure 2

Macrophage cell in patients with COPD. Cigarette/biomass smoke activate macrophages. These macrophages release inflammatory mediators (TNF-α, CXCL1, CXCL8, CCL2, LTB4, ROS) and produce elastolytic enzymes (MMP-2, MMP-9, MMP-12), regulated by the transcription factor NF-κB. The chemokines (CCL2, CXCL1) produced by macrophages enhance the chemotactic response of monocytes, which respond strongly to CXCL1, further attracting macrophages. Additionally, macrophages generate chemotactic effects on CD8+ Tc1 and CD4+ Th1 cells (via CXCL9, CXCL10, CXCL11). This cascade of events ultimately leads to chronic inflammation.

Figure 3

Neutrophil in patients with COPD. Cigarette smoke, infectious agents, and oxidative stress induce neutrophilia. Neutrophils migrate to the respiratory tract under the guidance of neutrophil chemotactic factors (LTB4, CXCL1, CXCL5, CXCL8). Neutrophils secrete serine proteases (NE, cathepsin G, proteinase-3, MMPs, MPO), leading to alveolar damage. Alpha-1 antitrypsin (AAT) inhibits serine proteases. AAT deficiency (AATD) results in insufficient inactivation of NE and other proteases, causing greater tissue damage. AAT, by binding to proteases, slows but does not completely prevent tissue damage. AAT augmentation therapy can slow the progression of COPD.

Figure 4

Eosinophils in patients with COPD. The type 2 inflammatory endotype is characterized by the production of IL-4, IL-5, and IL-13 by Th2 and ILC2 cells. GM-CSF and CCL5 facilitate the survival and recruitment of eosinophils. The effectiveness of ICS therapy is correlated with eosinophil counts: less than 100 cells/μL indicates low effectiveness, while counts of 300 cells/μL or higher indicate high effectiveness. Dupilumab, which blocks IL-4 and IL-13, can reduce exacerbations and improve both lung function and quality of life.