Neutrophilic Inflammation in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Abstract

Current paradigms of chronic obstructive pulmonary disease (COPD) treatment suggest stratifying patients by their symptoms, utilising three main drug classes, but it is unclear if this approach will substantially alter the progression of the disease in the long term. More treatment options are needed which target the underlying pathology of the condition. Whilst many inflammatory cells are implicated in COPD, the neutrophil is by far the most abundant and has been extensively associated with disease pathogenesis. Neutrophil products are thought to be key mediators of inflammatory changes in the airways of COPD patients, causing pathological features such as emphysema and hypersecretion of mucus. High rates of bacterial colonisation and recurrent infective exacerbations of COPD, as well as evidence of neutrophil-associated host damage suggest that neutrophil functions may be impaired in COPD. This concept is supported by studies demonstrating impaired migratory accuracy and increased degranulation and reactive oxygen species release, with some evidence of altered cellular signalling pathways which might be exploitable as therapeutic targets. This review discusses our evolving understanding of neutrophil function in both health and COPD and highlights the role of this cell in disease pathogenesis, to determine whether this key inflammatory mediator represents a viable therapeutic target to prevent disease progression.

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

“…Caused mostly by exposure to environmental factors such as tobacco smoke and pollution [138], COPD also depends on underlying genetic predispositions [139]. As with CF, lung disease in COPD is characterized by a heavy neutrophil component [140], with extracellular NE being associated with severity of disease and exacerbations [141][142][143]. In addition, it was observed by Chrysanthopoulou that exposure to cigarette smoke induces NET formation which contributes to lung fibrosis [144].…”

Granulocyte-targeted therapies for airway diseases

“…Chronic obstructive pulmonary disease (COPD) COPD is a chronic inflammatory lung disease with persistent airflow obstruction that is presented clinically as emphysema, obstructive bronchitis, exacerbation and lung function decline [124]. COPD continues to be a leading cause of morbidity and mortality worldwide, with an estimated prevalence of 328 million people already being the third leading cause of death worldwide [125].…”

“…Smoking can release both GM-CSF and granulocyte colony-stimulating factor (G-CSF) from epithelial cells and macrophages, which can stimulate granulocyte production, release and survival [127]. Neutrophils in the peripheral blood bind to endothelial cells via E-selectin and are drawn to the airway by neutrophil chemoattractants, such as CXC ligand-1 (CXCL1), CXCL5, CXCL8 and LTB 4 [124]. Secreted granule proteins and serine proteases from neutrophils contribute towards alveolar destruction, inflammation and oxidative stress.…”

High Serum Level of IL-17 in Patients with Chronic Obstructive Pulmonary Disease and the Alpha-1 Antitrypsin PiZ Allele

“…Neutrophilic inflammation in airways is considered central to the pathogenesis of COPD, regardless of the clinical phenotype, severity of disease, rapidity of lung function decline, and age of onset [14]. It was found that the proinflammatory cytokine IL-17 played a crucial role in COPD progression [15,16].…”