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Clinical studies have confirmed that symptomatic chronic bronchitismarked by chronic cough and sputum productionis associated with increased frequency of acute COPD exacerbations and accelerated decline in pulmonary function ( 4.1.1 Core cell types and their roles As the main inflammatory cells infiltrating the airways, neutrophils disrupt the integrity of the airway epithelium by releasing elastase and matrix metalloproteinases (MMP-9), while secreting IL-8 and TNF- to amplify the inflammatory cascade ( 4.1.2 Key cytokines and regulatory networks Chemokines (IL-8, CXCL1) are secreted by airway epithelial cells and macrophages to specifically recruit neutrophils to sites of airway inflammation, and their expression is regulated by transcription factors NF-B and AP-1 ( 4.1.3 Regulatory roles of transcription factors NF-B is persistently activated in airway epithelial cells and macrophages, serving as a core transcription factor mediating chronic inflammation

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The PANK1 gene is located on chromosome 10q23.31 and is composed of 11 exons that generate three alternatively spliced mRNAs each of which encode unique isoforms of the enzyme

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