New Concepts in the Pathobiology of Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal persistent inflammatory response to cigarette smoke. This noxious insult leads to emphysema and airway remodeling, manifested by squamous and mucous metaplasia of the epithelium, smooth muscle hypertrophy, and airway wall fibrosis. These pathologic abnormalities interact synergistically to cause progressive airflow obstruction. Although it has been accepted that the spectrum of COPD is vast, the reasons for the development of different phenotypes from the same exposure to cigarette smoke have not been determined. Furthermore, it is becoming increasingly clear that airways disease and emphysema often coexist in many patients, even with a clear clinical phenotype of either emphysema or chronic bronchitis. Recent studies have focused on the nature of the inflammatory response to cigarette smoke, the inflammatory cell lines responsible for COPD pathogenesis, and new biomarkers for disease activity and progression. New cytokines are being discovered, and the complex interactions among them are being unraveled. The inflammatory biomarker that has received the most attention is Creactive protein, but new ones that have caught our attention are interleukin (IL)-6, tumor necrosis factor-a, IL-8, and IL-10. Further research should focus on how these new concepts in lung inflammation interact to cause the various aspects of COPD pathology.

Diagnostic Utility of Biomarkers in COPD

“…[24][25][26] A new biomarker, surfactant protein D (SPD), the serum levels of which are elevated in response to lung pathology, has been suggested as a useful lung-specific marker of COPD. 27 As the search for COPD biomarkers continues 28 and implementation of biomarkers for COPD in actual clinical practice requires much research and validation, 29 this study aimed to explore the utility of levels of superoxide dismutase 3, glutathione peroxidase, catalase, and ceruloplasmin ferroxidase activity (enzyme antioxidants); C-reactive protein (inflammatory marker); and SPD (lungspecific protein) as biomarkers for diagnosis of COPD.…”

The Inflammatory Tumor Microenvironment, Epithelial Mesenchymal Transition and Lung Carcinogenesis

“…Inflammatory Mediators in the Developing TME Chronic or deregulated inflammation in the pulmonary microenvironment is characteristic of pulmonary diseases that have the greatest risk for developing lung cancer, such as emphysema, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis [17][18][19]. These diseases are driven by common inflammatory mediators.…”

“…However, in an inflammatory environment, TNF-α is often overexpressed and its control systems are frequently dysregulated. Studies associated TNF-α with a number of pulmonary diseases, such as asthma, chronic bronchitis and smoking-induced emphysema [18]. TNF-α overexpression in the TME can lead to EMT, the recruitment of leukocytes and the depletion of antioxidants from the microenvironment, which can lead to cellular oxidative stress [30].…”

Up-regulation of bradykinin receptors in rat bronchia via IκB kinase-mediated inflammatory signaling pathway

“…IL-6 is a potent pro-inflammatory cytokine that exerts inflammatory effects by activating both leukocytes and structural cells including pulmonary epithelial cells. The levels of IL-6 are increased in the induced sputum, bronchoalveolar lavage, and in peripheral blood of patients with COPD (Bhowmik et al, 2000;Bucchioni et al, 2003;Kim et al, 2008).…”