Resp Res
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Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms. ⋯ Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior.
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Epithelial-mesenchymal transition (EMT) plays a crucial role in small airway fibrosis of patients with chronic obstructive pulmonary disease (COPD). Increasing evidence suggests that the urokinase plasminogen activator receptor (uPAR) is involved in the pathogenesis of COPD. Increased uPAR expression has been implicated in the promotion of EMT in numerous cancers; however the role of uPAR in EMT in small airway epithelial cells of patients with COPD remains unclear. In this study, we investigated the degree of EMT and uPAR expression in lung epithelium of COPD patients, and verified the effect of uPAR on cigarette smoke extract (CSE)-induced EMT in vitro. ⋯ A uPAR-dependent signaling pathway is required for CSE-induced EMT, which contributes to small airway fibrosis in COPD. We propose that increased uPAR expression in the small airway epithelium of patients with COPD participates in an active EMT process.
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Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear. ⋯ These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.
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It has been debated whether treatment should be started early in subjects with mild to moderate COPD. An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD. ⋯ The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD. All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups. This suggests that symptom-based methods are not suitable screening tools in a healthy general population.
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Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung. In this study, we evaluated the role of TG2 in the pathogenesis of allergic asthma, particularly whether TG2 affects initial activation signaling leading to Th2 differentiation against antigens. ⋯ We found that pulmonary epithelial cells damaged by allergens triggered TG2-mediated IL-33 expression leading to type 2 responses by recruiting both innate and adaptive arms of the immune system.