Molecular Mechanisms of Inflammation During Exacerbations of Chronic Obstructive Pulmonary Disease

Introduction: Chronic obstructive pulmonary disease (COPD) is characterised by an inflammatory and systemic response that increases during exacerbations of the disease (ECOPD), although the mechanisms of this inflammatory process are not well known. Objectives: To explore the inflammatory changes and possible mechanisms during ECOPD. Methods: We determined the inflammatory cell concentrations in blood and sputum, nitric oxide in exhaled air (FeNO), reactive C-reactive protein (CRP) in plasma, cytokines (IL-6, 8, 1 beta, 10, 12, TNF-alpha) and SLPI and total antioxidant activity (TAS) in blood and sputum, the activity of nuclear kappa B factor (NF-kB) and of the histone deacetylase enzymes (HDAC) in 17 patients during ECOPD, in stable phase and in 17 smoking controls and 11 non-smoking. Results: ECOPD is characterised by higher levels of FeNO (P<.05), plasma CRP (P<.001) and IL-8, IL-1B, IL-10 in sputum (P<.05) compared with stable COPD and controls. The TAS levels in sputum were lower in the exacerbated than in stable phase (P<.05) although significantly higher than the controls (P<.05). These findings were accompanied by a greater activation of NF-kB in sputum macrophages during the ECOPD with no changes in the HDAC activity or in the number of neutrophils in sputum, and a statistically significant deterioration (P<.05) of lung function. Conclusions: Changes were observed in different pulmonary and systemic inflammatory markers during ECOPD, that were not completely resolved during stability. However, current treatment does not allow the modification of HDAC activity, which limits its anti-inflammatory effects. (C) 2010 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.