Disturbed fatty acid metabolism in airway secretions of patients with Chronic Obstructive Pulmonary Disease

Abstract

Tobacco smoke is the main risk factor for development of Chronic Obstructive Pulmonary Disease (COPD), a disease characterized by chronic airway inflammation and tissue remodelling resulting in loss of lung function. Airway inflammation in COPD persists even after smoking cessation, suggesting a problem with inflammatory resolution. The resolution phase of inflammation is initiated by pro-resolving compounds, derived from e.g. polyunsaturated fatty acids (PUFAs) that are stored in cell membranes and uncoupled upon inflammatory triggering. PUFAs are subsequently converted into lipid mediators such as pro-inflammatory leukotrienes and prostaglandins, or into pro-resolving mediators such as protectins and resolvins. To investigate if fatty acid metabolism was affected in patients with stable COPD, and during or after an acute exacerbation, we analysed induced sputum samples from the Bergen COPD Cohort and COPD Exacerbation study. Induced sputum from 27 controls without COPD, 29 stable COPD patients, 37 COPD patients during exacerbation and 27 COPD patients post exacerbation underwent LC-MS/MS analysis to determine free fatty acid (FFA) and oxylipin levels. Analysis revealed lower FFA levels in sputum from stable COPD patients compared to controls. Furthermore, 5- and 12-lipoxygenase (LOX)-mediated oxylipin levels were generally reduced in COPD patients compared to controls. 15-LOX and cyclooxygenase-2-mediated oxylipin levels (e.g. prostaglandins and TXB2) were comparable between stable COPD patients and control, however increased during exacerbation, some of which remained elevated thereafter. Our findings show marked differences in fatty acid metabolism in COPD patients that may contribute to future strategies to promote inflammatory resolution in the lungs of COPD patients.