Impact of Systemic Inflammation and Oxidative Stress on HDL Function in the Natural Course of Chronic Obstructive Pulmonary Disease A Hospital Based Double Blinded Randomized Placebo Controlled study

Abstract

The study examined the oxidative biology and related changes in HDL function among COPD subjects recovering from severe exacerbation to remission state during a two month follow up period. The study population was 100% males, ever smokers with no significant exposure to other noxious stimuli (biomass smoke etc.) that can contribute to development of COPD. Most of them had moderate to severe COPD. Comorbidity burden was low and clinically insignificant. None had dyslipidemia / IHD / CVD. All subjects had a significant clinical recovery to remission at the end of two months from randomization (during AECOPD), as uniformly defined by a multimodal approach to measure and compare symptomatology and clinical signs. Serum total cholesterol was significantly higher and HDL cholesterol was significantly lower during remission at 2 months as compared with AECOPD. The observed dynamics in lipid metabolism were modestly influenced by Anthonisen s type I and II (infective) exacerbation of COPD, baseline hsCRP at AECOPD, severity of COPD and smoking intensity. Serum hsCRP was significantly lower during remission, indicating significant reduction in the inflammatory burden of disease from the states of AECOPD to remission during two month follow up. COPD exacerbation is associated with significant burst of systemic inflammation and oxidative stress whose burden decreases on recovery to remission. COPD exacerbation is also associated with inactivation of PON1 enzyme, the most important determinant of antioxidant function of HDL cholesterol. HDL cholesterol was in pro-oxidant state which showed improvement towards remission but the difference did not reach statistical significance. Inhaled steroids did not have impact on dynamics of systemic inflammation, oxidative stress and HDL function during recovery from AECOPD to remission. Further research is strongly recommended to substantiate our findings and explore novel therapeutic targets in management of COPD and IHD coexistence. newline