Introduction: COPD is a common preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and co-morbidities contribute to overall severity in individual patients. Oxidative stress represents one of the key pathogenic mechanisms in the development of COPD. MDA increased production of interleukin (IL)-8 and tumor necrosis factor-a (TNF-a), both attract inflammatory cells and increase oxidant production by these cells. Attenuation of oxidative stress would be expected to result in reduced pulmonary damage and a decrease in local infections, contributing to attenuation of the progression of COPD.Aim of the study: To compare the effects of high dose NAC versus regular dose on inflammatory response, oxidative stress, pulmonary functions and clinical outcome in patients with COPD acute exacerbations.Patients and methods: This randomized controlled study included 45 COPD acute exacerbation patients. All patients received standard COPD exacerbation treatment and were randomly assigned to either; control group (A) with no add on therapy, low dose group (B) received NAC 200 mg sachets TID, high dose group (C) received NAC 400 mg sachets TID for 10 days. IL8, malondialdehyde (MDA), arterial blood gases and spirometric parameters were evaluated at baseline and after treatment.Results: IL8 levels significantly decreased (p < 0.001) in group C (3.47 ± 0.81), versus Group B (5.57 ± 1.66) and group A (8.33 ± 1.69). MDA levels significantly decreased (p < 0.001) in group C and group B over time. Pulmonary functions (FEV 1 , FVC and FEV 1 /FVC) and partial pressure of oxygen PaO 2 significantly improved (p < 0.001) in group C versus group B and A over time. The P/F ratio significantly improved (p < 0.001) in group C versus group A. No side effects were reported with NAC administration.Conclusion: High dose NAC improves clinical outcome of COPD exacerbation patients by ameliorating oxidative stress and inflammatory response thereby improving lung spirometry and pulmonary oxygenation.

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