The Effect of N-Acetyl-L-Cysteine, on Inflammatory and Oxidative Stress Markers in Pulmonary Sarcoidosis

The Effect of N-Acetyl-L-Cysteine, on Inflammatory and Oxidative Stress Markers in Pulmonary Sarcoidosis

The Effect of an Oral Antioxidant, N-Acetyl-L-Cysteine, on Inflammatory and Oxidative Stress Markers in Pulmonary Sarcoidosis

This is a pilot study investigating the effect of an antioxidant, N-Acetyl-L-Cysteine (NAC), on inflammation and oxidative stress in sarcoidosis.

Sarcoidosis is a granulomatous lung disease predominantly affecting the lungs. Reactive oxidative species are produced secondary to oxidative stress and inflammation and can affect key cellular processes. The investigators have shown a role for oxidative stress in chronic beryllium disease (CBD), a granulomatous disease that resembles sarcoidosis, and have also shown that antioxidant therapy reduces inflammation in CBD. Oxidative stress also plays a role in sarcoidosis but the exact mechanism and potential effect of antioxidant therapy on sarcoidosis is unknown. The investigators propose conducting a pilot study investigating the effect of an antioxidant, N-Acetyl-L-Cysteine (NAC), on inflammation and oxidative stress in sarcoidosis. The investigators will measure and compare markers of inflammation and oxidative stress in the lungs of sarcoidosis patients before and after treatment with NAC. The results of this study will prepare the investigators for a larger study investigating the role of NAC as a therapy for sarcoidosis with changes in lung function and x-ray as our primary outcome. This will provide the investigators with a new non-toxic therapy for sarcoidosis that can be used on its own or to supplement other therapies minimizing their toxicity.

Baseline peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) lymphocyte percentages and lipopolysaccharide (LPS) stimulated tumor necrosis factor-α levels (pg/ml)

We measured changes at baseline and at 8 weeks in BAL whole cell total GSH levels and cellular 8-OHdG before and after treatment with NAC/placebo.

Inclusion Criteria: Biopsy proven sarcoidosis. Pulmonary parenchymal involvement with a Scadding chest x-ray stage II, III or IV. Abnormal spirometry and/or DLCO (< 80% of predicted). Consenting adults : Age 18 years and above Exclusion Criteria: Positive lung washing or biopsy cultures for fungi or mycobacterial disease; Presence of other co-morbid conditions that may affect the patient's outcome. Patient inability to undergo venipuncture and BAL procedures. Current use of tobacco (smoking or otherwise) in the past 6 months Treatment with immunosuppressive therapy within the past 6 months. On oral anti-oxidant supplements. Active peptic ulcer disease.