The effect of simvastatin, omega-3 fatty acids and antioxidants on lung function in ex-smokers with symptomatic airflow obstruction

In this study, we aim to examine two interventions that could potentially slow disease progression in middle aged ex-smokers with mild to moderate chronic lung disease. There is evidence that some individuals experience a progressive decline in lung function even after ceasing smoking. This may be related to persistent lung inflammation. We will examine whether omega-3 fatty acids and nutrient antioxidants and/or statins, a treatment used to lower cholesterol, can slow the rate of decline of lung function in people with COPD. Levels of nutrient antioxidants and omega-3 fatty acids have been shown to be related to levels of lung function in epidemiological studies. Statins, which are widely used as cholesterol lowering drugs, are known to have anti-inflammatory effects. Patients with COPD who are taking statins appear to have a lower risk of death than those not taking statins. Other retrospective studies have shown that statins slow the rate of lung function decline. We propose that nutrient antioxidant and omega-3 fatty acid supplementation and statin treatment will reduce inflammation, and hence slow the progressive decline in lung function in people with obstructive lung disease. This randomised controlled trial will test both nutrient supplements (lycopenes and omega 3-fatty acids) and simvastatin treatment in patients with COPD. Eligible participants will be 35- to 60-year-old ex-smokers with post-bronchodilator airflow obstruction, a history of lower respiratory tract illness in the last 12 months or a history of chronic cough, sputum production or breathlessness in the last 12 months and C-reactive protein = 3 mg/L. There will be four study groups: Group A (active nutrient supplement intervention, active statin treatment), Group B (active nutrient supplement intervention, no statin treatment), Group C (placebo nutrient supplement intervention, active statin treatment), and Group D (placebo nutrient supplement intervention, no statin treatment). Duration of treatment will be 6 months in the pilot study and 4 years in the main study. In the pilot study, we aim to recruit a total of 40 participants from the community through advertising. The aim of the pilot study is to assess feasibility of recruitment, implementation of interventions and measurement of outcomes. The number of participants for the final multi-centre study will be determined, in part, by information obtained in the pilot study. Patients will be seen before treatment commences and then 6, 12 and 24 weeks after treatment commences for the pilot study. The primary outcome is the change in lung function (FEV1 and FVC) over 6 months (24 weeks). Secondary outcomes include systemic inflammatory markers (hs-CRP), questionnaire (regarding quality of life, breathlessness, and exacerbations), exhaled nitric oxide, induced sputum, and exercise capacity. The first hypothesis to be tested is that statins and omega-3 fatty acids/ antioxidants have a synergistic beneficial effect (multiplicative) on outcomes. If this is not supported, the second hypothesis that the two interventions, separately, have an effect on the outcomes. Relationships between the change in lung function and inflammatory markers will also be explored.