Phase 2 Study of Antioxidant Therapy in Lean and Obese Asthmatics

Asthma & Obesity are both growing public health crises that also may be critically interrelated for many patients. Obesity increases the risk for asthma in both adults and children, and obesity increases the severity of existing asthma. Obesity leads to increased systemic oxidative stress, however little is know about obesity-related oxidative stress within the airway. Since oxidative stress contributes to the pathogenesis of asthma, obesity may influence asthma risk and severity through this mechanism. Asthmatics have low serum antioxidant activity. There is conflicting evidence about whether or not antioxidant supplementation reduces asthma severity. This may be related to asthma's heterogeneous nature. Antioxidant supplementation may be effective in select subgroups that have the greater oxidative stress, such as asthmatics with occupational exposures or obesity. In fact, the evidence supporting antioxidant supplementation in asthma involved subjects with oxidant-related triggers. We hypothesize that obesity-related oxidant stress puts asthmatics at risk for increased airway oxidative stress and greater asthma severity. We hypothesize that supplementation with common antioxidants will significantly reduce airway inflammation and oxidative stress, and lead to improved pulmonary function and daily asthma control. This pilot study is designed as a randomized, double-blinded, placebo-controlled, parallel intervention trial involving lean and obese adolescents and young adults with asthma. After the 2-week run-in period, all subjects will undergo baseline testing (see figure 1). At randomization they will receive either placebo or a multivitamin antioxidant for 42 days. At the end of the 42 day intervention all subjects will undergo final testing. Primary Hypothesis: In young asthmatics, antioxidant supplementation increases plasma and airway antioxidant levels leading to improved lung function and asthma control. Secondary Hypotheses: 1) Obesity-related systemic oxidant stress is associated with increased oxidative stress within the airway. 2) Antioxidant supplementation will lead to greater improvements in asthma control among obese compared to lean (not underweight) asthmatics. 3) Antioxidant supplementation will lead to greater improvements in airway markers of inflammation and oxidative stress among obese compared to lean asthmatics. We will assess asthma control and lung function before and after therapy.