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.

Inclusion Criteria:

- age 12-25,

- physician-diagnosed persistent asthma on daily controller therapy,

- FEV1% >= 60% predicted,

- Lung responsiveness (>= 12% BD reversibility or PC20 MCT <= 16mg/ml)

Exclusion Criteria:

- taking daily MVI,

- chronic oral steroid therapy,

- BMI<20th percentile,

- smoking history,

- pregnancy,

- milk allergy,

- celiac disease