Phase 2 Study: GCRC: Effects of L-arginine Supplementation on Exhaled Nitric Oxide and Clinical Exacerbations in Adults With Moderate to Severe Asthma

The primary objective of this 3 month clinical study is to determine if supplemental L-arginine can decrease the number of asthma exacerbations in patients with severe asthma. L-arginine, a natural amino acid, produces nitric oxide (NO) when it is converted to L-citrulline in the presence of the nitric oxide synthase enzymes. We and others have found that NO can protect against allergic airway inflammation, airway hyperresponsiveness and airway fibrosis in various animal models. In addition, we have found that arginase I expression correlates strongly with the lymphocyte and eosinophil influx into the lung and this enzyme may regulate the airway inflammatory response. Our central hypothesis is that L-arginine will increase NO levels in the lung and decrease the number of acute exacerbations of asthma. It may do this by either decreasing the number of Th2 lymphocytes or down-regulating arginase I expression or both.

Our specific aims are, therefore,

1. To test the hypothesis, in a randomized, double-blinded, placebo controlled trial, that 3 months of L-arginine supplementation will decrease the number of acute asthma exacerbations in severe asthmatic patients,
2. To determine whether L-arginine decreases the ratio of peripheral blood Th2 to Th1 lymphocytes and
3. To determine whether L-arginine will modulate serum arginase I/II levels and their downstream products.

Patients will be recruited primarily from the UC Davis Asthma Network (UCAN) clinics, which focus on the care of severe asthmatics, and the study will be performed at the UC Davis/VA General Clinical Research Center.