Effects of L-arginine Supplementation in Adults With Moderate to Severe Asthma
Effects of L-arginine Supplementation in Adults With Moderate to Severe Asthma
Nitric oxide is an important marker of airway inflammation in asthma. Nitric oxide may have a
 protective role in patients with moderate to severe asthma. The investigators believe that a
 natural amino acid, L-arginine, that augments nitric oxide levels can decrease asthma
 exacerbations and improve the asthma care of moderate to severe asthma patients.

 This study is a randomized, placebo controlled trial in which subjects will receive either 3
 months of L-arginine supplementation or a placebo. The investigators will monitor subjects'
 symptoms, the number of asthma exacerbations, and lung function. In addition, we will draw
 blood, obtain induced sputum samples and measure exhaled breath nitric oxide levels at each
 monthly visit.
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.
Inclusion Criteria:

 -  Moderate to severe persistent asthma

 -  Subject is stable on same asthma medications for at least one month

 -  If the subject is a woman of child-bearing age, a negative pregnancy test

 Exclusion Criteria:

 -  Less than 18 yrs/ age

 -  Baseline Forced Expiratory Volume in 1 second (FEV1) <40% predicted

 -  Known or suspected allergy to L-arginine

 -  Pregnant women, nursing women, or women actively trying to achieve pregnancy

 -  Current smokers

 -  Subjects with more than a 15 pack-year history of smoking