Alterations of the Arginine Metabolome in Asthma

Alterations of the Arginine Metabolome in Asthma,Abigail Lara,Sumita B. Khatri,Zeneng Wang,Suzy A. A. Comhair,Weiling Xu,Raed A. Dweik,Melanie Bodine,

Alterations of the Arginine Metabolome in Asthma   (Citations: 9)
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Abigail Lara, Sumita B. Khatri, Zeneng Wang, Suzy A. A. Comhair, Weiling Xu, Raed A. Dweik, Melanie Bodine, Bruce S. Levison, Jeffrey Hammel, Eugene Bleecker, William Busse, William J. Calhoun
Rationale: As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. Objectives: We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Methods: Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (FENO), IgE, skin test positivity to allergens, bronchoal- veolar lavage, and blood eosinophils, were also evaluated. Measurements and Main Results: Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of FENO and serum arginase activity. However, Arg bioavailability was positively associated with FENO only in healthy control subjects; Arg bioavail- ability was unrelated to FENO or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow ob- struction only in severe asthma. Conclusions :U nlike FENO, Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.
Published in 2008.
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