Alterations of the arginine metabolome in asthma.
BACKGROUND
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.


OBJECTIVE
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 (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated.


RESULTS
Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) 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 obstruction only in severe asthma.


CONCLUSIONS
Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.
Lara
Abigail
A
Department of Pathobiology, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Khatri
Sumita B
SB
Wang
Zeneng
Z
Comhair
Suzy A A
SA
Xu
Weiling
W
Dweik
Raed A
RA
Bodine
Melanie
M
Levison
Bruce S
BS
Hammel
Jeffrey
J
Bleecker
Eugene
E
Busse
William
W
Calhoun
William J
WJ
Castro
Mario
M
Chung
Kian Fan
KF
Curran-Everett
Douglas
D
Gaston
Benjamin
B
Israel
Elliot
E
Jarjour
Nizar
N
Moore
Wendy
W
Peters
Stephen P
SP
Teague
W Gerald
WG
Wenzel
Sally
S
Hazen
Stanley L
SL
Erzurum
Serpil C
SC
D000328:Adult; D001119:Arginase / Q000097:blood / Q000378:metabolism*; D001120:Arginine / Q000097:blood / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001682:Biological Availability; D001944:Breath Tests; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D013147:Spirometry
D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase