An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype.

TitleAn association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype.
Publication TypeJournal Article
Year of Publication2013
AuthorsHolguin F, Comhair SAA, Hazen SL, Powers RW, Khatri SS, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Fitzpatrick AM, Gaston B, Israel E, Jarjour NN, Moore WC, Peters SP, Teague GW, Chung K F, Erzurum SC, Wenzel SE
JournalAm J Respir Crit Care Med
Volume187
Issue2
Pagination153-9
Date Published2013 Jan 15
ISSN1535-4970
KeywordsAdolescent, Adult, Age of Onset, Aged, Arginine, Asthma, Body Mass Index, Cross-Sectional Studies, Forced Expiratory Volume, Humans, Middle Aged, Nitric Oxide, Obesity, Phenotype, Young Adult
Abstract

RATIONALE: Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (Fe(NO)). This may be explained by an increase in the concentration of asymmetric dimethyl arginine (ADMA) relative to L-arginine, which can lead to greater nitric oxide synthase uncoupling.

OBJECTIVES: To compare this mechanism across age of asthma onset groups and determine its association with asthma morbidity and lung function.

METHODS: Cross-sectional study of participants from the Severe Asthma Research Program, across early- (<12 yr) and late- (>12 yr) onset asthma phenotypes.

MEASUREMENTS AND MAIN RESULTS: Subjects with late-onset asthma had a higher median plasma ADMA level (0.48 μM, [interquartile range (IQR), 0.35-0.7] compared with early onset, 0.37 μM [IQR, 0.29-0.59], P = 0.01) and lower median plasma l-arginine (late onset, 52.3 [IQR, 43-61] compared with early onset, 51 μM [IQR 39-66]; P = 0.02). The log of plasma L-arginine/ADMA was inversely correlated with BMI in the late- (r = -0.4, P = 0.0006) in contrast to the early-onset phenotype (r = -0.2, P = 0.07). Although Fe(NO) was inversely associated with BMI in the late-onset phenotype (P = 0.02), the relationship was lost after adjusting for L-arginine/ADMA. Also in this phenotype, a reduced L-arginine/ADMA was associated with less IgE, increased respiratory symptoms, lower lung volumes, and worse asthma quality of life.

CONCLUSIONS: In late-onset asthma phenotype, plasma ratios of L-arginine to ADMA may explain the inverse relationship of BMI to Fe(NO). In addition, these lower L-arginine/ADMA ratios are associated with reduced lung function and increased respiratory symptom frequency, suggesting a role in the pathobiology of the late-onset phenotype.

DOI10.1164/rccm.201207-1270OC
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID23204252