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

Fernando Holguin, Suzy A.A. Comhair, Stanley L. Hazen, Robert W. Powers, Sumita S. Khatri, Eugene R. Bleecker, William W. Busse, William J. Calhoun, Mario Castro, Anne M. Fitzpatrick, Benjamin Gaston, Elliot Israel, Nizar N. Jarjour, Wendy C. Moore, Stephen P. Peters, W. Gerald Teague, Kian Fan Chung, Serpil C. Erzurum, Sally E. Wenzel

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


Rationale: Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (FENO). Thismaybeexplained 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 fromthe 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 = 20.4, P = 0.0006) in contrast to the early-onset phenotype (r = 20.2, P = 0.07). Although FENO 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: Inlate-onsetasthmaphenotype,plasmaratiosof L-arginine to ADMA may explain the inverse relationship of BMI to FENO. 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.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number2
StatePublished - Jan 15 2013


  • ADMA
  • Age of asthma onset
  • Arginine
  • Asthma
  • Obesity

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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