• 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, and Sally E Wenzel.
• Asthma Institute, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, MUH 628, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA. holguinf@upmc.edu
• Am. J. Respir. Crit. Care Med.. 2013 Jan 15;187(2):153-9.

RationaleIncreasing 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.ObjectivesTo compare this mechanism across age of asthma onset groups and determine its association with asthma morbidity and lung function.MethodsCross-sectional study of participants from the Severe Asthma Research Program, across early- (<12 yr) and late- (>12 yr) onset asthma phenotypes.Measurements And Main ResultsSubjects 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.ConclusionsIn 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.

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