title: An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 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
authors.forename: Fernando
authors.initials: F
authors.lastname: Holguin
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Powers
authors.forename: Sumita S
authors.initials: SS
authors.lastname: Khatri
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000502:physiology; D001249:Asthma / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D010641:Phenotype; D055815:Young Adult
chemical_list: D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine