title: Breath formate is a marker of airway S-nitrosothiol depletion in severe asthma.
abstract: BACKGROUND
  Children with severe asthma have poor symptom control and elevated markers of airway oxidative and nitrosative stress. Paradoxically, they have decreased airway levels of S-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism.
  
  
  RESULTS
  We collected EBC samples from children and adolescents, including 38 with severe asthma, 46 with mild-to-moderate asthma and 16 healthy adolescent controls, and the concentration of ionic constituents was quantified using ion chromatography. The concentrations of EBC components with volatile conjugates were log-normally distributed. Formate was the principal ion that displayed a significant difference between asthma status classifications. The mean EBC formate concentration was 40% higher in samples collected from all asthmatics than from healthy controls (mean = 5.7 microM, mean+/-standard deviation = 3.1-10.3 microM vs. 4.0, 2.8-5.8 microM, p = 0.05). EBC formate was higher in severe asthmatics than in mild-to-moderate asthmatics (6.8, 3.7-12.3 microM vs. 4.9, 2.8-8.7 microM, p = 0.012). In addition, formate concentration was negatively correlated with methacholine PC(20) (r = -0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose.
  
  
  CONCLUSIONS
  We conclude that EBC formate concentration is significantly higher in the breath of children with asthma than in those without asthma. In addition, amongst asthmatics, formate is elevated in the breath of those with severe asthma compared to those with mild-to-moderate asthma. We suggest that this difference is related to asthma pathology and may be a product of increased catabolism of endogenous S-nitrosothiols.
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America. roby.greenwald@emory.edu
authors.forename: Roby
authors.initials: R
authors.lastname: Greenwald
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Nadzeya V
authors.initials: NV
authors.lastname: Marozkina
authors.forename: Serpil
authors.initials: S
authors.lastname: Erzurum
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005561:Formates / Q000032:analysis*; D006801:Humans; D008297:Male; D026403:S-Nitrosothiols / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005561:Formates; D026403:S-Nitrosothiols; C030544:formic acid