Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma 英文参考文献.docVIP

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Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma 英文参考文献.doc

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Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma 英文参考文献

BreathFormateIsaMarkerofAirwayS-Nitrosothiol DepletioninSevereAsthma RobyGreenwald1*,AnneM.Fitzpatrick2,BenjaminGaston3,NadzeyaV.Marozkina3,SerpilErzurum4 ,W. GeraldTeague3* 1DepartmentofEnvironmentalHealth,RollinsSchoolofPublicHealth,EmoryUniversity,Atlanta,Georgia,UnitedStatesofAmerica,2DepartmentofPediatrics,Emory University School of Medicine, Atlanta, Georgia, United States of America, 3Department of Pediatrics, University of Virginia, Charlottesville, Virginia, United States of America,4DepartmentofMedicineandPathobiology,ClevelandClinic,Cleveland,Ohio,UnitedStatesofAmerica Abstract Background: Children with severe asthma have poor symptom control and elevated markers of airway oxidative and nitrosativestress.Paradoxically,theyhavedecreasedairwaylevelsofS-nitrosothiols(SNOs),aclassofendogenousairway smoothmusclerelaxants.ThisdeficiencyresultsfromincreasedactivityofanenzymethatbothreducesSNOstoammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate(EBC)thanSNOs.WethereforehypothesizethatdepletionofairwaySNOsisrelatedtoasthmapathology,and breathformateconcentrationmaybeaproxymeasureofSNOcatabolism. MethodsandFindings:WecollectedEBCsamplesfromchildrenandadolescents,including38withsevereasthma,46with mild-to-moderateasthmaand16healthyadolescentcontrols,andtheconcentrationofionicconstituentswasquantified usingionchromatography.TheconcentrationsofEBCcomponentswithvolatileconjugateswerelog-normallydistributed. Formatewastheprincipalionthatdisplayedasignificantdifferencebetweenasthmastatusclassifications.ThemeanEBC formateconcentrationwas40%higherinsamplescollectedfromallasthmaticsthanfromhealthycontrols(mean=5.7 mM, mean6standarddeviation=3.1210.3mMvs.4.0,2.825.8mM,p=0.05).EBCformatewashigherinsevereasthmaticsthanin mild-to-moderate asthmatics (6.8, 3.7212.3mM vs. 4.9, 2.828.7mM, p=0.012). In addition, formate concentration was negativelycorrelatedwithmethacholinePC20(r=20.39,p=0.