PAPERwww.rsc.org/metallomics|MetallomicsMetallicelementsinexhaledbreathcondensateandserumofpatientswithexacerbationofchronicobstructivepulmonarydiseaseMassimoCorradi,aOlgaAcampa,bMatteoGoldoni,abRobertaAndreoli,abDonaldMilton,cSusanR.Sama,cdRichardRosiello,dGiuseppedePalma,ePietroApostolieandAntonioMutti*aReceived15thApril2009,Accepted28thMay2009FirstpublishedasanAdvanceArticleontheweb18thJune2009DOI:10.1039/bbBiomarkersinexacerbatedchronicobstructivepulmonarydiseasemaybeusefulinaidingdiagnosis,definingspecificphenotypesofdisease,monitoringthediseaseandevaluatingtheeectsofdrugs.Theaimofthisstudywasthecharacterizationofmetallicelementsinexhaledffbreathcondensateandserumasnovelbiomarkersofexposureandsusceptibilityinexacerbatedchronicobstructivepulmonarydiseaseusingreferenceanalyticaltechniques.C-Reactiveproteinandprocalcitoninwereassessedaspreviouslyvalidateddiagnosticandprognosticbiomarkerswhichhavebeenassociatedwithdiseaseexacerbation,thususefulasabasisofcomparisonwithmetallevels.Exhaledbreathcondensateandserumwereobtainedin28patientsatthebeginningofanepisodeofdiseaseexacerbationandwhentheyrecovered.Traceelementsandtoxicmetalsweremeasuredbyinductivelycoupledplasma-massspectrometry.Serumbiomarkersweremeasuredbyimmunoassay.Exhaledmanganeseandmagnesiumlevelswereinfluencedbyexacerbationofchronicobstructivepulmonarydisease,anincreaseintheirconcentrations—respectivelyby20and50%—beingobservedatexacerbationincomparisonwithvaluesobtainedatrecovery;serumelementalcompositionwasnotmodifiedbyexacerbation;serumlevelsofC-reactiveproteinandprocalcitoninatexacerbationwerehigherthanvaluesatrecovery.Inoutpatientswhoexperiencedamild–moderatechronicobstructivepulmonarydiseaseexacerbation,manganeseandmagnesiumlevelsinexhaledbreathcondensateareelevatedatadmissionincomparisonwithvaluesatrecovery,whereasnootherchangeswereobservedinmetallicelementsatboththepulmonaryandsystemiclevel.IntroductionChronicobstructivepulmonarydisease(COPD)isapreventableandpartiallytreatablediseasewithsomesignificantextrapulmonaryeectsthatmaycontributetoseverityinindividualffpatients.Itspulmonarycomponentischaracterizedbyairflowlimitationthatisnotfullyreversible.Theairflowlimitationisusuallyprogressiveandassociatedwithanabnormalinflammatoryresponseofthelungtonoxiousparticlesorgases.1TheclinicalcourseofCOPDisfrequentlyaggravatedbyepisodesofacuteworseningofrespiratorysymptomswithanincreaseinairflowobstructionandairtrapping,whichusuallyrequiresadditionaltherapies.1,2COPDexacerbationsacceleratetheprogressivedeclineinlungfunctionandareimportantcausesofmorbidityandmortalityassociatedwiththedisease.3–5COPDexacerbationsarecausedmainlybyrespiratorytractaLaboratoryofIndustrialToxicology,DepartmentofClinicalMedicine,NephrologyandHealthSciences,UniversityofParma,Italy.E-mail:antonio.mutti@unipr.it;Fax:+390521;Tel:+390521bISPESLResearchCentreattheUniversityofParma,ItalycDepartmentofWorkEnvironment,UniversityofMassachusetts,Lowell,MA,USAdFallonClinic,Worcester,MA,USAeLaboratoryofIndustrialHygiene,DepartmentofExperimentalandAppliedMedicine,UniversityofBrescia,ItalyThisjournaliscTheRoyalSocietyofChemistry2009infections,buttriggeringfactorsalsoincludenon-infectivecauses,suchasexposuretoenvironmentalpollutants.However,thecauseofexacerbationscannotbeidentifiedinapproximatelyone-thirdofallcases.1,2TheheterogeneityofCOPDexacerbations,d...