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Asthma
Author:MichaelJMorris,MD,FACP,FCCPChiefEditor:ZabMosenifar,MD,FACP,FCCPmore...
Updated:May14,2015

PracticeEssentials
Asthmaisacommonchronicdiseaseworldwideandaffectsapproximately24millionpersonsintheUnitedStates.
Itisthemostcommonchronicdiseaseinchildhood,affectinganestimated7millionchildren.Thepathophysiology
ofasthmaiscomplexandinvolvesairwayinflammation,intermittentairflowobstruction,andbronchial
hyperresponsiveness.Seetheimagebelow.

Pathogenesisofasthma.Antigenpresentationbythedendriticcellwiththelymphocyteandcytokineresponseleadingtoairway
inflammationandasthmasymptoms.

Signsandsymptoms
Signsandsymptomsofasthmaincludethefollowing:
Wheezing
Coughing
Shortnessofbreath
Chesttightness/pain
Othernonspecificsymptomsininfantsoryoungchildrenmaybeahistoryofrecurrentbronchitis,bronchiolitis,or
pneumoniaapersistentcoughwithcoldsand/orrecurrentcrouporchestrattling.
SeeClinicalPresentationformoredetail.

Diagnosis
UpdatedguidelinesfromtheNationalAsthmaEducationandPreventionProgramhighlighttheimportanceof
correctlydiagnosingasthma,byestablishingthefollowing[4]:
Episodicsymptomsofairflowobstructionarepresent
Airflowobstructionorsymptomsareatleastpartiallyreversible
Exclusionofalternativediagnoses
Spirometrywithpostbronchodilatorresponseshouldbeobtainedastheprimarytesttoestablishtheasthma
diagnosis.Pulseoximetrymeasurementisdesirableinallpatientswithacuteasthmatoexcludehypoxemia.The
chestradiographremainstheinitialimagingevaluationinmostindividualswithsymptomsofasthma,butinmost
patientswithasthma,chestradiographyfindingsarenormalormayindicatehyperinflation.Exercisespirometryis
thestandardmethodforassessingpatientswithexerciseinducedbronchospasm.
SeeWorkupformoredetail.

Management
Forallbutthemostseverelyaffectedpatients,theultimategoalistopreventsymptoms,minimizemorbidityfrom
acuteepisodes,andpreventfunctionalandpsychologicalmorbiditytoprovideahealthy(ornearhealthy)lifestyle
appropriatetotheageofchild.
Pharmacologictreatment
Pharmacologicmanagementincludestheuseofreliefandcontrolagents.Controlagentsincludeinhaled
corticosteroids,inhaledcromolyn(Intal)ornedocromil(Tilade),longactingbronchodilators,theophylline(Theo24,
Theochron,Uniphyl),leukotrienemodifiers,andantiIgEantibodies.Reliefmedicationsincludeshortacting
bronchodilators,systemiccorticosteroids,andipratropium(Atrovent).
Thepharmacologictreatmentofasthmaisbasedonstepwisetherapy.Asthmamedicationsshouldbeaddedor
deletedasthefrequencyandseverityofthepatient'ssymptomschange.
Allergenavoidance
Environmentalexposuresandirritantscanplayastrongroleinsymptomexacerbations.Theuseofskintestingorin
vitrotestingtoassesssensitivitytoperennialindoorallergensisimportant.Oncetheoffendingallergensare
identified,counselpatientsonhowtoavoidthem.Effortsshouldfocusonthehome,wherespecifictriggersinclude
dustmites,animals,cockroaches,mold,andpollen.
SeeTreatmentandMedicationformoredetail.

Background
Asthmaisacommonchronicdiseaseworldwideandaffectsapproximately24millionpersonsintheUnitedStates.
Itisthemostcommonchronicdiseaseinchildhood,affectinganestimated7millionchildren,anditisacommon
causeofhospitalizationforchildrenintheUnitedStates.

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Thepathophysiologyofasthmaiscomplexandinvolvesairwayinflammation,intermittentairflowobstruction,and
bronchialhyperresponsiveness.Themechanismofinflammationinasthmamaybeacute,subacute,orchronic,and
thepresenceofairwayedemaandmucussecretionalsocontributestoairflowobstructionandbronchialreactivity.
Varyingdegreesofmononuclearcellandeosinophilinfiltration,mucushypersecretion,desquamationofthe
epithelium,smoothmusclehyperplasia,andairwayremodelingarepresent. [5,6]
Airwayhyperresponsivenessorbronchialhyperreactivityinasthmaisanexaggeratedresponsetonumerous
exogenousandendogenousstimuli.Themechanismsinvolvedincludedirectstimulationofairwaysmoothmuscle
andindirectstimulationbypharmacologicallyactivesubstancesfrommediatorsecretingcellssuchasmastcellsor
nonmyelinatedsensoryneurons.Thedegreeofairwayhyperresponsivenessgenerallycorrelateswiththeclinical
severityofasthma.
Spirometrywithpostbronchodilatorresponseshouldbeobtainedastheprimarytesttoestablishtheasthma
diagnosis.Pulseoximetrymeasurementisdesirableinallpatientswithacuteasthmatoexcludehypoxemia.The
chestradiographremainstheinitialimagingevaluationinmostindividualswithsymptomsofasthma,butinmost
patientswithasthma,chestradiographyfindingsarenormalormayindicatehyperinflation.Exercisespirometryis
thestandardmethodforassessingpatientswithexerciseinducedbronchospasm.
Physicalfindingsvarywiththeseverityoftheasthmaandwiththeabsenceorpresenceofanacuteepisodeandits
severity.Theseverityofasthmaisclassifiedasintermittent,mildpersistent,moderatepersistent,orsevere
persistent.Patientswithasthmaofanylevelofseveritymayhavemild,moderate,orsevereexacerbations.
Pharmacologicmanagementincludestheuseofreliefandcontrolagents.Controlagentsincludeinhaled
corticosteroids,inhaledcromolyn(Intal)ornedocromil(Tilade),longactingbronchodilators,theophylline(Theo24,
Theochron,Uniphyl),leukotrienemodifiers,andantiIgEantibodies.Reliefmedicationsincludeshortacting
bronchodilators,systemiccorticosteroids,andipratropium(Atrovent).Withsevereexacerbations,indicationsfor
hospitalizationarebasedonfindingsafterthepatientreceives3dosesofaninhaledbronchodilator.Ingeneral,
patientsshouldbeassessedevery16monthsforasthmacontrol.

Anatomy
Theairwaysofthelungsconsistofthecartilaginousbronchi,membranousbronchi,andgasexchangingbronchi
termedtherespiratorybronchiolesandalveolarducts.Whilethefirst2typesfunctionmostlyasanatomicdead
space,theyalsocontributetoairwayresistance.Thesmallestnongasexchangingairways,theterminalbronchioles,
areapproximately0.5mmindiameterairwaysareconsideredsmalliftheyarelessthan2mmindiameter. [7]
Airwaystructureconsistsofthefollowing:
Mucosa,whichiscomposedofepithelialcellsthatarecapableofspecializedmucousproductionanda
transportapparatus
Basementmembrane
Asmoothmusclematrixextendingtothealveolarentrances
Predominantlyfibrocartilaginousorfibroelasticsupportingconnectivetissue.
Cellularelementsincludemastcells,whichareinvolvedinthecomplexcontrolofreleasinghistamineandother
mediators.Basophils,eosinophils,neutrophils,andmacrophagesalsoareresponsibleforextensivemediator
releaseintheearlyandlatestagesofbronchialasthma.Stretchandirritantreceptorsresideintheairways,asdo
cholinergicmotornerves,whichinnervatethesmoothmuscleandglandularunits.Inbronchialasthma,smooth
musclecontractioninanairwayisgreaterthanthatexpectedforitssizeifitwerefunctioningnormally,andthis
contractionvariesinitsdistribution.

Pathophysiology
The2007ExpertPanelReport3(EPR3)oftheNationalAsthmaEducationandPreventionProgram(NAEPP)
notedseveralkeychangesintheunderstandingofthepathophysiologyofasthma[8]:
Thecriticalroleofinflammationhasbeenfurthersubstantiated,butevidenceisemergingforconsiderable
variabilityinthepatternofinflammation,thusindicatingphenotypicdifferencesthatmayinfluencetreatment
responses
Oftheenvironmentalfactors,allergicreactionsremainimportant.Evidencealsosuggestsakeyand
expandingroleforviralrespiratoryinfectionsintheseprocesses
Theonsetofasthmaformostpatientsbeginsearlyinlife,withthepatternofdiseasepersistencedetermined
byearly,recognizableriskfactorsincludingatopicdisease,recurrentwheezing,andaparentalhistoryof
asthma
Currentasthmatreatmentwithantiinflammatorytherapydoesnotappeartopreventprogressionofthe
underlyingdiseaseseverity
Thepathophysiologyofasthmaiscomplexandinvolvesthefollowingcomponents:
Airwayinflammation
Intermittentairflowobstruction
Bronchialhyperresponsiveness

Airwayinflammation
Themechanismofinflammationinasthmamaybeacute,subacute,orchronic,andthepresenceofairwayedema
andmucussecretionalsocontributestoairflowobstructionandbronchialreactivity.Varyingdegreesofmononuclear
cellandeosinophilinfiltration,mucushypersecretion,desquamationoftheepithelium,smoothmusclehyperplasia,
andairwayremodelingarepresent. [5]Seetheimagebelow.

Pathogenesisofasthma.Antigenpresentationbythedendriticcellwiththelymphocyteandcytokineresponseleadingtoairway
inflammationandasthmasymptoms.

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Someoftheprincipalcellsidentifiedinairwayinflammationincludemastcells,eosinophils,epithelialcells,
macrophages,andactivatedTlymphocytes.Tlymphocytesplayanimportantroleintheregulationofairway
inflammationthroughthereleaseofnumerouscytokines.Otherconstituentairwaycells,suchasfibroblasts,
endothelialcells,andepithelialcells,contributetothechronicityofthedisease.Otherfactors,suchasadhesion
molecules(eg,selectins,integrins),arecriticalindirectingtheinflammatorychangesintheairway.Finally,cell
derivedmediatorsinfluencesmoothmuscletoneandproducestructuralchangesandremodelingoftheairway.
Thepresenceofairwayhyperresponsivenessorbronchialhyperreactivityinasthmaisanexaggeratedresponseto
numerousexogenousandendogenousstimuli.Themechanismsinvolvedincludedirectstimulationofairway
smoothmuscleandindirectstimulationbypharmacologicallyactivesubstancesfrommediatorsecretingcellssuch
asmastcellsornonmyelinatedsensoryneurons.Thedegreeofairwayhyperresponsivenessgenerallycorrelates
withtheclinicalseverityofasthma.
AstudybyBalzaretalreportedchangesinairwayresidentmastcellpopulationsfromalargegroupofsubjectswith
asthmaandnormalcontrolsubjects. [9]Agreaterproportionofchymasepositivemastcellsintheairwaysand
increasedprostaglandinD2levelswereidentifiedasimportantpredictorsofsevereasthmaascomparedwithother
steroidtreatedsubjectswithasthma.
Chronicinflammationoftheairwaysisassociatedwithincreasedbronchialhyperresponsiveness,whichleadsto
bronchospasmandtypicalsymptomsofwheezing,shortnessofbreath,andcoughingafterexposuretoallergens,
environmentalirritants,viruses,coldair,orexercise.Insomepatientswithchronicasthma,airflowlimitationmaybe
onlypartiallyreversiblebecauseofairwayremodeling(hypertrophyandhyperplasiaofsmoothmuscle,angiogenesis,
andsubepithelialfibrosis)thatoccurswithchronicuntreateddisease.
Airwayinflammationinasthmamayrepresentalossofnormalbalancebetweentwo"opposing"populationsofTh
lymphocytes.TwotypesofThlymphocyteshavebeencharacterized:Th1andTh2.Th1cellsproduceinterleukin
(IL)2andIFN,whicharecriticalincellulardefensemechanismsinresponsetoinfection.Th2,incontrast,
generatesafamilyofcytokines(IL4,IL5,IL6,IL9,andIL13)thatcanmediateallergicinflammation.Astudyby
GauvreauetalfoundthatIL13hasaroleinallergeninducedairwayresponses. [10]
Thecurrent"hygienehypothesis"ofasthmaillustrateshowthiscytokineimbalancemayexplainsomeofthe
dramaticincreasesinasthmaprevalenceinwesternizedcountries. [11]Thishypothesisisbasedontheconceptthat
theimmunesystemofthenewbornisskewedtowardTh2cytokinegeneration(mediatorsofallergicinflammation).
Followingbirth,environmentalstimulisuchasinfectionsactivateTh1responsesandbringtheTh1/Th2relationship
toanappropriatebalance.

Airflowobstruction
Airflowobstructioncanbecausedbyavarietyofchanges,includingacutebronchoconstriction,airwayedema,
chronicmucousplugformation,andairwayremodeling.Acutebronchoconstrictionistheconsequenceof
immunoglobulinEdependentmediatorreleaseuponexposuretoaeroallergensandistheprimarycomponentofthe
earlyasthmaticresponse.Airwayedemaoccurs624hoursfollowinganallergenchallengeandisreferredtoasthe
lateasthmaticresponse.Chronicmucousplugformationconsistsofanexudateofserumproteinsandcelldebris
thatmaytakeweekstoresolve.Airwayremodelingisassociatedwithstructuralchangesduetolongstanding
inflammationandmayprofoundlyaffecttheextentofreversibilityofairwayobstruction. [12]
Airwayobstructioncausesincreasedresistancetoairflowanddecreasedexpiratoryflowrates.Thesechangeslead
toadecreasedabilitytoexpelairandmayresultinhyperinflation.Theresultingoverdistentionhelpsmaintain
airwaypatency,therebyimprovingexpiratoryflowhowever,italsoalterspulmonarymechanicsandincreasesthe
workofbreathing.

Bronchialhyperresponsiveness
Hyperinflationcompensatesfortheairflowobstruction,butthiscompensationislimitedwhenthetidalvolume
approachesthevolumeofthepulmonarydeadspacetheresultisalveolarhypoventilation.Unevenchangesin
airflowresistance,theresultingunevendistributionofair,andalterationsincirculationfromincreasedintraalveolar
pressureduetohyperinflationallleadtoventilationperfusionmismatch.Vasoconstrictionduetoalveolarhypoxia
alsocontributestothismismatch.Vasoconstrictionisalsoconsideredanadaptiveresponsetoventilation/perfusion
mismatch.
Intheearlystages,whenventilationperfusionmismatchresultsinhypoxia,hypercarbiaispreventedbytheready
diffusionofcarbondioxideacrossalveolarcapillarymembranes.Thus,patientswithasthmawhoareintheearly
stagesofanacuteepisodehavehypoxemiaintheabsenceofcarbondioxideretention.Hyperventilationtriggered
bythehypoxicdrivealsocausesadecreaseinPaCO2.Anincreaseinalveolarventilationintheearlystagesofan
acuteexacerbationpreventshypercarbia.Withworseningobstructionandincreasingventilationperfusionmismatch,
carbondioxideretentionoccurs.Intheearlystagesofanacuteepisode,respiratoryalkalosisresultsfrom
hyperventilation.Later,theincreasedworkofbreathing,increasedoxygenconsumption,andincreasedcardiac
outputresultinmetabolicacidosis.Respiratoryfailureleadstorespiratoryacidosis.

Etiology
Factorsthatcancontributetoasthmaorairwayhyperreactivitymayincludeanyofthefollowing:
Environmentalallergens(eg,housedustmitesanimalallergens,especiallycatanddogcockroach
allergensandfungi)
Viralrespiratorytractinfections
Exercise,hyperventilation
Gastroesophagealrefluxdisease
Chronicsinusitisorrhinitis
Aspirinornonsteroidalantiinflammatorydrug(NSAID)hypersensitivity,sulfitesensitivity
Useofbetaadrenergicreceptorblockers(includingophthalmicpreparations)
Obesity [13]
Environmentalpollutants,tobaccosmoke
Occupationalexposure
Irritants(eg,householdsprays,paintfumes)
Varioushighandlowmolecularweightcompounds(eg,insects,plants,latex,gums,diisocyanates,
anhydrides,wooddust,andfluxesassociatedwithoccupationalasthma)
Emotionalfactorsorstress
Perinatalfactors(prematurityandincreasedmaternalagematernalsmokingandprenatalexposureto
tobaccosmokebreastfeedinghasnotbeendefinitelyshowntobeprotective)

Aspirininducedasthma
Thetriadofasthma,aspirinsensitivity,andnasalpolypsaffects510%ofpatientswithasthma.Mostpatients

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experiencesymptomsduringthethirdtofourthdecade.Asingledosecanprovokeanacuteasthmaexacerbation,
accompaniedbyrhinorrhea,conjunctivalirritation,andflushingoftheheadandneck.Itcanalsooccurwithother
nonsteroidalantiinflammatorydrugsandiscausedbyanincreaseineosinophilsandcysteinylleukotrienesafter
exposure. [14]
AstudybyBeasleyetaldemonstratedsomeepidemiologicalevidencethatexposuretoacetaminophenis
associatedwithanincreasedriskofasthma. [15]However,noclinicalstudieshavedirectlylinkedasthmasymptoms
withacetaminophenuse.
Primarytreatmentisavoidanceofthesemedications,butleukotrieneantagonistshaveshownpromiseintreatment,
allowingthesepatientstotakedailyaspirinforcardiacorrheumaticdisease.

Gastroesophagealrefluxdisease
Thepresenceofacidinthedistalesophagus,mediatedviavagalorotherneuralreflexes,cansignificantlyincrease
airwayresistanceandairwayreactivity.Patientswithasthmaare3timesmorelikelytoalsohaveGERD. [16]Some
peoplewithasthmahavesignificantgastroesophagealrefluxwithoutesophagealsymptoms.Gastroesophageal
refluxwasfoundtobeadefiniteasthmacausingfactor(definedbyafavorableasthmaresponsetomedical
antirefluxtherapy)in64%ofpatientsclinicallysilentrefluxwaspresentin24%ofallpatients. [16]

Workrelatedasthma
Occupationalfactorsareassociatedwith1015%ofadultasthmacases.Morethan300specificoccupationalagents
havebeenassociatedwithasthma.Highriskjobsincludefarming,painting,janitorialwork,andplastics
manufacturing.Giventheprevalenceofworkrelatedasthma,theAmericanCollegeofChestPhysicians(ACCP)
supportsconsiderationofworkrelatedasthmainallpatientspresentingwithnewonsetorworseningasthma.An
ACCPconsensusstatementdefinesworkrelatedasthmasasincludingoccupationalasthma(ie,asthmainducedby
sensitizerorirritantworkexposures)andworkexacerbatedasthma(ie,preexistingorconcurrentasthmaworsened
byworkfactors). [17]
Twotypesofoccupationalasthmaarerecognized:immunerelatedandnonimmunerelated.Immunemediated
asthmahasalatencyofmonthstoyearsafterexposure.Nonimmunemediatedasthma,orirritantinducedasthma
(reactiveairwaydysfunctionsyndrome),hasnolatencyperiodandmayoccurwithin24hoursafteranaccidental
exposuretohighconcentrationsofrespiratoryirritants.Paycarefulattentiontothepatient'soccupationalhistory.
Thosewithahistoryofasthmawhoreportworseningofsymptomsduringtheweekandimprovementduringthe
weekendsshouldbeevaluatedforoccupationalexposure.Peakflowmonitoringduringwork(optimally,atleast4
timesaday)foratleast2weeksandasimilarperiodawayfromworkisonerecommendedmethodtoestablishthe
diagnosis. [17]
ToseecompleteinformationonAllergicandEnvironmentalAsthma,pleasegotothemainarticlebyclickinghere.

Viralexposureinchildren
Evidencesuggeststhatrhinovirusillnessduringinfancyisasignificantriskfactorforthedevelopmentofwheezingin
preschoolchildrenandafrequenttriggerofwheezingillnessesinchildrenwithasthma. [18]HumanrhinovirusC
(HRVC)isanewlyidentifiedgenotypeofHRVfoundinpatientswithrespiratorytractinfections.Astudyofchildren
withacuteasthmawhopresentedtotheemergencydepartmentfoundHRVCpresentinthemajorityofpatients.
ThepresenceofHRVCwasalsoassociatedwithmoresevereasthma. [19]
Approximately8085%ofchildhoodasthmaepisodesareassociatedwithpriorviralexposure.Priorchildhood
pneumoniaduetoinfectionbyrespiratorysyncytialvirus,Mycoplasmapneumoniae,and/orChlamydiaspecieswas
foundinmorethan50%ofasmallsampleofchildrenaged79yearswholaterhadasthma. [20]Treatmentwith
antibioticsappropriatefortheseorganismsimprovestheclinicalsignsandsymptomsofasthma.

Sinusitis
Ofpatientswithasthma,50%haveconcurrentsinusdisease.Sinusitisisthemostimportantexacerbatingfactorfor
asthmasymptoms.Eitheracuteinfectioussinusdiseaseorchronicinflammationmaycontributetoworseningairway
symptoms.Treatmentofnasalandsinusinflammationreducesairwayreactivity.Treatmentofacutesinusitis
requiresatleast10daysofantibioticstoimproveasthmasymptoms. [21]

Exerciseinducedasthma
Exerciseinducedasthma(EIA),orexerciseinducedbronchospasm(EIB),isanasthmavariantdefinedasa
conditioninwhichexerciseorvigorousphysicalactivitytriggersacutebronchospasminpersonswithheightened
airwayreactivity.Itisobservedprimarilyinpersonswhohaveasthma(exerciseinducedbronchospasminasthmatic
persons)butcanalsobefoundinpatientswithnormalrestingspirometryfindingswithatopy,allergicrhinitis,or
cysticfibrosisandeveninhealthypersons,manyofwhomareeliteathletes(exerciseinducedbronchospasmin
athletes).Exerciseinducedbronchospasmisoftenaneglecteddiagnosis,andtheunderlyingasthmamaybesilent
inasmanyas50%ofpatients,exceptduringexercise. [22,23]
Thepathogenesisofexerciseinducedbronchospasmiscontroversial.Thediseasemaybemediatedbywaterloss
fromtheairway,heatlossfromtheairway,oracombinationofboth.Theupperairwayisdesignedtokeepinspired
airat100%humidityandbodytemperatureat37C(98.6F).Thenoseisunabletoconditiontheincreasedamount
ofairrequiredforexercise,particularlyinathleteswhobreathethroughtheirmouths.Theabnormalheatandwater
fluxesinthebronchialtreeresultinbronchoconstriction,occurringwithinminutesofcompletingexercise.Results
frombronchoalveolarlavagestudieshavenotdemonstratedanincreaseininflammatorymediators.Thesepatients
generallydeveloparefractoryperiod,duringwhichasecondexercisechallengedoesnotcauseasignificantdegree
ofbronchoconstriction.
Factorsthatcontributetoexerciseinducedbronchospasmsymptoms(inbothpeoplewithasthmaandathletes)
includethefollowing:
Exposuretocoldordryair
Environmentalpollutants(eg,sulfur,ozone)
levelofbronchialhyperreactivity
Chronicityofasthmaandsymptomaticcontrol
Durationandintensityofexercise
Allergenexposureinatopicindividuals
Coexistingrespiratoryinfection
Theassessmentanddiagnosisofexerciseinducedbronchospasmismademoreofteninchildrenandyoungadults
thaninolderadultsandisrelatedtohighlevelsofphysicalactivity.Exerciseinducedbronchospasmcanbe
observedinpersonsofanyagebasedonthelevelofunderlyingairwayreactivityandthelevelofphysicalexertion.

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Genetics
Researchongeneticmutationscastsfurtherlightonthesynergisticnatureofmultiplemutationsinthe
pathophysiologyofasthma.Polymorphismsinthegenethatencodesplateletactivatingfactorhydrolase,anintrinsic
neutralizingagentofplateletactivatingfactorinmosthumans,mayplayaroleinsusceptibilitytoasthmaand
asthmaseverity. [24]
Evidencesuggeststhattheprevalenceofasthmaisreducedinassociationwithcertaininfections(Mycobacterium
tuberculosis,measles,orhepatitisA)rurallivingexposuretootherchildren(eg,presenceofoldersiblingsand
earlyenrollmentinchildcare)andlessfrequentuseofantibiotics.Furthermore,theabsenceoftheselifestyle
eventsisassociatedwiththepersistenceofaTh2cytokinepattern.Undertheseconditions,thegeneticbackground
ofthechild,withacytokineimbalancetowardTh2,setsthestagetopromotetheproductionofimmunoglobulinE
(IgE)antibodytokeyenvironmentalantigens(eg,dustmites,cockroaches,Alternaria,andpossiblycats).Therefore,
agenebyenvironmentinteractionoccursinwhichthesusceptiblehostisexposedtoenvironmentalfactorsthatare
capableofgeneratingIgE,andsensitizationoccurs.
Areciprocalinteractionisapparentbetweenthe2subpopulations,inwhichTh1cytokinescaninhibitTh2generation
andviceversa.AllergicinflammationmaybetheresultofanexcessiveexpressionofTh2cytokines.Alternatively,
recentstudiessuggestthepossibilitythatthelossofnormalimmunebalancearisesfromacytokinedysregulationin
whichTh1activityinasthmaisdiminished. [25]
Inaddition,somestudieshighlighttheimportanceofgenotypesinchildren'ssusceptibilitytoasthmaandresponse
tospecificantiasthmamedications. [26,27,28,29]

Obesity
AstudybyCottrelletalexploredtherelationshipbetweenasthma,obesity,andabnormallipidandglucose
metabolism. [30]Thestudyfoundthatcommunitybaseddatalinkedasthma,bodymass,andmetabolicvariablesin
children.Specifically,thesefindingsdescribedastatisticallysignificantassociationbetweenasthmaandabnormal
lipidandglucosemetabolismbeyondbodymassassociation.
Acceleratedweightgaininearlyinfancyisassociatedwithincreasedrisksofasthmasymptomsaccordingtoone
studyofpreschoolchildren. [31]

Epidemiology
Asthmaaffects510%ofthepopulationoranestimated23.4millionpersons,including7millionchildren. [17]The
overallprevalencerateofexerciseinducedbronchospasmis310%ofthegeneralpopulationifpersonswhodonot
haveasthmaorallergyareexcluded,buttherateincreasesto1215%ofthegeneralpopulationifpatientswith
underlyingasthmaareincluded.Asthmaaffectsanestimated300millionindividualsworldwide.Annually,theWorld
HealthOrganization(WHO)hasestimatedthat15milliondisabilityadjustedlifeyearsarelostand250,000asthma
deathsarereportedworldwide. [32]
IntheUnitedStates,asthmaprevalence,especiallymorbidityandmortality,ishigherinblacksthaninwhites.
Althoughgeneticfactorsareofmajorimportanceindeterminingapredispositiontothedevelopmentofasthma,
environmentalfactorsplayagreaterrolethanracialfactorsinasthmaonset.Anationalconcernisthatsomeofthe
increasedmorbidityisduetodifferencesinasthmatreatmentaffordedcertainminoritygroups.Largerasthma
associatedlungfunctiondeficitsarereportedinHispanics,especiallyfemales. [33]
AsthmaiscommoninindustrializednationssuchasCanada,England,Australia,Germany,andNewZealand,
wheremuchoftheasthmadatahavebeencollected.Theprevalencerateofsevereasthmainindustrialized
countriesrangesfrom210%.Trendssuggestanincreaseinboththeprevalenceandmorbidityofasthma,
especiallyinchildrenyoungerthan6years.Factorsthathavebeenimplicatedincludeurbanization,airpollution,
passivesmoking,andchangeinexposuretoenvironmentalallergens.
Asthmapredominantlyoccursinboysinchildhood,withamaletofemaleratioof2:1untilpuberty,whenthemale
tofemaleratiobecomes1:1.Asthmaprevalenceisgreaterinfemalesafterpuberty,andthemajorityofadultonset
casesdiagnosedinpersonsolderthan40yearsoccurinfemales.Boysaremorelikelythangirlstoexperiencea
decreaseinsymptomsbylateadolescence.
Asthmaprevalenceisincreasedinveryyoungpersonsandveryoldpersonsbecauseofairwayresponsivenessand
lowerlevelsoflungfunction. [34]Twothirdsofallasthmacasesarediagnosedbeforethepatientisaged18years.
Approximatelyhalfofallchildrendiagnosedwithasthmahaveadecreaseordisappearanceofsymptomsbyearly
adulthood. [35]

Prognosis
Internationalasthmamortalityisreportedashighas0.86deathsper100,000personsinsomecountries.US
asthmamortalityratesin2006werereportedat1.2deathsper100,000persons.Mortalityisprimarilyrelatedto
lungfunction,withan8foldincreaseinpatientsinthelowestquartile,butmortalityhasalsobeenlinkedwith
asthmamanagementfailure,especiallyinyoungpersons.Otherfactorsthatimpactmortalityincludeageolderthan
40years,cigarettesmokingmorethan20packyears,bloodeosinophilia,forcedexpiratoryvolumeinonesecond
(FEV 1)of4069%predicted,andgreaterreversibility. [36]
Theestimateoflostworkandschooltimefromasthmaisapproximately100milliondaysofrestrictedactivity.
Approximately500,000annualhospitalizations(40.6%inindividualsaged18yoryounger)areduetoasthma.Each
year,anestimated1.81millionpeople(47.8%ofthemaged18yoryounger)requiretreatmentinanemergency
department. [37]For2010,theannualexpendituresforhealthandlostproductivityduetoasthmaareprojectedtobe
$20.7billion. [38]
Nearlyonehalfofchildrendiagnosedwithasthmahaveadecreaseinsymptomsandrequirelesstreatmentbylate
adolescenceorearlyadulthood.Inastudyof900childrenwithasthma,6%requirednotreatmentafter1year,and
39%onlyrequiredintermittenttreatment.
Patientswithpoorlycontrolledasthmadeveloplongtermchangesovertime(ie,withairwayremodeling).Thiscan
leadtochronicsymptomsandasignificantirreversiblecomponenttotheirdisease.Manypatientswhodevelop
asthmaatanolderagealsotendtohavechronicsymptoms.

PatientEducation
Theneedforpatienteducationaboutasthmaandtheestablishmentofapartnershipbetweenpatientandclinician
inthemanagementofthediseasewasemphasizedbyEPR3. [4]

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Thekeypointsofeducationincludethefollowing:
Patienteducationshouldbeintegratedintoeveryaspectofasthmacare
Allmembersofthehealthcareteam,includingnurses,pharmacists,andrespiratorytherapists,should
provideeducation.
Cliniciansshouldteachpatientsasthmaselfmanagementbasedonbasicasthmafacts,selfmonitoring
techniques,theroleofmedications,inhaleruse,andenvironmentalcontrolmeasures. [39,40,41]
Treatmentgoalsshouldbedevelopedforthepatientandfamily.
Awritten,individualized,dailyselfmanagementplanshouldbedeveloped.
Severalwellvalidatedasthmaactionplansarenowavailableandarekeyinthemanagementofasthmaand
shouldthereforebereviewed:ACT(AsthmaControlTest),ATAQ(AsthmaTherapyAssessment
Questionnaire),andACQ(AsthmaControlQuestionnaire). [42]
Schoolbasedasthmaeducationprogramsimprovedknowledgeofasthma,selfefficacy,andselfmanagement
behaviorsinchildrenaged417years,accordingtoasystematicliteraturereviewbyCoffmanetal,butthe
programshadlesseffectonqualityoflife,daysofsymptoms,nightswithsymptoms,andschoolabsences. [43]
The2009VeteransAdministration/DepartmentofDefense(VA/DoD)clinicalpracticeguidelineformanagementof
asthmainchildrenandadultsconcurswithEPR3inrecommendingselfmanagementeducationforboththepatient
andcaregiveraspartofthetreatmentprogram. [44]
Forexcellentpatienteducationresources,visiteMedicineHealth'sAsthmaCenter.Also,seeeMedicineHealth's
patienteducationarticlesAsthma,AsthmaFAQs,AsthmainChildren,andUnderstandingAsthmaMedications.

ContributorInformationandDisclosures
Author
MichaelJMorris,MD,FACP,FCCPClinicalFaculty,PulmonaryDisease/CriticalCareService,Departmentof
Medicine,BrookeArmyMedicalCenterAssociateProgramDirector,SAUSHECInternalMedicineResidency,
SanAntonioMilitaryMedicalCenterClinicalAssistantProfessor,UniversityofTexasSchoolofMedicineatSan
AntonioProfessor,UniformedServicesUniversityoftheHealthSciences
MichaelJMorris,MD,FACP,FCCPisamemberofthefollowingmedicalsocieties:AmericanAssociationfor
RespiratoryCare,AmericanCollegeofChestPhysicians,AmericanCollegeofPhysicians,andAssociationof
MilitarySurgeonsoftheUS
Disclosure:Pfizer/BoehringerIngelheimHonorariaSpeakingandteaching
ChiefEditor
ZabMosenifar,MD,FACP,FCCPGeriandRichardBrawermanChairinPulmonaryandCriticalCare
Medicine,ProfessorandExecutiveViceChairman,DepartmentofMedicine,MedicalDirector,Women'sGuild
LungInstitute,CedarsSinaiMedicalCenter,UniversityofCalifornia,LosAngeles,DavidGeffenSchoolof
Medicine
ZabMosenifar,MD,FACP,FCCPisamemberofthefollowingmedicalsocieties:AmericanCollegeofChest
Physicians,AmericanCollegeofPhysicians,AmericanFederationforMedicalResearch,andAmericanThoracic
Society
Disclosure:Nothingtodisclose.
AdditionalContributors
EdwardBessman,MD,MBAChairmanandClinicalDirector,DepartmentofEmergencyMedicine,John
HopkinsBayviewMedicalCenterAssistantProfessor,DepartmentofEmergencyMedicine,JohnsHopkins
UniversitySchoolofMedicine
EdwardBessman,MD,MBAisamemberofthefollowingmedicalsocieties:AmericanAcademyofEmergency
Medicine,AmericanCollegeofEmergencyPhysicians,andSocietyforAcademicEmergencyMedicine
Disclosure:Nothingtodisclose.
PaulBlackburn,DO,FACOEP,FACEPAttendingPhysician,DepartmentofEmergencyMedicine,Maricopa
MedicalCenter
PaulBlackburn,DO,FACOEP,FACEPisamemberofthefollowingmedicalsocieties:AmericanCollegeof
EmergencyPhysicians,AmericanCollegeofOsteopathicEmergencyPhysicians,AmericanMedicalAssociation,
andArizonaMedicalAssociation
Disclosure:Nothingtodisclose.
BarryEBrenner,MD,PhD,FACEPProfessorofEmergencyMedicine,ProfessorofInternalMedicine,
ProgramDirectorforEmergencyMedicine,CaseMedicalCenter,UniversityHospitals,CaseWesternReserve
UniversitySchoolofMedicine
BarryEBrenner,MD,PhD,FACEPisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,
AmericanAcademyofEmergencyMedicine,AmericanCollegeofChestPhysicians,AmericanCollegeof
EmergencyPhysicians,AmericanCollegeofPhysicians,AmericanHeartAssociation,AmericanThoracic
Society,ArkansasMedicalSociety,NewYorkAcademyofMedicine,NewYorkAcademyofSciences,and
SocietyforAcademicEmergencyMedicine
Disclosure:Nothingtodisclose.
HelenMHollingsworth,MDDirector,AdultAsthmaandAllergyServices,AssociateProfessor,Departmentof
InternalMedicine,DivisionofPulmonaryandCriticalCare,BostonMedicalCenter
HelenMHollingsworth,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofAllergy
AsthmaandImmunology,AmericanCollegeofChestPhysicians,AmericanThoracicSociety,and
MassachusettsMedicalSociety
Disclosure:Nothingtodisclose.
RobertEO'Connor,MD,MPHProfessorandChair,DepartmentofEmergencyMedicine,UniversityofVirginia
HealthSystem
RobertEO'Connor,MD,MPHisamemberofthefollowingmedicalsocieties:AmericanAcademyofEmergency
Medicine,AmericanCollegeofEmergencyPhysicians,AmericanCollegeofPhysicianExecutives,American
HeartAssociation,AmericanMedicalAssociation,MedicalSocietyofDelaware,NationalAssociationofEMS
Physicians,SocietyforAcademicEmergencyMedicine,andWildernessMedicalSociety

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Disclosure:Nothingtodisclose.
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment

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