EditorialOfficeNotes: RES11479.

R1 INVITEDREVIEWSERIES:ObesityandRespiratorydisorders SeriesEditor:AmandaJPiper Received:15August2011 Invitedtorevise:24August2011 Revised:29August2011 Accepted:3September2011

Theimpactofobesityonrespiratoryfunction *
StephenW.Littleton,MD Pulmonary, Critical Care, and Sleep Medicine, Cook County Hospital and Rush University MedicalCenter;Chicago,USA Correspondingauthor: StephenW.Littleton,MD Pulmonary,CriticalCare,andSleepMedicine AttendingPhysician,CookCountyHospital AssistantProfessorofMedicine,RushUniversityMedicalCenter 1900W.PolkSt.,Rm.1416 Chicago,IL60612 (312)8647380,fax(312)8647394 slittleton@cookcountyhhs.org Authorsbiography: Dr.LittletonisanattendingphysicianinthedivisionofPulmonary,CriticalCare,andSleep MedicineatCookCountyHospitalinChicago,andanAssistantProfessorofmedicineatRush UniversityMedicalCenter.Hisresearchinterestsincludethepathophysiologyofrespiratory failureandhypercapnia.

This is an Accepted Article that has been peer-reviewed and approved for publication in the Respirology, but has yet to undergo copy-editing and proof correction. Please cite this article as an "Accepted Article"; doi: 10.1111/j.1440-1843.2011.02096.x

Abstract Obesityhaslongbeenrecognizedashavingsignificanteffectsonrespiratoryfunction.

Thetopichasbeenstudiedforatleastthelasthalfcentury,andsomeclearpatternshave emerged.Obesepatientstendtohavehigherrespiratoryratesandlowertidalvolumes.Total respiratorysystemcomplianceisreducedforavarietyofreasons,whichwillbediscussed.Lung volumestendtobedecreased,especiallyexpiratoryreservevolume(ERV).Spirometry,gas exchange,andairwayresistancealltendtoberelativelywellpreservedwhenadjustedforlung volumes.Patientsmaybemildlyhypoxaemic,possiblyduetoventilationperfusion mismatchingatthebaseofthelungs,wheremicroatelectasisislikelytooccur.Weightloss leadstoareversalofthesechanges.Forallofthesechanges,thedistributionoffat,i.e.,upper versuslowerbody,maybemoreimportantthanbodymassindex. Keywords:lungvolumes,obesity,pulmonaryfunctiontests,pulmonarygasexchange, respiratorymechanics. Shorttitle:Impactofobesityonrespiratoryfunction

Introduction Theassociationbetweenobesityandrespiratorydysfunctionisalmostasoldas

recordedhistory.Dionysius,atyrantofHeraclea,wasborninapproximately360BC.Hewas describedasbeingveryobese,andthroughdailygluttonyandintemperance,increasedtoan extraordinarydegreeofCorpulencyandFatness,byreasonwhereofhehadmuchadoetotake breath.Itwasalsowrittenofhimthathewaschokedbyhisownfat.1 DionysiuswasnotuniqueinancientGreektimes.Magas,theKingofCyrene,whodiedin approximately258BC,wasweighteddownwithmonstrousmassesoffleshinhislastdays;in facthechokedhimselftodeath.1 Therehavebeensimilardescriptionsofobesityinmorerecenttimesaswell.In1816,

WilliamWadd,whosetitlewasSurgeonExtraordinarytotheKing,publishedatreatisein whichhenoted,accumulationoffat...cannotfailtoimpedethefreeexerciseoftheanimal functions.Respirationisperformedimperfectly,orwithdifficulty.Intheappendix,he mentionedthreepatientswhohadbeensuffocatedbyfat.1But,specifically,whatarethe imperfectionsintherespirationofobesepatients? Breathingpatternsofobesepatients Patientswhoaremorbidlyobese(BMI40kg/m2)haveincreasedrespiratoryratesas

comparedwithnormalsubjects.Infourstudies,themeanrespiratoryrateofobesesubjects rangedfrom15.321breathsperminute,whilethatofnormalsubjectsrangedfrom1012 breathsperminute.25Tidalvolumetendstobesignificantlylowerinobesesubjects,35 althoughthisfindingisnotuniversal.2Despitethedecreaseintidalvolume,theincreasein

respiratoryrateissuchthatminuteventilationissignificantlyincreased,andwasshowntobe 11L/minorgreaterinmoststudies.2,4,5 Howdoestheobesepatientachievethishigherrespiratoryrate?Isthereachangein

breathtiming,oristheflowratehigher?Itseemsthatthereisachangeinbreathtiming,but reportsonexactlywhatthosechangesarehavebeeninconsistent.Sampsonshowedthatthere wasadecreaseininspiratorytime[TI],withoutasignificantdecreaseinexpiratorytime[TE],and nochangeinmeaninspiratoryflow.3Incontrast,bothBurkiandBaker,andChlifetal.showed thatTEdecreasedwithoutanychangeinTIorinspiratoryflowrates(aswellassimilarexpiratory flowrates).2,5Finally,PankowshowedthatTIandTEweredecreasedbutdidnotreportthe statisticsonflowrates.4DecreasesinTImayarisefromincreasedactivityofchestwall receptorsorfromchangesincentralbreathtiming,3whereasdecreasesinTEcouldbeduetoan increasedexpiratoryflowrateasaresultofdecreasedtotalrespiratorycompliance,2or persistentdiaphragmaticactivityextendingintoexhalation.3ItseemsthatbothTIandTEare affectedbyobesity,althoughtheexactpatternofchangesmayvaryamongindividuals. Respiratorymechanics Totalrespiratorysystemcomplianceisundoubtedlyreducedinobesepatients.610

However,theresultsarecontradictoryastowhetherthisreducedcomplianceisduetoreduced chestwallcompliance,lungcompliance,orsomecombinationofthetwo. In1960,NaimarkandCherniackshowedthatchestwallcompliancewasreducedin obeseindividuals(andwasespeciallyreducedinthesupineposition),whereaslungcompliance wasnormal.7Fouryearslater,Sharpetal.showednearlytheexactopposite:thatadecreasein

lungcompliancewaslargelyresponsible.8Usinganoninvasivemethod,Surattetal.showed thechestwallofobesepatientstobenormalwhiletheywereseated.11Oesophagealpressures, andthereforecalculationsoflungandchestcompliance,changedbetweentheseatedand supinepositions.7,12Thesestudieswereperformedonawakepatients,inwhomrespiratory muscleactivitymayhaveinterferedwiththemeasurements. WhenHedenstiernaandSantessonperformedsimilarstudiesonparalyzed,supine

subjects,chestwallcompliancewasfoundtobenormalandlungcompliancewasreduced.9 Pelosietal.studiednearlyequallyobesepatientsunderthesameconditions,andfoundthat bothchestandlungcompliancewerereduced.10 Itislikelythatbothdecreasedlungcomplianceanddecreasedchestwallcompliance

contributetoalesscompliantrespiratorysysteminobesepatients.Decreasedlungcompliance islikelytobetheresultofdecreasedlungvolumes,leadingtomicroatelectasis,whichshifts normalrespirationsintothesinusoidalratherthanthelinearportionofthepressurevolume curve.9,10Chestwallcompliancemaybedependentonthepatternoffatdistributionina particularpatient.Itisknownthatmassloadingofthelowerthoraxandupperabdomenof supine,paralyzedsubjectsaffectschestwallcompliancemoresothanmassloadingofthe upperthorax.13Therefore,chestwallcompliancemaybemorerelevantinpatientswithhigher waisttohipratios.

Lungvolumes Theeffectsofobesityonlungvolumeshavebeenstudiedextensively.Figure1

summarizestheeffectsofobesityonlungvolumes.Oneofthemostconsistenteffectsof obesityonlungvolumesisadecreaseinexpiratoryreservevolume(ERV).1421ERVdecreasesas BMIincreases.14,17,19,22,23Onestudyofpulmonaryfunctiontestsin373patientswithawide rangeofBMIshowedthatthosewithmildobesity(BMI3035kg/m2)hadanERVofonly42.4 29.3%ofpredicted.ThatstudyalsoshowedthatERVdecayedexponentiallywithincreasing BMI(Fig.2).17Anotherstudyshowedthatsuperobeseindividuals(BMI60kg/m2,ora height/weightratioof1)hadanERVofonly17.89.6%ofpredicted.19 AnequallyconsistentnegativecorrelationbetweenobesityandFRCcanbe

demonstrated,althoughthechangesarelessdramatic.14,17,23,24IndividualswithaBMI>40 kg/m2haveanFRCof66.612.3%ofpredicted.Ifthereisanexponentialrelationshipbetween BMIandERV,thenthesameshouldholdtrueofFRC,andthiswasshowntobethecase.Given thatthereisasignificantbutverymodesteffectofBMIonRV,thenthereductioninFRCisdue tothereductioninERV.17 IfobesityreducesERVandFRC,thenwemightexpectasimilareffectonTLC.Inreality, TLCisnotaffectedunlesspatientsaremassivelyobese.Olderstudieswithlimitednumbersof patientsshowedasignificantdifference,onlywhennormalsubjectswerecomparedtothose withaheighttoweightratioof1.11.2(BMIof55kg/m2foraperson183cmtall,andgreaterif thepersonisshorter),22orifthecohorthadameanbodyweightof23439.6%oftheideal (BMIofapproximately46.6kg/m2).2Asmallbutmorerecentstudydidnotfindasignificant

differenceinTLCwhentwogroupswithmeanBMIsof25.5and38.8werecompared.25 However,whentheBMIoftheobesegroupwas47,whereasthatofthenormalgroup remainedat25,asignificantdifferenceemerged.21Significantbutprobablyclinically unimportantdifferencesdidemergewhenlargergroupsofpatientswerestudied.Onestudy foundthattheTLCofagroupofsubjectswithameanBMIof34was15%belowpredicted whencomparedwiththatofagroupwithameanBMIof27.20Inanotherstudy,therewasa 0.5%decreaseinpredictedTLCforeachunitincreaseinBMI,althoughmeanTLCinthegroup withBMI40wasonly12%belowpredicted,onaverage.17 Howdoesobesityhavetheseeffectsonlungvolumes?Oneproposedmechanismisthat abdominalfatdisplacesthediaphragmintotheabdomen.26Thisissupportedbyonestudythat showedlungvolumeswereaffectedmoreinpatientswithawaisttohipratio>0.95(upper bodyfatdistribution).27Inaddition,chestwalladipositymaysimplycompressthethoraciccage, leadingtolowerlungvolumes.26Thisissupportedbythesimilarpatternobservedwhenlung volumesaremeasuredafterelasticstrappingofthechest,28althoughthereissomequestionas towhetherobesityactsasamass(threshold)loadoranelasticload.13Itislikelythatbothplay aroleindecreasinglungvolumes,anditwouldbedifficulttoisolateandstudyonecomponent independently. Recently,MRIhasbecomethepreferredmethodforlocalizingandquantifying adiposity.29Nostudieshavebeendoneyetonwhetherabdominaladiposityasdeterminedby MRIiscorrelatedwithreducedlungvolumes,butarecentpreliminarystudyexploredathird possiblemechanismfortheeffectofobesityonlungvolumes:isthereanincreaseinthoracicor

mediastinalfatinobesepatients?Normalweightsubjects(BMI25.0)werecomparedwith obesesubjects(BMI38.8).Theobesesubjectswerethendividedintotwogroups:thosewitha TLC<80%ofpredicted(obeserestricted)andthosewithaTLC>80%ofpredicted(obese normal).Althoughobesesubjectsdidhavemoremediastinalfatthannormalsubjects,there wasnodifferenceinmediastinalfatbetweentheobeserestrictedandtheobesenormal subjects.Infact,theonlydiscernibledifferencebetweenthetwoobesegroupswasthe intrathoracicvolumeatfullbreathhold;124%ofpredictedTLCintheobesenormalgroup,and 105%ofpredictedTLCintheobeserestrictedgroup.Theauthorshypothesizedthatareduction indiaphragmaticexcursionduetoabdominalfatwasresponsible.25 AnotherrecentstudyusedMRItocompareendexpiratorylungvolume(EELV)andfat distributioninobesemenandwomen(BMIof354and372,respectively)withthatin normalsubjects.Surprisingly,thatstudyshowedlittlevariationinthedistributionoffat betweennormalsubjectsandobesesubjects,forbothmenandwomen.Thisunderscoresthe difficultyofteasingouttherelativecontributionsofchestwallandabdominalfattoalterations inlungvolumes.Thestudydidshowasignificantrelationshipbetweenvisceralfat,i.e.,fat surroundingtheabdominalorgans,anteriorsubcutaneousfat(bothabdominalandchestwall), andEELV(expressedas%TLC).30Thestudyalsohighlightedthefactthatbothchestwalland abdominalfatlikelyplayaroleinderangementoflungvolume. FurtherresearchonquantificationofabdominalfatbyMRIislikelytobeforthcoming, andwillbeveryhelpfulinelucidatingtheexactmechanismsthatareatwork.

Spirometry ObesitygenerallydoesnotdepressFEV1orFVCunlesspatientsaremassivelyobese.The

FEV1/FVCratioispreserved.2,17,1921,24,25,27,3133Figure1showsthetypicalspirogramofanobese patient.Onelargestudyshowedastatisticallysignificanttrendinmenandanearlysignificant correlationinwomen,betweenFEV1,FVC,andBMI,althoughFEV1inmenwithameanBMIof 33.6wasclosetonormalat93%ofpredicted.32Eveninmassivelyobeseindividuals,theeffects aremodest.OnestudyshowedthatthemeanFEV1in18patientswithweighttoheightratios >1was68.75.9%ofpredicted.19TheseeffectsdisappearedwhenFEV1andFVCwereadjusted forthesmallreductioninlungvolumes. Again,itseemsthatthepatternofobesityismoresignificantthanBMIalone.

AbdominalobesityisgenerallycorrelatedwithreductionsinFEV1andFVC,withsome exceptionsbeingnotedforwomenandcertainagegroups,dependingonthestudy.27,31,32,34 Thelargeststudyinvolvedalmost20,000subjectsandshowedaninverselinearcorrelation betweenwaisttohipratioandFEV1andFVC.34Othermeasurementsofabdominalobesitythat haveshownassociationswithspirometricparametersarebiceps27andsubscapularskinfold thickness,31waistcircumference,35andabdominalheight.32 Airwayresistance Airwayresistanceisusuallyincreasedinobeseindividuals,andthisisatleastpartly

relatedtothelowerlungvolumesatwhichobesepatientsnormallybreathe,leadingtoclosure ofthesmallerairways.20,21,24Onecasecontrolledstudyof190subjectsshowedthattheairway resistanceofobesemen(meanBMI47)wasalmosttwicethatofnormalcontrolsubjects.

Interestingly,althoughthedifferencesinairwayresistancebetweennormalweightandobese womenweresignificant,theyweremuchlessprofound.However,whenairwayresistancewas adjustedforlungvolumes,therewasnodifferencebetweenthenormalsubjectsandtheobese subjects.21Anotherstudyshowedaverystrongcorrelationbetween%predictedFRCand airwayconductance(theinverseofairwayresistance),butnotbetweenconductanceandBMI. DirectmeasurementsconfirmedthatairwaycalibreandBMIwerecorrelatedinmen,butonly weaklycorrelatedinwomen.However,thesamestudyshowedthatthedecreaseinlung volumesonlyaccountedforaportionoftheincreaseinairwayresistance.36Similarly,another studyshowedthatthedecreaseinmidtidallungvolumedidnotaccountfortheincreasein totalrespiratoryresistancemeasuredatthemouth.24 Thereasonsfortheinconsistencyinthesefindings,especiallythedifferencesbetween

thegenders,areunclear.Airwayremodellingsecondarytoinflammatoryadipokines,oreven directlipiddepositionintheairwaysaretwopossibleexplanations.37Giventhedifferences betweenthegenders,somehormonalinterplaymayalsobeinvolved. Oxygenation,ventilation,perfusionandgasexchange Obesepatientsmayhaveanormal,8,3840,orslightlyreducedPaO2.16,19Thereasonsfor

thedifferencesintheresultsofthesestudiesareunclear,butmayberelatedtoobesity hypoventilationsyndrome,sinceonestudyshowedameanPaCO2of46.72.5mmHg.19One studyof37massivelyobesepatients(BMIofapproximately50)showedarelativelynormal meanPaO2of83.22.5mmHg,38whereasanotherstudyof25patientswithameanBMIof

49.0showedanearlyidenticalmeanPaO2of887mmHg.40Itisnotclearwhethersimple obesity,inandofitself,issufficienttocausearterialhypoxaemia. Itdoesseem,however,thatobesitycausesamildwideningoftheAaO2gradient.Inthe

twopreviouslymentionedstudies,thesubjectswithBMIsof4950werefreeofpulmonary diseaseandhadAaO2gradientsof22.62.838and199mmHg,40respectively.Therefore, althoughobesitycancauseamildwideningoftheAaO2gradient,thisisnotsufficienttocause frankhypoxaemia. ThewideningoftheAaO2gradientislikelycausedbyventilationperfusionmismatch.

Thelungbasesarerelativelyoverperfusedandunderventilatedwhenobesepatientsare studiedinthesittingposition,41andwhentheyarerecumbent.42Thisisduetotheclosureof smallairwaysindependentlungzones.43Thiswouldcausethepatterndiscussedearlier;i.e.,a reductioninERVwitharelativelyunchangedRV. Furthermore,thereisalsoacorrelationbetweenERVandbothhypoxaemiaandAaO2 gradient.Inonestudy,V/QwasmuchmorecloselymatchedinfourobesesubjectswithanERV of49%ofpredictedthaninfoursubjectswithanERVof21%ofpredicted.Theselattersubjects hadidenticalperfusiontothelowerlungzones,butamuchhigherproportionofventilationto theupperlungzones.41AnotherstudyshowedalinearrelationshipbetweenPaO2andabsolute ERV,andmanyofthesepatientshadaclosingvolumeinexcessofERV.39Onceagain,weseea significantrelationshipbetweenthepatternofobesityandpulmonaryfunction.Recentwork hasshownasignificantlinearrelationshipbetweenwaisttohipratioandPaO2,PaCO2,andA aO2gradient.40

Gasexchange(DLCO)seemstoberelativelywellpreservedinsubjectswithsimple obesity.8,19,22,44,45Whencorrectedforlungvolume(DLCO/VA),valuesmaybeelevatedin extremelyobese(height/weightratio>1.10)comparedtonormalweightindividuals,22although thisfindinghasnotbeenconsistentlyreported.19Onestudyinwhichfactorsthatwere correlatedwithanincreasedDLCO/VAwereexaminedretrospectively,showedthatareduction inVCwasacommonfinding,andthatobesitywasacommoncauseofthisreduction.46 DLCO/VAmaybeincreasedinobesepatientsduetoanincreaseinpulmonarybloodvolume8,46 Exercise Sinceobeseindividualshaveahigherbasalmetabolicrate(VO2)thanleansubjects,itis

notsurprisingthattheyhaveahigheroxygenconsumptionduringexerciseforanygivenwork rate.44,47,48,45TheslopesoftheVO2toworkratelinesarethesameasinnormalweight individuals,implyingthatitistheincreaseinbasalratethatisresponsiblefortheincreasein VO2atagivenworkrate,althoughthismayalsoresultfromtheextraenergyneededtomove heavierlegsduringcyclingexerciseprotocols.49Obesepatientsalsotendtohavealower anabolicthreshold.50TheAaO2gradient,andPaO2ifitisabnormal,actuallyimproveduring exercise.49Augmentedtidalvolumeshelptoopentheclosed,dependentlungunits,whichare thoughttobetheprimarycauseoftheincreasedAaO2gradient.51 InadditiontohavingalowerAaO2gradient,obesepatientsaugmenttheiroxygen

intakebyincreasingtheirtidalvolumesandrespiratoryratesduringexercise,similartonormal weightsubjects.However,astheyburnmoreoxygen,theyneedtoaugmenttheirminute ventilationtoanevengreaterextentthannormalweightsubjects.Thisisachievedmainly

throughahigherrespiratoryrate,astheirtidalvolumesarenotgenerallygreater.44,48,50The reasonwhyisunclear.Itmaybesimplyduetocentralbreathtiming,butagain,weseesome evidencethatitcouldberelatedtobodyfatdistributionleadingtoimpaireddiaphragmatic excursion,andthereforeaninabilitytoaugmentexercisetidalvolumesanyfurther. Inonelarge,relativelyrecentstudy,164morbidlyobesefemales(BMI44.81.3kg/m2)

weredividedintotwogroups:thosewithanupperbodydistributionoffat(waisthip circumferenceratio0.80)andthosewithalowerbodydistributionoffat.Allsubjectswere exercisedtothepointofmaximumeffort.Thosewithanupperbodydistributionoffathada significantlyloweranaerobicthreshold,andasignificantlyhigherVO2max.Inaddition,the groupwithupperbodyfathadasignificantlyhigherrespiratoryrateandminuteventilationat bothanaerobicthresholdandmaximalexercise,whereastidalvolumedidnotdiffer significantly.Maximalexerciseworkloadwasequivalentinthetwogroups.50Theresultsfrom thisstudyimplythatthegroupwithupperbodyfatwassimplyunabletoaugmenttheirtidal volumeasmuchasthegroupwithlowerbodyfat,andtheincreaseinminuteventilationwas insufficienttomeetmetabolicneeds.Thehigheroxygenconsumptioninthegroupwithupper bodyfatmayhavebeenduetoahigheroxygencostofworkofbreathing(seebelow).Further studiesusingMRIquantificationanddeterminationoffatdistributionarenecessarytoconfirm theseinterestingfindings. Dyspnoea Obesityhaslongbeenthoughttobeacauseofdyspnoea,especiallyonexertion,but

datasupportingthishasbeenscarce.Arelativelyrecent,largestudyinvolving16,171

participantsshowedthatobesitywasariskfactorforselfreporteddyspnoea.Individualsinthe highestquintileofBMI(>31.0kg/m2)hadanoddsratioof2.66(95%CI2.353.00,P=0.001)for reportingdyspnoeawhenwalkingupahill,ascomparedwiththoseinthecontrolquintile(BMI 22.124.8kg/m2).IndividualsinthehighestquintileofBMIwerealsomorelikelytoselfreport asthmaortohaveusedabronchodilatorinthelastmonth,butweretheleastlikelytoactually haveairflowobstruction(8.7%,comparedwith12.8%ofthoseinthecontrolquintile,P= 0.001).52Thishighlightsthefrequencyofmisdiagnosisamongthesepatients. Whataretheoriginsofobesityrelateddyspnoea?Thedatainthisregardare

inconclusive,andgiventhecomplexmechanismsunderlyingdyspnoea,53thecauseislikelyto bemultifactorial.Manypotentialcauseshavebeeninvestigated.Inonestudy,28obese patientsweredividedintotwogroups:thosewithmildtomoderatedyspnoeaandthosewith severedyspnoea.AlthoughBMIdidnotdiffersignificantlybetweenthegroups(47.57and 48.76kg/m2,respectively)thegroupwithseveredyspnoeahadsignificantlylowerTLC,FRC andERVvalues,andtendedtohaveahigherrespiratorydrive.54Otherstudieshaveshownthat dyspnoeainobesesubjectsisrelatedtorespiratorymuscleperformance23,55orribcagemuscle activity,56afferentfeedbackfromwhichisknowntocontributetothesensationofdyspnoea.53 Furthersupportingtheideathatincreasedrespiratorymuscleworkleadstodyspnoeainthese patientsistheobservationthattheyalsohaveanincreasedoxygencostofbreathing. Itisalreadyknownthatobesepatientshaveahigheroxygencostofbreathing,evenat

rest.57Inarecentstudy,twogroupsofobesewomen,eightwithexertionaldyspnoea(BMI37 4kg/m2)andeightwithout(BMI365kg/m2),wereinvestigated.Theywereexercisedata

constantworkrateandalsounderwentaeucapnicvoluntaryhyperpnoeamanoeuvre.Their perceptionsofbreathlessness,aswellastheoxygencostofbreathingweremeasuredduring bothexperiments.Therewerenodifferencesbetweenthegroupswithrespecttopulmonary functiontestsorrespiratorymechanics.Therewasastrong,statisticallysignificantrelationship betweenoxygencostofbreathingandperceivedbreathlessness(Fig.4).Veryinterestingly, therewerenodifferencesinpeakcardiovascularexercisecapacityorfatdistributionas determinedbyMRI,betweenthegroups.58Itremainsunclearwhycertainobeseindividuals haveahigheroxygencostofbreathingcomparedwithothers. Effectsofweightlossonpulmonaryfunction Perhapsoneofthebestwaysofstudyingtheeffectsofobesityonpulmonaryfunctionis

tostudythesamegroupofpatientsbeforeandafterweightloss.Itseemsthatmostofthe changesassociatedwithobesityarereversedaftersignificantweightloss,andaretherefore likelytobecausedbyobesityitself.ERV,thepulmonaryparameterthatismostconsistently alteredinobesity,improvesafterweightloss.16,18,33,38,39,54,59,60Onestudyshowedatriplingof absoluteERVinpatientswhosemeanBMIdecreasedfrom45to39kg/m2afteraverylow caloriediet.60Evenmodestweightloss(reductionofBMIfrom35to33kg/m2)leadstomodest butsignificantimprovementsinERV.33FRCandTLCalsoimprovetovaryingdegrees.16,18,38,59,60 TheAaO2gradientalsotendstoimproveifBMIis>20kg/m2afterjejunoilealbypass.TheA aO2gradientislinearlycorrelatedwithBMI.39ThissupportsthehypothesisthatawidenedA aO2gradientinobesityiscausedbyclosureofsomelungunitsfromaclosingvolumethatis aboveERV,withresultantV/Qmismatch.Respiratorymuscleendurancealsoimproves,59 althoughmaximumvoluntaryventilationdoesnot.54AreductioninBMIfrom47.37.2to31.8

5.1asaresultofgastricbypassledtoadecreaseinrespiratorydriveanddecreaseddyspnoea in10patients.54Furtherstudyofthistopiccouldhelpexplainwhysomeobesepatients experiencedyspnoea,whereasothersdonot. Conclusion Obesityhasmyriadeffectsonpulmonaryfunction.Respiratoryrateisusuallyincreased

inordertocompensateforthenormallydepressedtidalvolumes.Totalrespiratorysystem complianceisdecreased;however,partitioningthisintochestwallandlungcomponentshas shownconflictingresults.Lungvolumes,andespeciallyERV,arethemostconsistentlyaffected respiratoryparameters.Oxygenationmaybeaffected,probablyasaconsequenceof microatelectasisatthelungbases.Inindividualpatients,thedistributionoffatmaybemore importantthanBMI.Notableomissionsfromthisreviewaretheeffectsofobesityon respiratorymusclefunction,respiratorydrive,andupperairwaycollapsibility;thesetopicswill beaddressedinotherreviewsinthisseries.Furtherresearchonthedistributionoffatandits effectsmayhelptoelucidatethestillelusiveconceptsofdyspnoea,centralbreathtiming,and chestwallmechanicsinobeseindividuals.

References 1 KrygerMH.Sleepapnea.FromtheneedlesofDionysiustocontinuouspositiveairway pressure.Arch.Intern.Med.1983;143:23012303. 2 BurkiNK,BakerRW.Ventilatoryregulationineucapnicmorbidobesity.Am.Rev.Respir. Dis.1984;129:538543. 3 SampsonMG,GrassinoAE.Loadcompensationinobesepatientsduringquiettidal breathing.JApplPhysiol.1983;55:12691276. 4 PankowW,PodszusT,GutheilT,etal.Expiratoryflowlimitationandintrinsicpositiveend expiratorypressureinobesity.J.Appl.Physiol.1998;85:12361243. 5 ChlifM,KeochkerianD,ChoquetD,etal.Effectsofobesityonbreathingpattern, ventilatoryneuraldriveandmechanics.RespirPhysiolNeurobiol.200930;168:198202. 6 7 LourenoRV.Diaphragmactivityinobesity.J.Clin.Invest.1969;48:16091614. NaimarkA,CherniackRM.Complianceoftherespiratorysystemanditscomponentsin healthandobesity.JApplPhysiol.1960;15:377382. 8 SharpJT,HenryJP,SweanySK,etal.TheTotalWorkofBreathinginNormalandObese Men.J.Clin.Invest.1964;43:728739.

HedenstiernaG,SantessonJ.Breathingmechanics,deadspaceandgasexchangeinthe extremelyobese,breathingspontaneouslyandduringanaesthesiawithintermittent positivepressureventilation.ActaAnaesthesiol.Scand.1976;20:248254.

10 PelosiP,CrociM,RavagnanI,etal.Totalrespiratorysystem,lung,andchestwall mechanicsinsedatedparalyzedpostoperativemorbidlyobesepatients.Chest1996;109: 144151. 11 SurattPM,WilhoitSC,HsiaoHS,etal.Complianceofchestwallinobesesubjects.J.Appl. Physiol.1984;57:403407. 12 MeadJ,GaenslerEA.Esophagealandpleuralpressuresinman,uprightandsupine.J.Appl. Physiol.1959;14:8183. 13 SharpJT,HenryJP,SweanySK,etal.Effectsofmassloadingtherespiratorysysteminman. J.Appl.Physiol.1964;19:959966. 14 LadoskyW,BotelhoMA,AlbuquerqueJPJr.Chestmechanicsinmorbidlyobesenon hypoventilatedpatients.Respir.Med.2001;95:281286. 15 KellyTM,JensenRL,ElliottCG,etal.Maximumrespiratorypressuresinmorbidlyobese subjects.Respiration1988;54:7377. 16 ThomasPS,CowenER,HulandsG,etal.Respiratoryfunctioninthemorbidlyobesebefore andafterweightloss.Thorax1989;44:382386.

17 JonesRL,NzekwuMMU.Theeffectsofbodymassindexonlungvolumes.Chest2006;130: 827833. 18 EmirgilC,SobolBJ.Theeffectsofweightreductiononpulmonaryfunctionandthe sensitivityoftherespiratorycenterinobesity.Am.Rev.Respir.Dis.1973;108:831842. 19 BiringMS,LewisMI,LiuJT,etal.Pulmonaryphysiologicchangesofmorbidobesity.Am.J. Med.Sci.1999;318:293297. 20 ZerahF,HarfA,PerlemuterL,etal.Effectsofobesityonrespiratoryresistance.Chest1993; 103:14701476. 21 RubinsteinI,ZamelN,DuBarryL,etal.Airflowlimitationinmorbidlyobese,nonsmoking men.Ann.Intern.Med.19901;112:828832. 22 RayCS,SueDY,BrayG,etal.Effectsofobesityonrespiratoryfunction.Am.Rev.Respir.Dis. 1983;128:501506. 23 ColletF,MallartA,BervarJF,etal.Physiologiccorrelatesofdyspneainpatientswith morbidobesity.Int.J.Obes(Lond).2007;31:700706. 24 WatsonRA,PrideNB.Posturalchangesinlungvolumesandrespiratoryresistancein subjectswithobesity.J.Appl.Physiol.2005;98:512517. 25 WatsonRA,PrideNB,ThomasEL,etal.Reductionoftotallungcapacityinobesemen: comparisonoftotalintrathoracicandgasvolumes.J.Appl.Physiol.2010;108:16051612.

26 KoenigSM.Pulmonarycomplicationsofobesity.Am.J.Med.Sci.2001;321:24979. 27 CollinsLC,HobertyPD,WalkerJF,etal.Theeffectofbodyfatdistributiononpulmonary functiontests.Chest1995;107:12981302. 28 CaroCG,ButlerJ,DuboisAB.Someeffectsofrestrictionofchestcageexpansionon pulmonaryfunctioninman:anexperimentalstudy.J.Clin.Invest.1960;39:573583. 29 HeymsfieldSB.Developmentofimagingmethodstoassessadiposityandmetabolism.Int. J.Obes(Lond).2008;32Suppl7:S7682. 30 BabbTG,WyrickBL,DeLoreyDS,etal.Fatdistributionandendexpiratorylungvolumein leanandobesemenandwomen.Chest2008;134:704711. 31 LazarusR,SparrowD,WeissST.Effectsofobesityandfatdistributiononventilatory function:thenormativeagingstudy.Chest1997;111:891898. 32 OchsBalcomHM,GrantBJB,MutiP,etal.Pulmonaryfunctionandabdominaladiposityin thegeneralpopulation.Chest2006;129:853862. 33 BabbTG,WyrickBL,ChasePJ,etal.Weightlossviadietandexerciseimprovesexercise breathingmechanicsinobesemen.Chest2011;140:454460. 34 CanoyD,LubenR,WelchA,etal.Abdominalobesityandrespiratoryfunctioninmenand womenintheEPICNorfolkStudy,UnitedKingdom.Am.J.Epidemiol.2004;159:1140 1149.

35 ChenY,RennieD,CormierYF,etal.Waistcircumferenceisassociatedwithpulmonary functioninnormalweight,overweight,andobesesubjects.Am.J.Clin.Nutr.2007;85:35 39. 36 KingGG,BrownNJ,DibaC,etal.Theeffectsofbodyweightonairwaycalibre.Eur.Respir.J. 2005;25:896901. 37 SalomeCM,KingGG,BerendN.Physiologyofobesityandeffectsonlungfunction.J.Appl. Physiol.2010;108:206211. 38 VaughanRW,CorkRC,HollanderD.Theeffectofmassiveweightlossonarterial oxygenationandpulmonaryfunctiontests.Anesthesiology1981;54:325328. 39 FarebrotherMJ,McHardyGJ,MunroJF.Relationbetweenpulmonarygasexchangeand closingvolumebeforeandaftersubstantialweightlossinobesesubjects.Br.Med.J.1974; 3:391393. 40 ZavorskyGS,MuriasJM,KimDJ,etal.Waisttohipratioisassociatedwithpulmonarygas exchangeinthemorbidlyobese.Chest2007;131:362367. 41 HolleyHS,MilicEmiliJ,BecklakeMR,etal.Regionaldistributionofpulmonaryventilation andperfusioninobesity.J.Clin.Invest.1967;46:475481. 42 HurewitzAN,SusskindH,HaroldWH.Obesityaltersregionalventilationinlateraldecubitus position.J.Appl.Physiol.1985;59:774783.

43 DouglasFG,ChongPY.Influenceofobesityonperipheralairwayspatency.J.Appl.Physiol. 1972;33:559563. 44 DempseyJA,ReddanW,RankinJ,etal.Alveolararterialgasexchangeduringmuscular workinobesity.J.Appl.Physiol.1966;21:18071814. 45 SalvadoriA,FanariP,MazzaP,etal.Breathingpatternduringandaftermaximalexercise testinginyounguntrainedsubjectsandinobesepatients.Respiration1993;60:162169. 46 BaylorP,GoebelP.Clinicalcorrelatesofanelevateddiffusingcapacityforcarbonmonoxide correctedforalveolarvolume.Am.J.Med.Sci.1996;311:266271. 47 SalvadoriA,FanariP,MazzaP,etal.Workcapacityandcardiopulmonaryadaptationofthe obesesubjectduringexercisetesting.Chest1992;101:674679. 48 BabbTG,KorzickD,MeadorM,etal.Ventilatoryresponseofmoderatelyobesewomento submaximalexercise.Int.J.Obes.1991;15:5965. 49 WhippBJ,DavisJA.Theventilatorystressofexerciseinobesity.Am.Rev.Respir.Dis.1984; 129:S9092. 50 LiJ,LiS,FeuersRJ,etal.Influenceofbodyfatdistributiononoxygenuptakeand pulmonaryperformanceinmorbidlyobesefemalesduringexercise.Respirology2001;6:9 13. 51 SoodA.Alteredrestingandexerciserespiratoryphysiologyinobesity.Clin.ChestMed. 2009;30:445454,vii.

52 SinDD,JonesRL,ManSFP.Obesityisariskfactorfordyspneabutnotforairflow obstruction.Arch.Intern.Med.2002;162:14771481. 53 StulbargM,AdamsL.Dyspnea.In:MasonRJ,MurrayJF,BroaddusVC,etal.(eds.)Murray andNadelsTextbookofRespiratoryMedicine.ElsevierScienceHealthSciencediv;p.816 818. 54 ElGamalH,KhayatA,ShikoraS,etal.Relationshipofdyspneatorespiratorydriveand pulmonaryfunctiontestsinobesepatientsbeforeandafterweightloss.Chest2005;128: 38703874. 55 SahebjamiH.Dyspneainobesehealthymen.Chest1998;114:13731377. 56 LottiP,GigliottiF,TesiF,etal.Respiratorymusclesanddyspneainobesenonsmoking subjects.Lung2005;183:311323. 57 KressJP,PohlmanAS,AlverdyJ,etal.Theimpactofmorbidobesityonoxygencostof breathing(VO(2RESP))atrest.Am.J.Respir.Crit.CareMed.1999;160:883886. 58 BabbTG,RanasingheKG,ComeauLA,etal.Dyspneaonexertioninobesewomen: associationwithanincreasedoxygencostofbreathing.Am.J.Respir.Crit.CareMed.2008; 178:116123. 59 WeinerP,WaizmanJ,WeinerM,etal.Influenceofexcessiveweightlossaftergastroplasty formorbidobesityonrespiratorymuscleperformance.Thorax1998;53:3942.

60 HakalaK,MustajokiP,AittomkiJ,etal.Effectofweightlossandbodypositionon pulmonaryfunctionandgasexchangeabnormalitiesinmorbidobesity.Int.J.Obes.Relat. Metab.Disord.1995;19:343346.

Legendsforfigures: Figure1Summaryoftheeffectofobesityonlungvolumes.Expiratoryreservevolume(ERV)is decreasedinobesity.Functionalresidualcapacity(thesumofERVandresidualvolume)is usuallydecreasedaswell,buttoalesserextent,sinceRVisusuallyrelativelywellpreserved. Tidalvolumeisusuallyreduced,butnottotheextentthatitisapparentinthisschematic.Total lungcapacitycanbeslightlyreducedornormal.From:SoodA.Alteredrestingandexercise respiratoryphysiologyinobesity.Clin.ChestMed.2009;30:445454. Figure2Exponentialrelationshipbetweenexpiratoryreservevolume(ERV)andBMI.Notethat ERVfallsbelowtherangeofnormal(<80%predicted)ataBMIof25kg/m2,whichisconsidered merelyoverweight.Ther2valueforERVis0.49(P<0.0001).FromJonesR,NzekwuM.The effectsofbodymassindexonlungvolumes.Chest2006;130:827833. Figure3Flowvolumeloopsfromahealthyobesefemale,aged35,BMI43kg/m2,withreduced TLC,FRC,andVC,butwellpreservedexpiratoryfollows.Thedashedlineshowsthepredicted flowvolumeloop,andthesolidlinetheactualloop.Thepredictedlungvolumesareshownon thebar,theverticalarrowshowspredictedflowat50%capacity,andthehorizontalarrow showstheactualvolume.From:SalomeCM,KingGG,BerendN.Physiologyofobesityand effectsonlungfunction.J.Appl.Physiol.2010;108:206211. Figure4Relationshipbetweenoxygencostofbreathingandratingofperceivedbreathlessness (RPB)inobesewomenwith(n=7)orwithout(n=7)exertionaldyspnoeaduringavoluntary eucapnichyperpnoeaprotocol.ReprintedwithpermissionoftheAmericanThoracicSociety. CopyrightAmericanThoracicSociety.From:TGBabb,KGRanasinghe,LAComeau,TLSemon, BSchwartz;2008;Dyspneaonexertioninobesewomen;AmericanJournalofRespiratoryand CriticalCareMedicine;Volume178,pp.116123.OfficialJournaloftheAmericanThoracic Society.

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