AdvAnces in GeRd...GERD. Therefore, if an asthma patient who has severe GERD continues to have GERD...
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Gastroenterology & Hepatology Volume 8, Issue 6 June 2012 401 GERD ADVANCES IN GERD Section Editor: Joel E. Richter, MD Current Developments in the Management of Acid-Related GI Disorders Is There a Relationship Between GERD and Asthma? John G. Mastronarde, MD Professor of Internal Medicine Director, The Ohio State University Asthma Center The Wexner Medical Center at The Ohio State University Columbus, Ohio G&H How prevalent is gastroesophageal reflux disease in asthma patients? JGM Approximately 25 million Americans have asthma. How many of these individuals have gastroesophageal reflux disease (GERD) depends on how GERD is defined. e prevalence of GERD certainly appears to be higher in asthma patients than in the general population, but stud- ies have used different definitions of GERD, making it difficult to compare their findings and compile data. e prevalence of GERD in asthma patients has ranged from 25% to 80% in studies, many of which use self-reported GERD. In a study conducted by the American Lung Association Asthma Clinical Research Centers (ACRC) Network, 38% of asthma patients had GERD (as defined by a positive pH probe). G&H Do all patients with asthma and GERD exhibit classic symptoms of GERD? JGM ere is certainly a population of asthma patients who have classic symptoms of GERD, including heart- burn. Among these symptomatic GERD patients, pulmo- nary symptoms, notably cough, may also occur. However, a significant number of asthma patients have silent GERD (ie, GERD only detected by pH probes). In the previously mentioned ACRC study, none of the 38% of patients who had a positive pH probe had classic symptoms of GERD. G&H What has been the historical understanding of the relationship between GERD and asthma? JGM It has long been thought that treatment of reflux in asthma patients improves their asthma. is belief was even reflected in the last set of guidelines from the National Institutes of Health (NIH) for the treatment of asthma. ese guidelines recommended that physi- cians consider administering an empiric trial of antireflux therapy to patients with poorly controlled asthma, even in the absence of GERD symptoms. ese guidelines were based on both animal studies, where acid instilled in the esophagus resulted in airway hyperresponsiveness, and previous clinical trials that all had significant limitations such as small sample size, poorly defined asthma, poorly defined GERD, and inadequate treatment time. G&H What is the current understanding of the relationship between GERD and asthma? JGM e answer to this question is a bit controver- sial. Again, it depends on how GERD is defined and if GERD is symptomatic or not. In terms of acid reflux, there appears to be 2 different groups of patients with asthma and GERD, as previously mentioned. One group has asthma and classic GERD symptoms. Some data suggest that GERD treatment in these patients improves their quality of life and may improve asthma exacerbations. In addition, GERD treatment may cause small increases in lung function that are statistically sig- nificant but of questionable clinical significance. us, at this time, it appears that there may be some relation- ship between symptomatic GERD and asthma-related quality of life and, possibly, exacerbations in these patients, and treatment of GERD in these patients may have some impact on their asthma. e second group of patients have asthma and silent GERD. Several large studies, including a recent pedi- atric study conducted by the American Lung Associa- tion ACRC Network that was recently published in e
Transcript of AdvAnces in GeRd...GERD. Therefore, if an asthma patient who has severe GERD continues to have GERD...
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AdvAnces in GeRd
section editor: Joel e. Richter, Md
C u r r e n t D e v e l o p m e n t s i n t h e M a n a g e m e n t o f A c i d - R e l a t e d G I D i s o r d e r s
Is There a Relationship Between GERD and Asthma?
John G. Mastronarde, MDProfessor of Internal MedicineDirector, The Ohio State University Asthma CenterThe Wexner Medical Center at The Ohio State UniversityColumbus, Ohio
G&H How prevalent is gastroesophageal reflux disease in asthma patients?
JGM Approximately25millionAmericanshaveasthma.How many of these individuals have gastroesophagealrefluxdisease(GERD)dependsonhowGERDisdefined.TheprevalenceofGERDcertainlyappearstobehigherinasthmapatientsthaninthegeneralpopulation,butstud-ieshaveuseddifferentdefinitions ofGERD,making itdifficulttocomparetheirfindingsandcompiledata.TheprevalenceofGERDinasthmapatientshasrangedfrom25%to80%instudies,manyofwhichuseself-reportedGERD. In a study conducted by the American LungAssociation Asthma Clinical Research Centers (ACRC)Network,38%ofasthmapatientshadGERD(asdefinedbyapositivepHprobe).
G&H Do all patients with asthma and GERD exhibit classic symptoms of GERD?
JGM There is certainly a populationof asthmapatientswho have classic symptoms of GERD, including heart-burn. AmongthesesymptomaticGERDpatients,pulmo-narysymptoms,notablycough,mayalsooccur.However,asignificantnumberofasthmapatientshavesilentGERD(ie,GERDonlydetectedbypHprobes).InthepreviouslymentionedACRCstudy,noneofthe38%ofpatientswhohadapositivepHprobehadclassicsymptomsofGERD.
G&H What has been the historical understanding of the relationship between GERD and asthma?
JGM Ithas longbeenthoughtthat treatmentofrefluxin asthma patients improves their asthma. This belief
was even reflected in the last setofguidelines from theNational Institutes of Health (NIH) for the treatmentof asthma. These guidelines recommended that physi-ciansconsideradministeringanempirictrialofantirefluxtherapytopatientswithpoorlycontrolledasthma,evenintheabsenceofGERDsymptoms.Theseguidelineswerebasedonbothanimalstudies,whereacidinstilledintheesophagus resulted in airway hyperresponsiveness, andpreviousclinicaltrialsthatallhadsignificantlimitationssuchassmallsamplesize,poorlydefinedasthma,poorlydefinedGERD,andinadequatetreatmenttime.
G&H What is the current understanding of the relationship between GERD and asthma?
JGM The answer to this question is a bit controver-sial.Again,itdependsonhowGERDisdefinedandifGERDissymptomaticornot.Intermsofacidreflux,thereappearstobe2differentgroupsofpatientswithasthma and GERD, as previously mentioned. OnegrouphasasthmaandclassicGERDsymptoms.Somedata suggest that GERD treatment in these patientsimprovestheirqualityoflifeandmayimproveasthmaexacerbations.Inaddition,GERDtreatmentmaycausesmallincreasesinlungfunctionthatarestatisticallysig-nificantbutofquestionableclinicalsignificance.Thus,atthistime,itappearsthattheremaybesomerelation-shipbetween symptomaticGERDandasthma-relatedquality of life and, possibly, exacerbations in thesepatients,andtreatmentofGERDinthesepatientsmayhavesomeimpactontheirasthma.
ThesecondgroupofpatientshaveasthmaandsilentGERD. Several large studies, including a recent pedi-atric study conducted by the American Lung Associa-tionACRCNetworkthatwasrecentlypublishedinThe
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Journal of the American Medical Association,haveprettyconvincingly demonstrated that asthma patients (bothadults and children) who have asymptomatic GERDdemonstrated by pH probe testing do not have anyimprovementsintheirasthmacontrolorlungfunctionwhentreatedwithprotonpumpinhibitors.
Theserecent,largeclinicaltrialshavefocusedonthetreatmentofacidreflux.Atheoryhasbeenputforththatalkali GERD may worsen asthma control; however, todate,thistheoryhasbeenlargelyunproven,asonlyafewsmallstudieshaveevaluatedthistypeofGERD.Alargerandomized controlled trial with well-defined asthmapatientsandobjectivedocumentationofalkaliGERDisrequiredtoanswerthisimportantclinicalquestion.
Thus, to date, although GERD treatment mayresult in nonspecific improvements in quality of lifein patients with symptomatic GERD and asthma, bynowIthinktherehavebeenenoughstudies,includingthe ACRC study, to conclude that treatment of silentGERDdoesnotimproveasthmaatall.Thisconclusionisasignificantchangefromwhatdoctorshavebelievedfor a long time. I amnot certain thatGERD-inducedasthmaexists.Clearly, somepatientswithGERDhaverespiratory symptoms, primarily cough, but the exactmechanism for this relationship is unclear, which, Ithink, is part of the confusion in this area. However,I do not believe that the presence of these respiratorysymptoms isequivalentor sufficient tomakethediag-nosisofchronicinflammatoryasthma.IwonderifthereareothereffectsofGERD,suchasworseningofvocalcorddysfunction,thatmaymimicasthmaandhaveledusinthepasttoerroneouslyconcludethatGERDwasworseningasthma.
G&H Why then is GERD more common in asthma patients than in the general population?
JGM ItisnotentirelyclearwhyGERDismorecommoninasthmapatients.Severaltheorieshavebeenadvanced,withthemostcommononebeingthatpressureswingsin the thorax of asthmatics allow more acid to refluxinto the esophagus.There are animal studies that sug-gestthatinstillationofacidintheesophagusstimulatesvagal tone and may increase respiratory resistance and“prime”theairwaysforbronchoconstriction.Theseandother animal studies suggest that chronic microaspira-tion from GERD may trigger bronchoconstrictionandalsopossiblyincreaseinflammationintheairways.However,thishypothesishasnotbeenadequatelytestedin humans. In addition, some asthma medications,specificallyb-agonistsandtheophylline,mayreducetheloweresophagealsphinctertoneand,thus,promoteacid
refluxinasthmatics;however,againtheclinicalimpactof these changes does not appear to be significant, atleastinpatientswithasymptomaticGERD.
G&H Why does GERD treatment improve (albeit only by a little) quality of life in patients with symptomatic GERD?
JGM Iamnotcertainthat there isagoodanswertothis question. It may be that effective treatment ofGERDresultsinanimprovementinoverallwell-beingandis,thus,reflectedinimprovedqualityofliferelatedtoasthma.
G&H Have any studies examined the impact of nonmedical GERD treatment on asthma?
JGM Most studies looking at GERD treatment andasthmahaveevaluatedeitherH2blockersorprotonpumpinhibitors,which,asisknown,donotcurereflux.SomeresearchershavestartedtowonderwhetherotherGERDtreatments,suchasNissenfundoplication,wouldimprovepatients’ asthma. Thus far, all of the studies evaluatingwhetherNissen fundoplication(orother surgicalproce-dures that eliminate reflux) improves asthma outcomeshave been case reports or very small cohort studies; norandomizedtrialshaveyetbeenconductedonthisissue.Asthefindingshavebeenvariable,definitivelyansweringthis question would require a large randomized trial ofNissenfundoplicationversusshamNissenfundoplicationin well-defined asthma patients with objective evidenceofGERD.However, thisstudywouldbeexpensiveandchallengingtoconduct,soIamnotcertainthatwewillgetagoodanswertothisquestion.
G&H Should patients with asthma and symptomatic GERD receive the same treatment as GERD patients without asthma?
JGM Yes, anasthmapatientwith symptomaticGERDshould be treated the same as a nonasthmatic patientwith symptomatic GERD. GERD treatment should befocused on reducing GERD symptoms and preventingsequelae,as itdoesnothavemuchofan impactonthepatient’sasthma,aspreviouslydiscussed.
Likewise,whendeterminingwhetherthesepatientsshould receive surgical therapy,doctors should followthe standard guidelines for treatment of refractoryGERD.Therefore,ifanasthmapatientwhohassevereGERD continues to have GERD symptoms despitestandard medical treatment, a Nissen fundoplicationshouldbeconsidered,justasifthepatientwereanon-asthmaticwithsevereGERD.
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G&H Has the general community adopted these new treatment guidelines (ie, that asthma patients with silent GERD should no longer receive GERD treatment)? Is there harm in continuing to administer GERD treatment to patients with silent GERD?
JGM Therearenodataavailableontheimpactoftheserecent data on clinical practice. It will be interesting toseehowtheNIHasthmaguidelinesreviewthisissue,asIexpectthattheNIHmaychangeitspreviousrecommen-dation fora trialof empiricGERDtreatment inpoorlycontrolledasthmatics.
Therearegrowingconcernsofsideeffectsofprotonpumpinhibitortherapy,includingapotentialincreaseinupperrespiratoryinfectionsorpneumoniasaswellasfrac-turesinchildren.Inaddition,thesemedicationsareveryexpensive. However, my major concern is that a protonpumpinhibitortrialinasthmapatientswithasymptomaticGERDwillhavenoimpactontheirasthmaandjustdelaysothertherapiesfocusedontheirasthma.
G&H What are the next steps in research?
JGM As mentioned above, the relationship betweenalkali refluxandasthma shouldbe further investigated.It would also be good to conduct a definitive trial ofGERDandasthmacomparingsurgicaltreatments(suchasNissen fundoplicationor laparoscopic therapies)andmedical treatments; however, as mentioned previously,this trialwouldbeexpensive, require shamprocedures/surgery, and need a very large patient population for
adequatepower. Atthistime,themajorneediseducationregarding the new evidence that asymptomatic GERDdoesnot impact asthma,whichwill hopefully steer cli-nicians toward other, more effective therapies for theirpatientswithpoorlycontrolledasthma.
Suggested Reading
WritingCommitteefortheAmericanLungAssociationAsthmaClinicalResearchCenters;Holbrook JT,WiseRA,GoldBD,et al.Lansoprazole for childrenwithpoorlycontrolledasthma:arandomizedcontrolledtrial.JAMA.2012;307:373-381.
Riscili BP, Parsons JP, Mastronarde JG. Treating silent reflux disease does notimprovepoorlycontrolledasthma.Cleve Clin J Med.2010;77:155-160.
DiMangoE,HolbrookJT,SimpsonE,etal;AmericanLungAssociationAsthmaClinical Research Centers. Effects of asymptomatic proximal and distal gastro-esophagealrefluxonasthmaseverity.Am J Respir Crit Care Med.2009;180:809-816.
Parsons JP, Mastronarde JG. Gastroesophageal reflux disease and asthma. Curr Opin Pulm Med.2010;16:60-63.
AmericanLungAssociationAsthmaClinicalResearchCenters;MastronardeJG,AnthonisenNR,CastroM,etal.Efficacyofesomeprazolefortreatmentofpoorlycontrolledasthma.N Engl J Med.2009;360:1487-1499.
Littner MR, Leung FW, Ballard ED 2nd, Huang B, Samra NK; LansoprazoleAsthma Study Group. Effects of 24 weeks of lansoprazole therapy on asthmasymptoms,exacerbations,qualityof life,andpulmonaryfunctioninadultasth-maticpatientswithacidrefluxsymptoms.Chest.2005;128:1128-1135.
KiljanderTO,HardingSM,FieldSK,etal.Effectsofesomeprazole40mgtwicedailyonasthma:arandomizedplacebo-controlledtrial.Am J Respir Crit Care Med.2006;173:1091-1097.
KiljanderTO,JunghardO,BeckmanO,LindT.Effectofesomeprazole40mgonceortwicedailyonasthma:arandomized,placebo-controlledstudy.Am J Respir Crit Care Med.2010;181:1042-1048.
ChanWW,ChiouE,ObsteinKL,TignorAS,WhitlockTL.Theefficacyofprotonpumpinhibitorsforthetreatmentofasthmainadults:ameta-analysis.Arch Intern Med.2011;171:620-629.
BenningerC,Parsons JP,Mastronarde JG.Vocal corddysfunctionandasthma.Curr Opin Pulm Med.2011;17:45-49.
