Ineffective esophageal motility does not equate to GERD

EDITORIALSIneffective Esophageal Motility Does Not Equate to GERDIn this issue of The American Journal of Gastroenterology, Vinjirayer et al.(1)test the hypothesis that ineffective esophageal motility(IEM)is a marker of gastroesophageal reflux disease(GERD)and conclude otherwise(2,3).By way of background,IEM is characterized by frequent hy-potensive or failed peristaltic contractions and is found in 20–50%of GERD patients(2–5).Studies have also reported that patients with IEM have increased esophageal acid ex-posure compared with patients with normal peristalsis,im-plying a causal relationship(2–4,6).Thesefindings have led some investigators to suggest that IEM be considered a marker for GERD,that the disorder has pathophysiological significance,and that GERD severity may parallel the se-verity of this motor abnormality(2,3).The current study by Vinjirayer et al.(1)suggests that the relationship between IEM and GERD may have been somewhat overstated. Using ambulatory pH data as an indicator of GERD, Vinjirayer et al.retrospectively compared the prevalence of IEM in patients with either normal or abnormal esophageal acid exposure(1)and found a similar prevalence of IEM to that previously reported.However,contrary to expectation, there was no difference in the prevalence of IEM in patients with or without abnormal esophageal acid exposure,and no parallel existed between the severity of IEM and esophageal acid exposure.This led the authors to both challenge the association between IEM and GERD and to question the pathophysiological significance of the entity.Each of these issues deserves careful scrutiny.In challenging the association between IEM and GERD, Vinjirayer et al.(1)are suggesting that the null hypothesis is true(e.g.,that no association exists,and IEM might simply be an age-related phenomenon).Alternatively,Vin-jirayer et al.may have found no association because their method for defining GERD and stratifying disease severity was seriouslyflawed(1).Is it reasonable,after all,to take a symptomatic group of patients and conclude that only the subset with excessive esophageal acid exposure during an ambulatory esophageal pH monitoring study had GERD?If such were the case,life as an esophagologist would be simple to the point of boredom.Ambulatory pH monitoring may well be the best available test for diagnosing GERD, but it has a sensitivity as low as70%in patients with esophagitis and substantially lower in patients with nonero-sive disease(7).GERD is a multifaceted entity that has consistently defied any attempt at a simple definition.Con-sider for example the definition recently labored over by the Genval workshop:“...all individuals who are exposed to the risk of physical complications from gastrooesophageal reflux,or who experience clinically significant impairment of health related well being(quality of life)due to reflux related symptoms,after adequate assurance of the benign nature of their symptoms”(8).Examined within the context of the Genval definition, most if not all of the patients in the study by Vinjirayer et al.(1)probably had GERD,and the failure to demonstrate stratification of IEM by disease severity was probably re-flective of this being a relatively homogenous GERD pop-ulation without adequate representation of either nondis-eased individuals or severely diseased individuals.To achieve the latter would require incorporation of both en-doscopic and acid sensitivity data as was done in one of the original descriptions of the relationship between peristaltic dysfunction in GERD(9).That study of177patients and asymptomatic controls used a somewhat more stringent definition of peristaltic dysfunction than IEM and found it to be present in9%of normal controls,21%of patients with nonerosive GERD,26%of patients with mild esophagitis, and48%of patients with severe esophagitis.Although peri-staltic dysfunction was more common with increasing se-vere esophagitis,it was neither a prerequisite for the disease nor afinding unique to the patient populations.Clearly,a definitive analysis of the relationship between IEM and GERD would ultimately require population-based data but, short of that,it seems appropriate that the percentages de-scribed in the earlier report should prevail.The other issue raised in the report by Vinjirayer et al.(1) was of the pathophysiological significance of IEM.Con-ceivably,IEM could be associated with dysphagia or,as focused on in the current report,acid clearance.The period that the esophageal mucosa remains at a pHϽ4after gas-troesophageal reflux is defined as the acid clearance time. Acid clearance begins with emptying the refluxedfluid from the esophagus and is completed by titration of residual acid by swallowed saliva.Previous analysis of the relationship between peristaltic dysfunction and the efficacy of esopha-geal emptying using concurrent manometry andfluoroscopy illustrated that absent or incomplete peristaltic contractions invariably resulted in little or no volume clearance(10). Additionally,regional hypotensive peristalsis was some-times associated with incomplete volume clearance by the mechanism of retrograde escape of barium through the region of hypotensive contraction.The lower the peristaltic amplitude the greater the likelihood of impaired clearance. For example,peristaltic amplitudes in the distal esophagus Ͼ30mm Hg were almost always completely effective, amplitudes between26and30mm Hg were effective60% of the time,and amplitudesϽ25mm Hg were almost always ineffective.Thus,peristaltic dysfunction could po-tentially prolong esophageal acid clearance by delaying the first phase,that of esophageal emptying.T HE A MERICAN J OURNAL OF G ASTROENTEROLOGY Vol.98,No.4,2003©2003by Am.Coll.of Gastroenterology ISSN0002-9270/03/$30.00 Published by Elsevier Science Inc.Recognizing the relationship between peristaltic function and esophageal emptying,Leite et al.attempted to re fine manometric diagnoses in the context of GERD by quanti-fying the occurrence of manometric findings with functional relevance:failed or hypotensive peristalsis (6).They de fined IEM by the occurrence of low amplitude (Ͻ30mm Hg)or nontransmitted contractions in the distal esophagus with 30%or more of water swallows (6).A retrospective review of 600consecutive manometric tracings from patients re-ferred to the motility laboratory at the Graduate Hospital then identi fied 61with IEM and,of these,35also had ambulatory esophageal pH monitoring studies.These 35ambulatory pH studies were then compared with those of 150other patients without IEM.The comparison revealed that the IEM patients had signi ficantly prolonged esopha-geal acid clearance in both the upright and recumbent po-sitions compared with patients with normal motility.Thus,the relationship between acid clearance and IEM was first suggested in the literature.However,the impact of IEM on esophageal acid clearance needs to be viewed in the context that it is only one of two potential mechanisms of impaired acid clearance in GERD;the other is re-re flux from a hiatal hernia (11–13).A number of analyses suggest that the most profound determinant of prolonged acid clearance is hiatus hernia (14,15),and neither the report by Leite et al.(6)nor the current report by Vinjirayer et al.(1)provide data on hiatus hernia.A mechanistic study evaluating the ef ficacy of esophageal emptying in a large group of GERD patients and normal controls provided some insight into the relative signi ficance of peristaltic dysfunction and hiatus hernia in the impair-ment of acid clearance (13).Re flux patients exhibited pro-gressive impairment of esophageal emptying compared with controls,and the degree of impairment was greatest in patients with esophagitis (Fig.1).Furthermore,the domi-nant site of impaired emptying was from the phrenic am-pulla (likely hiatus hernia in many cases)as opposed to the tubular esophagus,suggesting that hiatus hernia is the dom-inant in fluence.Failure to demonstrate a signi ficant effect of IEM on acid clearance in the current paper (1)is likely attributable to ignoring the more dominant determinant.Conversely,the demonstration of a signi ficant correlation between IEM and prolonged clearance by Liete et al.(6)was likely attributable to the co-occurrence of hiatus hernia in the IEM group who are also more likely to have had esophagitis.The above arguments are structured to place IEM in perspective.GERD can potentially result from any combi-nation of the numerous physiological aberrations that have been identi fied in GERD populations.Attempting to equate IEM with GERD withstands scrutiny no better than does equating a hypotensive lower esophageal sphincter to GERD or hiatus hernia to GERD.However,although Vin-jirayer et al.(1)do illustrate that IEM in and of itself is unlikely to be the major determinant of abnormal esopha-geal acid exposure,the data presented here do not disprove some association between GERD and IEM.Rather,IEM joins the ever-lengthening list of physiological abnormali-ties associated with GERD but is incapable of standing alone in the diagnosis ofGERD.Figure 1.Esophageal emptying characteristics among study groups.Emptying in each esophageal region was scored from 0to 3(0if there was no residue,1if there was residue estimated to be less than one fourth of the ingested bolus,2for one fourth to one half of the ingested bolus,and 3if the residue was more than one half the ingested bolus).Group data are expressed as mean ϮSD.Modi fied from Lin et al.(13).ENRD ϭEndoscopy negative re flux disease.716Editorials AJG –Vol.98,No.4,2003ACKNOWLEDGMENTThis work was supported by grant RO1DC00646(PJK)and K23DK62170-01(JEP)from the Public Health Service.Peter J.Kahrilas,M.D.John E.Pandolfino,M.D.Department of MedicineNorthwestern UniversityThe Feinberg School of MedicineChicago,IllinoisREFERENCES1.Vinjirayer E,Gonzalez B,Brensinger C,et al.Ineffectivemotility is not a marker for gastroesophageal reflux disease.Am J Gastroenterol2003;98:771–6.2.Diener U,Patti MG,Molena D,et al.Esophageal dysmotilityand gastroesophageal reflux disease.J Gastrointest Surg2001;5:260–5.3.Ho SC,Chang CS,Wu CY,et al.Ineffective esophagealmotility is a primary motility disorder in gastroesophageal reflux disease.Dig Dis Sci2002;47:652–6.4.Fouad YM,Katz PO,Hatlebakk JG,et al.Ineffective esoph-ageal motility:The most common motility abnormality in patients with GERD-associated respiratory symptoms.Am J Gastroenterol1999;94:1464–7.5.Knight RE,Wells JR,Parrish RS.Esophageal dysmotility asan important co-factor in extraesophageal manifestations of gastroesophageal reflryngoscope2000;110:1462.6.Leite LP,Johnston BT,Barrett J,et al.Ineffective esophagealmotility(IEM):The primaryfinding in patients with nonspe-cific esophageal motility disorder.Dig Dis Sci1997;42:1859–65.7.Kahrilas PJ,Quigley EM.Clinical esophageal pH recording:Atechnical review for practice guideline development.Gastro-enterology1996;110:1982–96.8.Dent J,Brun J,Fendrick AM,Fennerty MB,Janssens J,Kahrilas PJ,Lauritsen K,Reynolds JC,Shaw M,Talley NJ on behalf of the Genval Workshop Group.An evidence-based appraisal of reflux disease management–The Genval Work-shop Report.Gut1999;44(suppl2):S1–16.9.Kahrilas PJ,Dodds WJ,Hogan WJ,et al.Esophageal peristal-tic dysfunction in peptic esophagitis.Gastroenterology1986;91:897–904.10.Kahrilas PJ,Dodds WJ,Hogan WJ.Effect of peristaltic dys-function on esophageal volume clearance.Gastroenterology 1988;94:73–80.11.Mittal RK,Lange RC,McCallum RW.Identification andmechanism of delayed esophageal acid clearance in subjects with hiatus hernia.Gastroenterology1987;92:130–5.12.Sloan S,Kahrilas PJ.Impairment of esophageal emptying withhiatal hernia.Gastroenterology1991;100:596–605.13.Lin S,Ke M,Xu J,et al.Impaired esophageal emptying inreflux disease.Am J Gastroenterol1994;89:1003–6.14.Johnson LF.24-hour pH monitoring in the study of gastro-esophageal reflux.J Clin Gastroenterol1980;2:387–99. 15.Jones MP,Sloan SS,Rabine JC,et al.Hiatal hernia size is thedominant determinant of esophagitis presence and severity in gastroesophageal reflux disease.Am J Gastroenterol2001;96: 1711–7.Reprint requests and correspondence:Peter J.Kahrilas,M.D., Northwestern University,Feinberg School of Medicine,Depart-ment of Medicine,Division of Gastroenterology,676N.St.Clair Street,Suite1400,Chicago,IL60611.Received Dec.13,2002;accepted Jan.2,2003.The Real Cost of Pediatric Crohn’s Disease:The Role of Infliximab in the Treatment of Pediatric IBDThe true incidence and prevalence of inflammatory bowel disease(IBD)in children is unknown,but25%of the patients diagnosed with IBD are younger than21years of age.In Western populations,the estimated incidence in childhood ranges from two tofive cases per100,000pop-ulation per year with a prevalence of approximately20per 100,000population.Most children develop symptoms as teenagers with60%of affected children presenting between 16and21years and30%between11and15years of age. About10%of the children diagnosed with IBD areϽ10 years of age.Crohn’s disease is approximately twice as common as ulcerative colitis in children and adolescents. Children with IBD suffer from a variety of conditions associated with the disease and complications of medica-tions used to treat the disease.At diagnosis,the most com-mon symptom of Crohn’s disease is weight loss,which occurs in90%of children.Two thirds of the children have diarrhea,and half will suffer from recurrent bouts of ab-dominal pain.Rectal bleeding and fever occur in20–25%of children.Ten percent of children will have arthritis that may precede the development of bowel symptoms.Like adults, children also are prone to a number of other extraintestinal manifestations of IBD including erythema nodosum,pyo-derma gangrenosum,iritis,episcleritis,uveitis,and a pre-disposition to renal calculi.IBD-associated hypercoaguabil-ity in children has been linked with the development of deep vein thrombosis,pulmonary emboli,and neurovascular complications.The frequency of extraintestinal manifesta-tions tends to increase with duration of disease in childhood. Crohn’s disease with an onset before the age of10years may be particularly devastating(1,2).One of the most troubling effects of Crohn’s disease with an onset in child-hood is linear growth retardation.In adult populations with childhood-onset IBD,longitudinal studies demonstrate that about one third of the patients have permanent deficits in height.In a report of834children with Crohn’s disease followed over30years,9%were found to be less than the third percentile in height(3).Kirschner followed30children with Crohn’s disease presenting in thefirst2decades of life into adulthood and found that half the individuals were less than the10th percentile in height(4).Markowitz and Daum followed48adults with childhood-onset IBD and found that 25%of the Crohn’s disease patients were less than thefifth percentile in height compared with10%of patients suffer-ing from ulcerative colitis(5).717AJG–April,2003Editorials。