Esophageal Hypervigilance and Visceral Anxiety Are Contributors to Symptom Severity Among Patients Evaluated With High-Resolution Esophageal Manometry.

OBJECTIVES: Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM. METHODS: Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM. RESULTS: Two hundred thirty-six patients, aged 18-85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (Radj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: Radj = 0.118 (P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant. DISCUSSION: In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

Role of esophageal manometry in children with refractory gastroesophageal reflux symptoms.

BACKGROUND: We investigated the prevalence of psychiatric referral, frequency of repeat upper gastrointestinal (UGI) contrast studies, and esophagogastroduodenoscopy (EGD) in children with ineffective esophageal motility (IEM) before the confirmation of esophageal dysmotility. METHODS: A total of 19 children (nine boys, 10 girls; mean age, 13.80 ± 5.10 years) with symptoms of refractory gastroesophageal reflux (GER) who underwent high-resolution esophageal impedance manometry (HRIM) were enrolled in this retrospective analysis. Refractory GER symptoms were defined as persistent symptoms even under acid-suppression therapy for 8 weeks in this study. Clinical data including age, gender, time from symptom onset to diagnosis, and number of UGI contrast studies and EGD before diagnosis were obtained. HRM parameters and the prevalence of psychiatric referral were also analyzed. RESULTS: There are 14 children (73.68%) diagnosed with IEM by HRIM, and another 5 children (26.32%) diagnosed as GER disease (GERD) by EGD. A significant proportion of IEM children were misdiagnosed with psychological problems compared with the GERD children (78.57% vs 20.00%, P = 0.04). Three IEM children (21.43%) received antipsychotic and antidepressant agents before diagnosis of IEM, and all of them discontinued these medications after diagnosis. IEM children underwent a greater number of UGI contrast studies (1.07 ± 0.92 vs 0.20 ± 0.45; P = 0.02) and EGD (2.36 ± 2.50 vs 0.60 ± 0.55; P = 0.03) before HRM than GERD children. CONCLUSIONS: Esophageal manometry for the diagnosis of IEM should be considered in children with GER symptoms refractory to acid-suppression therapy for 8 weeks to avoid repeat UGI contrast studies, EGD, and psychological therapy.

Impact of symptom burden and health-related quality of life (HRQOL) on esophageal motor diagnoses.

BACKGROUND: High-resolution manometry (HRM) categorizes esophageal motor processes into specific Chicago Classification (CC) diagnoses, but the clinical impact of these motor diagnoses on symptom burden remain unclear. METHODS: Two hundred and eleven subjects (56.8±1.0 years, 66.8% F) completed symptom questionnaires (GERDQ, Mayo dysphagia questionnaire [MDQ], visceral sensitivity index, short-form 36, dominant symptom index, and global symptom severity [GSS] on a 100-mm visual analog scale) prior to HRM. Subjects were stratified according to CC v3.0 and by dominant presenting symptom; contraction wave abnormalities (CWA) were evaluated within "normal" CC. Symptom burden, impact of diagnoses, and HRQOL were compared within and between cohorts. KEY RESULTS: Major motor disorders had highest global symptom burden (P=.02), "normal" had lowest (P<.01). Dysphagia (MDQ) was highest with esophageal outflow obstruction (P=.02), but reflux symptoms (GERDQ) were similar in CC cohorts (P=ns). Absent contractility aligned best with minor motor disorders. Consequently, pathophysiologic categorization into outflow obstruction, hypermotility, and hypomotility resulted in a gradient of decreasing dysphagia and increasing reflux burden (P<.05 across groups); GSS (P=.05) was highest with hypomotility and lowest with "normal" (P=.002). Within the "normal" cohort, 33.3% had CWA; this subgroup had symptom burden similar to hypermotility. Upon stratification by symptoms, symptom burden (GSS, MDQ, HRQOL) was most profound with dysphagia. CONCLUSIONS AND INFERENCES: Chicago Classification v3.0 diagnoses identify subjects with highest symptom burden, but pathophysiologic categorization may allow better stratification by symptom type and burden. Contraction wave abnormalities are clinically relevant and different from true normal motor function. Transit symptoms have highest yield for a motor diagnosis.

Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk Factors, and Effects on Quality of Life.

BACKGROUND & AIMS: Systemic scleroderma (SSc) is associated with esophageal aperistalsis and hypotensive esophagogastric junction pressure, although there could be a gradation in esophageal motor dysfunction. We characterized esophageal motor function by high-resolution esophageal manometry (HRM) and assessed associations between SSc severity, health-related quality of life (HRQOL), and HRM findings in patients. METHODS: We performed a prospective study of 200 patients with SSc and 102 patients without SSc (controls) who underwent HRM at Mayo Clinic Arizona from May 2006 through January 2015. We used data on integrated relaxation pressure, distal contractile integral, and distal latency to classify esophageal motility disorders according to the Chicago Classification v 3.0. A subset of subjects (n = 122) completed SSc-specific gastrointestinal symptom and HRQOL questionnaires. HRM findings, symptoms, and HRQOL data were compared among diffuse SSc, limited SSc, and control subjects. Categorical variables were compared by using the χ2 or Fisher exact test; continuous variables were compared by using Mann-Whitney or Kruskal-Wallis test. Multivariable logistic regression was used to assess the association between severity of esophageal dysmotility and baseline clinical factors. RESULTS: Among patients with SSc, 83 had diffuse SSc (42%), and 117 had limited SSc (58%). Absent contractility was more frequent in patients with SSc than in controls (56% vs 13%; P < .001). HRM findings varied among the patients; absent contractility (56%) was the most frequent diagnosis, followed by normal motility (26%) and ineffective esophageal motility (10%). Classic scleroderma esophagus (esophagogastric junction pressure with absent contractility) was only observed in 33% of patients (34% with diffuse SSc vs 32% limited SSc) (P = .880). Severe esophageal dysmotility was associated with disease duration, interstitial lung disease, and higher gastrointestinal symptom scores (P < .001). HRQOL was decreased in patients with SSc and severe esophageal dysmotility. CONCLUSIONS: Although severe dysmotility is more common in patients with SSc than in controls, we observed the so-called scleroderma esophagus in only one-third of patients with SSc. Esophageal motor function appears to be heterogeneous in SSc. Esophageal dysmotility reduces HRQOL in patients with SSc.

Sensation of stasis is poorly correlated with impaired esophageal bolus transport.

BACKGROUND: It is common belief that symptoms of patients with non-obstructive dysphagia are the result of impaired bolus clearance in the esophagus, usually caused by esophageal motility disorders. We therefore investigated the relationship between transit of swallowed boluses and the symptom dysphagia. METHODS: Twenty healthy volunteers and 20 patients with dysphagia underwent videofluoroscopy. Success of bolus transport was graded on a 7-point scale. Each subject swallowed five liquid and five solid barium boluses. KEY RESULTS: For liquids, patients reported dysphagia during 1 [0-3] of the five swallows, while controls reported no dysphagia (median 0 [0-0]; p = 0.003). For solids, patients reported dysphagia during 3 [2-4] of five swallows, while controls reported dysphagia in 0.5 [0-2] of five swallows (p = 0.001). When correlating dysphagia to ineffective clearance (score ≥ 3), in 3 [2-4] of five liquids, the subjects perception of clearance was related to the clearance result on fluoroscopy in patients and also 3 [1-5] were correctly perceived in controls (p = 0.6). For solids, in 4 [3-5] of five swallows, the subjects perception of clearance was related to the clearance result on fluoroscopy in patients, but only 2 [1-3] of five swallows were correctly perceived by controls, the difference being statistically significant. CONCLUSIONS & INFERENCES: Patients very frequently report dysphagia when bolus clearance is successful. Therefore, the major underlying problem in patients with non-obstructive dysphagia is disordered perception and increased sensitivity to physiological bolus stasis. Treatment should therefore be directed at reducing increased sensitivity rather than at improving motility.

Esophageal motility and psychiatric factors in functional dyspepsia patients with or without pain.

Subtypes of functional dyspepsia (FD), including refluxlike dyspepsia, ulcerlike dyspepsia, dysmotility-like dyspepsia, and nonspecific dyspepsia, have been described and are widely used clinically. However, these symptom patterns often overlap, and the terms are insufficient for indicating all FD symptoms. In this study, we divided 71 FD patients into two groups: patients with or without pain. Group I, the pain dyspepsia group, included patients in whom the main symptoms were epigastralgia and/or chest pain. Group II, the painless dyspepsia group, included patients without pain, in whom the symptoms were nausea, vomiting, and heartburn. We examined the relationship between esophageal function and psychiatric factors in the test groups and compared them with a control group. Of the FD patients, 19.7% [8 (25%) of 32 group I patients, 6 (15.4%) of 39 group II patients] had esophageal motility disorders, such as nutcracker esophagus and diffuse esophageal spasm. The LES pressure of group I was higher than that of group II by esophageal manometry (P < 0.05). In 17 (53.1%) of 32 group I patients and 31 (79.5%) of 39 group II patients, psychiatric disorders (38.0% had depressive disorder and 21.1% had an anxiety disorder) were diagnosed following DSM III-R criteria. Group II tended to be more depressive than group I (P = 0.0508). Psychological assessment scores, STAI-I and STAI-II, were higher in groups I and II than in the control group (P < 0.001). Long-term distress, anxiety, and depression seem to influence the symptoms of FD patients. Esophageal dysmotility may be an important functional abnormality of FD.

Functional esophageal disorders.

The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or pathological reflux, defined by evidence of reflux esophagitis or abnormal acid exposure time during ambulatory esophageal pH monitoring. Management is largely empirical, although efficacy of psychopharmacological agents and psychological or behavioral approaches has been established for several of the functional esophageal disorders. As gastroesophageal reflux disease overlaps in presentation with most of these disorders and because symptoms are at least partially provoked by acid reflux events in many patients, antireflux therapy also plays an important role both in diagnosis and management. Further understanding of the fundamental mechanisms responsible for symptoms is a priority for future research efforts, as is the consideration of treatment outcome in a broader sense than reduction in esophageal symptoms alone. Likewise, the value of inclusive rather than restrictive diagnostic criteria that encompass other gastrointestinal and non-gastrointestinal symptoms should be examined to improve the accuracy of symptom-based criteria and reduce the dependence on objective testing.

Oesophageal motility disorders in patients with psychiatric disease.

Clinical and experimental observations indicate that the motility of the oesophagus may be affected by emotional stimuli. The aim of this study was to evaluate the incidence of oesophageal contractility impairment in patients suffering from a psychiatric disorder. Fifty-one patients admitted to the psychiatric department were submitted to an oesophageal transit study by means of krypton-81m. All patients with an abnormal oesophageal transit underwent manometry and endoscopy. The level of depression and anxiety was evaluated by the treating psychiatrist, using the Hamilton Depression and Anxiety Rating Scales. The oesophageal transit was abnormal in 13 patients. Two of these 13 patients refused manometric investigation. In ten of the 11 remaining patients, the manometry revealed functional motor abnormalities. Endoscopy, performed in all these ten patients, was normal. In conclusion, a high percentage of oesophageal contractility disturbances was found in psychiatric patients complaining of anxiety and/or depression. These abnormalities were detected by scintigraphy as well as by manometry. Owing to the normal endoscopic findings, these contraction abnormalities are likely to reflect a functional motor impairment.

Life events and daily hassles in patients with atypical chest pain.

The impact of major life events and daily hassles on atypical chest pain is unknown. The aim of the present study was to investigate the relationship of the occurrence and perception of major life events and daily hassles in atypical chest pain patients. Five groups of subjects were studied. They were healthy controls, atypical chest pain patients without motility/reflux changes, atypical chest pain patients with motility/reflux changes, dyspeptic patients, and patients with chronic obstructive airway disease/peptic ulcer/gallstone. A questionnaire concerning the occurrence and perception of major life events and daily hassles was administered to all five groups of subjects. Using analysis of variance, we found that atypical chest pain patients without underlying motility/reflux changes had significantly higher scores of negative life events and total life events than healthy controls, atypical chest pain patients with underlying motility/reflux changes, and patients with chronic obstructive airway disease/peptic ulcer/gallstone. There were no significant differences between atypical chest pain patients without underlying motility/reflux changes and patients with dyspepsia in terms of the number of negative life events, negative scores, number of positive life events, positive scores, and total life events. Discriminate analysis identified five of the 47 major life events (major changes in sleeping habits, change in work situation, major changes in financial status, retirement, and suffering from severe illness or injury) to be useful for discriminating atypical chest pain patients without underlying motility/reflux changes from the healthy controls and from atypical chest pain patients with underlying motility/reflux changes. The overall correct classification rate was 81.8%. In conclusion, psychological factors, such as perception of negative life events and occurrence and perception of daily hassles, may play a role in the pathogenesis of atypical chest pain.

Chest pain of undetermined origin.

Chest pain of undetermined origin (CPUO) can be a diagnostic dilemma for both the primary care physician and subspecialist. This article focuses on the diagnostic tools used in the evaluation of CPUO, which include: prolonged ambulatory intraesophageal pH monitoring; esophageal manometry with provocative testing; ambulatory intraesophageal pressure monitoring; the role of radiology and endoscopy in the evaluation of chest pain; the role of psychological abnormalities and abnormal nociception in the pathogenesis of chest pain; and the clinical approach and treatment rationale for CPUO.

Globus pharyngis, commonly associated with esophageal motility disorders.

OBJECTIVES: To evaluate the role of gastrointestinal and psychiatric etiology in globus sensation. METHODS: The study population consisted of 32 consecutive patients with globus sensation without dysphagia referred to the Department of Otorhinolaryngology in Helsinki University Hospital. Eleven patients were excluded from the study: two because of advanced age, one prisoner, and six patients refused further studies. Only two patients (6%) were found to have abnormal otorhinolaryngological status. These patients were also excluded from the study. Esophagogastroduodenoscopy, 24-h pH recording, esophageal manometry, and Bernstein acid perfusion test were carried out in 21 patients (13 females, eight males, mean age 49 yr). Psychiatric evaluation was done in 20 patients; one patient refused the psychiatric consultation. RESULTS: Abnormal endoscopy was found in 12/21 (57%) of the patients, with antral gastritis and hiatal hernia being the most common findings. Two patients had esophagitis. Sixty-seven percent demonstrated abnormalities in esophageal manometry, the most frequent finding being a nonspecific esophageal motility disorder (29%). pH monitoring was normal in 16/21 of patients (76%), whereas the Bernstein test showed positive results in 13/21 (62%). With DSM IIIR as the diagnostic tool, five of 20 patients (25%) received a psychiatric diagnosis. CONCLUSIONS: Globus sensation has a multiple etiology, and local reasons are rare but should first be ruled out. Abnormalities in esophageal motility are commonly found, and these patients seem to be sensitive to esophageal acidity. Esophageal manometry and ambulatory 24-h pH recording should be included in the evaluation of a globus patient. The number of psychiatric disorders does not differ from that in the general population. Treatment of globus sensation should be directed toward the abnormality found behind the symptom.

High incidence of esophageal motor disorders in consecutive patients with globus sensation.

Thirty consecutive patients with globus sensation who were referred to a psychosomatic clinic prospectively underwent otolaryngological, videokinematographic, and manometric examinations of pharynx and esophagus to evaluate whether morphological abnormalities or motility disorders underlay their symptom. When indicated by findings, 24-hour pH-metry, scintigraphy of bolus transport, and esophagogastroscopy were performed. Seven patients were shown to have achalasia, 10 had "hypochalasia" (lower esophageal sphincter relaxation less than 75% with esophageal contraction abnormalities but no complete distal aperistalsis), and 1 had diffuse esophageal spasms; 2 patients had also hyperplastic lingual tonsils, 1 had tonsillitis, and 1 had a cervical spondylophyte. Nutcracker esophagus and nonspecific contraction abnormalities were found in 7 patients, and gastroesophageal reflux with esophagitis and a low lower esophageal sphincter resting pressure was found in 1; only 3 patients had normal esophageal motility. None had volunteered dysphagic symptoms at primary evaluation. Psychometric investigations in consenting patients showed no higher mean scores for state and trait anxiety, depression, hysteria, and hypochondriasis than in general medical outpatients. Esophageal motor disorders may, before giving rise to dysphagia, be sensed more vaguely and induce the globus sensation. However, only disappearance of the sensation after treatment allows inferring an etiological significance of such a disorder.

Psychiatric disorders in patients with esophageal disease.

Psychiatric disorders have potentially important roles in the manifestations of esophageal disease. A primary causative role for psychiatric factors in the common motility disorders associated with chest pain (esophageal spasm and the nonspecific motor disorders) remains unproven, but psychiatric disorders appear particularly prevalent in this group. In most other esophageal diseases, psychiatric factors interact through recognized psychophysiologic or behavioral mechanisms to affect the clinical presentation. Recognizing the possible levels of interaction has significant therapeutic implications.

Noncardiac chest pain in patients with heart disease.

This is a retrospective study of cardiac patients with noncardiac chest pain referred for evaluation of esophageal motility. Sixty-eight patients with heart disease were compared with 210 patients without heart disease according to findings from symptom questionnaires and a psychologic test (Brief Symptom Inventory). More than 70% of each group qualified for an anxiety or depressive diagnosis on the symptom questionnaire. These diagnoses were supported by significant elevations of scores on the anxiety and depression scales of the Brief Symptom Inventory. Male gender and a diagnosis of panic disorder occurred significantly more often in the patients with heart disease. "Stress" was cited as the cause of illness in about half the sample, but this led to less than satisfactory rates of psychiatric evaluation or pharmacotherapy. This is of particular concern for the cardiac patients because of the known adverse effect of anxiety and depression in those with heart disease.

Hypertensive lower esophageal sphincter: what does it mean?

The hypertensive lower esophageal sphincter (LES) (mean LES pressure greater than 45 mm Hg; LES relaxation greater than 75%; normal peristalsis) is a poorly characterized motility disorder associated with chest pain and dysphagia. Therefore, we carried out a multidisciplinary study to assess esophageal pressures and function in 15 symptomatic hypertensive LES patients (3 men, 12 women; mean age, 53 years). On-line computer analysis showed a significant (p less than 0.05) increase in LES pressure (55.5 versus 14.9 mm Hg) and residual pressure (6.8 versus 1.1 mm Hg) as well as a decrease in percentage of LES relaxation (87 versus 93%) in patients compared with age-matched controls. All patients had normal peristalsis but 7 of 15 had nutcracker esophagus (mean distal amplitude, 216 mm Hg). No patient had evidence of impaired liquid transport on barium esophagram. The emptying of solids as assessed by radionuclide scans was normal in 14 of 15 patients. Of the 12 patients who completed both psychological inventories, nine had elevated scores on scales assessing anxiety and somatization. The heterogenous nature of this disorder is illustrated by a patient with a changeable narrowing in the distal esophagus associated with the transient impaction of a marshmallow. Dysphagia but not chest pain improved after pneumatic dilatation. We conclude that the hypertensive LES is a heterogenous disorder. Despite abnormal LES parameters, most patients have normal esophageal function, and frequent psychological abnormalities may contribute to their report of symptoms. A minority have abnormal esophageal transit.

Esophageal chest pain: current controversies in pathogenesis, diagnosis, and therapy.

PURPOSE: To evaluate the importance of esophageal abnormalities as a potential cause of recurrent noncardiac chest pain. DATA IDENTIFICATION: We discuss the rapidly evolving new knowledge in this field after analyzing the literature in English published since 1979. STUDY SELECTION: We reviewed 117 articles on recurring chest pain and paid specific attention to the following nine controversial issues: the potential mechanisms of esophageal pain, the differentiation of cardiac and esophageal causes, the evaluation of new esophageal motility disorders, the use of esophageal tests in evaluating noncardiac chest pain, the usefulness of techniques for prolonged monitoring of intraesophageal pressure and pH, the relation of psychologic abnormalities to esophageal motility disorders, the possible mechanisms for decreased visceral pain thresholds in these patients, the relation of esophageal chest pain to the irritable bowel syndrome, and the appropriate therapies for these patients. RESULTS OF DATA SYNTHESIS: Through our review of the literature, we identified areas of concordance and disagreement. These areas are discussed and an overall perspective is provided. CONCLUSIONS: Continuing attempts to develop rational diagnostic and therapeutic approaches to patients with noncardiac chest pain should include a multidisciplinary approach involving basic scientists, gastroenterologists, psychologists, and other clinical experts in the field of pain research.