Inder Mainie

Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy. A multicentre study using combined ambulatory impedance-pH monitoring

Background and aims: Empiric proton pump inhibitor (PPI) trials have become increasingly popular leading to gastroenterologists frequently evaluating gastro-oesophageal reflux disease (GORD) patients only after they have “failed” PPI therapy. Combined multichannel intraluminal impedance and pH (MII-pH) monitoring has the ability to detect gastro-oesophageal reflux (GOR) episodes independent of their pH and evaluate the relationship between symptoms and all types of GOR. Using this technique, we aimed to characterise the frequency of acid and non-acid reflux (NAR) and their relationship to typical and atypical GOR symptoms in patients on PPI therapy. Methods: Patients with persistent GORD symptoms referred to three centres underwent 24 hour combined MII-pH monitoring while taking PPIs at least twice daily. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15, and 17 cm above the lower oesophageal sphincter (LOS) and classified into acid or non-acid based on pH data from 5 cm above the LOS. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes. Results: A total of 168 patients (103 (61%) females and 65 (39%) males; mean age 53 (range 18–85) years) underwent combined MII-pH monitoring while taking PPIs at least twice daily. One hundred and forty four (86%) patients recorded symptoms during the study day and 24 (15%) patients had no symptoms during testing. Sixty nine (48%) symptomatic patients had a positive SI for at least one symptom (16 (11%) with acid reflux and 53 (37%) with NAR) and 75 (52%) had a negative SI. A total of 171 (57%) typical GORD symptoms were recorded, 19 (11%) had a positive SI for acid reflux, 52 (31%) for NAR, and 100 (58%) had a negative SI. One hundred and thirty one (43%) atypical symptoms were recorded, four (3%) had a positive SI for acid reflux, 25 (19%) had a positive SI for NAR, and 102 (78%) had a negative SI. Conclusion: Combined MII-pH identifies the relation of reflux of all types to persistent symptoms and the importance of NAR in patients taking PPIs.

Combined multichannel intraluminal impedance–pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication

Combined multichannel intraluminal impedance‐pH (MII‐pH) monitoring detects gastro‐oesophageal reflux and identifies acid and non‐acid reflux events. It can be used in patients with persistent symptoms on proton‐pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII‐pH monitoring.

Characteristics of Symptomatic Reflux Episodes on Acid Suppressive Therapy

BACKGROUND:Persistent symptoms on acid suppressive therapy are due to either acid or nonacid gastroesophageal reflux (GER) episodes or are not related to reflux.AIM:To compare physical and chemical characteristics of GER episodes associated with symptoms in patients on acid suppressive therapy.METHODS:Patients with persistent symptoms on acid suppressive therapy underwent combined impedance-pH monitoring. Reflux episodes were classified as acid if nadir pH was <4.0, and nonacid if it remained at ≥4.0, separated into liquid-only or mixed (liquid-gas), and considered to reach the proximal esophagus if liquid was present 15 cm above the lower esophageal sphincter (LES). Reflux episodes were considered symptomatic if patients recorded a symptom within 5 min after the reflux episode. Risk factors of symptomatic reflux episodes were identified using multivariable generalized estimating equations (GEEs).RESULTS:One hundred twenty patients (85 women, median age 54 yr, range 18–85 yr) recorded 3,547 reflux episodes (84.3% nonacid, 50.6% mixed), of which 468 (13.2%) were symptomatic. Based on multivariable GEE analysis with episode-level symptom status (symptomatic vs nonsymptomatic) as the outcome variable, reflux episode acidity was not significantly associated with symptoms (P = 0.40). Mixed reflux episodes were significantly associated with symptoms relative to liquid-only episodes (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.19–1.87, P = 0.0005), as were reflux episodes reaching the proximal esophagus compared with those reaching the distal esophagus only (OR 1.28, 95% CI 1.06–1.55, P = 0.012).CONCLUSION:The majority of reflux episodes on acid suppressive therapy are asymptomatic. Reflux episodes extending proximally and having a mixed (liquid-gas) composition are significantly associated with symptoms, irrespective of whether pH is acid (<4) or nonacid (≥4).

Nonacid reflux episodes reaching the pharynx are important factors associated with cough.

Background Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. Methods Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. Results A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. Conclusions Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

Symptom and function heterogenicity among patients with distal esophageal spasm : Studies using combined impedance-manometry

BACKGROUND:Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a clinically available tool that assesses the functional defect of various manometric abnormalities. The aim of our study was to evaluate esophageal bolus transit in patients with manometrically defined distal esophageal spasm (DES).METHODS:Patients referred for esophageal function testing underwent combined MII-EM studies including 10 liquid and 10 viscous swallows. Individual swallows were classified using previously published manometric and impedance criteria. DES is traditionally defined as ≥20% simultaneous contractions in the distal esophagus. Diagnosis of esophageal transit abnormalities was defined by the presence of ≥30% incomplete liquid or ≥40% incomplete viscous swallows.RESULTS:Data from 71 patients (43 female, mean age 57 yr, range 16–85) with a manometric diagnosis of DES were analyzed. During liquid swallows, patients with chest pain had higher (p < 0.05) distal esophageal amplitudes (202.3 ± 34.5 mmHg) and a higher (p < 0.05) percentage of swallows with complete bolus transit (89%± 3%) compared to patients presenting with dysphagia (amplitude 117.8 ± 8.7 mmHg; percentage of complete transit 69%± 5%) and patients with reflux symptoms (amplitude 116.4 ± 12.7 mmHg; percentage of complete transit 74%± 5%). Fifty-one percent of the DES patients had a normal bolus transit for liquid and viscous, 24% abnormal bolus transit for one substance, and 25% abnormal bolus transit for liquid and viscous.CONCLUSION:Pressure and bolus transit information in patients with manometrically defined DES points toward heterogenicity of this group of patients. Outcomes data are warranted to evaluate whether stratifying DES patients based on pressure and bolus transit information may improve the clinical approach.

Clinical relevance of the nutcracker esophagus: suggested revision of criteria for diagnosis.

Background Nutcracker esophagus (NE) is a manometric finding defined by peristaltic contractions with a mean distal esophageal amplitude (DEA) >180 mm Hg. This threshold has been selected as it exceeds the average DEA in healthy volunteers by 2 SDs. Since its introduction the clinical significance of this finding has been challenged, as many patients with NE are asymptomatic. Aim To evaluate whether defining NE based on a different DEA threshold would be clinically more meaningful. Methods Retrospective review of prospectively collected manometry data between October 2001 and December 2003. Using previously published normal DEA values (mean and SD) patients with NE were stratified into 3 groups: group A (2 to 3 SD above mean): DEA 180 to 220 mm Hg; group B (3 to 4 SD above mean): DEA 220 to 260 mm Hg; and group C (>4 SD above mean): DEA >260 mm Hg. Symptoms, esophageal acid exposure, bolus transit data, and lower esophageal sphincter data were reviewed. Results The stratification of 56 NE patients into groups A, B, and C were 31, 16, and 9, respectively. The proportion of patients presenting with chest pain increased from 23% in group A to 69% in group B and 100% in group C. Patients in group C had significantly (P<0.05) higher mean lower esophageal sphincter pressure, shorter bolus transit time, and lower frequency of abnormal reflux. Conclusions A revised definition of NE to include patients with a DEA >260 mm Hg, and possibly those with >220 may have greater clinical relevance.

Fundoplication eliminates chronic cough due to non-acid reflux identified by impedance pH monitoring

The symptoms of extra-oesophageal gastro-oesophageal reflux disease (GORD) (such as chronic cough and hoarseness) are traditionally more difficult to treat than typical GORD symptoms (heartburn and regurgitation). Patients with extra-oesophageal manifestations may require longer and higher doses of acid suppressive therapy. In patients not responding to acid suppressive therapy the physician faces a dilemma as to whether the symptoms are due to ongoing acid reflux, non-acid reflux, or not associated with reflux. We report the case of a 45 year old woman with a history of a chronic cough referred for fundoplication after documenting her symptoms were associated with non-acid reflux using multichannel intraluminal impedance and pH (MII-pH).

Addition of a H2 receptor antagonist to PPI improves acid control and decreases nocturnal acid breakthrough.

Background The addition of a bedtime H2 receptor antagonist (H2RA) to proton pump inhibitor (PPI) b.i.d. to inhibit nocturnal acid breakthrough (NAB) is controversial. H2RA tolerance has been documented suggesting limitations in its long-term effect. Aim To compare the intragastric pH and NAB occurring with twice daily PPI with or without the addition of a H2RA. Method Multichannel intraluminal impedance-pH studies in 100 patients were reviewed. Fifty-eight patients (female 41; mean age, 54 y; range, 17 to 85) were studied on twice daily PPI. Forty-two patients (female 36; mean age, 53 y; range 20 to 85) were studied on a PPI b.i.d.+H2RA for at least 1 month at bedtime. The percentage time of intragastric pH<4 (upright, recumbent, and total) and NAB were compared between the groups. Results In the patients with PPI b.i.d. 64% had NAB, compared with only 17% of patients on PPI b.i.d. and H2RA q.h.s. (P<0.001). The percent time intragastric pH<4 for patients on PPI b.i.d. was significantly higher (P<0.01) compared with patients on PPI b.i.d.+H2RA q.h.s. during upright (29.1±3.0 vs. 18.3±2.9), recumbent (33.5±3.4 vs. 12.5±3.1), and entire period (31.5±2.8 vs. 18.0±3.0). Conclusions The addition of a bedtime H2RA reduces the percentage time of the intragastric pH<4 and also NAB. H2RA should be considered as adjunct therapy in whom greater suppression of gastric acid control is considered desirable.

Bethanechol improves smooth muscle function in patients with severe ineffective esophageal motility

Background There is no therapeutic intervention that reliably restores smooth muscle contractility for patients with ineffective esophageal motility (IEM). Bethanechol, a direct-acting muscarinic receptor agonist, has been shown in healthy volunteers to produce a significant increase in peristaltic amplitude in the distal esophagus. Aim To identify whether bethanechol improves smooth muscle contractility and bolus transit in patients with IEM. Methods Seven patients diagnosed with severe IEM documented by combined multichannel intraluminal impedance and esophageal manometry were asked to participate. IEM was defined by using the new proposed criteria of greater than or equal to 50% saline swallows with contraction amplitude <30 mm Hg either 5 and/or 10 cm above the lower esophageal sphincter (LES). In the supine position, the patients were given 10 swallows of 5 mL of normal saline then 10 swallows of viscous solution, each 20 to 30 seconds apart. Patients were then given 50 mg oral bethanechol. After 20 and 40 minutes, 5 swallows of saline and viscous solution were repeated. Studies were then analyzed by an investigator blinded to the relationship of bethanechol administration to the swallows. The analysis included measurement of distal esophageal amplitude (DEA) or the mean amplitude at 5 and 10 cm above the LES. Results The use of bethanechol significantly increased (P<0.05) the esophageal contraction pressures at 5 and 10 cm above the LES. The DEA increased (P<0.05) for liquid and viscous, 20 minutes after its administration. Forty minutes after bethanechol administration, DEA and also individual pressures at 5 and 10 cm above the LES were still increased (P<0.05) for liquid, but only the DEA increased (P<0.05) with viscous solution. There was also a significant increase in complete bolus transit for saline swallows, both 20 and 40 minutes (P=0.03 and 0.01, respectively) after bethanechol. Conclusions Oral bethanechol significantly improves contraction pressures and bolus transit in the smooth muscle portion of the esophagus in patients with severe IEM.

Effects of a 5-HT4 receptor agonist on oesophageal function and gastro-oesophageal reflux: studies using combined impedance-manometry and combined impedance-pH

5‐HT4 receptor agonists are used as promotility agents of the stomach, small and large intestine. There is limited information on the influence of 5‐HT4 receptor agonists on oesophageal function and gastro‐oesophageal reflux.