The critical importance of pharyngeal contractile forces on the validity of intrabolus pressure as a predictor of impaired pharyngo-esophageal junction compliance.

INTRODUCTION: Restrictive defects of the pharyngo-esophageal junction (PEJ) are common in both structural and neurological disorders and are amenable to therapies aiming to reduce outflow resistance. Intrabolus pressure (IBP) acquired with high-resolution manometry and impedance (HRMI) is an indicator of resistance and a marker of reduced PEJ compliance. Constraints and limitations of IBP as well as the optimal IBP parameter remain undefined. AIMS: To determine: (i) the impact of peak pharyngeal pressure (PeakP) on the diagnostic accuracy of IBP for the detection of a restrictive defect at the PEJ and (ii) the optimal IBP parameter for this purpose. METHODS: In 52 dysphagic patients previously treated for head and neck cancer. Five candidate IBP measures and PeakP were obtained with HRMI, as well as a presence of a stricture determined by a mucosal tear after endoscopic dilatation. Predictive values of IBP measures were evaluated by receiver operating characteristic (ROC) analysis for all patients and reiterated as patients with lowest PeakP were progressively removed from the cohort. RESULTS: All IBP parameters had fair to good accuracy at predicting strictures. Intrabolus pressure measured at a discrete point of maximum admittance 1 cm above the maximal excursion of the upper esophageal sphincter had highest sensitivity (0.76) and specificity (0.78). When PeakP was at least 57 mm Hg both sensitivity and specificity improved to 0.9. CONCLUSIONS: Pharyngeal propulsive force has substantial impact on the accuracy of IBP as a predictor of a PEJ stricture. When PeakP is ≥57 mm Hg, an elevated IBP is highly predictive of a restrictive defect at the PEJ.

Physiological augmentation of esophageal distension pressure and peristalsis during conditions of increased esophageal emptying resistance.

BACKGROUND: Abdominal compression has been implemented as a provocative maneuver in high-resolution impedance manometry (HRIM) to "challenge" normal esophageal physiology with the aim of revealing abnormal motor patterns which may explain symptoms. In this study, we measured the effects of abdominal compression on esophageal functioning utilizing novel pressure-impedance parameters and attempted to identify differences between healthy controls and globus patients. METHODS: Twenty-two healthy volunteers (aged 23-32 years, 41% female) and 22 globus patients (aged 23-72 years, 68% female) were evaluated with HRIM using a 3.2-mm water perfused manometric and impedance catheter. All participants received 10 × 5 mL liquid swallows; healthy controls also received 10 × 5 mL liquid swallows with abdominal compression created using an inflatable cuff. All swallows were analyzed to assess esophageal pressure topography (EPT) and pressure-flow metrics, indicative of distension pressure, flow timing and bolus clearance were derived. KEY RESULTS: The effect of abdominal compression was shown as a greater contractile vigor of the distal esophagus by EPT and higher distension pressure based on pressure-flow metrics. Age and body mass index also increased contractile vigor and distension pressure. Globus patients were similar to controls. CONCLUSIONS AND INTERFERENCES: Intrabolus pressure and contractile vigor are indicative of the physiological modulation of bolus transport mechanisms. Provocative testing by abdominal compression induces changes in these esophageal bolus dynamics.

Discriminating movements of liquid and gas in the rabbit colon with impedance manometry.

BACKGROUND: High-resolution impedance manometry is a technique that is well established in esophageal motility studies for relating motor patterns to bolus flow. The use of this technique in the colon has not been established. METHODS: In isolated segments of rabbit proximal colon, we recorded motor patterns and the movement of liquid or gas boluses with a high-resolution impedance manometry catheter. These detected movements were compared to video recorded changes in gut diameter. Using the characteristic shapes of the admittance (inverse of impedance) and pressure signals associated with gas or liquid flow we developed a computational algorithm for the automated detection of these events. KEY RESULTS: Propagating contractions detected by video were also recorded by manometry and impedance. Neither pressure nor admittance signals alone could distinguish between liquid and gas transit, however the precise relationship between admittance and pressure signals during bolus flow could. Training our computational algorithm upon these characteristic shapes yielded a detection accuracy of 87.7% when compared to gas or liquid bolus events detected by manual analysis. CONCLUSIONS & INFERENCES: Characterizing the relationship between both admittance and pressure recorded with high-resolution impedance manometry can not only help in detecting luminal transit in real time, but also distinguishes between liquid and gaseous content. This technique holds promise for determining the propulsive nature of human colonic motor patterns.

Intra- and interrater reliability of the Chicago Classification of achalasia subtypes in pediatric high-resolution esophageal manometry (HRM) recordings.

BACKGROUND: Subtyping achalasia by high-resolution manometry (HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter- and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification (CC) V3.0. METHODS: Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non-achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), intrabolus pressurization pattern (IBP), and distal latency (DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss' κ (>2 raters) and the intraclass correlation coefficient (ICC) were used for categorical and ordinal data, respectively. RESULTS: Based on the results of dedicated analysis software only, intra- and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non-achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software-driven diagnosis according to their own interpretation of the manometric patterns, intra- and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). CONCLUSIONS: Intra- and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software-driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise.

Objectively diagnosing rumination syndrome in children using esophageal pH-impedance and manometry.

BACKGROUND: Rumination syndrome is characterized by recurrent regurgitation of recently ingested food into the mouth. Differentiation with other diagnoses and gastroesophageal reflux disease (GERD) in particular, is difficult. Recently, objective pH-impedance (pH-MII) and manometry criteria were proposed for adults. The aim of this study was to determine diagnostic ambulatory pH-MII and manometry criteria for rumination syndrome in children. METHODS: Clinical data and 24-hour pH-MII and manometry recordings of children with a clinical suspicion of rumination syndrome were reviewed. Recordings were analyzed for retrograde bolus flow extending into the proximal esophagus. Peak gastric and intraesophageal pressures closely related to these events were recorded and checked for a pattern compatible with rumination. Events were classified into primary, secondary, and supragastric belch-associated rumination. KEY RESULTS: Twenty-five consecutive patients (11 males, median age 13.3 years [IQR 5.9-15.8]) were included; recordings of 18 patients were suitable for analysis. Rumination events were identified in 16/18 patients, with 50% of events occurring <30 minutes postprandially. Fifteen of 16 patients showed ≥1 gastric pressure peak >30 mmHg, while only 50% of all events was characterized by peaks >30 mmHg and an additional 20% by peaks >25 mmHg. Four patients had evidence of acid GERD, all showing secondary rumination. CONCLUSIONS AND INFERENCES: Combined 24-hour pH-MII and manometry can be used to diagnose rumination syndrome in children and to distinguish it from GERD. Rumination patterns in children are similar compared with adults, albeit with lower gastric pressure increase. We propose a diagnostic cutoff for gastric pressure increase >25 mmHg associated with retrograde bolus flow into the proximal esophagus.

Impaired bolus clearance in asymptomatic older adults during high-resolution impedance manometry.

BACKGROUND: Dysphagia becomes more common in old age. We performed high-resolution impedance manometry (HRIM) in asymptomatic healthy adults (including an older cohort >80 years) to assess HRIM findings in relation to bolus clearance. METHODS: Esophageal HRIM was performed in a sitting posture in 45 healthy volunteers (n = 30 young control, mean age 37 ± 11 years and n = 15 older subjects aged 85 ± 4 years) using a 3.2-mm solid-state catheter (Solar GI system; MMS, Enschede, The Netherlands) with 25 pressure (1-cm spacing) and 12 impedance segments (2-cm intervals). Five swallows each of 5- and 10-mL liquid and viscous bolus were performed and analyzed using esophageal pressure topography metrics and Chicago classification criteria as well as pressure-flow parameters. Bolus transit was determined using standard impedance criteria. A p-value <0.05 was considered significant. KEY RESULTS: Impaired bolus clearance occurred more frequently in asymptomatic older subjects compared with young controls (YC) during liquid (40 vs 18%, χ2  = 4.935; p < 0.05) and viscous (60 vs 17%; χ2  = 39.08; p < 0.001) swallowing. Longer peristaltic breaks (p < 0.05) and more rapid peristalsis (L: p < 0.004, V: p = 0.003) occurred in the older cohort, with reduced impedance-based clearance for both bolus consistencies (L: p < 0.05, V: p < 0.001). Decreased peristaltic vigor (distal contractile integral <450 mmHg/s/cm) was associated with reduced liquid clearance in both age groups (p < 0.001) and of viscous swallows in the older group (p < 0.001). Impedance ratio, a marker of bolus retention, was increased in older subjects during liquid (p = 0.002) and viscous (p < 0.001) swallowing. CONCLUSIONS & INFERENCES: Impaired liquid and viscous bolus clearance, esophageal pressure topography, and pressure-flow changes were seen in asymptomatic older subjects.

Remifentanil alters sensory neuromodulation of swallowing in healthy volunteers: quantification by a novel pressure-impedance analysis.

Exposure to remifentanil contributes to an increased risk of pulmonary aspiration, likely through reduced pharyngeal contractile vigor and diminished bolus propulsion during swallowing. We employed a novel high-resolution pressure-flow analysis to quantify the biomechanical changes across the upper esophageal sphincter (UES). Eleven healthy young (23.3 ± 3.1 yr old) participants (7 men and 4 women) received remifentanil via intravenous target-controlled infusion with an effect-site concentration of 3 ng/ml. Before and 30 min following commencement of remifentanil administration, participants performed ten 10-ml saline swallows while pharyngoesophageal manometry and electrical impedance data were recorded using a 4.2-mm-diameter catheter housing 36 circumferential pressure sensors. Remifentanil significantly shortened the duration of UES opening (P < 0.001) and increased residual UES pressure (P = 0.003). At the level of the hypopharynx, remifentanil significantly shortened the latency from maximum bolus distension to peak contraction (P = 0.004) and significantly increased intrabolus distension pressure (P = 0.024). Novel mechanical states analysis revealed that the latencies between the different phases of the stereotypical UES relaxation sequence were shortened by remifentanil. Reduced duration of bolus flow during shortened UES opening, in concert with increased hypopharyngeal distension pressures, is mechanically consistent with increased flow resistance due to a more rapid bolus flow rate. These biomechanical changes are congruent with modification of the physiological neuroregulatory mechanism governing accommodation to bolus volume.

Maximum upper esophageal sphincter (UES) admittance: a non-specific marker of UES dysfunction.

BACKGROUND: Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. METHODS: Sixty-six healthy subjects (n = 50 controls 20-80 years; n = 16 elderly >80 years), 11 patients with CPB (51-83 years) and 16 with MND (58-91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. KEY RESULTS: In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. CONCLUSIONS & INFERENCES: The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction.

Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy.

Pressure-flow analysis quantifies the interactions between bolus transport and pressure generation. We undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the esophagogastric junction (EGJ). We hypothesized that findings of abnormal pressure-flow metrics would correlate with impaired bolus clearance and reduced flow across the EGJ. Videofluoroscopic images, impedance, and pressure were recorded simultaneously in nine patients with dysphagia (62-82 years, seven male) tested with liquid barium boluses. A 3.6 mm diameter solid-state catheter with 25 × 1 cm pressure/12 × 2 cm impedance was utilized. Swallowed bolus clearance was assessed using a validated 7-point radiological bolus transport scale. The cumulative period of bolus flow across the EGJ was also fluoroscopically measured (EGJ flow time). Pressure only parameters included the length of breaks in the 20 mmHg iso-contour and the 4 second integrated EGJ relaxation pressure (IRP4s). Pressure-flow metrics were calculated for the distal esophagus, these were: time from nadir impedance to peak pressure (TNadImp to PeakP) to quantify bolus flow timing; pressure flow index (PFI) to integrate bolus pressurization and flow timing; and impedance ratio (IR) to assess bolus clearance. When compared with controls, patients had longer peristaltic breaks, higher IRs, and higher residual EGJ relaxation pressures (break length of 8 [2, 13] vs. 2 [0, 2] cm, P = 0.027; IR 0.5 ± 0.1 vs. 0.3 ± 0.0, P = 0.019; IRP4s 11 ± 2 vs. 6 ± 1 mmHg, P = 0.070). There was a significant positive correlation between higher bolus transport scores and longer peristaltic breaks (Spearman correlation r = 0.895, P < 0.001) and with higher IRs (r = 0.661, P < 0.05). Diminished EGJ flow times correlated with a shorter TNadImp to PeakP (r = -0.733, P < 0.05) and a higher IR (r = -0.750, P < 0.05). Longer peristaltic breaks and higher IR correlate with failed bolus clearance on videofluoroscopy. The metric TNadImp to PeakP appears to be a marker of the period of time over which the bolus flows across the EGJ.

Inter-rater reliability and validity of automated impedance manometry analysis and fluoroscopy in dysphagic patients after head and neck cancer radiotherapy.

BACKGROUND: Pharyngeal automated impedance manometry (AIM) analysis is a novel non-radiological method to analyze swallowing function based on impedance-pressure recordings. In dysphagic head and neck cancer patients, we evaluated the reliability and validity of the AIM-derived swallow risk index (SRI) and a novel measure of postswallow residue (iZn/Z) by comparing it against videofluoroscopy as the gold standard. METHODS: Three blinded experts classified 88 videofluoroscopic swallows from 16 patients for aspiration and degree of postswallow residue. Pressure-impedance recordings of the patient and age-matched control swallows were analyzed using AIM by three observers who derived the SRI and iZn/Z. Intra-class correlation coefficients (ICC) were calculated for videofluoroscopic and AIM measures. Patient pressure/impedance measurements were compared with videofluoroscopy scores and control subjects to determine validity for detecting clinically relevant swallowing dysfunction. KEY RESULTS: Agreement among observers assessing presence of penetration and aspiration was modest (ICC 0.57) for videofluoroscopy and good (ICC 0.71, 0.82) for AIM-derived SRI and iZn/Z. When compared with age-matched controls, the SRI was higher in patients with aspiration (mean diff. 28.6, 95% CI [55.85, 1.355], p < 0.05). The iZn/Z had moderate positive correlation with bolus residue on fluoroscopy (BRS score) (rs (86) = 0.4120, p < 0.0001) and was increased in both patients with aspiration (∆244 [419.7, 69.52; p < 0.05]) and penetration (∆240 [394.3, 85.77]; p < 0.05) compared to controls. CONCLUSIONS & INFERENCES: AIM-based measures of swallowing function have better inter-rater reliability than comparable fluoroscopically derived measures. These measures are easily determined and objective markers of clinically relevant features of disordered swallowing following radiotherapy.

Inter- and intrarater reliability of the Chicago Classification in pediatric high-resolution esophageal manometry recordings.

BACKGROUND: The Chicago Classification (CC) facilitates interpretation of high-resolution manometry (HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software-based CC diagnosis in a pediatric cohort. METHODS: Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non-experts). Software-placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL) and break size (BS), and an overall CC diagnosis were software-generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss' kappa (κ) and intraclass correlation coefficient (ICC). KEY RESULTS: Intra- and interrater reliability of software-generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate-substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software-generated and subjective diagnosis of normal motility was high (κ = 0.81 and κ = 0.79). Intra- and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non-experts for DL (ICC = 0.65 vs ICC = 0.36 respectively) and the software-generated diagnosis diffuse esophageal spasm (DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate-substantial (κ = 0.45-0.82). CONCLUSIONS & INFERENCES: Inter- and intrarater reliability of software-based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia.

Applying the Chicago Classification criteria of esophageal motility to a pediatric cohort: effects of patient age and size.

BACKGROUND: Applying the 2012 Chicago Classification (CC) of esophageal motility disorders to pediatric patients is problematic as it relies upon adult-derived criteria. As shorter esophageal length and smaller esophago-gastric junction (EGJ) diameter may influence CC metrics, we explored the potential for age- and size-adjustment of diagnostic criteria. METHODS: We evaluated 76 high-resolution solid state impedance-manometry recordings in children referred for manometry (32M; mean age 9 ± 1 years) and 25 recordings from healthy adult subjects (7M; mean age 36 ± 2 years). CC metrics; integrated relaxation pressure (IRP4s, mmHg), contractile front velocity (CFV, cm/s), distal contractile integral (DCI, mmHg cm/s), distal latency (DL, s), and peristaltic break size (BS, cm) were derived for 10 liquid swallows using CC analysis software. Effects of age and size were examined using regression analysis. KEY RESULTS: Younger patient age and shorter size correlated significantly with greater IRP4s (p < 0.05), shorter DL (p < 0.001) and smaller BS (p < 0.05). Standard diagnostic CC criteria were adjusted using the slope of the linear regression equation to define the age/size-related trend. Sixty-six percent of the pediatric cohort showed abnormal motility when applying standard CC criteria. Adjustment for age and size reduced this to 50% and 53% respectively, with the largest reduction being in the IRP4s- and DL-dependent disorders EGJ outflow obstruction and diffuse esophageal spasm (13% to 7% and 5% and 14% to 1 and 5%, respectively). CONCLUSIONS & INFERENCES: CC metrics, particularly IRP4s and DL, are age and size dependent, and therefore, require adjustment to improve accuracy of diagnosis of esophageal motility disorders in children.

Automated impedance manometry analysis as a method to assess esophageal function.

BACKGROUND: Diagnostic evaluation of non-achalasia esophageal dysphagia remains challenging because of a lack of a clear relationship between symptoms, esophageal contraction patterns, and esophageal bolus flow. This study evaluates a novel approach to pressure-impedance analysis called automated impedance manometry (AIM) analysis in relation to bolus characteristics, Chicago classification metrics, bolus perception, and dysphagia. METHODS: AIM analysis was performed on esophageal high resolution manometry-impedance recordings from 12 healthy controls and 15 patients with dysphagia. In each subject, 10 liquid, 10 semisolid, and 10 solid swallows were analyzed using AIMplot software. KEY RESULTS: This study demonstrated that (i) esophageal pressure-flow parameters differ with bolus type (liquid, semisolid, and solids), (ii) impedance at peak pressure parameter can discriminate normal from dysphagic subjects with high accuracy on a cut-off threshold at 2400 Ohms (kappa 0.77, sensitivity 0.83, and specificity 0.93), and (iii) nadir impedance and impedance at peak pressure highly correlate with perception of esophageal bolus flow (r = -0.65, p = 0.02; r = -0.70, p = 0.01 resp). CONCLUSIONS & INFERENCES: This study presents novel esophageal pressure-flow variables in control subjects and in a cohort of patients with dysphagia. These variables are altered in relation to bolus consistency and can discriminate between subjects with and without symptoms of dysphagia. For the first time, we present high resolution esophageal pressure-flow variables that accurately link in with patient perception of esophageal bolus hold up.

Inter- and intra-rater reproducibility of automated and integrated pressure-flow analysis of esophageal pressure-impedance recordings.

BACKGROUND: Automated impedance manometry pressure-flow analysis (AIM analysis) determines pressure measurements relative to bolus flow and has to date shown subtle variations in esophageal motility in relation to dysphagia. In this study, we assessed intra- and inter-rater reproducibility of AIM metrics derived using purpose designed software. METHODS: Fifty patients referred for evaluation of gastro-esophageal reflux symptoms (33 men, age 52 ± 1.9 years) underwent combined high-resolution impedance manometry and completed a dysphagia questionnaire. From 10 liquid and 10 viscous swallows, a subset of four swallows (two saline and two viscous) was systematically selected from each patient for manual and AIMplot analysis, which was performed twice by five observers (two experts, three non-experts). Intra- and inter-rater agreement were determined using intraclass correlation coefficients. KEY RESULTS: AIMplot-based analysis showed high intra-rater and inter-rater reproducibility for all metrics (mean ICCs of 0.95 and 0.94, respectively). Reproducibility of metrics derived for liquid and viscous did not differ (ICCs of 0.96 and 0.91 for liquid and viscous, respectively). In addition, metrics derived by experts had an equivalent level of reproducibility compared to non-experts (ICCs of 0.96 and 0.94, respectively). Variables that could be derived with commercial software (ManoView™) correlated highly with variables from AIMplot-based analysis, such as 4-s integrated relaxation pressure (r = 0.85) and the 20-mmHg isobaric contour defect (r = 0.92). CONCLUSIONS & INFERENCES: Esophageal AIM analysis is highly reproducible, independent of an observer's level of experience in esophageal motility. Therefore, AIM analysis produces data that are reliable for clinical and research purposes.

Swallowing dysfunction in healthy older people using pharyngeal pressure-flow analysis.

BACKGROUND: Age-related loss of swallowing efficiency may occur for multiple reasons. Objective assessment of individual dysfunctions is difficult and may not clearly differentiate these from normal. Pharyngeal pressure-flow analysis is a novel technique that allows quantification of swallow dysfunction predisposing to aspiration risk based on a swallow risk index (SRI). In this study, we examined the effect of ageing on swallow function. METHODS: Studies were performed in 68 healthy subjects aged 20-91 years (mean 59 years; 29 male), asymptomatic for oropharyngeal disease. Swallowing of liquid and viscous boluses was recorded with a pressure-impedance catheter. Indices of swallow function including the SRI, postswallow residues, upper esophageal sphincter opening and bolus transit time were derived using purpose designed software. KEY RESULTS: Swallow function worsened with increasing age with a significant decline after 80 years. Higher SRI correlated with increasing age (r = 0.257, p < 0.05 for liquids and r = 0.361, p < 0.005 viscous bolus). Subjects over 80 years were overrepresented amongst those with an SRI considered diagnostically relevant (SRI > 15). In addition, upper esophageal sphincter opening was reduced and postswallow residues increased in older subjects. CONCLUSIONS & INFERENCES: Pharyngeal pressure-flow analysis reveals multiple functional abnormalities in older individuals. The higher SRI levels seen in asymptomatic elders possibly reflect a loss of functional reserve with ageing. Automated impedance manometry analysis of swallow function may allow the risk of developing disordered swallowing to be quantified numerically.

New insights in gastroesophageal reflux, esophageal function and gastric emptying in relation to dysphagia before and after anti-reflux surgery in children.

In children with gastroesophageal reflux (GER) disease refractory to pharmacological therapies, anti-reflux surgery (fundoplication) may be a treatment of last resort. The applicability of fundoplication has been hampered by the inability to predict which patient may benefit from surgery and which patient is likely to develop post-operative dysphagia. pH impedance measurement and conventional manometry are unable to predict dysphagia, while the role of gastric emptying remains poorly understood. Recent data suggest that the selection of patients who will benefit from surgery might be enhanced by automated impedance manometry pressure-flow analysis (AIM) analysis, which relates bolus movement and pressure generation within the esophageal lumen.

Automated impedance-manometry analysis detects esophageal motor dysfunction in patients who have non-obstructive dysphagia with normal manometry.

BACKGROUND: Automated integrated analysis of impedance and pressure signals has been reported to identify patients at risk of developing dysphagia post fundoplication. This study aimed to investigate this analysis in the evaluation of patients with non-obstructive dysphagia (NOD) and normal manometry (NOD/NM). METHODS: Combined impedance-manometry was performed in 42 patients (27F : 15M; 56.2 ± 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2 ± 2.9 years). Both liquid and viscous boluses were tested. MATLAB-based algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure (PP), and timing of bolus flow relative to peak pressure (TNadImp-PP). An index of pressure and flow (PFI) in the distal esophagus was derived from these variables. KEY RESULTS: Diagnoses based on conventional manometric assessment: diffuse spasm (n = 5), non-specific motor disorders (n = 19), and normal (n = 11). Patients with achalasia (n = 7) were excluded from automated impedance-manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of flow abnormality on conventional impedance analysis. Several variables derived by integrated impedance-pressure analysis were significantly different in patients as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope (P < 0.05), and shorter TNadImp_PP (P = 0.01). The PFI of NOD/NM patients was significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous: 27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the addition of AIM analysis provided diagnoses and/or a plausible explanation in 95% (40/42) of patients who presented with NOD. CONCLUSIONS & INFERENCES: Compared with conventional pressure-impedance assessment, integrated analysis is more sensitive in detecting subtle abnormalities in esophageal function in patients with NOD and normal manometry.

An impedance-manometry based method for non-radiological detection of pharyngeal postswallow residue.

BACKGROUND: Postswallow residue is indicative of impaired pharyngeal bolus clearance. The integrated nadir impedance to impedance ratio (iZn/Z) is a novel functional variable that can be derived using automated impedance manometry (AIM). In this study, the postswallow pharyngeal iZn/Z was evaluated as a potential correlated postswallow residue and therefore predictor of ineffective swallowing. METHODS: Optimal iZn/Z criteria were determine using a database of 50 randomly selected bolus swallows recorded with impedance, manometry, and videofluoroscopy. The iZn/Z was derived for a region of interest (ROI), spanning the mid-point of the pharyngeal stripping wave to the upper esophageal sphincter proximal margin, and from 0.25 to 1.25 s after the peak of the pharyngeal stripping wave. Videofluorscopy was scored by four experts using a six-point bolus residue scale (BRS) score. Optimized criteria for iZn/Z were then applied to a much larger database of 225 swallows scored for residue by one expert observer. KEY RESULTS: Among individual database, swallows iZn/Z was significantly correlated with average expert BRS score (r = 0.748, P < 0.0001). An iZn/Z of ≥ 500 was optimally predictive of swallows with residue defined by a BRS score of 4 or more. Within the larger cohort, iZn/Z was higher in dysphagia patient swallows compared with controls [2 (1, 4) vs 1 (1, 3), P < 0.005] and swallows with an iZn/Z ≥ 500 had higher bolus residue scores [4 (1, 6) vs 2 (1, 4), P < 0.001]. CONCLUSIONS & INFERENCES: The AIM derived iZn/Z is an easily determined objective non-radiological marker of clinically relevant postswallow residue and therefore has potential diagnostic relevance as a predictor of ineffective swallowing.

Susceptibility to dysphagia after fundoplication revealed by novel automated impedance manometry analysis.

BACKGROUND: Conventional measures of esophageal pressures or bolus transport fail to identify patients at risk of dysphagia after laparoscopic fundoplication. METHODS: Liquid and viscous swallows were evaluated with impedance/manometry in 19 patients with reflux disease before and after surgery. A new method of automated impedance manometry (AIM) analysis correlated esophageal pressure with impedance data and automatically calculated a range of pressure and bolus movement variables. An iterative analysis determined whether any variables were altered in relation to dysphagia. Standard measures of esophago-gastric junction pressure, bolus presence time, and total bolus transit time were also evaluated. KEY RESULTS: At 5 months postop, 15 patients reported some dysphagia, including 7 with new-onset dysphagia. For viscous boluses, three AIM-derived pressure-flow variables recorded preoperatively varied significantly in relation to postoperative dysphagia. These were: time from nadir esophageal impedance to peak esophageal pressure (TNadImp-PeakP), median intra-bolus pressure (IBP, mmHg), and the rate of bolus pressure rise (IBP slope, mmHgs(-1) ). These variables were combined to form a dysphagia risk index (DRI=IBP×IBP_slope/TNadImp-PeakP). DRI values derived from preoperative measurements were significantly elevated in those with postoperative dysphagia (DRI=58, IQR=21-408 vs no dysphagia DRI=9, IQR=2-19, P<0.02). A DRI >14 was optimally predictive of dysphagia (sensitivity 75% and specificity 93%). CONCLUSIONS & INFERENCES: Before surgery, a greater and faster compression of a swallowed viscous bolus with less bolus flow time relates to postoperative dysphagia. Thus, susceptibility to postfundoplication dysphagia is related to a pre-existing sub-clinical variation of esophageal function.

Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy.

BACKGROUND: Esophageal impedance monitoring records changes in conductivity. During esophageal rest, impedance baseline values may represent mucosal integrity. The aim of this study was to assess the influence of acid suppression on impedance baselines in a placebo-controlled setting. METHODS: Impedance recordings from 40 infants (0-6 months) enrolled in randomized placebo-controlled trials of proton pump inhibitor (PPI) were retrospectively analyzed. Infants underwent 24 h pH-impedance monitoring prior to and after 2 weeks of double blind therapy with placebo or a PPI. Typical clinical signs of gastro-esophageal reflux (GER) were recorded and I-GERQ-R questionnaire was completed. KEY RESULTS: Median (IQR) impedance baseline increased on PPI treatment (from 1217 (826-1514) to 1903 (1560-2194) Ω, P < 0.001) but not with placebo (from 1445 (1033-1791) to 1650 (1292-1983) Ω, P = 0.13). Baselines before treatment inversely correlate with the number of GER, acid GER, weakly acid GER, acid exposure, and symptoms. The change in baseline on treatment inversely correlates with acid exposure and acid GER. Patients with initial low baselines have no improved symptomatic response to treatment. CONCLUSIONS & INFERENCES: Impedance baselines are influenced by GER and increase significantly more with PPI therapy than with placebo. Clinical impact of this observation remains undefined as targeting therapy at infants with low baselines does not improve symptomatic response to treatment.