A Method to Objectively Assess Swallow Function in Adults With Suspected Aspiration

GASTROENTEROLOGY 2011;140:1454 1463 A Method to Objectively Assess Swallow Function in Adults With Suspected Aspiration TAHER I. OMARI,*, EDDY DEJAEGER, DIRK VAN BECKEVOORT, ANN GOELEVEN,,# GEOFFREY P. DAVIDSON,*, JOHN DENT,** JAN TACK, and NATHALIE ROMMEL #, *Gastroenterology Unit, Child, Youth & Women s Health Service, North Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia; Geriatric Medicine, University Hospital Leuven, Leuven, Belgium; Radiology, University Hospital Leuven, Leuven, Belgium; ENT, Head and Neck Surgery, MUCLA, University Hospital Leuven, Leuven, Belgium; # Department of Neurosciences, ExpORL, University of Leuven, Leuven, Belgium; **Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia; Neurogastroenterology Clinic, University Hospital Leuven, Leuven, Belgium BACKGROUND & AIMS: Pharyngeal manometry and impedance provide information on swallow function. We developed a new analysis approach for assessment of aspiration risk. METHODS: We studied 20 patients (30 95 years old) with suspected aspiration who were referred for videofluoroscopy, along with controls (ages 24 47 years). The pharyngeal phase of liquid bolus swallowing was recorded with manometry and impedance. Data from the first swallow of a bolus and subsequent clearing swallows were analyzed. We scored fluoroscopic evidence of aspiration and investigated a range of computationally derived functional variables. Of these, 4 stood out as having high diagnostic value: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp PeakP), and the interval of impedance drop in the distal pharynx (flow interval). RESULTS: During 54 liquid, first swallows and 40 clearing swallows, aspiration was observed in 35 (13 patients). Compared to those of controls, patient swallows were characterized by a lower PeakP, higher PNadImp, longer flow interval, and shorter TNadImp PeakP. A Swallow Risk Index (SRI), designed to identify dysfunctions associated with aspiration, was developed from iterative evaluations of variables. The average first swallow SRI correlated with the average aspiration score (r 0.846, P.00001 for Spearman Rank Correlation). An average SRI of 15, when used as a cutoff, predicted aspiration during fluoroscopy for this cohort ( 1.0). CONCLUSIONS: Pressure-flow variables derived from automated analysis of combined manometric/impedance measurements provide valuable diagnostic information. When combined into an SRI, these measurements are a robust predictor of aspiration. Keywords: Manometry Impedance; Esophagus; Clinical Trial; Swallowing Defects. Manometry has been used to assess pharyngoesophageal motor function in a variety of pathologies that cause pharyngeal weakness or impaired upper esophageal sphincter (UES) relaxation. Such disorders lead to ineffective pharyngeal bolus clearance and/or aspiration. The manometric technologies used for this assessment have evolved from single point sensors, to movement-tolerant sleeve sensors and, most recently, multiple closely spaced solid-state point sensors, that is, high resolution manometry. These manometric methods have been used to describe the alterations in pressure patterns in relation to well-recognized causes of aspiration. These include age-related changes, neurodegenerative disease, postsurgical dysfunctions, and abnormalities of UES opening due to various factors. 1 8 Use of manometry for assessment of aspiration risk has been very limited in routine clinical practice. This is because manometric criteria alone have not been shown to accurately assess risk of aspiration and/or post-swallow bolus residue (henceforth called residue). Consequently, swallow assessment with videofluoroscopy (henceforth called fluoroscopy) is often considered necessary, irrespective of whether manometry is performed. Intraluminal impedance measurement has emerged in recent years as a technique that can be used to detect failed esophageal bolus transport and, when combined with esophageal manometry, several patterns of ineffective esophageal body peristalsis. By contrast, the application of impedance measurement to the pharynx has proven extremely challenging. Pharyngeal swallow events occur over a much shorter time span than esophageal peristalsis and several factors cause large variations of the baseline level of impedance, such as variable mucosal contact, residue, and secretions. These factors cause impedance signals to be much more noisy than in the Abbreviations used in this paper: IQR, interquartile range; msu, median standardized units; NadImp, nadir impedance; NadUESP, UES nadir relaxation pressure; OR, odds ratio; PNadImp, pressure at nadir impedance; ROI, region of interest; SRI, Swallow Risk Index; TNadImp- PeakP, time from nadir impedance to peak pressure; UES, upper esophageal sphincter; UES-IBP, UES median intrabolus pressure; UES- RI, UES relaxation interval. 2011 by the AGA Institute 0016-5085/$36.00 doi:10.1053/j.gastro.2011.02.051

May 2011 A METHOD TO ASSESS SWALLOW FUNCTION 1455 esophagus, so that attempts to optimize criteria that identify aberrant bolus flow events and residue have only been partially successful. 9 11 Observation of pharyngoesophageal bolus transit using fluoroscopy is considered the gold standard for evaluation of direct aspiration; however, fluoroscopy requires exposure to ionizing radiation and the information provided is mainly qualitative, although it is possible to derive some numerical measures; such as the timing of opening or closing of the glossopharyngeal junction, velopharyngeal junction, laryngeal vestibule, and UES, which provides information on the function of the mechanisms of airway protection and can be used to assess aspiration risk. 12,13 Quantitative fluoroscopy measures such as these are not derived routinely, presumably because they are considered too time-consuming and cumbersome, although possible. In typical clinical scenarios, patients are not usually referred for fluoroscopy until they have deteriorated clinically with major symptoms. Fluoroscopy is, therefore, used most frequently as an assessment method for symptomatic patients rather than as a screening test for patients at risk but are otherwise doing well. Such patients can benefit from repeated screening over time to catch aspiration before symptoms develop. It is, however, difficult to justify repeated screening using fluoroscopy because of the radiation exposure and clear evidence that fluoroscopy is a relatively poor predictor of development of aspiration pneumonia. 14,15 This is probably due to the fact that susceptibility to aspiration pneumonia is multifactorial. 16 Nevertheless, if a sensitive and specific approach were available that did not require radiology and was relatively simple to perform, then such a test would have a potential role in identifying patients with deglutitive aspiration at a time when aspiration-associated complications might be prevented by intervention. The aim of this study was to develop a new approach for the objective assessment of pharyngeal mechanical function relevant to aspiration using high-resolution intraluminal manometry combined with impedance measurement (hence forth call manometry and impedance). These data were explored for criteria that would enable recognition of individuals at high risk for clinically significant aspiration, without performance of fluoroscopy. Materials and Methods Subjects Twenty patients (13 male; mean, 68.2 years; range, 30 95 years) were studied and underwent simultaneous manometry and impedance and fluoroscopy. All were referred to the swallowing clinic for a videomanometric study of the pharynx and esophagus because of clinical suspicion of deglutitive aspiration due to a deglutition disorder. Underlying diseases/conditions were identified through a review of medical records. The majority of Figure 1. A summary of the patient cohort according underlying medical pathology and presence of aspiration-penetration as detected on videofluoroscopy. patients had a history of neurological disease or neurosurgery (Figure 1). For comparison, 10 healthy adult subjects were recruited who had no swallowing difficulties or other symptoms suggestive of a motility disorder (5 male; mean, 36.6 years; range, 24 47 years). The study protocol was approved by the Research Ethics Committee, University Hospitals Leuven, Belgium. Measurement Technique Studies were performed in the Radiology Department, University Hospitals Leuven with a 3.2-mm diameter solid state manometric and impedance catheter incorporating twenty-five 1-cm spaced pressure sensors and 12 adjoining impedance segments, each 2 cm (Unisensor USA Inc, Portsmouth, NH). Subjects were intubated after topical anesthesia (lignocaine spray) and the catheter was positioned with sensors straddling the entire pharyngoesophageal segment (velopharynx to proximal esophagus). Pressure and impedance data were acquired at 20 Hz (Solar GI Acquisition System, MMS, The Netherlands) with the patient sitting upright. As per routine clinical fluoroscopy, test boluses of 5 and/or 10 ml liquid were administered orally via syringe. The boluses given were standardized across all the patients and controls studied. A standard liquid contrast material (MicropaqueH) was given as liquid bolus. A low osmotic hydrosoluble iodium compound (UltravistH) was used when aspiration was suspected. The viscosity of the administered boluses was determined by a Rheomat 115 Viscometer. The Bingham viscosity of the liquid Barium (MicropaqueH) was 0.22PA s. All bolus stock contained 1% NaCl to enhance conductivity. Video-loops of the fluoroscopic images of swallows were simultaneously acquired at 25 frames/s. The first swallow that followed bolus administration to the mouth

1456 OMARI ET AL GASTROENTEROLOGY Vol. 140, No. 5 was termed the first swallow. If the first swallow failed to clear the bolus from the oral cavity, tongue-base, valleculae, and/or piriform sinus, then the patient was asked to swallow again; these subsequent swallows were termed clearing swallows. For controls, 8 10 ml liquid boluses were administered, 3 of these being recorded during fluoroscopy (including the first swallow and any subsequent clearing swallows), which was the maximum allowed by the Research Ethics Committee, KU Leuven. The additional 5 boluses were recorded with only manometry and impedance. Fluoroscopic Assessment of Aspiration/Penetration Fluoroscopic images from patient and control studies were scored for residue and the occurrence of aspiration-penetration by author (NR) who was blind to all manometric-impedance findings. Aspiration-penetration was assessed using a validated 8-point score, 17 which assessed the depth to which material passes in the airway and by whether or not material entering the airway is expelled during the swallow sequence (score 1 no aspiration, 2 5 penetration, 6 8 aspiration). Swallows were also assessed dichotomously for the presence or absence of post-swallow residue in the valleculae, piriform sinus, and/or posterior pharyngeal wall. Data Analysis Manometry and impedance recordings were correlated precisely in time with fluoroscopic images and analyzed to derive 4 different pharyngeal pressure-flow variables indicative of timing and duration of maximal bolus flow, pressure during maximal bolus flow and pharyngeal contractile pressure. The derivation of variables is described here. Raw manometric and impedance data for each fluoroscopically observed swallow were exported from the recording system in ASCII text format and then analyzed by a separate computer using MATLAB (version 7.9.0.529; The MathWorks Inc). Pressure and impedance data were smoothed by a cubic interpolation method, which doubled the temporal data and increased the amount of spatial data by a factor of 10 (pressure) and 20 (impedance), achieving a virtual increase from 1 pressure and 0.5 impedance values per 1 cm sampled every 5 ms (20 Hz) to 10 pressure and impedance values per cm sampled every 2.5 ms (40 Hz). As we have previously demonstrated, 9 11 baseline levels of impedance vary greatly along the pharyngoesophageal segment due to variability of mucosa to electrode contact and the presence of secretion or residue. This makes the standard approach to impedance analysis (time below/above variably defined thresholds relative to baseline) very unreliable. A new method of impedance analysis was developed that analyzed the shape of the impedance waveform, rather than the magnitude of impedance change. In order to do this reliably, the raw impedance data were standardized to the median impedance (presented as median standardized units [msu] rather than ohms). Pharyngeal Pressure-Flow Variables From the pressure color iso-contour plot, 2 regions of interest (ROI) were defined. The first ROI demarcated the extent of the entire pharyngeal stripping wave for assessment of pressures along and relative to the stripping wave (see First ROI Analysis). The second ROI defined the region of the pharynx distal from the tongue base and was used to determine the pattern of impedance drop and recovery as a marker of bolus presence in the distal pharynx (see Second ROI Analysis). First ROI Analysis The first ROI encompassed the spatial region from velopharynx to the proximal margin of the UES high-pressure zone and the time interval from 0.5 s before to 1.0 s after swallow onset (Figure 2A, B). The timing of the pharyngeal impedance nadir (NadImp) and peak pressure was determined (Figure 2B) at all positions along the first ROI. The average pressure at NadImp (PNadImp), average peak pressure and average time delay from NadImp to peak pressure (TNadImp-PeakP) for the first ROI (Figure 2C) were then calculated from these point data. Second ROI Analysis The second ROI encompassed the pharyngeal stripping wave from tongue-base to proximal margin of the UES high-pressure zone; measurements were analyzed from 0.25 s before to 2.5 s after swallow onset (Figures 2A, D). The interval of impedance drop within the ROI was determined with a method based on one previously described for measurement of UES relaxation interval from pressure values recorded in the region of the UES high-pressure zone. 17 The maximum impedances within the second ROI were measured at all time points and plotted spatially (Figure 2E). An impedance vs cumulative time plot was derived by progressively increasing impedance thresholds from 0 2 msu in steps of 0.01 msu and determining the amount of time that the impedance was below each step level (Figure 2F), this plot was then mathematically described using third-order polynomial equation (the typical equation for a curve with one inflexion). The cumulative time of the inflexion point of a smoothed best-fit curve was used to objectively calculate the flow interval (Figure 2F). UES Relaxation Variables UES relaxation characteristics were measured using the established method of Ghosh et al, 18 which objectively calculated UES relaxation interval (UES-RI), the UES nadir relaxation pressure (NadUESP), the median

May 2011 A METHOD TO ASSESS SWALLOW FUNCTION 1457 Figure 2. Calculation of pharyngeal swallow variables, pressure at nadir impedance (PNadImp), peak pressure, time from nadir impedance to peak pressure (TNadImp-PeakP), and flow interval. (A) The pressure color iso-contour plot showing first region of interest (1 st ROI), used to calculate PNadImp, peak pressure and TNadImp-PeakP, and the second ROI (2 nd ROI), used to calculate flow interval. (B) Pressure impedance iso-contour plot for the 1 st ROI showing the timing of pharyngeal nadir impedance and peak pressure. (C) Plots of TNadImp-PeakP, PNadImp, and peak pressure with average values shown. (D) Pressure impedance iso-contour plot for the 2 nd ROI. (E) The plot of maximum impedance (along y-axis of 2 nd ROI) over time (x-axis of 2 nd ROI). (F) Impedance cumulative time plot (derived using data in D) showing raw data, the third-order polynomial best fit and the inflexion point of the best-fit curve used to define the flow interval. UES, upper esophageal sphincter. intrabolus pressure (UES-IBP), and the UES resistance (calculated as NadUESP/UES-IBP). Statistical Analysis Nonparametric grouped data were presented as medians (interquartile range [IQR]) and compared using the Mann-Whitney rank sum test. For multiple comparisons, Kruskal-Wallis analysis of variance on ranks with pair-wise multiple analysis procedures (Dunn s method) was used. Correlation was determined using Spearman rank-order correlation. The association of variables with presence of aspiration was assessed using multiple logistic regression and analysis of variance with odds ratio (95% confidence interval). The sensitivities and specificities were determined for the different objective variables to detect fluoroscopically defined aspiration. The level of concordance between criteria and the presence of aspiration was expressed with Cohen s -statistic. The scale for values is: 0.00 no agreement, 0.00 0.2 slight, 0.21 0.40 fair, 0.41 0.60 moderate, 0.61 0.8 substantial, 0.81 1.00 almost perfect. For all tests, a P.05 indicated statistical significance. Results In the patients, 54 first swallows were evaluated with the 3 modalities of fluoroscopy, manometry, and impedance; of these, 28 swallows (in 17 patients) failed to

1458 OMARI ET AL GASTROENTEROLOGY Vol. 140, No. 5 clear the bolus fully and in these patients an additional 40 clearing swallows were recorded. Deglutitive aspiration was observed during a total of 35 swallows comprising 14 first and 21 clearing (in 13 patients). In the primary swallows, 36% of aspiration occurred before, 57% during, and 7% after the pharyngeal phase. In clearing swallows, 5% of aspiration occurred before, 86% during, and 9% after the pharyngeal phase. The median (IQR) aspiration-penetration score was 7 for these aspirationassociated swallows. 5,8 Clearance failure was a weak risk factor for aspiration (odds ratio [OR] 1.24; 95% confidence interval, 1.04 1.48; P.05). In controls, 26 first swallows were evaluated with the 3 modalities, and 47 were recorded without fluoroscopy. Of fluoroscopically recorded swallows, 8 (in 4 controls) exhibited trace amounts of residue and therefore failed to clear. Deglutitive aspiration-penetration was never observed during any fluoroscopically recorded control swallows. First Swallows: Controls vs Patients For first swallows, UES-IBP and NadUESP were the only variables that were not significantly different in patients compared to controls (Table 1). Patient first swallows with aspiration had a lower peak pressure, longer flow interval, shorter TNadImp-PeakP, and longer UES-RI than those without aspiration (Table 1). Patient first swallows with residue had a longer flow interval than those without residue (median, 1290 [IQR, 580 2300] ms vs median, 490 [IQR, 320 1120] ms, respectively; P.008). Other first swallow variables were not different in relation to the presence/absence of residue. Fluoroscopically recorded control first swallows with residue had a higher peak pressures (median, 183 [IQR, 137 246] mm Hg vs median, 116 [IQR, 95.6 1334] mm Hg, respectively; P.01) and longer PNadImp-PeakP (median, 470 [IQR, 450 510] ms vs median, 400 [IQR, 370 450] ms, respectively; P.01) than those without residue. The flow interval was not different during swallows with residue (median, 320 [IQR, 230 560] ms vs median, 300 [IQR, 210 380] ms, respectively; P.483), neither were other first swallow variables; however, we noted that the variables most likely to be influenced by UES resistance were all evaluated in relation to residue (PNadImp 17 vs 6 mm Hg; P.162; UES-IBP 13 vs 21 mm Hg; P.091; NadUESP 16 vs 8 mm Hg; P.128; UES resistance 42 vs 25 mm Hg/s; P.162). Clearing Swallows: Patients Clearing swallows in patients with aspiration had a longer flow interval than those without aspiration (median, 2400 [IQR, 2120 2540] ms vs median, 450 [IQR, 380 930] ms, respectively; P.001). No other clearing swallow variables were significantly different in relation to aspiration. Patient clearing swallows with residue had a longer flow interval than those without residue (median, 2240 [IQR, 860 2520] ms vs median, 440 [IQR, 390 2060] ms, respectively; P.022). Clearing swallows with residue also had a higher UES-IBP (median, 20 [IQR, 10 28] mm Hg vs median, 12 [IQR, 4 20] mm Hg, respectively; P.047), a higher NadUESP (median, 10 [IQR, 5 14] mm Hg vs median, 2 [IQR, 1 6] mm Hg, respectively; P.007) and higher UES Resistance (median, 26 [IQR, 12 34] mm Hg/s vs median, 14 [IQR, 6 21] mm Hg/s, respectively; P.049). Peak pressure, PNadImp, TNadImp-PeakP, and UES-RI were not significantly different in relation to residue. Derivation of the Swallow Risk Index Having observed that swallows in patients with suspected aspiration have lower peak pressure, higher PNadImp, longer flow interval and shorter TNadImp- Table 1. Summary Data of 126 First Swallows in Controls and Patients Showing the Relationships Among Important Objective Variables and the Presence of Aspiration-Penetration Controls Patients All first swallows All first swallows (P value vs control) First swallows without aspiration First swallows with aspiration (P value vs no aspiration) No. of swallows analyzed 72 54 40 14 Peak pressure, a mm Hg 138 [110 178] 99 (.001) [66 163] 118 [72 193] 72 (.018) [28 111] Pressure at nadir impedance, a mm Hg 12 [5 17] 21 (.001) [13 36] 24 [14 53] 21 (.547) [13 34] Flow interval, a ms 320 [210 590] 800 (.001) [470 2090] 640 [340 1300] 1980 (.001) [1170 2530] Time nadir impedance to peak 320 [210 590] 190 (.001) [30 300] 260 [100 350] 50 (.006) [20 160] pressure, a ms UES relaxation interval, ms 520 [400 580] 1030 (.001) [750 1300] 980 [660 1220] 1250 (.015) [900 1970] UES intrabolus pressure, mm Hg 12 [6 20] 13 (.311) [9 22] 10 [6 24] 14 (.453) [9 22] Nadir UES pressure, mm Hg 6 [1 13] 5 (.627) [2 10] 5 [2 10] 5 (.898) [0 13] UES resistance, mm Hg/s 22 [11 41] 13 (.012) [8 25] 14 [10 26] 9 (.082) [4 24] NOTE. Data presented as median [interquartile range]. P values of Mann Whitney Rank Sum Test for control vs patient and no aspiration vs aspiration shown in parentheses. Data for which P.05 are presented in bold. UES, upper esophageal sphincter. a Pharyngeal variable.

May 2011 A METHOD TO ASSESS SWALLOW FUNCTION 1459 PeakP than asymptomatic controls, we derived a Swallow Risk Index (SRI) based on the following formula: SRI Flow Interval PNadImp 100 Peak Pressure TNadImp PeakP 1 Overall median SRI for first swallows was significantly elevated in patients compared to controls (SRI median, 17.4 [IQR, 5.7 59.6] vs median, 1.7 [IQR, 0.6 3.7], respectively; P.001). Among swallows from the patient cohort, the median SRI for swallows during which no aspiration was observed were lower compared to swallows with aspiration (first swallow SRI median, 11.9 [IQR, 3.9 21.3] without aspiration vs median, 66.8 [IQR, 24.6 136.8] with aspiration; P.001; clearing swallow mean SRI was 22.4 [IQR, 10.5 56.3] without aspiration vs SRI mean, 64.9 [IQR, 35.7 105.2] with aspiration; P.01). Logistic regression also revealed that the OR for the correlation of aspiration with SRI was 8.1 (CI, 2.0 32.6) (P.003) for first swallows and OR 19.6 (CI, 2.3 164.8) (P.006) for clearing swallows. The SRI increased significantly in line with increased severity of aspiration as is shown in Figure 3 for first swallows. The median SRI also differentiated clearing swallows with penetration (SRI median, 22.4 [IQR, 10.5 56.3]) and aspiration (SRI median, 79.1 [IQR, 49.3 107.3]), from clearing swallows with no aspiration (SRI median, 15.7 [IQR, 5.8 89.8]) (analysis of variance P.002, pair-wise P.05 aspiration vs no aspiration). Bolus volume had no significant effect on the SRI (first swallow SRI median, 23.0 [IQR, 6.8 72.4] vs median, 15.9 [IQR, 3.6 24.6]; P.169 and clearing swallow SRI median, 56.3 [IQR, 22.4 91.4] vs median, 24.6 [IQR, 12.8 78.1]; P.267 for 5 ml and 10 ml boluses, respectively). Predictive Value of First Swallow SRI We assessed whether the first swallow SRI recorded in an individual patient could predict the presence/absence of aspiration during fluoroscopy. The average first swallow SRI correlated strongly with the average aspiration score for all fluoroscopically recorded swallows (Spearman rank order correlation 0.846; P.00001) (Figure 4A). An average first swallow SRI of 15.0 was a perfect threshold for accurate prediction of aspiration in the patient cohort (Figure 4B) and was also optimal in terms of sensitivity and specificity (Figure 4C). Discussion A novel automated approach to the analysis of pharyngeal manometry and impedance recordings was used to identify patients with deglutitive aspiration. We developed an SRI that is based upon the objective calculation of 4 pharyngeal pressure-flow variables. This new methodology has the potential to identify individual patients at deglutitive aspiration risk without use of fluoroscopy. The approach is based on the premise that the pathophysiology of deglutitive aspiration is multifactorial. Hence, prediction of deglutitive aspiration risk requires the measurement of pressure and flow with high spatial resolution along the entire pharynx and the derivation of measures that assess the timing of bolus propulsion (TNadImp-PeakP), pressure during bolus flow (PNadImp), peak pharyngeal pressure, and pharyngeal flow interval (a summary of these objective variables including reference values can be found in Supplementary Table 2). Previous approaches to the evaluation of the mechanics of pharyngeal bolus flow with pressure/impedance have only been partially successful. 9 11 These earlier studies concentrated on optimizing impedance-based criteria for bolus detection, but the interpretation of the impedance signal is especially difficult in patients with suspected aspiration, because of pooling of secretions and altered motor function of the pharynx and UES. Our data show that incomplete pharyngeal emptying (ie, residue after an initial swallow) on its own is a relatively insensitive indicator of patterns of motor function that result in aspiration (OR 1.240; P.05). Indeed, pha- Figure 3. Box plot showing median and interquartile ranges for first swallow Swallow Risk Index in controls and patients. Patient data are further stratified based on aspiration score. No aspiration score 1, penetration score 2 5, and aspiration score 6 8. Gray circles show the data from individual swallows. Groups were compared using Kruskal-Wallis 1-way analysis of variance (ANOVA) on ranks and pairwise multiple comparison procedures (Dunn s method).

1460 OMARI ET AL GASTROENTEROLOGY Vol. 140, No. 5 Figure 4. (A) Correlation of patient average aspiration score with average first swallow Swallow Risk Index (SRI). (B) Agreement between individual and average first swallow SRI cutoff values and the presence/ absence of aspiration-penetration during fluoroscopy. An ROC curve for individual and average first swallow SRI is shown also in graphs (C) and (D), respectively. ryngeal/ues motor function does not always empty the pharynx in health, as our data from our control subjects show. We have addressed the limitations of impedance recording by strategies that extract more reliable information from the impedance signal, which was then used to guide the analysis of pharyngeal pressures. This approach achieved a more direct measure of the spatial organization of pharyngeal motor function. This contrasts with the standard approach that evaluates impedance and pressure findings separately. The combined manometry and impedance recordings were evaluated with automated analysis algorithms that derived the variables presented in this article. The entire impedance signal during swallowing was also analyzed automatically and processed in a way that reduced its noisiness. This is a novel approach to evaluation of impedance signals, which are usually scored according to periods of time during which impedance is above or below a certain cutoff value. Conceptually, the calculation of flow interval using impedance is based on the method used by Ghosh et al 18 to estimate UES relaxation interval using manometry. The flow interval was designed to be an objective estimate of impedance drop interval and therefore bolus clearance time. Interestingly, the flow interval for first swallows was not elevated in relation to the presence of residue in controls and, while elevated with residue in patients, correlated more strongly with aspiration-penetration (OR 3.3; 95% CI, 1.5 7.4; P.004) than bolus residue (OR 2.4; 95% CI, 1.1 5.2; P.021), suggesting that the flow interval is a very useful single measure of deglutitive function/dysfunction. However, flow interval alone cannot diagnose the cause of dysfunction, hence the importance of inclusion of other direct measures. As illustrated in Figures 5 and 6, the pattern of abnormal pharyngeal and UES motor function in patients varies with different pathologies that lead to obstruction or weakness. Because the SRI takes into account several different measures of function, it delivers an accurate assessment of aspiration risk, regardless of the pattern of functional impairment. Recognition of particular patterns of impairment of pressure-flow variables should allow a relatively specific diagnosis of varying mechanical dysfunctions that result in aspiration. From such analysis, it may be possible to devise welltargeted therapeutic interventions. It has been previously shown that precise mechanistic analysis of the coordination of opening or closing of the glossopharyngeal junction, velopharyngeal junction, laryngeal vestibule, and UES in relation to aspiration during swallowing can similarly predict circumstances during which aspiration is likely. 12 Although the methodology is obviously different, the essential findings parallel those of the current study and demonstrate the value of combining key measures for determination of the adequacy of swallowing and estimation of risk of aspiration. However, although the spatial analysis of movement of laryngeal structures can be performed using interactive software, such methods still require that radiology be performed and to date are not widely in clinical use.

May 2011 A METHOD TO ASSESS SWALLOW FUNCTION 1461 Figure 5. Example tracings of first swallows (10 ml liquid) recorded in a control subject and 2 patients (individual results for pharyngeal variables and aspiration-penetration scores are shown in Figure 6). (A) A 39-year-old asymptomatic male control. (B) A 58-year-old man who developed symptoms post-anterior cervical fusion (C5 C6) surgery in whom fluoroscopy demonstrated high obstruction and no evidence of aspiration (aspiration-penetration score 1). (C) A 57-year-old stroke patient (male, right hemisphere) who had continuous signs of aspiration on liquids and in whom fluoroscopy demonstrated aspiration (aspiration-penetration score 7). Top row: Color iso-contour plots of pressure only. Second row: Pressure-impedance iso-contour plots showing pressure as lines (10 mm Hg iso-contours) with impedance superimposed (color iso-contour showing impedance levels 1 median standardized units [msu]). Iso-contour plots of pressure within the dotted box are in the third row. In these plots dotted and solid lines define the timing of nadir impedance (NadImp) and the timing of peak pressure, respectively. UES, upper esophageal sphincter. The automated and objective methods used for deriving pharyngeal pressure-flow variables is a major strength of this study. Although these methods are complex in themselves, they are simple to apply because the operator only needs to define the ROI on the specially developed analysis system. This new method receives the data directly from high-resolution manometric systems as text, a standard output of such equipment. Since completion of data analysis for the current study we have developed analysis software to simplify the analysis process for derivation of the SRI and have found this to have high inter-rater reproducibility among blinded observers (mean intraclass correlation coefficient 0.937; range, 0.869 0.980). This study also evaluated UES relaxation pressure-time variables (UES-RI, NadUESP, UES-IBP, and UES resistance 18 ). Although UES-RI and UES resistance were significantly different in our patients, only UES-RI was significantly altered in relation to the presence of aspiration-penetration. This is an interesting finding, given that the most frequently used interventions for aspiration, ie, UES myotomy and Botulinum toxin injection, are aimed at weakening the UES. Such interventions are, however, known to have inconsistent efficacy in patients with central nervous system damage, 19 who represent the majority of the patients in our study cohort. Undoubtedly there are patients who have problems with aspiration-penetration because of impaired UES opening, but these were not well represented in the cohort. Our analysis of a large number of variables recorded with very high time resolution from the manometric and impedance tracings would have been impossible without automation. This wealth of variables that we measured allowed us to explore which combinations of these were most effective for identifying patients with aspirationpenetration, hence the derivation of the SRI. Our results show that patient average SRI data can estimate a patient s aspiration risk. This is an important initial study,

1462 OMARI ET AL GASTROENTEROLOGY Vol. 140, No. 5 Figure 6. Comparison of pharyngeal variables and aspiration-penetration scores for the 3 subjects for which data from sample individual swallows are shown in Figure 5. Individual data for peak pressure, pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), flow interval, aspiration penetration score and Swallow Risk Index (SRI) are shown. The Patient Average SRI is based on the average of all first swallows recorded in each subject (diagnostic cutoff of 15 aspiration-penetration). Control ranges for each variable are shown by gray shading; abnormal findings compared to controls are indicated as black bars. For graphs comparing patient average SRI, the gray line indicates the optimal cutoff criteria. NOTE: Obstruction patient B, compared to stroke patient C, had a normal peak pressure but elevated PNadImp. Stroke patient C had a mean TNadImp-PeakP 0 (ie, on average nadir impedance occurred after peak pressure), this is suggestive of highly ineffective bolus propulsion in advance of the pharyngeal stripping wave. Stroke patient C had the highest average SRI, which exceeded our cutoff of 15. This is consistent with fluoroscopy findings of aspiration in patient C. UES, upper esophageal sphincter. which now opens the door to undertake further investigations. Volitional control would be worthy of study; to date we have not tested any swallow maneuvers or the difference between cued and noncued swallows. 20 Swallows in the current studies were cued by the radiologist to ensure optimal radiological registration. The extent to which volitional control or cueing a swallow can influence the SRI remains to be determined. Our studies were all performed using topical anesthesia. Topical anesthesia is important for providing a level of comfort so that the procedure can be performed quickly and effectively. Used judiciously, mucosal anesthesia appears to have had no effect on the outcomes, given the large differences seen between patients and controls and swallows with or without aspiration. A possible factor that may have influenced our findings is the fact that our control group was relatively young compared to the patient group. This is relatively unimportant, as our major analysis and conclusions with respect to aspiration are based on exploration of data from patients only. Our patient cohort predominantly had neurological diseases but was varied and included patients with a wide age range. We studied patients prospectively as they were referred for investigation and therefore had no control over which patients were to be investigated in our study. This study design means that the cohort is typical of the overall population of patients in whom aspiration is suspected on clinical grounds. The fact that the predictive value of the SRI appears to be robust in the face of the potential confounding factors discussed engenders confidence that this methodology has very real potential for clinical implementation as a screening tool for aspiration risk. There are many populations at risk for aspiration-penetration, such as poststroke patients, patients with diverse neurological and muscle diseases, or those who have had pharyngeal or neurological surgery. These patients are well-represented in the study cohort and demonstrated elevated SRI in

May 2011 A METHOD TO ASSESS SWALLOW FUNCTION 1463 relation to aspiration. These patients are most often not investigated by fluoroscopy until they demonstrate clinical signs and symptoms of aspiration. The value of using this methodology as a screening tool to trigger early intervention requires further investigation by way of outcomes studies to determine if, for example, SRI predicts clinical deterioration and what interventions are of most value. In conclusion, we present novel findings in control subjects and in a cohort of patients with predominantly neurological problems who were referred for investigation of suspected aspiration. These show that combined high-resolution, solid-state manometry and impedance recordings can be objectively and automatically analyzed to derive robust multiple pressure-flow variables that are altered in relation to pathology. Importantly, an SRI can be derived through the combination of these pressureflow variables and used to predict circumstances when aspiration is likely. References 1. Bardan E, Kern M, Arndorfer RC, Hofmann C, Shaker R. Effect of aging on bolus kinematics during the pharyngeal phase of swallowing. Am J Physiol Gastrointest Liver Physiol 2006;290:G458 G465. 2. Cook IJ, Weltman MD, Wallace K, et al. Influence of aging on oral-pharyngeal bolus transit and clearance during swallowing: scintigraphic study. Am J Physiol Gastrointest Liver Physiol 1994; 266:G972 G977. 3. Shaker R, Lang IM. Effect of aging on the deglutitive oral, pharyngeal, and esophageal motor function. Dysphagia 1994;9: 221 228. 4. Shaker R, Ren J, Podvrsan B, et al. Effect of aging and bolus variables on pharyngeal and upper esophageal sphincter motor function. Am J Physiol Gastrointest Liver Physiol 1993;264: G427 G432. 5. Yokoyama M, Mitomi N, Tetsuka K, Tayama N, Niimi S. Role of laryngeal movement and effect of aging on swallowing pressure in the pharynx and upper esophageal sphincter. Laryngoscope 2000;110:434 439. 6. Cook IJ, Blumbergs P, Cash K, Jamieson GG, Shearman DJ. Structural abnormalities of the cricopharyngeus muscle in patients with pharyngeal (Zenker s) diverticulum. J Gastroenterol Hepatol 1992;7:556 562. 7. Dantas RO, Cook IJ, Dodds WJ, Kern MK, Lang IM, Brasseur JG. Biomechanics of cricopharyngeal bars. Gastroenterology 1990; 99:1269 1274. 8. Wang AY, Kadkade R, Kahrilas PJ, Hirano I. Effectiveness of esophageal dilation for symptomatic cricopharyngeal bar. Gastrointest Endosc 2005;61:148 152. 9. Omari TI, Rommel N, Szczesniak MM, et al. Assessment of intraluminal impedance for the detection of pharyngeal bolus flow during swallowing in healthy adults. Am J Physiol Gastrointest Liver Physiol 2006;290:G183 G188. 10. Szczesniak MM, Rommel N, Dinning PG, Fuentealba SE, Cook IJ, Omari TI. Optimal criteria for detecting bolus passage across the pharyngo-oesophageal segment during the normal swallow using intraluminal impedance recording. Neurogastroenterol Motil 2008;20:440 447. 11. Szczesniak MM, Rommel N, Dinning PG, Fuentealba SE, Cook IJ, Omari TI. Intraluminal impedance detects failure of pharyngeal bolus clearance during swallowing: a validation study in adults with dysphagia. Neurogastroenterol Motil 2009;21:244 252. 12. Kahrilas PJ, Lin S, Rademaker AW, Logemann JA. Impaired deglutitive airway protection: a videofluoroscopic analysis of severity and mechanism. Gastroenterology 1997;113:1457 1464. 13. Power ML, Hamdy S, Singh S, Tyrrell PJ, Turnbull I, Thompson DG. Deglutitive laryngeal closure in stroke patients. J Neurol Neurosurg Psychiatry 2007;78:141 146. Epub 2006 Sep 29. 14. Croghan JE, Burke EM, Caplan S, Denman S. Pilot study of 12-month outcomes of nursing home patients with aspiration on videofluoroscopy. Dysphagia 1994;9:141 146. 15. Aviv JE, Sacco RL, Mohr JP, et al. Laryngopharyngeal sensory testing with modified barium swallow as predictors of aspiration pneumonia after stroke. Laryngoscope 1997;107:1254 1260. 16. Langmore SE, Terpenning MS, Schork A, et al. Predictors of aspiration pneumonia: how important is dysphagia? Dysphagia 1998;13:69 81. 17. Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia 1996;11:93 98. 18. Ghosh SK, Pandolfino JE, Zhang Q, Jarosz A, Kahrilas PJ. Deglutitive upper esophageal sphincter relaxation: a study of 75 volunteer subjects using solid-state high resolution manometry. Am J Physiol Gastrointest Liver Physiol 2006;291:525 531. 19. MP Kos, EF David, EC Klinkenberg-Knol, HF Mahieu. Long-term results of external upper esophageal sphincter myotomy for oropharyngeal dysphagia. Dysphagia 2010;25:169 176. 20. Logemann, JA, Pauloski, BR, Colangelo L, Lazarus C, Fujiu M, Kahrilas PJ. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995;38:556 563. Received September 18, 2010. Accepted February 6, 2011. Reprint requests Address requests for reprints to: Taher Omari, PhD, Gastroenterology Unit, Child, Youth & Women s Health Service, 72 King William Road, North Adelaide SA 5006, South Australia, Australia. e-mail: taher.omari@adelaide.edu.au; fax: 61 8 81616088. Conflicts of interest The author discloses no conflicts. Funding This study was supported by the Thrasher Research Fund, Salt Lake City, Utah and a Methusalem Grant from Leuven University to Prof J. Tack.