The acoustic cough monitoring and manometric profile of cough and throat clearing

Original article

The acoustic cough monitoring and manometric profile of cough andthroat clearing

Y. Xiao,1,3 D. Carson,1 L. Boris,1 J. Mabary,2 Z. Lin,1 F. Nicodème,1,4 M. Cuttica,1 P. J. Kahrilas,1

J. E. Pandolfino1

1Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois,2Sandhill Scientific Inc., Denver, Colorado, USA; 3Department of Gastroenterology and Hepatology, FirstAffiliated Hospital, Sun Yat-sen University, Guangzhou, China; and 4Department of Thoracic Surgery,Université de Montréal, Montréal, Quebec, Canada

SUMMARY. Cough and throat clearing might be difficult to differentiate when trying to detect them acousticallyor manometrically. The aim of this study was to assess the accuracy of acoustic monitoring for detecting cough andthroat clearing, and to also determine whether these two symptoms present with different manometric profiles onesophageal pressure topography. Ten asymptomatic volunteers (seven females, mean age 31.1) were trained tosimulate cough and throat clearing in a randomized order every 6 minutes during simultaneous acoustic monitoringand high-resolution manometry. The accuracy of automated acoustic analysis and two blinded reviewers werecompared. The pattern of the events and the duration of the pressure changes were assessed using the 30 mmHgisobaric contour. There were 50 cough and 50 throat-clearing events according to the protocol. The sensitivity andspecificity of automated acoustic analysis was 84% and 50% for cough, while the blinded analysis using soundrevealed a sensitivity and specificity of 94% and 92%. The manometric profile of both cough and throat clearing wassimilar in terms of qualitative findings; however, cough was associated with a greater number of repetitivepressurizations and a more vigorous upper esophageal sphincter contraction compared with throat clearing. Theacoustic analysis software has a moderate sensitivity and poor specificity to detect cough. The profile of cough andthroat clearing in pressure topography revealed a similar qualitative pattern of pressurization with more vigorouspressure changes and a greater rate of repetitive pressurizations in cough.

KEY WORDS: acoustic monitoring, cough, high-resolution manometry, throat clearing.

INTRODUCTION

Gastroesophageal reflux is a potential cause ofchronic cough.1,2 However, accurate assessment ofthe relationship between cough and reflux requiresprecise timing of both the reflux and cough eventsbecause the time sequence between the two events isextremely close, and patients are unable to signal theevent marker with enough precision to provide avalid assessment during ambulatory reflux testing.3 Inorder to improve the detection of reflux-associatedcough, two adjuvant techniques have been incor-porated into ambulatory reflux monitoring toimprove the identification of cough: acoustic cough

monitoring and manometry. Acoustic cough moni-toring was developed to detect the cough eventthrough sound to remove the variability of patientself-reporting.4 Similarly, ambulatory manometryhas been added to reflux testing to detect the pressurechanges associated with cough to improve accuracy.However, both techniques are still in the investigativestage and are currently not used widely in clinicalpractice.

A potential confounder in the utilization of acous-tic cough monitoring and ambulatory manometryis the difficulty in distinguishing cough from throatclearing. Both are protective mechanisms to propelirritants away from the airway. Throat clearing is aconscious or unconscious attempt to remove an irri-tant in the throat. The sound of throat clearing issimilar to cough potentially making it difficult to dis-tinguish between the two by sound alone. Addition-ally, throat clearing may also be associated with

Address correspondence to: Dr Yinglian Xiao, MD, PhD,Department of Gastroenterology and Hepatology, FirstAffiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road2, Guangzhou, 510080, China. Email: [email protected]

Diseases of the Esophagus (2013) ••, ••–••DOI: 10.1111/dote.12038

© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus 1

changes in the intrathoracic and intra-abdominalpressures that may potentially mimic cough onmanometry. Hence, more information regarding theacoustics and pressure topography patterns of throatclearing may be helpful in understanding the patho-genesis of cough and differentiating it from throatclearing.5,6

The aim of this study was to evaluate the acousticsignal for both cough and throat clearing using anew acoustic cough-monitoring system that utilizesa combination of tracheal, chest wall, and ambientsound sensors to record acoustic signals that are thenanalyzed with computer software to identify coughevents. We hypothesize that this technique may beable to distinguish cough from throat clearing basedon key elements of the cough signal. Given thatmanometry has also been used to refine reflux testingin terms of cough detection, we also sought to definethe manometric signature of throat clearing as thishas not been rigorously studied.

METHODS

Subjects and study protocols

Ten asymptomatic volunteers (seven females, meanage 31.1) were included. Volunteers were recruited byadvertisement or word of mouth and had no historyof gastrointestinal symptoms, pulmonary symptoms,or surgery. All subjects underwent simultaneousacoustic cough monitoring, high-resolution manom-etry (HRM), and esophageal multichannel intralu-minal impedance-pH (MII-pH) monitoring for 80minutes. The subjects were trained to simulate coughand throat clearing in a randomized order every 6minutes during the study after an accommodationperiod. Altogether, five episodes of cough and fiveepisodes of throat clearing for each subject wererequired. An investigator was observing the subjectsduring the measurements. The investigator wouldmake a note in the manometry procedure protocolwhen the subject had a spontaneous natural coughor throat clearing event outside of the protocol. Thestudy protocol was approved by the NorthwesternUniversity Institutional Review Board, and informedconsent was obtained from each subject.

Esophageal HRM

HRM studies were performed using a 4.2-mm outerdiameter solid-state assembly with 36 circumferentialsensors at 1-cm intervals (Sierra Scientific Instru-ments, Los Angeles, CA, USA). Transducers werecalibrated at 0 and 300 mmHg using externallyapplied pressure. The manometric assembly wasplaced transnasally and positioned to record from thehypopharynx to the stomach with three intragastric

sensors. The study was carried out with the subjectsin the upright position.

Acoustic cough monitoring

Acoustic cough monitoring (Sandhill Scientific Inc.,Denver, CO, USA) was used to detect the coughthrough a combination of the following: (i) a vibra-tory sensor placed above the sternal notch to recordthe vibration of the trachea (tracheal sensor); (ii) avibratory sensor placed at the second intercostalspace in the midclavicular line to record the chest wallsounds (thoracic sensor); (iii) a microphone on thecollar to record the ambient sound; and (iv) a respi-ratory belt positioned on the lower thoracic cavity tomonitor respiration (Fig. 1). This monitor has neverbeen validated before in cough patients.

MII-pH monitoring

MII-pH monitoring was performed using a Sleuthsystem – Multichannel Intraluminal ImpedanceAmbulatory System (Sandhill Scientific Inc.), whichincludes a portable data logger with impedance-pHamplifiers and a catheter containing two pH channelsand six impedance channels. The catheter was cali-brated at pH 4 and 7 with buffer solutions beforeintubation. It was placed transnasally alongside ofthe HRM catheter and positioned to record the pHchange 5 cm above the lower esophageal sphincter(LES) and impedance change 3, 5, 7, 9, 15, and 17 cmabove the LES. The MII-pH monitoring was syn-chronized with the acoustic cough monitoring using asynchronizer (Sandhill Scientific Inc.).

Data analysis

The HRM for each subject was reviewed manuallyusing the Smart Mouse tool in ManoView soft-ware (Given Imaging, Duluth, GA, USA). Intra-esophageal pressure, intragastric pressure, and thegastroesophageal pressure gradient were analyzed5 seconds before the event as well as during the cough

Fig. 1 Sensor placement for acoustic cough monitoring.

2 Diseases of the Esophagus

© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

and throat-clearing events using the smart mouse. Theintra-esophageal pressure was measured by calculat-ing the average pressure 5 cm above the esophagogas-tric junction (EGJ) across at least three channels. Theintragastric pressure was measured by calculatingthe average pressure 1 cm below the EGJ across abouttwo channels. When more than one componentoccurred during the event, the mean pressure throughthe whole event was measured. The pattern of theevents and the duration of the pressure changes wereassessed using the 30 mmHg isobaric contour to deter-mine whether distinct patterns could be identified.Occlusive maximal pressure force along the length ofthe upper esophageal sphincter (UES) and EGJ wasmeasured using the e-Sleeve and referenced to gastricpressure (Fig. 2).

For acoustic cough-monitoring analysis, auto-mated cough detection analysis was performed withPulmoTrack computer software (iSonia, RanchoCucamonga, CA, USA) to identify cough events andtime of onset. The automated analysis used a two-stepanalysis algorithm in which cough ‘candidates’ areidentified based on sound amplitude patterns. In thesecond step the ‘candidates’ are verified based on fitto a cough pattern in both the time and frequency

domains. Two blinded investigators reviewed theaudio recordings to verify the timing of the cough andthroat clearing independently; a third investigatorreviewed the sounds when there was discrepancybetween the previous two investigators. The mecha-nisms of both cough and throat clearing wereexplained to the blinded reviewers, and then theywould listen to the audio recorded from the patients.The accuracy of the automated acoustic analysis andthe blinded reviewers were compared against the origi-nal protocol.

Impedance-pH tracings were analyzed manually;all reflux episodes were characterized as acidic (pH <4), weakly acidic (4 � pH � 7), or weakly alkaline(pH > 7) according to a consensus report on thedetection and definitions of gastroesophageal reflux.7

The contents of refluxate including liquid, gas, andmixed were detected as previously described.8

Statistical analysis

All the parameters were presented as a median value(interquartile range). The sensitivity and specificity forboth the acoustic cough monitoring and the blindedinvestigator to define the cough were calculated tovalidate the accuracy of the device. Manometric mea-sures of cough and throat clearing were comparedusing the Mann–Whitney test. All P-values were two-tailed, with the level of significance defined at 0.05.

RESULTS

The accuracy of acoustic cough monitoring

In total, there were 100 events during the study pro-tocol; 50 cough and 50 throat clearing. One episodeof cough might contain one or numerous sounds,while one throat clearing contains only one throat-clearing sound. Using the protocol as the gold stan-dard, eight episodes of cough (16%) were missed bythe automated acoustic analysis, and 25 episodes ofthroat clearing (50%) were mistakenly detected ascough. Thus, the sensitivity and specificity of auto-mated acoustic analysis was 84% and 50% for coughcompared with the protocol (Table 1). The positiveand negative predictive values were 62.7% and 66.7%,respectively. There were 31 spontaneous naturalsounds outside of the protocol that were recordedand documented by the investigator monitoring the

Fig. 2 Methodology for measurement of occlusive upperesophageal sphincter (UES) and esophagogastric junction (EGJ)pressure using the e-Sleeve. The pressure within the e-Sleeve forthe EGJ and UES measurement is referenced to intragastricpressure so the two sphincters can be compared directly.

Table 1 The accuracy of acoustic cough monitoring and the blinded investigator to detect the cough

Event detected by acousticcough monitoring

Event detected by theinvestigator through sound

TotalCough Throat clearing Cough Throat clearing

Protocol cough (n = 50) 42 8 47 3 50Protocol throat clearing (n = 50) 25 25 4 46 50

Differentiate cough and throat clearing 3


patient. These were noted during the protocol anddefined as cough (n = 7), throat clearing (n = 12),belching (n = 7), and laughing (n = 5). The automatedacoustic analysis missed one of the seven spontane-ous cough events (14%), and 10 other spontaneoussounds (32%) were misclassified as cough (five spon-taneous throat clearings and five laughs).

The manual assessment of listening to the eventsby the independent blinded reviewers revealed ahigher sensitivity and specificity compared with theautomated acoustic analysis. The kappa statistic wasperformed to assess the agreement between these tworeviewers; the kappa value was 0.82. Three episodesof cough (6%) were missed, and four episodes ofthroat clearing (8%) were mistakenly categorized ascough by the investigators. Using the protocol as thegold standard, the blinded analysis based on soundalone revealed a sensitivity and specificity for coughof 94% and 92%, respectively (Table 1). The positiveand negative predictive values were 92.2% and 93.9%,respectively.

The manometric profile of cough and throat clearing

Fifty episodes of cough and 50 throat-clearingevents were analyzed manometrically. Typical pres-

sure topography of cough and throat-clearing eventsare illustrated in Figure 3. Both events began witha decrease in esophageal pressure (brief inspiration),followed by a distal excursion of the EGJ high-pressure zone and UES, with a concomitant increasein UES and EGJ occlusive pressure relative to intra-gastric pressure; this is followed shortly by an abruptsimultaneous increase in gastric and esophageal pres-sure (Fig. 3). All throat-clearing events had a single-pressure burst, while the cough events had burststhat varied from 1 to 3 with a median of 2. Thus, thecoughs were typically associated with more repetitivepressurizations.

Comparison of the manometric profile betweencough and throat clearing (Table 2) revealed a highergastroesophageal pressure gradient within 5 secondsbefore coughing than before throat clearing (P =0.048). Additionally, there were greater occlusiveUES pressure, intragastric (P < 0.001), and intra-esophageal pressures (P < 0.001) during cough. Thedistal gastroesophageal junction shift was also morepronounced during cough (P < 0.001). Furthermore,the total duration of sustained pressure increase wassignificantly longer in cough than throat clearing(P < 0.001). However, when the duration of only asingle-pressure burst was compared, the first pressure

Fig. 3 The manometric profile of throat clearing and cough. Panel (A) illustrates a typical throat clearing, panel (B) illustrates aone-component cough, panel (C) illustrates a two-component cough, and panel (D) illustrates a three-component cough.



burst of cough and throat clearing had similar dura-tion (P = 0.131). Cough and throat clearing wereequally likely to be followed by swallows (52.9% vs.43.4%, P = 0.391), whereas the throat clearing had ashorter latency for swallows following the event (1.5seconds vs. 3.5 seconds, P = 0.036). Interestingly, thegastroesophageal gradient and the occlusive EGJpressure were similar during the events. Comparisonof the manometric parameters between the protocolcough events detected and those missed by the acous-tic cough automated analysis was performed to deter-mine whether cough events that were misclassifiedwere overtly different in terms of the pressures gen-erated during the event, and there was no significantdifference between the coughs that were detected andthose that were missed (Table 3).

In order to validate the manometric pattern weobtained from the protocol cough and throat-clearing events, we also analyzed spontaneousrandom events. We identified 19 cough and throatclearings among 31 spontaneous events outside of theprotocol to review. Two throat clearings were tooweak to cause any change on the esophageal pressuretopography, leaving 10 spontaneous throat-clearingevents and seven spontaneous coughs for analysis.The sensitivity and specificity of the manometric pat-terns defined by the protocol to detect cough were71.4% and 50%. The spontaneous cough events thatwere mistakenly categorized as throat clearing wereall associated with a single pressurization.

The simultaneous MII-pH tracing were reviewedmanually. In total there were five reflux episodes

Table 2 Manometric profile of cough and throat clearing (median [25th, 75th])

Cough (n = 50) Throat clearing (n = 50) P-value

Pre-event pressure (mmHg)Occlusive UES pressure† 36.7 (24.4, 48.6) 39.6 (21.6, 52.1) 0.508Intra-esophageal -9.0 (-12.0, -4.0) -6.0 (-10.0, -3.0) 0.052Intragastric 10.0 (7.8, 13.3) 10.0 (7.8, 13.3) 1Gastroesophageal gradient 20.0 (14.2, 26.3) 16.0 (13.0, 21.3) 0.048Occlusive EGJ pressure† 20.6 (8.1, 33.5) 22.7 (11.9, 29.6) 0.484

During the event pressure (mmHg)Occlusive UES pressure† 152.5 (106.9, 183.8) 79.1 (24.5, 125.1) <0.001Intra-esophageal 54.0 (27.5, 72.0) 26.5 (17.0, 33.0) <0.001Intragastric 65.5 (38, 76.3) 38.0 (30.0, 46.0) <0.001Gastroesophageal gradient 11.5 (7.0, 15.0) 12.0 (9.0, 16.5) 0.303Occlusive EGJ pressure† 19.4 (11.1, 29.8) 23.4 (11.6, 29.6) 0.361Junction shift (cm) -1.6 (0.9, 1.2) -0.68 (0, 1.0) <0.001Event duration (seconds) 0.68 (0, 1.0) 0.4 (0.1, 0.9) 0.001

First component characteristic of the eventIntra-esophageal 68.0 (40.8, 92.2) 26.5 (17.0, 33.0) <0.001Intragastric 77.0 (53.0, 102.0) 38.0 (30.0, 46.0) <0.001Gastroesophageal gradient 12.0 (7.8, 16.0) 12.0 (9.0, 16.5) 0.250First component duration (seconds) 0.4 (0.16, 0.5) 0.3 (0, 0.6) 0.131

†Referenced to gastric pressure, all other values were referenced to atmospheric pressure. EGJ, esophagogastric junction; UES, upperesophageal sphincter.

Table 3 Comparison of manometric profile between detected and missed cough by the automated acoustic cough analysis (median[25th, 75th])

Detected cough (n = 42) Missed cough (n = 8) P-value

Pre-event pressure (mmHg)Occlusive UES pressure† 37.4 (24.4, 50.3) 35.8 (23.9, 40.8) 0.612Intra-esophageal -8.6 (-12.5, -4.1) -8.7 (-10.1, -11.1) 0.887Intragastric 10.3 (7.5, 14.3) 9.3 (7.2, 11.2) 0.490Gastroesophageal gradient† 20.2 (13.8, 27.4) 18.3 (14.6, 22.1) 0.524Occlusive EGJ pressure 20.6 (6.4, 34.0) 20.2 (14.8, 28.6) 0.746

During the event pressure (mmHg)Occlusive UES pressure† 155.9 (113.6, 195.6) 133.1 (105.7, 153.9) 0.458Intra-esophageal 58.0 (35.3, 72.0) 35.0 (17.8, 56.2) 0.117Intragastric 68.0 (42.0, 79.3) 44.5 (33.5, 71.2) 0.176Gastroesophageal gradient 11.0 (7.0, 15.0) 14.0 (6.0, 17.2) 0.397Occlusive EGJ pressure† 20.2 (10.6, 30.1) 17.9 (13.9, 30.4) 0.990EGJ shift (cm) -2.1 (1.6, 2.9) -1.8 (1.0, 2.7) 0.278First burst duration (seconds) 0.4 (0.2, 0.5) 0.2 (0.2, 0.4) 0.105Event duration (seconds) 0.8 (0.2, 1.0) 0.5 (0.2, 0.9) 0.290

†Referenced to gastric pressure, all other values were referenced to atmospheric pressure. EGJ, esophagogastric junction; UES, upperesophageal sphincter.



during the procedure, and no reflux events occurredduring the throat-clearing or cough events. Oneweakly acidic gas reflux occurred 30 seconds afterthroat clearing; one weakly acidic mixed reflux andone weakly acidic gas reflux occurred 42 secondsafter cough. The other two weakly acidic gas refluxepisodes occurred during belching.

DISCUSSION

Studies on the cough–reflux relationship have beenhampered by difficulty in accurately identifying thetime sequence between cough and reflux on ambula-tory reflux testing. The acoustic cough-monitoringsystem is a newly developed device to detect coughthrough an automated sound recognition paradigmthat would remove the unreliable nature of patientevent marking.4 However, we hypothesized that theaccuracy of acoustic monitoring could be com-promised by throat clearing, which has similarsound characteristics and is also potentially related toreflux. Our results support that the automated cough-detection system was associated with good sensitivitybut was unable to accurately distinguish cough fromthroat clearing, with 50% of the protocol throat-clearing events being scored as a cough. Additionally,we also discovered that the manometric profile ofcough and throat clearing are similar in qualitativepattern but differ in that the former had more vigor-ous pressure changes and was often associated withrepetitive pressurizations. These findings suggest thatthroat clearing may be difficult to distinguish fromcough either manometrically or acoustically.

Acoustic cough analysis uses a combination ofchest wall sound, vocal cord sound, ambient sound,and respiratory movement to detect cough and dis-tinguish it from potential confounders. Based on ourresults this technique appeared to be extremely reli-able when the four variables are utilized. However,throat clearing shared a similar sound pattern, andthus the system overdiagnosed cough resulting inpoor overall specificity. The difficulty in distinguish-ing cough from throat clearing may result from thefact that they share similar physiology. Cough iscaused by stimuli in the trachea, clearing the materialin the airway, while throat clearing is caused by astimuli in the throat and clears the larynx. Hence,they both represent physiological clearing mecha-nisms. To our knowledge this was the the first studyto compare the manometric profile of throat clearingand cough. We observed that cough and throat clear-ing shared a similar pattern: (i) an initial decrease ofesophageal pressure caused by thoracic movementand deep inspiration; (ii) a distal excursion of theEGJ high-pressure zone with downward diaphrag-matic movement that was associated with an increasein EGJ and UES pressure; followed by (iii) an abrupt

increase of intragastric and intra-esophageal pres-sure. Thus, both events utilize a sharp change inintra-abdominal and intrathoracic pressure in anattempt to expel the irritant from the airway. Thepressure changes associated with cough were morevigorous and were often associated with a repetitivepressure change related to multiple bursts of cough.In fact, throat clearing was rarely associated withrepetitions of pressurization on manometry, andthis represented a reliable distinguishing feature onmanometry. Thus, one could rationalize that throatclearing is similar to a mild cough, and a mild coughcan function as an attempt to throat clear.

The finding that the EGJ and UES pressures areaugmented to a level above intragastric and intra-esophageal pressure during the events in asymptom-atic controls suggests that this may be a defensemechanism preventing reflux during periods ofincreased intragastric pressure (Fig. 4). This was sup-ported by the impedance data, which did not revealany episodes of reflux during the actual cough andthroat-clearing events. Whether compromise of theEGJ or UES is associated with clinically relevantgastroesophageal or laryngopharyngeal reflux duringcoughing and throat clearing will require furtherstudy in well-defined patient populations.

Previous studies have tried to use 24-hour ambula-tory esophageal manometry as an adjunct tool todefine cough.5 The study by Bogte et al. showed thatcombined 24-hour pH and pressure monitoring wasuseful in the evaluation of patients with chronic unex-plained cough.5 In that study only a minority (39.2%)of the cough bursts detected manometrically weremarked by patients who had undergone both com-bined 24-hour pH and pressure recording. Thatlow detection rate of cough might be due to the factthat the patient did not report throat clearing andthis symptom could have mimicked cough mano-metrically. While one could make the argumentthat these two symptoms could be lumped togetherbecause they both facilitate airway clearance, it is stilluseful to distinguish between them in research andclinical practice. Even though the automated systemutilized in the study was poor in distinguishing coughfrom throat clearing, the manual assessment wasvery accurate, and thus there is still hope that furthermodifications to the automated acoustic analysis maybe helpful.

One limitation of the current study was the natureof the simulation of the cough and throat clearing bythe volunteers. The mechanism of cough and throatclearing may be different when one is associated witha stimulated reflex or a involuntary effort to expel anirritant. All protocol events were voluntary simula-tions, which might be more or less vigorous thanspontaneous events, and the actual throat clearingcould be more than one component, and this couldhave altered the manometric pattern. However, we



were able to identify a small number of spontaneouscoughs and throat clearings during the study, andthe manometric profile of those events were consis-tent with the simulated events. Certainly, a more vig-orous assessment of spontaneous events in a morewell-defined patient population will be required toimprove acoustic detection and also to validatewhether the manometric pattern of cough and throatclearing can be utilized to distinguish these events.Additionally, these findings will also have to considerhow the pathophysiology of cough and throat clear-ing are altered by the perception of the stimuli andthe potential that these events may be modulatedby behavioral and psychological factors. Finally, thepresence of the HRM catheter might potentiallyaffect the sound characteristics of cough and throatclearing.

In conclusion, the automated acoustic method ofcough detection was associated with good sensitivityand poor specificity, suggesting that investigator veri-fication is requisite until software modifications facili-tate distinguishing cough from throat clearing. Ourdata also suggest that esophageal pressure topogra-phy may help distinguish cough from throat clearing.However, it also suggests that they share similar pres-sure patterns, and this may hamper our ability todifferentiate these two respiratory defense mecha-nisms. While it is tempting to suggest that cough andthroat clearing can be lumped together when assess-ing an associated reflux etiology, further workis required to better define the associated laryngealmechanisms and neurologic control of these defensemechanisms. However, it appears that manual verifi-cation of automated acoustic monitoring is an accu-rate tool to assess the association of cough and throat

clearing with reflux, and its utility can expand toother physiologic phenomenon associated with thesesymptoms in the ambulatory setting.

Acknowledgments

Specific author contributions

Study concept, acquisition of data, analysis, drafting,and study supervision: Yinglian Xiao; acquisition ofdata and analysis: Dustin Carilson, Lubomyr Boris,and Frédéric Nicodème; technical support: JerryMabary and Zhiyue Lin; preparation of the manu-script: Michael Cuttica; study concept, acquisitionof data, analysis, drafting, study supervision, andfinalizing the manuscript: Peter J. Kahrilas and JohnE. Pandolfino.

Funding

This work was supported by R01 DK079902 (JEP)and R01 DK56033 (PJK) from the Public HealthService. Equipment was provided by Sandhill Scien-tific Inc.

Conflict of interest

John E. Pandolfino (Given Imaging [consulting, edu-cational], SandhIll Scientific Inc. [Consulting])

Jerry Mabary works for the Sandhill Scientific Inc.No other conflicts for remaining authors (YX,

DC, LB, ZL, FN, MC, PJK).

References

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Fig. 4 The spatial pressure variation along the length of the esophagus. The two panels represent an esophageal pressuretopography (EPT) plot of a (A) throat-clearing event and (B) a cough. The white overlaid lines represent the pressure at a distincttime point (0.2 second) to highlight the pressure gradients through the esophagogastric junction (EGJ) and upper esophagealsphincter (UES). The pressure levels at the EGJ are greater than intragastric pressure supporting that reflux is unlikely based onpressure gradients during both event types. Similarly, the UES pressure is much greater than the intra-esophageal pressure makingbelching or laryngopharyngeal reflux unlikely based on the pressure gradients.



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The acoustic cough monitoring and manometric profile of cough and throat clearing

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