Study / Study type / Patient group / Technique / Main conclusions
Halum 2005S1 / Case report / 1 patient with globus / Manometry (low resolution) / UES resting pressure was increased (>300mmHg), injection of the cricopharyngeal muscle with botulinum toxinum decreased UES resting pressure to 100mmHg and globus sensation resolved
Arts 2009S2 / Case series / 40 patients with globus / Manometry / 17/40 patients had increased UES resting pressure (>140mmHg)
Corso 1998S3 / Case control / 650 patients without hypertensive UES, 101 patients with hypertensive UES / Manometry (low resolution, solid state) / 17/650 (3%) patients without hypertensive UES (>118mmHg) had globus versus 28/101 (28%) patients with hypertensive UES had globus
Of all patients with globus 28/45 (62%) patients had hypertensive UES
No association was found between GERD and UES pressure within the group of globus patients
Watson 1974S4 / Case control / 9 patients with globus (alone or accompanied by other symptoms)
22 controls without globus (healthy subjects or patients with epigastric pain or GER) / Manometry (low resolution, water-perfused) / Within controls UES resting pressure ranged from 70 to 140mmHg
In patients with globus this was from 140 to 220mmHg (P<0.001)
Kriengkirakul 2011S5 / Case control / Patients with globus as main symptom (n=28) or non-dominant symptom (n=34)
Control patients without globus but with chronic upper gastrointestinal or ENT symptoms (n=43) / Manometry (high resolution) / UES resting pressure in patients with globus was 90±1.2 (dominant symptom) and 66±4.3mmHg (non-dominant symptom)
Both were significantly higher than in patients with no globus symptoms (44±2.6mmHg) (P0.05).
Tokashiki 2010S6 / Controlled cross-over trial / 20 healthy individuals / Manometry (with sleeve pressure sensor)+distal esophageal acid/ distilled water infusion) / Globus sensation occurred in 13/20 patients with esophageal acid perfusion, in all cases accompanied by a significant rise in UES pressure
In the group without globus, UES pressure did not rise significantly
During distilled water infusion, none reported globus and UES pressure did not rise significantly.
Rees 2010S7 / Retrospec-tive cohort study / 19 patients undergoing cricopharyngeal muscle Botox injection (and dilation) for globus / / / 13/19 patients (68%) had at least partial resolution of symptoms, 7/19 had complete resolution
Success rate was higher in patients with initial hypertensive UES 11/13 (85%) partial resolution, compared to 1/6 (33%) of patients without initial hypertensive UES.
Kwiatek 2009S8 / Case control / 131 patients with globus
68 healthy controls
46 GERD patients without globus / Manometry (high resolution, solid state) / Rise in UES pressure during inspiration is a physiologic phenomenon but is significantly more prominent in globus patients versus controls (more than 3 times greater rise)
80/131 (61%) of patients with globus exhibited abnormal pressure rise (>27mmHg), compared to 4/68 (5%) of normal controls and 7 of 46 (15%) of GERD patients without globus.
Kiebles 2010S9 / Case series / 10 patients with globus / Manometry (high resolution, solid state) / 0/10 patients had increased UES resting pressure (>118mmHg)
1/10 patients had abnormal respiratory UES variation (>27mmHg)
Choi 2012S10 / Case control / 57 patients with globus
7 healthy controls / Manometry (high resolution) / No significant differences in UES resting pressure between patients with globus (median 59.40 IQR [40.9580.25mmHg] and controls (median 84.50mmHg IQR [57.7093.60] (P=0.171)
Wilson 1989S11 / Case control / 48 patients with globus
50 controls / Manometry (8-channel, perfused, stationary pull through) / No significant differences in UES resting pressure between patients with globus (mean 40.7mmHg; SEM 2.9) and controls (mean 39.6mmHg; SEM 2.1)
Cook 1989S12 / Case control / 7 patients with globus
13 controls / Manometry (low resolution, sleeve, perfused) / UES resting pressure (mean±SEM) in patients (40.4±4.6mmHg) did not differ significantly from controls (46.5±4.7mmHg)
No difference in stress induced (dichotic listening task) UES pressure rise between patients with globus and controls
Lee 2010S13 / Case control / 39 patients with globus
60 patients with NERD+heartburn / No information available / No differences in UES resting pressure between patients and controls
Tsutsui 2012S14 / Case control / 119 patients with globus resistant to PPI therapy
119 age-matched and sex-matched healthy controls / Manometry (high resolution, solid state) / Lower UES resting pressure in patients with globus (52.0±20.3mmHg) compared to controls (71.1±31.0mmHg).
Lehtinen 1976S15 / Case series / 20 patients with globus / Perfused, open-tip catheter / 3/20 patients demonstrated slightly elevated resting pressures (not defined), however these were of no essential importance
Abbreviations: GER, gastro-oesophageal reflux; SEM, standard error of the mean; UES, upper oesophageal sphincter.
supports hypothesis globus ~ UES resting pressure
does not support hypothesis globus ~ UES resting pressure
Supplementary table 2 | Prevalence of GERD in patients with globusStudy / Country / Diagnostic tools / GERD definition / Prevalence of GERD in patients with globus*
(n) (%)
Tsutsui et al. (2012)S14 / Japan / Endoscopy or FSSG / Reflux oesophagitis AND/OR a score of ≥8 on the FSSG / 214/337 (64)
Oh et al. (2012)S16 / Korea / Endoscopy; 24h pH monitoring; Bernstein test / Erosive oesophagitis according to the Los Angeles classification AND/OR pathological acid reflux, defined as
pH 4, lasting for 4% of the 24h
AND/OR positive Bernstein test
AND/OR positive symptom index in the 24h pH monitoring test / 17/36 (47)
Sinn et al. (2012)S17 / Korea / pH-impedance monitoring; endoscopy / Pathological bolus exposure
AND/OR pathological acid exposure
AND/OR oesophagitis / Not clear (42)
Hori et al. (2010)S18 / Japan / Endoscopy / Reflux esophagitis
AND/OR reflux symptoms (heartburn or acid regurgitation at least once a week for the past 3months) / 41/80 (51)‡
Dimitrijevic et al. (2009)S19 / Serbia / Endoscopy; medical history / Endoscopic evidence on oesophageal inflammation AND complaints / 5/38 (13)
Sinn et al. (2008)S20 / Korea / 24h pH monitoring; endoscopy; symptom questionnaire / Intra-oesophageal pH of <4, for 4% of the recording time or a DeMeester score of 14.7
OR reflux esophagitis OR symptoms / 41/64 (64)
Färkkilä et al. (1994)S21 / Finland / 24h pH monitoring; endoscopy; histology / Savary-Miller classification of oesophagitis
pH <4 for >5% of time / 7/21 (33)
*Comparison is not always straightforward owing to differences in manometric devices (low resolution versus high resolution) and criteria used to define abnormal motility and terminology. ‡GERD was also prevalent in controls from the study (260/1,504; 17%). Abbreviation: FSSG, Frequency Scale for Symptoms of GERD.
Supplementary table 3 | Acid exposure in globus
Study / N / Reflux type / Criteria / Percentage abnormal / Comparison with control group
Knight 2000S22 / 9 / Oesophageal and or pharyngeal (probe above UES) / Normal values for oesophageal acid exposure times (% of time that pH < 4.0): <8.2% upright; <3.0% supine; and <5.5% of total duration
A single acid reflux episode detected by the proximal or pharyngeal probe is considered indicative of GER / 77% / No
Smit 2000S23 / 27 / Oesophageal and/or pharyngeal (probe in UES) / Normal values for oesophageal acid exposure times (% of time that pH <4.0): <8.2% upright; < 3.0% supine; and < 5.5% total duration
A single acid reflux episode detected by the proximal or pharyngeal probe is considered indicative of GER
A pH drop below 4, recorded by the proximal probe is considered to be positive evidence for GPR only if it is preceded by a pH drop at the distal probe of similar or larger magnitude. / 30% / No
Corso 1998S3 / 23 / Distal oesophageal / Abnormal distal reflux was defined as a pH <4 at 5cm above the LES >6% of the time while upright, >2% of the time while supine, or >4.5% of the total time / 26% / 9/23 (39%) patients with heartburn, non-cardiac chest pain or dysphagia (NS)
Moser 1998S24 / 88 / Oesophageal / Percentages of time with a pH of <4 >6.3% of time in the upright position, >1.2% in the supine position, and >4.2% of the total recording time were considered abnormal / 15% / No
Woo 1996S25 / 31 / Distal oesophageal / A composite score of ≥22 on the Johnson and DeMeester table / 55% / No
Patcharatrakul 2011S26 / 19 / Distal oesophageal / Time pH<4 at lower oesophagus >4.5% / 32% / 5/20 (25%) of patients with dyspepsia, typical reflux and chronic idiopathic ENT problems as their main symptoms (NS)
Hill 1997S27 / 88 / Distal and proximal oesophagus / DeMeester acid score >15 considered as abnormal / 15% / 1/20 (5%) nonulcer-dyspepsia patients (significant)
Curran 1995S28 / 21 / Distal oesophageal / Johnston and De Meester criteria (pH<4 during >4.2% of total time) / 38% / No
Chevalier 2003S29 / 20 / Distal and proximal (4 electrodes) / Based upon the work of Johnson and DeMeester and Jamieson etal.,10 seven parameters were assessed: the total, supine and erect percent time of pH<4, the total number of reflux episodes, the time of the longest episode, the number of reflux episodes lasting >5min and the DeMeester score
No specific normalization data regarding the use of proximal pH catheters were available / 65% / No
Lee 2010S30 / 39 / Not clear / Not clear / 54% / No
Yanova 2012S31 / 27 / Not clear / Not clear / 6/27 (22%) / No
Arts 2009S2 / 40 / Oesophageal / Not clear / 36% / No
Chen 2007S32 / 23 / Oesophageal / Abnormal distal oesophageal reflux and proximal reflux were defined respectively as the percentage of oesophageal total acid exposure (pH <4) of 4.2% and 1% / 0% / No
Färkkilä 1994S21 / 21 / Oesophageal / Percentage of pH<4 >5% / 24% / No
Ott 1994S33 / 22 / Oesophageal and pharyngeal / Pharynx (abnormal, pH <4) and oesophagus (abnormal, 6% or more total acid exposure) / 9% pharynx
18% oesophagus / No
Abbreviations: GPR, gastro-pharyngeal reflux; LES, lower oesophageal sphincter; NS, not significant; UES, upper oesophageal sphincter.
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