ORIGINAL PAPERS

 

Normal values in ambulatory oesophageal pH monitoring at two levels in Spain

Valores normales en pHmetría esofágica ambulatoria a dos niveles en España

 

 

Grupo Español para el Estudio de la Motilidad Digestiva (GEMD)*

This study was partially supported by Novartis Farmacéutica SA and Synectics Medical.

*Members of the GEMD are listed at the end of the article.

Correspondence

 

 

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ABSTRACT

Aim: upper oesophageal pH monitoring may play a significant role in the study of extra-oesophageal GERD, but limited normal data are available to date. Our aim was to develop a large series of normal values of proximal oesophageal acidification.
Methods: 155 healthy volunteers (74 male) participated in a multi-centre national study including oesophageal manometry and 24 hours oesophageal pH monitoring using two electrodes individually located 5 cm above the LOS and 3 cm below the UOS.
Results: 130 participants with normal manometry completed all the study. Twelve of them were excluded for inadequate pH tests. Twenty-seven subjects had abnormal conventional pH. The remaining 91 subjects (37 M; 18-72 yrs age range) formed the reference group for normality. At the level of the upper oesophagus, the 95^th percentile of the total number of reflux events was 30, after eliminating the meal periods 22, and after eliminating also the pseudo-reflux events 18. Duration of the longest episodes was 5, 4 and 4 min, respectively (3.5 min in upright and 0.5 min in supine). The upper limit for the percentage of acid exposure time was 1.35, 1.05 and 0.95%, respectively. No reflux events were recorded in the upper oesophagus in 8 cases.
Conclusion: this is the largest series of normal values of proximal oesophageal reflux that confirm the existence of acid reflux at that level in healthy subjects, in small quantity and unrelated to age or gender. Our data support the convenience of excluding pseudo-reflux events and meal periods from analysis.

Key words: 24-hour pH monitoring. Extra-oesophageal reflux. Dual pH monitoring. Proximal oesophageal pHmetry. pH testing. Normal oesophageal pH data.

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RESUMEN

Objetivo: la pHmetría con electrodo proximal puede jugar un papel importante en el estudio de las manifestaciones extraesofágicas de la ERGE, pero no existen series amplias que permitan establecer los valores de referencia con fiabilidad.
Métodos: se incluyeron 155 voluntarios sanos (74 H) en un estudio multicéntrico a nivel nacional con manometría esofágica y pHmetría de 24 horas con dos electrodos individuales a 5 cm por encima del borde superior del EEI y a 3 cm por debajo del borde inferior del EES.
Resultados: completaron todos los estudios 130 sujetos. Se desestimaron 12 por pHmetrías deficientes y 27 por presentar una pHmetría patológica en el esófago distal. Los 91 voluntarios restantes -37 H; media de edad: 28,5 años (rango 18-72)- constituyeron el grupo de referencia para valores de normalidad. A nivel del esófago superior el percentil 95 del número total de episodios fue 30, al eliminar los periodos de ingesta 22, y al eliminar además los seudo-reflujos 18. Los valores para la duración del episodio más largo fueron 5, 4 y 4 min (3,5 min en bipedestación y 0,5 min en decúbito), respectivamente. El límite superior para el % de tiempo de exposición ácida fue de 1,35, 1,05 y 0,95%, igual respectivamente. No se registraron episodios de reflujo en el esófago superior en 8 casos (17 al eliminar el periodo de ingesta o los seudo-reflujos).
Conclusión: esta es la serie más amplia de valores normales de reflujo en el esófago proximal, con datos de referencia a nivel de la población española que confirman la existencia de reflujo ácido a ese nivel en sujetos sanos, de escasa cuantía y sin relación con la edad o sexo. Nuestros resultados apoyan la conveniencia de eliminar los seudo-reflujos y periodos de ingesta en el análisis.

Palabras clave: pHmetría de 24 horas. Reflujo extraesofágico. pHmetría doble esofágica. pHmetría en esófago superior. Valores normales de pHmetría esofágica.

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Introduction

Ambulatory oesophageal pH measurement has been considered the gold standard for the diagnosis of gastro-oesophageal reflux. However, the standard procedure using a recording electrode 5 cm above the lower oesophageal sphincter (LES) is not suitable for the correct evaluation of extra-oesophageal syndromes of the gastro-oesophageal reflux disease, because in a large percentage of these patients distal oesophageal acid exposure is normal (1). These cases require an additional recording electrode located in upper oesophagus (1,2). However, pH recording in the upper oesophagus is fraught with technical and methodological problems, due to the lack of agreement on the optimum recording site, the high variability and low reproducibility of the results, the high number of artefacts and the lack of large series of normal values.

The aim of this study was to determine, the normal values of acid reflux at the upper oesophageal level (3 cm below the upper oesophageal sphincter), and to define their characteristics with respect to the moment of appearance, duration, impact of the meal periods and pseudo-reflux events in a large series of healthy subjects.

 

Material and methods

Participants

One hundred fifty-five healthy subjects (74 males, 81 females; 18-75 yrs age range) with normal body weight, without digestive symptoms and a previous normal oesophageal manometry were included in the study. The protocol for the study was approved by the Ethics Committees of each of the participating centres and all participants gave written informed consent.

Oesophageal manometry

Perfusion manometry was performed using a standard stationary pull-through technique as previously described (3,4).

Ambulatory 24-hour oesophageal pHmetry

Ambulatory pH monitoring was carried out with two antimony electrodes (Synectics Medical, Medtronic Inc.) independently connected to the pHmeter using a device provided by the manufacturer. Based on manometric data, the distal pH electrode was placed 5 cm above the upper margin of the lower oesophageal sphincter (LOS), and the proximal electrode was placed 3 cm below the lower margin of the upper oesophageal sphincter (UOS). Both electrodes were tied together and taped to the nose. Data were recorded by a Mark II, Mark III or Delta indistinctly (Synectics Medical, Medtronic Inc.). During the recording participants were allowed to carry out a normal life, without dietary restrictions, and were instructed to record the start and end of meals and the periods of decubitus.

Procedure and experimental design

A national multi-centre study was carried out including 18 centres in Spain. Each participant underwent an oesophageal manometry. Participants in whom no manometric alterations were detected and with a LOS pressure ≥ 6 mmHg were selected for the study and an oesophageal pHmetry was performed.

Analysis of data

The distance between the nostril to both sphincters was measured during oesophageal manometry. All the pH recordings were analysed using the same constants by the same team of researchers (JPS, ARL and MCS). Automatic study analysis was performed using a commercially available programme (Polygram.Net; Synectics Medical, Medtronic Inc.) together with a specially designed programme which permits the elimination of pseudo-reflux events. A reflux event was defined, both at proximal and distal levels, as a drop in the pH below 4.0 for at least 8 seconds. The end of the event was established when the pH again rose above 4.0. Pseudo-reflux events were defined as a drop in pH on the proximal electrode lower to pH 4.0 in absence of reflux (pH < 4.0) simultaneously or in the previous 8 seconds in the distal oesophagus (Fig. 1). Artefacts identified by visual inspection were excluded from analysis. Abnormal acid exposure was considered as abnormal when DeMeester score value was above 14.72 in the distal oesophagus.

Analysis for the whole group and excluding those with abnormal distal acid exposure were performed at both proximal and distal oesophageal sites: a) for the total recording period; b) excluding meal periods; and c) also excluding the pseudo-reflux events.

Statistical analysis

The results of the different parameters are expressed as median, range and 95th percentile. The 95^th percentile was taken as the upper limit of normality (ULN). Comparisons between gender and age groups were performed using the Wilcoxon or Fisher exact test, as required.

 

Results

One hundred thirty participants (61 men and 69 women) had a normal manometry and completed both studies. Of these, 12 were rejected for having an inadequate pHmetry due to displacement of any of the electrodes, multiple artefacts and/or valid recordings of less than 20 hours. Therefore, the final group included 118 subjects (55 M, 63 F; 22 yrs median age; 18-72 age range). The mean recording time was 23 hours (range 20-24 h).

Distal oesophagus (Table I)

From the 118 participants, 27 had abnormal acid exposure in the distal oesophagus (DeMeester score > 14.72) and in 91 participants (37 M, 54 F, 18-72 yrs age range) distal pH was within the normal range. Data were analyzed for the whole group and for the last 91 patients referred. Elimination of meal periods had little impact on the results at this level with a discreet reduction in the upper limits of normality. Specifically, in the group with normal pH (DeMeester score ≤ 14.72), the upper limit of normality of the number of reflux episodes fell from 66.5 to 60.5 and the percentage time of distal oesophageal acid exposure fell from 3.65 to 3.45%.

Proximal oesophagus (Table II)

Elimination of the meal periods in the proximal oesophagus notably reduced the total number of reflux episodes. One episode of reflux longer than 5 min (7 min) was recorded only in one case in upright. Elimination of meal periods reduced the duration of the longest reflux episode to 4 min in the total period, and to 0.5 min in supine, but not during the upright recording period. In addition, on elimination of pseudo-reflux episodes, the upper limit of normality for the duration of the longest episode in upright fell to 3.5 min and to 0.4 min in supine, without any changes in the total period.

Elimination of the meal periods reduced the percentage time of acid exposure from 1.35 to 1.05%, and to 0.95% when the pseudo-reflux events are also eliminated.

Eight participants did not present any reflux episode in the upper oesophagus. When the meal period was eliminated from the analysis there were 17 cases without any reflux episode at this level. In 25 cases (27.5%) there were some reflux episode in supine and all of them have also reflux episodes in upright.

No age or gender statistically significant differences were observed in respect to acid exposure time in both the distal or proximal oesophagus.

 

Discussion

This national multi-centre study provides the largest series to date on normal values of acidification at upper oesophageal level. Most series of literature have a small number of controls. Although it is on asymptomatic subjects, we found abnormal pH monitoring at the distal level in 27 out of 118 subjects with valid studies (22.9%), and they were excluded for the study at the proximal level. Our results in the upper oesophagus are similar to that of previously published data (5,6) and show that the existence of reflux at proximal level is an uncommon phenomenon and very variable throughout the day (2.7). The determination of pH at this level in healthy volunteers also has a good reproducibility.

In line with the results of other studies (2,5,8-11) we have appreciated that the pattern of presentation of reflux episodes at the proximal level is similar to that of the distal oesophagus, usually appearing in the upright position, during meals and in the postprandial period. However, the complete absence of acid reflux episodes is not exceptional. In our series it occurred in 17 cases (18.7%). The absence of episodes with pH < 4 is reported in 17.5-57.7% in studies at pharyngeal level (5,11).

The presence of artefacts makes the interpretation of the pHmetry in the upper oesophagus difficult. Artefacts may be related to meal ingestion or may occur independently of it. The latter known as pseudo-reflux events, represent a technical "failure", usually of the electrode and are related to oxidation, desiccation processes or blockage due to mucus or refluxed material. They usually take place at night and are characterised by a drop in pH in the upper oesophagus independently of the presence of acid in the lower oesophagus (9,11) (Fig. 1). The criteria used to define a reflux episode in the pharynx or proximal oesophagus are as follows (1,14): drop in pH below 4.0, rapid, sharp and greater than 2.0 units, during or immediately after acid exposure of the distal oesophagus and unrelated to meal or deglutition. Commercially available programmes do not allow automatic elimination of these artefacts, and visual inspection is required. In this study we have performed a double correction for artefacts, using the commercial software a well as a second program specifically designed for automatic elimination of pseudo-reflux events. This possibility should be included in commercial software for analysis.

The acidity of certain foodstuffs may affect oesophageal pH recording by overestimating the number of reflux episodes (15,16), but its real impact is small (1,9,17,18). Our results support the limited role of meals on distal reflux: including or excluding the meal periods made little difference at distal level (Table I). However, this is not the case in the proximal oesophagus (7) (Table II) where the majority of acidification events are related to food ingestion and may be the only episodes of pH decrease recorded.

For the study of patients with extra-oesophageal syndromes, different placements of the pH electrode have been employed: upper oesophagus (11,19,20), UOS (6,9), trachea (21,22), pharynx (5.11,23,24), oropharynx (25) or simultaneously in the upper oesophagus and pharynx (26), considering that for an improved assessment, the proximal pH electrode should be placed as close as possible to the organ in question (larynx or pharynx) (9,24). To date no comparisons have been established in this respect in normal subjects (11,23,24) but in those with laryngitis (27). The use of probes with two electrodes 15 cm apart allows individual adjustment of the proximal electrode using the distal electrode only for identifying the pseudo-reflux events (9). However, it underestimates the distal reflux that it is possible to study by means of the method of the present paper. In addition, placement above the UOS has, at least from a theoretical point of view, the disadvantages of increased risk of artefacts caused by desiccation, blockade of the electrode due to mucus in the upper airway, and/or the dilution of the acid material in the relatively large volume of the hypopharynx (9,24,26,28). Although some authors reported that artefacts at this level are usually of short duration and their exclusion has little effect on overall outcome (5), manual review is encouraged.

As noted, the reflux in the proximal oesophagus is rare and available normal values vary widely among different laboratories whatever the point of placement of the recording electrode. Also, to as in the present study there are not significant differences related to age or sex (5). Our results using a simple methodology to adjust the electrode distance in terms of patient characteristics are similar to those of other authors (Table III) (5,7,8,19,29-31). Moreover, it does not seem to be important differences between studies in western or eastern populations (11). However, it must always be borne in mind that the comparison is not easy for the technical and/or methodological differences already mentioned. The elimination of meal periods and pseudo-reflux events provides a more adjusted vision to the reality of the small size that the gastro-oesophageal (in the upper oesophagus) or gastro-pharyngeal reflux have in healthy subjects as shown in Table III (5,6,9,18,23,29). As occurs in the lower oesophagus, the number of reflux episodes has limited value because its low reproducibility (2,24), while the most useful parameter is the % time with pH < 4.

It is generally accepted that the reflux episode suffers an almost linear decrease of the pH as it rise to the hypopharynx (1,5,6,19,30) and it is likely that at the proximal level, the episodes are weakly acidic. However, other cut-off points with pH > 4 have been little studied (2,7,10). Recently, impedance-pH monitoring may clarify aspects of proximal reflux albeit with some limitations arising from the difficulty of interpretation (32).

In conclusion, our results confirm the existence of acid reflux at the proximal level of the oesophagus in healthy subjects, albeit in small amounts and without relationship to age or sex, and the desirability of eliminating the pseudo-reflux events and meal periods for analysis.

 

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*Authors from the Grupo Español para el Estudio de la Motilidad Digestiva (GEMD)

Azpiroz F. Hospital Vall d'Hebron. Barcelona.
Baudet JS. Hospital Nuestra Sra. de la Candelaria. Santa Cruz de Tenerife.
Benages A. Hospital Clínico. Valencia.
Canga F. Hospital 12 de Octubre. Madrid.
Carrasco. J. Hospital Universitario Puerta del Mar. Cádiz.
Ciriza C. Hospital del Bierzo. Ponferrada, León.
Cucala M. Novartis. S.A.
Domínguez E. Hospital Clínico Universitario de Santiago de Compostela. A Coruña.
Faro V. Hospital Ramón y Cajal. Madrid.
Garrigues V. Hospital La Fe. Valencia.
Giganto F. Hospital Central de Asturias. Oviedo.
Herrerías JM. Hospital Universitario Virgen Macarena. Sevilla.
Iglesias J. Hospital Clínico Universitario de Santiago de Compostela. A Coruña.
Lacima G. Hospital Clínic. Barcelona.
López P. Hospital de Aránzazu. Donosti.
Llabrés M. Hospital Son Dureta. Palma de Mallorca.
Mearin F. Centro Médico Teknon. Barcelona.
Mínguez M. Hospital Clínico. Valencia.
Monés J. Hospital Sant Pau. Barcelona.
Mora F. Hospital Clínico Universitario. Valencia.
Muñoz C. Hospital Virgen Blanca. Toledo.
Pérez de la Serna J. Hospital Clínico San Carlos. Madrid.
Ponce J. Hospital La Fe. Valencia.
Rodríguez-Téllez M. Hospital Universitario Virgen Macarena. Sevilla.
Romero MJ. Hospital del Bierzo. Ponferrada, León.
Ruiz de León A. Hospital Clínico San Carlos. Madrid.
Ruiz-Cabello M. Hospital Universitario Virgen de las Nieves. Granada.
Sánchez-Gey S. Hospital Universitario Virgen Macarena. Sevilla.
Sanchíz V. Hospital Clínico. Valencia.
Serra J. Hospital Vall d'Hebron. Barcelona.
Sevilla MC. Hospital Clínico San Carlos. Madrid.
Sopeña F. Hospital Clínico Universitario de Zaragoza.
Soria MJ. Hospital Universitario Puerta del Mar. Cádiz.

 

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Correspondence:
Julio Pérez de la Serna.
Servicio de Aparato Digestivo.
Hospital Clínico San Carlos.
C/ Profesor Martín Lagos, s/n.
28040 Madrid, Spain.
e-mail: jperezsernab@gmail.com

Received: 02-02-10.
Accepted: 03-02-10.