Original Paper
Digestion 1992;51:152-160
Gastrointestinal Unit, L. Sacco Hospital, Milan. Italy
KeyW ords Gastroesophageal reflux Intraesophageal pH monitoring Reflux esophagitis
pH Fluctuations versus Reflux Episodes in Patients with Gastroesophageal Reflux Disease: Their Optimal Thresholds and Significance in Diagnosis
Abstract
In physiological and pathological conditions, pH monitoring in the esophagus shows small variations as well as more pro nounced deflections. However, only the latter are traditionally taken into account in 24-hour pH monitoring analysis. The present study was designed to establish optimal thresholds of pH fluctuations versus reflux episodes in separating physio logical and pathological gastroesophageal reflux (GER) and to evaluate their significance in the diagnosis. Twenty-four-hour intraesophageal pH monitoring and endoscopy were per formed in 62 patients with GER symptoms and in 42 healthy controls. The results showed that the percentages of the time with pH fluctuations in patients with and without esophagitis and in healthy controls were, on average, 12.65,9.5 and 2.76% in 24 h, respectively, and the respective percentages of the time with reflux episodes in the same groups in 24 h were, on average, 3.12, 2.04 and 0.18%, respectively. Using a receiveroperating-characteristic curve analysis, 0.5 pH units/s to a pH < 4 . might be differentiated from fluctuations, those being reflux events which do not fulfil the above criteria. Although the authors evaluated the responsibility of both types of pH variations in the development of esophagitis, the significance of this classifica tion in the diagnosis of GER has yet to be demonstrated, and the definition of pH fluc tuations is uncertain. The aims of the present study were: (1 ) to define pH fluctuations and
Table 2. Parameters of GER Groups
pH fluctuations n
Reflux episodes
duration min
time. % 24 h
n
duration min
time. % 24 h
191.7± 118.9 124.0 ±97.5 50.1 ±35.4
12.7 ± 6.5 8.2 ±4.6 3.3 ±4.5
22 ± 31 15 ± 13 7 ± 10
45.4± 110.6 19.1 ±58.7 22.8 ±64.7
3.1 ±7.5 1.3 ±2.7 1.5 ±4.8
50 ±18 41 ± 14 9±8
130.4 ±57.5 94.0±35.7 36.3 ±26.4
9.5 ±2.8 6.8 ±3.5 2.6 ±3.1
14± 14 11 ± 7 3±6
27.4 ±68.3 18.8 ±45.2 8.6 ±24.7
2.0 ±5.0 1.4± 12.9 0.6 ±2.2
23 ±16 20± 11 3±5
41.3 ±30.7 37.3 ±24.1 4.1 ±3.9
2.7 ±2.0 2.5± 1.9 0.3 ±0.4
3±3 2±2 l± l
3.0 ±5.7 2.0 ±2.4 1.0 ±2.1
GER patients with esophagitis Total Day Night
67 ±46 55 ±34 12 ± 8
GER patients without esophagitis Total Day Night
Controls Total Day Night
0.2 ±0.4 0.1 ±0.2 0.1 ±0.1
Difference between GER patients with esophagitis and controls in time: p < 0.001: difference between GER patients without esophagitis and controls in time: p < 0.001: p < 0.05. and difference between GER patients with and without esophagitis in time: p > 0.05.
154
Statistical A nalysis The Wilcoxon rank sum test was used to compare the percentages of the time with both types of pH vari ations (pH fluctuations and reflux episodes) in the three groups.Spearman's rank correlation was used for the analysis of relationships between total recording time with pH < 4 and the time (%) with both types of pH variations. Differences between GER patients with/witlioul esophagitis and healthy controls in the distribution of pH fluctuations and reflux episodes were analyzed by means of the x2 test. Using receivcroperating-characteristic (ROC) curves [15. 16], opti mal threshold values were identified for each parame ter and combined parameters (pH fluctuations and reflux episodes). For these thresholds, the percentages of true-positive decisions (sensitivity) and false-posi tive decisions (100% - specificity) were calculated and charted. The more the line curves towards the point of 100% true positivity and 0% false positivity, the better the diagnostic value o f the test. Lowering of the thresh old decreases sensitivity, but increases specificity, and vice versa.
Zhu/Pacc/Sangaletti/Santalucia/ Bianchi Porro
Reflux Episodes and pH in Retlux Disease
Downloaded by: King's College London 137.73.144.138 - 3/6/2018 8:34:35 PM
Miller [ 10]. Only a few patients presented grades II and III, and therefore groups I and 11. and III and IV. respectively, were grouped together. Twenty-four-hour esophageal pH monitoring was carried out in accor dance with the method described elsewhere [11. 12]. Briefly, subjects were advised to take a standard meal of approximate 2,200 kcal during 24-hour intraesophageal pH monitoring. A glass pH electrode with an incorporated potassium chloride reference (Ingold electrode. No. 440) was introduced via the nasoesophageal route and positioned with the tip 5 cm above the gastroesophageal junction identified by the pH meter according to previous methods [11-14]. The output from the pH probe was recorded on a solidstate recorder (Autronicord CM 18). which the patient carried on a belt. Data were analyzed on a computer by means of a self-written computer program. The param eters recorded included the frequency and duration of the 24-hour reflux episodes and pH fluctuations. The pl-1 fluctuations were defined as a decrease from pH < 4 to pH 2 lasting more than 20 s. and reflux episodes were determined as a decrease below pH 2 lasting more than 20 s.
• 3 9 .8 % • 17% • • 8 .3 % * 7 1%
b
• 2 8 .3 % • 4 .7 % • 3 .6 % • 3 .4 %
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Results
Anamnestic data and endoscopical find ings are given in table I. The individual val ues of the percentages of the time with pH fluctuations and reflux episodes in GER pa tients with and without esophagitis and healthy controls are shown in figure l . Table 2 shows the frequency, duration and percentage of the time with pH fluctuations and reflux episodes in GER patients with and without esophagitis and in healthy controls. The per centages of the time with pH fluctuations in
GER patients with and without esophagitis and healthy controls were on average, 12.7, 9.5 and 2.7%. respectively, whilst the percent ages of the time with reflux episodes in the same groups were, on average, 3.1, 2.0 and 0.2%. respectively. Both patients with and without esophagitis showed statistically sig nificant differences compared to the healthy controls (p < 0.001). There was no significant difference between the patients with esopha gitis and those without esophagitis in the per centage of the time with pH fluctuations and reflux episodes (p > 0.05).
155
Downloaded by: King's College London 137.73.144.138 - 3/6/2018 8:34:35 PM
Fig. 1. Individual values of the percentages of time with pH fluctuations (a) and reflux episodes (b) in GER patients with (E+) and without (E-) esophagitis and in healthy controls.
Fig. 2. Distribution of the duration (a) and frequency (b) of pH fluctuations ( □ ) and reflux episodes (|$ ) in GER patients with (E+) and without (E-) esophagitis and in healthy con trols.
Table 3. Correlations betw een the percentages of the time with pH fluctuations/reflux epi sodes and the total duration and numbers of episodes
Groups
Total duration
Total numbers
r
r
P
P
GER patients with esophagitis Time (%) with pH fluctuations Time (%) with reflux episodes
0.92 0.67
Digestion 1992;51:152-160
Gastrointestinal Unit, L. Sacco Hospital, Milan. Italy
KeyW ords Gastroesophageal reflux Intraesophageal pH monitoring Reflux esophagitis
pH Fluctuations versus Reflux Episodes in Patients with Gastroesophageal Reflux Disease: Their Optimal Thresholds and Significance in Diagnosis
Abstract
In physiological and pathological conditions, pH monitoring in the esophagus shows small variations as well as more pro nounced deflections. However, only the latter are traditionally taken into account in 24-hour pH monitoring analysis. The present study was designed to establish optimal thresholds of pH fluctuations versus reflux episodes in separating physio logical and pathological gastroesophageal reflux (GER) and to evaluate their significance in the diagnosis. Twenty-four-hour intraesophageal pH monitoring and endoscopy were per formed in 62 patients with GER symptoms and in 42 healthy controls. The results showed that the percentages of the time with pH fluctuations in patients with and without esophagitis and in healthy controls were, on average, 12.65,9.5 and 2.76% in 24 h, respectively, and the respective percentages of the time with reflux episodes in the same groups in 24 h were, on average, 3.12, 2.04 and 0.18%, respectively. Using a receiveroperating-characteristic curve analysis, 0.5 pH units/s to a pH < 4 . might be differentiated from fluctuations, those being reflux events which do not fulfil the above criteria. Although the authors evaluated the responsibility of both types of pH variations in the development of esophagitis, the significance of this classifica tion in the diagnosis of GER has yet to be demonstrated, and the definition of pH fluc tuations is uncertain. The aims of the present study were: (1 ) to define pH fluctuations and
Table 2. Parameters of GER Groups
pH fluctuations n
Reflux episodes
duration min
time. % 24 h
n
duration min
time. % 24 h
191.7± 118.9 124.0 ±97.5 50.1 ±35.4
12.7 ± 6.5 8.2 ±4.6 3.3 ±4.5
22 ± 31 15 ± 13 7 ± 10
45.4± 110.6 19.1 ±58.7 22.8 ±64.7
3.1 ±7.5 1.3 ±2.7 1.5 ±4.8
50 ±18 41 ± 14 9±8
130.4 ±57.5 94.0±35.7 36.3 ±26.4
9.5 ±2.8 6.8 ±3.5 2.6 ±3.1
14± 14 11 ± 7 3±6
27.4 ±68.3 18.8 ±45.2 8.6 ±24.7
2.0 ±5.0 1.4± 12.9 0.6 ±2.2
23 ±16 20± 11 3±5
41.3 ±30.7 37.3 ±24.1 4.1 ±3.9
2.7 ±2.0 2.5± 1.9 0.3 ±0.4
3±3 2±2 l± l
3.0 ±5.7 2.0 ±2.4 1.0 ±2.1
GER patients with esophagitis Total Day Night
67 ±46 55 ±34 12 ± 8
GER patients without esophagitis Total Day Night
Controls Total Day Night
0.2 ±0.4 0.1 ±0.2 0.1 ±0.1
Difference between GER patients with esophagitis and controls in time: p < 0.001: difference between GER patients without esophagitis and controls in time: p < 0.001: p < 0.05. and difference between GER patients with and without esophagitis in time: p > 0.05.
154
Statistical A nalysis The Wilcoxon rank sum test was used to compare the percentages of the time with both types of pH vari ations (pH fluctuations and reflux episodes) in the three groups.Spearman's rank correlation was used for the analysis of relationships between total recording time with pH < 4 and the time (%) with both types of pH variations. Differences between GER patients with/witlioul esophagitis and healthy controls in the distribution of pH fluctuations and reflux episodes were analyzed by means of the x2 test. Using receivcroperating-characteristic (ROC) curves [15. 16], opti mal threshold values were identified for each parame ter and combined parameters (pH fluctuations and reflux episodes). For these thresholds, the percentages of true-positive decisions (sensitivity) and false-posi tive decisions (100% - specificity) were calculated and charted. The more the line curves towards the point of 100% true positivity and 0% false positivity, the better the diagnostic value o f the test. Lowering of the thresh old decreases sensitivity, but increases specificity, and vice versa.
Zhu/Pacc/Sangaletti/Santalucia/ Bianchi Porro
Reflux Episodes and pH in Retlux Disease
Downloaded by: King's College London 137.73.144.138 - 3/6/2018 8:34:35 PM
Miller [ 10]. Only a few patients presented grades II and III, and therefore groups I and 11. and III and IV. respectively, were grouped together. Twenty-four-hour esophageal pH monitoring was carried out in accor dance with the method described elsewhere [11. 12]. Briefly, subjects were advised to take a standard meal of approximate 2,200 kcal during 24-hour intraesophageal pH monitoring. A glass pH electrode with an incorporated potassium chloride reference (Ingold electrode. No. 440) was introduced via the nasoesophageal route and positioned with the tip 5 cm above the gastroesophageal junction identified by the pH meter according to previous methods [11-14]. The output from the pH probe was recorded on a solidstate recorder (Autronicord CM 18). which the patient carried on a belt. Data were analyzed on a computer by means of a self-written computer program. The param eters recorded included the frequency and duration of the 24-hour reflux episodes and pH fluctuations. The pl-1 fluctuations were defined as a decrease from pH < 4 to pH 2 lasting more than 20 s. and reflux episodes were determined as a decrease below pH 2 lasting more than 20 s.
• 3 9 .8 % • 17% • • 8 .3 % * 7 1%
b
• 2 8 .3 % • 4 .7 % • 3 .6 % • 3 .4 %
y 2.5 •
t •
• •• •
2.0
• •
- 1.5
5? ai E
• • • • • •• • •• •• •• •• • • • • •• •
•
•• • . A •• • •• • • ••
-
•
1.0
0.5
• r n O iV i
0.0
Results
Anamnestic data and endoscopical find ings are given in table I. The individual val ues of the percentages of the time with pH fluctuations and reflux episodes in GER pa tients with and without esophagitis and healthy controls are shown in figure l . Table 2 shows the frequency, duration and percentage of the time with pH fluctuations and reflux episodes in GER patients with and without esophagitis and in healthy controls. The per centages of the time with pH fluctuations in
GER patients with and without esophagitis and healthy controls were on average, 12.7, 9.5 and 2.7%. respectively, whilst the percent ages of the time with reflux episodes in the same groups were, on average, 3.1, 2.0 and 0.2%. respectively. Both patients with and without esophagitis showed statistically sig nificant differences compared to the healthy controls (p < 0.001). There was no significant difference between the patients with esopha gitis and those without esophagitis in the per centage of the time with pH fluctuations and reflux episodes (p > 0.05).
155
Downloaded by: King's College London 137.73.144.138 - 3/6/2018 8:34:35 PM
Fig. 1. Individual values of the percentages of time with pH fluctuations (a) and reflux episodes (b) in GER patients with (E+) and without (E-) esophagitis and in healthy controls.
Fig. 2. Distribution of the duration (a) and frequency (b) of pH fluctuations ( □ ) and reflux episodes (|$ ) in GER patients with (E+) and without (E-) esophagitis and in healthy con trols.
Table 3. Correlations betw een the percentages of the time with pH fluctuations/reflux epi sodes and the total duration and numbers of episodes
Groups
Total duration
Total numbers
r
r
P
P
GER patients with esophagitis Time (%) with pH fluctuations Time (%) with reflux episodes
0.92 0.67
