Influence of smoking and esophageal intubation on esophageal pH-metry

Influence of smoking and esophageal intubation on esophageal pH-metry

GASTROENTEROLOGY 1987;92:1994-7 Influence of Smoking ahd Esophageal Intubation on Esophageal pH-metry NORBERT E. SCHINDLBECK, CHRISTÌNE HEINRICH, AND...

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GASTROENTEROLOGY 1987;92:1994-7

Influence of Smoking ahd Esophageal Intubation on Esophageal pH-metry NORBERT E. SCHINDLBECK, CHRISTÌNE HEINRICH, ANDREAS DENDORFER, FABIO PACE, and STEFAN A. MULLER-LISSNER Medizinische

Klinik Innenstadt,

University

of Munich, Munich, Federal Republic of Germany

The effect of cigarette smoking on gastroesophageal reflux and the eflect of the pH electrode on salivary secretion and swallowing frequency were studied in 30 healthy vohmteers (15 habitual smokers, 15 nonsmokers) and in 10 smoking patients with proven gastroesophageal reflux disease. Twenty-four-hour pH profiles were measured while the subjects were ambulatory using a combined glass electrode connected to a portable recorder. In 8 of the smoking volunteers, swallowing frequency and salivary secretion were measured, both when smoking and when not. Smokers had more reflux episodes than nonsmokers [median per hour 2.8 [range 0.4-7.1) for the upright body position and 0.5 [range 0.0-1.7) for the supine body position vs. 1.4 (range 0.0-2.1) upright and 0.0 (range 0.0-0.7) supine, p < 0.031, but the total time of exposure of the esophageal mucosa to acid was aflected neither by the status of being a smoker nor by actual smoking. Nasopharyngeal intubation with the pH electrode did not affect the swaliowing frequency, but it increased salivary secretion two- to threefold for a period of 4 h. Six hours after introduction of the pH electrode and later, salivaryflow was similar to baseline. lt is concluded that smoking and nasopharyngeal intubation does not adversely a#ect the results of 24-h pH-metry. During the last few years, 24-h esophageal pH monitoring has become the gold standard for the measurement of gastroesophageal reflux (1-6). However, there may be confounding factors inherent in the Received August 1, 1986. Accepted January 26, 1987. Address requests for reprints to: Norbert E. Schindlbeck, M.D., Medizinische Klinik Innenstadt der Universität München, Ziemssenstrasse 1, D-8000 Munich 2, Federal Republic of Germany. This study was supported by Deutsche Forschungsgemeinschaft DFG (Mu 629/1-4).Norbert Schindlbeck is the recipient of

a grant from the Deutsche Forschungsgemeinschaft DFG (Mu 629/1-5). 0 1987 by the American Gastroenterological Association 0016-5085/87f$3.50

method itself. As short-term nasogastric intubation with standard gastric tubes has been found to stimulate salivary secretion (7), the pH electrode might improve esophageal acid clearance in this way. Also, there is uncertainty whether actual smoking and the status of being a smoker affects pH-metry. The present study therefore was designed to evaluate (a) the effect of smoking on gastroesophageal reflux and (b) the effect of the pH electrode on salivary secretion and swallowing frequency.

Methods Subjects Thirty healthy volunteers (16 men, 14 women) were included in the study. Fifteen subjects were absolute nonsmokers and 15 subjects habitually smoked at least 20 cigarettes a day. The age of the nonsmokers and smokers ranged from 19 to 41 yr (mean 24.9 yr) and from 18 to 42 yr (mean 25.2 yr), respectively. In addition, 10 patients (30-57 yr old, mean age 44.3 yr) with typical symptoms of gastroesophageal reflux who regularly smoked about 20 cigarettes a day were studied. Al1 patients had pathological test results in 24-h pH-metry (esophageal acid exposure time >10.5% for the upright body position or >6.0% for the supine body position, or both]. The study protocol had been approved by the local ethica1 committee. Twenty-Four-Hour

pH-metry

Twenty-four-hour pH-metry was performed using a combined glass electrode (440-M4; Ingold, Switzerland) connected to a portable recorder (Autronicord CM 18 pH; Autronic, F.R.G.). The rigid part of the electrode had a diameter of 4 mm and a length of 22 mm. The cable of the electrode had a diameter of 3 mm. An in vitro calibration of the electrode and the recording system was carried out with buffer solutions of pH 1.7 and 7 before and after each test. The electrode was introduced via the nose of the sitting subject into the stomach until acid pH was recorded. Then the subject lay supine and the electrode was slowly withdrawn. In each case a rapid change in pH from acid to clearly above pH 5 could be identified. The elec-

June 1987

trode was placed 5 cm above the sudden pH change. A stable position of the electrode was ensured by anchoring the cable to the subject’s nose with adhesive tape. The recording device measured pH values every 0.25 s and stored the mean of 20 values every 5 s. During the study, the subject noted time and type of meals, times of smoking (when permitted), body position (upright or supine), and time of retiring to bed on a diary card. NO restrictions were imposed on the subject’s activities or diet, except for drinking liquids with a pH of <4 and for smoking (see below). The stored data were transmitted to a computer for analysis. For visual control the data were written out by a two-Channel strip chart recorder (Omni Scribe; Houston Instruments, Houston, Tex.). Gastroesophageal reflux was defined as episodes with esophageal pH of ~4. The following components were calculated separately for periods of upright and supine body position, respectively: percentage of time with esophageal pH of ~4, number of reflux episodes per hour, and mean duration of reflux episodes. In addition, in both patients and volunteers, percentage of time with esophageal pH of <4 and the number of reflux episodes were calculated for periods of 10 min when smoking a cigarette and for corresponding 10-min periods without smoking (see below).

Study Design Influence of smoking on the result of esophageal pH-metry. Twenty-four-hour pH-metry was carried out in 15 healthy smokers and 15 healthy nonsmokers. The nonsmokers did not smoke; the smokers smoked 20 cigarettes within 24 h (0.9 mg nicotine, 13 mg tar). In the smoking experiments the volunteers were advised to smoke one cigarette in the fasting state immediately after getting out of bed. Times of smoking the remaining 19 cigarettes were not standardized, but the subjects had to record each cigarette on the diary card. Ten of the smokers were investigated on a second occasion when refraining from smoking. The two experiments were done in random order. Finally, 24-h pH-metry was performed in 10 habitually smoking patients. They were allowed to smoke ad libitum, but had to record each cigarette on a diary card. To test the chronic effect of smoking, we compared the final results of 24-h pH-metries that were performed on the two different days in the 10 smokers when smoking and when not smoking (10 paired experiments) and also compared the results of the 15 smoking smokers with those of the 15 nonsmokers (2 x 15 unpaired experiments). The acute effect of smoking was evaluated by comparing the 10 min after lighting a cigarette with the 10 min before lighting up in both patients and controls. In volunteers, the 10 min period after getting out of bed, when smoking the first cigarette in the fasting state, was compared with the corresponding time period of the nonsmoking day. Influence of esophageal intubation on salivaryflow and swallowing. In 8 of the smoking volunteers, swallowing frequency and salivary flow also were measured, both when smoking and when not. The swallowing rate was determined by the subject over a period of 15 min. Saliva was collected over another i5-min period by expectorating

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Figure 1. Percentage of time with pH <4 and the number (n/h) and duration (min/epi) of reflux episodes for the upright and the supine body position in the control group

of 15 nonsmokers (CC]and in 15 smoking smokers (SS). Medians (middfe horizontol bars), 25% and 75% quartiles (broken horizontal bars), and ranges (lower and upper horizontal bars). * p < 0.01 when compared to nonsmokers; * p < 0.005 when compared to corresponding upright value.

into a beaker. The two sampling periods were randomized in order. Measurements were done before and immediately after insertion of the pH electrode, 1, 2, 3, 4, and 6 h later, and before and after the removal of the electrode. Statistics Data are given as medians and ranges or in the case of normally distributed data as means with SEM. The Wilcoxon test [Biomedical Computer Programs (BMDP), University of California, Los Angeles, Calif., program 3S] for unpaired or paired data was applied to evaluate the effect of smoking on the components of 24-h pH-metry. The analysis of variante and covariance with repeated measures (BMDP, program 2V) was used to test the influence of the pH electrode on salivary flow and swallowing frequency. Al1 statistical tests were done in combination with Bonferroni-Holm’s sequentially rejective multiple test procedure (8).

Results Gastroesophageal

Reflux

The results of esophageal pH measurements in volunteers are given in Figures 1 and 2. The number of reflux episodes and the percentage of time with pH <4 were smaller in the supine than in the upright body position. Smokers had significantly more reflux episodes than absolute nonsmokers, both in the upright and supine body position (Figure 1). The percentage of time with an esophageal pH of <4 and the duration of reflux episodes were similar in both groups (Figure 1). Twenty-four hour refrainment from smoking had no significant influence on 24h pH-metry (Figure 2). Neither volunteers nor patients experienced an increase in gastroesophageal

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SCHINDLBECK ET AL.

GASTROENTEROLOGY Vol. 92, No. 6

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SS

UPRICHT SURNE

UPRIGHT SURNE

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Figure 2. Percentage of time with pH <4 and the number (n/h) and duration (mimepi) of reflux episodes for the upright and the supine body position in 10 smokers studied twice [when smoking (SS) and when not (CS)]. Medians (middle horizontal bars), 25% and 75% quartiles (broken horizontal bars), and ranges (lower and upper horizontal bars). * p < 0.005 when compared to corresponding upright value.

reflux while smoking a cigarette, irrespective whether they were in the fasting state (Table 1). Salivary

Flow and Swallowing

1

n/15min

b

_

of

Frequency

Nasopharyngeal intubation with the pH electrode increased salivary secretion two- to threefold. Secretion remained significantly higher than baseline secretion for 4 h. Salivary secretion did not differ from baseline salivary secretion 6 h after introduction and immediately before and after the removal of the pH electrode (Figure 3). The pH electrode did not significantly influence the swallowing frequency (Figure 3). Neither salivary secretion nor swallowing frequency was influenced by whether the subjects actually smoked or not (Figure 31.

Discussion It has been reported that cigarette smoking decreases lower esophageal sphincter pressure (9-11). In addition, a higher frequency of episodes of gastroesophageal reflux was observed when smokers with proven gastroesophageal reflux smoked cigarettes during the night or performed maneuvers that might provoke reflux during smoking (9). These authors therefore concluded that cigarette smoking is a common reversible cause of gastroesophageal reflux. We cannot support the hypothesis that this decrease in sphincter pressure of remarkably short duration plays a major role in the pathogenesis of reflux and is therefore deleterious for patients with reflux disease. Our data did not confirm an acute effect of cigarette smoking on gastroesophageal reflux, neither in patients nor in volunteers, and 24h refrainment from smoking did not reduce reflux frequency and duration in volunteers. As a similar

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21 hours

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Figure 3. Salivary secretion (upper panel) and swallowing frequency (lower panel) in 8 healthy smokers. Values are mean C SEM. Closed circles, smoking 20 cigarettes within 24 h; open circles, not smoking. * p < 0.05 when compared to baseline salivary secretion.

decrease in lower esophageal sphincter pressure was found in both reflux patients and asymptomatic healthy smokers (ll), an effect of smoking on reflux should be accompanied by an effect on 24h pHmetry in volunteers. Although we found more reflux episodes in smokers as compared to nonsmokers, it is improbable that chronic smoking results in gastroesophageal reflux disease inasmuch as the percentage of time with esophageal pH of <4 was similar in both groups. The factor that is probably most relevant, namely total time of exposure of the esophageal mucosa to acid, was therefore affected neither by the status of being a Table

1.

Acute Defect of Cigarette Smoking Gastroesouhaeeal Reflux

on

Percentage of time pH <4 Volunteers Control period Fasting cigarette 10 min before smoking 10 min smoking a cigarette Patients 10 min before smoking 10 min smoking a cigarette Median (range]; differences

No. of reflux episodes1 10 min

o (0-1)

0 (0-5) 0 (0-10) 0 (O-lO] 0 (0-10)

0 (0-21 0 (0-1) 0 (0-21

5 (0-75)

1@-5)

5

not significant.

(o-70)

1 uJ-a

June1987

smoker nor by actual smoking. The discrepancies between our and previous findings may wel1 be due to some methodologie differences: e.g., the number of reflux episodes during the relatively short period of the night when volunteers smoked a cigarette was compared with the number of reflux episodes during the rest of the night (9). It is conceivable that the increase in reflux frequency is due to waking up during the night or to changes in body position during smoking, and not to smoking itself. Furthermore, it is questionable whether provocative maneuvers are a valuable tool in studying the pathophysiology of reflux. From the present data it seems unnecessary to exclude smokers from pH-metric studies or to prohibit smoking during pH-metry. In addition, it is questionable whether abstaining from smoking has a beneficial effect in patients with reflux disease. It has been shown that saliva is capable of clearing It is also known that intraesophageal acid (7,12-14). oral stimuli such as chewing of paraffin wax or nasopharyngeal intubation with a 5-mm tube increase the flow of saliva more than threefold (7). Therefore, it has been suggested that pH-monitoring may underestimate the percentage of time with esophageal pH <4 (7). We also found a significant increase in salivary secretion during nasopharyngeal intubation with a pH electrode. This effect, however, was limited in time. Six hours after intubation and later we could not find a significant differente in salivary secretion when compared to baseline. Because swallowing frequency was not affected by the pH electrode, an intubated person may swallow a slightly greater volume of saliva with each swallow. As volume clearance has been suggested to be the first step of esophageal acid clearance (14,15), the increase in salivary secretion may improve esophageal acid clearance to a certain extent during the first few hóurs of 24-h pH monitoring. As this increased salivary secretion was limited to 4 h, the main period and the final result of 24h pH monitoring probably

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is not influenced by an improved esophageal acid clearance. In conclusion, we consider the diagnostic value of 24h pH-metry not to be diminished by the effects of nasopharyngeal intubation.

References 1.

Atkinson M, Van Gelder A. Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences. Dig Dis Sci 1977;22:365-70. 2. Branicki FJ, Evans DF, Ogilvie AL, et al. Ambulatory monitoring of oesophageal pH in the reflux oesophagitis using a portable radiotelemetry system. Gut 1982;23:992-8. 3. DeMeester TR, Wang Ch-1, Wernly JA, et al. Technique, indications, and clinical use of 24 hour esophageal pH monitoring. J Thorac Cardiovasc Surg 1980;79:656-70. 4. DeMeester TR, O’Sullivan GC, Bermudez G, et al. Esophageal function in patients with angina-type chest pain and normal coronary angiograms. Ann Surg 1982;196:488-98. 5. Euler AR, Byrne WJ. Twenty-four-hour esophageal intralumina1 pH probe testing: a comparative analysis. Gastroenterology 1981;80:957-81. 6. Fink SM, McCallum RW. The role of prolonged esophageal pH monitoring in the diagnosis of gastroesophageal reflux. JAMA 1984;252:1160-4. 7. Helm JF, Dodds WJ, Hogan WJ, et al. Acid neutralizing capacity of human saliva. Gastroenterology 1982;83:69-74. 8. Holm S. A simple sequentially rejective multiple test procedure. Stand J Statist 1979;6:65-70. 9. Stanciu C, Bennett JR. Smoking and gastro-oesophageal reflux. Br Med J 1972;3:793-5. 10. Dennish GW, Castell DO. Inhibitory effect of smoking on the lower esophageal sphincter. N Eng1 J Med 1971;284:1136-7. 11. Chattopadhyay DK, Greaney MG, Irvin TT. Effect of cigarette smoking on the lower oesophageal sphincter. Gut 1977;18: 833-5. 12. Sonnenberg A, Steinkamp U, Weise A, et al. Salivary secretion in reflux esophagitis. Gastroenterology 1982;83:889-95. 13. Helm JF, Dodds WJ, Riedel DR, et al. Determinants of esophageal acid clearance in normal subjects. Gastroenterology 1983;85:607-12. 14. Allen ML, Orr WC, Woodruff DM, et al. The effects of swallowing frequency and transdermal scopolamine on esophageal acid clearance. Am J Gastroenterol 1985;80: 669-72. 15. Helm JF, Dodds WJ, Pelc LR, et al. Mechanisms of esophageal acid clearance in supine normal subjects: a unifying hypothesis (abstr). Gastroenterology 1981;80:1171.