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Ann
0101
Rhinal
LarVI1[(olllO:200I
EFFECT OF CIGARETTE SMOKING ON GASTROPHARYNGEALAND
GASTROESOPHAGEAL REFLUX
CONRAD
F.
SMIT,
MD
MARCEL
P.
COPPER,
MD, PHD
JUSTIN
A. M. J.
VAN
LEEUWEN,
MD
Iva G.
SCHOOTS,
MD
LAKI
D.
STANOJCIC,
MD
AMSTERDAM,
THE
NETHERLANDS
Gastropharyngeal
reflux
appears
tobe
associated
with
various
otolaryngological
complaints.
Cigarette
smoking
is
known
to
affect
adversely
the
defense
mechanisms
against
reflux
of
acid
gastric
contents
into
the
esophagus.
To
study
the
relationship
between
gastropharyngeal,
as
well
as
gastroesophageal,
reflux
and
cigarette
smoking,
15
subjects
underwent
24-hour
double-probe
pH
moni-
toring
while
smoking
their
daily
amount
of
cigarettes.
The
percentage
of
time
the
pH
was
below
4
during
the
smoking
period
was
significantly
higher
than
the
percentage
of
time
the
pH
was
below
4
during
the
nonsmoking
period,
proximal,
at
the
level
of
the
upper
esophageal
sphincter,
as
well
as
distal,
above
the
lower
esophageal
sphincter.
These
findings
demonstrate
that
smoking
increases
gastropharyngeal
and
gastroesophageal
reflux.
Smokers
with
complaints
and
disorders
caused
by
reflux
should
therefore
be
advised
to
stop
smoking
in
order
to
reduce
reflux.
KEY
WORDS
-
acid,
cigarette
smoking,
gastroesophageal
reflux,
gastropharyngeal
reflux,
pH
monitoring.
INTRODUCTION
Cigarette smoking is supposed to increase gastro-
esophageal reflux
(GER).1-12
The effect of cigarette
smoking on gastropharyngeal reflux (GPR), however,
is less known. Under normal conditions, reflux of
acid gastric fluid and its noxious effect are prohib-
ited by the so-called antireflux barrier. The most im-
portant components ofthis barrier are the lower esoph-
ageal sphincter(LES) tone, inclose connection to the
influence of the crura of the diaphragm, esophageal
acid clearance, esophageal epithelial resistance, and
the upper esophageal sphincter (UES) tone.l> Smok-
ing decreases theLES pressure during the act of smok-
ing.I-3,6,7,12 Almost immediately after the start of
smoking, the sphincter pressure falls, and it returns
to normal within 8 minutes after the smoker finishes
the cigarette.
1,2
Cigarette smoking also has a nega-
tive effect on esophageal acid clearance.v-
10
salivary
output.>and gastric emptying.s-? Furthermore, smok-
ing diminishes both the pharyngo-UES contractile
reflex and the pharyngeal reflexive swallow.
12
These
two supraesophagealreflexes prevent the entry of re-
flux materials into the larynx, pharynx, and lungs.
Defective reflexes might be associated not only with
aspiration of gastric contents, but also with reflux-
related otolaryngological disorders. To assess the di-
rect effect of cigarette smoking on GPR and GER,
we performed ambulatory 24-hour double-probe pH
monitoring in cigarette smokers.
PATIENTS AND METHODS
Patients. Fifteen subjects (9 men, 6women; mean
age, 41 years; range, 24 to 61 years) with a history of
smoking at least 15cigarettes per day for more than
5years were studied.
All subjects underwent 24-hour double-probe pH
monitoring in an ambulatory setting. The subjects
were asked to continue their normal daily smoking
habits during the monitoring.
Eleven subjects presented with otolaryngological
complaints (globus, dysphonia); the other 4 were
healthy normal subjects (patients
7,8,9,
and 10).
pH Measurement. Double-probe pH monitoring
was performed with 2 monocrystalline antimony pH
sensors positioned along a single catheter (diameter,
2.1 mm) with the sensors 15 to 20 ern apart and a
silver-silver chloride cutaneous reference electrode
(Digitrapper Mark III, Medtronic Synectics, Maas-
tricht, the Netherlands). Both probes (pH sensors)
were calibrated simultaneously in buffer solutions
pH 7and pH 1before monitoring. Under endoscopic
view, the proximal probe was placed in the UES in
such a way that the probe was just surrounded by the
esophageal mucosa. A recent study showed that en-
doscopic placementof the proximal probe in the UES
without manometry is an accurate method.
14
Accord-
ingly, the second probe (distal pH sensor) was posi-
tioned 15or 20 cm distal to the proximal probe, de-
From
the
Department
of
Otorhinolaryngology-Head
and
Neck
Surgery,
Academic
Medical
Center,
University
of
Amsterdam, Amsterdam,
the
Netherlands.
CORRESPONDENCE
-
Laki
D.
Stanojcic,
MD,
Dept
of
Otorhinolaryngology-Head
and
Neck
Surgery,
Academic
Medical
Center,
University
of
Amsterdam,
PO
Box
22700,
1105
DE
Amsterdam,
the
Netherlands.
190
Smit et al, Reflux &Cigarette Smoking
TABLE I. NUMBER OF CIGARETTES AND PERCENTAGE OF TIME PH <4DURING 24-HOUR PH MONITORING
No.
of
Cigarettes Proximal Prohe Distal Probe
Daily During (% Time pH <4) (% Time pH <4)
Patient Use Monitoring Total Upright Supine Total Upright Supine
120 17 0.0 0.0 0.0 1.7 2.4 0.0
225 20 0.0 0.0 0.0 1.6 2.1 0.0
320 9 0.0 0.0 0.0 2.5 3.5 0.8
4IS 60.0 0.0 0.0 0.3 0.5 0.2
520 IS 0.1 0.1 0.0 0.3 0.5 0.0
6IS 14 0.0 0.0 0.0 0.8 1.2 0.0
720 17 0.0 0.0 0.0 3.9 5.7 0.0
8IS 13 0.1 0.1 0.1 2.1 0.6 2.5
916 8 0.2 0.3 0.0 1.1 1.7 0.0
10 20 16 0.2 0.4 0.0 0.9 1.5 0.0
11 30 18
1.1
1.6 0.0 4.0 5.6 0.7
12 IS 70.2 0.3 0.0 2.4 3.4 0.0
13 35 30 0.3 0.3 0.5 12.6 16.4 3.8
14 25 23 2.8 3.9 0.0 5.8 7.9 0.1
15 IS 11 0.0 0.0 0.0 8.6 4.2 29.1
191
pending on the distance from the tip of the nose to
the LES. This distance was determined by using the
pH transition point (withdrawal technique) in order
to achieve aposition of the distal probe 5 to 10 em
above the LES.
A pH drop below 4recorded by the proximal probe
was considered to be positive evidence of
GPR
only
if it was preceded by a distal pH drop of similar or
larger magnitude.IS
The subjects were encouraged to eat their regular
meals without restrictions and to continue their nor-
mal daily and nocturnal routines. In a diary, the sub-
jects reported body position, meals, drinks, and ciga-
rette smoking.
Data Analysis. At the end
of
the measurement, the
pH data from the portable recorder were downloaded
into a personal computer for analysis. The percent-
age of time the pH was below 4 for the total time,
time in upright position, and time in supine position,
as well as for the smoking-related and
non-smok-
ing-related periods was calculated with the EsopHo-
gram software program (Medtronic Synectics).
For the distal probe, the criteria of Richter et al16
were used to distinguish between physiological and
pathological GER. Richter et al defined as normal a
pH below
4less
than 5.5% of the total time, less than
8.2%
ofthe
time in the upright position, and less than
3% of the time in the supine position.
For the proximal probe placed at the entrance of
theesophagus, our normal values for GPR, established
recently, were used.l"We considerpercentagesof time
with a pH below 4 of more than 0.1 %for the total
time, 0.2% for the time upright, and 0% for the time
supine to be pathological.
All pH tracings were reviewed manually in order
to assess real reflux episodes at the proximal probe.
Reflux episodes that occurred during the time of
smoking and within 8minutes after ending smoking
were considered to be smoking-related. Otherreflux
episodes that occurred during the time that the sub-
ject
was awake were considered to be non-smoking-
related.
The percentages
of
time that the pH was below 4
were compared for the smoking-related period and
the nonsmokingperiod by use of Wilcoxon's matched-
pairs signed ranks test for nonparametric data (1-
tailed).
RESULTS
Sevenof the 15 subjects (Nos. 1through 7) did not
have any pathological reflux, according to the above-
mentioned criteria. Five subjects (Nos. 8 through 12)
had pathological values for GPR, 2subjects (Nos.
13 and 14) had pathological values for GPR as well
as GER, and 1subject (No. 15) had pathological val-
ues for
GER
(Table 1).
The
percentages of time the pH was below 4 dur-
ing the smoking-related period and during the non-
smoking period, measured at the proximal probe and
at the distal probe, are shown in Table 2. At the level
of
the DES, the median percentage of time the pH
was below 4 for the smoking period was 0.1%, ver-
sus 0% for the
nonsmoking
period. In the distal
esophagus, the median percentage of time the pH
192 Smit et al, Reflux &Cigarette Smoking
TABLE 2. PERCENTAGE OF TIME PH <4 WITH NO
SMOKING AND DURING SMOKING AT PROXIMAL
AND DISTAL PROBES
Proximal Probe Distal Probe
(% Time pH <4) (% Time pH <4)
Period Period
Awake Smoking- Awake Smoking-
and Not Related and Not Related
Patient Smoking Period Smoking Period
I00 2.2 2.6
20 0.2 0.9 7.1
3 0 0 2.9 7.7
4 0 0 0.3 1.6
5 0.1 0 0.6 0.1
6 0 0.1 0.7 2.9
7 0 0 5.5 6.2
80.1 0 0.8 0
9 0 1.1
I.l
5.8
10 0.3 0.6 0.9 3.5
11
1.1 2.7 4.7 7.2
12 1.4 3.7 4.2 12.6
13 0.9 2.8 3.9 9.8
14 3.4 4.9 6.9 10.0
15 0 0.1 4.0 4.9
Median 0 0.1 2.2 5.8
Range 0-3.4 0-4.9 0.3-6.9 0-12.6
was below 4 for the smoking period was 5.8%, and
for the nonsmoking period, 2.2%.
When the percentage
of
time the pH was below 4
during the smoking period was compared with the
percentage of time the pH was below 4 during the
nonsmoking period, the difference was statistically
significant, proximal, at the level of the DES (p <
.01), as well as distal, above the LES (p < .001).
When the smoking-related periods were excluded
from the analysis, the values of 1 subject (No. 14)
with pathological GPR and GER turned into normal
values for GER. (The percentages of time the pH was
below 4 for the total time, time in the upright posi-
tion, and time in the supine position changed from
5.8%, 7.9%, and 0.1% into
4.5%,6.8%,
and 0.1%.)
According to our criteria, the values
of
2subjects
(Nos. 9 and 12) with only pathological GPR turned
into normal values for GPR. (The percentages of time
the pH was below 4 for the total time, time in the
upright position, and time in the supine position
changed, respectively, from 0.2%, 0.3%, and 0.0%
into 0.1%, 0.2%, and 0.0% and from 0.2%, 0.3%,
and 0.0% into 0.0%, 0.0%, and 0.0%).
DISCUSSION
In this study, a significant increase of GPR, as well
as GER, during smoking was found. Animal studies
have shown that minute amounts of gastric fluids are
capable
of
inducing damage to laryngeal struc-
tures. 17,18 Furthermore, GPR appears to be associ-
ated with various otolaryngological disorders such
as hoarseness, chronic throat-clearing, posterior lar-
yngitis, laryngeal granulomas, subglottic stenosis, and
carcinomas
of
the aerodigestive tract.17-19 Because
there is a relationship between smoking and several
of these otolaryngological disorders as well, we stud-
ied the effect of cigarette smoking on GPR and GER.
To detect GPR and GER, ambulatory 24-hour dou-
ble-probe pH monitoring was performed. This tech-
nique is one
of
the most reliable methods for detect-
ing both low and high esophageal refluxes of acid
gastric juice.20,2 1 The advantage of pH monitoring
in an ambulatory setting is the achievement of an as-
normal-as-possible situation during the monitoring
period. Therefore, it is advised for the measurement
of GER to minimize restrictions during the 24-hour
monitoring period in order to get an as representa-
tive a result as possible.F Consequently, subjects who
smoke should actually continue their normal daily
smoking habits during the pH monitoring.
After many attempts to define the most reliable
parameter and the best applicable normal values, a
consensus was reached that the percentage of time
(total, upright, supine) the pH is below 4 is the most
useful discriminatorbetween physiological and path-
ological reflux.P The impact ofreflux that occurred
during the smoking periods, however, was not always
detectable when the percentages
of
time the pH was
below 4 (total time, time in upright position, and time
in supine position) were calculated by the computer.
For example, subject 2 and subject 6showed some
reflux at the proximal probe during the smoking pe-
riod (Table 2); however, on the overall analysis, these
values were reduced to 0.0% (Table I). Neverthe-
less, according to our criteria of normal values, the
diagnosis would change in 3 subjects (Nos. 9, 12,
and 14) if the smoking periods were excluded.
In single-probe pH studies, an increase in reflux
episodes distal in the esophagus was also found dur-
ing
smoking,6,7,11,23
although some investigators
could not find a significant increase in the total esoph-
ageal acid exposure time.6,23
To our knowledge, this is the first study on GER
and GPR in subjects who smoke, and our results are
in agreement with the finding of Dua et al 12 that smok-
ing may have implications for the development
of
supraesophageal reflux-related complications (oto-
laryngological and respiratory).
Cigarette smoking may influence reflux; therefore,
smokers with complaints and disorders caused by re-
flux should strongly be advised to stop smoking.
Smit et al, Reflux &Cigarette Smoking
REFERENCES
193
I. Dennish GW, Castell DO. Inhibitory effect
of
smoking
on the lower esophageal sphincter. N Engl J Med 1971 ;284:
1136-7.
2. Stanciu C, BennettJR. Smoking and gastro-oesophageal
reflux. Br Med J 1972;3:793-5.
3. Chattopadhyay DK, Greaney MG, Irving TT. Effect of
cigarette smoking on the lower oesophageal sphincter. Gut
1977;18:833-5.
4. Kjellin G, Tibbling L. Influence of body position, dry
and wet swallows, smoking and alcohol on esophageal acid
clearing. Scand JGastroenterol 1978;13:283-8.
5. Kahrilas PJ, Gupta RR. The effect of cigarette smoking
on salivation and esophageal clearance. J Lab Clin Med 1989;
114:431-8.
6. Waring JP, Eastwood TF, Austin JM, Sanowski RA. The
immediate effects
of
cessation of cigarette smoking on gastro-
esophageal reflux. Am J Gastroenterol 1989;84: 1076-8.
7. Kahrilas PJ, Gupta RR. Mechanisms of acid reflux as-
sociated with cigarette smoking. Gut 1990;31 :4-1
O.
8. Johnson RD, Horowitz M, Maddox AF, Wishart JM,
Shearman DJC. Cigarette smoking and rate
of
gastric empty-
ing: effect on alcohol absorption. BMJ 1991;302:20-3.
9. Scott AM, Kellow
IE,
Shuter B, Nolan JM, Hoschl R,
Jones MP. Effect of cigarette smoking on solid and liquid in-
tragastric distribution and gastric emptying. Gastroenterology
1993;104:410-6.
10. Rahal PS, Wright RA. Transdermal nicotine and gastro-
esophageal reflux. Am J Gastroenterol 1995;90:919-21.
II.
Kadakia SC, Kikendall JW, Maydonovitch C, Johnson
LF. Effect of cigarette smoking on gastroesophageal reflux
measured by 24-h ambulatory esophageal pH monitoring. Am
JGastroenterol 1995;90:1785-90.
12. Dua K, Bardan E, Ren J, Sui Z, Shaker R. Effect of
chronic and acute cigarette smoking on the
pharyngo-upper
oesophageal sphincter contractile reflex and reflexive pharyn-
geal swallow. Gut 1998;43:537-41.
13. Boermeester MA, van Sandick JW, van Lanschot JJB,
Boeckxstaens GE, Tytgat GNJ, Obertop H. Gastro-oesofageale
refluxziekte: pathofysiologie, diagnostiek en medicamenteuze
therapie. Ned Tijdschr Geneeskd 1998;142: 1306-10.
14.
Smit
CF, Tan J, Devriese PP, Mathus-Vliegen EMH,
Brandsen M, Schouwenburg PF. Ambulatory pH monitoring at
the upper esophageal sphincter. Laryngoscope 1998;108:299-
302.
15. Katz PO. Ambulatory esophageal and hypopharyngeal
pH monitoring in patients with hoarseness. Am J Gastroenterol
1990;85:38-40.
16. Richter IE, DeMeester TR, Wu WC, Sinclair JW, Schan
C, Bradley LA. Normal 24-hour esophageal pH values: influ-
ence
of
age and gender [Abstract]. Gastroenterology 1990;98:
A122.
17. Koufman JA. The otolaryngologic manifestations of gas-
troesophageal reflux disease (GERD): aclinical investigation
of 225 patients using ambulatory 24-hour pH monitoring and
an experimental investigation of the role of acid and pepsin in
the development of laryngeal injury. Laryngoscope 1991;101
(suppI53).
18. Delahunty JE, Cherry 1. Experimentally produced vocal
cord granulomas. Laryngoscope 1968;78:1941-7.
19. Toohill RJ, Kuhn JC. Role of refluxed acid in the patho-
genesis of laryngeal disorders. Am J Med 1997; 103(suppl 5A):
100S-106S.
20. Dobhan R, Castell DO. Normal and abnormal proximal
esophageal acid exposure: results of ambulatory dual-probe pH
monitoring. Am J Gastroenterol 1993;88:25-9.
21. Wiener GJ, Morgan TM, Copper JB, et al. Ambulatory
24-hour esophageal pH monitoring. Reproducibility and vari-
ability of pH parameters. Dig Dis Sci 1988;33: 1127-33.
22. Kahrilas PJ, Quigley EMM. Clinical esophageal pH re-
cording: atechnical review for practice guideline development.
Gastroenterology 1996;110: 1982-96.
23. Schindlbeck NE, Heinrich C, DendorferA, Pace F, Mul-
Ier-Lissner SA. Influence
of
smoking and esophageal intuba-
tion on esophageal pH-metry. Gastroenterology 1987;92: 1994-
7.
