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Gastroesophageal reflux is a potential trigger of asthma that may Patients with asthma aggravated by gastroesophageal re-
be clinically silent. This study examines the prevalence of gastro- flux may not have classic reflux symptoms of heartburn or re-
esophageal reflux in asthma patients without reflux symptoms. This gurgitation, leaving the clinician unaware that gastroesoph-
prospective cohort study evaluated 26 patients with stable asthma ageal reflux may be a trigger for the asthma. A mbulatory 24-h
without reflux symptoms using esophageal manometry and 24-h esophageal pH testing plays a key diagnostic role in asthma
esophageal pH testing. Gastroesophageal reflux was considered patients without reflux symptoms. U sing this test, Irwin and
present if esophageal acid contact times were abnormal. Demo- coworkers studied a group of difficult-to-control asthma pa-
graphic variables were analyzed to determine if they predicted the
tients and found that gastroesophageal reflux was clinically
presence of gastroesophageal reflux. Asthma patients with asymp-
silent in 24% (9). They observed that vigorous treatment of
tomatic gastroesophageal reflux were compared with 30 age-
gastroesophageal reflux was helpful in converting difficult-to-
matched asthma patients with symptomatic gastroesophageal re-
flux. The prevalence of abnormal 24-h esophageal pH tests in
control asthma patients into ones who were no longer difficult
asthma patients without reflux symptoms was 62% (16 of 26). De- to control (9). More recently, in a retrospective review of 199
mographic variables did not predict abnormal 24-h esophageal pH asthma patients undergoing esophageal pH testing, we found
tests in asthma patients with asymptomatic gastroesophageal re- that 35 (18% ) did not have reflux symptoms, of which 10
flux. Asthma patients with asymptomatic gastroesophageal reflux (29% ) had abnormal esophageal acid contact times. Twenty-
had higher amounts of proximal esophageal acid exposure (p , four hour esophageal pH testing was well tolerated without
0.05) compared with asthma patients with symptomatic gastroe- untoward effects in these 199 asthma patients (10). The preva-
sophageal reflux. Because demographic variables do not predict lence and severity of gastroesophageal reflux in asthma pa-
abnormal 24-h esophageal pH tests in asthma patients without re- tients without reflux symptoms has not been carefully studied
flux symptoms, 24-h esophageal pH testing is required. This study in a prospective manner. Thus, the aims of this study are to
suggests that gastroesophageal reflux is present in asthma pa- prospectively determine the prevalence and severity of gas-
tients, even in the absence of esophageal symptoms. troesophageal reflux in stable asthma patients of all severities
without reflux symptoms using 24-h esophageal pH testing
G astroesophageal reflux is common in adult asthma patients and to compare this group with asthma patients with reflux
and is a potential trigger of asthma (1). In a questionnaire sur- symptoms undergoing similar testing.
vey, Field and coworkers reported that 77% of asthma pa-
tients experienced heartburn, 55% complained of regurgita-
tion, and in the week prior to completing the questionnaire, M ETHODS
41% of the asthma patients reported reflux-associated respira-
Subjects
tory symptoms (2). Twenty-four hour esophageal pH testing
accurately diagnoses gastroesophageal reflux with a sensitivity This prospective cohort study was approved by the H uman U se Com-
and specificity of approximately 90% (3). The frequency of mittee at the U niversity of A labama at Birmingham on March 9, 1995.
Subjects were recruited from the outpatient pulmonary clinic at the
false-negative results of 24-h esophageal pH testing ranges be-
U niversity of A labama at Birmingham. Potential subjects were
tween 10% and 25% (4). E valuating 104 consecutive asthma screened over the telephone for the presence of reflux symptoms in-
patients, Sontag and coworkers observed that 82% of asthma cluding heartburn, regurgitation, water brash, dysphagia, and epigas-
patients had abnormal amounts of acid reflux on 24-h esoph- tric pain. If they denied symptoms, they were informed about the
ageal pH testing (5). Identifying gastroesophageal reflux in study and called back after 7 d to see if they were still interested in en-
asthma patients is important because aggressive treatment of rolling, and requestioned as to the presence of esophageal symptoms.
gastroesophageal reflux may result in improvement of respira- Consecutive asthma patients without reflux symptoms who met the
tory symptoms in selected patients (68). A double-blind, pla- entrance criteria and had asthma stability for at least 2 wk, and gave
cebo-controlled, multicentered trial evaluating asthma out- informed consent participated. Stable asthma was defined as stable
asthma symptoms and no change in asthma medications during the
come with aggressive medical therapy using a proton pump
2 wk before study entry. The subject population met the A merican
inhibitor has not been reported to date. Thoracic Societys definition of asthma, including: a 200-ml and a
12% improvement in FE V 1 with bronchodilators, or a 20% decrease
in FE V 1 after methacholine challenge, performed in accordance with
(Received in original form July 16, 1999 and in revised form December 8, 1999) the guidelines of the Lung H ealth Study; subjects were nonsmokers
Presented at Digestive Disease Week, American Gastroenterological Association, and had no symptoms consistent with chronic bronchitis nor other
Washington, DC, May 11, 1997. forms of chronic lung disease (1113). A sthma patients without reflux
Supported in part by a grant from Glaxo Wellcome, Inc. Dr. Harding is sup- symptoms had rare heartburn or regurgitation (once a month or less),
ported by a Sleep Academic Award, National Heart, Lung, and Blood Institute, no dysphagia, no history of esophageal, gastric surgery, or sclero-
National Institutes of Health, Grant HL03633. derma, and no previous treatment with antireflux medications includ-
Correspondence and requests for reprints should be addressed to Susan M. Har- ing H 2 antagonists, proton pump inhibitors, prokinetic agents, or reg-
ding, M.D., Division of Pulmonary, Allergy, and Critical Care Medicine, 215 Tins- ular use of antacids.
ley Harrison Tower, 1900 University Boulevard, University of Alabama at Birming- To assess the severity of gastroesophageal reflux in asthma pa-
ham, Birmingham, AL 35294. E-mail: sharding@uab.edu tients with asymptomatic gastroesophageal reflux ( 2Sx 1pH ), com-
Am J Respir Crit Care M ed Vol 162. pp 3439, 2000 parisons were made with asthma patients with symptomatic gastro-
Internet address: www.atsjournals.org esophageal reflux ( 1Sx 1pH ). This symptomatic gastroesophageal
Harding, Guzzo, and Richter: Asymptomatic Reflux in Asthmatics 35
reflux group is a previously described cohort group which participated nal symptoms, and a family history of asthma. A sthma symptoms,
in a reflux treatment trial in which subjects had asthma criteria as pre- medication usage, and health care utilization determined asthma se-
viously defined, reflux symptoms including the presence of heartburn verity in accordance with the National A sthma E ducation Program
and/or regurgitation at least twice monthly, had abnormal 24-h esoph- E xpert Panel R eport (21). G astroesophageal reflux questions in-
ageal pH tests, and were not on antireflux medication such as antac- cluded the presence and frequency of heartburn, regurgitation, chest
ids, H 2 antagonists, proton pump inhibitors, or prokinetic agents (7). pain, dysphagia, hoarseness, and sore throat.
the total period, with five (28% ) having supine reflux. Proxi- acid exposure [p 5 0.13] and the number of episodes lasting
mal reflux was frequent in the asthma patients with asymp- greater than 5 min at the proximal probe [p 5 0.14]).
tomatic gastroesophageal reflux with 12 (75% ) having abnor- A lthough 24-h esophageal pH monitoring is the best test
mal total amounts of esophageal acid and five (28% ) having available to assess gastroesophageal reflux, normal values vary
supine proximal reflux. E leven (69% ) asthma patients with as- from center to center and values near the definition of abnor-
ymptomatic gastroesophageal reflux had abnormal esoph- mal may not be reproducible (15). Figures 1 and 2 examine in-
ageal acid contact times at both the distal and proximal esoph- dividual esophageal acid contact times in the 26 asthma pa-
ageal pH probes, whereas one (6% ) had abnormal values at tients without reflux symptoms ( 2Sx) at the distal probe
the proximal probe only. D ata at the distal and proximal (Figure 1) and the proximal probe (Figure 2). Normal values
esophageal pH probes of the asymptomatic gastroesophageal are represented below the line on each variable. O pen circles
reflux group ( 2Sx 1pH ) show that 15 of 16 (94% ) subjects represent values from asthma patients with normal esophageal
had more than one abnormal esophageal pH parameter. Two acid contact times ( 2Sx 2pH ), and filled circles represent val-
subjects had two, three subjects had three, eight subjects had ues from asthma patients with abnormal esophageal acid con-
four, one subject had five, and one subject had six out of six tact times ( 2Sx 1pH ). There is a large range of values.
abnormal esophageal pH parameters.
R espiratory symptom correlation showed that 6 of 74 (8% ) Predictors of Gastroesophageal Reflux in Asthma
reported cough episodes, 2 of 2 (100% ) reported shortness of Patients without Reflux Symptoms
breath episodes, 0 of 1 (0% ) indicated sputum production epi- Chi-square and the Fisher exact test analyses showed that no de-
sodes, and 1 of 1 (100% ) had chest pain episodes associated mographic variable (including childhood onset asthma, family
with esophageal acid exposure. Wheezing or chest tightness history of asthma, asthma severity, seasonal variation, history of
was not reported during 24-h esophageal pH testing. atopy, nocturnal symptoms, sore throat, hoarseness, nocturnal
There were no differences in age, asthma duration, body awakenings associated with dyspnea, wheezing with eating or al-
mass index, lower esophageal sphincter pressure, percent peri- cohol use) predicted abnormal esophageal acid contact times.
staltic esophageal contractions, or upper esophageal sphincter
pressure between the asymptomatic reflux group ( 2Sx 1pH ) Demographic Variables of Asthma Patients with
and the group without gastroesophageal reflux ( 2Sx 2pH ) Symptomatic Gastroesophageal Reflux
(Table 1). A sthma patients with asymptomatic gastroesoph- Tables 1 and 2 review demographic and esophageal variables
ageal reflux had higher amplitude of esophageal contractions of the 30 asthma patients with symptomatic gastroesophageal
than those without gastroesophageal reflux (p , 0.005). A s ex- reflux ( 1Sx 1pH ). Pulmonary function data show a mean
pected, the group with gastroesophageal reflux had signifi- FE V 1 of 72 ( 6 25) percent predicted, FE V 1/FVC of 65 ( 6 13),
cantly higher amounts of esophageal acid exposure at both the FE F 2575% of 44 ( 6 35) percent predicted, and peak expiratory
proximal and distal esophageal pH probes than those with flow rate of 80 ( 6 25) percent predicted. Methacholine chal-
normal esophageal acid contact times (p , 0.01 in all esoph- lenge testing was not required for the diagnosis of asthma in
ageal pH variables shown in Table 1 except proximal supine these 30 patients. R espiratory symptom correlation showed
TABLE 1
ASTHM A PATIENTS WITHOUT REFLUX SYM PTOM S ( 2Sx), ASTHM A PATIENTS WITHOUT
REFLUX SYM PTOM S OR GASTROESOPHAGEAL REFLUX ( 2Sx 2pH), ASTHM A PATIENTS WITH
ASYM PTOM ATIC GASTROESOPHAGEAL REFLUX ( 2Sx 1pH), AND ASTHM A PATIENTS WITH
SYM PTOM ATIC GASTROESOPHAGEAL REFLUX ( 1Sx 1pH)*
Age, yr 42.9 6 16.1 37.6 6 14.7 44.5 6 17.6 46.4 6 12.8 0.63
Asthma duration, yr 13.3 6 13.0 10.7 6 9.1 14.9 6 14.9 17.4 6 14.8 0.43
Body mass index, kg/ m 2 28.4 6 6.1 27.7 6 6.6 28.8 6 6.0 29.5 6 6.9 0.72
Esophageal manometry
LES pressure, mm Hg, nl . 10 mm Hg 13.4 6 5.8 12.2 6 4.9 14.2 6 6.3 9.4 6 5.4 0.01
Mean amplitude contractions, mm Hg 7.8 6 39.4 55.6 6 18.8 94.3 6 42.0 78.1 6 34.5 0.23
Peristaltic contractions, % 88.4 6 26.3 91.0 6 20.3 86.7 6 30.2 90.3 6 21.0 0.77
UES pressure, mm Hg 52.4 6 23.0 56.0 6 24.2 50.0 6 22.7 45.0 6 22.9 0.49
Esophageal pH, distal probe
Total, nl , 5.8% 7.3 6 7.0 2.2 6 1.3 10.4 6 7.3 12.1 6 6.9 0.22
Upright, nl , 8.2% 8.6 6 9.0 3.2 6 1.7 11.9 6 10.1 12.6 6 6.5 0.14
Supine, nl , 3.5% 4.8 6 9.5 0.7 6 1.3 7.4 6 11.4 10.1 6 10.8 0.43
No. of episodes . 5 min, nl , 4 2.6 6 3.4 0.4 6 0.5 3.9 6 3.7 5.2 6 4.5 0.40
Longest episode, min, nl , 18.5 16.3 6 17.1 5.6 6 5.2 23.0 6 18.6 24.5 6 19.6 0.98
Esphageal pH proximal probe
Total, nl , 1.1% 2.5 6 6.1 0.5 6 0.3 3.8 6 7.6 1.4 6 1.6 0.03
Upright, nl , 1.7% 3.1 6 8.2 0.8 6 0.4 4.6 6 10.3 1.3 6 1.6 0.09
Supine, nl , 0.6% 1.0 6 2.2 0.0 6 0.1 1.5 6 2.6 1.3 6 3.2 0.61
No. of episodes . 5 min, nl 5 0 0.8 6 2.4 0.1 6 0.3 1.3 6 3.0 0.5 6 0.8 0.63
Longest episode, min, nl , 3 6.9 6 12.6 1.5 6 1.0 10.3 6 15.2 5.3 6 8.0 0.08
Definition of abbreviations: LES 5 lower esopphageal sphincter; nl 5 normal value; UES 5 upper esophageal sphincter.
* Data are expressed as mean 6 SD.
The 2Sx 2pH and the 2Sx 1pH groups are subsets of the 2Sx group.
p value comparing the 2Sx 1pH group with the 1Sx 1pH group.
Harding, Guzzo, and Richter: Asymptomatic Reflux in Asthmatics 37
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