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Health-related quality of life and severity of symptoms in patients with Barrett’s esophagus and gastroesophageal reflux disease patients without Barrett’s esophagus
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2000 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 95, No. 8, 2000 ISSN 0002-9270/00/$20.00 PII S0002-9270(00)01027-3
ORIGINAL CONTRIBUTIONS
Health-Related Quality of Life and Severity of Symptoms in Patients With Barrett’s Esophagus and Gastroesophageal Reflux Disease Patients Without Barrett’s Esophagus Mohamad A. Eloubeidi, M.D., M.H.S., and Dawn Provenzale, M.D., M.S. Institute for Clinical and Epidemiological Research, Veterans Affairs Medical Center, and the Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
OBJECTIVES: The aims of this study were: 1) to compare the health-related quality of life (HRQL) of patients with Barrett’s esophagus (BE) to that of patients with GERD who did not have BE;2) to compare HRQL of gastroesophageal reflux disease (GERD) patients to that of normative data for the US general population; and 3) to examine the impact of GERD symptom frequency and severity on HRQL. METHODS: The SF-36 and a validated GERD questionnaire were administered to 107 patients with biopsy-proven BE and to 104 patients with GERD but no BE by endoscopy. Frequent symptoms were defined as symptoms that occurred at least once weekly. Severity of symptoms was rated on a scale from 1 to 4 (mild to very severe). RESULTS: In all, 85% of the GERD patients and 82% of BE patients completed the questionnaires. There was no difference in the scores of the eight subscales of the SF-36 between BE patients and those with GERD but without BE (p ⬎ 0.05). However, both groups scored below average on all subscales of the SF-36 compared to published US norms for an age- and gender-matched group. Using multivariable linear regression, the social functioning subscale of the SF-36 correlated with the presence of heartburn or acid regurgitation, severity of acid regurgitation, frequency of heartburn, frequency of acid regurgitation, and number of comorbidities. Similarly, the physical functioning subscale correlated with age, frequency of heartburn, and number of comorbidities. The bodily pain subscale correlated with the frequency of heartburn and number of comorbidities. The bodily pain subscale correlated with the frequency of heartburn and the severity of dysphagia, whereas the role emotional subscale correlated with the frequency of heartburn and the presence of dysphagia. CONCLUSIONS: Although there were no differences in HRQL between BE and GERD patients, both groups scored below average on the subscales of the SF-36 compared to normal controls. GERD symptom frequency and severity were associated with bodily pain and with impaired social, emotional, and physical functioning, suggesting a profound
impact on daily living. (Am J Gastroenterol 2000;95: 1881–1887. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION Heartburn is a prevalent symptom experienced monthly by 44%, weekly by 15–20%, and daily, by 7% of the US population (1–3). Heartburn and acid regurgitation are associated with chest pain, dysphagia, dyspepsia, globus sensation, and hoarseness, symptoms that might have a profound impact on health-related quality of life (HRQL). Barrett’s esophagus (BE), intestinal metaplasia of the lower esophagus, is associated with gastroesophageal reflux disease (GERD) and with an increased risk for the development of esophageal adenocarcinoma (4). Several studies have shown that GERD has a profound effect on HRQL (5, 6). In one study, patients with GERD had a lower quality of life compared to patients with duodenal ulcers, hypertension, mild congestive heart failure, angina, and menopause (6). Our pilot study using the SF-36 showed that patients with BE have a diminished HRQL compared to either patients in the general medical clinic, or to the general population. Interrupted daily activity because of heartburn correlated with the role physical and role emotional subscales of the SF-36 (7). Although BE may be associated with severe GERD (8), there are currently no studies that compare HRQL of patients with BE to that of GERD patients without BE. Therefore, the aims of this observational study were 1) to compare HRQL of patients with BE and patients with GERD who do not have BE, 2) to compare HRQL of GERD patients to that of normative data for the US general population, and 3) to examine the impact of GERD symptom severity and frequency on HRQL in these patients.
MATERIALS AND METHODS Study Measures There are currently two types of HRQL instruments: the generic, and the disease-specific. The generic instruments detect the effects of several parameters on health status (e.g.,
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Table 1. The Eight Subscales or Domains of the MOS SF-36* Subscale Physical function Bodily pain Role limitation-physical Vitality General health Social function Role limitationemotional Mental health
Definition Extent to which health limits everyday physical activity Extent of bodily pain Extent to which physical problems interfere with usual daily activities such as work, housework, or school Ratings of energy level Ratings of current health in general Extent to which health interferes with social activities Extent to which emotional problems interfere with usual daily activities such as work, housework, or school Emotional well-being, including depression, anxiety, and positive well-being.
*MOS ⫽ Medical Outcomes Study; SF-36 ⫽ short form-36.
physical, social, emotional and psychological function). They allow comparisons of health status between several chronic disorders. The SF-36 (9) is an example of a generic health status measure. The SF-36 is a 36-item questionnaire that measures three major health attributes: 1) health status; 2) well-being (i.e., mental health, energy and fatigue, pain); and 3) an overall evaluation of health. Validated as part of the Medical Outcomes Study (MOS) (10), it has been subsequently validated in multiple populations including dialysis patients, diabetics, and elderly veterans (11–13). The SF-36 contains 36 questions on aspects of both physical and mental health. The scores for each question are used to calculate a score between 0 and 100 for each of the eight subscales. Higher scores reflect better quality of life. The eight subscales of the SF-36 are shown in Table 1. Although generic measures can assess quality of life of individuals with a variety of disorders, disease-specific measures focus on the aspects of HRQL that are specific to a given patient group. Therefore, they may be more sensitive or responsive to changes associated with interventions or to changes with time. The gastroesophageal reflux questionnaire (GERQ) described in this study (14) is an example of a disease-specific health status measure. Developed and validated as a population-based measure of GERD (14), the GERQ is a self-report instrument consisting of approximately 80 questions and a psychosomatic symptom checklist (PSC), a measure of somatization (15). The first 32 questions assess symptoms of heartburn, acid regurgitation, chest pain, and dysphagia. The remaining questions examine extraesophageal manifestations of GERD and associated disorders, clinic visits, medication use, and family history of GERD. Symptom frequency is measured on the following scale: 1 ⫽ none in the past year; 2 ⫽ less than once a month; 3 ⫽ about once a month; 4 ⫽ about once a week; 5 ⫽ several times a week; and 6 ⫽ daily. Symptoms occurring once a week or more are defined as frequent. Symptom severity is assessed on a 4-point scale as follows: mild (can be ignored), moderate (cannot be ignored but does not affect lifestyle), severe (affects lifestyle), and very severe (markedly affects lifestyle). Finally, the number of comorbidities were recorded and scored to derive the Charlson comorbidity index (19). The Charlson index is a measure of the number of associated comorbidities that predicts mortality
risk at one year. Higher scores reflect an increased mortality risk at one year. Summary data on HRQL scores for controls were obtained from the results of the Medical Outcomes Study (16). Patient Selection The SF-36 and the GERQ were distributed to patients with biopsy-proven BE and to consecutive patients with GERD. The questionnaires were self-administered. BE was diagnosed if EGD biopsies revealed specialized intestinal metaplasia in a columnar lined segment of esophagus (of any length). All esophageal biopsies were stained with hematoxylin and eosin stains. Only patients with macroscopic evidence of columnar lined esophagus were biopsied at endoscopy. Short-segment BE was defined as ⬍2 cm of columnar lined esophagus. Patients with GERD who had no evidence of BE on endoscopy were included and constituted the GERD group. Patients with GERD who had a history of gastric surgery and fundoplication were excluded. In addition, we excluded patients with GERD who had not undergone endoscopy. Patient charts were reviewed, and the number of comorbidities were abstracted and recorded. The study was approved by the institutional review board and subcommittee on Human Studies of the Durham Veterans Affairs Medical Center (DVAMC). All subjects gave informed written consent before their enrollment in the study. A total of 107 patients with BE esophagus and 104 patients with GERD were enrolled. Statistical Analysis To demonstrate a clinically significant difference in the physical functioning subscale of the SF-36 (10-point difference), we estimated that 86 patients per group would be required (80% power, ␣ ⫽ 0.05). With our total of 176 patients (those who actually returned the questionnaires), the study had sufficient power to detect a 10-point difference in the following subscales: vitality, social functioning, mental health, and general health (16). Clinical and demographic characteristics of patients with BE and GERD patients without BE were examined. Categorical variables were compared with either the 2 or Fisher’s exact test. Continuous variables were compared using the Wilcoxon rank sum test or the Student’s t test. Linear
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Quality of Life in Barrett’s and GERD Patients
Table 2. Baseline Characteristics of Patients With BE and in GERD Patients Without BE Characteristic
BE (N ⫽ 88)
GERD (N ⫽ 88)
Median age (IQR)* Race (% white)† Gender (% male)‡ Ever smoked (%)† Alcohol use (%)† Coffee use (%)† PPI use (%)† Charlson Index§ PSC scores§
64 (50–69) 88 98 65 19 51 68 0.98 ⫾ 1.37 42.10 ⫾ 24.20
57 (47–58) 81 92 68 31 49 57 0.72 ⫾ 1.15 41.80 ⫾ 22.82
All p values (except age) are ⬎0.05. * p ⫽ 0.04, Wilcoxon rank sum test. † 2 test. ‡ Fisher’s exact test. §Student’s t test. BE ⫽ Barrett’s esophagus; Charlson index ⫽ a measure of number of associated comorbidities; higher scores reflect an increased mortality risk at 1 yr; GERD ⫽ gastroesophageal reflux disease; IQR ⫽ interquartile range (25th to 75th percentile); PSC ⫽ psychosomatic symptom checklist, a measure of somatization.
regression analysis was performed to determine the association between the subscales of the SF-36 and the independent variables (age, race, duration of symptoms, severity of symptoms, frequency of symptoms, type of medical therapy, psychosomatic symptom checklist (PSC), and the presence of comorbid illnesses, as measured by the Charlson comorbidity index (17). The subscales of the SF-36 are reported as the median and the interquartile range, as the data were not normally distributed. All statistical analyses were performed using Statistical Analysis System (SAS, Cary, NC) software version 6.12. All p values are two-sided, with ␣ ⫽ 0.05 as the standard for significance.
RESULTS The questionnaires were administered to 107 BE patients and 104 patients with GERD. In all, 85% of the GERD
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patients and 82% of the BE patients returned the questionnaires. There was no difference between the responders and nonresponders in terms of age, gender, and the presence or absence of BE. However, nonresponders in general were more likely to be African-American (31% vs 15%, p ⬍ 0.02). There was no difference in terms of race in the BE patient group between the responders and nonresponders. GERD patients who responded were more likely to be white (82% vs 56%, p ⫽ 0.02). Of the BE patients, 71% had long-segment BE (⬎2 cm). Of the GERD patients, 44% had no evidence of erosive esophageal disease on endoscopy. The clinical and demographic characteristics of the groups are shown in Table 2. Although BE patients were older (median age 64 yr vs 57 yr, p ⫽ 0.04), there was no difference between the groups in terms of race, gender, the use of caffeine or alcohol, prior smoking status, number of comorbidities, PSC scores, or proton pump inhibitor use. Moreover, the two groups were similar in terms of endoscopic peptic complications of GERD: namely, esophagitis (44% vs 54%, p ⫽ 0.18), esophageal ulcers (17% vs 9%, p ⫽ 0.13), and strictures (9% vs 10%, p ⫽ 0.89). In addition, BE patients were more likely to have a hiatal hernia than those without BE (OR 2.48, 95% CI 1.28 – 4.79, 74% vs 53%, p ⫽ 0.0006). Figure 1 shows the duration of GERD symptoms in patients with BE and GERD patients. There was no difference in the duration of symptoms between the two groups, or the proportion of patients who had symptoms for ⬎10 yr (Table 3). Figure 2 shows that the proportion of patients reporting mild, moderate, severe, and very severe GERD symptoms was not different between the groups. However, BE patients were more likely to report less severe symptoms when symptoms were classified as moderate to severe versus mild (Table 3). In addition, patients with BE were less likely to report acid regurgitation at night compared to those with GERD (p ⫽ 0.04).
Figure 1. Duration of heartburn symptoms (yr) in patients with Barrett’s esophagus and in patients with gastroesophageal reflux disease.
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Table 3. Severity and Duration of Heartburn Symptoms in Patients With BE and in Patients With GERD
Duration (⬎10 yr) Frequency (at least once/wk) Severity* Night symptoms
BE (%)
GERD (%)
p Value
35 67 65 61
34 57 82 81
0.1 0.1 0.01 0.04
heartburn (p ⫽ 0.03) and the number of comorbidities (p ⫽ 0.004). The bodily pain subscale correlated with the frequency of heartburn (p ⫽ 0.002) and the severity of dysphagia (p ⫽ 0.002), whereas the role emotional subscale correlated with frequency of heartburn (p ⫽ 0.004) and the presence of dysphagia (p ⫽ 0.07). Both the general health and vitality subscales correlated with the frequency of heartburn and the number of comorbidities.
* Moderate to severe versus mild. All comparisons were performed with the 2 test. BE ⫽ Barrett’s esophagus; GERD ⫽ gastroesophageal reflux disease.
DISCUSSION There was no difference in the subscales of the SF-36 between BE patients and those with GERD but without BE (p ⬎ 0.05) (Table 4 and Fig. 3). However, both groups scored below average on all subscales of the SF-36 compared to published US norms for an age-matched group. The impact of GERD and its symptoms in both groups was most obvious on the physical functioning, role physical, bodily pain, and vitality scores of the SF-36, with scores at least ⱖ25 points lower than that of an age-matched population. Although we did not perform a formal statistical analysis between GERD and BE patients and the control group, a difference of 3–5 points has been considered to be clinically significant. A multivariable linear regression model was constructed to determine the effect of GERD symptoms in patients with GERD and in those with BE on HRQL. Adjusting for the psychosomatic index (PSC), the social functioning subscale correlated with the presence of heartburn or acid regurgitation (p ⫽ 0.03), the severity of acid regurgitation (p ⫽ 0.03), the frequency of heartburn (p ⫽ 0.003), the frequency of acid regurgitation (p ⫽ 0.02), and the number of comorbidities (p ⫽ 0.04). The physical functioning subscale correlated with age (p ⫽ 0.0009), the frequency of heartburn (p ⫽ 0.03), and the number of comorbidities (p ⫽ 0.002). The role physical subscale correlated with the frequency of
Health-related quality of life measurements are becoming increasingly important measures of patient-oriented outcomes. Although measurements of biochemical and physiological parameters are important, they might not necessarily capture the impact of an intervention on patient wellbeing. Measurements of HRQL may complement traditional outcome measures, as they assist physicians in understanding patient attitudes toward their illness. Ours is the first study to compare HRQL of patients with BE to that of GERD patients. This study showed that there was no difference in HRQL between patients with GERD and those with BE. Similar to the results of many other studies, our data suggest that patients with GERD experience diminished HRQL. Revicki et al. (18) compared the HRQL of GERD patients to normative data on HRQL for the US general population, to the HRQL of diabetics, the clinically depressed, and hypertensive patients from the Medical Outcomes Study. They also examined differences in HRQL between patients who did and did not respond to treatment for GERD. At baseline, the mean SF-36 scores for all subscales for GERD patients were significantly lower than those of the general US population and a healthy group. In addition, patients with GERD had lower mean SF-36 scores on the bodily pain, social functioning, and mental health scales compared with patients with hypertension. When
Figure 2. Severity of reflux symptoms in patients with Barrett’s esophagus and in patients with gastroesophageal reflux disease who reported any episodes in the last year.
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Table 4. Median SF-36 Scores and Interquartile Range (IQR) for GERD Patients, BE Patients, and Those for an Age and GenderMatched Group (Higher scores reflect better quality of life) Subscale
GERD, Median (IQR)
BE, Median (IQR)
Physical functioning Role-physical Bodily pain General health perceptions Vitality Social functioning Role-emotional Mental health
45 (30–65) 23 (0–50) 41 (22–52) 40 (20–62) 35 (20–50) 62.5 (25–87.5) 66.67 (0–100) 68 (48–80)
40 (17.5–65) 26 (0–37.5) 41 (31–62) 35 (20–60) 40 (20–55) 62.5 (37.5–87.5) 66.67 (0–100) 68 (52–84)
p Value
Controls, Median (IQR)
0.15 0.78 0.34 0.83 0.61 0.26 0.90 0.60
85 (60–95) 100 (50–100) 72 (51–84) 67 (50–82) 65 (45–80) 100 (62.5–100) 100 (66.7–100) 80 (64–92)
All comparisons between the two groups were carried out with the Wilcoxon rank sum test. BE ⫽ Barrett’s esophagus; GERD ⫽ gastroesophageal reflux disease.
comparing patients who were responsive to those who did not respond to GERD therapy, treatment responders reported better mean bodily pain, physical function, social function, and vitality scale scores compared with nonresponders. In addition, severity of symptoms as assessed by the increasing number of symptoms was associated with lower SF-36 scores. Chal et al. (19), in a similar study, demonstrated that GERD patients had impaired pain, vitality, mental health, and role limitation scores on the SF-36. To measure the impact of GERD and its treatment on HRQL, Dimenas et al. (20) used the Psychological General Well-being Index (PGWB) and two other disease-specific measures for gastrointestinal symptoms. In this study, symptomatic patients with evidence of endoscopic esophagitis had lower HRQL measured by the PGWB compared to patients with normal endoscopy findings. After 4 wk of treatment, however, GERD patients had significant improvement in both general well-being and symptom specific
Figure 3. Median scores for the MOS SF-36 (eight subscales) for controls, GERD patients, and BE patients. Abbreviations: BE ⫽ Barrett’s esophagus; BP ⫽ bodily pain; GERD ⫽ gastroesophageal reflux disease; GH ⫽ general health; MH ⫽ mental health; MOS SF-36 ⫽ Medical Outcomes Study, short form; PF ⫽ physical functioning; RE ⫽ role emotional; RP ⫽ role physical; SF ⫽ social functioning; VT ⫽ vitality. Higher scores are associated with a better quality of life.
scores. In another study (6), patients with GERD had impaired psychological well-being compared with patients with untreated hypertension, mild heart failure, or angina. Similarly, a study by Mcdougall et al. (5) showed that esophagitis was significantly associated with impaired quality of life. Esophagitis patients had significantly lower scores on general health and social functioning subscales of the SF-36 compared to the population of Northern Ireland. In addition, the same group showed that treatment of esophagitis with a proton pump inhibitor was associated with improvement of the bodily pain and vitality subscales of the SF-36 (21). Watson and colleagues (22), in a double-blind crossover, placebo-controlled trial, showed that GERD patients responding to a proton pump inhibitor had significantly better bodily pain and vitality scores on the SF-36 compared to the nonresponders. Recently, Havelund et al. (23) showed that patients with GERD but no esophagitis treated with a PPI had significant improvement in the PGWB index and the Gastrointestinal Symptom Rating Scale (GSRS) compared to placebo. All dimensions of the PGWB index improved on treatment with a PPI, but the improvements were most pronounced in the dimensions depicting anxiety, depressed mood, and self-control. In a typical family practice setting (24), GERD patients treated with an H2-receptor antagonist had significant improvement in their symptoms as well as in their health-related quality of life as reflected on the physical functioning, bodily pain, and vitality scales of the SF-36 compared to those treated with placebo. These studies, like ours, demonstrate that HRQL is decreased in GERD patients. Our study is not without limitations. First, this study was conducted in a Veterans Affairs hospital and this might limit its generalizability. The VA population is not representative of the US population in terms of gender, ethnicity, or socioeconomic status. We compared the results of the SF-36 scores to those of an age- and sex-adjusted normal group. Although the difference in HRQL could have been explained by differences in comorbidities in our population, we have shown that frequent and severe GERD symptoms correlated with lower SF-36 scores, thus significantly impacting HRQL. In addition, the HRQL of patients with BE
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was comparable to that of patients with GERD. The lack of significant difference between the two groups could perhaps be explained by the fact that our GERD patients represented a referral group with refractory symptoms or worse symptoms as judged by their primary care physicians. In fact, in this cohort of patients, there was no difference in the BE patients and the GERD patients in terms of esophagitis and the presence of esophageal strictures and ulcers. This substantiates our findings of no difference in HRQL between the two groups. In addition, there was no difference in the reported duration of disease between patients with BE and GERD patients suggesting that symptoms were chronic in our GERD group. Patients with BE were less likely to report severe acid regurgitation symptoms than patients with GERD. This observation is consistent with the finding that patients with Barrett’s esophagus have significantly reduced esophageal acid sensitivity and have an impaired ability to recognize acid reflux (25). The finding that patients with BE were less likely to have nocturnal symptoms is inconsistent with the finding of others (8) and could be explained by the lack of esophageal sensitivity in these patients. In summary, we have shown that patients with BE have an impairment in HRQL that was similar to that of GERD patients. However, it is evident that both groups have considerable compromise in their HRQL compared to an agematched control group. The impairment in HRQL can be explained, at least in part, by the presence of GERD and its related esophageal complications, and by other comorbid illnesses. In our study, the frequency and severity of acid regurgitation impacted directly on patients’ sense of wellbeing, social functioning, and general health. These findings are similar to those of other investigations. Although ours was an observational study, other studies have shown that therapy for GERD had a significant positive impact on HRQL. Future efficacy studies of therapies for GERD should routinely assess patient-centered outcomes in addition to physiological parameters to demonstrate their impact on HRQL.
ACKNOWLEDGMENT We are indebted to the nursing staff of the Durham VAMC GI clinic and the GI fellows who facilitated enrollment of the patients in this study. We thank Jerry Schoendorf for his assistance with graphical design. Dr. Eloubeidi was supported by a VA Health Services Research Training grant, and Dr. Provenzale is supported by the VA Health Services Research Career Development Program. Reprint requests and correspondence: Mohamad A. Eloubeidi, M.D., M.H.S., Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, 406 Lyons-Harrison Research Building, 701 19th Street South, Birmingham, AL 35294. Received Aug. 27, 1999; accepted Feb. 14, 2000.
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REFERENCES 1. The Gallup Organization I. A Gallup survey of heartburn across America. Princeton, NJ. The gallop Organization 1988. 2. Nebel OT, Fornes MF, Castell DO, et al. Symptomatic gastroesophageal reflux: Incidence and precipitating factors. Dig Dis Sci 1976;21:953– 6. 3. Locke GR, Talley NJ, Fett SL, et al. Prevalence and clinical spectrum of gastroesophageal reflux: A population-based study in Olmsted County, Minnesota. Gastroenterology 1997; 112:1448 –56. 4. Spechler SJ, Goyal RK. Barrett’s esophagus. N Engl J Med 1986;315:362–71. 5. McDougall NI, Johnston BT, Kee F, et al. Natural history of reflux oesophagitis: A 10-year follow up of its effect on patient symptomatology and quality of life. Gut 1996;38:481– 6. 6. Dimenas E. Methodological aspects of evaluation of quality of life in upper gastrointestinal diseases. Scand J Gastroenterol 1993;199:18 –21. 7. Eloubeidi MA, Uslick B, Provenzale D. Health related quality of life in patients with Barrett’s esophagus. Gastroenterology 1998;112:A14. 8. Eisen GM, Sandler RS, Murray S, et al. The relationship between gastroesophageal reflux disease and its complications with Barrett’s esophagus. Am J Gastroenterol 1997;92:27–31. 9. Stewart AL, Greenfield S, Hays RD, et al. Functional status and well-being of patients with chronic conditions. Results from the Medical Outcomes Study. JAMA 1989;262:907–13. 10. Stewart AL, Hays RD, Ware JE Jr., et al. The MOS short-form general health survey. Reliability and validity in a patient population. Med Care 1988;26:724 –35. 11. Kurtin PS, Davies AR, Meyer KB, et al. Patient-based measures in outpatient dialysis. Early experiences in developing an outcomes assessment program. Med Care 1992;30:136S– 149S. 12. Nerenz DR, Repasky DP, Whitehouse FW, et al. Ongoing assessment of health status in patients with diabetes mellitus. Med Care 1992;30:MS112–124. 13. Weinberger M, Samsa GP, Hanlon JT, et al. An evaluation of a brief health status measure in elderly veterans. J Am Geriatr Soc 1991;39:691– 4. 14. Locke GR, Talley NJ, Weaver AL, et al. A new questionnaire for gastroesophageal reflux disease. Mayo Clin Proc 1994;69: 539 – 47. 15. Attanasio V, Andrasik F, Blanchard EB, et al. Psychometric properties of the SUNYA revision of the psychosomatic symptom checklist. J Behav Med 1984;7:247–58. 16. SF-36 Health Survey Manual & Interpretation Guide Ware, J. E. SF-36 Health Survey Manual & Interpretation Guide. 1993. 17. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chron Dis 1987;40:373– 83. 18. Revicki DA, Wood M, Maton PN, et al. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med 1998;104:252– 8. 19. Chal KL, Stacey JH, Sacks GE, et al. The effect of ranitidine on symptom relief and quality of life of patients with gastrooesophageal reflux disease. Br J Clin Pract 1995;49:73–7. 20. Dimenas E, Glise H, Hallerback B, et al. Quality of life in patients with upper gastrointestinal symptoms. An improved evaluation of treatment regimens? Scand J Gastroenterol 1993; 28:681–7. 21. McDougall NI, Johnston BT, Kee F, et al. The effect of healing esophagitis on patient quality of life. Gut 1994;35:S13 (abstract). 22. Watson RG, Tham TC, Johnston BT, et al. Double blind
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cross-over placebo controlled study of omeprazole in the treatment of patients with reflux symptoms and physiological levels of acid reflux—the “sensitive oesophagus”. Gut 1997;40: 587–90. 23. Havelund T, Lind T, Wilkund I, et al. Quality of life in patients with heartburn but without esophagitis: Effects of treatment with omeprazole. Am J Gastroenterol 1999;94:1782–9.
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24. Rush DR, Stelmach WJ, Young TL, et al. Clinical effectiveness and quality of life with ranitidine vs placebo in gastroesophageal reflux disease patients: A clinical experience network (CEN) study. J Fam Pract 1995;41:126 –36. 25. Johnson DA, Winters C, Spurling TJ, et al. Esophageal acid sensitivity in Barrett’s esophagus. J Clin Gastroenterol 1987; 9:23–7.
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ORIGINAL CONTRIBUTIONS
Health-Related Quality of Life and Severity of Symptoms in Patients With Barrett’s Esophagus and Gastroesophageal Reflux Disease Patients Without Barrett’s Esophagus Mohamad A. Eloubeidi, M.D., M.H.S., and Dawn Provenzale, M.D., M.S. Institute for Clinical and Epidemiological Research, Veterans Affairs Medical Center, and the Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
OBJECTIVES: The aims of this study were: 1) to compare the health-related quality of life (HRQL) of patients with Barrett’s esophagus (BE) to that of patients with GERD who did not have BE;2) to compare HRQL of gastroesophageal reflux disease (GERD) patients to that of normative data for the US general population; and 3) to examine the impact of GERD symptom frequency and severity on HRQL. METHODS: The SF-36 and a validated GERD questionnaire were administered to 107 patients with biopsy-proven BE and to 104 patients with GERD but no BE by endoscopy. Frequent symptoms were defined as symptoms that occurred at least once weekly. Severity of symptoms was rated on a scale from 1 to 4 (mild to very severe). RESULTS: In all, 85% of the GERD patients and 82% of BE patients completed the questionnaires. There was no difference in the scores of the eight subscales of the SF-36 between BE patients and those with GERD but without BE (p ⬎ 0.05). However, both groups scored below average on all subscales of the SF-36 compared to published US norms for an age- and gender-matched group. Using multivariable linear regression, the social functioning subscale of the SF-36 correlated with the presence of heartburn or acid regurgitation, severity of acid regurgitation, frequency of heartburn, frequency of acid regurgitation, and number of comorbidities. Similarly, the physical functioning subscale correlated with age, frequency of heartburn, and number of comorbidities. The bodily pain subscale correlated with the frequency of heartburn and number of comorbidities. The bodily pain subscale correlated with the frequency of heartburn and the severity of dysphagia, whereas the role emotional subscale correlated with the frequency of heartburn and the presence of dysphagia. CONCLUSIONS: Although there were no differences in HRQL between BE and GERD patients, both groups scored below average on the subscales of the SF-36 compared to normal controls. GERD symptom frequency and severity were associated with bodily pain and with impaired social, emotional, and physical functioning, suggesting a profound
impact on daily living. (Am J Gastroenterol 2000;95: 1881–1887. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION Heartburn is a prevalent symptom experienced monthly by 44%, weekly by 15–20%, and daily, by 7% of the US population (1–3). Heartburn and acid regurgitation are associated with chest pain, dysphagia, dyspepsia, globus sensation, and hoarseness, symptoms that might have a profound impact on health-related quality of life (HRQL). Barrett’s esophagus (BE), intestinal metaplasia of the lower esophagus, is associated with gastroesophageal reflux disease (GERD) and with an increased risk for the development of esophageal adenocarcinoma (4). Several studies have shown that GERD has a profound effect on HRQL (5, 6). In one study, patients with GERD had a lower quality of life compared to patients with duodenal ulcers, hypertension, mild congestive heart failure, angina, and menopause (6). Our pilot study using the SF-36 showed that patients with BE have a diminished HRQL compared to either patients in the general medical clinic, or to the general population. Interrupted daily activity because of heartburn correlated with the role physical and role emotional subscales of the SF-36 (7). Although BE may be associated with severe GERD (8), there are currently no studies that compare HRQL of patients with BE to that of GERD patients without BE. Therefore, the aims of this observational study were 1) to compare HRQL of patients with BE and patients with GERD who do not have BE, 2) to compare HRQL of GERD patients to that of normative data for the US general population, and 3) to examine the impact of GERD symptom severity and frequency on HRQL in these patients.
MATERIALS AND METHODS Study Measures There are currently two types of HRQL instruments: the generic, and the disease-specific. The generic instruments detect the effects of several parameters on health status (e.g.,
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Table 1. The Eight Subscales or Domains of the MOS SF-36* Subscale Physical function Bodily pain Role limitation-physical Vitality General health Social function Role limitationemotional Mental health
Definition Extent to which health limits everyday physical activity Extent of bodily pain Extent to which physical problems interfere with usual daily activities such as work, housework, or school Ratings of energy level Ratings of current health in general Extent to which health interferes with social activities Extent to which emotional problems interfere with usual daily activities such as work, housework, or school Emotional well-being, including depression, anxiety, and positive well-being.
*MOS ⫽ Medical Outcomes Study; SF-36 ⫽ short form-36.
physical, social, emotional and psychological function). They allow comparisons of health status between several chronic disorders. The SF-36 (9) is an example of a generic health status measure. The SF-36 is a 36-item questionnaire that measures three major health attributes: 1) health status; 2) well-being (i.e., mental health, energy and fatigue, pain); and 3) an overall evaluation of health. Validated as part of the Medical Outcomes Study (MOS) (10), it has been subsequently validated in multiple populations including dialysis patients, diabetics, and elderly veterans (11–13). The SF-36 contains 36 questions on aspects of both physical and mental health. The scores for each question are used to calculate a score between 0 and 100 for each of the eight subscales. Higher scores reflect better quality of life. The eight subscales of the SF-36 are shown in Table 1. Although generic measures can assess quality of life of individuals with a variety of disorders, disease-specific measures focus on the aspects of HRQL that are specific to a given patient group. Therefore, they may be more sensitive or responsive to changes associated with interventions or to changes with time. The gastroesophageal reflux questionnaire (GERQ) described in this study (14) is an example of a disease-specific health status measure. Developed and validated as a population-based measure of GERD (14), the GERQ is a self-report instrument consisting of approximately 80 questions and a psychosomatic symptom checklist (PSC), a measure of somatization (15). The first 32 questions assess symptoms of heartburn, acid regurgitation, chest pain, and dysphagia. The remaining questions examine extraesophageal manifestations of GERD and associated disorders, clinic visits, medication use, and family history of GERD. Symptom frequency is measured on the following scale: 1 ⫽ none in the past year; 2 ⫽ less than once a month; 3 ⫽ about once a month; 4 ⫽ about once a week; 5 ⫽ several times a week; and 6 ⫽ daily. Symptoms occurring once a week or more are defined as frequent. Symptom severity is assessed on a 4-point scale as follows: mild (can be ignored), moderate (cannot be ignored but does not affect lifestyle), severe (affects lifestyle), and very severe (markedly affects lifestyle). Finally, the number of comorbidities were recorded and scored to derive the Charlson comorbidity index (19). The Charlson index is a measure of the number of associated comorbidities that predicts mortality
risk at one year. Higher scores reflect an increased mortality risk at one year. Summary data on HRQL scores for controls were obtained from the results of the Medical Outcomes Study (16). Patient Selection The SF-36 and the GERQ were distributed to patients with biopsy-proven BE and to consecutive patients with GERD. The questionnaires were self-administered. BE was diagnosed if EGD biopsies revealed specialized intestinal metaplasia in a columnar lined segment of esophagus (of any length). All esophageal biopsies were stained with hematoxylin and eosin stains. Only patients with macroscopic evidence of columnar lined esophagus were biopsied at endoscopy. Short-segment BE was defined as ⬍2 cm of columnar lined esophagus. Patients with GERD who had no evidence of BE on endoscopy were included and constituted the GERD group. Patients with GERD who had a history of gastric surgery and fundoplication were excluded. In addition, we excluded patients with GERD who had not undergone endoscopy. Patient charts were reviewed, and the number of comorbidities were abstracted and recorded. The study was approved by the institutional review board and subcommittee on Human Studies of the Durham Veterans Affairs Medical Center (DVAMC). All subjects gave informed written consent before their enrollment in the study. A total of 107 patients with BE esophagus and 104 patients with GERD were enrolled. Statistical Analysis To demonstrate a clinically significant difference in the physical functioning subscale of the SF-36 (10-point difference), we estimated that 86 patients per group would be required (80% power, ␣ ⫽ 0.05). With our total of 176 patients (those who actually returned the questionnaires), the study had sufficient power to detect a 10-point difference in the following subscales: vitality, social functioning, mental health, and general health (16). Clinical and demographic characteristics of patients with BE and GERD patients without BE were examined. Categorical variables were compared with either the 2 or Fisher’s exact test. Continuous variables were compared using the Wilcoxon rank sum test or the Student’s t test. Linear
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Table 2. Baseline Characteristics of Patients With BE and in GERD Patients Without BE Characteristic
BE (N ⫽ 88)
GERD (N ⫽ 88)
Median age (IQR)* Race (% white)† Gender (% male)‡ Ever smoked (%)† Alcohol use (%)† Coffee use (%)† PPI use (%)† Charlson Index§ PSC scores§
64 (50–69) 88 98 65 19 51 68 0.98 ⫾ 1.37 42.10 ⫾ 24.20
57 (47–58) 81 92 68 31 49 57 0.72 ⫾ 1.15 41.80 ⫾ 22.82
All p values (except age) are ⬎0.05. * p ⫽ 0.04, Wilcoxon rank sum test. † 2 test. ‡ Fisher’s exact test. §Student’s t test. BE ⫽ Barrett’s esophagus; Charlson index ⫽ a measure of number of associated comorbidities; higher scores reflect an increased mortality risk at 1 yr; GERD ⫽ gastroesophageal reflux disease; IQR ⫽ interquartile range (25th to 75th percentile); PSC ⫽ psychosomatic symptom checklist, a measure of somatization.
regression analysis was performed to determine the association between the subscales of the SF-36 and the independent variables (age, race, duration of symptoms, severity of symptoms, frequency of symptoms, type of medical therapy, psychosomatic symptom checklist (PSC), and the presence of comorbid illnesses, as measured by the Charlson comorbidity index (17). The subscales of the SF-36 are reported as the median and the interquartile range, as the data were not normally distributed. All statistical analyses were performed using Statistical Analysis System (SAS, Cary, NC) software version 6.12. All p values are two-sided, with ␣ ⫽ 0.05 as the standard for significance.
RESULTS The questionnaires were administered to 107 BE patients and 104 patients with GERD. In all, 85% of the GERD
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patients and 82% of the BE patients returned the questionnaires. There was no difference between the responders and nonresponders in terms of age, gender, and the presence or absence of BE. However, nonresponders in general were more likely to be African-American (31% vs 15%, p ⬍ 0.02). There was no difference in terms of race in the BE patient group between the responders and nonresponders. GERD patients who responded were more likely to be white (82% vs 56%, p ⫽ 0.02). Of the BE patients, 71% had long-segment BE (⬎2 cm). Of the GERD patients, 44% had no evidence of erosive esophageal disease on endoscopy. The clinical and demographic characteristics of the groups are shown in Table 2. Although BE patients were older (median age 64 yr vs 57 yr, p ⫽ 0.04), there was no difference between the groups in terms of race, gender, the use of caffeine or alcohol, prior smoking status, number of comorbidities, PSC scores, or proton pump inhibitor use. Moreover, the two groups were similar in terms of endoscopic peptic complications of GERD: namely, esophagitis (44% vs 54%, p ⫽ 0.18), esophageal ulcers (17% vs 9%, p ⫽ 0.13), and strictures (9% vs 10%, p ⫽ 0.89). In addition, BE patients were more likely to have a hiatal hernia than those without BE (OR 2.48, 95% CI 1.28 – 4.79, 74% vs 53%, p ⫽ 0.0006). Figure 1 shows the duration of GERD symptoms in patients with BE and GERD patients. There was no difference in the duration of symptoms between the two groups, or the proportion of patients who had symptoms for ⬎10 yr (Table 3). Figure 2 shows that the proportion of patients reporting mild, moderate, severe, and very severe GERD symptoms was not different between the groups. However, BE patients were more likely to report less severe symptoms when symptoms were classified as moderate to severe versus mild (Table 3). In addition, patients with BE were less likely to report acid regurgitation at night compared to those with GERD (p ⫽ 0.04).
Figure 1. Duration of heartburn symptoms (yr) in patients with Barrett’s esophagus and in patients with gastroesophageal reflux disease.
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Table 3. Severity and Duration of Heartburn Symptoms in Patients With BE and in Patients With GERD
Duration (⬎10 yr) Frequency (at least once/wk) Severity* Night symptoms
BE (%)
GERD (%)
p Value
35 67 65 61
34 57 82 81
0.1 0.1 0.01 0.04
heartburn (p ⫽ 0.03) and the number of comorbidities (p ⫽ 0.004). The bodily pain subscale correlated with the frequency of heartburn (p ⫽ 0.002) and the severity of dysphagia (p ⫽ 0.002), whereas the role emotional subscale correlated with frequency of heartburn (p ⫽ 0.004) and the presence of dysphagia (p ⫽ 0.07). Both the general health and vitality subscales correlated with the frequency of heartburn and the number of comorbidities.
* Moderate to severe versus mild. All comparisons were performed with the 2 test. BE ⫽ Barrett’s esophagus; GERD ⫽ gastroesophageal reflux disease.
DISCUSSION There was no difference in the subscales of the SF-36 between BE patients and those with GERD but without BE (p ⬎ 0.05) (Table 4 and Fig. 3). However, both groups scored below average on all subscales of the SF-36 compared to published US norms for an age-matched group. The impact of GERD and its symptoms in both groups was most obvious on the physical functioning, role physical, bodily pain, and vitality scores of the SF-36, with scores at least ⱖ25 points lower than that of an age-matched population. Although we did not perform a formal statistical analysis between GERD and BE patients and the control group, a difference of 3–5 points has been considered to be clinically significant. A multivariable linear regression model was constructed to determine the effect of GERD symptoms in patients with GERD and in those with BE on HRQL. Adjusting for the psychosomatic index (PSC), the social functioning subscale correlated with the presence of heartburn or acid regurgitation (p ⫽ 0.03), the severity of acid regurgitation (p ⫽ 0.03), the frequency of heartburn (p ⫽ 0.003), the frequency of acid regurgitation (p ⫽ 0.02), and the number of comorbidities (p ⫽ 0.04). The physical functioning subscale correlated with age (p ⫽ 0.0009), the frequency of heartburn (p ⫽ 0.03), and the number of comorbidities (p ⫽ 0.002). The role physical subscale correlated with the frequency of
Health-related quality of life measurements are becoming increasingly important measures of patient-oriented outcomes. Although measurements of biochemical and physiological parameters are important, they might not necessarily capture the impact of an intervention on patient wellbeing. Measurements of HRQL may complement traditional outcome measures, as they assist physicians in understanding patient attitudes toward their illness. Ours is the first study to compare HRQL of patients with BE to that of GERD patients. This study showed that there was no difference in HRQL between patients with GERD and those with BE. Similar to the results of many other studies, our data suggest that patients with GERD experience diminished HRQL. Revicki et al. (18) compared the HRQL of GERD patients to normative data on HRQL for the US general population, to the HRQL of diabetics, the clinically depressed, and hypertensive patients from the Medical Outcomes Study. They also examined differences in HRQL between patients who did and did not respond to treatment for GERD. At baseline, the mean SF-36 scores for all subscales for GERD patients were significantly lower than those of the general US population and a healthy group. In addition, patients with GERD had lower mean SF-36 scores on the bodily pain, social functioning, and mental health scales compared with patients with hypertension. When
Figure 2. Severity of reflux symptoms in patients with Barrett’s esophagus and in patients with gastroesophageal reflux disease who reported any episodes in the last year.
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Table 4. Median SF-36 Scores and Interquartile Range (IQR) for GERD Patients, BE Patients, and Those for an Age and GenderMatched Group (Higher scores reflect better quality of life) Subscale
GERD, Median (IQR)
BE, Median (IQR)
Physical functioning Role-physical Bodily pain General health perceptions Vitality Social functioning Role-emotional Mental health
45 (30–65) 23 (0–50) 41 (22–52) 40 (20–62) 35 (20–50) 62.5 (25–87.5) 66.67 (0–100) 68 (48–80)
40 (17.5–65) 26 (0–37.5) 41 (31–62) 35 (20–60) 40 (20–55) 62.5 (37.5–87.5) 66.67 (0–100) 68 (52–84)
p Value
Controls, Median (IQR)
0.15 0.78 0.34 0.83 0.61 0.26 0.90 0.60
85 (60–95) 100 (50–100) 72 (51–84) 67 (50–82) 65 (45–80) 100 (62.5–100) 100 (66.7–100) 80 (64–92)
All comparisons between the two groups were carried out with the Wilcoxon rank sum test. BE ⫽ Barrett’s esophagus; GERD ⫽ gastroesophageal reflux disease.
comparing patients who were responsive to those who did not respond to GERD therapy, treatment responders reported better mean bodily pain, physical function, social function, and vitality scale scores compared with nonresponders. In addition, severity of symptoms as assessed by the increasing number of symptoms was associated with lower SF-36 scores. Chal et al. (19), in a similar study, demonstrated that GERD patients had impaired pain, vitality, mental health, and role limitation scores on the SF-36. To measure the impact of GERD and its treatment on HRQL, Dimenas et al. (20) used the Psychological General Well-being Index (PGWB) and two other disease-specific measures for gastrointestinal symptoms. In this study, symptomatic patients with evidence of endoscopic esophagitis had lower HRQL measured by the PGWB compared to patients with normal endoscopy findings. After 4 wk of treatment, however, GERD patients had significant improvement in both general well-being and symptom specific
Figure 3. Median scores for the MOS SF-36 (eight subscales) for controls, GERD patients, and BE patients. Abbreviations: BE ⫽ Barrett’s esophagus; BP ⫽ bodily pain; GERD ⫽ gastroesophageal reflux disease; GH ⫽ general health; MH ⫽ mental health; MOS SF-36 ⫽ Medical Outcomes Study, short form; PF ⫽ physical functioning; RE ⫽ role emotional; RP ⫽ role physical; SF ⫽ social functioning; VT ⫽ vitality. Higher scores are associated with a better quality of life.
scores. In another study (6), patients with GERD had impaired psychological well-being compared with patients with untreated hypertension, mild heart failure, or angina. Similarly, a study by Mcdougall et al. (5) showed that esophagitis was significantly associated with impaired quality of life. Esophagitis patients had significantly lower scores on general health and social functioning subscales of the SF-36 compared to the population of Northern Ireland. In addition, the same group showed that treatment of esophagitis with a proton pump inhibitor was associated with improvement of the bodily pain and vitality subscales of the SF-36 (21). Watson and colleagues (22), in a double-blind crossover, placebo-controlled trial, showed that GERD patients responding to a proton pump inhibitor had significantly better bodily pain and vitality scores on the SF-36 compared to the nonresponders. Recently, Havelund et al. (23) showed that patients with GERD but no esophagitis treated with a PPI had significant improvement in the PGWB index and the Gastrointestinal Symptom Rating Scale (GSRS) compared to placebo. All dimensions of the PGWB index improved on treatment with a PPI, but the improvements were most pronounced in the dimensions depicting anxiety, depressed mood, and self-control. In a typical family practice setting (24), GERD patients treated with an H2-receptor antagonist had significant improvement in their symptoms as well as in their health-related quality of life as reflected on the physical functioning, bodily pain, and vitality scales of the SF-36 compared to those treated with placebo. These studies, like ours, demonstrate that HRQL is decreased in GERD patients. Our study is not without limitations. First, this study was conducted in a Veterans Affairs hospital and this might limit its generalizability. The VA population is not representative of the US population in terms of gender, ethnicity, or socioeconomic status. We compared the results of the SF-36 scores to those of an age- and sex-adjusted normal group. Although the difference in HRQL could have been explained by differences in comorbidities in our population, we have shown that frequent and severe GERD symptoms correlated with lower SF-36 scores, thus significantly impacting HRQL. In addition, the HRQL of patients with BE
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was comparable to that of patients with GERD. The lack of significant difference between the two groups could perhaps be explained by the fact that our GERD patients represented a referral group with refractory symptoms or worse symptoms as judged by their primary care physicians. In fact, in this cohort of patients, there was no difference in the BE patients and the GERD patients in terms of esophagitis and the presence of esophageal strictures and ulcers. This substantiates our findings of no difference in HRQL between the two groups. In addition, there was no difference in the reported duration of disease between patients with BE and GERD patients suggesting that symptoms were chronic in our GERD group. Patients with BE were less likely to report severe acid regurgitation symptoms than patients with GERD. This observation is consistent with the finding that patients with Barrett’s esophagus have significantly reduced esophageal acid sensitivity and have an impaired ability to recognize acid reflux (25). The finding that patients with BE were less likely to have nocturnal symptoms is inconsistent with the finding of others (8) and could be explained by the lack of esophageal sensitivity in these patients. In summary, we have shown that patients with BE have an impairment in HRQL that was similar to that of GERD patients. However, it is evident that both groups have considerable compromise in their HRQL compared to an agematched control group. The impairment in HRQL can be explained, at least in part, by the presence of GERD and its related esophageal complications, and by other comorbid illnesses. In our study, the frequency and severity of acid regurgitation impacted directly on patients’ sense of wellbeing, social functioning, and general health. These findings are similar to those of other investigations. Although ours was an observational study, other studies have shown that therapy for GERD had a significant positive impact on HRQL. Future efficacy studies of therapies for GERD should routinely assess patient-centered outcomes in addition to physiological parameters to demonstrate their impact on HRQL.
ACKNOWLEDGMENT We are indebted to the nursing staff of the Durham VAMC GI clinic and the GI fellows who facilitated enrollment of the patients in this study. We thank Jerry Schoendorf for his assistance with graphical design. Dr. Eloubeidi was supported by a VA Health Services Research Training grant, and Dr. Provenzale is supported by the VA Health Services Research Career Development Program. Reprint requests and correspondence: Mohamad A. Eloubeidi, M.D., M.H.S., Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, 406 Lyons-Harrison Research Building, 701 19th Street South, Birmingham, AL 35294. Received Aug. 27, 1999; accepted Feb. 14, 2000.
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