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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

Aim : To examine the prevalence of functional dyspepsia in the general population, and to evaluate the natural history/clinical course of patients with functional dyspepsia.

Methods : Full-length published manuscripts during 1980–2002 were included if: (i) participants had uninvestigated or functional dyspepsia; (ii) dyspepsia was defined; (iii) for prevalence, population-based samples were evaluated; (iv) for prognosis, the total number of the inception cohort and the total number of individuals available at the end of follow-up were reported.

Results : Twenty-two studies (1976–2002) that examined the prevalence of dyspepsia fulfilled the inclusion and exclusion criteria; 17 studies examined more than 1000 participants, but only two studies provided information sufficient to calculate the prevalence of functional dyspepsia (11.5–14.7%). The prevalence of uninvestigated dyspepsia was in the range 10–40%. When the definition of dyspepsia was restricted to participants with upper abdominal pain, irrespective of the presence of heartburn or acid regurgitation, the prevalence rate estimate was 5–12%. Thirteen studies examined the clinical course of functional dyspepsia (seven retrospective and six prospective). Sample sizes were small (n = 35–209). A follow-up ascertainment of symptoms amongst individuals in the original cohorts was obtained in 92.5–98.2% of prospective studies and in 67.7–82.2% of retrospective studies. The follow-up duration was in the range 1.5–10 years for prospective studies and 5–27 years for retrospective studies; the median follow-up duration for all studies was approximately 5 years. A variable prognosis was reported. An outcome of symptom improvement or becoming asymptomatic was reported in at least one-half of patients in 10 of the 13 studies, and in at least two-thirds of patients in six of the 13 studies. Prognostic factors were inconsistent and, in general, poorly described.

Conclusions : Functional dyspepsia is prevalent world-wide, but the prognosis remains poorly defined. There is a need for population-based studies to examine the prevalence and clinical course of documented functional dyspepsia.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

Dyspepsia is a common complaint, but the definition of dyspepsia has evolved over the past 50 years.1–5 Despite consensus meetings that have proposed standardized definitions for dyspepsia, there remains controversy, particularly about the overlap between heartburn and upper abdominal pain or discomfort.1–4 Cultural differences have been identified in terms of what constitutes abdominal pain vs. discomfort, which also continue to confound the field.5 Other difficulties are created by the fact that dyspepsia is not a term usually understood by patients,6 and is not measurable as a self-reported item. Ascertaining the presence of dyspepsia requires the assessment of multiple symptoms that may be variably interpreted by the physician.

Dyspepsia, however it is defined, can have multiple causes, including, most frequently, gastro-oesophageal reflux disease, peptic ulcer or functional dyspepsia.4 Functional dyspepsia is a disorder characterized by the presence of chronic or recurrent symptoms of upper abdominal pain or discomfort in the absence of any known specific structural cause.4

Functional dyspepsia is generally a non-life-threatening disorder that is not associated with a need for surgery or a reduction in survival. The impact of functional dyspepsia can be partly measured in terms of its prevalence, natural history and clinical course. A previous systematic review reported the prevalence of uninvestigated dyspepsia up to 1997, but the prevalence of functional dyspepsia was not specifically examined and remains poorly defined.7 The prognosis of functional dyspepsia also remains relatively poorly described.4 In particular, the periodicity of symptoms and the rates of persistence of symptoms have not been well characterized, in part because the use of terminology has been relatively inconsistent in the literature. A previous systematic review by Janssen et al. suggested surprisingly diverse outcomes in studies up to 1997.8 Further studies have since been published, which may shed more light on the heterogeneity previously identified.

We have performed a systematic review of the literature to examine the prevalence of functional dyspepsia, and to evaluate the natural history and clinical course of patients with documented functional dyspepsia.

Literature search

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

For the prevalence studies, we performed searches of all English and non-English articles from 1966 to 2002 in MEDLINE, Current Contents and EMBASE, combining ‘dyspepsia’, ‘functional dyspepsia’ and ‘non-ulcer dyspepsia’ with ‘prevalence’ or ‘frequency’. For the clinical course studies, we employed similar searches using ‘natural history’, ‘clinical course’ or ‘prognosis’. We also reviewed information contained in two previously published systematic reviews.7, 8

Study selection criteria

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

The following inclusion and exclusion criteria were used. These criteria were modified from those used in the previous reviews. Only fully published manuscripts were considered. As it was assumed that there would be few studies that examined the prevalence of functional dyspepsia as a primary aim, we examined studies of uninvestigated dyspepsia for possible findings suggestive of functional dyspepsia.

The inclusion criteria for the prevalence studies were: (i) participants should have uninvestigated or functional dyspepsia; (ii) dyspepsia should be defined and include epigastric pain in the definition; and (iii) population-based samples should be evaluated. The exclusion criteria were: (i) no mention of sample size; (ii) sample size of less than 50; (iii) response rate not reported or is less than 30%; (iv) no mention of the underlying population; (v) no mention of the period during which dyspepsia was reported; and (vi) studies examining blood donors or health care screening clinics, as these may not be representative of the general population. The inclusion criteria for the natural history/clinical course studies were: (i) documented functional dyspepsia; (ii) dyspepsia should be defined; (iii) the total number of the inception cohort should be available; (iv) the total number of persons available at the end of follow-up should be reported; and (v) the study should be observational. The exclusion criteria were: (i) uninvestigated dyspepsia; (ii) therapy trial in which more than 50% of patients received a specific intervention; (iii) outcomes at the end of follow-up did not include dyspepsia; and (iv) cross-sectional studies with no follow-up.

Two investigators performed the searches and data abstraction. The data were presented in tabular and graphic format. The crude prevalence rates were the main outcome for the prevalence studies (Table 1). A priori, we decided to examine the effect on the prevalence of the definition of dyspepsia, geographical location of the study sample and the time during which the study was conducted. For the clinical course studies, the proportion of asymptomatic or improved individuals at the end of follow-up was the main outcome summarized. Drop-out rates were presented or calculated from the available data. To examine for publication bias, we constructed funnel plots in which the sample size in each study was plotted against the prevalence rates in the prevalence studies, or the proportion of individuals with no or improved symptoms by the end of follow-up in the clinical course studies.

Table 1.  Description of 22 studies examining the prevalence of uninvestigated dyspepsia that fulfilled the inclusion and exclusion criteria for this systematic review
ReferenceYearCountryPopulation studiedAge group (years)Sample sizeResponse rate (%)Method of data collectionPeriod studiedDescription of UASPrevalence of UAS (%)Prevalence w/o H/R (per 100)
  1. GERD, gastro-oesophageal reflux disease; H/R, heartburn/regurgitation; UAS, upper abdominal symptoms; UGI, upper gastrointestinal.

Hu321996Hong KongEthnic Chinese households in Hong Kong38 (mean)2640 62Phone interview with structured questionnaires1 yearRecurrent or chronic pain or discomfort centred in the upper abdomen for > 3 months18.4NA
Westbrook & Talley30NAAustraliaRandom population sample from one county> 182300 69Telephone3 monthsEpigastric pain and bloating, early satiety, and heartburn and regurgitation32.511.4
Boekema et al.27NANetherlandsOne city of 324 000> 18 500 85Phone interview with structured questionnaires1 yearUpper abdominal pain or discomfort > 6 times/past year, and 3 out of 6 UGI symptoms14 (same for men and women)NA
Reshetnikov et al.28NAWestern SiberiaFour schools14–17 449100Interview with structured questionnaire1 yearUpper abdominal pain or discomfort > 6 times/past year14 (11.5 in boys, 17 in girls)NA
Ho et al.33NASingaporeOne town≥ 21 953 74Interview with structured questionnaire1 yearUpper abdominal pain, nausea, vomiting, or both > 1/month7.9 (8.1 for Chinese, 7.3 for Malays and 7.5 for Indians)NA
Agreus et al.341995SwedenOne municipality of 22 58021–861422 80Postal questionnaire1 yearAbdominal pain or ache more than twice in the past 3 months or more than 6 times per year not located below the navel14.5NA
Moayyedi et al.31NAUK2 counties: with a population of 1 200 00040–499262 91Interview with a structured questionnaire6 monthsEpigastric pain and/or other symptoms (nausea, vomiting, and belching as associated with GERD)38 (44% in H. pylori- positive vs. 36% in H.pylori negative)773/8349 (9%)
Haque et al.26NANew ZealandOne region of 212 382> 18 95282Postal questionnaire1 yearPersistent or recurrent symptoms of abdominal pain or discomfort with a frequency > 1/month or a severity > mild34.215 (44% of 34.2)
Caballero- Palesencia et al.25NASpainOne city of 32 16420–84 30088Interview with structured questionnaire6 monthsUpper abdominal pain or daily heartburn/ regurgitation for 1 week23.9 (51% ulcer- like, 60% reflux- like, 30% dysmotility, 14% unspecified)9.5 (39.7% of 23.9)
Talley et al.23NAAustraliaOne district of 27 39320–89113564Postal questionnaire1 yearUpper abdominal pain, recurrent or chronic12 (83% ulcer, dysmotility or reflux, 17% unspecified)7.6 (63.2% of 12)
Locke et al.91996USACounty of 100 00025–74207373Postal questionnaire1 yearPain or ache mainly in upper abdomen10.63.9
Kay et al.101990DenmarkCounty of 330 00070111972Interview with structured questionnaire1 yearEpigastric painMale 8 Female 12NA
Agreus et al.11–131988SwedenMunicipality of 21 33820–79129090Postal questionnaire3 monthsTroublesome upper abdominal pain or discomfort32.2 in the 1995 study Male 16.7 Female 29.913.8 in 1995 8.9
Kay & Jorgensen141982–1984DenmarkCounty of 336 53330–60458179Postal questionnaire1 yearEpigastric painMale 16.2 {frequent 8.4} Female 20.8 {frequent 11.7}Male 4.5 Female 7.0
Talley et al.22NAUSAOne county of 100 00020–64215377Postal questionnaire1 yearUpper abdominal pain, nausea, or both > 6 times in past year21.8 Male 19.6 Female 23.9 (49% ulcer, 23% dysmotility, 35% reflux)14.2 (65% of 21.8)
Drossman et al.241993USA400 000 households in 48 states20–64825066Postal questionnaire3 monthsUpper abdominal pain, excluding structural lesionsNot reported2.7
Talley et al.151988– 1991USACounty of 100 00030–64102182Postal questionnaire1 yearUpper abdominal pain25.8 {frequent 15.7} Male 26.9 Female 24.79.8 (38% of 25.8)
Bernersen et al.16, 171987NorwayTown of 350020–69202789Postal questionnaireLifetimeUpper abdominal pain for at least 2 weeks27.512.1
Jones et al.181989England & Scotland7 primary care communities (56 500)20–69993675Postal questionnaire6 monthsUpper abdominal symptoms for more than a few days4110.7 (26% of 41)
Jones & Lydeard191988England2 primary care communities (patients)> 20269777Postal questionnaire6 monthsUpper abdominal symptoms for more than a few days3812.4 (32.6% of 38)
Johnsen et al.201979– 1980NorwayMunicipality20–5421 32967Interview with structured questionnaireLifetimeOften had gnawing epigastric painMale 12.6 Female 12.3NA
Hollnagel et al.211976–1977DenmarkRegion40119888Self-administered questionnaireLifetime & 1 yearUpper gastric painMale 25 Female 31NA

Prevalence of dyspepsia

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

We found 130 relevant titles for prevalence and functional dyspepsia, and an additional 303 titles for prevalence and non-ulcer dyspepsia. Twenty-two studies examining the prevalence of dyspepsia fulfilled the inclusion and exclusion criteria. We included the 10 studies previously analysed by Heading,7 i.e. refs. 9–21, added two more that excluded some participants with other medical conditions, and hence did not satisfy one of Heading's inclusion criteria,22, 24 and identified 10 more recent prevalence studies.23, 25–28, 30–34 Similar to Heading's review,7 we excluded studies of blood donors29, 35 and health care screening clinics.36 Studies that described the same population were included only once.14, 37

The prevalence studies examined uninvestigated as well as functional dyspepsia. The detailed description of these studies is shown in Table 1. Twelve of the 22 studies employed postal questionnaires, six used a personal interview with structured questionnaires, three used a phone questionnaire and one used self-administered questionnaires. In general, these studies had relatively large sample sizes, with 16 of the 22 studies examining more than 1000 participants. The studies were conducted over a wide time period between 1976 and 2002. Most studies examined equivalent proportions of men and women. Most studies (19 of 22) examined a wide range of ages (18–84 years), one study examined only adolescents (14–17 years), one study examined those between 40 and 49 years, and one the elderly (≥ 65 years). The prevalence of dyspepsia was reported from 13 countries in four continents (Asia, North America, Europe, Oceania). The reported prevalence rates ranged widely among the 22 studies (Table 1). A funnel plot (Figure 1a) was not indicative of publication bias.

image

Figure 1. (a) Funnel plot depicting the distribution of estimates of the prevalence of dyspepsia amongst 22 studies according to the sample size. The plot is not suggestive of publication bias, as there is an even spread of prevalence estimates over a range of sample sizes. (b) Funnel plot depicting the distribution of estimates of the proportion of patients with functional dyspepsia who either improved or were completely relieved of symptoms by the end of the follow-up period in 13 studies, according to the sample size. The plot is not suggestive of publication bias, as there is an even spread over a range of sample sizes of the estimates of the proportions of patients who were either improved or relieved.

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Only two of the 22 studies provided information sufficient to calculate the prevalence of functional dyspepsia. One was population-based and was conducted in a town in Norway;16, 17 2027 potential participants were contacted and an 89% response rate was achieved. The lifetime prevalence of uninvestigated dyspepsia in this study was 12.1 per 100 (and 27.1 per 100 if heartburn or regurgitation was included in the definition). The majority of participants with dyspepsia (88%) agreed to undergo endoscopy. The overall prevalence of functional dyspepsia was calculated to be 14.7%, which was equivalent to 54% of dyspeptics who underwent upper endoscopy. In the second study that examined the prevalence of functional dyspepsia,19 only 20% of participants with dyspepsia had an upper endoscopy performed; 93% of these were reported as having non-ulcer dyspepsia, giving a population-based prevalence of 11.5%.

The pooling of the prevalence rates of dyspepsia reported in the 19 studies was deemed to be inappropriate due to the significant heterogeneity in the definition as well as the results of these studies. We were also unable to conduct a meaningful multivariate analysis to examine the independent role of age, gender or time of publication, given the relatively small number of studies with this information.

We evaluated the role of the definition of dyspepsia in explaining the variability in the published prevalence rates. The overlap between upper abdominal pain and reflux symptoms (heartburn, regurgitation) was striking in all studies that examined these symptoms. The prevalence of uninvestigated dyspepsia was in the range 10–40% using a more inclusive definition of dyspepsia that incorporated heartburn or regurgitation even in the absence of upper abdominal or epigastric pain. Twelve studies contained sufficient information to calculate the prevalence of dyspepsia according to these two definitions, i.e. with and without heartburn or regurgitation (Figure 2). The author of one additional study provided us with information to calculate these figures.31 When the definition of dyspepsia was restricted to participants with upper abdominal pain, irrespective of the presence of heartburn or acid regurgitation, a lower but narrower range of prevalence rate estimates was obtained (5–12%).

image

Figure 2. The age-adjusted prevalence rates of uninvestigated dyspepsia reported from population-based studies that used two different definitions for dyspepsia. GI, gastrointestinal.

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The period during which symptoms were reported for the definition of dyspepsia (period prevalence) ranged from 3 months to a lifetime. There were no significant correlations between the prevalence and the time period during which the study was conducted (Figure 3), or the geographical region (data not shown). There were no population-based data on the prevalence of dyspepsia in African-Americans or Hispanics in the USA.

image

Figure 3. Correlation between the year of publication and the prevalence of dyspepsia; Pearson correlation coefficient, − 0.22; P = 0.39.

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Clinical course of functional dyspepsia

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

For ‘functional dyspepsia’ and each of ‘clinical history’ and ‘natural history’, we found nine and seven relevant titles, respectively. For ‘non-ulcer dyspepsia’ and ‘clinical course’, we found 19 titles, and seven additional titles for ‘natural history’. Thirteen studies examined fulfilled the inclusion and exclusion criteria for the natural history clinical course of functional dyspepsia.38–50 Two studies examined different questions in the same population,43, 44 and therefore were included once in Table 2. We identified two more studies than the Janssen review,8 published after 1997,49, 50 but excluded three other studies that were included in that review: one for including cases of gastro-oesophageal reflux disease only51 and one for not defining dyspepsia.52

Table 2.  Description of 13 studies that examined the clinical course of patients with functional dyspepsia
ReferenceInclusion criteriaExclusion criterianDuration of follow-upDrop-outsM/FAge (years)OutcomeType of study
  1. EGD, esophagogastroduodenoscopy; F, female; Hp, Helicobacter pylori; IBS, irritable bowel syndrome; M, male; NSAID, non-steroidal anti-inflammatory drug; PUD, peptic ulcer disease.

Brummer & Häkkinen38 (Finland)Dyspepsia (lowered gastric and duodenal pain threshold and an increased gastric and duodenal irritability)Organic lesions in the stomach, duodenum or gall-bladder at X-ray examination1025–6.5 years8 (7.8%) (reasons unknown)1/1.6Mean 4529% improved 3% unchanged 37% symptom free 26% PUD or gallstonesRetrospective
Krag39 (Denmark)Intermittent ‘cardialgia’ of a few weeks' duration alternating; hunger pain relieved by food; and no peptic ulcer on contrast imagingOther diseases that might explain symptoms; gastric bleeding17418–27 years17 (9.6%) (Not traced or had emigrated)3.8/110–7948% favourable course = symptom free + improved 40% developed ulcerUnclear
Gregory et al.40 (UK)Symptoms of peptic ulcer with normal barium-meal examination 1026 years17 (16%) (6 died; 11 not traced)1.6/120–7066% improvedRetrospective
Bonnevie41 (Denmark)Upper abdominal pain and normal barium meal and cholecystogramChange in diagnosis1095 yearsUnclearNANA32% symptom freeProspective
Thommesen & Funch-Jensen42 (Denmark)Upper abdominal pain and normal X-ray findings  735 years8 (11%) (1 died, 7 refused)1/1.225–5564% improved 7% worsened 27% remained the sameRetrospective
Talley et al.43, 44 (Australia)Pain, discomfort, or nausea in the upper abdomen, intermittent or continuous, present for at least 1 month, not precipitated by exertion and not relieved within 5 min by rest. No structural cause for the symptoms after clinical evaluationJaundice, dysphagia or bleeding, physical or mental disease, gastric surgery, peptic ulcer within 6 months before the study, patients unable to speak English and patients without telephone access11317 months2 (1.8%) (reasons unknown)1/0.67Median 48 (16–85)16% symptom free; 14% improvedProspective
Stene-Larsen et al.45 (Norway)Dyspepsia (epigastric pain and discomfort, nausea, and heartburn) 9024–60 months30 (33.3%) (14 refused; 16 moved)1.7/1Mean 41 (23–68)12% improved 82% same or improvedRetrospective
Sloth & Jorgensen46 (Denmark)Upper abdominal pain constantly for at least 1 year or periodically for at least 2 years. Normal findings at upper endoscopy, barium meal and cholecystography or ultrasonography. Normal serum levels of amylase, liver enzymes, haemoglobin, folic acid, vitamin B12 and calciumHistory of peptic ulcer or pancreatitis; previous GI or gall-bladder surgery except for appendicitis 404.6–7.1 years3 (7.5%) (moved; refused)1/1.4Mean 3551% symptom free or improvedProspective
Barnes et al.47 (UK)Any of the following symptoms for more than 2 weeks: upper abdominal pain or discomfort related to food, retrosternal or upper abdominal pain related to posture, pain relieved by alkalis or vomiting, pain experienced at nightAbnormal endoscopy and/or cholecystography1257–14 years12 (9.6%) (no reasons given)1/1Mean 5759% improvedRetrospective
Lindell et al.48 (Sweden)Dyspepsia (epigastric pain or discomfort with or without nausea, vomiting, regurgitation, early satiety)Patients with isolated reflux symptoms, patients with abnormal endoscopy, patients with organic disease that could be related within 12 months after referral27110 years46 (17%) (22 moved; 6 psychiatric illness; 20 refused)1/1.1Median 5136% symptom free, ulcer in 3 (expected 4)Retrospective
Hyams et al.49 (USA)Dyspepsia (abdominal pain, discomfort and/or nausea) for at least 1 monthOrganic disease on endoscopy 350.5–10 years1 (2.8%) lost to follow-up1/2.2Mean 12, minimum 570% symptom free or improved, 3% worse, rest no changeProspective
Hsu et al.50 (Taiwan)Dyspepsia (pain or discomfort centred in the upper abdomen) for at least 1 month, normal endoscopyHistory of PUD, NSAID or antibiotic use within 1 month before EGD, serious medical illness, history of Hp therapy, associated IBS2092 years01/1.2Mean for Hp– 53, Hp+ 45Symptom-free: 49% of Hp+ and 58% of Hp–, ulcer in 16 (7.7%)Prospective

There were seven retrospective and six prospective studies that examined the clinical course of functional dyspepsia. All studies described the source of the participants, defined dyspepsia and described the inclusion and exclusion (if any) criteria. Two studies examined patients seen in the primary care setting40, 47 and the rest examined patients seen in referral settings. None examined population-based samples. All studies were restricted to patients with functional dyspepsia. One study was conducted exclusively in children older than 5 years,49 whilst the rest of the studies were conducted in adults. The sample sizes ranged from 35 to 209, and eight studies had a sample size greater than 100 participants. Prospective studies were generally smaller than retrospective ones. A follow-up ascertainment of symptoms amongst individuals in the original cohorts was obtained in 92.5–98.2% of prospective studies and 67.7–82.2% of retrospective studies. All but two studies41, 45 had follow-up ascertainment of greater than 80%. The follow-up duration was in the range 1.5–10 years for prospective studies and 5–27 years for retrospective studies; the median follow-up duration for all studies was approximately 5 years.

A variable prognosis was reported in these studies. In general, a significant number of patients with functional dyspepsia were reported to either improve or become asymptomatic in one to several years. An outcome of symptom improvement or becoming asymptomatic was reported in at least one-half of patients in 10 of the 13 studies, and in at least two-thirds of patients in six of the 13 studies. Improvement or symptom-free status was slightly higher in retrospective (48–80%) than prospective (30–70%) studies. A funnel plot (Figure 2b) was not indicative of publication bias. The outcome of development of peptic ulcer was reported in four studies, and was high (40%) in an older study39 and low (1.1%) in a more recent study.48 In one study by Talley et al., the risk factors for the persistence of symptoms amongst 115 patients with functional dyspepsia who were followed for a median of 48 months were any gastro-oesophageal reflux disease treatment during follow-up, a past history of peptic ulcer or the use of aspirin before the inception point for follow-up.43 Krag found that patients who had their symptoms for longer than 2 years had a lower chance of remission irrespective of gender.39 Moreover, in the study by Bonnevie, a longer clinical history was associated with a worse clinical outcome.41 Patients with a lower education, and those scoring higher on a psychological vulnerability questionnaire, had a poorer prognosis in the study by Sloth and Jorgensen.46 Lastly, one recent study from Taiwan reported that patients with functional dyspepsia and Helicobacter pylori infection were less likely to be symptom free at the end of a 2-year follow-up than patients without H. pylori (49% vs. 58%).50

All studies measured dyspepsia symptoms as one of their outcomes. However, dyspepsia was not uniformly measured between the studies, or at different points within the same study. It was unclear whether patients developed new symptoms (such as heartburn, regurgitation or nausea) in addition to the symptoms recorded and reported at baseline. H. pylori status was not ascertained in 10 studies. In general, therapy was either not measured or adjusted for.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

The range of prevalence reported for dyspepsia is wide and has focused on uninvestigated rather than functional dyspepsia. We identified 21 prevalence studies, two of which were population-based endoscopic investigations that provided data on the prevalence of functional dyspepsia, which was in the range 12–15%.16, 19 One of the studies found very few diagnoses at endoscopy apart from functional dyspepsia,19 whilst the other identified nearly 50% with another potential explanation for their symptoms on upper endoscopy.16 However, the former study only endoscoped one-fifth of the participants.19 Factors such as the prevalence of H. pylori may explain some of this variation. Recent studies have suggested that the prevalence of oesophagitis, at least in some countries, may be much higher than has been reported previously. For example, in a study in primary care from Canada, prompt endoscopy was performed within 10 days of referral in 1040 out-patients who had uninvestigated dyspepsia; 43% had endoscopic oesophagitis, which was much more common than peptic ulcer (only found in 5%).53 The population-based study from Norway was performed over a decade ago16 and the epidemiology of the underlying causes of dyspepsia may be changing, with a rapidly decreasing prevalence of H. pylori in some parts of the world, and possibly a concurrent increase in the incidence of oesophagitis.54, 55 Hence, there remains the need for current population-based data on the prevalence of true functional dyspepsia; extrapolating from previous data in uninvestigated dyspepsia may be sub-optimal.

It is of interest to evaluate carefully whether the current Rome definition, which excludes predominant reflux symptoms from the definition of dyspepsia,4 influences the prevalence rates. This systematic review showed that, when a definition of dyspepsia was limited to upper abdominal symptoms, a lower but arguably more robust prevalence rate was calculated. Retrospective studies are potentially influenced by recall bias. On the other hand, the prevalence of dyspepsia did not appear to be altered by the time period evaluated; this may reflect the fact that individuals asked to consider back further than 3 months may not be able to do so adequately, or to telescope the last 3 months' experience into their annual or lifetime response. It was striking that the prevalence of dyspepsia was relatively high across all nations where this disorder was assessed.

A full understanding of the clinical course of functional dyspepsia is needed to plan interventions, but this remains remarkably poorly understood. In this systematic review, there were 13 studies identified that evaluated the natural history of functional dyspepsia, but the results were very inconsistent. All studies suggested that a proportion of patients will improve or go into symptom remission, but the rates of symptom disappearance varied widely. A number of factors may influence these rates in addition to natural fluctuations of the disorder, including medical therapy, although its benefits have been modest at best.56 Unfortunately, no population-based studies have examined the course of uninvestigated or functional dyspepsia, and hence referral bias in the published studies cannot be discounted. Moreover, no uniform set of predictors of symptom change have arisen from the studies. Furthermore, these studies may have been partially confounded by the inclusion of patients with reflux disease misclassified as functional dyspepsia, which also makes interpretation difficult.

This systematic review was conducted rigorously in order to minimize bias. We specifically sought to include both uninvestigated and functional dyspepsia in order to ensure that all relevant publications on prevalence were included. We excluded small studies and those with low response rates based on the premise that these would provide little useful information. In the studies included, funnel plots were not suggestive of publication bias. Although it might appear that we have set an unrealistically high bar by restricting the studies examining the prevalence of functional dyspepsia to population-based studies, it was necessary to highlight the deficiency in the available literature and identify areas of need for further research. We also ensured that the underlying population was adequately described for inclusion. In the study of prognosis, we excluded uninvestigated dyspepsia as we wanted to ensure that the patients examined had a firm diagnosis of functional dyspepsia and were followed up adequately. However, this review is necessarily restricted to available published data and, although not suggested by the funnel plots, publication bias could be present. Furthermore, due to varying definitions and missing information, it was also not possible to pool the data or evaluate for the independent role of potential prognostic factors, including age, gender or time of publication.

The present study suggests that dyspepsia is a common complaint world-wide and this cannot be explained by changes in definition over time. The data further suggest that the majority of patients with uninvestigated dyspepsia will fall into the functional dyspepsia category, but the exact prognosis of this group remains variable and unexplained. No information is currently available on the periodicity of individual dyspeptic symptoms over time; understanding the cycling pattern of symptoms could have important management implications. Further studies are needed in dyspepsia that are population-based, but incorporate investigations to subdivide the subjects into well-characterized disease subsets; only by this approach will a full understanding of the natural history be possible.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References

Dr El-Serag is a VA HSR&D Awardee (RCD00-013-2). This study was partly supported by funds from Novartis Pharmaceuticals.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Literature search
  6. Study selection criteria
  7. Results
  8. Prevalence of dyspepsia
  9. Clinical course of functional dyspepsia
  10. Discussion
  11. Acknowledgements
  12. References
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