- Email: [email protected]
Irritable bowel syndrome, gastro-oesophageal reflux disease and dyspepsia: Overlap analysis using loglinear models
Arab Journal of Gastroenterology 13 (2012) 20–23
Contents lists available at SciVerse ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Irritable bowel syndrome, gastro-oesophageal reflux disease and dyspepsia: Overlap analysis using loglinear models Asma pourhoseingholi a, Mohsen Vahedi b, Mohamad Amin Pourhoseingholi a, Sara Ashtari a, Bijan Moghimi-Dehkordi a,⇑, Azadeh Safaee a, Mohamad Reza Zali a a b
Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, Tehran, Iran
a r t i c l e
i n f o
Article history: Received 23 August 2011 Accepted 29 February 2012
Keywords: Irritable bowel syndrome Gastro-oesophageal reflux disease Dyspepsia Overlap Loglinear models
a b s t r a c t Background and study aims: Irritable bowel syndrome (IBS), gastro-oesophageal reflux disease (GERD) and dyspepsia are three most important gastrointestinal disorders which occur frequently together in patients. This study aims to assess the association between IBS, GERD and dyspepsia by using loglinear model analysis. Patients and methods: This cross-sectional household survey, the purpose of which was to find the prevalence of gastrointestinal symptoms, disorders and the related factors, has been done from May 2006 to December 2007 in Tehran province, Iran. Subjects were interviewed by trained personnel. GERD was diagnosed as the experience of heartburn and/or acid regurgitation at least once a week for the last 3 months. IBS and dyspepsia were diagnosed according to the Rome III criteria. Loglinear models were applied to investigate the simultaneous association between IBS, GERD and dyspepsia. Results: 77.9% of IBS patients had dyspepsia symptoms and 74.7% had GERD symptoms as well at the same time. As for the other two symptoms, 66% of GERD patients were also suffering from dyspepsia. Conclusions: These three symptoms frequently overlap; the overlap is systematic and not by chance or random. Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction From 5% to 25% of the world population suffers from irritable bowel syndrome (IBS). It is now recognised as the most common chronic bowel disorder [1,2]. For defining IBS, the Rome criteria are developed. According to these criteria, the occurrence of ‘‘abdominal pain or discomfort associated with changes in bowel habits and disordered defecation’’ is diagnosed as IBS [1,3,4]. Gastro-oesophageal reflux disease (GERD), the presence of heartburn and acid regurgitation [5], were experienced by 20% of the general population at least once a week and by 44% at least once a month [6,7]. According to recent studies, it seems that there is a strong overlap between GERD and IBS. This overlap occurs frequently; therefore, the prevalence of IBS was much higher in GERD patients compared with patients without GERD [8–10]. On the other hand, up to 30% of IBS patients had symptoms of reflux [9,11]. Another common gastrointestinal disorder in the population is dyspepsia [12]. According to the Rome criteria, a dyspeptic patient is a patient having been diagnosed with the disease for 6 months and has had one or more of the following symptoms for the last ⇑ Corresponding author. Address: 7th floor, Taleghani Hospital, Tabnak St. Yaman Ave, Velenjak, Tehran, Iran. Tel.: +98 212243251; fax: +98 2122432517. E-mail address: [email protected] (B. Moghimi-Dehkordi).
3 months. The symptoms include bothersome postprandial fullness, early satiety, epigastric pain and epigastric burning sensation [13]. The prevalence reported for dyspepsia is 7–34.2% in different countries [14–16]. A high prevalence of overlap between dyspepsia and IBS has been universally reported. Many studies have shown that the prevalence of IBS among dyspeptic patients varies from 13% to 29%, while the prevalence of dyspepsia among IBS patients ranges from 29% to 87% [15,17,18]. The prevalence of any of these diseases alone is less than that of the overlap of these entities. Many studies done in different parts of the world have examined the overlap between IBS and GERD, and between IBS and dyspepsia [11,19–23]. In this study, a generalised linear model was applied for investigating the overlap between these three symptoms. One of the special cases of generalised linear models for Poisson-distributed data is the loglinear model. Loglinear analysis is an extension of the two-way contingency table where the conditional relationship between two or more discrete, categorical variables is analysed by taking the natural logarithm of the cell frequencies within a contingency table. The variables investigated by loglinear models are all treated as ‘response variables’. In other words, no distinction is made between independent and dependent variables. Therefore, loglinear models only demonstrate association between variables
1687-1979/$ - see front matter Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajg.2012.02.005
21
A. pourhoseingholi et al. / Arab Journal of Gastroenterology 13 (2012) 20–23
[24]. Using these models, we consider IBS, GERD and dyspepsia as response variables and investigate the association between them simultaneously.
Patients and methods Study population The cross-sectional household survey done from May 2006 to December 2007 in Tehran province, Iran, was designed to find the prevalence of gastrointestinal symptoms and disorders and its related factors [2,11,25,26]. Random samples were selected according to the list of postal codes in Tehran, in which related addresses were drawn from the databank registry of Tehran central post office (approximately 5000 households were selected and all members surveyed). Then 18,180 adults were selected from this population randomly. The samples were taken from five cities including Tehran metropolitan, Damavand, Varamin, Firoozkouh, Pakdasht and their region constituencies. The first interview, covering the questions of the first part of our questionnaire, was carried out in all the 5000 selected houses by trained health-care workers from the respective local health centres. For ethical consideration, the interviewer explained the purpose of these questions to all eligible individuals and requested their participation before the interview. The research protocol was approved by the Ethics Committee of Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti Medical University, and all the participants signed a consent form. The questionnaire consisted of two parts. The first part of the questionnaire included a number of demographic data such as age, sex and educational level. In addition, participants were informed and asked about 11 gastrointestinal symptoms including abdominal pain, constipation, diarrhoea, bloating, heartburn, acid regurgitation, nausea and vomiting, weight loss, anorexia and difficulty in swallowing. The prevalence of these symptoms has been reported in a previous study [26]. Participants, who were reported to have at least one of these gastrointestinal symptoms, were selected for the second interview, which was performed by assigned physicians in the vicinity. The focus of questions in the second part of the questionnaire was on symptoms of IBS and dyspepsia based on ROME III criteria. It is noteworthy that this questionnaire was validated by Locke et al. in 1994 [27]. GERD was recognised as the experience of heartburn and/or acid regurgitation at least once a week for the last 3 months. Heartburn is described as a feeling of burning that rises through the chest. Acid regurgitation was defined as liquid coming back into the mouth and leaving a bitter or sour taste. Persons who regularly used anti-reflux medication were also reported as having reflux symptoms occurring so often that they could be included among the reflux patients [11].
Results Almost half of the total 18,180 persons who participated in this study were males. The mean age was 38.7 ± 17.1 years. Totally 2931 persons were reported to have at least one gastrointestinal symptom and so they were referred to the second questionnaire. Among the 2931 persons, 1547 persons had dyspepsia and 198 persons were found to have IBS based on Rome III criteria. The prevalence rates of dyspepsia and IBS were 8.5% and 1.1%, respectively. On the other hand, 1610 persons were found to have GERD; therefore, the prevalence of GERD was 8.85%. In this sample, 112 persons had both IBS and GERD, 127 persons had both IBS and dyspepsia and 1007 persons had both GERD and dyspepsia simultaneously. It means that 66% of patients with GERD had also dyspepsia symptoms, 74.7% of patients with IBS had GERD and 77.9% of IBS patients were suffering from dyspepsia simultaneously. In Table 1, numbers of subjects with all three disorders and their overlap are shown. After initial analysis, a loglinear model was fitted to the data. In this model, these three symptoms were investigated as dependent variables and their simultaneous association was studied. Among different models, according to the
Table 1 IBS, GERD and dyspepsia overlapping. IBS
Yes No
For investigating the prevalence of symptoms among the population, contingency tables were carried out. A p value less than 0.05 was considered statistically significant. Loglinear models were performed to investigate the association between IBS, GERD and dyspepsia simultaneously. The hierarchical effect was studied and the best model was selected according to the chi-squared goodness-of-fit tests. Larger v2 values had smaller p values and indicate poorer fits.
Yes No Yes No
Dyspepsia Yes
No
94 21 902 376
18 12 493 406
Table 2 Goodness-of-fit test for loglinear models relating IBS (I), GERD (G) and dyspepsia (D). Model
Liklihood ratio
Pearson chisquare
Degree of freedom
p value*
(I,G,D) (G,ID) (D,IG) (I,GD) (ID,IG) (IG,GD) (ID,GD) (ID,GD,IG) (IGD)
97.634 69.808 88.995 32.779 61.169 24.140 4.954 0.387 0.000
99.586 69.564 86.318 31.536 61.829 21.934 4.671 0.391 0.000
4 3 3 3 2 2 2 1 0
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.084 0.532 –
I: IBS, G: GERD, D: Dyspepsia. p value for Pearson chi-square statistics.
*
Table 3 Fitted value and standardised residual for best model. Symptoms
Statistical analysis
GERD
IBS
GERD
Dyspepsia
Yes
Yes
Yes No Yes No Yes No Yes No
No No
Yes No
I: IBS, G: GERD, D: Dyspepsia.
Observed count
Model (IG,ID,GD)
94 18 24 12 902 493 376 406
92.62 19.38 25.38 10.62 903.38 491.62 374.62 407.38
Fitted count
Standardised residuals 0.14 0.31 0.27 0.42 0.05 0.06 0.07 0.07
22
A. pourhoseingholi et al. / Arab Journal of Gastroenterology 13 (2012) 20–23
Table 4 Result of loglinear model. Association of IBS (I), GERD (G) and dyspepsia (D). Parameter
Estimate
Standard error
Estimated OR
p value
IG ID GD
0.441 0.956 0.692
0.199 0.211 0.089
1.51 2.60 1.99
0.038 <0.001 <0.001
Confidence interval for OR Lower
Upper
1.01 1.72 1.68
2.25 3.93 2.36
smallest value of chi-squared goodness-of-fit (v2 = 0.391 and p value = 0.532), the model with bidirectional effect was selected. Table 2 shows the result of model selection. After model selection, the exact value, according to the best model and the related standardised residual, was studied for quality and confirmation of the best model. The standardised residual below 2 shows a good fit (Table 3). This model reported odds ratio (OR) for two-by-two association simultaneously. According to this model, patients with IBS symptoms suffer from dyspepsia 2.6 times as much as those without IBS. The amount of suffering from GERD in IBS patients is also 1.51 times as much as in those without IBS. On the other hand, odds of having GERD in dyspepsia patient are 1.99 times more than that in people without dyspepsia (Table 4).
Discussion In this study, the overlap between three important gastrointestinal symptoms was investigated by using a special statistical technique. There are numerous studies in the world that have investigated the overlap between GERD, IBS and dyspepsia. A special feature of this article was the overlap between these three symptoms simultaneously and this approach led to valuable results. Various studies done in different parts of the world reported different prevalence of this overlap. Jung et al. reported the prevalence of GERD, IBS and overlap of GERD and IBS of 15%, 5% and 3%, respectively [19]. Gasiorowska stated in his study that 79% of IBS patients had GERD and 71% of GERD patients had IBS simultaneously [28]. A systematic review in 2008 in Iran reported significant variability of the range of prevalence for GERD in IBS patients from 17% to 80%. Much of this variable range refers to the method for diagnosing GERD in IBS patients [11]. The results showed that 74.7% of IBS patients were suffering from GERD and the prevalence was in these ranges too. Another systematic review showed that the prevalence of IBS in the non-GERD patients was much lower than that in the whole population, 5.1% versus 11.2% [10] showing that IBS could be relatively uncommon in the absence of GERD, and vice versa. There were two main hypotheses for this significant overlap. The first is that GERD and IBS are two distinct disorders with a common pathophysiologic process and the second is that IBS symptoms are part of GERD manifestations [29]. On the other hand, in some population-based studies, the estimated prevalence of dyspepsia among IBS patients was from 29% to 87% [17,18,30]. A study from Sweden reported prevalence of dyspepsia and IBS of 14% and 12.5%, respectively, and 87% of IBS patients had dyspepsia [18]. Because of high prevalence and high degree of symptom overlap, it has been suggested that IBS and dyspepsia represent the same disease, the irritable gut [18,31]. According to our results, prevalence was 77.9% and according to OR, the chance of having dyspepsia in IBS patients was 2.6 times more than in people without IBS. Hence, it seems that our results confirm this idea that IBS and dyspepsia may be the same disorder [31].
This study indicated that 66% of GERD patients were suffering from dyspepsia too. There are similar studies around the world that reported the prevalence of having dyspepsia in GERD patients: 25%, 43.1% 63% and 46.9% [16,32–34]. According to these results and those of other studies, it is clear that occurrence of dyspepsia in GERD patients is much higher than in the general population. All of these results showed the importance of overlap of these gastrointestinal symptoms. The prevalence reported by this study and other studies was mostly higher than 60%, which means that more than half of the patients were suffering from other symptoms. According to our previous study in the same population, these people have a relatively poor quality of life [35], and all of these three symptoms and their overlap impose a high economic burden to the populationMoreover, using a specific statistical method was important and led to more accurate and valuable results. In this method, we can apply triple association, but based on goodness-of-fit criterion, this model with triple interaction was not a good model and, because we always prefer to select the simplest model, we rejected the complex model with threefactor interaction and all interpretation was according to the model with two-factor interaction. The fundamental question that arises here is why we did not use the current approach to indicate association between factors. The answer is that usually in the situation that we can use models (ordinary regression models or general linear models such as loglinear models), applying these methods leads to precise and robust result compared to other approaches [24]. In conclusion, it seems that this statistical technique is helpful for analysing such studies. Conflicts of interest The authors declared that there was no conflict of interest. Acknowledgements The project was completely supported and funded by the Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran. References [1] Drossman DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123(6):2108–31. [2] Khoshkrood Mansoori B, Pourhoseingholi MA, Safaee A, et al. Irritable bowel syndrome: a population based study. J Gastrointest Liver Dis 2009;18(4): 413–8. [3] Hungin APS, Chang L, Locke GR, et al. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Alimen Pharmacol Therap 2005;21(11):1365–75. [4] Drossman DA. Rome III: the new criteria. Chin J Dig Dis 2006;7(4):181–5. [5] Dent J, El Serag HB, Wallander MA, et al. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005;54(5):710–7. [6] Agréus L, Svärdsudd K, Talley NJ, et al. Natural history of gastroesophageal reflux disease and functional abdominal disorders: a population-based study. Am J Gastroenterol 2001;96(10):2905–14. [7] Locke III 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(5):1448–56. [8] Pimentel M, Rossi F, Chow EJ, et al. Increased prevalence of irritable bowel syndrome in patients with gastroesophageal reflux. J Clin Gastroenterol 2002;34(3):221–4. [9] Talley NJ, Dennis EH, Schettler Duncan VA, et al. Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol 2003;98(11):2454–9. [10] Nastaskin I, Mehdikhani E, Conklin J, et al. Studying the overlap between IBS and GERD: a systematic review of the literature. Dig Dis Sci 2006;51(12):2113–20. [11] Solhpour A, Pourhoseingholi MA, Soltani F, et al. Gastro-oesophageal reflux disease and irritable bowel syndrome: a significant association in an Iranian population. Eur J Gastroenterol Hepatol 2008;20(8):719–25. [12] Flier SN, Rose S. Is functional dyspepsia of particular concern in women? A review of gender differences in epidemiology, pathophysiologic mechanisms,
A. pourhoseingholi et al. / Arab Journal of Gastroenterology 13 (2012) 20–23
[13] [14] [15]
[16]
[17] [18]
[19]
[20]
[21]
[22]
[23]
[24]
clinical presentation and management. Am J Gastroenterol 2006;101(Suppl. 3):S644–53. Barzkar M, Pourhoseingholi MA, Habibi M, et al. Uninvestigated dyspepsia and its related factors in an Iranian community. Saudi Med J 2009;30(3):397–402. Talley NJ. Drug treatment of functional dyspepsia. Scand J Gastroenterol Suppl 1991;182:47–60. Talley NJ, Zinsmeister AR, Schleck CD, et al. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology 1992;102(4): 1259–68. Haque M, Wyeth JW, Stace NH, et al. Prevalence, severity and associated features of gastro-oesophageal reflux and dyspepsia: a population-based study. N Z Med J 2000;113(1110):178–81. Crean GP, Holden RJ, Knill Jones RP, et al. A database on dyspepsia. Gut 1994;35(2):191–202. Agreus L, Svardsudd K, Nyren O, et al. Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology 1995;109(3):671–80. Jung HK, Halder S, McNally M, et al. Overlap of gastro-oesophageal reflux disease and irritable bowel syndrome: prevalence and risk factors in the general population. Alimen Pharmacol Therap 2007;26(3):453–61. Yarandi SS, Nasseri Moghaddam S, Mostajabi P, et al. Overlapping gastroesophageal reflux disease and irritable bowel syndrome: increased dysfunctional symptoms. World J Gastroenterol 2010;16(10):1232–8. Kennedy TM, Jones RH, Hungin APS, et al. Irritable bowel syndrome, gastrooesophageal reflux and bronchial hyper-responsiveness in the general population. Gut 1998;43(6):770–4. Gwee KA, Chua ASB. Functional dyspepsia and irritable bowel syndrome, are they different entities and does it matter? World J Gastroenterol 2006;12(17):2708–12. Savas LS, White DL, Wieman M, et al. Irritable bowel syndrome and dyspepsia among women veterans: prevalence and association with psychological distress. Alimen Pharmacol Therap 2009;29(1):115–25. Agresti A. An introduction to categorical data analysis. 2nd ed. WileyInterscience; 2007.
23
[25] Pourhoseingholi MA, Kaboli SA, Pourhoseingholi A, et al. Obesity and functional constipation; a community-based study in Iran. J Gastrointest Liver Dis 2009;18(2):151–5. [26] Pourhoseingholi A, Safaee A, Pourhoseingholi MA, et al. Prevalence and demographic risk factors of gastrointestinal symptoms in Tehran Province. Ital J Public Health 2010;7(1):42–6. [27] Locke GR, Talley NJ, Weaver AL, et al. A new questionnaire for gastroesophageal reflux disease. Mayo Clin Proc 1994;69(6):539–47. [28] Gasiorowska A, Poh CH, Fass R. Gastroesophageal reflux disease (GERD) and Irritable Bowel Syndrome (IBS)-is it one disease or an overlap of two disorders? Dig Dis Sci 2009;54(9):1829–34. [29] Hori K, Matsumoto T, Miwa H. Analysis of the gastrointestinal symptoms of uninvestigated dyspepsia and irritable bowel syndrome. Gut Liver 2009;3(3):192–6. [30] Talley NJ, Stanghellini V, Heading RC, et al. Functional gastroduodenal disorders. Gut 1999;45(Suppl. 2):II37–42. [31] Trimble KC, Farouk R, Pryde A, et al. Heightened visceral sensation in functional gastrointestinal disease is not site-specific evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995;40(8):1607–13. [32] Kaji M, Fujiwara Y, Shiba M, et al. Prevalence of overlaps between GERD, FD and IBS and impact on health-related quality of life. J Gastroenterol Hepatol 2010;25(6):1151–6. [33] Kitapçiogˇlu G, Mandiraciogˇlu A, Caymaz Bor C, et al. Overlap of symptoms of dyspepsia and gastroesophageal reflux in the community. Turk J Gastroenterol 2007;18(1):14–9. [34] De Vries DR, Van Herwaarden MA, Baron A, et al. Concomitant functional dyspepsia and irritable bowel syndrome decrease health-related quality of life in gastroesophageal reflux disease. Scand J Gastroenterol 2007;42(8):951–6. [35] Moghimi Dehkordi B, Vahedi M, Khoshkrood Mansoori B, et al. Economic burden of gastro-oesophageal reflux disease and dyspepsia: a communitybased study. Arab J Gastroenterol 2011;12(2):86–9.
Contents lists available at SciVerse ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Irritable bowel syndrome, gastro-oesophageal reflux disease and dyspepsia: Overlap analysis using loglinear models Asma pourhoseingholi a, Mohsen Vahedi b, Mohamad Amin Pourhoseingholi a, Sara Ashtari a, Bijan Moghimi-Dehkordi a,⇑, Azadeh Safaee a, Mohamad Reza Zali a a b
Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, Tehran, Iran
a r t i c l e
i n f o
Article history: Received 23 August 2011 Accepted 29 February 2012
Keywords: Irritable bowel syndrome Gastro-oesophageal reflux disease Dyspepsia Overlap Loglinear models
a b s t r a c t Background and study aims: Irritable bowel syndrome (IBS), gastro-oesophageal reflux disease (GERD) and dyspepsia are three most important gastrointestinal disorders which occur frequently together in patients. This study aims to assess the association between IBS, GERD and dyspepsia by using loglinear model analysis. Patients and methods: This cross-sectional household survey, the purpose of which was to find the prevalence of gastrointestinal symptoms, disorders and the related factors, has been done from May 2006 to December 2007 in Tehran province, Iran. Subjects were interviewed by trained personnel. GERD was diagnosed as the experience of heartburn and/or acid regurgitation at least once a week for the last 3 months. IBS and dyspepsia were diagnosed according to the Rome III criteria. Loglinear models were applied to investigate the simultaneous association between IBS, GERD and dyspepsia. Results: 77.9% of IBS patients had dyspepsia symptoms and 74.7% had GERD symptoms as well at the same time. As for the other two symptoms, 66% of GERD patients were also suffering from dyspepsia. Conclusions: These three symptoms frequently overlap; the overlap is systematic and not by chance or random. Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction From 5% to 25% of the world population suffers from irritable bowel syndrome (IBS). It is now recognised as the most common chronic bowel disorder [1,2]. For defining IBS, the Rome criteria are developed. According to these criteria, the occurrence of ‘‘abdominal pain or discomfort associated with changes in bowel habits and disordered defecation’’ is diagnosed as IBS [1,3,4]. Gastro-oesophageal reflux disease (GERD), the presence of heartburn and acid regurgitation [5], were experienced by 20% of the general population at least once a week and by 44% at least once a month [6,7]. According to recent studies, it seems that there is a strong overlap between GERD and IBS. This overlap occurs frequently; therefore, the prevalence of IBS was much higher in GERD patients compared with patients without GERD [8–10]. On the other hand, up to 30% of IBS patients had symptoms of reflux [9,11]. Another common gastrointestinal disorder in the population is dyspepsia [12]. According to the Rome criteria, a dyspeptic patient is a patient having been diagnosed with the disease for 6 months and has had one or more of the following symptoms for the last ⇑ Corresponding author. Address: 7th floor, Taleghani Hospital, Tabnak St. Yaman Ave, Velenjak, Tehran, Iran. Tel.: +98 212243251; fax: +98 2122432517. E-mail address: [email protected] (B. Moghimi-Dehkordi).
3 months. The symptoms include bothersome postprandial fullness, early satiety, epigastric pain and epigastric burning sensation [13]. The prevalence reported for dyspepsia is 7–34.2% in different countries [14–16]. A high prevalence of overlap between dyspepsia and IBS has been universally reported. Many studies have shown that the prevalence of IBS among dyspeptic patients varies from 13% to 29%, while the prevalence of dyspepsia among IBS patients ranges from 29% to 87% [15,17,18]. The prevalence of any of these diseases alone is less than that of the overlap of these entities. Many studies done in different parts of the world have examined the overlap between IBS and GERD, and between IBS and dyspepsia [11,19–23]. In this study, a generalised linear model was applied for investigating the overlap between these three symptoms. One of the special cases of generalised linear models for Poisson-distributed data is the loglinear model. Loglinear analysis is an extension of the two-way contingency table where the conditional relationship between two or more discrete, categorical variables is analysed by taking the natural logarithm of the cell frequencies within a contingency table. The variables investigated by loglinear models are all treated as ‘response variables’. In other words, no distinction is made between independent and dependent variables. Therefore, loglinear models only demonstrate association between variables
1687-1979/$ - see front matter Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajg.2012.02.005
21
A. pourhoseingholi et al. / Arab Journal of Gastroenterology 13 (2012) 20–23
[24]. Using these models, we consider IBS, GERD and dyspepsia as response variables and investigate the association between them simultaneously.
Patients and methods Study population The cross-sectional household survey done from May 2006 to December 2007 in Tehran province, Iran, was designed to find the prevalence of gastrointestinal symptoms and disorders and its related factors [2,11,25,26]. Random samples were selected according to the list of postal codes in Tehran, in which related addresses were drawn from the databank registry of Tehran central post office (approximately 5000 households were selected and all members surveyed). Then 18,180 adults were selected from this population randomly. The samples were taken from five cities including Tehran metropolitan, Damavand, Varamin, Firoozkouh, Pakdasht and their region constituencies. The first interview, covering the questions of the first part of our questionnaire, was carried out in all the 5000 selected houses by trained health-care workers from the respective local health centres. For ethical consideration, the interviewer explained the purpose of these questions to all eligible individuals and requested their participation before the interview. The research protocol was approved by the Ethics Committee of Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti Medical University, and all the participants signed a consent form. The questionnaire consisted of two parts. The first part of the questionnaire included a number of demographic data such as age, sex and educational level. In addition, participants were informed and asked about 11 gastrointestinal symptoms including abdominal pain, constipation, diarrhoea, bloating, heartburn, acid regurgitation, nausea and vomiting, weight loss, anorexia and difficulty in swallowing. The prevalence of these symptoms has been reported in a previous study [26]. Participants, who were reported to have at least one of these gastrointestinal symptoms, were selected for the second interview, which was performed by assigned physicians in the vicinity. The focus of questions in the second part of the questionnaire was on symptoms of IBS and dyspepsia based on ROME III criteria. It is noteworthy that this questionnaire was validated by Locke et al. in 1994 [27]. GERD was recognised as the experience of heartburn and/or acid regurgitation at least once a week for the last 3 months. Heartburn is described as a feeling of burning that rises through the chest. Acid regurgitation was defined as liquid coming back into the mouth and leaving a bitter or sour taste. Persons who regularly used anti-reflux medication were also reported as having reflux symptoms occurring so often that they could be included among the reflux patients [11].
Results Almost half of the total 18,180 persons who participated in this study were males. The mean age was 38.7 ± 17.1 years. Totally 2931 persons were reported to have at least one gastrointestinal symptom and so they were referred to the second questionnaire. Among the 2931 persons, 1547 persons had dyspepsia and 198 persons were found to have IBS based on Rome III criteria. The prevalence rates of dyspepsia and IBS were 8.5% and 1.1%, respectively. On the other hand, 1610 persons were found to have GERD; therefore, the prevalence of GERD was 8.85%. In this sample, 112 persons had both IBS and GERD, 127 persons had both IBS and dyspepsia and 1007 persons had both GERD and dyspepsia simultaneously. It means that 66% of patients with GERD had also dyspepsia symptoms, 74.7% of patients with IBS had GERD and 77.9% of IBS patients were suffering from dyspepsia simultaneously. In Table 1, numbers of subjects with all three disorders and their overlap are shown. After initial analysis, a loglinear model was fitted to the data. In this model, these three symptoms were investigated as dependent variables and their simultaneous association was studied. Among different models, according to the
Table 1 IBS, GERD and dyspepsia overlapping. IBS
Yes No
For investigating the prevalence of symptoms among the population, contingency tables were carried out. A p value less than 0.05 was considered statistically significant. Loglinear models were performed to investigate the association between IBS, GERD and dyspepsia simultaneously. The hierarchical effect was studied and the best model was selected according to the chi-squared goodness-of-fit tests. Larger v2 values had smaller p values and indicate poorer fits.
Yes No Yes No
Dyspepsia Yes
No
94 21 902 376
18 12 493 406
Table 2 Goodness-of-fit test for loglinear models relating IBS (I), GERD (G) and dyspepsia (D). Model
Liklihood ratio
Pearson chisquare
Degree of freedom
p value*
(I,G,D) (G,ID) (D,IG) (I,GD) (ID,IG) (IG,GD) (ID,GD) (ID,GD,IG) (IGD)
97.634 69.808 88.995 32.779 61.169 24.140 4.954 0.387 0.000
99.586 69.564 86.318 31.536 61.829 21.934 4.671 0.391 0.000
4 3 3 3 2 2 2 1 0
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.084 0.532 –
I: IBS, G: GERD, D: Dyspepsia. p value for Pearson chi-square statistics.
*
Table 3 Fitted value and standardised residual for best model. Symptoms
Statistical analysis
GERD
IBS
GERD
Dyspepsia
Yes
Yes
Yes No Yes No Yes No Yes No
No No
Yes No
I: IBS, G: GERD, D: Dyspepsia.
Observed count
Model (IG,ID,GD)
94 18 24 12 902 493 376 406
92.62 19.38 25.38 10.62 903.38 491.62 374.62 407.38
Fitted count
Standardised residuals 0.14 0.31 0.27 0.42 0.05 0.06 0.07 0.07
22
A. pourhoseingholi et al. / Arab Journal of Gastroenterology 13 (2012) 20–23
Table 4 Result of loglinear model. Association of IBS (I), GERD (G) and dyspepsia (D). Parameter
Estimate
Standard error
Estimated OR
p value
IG ID GD
0.441 0.956 0.692
0.199 0.211 0.089
1.51 2.60 1.99
0.038 <0.001 <0.001
Confidence interval for OR Lower
Upper
1.01 1.72 1.68
2.25 3.93 2.36
smallest value of chi-squared goodness-of-fit (v2 = 0.391 and p value = 0.532), the model with bidirectional effect was selected. Table 2 shows the result of model selection. After model selection, the exact value, according to the best model and the related standardised residual, was studied for quality and confirmation of the best model. The standardised residual below 2 shows a good fit (Table 3). This model reported odds ratio (OR) for two-by-two association simultaneously. According to this model, patients with IBS symptoms suffer from dyspepsia 2.6 times as much as those without IBS. The amount of suffering from GERD in IBS patients is also 1.51 times as much as in those without IBS. On the other hand, odds of having GERD in dyspepsia patient are 1.99 times more than that in people without dyspepsia (Table 4).
Discussion In this study, the overlap between three important gastrointestinal symptoms was investigated by using a special statistical technique. There are numerous studies in the world that have investigated the overlap between GERD, IBS and dyspepsia. A special feature of this article was the overlap between these three symptoms simultaneously and this approach led to valuable results. Various studies done in different parts of the world reported different prevalence of this overlap. Jung et al. reported the prevalence of GERD, IBS and overlap of GERD and IBS of 15%, 5% and 3%, respectively [19]. Gasiorowska stated in his study that 79% of IBS patients had GERD and 71% of GERD patients had IBS simultaneously [28]. A systematic review in 2008 in Iran reported significant variability of the range of prevalence for GERD in IBS patients from 17% to 80%. Much of this variable range refers to the method for diagnosing GERD in IBS patients [11]. The results showed that 74.7% of IBS patients were suffering from GERD and the prevalence was in these ranges too. Another systematic review showed that the prevalence of IBS in the non-GERD patients was much lower than that in the whole population, 5.1% versus 11.2% [10] showing that IBS could be relatively uncommon in the absence of GERD, and vice versa. There were two main hypotheses for this significant overlap. The first is that GERD and IBS are two distinct disorders with a common pathophysiologic process and the second is that IBS symptoms are part of GERD manifestations [29]. On the other hand, in some population-based studies, the estimated prevalence of dyspepsia among IBS patients was from 29% to 87% [17,18,30]. A study from Sweden reported prevalence of dyspepsia and IBS of 14% and 12.5%, respectively, and 87% of IBS patients had dyspepsia [18]. Because of high prevalence and high degree of symptom overlap, it has been suggested that IBS and dyspepsia represent the same disease, the irritable gut [18,31]. According to our results, prevalence was 77.9% and according to OR, the chance of having dyspepsia in IBS patients was 2.6 times more than in people without IBS. Hence, it seems that our results confirm this idea that IBS and dyspepsia may be the same disorder [31].
This study indicated that 66% of GERD patients were suffering from dyspepsia too. There are similar studies around the world that reported the prevalence of having dyspepsia in GERD patients: 25%, 43.1% 63% and 46.9% [16,32–34]. According to these results and those of other studies, it is clear that occurrence of dyspepsia in GERD patients is much higher than in the general population. All of these results showed the importance of overlap of these gastrointestinal symptoms. The prevalence reported by this study and other studies was mostly higher than 60%, which means that more than half of the patients were suffering from other symptoms. According to our previous study in the same population, these people have a relatively poor quality of life [35], and all of these three symptoms and their overlap impose a high economic burden to the populationMoreover, using a specific statistical method was important and led to more accurate and valuable results. In this method, we can apply triple association, but based on goodness-of-fit criterion, this model with triple interaction was not a good model and, because we always prefer to select the simplest model, we rejected the complex model with threefactor interaction and all interpretation was according to the model with two-factor interaction. The fundamental question that arises here is why we did not use the current approach to indicate association between factors. The answer is that usually in the situation that we can use models (ordinary regression models or general linear models such as loglinear models), applying these methods leads to precise and robust result compared to other approaches [24]. In conclusion, it seems that this statistical technique is helpful for analysing such studies. Conflicts of interest The authors declared that there was no conflict of interest. Acknowledgements The project was completely supported and funded by the Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran. References [1] Drossman DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123(6):2108–31. [2] Khoshkrood Mansoori B, Pourhoseingholi MA, Safaee A, et al. Irritable bowel syndrome: a population based study. J Gastrointest Liver Dis 2009;18(4): 413–8. [3] Hungin APS, Chang L, Locke GR, et al. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Alimen Pharmacol Therap 2005;21(11):1365–75. [4] Drossman DA. Rome III: the new criteria. Chin J Dig Dis 2006;7(4):181–5. [5] Dent J, El Serag HB, Wallander MA, et al. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005;54(5):710–7. [6] Agréus L, Svärdsudd K, Talley NJ, et al. Natural history of gastroesophageal reflux disease and functional abdominal disorders: a population-based study. Am J Gastroenterol 2001;96(10):2905–14. [7] Locke III 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(5):1448–56. [8] Pimentel M, Rossi F, Chow EJ, et al. Increased prevalence of irritable bowel syndrome in patients with gastroesophageal reflux. J Clin Gastroenterol 2002;34(3):221–4. [9] Talley NJ, Dennis EH, Schettler Duncan VA, et al. Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol 2003;98(11):2454–9. [10] Nastaskin I, Mehdikhani E, Conklin J, et al. Studying the overlap between IBS and GERD: a systematic review of the literature. Dig Dis Sci 2006;51(12):2113–20. [11] Solhpour A, Pourhoseingholi MA, Soltani F, et al. Gastro-oesophageal reflux disease and irritable bowel syndrome: a significant association in an Iranian population. Eur J Gastroenterol Hepatol 2008;20(8):719–25. [12] Flier SN, Rose S. Is functional dyspepsia of particular concern in women? A review of gender differences in epidemiology, pathophysiologic mechanisms,
A. pourhoseingholi et al. / Arab Journal of Gastroenterology 13 (2012) 20–23
[13] [14] [15]
[16]
[17] [18]
[19]
[20]
[21]
[22]
[23]
[24]
clinical presentation and management. Am J Gastroenterol 2006;101(Suppl. 3):S644–53. Barzkar M, Pourhoseingholi MA, Habibi M, et al. Uninvestigated dyspepsia and its related factors in an Iranian community. Saudi Med J 2009;30(3):397–402. Talley NJ. Drug treatment of functional dyspepsia. Scand J Gastroenterol Suppl 1991;182:47–60. Talley NJ, Zinsmeister AR, Schleck CD, et al. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology 1992;102(4): 1259–68. Haque M, Wyeth JW, Stace NH, et al. Prevalence, severity and associated features of gastro-oesophageal reflux and dyspepsia: a population-based study. N Z Med J 2000;113(1110):178–81. Crean GP, Holden RJ, Knill Jones RP, et al. A database on dyspepsia. Gut 1994;35(2):191–202. Agreus L, Svardsudd K, Nyren O, et al. Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology 1995;109(3):671–80. Jung HK, Halder S, McNally M, et al. Overlap of gastro-oesophageal reflux disease and irritable bowel syndrome: prevalence and risk factors in the general population. Alimen Pharmacol Therap 2007;26(3):453–61. Yarandi SS, Nasseri Moghaddam S, Mostajabi P, et al. Overlapping gastroesophageal reflux disease and irritable bowel syndrome: increased dysfunctional symptoms. World J Gastroenterol 2010;16(10):1232–8. Kennedy TM, Jones RH, Hungin APS, et al. Irritable bowel syndrome, gastrooesophageal reflux and bronchial hyper-responsiveness in the general population. Gut 1998;43(6):770–4. Gwee KA, Chua ASB. Functional dyspepsia and irritable bowel syndrome, are they different entities and does it matter? World J Gastroenterol 2006;12(17):2708–12. Savas LS, White DL, Wieman M, et al. Irritable bowel syndrome and dyspepsia among women veterans: prevalence and association with psychological distress. Alimen Pharmacol Therap 2009;29(1):115–25. Agresti A. An introduction to categorical data analysis. 2nd ed. WileyInterscience; 2007.
23
[25] Pourhoseingholi MA, Kaboli SA, Pourhoseingholi A, et al. Obesity and functional constipation; a community-based study in Iran. J Gastrointest Liver Dis 2009;18(2):151–5. [26] Pourhoseingholi A, Safaee A, Pourhoseingholi MA, et al. Prevalence and demographic risk factors of gastrointestinal symptoms in Tehran Province. Ital J Public Health 2010;7(1):42–6. [27] Locke GR, Talley NJ, Weaver AL, et al. A new questionnaire for gastroesophageal reflux disease. Mayo Clin Proc 1994;69(6):539–47. [28] Gasiorowska A, Poh CH, Fass R. Gastroesophageal reflux disease (GERD) and Irritable Bowel Syndrome (IBS)-is it one disease or an overlap of two disorders? Dig Dis Sci 2009;54(9):1829–34. [29] Hori K, Matsumoto T, Miwa H. Analysis of the gastrointestinal symptoms of uninvestigated dyspepsia and irritable bowel syndrome. Gut Liver 2009;3(3):192–6. [30] Talley NJ, Stanghellini V, Heading RC, et al. Functional gastroduodenal disorders. Gut 1999;45(Suppl. 2):II37–42. [31] Trimble KC, Farouk R, Pryde A, et al. Heightened visceral sensation in functional gastrointestinal disease is not site-specific evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995;40(8):1607–13. [32] Kaji M, Fujiwara Y, Shiba M, et al. Prevalence of overlaps between GERD, FD and IBS and impact on health-related quality of life. J Gastroenterol Hepatol 2010;25(6):1151–6. [33] Kitapçiogˇlu G, Mandiraciogˇlu A, Caymaz Bor C, et al. Overlap of symptoms of dyspepsia and gastroesophageal reflux in the community. Turk J Gastroenterol 2007;18(1):14–9. [34] De Vries DR, Van Herwaarden MA, Baron A, et al. Concomitant functional dyspepsia and irritable bowel syndrome decrease health-related quality of life in gastroesophageal reflux disease. Scand J Gastroenterol 2007;42(8):951–6. [35] Moghimi Dehkordi B, Vahedi M, Khoshkrood Mansoori B, et al. Economic burden of gastro-oesophageal reflux disease and dyspepsia: a communitybased study. Arab J Gastroenterol 2011;12(2):86–9.