Lower Gastrointestinal Tract Functional Disorders: Prevalence and Symptoms Characteristics in Outpatient Gastroenterology Clinic

  

    
Dependent variable (FGIDs)
    
Significance
    
OR
    
95% CI for OR
  
  

    
low bound
    
upper bound
  
  

    
Factors variables
  
  

    
anxiety
    
0.643
    
0.924
    
0.660
    
1.292
  
  

    
depression
    
0.065
    
3.352
    
0.929
    
12.090
  
  

    
panic disorder
    
0.488
    
0.789
    
0.404
    
1.541
  
  

    
stress
    
0.049
    
1.360
    
1.002
    
1.847
  
  

    
other psych.
    
0.418
    
0.802
    
0.470
    
1.368
  
  

    
Drugs intake
    
0.391
    
1.162
    
0.825
    
1.636
  

Table 9:  Relative risk of FGIDs if having psychological factors and drugs intake
history.

Discussion

Prevalence

Taking into account the number of criteria required to meet the definition of each disorder, the prevalence varies greatly under method, sample size, criteria used for diagnosis, type of population, geographic location, country etc. Minor changes in definition can change all the estimates.

Prevalence of overall FGIDs (FBDs and FAP) and overlapping syndrome: The overall FGID diagnosed is estimated at 55.7% in the population what demonstrates that FGID are common in this population. Indeed half of all adults who suffer from chronic abdominal pain and stools irregularity have functional bowel disorders according to Winfried et al. [10].

Studies in Japan outpatients [11] and china adolescents [7] found comparable results respectively 57.4% and 55.24%. However our rate is higher than those of Linda [12], Walsh [13], Liu [14], Fang-Yuan [15], Moghimi-Dehkordi [16] and Kheng-Seong [9] who found up to 40%, 41.2%, 27.8%, 26.2%, 10.9% and 33% respectively; but less than that of Thompson [8] who found 61.7%. These variations can be explained by the heterogeneity in measured outcomes, study design, samples size, symptoms definitions, indications for colonoscopy and/ or inclusion criteria, which may also reflect the discrepancies in the evolution of the definitions, and the still unknown etiologies of these nonspecific symptoms. Direct comparisons of results between studies, as well as generalization and recommendations for all individuals with FGIDs are therefore difficult [17].

Our study is conducted among hospital outpatient patients; this can make a big difference with population based studies which use bigger sample size and where subjects included did not seek for a medical care. We have also focused on two categories of FGIDs: FBD (C1-C5) and FAP (D1) among the six major categories of FGID which equals to six individuals FGIDs, this reason also can explain our rate. Findings in whole population may be quite different from findings in patients population in which the individual syndromes may be stable and less prone to transitions between syndromes [18]. Patient-based studies from health institutions are inherently biased by health care seeking because almost half of subjects consult a health care provider regarding their symptoms [12].

As FGIDs varies depending on the diagnostic criteria, the geographic area of evaluated population, age, gender and environmental factors; racial and cultural differences are also important to take into consideration. Indeed, studies revealed a greater prevalence of FGIDs in western countries than others and concomitantly FGIDs are more common in industrialized city than non industrialized city [19].

In a study by Ghoshal et al., while comparing the percentage of subjects fulfilling different diagnostic criteria for the same FGID in the same sample it was found rates for Manning: 91.122%, Rome I: 67.9% , Rome II: 40.1% ,Rome III: 52.5% and Asian criteria: 74.5% among 1618 patients; what proves the variation of prevalence through diagnostic criteria. The Rome III criteria were less restrictive and showed good agreement with the Rome II criteria. Considering all these above mentioned factors, it becomes very difficult or virtually impossible to compare prevalence rates from different time periods or geographic regions.

Overlapping among FGIDs is very common in this study and was estimated at 72.04% of total FGIDs with 29.39% having two coexisting FGID and 25.09% having three coexisting FGID. Comparatively Xiong [20] found 50.3% of patients with overlapping disorders with 37.4% having two coexisting FGID, 8.9% having three coexisting FGID, while Fang-Yuan [15] found 25.7% of overlapping between functional dyspepsia and other FGIDs and Nakajima [11] 42.6% of overlapping FGID with 29.6% having two coexisting FGID and 11.1% having 3 coexisting FGID. This phenomenon of overlapping implies that all the FGIDs may share a mutual underlying pathophysiology as they happen in the same patient and improvement of other symptoms is observed when treating one FGID [21]. Also, the flexibility of Rome III criteria allows this overlapping such that borders are blurred between disorders. Studies are increasingly supportive of the possibility that these disorders are multifactorials [22]. A commonly held perception is that FGIDs are chronic stable conditions, although symptoms may wax and wane [18]. Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution, this transition between FGIDs suggests a common etiopathogenesis. Among people with symptoms at baseline, approximately 20% had the same symptom, 40% had no symptoms, and 40% had different symptoms at follow-up [18].

IBS: IBS, the best known and most studied among FGIDs accounts for 20-50% of all gastroenterology consultations [23] and 20-50 % of referrals to gastroenterology clinic [24]. Epidemiological studies worldwide reported a prevalence of 6-25% of IBS [3]. However, disparities exist between countries and regions of the world, better still between sex and age.

Prevalence of IBS was 24.95% in our study. Similar studies found 25% in Canada [25], 23.4% in China [26] and 27 % [27] in Iran. Some authors found lower rate than ours: 4.4% [15], 6.90% [7], 11.1% [9], 17.2% [12], 10-20% [23], 18.8% [28] and others higher 32.5% [29], 40.2% [20], 47.1% [30], 70.3% [13].

Differences of prevalence are remarkable between several studies, these are unlikely due to true inter-country variations but rather than to different sociocultural perceptions and reporting of symptoms by subjects, or to different interpretations of symptoms by interviewers , or to the lack of correspondence in any single language between the native lay verbal definition of symptoms and the translated terminology [1]. Most studies indicate that the prevalence of IBS is higher in women than in men and in adults and elderly than in young subjects [2,29,31,32] also, the prevalence of IBS was decreasing with ageing [1].

In this study we found that IBS is highest in the age group 41-50 and decrease progressively after 50 years. This is comparable to a study by Adibi et al. who found that across Asia IBS prevalence is higher in the younger age groups, applying Rome II and it is significantly more prevalent in those below 50 years of age than those of 50 years and older.

While sub typing IBS based on the stool form we found IBSconstipation 25.25%, IBS-diarrhea 30%, mixed-IBS 19.1% and otherwise a 1:1 ratio. Comparatively in 2011 another study in outpatients in Wuhan found 10.7% of IBS , a 1:1 ratio, C-IBS 30.8% and D-IBS 45.2% by using Rome II criteria [26]. As in our study IBSdiarrhea is particularly most frequent in Asia and conversely IBSconstipation in European countries. One possible explanation may be the low-fiber diet in western cooking. The differences in results in IBS sub typing may be due to the diagnostic criteria, as a recent study from China that compared the Rome II and III criteria found the latter to be better [33]. Also there is poor agreement between sub typing of IBS patients based on Rome II versus Rome III criteria [34, 35].

Functional Abdominal Pain (FAP): The prevalence of Functional Abdominal Pain was 24.75% in this study. Linda [12] in 2006 found a rate greater than ours 33.3%, while others authors [8,13,18,20,36] lesser than ours: 20.2% (USA), 13-17% (USA), 7.9% (Ireland), 2.7% (Canada), 2.3% (China) respectively. This difference could be explained by the method used, sample size, nature of sample (patients or general population) and criteria used to define FAP. Basically it is easier to find higher prevalence in patient-based study than in population-based study. Better, it is established that sociocultural factors influence the pain behavior as do psychological factors, in our study psychological stress was found to have a strong link with FAP. Also, the combination of genetic factors, vulnerability factors, and adult stress may determine in part the effectiveness of endogenous pain modulation systems and thereby influence the development of FAPS [37]. Diagnosing a patient who presents with abdominal pain can be challenging since it can be difficult to properly evaluate these patients without overusing diagnostic tests and consultation [38]. To the same extent, children with FAP have a high utilization of health care system as, they, along with their parents; seek answers for the unexplained abdominal pain. Pain interferes with normal attendance and performance at school, peer relationships and participation in family activity. Fortunately, FAP is uncommon under 4-6years [36]. Increasing evidence from limited studies support that the morbidity associated with FGID is psychosocial [36].

In our study FAP is more common in male than in female although it is not statistically significant. However several studies [1,5,6,28,37,39,40,] indicate that FAP is more frequent in women and associated with significant work absenteeism and physician visits. This gender distribution of FAP is still not clear.

Functional diarrhea (Fd): We found a prevalence of 21.05% for functional diarrhea in this study. Other authors [7- 9,12,13,18,20,30,40] found 0.70%, 1.1%, 1.5%, 1.5%, 3.6%, 3.7%, 5.7%, 8.5%, 25.1% respectively. It is evident that prevalence widely differs through studies; this may be due to factors included and/or criteria used to diagnose this FGID.

For unknown or unclear reason diarrhea seems to be more frequent and troublesome symptom in men than women, also majority of FGID studies supports this fact, while other FGID symptoms were predominant in female [7,11,30,41].

Fd have a lower rate compare to other FGIDs, this is most likely due to IBS as that diarrhea is also part of criteria for its diagnosis. A study [9] had revealed that male gender and age > 60 years are predictive of diarrhea. Possible explanation may be that physiologically men’s colon transit is more rapid than women’s, although psychological distress, drugs, food intolerance can induce diarrhea. Understanding of Fd is limited because few studies had put interests in it compared to FD or IBS.

Functional constipation (Fc): Functional constipation prevalence was 22.75% in our study. By using Rome II or III criteria and diverse methods, increasingly some authors found a lower rate 2.1% [12], 4.1% [18], 4.4% [15], 8.1% [9], 8.1% [9], 11% [30], 12.6% [20], 14.9% [8], 3-16.7% [1], 16.95% [7], 22.5% [13] while others a higher rate 25.92% [42], 28% [27] compared to ours.

The prevalence of constipation varies with the different definitions used and in the different populations investigated. In our study we found an increase in prevalence with age and it is more frequent in adult female than in adult male as did Corazziari’s [1]. For Thompson et al. [31] constipation occurs in up to 20% of populations, depending on demographic factors, sampling and the definition used. Also literature stated that female sex, older age, inactivity, low caloric intake, taking a large number of medication, low-fiber diet, low income and low education levels could be risk factors of constipation. The incidence of constipation is three times higher in women, and women are twice as likely as men to schedule physician visits for constipation [40,17]. Studies have shown that bowel transit time in women tends to be slower than in men, and many women experience constipation during their menstrual period [43]. Environmental factors like living in rural areas and in colder temperatures, geographic localization and cultural eating habits can increase susceptibility to constipation. Fc in older adults may result from autonomic neuropathies, such as diabetes mellitus and Parkinson disease, or from use of medications, such as antacids especially with calcium, opioids, iron supplements and anticholinergics or from conditions such as depression, hypothyroidism, cerebrovascular disease and IBS [43].

Functional Unspecified Bowel Disorder (FUBD): The prevalence of functional unspecified bowel disorder was 11.87 % in this study. Comparatively the rate was lower in some studies 3.8% [30], 8.9% [15] and higher in others 13.9% [20], 18% [27], 26.58% [7], 38.7% [11] than ours. The difference lies in the choice of criteria (Rome II or III), the sample size, location of the study as well as nature of the population (patients, general population, city dweller, peasant, high education level, student). Most of the time this disorder is confounded with IBS, as is the case of Nakajima study [11] where FUBD have been reported to be the most prevalent (38.7%) bowel disorders. However, this FGID is uncommon as other FGIDs should be excluded before you are declared FUBD.

Functional bloating (Fb): Bloating is one of the most common and bothersome symptoms complained by a large proportion of patients [36]. In this study we found a Fb prevalence of 28.94%. The prevalence varies among studies 2.6% [20], 4.12% [7], 6.1% [9,40], 7% [44], 8.2% [13], 9.1% [30], 13.1% [8], 25% [27] thus our rate was highest. Prevalence’s rates vary widely, depending on diagnostic criteria and other factors. Epidemiologically, one in six to one in five healthy individuals reported bloating in population-based studies both in Western and East countries [45]. Thompson et al. [31] found 15% in a population based studies and bloating was more prevalent in women. Indeed there are great difficulties in terms of diagnosis due to lack of appropriate parameters that grade and assess bloating. It is still unclear to what extent the individual patient complaint of subjective bloating correlates with the objective evidence of abdominal distension.

Tuteja [44] stresses that bloating is a common symptom in otherwise healthy adults, and is often associated with but not predictive of functional bowel disorders and that smoking and highdose aspirin are associated with bloating.

FGIDs relation with age and gender

Our study has revealed a significant relationship between FGIDs and patient’s age and sex in general, and particularly in IBS (Table 5, 6). Indeed, there is difference in age and gender distribution among patient with FGID among studies. In ours, the age group (41- 50) years, is the largest but for Nakajima [11] (70-79) years was the largest. Mean of age also is different 57.8 years for [11] while for us it is 43.72 years. Other studies using Rome III criteria found a mean of age not far from ours, Tang [30], 45.55±10.68 and Liu [14] 44.36±0.35. Despite difference in methods between studies, the age related high frequency of disorders in [30-60years] in our case, is comparable to several studies’ [11,14,30,] as both normal physiological changes and pathological conditions are related to age. Consequently, the occurrence of symptoms is likely to vary in different age groups. In our study we found that FGIDs decrease with ageing, as did Fang-Yuan et al. [15]. Age may significantly be related to the prevalence of FGIDs, for example Chang [41] found that IBS, FAP, Fd decreased with age while Fc increased with age, and discordance for Fb. It is thought that the high prevalence among young adult is due to psychological factors as they are influenced by studying, job-seeking, or economic status [15]. Functional bowel symptoms nonetheless are common in the elderly, in whom they are more likely to be misdiagnosed or attributed to organic findings of uncertain significance [46].

Likewise majority of studies found that FGID is more prevalent in women, while other few studies found equal or male prevalence in FGID distribution. Corazziari [1] reported a 2:1 female: male ratio for chronic abdominal pain and constipation, a 1:1.5 male predominance for functional bloating. Others authors [7,10,15,41] found a greater prevalence of FGIDs in female except for functional diarrhea. We also found functional diarrhea to be more prominent in male in our study. According to Chang et al. [41] there is female sex hormone effect on patients with IBS in visceral pain perception and on psychological measures (Female > Male).

There is discordance in gender prevalence of IBS in Asia: while some countries have male predominant prevalence (Mumbai and Pan-India, Korea), others female predominant prevalence (Japan) and equal prevalence Pakistan and China [47]. For Husain et al. [48] the equal sex ratio of IBS in urban Pakistan could result from a close association between marked distress and IBS in men similar to that found in women in western studies. A FGID study in Taiwan general population [28] revealed that subjects affected were younger, had less vegetables and fruits intake, higher BSRS (brief-symptom rating scale) score and were of greater female predominance. Grodzinsky et al. [19], found that the gender difference might be randomly due to an unknown factor or to the fact that more women suffered from IBS and seek healthcare more often when their children have the same GI complaints.

Another study by Hammer [15] revealed that constipation and bloating were more frequent in females independently whether they have IBS or organic disease; all the diagnostic criteria for IBS had higher predictive value in females compared to males. The possible explanation for the apparent sex specificity in IBS includes the following: differences in symptom perception, GI function, or the socially learned response to symptoms by sex, difference in symptomatic response to treatment between sexes, women having slower gut transit times which explain why they report less frequent stools and a higher prevalence of constipation [29,41,49].

FGIDs relation with drugs intake

In this study 16.4% of the population reported a drug intake, out of them 58. 54 % have a FGID. However we found no correlation between drugs intake and FGIDs occurrence (P=0.42) unless in FAP (P=0.014). Through literature [23,50,51] drugs-induced GI symptoms are recognized and drugs like laxatives, NSAIDs, steroids, calcium antagonists, antiacids, antidepressant, iron pills, narcotics could cause FGIDs. Indeed, long-term narcotic use can cause the Narcotic Bowel Syndrome (NBS), a chronic or periodic abdominal pain that gets worse when the effect of the narcotic drug wears down. For Bhat [52], the likelihood of symptoms being functional increased even further if adverse reactions to both drugs and foods were reported. Patients with weight gain were more likely to report food allergy, and those with both features were very likely to have a functional disorder (OR: 4.58, 95% CI: 3.08�6.86) [52]. Patients with gastrointestinal symptoms who report drug or food allergies or worsening of symptoms with various foods are more likely to have functional than organic illness [52].

FGIDs and psychological factors

Studies have corroborated this association for a while. In our study we found prevalence of stress 25.27%, anxiety 17.03 %, depression 2.15%, panic disorder 3.77 % and others psychological conditions 5.2% however their degree of relation with FGIDs is variable. For example stress is significantly related to IBS (P=0.002), FUBD (P=0.007), FAP (P=0.009), Fc (P=0.009), Fb (P=0.026) and depression to FAP (P=0.001), FUBD (P=0.001), Fb (P=0.036). Routinely psychological factors had higher close relationships with FBDs [7] and FAP [38] than others FGIDs. Psychological factors have been reported in Chinese studies as in western studies to play a role in the pathogenesis of IBS [26]. A study by Monnikes et al. [53] found that stress induces differential motor effects on the upper and lower GI tract in healthy human subjects, better the role of stress and stressful events is well recognized in patients with FGID [54,55]. More precisely Mussel [39] found that the prevalence of severe levels of depression was nearly fivefold in patients with GI symptoms compared to patients without GI symptoms (19.1% vs. 3.9%; Pb.001), and the prevalence of severe levels of anxiety was nearly fourfold in patients with GI symptoms compared to patients without GI symptoms (19.4% vs. 5.6%; Pb.001). Psychological stress is widely believed to play a major role in IBS by precipitating exacerbation of symptoms. Body of evidence from experimental studies suggest that the central nervous system CNS response to stress modulates the autonomic nervous system outflow, activates the hypothalamicpituitary- adrenal axis and alters pain modulator mechanisms, these effects can be associated with changes in GI motility and visceral sensitivity [53]. Thus illness behaviors, life stress, psychosocial factors understanding were important in treatment as they are predictors of favorable outcome [49]. Indeed women with FGID appear to respond well to psychological treatment while men have shown less response [41]. Additionally another study by V. Lee et al. [56] confirmed that psychological factors are significantly associated with health-related quality of life in patients with IBS in primary care. In our study, stress and depression have a higher relationship with IBS compared to the remaining FGIDs. Drossman [57] found that in IBS patients, the most co-morbid psychiatric disorders were anxiety, mood disorder, and somatoform disorder. Anxiety and depression were found to be related to FAP [37] and IBS [58]. In opposition John [28] found no difference in rates of psychiatric illness in subjects according to the presence of functional GI symptoms.

There is evidence that colon is more sensitive to stress than other parts of GI tract, whether this explain the effects of stress in IBS and why IBS is the most common functional bowel disorder is unclear. Emotional distress may either stimulate or inhibit motility, contributing to diarrhea or constipation in the 30% of the US population with IBS [39]. Anxiety, major depression, social phobia, panic disorder, somatization etc. have been identified in more than 50% of patients with IBS [38]. IBS appears to be part of a continuum of GI and CNS reactions to external and internal stimuli and many people have functional GI symptoms in response to emotional stress [59].

The strength of our study is that the questionnaires were filled in front of a doctor or a trained assistant what resolve eventual misunderstanding immediately, contrary to a retrospective study or survey (mailed questionnaire). In addition all the enrolled subjects have undergone colonoscopy what improve our FGIDs diagnostic accuracy. More we have obtained “true FGIDs” prevalence unlike symptom-based diagnostic method which relies on absence of alarm symptoms and meeting of Rome III criteria.

The limit of our study is its patient-based footprint, while a population-based study will inform us better on a large sample distribution and in non healthcare seeking subjects such that the majority of FGIDs patients will not consult a practitioner for their symptoms. Also it is a transversal study so we don’t have any idea on the natural history and evolution of symptoms over the time compare to a follow up study.

Conclusion

Our study has revealed that 55.7% of symptomatic GI patients have a FGID; around 10% of patients are “unclassified patients”; a high overlapping among different FGIDs (72.04%). FGIDs are common and data have showed that FGIDs are strongly related to gender, we also found that these disorders are more frequent among under-50 years old and decrease after 50 years. There is relationship between FGIDs and psychological factors like stress and depression, a just as there is correlation in some drugs intake and the occurrence of FAP. Stress is found to be a risk factor for FGIDs. There is need for further studies to evaluate less investigated FGIDs such Fd, Fb, FUBD for better knowledge.

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