J Neurogastroenterol Motil 2024; 30(1): 64-72  https://doi.org/10.5056/jnm22197
The Disease Spectrum and Natural History of Patients With Abdominal Bloating or Distension: A Longitudinal Study
Fangfei Chen, Niandi Tan, Songfeng Chen, Qianjun Zhuang, Mengyu Zhang, and Yinglian Xiao*
Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Correspondence to: *Yinglian Xiao, MD
Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Tel: +86-20-87755766, E-mail: xyingl@mail.sysu.edu.cn

Fangfei Chen and Niandi Tan contributed equally to this study.
Received: November 16, 2022; Revised: February 23, 2023; Accepted: March 26, 2023; Published online: January 30, 2024
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
Abdominal bloating or distension (AB/D) is a common complaint in the outpatient of gastroenterology department. Since the potential contributors are numerous and complex, a longitudinal study on the disease spectrum and natural history of patients was performed to better understand the key factors of AB/D.
Methods
Consecutive patients with the chief complaint of AB/D referred to the outpatient clinic were screened. Functional gastrointestinal disorders (FGIDs) were diagnosed according to Rome IV criteria. A 3-year follow-up was performed to seek for the changes in symptoms as well as disease spectrum.
Results
A total of 261 participants were enrolled and 139 completed the follow-up. Most patients suffered from moderate to severe symptoms more than 1 day per week. Common causes of AB/D were FGIDs (51.7%) and organic diseases (17.2%). The latter group was older with lower body mass index (BMI). Functional dyspepsia was the most common type of FGIDs in AB/D. The symptoms of 18.0% of participants failed to improve at the end of the 3-year follow-up, and those diagnosed with FGIDs were most likely to continue to suffer. Abdominal pain was a positive predictive factor for good prognosis in the FGIDs group. Besides, only 22.7% of participants had a consistent diagnosis of FGIDs during follow-up.
Conclusions
FGIDs are the most common diagnosis in patients with AB/D. Symptoms were especially hard to be improved. Classification diagnoses of FGIDs in AB/D patients fluctuated significantly over time.
Keywords: Dyspepsia; Flatulence; Irritable bowel syndrome; Prognosis
Introduction

Abdominal bloating or distension (AB/D) is one of the most common complaints in patients of the gastroenterology department.1 Bloating refers to an uncomfortable feeling of increased pressure or fullness in the abdomen, while distension is an objective increase in abdomen girth. However, it is hard to distinguish bloating from distension in the Chinese language because these 2 symptoms share the same expression in Chinese.2 The prevalence of abdominal bloating with or without visible distension ranges from 16.0% to 31.0% in the general population.3 This symptom severely influences the quality of life of the patients, leading to repeated physician visits and heavy medical burden.4 Also, the pathogenesis of AB/D is complex, including food intolerances, altered intestinal microbiota, abnormal visceral sensation, delayed gastrointestinal motility, etc.3,5-8

AB/D could be a manifestation of many organic diseases such as gastrointestinal infection, bowel obstruction, and even neoplastic diseases. Moreover, it is one of the predominant symptoms in patients with functional gastrointestinal disorders (FGIDs), even though it has not been part of the Rome IV criteria for many FGIDs yet.9-12 It is reported that 67.0% to 90.0% of patients with irritable bowel syndrome (IBS) with constipation had suffered from AB/D.13-15 Besides, bloating is also common in other FGIDs, such as functional constipation (FC), functional dyspepsia (FD), functional diarrhea (FDr), and functional abdominal bloating/distension (FAB/D).16,17 Recently, a study of outpatients with FC or IBS with constipation suggests that bloating had a great impact on quality of life and satisfaction with treatment.18 Although AB/D is common in the clinic, the constitution of underlying diseases as well as their association with long-term prognoses of patients with AB/D have seldom been investigated.

To help fill the gap, we conducted a longitudinal study to investigate the characteristics of symptoms and underlying disease spectrum of patients with AB/D. Meanwhile, a 3-year follow-up was conducted to assess the natural history of these patients in order to achieve a better understanding of AB/D as well as its prognosis.

Materials and Methods

Subjects and Data Collection

Consecutive adult patients with the chief complaint of AB/D no less than 6 months in the outpatient clinic of gastroenterology of our hospital from March 1st to May 31st, 2018 were screened. The main exclusion criteria were: lack of appropriate examinations for diagnosis, pregnancy, and incapability to complete the questionnaire.

During the first visit, subjects were required to fill in a questionnaire for baseline information collection. The questionnaire consisted of 2 parts: demographic and symptomatic data. Past medical history was also collected. Symptomatic data was comprised of the characteristics of bloating and distension (duration, frequency, severity, location, pattern, concomitant symptom, contributor, etc.) and a diagnostic questionnaire for FGIDs. We used the Chinese version of the Rome IV Diagnostic Questionnaire for Adults to identify FGIDs patients (see the English version in Appendix).19-21 Clinical examinations records were reviewed, including laboratory tests, endoscopy, ultrasound, MRI, or CT scan of the abdomen, and tests for Helicobacter pylori infection. All subjects included had gastroduodenoscopy within 3 months from the first visit. The diagnosis was made by 2 experienced physicians (Y.X. and N.T.) independently. Subjects were classified as “undetermined group” who could not meet the criteria for FGIDs and had no evidence of organic diseases concurrently. A 3-year follow-up survey was performed by telephone, and the same questionnaire was inquired again as the baseline. Additional examination data, therapy, and treatment outcomes were also recorded.

Informed consent was obtained from every subject included. The study was approved by the ethics committees of the First Affiliated Hospital of Sun Yat-sen University (Approval No. [2017]248).

Definition and Evaluation of Symptoms

Bloating referred to a subjective uncomfortable feeling of increased pressure or fullness in the abdomen. While distension referred to an objective increase in abdomen circumference. Pictographs were adopted for better distinction between bloating and distension.22,23 Location of discomfort was determined based on abdominopelvic quadrants. The severity of AB/D was evaluated by a scoring system ranging from 0 to 5 points: 0, none; 1, very mild; 2, ignorable unless thinking of it; 3, unignorable with little or no impact on life; 4, moderate impact on life; and 5, great impact on life. Severity was further divided into 3 degrees according to the score: 0-1 was defined as mild, 2-3 as moderate, and 4-5 as severe. The frequency of AB/D was also assessed using scores: 0, none; 1, less than one day per month; 2, one day per month; 3, twice or three days per month; 4, one day per week; 5, twice or three days per week; 6, four to six days per week; and 7, every day. Symptom resolution was defined as the disappearance of any symptom including AB/D as well as concomitant symptoms.

Statistical Methods

SPSS (version 23.0; IBM Corp, Armonk, NY, USA) was applied for the statistical analysis. A t test and one-way ANOVA was performed for comparison of continuous variables that complied with the normal distribution. Otherwise, the Mann-Whitney U test was used. Chi-square and Fisher’s exact tests were conducted for the comparison of categorical variables, such as sex, severity, and frequency of symptoms in different groups. A forward stepwise multiple logistic regression model was created to explore the predictive factors for organic diseases and prognosis. The level of significance was set at 0.05.

Results

Characteristics of Subjects

A total of 8461 patients visited the outpatient clinic of gastroenterology during this period, and 470 (5.6%) of them had a chief complaint of AB/D. Among them, 304 subjects agreed to participate and filled in the questionnaires, and 85.8% (261/304) of them were enrolled in the final analysis with an average age of 45.7 years old (Supplementary Figure). The remaining 43 subjects were excluded from the final analysis for the following reasons: incomplete questionnaires (n = 6), symptom duration less than 6 months (n = 20), and lack of appropriate examinations to ensure a diagnosis (n = 17).

Bloating was more common than distension as depicted by participants (77.0% vs 23.0%). The demographic and symptomatic characteristics of participants with bloating or distension had no significant differences (Supplementary Table). The severity of symptoms was most often rated as moderate (52.9%). Still, 24.5% of subjects had severe symptoms that impaired their daily life. For the majority of subjects, the frequency of symptoms is no less than 1 day per week (97.7%), and symptoms were most often located in the upper abdomen.

A total of 139 subjects completed the 3-year follow-up, while the others were lost to follow-up because of death (2) (due to gastrointestinal carcinoma and relevant complications), unavailability (117), or declined further participation in the study (3). The characteristics of the participants were listed in Table 1. There was no significant difference between participants who completed follow-up and who were lost concerning the demographic features and characteristics of symptoms.

Table 1 . The Characteristics of Participants at Baseline and Follow-up

CharacteristicsBaseline
(n = 261)
Follow-up
(n = 139)
Lost
(n = 122)
P-value
Age (yr)45.7 ± 15.645.1 ± 15.246.4 ± 16.00.517
Sex
Male112 (42.9)63 (45.3)49 (40.2)0.401
Female149 (57.1)76 (54.7)73 (59.8)
BMI (kg/m2)22.0 ± 3.222.0 ± 3.121.9 ± 3.40.759
Symptom
Bloating201 (77.0)110 (79.1)91 (74.6)0.384
Distension60 (23.0)29 (20.9)31 (25.4)
Severity
Mild59 (22.6)31 (22.3)28 (23.0)0.869
Moderate138 (52.9)71 (51.1)65 (53.2)
Severe64 (24.5)37 (26.6)29 (23.8)
Frequency
Less than 1 day a week6 (2.3)5 (3.6)1 (0.8)0.315
1-3 days a week78 (29.9)41 (29.5)39 (32.0)
More than 3 days a week177 (67.8)93 (66.9)82 (67.2)
Locations
Upper abdomen153 (58.6)85 (61.2)68 (55.7)0.661
Lower abdomen75 (28.7)38 (27.3)37 (30.3)
Whole abdomen33 (12.7)16 (11.5)17 (14.0)

BMI, body mass index.

Data are presented as mean ± SD or n (%).

The P-value of comparison between subjects with follow-up and those who were lost was given.



Disease Spectrum at Baseline

Of the 261 subjects enrolled at baseline, 135 (51.7%) met the criteria for FGIDs, and 45 (17.2%) subjects were detected with organic causes after necessary examinations (Fig. 1). The remaining 81 (31.0%) subjects were included in the undetermined group.

Figure 1. The disease spectrum in participants with abdominal bloating/distention at baseline. (A) Diagnostic constitution of all subjects. (B) Detailed constitution of diagnosis in subjects of the organic group. (C) Detailed constitution of diagnosis in subjects of functional gastrointestinal disorders (FGIDs) group. FD, functional dyspepsia; FC, functional constipation; FDr, functional diarrhea; FAB/D, functional abdominal bloating/distension; IBS, irritable bowel syndrome.

Peptic ulcer disease was the most common organic disorder, accounting for 55.6% of subjects in the organic group. While 8 subjects (17.8%) were found to have neoplasm, and the rest were diagnosed with cholecystitis, bowel obstruction, etc (Fig. 1).

In the FGIDs group, the most common diagnosis was FD (34.1%), followed by FAB/D (18.5%), and the proportion of FDr and FC was 10.4% and 6.7%, respectively. Irritable bowel syndrome (IBS) made up the other 6.7%. Overlapping of FGIDs was also quite common, including FC overlapped with FD (10.4%), FDr overlapped with FD (8.9%), and IBS overlapped with FD (4.4%).

Subjects with organic diseases at baseline were generally older than the other 2 groups and had relatively lower BMI. There was no significant difference in severity or frequency among the 3 groups at baseline (Table 2). BMI and locations of AB/D symptoms were found to be predictive factors of organic causes by logistic regression (P = 0.004 for BMI, P = 0.036 for locations).

Table 2 . The Characteristics of Participants With Different Diagnoses at Baseline

CharacteristicsOrganic
(n = 45)
FGIDs
(n = 135)
Undetermined (n = 81)P-value
Age (yr)50.5 ± 18.246.7 ± 15.241.4 ± 13.60.004
Sex
Male19 (42.2)56 (41.5)37 (45.7)0.829
Female26 (57.8)79 (58.5)44 (54.3)
BMI (kg/m2)20.8 ± 2.922.4 ± 3.321.8 ± 3.20.016
Severity
Mild9 (20.0)28 (20.7)22 (27.1)0.205
Moderate27 (60.0)66 (48.9)43 (53.1)
Severe9 (20.0)41 (30.4)16 (19.8)
Frequency
Less than one day a week1 (2.2)3 (2.2)2 (2.5)0.260
1-3 days a week9 (20.0)45 (33.3)26 (32.1)
More than 3 days a week35 (77.8)87 (64.5)53 (65.4)
Pattern
Persistent15 (33.3)51 (37.8)24 (29.6)0.510
Intermittent30 (66.7)83 (61.5)55 (67.9)
Missing0 (0.0)1 (0.7)2 (2.5)
Sites
Upper abdomen29 (64.4)74 (54.8)50 (61.7)0.120
Lower abdomen9 (20.0)48 (35.6)18 (22.2)
Whole abdomen7 (15.6)13 (9.6)13 (16.0)
Contributors
Diet35 (77.7)107 (79.0)55 (67.9)0.159
Emotion or psychological pressure3 (6.7)7 (5.0)6 (7.4)0.794
Accompanying symptoms
Abdominal pain13 (28.9)41 (30.0)30 (37.0)0.418
Reflux or heartburn7 (15.6)22 (16.0)12 (14.8)0.977
Constipation6 (13.3)18 (13.0)4 (4.9)0.147

BMI, body mass index.

Data are presented as mean ± SD or n (%).

The P-value of comparison among the three groups with different diagnoses was given.



The Natural History of Patients With Abdominal Bloating or Distension

Of the 139 subjects who completed the 3-year follow-up, 114 (82.0%) got symptom improvement regarding frequency and severity, of which 60 (43.2%) achieved complete remission of any symptoms. The remaining subjects (18.0%) still suffered from similar or even worse symptoms.

Change of symptoms at follow-up was compared between the FGID group with the undetermined group (Fig. 2). Although the severity and frequency of AB/D were similar at the baseline, subjects in the FGIDs group were less likely to have an improvement in symptoms concerning both severity and frequency at follow-up, compared to the undetermined group (average change in the score of severity: 1.56 ± 0.21 in FGIDs group vs 2.00 ± 0.22 in undetermined group, P = 0.040; average change in the score of frequency: 3.45 ± 0.37 in FGIDs group vs 4.89 ± 0.42 in undetermined group, P = 0.024). Besides, 50.7% of subjects in the FGIDs group continued to suffer from AB/D. The proportion was also larger than the undetermined group (31.8% in the undetermined group, P = 0.045). Twenty-five percent of subjects in the undetermined group developed FGIDs at follow-up. In the 20 subjects with organic causes who completed follow-up, 8 subjects still suffered from AB/D, 4 of which met the diagnostic criteria of FGID at follow-up. There was no discrepancy in the severity or frequency of symptoms between subjects with bloating and those with distension at follow-up (Supplementary Table).

Figure 2. The change in frequency (A) and severity (B) of abdominal bloating/distention symptoms during 3-year follow-up among participants with different initial diagnoses. FGID, functional gastrointestinal disorder.

Predictive factors for prognosis were examined in both groups. In the FGID group, the cure rate in subjects with and without abdominal pain at baseline was 50.0% vs 23.2%, respectively (P = 0.031). While in the undetermined group, 58.3% of subjects with persistent AB/D were diagnosed with FGID at follow-up, and that the proportion in subjects with intermittent symptoms was 12.5% (P = 0.006).

The Natural History of Functional Gastrointestinal Disorders in Patients With Abdominal Bloating or Distension

There were 75 subjects diagnosed with FGIDs at baseline and also finished the 3-year follow-up. Among them, 58.7% (44/75) still met the diagnostic criteria for FGIDs. However, the disease spectrum changed remarkably (Fig. 3). Only 17 (22.7%) subjects had a consistent diagnosis. FC seemed to be the most stable FGID diagnosis in bloating patients, with 64.3% of them continuing to have the same diagnosis after 3 years.

Figure 3. The change in diagnoses of subjects with functional gastrointestinal disorders (FGIDs) after 3 years. This figure showed how the subtypes of FGIDs transformed at follow-up from baseline. The subtypes of FGIDs at baseline were given on the left, and the bar next to them showed the constitution of FGIDs subtypes 3 years later. FAB/D, functional abdominal bloating/distension; FDr, functional diarrhea; FC, functional constipation; IBS, irritable bowel syndrome; FD, functional dyspepsia.
Discussion

In this longitudinal study, we prospectively examined the change of symptoms as well as diagnoses in the outpatients with a chief complaint of AB/D in a tertiary hospital in south China. Two hundred and sixty-one participants were included in the study, of which 139 completed the 3-year follow-up. Those who completed the study and subjects lost during the follow-up did not have significant differences concerning demographic characteristics or symptomatic features. At baseline, more than half of the patients suffered from moderate AB/D symptoms. One-quarter suffered from severe discomfort. The ratio was in accordance with a previous study in the United States (US).24 Two-thirds of subjects had a symptom frequency of more than 3 times a week. The upper abdomen was the most common site affected, and the majority of patients regarded diet as a contributor to their symptoms. Indeed, AB/D was usually comprehended as discomfort in the stomach in Chinese sociocultural perspectives, and diet had a strong association with disorders of gut-brain interaction, as mentioned in previous studies.2,25-27 Consistent with other studies, bloating was more prevalent than distension28 and there was no significant difference between the bloating group and the distension group, in terms of demographic or clinical characteristics, as well as prognosis. An epidemiological study on a representative US population also suggested that bloating had similar risk factors with distension.29 These results indicate that though different in presentation, bloating and distension may share the same mechanism. As for accompanying symptoms, abdominal pain was the most common symptom, reported in one-third of subjects.

As for the underlying disease spectrum, FGIDs contributed to almost half of the patients with bloating or distension in our research population. While about a fifth of individuals were found to have organic diseases. The proportion is consistent with a recent study conducted in the outpatient clinic in a medical center in the US, in which 170 patients were diagnosed with organic disorders in 922 subjects screened.30 In regard to specific diseases, ulceration was the most common organic disease found in bloating individuals in our study. Indeed, the peptic ulcer was the only finding encountered more frequently in subjects with dyspepsia than those without in 2 meta-analyses of endoscopic findings in people with dyspepsia.31,32 More recently, a community study in Bangladesh also found peptic ulcer to be the most common endoscopic finding in dyspepsia individuals.33

Given the considerable proportion and possibly distinct therapeutic options, it is necessary to rule out organic causes in bloating and distension before considering functional conditions. However, as mentioned in a previous research,34 it was hard to discriminate organic diseases from functional disorders according to the degree or frequency of symptoms. In the current study, subjects with organic diseases were found to have older ages and relatively lower BMI compared with those FGIDs patients. Besides, bloating was more likely to occur in the upper abdomen or involve the whole abdomen in subjects with organic disorders. This indicates that age and BMI should be considered when screening for underlying organic problems, as suggested in the guideline.3 Sites of bloating might also provide clues for diagnosis and gastroscopy is an effective tool during this process.

A few studies have explored the incidence rate of FGIDs in patients with bloating. For example, a cross-sectional study of 1069 employees in a healthcare system in the US explored the relationship between bloating and gastrointestinal disorders.35 Consistent with our study, the most common disorder in participants with bloating was dyspepsia, accounting for 30.0%, followed by non-IBS with constipation (25.0%), IBS with diarrhea (11.0%), and alternating IBS (11.0%) in this research. Another recent study also suggested that FD was the most common FGID in bloating patients, with a prevalence rate as high as 72.0% in patients with severe bloating symptoms.30 Overlapping of FD with other FGIDs was common, as indicated in another study.36 However, long-term follow-up of the participants should be provided to grasp the information on the evolution of symptoms.

To further explore the prognosis of patients with AB/D, follow-up was conducted 3 years after the first visit. The bloating symptoms of most participants got improved at follow-up. However, nearly a fifth of participants did not have any remission or even worsened. Even though the symptomatic features were quite similar at the beginning, patients with FGIDs made less improvement compared to those in the undetermined group, both in frequency (P = 0.024) and severity (P = 0.040). This indicated that FGIDs had different prognoses from those who could not meet the diagnostic criteria. AB/D of FGIDs patients was quite challenging to manage. This could be partly attributed to the complicated etiology of FGIDs. Unlike most organic disorders which had a clear culprit and thus could be eradicated accordingly, FGIDs were usually a result of problems in the interaction of physical and psychological systems.37 Therefore, it is important for clinicians to distinguish FGIDs in patients with AB/D. It was worth noting that some subjects in the organic group continued to suffer from AB/D after management. This probably suggests that some patients diagnosed with organic disorders actually had complicated FGIDS.

Factors with potential correlations with prognosis were also examined in the study. Accompanying abdominal pain at the beginning was demonstrated to be a sign of a good prognosis in FGIDs. Individuals in the FGIDs group with abdominal pain had significantly higher cure rates than those without pain. Also, in the undetermined group, a persistent pattern of AB/D might be a risk factor for transformation to FGIDs at the follow-up three years later.

In addition, the constitution of FGIDs diagnosis fluctuated greatly over 3 years. Less than a quarter of patients had a consistent diagnosis of FGIDs during follow-up. Similar to our study, some other studies had investigated the natural history of FGIDs. Although the Rome IV criteria categorize FGIDs into distinct disorders, those disorders actually exist in a continuum rather than separated diseases.38 The diagnosis is likely to fluctuate from one to another during the disease process. A prospective cohort study of 1365 residents in the US over 12 years found a high turnover rate in symptom status in FGIDs.39 Several studies conducted on different populations had similar findings.40-43 Most of the studies were performed before the release of Rome IV in 2016. Many changes had been made to these criteria.44 A recent study examined the natural history of five functional bowel diseases over 12 months in 1372 adults in the United Kingdom, of which 782 completed the follow-up.45 It was suggested that IBS was the most stable functional bowel disease. About 70.0% of IBS patients still met the criteria for IBS after 1 year. While our study showed that FC was the most stable diagnosis. The inconsistency of the results probably lies in subject selection. Their study recruited participants who self-identified as having IBS and data was collected by online questionnaires. These may contribute to sampling bias in results.

Our study has several strengths that may aid the understanding of bloating. This study is the first to focus on the underlying disease spectrum and its influence on prognosis in the group of bloating. Exhaustive tests were completed to identify organic disorders. Diagnosis of FGIDs was made according to the latest Rome criteria. A long follow-up of 3 years enabled a deep comprehension of the natural history of bloating, as well as FGIDs. However, some limitations in our research should be pointed out. The subjects were recruited from the outpatient clinic of a single center in China, which may not be representative of the general population. Nearly half of the subjects could not be reached during follow-up. Despite a similar missing rate to other longitudinal studies with the same time frame, this can still lead to bias in results.45-47 Besides, Multi-centered studies of the general population on a larger scale are necessary for further evidence in the future. Psychological evaluations were not involved in this study such as scales of depression and anxiety, which proved to have a strong correlation with FGIDs. Even though only a small proportion of subjects enrolled recognized the relationship between psychological factors and their physical discomfort in the questionnaire, this might be a result of a general ignorance of mental disorders in China. Psychological comorbidities should have a particular emphasis in future researches.

In conclusion, our study demonstrated the prevalence of organic disorders and FGIDs in AB/D patients and found that symptoms in FGIDs patients were most likely to persist over time. The specific diagnoses of FGIDs subtypes were unstable and tend to fluctuate during follow-up. Therefore, FGIDs should be paid special attention to during the management of AB/D.

Supplementary Materials

Note: To access the supplementary figure and table mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm22197.

Financial support

The study was supported by grants from the National Natural Science Foundation of China (81970479 and 82170577).

Conflicts of interest

None.

Author contributions

Fangfei Chen contributed to the study concept and design, acquisition, analysis, and interpretation of the data, and drafting of the manuscript; Nandi Tan contributed in the acquisition, analysis, and interpretation of the data; Songfeng Chen and Qianjun Zhuang contributed in the analysis and interpretation of the data; Mengyu Zhang contributed in the study concept and design; and Yinglian Xiao contributed in the study concept and design, acquisition of funds, and finalizing and approving the manuscript. All authors approved the final version of the manuscript.

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