Association between gastroesophageal reflux disease and functional dyspepsia: A systematic review and meta-analysis

Table 1 Basic characteristics of the included studies

Ref.	Countries	Study type	Sample size	Men (%)	Age, mean, median or range	GERD diagnosis criteria	FD diagnosis criteria	Confounders adjusted	Quality scores
Locke et al[17], 2000	United States	Cross-sectional study	643	47.6%	48	Modified BDQ	Modified BDQ	Age, sex, and somatic symptom score	AHRQ scores 8
Noh et al[18], 2010	South Korea	Cross-sectional study	2388/360	44.1%/80.0%	43.2 ± 8.4/43.0	Modified Korean BDQ, Endoscopy	Modified Korean BDQ, Rome III	Age, sex, BMI, SSC, smoking status, alcohol use, marital status, and education	AHRQ scores 8
Fujiwara et al[19], 2011	Japan	Cross-sectional study	2680	65.7%	40.0	Self-report questionnaire, GERD symptoms	Self-report questionnaire, Rome III	Age, sex, BMI, smoking habits, drinking habits	AHRQ scores 7
Choi et al[20], 2013	South Korea	Cross-sectional study	4565/678	51.9%	46.3 ± 10.3	Modified Korean BDQ, endoscopy	Modified Korean BDQ, Rome III	Age, sex, BMI, hiatal hernia, SSC score	AHRQ scores 8
Jarbøl et al[21], 2017	Denmark	Cross-sectional study	47090	47.7%	51.7 ± 15.5	Comprehensive questionnaire-extracted from RIIIAQ, Montreal definition	Comprehensive questionnaire-extracted from RIIIAQ, Rome III	Age and sex	AHRQ scores 9
Lee et al[22], 2009	South Korea	Cross-sectional study	1443	46.6%	48.6	Questionnaire, GERD symptoms	Questionnaire, Rome II	Age	AHRQ scores 7
Nakov et al[23], 2023	Bulgaria	Cross-sectional study	1896	26.9%	35.5 ± 11.7	Questionnaire on general and GI health, modified Montreal definition	Questionnaire on general and GI health, Rome IV	—	AHRQ scores 7
Hu et al[24], 2002	China (Hong Kong)	Cross-sectional study	1649	47.0%	37.9 ± 15.0	Validated bowel symptom questionnaire, GERD symptoms	Validated bowel symptom questionnaire, Rome I	Age, sex, occupation, educational level, frequency and severity of symptoms and the degree of depression score	AHRQ scores 8
Choung et al[25], 2012	United States	Cross-sectional study	3527	48.0%	61 ± 15	Modified BDQ, GERD symptoms	Modified BDQ, Rome III	Age, sex, SSC score, constipation, diarrhea, IBS	AHRQ scores 8
Shaib and El-Serag[26], 2004	15 low- and middle-income countries	Cross-sectional study	5506	41.8%	32.7 ± 14.3	Questionnaire, GERD symptoms	Questionnaire, FD symptoms	-	AHRQ scores 6
Hongo[27], 2011	Japan	Cross-sectional study	Electronic survey (n = 2125); postal survey (n = 11020)	-	-	Questionnaires on GI symptoms, all items were evaluated in 3 to 5 Likert scales, GERD symptoms	Questionnaires on GI symptoms, all items were evaluated in 3 to 5 Likert scales, FD symptoms	-	AHRQ scores 5
Pleyer et al[28], 2014	United States	Cohort study	382	-	-	The international classification of diseases, 2nd edition (HICDA-2) coding system codes	The international classification of diseases, 2nd edition (HICDA-2) coding system codes	Age, sex, calendar year	NOS scores 7
Ohara et al[29], 2011	Japan	Cross-sectional study	1076	44.1%	55.8 ± 3.3	Questionnaire based on symptoms defined according to the Montreal definition, endoscopy	Questionnaire based on symptoms defined according to the Rome III criteria	—	AHRQ scores 7
Chirila et al[30], 2016	Romania	Cross-sectional study	184	42.4%	49.4	Questionnaire, Montreal definition	Questionnaire, Rome III	Age, sex, educational level, smoking status, physical activity level, BMI, perceived stress level, general wellbeing, frequency of other food items	AHRQ scores 8
Jones et al[31], 2022	Australia	Cohort study	1312	51.0%	62 ± 14	A single question as the Montreal definition	Questionnaire, Rome III	Age, sex	NOS scores 6
Caballero-Mateos et al[32], 2023	Spain	Cross-sectional study	338	38.5%	47.9	GERDQ, endoscopy	Rome IV	Age, sex, BMI, alcohol consumption, use of calcium channel blockers, use of inhalers, HADS score	AHRQ scores 8
Fujita et al[33], 2024	Japan	Cross-sectional study	3085	53.5%	48.8 ± 9.1	Questionnaire, endoscopy	Questionnaire, Rome III	Age, sex, BMI, current smoking, alcohol consumption, anxiety (high STAI score), hiatal hernia, FD subtype, frequency of acid reflux symptoms	AHRQ scores 10
Lee et al[34], 2022	South Korea	Cohort study	733	41.3%	52.7 ± 13.1	Korean BDQ, GERDQ, endoscopy	Korean BDQ, GERDQ, Rome III	Age, sex, BMI, smoking, alcohol, marital status, education, HADS score	NOS scores 5
Mochizuki et al[35], 2018	Japan	Cohort study	7552	63.1%	52.4 ± 10.0	Questionnaire, GERD symptoms, endoscopy	Questionnaire, Rome III	Age, sex, BMI, smoking, alcohol consumption, hiatal hernia, atrophic gastritis, Barrett’s mucosa, anxiety (STAI), stress, overlapping FD, LA grade, and medication use	NOS scores 7
Wu et al[36], 2007	China (Hong Kong)	Cross-sectional study	224	46.9%	50.6	Symptom assessment, endoscopy, esophageal manometry, esophageal pH monitoring	Symptom assessment, Rome II	Age, sex, severity of heartburn, disease duration, obesity, smoking, alcohol, FD, IBS, psychological disorders, hiatal hernia, Helicobacter pylori infection, esophageal dysmotility, positive acid perfusion test result, abnormal esophageal pH study	AHRQ scores 9
Lee et al[37], 2015	China (Taiwan)	Cross-sectional study	222	49.6%	46.7	Modified Chinese GERDQ, Montreal definition, endoscopy	Rome III	Age, sex	AHRQ scores 6
Lee et al[38], 2014	China (Taiwan)	Cross-sectional study	171	49.6%	46.7	modified Chinese GERDQ, Montreal definition, endoscopy	Rome III	-	AHRQ scores 5
Saberi-Firoozi et al[39], 2007	Shiraz, southern Iran	Cross-sectional study	304	29.4%	49.9 ± 11.1	Questionnaire, GERD symptoms	-	-	AHRQ scores 6
Locke et al[40], 1997	United States	Cross-sectional study	303	-	25-74	Questionnaire, GERD symptoms	-	Age, sex, PSC score, other atypical symptoms	AHRQ scores 9
Yi et al[41], 2012	China (Taiwan)	Cross-sectional study	210	35.7%	45.9	Questionnaire, GERD symptoms, endoscopy	-	-	AHRQ scores 6
Mwandri et al[42], 2014	Northern Tanzania	Cross-sectional study	92	53%	47.3 ± 17.0	Questionnaire, GERD symptoms, endoscopy	-	-	AHRQ scores 5
Bor et al[43], 2016	Moscow	Cross-sectional study	251	-	-	modified Mayo Clinic GERD questionnaire, GERD symptoms	-	-	AHRQ scores 7
Alsulobi et al[44], 2017	Arar city, Northern Saudi Arabia	Cross-sectional study	186	29.0%	-	Questionnaire, GERD symptoms	-	-	AHRQ scores 4
Savarino et al[45], 2009	Switzerland and Italy	Cross-sectional study	200	47.5%	48	Symptom questionnaire, oesophageal multichannel intraluminal impedance and pH monitoring, endoscopy	-	-	AHRQ scores 7
Sarwar et al[46], 2021	Pakistan	Cross-sectional study	218	0	30	GERDQ, Montreal definition	-	-	AHRQ scores 7
Kitapçioğlu et al[47], 2007	Turkey	Cross-sectional study	126	-	43.7	Reflux questionnaire derived from Locke	-	-	AHRQ scores 8
Nagami et al[48], 2011	Japan	Cross-sectional study	GERD: 210/FD: 378	33.6%	60	Self-reporting type of questionnaire, GERD symptoms, endoscopy	Self-reporting type of questionnaire, Rome III	-	AHRQ scores 5
Bytzer et al[49], 2000	Denmark	Cross-sectional study	217	5%	43	-	Questionnaire on dyspeptic symptoms, Endoscopy	-	AHRQ scores 7
Bolling-Sternevald et al[50], 2002	Denmark and Sweden	Cross-sectional study	404	41%	42.8 ± 14.1	-	GSRS, the Carlsson-Dent Questionnaire, PGWB, Endoscopy, Rome I	Age, sex, GSRS, PGWB, Carlsson-Dent index total score	AHRQ scores 8
Peura et al[51], 2004	United States	Randomized controlled trial	921	37.8%	43	-	A dyspepsia symptom questionnaire, endoscopy, Rome criteria	Age, sex, race, Helicobacter pylori status, baseline endoscopic findings, weight, alcohol use, tobacco use, caffeine use	AHRQ scores 10
Tack et al[52], 2018	Belgium	Cross-sectional study	247	32.8%	44	-	Symptom questionnaire, ambulatory pH monitoring, gastric emptying studies, sensitivity to gastric distention and gastric accommodation, Rome II criteria	Age, sex, BMI, Helicobacter pylori infection status, delayed gastric emptying, hypersensitivity to gastric distention, impaired gastric accommodation	AHRQ scores 7
Xiao et al[53], 2010	China	Cross-sectional study	186	38.7%	39 ± 12	-	Questionnaire based on the Rome III, abdominal ultrasound, endoscopy, Ambulatory 24-hour esophageal-gastric dual pH monitoring	-	AHRQ scores 8
Aro et al[54], 2011	Sweden	Cross-sectional study	157	49%	54	-	Extended ASQ, Rome III, endoscopy	Anxiety, depression, use of proton pump inhibitors, age, sex	AHRQ scores 9
Aro et al[55], 2015	Sweden	Cohort study	110/93	48.1%	53/63.2	-	ASQ, Rome III, esophagogastroduodenoscopy	Age, sex, BMI, smoking, high alcohol consumption, Helicobacter pylori infection, use of NSAIDs and/or aspirin, use of PPIs, anxiety, depression	NOS scores 9
Rahman et al[56], 2021	Bangladesh	Cross-sectional study	232	32.8%	41.1	-	Enhanced Asian Rome III questionnaire, endoscopy, including Helicobacter pylori tests from gastric biopsies	Age, sex, marital status, family income, use of NSAIDs and aspirin, psychological distress, history of acute gastroenteritis, education	AHRQ scores 8

GERD: Gastroesophageal reflux disease; FD: Functional dyspepsia; BDQ: Bowel disease questionnaire; AHRQ: Agency for healthcare research and quality; BMI: Body mass index; SSC: Somatization symptom checklist; IBS: Irritable bowel syndrome; RIIIAQ: ROME III questionnaires; GI: Gastrointestinal; HICDA-2: Hospital international classification of diseases adaptation, second edition; NOS: Newcastle-Ottawa Scale; HADS: Hospital Anxiety and Depression Scale; STAI: State-Trait Anxiety Inventory; GERDQ: Gastroesophageal reflux disease questionnaire; PSC: Psychosomatic symptom checklist; GSRS: Gastrointestinal Symptom Rating Scale; PGWB: Psychological General Well-Being Questionnaire; ASQ: Abdominal Symptom Questionnaire; NSAIDs: Non-steroidal anti-inflammatory drugs; PPIs: Proton pump inhibitors; NSAIDs: Non-steroidal anti-inflammatory drugs.