Application of Diaphragmatic Breathing in Patients With Disorders of Gut-brain Interaction: Impact on Gastrointestinal and Psychological Symptoms as Well as Autonomic Nervous System
Phase: NA
Conditions: Irritable Bowel Syndrome, Healthy Subjects, Functional Gastrointestinal Disorders, Laryngopharyngeal Reflux
Sponsor: Buddhist Tzu Chi General Hospital

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E6A0021096-10                                                           Total 30 Page, Page 1 
Hualien Tzu Chi Hospital  
Medical TechnologyResearch Project Proposal In the 
hospital 
A. 
Basic information            Application number：________________ 
Project Category 
(Single choice) 
■Individual Research Project: The principal investigator of this project is a 
senior member of our institution. 
■Experimental Research (up to 800,000 NT Dollars)  
□ Non-experimental Research (up to 400,000 NT Dollars) 
□Integrated Care Department Project (Maximum Budget: 800,000 NT Dollars) 
(Restricted to Department Heads for Application) 
□New Staff Research Project (Up to 200,000 NT Dollars)  
□School-Industry Collaboration Research Project (Up to 400,000 NT Dollars)  
□Transfer In-House Project of the Ministry of Science and Technology 
(Maximum Funding: 800,000 NT Dollars) 
□Medical Education Research Project (Up to 400,000 NT Dollars) 
人員類別 
(單選) 
■Physician 
□Non-Physician 
The Project 
Name 
Application of diaphragmatic breathing in patients with disorders of gut-brain 
interaction: impact on gastrointestinal and psychological symptoms as well as 
autonomic nervous system 
Principal 
Investigator 
Name 
Wong, 
Ming-Wun 
Job Title Attending Physician 
Applicant 
Department or 
Division 
Gastroenterology 
Project 
Execution 
Deadline 
From September 1, 2023 to December 31, 2024, a total of 1 year. 
Nature and 
Classification of 
Research 
□Fundamental Research ■Applied Research 
□Technological 
Development 
(Note: Innovators engaged in applied research and technological development 
should select the category of innovative research and development) 
Innovation and Research & Development Classification：■(1) Clinical Research 
□(2) Translational Research □(3)Medical Engineering and Materials □(4) 
Information □(5) Medical Assistance Operations □(6) Other, please specify 
______________。 
Holistic Care 
(Please refer to 
the noun 
explanations, 
multiple 
selections 
allowed) 
Holistic Care Classification： 
(1) Patient-Centered （■physiological ■psychological ■environmental 
□spiritual） 
(2) Health Education ( ■behavior 
change□health 
promotion■Disease 
Prevention■early diagnosis 
 
■Early Treatment) 
(3) Other, please specify __________________________________。 
Has the current in-house project ever applied for the 112th-year Ministry of Science and Technology 
Special Research Project? ■No  □Yes 
Has any application been made for government grants for various research projects in the current 
year?   □No  ■Yes, Total  1  items. 
This year, PI have applied to host a total of 1 research project within the institute. (Projects co-led 
with others will not be counted.) 
The priority order of this project is 1 . 

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E6A0021096-10                                                           Total 30 Page, Page 2 
Does this project require □No ■Human experiments/human specimens (including human 
embryos/human embryonic stem cells)□Animal Experimentation 
□Biosafety (including recombinant DNA experiments/genetically modified field trials/second-level 
or higher infectious biological materials) ?【Please check】 
Project Contact 
Person 
Name：Wong, Ming-Wun  Telephone：(03)8561825#13224 / 0982-098812  
E-MAIL：hypertr42@gmail.com 
 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 3 
B. 
Apply for Financial Assistance（Budget allocation will be included in the 
review scoring criteria; please do not inflate the budget.） 
In accordance with the actual needs of the research project, subsidies can be applied 
for the following items: For individual research projects, the upper limit for 
experimental researchers is 800,000 NT dollars, and for non-experimental researchers, 
the principle upper limit is 400,000 NT dollars. For newly recruited personnel research 
projects, the total research budget is capped at 200,000 NT dollars. For university-
industry collaborative research projects, the total research budget is capped at 400,000 
NT dollars. For projects under the Department of Whole Person Care, the budget 
ceiling is 800,000 NT dollars. Technology transfer projects within the Ministry of 
Science and Technology have a maximum budget limit of 800,000 NT dollars. 
 
Subsidy Programs 
Requested Amount 
Business 
expenses 
1. Research personnel 
expenses 
83,016 
2. Animal testing 
expenses 
 
3. Consumables, 
Supplies, Books, and 
Miscellaneous expenses 
716,984 
Research equipment expenses 
 
Total 
800,000 
 
 
C. 
Equipment configuration 
The principal instruments required for this project, their respective locations, and the 
signatures of the individuals authorized to use them.。 
Instrument Name 
Location Setup 
(Department) 
Signature of the Unit 
Supervisor/Manager agreeing 
to the use of the equipment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 4 
D.  Personnel involved in the project 
1. Mainly researching human resources 
Category  
(Host, co-host, co-presenter, 
research assistant, etc. ) 
Name 
Current position 
Nature, projects, and scope of work 
involved in this research project. 
Host 
Wong, Ming-
Wun 
Attending Physician of 
Gastroenterology 
Project schedule supervision, research progress 
tracking and plan development, data analysis and 
report writing. 
Co-host 
Chen, Chien-
Lin 
Director of 
Gastroenterology 
Actual case handling procedures, such as inspection 
operations, in the planned project. 
Co-host 
Yi, Chih-Hsun Attending Physician of 
Gastroenterology 
Actual case handling procedures, such as inspection 
operations, in the planned project. 
Co-host 
Liu, Tso-Tsai 
Director of Endoscopy 
Department 
Actual case handling procedures, such as inspection 
operations, in the planned project. 
Co-host 
Lei, Wei-Yi 
Attending Physician of 
Gastroenterology 
Actual case handling procedures, such as inspection 
operations, in the planned project. 
Co-host 
Hung, Jui-
Sheng 
Attending Physician of 
Gastroenterology 
Actual case handling procedures, such as inspection 
operations, in the planned project. 
Research assistant 
Chen, Yan-Zhu 
Research assistant 
Organize data, data analysis and statistics and 
handle administrative affairs. 
Research assistant 
Jian,Yu-xuan 
Research assistant 
Organize data, data analysis and statistics and 
handle administrative affairs. 
 
2. Research projects that the host, co-hosts, and co-researchers have participated in in 
the past three years. 
Surname 
name 
Count painting name say 
Jobs within the plan From year 
to month 
Grant 
agencies 
Wong, 
Ming-Wun 
Antireflux mucosal ablation for the treatment of 
PPI-dependent gastroesophageal reflux disease: 
treatment efficacy and physiological alteration 
Host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Exploring pathophysiological mechanisms of 
laryngopharyngeal 
reflux: 
utilization 
with 
artificial intelligence and clinical implication for 
precision diagnosis and personalized treatment 
strategies 
Host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Wong, 
Ming-Wun 
Supervised Learning Artificial Intelligence in 24-
h Impedance-pH: Technique Performance and 
Clinical Implications for Diagnosing GERD 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden in patients 
with disorders of long COVID gut brain 
interaction a doub le blind, randomized,placebo 
controlled study 
Co-host 
2023/01/01~ 
2023/12/31 
Tzu Chi 
Medical 
Corporation 
Wong, 
Ming-Wun 
Interaction 
among 
supragastric 
belching, 
psychologic distress and esophageal acid reflux: 
Implications for optimal management of GERD 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Relevance 
of 
esophageal 
hypervigilance, 
functional 
gastrointestinal 
disorders, 
and 
psychological distress as pathophysiological 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 5 
mechanisms to esophageal symptoms  
Wong, 
Ming-Wun 
Oropharyngeal swallowing physiology in patients 
with esophageal hypomotility: Studies with 
HRPM 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Exploring capsaicin sensitization, sensorimotor 
function, 
psychophyiological 
reflux 
characteristics in human esophagus: therapeutic 
implications for esophageal dysfunction and 
gastroesophageal reflux disease 
Co-host 
2023/8/1~ 
2026/07/31 
Ministry of 
Science and 
Technology 
Wong, 
Ming-Wun 
Utility of high resolution pharyngeal manometry 
and Sydney Swallow Questionnaire for evaluation 
of oropharyngeal dysphagia and voice disorder 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Application of Artificial Intelligence in High-
resolution Esophageal Function Testing: A Study 
on Unsupervised Deep Learning Algorithms 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Impact of regulating diet and exercise on clinical 
characteristics and intestinal microbiota in 
patients with metabolic-related fatty liver 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Wong, 
Ming-Wun 
Diagnosis and establishment of indications for 
proton pump inhibitors in the improvement of 
laryngopharyngeal reflux based on nighttime 
average basal impedance values of the proximal 
esophagus 
Host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Wong, 
Ming-Wun 
Interrelationships among esophageal peristalsis, 
mucosa 
integrity, 
and 
mucosa 
afferent 
innervation: 
mechanisms 
for 
esophageal 
dysfunction and gastroesophageal reflux 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Wong, 
Ming-Wun 
Exploring the role of esophageal microbiome in 
the 
novel 
impedance 
parameters, 
clinical 
classification, 
and 
hypersensitivity 
in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Exploring the interrelationship and pathogenesis 
of esophageal acid sensitivity, esophageal 
secondary 
peristalsis, 
and 
subtypes 
of 
gastroesophageal reflux 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Wong, 
Ming-Wun 
Clinical application of high-resolution impedance 
pharyngeal function examination in the study of 
pharyngeal swallowing difficulties and drug 
response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden in patients 
with disorders of long COVID gut brain 
interaction a doub le blind, randomized,placebo 
controlled study 
Host 
2023/01/01~ 
2023/12/31 
Tzu Chi 
Medical 
Corporation 
Chen, 
Chien-Lin 
Interaction 
among 
supragastric 
belching, 
psychologic distress and esophageal acid reflux: 
Implications for optimal management of GERD 
Host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Exploring capsaicin sensitization, sensorimotor 
function, 
psychophyiological 
reflux 
characteristics in human esophagus: therapeutic 
Host 
2023/8/1~ 
2026/07/31 
Ministry of 
Science and 
Technology 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 6 
implications for esophageal dysfunction and 
gastroesophageal reflux disease 
Chen, 
Chien-Lin 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden 
Host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Chen, 
Chien-Lin 
Exploration of esophageal reflux clearance, 
mucosa 
integrity, 
and 
psychological 
characteristics: 
pathophysiological 
and 
therapeutic implications for gastroesophageal 
reflux disease 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Relevance 
of 
esophageal 
hypervigilance, 
functional 
gastrointestinal 
disorders, 
and 
psychological distress as pathophysiological 
mechanisms to esophageal symptoms  
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Antireflux mucosal ablation for the treatment of 
PPI-dependent gastroesophageal reflux disease: 
treatment efficacy and physiological alteration 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Oropharyngeal swallowing physiology in patients 
with esophageal hypomotility: Studies with 
HRPM 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Exploring pathophysiological mechanisms of 
laryngopharyngeal 
reflux: 
utilization 
with 
artificial intelligence and clinical implication for 
precision diagnosis and personalized treatment 
strategies 
Co-host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Chen, 
Chien-Lin 
Relationships 
among 
mucosal 
afferent 
innervation, 
esophageal 
peristalsis 
and 
pharmacological modulation in the human 
esophagus: implications for pathophysiology and 
management in patients with GERD 
Co-host 
20 2 2/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Chen, 
Chien-Lin 
Impact of opioids on esophageal peristalsis and 
acid 
reflux 
characteristics:relevance 
for 
esophageal pathophysiology and therapeutic 
implications 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Supervised Learning Artificial Intelligence in 24-
h Impedance-pH: Technique Performance and 
Clinical Implications for Diagnosing GERD 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Utility of high resolution pharyngeal manometry 
and Sydney Swallow Questionnaire for evaluation 
of oropharyngeal dysphagia and voice disorder 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Application of Artificial Intelligence in High-
resolution Esophageal Function Testing: A Study 
on Unsupervised Deep Learning Algorithms 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Impact of regulating diet and exercise on clinical 
characteristics and intestinal microbiota in 
patients with metabolic-related fatty liver 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Exploring the role of esophageal microbiome in 
the 
novel 
impedance 
parameters, 
clinical 
classification, 
and 
hypersensitivity 
in 
gastroesophageal reflux disease 
Host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Exploring the interrelationship and pathogenesis 
of esophageal acid sensitivity, esophageal 
secondary 
peristalsis, 
and 
subtypes 
of 
gastroesophageal reflux 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 7 
Chen, 
Chien-Lin 
Clinical application of high-resolution impedance 
pharyngeal function examination in the study of 
pharyngeal swallowing difficulties and drug 
response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Chen, 
Chien-Lin 
Relationships 
among 
mucosal 
afferent 
innervation, 
esophageal 
peristalsis 
and 
pharmacological modulation in the human 
esophagus: implications for pathophysiology and 
management in patients with GERD 
Co-host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Chen, 
Chien-Lin 
Diagnosis and establishment of indications for 
proton pump inhibitors in the improvement of 
laryngopharyngeal reflux based on nighttime 
average basal impedance values of the proximal 
esophagus 
Co-host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Chen, 
Chien-Lin 
Interrelationships among esophageal peristalsis, 
mucosa 
integrity, 
and 
mucosa 
afferent 
innervation: 
mechanisms 
for 
esophageal 
dysfunction and gastroesophageal reflux 
Host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Yi, Chih-
Hsun 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden in patients 
with disorders of long COVID gut brain 
interaction a doub le blind, randomized,placebo 
controlled study 
Co-host 
2023/01/01~ 
2023/12/31 
Tzu Chi 
Medical 
Corporation 
Yi, Chih-
Hsun 
Interaction 
among 
supragastric 
belching, 
psychologic distress and esophageal acid reflux: 
Implications for optimal management of GERD 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Relevance 
of 
esophageal 
hypervigilance, 
functional 
gastrointestinal 
disorders, 
and 
psychological distress as pathophysiological 
mechanisms to esophageal symptoms  
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Antireflux mucosal ablation for the treatment of 
PPI-dependent gastroesophageal reflux disease: 
treatment efficacy and physiological alteration 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Oropharyngeal swallowing physiology in patients 
with esophageal hypomotility: Studies with 
HRPM 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Exploring capsaicin sensitization, sensorimotor 
function, 
psychophyiological 
reflux 
characteristics in human esophagus: therapeutic 
implications for esophageal dysfunction and 
gastroesophageal reflux disease 
Co-host 
2023/8/1~ 
2026/07/31 
Ministry of 
Science and 
Technology 
Yi, Chih-
Hsun 
Exploration of esophageal reflux clearance, 
mucosa 
integrity, 
and 
psychological 
characteristics: 
pathophysiological 
and 
therapeutic implications for gastroesophageal 
reflux disease 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Impact of opioids on esophageal peristalsis and 
acid 
reflux 
characteristics:relevance 
for 
esophageal pathophysiology and therapeutic 
implications 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Utility of high resolution pharyngeal manometry 
and Sydney Swallow Questionnaire for evaluation 
of oropharyngeal dysphagia and voice disorder 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 8 
Yi, Chih-
Hsun 
Application of Artificial Intelligence in High-
resolution Esophageal Function Testing: A Study 
on Unsupervised Deep Learning Algorithms 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Supervised Learning Artificial Intelligence in 24-
h Impedance-pH: Technique Performance and 
Clinical Implications for Diagnosing GERD 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Impact of regulating diet and exercise on clinical 
characteristics and intestinal microbiota in 
patients with metabolic-related fatty liver 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Yi, Chih-
Hsun 
Exploring the interrelationship and pathogenesis 
of esophageal acid sensitivity, esophageal 
secondary 
peristalsis, 
and 
subtypes 
of 
gastroesophageal reflux 
Host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Exploring the role of esophageal microbiome in 
the 
novel 
impedance 
parameters, 
clinical 
classification, 
and 
hypersensitivity 
in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Clinical application of high-resolution impedance 
pharyngeal function examination in the study of 
pharyngeal swallowing difficulties and drug 
response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Yi, Chih-
Hsun 
Interrelationships among esophageal peristalsis, 
mucosa 
integrity, 
and 
mucosa 
afferent 
innervation: 
mechanisms 
for 
esophageal 
dysfunction and gastroesophageal reflux 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Yi, Chih-
Hsun 
Impact of regulating diet and exercise on clinical 
characteristics and intestinal microbiota in 
patients with metabolic-related fatty liver 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden in patients 
with disorders of long COVID gut brain 
interaction a doub le blind, randomized,placebo 
controlled study 
Co-host 
2023/01/01~ 
2023/12/31 
Tzu Chi 
Medical 
Corporation 
Liu, Tso-
Tsai 
Interaction 
among 
supragastric 
belching, 
psychologic distress and esophageal acid reflux: 
Implications for optimal management of GERD 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Relevance 
of 
esophageal 
hypervigilance, 
functional 
gastrointestinal 
disorders, 
and 
psychological distress as pathophysiological 
mechanisms to esophageal symptoms  
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Oropharyngeal swallowing physiology in patients 
with esophageal hypomotility: Studies with 
HRPM 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Antireflux mucosal ablation for the treatment of 
PPI-dependent gastroesophageal reflux disease: 
treatment efficacy and physiological alteration 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Exploring capsaicin sensitization, sensorimotor 
function, 
psychophyiological 
reflux 
characteristics in human esophagus: therapeutic 
implications for esophageal dysfunction and 
gastroesophageal reflux disease 
Co-host 
2023/8/1~ 
2026/07/31 
Ministry of 
Science and 
Technology 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 9 
Liu, Tso-
Tsai 
Exploration of esophageal reflux clearance, 
mucosa 
integrity, 
and 
psychological 
characteristics: 
pathophysiological 
and 
therapeutic implications for gastroesophageal 
reflux disease 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Impact of opioids on esophageal peristalsis and 
acid 
reflux 
characteristics:relevance 
for 
esophageal pathophysiology and therapeutic 
implications 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Utility of high resolution pharyngeal manometry 
and Sydney Swallow Questionnaire for evaluation 
of oropharyngeal dysphagia and voice disorder 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Supervised Learning Artificial Intelligence in 24-
h Impedance-pH: Technique Performance and 
Clinical Implications for Diagnosing GERD 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Application of Artificial Intelligence in High-
resolution Esophageal Function Testing: A Study 
on Unsupervised Deep Learning Algorithms 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Liu, Tso-
Tsai 
Exploring the role of esophageal microbiome in 
the 
novel 
impedance 
parameters, 
clinical 
classification, 
and 
hypersensitivity 
in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Exploring the interrelationship and pathogenesis 
of esophageal acid sensitivity, esophageal 
secondary 
peristalsis, 
and 
subtypes 
of 
gastroesophageal reflux 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Clinical application of high-resolution impedance 
pharyngeal function examination in the study of 
pharyngeal swallowing difficulties and drug 
response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Liu, Tso-
Tsai 
Interrelationships among esophageal peristalsis, 
mucosa 
integrity, 
and 
mucosa 
afferent 
innervation: 
mechanisms 
for 
esophageal 
dysfunction and gastroesophageal reflux 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Lei, Wei-
Yi 
Relevance 
of 
esophageal 
hypervigilance, 
functional 
gastrointestinal 
disorders, 
and 
psychological distress as pathophysiological 
mechanisms to esophageal symptoms  
Host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Relationships 
among 
mucosal 
afferent 
innervation, 
esophageal 
peristalsis 
and 
pharmacological modulation in the human 
esophagus: implications for pathophysiology and 
management in patients with GERD 
Host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Lei, Wei-
Yi 
Impact of opioids on esophageal peristalsis and 
acid 
reflux 
characteristics:relevance 
for 
esophageal pathophysiology and therapeutic 
implications 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden in patients 
with disorders of long COVID gut brain 
interaction a doub le blind, randomized,placebo 
Co-host 
2023/01/01~ 
2023/12/31 
Tzu Chi 
Medical 
Corporation 

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E6A0021096-10                                                           Total 30 Page, Page 10 
controlled study 
Lei, Wei-
Yi 
Interaction 
among 
supragastric 
belching, 
psychologic distress and esophageal acid reflux: 
Implications for optimal management of GERD 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Oropharyngeal swallowing physiology in patients 
with esophageal hypomotility: Studies with 
HRPM 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Antireflux mucosal ablation for the treatment of 
PPI-dependent gastroesophageal reflux disease: 
treatment efficacy and physiological alteration 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Exploring capsaicin sensitization, sensorimotor 
function, 
psychophyiological 
reflux 
characteristics in human esophagus: therapeutic 
implications for esophageal dysfunction and 
gastroesophageal reflux disease 
Co-host 
2023/8/1~ 
2026/07/31 
Ministry of 
Science and 
Technology 
Lei, Wei-
Yi 
Exploration of esophageal reflux clearance, 
mucosa 
integrity, 
and 
psychological 
characteristics: 
pathophysiological 
and 
therapeutic implications for gastroesophageal 
reflux disease 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Utility of high resolution pharyngeal manometry 
and Sydney Swallow Questionnaire for evaluation 
of oropharyngeal dysphagia and voice disorder 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Application of Artificial Intelligence in High-
resolution Esophageal Function Testing: A Study 
on Unsupervised Deep Learning Algorithms 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Supervised Learning Artificial Intelligence in 24-
h Impedance-pH: Technique Performance and 
Clinical Implications for Diagnosing GERD 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Impact of regulating diet and exercise on clinical 
characteristics and intestinal microbiota in 
patients with metabolic-related fatty liver 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Lei, Wei-
Yi 
Relationships 
among 
mucosal 
afferent 
innervation, 
esophageal 
peristalsis 
and 
pharmacological modulation in the human 
esophagus: implications for pathophysiology and 
management in patients with GERD 
Host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Lei, Wei-
Yi 
Interrelationships among esophageal peristalsis, 
mucosa 
integrity, 
and 
mucosa 
afferent 
innervation: 
mechanisms 
for 
esophageal 
dysfunction and gastroesophageal reflux 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Lei, Wei-
Yi 
Exploring the role of esophageal microbiome in 
the 
novel 
impedance 
parameters, 
clinical 
classification, 
and 
hypersensitivity 
in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Lei, Wei-
Yi 
Exploring the interrelationship and pathogenesis 
of esophageal acid sensitivity, esophageal 
secondary 
peristalsis, 
and 
subtypes 
of 
gastroesophageal reflux 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 11 
Lei, Wei-
Yi 
Clinical application of high-resolution impedance 
pharyngeal function examination in the study of 
pharyngeal swallowing difficulties and drug 
response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Oropharyngeal swallowing physiology in patients 
with esophageal hypomotility: Studies with 
HRPM 
Host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Utility of high resolution pharyngeal manometry 
and Sydney Swallow Questionnaire for evaluation 
of oropharyngeal dysphagia and voice disorder 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden in patients 
with disorders of long COVID gut brain 
interaction a doub le blind, randomized,placebo 
controlled study 
Co-host 
2023/01/01~ 
2023/12/31 
Tzu Chi 
Medical 
Corporation 
Hung, Jui-
Sheng 
Interaction 
among 
supragastric 
belching, 
psychologic distress and esophageal acid reflux: 
Implications for optimal management of GERD 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Relevance 
of 
esophageal 
hypervigilance, 
functional 
gastrointestinal 
disorders, 
and 
psychological distress as pathophysiological 
mechanisms to esophageal symptoms  
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Antireflux mucosal ablation for the treatment of 
PPI-dependent gastroesophageal reflux disease: 
treatment efficacy and physiological alteration 
Co-host 
2023/01/01~ 
2023/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Exploring capsaicin sensitization, sensorimotor 
function, 
psychophyiological 
reflux 
characteristics in human esophagus: therapeutic 
implications for esophageal dysfunction and 
gastroesophageal reflux disease 
Co-host 
2023/8/1~ 
2026/07/31 
Ministry of 
Science and 
Technology 
Hung, Jui-
Sheng 
Exploration of esophageal reflux clearance, 
mucosa 
integrity, 
and 
psychological 
characteristics: 
pathophysiological 
and 
therapeutic implications for gastroesophageal 
reflux disease 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Impact of opioids on esophageal peristalsis and 
acid 
reflux 
characteristics:relevance 
for 
esophageal pathophysiology and therapeutic 
implications 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Supervised Learning Artificial Intelligence in 24-
h Impedance-pH: Technique Performance and 
Clinical Implications for Diagnosing GERD 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Application of Artificial Intelligence in High-
resolution Esophageal Function Testing: A Study 
on Unsupervised Deep Learning Algorithms 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Impact of regulating diet and exercise on clinical 
characteristics and intestinal microbiota in 
patients with metabolic-related fatty liver 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Jing Si Herbal Tea in the treatment of dyspeptic 
symptoms and psychophysical burden 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Hung, Jui-
Sheng 
Clinical application of high-resolution impedance 
pharyngeal function examination in the study of 
pharyngeal swallowing difficulties and drug 
Host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 4,11/13/2023) 
E6A0021096-10                                                           Total 30 Page, Page 12 
response 
Hung, Jui-
Sheng 
Exploring the role of esophageal microbiome in 
the 
novel 
impedance 
parameters, 
clinical 
classification, 
and 
hypersensitivity 
in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Exploring the interrelationship and pathogenesis 
of esophageal acid sensitivity, esophageal 
secondary 
peristalsis, 
and 
subtypes 
of 
gastroesophageal reflux 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Hung, Jui-
Sheng 
Interrelationships among esophageal peristalsis, 
mucosa 
integrity, 
and 
mucosa 
afferent 
innervation: 
mechanisms 
for 
esophageal 
dysfunction and gastroesophageal reflux 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 

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E6A0021096-10                                                           Total 30 Page, Page 13 
E. Research-related expenses 
Project Name 
Explanation 
Unit 
price 
Quantity 
Total 
Price 
Notes 
i. Business expenses 
1.Research 
manpower costs 
(please 
consult 
the 
Human 
Resources 
Department 
for 
related insurance 
expenses) 
(1) Dedicated Personnel 
(Limited to Individual Project 
Applications)： 
Remuneration for work 
(including year-end bonus) is the 
responsibility of the 
employer for labor insurance 
and health insurance. The 
employer is also responsible 
for labor retirement benefits 
(insured at 6% of salary) 
 
 
 
 
(2) "Part-time staff (must be 
current students)： 
Work remuneration 
□College graduates 
□Master's students 
□Other：        
Labor and health insurance 
borne by the employer 
Employer's contribution to 
labor retirement (insured salary 
6%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(3) Temporary worker： 
 Remuneration for work 
Labor and health insurance 
borne by the employer 
Employer's contribution to 
labor retirement (insured 
salary 6%) 
4,400 
936 
26 
1,286 
270 
12 
12 
12 
12 
12 
52,800 
11,232 
312 
15,432 
3,240 
Hourly 
wage 
$176 
25 hours 
per month. 
Subtotal: 
83,016 
NTD 
 
 
Subtotal： 83,016 
 
2. Animal testing 
expenses 
 
 
 
 
 
 
 
Subtotal：  
 
3. Consumables, 
Supplies, Books, 
and 
Miscellaneous 
expenses 
 
Participant Allowance 
 
Heart rate variability rental 
expenses for equipment 
 
Computer peripheral 
consumables expenses: Toner 
cartridge, ink cartridge, printer photosensitive 
drum/photoreceptor, special printing paper, etc. 
 
Miscellaneous: Postage and 
telecommunication expenses, printing expenses, 
photocopy paper expenses, photocopying 
expenses, binding expenses, stationery expenses, 
poster production expenses, computer data 
1,000 
 
9,000 
 
5,000 
 
 
3,984 
 
 
600 
 
12 
 
1 
 
 
1 
 
 
600,000 
 
108,000 
 
5,000 
 
 
3,984 
 
 
 

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E6A0021096-10                                                           Total 30 Page, Page 14 
statistical expenses, computer data analysis 
expenses, thesis submission fees, thesis 
publication fees, slicing, embedding, and 
immunostaining expenses 
 
 
Subtotal： 716,984 
 
ii. Research 
equipment expenses 
(According to regulations, 
books, computers, and 
peripheral equipment are 
not eligible for subsidies. 
The necessity of medium 
and large-sized 
instruments will be 
determined by the 
Research Department, and 
applications for their 
unified use will be 
submitted) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subtotal： 0 
 
Total 
800,000 
 
 

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E6A0021096-10                                                           Total 30 Page, Page 15 
F.  Project Abstract  
Please provide a brief overview of the key points of this project within 500 words 
and customize keywords based on the nature of the project. 
 
Patients with disorders of gut-brain interaction (DGBI) often present gastrointestinal symptoms 
that do not show noticeable irregularities in standard examinations. However, due to unclear causes 
and a high prevalence rate, this condition often exerts a profound impact on the physical and mental 
health of patients. The scope of DGBI encompasses conditions such as laryngopharyngeal reflux, 
functional dyspepsia, and irritable bowel syndrome. Previous research has confirmed that in patients 
with DGBI, their autonomic nervous system exhibits an imbalance, characterized by decreased 
parasympathetic activity and dominant sympathetic activity. Diaphragmatic breathing helps reduce 
the respiratory rate and can stimulate parasympathetic activity while suppressing sympathetic activity. 
Hence, it is now officially recommended as an effective adjunct therapy for relieving symptoms of 
gastroesophageal reflux. Accordingly, this study plans to implement a randomized controlled trial, 
introducing diaphragmatic breathing to patients with DGBI who exhibit normal results in objective 
examinations. This work allows evaluate changes in their psychophysical symptoms before and after 
treatment, as well as alterations in the autonomic nervous system. 
 
Key words: disorders of gut-brain interaction, psychophysical symptoms, diaphragmatic breathing, 
autonomic nervous system 
 
 
 
 
 
 

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G.  Background and Objectives of the Research Project 
Please elaborate on the background, objectives, significance, as well as the domestic 
and international research status related to this research project. Provide a review of 
the important references and literature relevant to this project. 
Research Background 
Disorders of gut-brain interaction, DGBI 
Functional GI Disorders, currently referred to as Disorders of gut-brain interaction (DGBI), 
encompass gastrointestinal symptoms for which, upon objective examination, no organic cause can 
be identified. Nevertheless, patients still endure the distressing symptoms related to the 
gastrointestinal tract.1 The symptoms of gastrointestinal disorders are diverse, encompassing the 
esophagus, stomach, small intestine, and large intestine. The origin of these symptoms is complex 
and includes factors such as imbalance in the intestinal microbiota, changes in mucosal immune 
function, alterations in signaling around the intestinal area, and dysregulation of central nervous 
system control over intestinal signaling and motor function (Figure 1).2 If it affects the upper digestive 
tract, it may lead to symptoms such as upper abdominal pain and bloating; these symptoms are 
referred to as Functional Dyspepsia (FD). If it affects the lower digestive tract, there may be issues 
such as abdominal pain, diarrhea, and constipation; this condition is classified as Irritable Bowel 
Syndrome (IBS).2 The recent research we have conducted indicates that among patients with 
symptoms of gastroesophageal reflux disease (GERD), only about 20% show pathological evidence 
of reflux. However, among those with throat reflux symptoms (such as hoarseness, sensation of a 
lump in the throat, chronic cough, and frequent throat clearing), their Esophageal Hypervigilance and 
Anxiety Scale (EHAS) scores are higher compared to individuals without throat reflux symptoms, 
even in the absence of pathological reflux evidence.3 These DGBIs (Functional Gastrointestinal 
Disorders) do not respond well to conventional gastrointestinal medications, so sometimes it is 
necessary to supplement treatment with neuromodulators from the field of psychosomatic medicine.4  
The Relationship Between the Autonomic Nervous System and the Disorders of gut-brain 
interaction 
The gastrointestinal tract is governed by the intrinsic Enteric nervous system (ENS) and the 
extrinsic Autonomic nervous system (ANS).5, 6 ENS can automatically regulate the gastrointestinal 
tract, while the Central Nervous System (CNS) interacts with the Enteric Nervous System (ENS) 
through the Autonomic Nervous System (ANS), providing external neural input to regulate and 
control gastrointestinal functions (Figure 1).7-9 The Parasympathetic Nervous System (PNS) or 
Sympathetic Nervous System (SNS), either singly or both, may encounter disruptions, leading to 
impaired communication between the gastrointestinal tract and the brain, subsequently resulting in 
Functional Gastrointestinal Disorders (FGID).5, 10 The upper gastrointestinal tract (esophagus, 
stomach, small intestine, ascending colon) is innervated by the parasympathetic nervous system, with 
the main source being the Vagus nerve. In contrast, the lower gastrointestinal tract (transverse colon, 
descending colon, sigmoid colon, external anal sphincter muscles) receives parasympathetic 
innervation from the Lumbosacral spinal cord's pre-ganglionic neurons, primarily originating from 
the S1–S4 segments.11-13 Most research reports consistently find that patients with Functional 
Gastrointestinal Disorders (DGBI) exhibit reduced parasympathetic nervous system activity and an 
increased dominance of sympathetic nervous system activity. These findings align with the autonomic 
control of gastrointestinal motility: activation of the parasympathetic nervous system enhances 

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gastrointestinal motility, while activation of the sympathetic nervous system inhibits gastrointestinal 
motility.14 
 
Figure 1. The possible etiology of DGBI includes microbial imbalance in the intestinal tract, changes 
in mucosal immune function, alterations in peripheral signaling around the intestines, and 
dysregulation of central nervous system control over intestinal signaling and motor function. Among 
these factors, the autonomic nervous system plays a crucial role as a communication bridge between 
the brain (central) and the gastrointestinal tract (peripheral).1 
Heart rate variability 
Early studies have shown that through Heart Rate Variability (HRV), the autonomic nervous 
system (ANS) can be assessed to evaluate the functional status of the gastrointestinal system.15, 16 The 
reason is that the autonomic nervous system (ANS) includes both the parasympathetic and 
sympathetic nervous systems, which regulate the outgoing and incoming fibers of the gastrointestinal 
tract through the nucleus tractus solitarius (NTS). The NTS also contains other autonomic neural 
control over organs whose functions are regulated by the central nervous system (CNS) through the 
ANS, such as cardiovascular functions.13, 15 Therefore, the central nervous system (CNS) also 
influences cardiovascular function through the autonomous regulation of sensory inputs from the 
gastrointestinal tract. This is because there is interaction between subnuclei in the nucleus tractus 
solitarius (NTS), regulating the rhythm or variability of the heart, known as heart rate variability 
(HRV).13 In addition to assessing the autonomic nervous system (ANS), the analysis of heart rate 
variability (HRV) has also been found to be clinically effective in evaluating the therapeutic efficacy 
of the autonomic nervous system for disorders of gut-brain interaction (DGBI). HRV parameters can 
be used as biological markers for assessing treatment outcomes.14 For example, electrical stimulation 
therapy is an emerging treatment method for these diseases.17 Numerous studies consistently 
demonstrate that neurostimulation therapy improves symptoms of DGBI by enhancing autonomic 
nervous system dysfunction assessed through HRV.18-20 

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HRV is influenced by two main physiological mechanisms: the first originates from the complex 
and dynamic interplay between the sympathetic and parasympathetic nervous systems; the second 
arises from regulatory mechanisms controlling heart rate, including RSA, blood pressure reflexes, 
and rhythmic variations in vascular tone. HRV is primarily applied in the assessment of the autonomic 
nervous system (ANS). As follows：21 
1. Time Domain Indicator  
 Root mean square of successive differences (RMSSD): RMSSD reflects the variability 
between heartbeats and is primarily used to estimate the changes in parasympathetic nervous 
system activity, especially the vagus nerve, in Heart Rate Variability (HRV).22 RMSSD is 
considered to be an important indicator of HRV.23 The RMSSD values over a 24-hour period 
are highly correlated with the difference in adjacent normal heartbeat intervals exceeding 
pNN50 and high-frequency (HF) power.24 The lower RMSSD values are positively correlated 
with the risk assessment of sudden unexplained death in epilepsy.25 
 Adjacent normal heartbeat interval differences exceeding pNN50: The deviation of adjacent 
normal heartbeat interval differences beyond pNN50 is closely associated with 
parasympathetic nervous system activity26 and is related to RMSSD and HF power. However, 
RMSSD typically provides a better assessment of parasympathetic nervous system activity 
(especially in the elderly). Therefore, most researchers tend to choose RMSSD over the 
adjacent normal-to-normal heartbeat interval differences exceeding pNN50.27 
2. Frequency Domain Indices  
 Low frequency (LF)：The low frequency (LF: 0.04-0.15 Hz) reflects the mixed activity of the 
sympathetic and parasympathetic nervous systems. In certain situations, LF can be used to 
assess the influence of the sympathetic nervous system, but this requires consideration of 
respiratory and other physiological influencing factors. 
 High frequency (HF) ：The high frequency (HF: 0.15-0.4 Hz) primarily reflects 
parasympathetic nervous system activity, especially vagal nerve activity. This can be 
observed through Respiratory Sinus Arrhythmia (RSA).28 
 LF/HF ratio：The LF/HF ratio is used to assess the balance between the sympathetic nervous 
system and the parasympathetic nervous system. 
Diaphragmatic breathing 
The relationship between respiration and the autonomic nervous system (ANS) is closely 
intertwined, as the phrenic nerve, responsible for controlling the movement of the diaphragm, is 
connected to the vagus nerve of the parasympathetic nervous system.29 The respiratory cycle reflects 
the balance between the parasympathetic and sympathetic nervous systems in the Autonomic Nervous 
System (ANS), which can be observed through Heart Rate Variability (HRV). The ANS state shifts 
from the parasympathetic nervous system to the sympathetic nervous system during inhalation, while 
it transitions from the sympathetic nervous system to the parasympathetic nervous system during 
exhalation. In HRV, an increase in heart rate indicates enhanced sympathetic nervous system activity 
during inhalation, whereas a decrease in heart rate signifies increased parasympathetic nervous 
system activity during exhalation.30 

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Diaphragmatic breathing can be achieved by reducing the respiratory rate, promoting 
parasympathetic nervous system activity, and concurrently inhibiting sympathetic nervous system 
activity.31, 32 Due to the increase in tidal volume during diaphragmatic breathing, the Hering-Breuer 
reflex is activated. This reflex reduces chemoreflex sensitivity and enhances baroreflex, further 
lowering sympathetic nervous system activity.33 The rhythm of diaphragmatic breathing is as follows: 
Step 1: Inhale through the nose for about 4 seconds, feeling the expansion of the abdomen; Step 2: 
Hold the breath for 2 seconds; Step 3: Exhale slowly and steadily through the mouth for about 6 
seconds (see Figure 2). (Diaphragmatic Breathing for GI Patients - Michigan Medicine) Currently, 
diaphragmatic breathing is formally recommended for alleviating symptoms of gastroesophageal 
reflux disease (GERD) and is proven effective in reducing the frequency of reflux occurrences in 
randomized controlled trials. It is now recognized as an effective adjunctive therapy.34, 35 However, 
currently, there is still no randomized controlled experiment confirming the effects of abdominal 
breathing on other functional gastrointestinal disorders (DGBI issues). 
 
Figure 2.  Diaphragmatic breathing：When inhaling in the left image, the diaphragm descends, 
causing the abdomen to protrude. In the right image, during exhalation, the diaphragm ascends, and 
the abdomen returns to a flat state. 
Figure 3.  During the high-resolution esophageal impedance measurement period after a 20-minute 
meal, under random allocation, both the healthy control group (a) and the patient group (b) 
demonstrated a significant reduction in the number of reflux events with diaphragmatic breathing. In 
contrast, the sham (normal) breathing group showed no significant difference in reflux events.35 
Research Purpose 
For patients with DGBI (Functional Gastrointestinal Disorders) who exhibit gastrointestinal 
symptoms that cannot identify organic causes after objective examinations, current treatment options 
are significantly limited. Dysregulation of the autonomic nervous system is one contributing factor. 
Abdominal breathing, by reducing respiratory frequency, promotes parasympathetic nervous system 
activity while inhibiting sympathetic nervous system activity. It is now officially recommended by 

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E6A0021096-10                                                           Total 30 Page, Page 20 
international consensus conferences as an adjunctive therapy to alleviate symptoms of 
gastroesophageal reflux. 
 The purpose of this study is to investigate the autonomic nervous system responses through 
standardized autonomic nervous system monitoring, focusing on the impact of diaphragmatic 
breathing on the autonomic nervous system in both healthy subjects and patients with Functional 
Gastrointestinal Disorders (DGBI). Additionally, the study aims to confirm whether the 
implementation of diaphragmatic breathing can improve symptoms in DGBI patients, providing a 
basis for future reference in the treatment of DGBI patients. 
 
Research hypothesis 
Hypothesis 1：Diaphragmatic breathing can change Autonomic nervous system 
Hypothesis 1-1：Diaphragmatic breathing can increase the activity of the parasympathetic nervous 
system and decrease the activity of the sympathetic nervous system in healthy subjects. 
Hypothesis 1-2：Diaphragmatic breathing can increase parasympathetic nervous system activity and 
decrease sympathetic nervous system activity in patients with DGBI. 

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Hypothesis 2：Diaphragmatic breathing can improve symptoms in patients with DGBI. 
Hypothesis 2-1：Introducing diaphragmatic breathing can improve symptoms in patients with 
Laryngopharyngeal Reflux Disease (LPR). 
Hypothesis 2-2：Introducing diaphragmatic breathing can improve symptoms in patients with 
Functional Dyspepsia (FD). 
Hypothesis 2-3：Introducing diaphragmatic breathing can improve symptoms in patients with Irritable 
Bowel Syndrome (IBS). 
 
 
 
 
 
 
 
 

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H.  Research methods, procedures, and execution progress. 
1.Please elaborate on the research methods adopted in this project and the reasons behind their 
selection. 
2.Anticipated difficulties and possible solutions. 
3.If it is a consecutive project, please also attach the annual research progress report or primary 
data for the corresponding year. 
Research Methods 
Participant 
 
The trial is expected to last for 1 year, with a research period ending on December 31, 2024. It 
aims to recruit 600 participants, including 150 healthy volunteers to be solicited through 
advertisements. Additionally, 150 participants with Laryngopharyngeal Reflux (LPR) will be 
recruited from the Gastroenterology Outpatient Department, along with 150 participants with 
Functional Dyspepsia (FD) and 150 participants with Irritable Bowel Syndrome (IBS). The inclusion 
and exclusion criteria for participants are as follows：  
Inclusion Criteria for Participants： 
Inclusion criteria for healthy subjects： 
1. 
Aged between 18 and 70 years old, clear consciousness, and willing to sign the informed 
consent form for the study. 
2. 
Without any gastrointestinal symptoms or the use of gastrointestinal medications. 
Inclusion criteria for Laryngopharyngeal reflux disease subject： 
1. 
Aged between 18 and 70 years old, clear consciousness, and willing to sign the informed 
consent form for the study. 
2. 
The definition of Laryngopharyngeal Reflux (LPR) is characterized by the presence of 
symptoms lasting for more than three months, including hoarseness, a sensation of a lump 
in the throat, chronic cough, and frequent throat clearing. These symptoms occur at least 
once a week. Diagnosis is confirmed through a standardized LPR assessment questionnaire 
(Reflux Symptom Index - RSI), which consists of nine reflux-related symptoms. Each 
symptom is rated on a severity scale from 0 (asymptomatic) to 5 (most severe). If the total 
score exceeds 13 points, the patient meets the criteria for Laryngopharyngeal Reflux. 
Inclusion criteria for Functional dyspepsia subject： 
1. 
Aged between 18 and 70 years old, clear consciousness, and willing to sign the informed 
consent form for the study. 
2. 
Those who meet the FD definition Functional dyspepsia is characterized by chronic 
(occurring at least once a week, lasting for a minimum of three months, with the first 
symptoms manifesting at least six months ago) upper gastrointestinal symptoms (any of the 
following): postprandial bloating, a tendency to feel full easily, upper abdominal pain or a 
burning sensation, without symptoms of gastrointestinal bleeding or significant weight loss, 
and with no abnormalities found upon upper gastrointestinal endoscopic examination. 

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Inclusion criteria for Irritable bowel syndrome subject： 
1. 
Aged between 18 and 70 years old, clear consciousness, and willing to sign the informed 
consent form for the study. 
2. 
Those who meet the definition of IBS. Irritable bowel syndrome (IBS) is a chronic 
condition characterized by lower gastrointestinal symptoms occurring at least once a week 
and lasting for a minimum of three months. These symptoms include abdominal pain 
accompanied by either diarrhea or constipation, without any signs of gastrointestinal 
bleeding or significant weight loss. Individuals with IBS exhibit no abnormalities upon 
examination through colonoscopy. 
Exclusion Criteria for Participants： 
1. 
Pregnant or lactating women. 
2. 
Infection currently undergoing antibiotic treatment. 
3. 
In the past two months, underwent tracheal intubation. 
4. 
Those with myocardial hypoxia or who have recently experienced a myocardial infarction. 
5. 
Unable to collaborate. 
Research Process Diagram 
 
 
Research Steps 
The subjects who meet the inclusion criteria of this study will undergo an initial assessment of 
heart rate variability and psychosomatic symptoms after enrollment. Subsequently, a two-week 

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experiment will be conducted, during which the subjects will receive one session of diaphragmatic 
breathing training by the researchers. After the guided training, the subjects will undergo another 
assessment of heart rate variability. In the first week, participants will engage in self-practice of the 
instructed content twice daily, each session lasting 5 minutes, and will record a weekly diaphragmatic 
breathing diary. 
After the first week, subjects will undergo another assessment of heart rate variability and 
psychosomatic symptoms. In the second week, participants will continue daily self-practice with two 
sessions of instructed content, each lasting 5 minutes, and will maintain a diaphragmatic breathing 
diary. Following the second week, subjects will undergo a final assessment of heart rate variability 
and psychosomatic symptoms, completing the experiment. 
Researchers recommend spending approximately 15 minutes on diaphragmatic breathing 
training, 15 minutes on measuring heart rate variability, and approximately 20 minutes for 
questionnaire completion. The measurement of heart rate variability utilizes a non-invasive device 
called "LEADTEK" portable electrocardiogram recorder (Ministry of Health and Welfare Medical 
Device Manufacturing License No. 006972). If participants have any questions or concerns during 
the abdominal breathing training process, they are encouraged to contact the researchers. 
Diaphragmatic Breathing (It takes about 15 minutes) 
1. Sit in a comfortable place and close your eyes. 
2. Place one hand on the chest and the other hand on the abdomen to practice diaphragmatic 
breathing: During diaphragmatic breathing exercises, the hand on the abdomen will rise with 
inhalation and fall with exhalation, while the hand on the chest remains stationary. 
3. Inhale through the nose for about 4 seconds, feeling the expansion of the abdomen. (Upon the 
first inhalation, there may be a slight sense of tension.) 
4. Hold your breath for 2 seconds. 
5. Exhale slowly and steadily through the mouth for approximately 6 seconds, keeping the mouth 
relaxed throughout the process. 
6. Repeat this breathing cycle for 5 minutes. 
ANS Protocol (It takes about 15 minutes) 
The ANS Protocol is a standardized and validated method used to assess the autonomic nervous 
system's (ANS) responses to baseline conditions and stress stimuli. It consists of three stages: a resting 
phase (5 minutes), a mental arithmetic test under stress conditions (3 minutes), and a recovery period 
(5 minutes) during which heart rate variability (HRV) is measured. The mental arithmetic test 
involves subjects performing continuous subtraction of 7 from a randomly generated four-digit 
number using mental calculation only. If an error occurs, the process is restarted, and the entire 
procedure lasts for 3 minutes.36 
ANS Detection Steps： 

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1. Confirm that the status indicator light is in a measurable state (LED color: green), and then 
attach the electrode patches.。 
2. R (Red dot): Please paste on the inner side of the right wrist. 
3. L (Yellow dot): Please paste on the inner side of the left wrist. 
4. F (Green Marking): Please paste on the inside of the left wrist. 
5. Press the measurement button on the device to initiate the measurement. 
6. Before the formal commencement of measurements, the device will conduct a preliminary 
signal quality check. Participants are advised to remain still and refrain from engaging in 
conversation during this process. 
7. The measurement officially begins at 7: Please instruct the subjects to remain still and refrain 
from talking, waiting quietly for 3 to 5 minutes until the measurement is completed.。 
8. Measurement Completed: Display Measurement Results. 
The HRV indicators for assessing the ANS are as follows：21 
1. Time Domain Indicators  
 The square root of the mean of the sum of the squares of the Successive differences 
(RMSSD)：Assessing Parasympathetic Nervous System Activity 
2. Frequency Domain Indicators  
 Low frequency power (LF)：Assessing Sympathetic Nervous System Activity 
 High frequency power (HF)：Assessing Parasympathetic Nervous System Activity 
 Low-frequency/High-frequency Power Ratio (LF/HF ratio)：Assessing the balance of 
the sympathetic and parasympathetic nervous systems. 
Questionnaire Evaluation Tool (It takes about 20 minutes) 
Disease Questionnaire Assessment： 
 
Gastroesophageal Reflux Disease Questionnaire (GERDQ)37 The questionnaire score 
exceeding 12 points indicates a high likelihood of having GERD. 
 
Reflux Symptom Index (RSI) 38 The nine reflux-related symptoms are graded on a severity 
scale from 0 (no symptoms) to 5 (most severe), and a total score exceeding 13 indicates a 
higher probability of suffering from laryngopharyngeal reflux. 
 
Functional Dyspepsia (FD)39 The subjective assessment revolves around symptoms and 
quality of life, primarily including postprandial fullness, early satiety, and upper abdominal 
bloating as digestive discomfort symptoms. Each item is scored from 0 to 6 points, with 0 
points indicating no symptoms and 6 points indicating extremely severe symptoms. The total 
score ranges from 0 to 52 points, with higher scores indicating more severe symptoms.  
 
Irritable Bowel Syndrome (IBS)39 Diagnostic criteria reference Rome IV, The main symptoms 
began at least 6 months ago, with recurrent abdominal pain occurring at least once a week on 
average in the past three months. Additionally, at least two of the following symptoms are 
present: abdominal pain related to bowel movements, changes in bowel frequency, and 
alterations in the appearance of stool. 
 
Gastrointestinal Symptom Rating Scale (GSRS)40 Applicable to the general population with 
gastrointestinal symptoms for measurement and evaluation of treatment effectiveness, using 
a Likert 4-point scoring system. Positive scoring is employed, where higher scores indicate 
greater severity of symptoms, and lower scores represent higher levels of health. 

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Physical and Mental Stress Questionnaire Assessment： 
 
Pittsburgh Sleep Quality Index (PSQI) 41 is not only suitable for evaluating sleep quality of 
patients with sleep disorders and mental disorders, but also suitable for the evaluation of sleep 
quality of ordinary people. 18 items are composed of 7 components, each component is scored 
on a scale of 0-3 , and the total score ranges from 0-21 points. The higher the score, the worse 
the sleep quality . 
 
Taiwanese Depression Scale (TDQ) 42 includes three parts: emotion, cognition and body, with 
a total of 18 questions, and the scale is scored on a four-point scale. Each question is scored 
on a scale from 0 to 3 , and the total score ranges from 0 to 54 points. Those with a score 
greater than 18 indicate depressive symptoms. 
 
State-Trait Anxiety. Inventory (STAI) 43 includes two subscales, the Situational and Trait 
Anxiety Scale, with a minimum score of 20 and a maximum score of 80 , with higher scores 
representing anxiety symptoms. 
 
The Perceived Stress Scale (PSS-10) 44 is to evaluate the degree of stress in personal life 
situations, and the higher the score, the greater the stress. 
 
Esophageal Hypervigilance and Anxiety Scale (EHAS) 41 Esophageal hypervigilance and 
anxiety can cause symptoms in patients with chronic esophageal diseases, including 
gastroesophageal reflux, esophageal atlasia and functional esophageal diseases. The 
questionnaire contains 15 items and can be divided into two main categories . Section: 
Symptoms of Esophageal Hypervigilance and Symptoms of Esophageal Anxiety. This 
questionnaire can not only assess the sensory system symptoms of any esophagus-related 
diseases, but also assist in the diagnosis of functional esophageal diseases. 
 
Laryngeal Hypervigilance and Anxiety Scale (LHAS) 41 Throat hypervigilance and anxiety 
can trigger symptoms in patients with chronic esophageal disease. The questionnaire contains 
15 items and can be divided into two main parts: throat hypervigilance symptoms and throat 
anxiety symptoms. This questionnaire can not only assess the sensory system symptoms of 
any esophagus-related diseases, but also assist in the diagnosis of functional esophageal 
diseases. 
 
Visceral Sensitivity Index (VSI) 45 measures anxiety specific to the gastrointestinal tract. It 
includes 15 items, with a minimum score of 0 and a maximum of 5 points for each item, and 
a minimum score of 0 and a maximum score of 75 points for the total score. 
Statistical Analysis 
If a continuous variable follows a normal distribution, it is represented by the mean and standard 
deviation; if it does not follow a normal distribution, it is represented by the median and interquartile 
range. The treatment effectiveness is presented as the improvement percentage based on the pre- and 
post-treatment sleep habit questionnaire, depression questionnaire, anxiety questionnaire, stress 
questionnaire, digestive symptom questionnaire, and irritable bowel syndrome questionnaire. The 
efficacy of diaphragmatic breathing was assessed using a Chi-squared test to compare percentages. 
A P-value less than 0.05 was considered statistically significant. The statistical analysis software used 
is SPSS 19 (SPSS, Inc, Chicago, IL, USA). 
The clinical significance and originality of this study 

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This study will be the first to extensively apply diaphragmatic breathing to the management of 
functional gastrointestinal disorders (FGIDs). In addition to assessing gastrointestinal symptoms, it 
will also evaluate physical and mental symptoms, sleep quality, stress indicators, and visceral 
sensitivity. Further understanding of autonomic nervous system changes through heart rate variability 
(HRV). This study aims to investigate the efficacy and mechanism of non-invasive, non-
pharmacological diaphragmatic breathing on patients with disorders of the gut-brain axis (DGBI). 

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I.  Expected deliverables and specific outcomes of the planned tasks 
1.Please list the work items expected to be completed within the implementation period. 
2.Anticipated contributions to academic research and other applications. 
3.For participating staff, the training expected to be available. 
1. Expected tasks to be completed 
This study expects that diaphragmatic breathing may potentially improve the psychosomatic 
symptoms of Disorders of Gut-Brain Interaction (DGBI), and it may be achieved by altering 
autonomic nervous system regulation. 
2. Expected contributions to academic research, national development, and other applications 
The results of this study will provide empirical evidence for the use of diaphragmatic breathing 
in the treatment of disorders of the gut-brain axis (DGBI). In the future, we hope to participate in the 
evaluation of the National Healthcare Quality Awards by the Taiwan Medical Association to help a 
large number of DGBI patients. 
3. Expected training for participating staff 
Participants will receive not only general research training, such as experimental design and 
execution, result analysis and statistics, data visualization, oral presentations, paper writing, and 
manuscript submission process, but also have the opportunity to gain exposure to various 
experimental techniques and skills due to the diversity of their tasks. 
 

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