Reflux hypersensitivity is the disease that causes chest pain, heartburn and regurgitation and can impair patients' quality of life. Pain modulators are often used for the treatment of reflux hypersensitivity, but the effect is not enough and more effective therapy is needed.

Slow deep breathing is the validated method to modulate the autonomic nervous system. In our previous study, slow deep breathing could increase the threshold of oesophageal pain in healthy volunteers. Therefore, slow deep breathing has the potential to be an effective treatment for reflux hypersensitivity and further study is warranted in the patient group.

The aims of this study are (1) to evaluate the feasibility of slow deep breathing and (2) to investigate the effect of autonomic nerve modulation by slow deep breathing on symptoms in patients with reflux hypersensitivity.

This is a randomized single-blinded parallel study and the investigators aim to recruit 40 participants.

Patients will be enrolled for a period of 4 weeks and don't have to attend our institution. A video chat on day 1 will consist of confirming eligibility, after which the patient will be randomised to follow either the slow deep breathing protocol or the sham breathing protocol in a single blinded fashion. That is, the patient will be unaware of which the active breathing exercise is. Once randomised during a video chat, they will undergo baseline heart rate variability (HRV) measurements using a smartphone app, answer the questionnaires on Research Electronic Data Capture (REDCap), and then practice the relevant breathing exercise with an instruction video. The patient will then be trained to self-administer the breathing exercise during a video chat, which will be used twice a day for 10 minutes over the next 4 weeks with a standardized instruction video.

This study finishes when participants answer the online questionnaire and record HRV on day 29.

The investigators will set up this questionnaire on our electronic data capture system (Research Electronic Data Capture: REDCap). Participants will answer questionnaires using this online system on day 1, day 8, day15, day 22, and day 29 (end of the study).

Therefore, participants will also be trained on how to use REDCap and answer questionnaires under supervision on day 1 during a video chat. Questionnaires on day 8, 15, 22, and 29 will be answered at home. The investigators will send a reminder message to participants using a REDCap system the day before they answer the questionnaire.

Participants will be asked to record their HRV using a smartphone app on day 1, 8, 15, 22, and 29.

Inclusion Criteria:

• Male and female patients over the age of 18 years.
• Women in the follicular phase of the menstrual cycle (visits will be arranged so that in menstruating women, the study will be started in the follicular phase of the menstrual cycle to standardise for possible confounding effects of the menstrual cycle on symptom perception).
• Able to give informed consent
• Able to speak and understand English without the need for an interpreter
• No evidence of erosive esophagitis by OGD
• Presence of chest pain, heartburn, and/or regurgitation ≥ 3 days/week
• Normal acid exposure on MII-pH
• Positive symptom reflux association on MII-pH (symptom index ≥ 50% and symptom association probability ≥ 95%)
• OGD is performed within 2 years before the enrolment
• MII-pH study is performed within 2 year before the enrolment

Exclusion Criteria:

• Current or previous GI or medical illnesses that may affect ANS / GI function

• Current or previous significant CNS illness

• Current medications affecting the CNS, GI or ANS systems

• Pregnancy and lactation

• Cardiac dysrhythmias

• Those who do not have access to the internet-based questionnaire

  • The use of acid suppression therapies (e.g. proton pump inhibitor or H2 blocker) or pain modulators (e.g. low-dose Tricyclic Antidepressants, TCAs or Selective Serotonin Reuptake Inhibitors, SSRI) does not change the decision of participation as long as above-mentioned symptoms remain.

Patients are asked to refrain from smoking for 12 hours and drinking alcohol as well as using recreational drugs for 48 hours prior to study visit.

Participants and outcomes assessors will be masked.