Mechanisms Preventing Pharyngeal Reflux

Pathophysiology of Pharyngo-esophageal Junction and Esophageal Mechanisms Preventing Pharyngeal Reflux of Gastric Content

The overall goal is to define and characterize the manometric characteristics of UES incompetence associated with objectively documented pharyngeal reflux. The investigators will use endoscopic reflux detection as gold standard.

1. Characterization of UES pressure response to liquid refluxate . Hypothesis 1: UES pressure responses to liquid refluxate are significantly different in patients suffering from both pharyngeal reflux (regurgitation) and SE-GERD compared to healthy controls and GERD patients without regurgitation and SE-GERD. Hypothesis 2: these differences are significantly more pronounced during sustained esophageal distensions induced by slow intra-esophageal infusions compared to those due to rapid infusions.
2. Determination and characterization of the contribution of sub-sphincteric striated esophagus to the UES pressure barrier. Hypothesis 3: In healthy individual, in addition to the UES, proximal striated esophagus distal to the area normally incorporated in UES high pressure zone contracts in response to liquid reflux irrespective of secondary peristalsis. This contraction potentially prevents contact of refluxate with UES and provides an added layer of protection against pharyngeal reflux. Hypothesis 4: in patients with SE-GERD and perception of regurgitation associated with true pharyngeal reflux, both UES and sub-sphincteric responses are abnormal. Hypothesis 5: in patients with perception of regurgitation but without entry of refluxate into the pharynx, only the sub-sphincteric contraction will be abnormal.
3. Characterization of reflux- induced esophageal motor activity. Hypothesis 6: While in healthy individuals the predominant esophageal response to reflux is secondary peristalsis, in patients with regurgitation and SE-GERD this response is significantly altered and includes simultaneous, segmental contraction, partially propagated or low amplitude secondary peristalsis and absence of motor response.
4. Mechanisms of esophago- pharyngeal reflux. Hypothesis 7: pharyngeal reflux occurs when the reflux-induced intra-esophageal pressure exceeds the concurrent UES pressure. This can occur during the following conditions, a. partial UES relaxation, b. complete UES relaxation, c. absence of esophago-UES contractile reflex, d. Belch, e. incomplete swallow and f. excessive intra-esophageal pressure. The investigators will investigate these mechanisms under simulated reflux conditions testing different reflux variables.
5. Characterization of UES pressure response to liquid refluxate in asthma patients. Hypothesis 8: UES pressure responses to liquid refluxate are significantly different in patients suffering from asthma compared to healthy controls. Hypothesis 9: these differences are significantly more pronounced during sustained esophageal distensions induced by slow intra-esophageal infusions compared to those due to rapid infusions.
6. Characterization of UES pressure response to liquid refluxate at various levels of the esophagus in healthy controls. Hypothesis 10: The UES pressure response is significantly different for various locations of liquid refluxate in the esophagus. Hypothesis 11: the closer the liquid refluxate to the UES, the stronger the response will be.
7. Characterization of UES pressure response to liquid refluxate at various levels of the esophagus in GERD patients. Hypothesis 12: The UES pressure response to liquid refluxate at various levels of the esophagus will be significantly different in GERD patients compared to healthy participants. Hypothesis 13: Overall, the UES pressure response to liquid refluxate in GERD patients will be less pronounced than in healthy controls. Hypothesis 14: As the liquid refluxate gets closer to the UES, the UES pressure response to liquid refluxate will increase.
8. Characterization of UES and esophageal body response to rapid intra-esophageal air injection after esophageal acid sensitization. Supra-esophageal reflux disease is associated with changing in esophageal reflexes, such as esophago-contractile reflex (EUCR) and esophago-relaxation reflex (EURR). Intra-esophageal rapid injection can trigger EURR. 15: The investigators hypothesize that acid sensitization will affect UES and esophageal body response to rapid air injection. Hypothesis 16:The effect of of UES and esophageal body response to rapid air injection after esophageal acid sensitization will be different in healthy compared to GERD patients.
9. Characterization of deglutition before and after intra-esophageal acid or saline infusion. Supra-esophageal reflux disease is associated with changes in deglutitive pressures in UES, esophageal body and LES. The investigators hypothesize that esophageal acidification will affect UES, esophageal body and LES pressures during swallowing. The effect may be different in healthy compared to GERD patients. The investigators also expect to see a difference in parameter's between diseased Barrett's esophagus patients and the healthy population.
10. Characterization of deglutition at different phases of the breathing cycle. Typical pattern in healthy adults is swallowing near the end of expiration followed by expiration after swallow. The investigators hypothesize that swallowing at different phases of breathing will affect the UES, esophageal body, and LES pressures during swallowing.
11. Characterization of UES pressure response to liquid refluxate at various level of the esophagus in SERD patients. Hypothesis 17: As the liquid refluxate gets closer to the UES, SERD patients will have a lower compensatory response compared to GERD and healthy controls and lower contraction of the proximal striated esophagus (measured by the Pharyngeal Contractile Integral)

Inclusion Criteria:

• Age 18 to 85

  • GERD patients with complaints of regurgitation and supra-esophageal symptoms will be included and recruited from our GI & Otolaryngology clinics
  • GERD patients without complaint of supra-esophageal symptoms and regurgitation will be included and recruited from our GI & Otolaryngology clinics
  • Asthma patients with and without supra-esophageal symptoms will be included and recruited from clinics affiliated with Medical College of Wisconsin. Asthma patients with the following classifications of asthma severity will be included: intermittent, mild persistent, moderate persistent, and severe persistent (as long as no acute asthma exacerbation at the time of the study)
  • Patient definition will be based on position statement and technical reviews of the American Gastroenterological Association and Montreal definition and classification of gastroesophageal and reflux disease (Am J Gastroenterol. 2006;101:1900-1920).
  • SERD is defined as patients on long term acid suppressive therapy complaining of persistent regurgitation along with supra-esophageal manifestations such as burning throat, asthma, chronic cough, or hoarseness. Patients will be screened by Reflux Symptom Index > 13.
  • Barrett's esophagus patients will be recruited based on histological diagnosis from previous endoscopic biopsy that will be found using the clinical database warehouse.

Exclusion Criteria:

• Age <18 or >85

  • Active alcohol or drug abuse
  • History of ear, nose, throat and pulmonary diseases suspected of being GERD induced
  • History of head and neck malignancy and chemo-radiation therapy to the head and neck
  • Unable to give consent
  • Pregnant women (see justification in the Women and Minority Inclusion in Clinical Research section)
  • History of allergy to Lidocaine for nasal topical anesthesia
  • Allergy to green food dye
  • Asthma patients with an acute asthma exacerbation with symptoms including breathlessness, wheezing, and chest tightness