Cough Reflex Sensitivity and Bronchial Hyper-responsiveness

NCT ID: NCT01777867

Last Updated: 2017-02-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-02-29

Brief Summary

The aim of this study is to provide pilot data on the possible gastrointestinal predictors of respiratory hyper-responsiveness and how these relate to the clinical sub-types of gastroesophageal reflux disease (GERD) and visceral acid hypersensitivity.

Detailed Description

This study recruited participants into three groups: reflux patients with non-erosive disease (NERD) with abnormal levels of acid reflux, NERD patients with normal levels of reflux and healthy volunteers. Participants were assessed for cough reflex sensitivity (CRS) to citric acid and bronchial-hyperresponsiveness (BHR) to methacholine challenge, both before (baseline) and after esophageal acid infusion (HCl, 0.15M) or normal saline control (8ml/min). The order of CRS and BHR was randomized, as was the order of the acid/saline infusions.

Conditions

Gastroesophageal Reflux Disease; Chronic Cough; Broncho-hyperreactivity

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy Volunteers

Subjects in this arm were healthy volunteers. Subjects underwent both Cough Reflex Sensitivity and the Methacholine Challenge procedures.

Cough Reflex Sensitivity

Intervention Type: PROCEDURE

Subjects inhaled increasing concentrations of citric acid, which induces coughing in a dose-dependent, reproducible matter. Following each inhalation, the number of coughs in the subsequent 15 seconds was counted and recorded. The challenge was terminated once the citric acid induced 5 or more coughs and the logarithmic (base 10) concentration provoking 5 coughs was recorded.

Methacholine Challenge

Intervention Type: PROCEDURE

A baseline spirometry was used to assess how well the participant's lungs work by measuring how much air was inhale, how much was exhale and how quickly the participant exhaled. If this was normal, the subject inhaled slowly and deeply the methacholine test solution from a nebulizer and was told to hold their breath for 5 seconds. This was repeated until 5 inhalations were performed in no more than two minutes.

Non-erosive reflux disease with reflux

Subjects enrolled in this arm had non-erosive reflux disease with reflux (heartburn) for at least 6 of the preceding 12 months. Subjects underwent both Cough Reflex Sensitivity and the Methacholine Challenge procedures.

Cough Reflex Sensitivity

Intervention Type: PROCEDURE

Subjects inhaled increasing concentrations of citric acid, which induces coughing in a dose-dependent, reproducible matter. Following each inhalation, the number of coughs in the subsequent 15 seconds was counted and recorded. The challenge was terminated once the citric acid induced 5 or more coughs and the logarithmic (base 10) concentration provoking 5 coughs was recorded.

Methacholine Challenge

Intervention Type: PROCEDURE

A baseline spirometry was used to assess how well the participant's lungs work by measuring how much air was inhale, how much was exhale and how quickly the participant exhaled. If this was normal, the subject inhaled slowly and deeply the methacholine test solution from a nebulizer and was told to hold their breath for 5 seconds. This was repeated until 5 inhalations were performed in no more than two minutes.

Non-erosive reflux disease without reflux

Subjects enrolled in this arm had non-erosive reflux disease with normal levels of reflux (heartburn). Subjects underwent both Cough Reflex Sensitivity and the Methacholine Challenge procedures.

Cough Reflex Sensitivity

Intervention Type: PROCEDURE

Subjects inhaled increasing concentrations of citric acid, which induces coughing in a dose-dependent, reproducible matter. Following each inhalation, the number of coughs in the subsequent 15 seconds was counted and recorded. The challenge was terminated once the citric acid induced 5 or more coughs and the logarithmic (base 10) concentration provoking 5 coughs was recorded.

Methacholine Challenge

Intervention Type: PROCEDURE

A baseline spirometry was used to assess how well the participant's lungs work by measuring how much air was inhale, how much was exhale and how quickly the participant exhaled. If this was normal, the subject inhaled slowly and deeply the methacholine test solution from a nebulizer and was told to hold their breath for 5 seconds. This was repeated until 5 inhalations were performed in no more than two minutes.

Interventions

Cough Reflex Sensitivity

Subjects inhaled increasing concentrations of citric acid, which induces coughing in a dose-dependent, reproducible matter. Following each inhalation, the number of coughs in the subsequent 15 seconds was counted and recorded. The challenge was terminated once the citric acid induced 5 or more coughs and the logarithmic (base 10) concentration provoking 5 coughs was recorded.

Intervention Type: PROCEDURE

Methacholine Challenge

A baseline spirometry was used to assess how well the participant's lungs work by measuring how much air was inhale, how much was exhale and how quickly the participant exhaled. If this was normal, the subject inhaled slowly and deeply the methacholine test solution from a nebulizer and was told to hold their breath for 5 seconds. This was repeated until 5 inhalations were performed in no more than two minutes.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• symptomatic reflux (i.e., one symptom at least one day a week, with at least 'moderate' severity)
• no evidence of esophagitis
• non-smokers

Exclusion Criteria

• previous gastrointestinal surgery (excluding minor surgeries, such as cholecystectomy, appendectomy
• active peptic ulcer disease
• Zollinger Ellison Syndrome
• Barrett's esophagus
• eosinophilic esophagitis
• cardiac disease
• diabetes or neurological deficit
• use of tricyclics
• selective serotonin reuptake inhibitors
• narcotics or benzodiazepines
• current use of medications that may affect symptoms of perception,lower esophageal sphincter basal pressure, acid clearance time or acid suppression
• antibiotics within 60 days
• Nursing mothers will be excluded
• allergies to citrus
• asthma
• chronic lung disease
• heart attack or stroke within the last three months
• hypersensitivity to methacholine products
• know aortic aneurysm
• uncontrolled hypertension (defined as systolic pressure greater than 200 or diastolic greater than 100)
• reduced pulmonary function test (forced expiratory volume in one second (FEV1) or the FEV1 to forced vital capacity (FVC) ratio (FEV1/FVC) of less that 70% of predicted value)
• None of the controls will have any GERD symptoms or ever used antireflux treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Manchester

OTHER

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Kenneth R. DeVault, M.D.

Professor, College of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenneth R. DeVault, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Florida

Jacksonville, Florida, United States

Countries

United States

Other Identifiers

11-006873

Identifier Type: -

Identifier Source: org_study_id