Cough Reflex Sensitivity and Bronchial Hyper-responsiveness

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pilot Studies Evaluating Cough Reflex Sensitivity and Bronchial Hyper-responsiveness: The Road to Cough and Wheeze in Patients With Gastroesophageal Reflux.

Conditions
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Gastroesophageal Reflux Disease, Chronic Cough, Broncho-hyperreactivity

Intervention / Treatment
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* Procedure: Cough Reflex Sensitivity
* Procedure: Methacholine Challenge


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Volunteers<br>Subjects in this arm were healthy volunteers. Subjects underwent both Cough Reflex Sensitivity and the Methacholine Challenge procedures. | Procedure: Cough Reflex Sensitivity<br>* 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.<br>Procedure: Methacholine Challenge<br>* 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.<br>|
| Non-erosive reflux disease with reflux<br>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. | Procedure: Cough Reflex Sensitivity<br>* 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.<br>Procedure: Methacholine Challenge<br>* 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.<br>|
| Non-erosive reflux disease without reflux<br>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. | Procedure: Cough Reflex Sensitivity<br>* 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.<br>Procedure: Methacholine Challenge<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cough reflex sensitivity (CRS) |  | baseline, approximately 4 weeks |