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.

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.

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.

This study will recruit participants into three groups ages 18-60 years: 12 reflux patients with non-erosive disease (NERD) with abnormal levels of acid reflux, 12 NERD patients with normal levels of reflux and 12 healthy volunteers.