• 1) Differences between the Cough-Specific Quality of Life Questionnaire between active treatment and placebo groups, and,
• 2) Differences in Fisman Cough Frequency/Cough Severity Scores between active treatment and placebo groups.

• 1) The percentage of subjects with cough secondary to GER (defined as a response to therapy as demonstrated by an improvement of 1 standard deviation or greater on the Cough-Specific Quality of Life Questionnaire),
• 2) The percentage of cough episodes that are accompanied by a reflux event,
• 3) The correlation of pharyngeal probe acid exposure to cough events,
• 4) The percentage of subjects with abnormal findings consistent with GERD on larygoscopy who respond to anti-reflux therapy,
• 5) The change in appearance of the posterior larynx in those with chronic cough after anti-reflux therapy (as measured by the Reflux Finding Score 18 ).
• 6) Pre- and post treatment differences between the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS-ds) amongst active treatment and placebo groups.

The purpose of this research study is to investigate different doses of proton pump inhibitors in reducing cough symptoms felt to be associated with Gastroesophageal reflux disease (GERD). Proton pump inhibitors are medicines used to treat GERD, which work by lowering the amount of acid in the stomach.

The proton pump inhibitor used in this study is called, Esomeprazole (brand name Nexium), and is already marketed for treating GERD. Patients with GERD may experience all or some of the following symptoms: stomach acid or partially digested food re-entering the esophagus (which is sometimes referred to as heartburn or regurgitation), belching and coughing. Even very small, unnoticeable amounts of rising stomach acid may cause patients to cough.

Because there may be a link between chronic cough and GERD, study doctors are interested in learning if giving high-dose Nexium (40 milligrams, twice daily) will help in treating chronic cough.

This study will be a randomized, double-blind, placebo controlled, comparative parallel-group trial of subjects with chronic cough of unknown origin presenting to the Otolaryngology/ Head and Neck Surgery, Pulmonary Medicine, and Gastroenterology outpatient clinics at the University of North Carolina Hospital system.

Potential subjects with chronic cough of unknown origin will be identified through the above outpatient clinics. Those who meet the inclusion and exclusion criteria will be asked to join the study testing the efficacy of twice daily esomeprazole 40 mg taken for 3 months in the setting of chronic cough. Potential subjects will be consented for the study prior to leaving the enrolling clinic. A total of 40 subjects will be recruited into our study.

• Cough
• GERD

• Drug: Esomeprazole
• Drug: Placebo

• Experimental: 40mg Esomeprazole BID
• Placebo Comparator: placebo capsules

Inclusion Criteria:

1. males and females (of non-childbearing potential. ie-surgically sterile, or willing to use an approved form of birth control) between the ages of 18 and 70 who speak and write in English,
2. chronic cough (> 8 wks/another article used > 6 wks) with symptom severity criteria of 2 or greater on the Fisman Cough Severity Score and 3 or greater or the Fisman Cough Frequency Score, and,
3. failure to respond to post nasal drip therapy.

Exclusion Criteria:

1. abnormal chest x-ray,
2. patients taking H2 blockers within the previous 3 days or PPI's within the previous 7 days,
3. failure to respond to past PPI therapy given for cough that lasted at least 12 weeks,
4. use of an investigational drug within the past 30 days,
5. previous surgical antireflux or non-surgical endoscopic anti-reflux procedure (ex., Stretta or endoscopic sewing device),
6. previous aerodigestive malignancy,
7. current smokers, or ex-smokers (defined as those who quit smoking less than 3 months prior to study enrollment or those who have quit, but have a 20 pack year smoking history),
8. upper respiratory infection within 8 weeks prior to study enrollment,
9. current use of a B- blocker, ACE-I, or anticholinesterases at time of enrollment.