Gastroesophageal reflux disease (GERD) is a common problem in cystic fibrosis (CF). It may lead to worsening lung function and more respiratory infections for a person with CF. This study will look at treating GERD with a medication, esomeprazole. The medication stops stomach acid from being made. The study will see if there are fewer respiratory infections and improved lung function in patients with CF when taking esomeprazole.

This is a randomized, placebo controlled intervention study in patients with CF who have a history of frequent exacerbations. Treatment duration is 6 months.

Inclusion Criteria:

1. Cystic fibrosis
2. Age > 18 years
3. Stable maintenance medical regimen during the previous 6 weeks.
4. Negative pregnancy test (women of childbearing potential) at both screening and baseline visits.
5. Women of childbearing potential must be using medically acceptable contraception.
6. At least two respiratory exacerbations per year requiring oral and/or intravenous antibiotics for each of the two years prior to study entry, but no more than 4 exacerbations requiring intravenous antibiotics during either of those years.

Exclusion Criteria:

1. Previous anti-reflux or peptic ulcer surgery,
2. Use of proton pump inhibitor (PPI) within the past two weeks
3. Pulmonary exacerbation requiring antibiotics within the previous 2 weeks
4. Parenteral hyperalimentation
5. Cigarette smoking
6. Treatment with azoles, iron, anti-coagulants, digitalis
7. Use of any investigative drugs within the previous month.
8. Use of over the counter acid suppressor agents (not including acid neutralizers)

Study findings are limited by small sample size without adequate power to detect significant differences between participants treated with esomeprazole compared with placebo.