Exercise-Induced Bronchospasm in Cystic Fibrosis

We anticipate that Visit 1 will take approximately three hours. This will include obtaining
informed consent, completing baseline demographic and quality of life questionnaires, brief
physical exam, measuring exhaled nitric oxide level, skin allergy testing, obtaining blood
and sputum samples, and performing pulmonary function testing before and after
bronchodilators.

Visit 2 will take approximately two and one-half hours. This will include performing
Eucapnic Voluntary Hyperventilation, measuring exhaled nitric oxide levels, and obtaining
blood and sputum samples.

Visit 3 will take approximately two and one-half hours. This will include performing
Cardiopulmonary exercise testing followed by serial spirometry, measuring exhaled nitric
oxide levels, and obtaining blood and sputum samples.

Inclusion Criteria:

1. Males and females with confirmed diagnosis of Cystic Fibrosis:

- 2 positive sweat chloride tests (or)

- genetic testing

2. Age 12 years and older

3. Baseline FEV1 ≥70% predicted

4. Clinically stable over past 28 days:

- no change in chronic respiratory symptoms

- no need for antibiotics other then chronic maintenance therapies

- no need for oral steroids

- no increased use of bronchodilators

5. Visit 1 FEV1 within 10% of baseline

Exclusion Criteria:

1. History of Allergic Bronchopulmonary Aspergillosis (ABPA)

2. Chronic airway colonization with Burkholderia cepacia (defined as 2 or more prior
positive sputum or BAL cultures)

3. Pregnancy

4. Chronic oral corticosteroid use

5. Febrile illness within two weeks of Visit 1

6. Unable to provide consent (patients under age of 18 will require both parental
consent AND patient assent)

7. Current cigarette smoking, cessation of smoking within 6 weeks of Visit 1, or more
than 10 pack-years of prior smoking