The Lung Clearance Index (LCI) is a non invasive measure of lung function that is more sensitive than FEV1. It can be used to measure lung function in children younger than 6 years of age. Therefore, it has a future role in assessing novel therapeutics in the Cystic Fibrosis (CF) population. As such, determining if it can be used as a short term pharmacodynamic biomarker is paramount.

Inhaled Hypertonic saline (7%) is a treatment intervention for Cystic Fibrosis patients and has previously been shown to improve lung function and decrease the number of pulmonary exacerbations. The Cystic Fibrosis Transmembrane Regulator Gene (CFTR) protein is essential for maintaining fluid and electrolyte homeostasis in the lung and CFTR defects cause depletion of the periciliary liquid layer which results in impaired mucociliary clearance. Inhaled hypertonic saline (7%) acts as an osmotic agent in the lungs; it repletes the airway surface liquid (ASL) and improves mucociliary clearance.

In addition, we have recently demonstrated that the Lung Clearance Index (LCI) is also a responsive outcome measure. In an intervention study in which patients were treated with hypertonic saline inhalation twice daily for 28 days, LCI but not FEV1 significantly improved in 17 pediatric Cystic Fibrosis (CF) patients with mild lung disease. In this study, LCI was more sensitive to a change in response to treatment than spirometry in a small number of patients. However, it still remains unknown if the LCI will be able to detect a treatment effect on a shorter time scale after an intervention. Its use as a short-term pharmacodynamic biomarker in CF patients remains unknown. The ability of the LCI to detect treatment effects within hours after an intervention would be invaluable to the development of new therapeutic interventions for CF patients.

Inclusion Criteria:

• Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
• Informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject
• At least six years of age at enrolment
• Able to perform reproducible spirometry meeting American Thoracic Society standards
• Pre-bronchodilator FEV1 % predicted > or equal to 40 % predicted
• Ability to perform a reproducible LCI maneuver at screening

Exclusion Criteria:

• Known respiratory culture positive for Burkholderia cepacia
• Previous lung transplantation
• Use of intravenous antibiotics within 14 days of screening
• Use of oral antibiotics including prophylactic antibiotics (e.g., augmentin, tetracycline, cloxacillin, cephalosporins, septra, bactrim) within 14 days of screening
• Initiation of a new maintenance (e.g high dose ibuprofen, Pulmozyme®, aerosolized antibiotics) within 14 days of screening
• Use of systemic corticosteroids within 14 days of screening
• Investigational drug use within 30 days of screening
• Use of hypertonic saline (7%) < 4 weeks before screening or outside of the study protocol
• Participation in any therapeutic clinical study <4 weeks or, 5 half-lives, whichever is longer, before screening
• Smoking < 3 months before screening
• Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data