This study is examining the effect of hypertonic saline compared to placebo on the Lung Clearance Index in Cystic Fibrosis patients.

The life expectancy of patients with Cystic Fibrosis (CF) has greatly increased over time due to improved clinical care. While this is certainly beneficial to CF patients, the overall stability in lung function has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 (forced expiratory volume in 1 second) remains the primary outcome measure for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2% in large specialized centres. Therefore, additional parameters are needed that are more sensitive parameters to define abnormalities in CF patients and be used in therapeutic trials.

One such promising parameter is the Lung Clearance Index (LCI). The LCI is a test to quantify ventilation inhomogeneity by assessing the washout of an inhaled inert gas. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways.

Interventions that improve mucus accumulation are expected to improve the LCI. Hypertonic saline has been shown to increase airway surface liquid (ASL), mucociliary clearance and pulmonary function. Therefore, this study will examine the effect of hypertonic saline compared to placebo on the Lung Clearance Index in Cystic Fibrosis 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
• 6-18 years of age at enrolment and able to perform reproducible spirometry
• Clinically stable at enrolment
• FEV1 % predicted ≥ 80 % as calculated by the Wang reference equations
• Ability to comply with medication use, study visits and study procedures

Exclusion Criteria:

• Respiratory culture positive for NTM or B. cepacia complex within past year or screening
• Use of intravenous antibiotics or oral quinolones within 14 days of screening
• Investigational drug use within 30 days of screening
• Physical findings at screening that would compromise the safety of the participant or the quality of the study data