Cystic fibrosis (CF) is a genetic condition characterised by recurrent lung infections, inflammation and progressive lung damage. Patients with CF and advanced lung disease are limited when exercising and performing activities of daily life, due to increased breathlessness and lower oxygen levels.

Exercise is an important part of treatment in CF, having been shown to slow down the lung disease and improve quality of life. Patients with CF are encouraged to exercise both at home and during hospital admissions, even when the lung disease is advanced. Often, oxygen therapy is used in patients whose oxygen levels are otherwise too low during. This, however, does not improve their breathlessness.

Recently, a device to deliver air at flows higher than what other device allow has become available. High flow nasal therapy (HFNT) provides patients with air or a blend of air and oxygen at flows up to 60 L/min. HFNT can improve oxygen levels and reduce shortness of breath in many situations both in the acute and chronic setting. HFNT was shown to improve the tolerance to exercise in patients with other respiratory conditions (chronic obstructive pulmonary disease).

In CF, HFNT is routinely used for patients admitted with acute respiratory failure (inability to maintain adequate oxygenation) with positive results.

In this study, the Investigators aim to understand if HFNT can improve the exercise tolerance in patients with CF and advanced lung disease, by reducing breathlessness and avoiding the drop in oxygenation observed during simple training.

The Investigators propose a short study to assess if further large clinical trials are feasible and practical, and will therefore collect preliminary data to have some results to use for planning other studies. All patients who are admitted in the Leeds Regional Adult CF Unit will be considered for participation in the study.

Regular high-level exercise in people with CF has been linked with reduced rate of decline in lung function, is positively related to quality of life and improvement in bone mineralisation. Unfortunately, exercise tolerance in patients with cystic fibrosis (CF) and severe lung disease is limited by dyspnoea, exercise-induced desaturations (EID) and fatigue. Therefore, a reduction in patients' activity level can be observed, which would lead to further deconditioning.

High-flow nasal therapy (HFNT) delivers heated, humidified and oxygenated gas with flow rates up to 60 L/min at FIO2 adjustable between 0.21 and 1.0 via soft, loose fitting, large bore nasal prongs (Airvo2/OptiflowTM). HFNT has been shown to (a.) Wash out nasopharyngeal dead space, minimizing rebreathing of CO2 and acting as a reservoir for fresh air, thus contributing to improved gas exchange with respect to CO2 and O2. (b) Lower respiratory rate and provide a small positive end expiratory effect. (c) Provide oxygenated gas at a flow that matches more closely the patient's spontaneous inspiratory flow rate, thus attenuating inspiratory resistance within the nasopharynx and eliminating the related increase in work of breathing. (d) Provide warmed and humidified gas (37°C and 44 mg/L H2O) thus reducing airway dryness, enhancing patient comfort and reducing the metabolic work associated with gas conditioning. (e) Moisten secretion and facilitate mucociliary clearance.

HFNT is being extensively studied, in comparison to NIV and conventional oxygen therapy, in de novo acute respiratory failure, in post-surgical and post-extubation setting and in do-not-intubate patients. One pilot study has demonstrated that HFNT can increase exercise tolerance in stable patients with severe COPD, with improvement in oxygen saturation and perceived dyspnea and muscle fatigue.

As the main limiting factors for exercise tolerance in patients with CF and severe lung disease are perceived dyspnoea, and hypoxaemia related symptoms, secondary to static and dynamic hyperinflation, it is conceivable that HFNT could have beneficial effects in improving exercise tolerance and reducing symptoms.

The Investigators propose here a pilot study to assess a feasibility of a subsequent trial of long-term use of HFNT during exercise training in patients with CF compared to standard oxygen or room air.

A single-centre, short-term, open, randomized, cross-over study is planned. The Investigators will compare the results of 6-MWT on HFNT and without HFNT (either on conventional oxygen therapy or room air). The Investigators plan to enroll 25 subjects, expecting a drop-out rate of 5%, to have 20 subjects completing the study. Each subject will serve as their own control.

Participants in the study will be asked to fill in a questionnaire which is routinely used in the assessment of exercise and activity among patients with CF, and has been previously validated in other CF Centre.

Study procedures will consist in:

• Two 6-minute walking test (24 to 48 hours apart). The 6-minute walking test is a simple assessment of exercise and consist in the patient having a brisk walk for 6 minutes. Patients can increase or decrease the speed at their will while walking. Oxygen and carbon dioxide (the waste gas) levels will be measured through a sensor applied to the skin. Patients will be asked to score their breathlessness, comfort and fatigue, before, during and after the test. One of the tests will be performed under the usual condition, the other test on HFNT.
• Lung function before and after each 6-minute walking test. Lung function is a standard assessment in CF, consisting in blowing air into a machine to measure lung volumes and flows.

Measures related to the 6-minute walking test and the lung function will be recorded as part of the study. The Investigators will record patients' feedback on shortness of breath, comfort and fatigue, but also oxygen and carbon dioxide levels, frequency of breathing and distance walked during the 6 minutes.

Inclusion Criteria:

• Diagnosis of CF
• Severe lung disease (FEV1 ≤40%)

Exclusion Criteria:

• Acute viral illness
• Requirements of >6 L/min nasal O2 to maintain SpO2 >88% at rest
• Acute respiratory acidosis
• Arthritis exacerbation
• Inability to obtain informed consent
• Recent pneumothorax (<6 weeks)
• Usual contraindication to exercise testing