In this trial real-world data on the safety (side effects and medication interactions) and efficacy (evolution of lung function testing, chronic bacterial airway infection, quality of life and endo- and exocrine pancreatic function) will be collected in adult people with cystic fibrosis (pwCF) eligible for elexacaftor-tezacaftor-ivacaftor (ETI) up until 2 years after the start of this therapy.

PwCF group A: CFTR-modulator-naive pwCF eligible for ETI (based on age and CFTR genotype)

PwCF group B: pwCF already on CFTR modulating therapy (i.e. ivacaftor-lumacaftor or ivacaftor-tezacaftor) and switching to ETI.

Patients in both groups will undergo these examinations:

• Physical examination (including weight)
• Anamnesis for current and recent medication use (including dosage of pancreatic enzymes) and for acute respiratory exacerbations
• Lung function testing including spiometry, multiple breath washout testing and fractional exhaled nitric oxide
• Blood sampling: liver function tests, creatine kinase, albumin, PT, red and white blood cell count, platelet count
• Sputum/cough swab sampling
• fecal elastase measurement
• Cystic fibrosis questionnaire-revised (CFQ-R) questionnaire
• Patient health questionnaire-9 (PHQ-9) questionnaire
• General anxiety disorder-7 (GAD-7) questionnaire
• Sino-nasal outcome test-22 (SNOT-22) questionnaire

These will be performed at baseline (prior to the start of ETI, on the same day of start of ETI), and every 3 months (+/- 7 days) thereafter. A blood sample will also be performed 14 (+/- 7 days) days after start of ETI (for safety). Fecal elastase measurement will only be performed at baseline if not available in the patient's medical record, and only 6 months after start of ETI.

Inclusion Criteria:

• eligible for ETI (i.e. age above 18 years and CFTR genotype F508del/any) based on reimbursement criteria in Belgium

Exclusion Criteria:

• inability to perform lung function testing