This is an observational study of people with severe cystic fibrosis that are eligible for Vertex's triple combination therapy through its expanded access. Pulmonary health, intestinal health, and the overall health of individuals will be tracked for a year to see how effective triple combination therapy is in these people with severe cystic fibrosis disease.

Inclusion Criteria:

• Confirmed diagnosis of Cystic Fibrosis
• Ability to reproducibly perform spirometry (according to ATS criteria)
• Physician decision to treat with TCT through the EAP program
• Ability to understand and sign a written informed consent or assent and comply with the requirements of the study

Exclusion Criteria:

• History of hypersensitivity to VX 445, VX 659, tezacaftor and/or ivacaftor
• Any acute lower respiratory symptoms treated with oral, inhaled or IV antibiotics or systemic corticosteroids within the 2 weeks prior to Visit 1.
• Major or traumatic surgery within 12 weeks prior to Visit 1.
• Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 1.
• Use of an investigational agent within 28 days prior to Visit 1.
• History of lung or liver transplantation or listing for organ transplantation.

Patients at National Jewish Health with Cystic Fibrosis who are eligible to enroll in Vertex's triple combination therapy expanded access program.