This is a prospective, multi-center observational study. The study is designed to measure the clinical effectiveness of elexacaftor, tezacaftor and ivacaftor triple combination therapy (TCT) in people with one or more copies of the F508del mutation, study the effects of TCT across a number of CF disease manifestations, and collect specimens for future research. Subjects in the study will have one "before TCT" visit within 30 days before initiation of the therapy and five "after TCT" visits over a 24-month follow-up period. Most participating sites will be divided into sub-study groups; each sub-study group will have specific non-optional procedures conducted in addition to the "Core" procedures. Finally there are four optional procedures (pH pill, transient elastography, and nasal cell procurement) that will be offered to subjects at certain sites. The duration of participation for each subject is 25 months. NOTE: FDA is currently reviewing the New Drug Application (NDA) for the TCT. Study will not begin unless and until FDA approval is granted.