This will be a randomized controlled trial design with 2:1 randomization (2 to symptom driven to 1 in continuous) for this pilot study to determine if symptom-driven airway clearance after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy is feasible and can eventually determine if it is non-inferior to continuing airway clearance therapies. The study will be performed as an intention to treat protocol. All participants who are eligible and enrolled will be asked to perform airway clearance twice daily for 12 weeks prior to randomization and then will be followed for 12 weeks including study visits at week 0, week 4, week 8, and week 12. The study will require no change in current use of inhaled antibiotics nor adjust the frequency of the medication during the study. Airway clearance methods to be recorded include aerobika or flutter valve, high frequency chest oscillation therapy (vest), intrapulmonary percussive ventilator, or exercise performed specially for airway clearance. The medications to be monitored included nebulized Albuterol, nebulized hypertonic saline, nebulized Pulmozyme, and nebulized mannitol. The continuous arm (control arm) will be asked to perform airway clearance twice daily for the entirety of the study and record all therapies performed daily. The symptom driven arm will perform airway clearance on their own discretion, whether this be from steady decline in baseline respiratory status or acute flair of symptoms related to infectious etiology. At baseline participants will undergo pulmonary function testing, sputum/throat culture and Cystic Fibrosis Questionnaire Revise (CFQ-R). On week 0, week 4, week 8 and week 12 visits the participants will undergo pulmonary function testing and CFQ-R with addition of sputum/throat cultures on week 12. Between each study visit participants will be asked to perform home spirometry once weekly for the 12-week trial period. For participants enrolled in the continuous group the investigators will ask for participants to perform home spirometry after either twice daily airway clearance routine or for the symptom-based group to perform at roughly the same time of day for each test. Participants will also be asked to keep a daily cystic fibrosis diary during the run-in period and study period in which participants will record if, and how frequent, participants use any airway clearance medications or devices during the day. A reduction in percent predicted forced expiratory volume in 1 second (ppFEV1%) or percent predicted forced vital capacity (ppFVC%) of more than 10% in laboratory PFT testing for 2 consecutive weeks will be deemed an adverse event and lead to the participant in the symptom driven arm being instructed to perform daily airway clearance therapy. A reduction in ppFEV1% and/or ppFVC% in home spirometry by more than 10% will trigger a need for in lab PFT testing to determine if participants have developed an adverse event leading to performing daily airway clearance therapy or if participants are to continue symptom-based airway clearance. Other criteria for participants to be evaluate in-person between study visits include use of daily airway clearance for more than 7 consecutive days in the symptom-based arm or signs and symptoms of a possible acute pulmonary exacerbation. If participants develop an exacerbation from an identifiable cause other than their primary CF lung disease (viral infection, asthma exacerbation, pulmonary embolism, etc.) participants will undergo appropriate treatment, and while the event will be deemed an adverse event, participants will continue with their current treatment protocol. Participants who are treated for an acute severe pulmonary exacerbation requiring IV antibiotics and/or hospitalization will either continue in the continuous treatment arm or if in the symptom driven arm be instructed to perform daily airway clearance for the duration of the study. In participants with concurrent asthma diagnoses, the investigators will not require any discontinuation of additional inhaler/nebulized therapies that are asthma specific, but no bronchodilators will be started specifically for the study.