The investigators are doing this study to discover if it is appropriate for people with Cystic Fibrosis (CF) on highly effective modulator therapy (HEMT) to stop using certain standard Sino nasal therapies such as high-volume nasal saline irrigations, topical nasal steroids, and topical nasal antibiotics. They are also going to study the fluid inside the nose to see if there are changes when stopping these therapies. Right now, they are not sure if it is suggested to stop these treatments when patients begin highly effective modulator therapy (HEMT)

Cystic fibrosis (CF) is a widely known genetic disorder causing patients significant sinopulmonary disease. (1) The advent of highly effective modulator therapy (HEMT) has led to tremendous improvements in manifestations of disease in the lungs, sinuses, along with other organ systems, raising the question of whether and how to de-escalate other treatments for the airways. Specifically for CF, no protocols exist for the de-escalation of the most common sinonasal therapies: high-volume nasal saline irrigations, topical nasal steroids, and topical nasal antibiotics. Establishing such protocols would benefit patients by removing these cumbersome medication regimens, reducing the cost of medications, and lowering risks of side effects and complications from therapies that may no longer provide clinical benefit. This study aims to sample the sinonasal environment for inflammatory markers in patients with cystic fibrosis (PwCF )on HEMT and correlate to subjective and objective clinical findings during de-escalation trials from saline nasal irrigations, topical nasal steroids and/or antibiotics.

The investigators will prospectively follow adult cystic fibrosis patients with chronic rhinosinusitis with or without history of sinus surgery currently using CFTR modulator therapy via diagnostic methods (nasal endoscopy, FEV1, BMI) which are standard of care evaluations currently performed at both Rhinologic and Pulmonary visits. Questions regarding health care utilization (antibiotics, steroids, hospital admissions, doctor visits) will be reviewed, which are also part of the standard history taken at patient intake for these visits. Patient reported outcome measures (PROMS) (SNOT-22, Cystic Fibrosis Questionnaire- Revised (CFQ-R), Patient Health Questionnaire-9 (PHQ-9)) are also routinely collected at these Rhinologic and Pulmonary visits, thus patients are accustomed to these items in routine standard of care followups. Upon enrollment to the study after informed consent obtained, the patients will be randomly assigned to continue or stop topical medicated nasal irrigations. Participants will continue the 1-2 times per day they currently perform the saline topical nasal irrigations, or told to discontinue completely.

To better understand the inflammatory microenvironment on and off HEMT therapy, nasal leukosorb analyses will be studied from at 4-week intervals in the PwCF enrolled in aim 1 for the 12-week study period, to determine trends of inflammation for patients in each arm of the de-escalation study. Following protocols established by Rebuli et al, patients will moisten their nostrils with ~100uL of 0.9% sterile normal saline solution, followed by applying a cut sheet of Leukosorb medium of 4x40mm in length into each nostril onto the anterior part of the inferior turbinate. (19) The nostrils will then be clamped with a padded nose clip. The strips will be removed at 2 minutes, and placed into 1.5mL collection tubes and stored at -20 deg C until fluid elution and analysis.

Inclusion Criteria:

• Age 18 or older
• Cystic Fibrosis diagnosis on HEMT
• History of chronic rhinosinusitis
• Using topical nasal irrigations +/- additives (steroids, antibiotics)

Exclusion Criteria:

• Below age of 18 years old
• Cystic Fibrosis patient NOT on highly effective modulator therapy
• Pregnant patients
• Not currently using topical nasal irrigations +/- additives (steroids, antibiotics)
• History of sinonasal or nasopharyngeal tumors
• Active sinonasal infection or pulmonary infection
• Admission to hospital for pulmonary exacerbation within last 3 months
• Oral antibiotics within last one month for upper respiratory or lower respiratory infection