Ivacaftor for Acquired CFTR Dysfunction in Chronic Rhinosinusitis

This study is testing whether a medication called ivacaftor — originally developed to treat cystic fibrosis (CF) — can help patients with chronic rhinosinusitis (CRS), which is a long-term inflammation of the sinuses. Interestingly, even people without CF can develop dysfunction in a protein called CFTR (which ivacaftor targets) in their sinuses, especially when there is a chronic bacterial infection. Researchers believe this "acquired" CFTR dysfunction may worsen sinusitis, and that ivacaftor might help restore normal sinus function and mucus clearance. The study will test ivacaftor in patients who have already had sinus surgery, still have ongoing bacterial infections (particularly gram-negative bacteria like Pseudomonas), and have confirmed CFTR dysfunction. Participants will receive the medication and be monitored for improvements in sinus function and quality of life. You may be eligible if: - You are 18 years old or older - You have been diagnosed with chronic rhinosinusitis (CRS) - You have had a positive culture for gram-negative bacteria (e.g., Pseudomonas) within the last 30 days - You have already had sinus surgery with exposed maxillary and ethmoid sinuses - You have a recent CT scan confirming sinus disease - You have a negative pregnancy test (if applicable) You may NOT be eligible if: - You are under 18 - You are currently taking strong or moderate CYP3A inhibitor medications - You have had an asthma attack requiring emergency care or oral steroids in the past 2 months - You have a history of organ or bone marrow transplantation - You have known immunodeficiency, autoimmune, or granulomatous disease - You have abnormal kidney or liver function - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.