Modulator Therapy Improves Chronic Sinus Disease in Individuals with Cystic Fibrosis

Modulator Therapy Improves Chronic Sinus Disease in Individuals with Cystic Fibrosis 1024 683 Mary Bates, PhD

Following 1 year of therapy, patients showed improved sinus CT metrics and clinical outcomes.

Over the last decade, the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs has revolutionized the treatment of cystic fibrosis (CF). The most widely used modulator is the triple combination elexacaftor-tezacaftor-ivacaftor (ETI), which is approved for people with CF aged 6 years and older. Clinical trials of ETI therapy have shown that it results in significant improvement in respiratory function, inflammation, weight and body mass index, and quality of life for people with CF. However, CF is a multiorgan disease, and the effects of CFTR modulator therapy on other organ systems  in individuals with CF  are not well characterized.

“Approximately half of people with CF experience chronic sinus disease with significant morbidity,” says Shahid Sheikh, MD, a member of the Section of Pulmonary Medicine and Allergy/Immunology at Nationwide Children’s. “Since we have seen improvement in lung disease and function with ETI therapy, we were keen to see how it may affect the sinuses.”

In a new study, Dr. Sheikh and colleagues investigated the outcome of ETI therapy on chronic sinus disease in individuals with CF, as measured by changes in sinus computed tomography (CT) metrics and clinical parameters. For 64 participants, the researchers obtained sinus CT scans within one month of beginning ETI therapy and again following one year of therapy. The CT images were independently analyzed by pulmonary, radiology, and otolaryngology physicians using two scoring systems: the Lund-Mackay system (widely used in chronic sinus disease but not specific to CF) and the Sheikh-Lind system (a CF-specific scoring system developed at Nationwide Children’s).

Dr. Sheikh and colleagues noted improvements in sinus CT metrics after one year of ETI therapy in patients with CF, confirmed using both sinus CT scoring systems. The researchers also report that ETI therapy was associated with improved clinical outcomes and reductions in positive bacterial cultures done with sputum or throat swabs.

“During this one-year study, none of the patients required intravenous antibiotics for sinus disease, nor had surgeries for sinus disease,” says Dr. Sheikh, who is also a professor of clinical pediatrics at The Ohio State University College of Medicine. “And there was not a single patient in which sinus disease deteriorated during this one-year study, so we saw a mean improvement in most of the patient.”

While there were improvements in CT scan scores and clinical outcomes, most participants continued to have scores for both systems that indicated sinus disease.

“We conclude that despite significant progress in sinus disease, ETI therapy is not curative and there is still some residual disease after one year of treatment,” says Dr. Sheikh. “That means will still have room for improvement, and we are hopeful that, with time, even better therapies for CF will be available.”



Sheikh S, Ho ML, Eisner M, Gushue C, Paul G, Holtzlander M, Johnson T, McCoy KS, Lind M. Elexacaftor-Tezacaftor-Ivacaftor Therapy for Chronic Sinus Disease in Cystic Fibrosis. JAMA Otolaryngol Head Neck Surg. 2023 Dec 1;149(12):1075-1082. doi: 10.1001/jamaoto.2023.2701.


About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.