“Nearly all individuals with cystic fibrosis (CF) suffer from chronic rhinosinusitis (CRS),” notes David A. Gudis, MD. “The underlying pathophysiology of CF is due to a mutation in the CF transmembrane regulator (CFTR) protein that transports anions, mostly chloride, across the cell surface. When this protein is dysfunctional, mucus in the airways becomes too thick and excessively viscous, resulting in impaired mucociliary clearance. The airways then become an optimal environment for the colonization and growth of dangerous bacteria.”

According to Dr. Gudis, processes like bacterial colonization, diversity, and the development of mutations—including those that confer antibiotic resistance, among other things—are likely developing in the sinuses before they occur in the lungs. Previous research has also demonstrated that genotypically identical bacteria then grow in the lungs. As a result, the sinuses represent “a critical opportunity for medical and surgical intervention to potentially improve the overall health of a person with CF,” Dr. Gudis says, noting that there is much about CF CRS that is not yet fully understood. “However, CF CRS is distinct from other forms of CRS, and some of the management principles are different.”

For a paper published in International Forum of Allergy & Rhinology, Dr. Gudis and colleagues aimed to provide evidence-based recommendations for the management of CF CRS. They conducted a systematic literature search through January 2021 of all available papers on CF CRS for the generation of an evidence-based review with recommendations. “The rigorous methodology then included deliberation among a panel of co-investigators with extensive experience in managing CF CRS,” Dr. Gudis explains. The authors’ “strict inclusion criteria for evidence” resulted in four studies on the use of nasal saline in patients with CF CRS, four on intranasal corticosteroids (INCS), eight on topical antibiotics, 12 on CFTR modulator therapy, and 53 on endoscopic sinus surgery (ESS).

Nasal Saline & Sinus Surgery Recommended

Based on the results of their iterative process, Dr. Gudis and colleagues reported that nasal saline, ESS, and CFTR modulators are recommended for CF CRS when appropriate, while INCS and topical antibiotics are considered optional therapies (Table).

“Nasal saline is safe and effective for CRS; it helps to clear debris and pathogens from the sinuses,” Dr. Gudis explains. “ESS, while far from a cure, has proven to be a very effective intervention by reducing symptoms and bacterial burden; the combination of surgery and appropriate topical antibiotic therapy has been shown to completely eradicate pathogenic bacteria like Pseudomonas from CF sinuses. CFTRs are a wonderful new class of medications that have completely revolutionized CF treatment.”

Dr. Gudis notes that intranasal corticosteroids “are probably not very effective for CF CRS because the inflammatory profile in CF mucosal disease is more neutrophilic, rather than eosinophilic, and therefore less responsive to corticosteroids.” Additionally, while topical antibiotics “can be extremely effective for various sinonasal disorders including CF CRS, there is very limited data regarding the appropriate dose, delivery mechanism, and adverse effects.”

Agents Transform CF CRS Treatment

It is important for otolaryngologists, pulmonologists, and other clinicians to recognize CF CRS as a “distinct diagnostic entity” that necessitates a “complex and nuanced” management strategy, according to Dr. Gudis. “Pulmonologists don’t manage CF the same way they manage asthma,” he notes. “Likewise, otolaryngologists should not assume that CF CRS should be managed the way we manage other forms of CRS.  Patients with CF require a team approach, with multidisciplinary management by experienced clinicians.”

Dr. Gudis concludes that it is “an exciting time” to be treating patients with this disorder. “I am thrilled about the potential of CFTR modulators to completely transform the medical care and prognosis of patients with CF,” he says. “It is an exciting time to care for these patients and see the tremendous progress that scientists and physicians have made on their behalf. Patients with CF are the kindest, most resilient, down-to-earth patients whom I have had the privilege of treating, and I look forward to further efforts to improve their quality of life.”