Chronic rhinosinusitis in patients with cystic fibrosis—Current management and new treatments

Abstract

ObjectivesThe purpose of this article is to provide a state‐of‐the‐art review of the literature and summarize the latest publications on medical and surgical treatment of cystic fibrosis (CF) chronic rhinosinusitis (CRS), with an emphasis on describing recent advancements in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies.MethodsA comprehensive literature review was conducted utilizing the PubMed database with search phrases detailed within the body of the article. Abstracts were reviewed to include publications detailing medical, surgical, and CFTR modulating therapies for CF CRS. Findings from studies not previously reviewed and publications regarding CFTR modulators were emphasized.ResultsNo clear guidelines for treatment of CF CRS are available. Nasal saline rinses, topical steroids, topical antibiotics, and topical dornase alfa are reported medical therapies. Ivacaftor has some sinonasal symptomatic benefit. A new triple therapy CFTR modulator, elexacaftor/tezacaftor/ivacaftor, is capable of treating 90% of patients with CF and has shown the greatest FEV1 improvement of any CFTR modulator yet. There is no clear consensus on surgical indications or technique, though aggressive surgery in recalcitrant disease has shown some symptomatic benefit. Endoscopic sinus surgery after lung transplantation may benefit some patients in whom the sinuses serve as a reservoir for recurrent pulmonary infections by decreasing rates of bronchiolitis obliterans syndrome and improving 5 year survival.ConclusionAs lifespan increases for patients with CF, further investigation into medical therapy, CFTR modulator sinonasal outcomes, and surgical technique and outcomes for CF CRS is needed.Level of Evidence5.

Chronic rhinosinusitis in cystic fibrosis: a review of therapeutic options

“…The heterogeneity of genetic defects leading to CF development highlights the complex nature of this disease. It was discovered that the clinical manifestation of CF is determined by the type of the mutation in the CFTR gene and that the degree of CFTR dysfunction implies clinical presentation of the disease [10,11]. Additionally, genotype appears to influence the severity of CF-related sinonasal disease and presumably may also interfere with the degree of sinus cavity development [12].…”

“…Almost 90% of CF patients express at least one copy of F508del mutation. According to various authors, homozygosity for F508del was associated with more severe sinonasal disease, the presence of NPs and the higher propensity of endoscopic sinus surgery [10,11,14]. Berhout et al observed that CF individuals with class I-III mutations had significantly less developed frontal and sphenoid sinuses, higher opacification in the sinonasal area, and more frequent presence of bony sclerosis/osteoneogenesis, than those with other class mutations.…”

“…Heterozygotes for CFTR gene do not develop typical CF; however; the mutation in one allele could result in the development of CF-like disease [10]. It was reported that carriers of the one mutation in CFRT gene, non-presenting the typical spectrum of CF, were up to five times more prone to develop CRS than non-CF population [10]. Calton et al observed that CFTR heterozygotes with CRS had significantly smaller volume of the frontal and maxillary sinuses than those without mutations [16].…”

“…Calton et al observed that CFTR heterozygotes with CRS had significantly smaller volume of the frontal and maxillary sinuses than those without mutations [16]. It was also implied that patients with CRS and a history of juvenile NPs, purulent chronic pansinusitis, frontal and sphenoid sinus hypoplasia, chronic pulmonary dysfunction, or fertility disorders should be examined whether they are CFTR heterozygotes [10].…”

“…Mutations indistinct from CFTR genes could modify the clinical presentation of CF-related CRS. For example, homozygotes for F508del and the T2R38 bitter taste receptor genotype expressed better SNOT-22 scores than homozygotes lacking this genotype [10,11].…”