Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

Abstract

Background Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging.

Olfaction before and after initiation of elexacaftor‐tezacaftor‐ivacaftor in a cystic fibrosis cohort

“…Disease-causing genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene result in impaired chloride transport resulting in mucus dehydration, impaired mucociliary clearance and proliferation of microbial pathogens. 1 While bronchiectasis is the primary driver of disease-related mortality in cystic fibrosis (CF), the sinonasal cavity is almost universally affected, and many patients experience chronic rhinosinusitis, nasal polyps and olfactory dysfunction (OD). 1 OD affects between 60-95% of patients with CF 2 and is detrimental to quality of life, as well as potentially dangerous, impairing the ability to detect smoke, natural gas leak, or spoiled food.…”

“…Highly effective CFTR modulator therapy has revolutionized treatment of CF and decreased morbidity for eligible patients. 1 In 2019, Elexacaftor/Tezacaftor/Ivacaftor (ETI) was FDA approved for □ F508 heterozygote or homozygote patients 3 □ 12 years of age. 4 In June 2021, the FDA extended the approval down to age 6.…”

“…1 While bronchiectasis is the primary driver of disease-related mortality in cystic fibrosis (CF), the sinonasal cavity is almost universally affected, and many patients experience chronic rhinosinusitis, nasal polyps and olfactory dysfunction (OD). 1 OD affects between 60-95% of patients with CF 2 and is detrimental to quality of life, as well as potentially dangerous, impairing the ability to detect smoke, natural gas leak, or spoiled food. OD is also associated with appetite loss, 3 which may compound the malnutrition that frequently affects people with CF.…”

The Risks of Complications During Endoscopic Sinus Surgery in Cystic Fibrosis Patients: An Anatomical and Endoscopic Study

“…Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7, which encodes for a chloride ion transporter on the apical membrane of epithelial cells in multiple organs. 1,2 Historically regarded as a pediatric disease, thanks to the development of new pharmacological treatments, now CF is an adult condition, with a current median survival of 37 to 42 years. 3 Chronic rhinosinusitis (CRS) with or without nasal polyposis affects nearly one-half of all CF patients, as a result of their propensity to produce thick mucus and of the impairment of mucociliary clearance.…”

Staying Safe, Caring for Each Other, and Moving the Needle—Together

“…12 Chen et al 14 also present a thorough review and meta-analysis on barrier protection measures for the management of allergic rhinitis which is very informative. Finally in another systematic review, Lee et al 15 provide a detailed analysis of cystic fibrosis transmembrane conductance regulator modulator therapy which is an excellent overview on this complex topic.…”