Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation

Clin Otolaryngol. 2015 Feb;40(1):16-21. doi: 10.1111/coa.12310.

Abstract

Background: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated.

Objective: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease.

Design: Observational study.

Participants: Twelve patients with cystic fibrosis and a G551D-CFTR mutation.

Methods: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor.

Outcome measures: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared.

Results: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy.

Conclusions: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols / therapeutic use*
  • Child
  • Cohort Studies
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Mutation / genetics*
  • Paranasal Sinus Diseases / diagnostic imaging
  • Paranasal Sinus Diseases / drug therapy*
  • Paranasal Sinus Diseases / etiology
  • Quinolones / therapeutic use*
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Young Adult

Substances

  • Aminophenols
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor