Abstract
ImportanceSinonasal symptoms in patients suffering from cystic fibrosis can negatively influence the quality of life and sinuses can be a niche for pathogens causing infection and inflammation leading to a decrease of lung function. Ivacaftor, a potentiator of the Cystic Fibrosis Transmembrane Conductance Regulator protein, has shown improvement in pulmonary function in cystic fibrosis patients with different forms of class III gating mutations. However, the effects of ivacaftor on sinonasal pathology have hardly been studied.ObjectiveTo determine the impact of ivacaftor therapy on sinonasal pathology in patients with cystic fibrosis with an S1251N mutation.DesignProspective observational mono-center cohort study, between June 2015 and December 2016.SettingA tertiary referral center in Utrecht, The Netherlands.ParticipantsEight patients with cystic fibrosis with an S1251N mutation, treated with the potentiator ivacaftor were investigated.ExposuresIvacaftor (Kalydeco, VX-770) therapy. Computed tomography imaging of paranasal sinuses. Nasal nitric oxide concentration measurements and nasal endoscopy.Main outcomes and measuresPrimary outcome is opacification of paranasal sinuses examined with computed tomography scan analysis and scaled by the modified Lund-Mackay score before and one year after treatment. Secondary outcomes are nasal nitric oxide concentration levels, sinonasal symptoms and nasal endoscopic findings before and approximately two months and in some cases one year after treatment.ResultsComputed tomography scan analysis showed a significant decrease in opacification of the majority of paranasal sinuses comparing the opacification score per paranasal sinus before and after one year of treatment with ivacaftor. Median nasal nitric oxide levels significantly improved from 220.00 (IQR:136.00–341.18) to 462.84 (IQR:233.17–636.25) (p = 0.017) parts per billion. Likewise, the majority of sinonasal symptoms and nasal endoscopic pathology decreased or resolved at two months after the use of ivacaftor.Conclusion and relevanceIvacaftor appears to improve sinonasal outcome parameters and thereby sinonasal health in patients with cystic fibrosis with an S1251N mutation.
Highlights
Cystic fibrosis (CF) is one of the most common autosomal recessive genetic disorders in the Caucasian population, with an incidence of approximately 1 in 4000–5500 live births in the Netherlands.[1,2] This life-shortening disease is caused by mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes the CFTR protein, expressed as a chloride ion channel at the apical membranes of secretory epithelia
Computed tomography scan analysis showed a significant decrease in opacification of the majority of paranasal sinuses comparing the opacification score per paranasal sinus before and after one year of treatment with ivacaftor
Acknowledgment and treatment of upper airway problems in CF patients is important because it can cause a decrease in the quality of life. [6,7,9] Besides, it can be a niche for pathogens that can lead to pulmonary infections, which eventually leads to a decline in lung function and disease progression of CF.[7,9,10]
Summary
Cystic fibrosis (CF) is one of the most common autosomal recessive genetic disorders in the Caucasian population, with an incidence of approximately 1 in 4000–5500 live births in the Netherlands.[1,2] This life-shortening disease is caused by mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes the CFTR protein, expressed as a chloride ion channel at the apical membranes of secretory epithelia. Due to loss of chloride transport, CF patients produce thick, viscous mucus in different organs.[3,4,5] sinonasal disease is one of the systemic manifestations and occurs in almost all CF patients, with symptoms like upper respiratory tract infections, anosmia, headaches and nasal obstruction with or without nasal polyps.[6,7,8] Acknowledgment and treatment of upper airway problems in CF patients is important because it can cause a decrease in the quality of life. Class I-III mutations are associated with almost no functional CFTR protein and thereby a severe phenotype, with significantly higher incidence of hypoplasia or aplasia of the sinuses and more opacification in sinonasal area.[7,11] Class IV-VI mutations are associated with a reduced amount of functional CFTR and generally have a milder CF phenotype.[7]
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