Impact of high‐ versus low‐risk genotype on sinonasal radiographic disease in cystic fibrosis

Abstract

Objective Understanding of how specific mutations impact the cystic fibrosis transmembrane conductance regulator (CFTR) protein has given rise to the classification of CF patients into low‐risk and high‐risk genotypes. Few prior studies have investigated differences in sinonasal disease between low‐risk and high‐risk CF genotypes. This multi‐institutional review aimed to evaluate radiographic sinus disease severity based on genotype. Methods A review was conducted on adult patients with CF evaluated between 2005 to 2017 at three academic institutions. Data including age, gender, CFTR mutation, and presence of a maxillofacial/sinus computed tomography scan was collected. A modified Lund‐Mackay score (MLMS) was assigned to each scan, and the presence of sinus aplasia or hypoplasia was determined. Patients were further grouped depending on genotype into low‐ or high‐risk for comparison. Results A total of 126 patients were included with 99 patients in the high‐risk and 21 in the low‐risk groups. The high‐risk group had significantly higher MLMS than the low‐risk group (mean 13.88 vs. 8.06, P < 0.0001, 95% CI −8.196 to −3.462) The rate of frontal (P < 0.01), maxillary (P = 0.04), and sphenoid (P < 0.001) hypoplasia/aplasia was significantly higher in high‐risk patients compared to low‐risk. Conclusion This is one of the largest studies to date evaluating the impact of CF genotype on paranasal sinus development and disease. Genotype appears to impact sinonasal disease severity and also potentially paranasal sinus cavity development to a degree, although the exact mechanism is unknown. Level of Evidence 4 Laryngoscope, 129:788–793, 2019

Abstracts from the 25th Italian Congress of Cystic Fibrosis and the 15th National Congress of Cystic Fibrosis Italian Society

“…Proposed predictive criteria for ESS are: massive polyposis, prior history of ESS, high Lund-Mackay score, high SNOT-22 score and severe CFTR mutations [3,4]; delay in surgery did not affect post-operative improvement [5]. A preoperative evaluation of CT findings is essential to avoid complications; an intra-operative image guidance can be useful due to anatomic differences in CF patients, especially in revision cases [6]. ESS procedure in pediatric patients is totally safe [7].…”

“…Informed consent was obtained from all patients for data publication. 6 National Heart and Lung Institute, Imperial College London, London, United Kingdom 7 Lungenheilkunde München-Pasing, Munich, Germany; 8 Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal; 9 Assistance Publique-Hôpitaux de Paris, Adult Cystic Fibrosis Center, Cochin Hospital, Paris, France and Sorbonne Paris Cité, Université Paris Descartes, Paris, France; 10 Vertex Pharmaceuticals Incorporated, Boston, MA, USA Correspondence: Carlo Castellani (carlocastellani@gaslini.org) Italian Journal of Pediatrics 2020, 46(Suppl 1):A3…”

“…Disease progression and burden in patients with cystic fibrosis homozygous for F508del across Europe in an observational registry (VOICE study) Carlo Castellani 1 , Edward F McKone 2 , Harry Heijerman 3 , Amparo Sole 4 , Siobhán B Carr 5 , Jane C Davies 5,6 , Rainald Fischer 7 , Celeste Barreto 8 , Isabelle Fajac 9 , Zheng (Jason) Yuan 10 , Nils Kinnman 10…”

Sphenoid Bone Pneumatisation on Lateral Cephalograms of Patients With Neurofibromatosis Type 1

“…Sinus hypoplasia is so characteristic of this disease that it has been noted that CF diagnosis should be checked if the sphenoid's pneumatisation is apparently of normal size (105). Interestingly, there is a genotype-phenotype correlation for the sphenoid pneumatisation in CF (106,107). By far the most common mutation in the gene responsible for CF (108) is associated with a significantly lower sphenoid pneumatisation on lateral X-ray images of the skull compared to other pathogenic mutations in CF (106).…”

Surgical Management of Chronic Rhinosinusitis in Cystic Fibrosis

“…Complete ESS is especially important in CF CRS, as inspissated secretions may be trapped in partially removed partitions. A recent study also demonstrated high-risk CF mutations are associated with more severe radiographic findings as measured by modified Lund–Mackay scores, as well as higher prevalence of sinus hypoplasia/aplasia [18]. An understanding of CF pathophysiology is important in the surgical management of CF CRS patients to ensure surgical success.…”