Connexin 32 and 43 mutations: do they play a role in chronic rhinosinusitis?

OBJECTIVE: Dysfunction of the sinonasal epithelium may contribute to the pathogenesis of chronic rhinosinusitis (CRS) including recurrent acute rhinosinusitis (RARS). Mutations in connexin 32 and 43 proteins have been associated with a number of human diseases. The objective of this study is to investigate the role of mutations in connexin 32 or connexin 43 genes in CRS and RARS. METHODS: Prospective case series of 19 patients with CRS and /or RARS. Clinical and demographic factors were noted and buccal swabs were collected for DNA sequencing of connexin 32 and connexin 43 genes. RESULTS: One patient was found to have a conservative V193I mutation in the connexin 32 gene. Connexin 43 mutations were found in two patients - a silent R239R mutation and an AAA insertion after the stop codon in the 3' UTR. None of these mutations are associated with any known diseases or predicted to lead to protein dysfunction. CONCLUSION: Mutations in connexin 32 or 43 genes in patients with CRS, including RARS, appear to be rare. The etiologic role of connexin mutations in chromic rhinosinusitis is suspect, and routine sequencing for connexin mutations in patients with RARS or CRS is not cost effective.

Defining the Health Utility Value of Medical Management of Chronic Rhinosinusitis: A Prospective Pilot Study.

The extent to which medical management of chronic rhinosinusitis (CRS) may improve health utility value (HUV) remains unknown. We conducted a prospective pilot study to longitudinally assess HUV via the EQ-5D-5L questionnaire in patients with CRS who were receiving medical therapy but did not undergo sinus surgery. The primary study outcome was HUV at 12-month follow-up; secondary end points included HUV at baseline and 3- and 24-month follow-up. Our study enrolled 115 patients who received the following medical treatments: saline irrigations (n = 83, 72.2%), steroid sprays (n = 93, 80.9%), antihistamines (n = 64, 55.7%), steroid irrigations (n = 29, 25.2%), and oral antibiotics (n = 58, 50.4%). There was a statistically significant improvement (mean, +0.073; P = .003) in HUV at 12 months (minimum clinically important difference, 0.055) as compared with baseline. However, there was no statistically significant trend in HUV over time between baseline and 24-month follow-up (P = .3033). These findings can inform cost-effectiveness research as new medical therapies for CRS emerge.

A cost-effectiveness analysis of nasal surgery to increase continuous positive airway pressure adherence in sleep apnea patients with nasal obstruction.

OBJECTIVES/HYPOTHESIS: Nasal surgery has been implicated to improve continuous positive airway pressure (CPAP) compliance in patients with obstructive sleep apnea (OSA) and nasal obstruction. However, the cost-effectiveness of nasal surgery to improve CPAP compliance is not known. We modeled the cost-effectiveness of two types of nasal surgery versus no surgery in patients with OSA and nasal obstruction undergoing CPAP therapy. STUDY DESIGN: Cost-effectiveness decision tree model. METHODS: We built a decision tree model to identify conditions under which nasal surgery would be cost-effective to improve CPAP adherence over the standard of care. We compared turbinate reduction and septoplasty to nonsurgical treatment over varied time horizons from a third-party payer perspective. We included variables for cost of untreated OSA, surgical cost and complications, improved compliance postoperatively, and quality of life. RESULTS: Our study identified nasal surgery as a cost-effective strategy to improve compliance of OSA patients using CPAP across a range of plausible model assumptions regarding the cost of untreated OSA, the probability of adherence improvement, and a chronic time horizon. The relatively lower surgical cost of turbinate reduction made it more cost-effective at earlier time horizons, whereas septoplasty became cost-effective after a longer timespan. CONCLUSIONS: Across a range of plausible values in a clinically relevant decision model, nasal surgery is a cost-effective strategy to improve CPAP compliance in OSA patients with nasal obstruction. Our results suggest that OSA patients with nasal obstruction who struggle with CPAP therapy compliance should undergo evaluation for nasal surgery. LEVEL OF EVIDENCE: 2c Laryngoscope, 127:977-983, 2017.