SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM. METHODS: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains. RESULTS: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes. CONCLUSIONS: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains.

Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies.

BACKGROUND: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling. METHODS: Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL. RESULTS: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005). CONCLUSIONS: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL.

Recurrence patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.

OBJECTIVE: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). METHODS: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05). CONCLUSION: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS.

Long-term quality of life after treatment in sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under-studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year posttreatment time frame. METHODS: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow-ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL. RESULTS: One hundred ninety-four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01). CONCLUSION: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment.

Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults.

BACKGROUND: The study of pathogenic mechanisms in adult asthma is often marred by a lack of precise information about the natural history of the disease. Children who have persistent wheezing (PW) during the first 6 years of life and whose symptoms start before age 3 years (PW+) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma into adult life than are those who do not have PW (PW-). OBJECTIVE: Our aim was to determine whether nasal epithelial cells from PW+ asthmatic adults as compared with cells from PW- asthmatic adults show distinct biomechanistic processes activated by RV exposure. METHODS: Air-liquid interface cultures derived from nasal epithelial cells of 36-year old participants with active asthma with and without a history of PW in childhood (10 PW+ participants and 20 PW- participants) from the Tucson Children's Respiratory Study were challenged with a human RV-A strain (RV-A16) or control, and their RNA was sequenced. RESULTS: A total of 35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PW+ group from the PW- group at baseline and after RV-A stimulation. Notably, 22 transcriptomic pathways showed PW-by-RV interactions; the pathways were invariably overactivated in PW+ patients, and were involved in Toll-like receptor- and cytokine-mediated responses, remodeling, and angiogenic processes. CONCLUSIONS: Asthmatic adults with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in response to RV-A that are not present in patients without such a history. Targeting these mechanisms may slow the progression of asthma in these patients.

The GSDMB rs7216389 SNP is associated with chronic rhinosinusitis in a multi-institutional cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial disease with a high co-occurrence with asthma. In this multicohort study, we tested whether single nucleotide polymorphisms (SNPs) associated with childhood asthma and rhinovirus (RV)-associated disease are related to an increased susceptibility to adult CRS in a multicohort retrospective case-control study. METHODS: Participants at two tertiary academic rhinology centers, University of Arizona (UofA) and University of Pennsylvania (UPenn) were recruited. Cases were defined as those with physician diagnosed CRS (UofA, n = 149; UPenn, n = 250), and healthy controls were those without CRS (UofA, n = 66; UPenn, n = 275). Genomic DNA was screened for the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP. Gene dosage, or the number of combined risk alleles in a single subject was calculated. Meta-analysis of the association between GSDMB or CDHR3 genotypes and CRS was performed and additive gene dosage effect for each population calculated using p for trend. RESULTS: A meta-analysis revealed a combined increased risk for CRS in subjects with the GSDMB rs7216389 SNP (odds ratio [OR] 1.40; 95% confidence interval [CI], 1.16-1.76; p = 0.004). Both the UofA (OR 1.73; 95% CI, 1.23-2.43; p = 0.002) and UPenn (OR 1.27; 95% CI, 1.02-1.58; p = 0.035) populations showed a significant positive association between the number of combined risk alleles of GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP and risk for CRS. CONCLUSION: Carriers of the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP are at increased susceptibility for CRS. These data suggest that therapeutic approaches to target aberrant responses to RV infection may play a role in the treatment of unified airway disease.

Surgical approach is associated with complication rate in sinonasal malignancy: A multicenter study.

BACKGROUND: Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated. METHODS: Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling. RESULTS: Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19). CONCLUSIONS: Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings.

Development of a self-directed sinonasal surgical anatomy video curriculum: Phase 1 validation.

BACKGROUND: Sinusitis is a common outpatient diagnosis made by physicians and is a reason for referral to otolaryngologists. A foundation in basic sinonasal anatomy is critical in understanding sinus pathophysiology and avoiding complications. Our objective in this study was to develop and to validate a self-directed surgical anatomy video for medical students. METHODS: Two multimedia videos were developed highlighting sinonasal anatomy. In Video 1 we included audio narration and radiologic imaging. Video 2 incorporated highlighted images from a sinus surgery video. An assessment was developed to test sinonasal anatomy landmarks, spatial recognition of structures, and their clinical relevance. An expert panel of rhinologists scored face and content validity of the curriculum videos and assessment. Factor analysis was used to separate questions into face and content validity domains, and a one-sample t test was performed. RESULTS: The panel scored face validity (Videos 1 and 2: 4.4/5) and content validity (Video 1: 4.5/5, 0.83; Video 2: 4.3/5, 0.75) significantly higher than a neutral response. There were no statistical differences for face or content validity between videos. The assessment was rated suitable (29%) or very suitable (57%) for testing basic sinonasal surgical anatomy, and the majority (71%) of respondents agreed (14%) or strongly agreed (57%) that the assessment thoroughly covered the sinus anatomy content with which medical students should be familiar. CONCLUSION: We have developed two videos and an assessment that highlight and test sinonasal anatomy. Future studies will aim to identify whether the use of a self-directed video curriculum improves sinonasal anatomy awareness and whether incorporation of surgical endoscopic videos augments training.

International consensus statement on allergy and rhinology: rhinosinusitis 2021.

I. EXECUTIVE SUMMARY: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. METHODS: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. RESULTS: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. CONCLUSION: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

MUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo.

Goblet cell metaplasia (GCM) and mucin overproduction are a hallmark of chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease (COPD). In the airways, cigarette smoke (CS) induces activation of the epidermal growth factor receptor (EGFR) leading to GCM and overexpression of the gel-forming mucin MUC5AC. Although previous studies have demonstrated that a membrane-bound mucin, MUC1, modulates the activation of CS-induced EGFR, the role of MUC1 in CS-induced GCM and mucin overproduction has not been explored. In response to CS exposure, wild-type (WT) rats displayed Muc1 translocation from the apical surface of airway epithelium to the intracellular compartment of hyperplastic intermediate cells, EGFR phosphorylation, GCM, and Muc5ac overproduction. Similarly, human CRS sinonasal tissues demonstrated hyperplasia of intermediate cells enriched with MUC1 in the intracellular compartment, which was accompanied by GCM and increased MUC5AC expression. To further evaluate the role of Muc1 in vivo, a Muc1 knockout (KO) rat (MUC in humans and Muc in animals) was developed. In contrast to WT littermates, Muc1-KO rats exhibited no activation of EGFR, and were protected from GCM and Muc5ac overproduction. Genetic knockdown of MUC1 in human lung or Muc1 knockout in primary rat airway epithelial cells led to significantly diminished EGF-induced MUC5AC production. Together, these findings suggest that MUC1-dependent EGFR activation mediates CS-induced GCM and mucin overproduction. Strategies designed to suppress MUC1-dependent EGFR activation may provide a novel therapeutic approach for treating mucin hypersecretion in CRS and COPD.

Virtual coach: the next tool in functional endoscopic sinus surgery education.

BACKGOUND: Functional endoscopic sinus surgery (FESS) can be challenging as novices become accustomed to handling endoscopes and instruments while navigating complex sinonasal anatomy. Experts demonstrate fluid and efficient motions when addressing pathology. The training process from novice to expert relies on hands-on experience in cadaveric laboratories and preceptorship models that require significant time and expense. This study aims to validate the use of a virtual coach to guide users step-by-step through a basic FESS. METHODS: Seventeen surgeons were grouped into novice (n = 10) and expert (n = 7) based on self-reported levels of surgical experience. Users were trained using the maxillary antrostomy module in the Neurorhinological Surgery (NRS) simulator combining the physical craniofacial model with virtual reality (VR)-tracked surgical instruments in the VR operating room. The virtual coach guided the user using surgical videos, auditory, and visual cues. The coach recorded data for each subject including the number of times borders of the nasal cavity were encountered and time to completion. Users graded the usefulness of the virtual coach on a Likert questionnaire. RESULTS: Face validity of our NRS simulator was replicated by user questionnaires, and construct validity replicated by differentiation between novice and expert level surgeons (p < 0.01). Novices contacted a significantly higher number of anatomic borders (n = 17) and had a longer operative time (t = 370 seconds). All users reported high scores on the benefit and usefulness of the virtual coach. CONCLUSION: The virtual coach provides a useful tool to enhance FESS education by providing objective real-time data in a novel mixed-reality surgical environment.

High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia.

Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Mortality in CF patients is mostly due to respiratory sequelae. Challenges with gene delivery have limited attempts to treat CF using in vivo gene therapy, and low correction levels have hindered ex vivo gene therapy efforts. We have used Cas9 and adeno-associated virus 6 to correct the ΔF508 mutation in readily accessible upper-airway basal stem cells (UABCs) obtained from CF patients. On average, we achieved 30%-50% allelic correction in UABCs and bronchial epithelial cells (HBECs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentiated epithelia. Furthermore, we successfully embedded the corrected UABCs on an FDA-approved porcine small intestinal submucosal membrane (pSIS), and they retained differentiation capacity. This study supports further development of genetically corrected autologous airway stem cell transplant as a treatment for CF.

The effect of maxillary sinus antrostomy size on the sinus microbiome.

BACKGROUND: The optimal maxillary antrostomy size to surgically treat sinusitis is not well known. In this study, we examined clinical metrics of disease severity and symptom scores, measured secreted inflammatory markers, and characterized the sinus microbiome to determine if there were significant differences in outcome between different maxillary ostial sizes. METHODS: Prospective randomized, single-blinded clinical trial enrolling 12 individuals diagnosed with recurrent acute or chronic rhinosinusitis. Each patient was blinded and randomized to receive minimal maxillary ostial dilation via balloon sinuplasty on 1 side vs a mega-antrostomy on the contralateral side. Data collected included symptom scores (20-item Sino-Nasal Outcome Test [SNOT-20]), endoscopy, and radiologic Lund-Mackay scores. During surgery and at their postoperative visit swabs were obtained from each maxillary sinus, and 16S DNA and inflammatory cytokine levels analyzed. The use of each patient as their own control allowed us to minimize confounding variables. RESULTS: There was statistically significant improvement in SNOT-20 symptom scores postoperatively in all patients. There were no significant differences between maxillary ostial size in postoperative endoscopy scores, cytokine profile, or bacterial burden. There were statistically significant differences in relative postoperative abundance of Staphylococcus, Lactococcus, and Cyanobacteria between the mega-antrostomy and mini-antrostomy. CONCLUSIONS: The method used in surgical maxillary antrostomies had no effect on endoscopy scores or cytokine profiles. Microbiome analysis determined significant differences between the different antrostomy sizes in postoperative Staphylococcus, Lactococcus, and Cyanobacteria abundance. The clinical significance of these changes in the sinus microbiome are not known but may be a result of increased access to postoperative sinonasal irrigations.

Virtual Functional Endoscopic Sinus Surgery Simulation with 3D-Printed Models for Mixed-Reality Nasal Endoscopy.

The surgeon's knowledge of a patient's individual anatomy is critical in skull base surgery. Trainees and experienced surgeons can benefit from surgical simulation; however, current models are expensive and impractical for widespread use. In this study, we report a next-generation mixed-reality surgical simulator. We segmented critical anatomic structures for 3-dimensional (3D) models to develop a modular teaching tool. We then developed a navigation tracking system utilizing a 3D-printed endoscope as a trackable virtual-reality (VR) controller and validated the accuracy on VR and 3D-printed skull models within 1 cm. We combined VR and augmented-reality visual cues with our 3D physical model to simulate sinus endoscopy and highlight segmented structures in real time. This report provides evidence that a mixed-reality simulator combining VR and 3D-printed models is feasible and may prove useful as an educational tool that is low cost and customizable.

A Systematic Review of the Association between Cigarette Smoke Exposure and Chronic Rhinosinusitis.

Objectives Cigarette smoking and passive smoke exposure have been associated with chronic rhinosinusitis (CRS). Our goal in this systematic review was to (1) determine if there was a strong correlative effect in large population studies between cigarette smoke exposure and the prevalence of CRS, (2) investigate pathogenic mechanisms of cigarette smoke in the upper airway, and (3) determine if a history of cigarette smoking affects the medical and surgical outcomes of CRS. Data Sources MEDLINE, Embase, Cochrane CENTRAL, Web of Science SCI and CPCI-S, and websites. Methods A comprehensive literature review and quantitative meta-analysis of studies based on the PRISMA protocol and examining the relationship between cigarette smoke exposure and CRS was performed. A search strategy was developed using various terms such as sinusitis, rhinitis, rhinosinusitis, and smoking. The articles were categorized by (1) epidemiology, (2) pathophysiology, and (3) outcomes. Data regarding study design, population/setting, methods, and bias were collected. Results The initial search generated 2621 titles/abstracts with 309 articles undergoing secondary review and 112 articles for final review. We determined that there is a strong correlation between active and passive cigarette smoke with the prevalence of CRS. Cigarette smoke challenge to sinonasal epithelia results in the release of inflammatory mediators and altered ciliary beat frequency. Pediatric patients exposed to secondhand smoke appear to have particularly poor outcomes. Conclusion There is clear evidence that cigarette smoke is related to CRS, but longitudinal and mechanistic studies are required to determine a causative effect. This information is critical for greater understanding of CRS health outcomes.

Novel role of surfactant protein A in bacterial sinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS is comprised of 2 major subgroups, based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus, and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens. Surfactant protein A (SP-A) is a member of the collectin family secreted by the airway epithelia and plays a critical role in airway innate immunity, as it can aggregate bacteria. We hypothesized that SP-A plays a role in bacterial CRS. METHODS: Air-liquid interface (ALI) cultures of nasal epithelial cells were derived from human ex-vivo healthy and CRS sinus tissues (n = 26) and challenged with PA. SP-A levels were measured with western blot and quantitative reverse transcript-polymerase chain reaction (qRT-PCR) in ALI and sinus tissues. RESULTS: We determined that SP-A: (i) mRNA and protein levels are increased significantly in CRS tissues compared with healthy sinuses; (ii) although primarily expressed in the lung, it is also synthesized and expressed in sinonasal epithelia; (ii) is expressed in the sinuses of an SP-A humanized transgenic mouse but not in SP-A knockout mice; (iv) mRNA levels are upregulated significantly during PA challenge, but protein levels are downregulated 4 hours postchallenge and upregulated at 12 hours. CONCLUSION: Our data suggest that SP-A is expressed in the sinuses and that it plays a role in the sinus innate immune responses during bacterial infections.

Paranasal sinus size is decreased in CFTR heterozygotes with chronic rhinosinusitis.

BACKGROUND: Cystic fibrosis (CF) heterozygotes with a single mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are at significantly higher risk to develop chronic rhinosinusitis (CRS). However the reasons why remain unknown. We tested the hypothesis that CFTR heterozygotes would have smaller sinus volumes than healthy controls. To exclude sinus disease as a confounding factor we also assessed paranasal sinus volume in those with CRS, but without known CFTR mutations. METHODS: A total of 131 adults of white Northern European and Latino origin were recruited: 81 diagnosed with CRS and 50 healthy controls. Subjects were genotyped for 9 common CFTR mutations covering >80% of mutation prevalence. Those with CRS were separated by CFTR mutational status and matched demographically to healthy controls. Three-dimensional sinus volume, mucosal opacification, and skull volume were quantified to obtain the percentage of pneumatization and extent of mucosal disease in each sinus. Twenty-item Sino-Nasal Outcome Test (SNOT-20) and endoscopy scores were also analyzed. RESULTS: In individuals diagnosed with CRS we identified 7 CFTR heterozygotes (8.64%); no CFTR mutations were identified in our healthy controls. There were no significant differences between the 3 matched groups other than sinus pneumatization. The frontal and maxillary sinuses were significantly smaller in CFTR heterozygotes with CRS compared to CFTR wild-type subjects with or without disease. CONCLUSION: CFTR heterozygotes with CRS have significantly smaller frontal and maxillary sinus size compared to those without mutations, irrespective of disease state. This sinus hypoplasia may contribute to impaired mucus clearance and chronic sinus disease development.

The Triple Aim and its implications on the management of chronic rhinosinusitis.

INTRODUCTION: Accountable care organizations (ACO) and alternative payment models are a sign of the change in reimbursement from fee-for-service to value-based reimbursement. The focus of health care under ACOs is represented by the Triple Aim: to improve the experience of health care, improve the health of populations, and reduce the per capita costs. Individuals with chronic rhinosinusitis (CRS) are heavy consumers of health care services. Results of recent studies have indicated that there is the potential for improved outcomes and cost savings from early surgical intervention. Adhering to the principles of the Triple Aim may signal a paradigm shift in regard to timing of intervention for CRS in certain patients. METHODS: A scoping review was performed to analyze the current literature related to management of CRS and the impact on cost, population health outcomes, and the patient's experience of health care. RESULTS: A growing body of literature indicates that, in appropriately selected patients, when compared with medical management, endoscopic sinus surgery has the potential to improve patient outcomes and reduce the long-term cost burden of CRS. CONCLUSION: With the advent of ACOs, a paradigm shift in the treatment of CRS is inevitable to better conform to the goals of the Triple Aim. Future treatment algorithms will need to account for the heterogeneity within CRS and seek to identify appropriate timing and interventions for patients on an individual basis if the value of health care is to be improved.