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Key Points: Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes., (© 2024 ARS‐AAOA, LLC.)

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS., Methods and Analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines., Ethics and Dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals., Trial Registration: This study was registered on ClinicalTrials.gov (NCT04469439)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JAA is a consultant for OptiNose and Medtronic; on a speaker panel GSK; on GlycoMira board and is an equity holder. PHH is a consultant for Stryker, Medtronic, Slate Therapeutics; and Equity ownership in Sound Health Systems. AJK is a consultant for Acclarent. ZMS is a consultant for OptiNose, Regeneron, SanofiGenzyme, and Lyra; and on Medical Directory for Healthy Humming. Unrelated to this work, NIC has received grant support from the Burroughs Welcome Fund, American Rhinologic Society, and the National Cancer Institute. In the last 36 months, CHG has received grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Federal Drug Administration unrelated to this work. CHG has received fees from Enterprise Therapeutics for providing clinical trial design advice. He received honoraria from Gilead Sciences to serve as grant review committee chair and from Vertex Pharmaceuticals for speaking at the UK LEAD conference. He served as a DSMB Chair for a trial supported by Novartis and the European Commission. He serves as the Deputy Editor of the Annals of the American Thoracic Society. CHG has stock in Air Therapeutics. JLTC reports personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, she have been site Pl on studies for Vertex, 4DMT, and Eloxx; she have done consulting/provided clinical trial design advice for Vertex and 4DMT; she served as Chair of a Data Monitoring Committee for AbbVie. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: she have received grant funding from the CFF and NIH. Professional Memberships include CFF Clinical Research Executive Committee; CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING); ATS International Conference Committee Chair and Respiratory Health Awards Committee Member (Scientific Grant Review and Clinical Problems Programming Committee-complete); National Institutes of Health/National Heart, Blood, Lung Institute Clinical Trials Review Study Section. MTS receives funding from Cystic Fibrosis Foundation unrelated to this work. In the last 36 months, DMB has received grant support from CF Foundation related to this work as well as unrelated to this work. Unrelated to this work, DMB has received grant support from the International Society of Inflammation and Allergy of the Nose and the American Rhinologic Society, honoraria, and consulting fees from Amgen, on medicolegal cases, and at Garner Health (equity). CML, JLF, TEB, NIC, AEG, JCM, TLS have disclosed no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Priming is a psychological phenomenon where subconscious cues in the environment impact our behavioral responses in certain situations. Well studied in the worlds of business, marketing, and even politics, it is unclear how the priming phenomenon impacts patient perception of their own disease state nor how they report that perception using tools like the Sinonasal Outcomes Test (SNOT-22), used to measure that perception in chronic rhinosinusitis., Objective: To determine the impact of positive or negative priming on self-reported patient perception of their chronic rhinosinusitis disease using the SNOT-22 disease-specific quality of life instrument., Methods: Single-blind, randomized, prospective cohort pilot study of 206 consecutive adult patients with a clinical diagnosis of chronic rhinosinusitis presenting to a university rhinology clinic. Patients were randomized to receive "positive priming" (103) or "negative priming" (103) by reading a passage about the positive or negative aspects of chronic sinusitis and its treatment respectively. Patients were then asked to fill out the SNOT-22 and results between the two groups were compared., Results: The negative priming group had a higher median SNOT-22 score of 49 [IQR = 39] compared to the positive priming groups' score of 22 [IQR = 27], p < 0.0001), a difference of nearly three times the minimal clinical impactful difference (MCID). This effect was consistent regardless of age or sex of the patient. Subgroup analysis revealed a greater impact when priming was performed by the senior male attending regardless of patient age or sex (p < 0.001), while priming performed by the younger female research fellow had greater impact on older patients (>59 years, p = 0.001) and female patients (p = 0.003)., Conclusions: Priming impacts how patient's perceive their chronic rhinosinusitis as determined by the SNOT-22. It is imperative that the rhinologist understand this when using this instrument in research applications and in clinical decision-making for patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic rhinosinusitis (CRS) is common in individuals with cystic fibrosis (CF) and is marked by chronic inflammation and episodes of infection that negatively impact quality of life. Several studies have shown that elexacaftor-tezacaftor-ivacaftor (ETI) improves symptoms and examination findings in CF-CRS. The current study determines the effect of ETI on the sinonasal microbiota in CF., Methods: Sinonasal samples were collected under endoscopic visualization before and after starting ETI. Samples were subjected to 16S amplicon sequencing and sequences were processed with the QIIME2 pipeline with subsequent analysis using the vegan R-package., Results: Twenty-nine individual baseline samples and 23 sample pairs pre-/post-ETI were available. At baseline, the cohort had samples dominated by Staphylococcus, and alpha diversity was lower than that of a published reference set of individuals without sinonasal disease. Individuals with prior sinus surgery had lower alpha diversity as measured by Shannon Index, Observed Richness, and Faith's phylogenetic diversity Index. Beta diversity differed between individuals with and without allergic rhinitis, with higher Staphylococcus abundance in those with allergic rhinitis. No change in alpha or beta diversity was seen after a median of 9 months on ETI. With ETI, the Pseudomonas genus and the genus containing Burkholderia decreased in samples containing these taxa at baseline. Pseudomonas abundance decreased with treatment as measured by qPCR. Core sinonasal microbiome members Staphylococcus, Corynebacterium, and Streptococcus were unchanged, while Moraxella increased with ETI., Conclusions: Treatment with ETI leads to a reduction in Pseudomonas abundance within the sinonasal microbiome of individuals with Pseudomonas at baseline., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied., Methods: Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS., Results: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p = 0.004) was associated with pursing medical therapy., Conclusions: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden., (© 2023 ARS‐AAOA, LLC.)

Background: Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed., Methods: Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre-operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra-operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption., Results: Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients., Conclusions: Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models., Level of Evidence: 2 Laryngoscope, 134:1551-1555, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Key Points: Our findings suggest that primary ciliary dyskinesia (PCD)-related chronic rhinosinusitis (CRS) has a more significant impact on quality of life than CRS without nasal polyps and cystic fibrosis (CF). PCD and CF have similar mucociliary clearance defects, yet sinonasal symptom severity varies between the two., (© 2023 ARS-AAOA, LLC.)

Background: Empty nose syndrome (ENS) is characterized by the paradoxical perception of nasal obstruction despite patent sinonasal anatomy after surgery. We investigated the relationship between ENS, and anxiety, depression, obsessive-compulsive disorder, and somatic symptom disorder (SSD) compared to individuals with chronic rhinitis (CR) and chronic rhinosinusitis (CRS)., Methods: This cross-sectional survey study compared ENS and CR and CRS patients. A total of 116 patients participated: 58 ENS patients from digital support groups, and 58 CRS and CR patients from tertiary rhinology clinics. Study participants completed four validated surveys: (1) Empty Nose Syndrome 6-Item Questionnaire, (2) Rhinosinusitis Disability Index (RSDI), (3) Obsessive Compulsive Inventory - Revised (OCI-R), and (4) PRIME MD Patient Health Questionnaire (PHQ)., Results: ENS patients exhibited a mean RSDI of 78.6, 95% confidence interval [CI] 72.8-84.5, compared to 25.2, 95% CI 18.6-31.8 for CRS/CR patients (p < 0.0001). This difference was seen across all subdomains. Using the PHQ, 53% of ENS patients met diagnostic thresholds for SSD compared to 14% of CRS patients (p < 0.0001). In relation to obsessive compulsive disorder (OCD), 18.37% of ENS patients compared to 8.62% of CRS/CR patients scored above the diagnostic threshold (>21) on the OCI-R questionnaire (p = 0.159)., Conclusion: ENS patients had diminished sinonasal quality of life and a higher prevalence of comorbid anxiety and depression, compared to CR and CRS. ENS patients were more likely to exceed thresholds for OCD and SSD compared to controls. Future studies are needed to assess the role of SSD in ENS to help optimize treatment for these complex patients., (© 2022 ARS-AAOA, LLC.)

Background: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS., Methods: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence., Results: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS)., Conclusion: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder., (© 2021 ARS-AAOA, LLC.)

Objective: The aim of this study was to determine whether self-reported burn pit exposure is associated with increased subjective and objective sinus disease., Design: A cross-sectional study was performed evaluating consecutive adult patients presenting to a US Military rhinology clinic. Demographics, medical histories, sinonasal quality-of-life scores, and nasal endoscopy examinations were obtained. Participants were divided into three cohorts based on self-reported exposure histories and outcomes compared., Results: One hundred eighty-six patients met the inclusion criteria, the majority of whom were male. Patients with burn pit exposure had worse Sinonasal Outcome Test-22 scores (49.9) compared with those deployed without burn pit exposure (31.8) or never deployed (31.5). Endoscopic findings demonstrated worse disease within those exposed (Lund-Kennedy score, 3.3) compared with the other cohorts (1.8 and 1.7, respectively)., Conclusions: These novel findings suggest that deployment-related burn pit exposure is associated with increased subjective and objective sinus disease., Competing Interests: Funding/Conflicts of Interest: A.J.K., F.C.L., and Y.H. were supported by the National Center for Advancing Translational Sciences through grant KL2TR002490 (A.J.K.) and UL1TR002489 (F.C.L. and Y.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. No other authors have funding or conflicts of interest., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by excessive leukotriene production, diffuse polyp burden and osteitic bone changes. These bony changes have not been previously characterized., Objective: The aim of this radiographic study is to characterize the bony changes noted on computed tomography (CT) scans of the sphenoid sinus in patients with AERD compared to other diseased sinonasal inflammatory states and non-diseased controls., Methods: A retrospective review of 43 patients with clinically confirmed AERD were included and compared to 22 non-diseased, 9 allergic fungal sinusitis, and 43 chronic rhinosinusitis controls (23 without polyps and 18 with polyps). Comparative measurements were performed using fine-cut CT scans. Sites of comparison were the intersinus septum, the left and right lateral sphenoid wall, the roof, and left and right floor of the sphenoid sinus. Standardized measurements were averaged by two separate rhinologists., Results: Patients with AERD had an average statistically significant increase in bone thickness compared to healthy and diseased controls in nearly every site with the most pronounced changes in the intersinus septum (p < 0.05)., Conclusion: Patients with AERD have significantly increased thickness of the sphenoid bone compared to control groups with the most pronounced difference in the intersinus septum. These findings may help clinicians increase suspicion for a diagnosis of AERD who clinically have diffuse nasal polyposis.

Background: Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature., Objective: The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model., Methods: Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically., Results: Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time., Conclusions: While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.

Objective: Outcome measures in healthcare that presume a higher level of patient health and overall literacy may inadequately estimate the disease experiences of less-educated patients and further disadvantage them. Patient-Reported Outcome Measures (PROMs) are widely used communication tools for clinical practice and are often used to evaluate and guide management for chronic rhinosinusitis (CRS) and skull base diseases. However, their readability and subsequent incomprehensibility for patients have not been assessed. The aim of this study is to evaluate the readability of commonly used PROMs for these conditions and whether they meet recommended readability levels., Methods: Three readability measures, Gunning Fog, Simple Measure of Gobbledygook (SMOG), and FORCAST were used in the evaluation of commonly used PROMs for CRS and skull base disease. PROMs with sixth-grade readability level or lower were considered to meet health literacy experts' recommendations., Results: A total of 11 PROMs were reviewed (8 CRS, 3 skull base). Gunning Fog consistently estimated the easiest readability, whereas FORCAST the most difficult. One hundred percent of CRS and 67% of skull base PROMs were above National Institutes of Health and health literacy experts' recommended reading levels. PROMs developed more recently had easier readability., Conclusion: PROMs are important clinical tools in otolaryngology that help guide management of disease for improved patient-centered care. Like many other fields of medicine, those used in otolaryngology are beyond recommended reading levels. Development of PROMs in the future should meet recommended readability levels to fully assess the disease experience of our patients., Level of Evidence: 4 Laryngoscope, 130:2305-2310, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)