Particulate matter exposure is associated with increased inflammatory cytokines and eosinophils in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is thought to result from complex interactions between the host immune system, microbiota, and environmental exposures. Currently, there is limited data regarding the impact of ambient particulate matter ≤2.5 µm in diameter (PM2.5) in the pathogenesis of CRS, despite evidence linking PM2.5 to other respiratory diseases. We hypothesized that PM2.5 may result in differential cytokine patterns that could inform our mechanistic understanding of the effect of environmental factors on CRS. METHODS: We conducted an analysis of data prospectively collected from 308 CRS patients undergoing endoscopic sinus surgery. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Clinical and demographic data including zip codes were extracted and used to obtain tract-level income and rurality measures. A spatiotemporal machine learning model was used to estimate daily PM2.5 levels for the year prior to each patient's surgery date. Spearman correlations and regression analysis were performed to characterize the relationship between mucus cytokines and PM2.5. RESULTS: Several inflammatory cytokines including IL-2, IL-5/IL-13, IL-12, and 21 were significantly correlated with estimated average 6, 9, and 12-month preoperative PM2.5 levels. These relationships were maintained for most cytokines after adjusting for age, income, body mass index, rurality, polyps, asthma, and allergic rhinitis (AR) (p < .05). There were also higher odds of asthma (OR = 1.5, p = .01) and AR (OR = 1.48, p = .03) with increasing 12-month PM2.5 exposure. Higher tissue eosinophil counts were associated with increasing PM2.5 levels across multiple timeframes (p < .05). CONCLUSIONS: Chronic PM2.5 exposure may be an independent risk factor for development of a mixed, type-2 dominant CRS inflammatory response.

Current insight into treatment of chronic rhinosinusitis: Phenotypes, endotypes, and implications for targeted therapeutics.

Chronic rhinosinusitis is characterized by persistent locoregional mucosal inflammation of the paranasal sinuses and upper airway that has substantial associated health care costs. Personalized approaches to care that incorporate use of molecular biomarkers, phenotypes, and inflammatory endotypes is a major focus of research at this time, and the concurrent rise of targeted therapeutics and biologic therapies has the potential to rapidly advance care and improve outcomes. Recent findings suggest that improved understanding of chronic rhinosinusitis phenotypic and endotypic heterogeneity, and incorporation of these characteristics into clinical care pathways, may facilitate more effective selection of surgical and/or therapeutic interventions. Ultimately, these personalized approaches have the potential to target specific inflammatory pathways, increase efficacy, reduce costs, and limit side effects. This review summarizes recent advances in the identification and characterization of chronic rhinosinusitis phenotypes, endotypes, and biomarkers and reviews potential implications for targeted therapeutics.

Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting. OBJECTIVE: We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist. METHODS: Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis. RESULTS: AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines. CONCLUSIONS: AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.

Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.

BACKGROUND: Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined but might have important ramifications given a rapidly aging US and world population. OBJECTIVE: The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures. METHODS: Levels of 17 mucus cytokines and inflammatory mediators were measured in 147 patients with CRS. Hierarchical cluster analysis was used to identify and characterize inflammatory CRS endotypes, as well as to determine whether age was associated with specific immune signatures. RESULTS: A CRS endotype with a proinflammatory neutrophilic immune signature was enriched in older patients. In the overall cohort patients 60 years and older had increased mucus levels of IL-1ß, IL-6, IL-8, and TNF-α when compared with their younger counterparts. Increases in levels of proinflammatory cytokines were associated with both tissue neutrophilia and symptomatic bacterial infection/colonization in aged patients. CONCLUSIONS: Aged patients with CRS have a unique inflammatory signature that corresponds to a neutrophilic proinflammatory response. Neutrophil-driven inflammation in aged patients with CRS might be less likely to respond to corticosteroids and might be closely linked to chronic microbial infection or colonization.

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.

BACKGROUND: Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening. METHODS: Germline DNA samples from 417 patients with HNSCC aged <50 years were screened for sequence variants by targeted next-generation sequencing of the entire length of 16 FA genes. RESULTS: The sequence revealed 194 FA gene variants in 185 patients (44%). The variant spectrum was comprised of 183 nonsynonymous point mutations, 9 indels, 1 large deletion, and 1 synonymous variant that was predicted to effect splicing. One hundred eight patients (26%) had at least 1 rare variant that was predicted to be damaging, and 57 (14%) had at least 1 rare variant that was predicted to be damaging and had been previously reported. Fifteen patients carried 2 rare variants or an X-linked variant in an FA gene. Overall, an age cutoff for FA screening was not identified among young patients with HNSCC, because there were no significant differences in mutation rates when patients were stratified by age, tumor site, ethnicity, smoking status, or human papillomavirus status. However, an increased burden, or mutation load, of FA gene variants was observed in carriers of the genes FA complementation group D2 (FANCD2), FANCE, and FANCL in the HNSCC patient cohort relative to the 1000 Genomes population. CONCLUSIONS: FA germline functional variants offer a novel area of study in HNSCC tumorigenesis. FANCE and FANCL, which are components of the core complex, are known to be responsible for the recruitment and ubiquitination, respectively, of FANCD2, a critical step in the FA DNA repair pathway. In the current cohort, the increased mutation load of FANCD2, FANCE, and FANCL variants among younger patients with HNSCC indicates the importance of the FA pathway in HNSCC. Cancer 2017;123:3943-54. © 2017 American Cancer Society.

Frailty is an independent predictor of postoperative rescue medication use after endoscopic sinus surgery.

INTRODUCTION: The modified five-item frailty index (mFI-5) is a validated risk stratification tool with the ability to predict adverse outcomes following surgery. In this study, we sought to use mFI-5 to assess the potential relationship between unhealthy aging and postoperative endoscopic sinus surgery (ESS) outcomes. METHODS: Patients who underwent sinus surgery at Vanderbilt between 2014 and 2018 were identified and assessed using the mFI-5, which is calculated based on the presence of five comorbidities: diabetes mellitus, hypertension requiring medication, chronic obstructive pulmonary disease, congestive heart failure, and non-independent functional status. Multivariate regression analyses were performed to quantify the association of mFI-5 score on need for rescue oral antibiotics, oral steroids, and antibiotic irrigations within 1 year following ESS, adjusting for relevant potential confounders. RESULTS: Four hundred and three patients met inclusion criteria.  Within 6 months of surgery, 312 (77%) required rescue antibiotics, 243 (60%) required oral corticosteroids (OCS), and 31 (8%) initiated antibiotic irrigations. Increasing mFI-5 scores were significantly associated with higher postoperative use of rescue antibiotics (p < 0.0001), OCS (p = 0.032), and antibiotic irrigation (p < 0.0001). Frailty scores remained as an independent predictor of these outcomes after adjustment for age, polyp status, preoperative sinonasal outcomes test (SNOT-22) score, and revision surgery status. CONCLUSIONS: Modified frailty scores may be a useful clinical tool to predict the need for postoperative rescue medication use after ESS.

Forehead Flap Practices: A Cross-Sectional Survey of Facial Plastic and Reconstructive Surgeons.

Background: The paramedian forehead flap (PMFF) is a well-established technique utilized for reconstruction of complex nasal defects. Objective: To identify the different techniques and management of patients undergoing PMFF reconstruction and compare these with current literature. Methods: Members of the American Academy of Facial Plastic and Reconstructive Surgery were sent a practice survey highlighting various nuances in PMFF reconstruction. The survey included questions about flap design, operative techniques, and perioperative care. Results: In total, 172 responses were received (14% response rate). Mean years of practice after fellowship was 15.8 years with most respondents performing either 1-5 (33.1%) or 6-10 (27.3%) PMFFs per year. Common practices included the use of general anesthesia, elevation of PMFF in the subgaleal plane (59.6%), and pedicle division at 3 weeks (80%) (p < 0.001). Complication rates ranged between 1% and 5%. The nose was the most common site for revision (p < 0.001) and the average number of secondary procedures after forehead flap division was 1.1 (standard deviation 0.81). The most variability in responses was seen for methods of internal lining reconstruction. Conclusion: Reconstructive surgeons frequently divide the PMFF pedicle at 3 weeks or later and have variable approaches to reconstruction of the internal lining with low complication rates overall.

The Association of Mental Health Disorders with the Effectiveness of Treating Facial Synkinesis with Chemodenervation Using Botulinum Toxin A.

Background: Studies suggest that mood disorders may affect perception of facial synkinesis, though none have analyzed effects on perceived benefit from chemodenervation. Objective: To measure the effect of depression, appearance anxiety, and other variables on chemodenervation benefit among patients with post-paralytic facial synkinesis. Design Type: Prospective cohort. Methods: Patients volunteered and completed: Synkinesis Assessment Questionnaire (SAQ), Facial Clinimetric Evaluation Scale (FaCE), Center for Epidemiological Studies Depression Scale (CES-D), and Fear of Negative Appearance Evaluation Scale (FNAES). Multivariate regression was used to analyze the effect of CES-D, FNAES, and demographics on pre- and post-chemodenervation SAQ and FaCE. Results: In total, 100 patients participated, 90% were female. Mean age was 56.4 (SD 12.3) years. The most common paralysis etiology was idiopathic (47%). Average synkinesis duration was 7.6 (6.2) years and treatment duration 4.9 (4.8) years. Older age and prior treatment (p < 0.05) were associated with reduced SAQ improvement; worse CES-D approached significance (p = 0.09). Reported history of anxiety was associated with greater SAQ improvement (p = 0.05). Factors associated with reduced FaCE improvement included higher baseline CES-D and prior treatment (p < 0.05). Conclusions: Older age, worse depression scores, and prior treatments may be associated with reduced patient-graded improvement following chemodenervation. History of anxiety may be associated with greater improvement.

Effect of Underlying Mental Health Disorders on the Correlation Between Patient- and Surgeon-Graded Synkinesis Scores.

Background: Little is known about how depression and appearance anxiety affect patient reporting of synkinesis severity. Learning/Study Objective: Measure prevalence of depression and appearance anxiety in facial synkinesis and correlations between subjective and surgeon-graded synkinesis severity. Design Type: Prospective cohort. Methods: Patients with synkinesis volunteered and completed: Synkinesis Assessment Questionnaire (SAQ), facial clinimetric evaluation (FaCE) scale, Center for Epidemiological Studies Depression Scale (CES-D), and Fear of Negative Appearance Evaluation Scale (FNAES). Standardized videos were scored by facial plastic surgeons using Sunnybrook Scale and eFaCE. Multivariate linear regression was used to compare patient- and surgeon-graded metrics. Results: One hundred patients participated, 91 were female. Mean age was 56.4 (12.3). Eight percent identified as Black and 87% White. The most common nerve injury etiology was idiopathic (47%). Mean synkinesis duration was 7.6 years (6.2). Twenty percent and 15% reported history of an anxiety or depressive disorder, respectively. Patient (SAQ, FaCE) and clinician (Sunnybrook, eFaCE) scores were correlated (Pearson's r 0.223-0.294, p < 0.05). Upon adjusting for CES-D/FNAES, correlations between most patient and clinician metrics became stronger. As CES-D and FNAES worsened, patient-clinician correlations weakened. Conclusions: Depression and appearance anxiety may affect patient reporting of synkinesis severity. Worse mental health scores may decorrelate patient and clinician synkinesis assessments.

Investigating the Minimal Clinically Important Difference for AzBio and CNC Speech Recognition Scores.

OBJECTIVE: To assess the minimal clinically important difference (MCID) values for cochlear implant-related speech recognition scores, which have not been previously reported. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: Eight hundred sixty-three adult patients who underwent cochlear implantation between 2009 and 2022. MAIN OUTCOME MEASURES: MCID values for consonant-nucleus-consonant (CNC) word scores and AzBio sentences in quiet and noise scores using distribution-based methods (half-standard deviation, standard error of measurement, Cohen's d, and minimum detectable change). RESULTS: In this cohort, the mean preoperative CNC word score was 13.9% (SD, 15.6). The mean preoperative AzBio sentences in quiet score was 19.1% (SD, 22.1), and the mean preoperative AzBio sentences in noise score was 13.0% (SD, 12.0). The average MCID values of several distribution-based methods for CNC, AzBio in quiet, and AzBio in noise were 7.4%, 9.0%, and 4.9%, respectively. Anchor-based approaches with the Speech, Spatial, and Qualities of hearing patient-reported measure did not have strong classification accuracy across CNC or AzBio in quiet and noise scores (ROC areas under-the-curve ≤0.69), highlighting weak associations between improvements in speech recognition scores and subjective hearing-related abilities. CONCLUSIONS: Our estimation of MCID values for CNC and AzBio in quiet and noise allows for enhanced patient counseling and clinical interpretation of past, current, and future research studies assessing cochlear implant outcomes.

Impact of sinus surgery in people with cystic fibrosis and chronic rhinosinusitis in the era of highly effective modulator therapy: Protocol for a prospective observational study.

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).

Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy.

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.

Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

BACKGROUND: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied. METHODS: In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund-Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression. RESULTS: Seventy-three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (ß = â€’4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (ß = â€’2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (ß = â€’0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (ß = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (ß = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores. CONCLUSIONS: Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF. CLINICAL TRIALS: NCT04469439.

Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy.

INTRODUCTION: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. METHODS: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. RESULTS: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). CONCLUSION: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

BACKGROUND: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. METHODS: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019-2023). Participants were administered the 22-SinoNasal Outcome Test (SNOT-22) survey and a modified SNOT-22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT-22 symptom importance subdomains in two sets of subgroups-those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. RESULTS: Among 69 participants, the highest priorities were nasal congestion (n = 48, 69.6% important), post-nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n = 23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n = 49) (sleep median score = 19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p < 0.0001; psychological = 17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p = 0.002). ETI users had comparable SNOT-22 total symptom importance scores to non-ETI users (p = 0.14). Non-ETI users (n = 34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n = 35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p = 0.055). CONCLUSIONS: Nasal congestion and post-nasal discharge were top priorities reported by PwCF + CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre-operative discussions. Non-ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required.

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3965-3973, 2024.

Association of cytokine profile with prior treatment failure and revision surgery in chronic rhinosinusitis.

BACKGROUND: Inflammatory patterns in chronic rhinosinusitis (CRS) may predict disease severity, need for multiple sinus surgeries, and treatment response. This study analyzes nasal mucus inflammatory cytokine patterns in patients with (CRSwNP) and without (CRSsNP) nasal polyposis and their association with revision sinus surgery. METHODS: A total of 319 CRS patients who underwent sinus surgery were included. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Cytokine expression patterns in patients with 0, 1, and ≥2 previous surgeries were analyzed using Kruskal-Wallis and principal component (PC) regression analyses. RESULTS: There were 122 (38%) patients with CRSsNP and 197 (62%) with CRSwNP. On univariate analysis, interleukin (IL)-1ß, IL-6, IL-8, and IL-21 were associated with increasing number of sinus surgeries in CRSsNP, as were IL-2, IL-4, IL-5, IL-6, IL-9, IL-17A, and tumor necrosis factor (TNF)-α in CRSwNP. PC analysis with continuous Poisson regression in CRSwNP demonstrated that high IL-5 and IL-13 and low IL-1ß, IL-12, and IL-21 were associated with more prior surgeries. In CRSsNP low IL-13 and high IL-5 and regulated-on-activation, normal T-cell-expressed and secreted (RANTES) were associated with more prior surgeries. Age remained a significant covariate in the full regression model for CRSsNP, but was nonsignificant in CRSwNP. CONCLUSION: In CRSwNP, elevated IL-5 and IL-13 levels were higher at time of surgery in patients with more prior surgeries. Type 2 cytokines in CRSsNP demonstrated mixed associations with revision surgery. For both phenotypes, IL-10, IL-12, and IL-21 were consistently lower as number of prior surgeries increased, suggesting that treatment-resistant disease may be modulated by impairment in these signaling pathways.