Hyun Jin Min
Publication date 16-04-2024
Aurelia S. Monk, Shreyas Pyati, Meredith Lamb, Nick Melott, Ezer H. Benaim, Christoper Wiesen, Cristine Klatt‐Cromwell, Brian D. Thorp, Charles S. Ebert Jr., Adam J. Kimple, Brent A. Senior
Publication date 15-04-2024
Key points Correlation between symptom-based surveys and objective olfactory testing is variable.
For diagnosis and symptom monitoring, surveys should correlate with objective testing.
The Odor Awareness Scale (OAS) and Affective Importance of Odor Scale (AIO) showed significant but moderate positive correlations with University of Pennsylvania Scent Identification Test (UPSIT) score.
Amelia S. Lawrence, Rahul Alapati, Sarah F. Wagoner, Antonio Bon Nieves, Cole Bird, Robert Wright, Shah Jafri, Michael Rippee, Jennifer A. Villwock
Publication date 14-04-2024
Key points Patients with traumatic brain injury (TBI) had worse olfactory quality of life (QoL) and Sino-Nasal Outcome Test-22 scores compared to a normal cohort.
A worse olfactory QoL correlated with concussion symptom burden.
Olfactory dysfunction among TBI patients should be addressed to improve overall outcomes.
Sandeep K. Gill, Juan C. Hernaiz‐Leonardo, Thaddeus J. Edens, Athenea Pascual, Chris Tang, Judy Fan, Andrew Thamboo, Warren Mullings, Saad Alsaleh, Bader M. Alim, Amin R. Javer, Amee R. Manges
Publication date 14-04-2024
Key Points Sino Nasal Microbiota Transfer (SNMT) was safe with immediate benefit in all recipients, with sustained improvement in two of three recipients for up to 180 days.
The addition of antimicrobial photodynamic therapy worsened chronic rhinosinusitis.
These promising SNMT results warrant further study of safety and efficacy.
Zetian Li, Luisa Richter, Tanja Krueger, Herbert Eichwald, Antje Hähner, Thomas Hummel
Publication date 08-04-2024
Abstract Background Diagnosing parosmia is a challenge. The present study aimed to explore the distinctions between hyposmic patients with and without parosmia utilizing electroencephalography-derived olfactory event-related potentials (ERP).
Methods Forty-four patients with hyposmia were enrolled and divided into a group with parosmia (n = 23, mean age ± standard deviation = 48 ± 14 years, seven men) and a group without parosmia (n = 21, age = 52 ± 12 years, seven men) based on the clinical interview. Additionally, 21 healthy controls (mean age = 45 ± 14 years, six men) were included. Various measurements were obtained, including the Sniffin’ Stick test, threshold tests for the odorants furfural mercaptan and 2,6-nonadienal, a modified Sniffin’ Stick parosmia test, and well-being ratings. Chemosensory ERPs were recorded separately for each nostril using high-precision, computer-controlled air-dilution olfactometry.
Results Patients with parosmia had a decreased olfactory function similar to that observed in patients with hyposmia, although the odor sensitivity of patients with severe parosmia remained relatively unaffected. Patients with parosmia reported a decrease in well-being compared to controls. The severity of parosmia was positively correlated with odor sensitivity. Furthermore, patients with severe parosmia exhibited faster responses to unpleasant odors than patients without parosmia.
Conclusion Overall, the present findings support the idea that parosmia predominantly occurs during olfactory recovery, significantly disturbing patients and warranting the development of effective treatments. Notably, the relatively faster responses of hyposmic patients with severe parosmia suggest that the generation of distorted olfactory responses may involve early stages of the processing of olfactory information.
Katie Melder, Jess C. Mace, Garret Choby, Joao Paulo Almeida, Pierre‐Olivier Champagne, Erik Chan, Jeremy Ciporen, Mark B. Chaskes, Juan Fernandez‐Miranda, Nicholas K. Fung, Paul Gardner, Peter Hwang, Keven Seung Yong Ji, Aristotelis Kalyvas, Keonho A. Kong, Chirag Patel, Zara Patel, Maria Peris Celda, Carlos D. Pinheiro‐Neto, Carl Snyderman, Brian D. Thorp, Jamie J. Van Gompel, Georgios Zenonos, Nathan T. Zwagerman, Olabisi Sanusi, Eric W. Wang, Mathew Geltzeiler
Publication date 03-04-2024
Abstract Background With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence.
MethodsA retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses.
ResultsA final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence.
Conclusions Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.
Sarah M. Adams, Armo Derbarsegian, Ahmad R. Sedaghat, Katie M. Phillips
Publication date 01-04-2024
Key PointsCRS patients treated with medical management have improvement in ETD symptoms as reflected by lower ETDQ-7 scores However, appropriate CRS medical management may be limited in ability to significantly improve, or resolve, ETD
Pubmed PDF WebSabrina W. Leung, Tripti Brar, Stephen F. Bansberg, Michael J. Marino, Devyani Lal, Cullen Taylor, Amar Miglani
Publication date 01-04-2024
Key Points Combined endoscopic sinus surgery and nasal septal perforation repair is technically feasible.
NOSE-Perf is a recently developed patient-reported outcome measure for nasal septal perforation.
The decision to perform combined ESS and NSP repair should be made on a case-by-case basis.
Yeo E. Kim, Andrea Wang, Paul J. Christos, Katherine E. Valente, William R. Reisacher
Publication date 01-04-2024
Key Points This is the first study to quantify the accuracy, sensitivity, and specificity of the human olfactory system in detecting peanuts in common food items.
With more competing sensory input, the human olfactory sensitivity to peanuts decreases; this is especially evident when peanuts are mixed in sauces.
Metrics established in this study can be used to develop standards for determining the clinical utility of allergen detecting devices that are currently under development.
Mark B. Chaskes, Erin Mamuyac Lopez, K. Albert Kong, Charles S. Ebert Jr., Brent A. Senior, Brian D. Thorp, Adam J. Kimple
Publication date 01-04-2024
Key Points Primary ciliary dyskinesia (PCD) is a complex diagnosis without a universal diagnostic test Clinicians must have some skepticism of historic diagnoses of PCDClinicians should consider a diagnosis of PCD in patients with recalcitrant disease
Pubmed PDF WebNikita Chapurin, Rodney J. Schlosser, Jorge Gutierrez, Jess C. Mace, Timothy L. Smith, Todd E. Bodner, Sofia Khan, Jennifer K. Mulligan, Jose L. Mattos, Jeremiah A. Alt, Vijay R. Ramakrishnan, Zachary M. Soler
Publication date 01-04-2024
Abstract Background It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures.
Methods Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using “Sniffin’ Sticks” testing and Lund–Kennedy endoscopic score (LKES).
ResultsA total of 115 patients were clustered into type 2 inflammatory, non–type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (−28.3 standard deviation, ±16.2) and TDI (6.5 standard deviation, ±7.9) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures.
Conclusions All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes.
Chien‐Chia Huang, Pei‐Wen Wu, Chi‐Che Huang, Po‐Hung Chang, Chia‐Hsiang Fu, Ta‐Jen Lee
Publication date 01-04-2024
Key Points Empty nose syndrome (ENS) is characterized by a patent nasal airway and a sense of nasal obstruction.
ENS and psychological symptoms improved after surgery and remained stable for up to three years.
Identifying residual disease is necessary for enhancing therapeutic outcomes in ENS patients.
Cara M. Fleseriu, Daniel M. Beswick, Sabrina L. Maoz, Peter H. Hwang, Garret Choby, Edward C. Kuan, Erik P. Chan, Nithin D. Adappa, Mathew Geltzeiler, Anne E. Getz, Ian M. Humphries, Christopher H. Le, Waleed M. Abuzeid, Eugene H. Chang, Aria Jafari, Todd T. Kingdom, Michael A. Kohanski, Jivianne K. Lee, Seyed A. Nabavizadeh, Jayakar V. Nayak, James N. Palmer, Zara M. Patel, Carlos D. Pinheiro‐Neto, Adam C. Resnick, Timothy L. Smith, Carl H. Snyderman, Maie A. St. John, Jay Storm, Jeffrey D. Suh, Marilene B. Wang, Eric W. Wang
Publication date 01-04-2024
Abstract 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.
Sophie S. Jang, Kwang S. Pak, Allyssa Strom, Leslie Gomez, Kyubo Kim, Taylor A. Doherty, Adam S. DeConde, Allen F. Ryan, Carol H. Yan
Publication date 01-04-2024
Abstract Introduction While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling.
MethodsCOVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann–Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer.
Results Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts.
ConclusionIFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.
David Grimm, Rachel Daum, Bruna R. Castro Silva, Christine K. Lee, Juan C. Fernandez‐Miranda, Jayakar V. Nayak, Zara M. Patel, Peter H. Hwang, Michael T. Chang
Publication date 01-04-2024
Key PointsETD symptoms are present in 16% patients with underlying skull base pathology.
Preoperative ETD symptoms improve following surgical treatment of skull base pathology.
ETD symptoms may worsen in patients with central, posterior, or malignant skull base pathology.
Brandon M. Lehrich, Arash Abiri, Theodore V. Nguyen, Benjamin F. Bitner, Charles C. L. Tong, Edward C. Kuan
Publication date 01-04-2024
Key Points Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden.
A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation.
ROS1-mutated patients have improved overall survival likely due to high mutational burden.
Esther Wang, Kristen E. Wroblewski, Martha K. McClintock, Jayant M. Pinto, Leah J. Witt
Publication date 01-04-2024
Abstract Background Frailty is prevalent among older adults with asthma or chronic obstructive pulmonary disease (obstructive lung diseases OLDs). Frailty and OLDs co-occurrence is associated with increased hospitalization/mortality. Chemosensory dysfunction is closely connected to both OLD and frailty. We evaluated the utility of olfactory decline as a biomarker of frailty in the setting of OLD.
Methods We performed a prospective, longitudinal, nationally representative study of community-dwelling older US adults in the National Social Life, Health and Aging Project, an omnibus in-home survey. Respondents reported a physicians diagnosis of OLD. Decline in odor identification and sensitivity over 5 years and frailty (adapted fried frailty phenotype criteria) were measured using standard tools. Multivariate logistic regressions evaluated the association between OLD status, olfactory decline, and frailty.
Results We compared individuals with OLD (n = 98; mean age 71.2 years, 59.2% women) and those without OLD (n = 1036; mean age 69.5 years, 58.9% women). Olfactory identification decline was associated with developing frailty over the 5-year follow-up period in individuals with OLD (odds ratio OR = 9.1, 95% confidence interval CI = 2.1–38.6, p = 0.003). Olfactory decline predicted incidence of frailty in individuals with OLD (identification: OR = 4.8, 95% CI = 1.3–17.5, P = 0.018; sensitivity: OR = 6.1, 95%CI = 1.2–31.0, p = 0.030) but not in those without OLD adjusting for demographics, heavy alcohol use, current smoking, and comorbidity. Results were robust to different thresholds for olfactory decline and frailty development.
Conclusions Older adults with OLD who experience olfactory decline face higher odds of developing frailty. Use of olfactory decline as a biomarker to identify frailty could allow earlier intervention and decrease adverse outcomes for high-risk older adults with OLD.
Haotao Zeng, Jiangqi Liu, Lihua Mo, Minyao Li, Aifa Tang, Xianhai Zeng, Miao Zhao, Pingchang Yang
Publication date 01-04-2024
Key Points Nasal secretions of allergic rhinitis patients were analyzed by Olink proteomics.
Fifteen differentially expressed proteins (DEPs) were identified.
The DEPs were significantly correlated with the total nasal symptom scores of patients with allergic rhinitis.
Daniel M. Beswick, Ethan J. Han, Jess C. Mace, Karolin Markarian, Jeremiah A. Alt, Todd E. Bodner, Naweed I. Chowdhury, Patricia H. Eshaghian, Anne E. Getz, Peter H. Hwang, Ashoke Khanwalkar, Adam J. Kimple, Jivianne T. Lee, Douglas A. Li, Meghan Norris, Jayakar V. Nayak, Cameran Owens, Zara Patel, Katie Poch, Rodney J. Schlosser, Kristine A. Smith, Timothy L. Smith, Zachary M. Soler, Jeffrey D. Suh, Grant Turner, Marilene B. Wang, Jennifer L. Taylor‐Cousar, Milene Saavedra
Publication date 01-04-2024
Abstract 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 Sino Nasal 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.
Robert Hagedorn, Benton Tullis, Cassidy Nguyen, Ryan Stockard, Jess C Mace, Vijay R Ramakrishnan, Daniel M Beswick, Zachary M Soler, Timothy L Smith, Jeremiah A Alt, Amarbir S Gill
Publication date 01-04-2024
Abstract Background Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS-specific disease severity. We assessed the impact of air pollutants on sinonasal-specific and general quality-of-life (QOL) measures in a multi-institutional cohort of patients with CRS.
Methods Participants with CRS were prospectively enrolled in a cross-sectional study and self-selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22-item Sino Nasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association.
ResultsA total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation SD ± 2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT-22 or SF-6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ = 0.12, 95% confidence interval {CI}: 0.003, 0.234; p = 0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m3) did not correlate with change in total SNOT-22 or SF-6D scores after treatment. Nevertheless, sulfur dioxide (SNOT-22: ρ = –0.121 95% CI: –0.210, –0.030; p = 0.007; SF-6D: ρ = 0.095 95% CI: 0.002, 0.186; p = 0.04) and carbon monoxide (SNOT-22: ρ = -0.141 95% CI: –0.230, 0.050; p = 0.002) exposure did correlate with these outcome measures.
Conclusion Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship.
Yating Liu, Zaichuan Wang, Limin Zhao, Xue Wang, Xinyi Li, Zhennan Qu, Yuan Zeng, Yingyue Liu, Liusiqi Hao, Mengzhe Yang, Yuling Zhang, Shujian Zhang, Qiqi Wang, Yan Li, Feng Lan, Luo Zhang
Publication date 01-04-2024
Key Points Nasal tight junction module score correlates negatively to allergy module score in COVID-19.
Omicron variant may slow-down tight junction restoration in patients with AR.
Ying‐Ying Zhang, Min Zhang, Jia‐Qi Zhang, Qiu‐Qi Li, Mei‐Ping Lu, Lei Cheng
Publication date 01-04-2024
Abstract Background Allergen immunotherapy (AIT)-associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti-IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety.
Objective To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases.
Methods The MEDLINE/Pub Med, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random-effect model was established to estimate outcomes with a 95% confidence interval (CI).
ResultsA total of 11 eligible RCTs (involving 901 patients) were screened out for the meta-analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio OR = 2.43; 95% CI: 1.33–4.44; p = 0.004; I2 = 35%, and OR = 6.77; 95% CI: 2.10–21.80; p = 0.001; I2 = 36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR = 0.32; 95% CI: 0.18–0.59; p = 0.0003; I2 = 0%). Meanwhile, the improvements in symptom severity score (mean difference MD = −0.26), rescue medication daily means score (MD = −0.14), and number of patients consuming epinephrine in AIT (OR = 0.20) were all more evident than those in AIT alone.
Conclusion Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic AEs.
Publication date 01-04-2024
Xinru Gong, Yijie Fu, Lei Zhou, Aiming Wei, Chongsheng Pan, Tianmin Zhu, Hui Li
Publication date 01-04-2024
Abstract Background Chronic rhinosinusitis (CRS) is a common and intractable disease in otorhinolaryngology, laying a heavy burden on healthcare systems. The worldwide researchers are making efforts to find solutions to this disease. Metabolomics has recently gained more and more traction, and might become a promising tool to unravel the complexity of CRS. This paper provides an overview of current studies on the metabolomics of various CRS subtypes.
Methods We conducted a comprehensive literature search in Pub Med, Web of Science, EMBASE, Google Scholar, and Cochrane Library, up to May 25, 2023. Search strategies incorporated key terms such as “chronic rhinosinusitis” and “metabolomics” with relevant synonyms and MeSH terms. Titles and abstracts of 86 screened articles were assessed for relevance to CRS and metabolomics. Methodological robustness, data reliability, and relevance were considered for shortlisted articles.
Results After the refined process, a total of 26 articles were included in this study and sorted out by research themes, methodology and pivotal discoveries. These included studies identified the metabolic pathways and markers related to the pathophysiology in each subtype of CRS.
Conclusions Metabolomics helps to shed light on the complexity of CRS. The mentioned findings highlight the importance of specific metabolic pathways and markers in understanding the pathophysiology of CRS. Despite that, challenges and future directions in metabolomics research for CRS would be worth being further explored.
Wirach Chitsuthipakorn, Narissara Pracharktam, Juthaporn Phetpong, Patlada Kowatanamongkon, Kittichai Mongkolkul, Kornkiat Snidvongs
Publication date 31-03-2024
Abstract Introduction Euro Qol-5-dimensions-5-levels (EQ-5D-5L), visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG) are used for the assessment of Health Utility Scores (HUS) of chronic rhinosinusitis (CRS). This study aimed to determine the overall HUS of CRS, the factors which influence the HUS, and the preferable method.
MethodsA cross-sectional study was conducted. Patients with primary CRS were recruited. Clinical and socioeconomic data together with HUS were assessed. Four HUS scores determined from the four different methods were compared.
ResultsA total of 335 patients were enrolled. The overall HUS, as measured by EQ-5D-5L, VAS, TTO, and SG, was 0.88 ± 0.14, 0.79 ± 0.17, 0.89 ± 0.15, and 0.86 ± 0.16, respectively. The multivariable linear regression revealed that each increasing 22-item sinonasal outcome test (SNOT-22) score predicted a reduction of 0.002 to 0.003 in HUS (all methods, p < 0.01). Patients who scheduled for endoscopic sinus surgery had 0.06 to 0.11 HUS lower than other groups in EQ-5D-5L and VAS (all p < 0.05). Higher endoscopy score, age, presence of comorbid airway diseases, and lower education correlated with lower HUS (p < 0.05). Given the HUS results and regression models, the EQ-5D-5L is likely the preferable choice.
Conclusion The overall HUS of CRS was approximately 0.79–0.89. High SNOT-22 score and those who failed medications, presence of comorbid AR/asthma, increased age, high endoscopy score, and low education negatively impacted HUS. Our data suggest that EQ-5D-5L is a preferable method for measuring HUS in patients with CRS.
Jennifer E. Douglas, Nithin D. Adappa, Garret Choby, Corinna G. Levine, Mindy R. Rabinowitz, Raj Sindwani, Eric W. Wang, Bradford A. Woodworth, Edward C. Kuan
Publication date 30-03-2024
Abstract The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs.
Pubmed PDF WebHarish Dharmarajan, Garret Choby, Ralph Abi Hachem, Edward C. Kuan, Corinna G. Levine, Olabisi Sanusi, Theodore Schuman, Dennis Tang, Michael Yim, Mathew Geltzeiler
Publication date 25-03-2024
Abstract Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patients quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.
Pubmed PDF WebEzer H. Benaim, Saima Wase, Saif Zaidi, Aurelia Monk, Cristine Klatt‐Cromwell, Brian D. Thorp, Charles S. Ebert Jr., Adam J. Kimple, Brent A. Senior
Publication date 25-03-2024
Key Points Automated plagiarism-checking software can be a valuable tool for detecting plagiarism in manuscripts.
Twenty-five of 60 articles (42%) had at least one incidence of plagiarism, predominately text recycling.
A “similarity score” ranging from 22% to 35% could be a potential cut-off value when screening submitted manuscripts.
Anna Megow, George Bouras, Eng H. Ooi, Sarah Vreugde, Alkis Psaltis, Peter‐John Wormald
Publication date 13-03-2024
Key Points Nebulized budesonide is effective at half dose compared to budesonide irrigation in CRS.
Nasal nebulizers provide an alternative for delivery of topical steroids to the sinuses.
Dev Amin, Shreya Mandloi, Kathryn Nunes, Neha Garg, Chase Kahn, Alexander Duffy, Elina Toskala, Mindy Rabinowitz, Marc Rosen, Gurston Nyquist
Publication date 13-03-2024
Key Points Silent sinus syndrome (SSS) and chronic maxillary atelectasis (CMA) represent an overlapping clinical entity, both likely lying on the spectrum of one disease process.
There is widespread inconsistency of diagnosis in the literature of reported cases of SSS and CMA.
We propose a novel, comprehensive staging system to simplify diagnosis and inform management.
Maxime Fieux, Florent Carsuzaa, Yvan Bellanger, Sophie Bartier, Virginie Fournier, Jean Claude Lecron, Matthieu Bainaud, Bruno Louis, Stéphane Tringali, Xavier Dufour, André Coste, Laure Favot, Emilie Bequignon
Publication date 11-03-2024
Abstract Background Chronic rhinosinusitis with nasal polyp (CRSwNP) is a typical type 2 inflammation involving interleukin (IL)-4 and IL-13. Dupilumab is a fully human monoclonal antibody targeting IL-4 receptor α subunit, thereby blocking signaling by both cytokines. Our hypothesis was that IL-4 and IL-13, by inducing a severe epithelial dysregulation, are involved in CRSwNP pathogenesis. This study aimed to evaluate the in vitro direct effect of IL-4, IL-13, and dupilumab on nasal epithelial functions.
Methods Nasal polyps and control mucosa from 28 patients, as well as human nasal epithelial cells (HNEC) from 35 patients with CRSwNP were used.
Three major epithelial functions were investigated: the epithelial barrier function (characterized by transepithelial electrical resistance measurements and tight junction protein expression), the ciliary motion (characterized by the ciliary beating efficiency index), and wound healing (characterized by the wound repair rate) under various stimulations (IL-4, IL-13, and dupilumab). The main outcome was a significant change in epithelial functions following exposure to IL-4, IL-13, and dupilumab for 48 h in the basal media.
ResultsIL-4 (1, 10, and 100 ng/mL) but not IL-13 induced a significant decrease in occludin and zonula-occludens protein expression, ciliary beating efficiency, and wound repair rate in HNEC. Dupilumab (0.04 mg/mL) had no effect on HNEC and specifically restored all epithelial functions altered when cells were exposed to a 48-h IL-4 stimulation.
Conclusion Dupilumab, in vitro, restored epithelial integrity by counteracting the effect of IL-4 on the epithelial barrier (increased epithelial permeability, decreased ciliary beating efficiency, and decreased wound repair rate).
Vinay K. Rathi, Zachary M. Soler, Rodney J. Schlosser, Alan D. Workman, Nikita Chapurin, Nicholas R. Rowan, Stacie B. Dusetzina
Publication date 11-03-2024
Key Points In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA).
Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%.
Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%–60%.
Cheng‐Yu Hsieh, Wei‐Chieh Lin, Chung‐Ching Lin, Yi‐Fan Chou
Publication date 11-03-2024
Abstract Background To elucidate the role of balloon Eustachian tuboplasty (BET) in the management of chronic rhinosinusitis with obstructive Eustachian tube dysfunction (ETD), we evaluated the results of endoscopic sinus surgery (ESS) with and without BET in patients with chronic rhinosinusitis with obstructive ETD.
Methods This randomized controlled trial conducted in a single-institution tertiary care center setting included 50 patients diagnosed with primary chronic rhinosinusitis and obstructive ETD between July 2018 and June 2022. Twenty-five patients were prospectively enrolled for combined ESS/BET. The control group (25 patients) underwent ESS alone. Outcome measurements of the Sinonasal Outcome Test 22, modified Lund–Kennedy score, Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7), and serial Eustachian tube function test results were analyzed 3 months postoperatively.
Results The improvement (12.60 ± 6.50) in the ETDQ-7 score in the BET group was significantly higher than that in the control group (6.60 ± 5.58). The ratio of improvement in the ETDQ-7 score was also significantly higher in the BET than in the control group (92% vs. 68%, p = 0.034). Logistic regression analysis showed that performing BET (odds ratio OR: 5.41, 95% confidence interval CI: 1.02–28.79, p = 0.048) and a low post-modified Lund–Kennedy score (OR: 0.15, 95% CI: 0.04–0.54, p = 0.004) were significantly associated with ETDQ-7 score improvement.
Conclusion Combined BET/ESS could decrease otologic symptoms and improve Eustachian tube function. BET may be an appropriate adjunctive procedure for treating chronic rhinosinusitis with obstructive ETD.
Emily Garvey, Bita Naimi, Alexander Duffy, Chase Kahn, Douglas Farquhar, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Jessica Most, Elina Toskala, Gurston G. Nyquist
Publication date 26-02-2024
Key Points This study examines the impact of dupilumab on medication use for chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma patients.
Patients on dupilumab had a reduction in oral/inhaled/topical steroids, antibiotics, and leukotriene receptor antagonists (LTRAs).
The reduction in medication use had no impact on total polyp or SNOT-22 scores.
David Grimm, Z. Jason Qian, Michael Yong, Peter H. Hwang
Publication date 23-02-2024
Key PointsPM2.5 exposure is a risk factor for the development of acute sinusitis.
PM2.5 exposure affects acute sinusitis in a dose response fashion.
David R. Grimm, Daniel M. Beswick, Sabrina L. Maoz, Eric W. Wang, Garret W. Choby, Edward C. Kuan, Erik P. Chan, Nithin D. Adappa, Mathew Geltzeiler, Anne E. Getz, Ian M. Humphreys, Christopher H. Le, Waleed M. Abuzeid, Eugene H. Chang, Aria Jafari, Todd T. Kingdom, Michael A. Kohanski, Jivianne K. Lee, Jayakar V. Nayak, James N. Palmer, Zara M. Patel, Carlos D. Pinheiro‐Neto, Adam C. Resnick, Myung S. Sim, Timothy L. Smith, Carl H. Snyderman, Maie A. John St., Phillip Storm, Jeffrey D. Suh, Marilene B. Wang, Peter H. Hwang
Publication date 19-02-2024
Abstract 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.
Najm S. Khan, Yuki Yoshiyasu, Brian S. Wang, Antoine Khoudari, Dean M. Clerico, Jackson M. King, Toby O. Steele, Aatin K. Dhanda, Masayoshi Takashima, Omar G. Ahmed
Publication date 19-02-2024
Key Points Severe epistaxis occurs in 2% of PNN ablation cases, independent of method or device type.
Major epistaxis requiring intervention after PNN ablation can occur on average 20 days post-procedure.
Amarbir S. Gill, Benton Tullis, Jess C. Mace, Conner Massey, Vivek C. Pandrangi, Jorge A. Gutierrez, Vijay R. Ramakrishnan, Daniel M. Beswick, Zachary M. Soler, Timothy L. Smith, Jeremiah A. Alt
Publication date 17-02-2024
Abstract Objective Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes.
MethodsA total of 642 study participants with CRS were prospectively enrolled and self-selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22-item Sino Nasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded pre- and post-treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearmans correlation coefficients (Rs) and Cramers V effect size (φc) with 95% confidence interval (CI) were calculated.
ResultsA history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT-22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF-6D values (Rs = −0.20; 95% CI: −0.27, −0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within-subject improvement, or achievement of >1 minimal clinically important difference, in SNOT-22 or SF-6D scores after treatment were found.
Conclusions Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease-specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation.
Theodore V. Nguyen, Benjamin F. Bitner, Ellen M. Hong, Jonathan C. Pang, Leo Li Tang Meller, Cecilia Nguyen, Edward C. Kuan
Publication date 14-02-2024
Key Points The septal branch of the anterior ethmoid artery (sbAEA) is an underrecognized source of severe refractory epistaxis.
Herein, we describe the presentation, predisposing factors, treatment strategies, and outcomes of a series of patients with this condition.
Juan Carlos Hernaiz‐Leonardo, Changwan Ryu, Athenea Pascual, Judy Fan, Maria Caray, Rogério Pezato, Julia Yang, Don Sin, Andrew Thamboo
Publication date 11-02-2024
Abstract Background Dysregulation of the airway microbiota is thought to contribute to airway inflammation in both chronic rhinosinusitis (CRS) and asthma. However, the relationship between the upper and lower airway microbiome remains unclear.
Methods Sinus and lung brushes were collected from 29 CRS participants undergoing sinus surgery. DNA was extracted and submitted for 16s rRNA microbiome sequencing. Alpha and beta diversity metrics, taxonomic composition, and differences between individual taxa were compared for paired sinus and bronchial samples.
Results Twenty-three out of 29 participants had sufficient samples for analysis. The mean (standard deviation) age was 51.59 (14.57) years, and 10 (44%) patients were female. Twelve (52%) patients had comorbid asthma. Sinus brushes had significantly higher alpha diversity indexes (Shannon and Faith) compared to bronchial brushes (p < 0.001). Beta diversity metrics were significantly different between the sinus and bronchial samples. Principal coordinate analysis showed no clustering of paired nasal and bronchial samples. Sinus brushes had significantly more Lawsonella, Corynebacterium, and Staphylococcus compared to bronchia brushes, while the latter were enriched in Tropheryma and Sphingomonas, among others (false discovery rate FDR-adjusted p < 0.01). Finally, CRS patients with comorbid asthma had significantly higher Pseudomonas and Peptoniphilus in sinus brushes and lower Prevotella in bronchial brushes when compared to non-asthmatics (FDR-adjusted p < 0.01).
Conclusion The sinus and bronchial bacterial microbiomes differ in important ways. Our study suggests that migration of bacteria from the sinus into the lower airways is unlikely in patients with CRS.
Aurelia Monk, Brian D. Thorp, Brent A. Senior, Adam J. Kimple, Cristine Klatt‐Cromwell, Charles S. Ebert Jr.
Publication date 11-02-2024
"Achilles A. Kanaris, David J. Fei‐Zhang, Lily B. Fletcher, Stephanie S. Smith, Urjeet A. Patel, Jill N. DSouza, Daniel C. Chelius, Anthony M. Sheyn, Jeffrey C. Rastatter"
Publication date 11-02-2024
Key Points Social determinants of health interactively influence sinonasal cancer care and prognosis.
Housing-transportation and socioeconomic status showed the largest associations with disparities.
The social vulnerability index can reveal the social determinants of sinonasal cancers.
Christine M. Liu, Ethan J. Han, Jakob L. Fischer, Jess C. Mace, Jose L. Mattos, Karolin Markarian, Jeremiah A. Alt, Todd E. Bodner, Naweed I. Chowdhury, Patricia H. Eshaghian, Anne E. Getz, Peter H. Hwang, Ashoke Khanwalkar, Adam J. Kimple, Jivianne T. Lee, Douglas A. Li, Meghan Norris, Jayakar V. Nayak, Cameran Owens, Zara M. Patel, Katie Poch, Rodney J. Schlosser, Kristine A. Smith, Timothy L. Smith, Zachary M. Soler, Jeffrey D. Suh, Grant A. Turner, Marilene B. Wang, Jennifer L. Taylor‐Cousar, Milene T. Saavedra, Daniel M. Beswick
Publication date 11-02-2024
Abstract 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-Sino Nasal 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.
Christopher M. Low, Allan R. Wang, Michael Yong, Jayakar Nayak, Zara Patel, Peter H. Hwang
Publication date 31-01-2024
Key points Increased dupilumab utilization coincided with decreased ESS in patients with CRSwNP between 2019 and 2021.
One potential confounder was the concurrent COVID-19 pandemic, which may have negatively impacted surgery utilization rates.
Meghan Norris, Erin Lopez, Daniel Alicea Delgado, Brian Thorp, Christine Klatt‐Cromwell, Brent Senior, Adam Kimple, Charles S. Ebert Jr.
Publication date 31-01-2024
Key points All intranasal corticosteroid spray formulations are safe to use in patients on pre-exposure prophylaxis.
Beclomethasone nasal spray can be used safely with all HAART and PrEP regimens.
David J. Cvancara, Heather A. Wood, Mohamed Aboueisha, Thomas B. Marshall, Tzu‐Cheg Kao, James O. Phillips, Ian M. Humphreys, Waleed M. Abuzeid, Ashton E. Lehmann, Yoshiko Kojima, Aria Jafari
Publication date 24-01-2024
Abstract Background Patients with chronic rhinosinusitis (CRS) can experience cognitive dysfunction. The literature on this topic mostly reflects patient-reported measurements. Our goal was to assess cognitive function in patients with CRS using objective measures, including saccadic eye movements—a behavioral response reflecting cognitive and sensory information integration that is often compromised in conditions with impaired cognition.
Methods Participants (N = 24 with CRS, N = 23 non-CRS healthy controls) enrolled from rhinology clinic underwent sinonasal evaluation, quality of life assessment (Sino-nasal Outcome Test 22 SNOT-22), and cognitive assessment with the Neuro-QOL Cognitive Function-Short Form, the Montreal Cognitive Assessment (MoCA), and recording of eye movements using video-oculography.
Results Participants with CRS were more likely to report cognitive dysfunction (Neuro-QOL; 45.8% vs. 8.7%; p = 0.005) and demonstrate mild or greater cognitive impairment (MoCA; 41.7% vs. 8.7%; p = 0.005) than controls. Additionally, participants with CRS performed worse on the MoCA overall and within the executive functioning and memory domains (all p < 0.05) and on the anti-saccade (p = 0.014) and delay saccade (p = 0.044) eye movement tasks. Poorer performance on the MoCA (r = −0.422; p = 0.003) and the anti-saccade (r = −0.347; p = 0.017) and delay saccade (r = −0.419; p = 0.004) eye movement tasks correlated with worse CRS severity according to SNOT-22 scores.
Conclusion This study is the first to utilize objective eye movement assessments in addition to researcher-administered cognitive testing in patients with CRS. These patients demonstrated a high prevalence of cognitive dysfunction, most notably within executive functioning and memory domains, with the degree of dysfunction correlating with the severity of CRS.
Thomas Radulesco, Alberto Maria Saibene, Justin Michel, Luigi Angelo Vaira, Jérôme R. Lechien
Publication date 24-01-2024
Keypoints Chatbot Generative Pre-trained Transformer (ChatGPT)-4 indicated more than twice additional examinations than practitioners in the management of clinical cases in rhinology.
The consistency between ChatGPT-4 and practitioner in the indication of additional examinations may significantly vary from one examination to another.
The ChatGPT-4 proposed a plausible and correct primary diagnosis in 62.5% cases, while pertinent and necessary additional examinations and therapeutic regimen were indicated in 7.5%–30.0% and 7.5%–32.5% of cases, respectively.
The stability of ChatGPT-4 responses is moderate-to-high. The performance of ChatGPT-4 was not influenced by the human-reported level of difficulty of clinical cases.
Alessandro Vinciguerra, Mario Turri‐Zanoni, Marco Ferrari, Davide Mattavelli, Giorgio Sileo, Vittorio Rampinelli, Vincenzo Abbate, Benjamin Verillaud, Alberto Schreiber, Paolo Battaglia, Maurizio Bignami, Piero Nicolai, Paolo Castelnuovo, Philippe Herman
Publication date 24-01-2024
Key points Nasoseptal flap with extended pedicle dissection is a low morbidity and high success rate flap.
It is a flap that can be applied to reconstruct a wide range of ipsilateral skull base defects.
Kolin E. Rubel, Andrea Lopez, Rory J. Lubner, Diane L. Lee, Kristen Yancey, Rakesh K. Chandra, Naweed I. Chowdhury, Justin H. Turner
Publication date 24-01-2024
Abstract 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.
Masayoshi Takashima, J. Pablo Stolovitzky, Randall A. Ow, Stacey L. Silvers, Chad M. McDuffie, Marc Dean, Ahmad R. Sedaghat, Bobby A. Tajudeen
Publication date 24-01-2024
Abstract Background Minimally invasive temperature-controlled radiofrequency (TCRF) ablation of the posterior nasal nerve (PNN) demonstrated a significant larger treatment effect on the symptom burden of chronic rhinitis patients than a sham control (no energy delivery) at the 3-month primary endpoint of this trial.
Methods Two-year posttreatment outcomes for patients treated in a prospective, multicenter, patient-blinded randomized controlled trial were determined by combining the index active treatment-arm and index control-arm crossover patients into a single group (after the primary endpoint) to evaluate the treatment effect durability and long-term effects on concomitant chronic rhinitis medication usage.
Results The mean baseline reflective total nasal symptom score (rTNSS) was 8.2 (95% confidence interval CI, 7.9–8.6; N = 104). At 2 years (N = 79), the mean change in rTNSS was −5.3 (95% CI, −5.8 to −4.8; p < 0.001; 64.6% improvement). The 2-year responder rate (≥30% improvement in rTNSS) was 87.3% (95% CI, 78.0–93.8). All four components of the rTNSS (rhinorrhea, congestion, sneezing, and nasal itching) showed significant improvement over baseline, with rhinorrhea and congestion showing the most improvement. Postnasal drip and cough symptoms were also significantly improved. At 2 years, 81.0% (95% CI, 70.6–89.0) reported a minimal clinically important difference of ≥0.4-point improvement in the mini-rhinoconjunctivitis quality of life questionnaire score. Of 56 patients using chronic rhinitis medications at baseline, 25 of 56 (44.6%) either stopped all medication use (7/56 12.5%) or stopped/decreased (18/56 32.1%) use of ≥1 medication class at 2 years. No serious adverse events related to the device/procedure were reported over 2 years.
To determine the potential effect of patients who left the trial over 2 years on the responder rate, the responder statuses of the 14 patients with follow-up data who were lost to follow-up/withdrew/died were imputed by the last observation carried forward and the responder statuses of all nine patients who had an additional nasal procedure were imputed to nonresponder, resulting in a 2-year responder rate of 79.4% (95% CI, 70.3–86.8).
ConclusionTCRF ablation of the PNN is safe and resulted in a significant and sustained reduction in chronic rhinitis symptom burden through 2 years and a substantial reduction in concomitant medication burden.
"Eugenio De Corso, Silvia Baroni, Stefano Settimi, Maria Elisabetta Onori, Tiziana di Cesare, Rodolfo Francesco Mastrapasqua, Francesca Sarlo, Daniele Penazzi, Giuseppe DAgostino, Leandro Maria DAuria, Gabriele De Maio, Anna Rita Fetoni, Jacopo Galli"
Publication date 24-01-2024
Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients.
Methods This was a case–control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT-22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT-22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL-5 and calprotectin in both nasal secretions and nasal polyp tissue.
Results Calprotectin and IL-5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NSAID-ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID-ERD, and IL-5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease.
Conclusions Our data suggest that asthma, NSAID-ERD, and IL-5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries.
Soledad López‐Enríquez, Cristina Porras‐González, Ramón Moreno‐Luna, Francisca Palomares, José Luis Muñoz‐Bravo, Gonzalo Alba, Consuelo Santa‐María, Juan Maza‐Solano, Daniel Iván Martín‐Jiménez, Antonio Pérez‐Pérez, Rafael Moreno‐Luna, Víctor Sánchez‐Margalet, Serafín Sánchez‐Gómez
Publication date 24-01-2024
Key pointsT-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells.
The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP.
Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.
Mu Xian, Jiaqi Yu, Zheng Li, Yingshi Piao, Chegnshuo Wang, Junfang Xian, Luo Zhang
Publication date 21-01-2024
Abstract Background To date, an effective means to preoperatively predict the malignant transformation of sinonasal inverted papilloma (SIP) remains lacking due to similarities in clinical appearance. This study aimed to retrospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and microvessel structure in tumors with histologically confirmed SIP and inverted papilloma-associated squamous cell carcinoma (IP-SCC), as well as correlate DCE-MRI findings with angiogenesis biomarkers.
Methods Absolute quantitative DCE-MRI parameters (Ktrans, Kep, Ve) based on the Tofts model and model-free semi-quantitative indices (Tpeak, WR, Max Slope) of SIP (n = 22) and IP-SCC (n = 20) were investigated. Regions of interest (ROIs) were oriented according to the tumor subsites in the surgical records. Micro-vessel density (MVD) counts and tight junction protein (claudin-5) expression were evaluated in tumor specimens obtained during surgery. Differences in the above data were compared between the two groups. Correlations between DCE-MRI parameters and angiogenic biomarkers were analyzed.
Results Compared with SIP specimens, IP-SCC specimens were characterized by a significantly higher MVD and a leakier microvessel barrier. The values of Tpeak and Ve were significantly higher for SIP than those for IP-SCC, whereas WR, Max Slope, and Kep were significantly lower, indicating early enhancement and a faster dispersion model in IP-SCC. MVD was positively correlated with WR and Kep and negatively correlated with Tpeak. Tpeak was slightly positively correlated to claudin-5 expression.
ConclusionDCE-MRI can serve as a noninvasive biomarker of angiogenesis in the malignant transformation from SIP to IP-SCC. DCE-MRI may assist in the differentiation of malignancies and treatment selection.
Daniel I Martin‐Jimenez, Ramon Moreno‐Luna, Amparo Callejon‐Leblic, Alfonso Del Cuvillo Bernal, Charles S. Ebert Jr, Juan M Maza‐Solano, Jaime Gonzalez‐Garcia, Serafin Sanchez‐Gomez
Publication date 16-01-2024
Key points Expanded types of functional endoscopic sinus surgery (FESS) significantly improve quality of life and reduce revision surgeries rates, supporting their early application for moderate-to-severe cases.
Minimal clinically important difference may play as a crucial role in defining surgical treatment response (i.e., responder and super-responder conditions).
Expanded FESS benefits patients with chronic rhinosinusitis with nasal polyps but more data are required to have a clearer understanding of its uses due to varied approaches and reported outcomes in the literature.
"Bita R. Naimi, Emily Garvey, Megha Chandna, Alexander Duffy, Stephanie R. Hunter, Shreya Mandloi, Chase Kahn, Douglas Farquhar, Glen DSouza, Mindy Rabinowitz, Marc Rosen, Elina Toskala, Johannes B. Roedl, Adam Zoga, Gurston Nyquist, David Rosen"
Publication date 16-01-2024
Abstract Background Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD).
Methods Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts.
Results Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05).
ConclusionSGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.
Eli O. Meltzer, Joaquim Mullol, Jinnie Ko, Rebecca Saenz, John W. Steinke, Lauren A. Millette, Philippe Gevaert
Publication date 10-01-2024
Abstract Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have high incidence of sleep impairment. We evaluated the impact of omalizumab treatment on sleep characteristics and associated health status in patients with CRSwNP.
Methods Prespecified exploratory analysis assessed outcomes from patients included in the POLYP 1 and POLYP 2 phase 3 clinical trials and the open-label extension. Sleep was assessed by the sleep domain of the Sino-Nasal Outcome Test-22 (SNOT-22; MCID > 4 in patients with CRS) and the Medical Outcomes Study Sleep Scale (MOS-Sleep). Health status was assessed by Healthy Days Core Module (HDCM) and sinonasal-specific Patient Global Impression of Change (PGIC).
Results Omalizumab improved sleep as assessed by the SNOT-22 sleep domain. At week 24, adjusted mean (95%CI) SNOT-22 sleep scores had reduced from baseline by −8.5 (–9.9 to –7.1) with omalizumab versus –2.7 (–4.1 to –1.3) with placebo. At week 52 (all patents on OMA), adjusted mean (95%CI) SNOT-22 sleep scores had reduced from baseline by −10.1 (–11.4 to –8.7) with omalizumab. Improvements were observed in all eight items of the SNOT-22 sleep domain: difficulty falling asleep, fatigue, frustration/restlessness/irritability, lack good nights sleep, reduced concentration, reduced productivity, wake up tired, and wake up at night. In addition, omalizumab improved six of eight sleep outcomes on the MOS-Sleep scale. There were concurrent improvements in HDCM and PGIC.
Conclusion Omalizumab improved sleep and self-reported health status in patients with CRSwNP. This contributes to evidence that omalizumab provides value for patients beyond the reduction of sinonasal symptoms.
Robert J. Lee, Nithin D. Adappa, James N. Palmer
Publication date 10-01-2024
Abstract Background The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small-molecule Akt activator SC79 induces nasal cell NO production and suppresses IL-8 via the transcription factor Nrf-2. We hypothesized that SC79 NO production may additionally have antibacterial effects.
MethodsNO production was measured using fluorescent dye DAF-FM. We tested effects of SC79 during co-culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live–dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79-induced NO production and tested dependence on Akt.
ResultsSC79 induced dose-dependent, Akt-dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h.
Conclusions Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small-molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies.
Chunge Zheng, Xin Cui, Li Zhang, Lin Wang, Liwei Jiang, Xudong Yan, Yan Jiang, Longgang Yu
Publication date 10-01-2024
Key points Disease severity in acute radiation rhinosinusitis (ARRS) peaks after radiation therapy.
ARRS is mainly local inflammation, manifested by increased pro-inflammatory cytokines.
Intranasal corticosteroids are effective anti-inflammatory drugs in the treatment of ARRS.
Tian Wang, Jie Wang, Tianci Tang, Qiang Li, Yi Li, Xinmao Song
Publication date 28-12-2023
Jessa E. Miller, Jennifer L. Taylor‐Cousar, Stephen M. Humphries, Aastha Khatiwada, Haidee Chen, Alexandra Wilson, Eszter K. Vladar, David A. Lynch, Douglas A. Li, Daniel M. Beswick
Publication date 26-12-2023
Key Points Individual sinus opacification (ISO) is measurable via a convolutional neural network approach.
ISO decreased through 2 years after highly effective modulator therapy was initiated.
In adults with cystic fibrosis, ISO did not correlate with quality of life or olfaction.
Jessa E. Miller, Jennifer L. Taylor‐Cousar, Jonathan B. Overdevest, Aastha Khatiwada, Jess C. Mace, Jeremiah A. Alt, Todd E. Bodner, Naweed I. Chowdhury, Emily A. DiMango, Patricia H. Eshaghian, Anne E. Getz, David A. Gudis, Ethan J. Han, Peter H. Hwang, Claire L. Keating, Ashoke Khanwalkar, Adam J. Kimple, Jivianne T. Lee, Douglas Li, Karolin Markarian, Meghan Norris, Jayakar V. Nayak, Cameran Owens, Zara M. Patel, Katie Poch, Rodney J. Schlosser, Kristine A. Smith, Timothy L. Smith, Zachary M. Soler, Jeffrey D. Suh, Jeremy P. Tervo, Grant A. Turner, Marilene B. Wang, Milene T. Saavedra, Daniel M. Beswick
Publication date 25-12-2023
Abstract 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, Cronbachs 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 Cronbachs alpha was ≥0.85.
The MCID estimates were as follows: Cohens 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.
Alan D. Workman, Vinay K. Rathi, David K. Lerner, James N. Palmer, Nithin D. Adappa, Noam A. Cohen
Publication date 18-12-2023
Key points We created a Lang Chain/OpenAI API-powered chatbot based solely on International Consensus Statement of Allergy and Rhinology: Rhinosinusitis (ICAR-RS).
The ICAR-RS chatbot is able to provide direct and actionable recommendations.
Utilization of consensus statements provides an opportunity for AI applications in healthcare.
Kun Du, Min Zhang, Shuang Yao, Tao Luo, Hongmeng Yu, Hongfei Lou
Publication date 13-12-2023
Abstract Background Itching is a troublesome symptom that disturbs patients with allergic rhinitis (AR). The molecular mechanisms underlying itching in AR need to be further illuminated. The aim of this study was to investigate the role of epithelial cell-derived interleukin-31 (IL-31) in nasal itching in AR.
MethodsA total of 33 patients and 20 healthy control subjects were enrolled in this prospective study. The disease severity of patients with AR was assessed by the total visual analog scale score. The levels of IL-31, cysteinyl leukotriene receptor 1 (CysLT1R), and CysLT2R in the nasal brush specimens from the enrolled subjects were measured by quantitative real-time polymerase chain reaction (RT–PCR) and immunohistochemical staining. The expression of CysLT2R in a human nasal epithelial cell line (HNEpC) was assessed by immunofluorescence staining.
Results Compared with the control subjects, the protein and mRNA levels of IL-31 and CysLT2R were significantly increased in patients with AR. Higher levels of IL-31 and CysLT2R in nasal epithelial cells were associated with itching but not nasal congestion, rhinorrhea, or sneezing in AR. A significant relationship was found between IL-31 and CysLT2R in nasal epithelial cells, with a correlation coefficient of 0.93. Furthermore, RT–PCR and immunofluorescence staining revealed that IL-31 directly induced CysLT2R expression in HNEp Cs. Nasal steroid treatment inhibited IL-31 and CysLT2R expression in 13 patients with AR in vivo.
Conclusions Nasal epithelial cell-derived IL-31 might be associated with itching symptoms via CysLT2R in AR.
Ru Tang, Jiayao Zhou, Shiyao Zhang, Song Mao, Weitian Zhang
Publication date 11-12-2023
Background Aspiration pneumonitis (AP) secondary to cerebrospinal fluid (CSF) leak is underestimated and rarely discussed. This study aimed to evaluate the association between AP and CSF leaks.
Methods Clinical and surgical characteristics of CSF leak patients with and without AP between January 2010 and December 2022 were included and compared.
Results This study included 159 patients, 16 with CSF otorrhea and 143 with CSF rhinorrhea. Among them, 40 (25.2%) had AP. Bilateral pneumonitis was identified in 32 cases, of which 11 showed severe pneumonitis in the right upper lung lobe. Twenty-one (52.5%) asymptomatic and 19 (47.5%) symptomatic cases were documented. The major clinical manifestations included cough (n = 19, 47.5%) and expectoration (n = 9, 22.5%). The prevalence of pneumonitis was significantly higher in the spontaneous group than in the traumatic group. High-flow CSF leak was associated with AP (42.5% vs. 16.8%, p = 0.001). No significant differences were identified in defect locations between patients with and without AP. Patients with pneumonitis had a higher prevalence of meningitis (32.5% vs. 12.6%, p = 0.003). Multiple logistic regression results revealed that meningitis, spontaneous and high-flow CSF leaks are independent factors for AP occurrence. Both the CSF leak and pulmonary complications resolved following successful surgical repair.
ConclusionsAP secondary to CSF leaks is frequently underdiagnosed, with a higher incidence identified in spontaneous cases. The occurrence of AP was associated with high-flow CSF leak.
Jae‐Yoon Kang, Mi‐Ra Choi, Yong Min Kim
Publication date 11-12-2023
Abstract Background Interleukin (IL)-33, when cleaved into smaller fragments by proteases, becomes hyperactive, contributing to allergic inflammation. Povidone-iodine (PVP-I) is an iodine-based compound that exhibits antimicrobial properties and inhibits proteases. This study aimed to investigate whether PVP-I treatment inhibits IL-33 cleavage, improves allergic rhinitis (AR) symptoms, and suppresses allergic inflammation in a mouse model.
Methods In vitro experiments using full-length recombinant human IL-33 and allergens, including house dust mites or Dermatophagoides pteronyssinus 1, were conducted using western blotting. Fifty BALB/c mice were divided into five groups: control (CON), AR with phosphate-buffered saline treatment (AR), PVP-I treatment (AR + PVP), trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E64) treatment (AR + E64), and dexamethasone treatment (AR + Dexa). Nasal symptom scores, including rubbing and sneezing, were measured. The cytokine levels in the nasal lavage fluid (NLF) and the concentration of immunoglobulins in the blood serum were assessed. Nasal mucosa from each group was used for reverse transcriptase-polymerase chain reaction (RT-PCR) and histological analyses were conducted.
ResultsPVP-I treatment reduced nasal symptoms, suppressed allergic inflammation, and decreased the levels of IL-33, IL-5, and IL-13 in the NLF and total immunoglobulin E (IgE) and specific IgE in the serum. Histopathological analysis revealed a reduction in the number of eosinophils and goblet cells in the nasal mucosa of the AR + PVP group when compared to the AR group. RT-PCR and immunofluorescence staining confirmed the downregulation of genes and proteins associated with allergic inflammation.
Conclusions These findings suggest that nasal irrigation with PVP-I may be a promising therapeutic option for managing AR by inhibiting IL-33 activation and suppressing allergic inflammation.
Do‐Yeon Cho, Shaoyan Zhang, T. Graham Norwood, Daniel Skinner, Tonja A. Hollis, Marie L. Ehrhardt, Lydia C. Yang, Dong‐Jin Lim, Jessica W. Grayson, Ahmed Lazrak, Sadis Matalon, Steven M. Rowe, Bradford A. Woodworth
Publication date 11-12-2023
Abstract Introduction Hypoxia due to sinus obstruction is a major pathogenic mechanism leading to sinusitis. The objective of the current study is to define the electrophysiologic characteristics of hypoxia in vitro and in vivo.
Methods Cystic fibrosis bronchoepithelial cells expressing wild-type cystic fibrosis transmembrane conductance regulator (CFTR) and human sinonasal epithelial cells were exposed to 1% or atmospheric O2 for 24 h. Time-dependent production of cytoplasmic free radicals was measured. Cells were subjected to Ussing chamber and patch clamp technique where CFTR currents were recorded in whole-cell and cell-attached mode for single channel studies. Indices of mucociliary transport (MCT) were measured using micro-optical coherence tomography. In a rabbit hypoxic maxillary sinus model, tissue oxygenation, relative mRNA expression of HIF-1α, pH, sinus potential difference (SPD), and MCT were determined.
Results Ussing chamber (p < 0.05), whole-cell (p < 0.001), and single channel patch-clamp (p < 0.0001) showed significant inhibition of Cl− currents in hypoxic cells. Cytoplasmic free radicals showed time-dependent elevation peaking at 4 h (p < 0.0001). Airway surface liquid (p < 0.0001), periciliary liquid (p < 0.001), and MCT (p < 0.01) were diminished. Co-incubation with the free radical scavenger glutathione negated the impact of hypoxia on single channel currents and MCT markers. In sinusitis rabbits, mucosa exhibited low tissue oxygenation (p < 0.0001), increased HIF1α mRNA (p < 0.05), reduced pH (p < 0.01), and decreased MCT (p < 0.001). SPD measurements demonstrated markedly diminished transepithelial Cl− transport (p < 0.0001).
Conclusion Hypoxia induces severe CFTR dysfunction via free radical production causing reduced MCT in vitro and in vivo. Improved oxygenation is critical to reducing the impact of persistent mucociliary dysfunction.
Rema Anisha Kandula, Lauren A. Linquest, Sandeep Kandregula, Mackenzie Latour, Omar G. Ahmed, Michael T. Yim
Publication date 08-12-2023
Key points Hospital frailty risk score (HFRS) correlates with complications, length of stay, and non-routine discharge.
HFRS is a better predictor of postsurgical sequelae than age and Elixhauser comorbidity index.
Juliette Sliman, Florent Carsuzaa, Lei Tanaka, Patrice Gallet, Pierre‐Olivier Moser, Guillaume Captier, Valentin Favier
Publication date 29-11-2023
KEY POINTSAn unfavorable insertion of the middle turbinate for cryotherapy was present in 74.2% of cases.
Placing cryoprobe 15–30 mm above the nasal floor targets the nerves in 95.8% of cases.
Centering the cryoprobe 38 mm behind the inferior turbinate axilla targets the nerves in 94.6% of cases.
Mohamad R. Chaaban, Kewal Asosingh, Suzy Comhair, David Hoying
Publication date 23-11-2023
Abstract Background No studies have investigated the systemic and local sinonasal profile of obesity-related chronic rhinosinusitis (CRS), despite its observed association in recent retrospective studies. The objectives of our study were to assess the impact of obesity on the clinical and cytokine profile of patients with CRS and evaluate treatment response with functional endoscopic sinus surgery.
Methods This was a prospective observational study at the Cleveland Clinic that included patients with CRS (n = 54) between December 2021 and September 2022. Data collection included demographics, body mass index (BMI), comorbidities, baseline sinonasal outcome test scores, baseline radiologic scores (Lund–Mackay), postoperative sinonasal outcome test scores (at 3–4 months), and local and systemic alarmins/T-helper cytokines.
Results Out of the 54 CRS patients, there were 20 CRS patients without nasal polyps (37%) and 34 with nasal polyps (63%). Patients were categorized based on obesity (BMI ≥ 30 kg/m2). Obese CRS patients had lower systemic alarmins (interleukin IL-33 and Thymic stromal lymphopoietin (TSLP)) compared to non-obese CRS patients (IL-33: 744.2 ± 1164.6 pg/mL vs. 137.5 ± 320.0 pg/mL, p = 0.005; TSLP: 627.7 ± 1806.3 pg/mL vs. 28.1 ± 85.4 pg/mL, p = 0.017). CRS patients with nasal polyps with BMI ≥30 kg/m2 had higher postoperative sinonasal outcome test scores and lower levels of nasal eotaxin-3 and IL-33 compared to BMI <30 kg/m2 counterparts.
Conclusions In conclusion, patients with obese CRS and nasal polyps displayed diminished levels of intranasal alarmins and reduced intranasal eotaxin-3. These results potentially imply the presence of a unique, obese type 2-low CRS phenotype that warrants further exploration.
Sulgi Kim, Lang Li, Feng‐Chang Lin, Taylor Stack, Meredith M. Lamb, Ibtisam Mohammad, Meghan Norris, Cristine Klatt‐Cromwell, Brian D. Thorp, Charles S. Ebert Jr., Daniel Masters, Brent A. Senior, Frederic B. Askin, Adam J. Kimple
Publication date 23-11-2023
Key points We present the largest cohort of structured histopathology reports on primary ciliary dyskinesia-related chronic rhinosinusitis (PCD-CRS).
Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports.
Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.
Sarina Katrin Mueller, Olaf Wendler, Susanne Mayr, Maximilian Traxdorf, Michael Koch, Konstantinos Mantsopoulos, Matti Sievert, Philipp Grundtner, Heinrich Iro, Benjamin S. Bleier
Publication date 22-11-2023
Abstract Objective The objective of this study was to analyze advantages and disadvantages of mucus and serum for biomarker analysis.
Methods This study includes prospective study of 61 CRS with nasal polyps patients who were followed over 24 months and over nine time points after functional endoscopic sinus surgery. At each time points, the nasal polyp score (NPS) was assessed and mucus as well as serum was collected. Selected were measured in mucus and serum. Mean, standard deviation and variance, undetectable values, and the correlation of the biomarkers to the NPS over time and to early recurrences were calculated, and the effect of surgery on the biomarkers was assessed. Additionally, the diurnal rhythm of all biomarkers was measures in order to assure stable biomarker values during sampling times.
Results All biomarkers showed stable values during sampling times. Serum biomarker levels displayed higher percentages of undetectable values compared to mucus biomarkers. Mucus periostin (p < 0.001, r = 0.89), mucus IgE (p < 0.001, r = 0.51), serum periostin (p < 0.001, r = 0.53), mucus CST1 (p < 0.001, r = 0.27), and serum IgE (p < 0.01, r = −0.18) were the best marker and medium combinations to track the NPS over time and to predict recurrences. Mucus serpinF2 was negatively correlated and predicted early recurrences (p = 0.026, R2 = 0.015).
Conclusions Serum and mucus both represent viable mediums for “liquid biopsies.” The most promising biomarker/medium combinations over time to track disease severity were mucus periostin, mucus IgE, serum periostin, mucus CST1, and serum IgE. Mucus serpinF2 was the best biomarker to predict early recurrences.
Do Yeon Cho, Nicholas J. Rivers, Dong‐Jin Lim, Shaoyan Zhang, Daniel Skinner, Lydia Yang, Adithya J. Menon, Olivia Jo Kelly, Martin P. Jones, Brenton T. Bicknell, Jessica W. Grayson, Elex Harris, Steven M. Rowe, Bradford A. Woodworth
Publication date 17-11-2023
Abstract Introduction Cystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO3−) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO3 nanoparticles as novel strategy for CF airway disease.
MethodsGSH/NaHCO3 poly (lactic-co-glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose-release curves, surface pH, toxicity, and MCT indices using micro-optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy.
Results Sustained release of GSH and HCO3− with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) (p < 0.001) and 6.87 ± 0.05 at 14 days (p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy.
Conclusion Findings suggest that GSH/NaHCO3− nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis.
Gregory S. Hill, Michael W. Noller, Cristianah O. Olubajo, Anthony M. Tolisano, Charles A. Riley, Jakob L. Fischer
Publication date 13-11-2023
Key Points Military servicemembers reported high satisfaction rates of dupilumab treatment for CRSwNP.
Some service members fear that dupilumab treatment may limit their career progression.
Updated guidelines are needed for servicemembers to make decisions regarding dupilumab.
Arthur W. Wu, Dennis M. Tang, Kevin Hur, Aria Jafari, Philip G. Chen, Masayoshi Takashima, Elena E. Chang, Bonnie Balzer, Anna Mathew, Mukul Divatia, Haodong Xu, Juliana Robledo, Luv Amin, Benjamin Tam, David J. Cvancara, Amisheila G. Kinua, Tariq A. Syed, Dominique L. Paderin, Missael Vasquez, Omar G. Ahmed
Publication date 07-11-2023
Key points Hispanic-American patients with chronic rhinosinusitis with nasal polyps have a comparable level of tissue eosinophilia compared to their Caucasian counterparts in the United States.
Mixed inflammation involving both neutrophils and eosinophils is more common in this population compared to Caucasians.
Findings from this study may indicate that Hispanic-American patients have a unique endotype or endotypes that deserves further investigation.
Mark A. Eckert, Andreana Benitez, Zachary M. Soler, Judy R. Dubno, Rodney J. Schlosser
Publication date 28-10-2023
Abstract Background Age-related declines in olfaction contribute to low quality of life and appear to occur with declines in cognitive function, including diminished episodic memory. We tested the hypothesis that low gray matter volume within cortical regions that support olfaction and episodic memory can explain age-related differences in olfactory and episodic memory functions.
MethodsT1-weighted images, Sniffin’ Sticks olfactory measures, and the NIH Toolbox-Cognition Battery were administered to 131 middle-aged to older adults (50–86 years; 66% female). Correlation was used to examine the associations between these measures. A network-based image processing approach was then used to examine the degree to which spatial patterns of gray matter variance were related to the olfactory and cognitive measures. Structural equation modeling was used to characterize the relative specificity of olfactory, cognitive, gray matter, and aging associations.
Results Olfactory threshold, discrimination, and identification exhibited small to medium effect size associations with episodic memory performance (rs = 0.27–0.42, ps < 0.002). Gray matter volume within medial temporal and orbitofrontal cortex was also related to olfactory (discrimination and identification) and episodic memory function (rs = 0.21–0.36, ps < 0.019). Age and episodic memory explained the same variance in olfaction that was explained by the medial temporal and orbitofrontal pattern of gray matter volume.
Conclusions The results of this cross-sectional study suggest that identifying mechanisms contributing to differences in medial temporal and orbitofrontal cortex will advance our understanding of co-morbid olfactory and cognitive declines.
Jacob G. Eide, William Mason, Amrita Ray, John Carey, Bernard Cook, John R. Craig
Publication date 21-10-2023
Abstract Background Beta-2 transferrin (B2-Tf) gel electrophoresis (GE) is the preferred non-invasive diagnostic modality for confirming cerebrospinal fluid (CSF) in body fluids. While B2-Tf GE testing is highly sensitive and specific for CSF, false-positive (FP) and false-negative (FN) results can lead to diagnostic and therapeutic dilemmas. Several series have demonstrated potential causes of false B2-Tf GE results, but few studies have reported reasons for these errors. The purpose of this systematic review was to describe sources of B2-Tf GE errors.
MethodsA systematic review was performed by searching OVID, EMBASE, and Web of Science databases for B2-Tf GE studies. After applying exclusion criteria, original research studies directly addressing erroneous B2-Tf GE results underwent qualitative analysis.
Results Of the 243 abstracts screened, 71 underwent full-text review and 18 studies reporting B2-Tf GE errors were included for analysis. There were 15 potential FPs, 12 actual FPs, 12 potential FNs, 19 actual FNs, and 14 indeterminate results. There were also 246 potentially indeterminate results from in vitro studies. Reasons for B2-Tf GE errors included serum transferrin alterations (n = 17; all potential), infection related (n = 13; 9 potential), orbital or salivary contamination (n = 2; 1 potential), and collection related (n = 255; 246 potential). There were 31 false or indeterminate results with unspecified reasons. There were no reported errors due to laboratory processing.
Conclusions Multiple potential or actual reasons for false or indeterminate results have been reported for B2-Tf GE testing of rhinorrhea and otorrhea. Future studies should explore reasons for B2-Tf testing errors and how these may affect clinical decision making.
Anna C. Zemke, Yasmin Hilliam, Amanda L. Stapleton, Adam J. Kimple, Jennifer L. Goralski, Amber D. Shaffer, Joseph M. Pilewski, Brent A. Senior, Stella E. Lee, Vaughn S. Cooper
Publication date 14-10-2023
Abstract 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 Faiths 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.
Jiani Chen, Li Hu, Chen Zhang, Le Shi, Qianqian Zhang, Yumin Zhou, Fuying Cheng, Yingqi Gao, Houyong Li, Dehui Wang, Huan Wang, Xicai Sun
Publication date 12-10-2023
Abstract Background The chronic rhinosinusitis patient-reported outcome (CRS-PRO) is a recently published disease-specific questionnaire designed for CRS patients, with fewer entries and ease of completion. This study aimed to translate the CRS-PRO questionnaire into Chinese and assess its reliability, validity, and responsiveness to provide Chinese patients with a more concise and efficient subjective assessment instrument.
Methods The Chinese version of the CRS-PRO was created through forward-backward translations and cultural adaptation. Here, 168 CRS patients (118 patients CRS with nasal polyps CRSwNP and 50 patients with CRS without nasal polyps CRSsNP) and 43 healthy individuals were enrolled. All participants completed the CRS-PRO, 22-item Sinonasal Outcome Test (SNOT-22), and Euro Qol five dimensions questionnaire (EQ-5D) questionnaires preoperatively as well as 3 and 6 months after surgery.
Results The Chinese version of the CRS-PRO demonstrated good internal consistency, with a Cronbachs α of 0.813. It also exhibited a higher criterion validity (r = 0.65, p < 0.05) than the SNOT-22. A moderate association was found between the CRS-PRO and objective indicators such as the Lund–Mackay and endoscopic scores. Furthermore, the CRS-PRO, like the SNOT-22, could clearly distinguish CRS patients from healthy subjects (p < 0.01), as well as between the CRSwNP and CRSsNP subtypes (p < 0.01). Additionally, changes in the CRS-PRO exhibited a larger effect size compared to changes in the SNOT-22 (Cohens d = 1.05 and 0.93 vs. 0.71 and 0.90 for 3 and 6 months, respectively, all p < 0.01).
Conclusions The Chinese version of the CRS-PRO is a concise, reliable, and responsive instrument that can be utilized as a novel subjective evaluation tool for future clinical practice.