International Forum of Allergy and Rhinology 2024-11-13

Pathologic dural invasion is associated with regional recurrence in olfactory neuroblastoma: A multi‐institutional study

Anthony Tang, Suchet Taori, Nicholas Fung, Joao Paulo Almeida, Pierre‐Olivier Champagne, Juan C. Fernandez‐Miranda, Paul Gardner, Peter H. Hwang, Jayakar V. Nayak, Chirag Patel, Zara M. Patel, Maria Peris Celda, Carlos Pinheiro‐Neto, Olabisi Sanusi, Carl Snyderman, Brian D. Thorp, Jamie J. Van Gompel, Georgios A. Zenonos, Nathan T. Zwagerman, Eric W. Wang, Mathew Geltzeiler, Garret Choby

Publication date 13-11-2024


Abstract Objective Neck metastases are a poor prognostic factor in olfactory neuroblastoma (ONB). Pathologic dural invasion (pathDI) may increase the risk of neck metastases due to invasion of dural lymphatics. We aim to evaluate the prognostic value of pathDI in predicting rates of neck metastases and recurrence using a large, multicenter database of ONB patients.
Data sources Retrospective review of a prospective, multicenter database of electronic health records of all patients who presented with ONB between 2005 and 2021 at nine tertiary academic care centers within North America.
Review methods Clinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow-up time, and survival.
Results Of 258 ONB patients, 189 patients met the inclusion criteria. The 10-year neck recurrence-free survival (neck-RFS) rates were 85.7% (75.6‒97.3) and 61.8% (47.9‒79.8) for patients without and with pathDI, respectively (p = 0.018). Time-to-event multivariable regression analysis found pathDI to have an odds ratios of 9.7 (95% confidence interval CI 1.2–80.4, p = 0.04) for neck-RFS and 9.5 for RFS at any site (95% CI 1.1–83.3, p = 0.04).
Conclusion In multivariable analysis, the presence of pathDI appears to be the strongest predictor of neck recurrence and recurrence at any site. Future studies exploring the benefit of elective neck dissection or radiation for patients with pathDI may impact disease management.

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Hops bitter β‐acids have antibacterial effects against sinonasal Staphylococcus aureus but also induce sinonasal cilia and mitochondrial dysfunction

Yobouet Ines Kouakou, Joel C. Thompson, Li Hui Tan, Zoey A. Miller, Ray Z. Ma, Nithin D. Adappa, James N. Palmer, Noam A. Cohen, Robert J. Lee

Publication date 13-11-2024


Abstract Background Routine prescription of antibiotics to treat chronic rhinosinusitis (CRS) exacerbations may contribute to the propagation of antibiotic resistance. Hops bitter β-acids lupulone and colupulone possess potent antibacterial activities and, as T2R1, T2R14, and/or T2R40 agonists, may improve the impaired mucociliary clearance described in CRS patients. We investigated these molecules as alternative treatments to antibiotics in CRS management based on their antibacterial and T2Rs agonists properties.
Methods Human nasal primary cells (HNECs) and RPMI2650 cells cultures were used as study models. T2Rs expression in cell culture models and human nasal tissue was assessed using immunofluorescence, quantitative PCR, and Western blot. We performed calcium imaging and cilia beat frequency experiments to investigate T2Rs activation in study models in response to lupulone and colupulone stimulations. Finally, we studied hops β-acids cytotoxicity on cells using Cell Event, crystal violet, lactate dehydrogenase assays, immunofluorescence, and transepithelial electrical resistance assays.
Results We confirmed lupulone and colupulone potent antibacterial effect on CRS-relevant methicillin-resistant Staphylococcus aureus but found minimal impact on P. aeruginosa. We also report T2R1, T2R14 and T2R40 expression in HNECs and RPMI2650 cell cultures. Lupulone and colupulone induced an increase in cytosolic calcium that appeared dependent on T2Rs signaling. This response was accompanied by mitochondrial membrane depolarization, cellular energy stress, decreased cell proliferation, ciliostasis, and HNECs remodeling after a single exposure to lupulone at micromolar concentrations.
Conclusion Our data suggest that hops β-acids may not be beneficial as treatments in CRS patients and instead contribute to the disease by impairing cell health and further deteriorating the MCC.

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Real‐world predictors of dupilumab prescription in patients with chronic rhinosinusitis with nasal polyps

Christina Dorismond, Mason R. Krysinski, Yash Trivedi, Rory J. Lubner, Rakesh K. Chandra, Naweed I. Chowdhury, Justin H. Turner

Publication date 13-11-2024


Abstract Background Despite increasing dupilumab use for chronic rhinosinusitis with nasal polyps (CRSwNP), little is known about the factors influencing its use in real-world practice. We aimed to identify factors that may predict dupilumab prescription in CRSwNP patients who have undergone endoscopic sinus surgery (ESS).
MethodsA single-institution, retrospective cohort study of patients who underwent ESS for CRSwNP between 2015 and 2023 was conducted. Demographics, comorbidities, 22-item sinonasal outcome test (SNOT-22) scores, and dupilumab prescription date were extracted from patient records. Intraoperative nasal mucus cytokine levels were measured using a multiplex bead assay. Univariate logistic regression analysis was performed to identify factors associated with dupilumab prescription, and multivariate logistic regression was used to adjust for surgery date.
ResultsA total of 299 CRSwNP patients were included, including seventy (23.4%) who were prescribed dupilumab postoperatively. Patients were more likely to be prescribed dupilumab if they had asthma (odds ratio OR 2.304), aspirin-exacerbated respiratory disease (AERD, OR 3.375), elevated tissue eosinophils (OR 1.005), and higher 3-month postoperative SNOT-22 scores (OR 1.027). Patients prescribed dupilumab also had greater odds of having elevated mucus interleukin (IL)-5 (OR 1.128) and IL-13 (OR 1.213). When adjusting for surgery date, associated factors included: asthma (OR 2.444), AERD (OR 3.750), allergic rhinitis (OR 1.833), higher tissue eosinophils (OR 1.005), elevated 3-month SNOT-22 scores (OR 1.028), and higher IL-5 (OR 1.123) and IL-13 (OR 1.202) levels.
Conclusion Asthma, AERD, allergic rhinitis, and elevated tissue eosinophil, IL-5, and IL-13 levels are predictive of dupilumab prescription in CRSwNP patients. These may serve as clinical and inflammatory biomarkers and can aid in counseling patients about expected disease trajectory.

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Aging and frailty are associated with inflammatory endotypic shifts in patients with chronic rhinosinusitis

Mason R. Krysinski, Christina Dorismond, Yash Trivedi, Rory Lubner, Andrea A. Lopez, Kolin Rubel, Rakesh K. Chandra, Naweed I. Chowdhury, Justin H. Turner

Publication date 13-11-2024


Key points Frailty and aging are associated with a shift toward non-type 2 inflammation in chronic rhinosinusitis (CRS).
Frailty-related shifts in sinonasal inflammatory mediators may be linked to biological senescence.
Understanding the role of aging and frailty in CRS may have important treatment implications.

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Evaluation of mucosal barrier disruption due to Staphylococcus lugdunensis and Staphylococcus epidermidis exoproteins in patients with chronic rhinosinusitis

Mahnaz Ramezanpour, Sholeh Feizi, Hashan Dilendra Paththini Arachchige, George Bouras, Clare Cooksley, Gohar Shaghayegh, Peter‐John Wormald, Alkis James Psaltis, Sarah Vreugde

Publication date 08-11-2024


Abstract Background Chronic rhinosinusitis (CRS) is a persistent inflammatory condition of the sinus mucosa. While Staphylococcus aureus has been shown to play a significant role in mucosal barrier disruption in CRS patients, coagulase-negative staphylococci (CoNS) such as Staphylococcus epidermidis and Staphylococcus lugdunensis are also implicated in CRS pathophysiology. This study investigates the effects of exoproteins secreted by planktonic and biofilm forms of clinical isolates of S. epidermidis and S. lugdunensis on the nasal epithelial barrier.
Methods Thirty-one clinical isolates of CoNS were grown in planktonic and biofilm forms, and their exoproteins were concentrated. The epithelial barrier structure was assessed by measuring transepithelial electrical resistance (TEER) and the permeability of fluorescein isothiocyanate-dextran. Toxicity and inflammatory response were also studied.
Results Our findings demonstrate that exoproteins from all planktonic forms of S. lugdunensis disrupted the mucosal barrier, whereas only nine of 16 biofilm-derived exoproteins had similar effects. Conversely, 11 of 15 exoproteins from planktonic S. epidermidis significantly disrupted barrier integrity; however, biofilm exoproteins did not. The study also showed that some exoproteins from planktonic S. epidermidis significantly reduced cell viability, while exoproteins from planktonic and biofilm forms of S. lugdunensis and biofilm S. epidermidis did not induce any statistically significant change in cell viability. Notably, four of 16 biofilm exoproteins from S. lugdunensis induced higher interleukin-6 (IL-6) secretion, whereas none of the S. epidermidis isolates showed a significant increase in IL-6 secretion.
Conclusion Our results suggest that CoNS exoproteins may contribute to CRS etiopathogenesis.

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Guidance for the evaluation by payors of claims submitted using Current Procedural Terminology codes 95165, 95115, and 95117

J. Allen Meadows, Gary N. Gross, Anita N. Wasan, Dole P. Baker, Amber Patterson, Robert Puchalski, Anil Nanda, Jami Lucas, J. Wesley Sublett, Paul V. Williams

Publication date 06-11-2024


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Making “scents” of nutrients: Investigating the relationship between olfactory dysfunction and vitamin intake

Sophie E. Yu, Youn Soo Jung, Margaret B. Mitchell, Simon Chiang, Mitali Banerjee, Mengyuan Ruan, Tanujit Dey, Sarah E. Fleet, Stella E. Lee

Publication date 05-11-2024


Key points Decreased overall dietary consumption of micronutrients may be linked to an increased risk of olfactory dysfunction (OD) including subjective report of OD, subjective report of phantosmia, and objective OD.
Interactions were identified between these micronutrients, suggesting that outcomes may vary depending on the mixture of micronutrients taken.

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Surgery versus biologics for nasal polyposis: Perspective on contemporary data

Michael J. Ye, Rodney J. Schlosser, Zachary M. Soler, Jonathan B. Overdevest, David A. Gudis

Publication date 05-11-2024


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Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis

Graham Pingree, Mihai Bentan, Thomas Fitzpatrick, Theodore Schuman

Publication date 01-11-2024


Abstract Background Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETIs impact on functional endoscopic sinus surgery (FESS) remains unclear.
Methods The Tri NetX Analytics Research Network, consisting of 120 million global de-identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA-approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF-related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS.
ResultsETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval CI 1.5–2.75; p-value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54–5.85; p-value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non-CFTR modulator groups, except for reduced CF-related pulmonary exacerbations from 0 to 6 months post-FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators.
Conclusions In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.

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

Ethan J. Han, Christine M. Liu, Jakob L. Fischer, Jess C. Mace, Karolin Markarian, Jeremiah A. Alt, Todd E. Bodner, Naweed I. Chowdhury, Patricia H. Eshaghian, Yuqing A. Gao, 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 01-11-2024


Abstract Background Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied.
Methods In a prospective, multi-institutional study, adult PwCF completed the 22-Question Sino Nasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund–Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression.
Results Seventy-three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (β = ‒4.09, 95% confidence interval CI ‒6.08, ‒2.11, p < 0.001), female sex (β = ‒2.14, 95% CI ‒4.11, ‒0.17, p = 0.034), and increasing age (β = ‒0.14, 95% CI ‒0.22, ‒0.05, p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (β = 17.76, 95% CI 5.20, 30.32, p = 0.006) and >16 educational years (β = 13.50, 95% CI 2.21, 24.80, p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores.
Conclusions Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF.
Clinical TrialsNCT04469439

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American Rhinologic Society expert practice statement part 2: Postoperative precautions and management principles following endoscopic skull base surgery

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 01-11-2024


Abstract The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence regarding postoperative precautions for patients following endoscopic skull base surgery for intradural pathology. These topics include the administration of postoperative nasal hygiene; patient mobilization and activity level; the resumption of continuous positive airway pressure in patients with obstructive sleep apnea; and the timing and capacity with which a patient may be subjected to barotrauma, such as air travel postoperatively. This EPS was developed following the recommended methodology and approval process as previously outlined. Given the diverse practices and limited agreement on the accepted principles regarding postoperative precautions for patients following skull base surgery, this EPS seeks to summarize the existing literature and provide clinically relevant guidance to bring clarity to these differing practice patterns. Following a modified Delphi approach, four statements were developed, all of which reached consensus. Because of the paucity of literature on these topics, these statements represent a summation of the limited literature and the experts’ opinions. These statements and the accompanying evidence are summarized below, along with an assessment of future needs.

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Gender‐based linguistic differences in letters of recommendation for rhinology fellowship over time: A dual‐institutional follow‐up study using natural language processing and deep learning

Vikram Vasan, Christopher P. Cheng, Shaun Edalati, Shreya Mandloi, David K. Lerner, Anthony Del Signore, Madeleine Schaberg, Satish Govindaraj, Mindy Rabinowitz, Gurston Nyquist, Alfred Marc Iloreta

Publication date 01-11-2024


Key points This follow-up dual-institutional and longitudinal study further evaluated for underlying gender biases in LORs for rhinology fellowship.
Explicit and implicit linguistic gender bias was found, heavily favoring male applicants

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Longer‐term surveillance imaging and endoscopy critical for majority of patients in detection of sinonasal malignancy recurrence

Catherine Kwiecien, Alan D. Workman, Jadyn Wilensky, David K. Lerner, Vinay K. Rathi, Jennifer E. Douglas, Michael A. Kohanski, Edward C. Kuan, James N. Palmer, Nithin D. Adappa

Publication date 01-11-2024


Abstract Background Sinonasal malignancy surveillance paradigms are often based on Head and Neck National Comprehensive Cancer Network guidelines, which do not recommend standard surveillance imaging beyond 6 months without concerning symptomatology or physical examination findings.
Methods This was a retrospective analysis of all patients who underwent resection of sinonasal malignancy at a tertiary care center over a 20-year period from 2000 to 2020, with an ensuing surveillance period demonstrating recurrence.
Results Fifty-two patients with sinonasal malignancy recurrence were included, with an average time to recurrence of 30.9 months and a follow-up period of over 60 months. Recurrence was diagnosed by routine imaging or endoscopy in asymptomatic patients in a majority (60%) of cases, while the remaining minority of diagnoses followed new symptomatology. Asymptomatic recurrence was associated with perineural spread of tumor at initial resection (p = 0.025), but not with age (p = 0.85) or stage at diagnosis (p = 0.68). Expectedly, positron emission tomography/computed tomography (CT) more often detected regional or distant recurrence, while structural imaging (CT/magnetic resonance imaging) demonstrated more frequent detection of recurrence in those with perineural spread of tumor (p = 0.01).
Conclusions Our findings support high rates of asymptomatic recurrence in sinonasal malignancy, with the majority of recurrences diagnosed by routine endoscopy or imaging. Tailored and extended surveillance guidelines are necessary relative to those utilized for other head and neck mucosal cancers, and are especially appropriate when features such as perineural spread are present.

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Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system

Jae Yoon Lee, Do Hyun Kim, Sung Won Kim, Yeon Hee Im, Chan Soon Park, Dong Hyun Kim, Zainab Alkhars, Soo Whan Kim

Publication date 01-11-2024


Abstract Background Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes.
Methods This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field.
Results Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval CI, 0.670–0.835) in the estimation group, 0.729 (0.629–0.830) in the validation group, and 0.661 (0.584–0.738) in the 20-fold cross-validation with the entire dataset.
Conclusions We propose a novel scoring system that incorporates three key parameters: “novel score = blood eosinophil (%) + total Lund–Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present” greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.

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Histopathologic evaluation of Asian‐American patients with chronic rhinosinusitis with nasal polyps

Arthur W. Wu, Kevin Hur, Aria Jafari, Omar G. Ahmed, Philip G. Chen, Masayoshi Takashima, Elena E. Chang, Bonnie Balzer, Anna Matthew, Haodong Xu, Mukul Divatia, Benjamin Tam, Juliana Robledo, Luv Amin, David J. Cvancara, Amisheila Kinua, Tariq A. Syed, Dominique L. Paderin, Dennis M. Tang

Publication date 01-11-2024


Key points Asian-American (AA) patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have comparable rates of tissue eosinophilia compared to Caucasians when defined as >10 eosinophils/high-powered field (HPF).
AA patients with CRSwNP have significantly higher incidence of mixed inflammation defined as >10 eosinophils/HPF and >10 neutrophils/HPF.

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A methodological pipeline for the preclinical evaluation of novel topical agents for the treatment of CRS

Samuel J. M. Hale, Christian A. Lux, James E. Willoughby, Arne Koefoed, David Broderick, Kristi Biswas, Raymond Kim, Brett Wagner Mackenzie, Richard G. Douglas

Publication date 01-11-2024


Key points Novel topical therapeutics require extensive pre-clinical testing to assess efficacy and safety.
Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity.
Agents that are found to be effective and non-toxic ex vivo warrant further investigation in vivo.

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Intralesional cidofovir injections for the treatment of multifocal exophytic sinonasal papilloma

Florian Chatelet, Alessandro Vinciguerra, Morgane Marc, Philippe Herman, Benjamin Verillaud

Publication date 01-11-2024


Key points Intralesional cidofovir injections in combination with surgery is an effective treatment for recurrent multifocal sinonasal exophytic papilloma.
No malignant transformation has been observed in our experience.
Anosmia is a potential side effect that patients should be aware of.

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Role of social determinants of health on quality of life in pediatric chronic rhinosinusitis

Ryan S. Ziltzer, Sameer Shetty, Dominic Coutinho, Rafka Chaiban, Chadi A. Makary

Publication date 01-11-2024


Key points Social determinants of health link to worse quality of life in pediatric chronic rhinosinusitis.
The area deprivation index (ADI) may serve to predict health disparities in these patients.

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Efficacy of the nasal airflow‐inducing maneuver in the olfactory rehabilitation of laryngectomy patients: A systematic review and meta‐analysis

Kurtis Young, Frances T. Morden, Quinton Blount, Austin Johnson, Sameer Kejriwal, Hannah Bulosan, Elliott J. Koshi, Marianne Abouyared, Farrah Siddiqui, Jee‐Hong Kim

Publication date 01-11-2024


Abstract Introduction This is the first systematic review and meta-analysis to investigate the effectiveness of the nasal airflow-inducing maneuver (NAIM) in olfactory rehabilitation for total laryngectomy (TL) patients.
Methods We conducted a systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria required that patients must have undergone a TL with subsequent NAIM training for at least 2 weeks and olfactory evaluation. The impact of NAIM on olfactory outcomes compared to that at baseline was measured. Olfactory measures included the Sniffin’ Sticks Test, Smell Disk Test, Scandinavian Odor Identification Test, and Quick Odor Detection Test. The primary outcome measures were the proportion of patients with normosmia at baseline and after intervention.
Results Seven studies from 2000 to 2023 comprising a total of 290 TL patients met the inclusion criteria. The meta-analysis revealed that prior to intervention, the pooled proportion of patients with normosmia was 0.16 (95% confidence interval CI: 0.09‒0.27, p = 0.01). After intervention, the same proportion increased to 0.55 (95% CI: 0.45‒0.68, p = 0.001). Among the included patients, 88.3% were initially anosmic or hyposmic, which was reduced to 48.9% after NAIM practice, with 51.1% achieving normosmia. The percent improvement was not found to be significantly associated with the timing of intervention post-TL (p = 0.18).
ConclusionsNAIM increased the proportion of patients who achieved normosmia in TL patients. NAIM stands out as a safe, easily teachable maneuver with promising results. Further efforts are warranted to provide specific recommendations and guidelines for the use of NAIM in clinical practice.

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Matrix metalloproteinase‐11 regulates inverted papilloma epithelial cell migration and invasion

Kush Panara, Tan Li Hui, Deepa Keshari, Charles C. L. Tong, James N. Palmer, Nithin D. Adappa, Jennifer E. Douglas, Noam A. Cohen, Michael A. Kohanski

Publication date 01-11-2024


Abstract Background Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion.
Methods Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures.
ResultsIP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelias ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion.
Conclusion We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.

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There is no sinus without “us”: A randomized controlled study assessing the efficacy of shared decision‐making in the surgical management of chronic rhinosinusitis

Vivienne Li, Andrew Yousef, Divya Prajapati, Michael Oca, Leslie Gomez, Adam S. DeConde, Carol H. Yan

Publication date 01-11-2024


Key pointsCRS patients exhibit little decision conflict in their choice of pursuing surgery.
Standard counseling alone appears to suffice once patients express an interest in surgery.
Decision aids may increase patient knowledge and improve postoperative care understanding.

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Multi‐institutional validation of an AI‐based sinus CT analytic platform with olfactory assessments

Conner J. Massey, Stephen M. Humphries, Jess C. Mace, Timothy L. Smith, Zachary M. Soler, Vijay R. Ramakrishnan

Publication date 01-11-2024


Key pointsAI-based CT sinus analysis may have advantages over visual based systems, for example, Lund–Mackay score.
Here, we show multi-institutional validation of an AI algorithm using novel OMC classification.
Significant, robust correlations are seen between algorithm outputs and clinical outcomes.

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Chitosan‐based crosslinking for controlled topical drug release in rhinosinusitis

Do‐Yeon Cho, Dong Jin Lim, Olivia J. Kelly, Daniel Skinner, Shaoyan Zhang, Martin P. Jones, Jessica Grayson, Bradford A. Woodworth

Publication date 01-11-2024


Key points Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility.
Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity.
Hydrophilic drugs may require different strategies to obtain a sustained release profile.

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Contemporary practice patterns for chronic rhinosinusitis with nasal polyps

Noel F. Ayoub, Firas Sbeih, Benjamin S. Bleier

Publication date 01-11-2024


Key points Data on current practice patterns for the management of chronic rhinosinusitis with nasal polyps, including which medications are deemed by otolaryngologists to better manage patient symptoms, are limited.
This study demonstrated that contemporary practice patterns are largely consistent with published clinical consensus statements.
Off-label nasal steroid irrigations and dupilumab are the most commonly used topical and systemic therapies for chronic rhinosinusitis with nasal polyps, respectively.

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Issue Information

Publication date 01-11-2024


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Correction to “Increase in the prevalence of follicular regulatory T cells correlates with clinical efficacy of sublingual immunotherapy with house dust mites”

Publication date 01-11-2024


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Roles of noncoding RNA in allergic rhinitis

Xiangkun Zhao, Yuteng Yang, Yaqi Wang, Xi Chen, Yisong Yao, Ting Yuan, Jiaxuan Li, Yumei Li, Xicheng Song

Publication date 01-11-2024


Abstract Background Allergic rhinitis (AR) is one of the most common respiratory noninfectious diseases and chronic inflammatory diseases, the incidence of which has been increasing in recent years. The main pathological characteristics of AR are repeated inflammation, airway hyperreactivity, mucus hypersecretion, and reversible airway obstruction due to inflammatory cell response. AR occurrence is associated with various factors, including those of genetic and environmental origins. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases.
Methods Articles are selected based on Pubmeds literature review and the authors personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. Several recent studies have indicated the relationship of ncRNAs with the development of respiratory allergic diseases. NcRNAs, including miRNAs, lncRNAs, and circRNAs, are important gene expression regulatory factors. We review the expression and function of ncRNAs in AR, their role as disease biomarkers, and their prospective applicability in future research and clinically. We also discuss interactions between ncRNAs and their influence on AR comprehensively, these interactions are essential for determining the underlying pathological mechanisms further and discovering new drug therapeutic targets.
Results NcRNAs can be used as biomarkers for early AR diagnosis, disease surveillance and prognosis assessment. Various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. They are also therapeutic targets and biomarkers in other allergic diseases.
Conclusion This article demonstrates ncRNAs have a wide range of applications in AR treatment.
The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore. With further research and technological development, ncRNAs may provide additional innovative, effective solutions for AR treatment.

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Evaluation and treatment of rhinosinusitis with primary antibody deficiency in children: Evidence‐based review with recommendations

Chadi A. Makary, Antoine Azar, David Gudis, Anna Crawford, Paavali Hannikainen, Jean Kim, Stephanie Joe, Adam J. Kimple, Kent Lam, Jivianne T. Lee, Amber U. Luong, Sonya Marcus, Erica McArdle, Warren Mullings, Brian P. Peppers, Callum Lewandrowski, Sandra Y. Lin, Hassan H. Ramadan, Austin S. Rose, Lindsey Ryan, Elina Toskala, Fuad M. Baroody

Publication date 01-11-2024


Abstract Background There is clear evidence that prevalence of primary antibody deficiency (PAD) is higher in children with chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in children with PAD.
Methods The Pub Med, Embase, and Cochrane databases were systematically reviewed from inception through December 2023. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated.
ResultsA total of 50 studies were included in this evidence-based review. These studies were evaluated on the incidence of PAD in rhinosinusitis patients, the incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence varied across the reviewed domains.
Conclusion Based on the currently available evidence, the incidence of PAD in children with recalcitrant CRS can be significantly elevated. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher level studies that compare different treatments in children with PAD and rhinosinusitis.

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Ambient particulate matter and frequency of outpatient visits for chronic rhinosinusitis in the United States

Hong‐Ho Yang, David Grimm, Esther Velasquez, Peter H. Hwang

Publication date 30-10-2024


Abstract Background Emerging evidence has underscored the harmful effects of air pollution on the upper airway. We investigated the relationship between ambient particulate matter (PM) level and the frequency of outpatient visits for chronic rhinosinusitis (CRS).
Methods We conducted an ecological cohort study of US adults enrolled in The Merative Market Scan outpatient database from 2007 to 2020. For each geographical subunit (core-based statistical area CBSA), we calculated the annual rate of CRS-related outpatient visits per 1000 well-patient checkup visits (CRS-OV). Using data from the Environmental Protection Agencys Air Quality System, we mapped the rolling statistical average of daily PM2.5 and PM10 over the preceding year onto each CBSA × year combination. We employed multivariable negative binomial regression modeling to estimate the association between PM levels and subsequent CRS-OV.
Results Across 3933 observations (CBSA × year combinations), encompassing ∼4 billion visits, the median CRS-OV was 164 (interquartile range 110–267). The mean PM2.5 level was 8.9 µg/m3 (SD 2.6) and the mean PM10 level was 20.2 µg/m3 (SD 7.2). Adjusting for patient demographics and respiratory comorbidities, a compounded rise in subsequent CRS-OV was observed with increasing PM levels. Each µg/m3 rise in PM2.5 independently predicted a 10% increase in CRS-OV (adjusted incidence rate ratio aIRR) 1.10, 95% confidence interval CI 1.08–1.13) and each µg/m3 rise in PM10 independently predicted a 3% increase in CRS-OV (aIRR 1.03, 95% CI 1.02–1.04).
Conclusion Elevated ambient PM2.5 and PM10 levels are associated with a subsequent compounded increase in the frequency of CRS-OV, with PM2.5 predicting a more pronounced rise compared to PM10.

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Viral infection as an inciting event for development of chronic rhinosinusitis: A population‐based study

Najm S. Khan, Heli Majeethia, Vincent Provasek, Faizaan Khan, Zain Mehdi, Aatin K. Dhanda, Jeffrey T. Vrabec, Edward D. McCoul, Chadi A. Makary, Masayoshi Takashima, Omar G. Ahmed

Publication date 30-10-2024


Key points Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year.
Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year.
Recurrent viral infections pose a greater risk of chronic rhinosinusitis than single episodes.

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Letter to the editor regarding “Role of social determinants of health on quality of life in pediatric chronic rhinosinusitis”: Enhancing patient‐centered care in underdeveloped regions

Huimin Du, Tong Wu

Publication date 27-10-2024


Pubmed PDF Web

Reply to the letter to the editor regarding “Role of Social Determinants of Health on Quality of Life in Pediatric Chronic Rhinosinusitis”: Enhancing patient‐centered care in underdeveloped regions

Ryan S. Ziltzer, Sameer Shetty, Dominic Coutinho, Rafka Chaiban, Chadi A. Makary

Publication date 27-10-2024


Pubmed PDF Web

Development and validation of the four‐item Concise Aging adults Smell Test to screen for olfactory dysfunction in older adults

Zachary M. Soler, Mathew J. Gregoski, Preeti Kohli, Kristina A. LaPointe, Rodney J. Schlosser

Publication date 27-10-2024


Abstract Background Olfactory dysfunction (OD) in the elderly is common and associated with numerous comorbidities, yet often underrecognized. This study sought to develop an instrument for widespread screening of this condition.
Methods Demographic factors, comorbidities, and olfactory-related questions were examined in a focus group (N = 20) and development cohort (N = 190). The 4-item Concise Aging adults Smell Test (4-CAST) screening instrument was then developed to predict OD on Sniffin Sticks testing. An independent validation cohort (N = 147) was then examined to confirm ability of the 4-CAST to predict OD on Smell Identification Test 40 (SIT40).
Results The most important variables for predicting olfactory loss in older subjects were age, type II diabetes status, Visual Analog Scale (VAS) of overall rating of smell, and VAS of impact of smell upon safety. In the development cohort, the 4-CAST model yielded predictive probability (area under the curve) of 0.805 (p < 0.001) for predicting the bottom 25th percentile on Sniffin Sticks. Results were similar in the validation cohort, as the 4-CAST accurately classified 83.8% subjects (area under the curve AUC 0.789, p < 0.001) in the bottom 25th percentile of SIT40 testing. The 4-CAST was able to accurately classify 89.4% of subjects with anosmia.
Conclusion The 4-CAST is a quick screening instrument for predicting OD in older adults and has similar performance characteristics in independent populations using the two most common validated olfactory tests. Given the high prevalence of unrecognized olfactory loss in this population, this can be a useful tool for practitioners to determine which subjects may benefit from more extensive olfactory testing.

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A cradle‐to‐grave life cycle assessment of the endoscopic sinus surgery considering materials, energy, and waste

Zeinab Mousania, Darpan Kayastha, Ryan A. Rimmer, John D. Atkinson

Publication date 27-10-2024


Abstract Background Operating rooms generate 1.8 million tons of waste annually, or 20%‒30% of the total healthcare waste in the United States. Our objective was to perform a life cycle assessment (LCA) for endoscopic sinus surgeries (ESSs) in order to analyze its environmental impact.
MethodsA comprehensive LCA of ESS was performed considering energy, climate, and water use impacts associated with the materials and processes used. It focuses on the ESS performed at a large tertiary academic hospital and then extends the impacts to consider annual US surgeries. The assessment considers end-of-life waste management at both landfills and incinerators.
Results Single-use instrument production constitutes 89%‒96% of the total impacts throughout the life cycle of an ESS. Waste-to-energy incineration is shown to be a preferred end-of-life destination, as it recovers much of the input production energy of plastic items, ultimately reducing the input to 36%, although this is done at the expense of higher greenhouse gas emissions. For multi-use items, decontamination dominates environmental impact (>99% of totals), but consideration of reusable items reduces overall energy consumption and global warming potential (GWP) by 25%‒33%.
Conclusion Single-use items dominate the total environmental impact of ESS. While multi-use items require additional decontamination over their lifetimes, results show that their incorporation reduces energy consumption and GWP by 25%‒33%, demonstrating the clear environmental benefit.

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Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP

Audrey Pelletier, Leandra Mfuna Endam, Emmanuel Gonzalez, Sheherazade Jannat, Thea Irani, Martin Desrosiers

Publication date 23-10-2024


Abstract Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term.
Methods In this prospective, placebo-controlled, double-blinded trial. Thirty adult subjects with recurrent CRSwNP underwent ESS plus or minus 14 weeks of perioperative dupilumab, initiated 4 weeks (two injections) pre-ESS. Subjective and objective parameters of nasal patency, olfaction, quality of life (QoL), and adverse events were monitored up to 52 weeks post-ESS. Microbiological culture was performed to characterize pathogens colonization under both conditions.
ResultsESS safely improved subjective and objective measures of nasal patency, olfaction, and QoL in both groups. Olfaction was conserved longer in the dupilumab-treated group, with 33.3% of subjects presenting anosmia at 12 months after ESS in the dupilumab group compared to 50.0% with placebo. This was associated with persistent decreases in serum IgE, which were not seen with placebo treatment. No unusual safety signals were observed.
Conclusion Short-course adjuvant perioperative treatment with dupilumab is associated with improved long-term olfactory outcomes and persistent lowering of serum IgE.

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Potential of observing the diameter of the optic nerve sheath using computed tomography in diagnosing high intracranial pressure in patients with spontaneous CSF rhinorrhea

Shunke Li, Zengxiao Zhang, Huijuan Zhao, Xuehui Li, Lin Wang, Jisheng Zhang, Lin Han, Xudong Yan, Liwei Jiang, Zhaoxia Wei, Longgang Yu, Yan Jiang

Publication date 23-10-2024


Key points Spontaneous cerebrospinal fluid rhinorrhea (sCSFR) is often accompanied by an increase in intracranial pressure (ICP).
The widening of optic nerve sheath diameter (ONSD) is an indicator of increased ICP.
Using CT to measure ONSD is a simple and noninvasive auxiliary method for determining high ICP in sCSFR patients.

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A rare case of disseminated amebiasis in a patient on biologic therapy for chronic rhinosinusitis

Ariel Omiunu, Lindsey Brown, Darpan Kayastha, R. Peter Manes

Publication date 23-10-2024


Key points Dupilumab targets Th2-associated inflammatory mediators to reduce disease burden in CRSwNP.
While rare, potential sequelae include viral, helminth, and potentially amebic infections.

Pubmed PDF Web

Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience

Marisa Dorling, Masih Sarafan, Béatrice Voizard, Yousif Al Ammar, Juan Carlos Hernaiz‐Leonardo, Kieran Chalmers, Patrick MacInnis, James Nugent, Arif Janjua, Amin Javer, Doron Sommer, John Lee, Yvonne Chan, Andrew Thamboo

Publication date 18-10-2024


Abstract Background Type 2 biologics have been used increasingly for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, patterns of biologic switching are understudied, and established guidelines for sequential or simultaneous use do not yet exist.
Methods This is a Canadian multicenter retrospective study of real-world patient data. Patients were included if they had recurrent CRSwNP despite maximal medical and surgical management, and received at least one dose of a type 2 biologic. Patients who remained on their initial biologic comprised the continuous group. Patients with sequential or simultaneous use of more than one biologic comprised the switched group. We compared the characteristics of patients who continued and switched biologics.
Results Note that 225 consecutive patients were included. Thirty-six (16%) switched biologics at least once, and six (3%) switched twice. The most common switch was from mepolizumab to dupilumab, with poor control of CRSwNP symptoms being the leading cause for this switch. Lack of efficacy was the main reason for switching off mepolizumab and omalizumab, while adverse events were the leading cause for switching off dupilumab. Additionally, mepolizumab patients were more likely to switch biologics late in their treatment, while dupilumab patients rarely switched after 12 months of therapy (p-value < 0.001).
Conclusions Switching biologics for CRSwNP is frequent in Canadian rhinology practices, with 16% of patients switching at least once. The most common switch is from mepolizumab to dupilumab with inadequate CRSwNP control driving this switch. This study may help guide sequential or simultaneous use of biologics in CRSwNP patients.

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Temperature‐controlled radiofrequency treatment of the nasal valve in nasal airway obstruction patients with septal deviation

Dennis M. Tang, Philip G. Chen, Arthur W. Wu, William C. Yao

Publication date 18-10-2024


Key Points Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation.
Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment.
Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve.

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Efficacy and safety of omalizumab combined with allergen immunotherapy in children with moderate to severe allergic asthma

Wenxin Shen, Qianlan Zhou, Qinzhen Zhang, Lina Han, Li Chen, Xiaowen Li, Bing Dai, Si Liu, Lishen Shan

Publication date 15-10-2024


Key points Omalizumab enables children who are intolerant to AIT to initiate AIT successfully.
Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumab treatment.
Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

Pubmed PDF Web

Research progress in OX40/OX40L in allergic diseases

Rongrong Song, Huanlei Zhang, Zhuoping Liang

Publication date 15-10-2024


AbstractOX40/OX40L are costimulatory molecules in the tumor necrosis factor superfamily. Numerous studies have shown that OX40/OX40L are involved in immune regulation, especially in the proliferation and differentiation of T cells and the generation of memory T cells, which play important roles in allergic diseases. In recent years, the use of OX40/OX40L as therapeutic targets for treating T-cell-mediated diseases has attracted the interest of scholars. This paper reviews the role of OX40/OX40L in allergic diseases and the progress in clinical treatments targeting this signaling pathway.

Pubmed PDF Web

Orthonasal and retronasal olfactory function in patients with chronic rhinosinusitis without nasal polyps undergoing endoscopic sinonasal surgery

Paolo Boscolo‐Rizzo, Claire Hopkins, Thomas Hummel, Anna Menini, Francesco Uderzo, Giulia Provenza, Giacomo Spinato, Enzo Emanuelli, Giancarlo Tirelli

Publication date 10-10-2024


Abstract Background Olfactory dysfunction (OD) is a key symptom of chronic rhinosinusitis (CRS). Although extensively studied in CRS with nasal polyps (CRSwNP), OD in CRS without nasal polyps (CRSsNP) remains under-researched. This study aims to assess the prevalence of OD and its evolution in surgically naïve patients with CRSsNP undergoing endoscopic sinus surgery (ESS).
Methods This prospective study included 97 participants with CRSsNP (mean age, 46.5 years; 70.1% men) and 97 healthy controls (mean age, 46.5 years; 70.1% men). Participants underwent psychophysical evaluations of orthonasal (using the Sniffin’ Sticks test) and retronasal olfaction (using powdered aromas) at enrolment and 6 months post-ESS.
Results Out of 97 patients, 81 (83.5%) completed all assessments. At enrolment, 23 (28.4%) CRSsNP patients had OD based on composite threshold, discrimination, identification scores, compared with 7 (8.6%) controls (absolute % difference, 19.8% 95% CI, 8.2–31.4). Retronasal olfactory function was also significantly worse in CRSsNP patients. Six months post-ESS, 30 patients (37.0%) experienced a clinically significant improvement in olfactory, whereas nonsignificant changes were observed in retronasal olfactory score, and 3.7% of patients experienced a deterioration of the olfactory function.
Conclusions In conclusion, although 37% of patients experienced a clinically significant improvement in their sense of smell following ESS, the overall prevalence of OD in this surgically naive population appears relatively low, especially when compared to that observed in patients with CRSwNP. Therefore, ESS may offer some benefits for enhancing orthonasal olfactory function, but the extent of these improvements appears to be limited.

Pubmed PDF Web

A preliminary review of the utility of artificial intelligence to detect eosinophilic chronic rhinosinusitis

"Jayanth Rajan, Ross Rosen, Daniel Karasik, John Richter, Claudia Cabrera, Brian DAnza, Kenneth Rodriguez, Sanjeet V. Rangarajan"

Publication date 10-10-2024


Key points While typically diagnosed with biopsy, ECRS may be predicted preoperatively with the use of AI.
Various AI models have been used, with pooled sensitivity of 0.857 and specificity of 0.850.
We found no statistically significant difference between the accuracy of various AI models.

Pubmed PDF Web

Effects of functional endoscopic sinus surgery on asthma control in patients with comorbid chronic rhinosinusitis and asthma: A national database study

Mbuyi Madeleine Kabongo, Joshua M. Levy, Lauren T. Roland

Publication date 08-10-2024


Key points In patients with chronic rhinosinusitis and comorbid asthma, patients with surgical intervention required less asthma rescue medication, as compared to those who did not undergo surgery.
Following sinus surgery, patients with chronic rhinosinusitis and asthma required more asthma medication, as compared to the time period prior to surgery.

Pubmed PDF Web

Stepwise Empty Nose Syndrome Evaluation (SENSE) test—A modified cotton test for reduced bias in office diagnosis of empty nose syndrome

Lirit Levi, Angela Yang, Esmond F. Tsai, Yifei Ma, Nour Ibrahim, Sachi S. Dholakia, Vidya K. Rao, Axel Renteria, Xueying Cao, Michael T. Chang, Jayakar V. Nayak

Publication date 07-10-2024


Abstract Introduction Diagnosis of empty nose syndrome (ENS) relies on the ENS six-item questionnaire (ENS6Q) with a score of ≥11, followed by a “positive” cotton test yielding seven-point reduction from baseline ENS6Q score via cotton placement to the inferior meatus (IM). Given the intricacies of diagnosing ENS and the propensity for false positives with the standard cotton test, we modified the classic single-step cotton test into a four-part Stepwise Empty Nose Syndrome Evaluation (SENSE) cotton test to reduce bias and evaluate the placebo effect.
Methods Individuals diagnosed with ENS underwent the SENSE test, a single-blinded, four-step, office-based cotton test, without topical anesthesia or decongestants.
Conditions included: (1) placebo/no cotton placed; (2) complete cotton-blockade of nasal vestibule; (3) cotton placed medially against the nasal septum; and (4) cotton placed laterally in the IM (site of inferior turbinate tissue loss). With each condition, patients completed an ENS6Q.
Results Forty-eight ENS patients were included. Twenty-nine percent demonstrated a placebo effect (p < 0.001), 40.4% had a positive response to complete cotton-blockade (p < 0.001), 64.4% to septum-placed cotton, and 79.1% to IM-placed cotton (p < 0.001), corresponding to a mean ENS6Q reduction of 11.9 points (p < 0.001). Notably, the mean difference in ENS6Q scores between septum and IM placement was 1.7 (p < 0.001).
Conclusions The SENSE test offers further insight into subtleties of nasal breathing experienced by ENS patients. The placebo effect can be prominent and important to consider with individual patients. While most ENS patients prefer any intranasal cotton placement over baseline, blinded testing reveals these patients can accurately discriminate minimal changes in nasal aerodynamics.

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S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp

Sang Hyeon Ahn, Jun Taek Oh, Dae Hyun Kim, Eun Jung Lee, Min‐Seok Rha, Hyung‐Ju Cho, Chang‐Hoon Kim

Publication date 05-10-2024


Abstract Background Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS).
Methods Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed.
ResultsGO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r = 0.294, p = 0.022) and Lund–Mackay scores (r = 0.348, p = 0.006).
ConclusionS100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.

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The effect of allergen immunotherapy in patients with central compartment atopic disease post‐surgery

Christian M. Meerwein, Peta‐Lee Sacks, Jacqueline Ho, Christine Choy, Larry Kalish, Raewyn G Campbell, Ray R. Sacks, Richard J Harvey

Publication date 27-09-2024


Abstract Objective To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery.
MethodsA retrospective cohort of surgically treated, HDM-sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22-item sino-nasal outcome test (SNOT-22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin-exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell × 109/L), tissue eosinophilia (% > 100/HPF), and serum IgE (kU/L) were also recorded.
Results Eighty-six CCAD patients were assessed (41 ± 14 yrs, 64% female). AIT was applied in 37% (n = 32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p = 0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (% ≥ diffuse 15.6 vs. 52.9, p < 0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (% ≥ 4/week, 37.5 vs. 79.6%, p < 0.01). The rhinologic symptoms were similar (21.1 ± 17.1 vs. 20.1 ± 21.6, p = 0.83).
Conclusions Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation.

Pubmed PDF Web

Patient‐derived organoid model of olfactory ensheathing cell tumor

John B. Finlay, Ralph Abi Hachem, Patrick Codd, Bradley J. Goldstein

Publication date 27-09-2024


KEY POINTSWe developed a culture model of a human olfactory ensheathing cell tumor.
Cultured organoids resemble normal ensheathing cells.
Assays suggest that this model provides a tool for studying the roles of these glial cells in the maintenance of the peripheral olfactory system.

Pubmed PDF Web

Time is money: An analysis of cost drivers in ambulatory sinus surgery

David K. Lerner, Chau Phung, Alan D. Workman, Saawan Patel, Glenn Pennington, Robert Stetson, Jennifer E. Douglas, Michael A. Kohanski, James N. Palmer, Nithin D. Adappa

Publication date 26-09-2024


Abstract Background Functional endoscopic sinus surgery (FESS) is one of the most commonly performed otolaryngologic procedures and is associated with significant cost variability.
Methods We performed a retrospective analysis of all inflammatory sinus surgeries at a single tertiary care medical center from July 2021 to July 2023. The electronic medical record was reviewed for patient factors and cost variables for each procedure, and multivariable analysis was performed.
ResultsA total of 221 patients were included in analysis with a mean age of 48.2 years. There was a 44.8% incidence (n = 99) of nasal polyps and 31.2% (n = 69) of cases were revision surgeries. The average total cost for the surgical encounter was $8960.31 (standard deviation $1967.97). Operating room time represented $4912.46 (54.8% of all costs), while average operating room supply costs were $1296.06 (14.5%) and recovery room costs were $919.48 (10.3%). Total costs were significantly associated with length of surgery ($7.83/min, p = 0.04), in addition to presence of nasal polyps ($531.96, p = 0.04). There was no significant association between total costs and the remaining clinical and demographic factors.
Conclusions Costs associated with ambulatory FESS for inflammatory sinus disease vary across patients and this cost variability is predominantly driven by time efficiency within the operating room, as well as supply utilization and nasal polyposis to a lesser degree. As a result, operating room efficiency represents a primary target for cost-related interventions. Additionally, our data provide a framework for surgeons and hospitals to make evidence-based decisions on intraoperative equipment in a tradeoff between efficiency and supply costs. Our findings indicate that an approach focused on streamlining efficiency across the entire ambulatory surgery encounter will have the greatest impact on reducing healthcare expenses for both the patient and the health system.

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Real‐time augmentation of diagnostic nasal endoscopy video using AI‐enabled edge computing

Jonathan Bidwell, Dipesh Gyawali, Jonathan Morse, Vinayak Ganeshan, Thinh Nguyen, Edward D. McCoul

Publication date 24-09-2024


KEY POINTSAI-enabled augmentation of nasal endoscopy video images is feasible in the clinical setting.
Edge computing hardware can interface with existing nasal endoscopy equipment.
Real-time AI performance can achieve an acceptable balance of accuracy and efficiency.

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A cost utility analysis for the management of acute exacerbations of chronic rhinosinusitis

Matthew M. Chu, Jack T. Garcia, Ahmad R. Sedaghat, George A. Scangas, Katie M. Phillips

Publication date 20-09-2024


Abstract Background The management of acute exacerbations of chronic rhinosinusitis (AECRS) is understudied and the most cost-effective management of AECRS has not been previously investigated. The aim of this study is to determine the most cost-effective strategy for the initial management of AECRS.
Methods The study design consisted of a decision-tree economic model comparing three different initial strategies for managing a patient perceived AECRS: observation, upfront rescue medications, or clinic visit with diagnostic nasal endoscopy (DNE). The primary study outcome was the disease burden of a single AECRS, which was determined by the health utility value and the duration of symptoms. Strategies with an incremental cost-effectiveness ratio < $50,000/quality-adjusted life year (QALY) or equivalently < $137/quality-adjusted life day (QALD) were considered cost-effective.
Results Observation was the most cost-effective strategy at a willingness to pay of $137 per QALD. One-way sensitivity analysis demonstrated that observation was more effective than upfront rescue medications when the probability of bacterial infection as the cause of AECRS was <24.0%. Upfront rescue medications wer more cost effective than observation when the probability of bacterial infection exceeded 49.0%. Clinic visit with DNE was the most effective strategy to manage an AECRS, but it was not considered cost-effective.
Conclusion Observation is the most cost-effective strategy for the initial management of AECRS when there is a low likelihood of bacterial infection. When the probability of bacterial etiology of AECRS exceeds 49.0%, upfront rescue medications proved to be the most cost-effective strategy.

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Quantitative characterization of eosinophilia in nasal polyps with AI‐based single cell classification

Martin Stampe, Ida Skovgaard Christiansen, Vibeke Backer, Kasper Aanæs, Anne‐Sophie Homøe, Jens Tidemandsen, Emilie Neumann Nielsen, Sigrid Louise Hjorth Rasmussen, Rasmus Hartvig, Katalin Kiss, Thomas Hartvig Lindkær Jensen

Publication date 20-09-2024


Key Points Eosinophilic granulocytes have characteristic morphological features.
This makes them prime candidates for utilization of a single cell binary classification network.
Single cell binary classification networks can reliably help quantify eosinophils in nasal polyps.

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In office sampling of eosinophil peroxidase to diagnose eosinophilic chronic rhinosinusitis

Jacquelyn K. Callander, Annabelle R. Charbit, Kritika Khanna, John V. Fahy, Monica Tang, Maude Liegeois, Steven D. Pletcher, Andrew N. Goldberg, Jose G. Gurrola II, Andrew H. Murr, Anna Butrymowicz, Patricia A. Loftus

Publication date 13-09-2024


Abstract Background Practical biomarkers for endotypic characterization of chronic rhinosinusitis (CRS) remain elusive, hindering clinical utility. Eosinophil peroxidase (EPX) is an enzyme released by activated eosinophils. The objective of this study was to evaluate a clinic EPX assay as a marker of eosinophilic CRS.
Methods Subjects with and without CRS presenting to a tertiary care rhinology clinic were prospectively enrolled, and nasal cytology brushings were collected from the middle meatus during in-clinic nasal endoscopy. ELISA assay was used to quantify EPX levels, and a customized multiplex immunoassay was used to quantify inflammatory cytokine mediators. Findings were correlated with clinical data.
Results Forty-two subjects were enrolled, including 31 CRS subjects and 11 controls. Median EPX levels were 125.0 ng/mL (standard deviation SD 1745.8) and 6.5 ng/mL (SD 99.0) for CRS group and controls, respectively (p = 0.003). EPX levels were associated with history of asthma (p = 0.015), allergies (p = 0.028), polyps (p = 0.0006), smell loss (p = 0.006), and systemic eosinophilia or elevated immunoglobulin E (p ≤ 0.0001). Twenty-eight subjects from both the CRS and control groups had prior pathology for comparison, with histologic confirmation of local tissue eosinophilia (>10 eosinophils/hpf) in 11 subjects. This subgroup had a median EPX level of 967.5 ng/mL compared to 10.6 ng/mL in 17 subjects without local tissue eosinophilia (p = 0.0008). EPX levels were positively correlated to interleukin-5 levels (p = 0.0005).
ConclusionEPX levels can be measured via well-tolerated in-clinic collection of nasal mucus. EPX levels are associated with clinical markers of type 2 inflammation and tissue eosinophilia and may provide a valuable diagnostic tool to delineate eosinophilic CRS.

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Patient‐reported disease control versus overall symptom severity as global metrics of chronic rhinosinusitis disease status

Ryan A. Cotter, Jack T. Garcia, Ahmed Alsayed, Sven Schneider, David T. Liu, Julia Eckl‐Dorna, Firas A. Houssein, Robby S. Boparai, Nikhil A. Parail, Matthew M. Chu, Josh C. Meier, Saad Alsaleh, Katie M. Phillips, Ahmad R. Sedaghat

Publication date 13-09-2024


Abstract Background Overall symptom severity (OSS) and patient-reported chronic rhinosinusitis (CRS) control are global measures of CRS identified as consensus, essential criteria for CRS disease control assessment. We sought to determine the functional relationship between these two metrics.
Methods Using an international multicenter mixed-methods design, 260 CRS patients were recruited. OSS score was measured using a visual analog scale. Patient-reported CRS control was measured as “controlled,” “partly controlled,” and “uncontrolled.” Twelve participants underwent semi-structured interviews to discuss OSS and patient-reported CRS control.
Results The majority of interviewed participants felt OSS and patient-reported CRS control measured different constructs—while OSS only measured symptoms, patient-reported CRS control was more global, including not only symptom severity but also concepts such as medication usage, activity impairment, and exacerbations. Nevertheless, OSS score was strongly correlated with (ρ = 0.67, p < 0.001) and highly predictive of patient-reported CRS control. OSS score of >4 (95% confidence interval CI: 1.8–4.2) had 74.7% sensitivity and 93.2% specificity in identifying patients reporting their CRS as not controlled. OSS score of >6.6 (95% CI: 4.1–7.1) had 77.0% sensitivity and 75.9% specificity in identifying patients reporting their CRS as uncontrolled. The 22-item Sinonasal Outcome Test score was also predictive of patient-reported CRS disease control but OSS was significantly more predictive.
Conclusions Patients conceptually view patient-reported CRS control as a more global measure that subsumes OSS. Quantitatively, however, OSS is highly correlated with patient-reported CRS control, possibly reflecting their redundancy. For ease of use, we recommend patient-reported CRS control be reflected by OSS <4 for controlled, 4 ≤ OSS < 7 for partly controlled, and OSS ≥7 for uncontrolled CRS.

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Assessing adequacy of surgical extent in CRSwNP: The Completion of Surgery Index

Alan D. Workman, Krithika Kuppusamy, David K. Lerner, John V. Bosso, Jennifer E. Douglas, Michael A. Kohanski, Nithin D. Adappa, James N. Palmer

Publication date 12-09-2024


Abstract Background Endoscopic sinus surgery (ESS) maximized for topical steroid irrigations is highly effective for polyp disease. As extent and completeness of ESS varies widely by situation and practitioner, it is important to understand when revision surgery is appropriate, particularly in the era of biologic treatments.
MethodsA Completion of Surgery Index (CoSI) was developed to assess operative changes in polyp patients using pre- and postoperative computed tomography scans. The CoSI was then applied and tested in a cohort of consecutive chronic rhinosinusitis with nasal polyps (CRSwNP) patients, and examined within the context of quality-of-life improvements.
Results The CoSI assesses surgical extent on a scale of 0–100, with 100 representing the highest possible degree of surgical completeness. Among 100 consecutive CRSwNP patients undergoing ESS in 2021 with postoperative topical steroid irrigations, including 75 revision surgeries, SNOT-22 scores improved at 6 months postoperatively, with durable and consistent improvement at 24 months (p < 0.001). Preoperative CoSI scores in revision surgery patients were 49.4 ± 26.0, improving to 91.0 ± 8.1 postoperatively. SNOT-22 scores for primary ESS patients and patients with a preoperative CoSI score of less than 70 improved by 26.4 and 28.1 points, respectively, in contrast to patients with a preoperative CoSI of 70 or greater (14.1 points, p = 0.029).
Conclusions It is important to define extent of surgery in CRSwNP to stratify postsurgical patients based on likelihood to benefit from revision surgery or alternative medications. The CoSI can be utilized to identify patients who are likely to improve significantly with revision surgical intervention.

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Age‐related differences in olfactory training outcomes: A prospective cohort study

Amelia S. Lawrence, Jodi Veach, Rahul Alapati, Celina G. Virgen, Robert Wright, Frank Materia, Jennifer A. Villwock

Publication date 12-09-2024


Abstract Introduction While olfactory function decreases with age, it is unknown how age affects olfactory training (OT) efficacy.
This study compared OT in two cohorts of subjects: aged ≤50 (younger cohort) and aged 51+ (older cohort) with olfactory dysfunction (OD) primarily from COVID-19 infection.
Methods Subjects with OD primarily secondary to COVID-19 infection were prospectively recruited and enrolled into an OT registry. Baseline data were collected and they were provided with a training kit and asked to complete OT at home twice daily for 6 months. Participants were asked to follow-up at 3 and 6 months during training for olfactory testing and quality-of-life surveys (Sino-Nasal Outcomes Test-22 SNOT-22 and Questionnaire of Olfactory Disorders Negative Statements QoD-NS).
Results Fifty-six participants completed OT (younger cohort: n = 26, older cohort: n = 30). There were no significant differences between cohorts’ Affordable Rapid Olfactory Measurement Array (AROMA), QoD-NS, or SNOT-22 scores at any time point. Both cohorts showed significant AROMA score improvement of more than 16 points from baseline to 3 months (younger cohort: p = 0.001; older cohort: p = 0.008). The younger cohort had significant improvements in QoD-NS (p = 0.008) and SNOT-22 (p = 0.042) between baseline and 3 months while the older cohort improved from 3 to 6 months (QoD-NS: p = 0.027, SNOT-22: p = 0.049).
Conclusion Both cohorts demonstrated similar significant improvement in olfactory function after 3 months of OT. The timeline of subjective improvement was different between cohorts, with younger patients experiencing earlier improvement.

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A prospective longitudinal study assessing the impact of rhinovirus and bacterial infections in acute exacerbations of chronic rhinosinusitis

Nirushan Narendran, Sophia Volpe, Ibrahim Ramadan, Jacob Ryan Herbert, Bonnie LaFleur, Shireen Samargandy, Christopher H. Le, Eugene H. Chang

Publication date 03-09-2024


Abstract Background Acute exacerbations of chronic rhinosinusitis (AECRS) are thought to arise from common viral infections progressing to secondary bacterial infections. However, the pathophysiology of AECRS remains poorly understood due to a lack of prospective longitudinal studies.
Methods We conducted a one-year prospective longitudinal study involving chronic rhinosinusitis (CRS) adults. At baseline, we assessed subjective symptom scores using a validated upper respiratory infection questionnaire (WURSS), sinonasal outcome testing scores (SNOT-22), and endoscopic scores (modified Lund-Kennedy score). Every 2 weeks, we contacted subjects to collect WURSS and SNOT-22 scores. If WURSS scores were ≥1 and SNOT-22 scores were ≥ 8.9 compared with baseline, subjects underwent an AECRS assessment. We identified rhinovirus (RV) incidence through viral nasal brushings at each visit and bacterial infection through bacterial swabs if mucus scores were ≥1.
Results Thiry-five of 80 CRS subjects reported at least one AECRS episode during the year, predominantly occurring in the fall and winter seasons. RV infections were detected in 8 of 35 cases, bacterial infections in 17 of 35, and co-occurring infections in 7 of 35. All subjects with AECRS visits exhibited significantly higher endoscopic scores compared with baseline. Subjects with co-occurring RV and bacterial infections demonstrated higher disease severity compared with those with either RV or bacterial infection, or no infection.
Conclusions In a one-year prospective longitudinal study involving CRS adults, we identified significant risk factors for AECRS including seasonality and the presence of RV and bacterial infections. These data suggest a standard definition of AECRS and the need to target RV and bacterial infections if we are to help reduce disease severity.

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Use of bovine‐derived collagen matrix in the surgical treatment of empty nose syndrome

Brian H. Cameron, Jason Talmadge, Martin J. Citardi

Publication date 03-09-2024


Key points Bovine-derived collagen matrix (BDCM) is a safe augmentation material in patients with empty nose syndrome.
BDCM augmentation results in clinically and statistically significant improvement in nasal symptoms.
Improvements in nasal symptoms with BDCM augmentation may be durable and can be seen up to 2 years postoperative.

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Assessment of conflicts of interest in literature on monoclonal antibodies for chronic rhinosinusitis with nasal polyposis using the Open Payments Database

Christina Liu, Conrad W. Safranek, Rhys Richmond, Trinithas Boyi, Zachary Pickell, Ryan Rimmer, R. Peter Manes

Publication date 02-09-2024


Abstract Background Accurate conflict of interest (COI) information is essential for promoting transparency and trust in research. We aim to assess COI disclosure patterns in monoclonal antibodies (MABs) research for chronic rhinosinusitis with nasal polyposis (CRSwNP) using the Open Payments Database (OPD).
Methods Studies on FDA-approved MABs for CRSwNP (dupilumab, omalizumab, mepolizumab) published between 2019 and 2021 with at least one US author were identified through Pub Med. Industry-reported payments from the manufacturers (Sanofi, Regeneron, Genentech, Novartis, and Glaxo Smith Kline) between 2018 and 2021 in OPDs General Payments category were collected. Authors were cross-checked against OPD metadata using a previously published ChatGPT-based algorithm. Additionally, this novel algorithm analyzed COI statements for relevant author‒company specific disclosures, identifying disclosed and undisclosed payments made 3‒15 months prior to publication.
ResultsA total of 214 unique authors from 76 studies were included. Of 30 articles that received at least one relevant payment, 21 (70%) were found to have an undisclosed COI, with a mean total undisclosed payment of $4890 and a median of $10,331. Fifty-six authors had relevant OPD payments and 40 (71.4%) authors did not declare a potential COI. Interestingly, 158 authors had no relevant payments and 62 (39.2%) declared a potential COI. Author order was not significantly associated with potential under- or over-disclosure.
Conclusion This study characterizes COI disclosure patterns in rhinosinusitis-relevant MABs research using a novel automated approach. Given the discrepancy between disclosures and industry-reported payments, our findings suggest a need for improved disclosure education and practices.

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Generic competition and prices for azelastine‐fluticasone nasal spray

Akash M. Bhat, Zachary M. Soler, Rodney J. Schlosser, George A. Scangas, Alan D. Workman, Vinay K. Rathi

Publication date 30-08-2024


Key points The original manufacturer of azelastine‒fluticasone (AZ‒FL) prevented generic availability until 2020 via patent enforcement.
Following generic availability of AZ‒FL, Medicare utilization increased and spending decreased.
Retail prices for generic AZ‒FL remain high due to markup by manufacturers and pharmacies.

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The effect of open‐label placebo on allergic rhinitis symptoms: A systematic review and meta‐analysis of randomized controlled trials

Ebraheem Albazee, Abdullah M. Alharran, Mooza M. Alzayed

Publication date 30-08-2024


Key points The evidence regarding the open-label placebo effect on allergic rhinitis symptoms remains uncertain.
Open-label placebo significantly reduced the frequency of symptoms in allergic rhinitis patients with similar safety profiles; however, there was no effect on the severity of symptoms and impairment due to symptoms.
The statistically significant impact on symptom frequency can be considered not clinically significant.

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Evaluation of antibiofilm agents for treatment of cystic fibrosis‐related chronic rhinosinusitis

Saartje Uyttebroek, Lieven Dupont, Jeroen Wagemans, Rob Lavigne, Maya Merabishvili, Tom Coenye, Laura Van Gerven

Publication date 30-08-2024


Key points Treatment of cystic fibrosis-related chronic rhinosinusitis should target sinonasal biofilms.
NaHCO3 salts with/without xylitol have limited antibiofilm properties, whereas rhDNAse has not.
Phage effectivity varies and depends on the phage and the combination with antibiotics.

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CPAP‐induced sphenoid sinus pressures after endoscopic sinus surgery

"Glen E. DSouza, Alexander Duffy, Shreya Mandloi, Emily Garvey, Bita Naimi, Paavali Hannikainen, Peter Benedict, Gurston N. Nyquist, Christopher Farrell, Marc Rosen, Elina Toskala, James Evans, Mindy R. Rabinowitz"

Publication date 30-08-2024


Key Points Positive pressure transmitted from continuous positive airway pressure (CPAP) to the sinuses and skull base in the early post-operative period has not been studied in live subjects and controversy exists in when to restart this post-operatively.
This study found that approximately 32.76% and 13.52% of the delivered CPAP pressures reached the post-surgical sphenoid sinus and the mid-nasal cavity, respectively, suggesting that surgical factors such as tissue edema, nasal packing, blood, and nasal secretions may provide a protective effect.

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Comparative analysis of traditional machine learning and automated machine learning: advancing inverted papilloma versus associated squamous cell carcinoma diagnosis

Farideh Hosseinzadeh, S. Saeed Mohammadi, James N. Palmer, Michael A. Kohanski, Nithin D. Adappa, Michael T. Chang, Peter H. Hwang, Jayakar V. Nayak, Zara M. Patel

Publication date 26-08-2024


Key Points Inverted papilloma conversion to squamous cell carcinoma is not always easy to predict.
AutoML requires much less technical knowledge and skill to use than traditional ML.
AutoML surpassed the traditional ML algorithm in differentiating IP from IP-SCC.

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EDS‐FLU efficacy in patients with chronic rhinosinusitis with or without prior sinus surgery in ReOpen1 and ReOpen2 randomized controlled trials

Sarah K. Wise, Nithin D. Adappa, Rakesh K. Chandra, Greg E. Davis, Mahboobeh Mahdavinia, Ramy Mahmoud, John Messina, James N. Palmer, Zara M. Patel, Anju T. Peters, Rodney J. Schlosser, Raj Sindwani, Zachary M. Soler, Andrew A. White

Publication date 26-08-2024


Abstract Background The inability of topical medications to reach sinus cavities is a potential reason for lack of efficacy in chronic rhinosinusitis (CRS). One purpose of endoscopic sinus surgery (ESS) is to enable delivery of medications into the sinus cavities. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE) creates unique biomechanics that enable deposition of intranasal corticosteroid into sinuses and sinus drainage pathways but may have differing efficacy in operated versus unoperated sinuses. Two 24-week randomized trials (Re Open1/2) evaluated EDS-FLU versus EDS-placebo in patients with CRS, stratified by surgical status.
Methods Surgery-naive (n = 332) and prior-surgery (n = 215) patient groups were analyzed as pooled data from Re Open1/2. Outcome measures (least-squares mean change from baseline) included combined symptom score (CSS) and congestion score at weeks 4, 8, and 12 and average of percentages of opacified volume (APOV) of ethmoid/maxillary sinuses on CT and Sinonasal Outcome Test 22 (SNOT-22) total score at week 24.
Results Baseline scores suggested moderate–severe disease: mean CSS = 5.8; APOV = 67.2%. EDS-FLU produced significant improvement versus placebo (p < 0.05): CSS (surgery-naive, −0.68 vs. −1.42; prior ESS, −0.70 vs. −1.87); congestion (surgery-naive, −0.24 vs. −0.59; prior ESS, −0.24 vs. −0.69); and SNOT-22 (surgery-naive, −7.56 vs. −18.30; prior ESS, −10.72 vs. −18.74). Similar results were observed for APOV (p < 0.05). No statistically significant difference was observed between surgery subgroups with either EDS-FLU dose.
ConclusionEDS-FLU improved symptoms, sinus opacification, and quality of life in patients with CRS with or without prior ESS, suggesting a role for EDS-FLU in both populations.

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The impact of cadaveric donor transplant on the development of chronic rhinosinusitis and recalcitrant disease

Estephania Candelo, Anyull D. Bohorquez‐Caballero, Karol Avila‐Castano, Hani Wadei, Angela M Donaldson

Publication date 24-08-2024


Key points The study found a higher incidence of chronic rhinosinusitis (CRS) and recalcitrant CRS in cadaveric organ transplant recipients compared to those receiving living donor transplants. Recipients of cadaveric transplants were 1.32 times more likely to develop CRS and 1.68 times more likely to develop medically recalcitrant CRS.
Living kidney transplants significantly reduced the risk of developing CRS (OR = 0.12) and recalcitrant CRS (OR = 0.11), highlighting a potentially protective effect against these conditions. In contrast, cadaveric liver transplants were associated with an increased risk of CRS and medically recalcitrant CRS.
Kaplan–Meier survival analysis indicated a significant difference in time to CRS onset between cadaveric and living donor transplants. Median time to CRS onset was longer for living donor recipients (21.1 months) compared to cadaveric recipients (15.6 months). This study underscores the need for transplant teams and otolaryngologist to consider donor type during transplant follow-up due to differing risks of CRS development.

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Role of induction chemotherapy in advanced‐stage olfactory neuroblastoma

Sung‐Woo Cho, Bhumsuk Keam, Keun‐Wook Lee, Ji‐Won Kim, Doo Hee Han, Hyun Jik Kim, Jeong‐Whun Kim, Dong‐Young Kim, Chae‐Seo Rhee, Yun Jung Bae, Ji‐Hoon Kim, Keun‐Yong Eom, Hong‐Gyun Wu, Yong Hwy Kim, Chae‐Yong Kim, Sun Ha Paek, Hyojin Kim, Tae‐Bin Won

Publication date 20-08-2024


Abstract Objectives To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC).
Materials and methods The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders.
Results Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p = 0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p = 0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p = 0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p = 0.008).
Conclusion In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB.

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Interpretability of operative and pathological reports for radiotherapy planning of sinonasal carcinomas: An ancillary study of the GORTEC 2016‐02 SANTAL trial

Coline Labarre, Florent Carsuzaa, Maxime Fieux, Benjamin Verillaud, Antoine Moya Plana, Ludovic de Gabory, Vincent Patron, Francois‐Régis Ferrand, Juliette Thariat

Publication date 20-08-2024


Key points Interpretation of surgical mapping is essential for postoperative radiotherapy planning.
Operative and pathological reports lack comprehensive information on margins quality and tissue block mapping.
Standardizing reports is essential to reduce uncertainties, aiming for less morbid poRT.

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Oxymetazoline as a predictor of turbinate reduction surgery outcomes: Objective support from a prospective, single‐blinded, computational fluid dynamics study

Zachary T. Root, Zhenxing Wu, Thomas J. Lepley, Aspen R. Schneller, Robbie J. Chapman, Veronica L. Formanek, Kathleen M. Kelly, Bradley A. Otto, Kai Zhao

Publication date 12-08-2024


Abstract BackgroundA patients subjective response to topical nasal decongestant is often used to screen for turbinate reduction surgery suitability. However, this anecdotal strategy has not been objectively and quantitatively evaluated.
Methods Prospective, longitudinal, and single-blinded cohort study employing computational fluid dynamic modeling based on computed tomography scans at baseline, 30 min postoxymetazoline, and 2 months postsurgery on 11 patients with chronic turbinate hypertrophy.
Results Nasal obstruction symptom evaluation (NOSE) and visual analogue scale (VAS) obstruction scores significantly improved from baseline to postoxymetazoline and again to postsurgery (NOSE: 71.82 ± 14.19 to 42.27 ± 25.26 to 22.27 ± 21.04; VAS: 6.09 ± 2.41 to 4.14 ± 2.20 to 2.08 ± 1.56; each interaction p < 0.05), with significant correlation between the latter two states (r∼0.37–0.69, p < 0.05). Oxymetazoline had a broader anatomical impact throughout inferior and middle turbinates than surgery (many p < 0.05); however, the improvement in regional airflow is similar (most p > 0.05) and predominantly surrounding the inferior turbinate. Strong postoxymetazoline to postsurgery correlations were observed in decreased nasal resistance (r = 0.79, p < 0.05), increased regional airflow rates (r = -0.47 to −0.55, p < 0.05) and regional air/mucosa shear force and heat flux (r = 0.43 to 0.58, p < 0.05); however, only increasing peak heat flux significantly correlated to symptom score improvement (NOSE: r = 0.48, p < 0.05).
Conclusion We present the first objective evidence that the “topical decongestant test” can help predict turbinate reduction surgery outcomes. The predictive effect is driven by similar improvementin regional airflow that leading to improved air/mucosa stimulations (peak heat flux) rather than through reduced nasal resistance.

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Post‐operative outcomes of primary benign orbital tumor resection are independent of tumor size and morphology

Angela S. Zhu, Ryan A. Bartholomew, Yan Zhao, Margaret B. Mitchell, Benjamin S. Bleier, Barak Ringel

Publication date 07-08-2024


Key points Using 3D modeling, we studied the influence of orbital tumor morphology on post-operative outcomes.
Orbital tumor volume did not influence postoperative complication rates.
Less spherical tumors may be correlated with a more extensive surgical approach.

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Rate of dupilumab use and symptom severity of patients with chronic rhinosinusitis with nasal polyposis after Draf 3 frontal sinusotomy

Keven Ji, Hunter Kellerman, Jess C. Mace, Timothy L. Smith, Kara Y. Detwiller, Shyam R. Joshi, Mathew Geltzeiler

Publication date 07-08-2024


Abstract Background The indications for endoscopic modified Lothrop procedure (Draf 3) in patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) remain unclear. This study evaluates the effectiveness of Draf 3 for refractory CRSwNP focusing on improvements in disease severity and need for subsequent dupilumab rescue therapy.
Methods Retrospective review of patients with CRSwNP undergoing Draf 3 surgery at a tertiary center between 2012 and 2022. Clinicodemographic variables were compared across those who did versus did not require rescue with postoperative dupilumab. Time to postoperative dupilumab rescue was analyzed and longitudinal disease-specific outcomes were measured using the sinonasal outcomes test (SNOT-22).
Results Within 87 patients with CRSwNP, 24.1% had aspirin-exacerbated respiratory disease (AERD). Significant improvement in SNOT-22 score was found in CRSwNP with AERD (p < 0.001) and without AERD (p = 0.01) up to 24 months postoperative. 14.9% eventually required rescue with a dupilumab. More specifically, of 21 patients with AERD, 24.1% eventually required rescue with dupilumab. Dupilumab rescue was associated with a greater number of prior sinus surgeries (p = 0.02), prior aspirin desensitization (p = 0.02), and worse preoperative Lund-Mac Kay scores (p < 0.001). No association between biologic rescue and frontal recess antero-posterior diameter was found (p = 0.20).
Conclusions Draf 3 surgery in CRSwNP was associated with significant improvement in SNOT-22 score at 24 months. Furthermore, only 14.9% of patients required dupilumab rescue. Patients with AERD were more likely to require rescue with dupilumab even though 75.1% avoided treatment with the biologic over the study period.

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Identification and characterization of microplastics in human nasal samples

Hyun Jin Min, Kyung Soo Kim, Hyunjung Kim, Jiyoung Gong, Jinyoung Jeong

Publication date 07-08-2024


KEY POINTSHuman nasal cavity samples were collected, and presence of microplastics were evaluated.
Microplastics were present, and major types were polyethylene, polyester, acrylic polymer, and polypropylene.
Further research is needed regarding microplastics and its clinical impact on human nasal cavity.

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Nasal virus infection induces asthma exacerbation through B‐cell‐dependent recruitment of inflammatory monocytes

Kody A. Waldstein, Arman Issimov, Maria Ganama, Valerie Jinge, Stephen Tilley, Xiaoyang Hua

Publication date 07-08-2024


Abstract Background Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood.
Methods In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.
Results Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced TH2 and TH17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted infection with RSV recruited Ly6C+ inflammatory monocytes (IMs) into the lungs of mice with and without HDM-induced asthma. The expression of monocyte chemokines, including CCL2 and CCL7, also increased. Interestingly, nasal virus infection-induced AHR was abolished in mice depleted of IMs and in CCR2−/− mice, indicating that the recruited IMs play a key role in nasal virus infection-induced asthma exacerbations in mice. Lastly, we observed that recruitment of Ly6C+ IMs following URVI was abolished in mice lacking B cells and that nasal-restricted infection with RSV increased numbers of CCL2+CCL7+ B cells in the lungs of mice as compared to controls.
Conclusions Taken together, our data have shown that URVI enhances the allergic inflammatory response and AHR through a B cell‒monocyte regulatory axis.

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Co‐prevalence of chronic rhinosinusitis and inflammatory bowel disease: A large aggregated electronic health record study

Ravi Dhamija, Peng Ding, Nikita Das, Varunil N. Shah, David C. Kaelber, Mohamad R. Chaaban

Publication date 05-08-2024


Key pointsIBD patients have a 4.04-fold elevated likelihood of having CRS compared to non-IBD patients.
CRS patients have a 4.23-fold elevated likelihood of having IBD compared to non-CRS patients.
The risk of CRS development after IBD is five times higher than IBD development after CRS.

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The placebo effect of sham rhinologic procedures in randomized controlled trials: A systematic review and meta‐analysis

Neil P. Monaghan, Kelsey A. Duckett, Shaun A. Nguyen, Abigail A. Massey, Vinay Rathi, Zachary M. Soler, Rodney J. Schlosser

Publication date 31-07-2024


Key points Sham procedures produce a clinically significant impact on patient-reported outcome measures This effect should be considered when designing and interpreting the results of RCTs

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Transsphenoidal retrieval of a needlefish beak remnants from the optic canal

Firas Sbeih, Henry W. Zhou, Noel F. Ayoub, Barak Ringel, Carolina A. Chiou, Joseph F. Rizzo, Benjamin S. Bleier

Publication date 26-07-2024


Key Points Penetrating orbital trauma from marine creatures, especially needlefish, should be considered after injuries sustained in open water.
Advances in endoscopic sinus surgery have enabled surgeons to remove certain orbital foreign bodies through endoscopic endonasal approaches.3D segmentation is a valuable pre-operative tool in complex endoscopic orbital cases.

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V‐Y advancement flap for the repair of localized cutaneous defects following nasal closure in severe hereditary hemorrhagic telangiectasia

Guled M. Jama, Simon Gane

Publication date 16-07-2024


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