The relationship between survey-based subjective olfactory awareness and objective olfactory function.

KEY POINTS: Correlation between symptom-based surveys and objective olfactory testing is variable. For diagnosis and symptom monitoring, surveys should correlate with objective testing. The Odor Awareness Scale (OAS) and Affective Importance of Odor Scale (AIO) showed significant but moderate positive correlations with University of Pennsylvania Scent Identification Test (UPSIT) score.

Detection of plagiarism among rhinology scientific journals.

KEY POINTS: Automated plagiarism-checking software can be a valuable tool for detecting plagiarism in manuscripts. Twenty-five of 60 articles (42%) had at least one incidence of plagiarism, predominately text recycling. A "similarity score" ranging from 22% to 35% could be a potential cut-off value when screening submitted manuscripts.

The Surprising Effect of Priming on SNOT-22 Results.

BACKGROUND: Priming is a psychological phenomenon where subconscious cues in the environment impact our behavioral responses in certain situations. Well studied in the worlds of business, marketing, and even politics, it is unclear how the priming phenomenon impacts patient perception of their own disease state nor how they report that perception using tools like the Sinonasal Outcomes Test (SNOT-22), used to measure that perception in chronic rhinosinusitis. OBJECTIVE: To determine the impact of positive or negative priming on self-reported patient perception of their chronic rhinosinusitis disease using the SNOT-22 disease-specific quality of life instrument. METHODS: Single-blind, randomized, prospective cohort pilot study of 206 consecutive adult patients with a clinical diagnosis of chronic rhinosinusitis presenting to a university rhinology clinic. Patients were randomized to receive "positive priming" (103) or "negative priming" (103) by reading a passage about the positive or negative aspects of chronic sinusitis and its treatment respectively. Patients were then asked to fill out the SNOT-22 and results between the two groups were compared. RESULTS: The negative priming group had a higher median SNOT-22 score of 49 [IQR = 39] compared to the positive priming groups' score of 22 [IQR = 27], p < 0.0001), a difference of nearly three times the minimal clinical impactful difference (MCID). This effect was consistent regardless of age or sex of the patient. Subgroup analysis revealed a greater impact when priming was performed by the senior male attending regardless of patient age or sex (p < 0.001), while priming performed by the younger female research fellow had greater impact on older patients (>59 years, p = 0.001) and female patients (p = 0.003). CONCLUSIONS: Priming impacts how patient's perceive their chronic rhinosinusitis as determined by the SNOT-22. It is imperative that the rhinologist understand this when using this instrument in research applications and in clinical decision-making for patients.

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

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

The Toxicological Effects of e-Cigarette Use in the Upper Airway: A Scoping Review.

OBJECTIVE: While evidence continues to emerge on the negative health effects of electronic cigarettes (e-cigarettes) on the lungs, little is known regarding their deleterious effects on the upper airway. The purpose of this review is to summarize the toxicological effects of e-cigarettes, and their components, on the upper airway. DATA SOURCES: PubMed, SCOPUS, EMBASE databases. REVIEW METHODS: Systematic searches were performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines from 2003 to 2023. Studies were included if they investigated the toxicological effects of e-cigarette exposure on human or animal upper airway tissue. Two authors independently screened, reviewed, and appraised all included articles. RESULTS: A total of 822 unique articles were identified, of which 53 met inclusion criteria and spanned subsites including the oral cavity (22/53 studies), nasal cavity/nasopharynx (13/53), multiple sites (10/53), larynx (5/53), trachea (2/53), and oropharynx (1/53). The most commonly observed consequences of e-cigarette use on the upper airway included: proinflammatory (15/53 studies), histological (13/53), cytotoxicity (11/53), genotoxicity (11/53), and procarcinogenic (6/53). E-cigarette humectants independently induced toxicity at multiple upper airway subsites, however, effects were generally amplified when flavoring(s) and/or nicotine were added. Across almost all studies, exposure to cigarette smoke exhibited increased toxicity in the upper airway compared with exposure to e-cigarette vapor. CONCLUSION: Current data suggest that while e-cigarettes are generally less harmful than traditional cigarettes, they possess a distinct toxicological profile that is enhanced upon the addition of flavoring(s) and/or nicotine. Future investigations into underexamined subsites, such as the oropharynx and hypopharynx, are needed to comprehensively understand the effects of e-cigarettes on the upper airway.

"Left on their own": Left-handedness among rhinologists and otolaryngology trainees.

KEY POINTS: Left-hand-dominant (LHD) respondents reported higher rates of training difficulties because of handedness differences. LHD respondents cited particular difficulty with functional endoscopic sinus surgery. Both LHD and right-hand-dominant respondents perceived a need for laterality-specific training during residency.

Primary ciliary dyskinesia: An update on contemporary diagnosis.

KEY POINTS: Primary ciliary dyskinesia (PCD) is a complex diagnosis without a universal diagnostic test Clinicians must have some skepticism of historic diagnoses of PCD Clinicians should consider a diagnosis of PCD in patients with recalcitrant disease.

In Vivo Fluticasone Absorption in Surgical Patients.

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

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

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

Simple and safe resection of the crista galli.

A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several disadvantages. We reviewed the cases of patients with olfactory neuroblastomas who underwent an endoscopic endonasal transcribriform approach using a newly developed technique for crista galli resection. We performed a cadaveric study to measure the superior accessibility limits using the proposed method. We included 38 patients with olfactory neuroblastomas in this study. The tumor invaded the posterior crista galli in four patients. The anterior end of the crista galli was not invaded by the tumor. Our cadaveric study showed that the dura was approachable to the point that was 7.4 ± 1.3 mm superior and 23.2 ± 7.2 mm lateral to the foramen cecum following crista galli removal. By resecting the crista galli in advance, manipulation of the superior dura became feasible.

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

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

Characterizing Adverse Events of Biologic Treatment of T2 Disease: A Disproportionality Analysis of the FDA Adverse Event Reporting System.

INTRODUCTION: Over the last 3 years, the FDA has approved dupilumab, omalizumab, and mepolizumab for the treatment of CRSwNP; however, adverse events of these biologics have not been described in post-marketing surveillance trials. By utilizing the FDA Adverse Event Reporting System (FAERS), this study describes and compares biologic-associated adverse events in T2 disease. METHODS: This case-non-case study assessed disproportionate reporting rates using reporting odds ratios (RORs). RORs and p values for biologic-associated AEs were categorized and compared among dupilumab, omalizumab, and mepolizumab. This analysis included AEs associated with all treatment indications. Relative AE rates and outcomes were calculated. RESULTS: There were a total of 112,560, 24,428, and 18,741 unique AE reports associated with dupilumab, omalizumab, and mepolizumab, respectively. Omalizumab had the strongest association with anaphylaxis (ROR = 20.80, 95% confidence interval [CI]: 18.58, 23.29). Dupilumab had large relative proportions and positive signals in the ophthalmologic category (7.76%, ROR = 6.20, 95% CI: 6.06, 6.35), such as with blurry vision (ROR = 3.80, CI: 3.52, 4.12) and visual impairment (ROR = 1.98, CI: 1.80, 2.19). Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). DISCUSSION/CONCLUSION: This is the first large-scale comparative analysis of the AE profiles of dupilumab, omalizumab, and mepolizumab. Our data suggest possible relations between dupilumab and ophthalmologic and injection-site AEs. Omalizumab was the only biologic with a positive anaphylaxis signal. This FAERS investigation suggests important AE differences among these biologics.

Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis.

KEY POINTS: We present the largest cohort of structured histopathology reports on primary ciliary dyskinesia-related chronic rhinosinusitis (PCD-CRS). Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.

Elexacaftor-tezacaftor-ivacaftor decreases pseudomonas abundance in the sinonasal microbiome in cystic fibrosis.

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

Characteristics of olfactory dysfunction in patients with long-haul covid-19.

Background: A subset of individuals suffering from Coronavirus Disease 2019 (COVID-19) will experience ongoing symptoms that last longer than three months (i.e., long-haul COVID). This includes olfactory dysfunction (OD), which is currently estimated to occur in 1-63.5% of patients at one-year post-infection. However, OD in individuals with long-haul COVID-19 is poorly understood, and there is little information regarding how initial SARS-CoV-2 variants correlate with long-haul symptoms. In this study, we investigated the prevalence and severity of OD in patients with long-haul COVID-19 and investigated how OD severity varied with SARS-CoV-2 variants. Methods: Patients were recruited from the University of North Carolina-Chapel Hill COVID Recovery Clinic. Each patient completed the University of Pennsylvania Smell Identification Test (UPSIT). The dominant strain at the time of infection was determined using the date of COVID-19 diagnosis, and Centers for Disease Control and Prevention, World Health Organization, and North Carolina Department of Health and Human Services databases. Results: Nearly 85% of patients with long-haul COVID-19 reported some degree of OD, which persisted in some patients for two or more years from the date of the initial infection. There was no association between the time since COVID-19 infection and severity of OD. No difference was detected between OD in patients with long-haul COVID-19 based on the dominant variant at the time of infection (p=0.0959). Conclusion: A vast majority of patients with long-haul COVID-19 had some degree of ongoing olfactory complications, although the severity of symptoms was not dependent on the dominant SARS-CoV-2 variant at the time of infection.

Mucolytic treatment of chronic rhinosinusitis in a murine model of primary ciliary dyskinesia.

Background: Genetic defects in motile cilia cause primary ciliary dyskinesia (PCD), a rare disease with no specific therapeutics. Individuals with PCD often have impaired fertility and laterality defects and universally suffer from upper and lower airway diseases. Chronic rhinosinusitis is a universal feature of PCD, and mucus accumulation and subsequent infections of the sinonasal cavity cause significant morbidity in individuals with PCD. Despite this, there are no approved treatments that specifically target mucus. Objective: The goals of this study were to determine whether computed tomography (CT) imaging could be used to quantify mucus accumulation and whether the use of a mucolytic agent to reduce disulfide cross-links present in mucins would improve the effectiveness of nasal lavage at removing mucus in a murine model of PCD. Methods: Adult mice with a deletion of the axonemal dynein Dnaic1 were imaged using CT scanning to characterize mucus accumulation. The animals were then treated by nasal lavage with saline, with/without the disulfide-reducing agent tris(2-carboxyethyl)phosphine. Post-treatment CT scans were used to quantify improvement in the sinonasal cavity. Results: Mucus accumulation in the nasal cavity was readily quantified by CT. Compared to sham-treated control animals, nasal lavage with/without a mucolytic agent resulted in a significant reduction of accumulated mucus (p < 0.01). Treatment with the mucolytic agent showed a greater reduction of accumulated mucus than treatment with saline alone. Conclusion: The results suggest that inclusion of a mucolytic agent may increase the effectiveness of nasal lavage at reducing mucus burden in PCD.

Plasmacytoma of the Head and Neck: Case Series and Review of the Literature.

Solitary plasmacytoma is a rare neoplasm characterized by localized proliferation of monoclonal plasma cells and is classified as solitary bone or solitary extramedullary plasmacytoma. Here, we present two rare cases of plasmacytoma of the head and neck. The first is a 78-year-old male who presented with a 3-month history of epistaxis and progressive obstruction of the right nasal passage. Computerized tomography (CT) imaging revealed a mass in the right nasal cavity with destruction to the maxillary sinus. An excisional biopsy was performed revealing anaplastic plasmacytoma. The second is a 64-year-old male with a past medical history significant for prostate cancer who presented with a 2-month history of left ear pain and progressive non-tender temporal swelling. A PET/CT revealed a highly avid, destructive, and lytic left temporal mass with no other evidence of distant disease. A left temporal craniectomy and infratemporal fossa dissection revealed plasma cell dyscrasia with monoclonal lambda in situ hybridization. Although plasmacytomas are uncommon tumors of the head and neck, they may mimic other entities that require different treatment. Prompt and accurate diagnosis is critical for appropriate therapeutic decisions and prognosis.