International Forum of Allergy and Rhinology

International Forum of Allergy and Rhinology

Impact of margin status on survival after surgery for sinonasal squamous cell carcinoma

22-08-2019 – Aria Jafari, Sarek A. Shen, Jesse R. Qualliotine, Ryan K. Orosco, Joseph A. Califano, Adam S. DeConde

Journal Article

Background
Sinonasal squamous cell carcinoma (SNSCC) is the most common malignancy of the paranasal sinuses. Surgery is the mainstay of treatment, yet positive surgical margins (PSM) are common and the prognostic impact on overall survival (OS) is mixed. Given the heterogeneity of impact of PSM on OS within the literature, we hypothesized that extent of tumor extirpation (microscopic PSM vs macroscopic PSM) may play a role in OS.
Methods
Patients with SNSCC were identified in the National Cancer Database (NCDB, n = 7808). Of these, 4543 patients underwent surgery, 3265 patients underwent nonsurgical therapy. Kaplan‐Meier curves were used to compare OS between negative surgical margin (NSM), micro‐PSM, and macro‐PSM cohorts vs patients undergoing primary nonsurgical therapy in a propensity‐score‒matched analysis. Multivariable analysis of factors associated with macro‐PSM was also performed.
Results
One thousand thirty‐three (22.0%) of the surgery patients had PSM, and approximately half (n = 521, 50.6%) of these had macro‐PSM. When compared with nonsurgical treatment, propensity‐score‒matched results demonstrated improved OS in patients with NSM and micro‐PSM (p < 0.001), but macro‐PSM patients did not demonstrate improvement (p = 0.20). Tumor within the paranasal sinuses and advanced nodal classification (N2/N3) (odds ratio OR, 1.18; p = 0.02; and OR, 15.09; p = 005, respectively) was associated with increased odds of macro‐PSM on multivariable analysis.
Conclusions
We demonstrate that the degree of tumor extirpation correlates with OS. Macro‐PSM did not confer a benefit to OS when compared with nonsurgical therapy, and factors including tumor location and advanced nodal status affect whether surgery will result in macro‐PSM. Given these findings, informed, shared decisionmaking between patient and surgeon regarding nonsurgical alternatives should occur before electing to proceed with surgery in SNSCC.

The effect of olfactory training on odor identification in patients with traumatic anosmia

21-08-2019 – Rong‐San Jiang, Chih‐Wen Twu, Kai‐Li Liang

Journal Article

Background
This study investigates the effect of olfactory training on odor identification in patients with traumatic anosmia.
Methods
Patients with a clear history of loss of smell after head injury, and whose phenyl ethyl alcohol (PEA) odor detection thresholds remained at –1 after steroid and zinc treatment, were included in this study between July 2016 and July 2018. They were randomly divided into 2 groups, with patients in the 4‐odorant group given 4 bottles of PEA, lemon, eucalyptus, and clove oils and those in the PEA group given a bottle of PEA for 6‐month olfactory training. After 3‐month and 6‐month training, the olfactory function was evaluated by both the PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT‐TC). Magnetic resonance imaging was performed to measure the volume of olfactory bulbs after training.
Results
There were 45 patients completing 4‐odorant training and another 45 completing PEA training. The birhinal PEA threshold decreased significantly in both groups after 6‐month training, but the decrease was not significantly different between the 2 groups. The UPSIT‐TC score increased significantly in the PEA group but not in the 4‐odorant group. The volume of olfactory bulbs was not significantly different between these 2 groups.
Conclusion
Our results show that olfactory training can slightly improve odor threshold levels in patients with traumatic anosmia, but did not improve the odor identification ability. Nevertheless, clinical improvement or benefit in quality of life from olfactory training needs further investigation.

Are rhinoviruses implicated in the pathogenesis of sinusitis and chronic rhinosinusitis exacerbations? A comprehensive review

20-08-2019 – Usmaan Basharat, Mazen M. Aiche, Marianne M. Kim, Maheep Sohal, Eugene H. Chang

Journal Article, Review

Background
Rhinovirus (RV) infections are the most common cause of viral upper respiratory infections (URIs), and in the majority of persons they are self‐limiting. However, in others, viral URIs can progress to bacterial sinusitis and induce chronic rhinosinusitis (CRS) exacerbations.
Methods
We conducted a comprehensive Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) review through April 2018 based on MEDLINE, EMBASE, Web of Science–Science Citation Index (SCI), and Conference Proceedings Citation Index‐ Science (CPCI‐S) using keywords: RV, respiratory virus, sinusitis, and airway epithelial cells. The goal of this systematic review was to: (1) determine the prevalence between RV and CRS, (2) study the changes that occur after experimental RV inoculation, (3) investigate the pathophysiologic mechanisms by which RV induces sinonasal inflammation, and (4) explore the treatment options available for RV‐associated sinusitis. Data regarding study design, research question, intervention, subjects, outcomes, and biases was extracted.
Results
The initial search yielded 2395 unique abstracts, of which 614 were selected for full‐text review; 147 were included in the final review. We determined that (1) the prevalence of RV infections is increased in those with CRS, (2) humans challenged in vivo with RV secrete local inflammatory mediators with radiographic mucosal thickening, (3) RV species RV‐A and RV‐C challenges in vitro to sinonasal epithelia produce robust cytokine responses and differential gene changes, and (4) no current therapies have produced consistent and significant resolution of disease.
Conclusion
RV infections are common in persons with CRS, and incite inflammatory reactions that may result in CRS exacerbations and progression of disease. Further studies assessing RV species, and the host‐virome response are required to develop new strategies targeting RV‐induced CRS.

Escalation in mucus cystatin 2, pappalysin‐A, and periostin levels over time predict need for recurrent surgery in chronic rhinosinusitis with nasal polyps

20-08-2019 – Sarina K. Mueller, Olaf Wendler, Angela Nocera, Philipp Grundtner, Patrick Schlegel, Abbas Agaimy, Heinrich Iro, Benjamin S. Bleier

Journal Article

Background
Chronic rhinosinusitis with nasal polyps (CRSw
NP) is treated using oral/topical steroids and surgery. Despite maximal medical therapy, some patients remain recalcitrant. Mucus cystatin 2, pappalysin‐A, and periostin can predict the presence of CRSw
NP and correlate with disease severity. This study was designed to determine whether prospective sampling of these mucus proteins could predict medical failure and the need for revision surgery.
Methods
This investigation was an institutional review board‒approved, prospective study of 66 patients with CRSw
NP. All patients underwent surgery, administration of topical/oral steroids, and outpatient mucus sampling at 10 time‐points over 2 years. Five proteins, including cystatin 2 (CST2), pappalysin‐A (PAPP‐A), and periostin (PST), were analyzed and correlated with subjective parameters (including scores on the 22‐item Sino‐Nasal Outcomes Test SNOT‐22). Variables were then analyzed and compared between those requiring revision surgery within 2 years (n = 5) and those with stable disease (n = 61).
Results
All patients demonstrated a significant decline in CST2, PAPP‐A, and periostin after their initial surgery. The recalcitrant group demonstrated escalations in all proteins despite steroids, with levels higher than those of the stable group at 1 year (CST2: 258.1 ± 205.2 pg/m
L vs 235.3 ± 275.7 pg/m
L, p = 0.86; PAPP‐A: 170.3 ± 150.4 pg/m
L vs 74.6 ± 106.7 pg/m
L, p < 0.05; periostin: 188.8 ± 192.4 ng/m
L vs 54.5 ± 47.6 ng/m
L, p < 0.001). Escalation in all proteins correlated significantly with worsening SNOT‐22 score at each time‐point (domain 1: 8.2 ± 1.3 vs 5.5 ± 1.1; p < 0.05).
Conclusion
Early recurrences and medical recalcitrance in CRSw
NP may be predicted noninvasively through the serial, prospective sampling of mucus CST2, PAPP‐A, and periostin levels. These biosignatures may help to predict disease course and guide individualized therapy.

A brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis

20-08-2019 – Jose L. Mattos, Campbell Edwards, Rodney J. Schlosser, Madison Hyer, Jess C. Mace, Timothy L. Smith, Zachary M. Soler

Journal Article

Background
The Questionnaire of Olfactory Disorders‒Negative Statements (QOD‐NS) is a valuable instrument in the measurement of olfactory‐specific quality of life (QOL). In the clinical setting, patients can be overwhelmed with the time required to complete questionnaires. Our objective was to develop a brief version of the QOD‐NS to streamline clinical care and research.
Methods
QOD‐NS scores from 221 subjects were used to determine which subset of the 17 QOD‐NS questions best correlated with total and subdomain QOD‐NS scores. An initial pool of 11 questions was made by removing items with ρ < 0.80 to their respective subdomain scores. Next, 500 bootstrapped samples were taken. On each sampe, an all‐subsets regression was performed with total QOD‐NS scores and QOD‐NS subdomain scores as the outcomes. From this, our “top” and “bottom” 10 subsets were identified based on mean r2 value, representation in bootstrap analysis, and number of items.
Results
All of our top subsets had excellent correlation with total and subdomain QOD‐NS scores (mean r2 > 0.90). Our top choice has 7 total questions, is representative of all subdomains, has a mean r2 = 0.92, and was represented in 323 of our 500 bootstrapped samples. The worst‐performing subset has 5 items, mean r2 = 0.81, and was represented in only 1 bootstrapped sample.
Conclusions
Using less than half of the questions in the QOD‐NS, excellent correlations with both total and domain‐specific scores are achieved. A brief version of the QOD‐NS may prove useful in future clinical and research settings.

Erratum for “Scientific abstracts for RhinoWorld 2019”

20-08-2019 –

Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia

20-08-2019 – Justin P. McCormick, Christopher G. Weeks, Nicholas J. Rivers, Jacob D. Owen, David R. Kelly, Steven M. Rowe, George M. Solomon, Bradford A. Woodworth, Do‐Yeon Cho

Journal Article

Background
Mucociliary clearance is a main defense mechanism of the airway and is impaired in ciliary dyskinesia. The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia.
Methods
Bronchiectasis patients referred to a rhinology clinic for nasal brush biopsy (NBB) were included in this study. NBB was performed using a curettage technique whereby ciliated epithelial cells were obtained from the surface of the inferior nasal turbinate. Results of transmission electron microscopy findings, primary ciliary dyskinesia (PCD) gene (35 genes) analyses (Invitae), and sinus computed tomography (CT) scans were reviewed.
Results
Twenty‐three patients (age, 54 ± 2.9 years) were referred for NBB between 2015 and 2018. Thirteen patients (56.5%) met the criteria for diagnosis of CRS. Nineteen patients had ciliary ultrastructural defects. The most common finding was compound cilia (n = 11, 47.8%). Five patients (21.7%) had central microtubule defects (CMD) with higher forced expiratory volume in 1 second (FEV1) at the time of referral than those without CMD (CMD+, 91 ± 3.7%; CMD−, 73.5 ± 5.7%; p = 0.023). Of 15 subjects with a PCD gene panel, 67% (9 of 15) carried at least 1 gene associated with PCD. Only 1 patient reached diagnosis of PCD. Approximately 50% of non‐PCD carriers had a smoking history (p < 0.05). Lund‐Mackay scores did not significantly differ between PCD and non‐PCD carriers (p = 0.72).
Conclusion
Nearly half of bronchiectasis patients referred for NBB had concurrent CRS. The presence of ciliary abnormalities was not amplified in bronchiectasis patients with CRS compared to those without CRS. Extrinsic factors may be related to ciliary structural abnormalities in non‐PCD gene carriers.

The effect of neutrophil serine proteases on human nasal epithelial cell barrier function

12-08-2019 – Stephen Shih‐Teng Kao, Mahnaz Ramezanpour, Ahmed Bassiouni, Peter‐John Wormald, Alkis James Psaltis, Sarah Vreugde

Journal Article

Background
The neutrophil serine proteases neutrophil elastase (NE), cathepsin G (CG), and proteinase 3 (PR3) are implicated in the regulation of inflammatory conditions. Pseudomonas aeruginosa elastase (PE), also a serine protease, has been found to behave similarly to NE and has been proposed to assist the pathogen in evading the host immune response. The effect of serine proteases on human nasal epithelial barrier function requires further investigation to better understand the pathophysiology of inflammatory conditions.
Methods
Purified human neutrophil serine proteases and PE were applied to primary human nasal epithelial cells grown at air‐liquid interface (HNEC‐ALI) cultures from 6 patients. Barrier integrity and function was assessed via transepithelial electrical resistance (TER), permeability assays, immunofluorescence of Zona occludens‐1 (ZO‐1), and ciliary beat frequency (CBF) measurements. Cytotoxicity assays were employed to assess cell viability. Interleukin 6 (IL‐6) and IL‐8 enzyme‐linked immunosorbent assay (ELISA) assessed cytokine release from HNEC‐ALI.
Results
The application of serine proteases showed detrimental effects on HNEC‐ALI barrier integrity. Reduction in TER occurred with NE, CG, and PE with increased paracellular permeability with NE, CG, PR3, and PE. Discontinuous tight junctions with reduction in ZO‐1 expression were identified using immunofluorescence. Neutrophil serine proteases were not toxic cells to the HNECs and had no detrimental effects on the CBF.
Conclusion
Serine proteases derived from neutrophils and from P. aeruginosa showed detrimental effects on the mucosal barrier integrity with increased permeability, allowing for potential bacterial invasion. This finding may further assist in understanding the pathophysiology present in chronic inflammatory airway diseases.

Endoscopic repair of spontaneous skull base defects decreases the incidence rate of intracranial complications

12-08-2019 – Jordan J. Allensworth, Nicholas R. Rowan, Kristina A. Storck, Bradford A. Woodworth, Rodney J. Schlosser

Journal Article

Background
Spontaneous skull base defects can result in life‐threatening intracranial complications (ICCs), including meningitis and pneumocephalus. Endoscopic skull base reconstruction (ESBR) has traditionally been the treatment of choice, but its impact upon ICCs is not known. In this study, we aimed to describe the incidence rate of preoperative ICCs in patients with spontaneous skull base defects, risk factors associated with ICC development, and the impact of surgical repair on the incidence rate of ICCs.
Methods
A retrospective review was performed of all spontaneous skull base defects undergoing ESBR from 2005 to 2019 at 2 academic tertiary care medical centers. The incidence rate of ICCs and the demographics information and risk factors were collected.
Results
In 222 spontaneous skull base defects, preoperative ICCs occurred in 46 subjects (20.7%) with an incidence rate of 22.7 per 100 person‐years. Factors significantly associated with preoperative ICCs included symptom duration, reduced body mass index (BMI), resolved cerebrospinal fluid rhinorrhea, and location in the frontal or lateral sphenoid sinuses. Endoscopic repair was successful in 97.2% of subjects and the postoperative ICC incidence rate was significantly reduced at 0.8 per 100 person‐years (p < 0.001).
Conclusion
Spontaneous skull base defects pose significant risk for life‐threatening ICCs. Our findings reveal significantly elevated odds of ICC development associated with resolved CSF rhinorrhea, lower BMI, longer duration of symptoms, and defect location. Endoscopic repair is highly successful with low morbidity and significantly reduces the incidence rate of intracranial complications.

Survival outcomes and prognostic factors of squamous cell carcinomas arising from sinonasal inverted papillomas: a retrospective analysis of 120 patients

12-08-2019 – Yunxia Li, Chengshuo Wang, Ru Wang, Shizhi He, Ling Feng, Hongzhi Ma, Meng Lian, Qian Shi, Qi Zhong, Xiaohong Chen, Jugao Fang, Luo Zhang

Journal Article

Background
This study aimed to analyze the prognostic factors and survival outcomes of squamous cell carcinoma (SCC) originating from sinonasal inverted papillomas (IPs), based on data from a single institution.
Methods
The data from 120 patients treated at the affiliated Beijing Tongren Hospital, Capital Medical University, for SCC originating from sinonasal IPs between 2005 and 2018 were retrospectively reviewed. Data related to demographic features, tumor characteristics, treatment modality, and clinical outcomes were collected. Survival data were investigated using the Kaplan‐Meier method, Cox regression analysis, and the nomogram model predictive of survival probabilities.
Results
Among 1034 patients with sinonasal IPs, 120 patients (11.6%) with malignancy were identified. The overall survival (OS) and disease‐free survival (DFS) rates at 5 years were 56.0% and 42.3%, respectively. Multivariate analysis showed that synchronous tumors and tumor stage were independent predictive factors for the risk of mortality (hazard ratio HR, 1.954; 95% confidence interval CI, 1.022‐3.737, p = 0.043; HR, 1.737, 95% CI, 1.095‐2.770, p = 0.020, respectively). The surgical margin was another important independent predictor, with patients with negative margins demonstrating a more than 2‐fold improved survival compared to those with positive margins (HR, 2.095; 95% CI, 1.031‐4.243; p = 0.041).
Conclusion
The main factors affecting the prognosis and outcomes were synchronous tumors, advanced tumor stage, and positive surgical margins. These findings highlight the importance of tumor biology and early detection in patient outcomes. In addition, risk factors should be taken into consideration during treatment planning and subsequent tumor surveillance.

Interleukin‐17A potentiates interleukin‐13‒induced eotaxin‐3 production by human nasal epithelial cells from patients with allergic rhinitis

12-08-2019 – Wei Wei Wang, Kai Zhu, Hong Wei Yu, Yong Liang Pan

Journal Article

Background
Interleukin (IL)‐17A is involved in the pathogenesis of allergic rhinitis (AR). Increased expression of IL‐17A is correlated with disease severity and nasal eosinophilia. However, the molecular mechanisms by which IL‐17A contributes to T‐helper 2 cytokine IL‐13‒driven pathology in AR remain unclear. We sought to obtain mechanistic insight into how IL‐17A and IL‐13 regulate the epithelial production of eotaxin‐3 representing eosinophilic inflammation in AR.
Methods
Human nasal epithelial cells (HNECs) from AR patients were cultured and stimulated with IL‐17A, IL‐13, or IL‐17A and IL‐13. Phosphorylated signal transducer activator of transcription 6 (p‐STAT6) and suppressor of cytokine signaling 1 (SOCS1) in HNECs were assayed using Western blotting. Immunocytochemistry was used to determine p‐STAT6‒positive expression in the cells. Eotaxin‐3 expression in the cells and culture supernatants was evaluated using real‐time polymerase chain reaction and enzyme‐linked immunosorbent assays.
Results
Stimulation with IL‐13 alone induced STAT6 phosphorylation and promoted p‐STAT6 nuclear translocation, leading to eotaxin‐3 production by HNECs. These effects were further enhanced by cotreatment with IL‐13 and IL‐17A, whereas IL‐17A alone had no impact on STAT6 or eotaxin‐3 expression. Incubation with IL‐17A or IL‐13 increased the level of SOCS1 protein in the cells, whereas the addition of IL‐17A attenuated IL‐13‒induced SOCS1 expression.
Conclusion
IL‐17A potentiated IL‐13‒driven STAT6 activation through the downregulation of SOCS1 expression, leading to enhancement of eotaxin‐3 production by HNECs. These factors contributed to eosinophilic inflammation in AR.

Frontal sinus “mega‐trephination” in a tertiary rhinology practice

12-08-2019 – Mathew Geltzeiler, Alia Mowery, Kara Y. Detwiller, Jess C. Mace, Timothy L. Smith

Journal Article

Background
Frontal sinus trephination is traditionally performed through a small cutaneous incision and osteotomy, allowing irrigation of the frontal sinus. Utilizing the trephination osteotomy for endoscopic visualization and surgical manipulation requires a larger opening. This “mega‐trephination” is thought to carry an increased risk of cosmetic deformity given the increased bony removal at the anterior table. The purpose of our study was to clarify the risks of frontal sinus mega‐trephination and examine how this technique is incorporated into a modern, tertiary care rhinology practice.
Methods
Patients were identified through billing records and confirmed by retrospective chart review. All patients underwent frontal sinus mega‐trephination, which is defined as an osteotomy large enough for insertion of a 4‐mm endoscope and an operative instrument simultaneously. All patients had at least 2 years of follow‐up. The primary outcome was complication rate, including cosmetic deformity.
Results
Sixty‐four patients underwent frontal sinus mega‐trephination from 2006 to 2016. The most common surgical indications were chronic sinusitis (34%), mucocele (19%), osteoma (17%), acute sinusitis (11%), and inverting papilloma (9%). Ten patients (16%) underwent mega‐trephination alone, whereas the others had mega‐trephination with endoscopic sinus surgery. Twenty‐one patients (33%) had minor complications. The most common complications were self‐limited paresthesia (11%), infection (8%), and epistaxis (3%). No patient complained of permanent cosmetic deformity or required revision surgery for cosmesis.
Conclusion
Frontal sinus mega‐trephination is a useful tool to augment the rhinologists armamentarium in complex frontal sinus anatomy and pathology. This procedure is well tolerated, safe, and not associated with long‐term cosmetic deformity.

Diverse phenotypes and endotypes of fungus balls caused by mixed bacterial colonization in chronic rhinosinusitis

12-08-2019 – Dong‐Kyu Kim, Young Chan Wi, Su‐Jin Shin, Kyung Rae Kim, Dae Woo Kim, Seok Hyun Cho

Journal Article

Background
The pathogenic roles of fungus and bacteria in chronic rhinosinusitis (CRS) remain unclear. Recently, we described the bacterial ball, which is distinct from the fungus ball, as an unusual phenotype of bacterial infection. In this study, we investigated the clinical, histopathologic, and immunologic characteristics of sinonasal microorganic materials, including fungus ball and bacterial ball.
Methods
In this study, we enrolled 80 CRS patients with sinonasal microorganic materials and 10 control subjects who underwent skull base surgery or endoscopic dacryocystorhinostomy and had no signs or symptoms of nasal inflammation. All specimens were stained with hematoxylin‐eosin, Gomori‐methenamine‐silver, and Gram stain to identify fungal organisms and Gram‐positive/negative bacterial colonies. The expression of tumor necrosis factor (TNF)‐α; interleukin (IL)‐1β; S100A7; S100A8/A9; and short, palate, lung, and nasal epithelial clone 1 (SPLUNC1) were evaluated by enzyme‐linked immunosorbent assay using sinus lavage fluid.
Results
We histologically classified sinonasal microorganic materials into the following 4 groups: fungus ball (n = 45); bacterial ball (n = 6); mixed ball (formed by a mixture of fungus and bacteria, n = 27); and double ball (formed by separate fungal and bacterial balls, n = 2). Compared with the fungus ball, the mixed ball was more frequently detected in immunocompromised patients (p < 0.0001). In addition, TNF‐α expression was significantly higher in fungus and mixed balls than in control, whereas the mixed ball showed higher expression of IL‐1β compared with the fungus ball. Moreover, the expression of S100A7 and S100A8/A9 protein in the mixed ball was significantly decreased when compared with the fungus ball, whereas there was no significant difference in SPLUNC1 expression between fungus and mixed balls.
Conclusion
Our findings suggest that fungal and bacterial interactions are diverse in CRS. Specifically, the mixed ball is prevalent in CRS with an immunocompromised state and it may decrease epithelial barrier function.

Assessment of bioabsorbable implant treatment for nasal valve collapse compared to a sham group: a randomized control trial

07-08-2019 – Pablo Stolovitzky, Brent Senior, Randall A. Ow, Neelesh Mehendale, Nadim Bikhazi, Douglas M. Sidle

Journal Article

Background
Dynamic nasal valve collapse (NVC) is a common factor contributing to nasal obstruction; however, it is often underdiagnosed and untreated. An in‐office, minimally invasive procedure addressing dynamic NVC uses a bioabsorbable implant (Latera) to support the lateral nasal wall. This study aimed to evaluate the safety and effectiveness of the treatment in a randomized controlled trial (RCT) with sham control.
Methods
In this prospective, multicenter, single‐blinded RCT, 137 patients from 10 clinics were randomized into 2 arms: treatment arm (70 patients) and sham control arm (67 patients). Outcome measures were followed through 3 months after the procedure. The primary endpoint was the responder rate (percentage of patients with reduction in clinical severity by ≥1 category or ≥20% reduction in Nasal Obstruction Symptom Evaluation NOSE score).
Results
Before the procedure, there were no statistically significant differences in patient demographics and nasal obstruction symptom measures between the 2 arms. Three months after the procedure, responder rate was significantly higher for the treatment arm compared to the control (82.5% vs 54.7%, p = 0.001). Patients in the treatment arm also had a significantly greater decrease in NOSE score (–42.4 ± 23.4 vs –22.7 ± 27.9, p < 0.0001) and significantly lower visual analogue scale (VAS) scores (–39.0 ± 29.7 vs –13.3 ± 30.0, p < 0.0001) than the sham control arm. Seventeen patients reported 19 procedure/implant‐related adverse events, all of which resolved with no clinical sequelae.
Conclusion
Our study shows the safety and effectiveness of the bioabsorbable implant in reducing patients’ nasal obstruction symptoms.

Long‐term outcomes of endoscopic sinus surgery in the management of adult chronic rhinosinusitis

07-08-2019 – Timothy L. Smith, Rodney J. Schlosser, Jess C. Mace, Jeremiah A. Alt, Daniel M. Beswick, Adam S. DeConde, Kara Y. Detwiller, Jose L. Mattos, Zachary M. Soler

Journal Article

Background
There is a striking lack of long‐term, prospective outcomes data for endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) using validated instruments. Our primary objective in this study was to report long‐term outcomes (>10 years) after ESS for CRS obtained by prospective data collection.
Methods
An observational cohort (n = 59) of adult patients with CRS electing ESS was enrolled between 2004 and 2008. Long‐term, disease‐specific quality‐of‐life (QOL) outcomes, health utility values (HUV), revision surgery rate, development of asthma, and patient expectations/satisfaction with outcomes of ESS were examined using descriptive statistics and simple fixed‐effects linear modeling.
Results
Fifty‐nine adult patients were followed for 10.9 years (±13.8 months), on average. Mean QOL significantly improved between baseline and 6 months and remained durable to 10 years. HUV improved to normal. A 17% revision surgery rate within the 10‐year follow‐up period was observed with a 25% revision rate in CRS with polyposis. New‐onset asthma after ESS occurred at a rate of 0.8%/year. Patient satisfaction with ESS outcomes was generally high.
Conclusions
Ten‐year prospective outcomes of ESS for CRS demonstrate that the initial clinically significant improvements in QOL seen 6 months postoperatively are durable over the long term. Over 75% of patients reported clinically significant long‐term QOL and HUV improvement. HUV returned to normal. Revision surgery rate was 17% and worse postoperative endoscopy scores within 18 months of initial ESS were associated with higher likelihood of revision surgery. Most patients would pursue ESS again and recommend the procedure to other patients considering this treatment option.

Intranasal endoscopic identification of the nasal septal L‐strut: a cadaveric study

07-08-2019 – Riyadh Alhedaithy, Ahmed Alhussien, Ahmad Alroqi, Saud Alromaih, Mohammad Aloulah, Saad Alsaleh

Journal Article

Background
Preserving the L‐shaped strut during septoplasty is a crucial step in the prevention of several types of postoperative nasal deformities. In this study, we aimed to identify the intranasal anatomic landmarks to establish reliable and feasible measurements to preserve an adequate L‐strut during an endoscopic septoplasty.
Methods
A prospective study was conducted on 20 cadaver heads. Three measurements were studied within each side of the nasal cavity. The dorsal strut (DS) was measured from the dorsal line to the septal dorsum edge. Then, the caudal strut was measured from 2 different landmarks: the axilla of the inferior turbinate (CSIT) and the pyriform aperture (CSP).
Results
We examined a total of 40 nasal cavities from 20 cadavers. The DS showed an average length of 15.1 mm (standard deviation SD, 3.2 mm). The average lengths of the CSIT and CSP were 23.6 (SD, 3.6) mm and 19.4 (SD, 2.7) mm, respectively.
Conclusion
Suggested landmarks to identify the dorsal and caudal struts in endoscopic septoplasty are the axilla of the middle turbinate and pyriform aperture bone, respectively. The utilization of the inferior turbinate axilla as a caudal strut landmark showed larger variability and would potentially leave excessive caudal cartilage that could be manipulated if deviated.

Esophageal IgE, IgG4, and mucosal eosinophilia in individuals with dysphagia

07-08-2019 – Apoorva T. Ramaswamy, Jae Seong No, Lillye Anderson, Aliza Solomon, Thomas Ciecierega, Elaine Barfield, Kimberly Chien, Felice Schnoll‐Sussman, William R. Reisacher

Journal Article

Background
Eosinophilic esophagitis (Eo
E) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with Eo
E manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (Ig
E) is directed, if any, have not yet been characterized.
Methods
Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of Eo
E. Specific Ig
E (s
Ig
E) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal Ig
E response and Ig
G4 to food allergens, were measured.
Results
There was no difference in total Ig
E harvested between the 2 biopsy methods (p > 0.05) or between the Eo
E‐positive (N = 12) and Eo
E‐negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum Ig
E to any of the airborne or food proteins tested, but low levels of Ig
E specific to Candida and Staphylococcus enterotoxins were detected. Low levels of Ig
G4 specific to wheat, soy, peanut, and egg were also detected.
Conclusions
Both MBB and STB are able to harvest measureable levels of Ig
E and Ig
G4 from the esophageal mucosa. Low levels of serum‐specific Ig
E suggest that other inflammatory mechanisms, besides type I, Ig
E‐mediated, allergen‐specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both Ig
E‐mediated and non‒Ig
E‐mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia.

Role of inferior turbinate reduction in the quality of life of patients undergoing endoscopic sinus surgery for chronic rhinosinusitis

07-08-2019 – Ethan Soudry, Jess Mace, Timothy L. Smith, Peter H. Hwang

Journal Article

Background
The impact on quality of life (QoL) of bilateral inferior turbinate reduction (BITR) performed in the setting of endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) has been a point of controversy. The aim of this study was to determine whether addition of BITR to ESS is associated with improved QoL when compared with ESS alone.
Methods
This study presented findings a multi‐institutional, retrospective analysis of a prospective open cohort of patients electing ESS for failed medical management of CRS. QoL parameters were compared between patients who underwent ESS alone vs those who underwent ESS with BITR.
Results
A total of 571 patients with CRS who elected to undergo ESS were identified. Sixty‐one of these patients also underwent concurrent BITR, whereas 510 patients underwent ESS without BITR. Mean length of follow‐up was 15.1 months. Comparison between baseline and last postoperative QoL, olfaction, and endoscopic scores revealed significant improvement in both groups. Overall, BITR surgery was not significantly associated with clinically significant incremental improvement in QoL in either the polyp or non‐polyp group. Nevertheless, statistically significant improvement was noted for the nasal congestion/blockage symptom in polyp patients (p = 0.006) and in primary surgery patients (p = 0.027) who underwent BITR.
Conclusion
BITR in the setting of ESS for CRS is not associated with significant incremental improvement in overall QoL vs ESS alone. However, BITR in polyp and primary surgery patients undergoing ESS appears to offer a significant incremental improvement in nasal congestion/blockage symptoms compared with ESS alone. Future studies are warranted to better corroborate these findings.

Impact of endoscopic craniofacial resection on simulated nasal airflow and heat transport

07-08-2019 – Lauren F. Tracy, Saikat Basu, Parth V. Shah, Dennis O. Frank‐Ito, Snigdha Das, Adam M. Zanation, Julia S. Kimbell

Journal Article

Background
Endoscopic craniofacial resections (CFR) are performed for extensive anterior skull base lesions. This surgery involves removal of multiple intranasal structures, potentially leading to empty nose syndrome (ENS). However, many patients remain asymptomatic postoperatively. Our objective was to analyze the impact of CFR on nasal physiology and airflow using computational fluid dynamics (CFD). This is the first CFD analysis of post‐CFR patients.
Methods
Three‐dimensional sinonasal models were constructed from 3 postoperative images using Mimics
TM. Hybrid computational meshes were created. Steady inspiratory airflow and heat transport were simulated at patient‐specific flow rates using shear stress transport k‐omega turbulent flow modeling in Fluent
TM. Simulated average heat flux (HF) and surface area where HF exceeded 50 W/m2 (SAHF50) were compared with laminar simulations in 9 radiographically normal adults.
Results
Three adults underwent CFR without developing ENS. Average HF (W/m2) were 132.70, 134.84, and 142.60 in the CFR group, ranging from 156.24 to 234.95 in the nonoperative cohort. SAHF50 (m2) values were 0.0087, 0.0120, and 0.0110 in the CFR group, ranging from 0.0082 to 0.0114 in the radiographically normal cohort. SAHF50 was distributed throughout the CFR cavities, with increased HF at the roof and walls compared with the nonoperative cohort.
Conclusion
Average HF was low in the CFR group compared with the nonoperative group. However, absence of ENS in most CFR patients may be due to large stimulated mucosal surface area, commensurate with the nonoperative cohort. Diffuse distribution of stimulated area may result from turbulent mixing after CFR. To better understand heat transport post‐CFR, a larger cohort is necessary.

Inverted papilloma with multifocal attachment is associated with increased recurrence

07-08-2019 – Charles C. L. Tong, Neil N. Patel, Ivy W. Maina, Vasiliki Triantafillou, Carol H. Yan, Edward C. Kuan, Michael A. Kohanski, Peter Papagiannopoulos, Alan D. Workman, Noam A. Cohen, David W. Kennedy, Nithin D. Adappa, James N. Palmer

Journal Article

Background
Inverted papilloma (IP) is a benign sinonasal tumor with a well‐known propensity to recur, especially at its bony attachment site. Anecdotal evidence suggests lower rate of recurrence in primary resection. We also aimed to evaluate the effect of multifocal vs single focus of attachment in disease control.
Methods
This work is a retrospective review of 535 IP resections performed during the period from 2006 to 2016 at a tertiary‐care center. Demographic data, tumor location and attachment sites, and follow‐up duration data were obtained.
Results
Two hundred ten patients were eligible for analysis. The mean age was 57 years, with an average postoperative surveillance of 36.4 months. Patients who had a previous procedure at an outside institution have a recurrence rate of 22.3%, compared with 12.4% for patients who had primary surgery at our institution. The most common site of attachment was maxillary sinus (47.6%), followed by ethmoid sinus (39%). Individual tumor review showed 50% of the patients to have multifocal attachment disease, of which there is a higher prevalence in secondary cases when compared with primary cases (53.7% vs 44.9%). Multiple tumor attachment sites had a significant effect on recurrence (odds ratio, 3.5; 95% confidence interval, 1.6‐7.6; p = 0.002).
Conclusion
Primary resection and single‐focus attachment of inverted papilloma are associated with lower recurrence rates at 3‐year follow‐up.

The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head‐to‐head study

07-08-2019 – Jie Li, Yuying Wu, Yongshi Yang, Nan Huang, Wenjing Li, Shuchen Zhang, Qing Jiang, Lin Yang, Rongfei Zhu

Journal Article

Background
Several studies have demonstrated the efficacy of house dust mite (HDM) immunotherapy in allergic rhinitis (AR). We aimed to compare the efficacy and safety of 2 commercial HDM extracts in a Chinese AR population.
Methods
This was an open‐label study. HDM‐associated AR patients were randomized into Dermatophagoides pteronyssinus (Dp) extracts (Alutard SQ; ALK, Hørsholm, Denmark) and Dp/Dermatophagoides farinae (Df) extracts (Novo
Helisen Depot NHD; Allergopharma, Reinbek, Germany) groups. All patients received subcutaneous injections for 1 year, and were followed every 3 months during that 1‐year period. Symptom score, medication score, and adverse reactions were recorded. The primary endpoint was the total combined symptom and medication score (CSMS) during the efficacy evaluation period. Blood samples were taken for specific immunoglobulin E (Ig
E), Ig
G4, and Ig
E‐blocking factor tests at baseline and after the 1‐year treatment.
Results
A total of 230 AR patients were randomized; 29 patients dropped out. Analysis of the primary endpoint demonstrated significant reductions in CSMS of 1.8 vs 3.1 (p < 0.001) in the Alutard group and 1.8 vs 3.3 (p < 0.001) in the NHD group compared with baseline. The 2 groups presented equal effectiveness with regard to CSMS, symptom score, and medication score (p > 0.05). The treatment was well tolerated in both groups; 17 (14.8%) patients experienced systemic reactions (SRs) in the Alutard group and 13 (11.3%) in the NHD group. The rates of SRs showed no difference in the 2 groups (p > 0.05), and no anaphylaxis occurred. Ig
G4 and Ig
E‐blocking factor to Dp and Df were increased significantly in both groups after the 1‐year treatment.
Conclusion
Our study confirmed the equal efficacy and safety profile of both commercial extracts in HDM‐associated AR patients.

Postoperative epistaxis and sphenoid sinus ostial stenosis after posterior septal branch injury during sphenoidotomy

07-08-2019 – Joanna Kam, Abid Ahmad, Amy Williams, Edward L. Peterson, John R. Craig

Journal Article

Background
Postoperative arterial epistaxis and sphenoid sinus stenosis after sphenoidotomies for endoscopic sinus surgery (ESS) and transsphenoidal approaches (TSAs) are uncommon. One potential source of epistaxis after sphenoidotomy is the sphenopalatine arterys posterior septal branch (PSB). PSB injury, in addition to other factors, could increase the risk of sphenoid stenosis. The purpose of this study was to determine incidence of, and risks factors for, the following outcomes after sphenoidotomy: PSB injury; postoperative epistaxis from the injured PSB; and sphenoid stenosis after PSB injury.
Methods
A single‐institution, prospective case series was conducted based on 233 sphenoidotomies performed during ESS (n = 163) and TSAs (n = 70). Outcome measures included intraoperative PSB injury, postoperative epistaxis from the PSB, and sphenoid stenosis.
Results
The incidence of PSB injury was 17.2% during ESS‐related sphenoidotomies, and 5.7% during TSA‐related sphenoidotomies (p = 0.010). After PSB injury during ESS‐ and TSA‐related sphenoidotomies (n = 32), there was 1 instance of epistaxis from the PSB (3.1%). Of the 161 ESS‐related sphenoidotomies, 6 developed complete or near‐complete stenosis (3.7%), which was more likely to occur with smaller anterior sphenoid face dimensions (p = 0.001). PSB injury, revision sphenoidotomy, and other factors did not increase the risk of stenosis. None of the TSA‐related sphenoidotomies stenosed completely. Median follow‐up was 7 months.
Conclusion
PSB injury occurred in 17.2% of ESS‐related sphenoidotomies and 5.8% of TSA‐related sphenoidotomies. After PSB injury, postoperative epistaxis from the PSB was rare (3.1%). After ESS‐related sphenoidotomies, sphenoid stenosis was rare (3.7%), and was more likely to occur with smaller sphenoid dimensions, but not with PSB injury or other factors.

Use of a crossing suture to correct caudal septal deviations

07-08-2019 – Yeon‐Hee Joo, Hyun‐Jin Cho, Yung Jin Jeon, Sang‐Wook Kim

Journal Article

Background
Septoplasty usefully treats patients with nasal obstructions caused by septal deviations. However, correction of a caudal septal deviation remains surgically challenging; no standard procedure is available, although various procedures have been introduced. In this work we propose a simple, safe, and time‐saving technique for patients with caudal septal deviations.
Methods
The medical records of 50 patients with caudal septal deviations who underwent septoplasty using a crossing‐suture technique from October 2016 to October 2018 were retrospectively reviewed. Postoperative nasal obstruction status and patient satisfaction with their surgical outcomes were subjectively evaluated using the Nasal Obstruction Symptom Evaluation (NOSE) score and telephone interview, respectively. Pre‐ and postoperative endoscopic findings were evaluated and postoperative complications developing during follow‐up were recorded.
Results
The NOSE scores of all patients improved after septoplasty. The mean score fell from 13.46 to 3.97, and this change was significant (p < 0.0001). No complication related to use of the crossing suture was encountered.
Conclusion
The crossing‐suture technique is a simple, safe, and useful surgical option for correction of caudal septal deviations.

Kappa‐carrageenan sinus rinses reduce inflammation and intracellular Staphylococcus aureus infection in airway epithelial cells

07-08-2019 – Catherine Bennett, Mahnaz Ramezanpour, Clare Cooksley, Sarah Vreugde, Alkis James Psaltis

Journal Article

Background
Chronic rhinosinusitis (CRS) is a common disease, often refractory to conventional antimicrobial treatment. In this study we investigate the antimicrobial and anti‐inflammatory effects of adding kappa‐carrageenan to a commercially available sinus rinse.
Methods
Kappa‐carrageenan was added to Flo CRS and Flo Sinus Care sinus rinses and applied directly to air‐liquid interface cultured primary human nasal epithelial cells (HNECs) from 10 CRS patients. Inflammatory markers were measured using enzyme‐linked immunosorbent assay. Kappa‐carrageenan‒supplemented sinus rinses were applied to human bronchial epithelial cells (HBEs) in the presence of different Staphylococcus aureus strains to observe the effect on intracellular infection rates.
Results
Flo Sinus Care with kappa‐carrageenan rinse solutions resulted in a marked reduction of interleukin‐6 (IL‐6) production by HNECs from CRS patients (p = 0.007). Both Flo CRS and Flo Sinus Care rinses significantly reduced the S aureus intracellular infection of HBEs (p < 0.0001). The addition of kappa‐carrageenan to both Flo CRS and Flo Sinus Care rinses further reduced the intracellular infection rate by an average of 2%.
Conclusions
The commonly used sinus irrigation product Flo Sinus Care with added kappa‐carrageenan reduces IL‐6 production by HNECs in vitro. Flo CRS and Flo Sinus Care rinses significantly reduced S aureus intracellular infection rates of HBE cells. Our findings may have clinical relevance for CRS patient management.

Validation of a rhinologic virtual surgical simulator for performing a Draf 3 endoscopic frontal sinusotomy

07-08-2019 – Tae‐Bin Won, Sung‐Woo Cho, Myung‐Whun Sung, Sun Ha Paek, Sonny Chan, Kenneth Salisbury, Nikolas H. Blevins, Yona Vaisbuch, Peter Hwang

Journal Article

Background
We recently introduced a patient‐specific rhinologic virtual surgical environment (VSE) that has shown potential for surgical rehearsal of various skull base lesions. Our aim in this study was to validate the usefulness of the rhinology VSE in performing the Draf 3 procedure.
Methods
An outside‐in Draf 3 procedure was performed on 4 cadaver heads. Computed tomography (CT) scans were obtained before and after cadaver dissection (CD). Pre‐dissection CT scans were used to construct a cadaver‐specific VSE. A virtual Draf 3 dissection (VD) was performed using the same technique. Validation was conducted by comparing the final common frontal outflow tract. A subjective comparison of the post‐dissection endoscopic findings (CD vs VD) and an objective measurement using the post‐dissection CT scan for the CD and the reconstructed CT scan obtained from the data after the VD was performed.
Results
Subjective overall resemblance of the 2 dissections (CD vs VD) assessed by the 4‐point Likert scale (0‐3) was 2.5 (median interquartile range IQR, 0.25) for the 4 cadavers. The median difference for the anteroposterior dimension of the frontal neo‐ostium (CD vs VD) assessed in the midsagittal view was 0.11 mm, whereas the median difference for the lateral dimension assessed in the coronal view was 2.71 mm. Thus, no statistical difference was observed.
Conclusion
VD showed nearly matching results with the actual cadaver dissection. With further validation, our rhinologic VSE may be used for presurgical planning and rehearsal before the actual Draf 3 procedure is performed in the operating room.

Asymptomatic vs symptomatic septal perforations: a computational fluid dynamics examination

07-08-2019 – Chengyu Li, Guillermo Maza, Alexander A. Farag, Jillian P. Krebs, Bhakthi Deshpande, Bradley A. Otto, Kai Zhao

Journal Article

Background
A nasal septal perforation (NSP) can lead to frustrating symptoms for some patients while remaining completely asymptomatic for others, without a clear mechanism differentiating them.
Methods
We applied individual computed tomography (CT)‐based computational fluid dynamics (CFD) to examine the nasal aerodynamics differences between 5 asymptomatic and 15 symptomatic NSP patients. Patients’ symptoms were confirmed through interviews, 22‐item Sino‐Nasal Outcome Test score (asymptomatic, 25 ± 18.8; symptomatic, 53.7 ± 18.2), nasal obstruction symptom evaluation score (asymptomatic, 28.0 ± 32.1; symptomatic, 62.2 ± 32.2), and review of medical history.
Results
No statistical differences were found in perforation location, size (asymptomatic, 1.94 ± 1.88 cm2; symptomatic, 1.36 ± 1.44 cm2), nasal resistance (asymptomatic, 0.059 ± 0.012 Pa·s/m
L; symptomatic, 0.063 ± 0.022 Pa·s/m
L), and computed flow rate shunting across the perforation (asymptomatic, 52.9 ± 30.9 m
L/s; symptomatic, 27.4 ± 23.6 m
L/s; p > 0.05). However, symptomatic patients had significantly higher wall shear stress (WSS) and heat flux, especially along the posterior perforation margin (WSS, 0.54 ± 0.12 vs 1.15 ± 0.49 Pa, p < 0.001; heat flux, 0.21 ± 0.05 vs 0.37 ± 0.14 W/cm2, p < 0.01). A WSS cutoff at 0.72 Pa can separate asymptomatic vs symptomatic NSP with 87% sensitivity and 100% specificity. Flow visualization showed flow peaks toward the posterior margin that may be responsible for the high WSS and heat flux among symptomatic NSPs.
Conclusion
This study is the first CFD examination of asymptomatic and symptomatic NSP with regional aerodynamics and stress abnormalities, beyond size or location, being implicated as the mechanism behind the symptomology of NSP. This finding could serve as an objective basis for future personalized treatment decisions and optimization.

Estimation of surgeons’ ergonomic dynamics with a structured light system during endoscopic surgery

07-08-2019 – David Lobo, Pedro Anuarbe, José Miguel López‐Higuera, Jaime Viera, Nathalia Castillo, Roberto Megía

Journal Article

Background
The purpose of this study was to use motion capture to collect body posture information during simulated endoscopic sinus surgery interventions performed by both specialists and residents in standing and sitting positions and to analyze that information with the validated Rapid Upper Limb Assessment (RULA) tool, which allows calculation of a risk index of musculoskeletal overload.
Methods
Bilateral endoscopic sinus surgery was performed in 5 cadaver heads by 2 residents, and 4 practicing rhinologists. Musculoskeletal symptoms were evaluated before and after the dissection. Full‐body postural data were collected with the help of Kinect and a .
NET WPF (Windows Presentation Foundation) software application to record images of the surgical procedures, and then analyzed with the RULA tool to calculate a risk score indicative of the exposure of the individual surgeon to ergonomic risk factors associated with upper extremity musculoskeletal disorders.
Results
All subjects reported physical discomfort after nasal endoscopic procedures. An overall similar RULA score was obtained by the residents and the practicing rhinologists. The RULA score was slightly lower for the sitting position than for the standing position, mostly due to a lower score in group B (neck, trunk, and leg); however, the RULA score for group A (arm and wrist analysis) was higher, denoting a higher risk for the upper back and arms.
Conclusion
Significant musculoskeletal symptoms were reported after an endoscopic operation by both the resident and the practicing otolaryngologists. All surgeons obtained a high RULA score, meaning that urgent changes are required in the task.

Answers to some common rhinologic questions

07-08-2019 – Joseph K. Han

Editorial

Issue Information

07-08-2019 –

Erratum for “Steroid‐eluting sinus implant for in‐office treatment of recurrent polyposis: a pharmacokinetic study”

07-08-2019 –

Published Erratum

Erratum for “Safety and efficacy of a novel bioabsorbable, steroid‐eluting sinus stent”

07-08-2019 –

Published Erratum

Computational fluid dynamic analysis of aggressive turbinate reductions: is it a culprit of empty nose syndrome?

07-08-2019 – Jennifer Malik, Chengyu Li, Guillermo Maza, Alexander A. Farag, Jillian P. Krebs, Sam McGhee, Gabriela Zappitelli, Bhakthi Deshpande, Bradley A. Otto, Kai Zhao

Journal Article

Background
Empty nose syndrome (ENS) remains highly controversial, with aggressive inferior turbinate reduction (ITR) or mucociliary dysfunction frequently implicated. However, the appropriate degree of ITR is highly debatable.
Methods
We applied individual computed tomography (CT)‐based computational fluid dynamics (CFD) to 5 patients receiving relatively aggressive ITR but with no ENS symptoms, and compared them to 27 symptomatic ENS patients who all had histories of aggressive ITRs, and 42 healthy controls. Patients’ surgical outcomes were confirmed with 22‐item Sino‐Nasal Outcome Test (SNOT‐22) (ITR: 6.40 ± 4.56; ENS: 58.2 ± 15.9; healthy: 13.2 ± 14.9), Nasal Obstruction Symptom Evaluation (NOSE) scores (ITR: 4.00 ± 2.24; ENS: 69.4 ± 17.1; healthy: 11.9 ± 12.9), and Empty Nose Syndrome 6‐Item Questionnaire (ENS6Q) (≥11 for ENS).
Results
Both aggressive ITR without ENS symptoms and symptomatic ENS patients had significantly lower nasal resistance (ITR: 0.059 ± 0.020 Pa·s/m
L; ENS: 0.052 ± 0.015 Pa·s/m
L; healthy: 0.070 ± 0.021 Pa·s/m
L) and higher cross‐sectional areas surrounding the inferior turbinate (ITR: 0.94 ± 0.21 cm2; ENS: 1.19 ± 1.05 cm2; healthy: 0.42 ± 0.22 cm2) than healthy controls. The lack of significant differences among patient groups indicated similar degrees of surgeries between ITR with and without ENS symptom cohorts. However, symptomatic ENS patients have paradoxical significantly less airflow in the inferior meatus (ITR: 47.7% ± 23.6%; ENS: 25.8% ± 17.6%; healthy: 36.5 ± 15.9%; both p < 0.01), but higher airflow around the middle meatus (ITR: 49.7% ± 22.6%; ENS: 66.5% ± 18.3%; healthy: 49.9% ± 15.1%, p < 0.0001) than aggressive ITR without symptoms and controls. Aggressive ITR patients have increased inferior meatus airflow as expected (p < 0.05). This imbalanced airflow produced less inferior wall‐shear‐stress distribution among symptomatic ENS patients only (ITR: 42.45% ± 11.4%; ENS: 32.2% ± 12.6%; healthy: 49.7% ± 9.9%). ENS patients (n = 12) also had impaired nasal trigeminal function, as measured by menthol lateralization detection thresholds (ITR: 15.2 ± 1.2; ENS: 10.3 ± 3.9; healthy: 13.8 ± 3.09, both p < 0.0001). Surprisingly, aggressive ITR patients without ENS symptoms have better menthol lateralization detection thresholds (LDTs) than healthy controls.
Conclusion
Although turbinate tissue loss is linked with ENS, the degree of ITR that might distinguish postoperative patient satisfaction in their nasal breathing vs development of ENS symptoms is unclear. Our results suggest that a combination of distorted nasal aerodynamics and loss of mucosal sensory function may potentially lead to ENS symptomology.

Serum levels of stress hormones in Albanian patients with allergic rhinitis

01-08-2019 – Violeta Lokaj‐Berisha, Besa Gacaferri‐Lumezi, Naser Berisha

Journal Article

Background
The integration of the immune and endocrine systems through a network of signaling molecules—including cytokines and hormones—produces a consequent modulatory effect on immune function. In this study we aimed to comparatively evaluate the serum concentrations of dehydroepiandrosterone sulfate (DHEA‐S) and cortisol in patients with allergic rhinitis and healthy control subjects.
Methods
Morning fasting blood samples were obtained from 96 participants, including 66 patients with allergic rhinitis (mean age, 28 ± 10.7 years; range, 11‐59 years) and 30 healthy control subjects (mean age, 32.4 ± 11.1 years; range, 14‐57 years). Total immunoglobulin E (Ig
E), DHEA‐S, and cortisol concentrations were measured by radioimmunoassay.
Results
Female patients with allergic rhinitis exhibited lower DHEA‐S levels than male patients and control subjects (p < 0.001). Although no intergroup differences were observed in the morning:evening cortisol ratio, the DHEA‐S:cortisol ratio was the highest among female patients with allergic rhinitis (1:11). Total Ig
E levels were significantly higher among patients of both sexes (p < 0.05) than among the control subjects. There was a positive correlation between body mass index and age among all groups of participants (male and female patients: r = 0.6 and 0.7, respectively; male and female controls: r = 0.6 and 0.4, respectively) and a negative correlation between DHEA‐S level and age among females (patients and controls: r = −0.4 and −0.5, respectively) and healthy male subjects (r = −0.7).
Conclusion
In this study, female patients with allergic rhinitis exhibited significantly lower DHEA‐S levels than their healthy counterparts and male patients. These results should be confirmed in a larger group of participants.

Olfactory dysfunction persists after smoking cessation and signals increased cardiovascular risk

31-07-2019 – Jesse K. Siegel, Kristen E. Wroblewski, Martha K. McClintock, Jayant M. Pinto

Journal Article

Background
Olfaction plays a critical role in health and function in older adults, and impaired sense of smell is a strong predictor of morbidity and mortality. Smoking cigarettes causes olfactory impairment, but the mechanism of damage and ability to recover after cessation are unknown. We investigated the relationship between time since quitting and olfactory dysfunction in order to elucidate the mechanism(s) by which smoking damages the olfactory system and to inform patient counseling.
Methods
Using longitudinal data from the National Social Life Health and Aging Project (n = 3528 older adults, including 1526 former smokers), we analyzed the association between odor identification performance and time since smoking cessation using multivariate ordinal logistic regression, adjusting for cognition and demographic variables. To test whether vascular disease plays a role, we also assessed the relationship between olfactory decline and incidence of heart attack and heart disease.
Results
Former smokers who quit ≤15 years before testing had significantly impaired olfaction compared to never smokers (p = 0.04), but those who quit >15 years prior did not. Olfactory decline over 5 years showed modest evidence toward predicting increased incidence of heart attack or heart disease (p = 0.08).
Conclusion
Olfactory impairment in smokers persists 15 years after quitting, which is consistent with a vascular mechanism of impairment. Indeed, olfactory decline is a predictor of the development of cardiovascular disease. Taken together, these data suggest that olfactory loss may be a useful sign of underlying vascular pathology. Further investigation of olfactory loss as an early biomarker for cardiovascular disease is warranted.

Sinonasal quality‐of‐life outcomes after endoscopic endonasal skull base surgery

29-07-2019 – Prashant N. Bhenswala, Rodney J. Schlosser, Shaun A. Nguyen, Suqrat Munawar, Nicholas R. Rowan

Journal Article

Background
There are substantial gaps in our understanding of the influence of the endoscopic endonasal approach (EEA) for endoscopic skull base surgery on sinonasal‐specific quality of life (QOL) as well as the instruments available for assessment. Our primary objective in this study was to characterize postoperative changes in sinonasal QOL, specifically using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22), with a secondary objective of delineating weaknesses in our current understanding of patient symptomatology after EEA for skull base surgery.
Methods
A comprehensive literature review was conducted using PubMed, CINAHL, Cochrane Library, and SCOPUS for studies reporting SNOT‐22 data pre‐ and postoperatively in patients who underwent EEA for skull base pathologies. Studies were limited to patients ≥18 years of age and excluded patients diagnosed with chronic rhinosinusitis (CRS).
Results
Nineteen unique studies with 27 separate data sets and a total of 1025 patients were used in this meta‐analysis. Overall SNOT‐22 scores statistically improved at the 6‐month (p = 0.0009) and 1‐year (p = 0.002) time‐points. Patients with preoperative SNOT‐22 scores ≥20 achieved postoperative improvements at 12‐week (p < 0.00001), 6‐month (p < 0.0001), 1‐year (p < 0.00001), and long‐term follow‐up (p < 0.0001). Patients with preoperative SNOT‐22 scores <20 remained stable and did not worsen postoperatively.
Conclusion
Patients undergoing EEA for skull base pathologies who have impaired sinonasal QOL preoperatively demonstrated significant postoperative QOL improvements. Those patients with relatively normal preoperative sinonasal QOL remained asymptomatic postoperatively. This study supports the need for development of a contemporary disease‐ and approach‐specific, validated QOL instrument for skull base pathologies.

Nasal thallium‐201 uptake in patients with parosmia with and without hyposmia after upper respiratory tract infection

29-07-2019 – Hideaki Shiga, Koichi Okuda, Junichi Taki, Naoto Watanabe, Hisao Tonami, Seigo Kinuya, Takaki Miwa

Journal Article

Background
In this study, we aimed to determine whether nasal thallium‐201 uptake of the olfactory cleft and olfactory bulb (OB) differs between patients with parosmia with and without hyposmia after upper respiratory tract infection (URTI).
Methods
Twenty patients with parosmia after URTI were enrolled in this study (15 women and 5 men, 28 to 76 years old). Nasally administered thallium‐201 migration to the OB, nasal thallium‐201 uptake ratio in the olfactory cleft, and OB volume were determined in 10 patients with normal T&T olfactometry (Daiichi Yakuhin Sangyo, Tokyo, Japan) odor recognition thresholds (≤2.0) who still complained of parosmia (parosmia group), and 10 patients with T&T odor recognition thresholds >2.0 (parosmia and hyposmia group).
Results
The nasal thallium‐201 uptake ratio in the olfactory cleft was significantly higher in the parosmia group than in the parosmia and hyposmia group (p = 0.0015). Thallium‐201 migration to the OB was not significantly different between the 2 groups (p = 0.31). The OB volume was significantly larger in the parosmia group than that in the parosmia and hyposmia group (p = 0.029); however, the mean OB volume in both the groups was lower than the normal threshold value in healthy individuals.
Conclusion
Our results signify the recovery of the olfactory epithelium; however, the olfactory neural projections to the OB and regeneration of OB were not complete in patients with parosmia with normal T&T recognition thresholds after URTI.

Extent of maxillary sinus surgery and its effect on instrument access, irrigation penetration, and disease clearance

25-07-2019 – Revadi Govindaraju, Lisa Cherian, Luis Macias‐Valle, Jae Murphy, Michael Gouzos, Sarah Vreugde, Peter John Wormald, Ahmed Bassiouni, Alkis James Psaltis

Journal Article

Background
Middle meatal antrostomy (MMA) provides limited access to the anteromedial and inferior aspect of the maxillary sinus (MS) often resulting in residual disease and inflammatory burden. Newer extended procedures, such as mega‐antrostomy (Mega‐A) and extended modified mega‐antrostomy (EMMA), have been developed to address this limitation. This study assesses the effect of varying extent of MS surgery on irrigation penetration and access of instrumentation.
Methods
The MS of 5 fresh‐frozen cadavers were sequentially dissected. Irrigation was evaluated with a squeeze bottle (SB) in different head positions and using different volumes of fluid. Surgical reach and visualization were examined using common sinus instruments and different angled endoscopes. A disease simulation was also performed to check for residual debris after instrumentation and irrigations.
Results
Irrigation penetration improved as antrostomy size increased (p < 0.0001), with a significant difference observed between the extended procedures and MMA. The effect of the volume was significant for SB (p < 0.0001) but head positions appeared irrelevant (p = 0.613). Overall visualization improved for Mega‐A and EMMA. A similar trend was seen for the reach of the instruments to all sinus wall subsites. EMMA facilitated the most removal of “sinus disease” in the disease simulation model when compared with both MMA and Mega‐A, due to its reach of the anteroinferior aspects of the maxillary sinus.
Conclusions
High‐volume irrigation using SB achieved good sinus penetration, irrespective of head position. Extended MS procedures appear to further increase irrigation penetration as well as surgical access.

Sinus irrigation penetration after balloon sinuplasty vs functional endoscopic sinus surgery in a cadaveric model

23-07-2019 – Oliver Gantz, Arman Danielian, Alison Yu, Elisabeth H. Ference, Edward C. Kuan, Bozena Wrobel

Journal Article

Background
Nasal irrigation is a cornerstone of treatment for chronic rhinosinusitis. The purpose of this study was to quantify irrigation penetration to the sinuses following balloon sinuplasty and functional endoscopic sinus surgery (FESS).
Methods
Balloon sinuplasty followed by FESS was performed on 4 cadaver heads. Using a high‐volume, high‐flow bottle, each head was irrigated with fluorescein‐dyed water prior to and following each procedure, and recorded by rigid endoscopy through trephinations. Three blinded, fellowship‐trained rhinologists reviewed videos and scored the extent of staining (using an accepted scale of 0 to 3) for each site.
Results
The mean score prior to any procedure was maxillary sinus 1.67, frontal sinus 1.29, and nasal cavity 1.71. After balloon sinuplasty the mean was maxillary 2.25, frontal 2.04, and nasal cavity 2.17. After FESS the mean was maxillary 2.75, frontal 2.08, and nasal cavity 2.63. There was a statistically significant increase for both maxillary (p = 0.005) and frontal sinuses (p = 0.006) following balloon sinuplasty. There was a statistically significant increase following FESS compared to balloon for the maxillary sinus (p = 0.003), but not the frontal sinus (p = 0.96). Interrater reliability was good, with Cronbachs alpha of 0.85.
Conclusion
Irrigation improved in all sinuses following balloon sinuplasty and FESS. There was further improvement to the maxillary sinus after FESS; however, there was no difference in irrigation to the frontal sinuses following FESS compared to balloon sinuplasty. Extended frontal sinus approaches such as the Modified Lothrop procedure should be considered if more extensive access for irrigation is required.

Discriminant analysis followed by unsupervised cluster analysis including exosomal cystatins predict presence of chronic rhinosinusitis, phenotype, and disease severity

19-07-2019 – Michelle M. Miyake, Alan D. Workman, Angela L. Nocera, Dawei Wu, Sarina K. Mueller, Kristen Finn, Mansoor M. Amiji, Benjamin S. Bleier

Journal Article

Background
Cystatins are epithelial protease inhibitors that participate in sinonasal immunity and inflammation. Nasal mucus–derived exosomes (NMDEs) are small vesicles secreted by epithelial cells that carry protein cargo reflective of their host cell. NMDEs have been used as a noninvasive biomarker source to study chronic rhinosinusitis with nasal polyps (CRSw
NP) proteomics with superior sensitivity to whole mucus. The purpose of this study was to noninvasively quantify exosomal cystatins in a heterogenous population to determine their utility in predicting phenotype and disease severity.
Methods
This was an Institutional Review Board–approved study in which NMDEs were purified from 105 patients undergoing sinonasal surgery by ultracentrifugation. Demographic and clinical variables were collected and phenotypes were assigned a priori. Linear discriminant analysis was executed based on normalized Cystatin values as phenotype predictor variables. Unsupervised cluster analysis was performed using Wards linkage followed by Duda/Hart Je(2)/Je(1) index cluster stopping rules. Analysis of variance (ANOVA), Welchs test, and Fishers exact tests were used for continuous and categorical variables.
Results
NMDE Cystatin‐2 expression segregated by phenotype (mean ± standard error SEM): control (23.4 ± 4.2 pg/µg, n = 32); CRS without NP (CRSs
NP) (56.6 ± 8.3 pg/µg, n = 33); and CRSw
NP (130.5 ± 16.7 pg/µg, n = 40) (p < 0.0001). Seven clusters were identified among patients where the highest NMDE Cystatin‐2 levels clustered with asthma, tissue eosinophilia, and aspirin‐exacerbated respiratory disease (AERD).
Conclusion
Cystatin levels in NMDEs predict CRS phenotype and disease severity. As a “liquid biopsy,” noninvasive NMDE collection offers a promising opportunity to study disease pathophysiology, discriminate disease states, and potentially reveal novel therapeutic targets.

Development and validation of a nomogram for prognosis of sinonasal squamous cell carcinoma

18-07-2019 – Huatao Quan, Li Yan, Haiyan Zhang, Lifen Zou, Wei Yuan, Shengzi Wang

Journal Article

Background
Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with varied outcomes. The aim of this study was to develop a nomogram for predicting survival of patients with SNSCC.
Methods
From the Surveillance, Epidemiology, and End Results database, we identified 1766 patients diagnosed with SNSCC between 2004 and 2015. Patients were randomly separated into a training set and a validation set in 4:1 ratio. An external validation was also performed by a set of 74 SNSCC patients who had been treated in our department. We used the training set to build a nomogram based on stratified multivariable Cox proportional hazard models for predicting overall survival. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index and calibration curve.
Results
Based on 1412 cases of the training cohort, our Cox regression analysis revealed that age, marital status, primary site, differentiation, T stage, N classification, M stage, and treatment modalities were associated with overall survival. A nomogram was established based on the results of multivariate analysis. The C‐index values of the nomogram for predicting survival were superior to those of the tumor‐node‐metastasis staging system (0.745 vs 0.679 in the training cohort, 0.752 vs 0.656 in the validation set, and 0.678 vs 0.596 in the external validation set). The calibration plots demonstrated good consistency between the predicted and observed results.
Conclusion
We have developed a nomogram to accurately predict the clinical outcomes of SNSCC patients. This model was effective and can help clinicians to improve patient counseling.

Differential perception and tolerance of chronic rhinosinusitis symptoms as a confounder of gender‐disparate disease burden

17-07-2019 – Katie M. Phillips, Regan W. Bergmark, Lloyd P. Hoehle, Edina T. Shu, David S. Caradonna, Stacey T. Gray, Ahmad R. Sedaghat

Journal Article

Background
Previous studies have consistently shown that females with chronic rhinosinusitis (CRS) have a greater CRS symptom burden than males with CRS. Our objective was to determine whether differential disease perception could explain this phenomenon.
Methods
A total of 500 participants (239 males, 261 females) with CRS were recruited. CRS symptom burden was assessed with the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). General health‐related quality of life was assessed with the visual analog scale of the 5‐dimensional Euro
Qol questionnaire (EQ‐5D VAS). Participants were asked to rate their CRS symptom control as “Not at all,” “A little,” “Somewhat,” “Very,” and “Completely.” “Not at all,” “A little,” and “Somewhat” controlled symptoms were considered to reflect poorly controlled symptoms.
Results
SNOT‐22 score was significantly more severe (p < 0.001) among females (mean, 44.0; standard deviation SD, 22.5) than males (mean, 36.3; SD, 20.2). However, there was no significant difference in male‐ vs female‐reported CRS symptom control (p = 0.154). In addition, there was no significant difference (p = 0.109) in EQ‐5D VAS score between males (mean, 70.9; SD, 19.0) and females (mean, 68.4; SD, 19.5). Although a SNOT‐22 score of ≥25 was predictive of poorly controlled symptoms in males (sensitivity, 82.6%; specificity, 62.5%), a SNOT‐22 score of ≥30 was predictive of poorly controlled symptoms in women (sensitivity, 82.4%; specificity, 64.5%).
Conclusion
Females with CRS reported more severe SNOT‐22 scores, despite reporting a similar level of symptom control and general health‐related quality of life as men. Women had a higher SNOT‐22 threshold for poorly controlled symptoms. Female CRS patients may have greater perception and tolerance of CRS symptoms without a corresponding significant, disparate downstream impairment.

Sinonasal mucoepidermoid carcinoma: a review of the National Cancer Database

17-07-2019 – Vasiliki Triantafillou, Ivy W. Maina, Edward C. Kuan, Michael A. Kohanski, Charles C. Tong, Neil N. Patel, Ryan M. Carey, Alan D. Workman, James N. Palmer, Nithin D. Adappa, Jason A. Brant

Journal Article

Background
Primary sinonasal mucoepidermoid carcinoma (SN‐MEC) is a malignancy arising from seromucinous glands of the nasal cavity and paranasal sinuses. Given its rarity, few large‐scale studies have been performed. In this study we describe the incidence and determinants of survival of patients with SN‐MEC leveraging the National Cancer Database (NCDB).
Methods
This was a retrospective, population‐based cohort study of patients diagnosed with SN‐MEC between 2004 and 2012 within the NCDB. The main outcome measure was overall survival (OS).
Results
A total of 164 patients were identified. The cohort was composed of 47.6% males. Mean age at diagnosis was 59.7 years. The maxillary sinus was the most common primary site, accounting for 45.7% of cases. Eleven percent of patients presented with nodal disease, whereas 2.1% had distant metastases. Stage IV disease was seen in 30.4% of cases. A total of 79.8% of the patients underwent surgery, 61.0% received radiation therapy, and 15.1% had chemotherapy. OS at 1, 2, and 5 years was 83%, 77.0%, and 57%, respectively. On multivariate analysis, Medicaid insurance status (hazard ratio HR, 7.29; 95% confidence interval CI, 1.74‐30.57), advanced tumor size (HR, 4.94; 95% CI, 1.19‐20.5), and advanced nodal disease (N1: HR, 9.48; 95% CI, 1.66‐54.23; N2B: HR, 19.3; 95% CI, 1.07‐350.64) were associated with worse OS.
Conclusion
Mucoepidermoid carcinoma is the most common salivary gland malignancy but a rare sinonasal malignancy, with 5‐year survival for SN‐MEC approximating 50%. A significant proportion of patients present with advanced disease. Both socioeconomic factors and tumor characteristics are associated with survival.

HLA‐II genes are associated with outcomes of specific immunotherapy for allergic rhinitis

12-07-2019 – Yanming Zhao, Yali Zhao, Yuan Zhang, Luo Zhang

Journal Article

Background
Although the precise mechanisms underlying the efficacy of allergen‐specific immunotherapy (AIT) are not clear, some evidence suggests that this may be linked to polymorphisms in HLA‐II gene. We aimed to investigate the correlation between HLA‐II gene polymorphisms and house dust mite (HDM)‐specific immunotherapy efficacy, and evaluate specific polymorphisms as potential biomarkers in allergic rhinitis (AR) patients who would benefit most from AIT.
Methods
Fifty‐one Han Chinese patients with AR receiving HDM AIT were recruited. Genomic DNA was extracted from venous blood samples and genotyped for HLA‐DRB1 and HAL‐DQB1 alleles using the polymerase chain reaction sequence‐based genotyping method. Nasal and eye symptoms were investigated based on visual analogue scale and rhinoconjunctivitis quality of life.
Results
Allele DRB1*04:06; DRB1*14:05 showed a positive correlation with improvements in nasal blockage, nasal itching, eye itching, and activities. Similarly, DQB1*03:02:01; DQB1*05:03: 01 was positively correlated with improvements in nose blocking, nasal itching, eye itching, behavioral problems, and nasal symptoms scores; and DRB1*03:01; DRB1*04:06 positively correlated with nasal symptoms scores. In contrast, DRB1*07:01:01; DRB1*11:01 was negatively correlated with non‐pollen symptoms, behavioral problems, and nasal symptoms.
Conclusion
HLA‐DRB1 and HLA‐DQB1 gene polymorphism are associated with AIT efficacy in HDM‐sensitive Chinese patients with AR, of which DRB1*03:01; DRB1*04:06 and DQB1*03:02:01; DQB1*05:03:01 may be useful biomarkers of AR patient candidacy for effective AIT.

Adenosine‐induced transient hypotension for carotid artery injury during endoscopic skull‐base surgery: case report and review of the literature

10-07-2019 – Judd H. Fastenberg, Tomas Garzon‐Muvdi, Victor Hsue, Erin K. Reilly, Pascal Jabbour, Mindy R. Rabinowitz, Marc R. Rosen, James J. Evans, Gurston N. Nyquist, Christopher J. Farrell

Journal Article

Background
As the management of ventral skull‐base pathology has transitioned from open to endonasal treatment, there has been an increased focus on the prevention and endoscopic endonasal management of internal carotid artery (ICA) and major vascular injury. The use of adenosine to induce transient hypotension or flow arrest has been previously described during intracranial aneurysm surgery; however, there have been no reports of the technique being used during endonasal skull‐base surgery to achieve hemostasis following major vascular injury.
Methods
Case report (n = 1) and literature review.
Results
A 25‐year‐old female underwent attempted endoscopic endonasal resection of an advanced right‐sided chondrosarcoma. During resection of the tumor, brisk arterial bleeding was encountered consistent with focal injury to the right cavernous ICA. Stable vascular hemostasis could not be achieved with tamponade. An intravenous bolus dose of adenosine was administered to induce a transient decrease in systemic blood pressure and facilitate placement of the muscle patch over the direct site of vascular injury. The patient subsequently underwent endovascular deconstruction of the right ICA.
Conclusion
This is the first reported use of adenosine to induce transient hypotension for a major vascular injury sustained during endonasal skull‐base surgery. Based on well‐established safety data from neurosurgical application, adenosine has the potential to be used as a safe and effective adjunctive technique in similar endonasal circumstances and may represent an additional tool in the armamentarium of the skull‐base surgeon. Surgeons should consider having adenosine available when a risk of ICA injury is anticipated.

Clinical validation of the olfactory detection threshold module of the Snap & Sniff® olfactory test system

08-07-2019 – Richard L. Doty, Crystal Wylie, Mark Potter, Rachel Beston, Brooke Cope, Kelsey Majam

Journal Article

Background
Quantitative olfactory testing is essential to determine the validity and nature of a patients complaint, accurately monitor changes in function over time (including influences of pharmacological, surgical, or immunological interventions), detect malingering, and establish disability compensation. This work describes the clinical validation of an advanced rapid odor detection threshold test that standardizes odorant delivery and eliminates unsanitary sniff bottles, the need for blindfolds, and the possibility of touching an odorant stimulus to the nose.
Methods
Snap & Sniff® single‐staircase phenyl ethyl alcohol detection thresholds (S&S‐Ts) were assessed bilaterally in 736 patients with chemosensory complaints; 421 received both bilateral and unilateral testing. The results were correlated with scores from the University of Pennsylvania Smell Identification Test (UPSIT) and the Smell Threshold Test (STT), a widely‐used standardized threshold test. Test‐retest reliability data were obtained for 50 patients.
Results
S&S‐Ts were highly reliable (Spearman r = 0.84), correlated with the other olfactory test measures (rs > 0.65, ps < 0.0001), and required significantly shorter administration times than the STT (<10 minutes). Bilateral thresholds were systematically lower than unilateral thresholds, a phenomenon independent of presentation order but dependent upon the better functioning side of the nose. The S&S‐Ts were sensitive to age and sex. No systematic left:right nasal side threshold differences were evident.
Conclusion
The present study validates the use of Snap & Sniff® technology in the clinic setting. High test‐retest reliability and brief administration times were evident. The S&S‐T test allows for a reliable, valid, inexpensive, and rapid clinical means for quantitatively assessing human olfactory sensitivity.

Transnasal prelacrimal approach to the inferior intraconal space: a feasibility study

01-07-2019 – Lifeng Li, Nyall R. London, Samuel Silva, Daniel Prevedello, Ricardo L. Carrau

Journal Article

Background
Endonasal access to the inferomedial and inferolateral intraconal space via the orbital floor has not been reported. The primary purpose of this study was to assess the feasibility of accessing the inferior intraconal space through the orbital floor via a transnasal prelacrimal approach. Secondarily, it aims to highlight anatomical relationships of neurovascular structures in this space, as a requirement to prevent complications.
Methods
Six cadaveric heads (12 sides) were dissected using a transnasal prelacrimal approach. The orbital floor, medial to the infraorbital canal, was removed and the periorbita opened to expose the inferior rectus muscle. The inferomedial and inferolateral intraconal space was accessed alongside the medial and lateral border of inferior rectus muscle, respectively. Various anatomical relationships of adjacent neurovascular structures were recorded, and the distances among the recti muscles and optic nerve were also measured.
Results
The infraorbital nerve is located at the inferolateral aspect of inferior rectus muscle. In the inferomedial intraconal space, we identified the inferomedial muscular trunk of the ophthalmic artery, optic nerve, and branches of the oculomotor nerve; whereas the inferolateral intraconal space contained the inferolateral muscular trunk of ophthalmic artery, branches of the oculomotor and nasociliary nerve, and abducens nerve. Distances from the medial, inferior, and lateral recti muscles to the optic nerve were (mean ± standard deviation) 4.70 ± 1.18 mm, 5.60 ± 0.93 mm, and 7.98 ± 1.99 mm, respectively. Distances from the inferior rectus muscle to the inferior borders of medial and lateral recti muscles were 4.45 ± 1.23 mm and 8.77 ± 1.80 mm.
Conclusion
It is feasible to access the inferior intraconal space through the orbital floor via a transnasal prelacrimal approach. The access may be subdivided into inferomedial and inferolateral corridors according to the entry point at the medial or lateral border of the inferior rectus muscle. Neurovascular structures in the inferior intraconal space are visualized directly, which should enhance their preservation.

Effects of sphenoid surgery on nasal irrigation delivery

01-07-2019 – Jessica W. Grayson, Marina Cavada, Eugene Wong, Benjamin Lien, Marin Duvnjak, Raewyn Campbell, Larry Kalish, Raymond Sacks, Richard J. Harvey

Journal Article

Background
Nasal irrigation is an important component of medical management in chronic rhinosinusitis. Nasal irrigations facilitate topical medication of therapies and lavage of mucin. In this study we aim to compare the influence of increasing surgical sphenoid openings on the distribution, force, and clearance of nasal irrigations.
Methods
A study was performed on fresh‐frozen adult cadaver heads. The surgical ostium was modified on one side via a simple sphenoidotomy, a sphenoid sinusectomy (type 1), and sphenoid sinusectomy (type 3a). The nasal cavity was irrigated using a 240‐m
L squeeze bottle with 0.1% fluoroscein. An endoscope passed through the contralateral side through the sphenoid septum recorded the irrigation. Videos were recorded and blindly assessed. The distribution was defined as either no irrigation, less than one third of the sinus, less than or equal to two thirds of the sinus, or the complete sinus. The force was defined as minimal, minor, or major. The clearance was defined as no residual, less than one third of volume, less than or equal to two thirds of volume, and more than two thirds volume. Ordinal correlation scores were assessed using the Kendall tau‐B test.
Results
Nine specimens (sphenoid sinuses) were assessed (44.4% female; age, 75.0 ± 12.7 years). The use of a sphenoid sinusectomy or larger produced better distribution (percent specimens with more than one third: 100% vs 59%, p < 0.01), more force (percent major: 83% vs 29%, p < 0.01), and better clearance (percent with one third or less remaining: 56% vs 18%, p < 0.01).
Conclusion
Increasing sphenoid ostial size improves nasal irrigation penetration. We propose that greater sphenoid sinusectomy size allows for improved lavage and irrigation penetration. Complete removal of the anterior face appears to mitigate pooling of irrigation.

Loss of BMI1 in mature olfactory sensory neurons leads to increased olfactory basal cell proliferation

28-06-2019 – Rhea Choi, Sarah Kurtenbach, Bradley J. Goldstein

Journal Article

Background
Damage to olfactory sensory neurons (OSNs), situated within the neuroepithelium of the olfactory cleft, may be associated with anosmia. Although their direct contact with the nasal airspace make OSNs vulnerable to injury and death, multiple mechanisms maintain epithelium integrity and olfactory function. We hypothesized that BMI1, a polycomb protein found to be enriched in OSNs, may function in neuroprotection. Here, we explored BMI1 function in a mouse model.
Methods
Utilizing a mouse genetic approach to delete Bmi1 selectively in mature OSNs, we investigated changes in OE homeostasis by performing immunohistochemical, biochemical, and functional assays. Reverse transcription–quantitative polymerase chain reaction (RT‐q
PCR), immunostaining, and electro‐olfactograms were used to compare gene expression, cell composition, and olfactory function in OSN‐specific BMI1 knockout mice (n = 3 to 5) and controls. Chromatin studies were also performed to identify protein‐DNA interactions between BMI1 and its target genes (n = 3).
Results
OSN‐specific BMI1 knockout led to increased neuron death and basal cell activation. Chromatin studies suggested a mechanism of increased neurodegeneration due to de‐repression of a pro‐apoptosis gene, p19ARF. Despite the increased turnover, we found that olfactory neuroepithelium thickness and olfactory function remained intact. Our studies also revealed the presence of additional polycomb group proteins that may compensate for the loss of BMI1 in mature OSNs.
Conclusion
The olfactory neuroepithelium employs multiple mechanisms to maintain epithelial homeostasis. Our findings provide evidence that in a mouse model of BMI1 deletion, the overall integrity and function of the olfactory neuroepithelium are not compromised, despite increased neuronal turnover, reflecting a remarkable reparative capacity to sustain a critical sensory system.

Hyams grading as a predictor of metastasis and overall survival in esthesioneuroblastoma: a meta‐analysis

28-06-2019 – Khodayar Goshtasbi, Arash Abiri, Mehdi Abouzari, Ronald Sahyouni, Beverly Y. Wang, Bobby A. Tajudeen, Frank P. K. Hsu, Gilbert Cadena, Edward C. Kuan

Journal Article, Review

Background
Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, represents up to 3% of all sinonasal neoplasms. Hyams histologic grading is a promising tool in predicting metastases and establishing prognoses for this complex tumor.
Methods
A systematic literature search was performed in the PubMed, Ovid MEDLINE, and Cochrane databases. ENB patients with Hyams I‐II or III‐IV were categorized as low‐grade Hyams (LGH) or high‐grade Hyams (HGH), respectively. Binary and continuous random‐effects models were applied to calculate odds ratios (ORs) for the incidences of neck and distal metastases as well as for 5‐ and 10‐year overall survival rates.
Results
Of the 57 screened articles published from 1993 to 2018, 16 (525 patients) and 21 (563 patients) provided data for tumor metastases and overall survival rates, respectively. Neck metastasis was observed in 18.2% of HGH vs 7.9% of LGH patients. Distant metastasis was noted in 20.7% of HGH vs 8.9% of LGH patients. LGH patients had 5‐ and 10‐year overall survival rates of 81.2% and 64.0%, respectively, as compared with 60.9% and 40.6%, respectively, for HGH patients. In comparing HGHs vs LGHs, the collective ORs for neck and distant metastases were 2.08 (95% confidence interval CI, 1.09‐3.99; p = 0.03) and 2.37 (95% CI, 1.07‐5.26; p = 0.03), respectively. Moreover, in comparing LGHs vs HGHs, collective ORs for 5‐ and 10‐year overall survival rates were 3.39 (95% CI, 2.09‐5.49; p < 0.001) and 3.03 (95% CI, 1.82‐5.06; p < 0.001), respectively.
Conclusion
HGH ENBs, compared with LGH ENBs, are more likely to metastasize to neck or distal targets and to have lower overall survival rates.

Socioeconomic status impacts postoperative productivity loss and health utility changes in refractory chronic rhinosinusitis

27-06-2019 – Daniel M. Beswick, Jess C. Mace, Zachary M. Soler, Luke Rudmik, Jeremiah A. Alt, Kristine A. Smith, Kara Y. Detwiller, Vijay R. Ramakrishnan, Timothy L. Smith

Journal Article

Background
Social determinants of health can have a substantial impact on treatment outcomes. Prior study has shown that socioeconomic status influences the likelihood of improvement in quality‐of‐life (QOL) following endoscopic sinus surgery (ESS). However, the impact of socioeconomic factors on changes in productivity loss and health utility after ESS remains unknown.
Methods
Adult patients (≥18 years of age) with chronic rhinosinusitis (CRS) who underwent ESS were prospectively enrolled into a multi‐institutional cohort study. Productivity losses were calculated using the human capital approach and monetized using U.
S. government–estimated wage rates. Health utility values (HUVs) were derived from the Medical Outcomes Study Short‐Form‐12 survey using University of Sheffield algorithms. Independent socioeconomic factors of interest included: age, gender, ethnicity, insurance status, educational attainment, and household income categorized via the Thompson‐Hickey model.
Results
A total of 229 patients met inclusion criteria, and 163 (71%) provided postoperative follow‐up. All subjects reported significant, within‐subject improvement in both mean monetized productivity loss (p < 0.001) and HUV postoperatively (p < 0.001). Using paired sample statistics, patients with lowest income (≤$25,000/year) and with Medicare insurance did not report significant improvement in productivity loss (p ≥ 0.112) or HUV (p ≥ 0.081), although sample size limitations may have contributed to this finding. Patients in higher income tiers ($25,001 to $100,000/year and $100,001+/year) and those with employer‐provided/private health insurance reported significant postoperative improvements in productivity loss and HUV (all p ≤ 0.003).
Conclusion
Socioeconomic factors, including income and insurance provision, may impact improvements in productivity loss and HUV following ESS. Further research to validate these findings, ascertain mechanisms behind these results, and improve these outcomes is warranted.

Central compartment involvement in aspirin‐exacerbated respiratory disease: the role of allergy and previous sinus surgery

27-06-2019 – John M. DelGaudio, Joshua M. Levy, Sarah K. Wise

Journal Article

Background
Evidence for a relationship between allergy and chronic rhinosinusitus with nasal polyps (CRSw
NP) is equivocal. Central compartment (CC) atopic disease is a nasal inflammatory condition related to inhalant allergy. CC involvement is common in aspirin‐exacerbated respiratory disease (AERD), a subset of CRSw
NP, and we hypothesize it is related to allergic status.
Methods
This study was a retrospective analysis of a single‐institution database for the January 2016 to February 2019 time period. Data regarding endoscopic CC findings, clinical allergy history, and results of allergy testing were collected. Statistical analysis was performed, with significance set at p < 0.05.
Results
Seventy‐two AERD patients met the inclusion criteria. Fifty‐nine patients had CC involvement (53 bilateral, 6 unilateral). For patients with documented allergy status, 100% of patients with endoscopic CC disease had clinical allergic rhinitis (AR), and 45 of 48 (93.8%) had positive allergy testing. Thirteen patients had no CC involvement (4 with clinical AR; 3 of 7 with positive allergy testing). CC endoscopic findings in AERD were significantly associated with clinical allergy (p < 0.0001, phi = 0.771). Overall, patients with CC involvement averaged 3.8 surgeries vs 3.2 for those without CC involvement (p = not statistically significant). However, patients with septal involvement averaged 4.2 surgeries vs 2.0 for those without septal involvement (p = 0.004). As the number of sinus surgeries increases, middle turbinate (MT) resection (r = 0.300, p = 0.022) and septal involvement (r = 0.372, p = 0.004) significantly increase. All patients with MT resection had septal disease, whereas none without CC disease had MT resection.
Conclusion
Most AERD patients exhibit AR, and this correlates with CC disease. As the number of surgeries increases, MT resection may predispose to polyposis of the septum.

Predictive value of computed tomography in the recurrence of chronic rhinosinusitis with nasal polyps

25-06-2019 – Yifan Meng, Luo Zhang, Hongfei Lou, Chengshuo Wang

Journal Article

Background
Chronic rhinosinusitis with nasal polyps (CRSw
NP) is a nasal disease with a high tendency for recurrence. The aim of this study was to compare the use of computed tomography (CT) scan with other clinical parameters in predicting the recurrence of CRSw
NP.
Methods
A total of 272 consecutive CRSw
NP patients undergoing endoscopic functional sinus surgery were recruited. The demographic characteristics and clinical parameters, including CT scores, level of exhaled nitric oxide, and peripheral eosinophilia, were recorded. The degree of infiltration of inflammatory cells in the sinus mucosa was evaluated.
Results
Two hundred thirty of the 272 patients completed the study (118 patients with recurrence and 112 patients with no recurrence). The average follow‐up time was 24 months after the first surgery. The 2 groups were not significantly different with respect to age, gender distribution, comorbid allergy, exhaled oral fractional exhaled nitric oxide levels, nasal obstruction/runny nose/headache/facial pain scores, Lund‐Mackay score, peripheral eosinophil percentage, and peripheral eosinophil absolute count. The onset of surgical history and asthma, visual analog scores of CRS, anosmia score, ratio of total ethmoid sinus scores for both sides and maxillary sinus score for both sides (E/M ratio), Lund‐Kennedy score, tissue eosinophil percentage, and tissue eosinophil absolute count were significantly higher in the recurrence group. The E/M ratio showed high accuracy as a predictor for CRSw
NP recurrence. The cut‐off point of 2.55 for E/M ratio indicated the highest predictive value of CRSw
NP recurrence.
Conclusion
The E/M ratio is a useful predictor for the recurrence of CRSw
NP in the Chinese population.

Association between chronic rhinosinusitis and osteoporosis: a case‐control study using a national sample cohort

17-06-2019 – Hyo Geun Choi, Gyu Kong

Journal Article

Background
The purpose of this study was to further clarify the relationship between chronic rhinosinusitis (CRS) and osteoporosis in a Korean population.
Methods
The Korean National Health Insurance Service‒National Sample Cohort, with subjects ≥50 years old, was assessed for the time period 2002‐2013. In total, 68,459 osteoporosis participants were matched with 68,459 control participants at a ratio of 1:1 with respect to age, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed previous histories of CRS with/without nasal polyp in the osteoporosis and control groups. CRS and osteoporosis were included using codes from the International Classification of Diseases―tenth edition and claim codes. Crude and adjusted odds ratios (ORs) were analyzed using conditional logistic regression analyses. The 95% confidence intervals (CIs) were then calculated. Subgroup analyses were performed according to age and sex.
Results
The rate of CRS with/without nasal polyp was higher in the osteoporosis group (3.0% 2078 of 68,459) compared with the control group (2.0% 1344 of 68,459) (p < 0.001). The adjusted OR of CRS with/without nasal polyp was 1.47 (95% CI, 1.37‐1.58; p < 0.001) in the osteoporosis group. The results of the subgroup analyses were consistent.
Conclusion
The ORs of CRS were increased in osteoporosis participants. This relation was consistent in all age and sex groups.

Lateral nasal wall extension of the nasoseptal flap for skull‐base and medial orbital wall defects

07-06-2019 – Justin McCormick, Mark Allen, Joshua J. Kain, Jaime A Pena‐Garcia, Do‐Yeon Cho, Kristen O. Riley, Bradford A. Woodworth

Journal Article

Background
Sinonasal and skull‐base tumors that previously required open resection can often be completely resected via an endonasal approach. The nasoseptal flap (NSF) is the workhorse vascularized tissue flap for the endoscopic reconstruction of large skull‐base defects from tumor resections. The objective of the current article is to describe a novel modification of the NSF for simultaneous reconstruction of skull‐base and medial orbital wall defects.
Methods
An extension of the standard NSF to include mucosa of the lateral nasal wall was developed for closure of simultaneous skull‐base and medial orbital wall defects. Outcomes including successful cerebrospinal fluid (CSF) leak closure, orbital edema, and postoperative cosmesis are reported. Eyelid edema was characterized according to the Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) scale.
Results
Three patients underwent reconstruction using the modified NSF (average age 75 years). The average defect size of the skull base was 3.6 ± 0.1 cm by 2.3 ± 0.2 cm. The average defect size of the medial orbit was 2.7 ± 0.1 cm by 2.6 ± 0.1 cm. All defects were successfully covered intraoperatively using the lateral nasal wall extension of the NSF. Two patients developed mild eyelid edema, whereas 1 individual had no noticeable swelling (SPREE classification 2, 2, and 1). All patients were successfully sealed at last clinical follow up (average 28 weeks).
Conclusion
The modification of the NSF described here provides excellent coverage for reconstruction of large anterior skull‐base defects and simultaneous medial orbital wall defects.

Formation of papillary mucosa folds and enhancement of epithelial barrier in odontogenic sinusitis

08-01-2019 – Yuan Zhang, Feng Lan, Ying Li, Chengshuo Wang, Luo Zhang

Journal Article

Background
Odontogenic sinusitis (OS) presents more satisfactory therapeutic effect after endoscopic surgery compared with chronic rhinosinusitis (CRS) of other origin. The aim of the present study was to investigate the clinical characteristics, morphological features, and epithelial barrier function of sinus mucosa of OS and discuss the possible relationship with good prognosis.
Methods
A total of 25 subjects with OS, 7 CRS without nasal polyps (CRSs
NP), 10 CRS with nasal polyps (CRSw
NP), and 9 control subjects were recruited. The biopsy specimens were stained with hematoxylin and eosin for general observation of cytomorphologic features. Epithelial tight junctions (TJs) protein claudin‐4 expression was determined to evaluate the epithelial barrier integrity by using immunofluorescence and Image‐Pro Plus software analysis. The representative cytokine profiles regarding T helper 1 (Th1) (interferon IFN‐γ), Th2 (interleukin IL‐5), and Th17 (IL‐17) were examined by reverse transcription–polymerase chain reaction (RT‐PCR).
Results
Extensively small papillary protrusions could be seen in the maxillary sinus mucosa of OS patients under nasal endoscopy, similar to the morphological behavior, which also presented as papillary folds in the surface of the epithelium. The epithelium in OS kept an increased claudin‐4 expression compared with that seen in CRSs
NP, CRSw
NP, and control subjects. The inflammatory pattern analysis demonstrated that OS belonged to the lymphocyte and plasma cell‐dominant cellular phenotypes, whereas IL‐17 was dominant compared with IFN‐γ as well as IL‐5.
Conclusion
The odontogenic infections might induce the formation of papillary mucosa folds and enhance the epithelial TJ barrier function. OS exhibited as lymphocyte and plasma cell–dominant cellular phenotypes and Th17 cytokine profiles.

Fusarium: A potential cause of chronic rhinosinusitis?

28-02-2012 – Bradley Marple