International Forum of Allergy and Rhinology

International Forum of Allergy and Rhinology

Tissue microarray analysis reveals that cofilin expression is a poor prognostic factor in juvenile nasopharyngeal angiofibroma

17-10-2019 – Wanpeng Li, Huan Wang, Huapeng Yu, Jingjing Wang, Xiaole Song, Zhuofu Liu, Juan Liu, Li Hu, Han Li, Dehui Wang, Xicai Sun

Background
Juvenile nasopharyngeal angiofibroma (JNA) has a high recurrence rate after surgery. Cofilin overexpression is associated with increased tumor cell metastasis, and progression of various human cancers. However, studies on cofilin expression in JNA are rare. The purpose of this study was to investigate the expression and localization of cofilin in a tissue microarray (TMA) of JNA specimens. In addition, we also analyzed its correlation with clinicopathological features and recurrence.
Methods
Immunohistochemistry was performed to detect cofilin expression in a TMA of samples from 70 JNA patients and 10 control subjects. The association between clinicopathological variables and cofilin immunostaining was analyzed using Pearsons chi‐square test. Kaplan‐Meier survival analysis was used to calculate the disease‐free survival rate, and investigate the effect of cofilin expression on time to recurrence (TTR) in JNA patients. The Cox regression model was used for multivariate survival analysis.
Results
Cofilin was detected in irregular smooth muscle cells, pericytes, less differentiated stromal cells, and plump cells, but not in inactive fibroblasts and mature vascular endothelial cells of JNA specimens. The presence of cofilin in JNA was correlated with tumor stage (p = 0.012) and volume of intraoperative hemorrhage (p < 0.001). JNA patients with high cofilin expression had a higher recurrence rate than those with low cofilin expression (p = 0.012). Cofilin expression and patients age were significant predictors of TTR, and cofilin was a better predictor for disease recurrence (area under the receiver operating curve AUROC; 0.711; p = 0.005) than other clinicopathological features.
Conclusion
Cofilin is an independent prognostic marker for JNA patients who have undergone surgical treatment and may represent a novel therapeutic target for extensive JNA.

Probiotic extracts ameliorate nasal allergy by inducing interleukin‐35‒producing dendritic cells in mice

17-10-2019 – Jin‐Mei Xue, Fei Ma, Yun‐Fang An, Li‐Min Suo, Xiao‐Rui Geng, Yan‐Nan Song, Li‐Hua Mo, Xiang‐Qian Luo, Xiao‐Wen Zhang, Da‐Bo liu, Chang‐Qing Zhao, Ping‐Chang Yang

Background
The therapeutic efficacy of allergic rhinitis (AR) needs to be improved. Probiotics have immunoregulatory functions. In this study we evaluated the effects of protein extracts of probiotics in the amelioration of AR.
Methods
Extracts of Bifidobacterium infantis (EBI) were prepared by lysing the live probiotics. AR mice were developed to be used to evaluate the therapeutic efficacy of EBI.
Results
The results show that EBI induced interleukin (IL)‐10‒producing dendritic cells (DCs) via increasing IL‐35 and signal transducer and activator of transcription 3 (STAT3) phosphorylation. IL‐10‒expressing DCs induced IL‐10‒producing B cells (B10 cells), with the latter showing immunosuppressive functions. After challenge with specific antigens, AR mice showed sneezing, nasal itch, and increases in serum‐specific immunoglobulin E (Ig
E) and mouse mast cell protease‐1; higher levels of T helper 2 (Th2) cytokines (IL‐4, 67.17 ± 10.66; IL‐5, 62.83 ± 9.70; IL‐13, 51.00 ± 6.69, before treatment) in nasal mucosal protein extracts, which were significantly suppressed (IL‐4, 27.00 ± 6.66; IL‐5, 23.86 ± 4.53; IL‐13, 25.67 ± 4.93, after treatment (p < 0.001) by administration with EBI nasal drops.
Conclusion
EBI can suppress AR via inducing B10 cells. Thus, after carrying out required preclinical experiments and tests, EBI has the translational potential to be used in the treatment of AR and other allergic diseases.

Increased risk of psoriasis in children and elderly patients with asthma: a longitudinal follow‐up study using a national sample cohort

17-10-2019 – So Young Kim, Chanyang Min, Dong Jun Oh, Hyo Geun Choi

Background
Several previous studies reported the elevated risk of asthma in children with psoriasis. This study aimed to extend previous research regarding the risk of psoriasis in children with asthma to an entire population subdivided by age.
Methods
The 2002‐2013 Korean Health Insurance Review and Assessment Service–National Sample Cohort (HIRA‐NSC) was used. The 167,693 participants with asthma were matched with 167,693 control participants for age, sex, income, region of residence, hypertension history, diabetes history, and dyslipidemia history. In both the asthma and control groups, the occurrences of asthma were investigated. The crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis with respect to asthma status were determined using stratified Cox proportional hazards models. Subgroup analyses were conducted according to age and sex.
Results
The prevalence of psoriasis was 0.5% (95% CI, 0.4% to 0.5%; n = 771/167,693) in the asthma group and 0.4% (95% CI, 0.3% to 0.4%; n = 589/167,693) in the control group (p < 0.001). The asthma group (adjusted HR = 1.19; 95% CI, 1.07 to 1.33; p = 0.002) demonstrated higher HRs for psoriasis than did the control group. This result was consistent in the <15 years old, ≥60 years old, and women subgroups.
Conclusion
Asthma was associated with the elevated risk of psoriasis. The possible risk of psoriasis needs to be considered when managing asthma patients. Future study is warranted for the risk of psoriasis according to the endotypes of asthma.

Hypertonic saline and seawater solutions damage sinonasal epithelial cell air‐liquid interface cultures

14-10-2019 – Jian Jiao, Jun Yang, Jingyun Li, Ying Li, Luo Zhang

Journal Article

Background
Nasal irrigation (NI) is commonly used to treat several sinonasal diseases, including chronic rhinosinusitis with nasal polyps (CRSw
NP); however, the effects of NI on the sinonasal epithelium are not fully known. The aim of this study was to investigate the effects of commonly used NI solutions on epithelial mucociliary and barrier functionality in primary cultured human nasal epithelial cells (HNECs).
Methods
HNECs from control subjects and patients with CRSw
NP were established as air‐liquid interface (ALI) cultures. Differentiated cultures were treated with different NI solutions, including isotonic 0.9% and hypertonic 3.0% saline, isotonic and hypertonic seawater, and Ringer lactate solution. The changes in ciliary beat frequency (CBF), numbers of ciliated and goblet cells, and cytotoxicity were measured. Epithelial barrier functionality was assessed by measuring the transepithelial electric resistance (TER), paracellular flux, and expression of tight junction protein zonula occludens‐1 (ZO‐1) and occludin.
Results
Isotonic saline, isotonic seawater, and Ringer lactate solutions did not affect epithelial mucociliary and barrier function in either control or CRSw
NP‐derived ALI cultures; however, hypertonic saline induced a significant disruption of these cell functions in both cultures. Hypertonic seawater caused a transient decrease of CBF and TER in CRSw
NP‐derived ALI cultures, in contrast to inducing an obvious mucociliary and barrier dysfunction and cytotoxicity in control ALI cultures.
Conclusion
Although isotonic NI solutions appear to not affect epithelial mucociliary and barrier function in control and CRSw
NP‐derived ALI cultures, hypertonic saline and seawater solutions damaged sinonasal epithelial cells in ALI cultures. The safety and efficacy of these solutions requires further investigation.

A preliminary report on the effect of gabapentin pretreatment on periprocedural pain during in‐office posterior nasal nerve cryoablation

14-10-2019 – Toby O. Steele, Steven G. Hoshal, Minji Kim, Amarbir S. Gill, Machelle Wilson, Lane D. Squires, E. Bradley Strong, Jeffrey D. Suh

Journal Article

Background
Posterior nasal nerve (PNN) cryoablation is a novel surgical technique to address allergic and nonallergic rhinitis. Periprocedural pain has been reported after PNN cryoablation and there are no standardized protocols for optimal in‐office local anesthesia. This study sought to evaluate the effect of gabapentin on patient discomfort following in‐office PNN cryoablation.
Methods
Multi‐institutional prospective analysis of patients undergoing in‐office PNN cryoablation for allergic or nonallergic rhinitis between March 2018 and April 2019. Patients received local anesthesia with or without 600 mg oral gabapentin 1 hour preprocedure. Rhinitis diagnosis, demographics, and baseline disease‐specific quality of life (mini‐Rhinoconjunctivitis Quality of Life Questionnaire RQLQ and Total Nasal Symptom Score TNSS) were recorded. Patient discomfort was measured by the pain visual analogue scale (VAS) posttreatment and rated 0 to 10 on an ordinal scale. Fishers exact and Wilcoxon 2‐sample tests were used to evaluate differences between the 2 groups.
Results
A total of 26 patients were enrolled (gabapentin n = 15, control = 11). Baseline TNSS scores in the gabapentin vs control group were median 25th percentile to 75th percentile) 10 (7.5 to 11.0) and 9 (6.0 to 10.0) (p = 0.35). Baseline Mini‐RQLQ scores in gabapentin vs control groups were 3.21 (2.0 to 4.0) and 2.92 (2.78 to 4.35) (p = 0.51). The median VAS pain scores at 5, 20, and 30 minutes in the gabapentin vs control group were 0.0 (0.0 to 2.0) vs 3.0 (1.0 to 4.0), 2.0 (0.0 to 3.0) vs 8.0 (6.0 to 10.0), and 1.0 (0.0 to 1.0) vs 5.0 (4.0 to 6.0) (p = 0.02, p = 0.0043, and p = 0.003, respectively).
Conclusion
Preprocedure gabapentin significantly reduces immediate and delayed postprocedural patient discomfort following PNN cryoablation.

Predictors of efficacy for combination oral and topical corticosteroids to treat patients with chronic rhinosinusitis with nasal polyps

14-10-2019 – Madison V. Epperson, Katie M. Phillips, David S. Caradonna, Stacey T. Gray, Ahmad R. Sedaghat

Journal Article

Background
A short‐course oral corticosteroid taper and topical intranasal corticosteroids may be used to maximize the success of medical management for chronic rhinosinusitis with nasal polyps (CRSw
NP). In this study, we sought to identify characteristics that would be predictive of efficacy for this combination regimen.
Methods
Sixty‐four patients with CRS, bilateral polyps, a polyp score of at least 3, and a 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score ≥20 were prospectively enrolled and uniformly treated with a 15‐day prednisone taper and twice daily dilute budesonide irrigations. Participants were assessed at enrollment and at follow up, 2 to 5 months later. Clinical and demographic characteristics were assessed at enrollment. At both time points, CRS symptoms were assessed with SNOT‐22, and polyp score (range, 0 to 6) was assessed endoscopically. Associations were determined with regression.
Results
Pretreatment SNOT‐22 score (adjusted β = −0.83; 95% CI, −1.08 to −0.58; p < 0.001) and comorbid asthma (adjusted β = 15.75; 95% CI, 4.74 to 26.75; p = 0.007) were associated with a change in SNOT‐22 experienced over the study period. Achieving a greater‐than‐1 minimal clinically important difference (MCID) improvement in SNOT‐22 score was also associated with pretreatment SNOT‐22 score (adjusted OR = 1.09; 95% CI, 1.04 to 1.14; p < 0.001) and comorbid asthma (adjusted OR = 0.13; 95% CI, 0.03 to 0.72; p = 0.019). SNOT‐22 score ≥47 had 81.5% sensitivity and 78.4% specificity to detect patients experiencing 1 MCID improvement. Pretreatment polyp score was not associated with any outcome metric.
Conclusion
In treatment of CRSw
NP with prednisone and budesonide irrigations, pretreatment endoscopy was not informative of treatment response. Pretreatment SNOT‐22 and comorbid asthma may be more predictive.

Lightening in a bottle: comparison of ultraviolet light to traditional sterilization in saline irrigations bottles

10-10-2019 – Qasim Husain, Catherine Banks, Bradford A. Woodworth, Benjamin S. Bleier

Journal Article

Background
Nasal saline irrigations (NSIs) are commonplace in treatment of patients with sinonasal disorders. Contamination of both the water source and delivery bottle remains a challenge with this therapy. The goal of this study was to optimize a disinfection technique with various methods of preparation, disinfection, and delivery of NSIs.
Methods
Distilled and tap water sources in NSI bottles were contaminated by 4 bacterial strains: Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Legionella pneumophila. Contaminated bottles were cleaned with tap water, tap water with detergent, or microwave and swabbed for culture. Water‐source disinfection was performed with reverse osmosis, distillation, activated carbon filtration, boiling, or ultraviolet (UV) light treatment. Test samples from each experimental group (n = 3/group) were cultivated on the appropriate media with colony‐forming units (CFUs) reported.
Results
All methods of bottle cleaning with tap water with/without detergent and microwave significantly reduced bacterial load (CFUs) by >99% (p < 0.05). Distillation and boiling of the contaminated water source eliminated 100% of bacteria, whereas reverse osmosis and activated carbon filtration did not. A single UV treatment of contaminated water within a bottle eliminated 99% of bacteria within the water and 100% in the bottle.
Conclusion
Cleansing of NSI bottles with tap water with/without detergent or microwave produced robust bacterial disinfection. Distillation and boiling of a contaminated water source completely eliminated all bacteria. UV light treatment was capable of simultaneous disinfection of both the water source and bottle, suggesting this may be a convenient, 1‐step method of preparing NSIs for patients.

Central compartment atopic disease: prevalence of allergy and asthma compared with other subtypes of chronic rhinosinusitis with nasal polyps

10-10-2019 – Sonya Marcus, Joseph Schertzer, Lauren T. Roland, Sarah K. Wise, Joshua M. Levy, John M. DelGaudio

Journal Article

Background
Central compartment atopic disease (CCAD) is a recently described variant of chronic rhinosinusitis with nasal polyp (CRSw
NP) associated with inhalant allergy. An association with asthma was noted to be uncommon within our clinical practice. The purpose of this study was to determine allergy and asthma prevalence in CCAD and other CRSw
NP subtypes.
Methods
A retrospective analysis at a tertiary care institution was performed over the period from 2015 to 2019. CRSw
NP was grouped into the following subtypes: allergic fungal rhinosinusitis (AFRS); aspirin‐exacerbated respiratory disease (AERD); CCAD; and CRSw
NP not otherwise specified (CRSw
NP NOS). Patients with sinonasal polyps and concomitant polypoid disease in the central compartment (CRSw
NP/CC) were analyzed as a separate cohort for the purpose of this study. Prevalence of allergy and asthma was compared between groups.
Results
Three hundred fifty‐six patients were included. CRSw
NP NOS was the most common subtype (37.1%) and CRSw
NP/CC was the least common (3.7%), with other CRS subtypes ranging between 11.5% and 24.2%. Asthma prevalence was highest in AERD (100%) and CRSw
NP NOS (37.1%), but substantially lower in AFRS (19.0%) and CCAD (17.1%). Asthma was significantly more common in AERD and CRSw
NP NOS when compared with CCAD (p < 0.001 and p = 0.039, respectively). Prevalence of allergy was significantly higher in AFRS (100%), CCAD (97.6%), CRSw
NP/CC (84.6%), and AERD (82.6%) when compared with CRSw
NP NOS (56.1%) (p < 0.001).
Conclusion
CCAD represents a clinically distinct phenotype of CRSw
NP with a high prevalence of allergy and low prevalence of asthma. Patients with both CCAD and diffuse sinonasal polyps had an allergy prevalence approaching that of CCAD and an asthma prevalence approaching CRSw
NP NOS.

Computational fluid dynamics simulation to compare large volume irrigation and continuous spraying during nasal irrigation

07-10-2019 – Ludovic Gabory, Mélodie Kérimian, Yannick Baux, Nicolas Boisson, Laurence Bordenave

Journal Article

Background
Nasal irrigation is now widely recognized as a treatment for chronic rhinosinusitis and during the postoperative period. However, there are no guidelines for performing irrigation. This study used computational fluid dynamics (CFD) simulation objective physical parameters to optimize and increase the efficiency of nasal irrigation and to compare large‐volume, manual, and gravity pressure irrigation vs small‐volume continuous spraying.
Methods
A 3‐dimensional (3D) sinonasal model was constructed from a healthy adult high‐resolution computed tomography (CT) scan. The 3D nasal model was constructed using a tetrahedral and hex‐dominant mesh grid with TGRID™ 16 (ANSYS Inc., Villeurbanne, France) software. A structured hex mesh was created inside the domain using the Hexcore meshing method. The final mesh had a total of 9.6 × 106 cells with an average size of 0.29 mm3, or an average volume of 2.42 × 10−2 mm3. Navier‐Stokes equations were resolved with the standard k – ε  model.
Results
Large‐volume irrigation (15 m
L/s) covered all zones (136 to 310 cm2) rapidly with strong shear stress and prolonged contact time (310 m
Pa 3.26 seconds for gravity mode and 280 m
Pa 3.35 seconds for manual pressure mode). Continuous spraying (3 m
L/second) covered all areas (76 to 310 cm2) but with far less volume, more slowly, with low shear stress (50 m
Pa), and with shorter contact time (1.84 seconds). The surface wetted by time in contact was 135.4, 113.9, and 46.6 cm2 for gravity, manual pressure mode, and continuous spraying, respectively.
Conclusion
CFD simulation visualizes the circulation of water during nasal irrigation and makes it possible to determine objective parameters to decide which mode of irrigation may be used.

Sinonasal mucosal vasculature in yellow nail syndrome and chronic rhinosinusitis with or without polyps

07-10-2019 – “Kyriakos Chatzopoulos, Claudia N. Gutierrez, Joaquin J. Garcia, Janalee K. Stokken, Garret Choby, Erin K. OBrien”

Journal Article

Background
Lymphatic dysfunction is hypothesized to be an underlying factor in the pathophysiology of yellow nail syndrome (YNS) (yellow nails, lymphedema, pleural effusions, and frequently chronic rhinosinusitis CRS). It is unclear why some YNS patients develop CRS. We quantified lymphatic and total vasculature of sinonasal mucosa in YNS patients and compared it to controls from CRS patients with (CRSw
NP) or without polyps (CRSs
NP).
Methods
Immunohistochemistry was performed on archival sinonasal mucosal samples from 5 patients with YNS and 14 controls with antibodies against podoplanin and CD31, markers of lymphatics. Morphometric assessment was performed on digital images using ImageJ software.
Results
In YNS, the number of lymphatics/mm2 ranged from 7 to 18/mm2 (controls: 6 to 43/mm2, p = 0.343), with a mean perimeter between 92 and 201 µm (controls: 42 to 280 µm, p = 0.482). Total vasculature density was higher than lymphatics, ranging between 189 and 1159 vessels/mm2, average 669 (controls: 139 to 1467/mm2, average 503, p = 0.257) with smaller average perimeter, 40 to 117 µm, mean 64.8 µm (controls: 42 to 92 µm, mean 65.3 µm, p = 0.965). Lymphatics constituted only a small fragment of the total vasculature, ranging from 1.15% to 4.76%, average 2.34% (controls: 0.81% to 10.58%, average 4.88%, p = 0.156). CRSw
NP patients had significantly higher lymphatic density (p = 0.011) and ratio of lymphatics to total vasculature (p = 0.045) than patients with YNS or CRSs
NP.
Conclusion
This is the first histological analysis of sinus mucosa in patients with YNS. Vascular type, density, size, and distribution in the sinonasal mucosa of YNS patients are not statistically significantly different from those of the CRSs
NP group. Lymphatic density and ratio to total vasculature is higher in CRSw
NP patients.

Prevalence and characterization of chronic rhinosinusitis in patients with non‒cystic fibrosis bronchiectasis at a tertiary care center in the United States

07-10-2019 – Shaan N. Somani, Jason H. Kwah, Chen Yeh, David B. Conley, Leslie C. Grammer, Robert C. Kern, Michelle Prickett, Robert P. Schleimer, Stephanie S. Smith, Whitney W. Stevens, Bruce K. Tan, Kevin C. Welch, Anju T. Peters

Journal Article

Background
Chronic rhinosinusitis (CRS) is associated with bronchiectasis; however, this relationship has not been well studied in the United States (US) population. In this work we aimed to determine the prevalence of CRS among patients with bronchiectasis affiliated with a US tertiary medical center and identify which comorbid diseases are associated with the presence of CRS in patients with bronchiectasis.
Methods
This was a retrospective cohort study in which data were obtained from a large database warehouse at a tertiary care center. Patients with bronchiectasis were identified from 2007 to 2017 using diagnosis codes from the the ninth and tenth revisions of the International Classification of Diseases (ICD‐9/10) and confirmed by radiographic evidence of bronchiectasis on chest computed tomography (CT) scans. Patients were divided into cohorts based on presence or absence of concomitant CRS. Characteristics analyzed included demographics, comorbidities, peripheral eosinophil counts, and pulmonary function testing.
Results
CRS was present in 45% (408 of 900) of patients with bronchiectasis. Females represented a majority of bronchiectasis patients, both with and without CRS (69% and 64%, respectively, p = 0.09). After controlling for demographic factors, asthma (p < 0.01), allergic rhinitis (p < 0.01), gastroesophageal reflux disease (p < 0.01), and antibody deficiency (p < 0.01) were associated with the presence of CRS in patients with bronchiectasis.
Conclusion
CRS had a high prevalence and was associated with numerous comorbid conditions in patients with bronchiectasis. These findings have clinical implications for the treatment of patients with bronchiectasis and future research.

Readmissions after endoscopic skull base surgery: associated risk factors and prevention

07-10-2019 – Gennadiy Vengerovich, Ki Wan Park, Layal Antoury, Christine Wells, Jeffrey D. Suh, Jivianne T. Lee, Anthony P. Heaney, Marvin Bergsneider, Marilene B. Wang

Journal Article

Background
Unplanned readmissions within 30 days of discharge is a quality measure introduced by the Centers for Medicare Services. This measure has been used to rate hospital quality and also to penalize hospitals for excess readmissions. It has been hypothesized that shorter hospital stays and fewer readmissions are associated with endoscopic skull base procedures. In this study we analyze endoscopic skull base procedures performed at our institution over a 10‐year period to identify rates and factors associated with readmissions after endoscopic skull base surgery.
Methods
A retrospective chart review was performed at a tertiary care academic medical center identifying patients who underwent endoscopic skull base surgery over the past 10 years. Data on patient demographics and tumor variables, as well as patient variables such as body mass index (BMI), revision surgery, history of skull base radiation, medical comorbidities, intraoperative cerebrospinal fluid (CSF) leaks, and postoperative CSF leaks, were recorded.
Results
Eight hundred thirty‐three patients were included in our study. Sixty‐one patients (7.3%) were readmitted a total of 66 times within 30 days. The most common reasons were as follows: hyponatremia (n = 18); CSF leak (n = 17); epistaxis (n = 3); diabetes insipidus (n = 3); rhinorrhea (n = 3); as well as other reasons. Statistical analysis revealed that the presence of intraoperative CSF leak was the only statistically significant variable associated with increased rate of readmissions within 30 days of discharge (p < 0.001).
Conclusion
Presence of intraoperative CSF leak was the only statistically significant variable associated with an increased risk for readmission after surgery. Other tumor and patient variables were not associated with an increased risk of readmission within 30 days.

A minimally invasive endoscopic transnasal retropterygoid approach to the upper parapharyngeal space: anatomic studies and surgical implications

01-10-2019 – Juan Liu, Xicai Sun, Quan Liu, Yurong Gu, Houyong Li, Chunquan Zheng, Dehui Wang, Juan C. Fernandez‐Miranda, Carl H. Snyderman, Hongmeng Yu

Journal Article

Background
Surgery remains the mainstay of treatment for lesions in the parapharyngeal space. However, gaining access to the parapharyngeal space is often challenging. In this study we aim to describe a minimally invasive technique of approaching the upper parapharyngeal space through an endoscopic transnasal retropterygoid approach, based on anatomic studies and surgeries.
Methods
Six fresh human cadaver heads were prepared for anatomic study at the Surgical Neuroanatomy Laboratory of the Center for Cranial Base Surgery within the Department of Neurological Surgery at the University of Pittsburgh School of Medicine. Three clinical cases seen in the Department of Otolaryngology, Eye, Ear, Nose, and Throat Hospital, Shanghai Medical College of Fudan University, were used to illustrate the technique and feasibility of this approach and to assess its indications, advantages, and drawbacks.
Results
The medial pterygoid plate is the primary landmark of the endoscopic transnasal retropterygoid approach to the upper parapharyngeal space. Access to the upper parapharyngeal space could be obtained by removing the mucosa on the medial pterygoid plate and the mucosa below the pharyngeal orifice of the Eustachian tube. The 3 patients in our study tolerated the procedure well and had no serious complications after surgery.
Conclusion
The anatomic data and clinical cases in this study confirm that an endoscopic transnasal retropterygoid approach is a feasible and effective surgical treatment for selected tumors in the upper parapharyngeal space.

Effects of modifying visual inhaler spacer usage instructions on correct usage rate of untrained users

01-10-2019 – Erdem Topal, Mustafa Arga, Hakan Özmen, Mahmut Doğru, Cem Alataş, Elif Büşra Muştu, Mehmet Halil Çeliksoy

Journal Article

Background
Pressurized metered‐dose inhalers (p
MDIs) used with spacers are considered the method of choice for delivery of inhaled drugs in preschool‐age children. The aim of this study was to determine the effects of modifying the visual inhaler spacer usage guidelines on the correct usage rate.
Methods
The parents and caregivers of patients <6 years old who were prescribed inhalers with spacers for the first time were included in our study. The participants were randomly divided into a modified visual inhaler spacer usage guidelines group and an unmodified visual inhaler spacer usage guidelines group. All study participants underwent face‐to‐face interviews and completed questionnaires.
Results
A total of 510 participants with a median age of 31 (range, 20‐46) years were included in this study. The modified visual guidelines group included 254 (49.6%) participants, and the unmodified visual guidelines group included 256 (50.4%) participants. One hundred sixty‐five (65.2%) of the 254 participants in the modified visual guidelines group correctly demonstrated the inhaler spacer technique. In contrast, only 21 (8.2%) of the 256 participants in the unmodified visual guidelines group correctly demonstrated the inhaler spacer technique (p < 0.001). When comparing the inhaler spacer usage steps between the 2 groups, the modified visual guidelines group demonstrated the steps more correctly and more quickly (p < 0.001).
Conclusion
The current visual inhaler spacer usage guidelines are insufficient. We believe that improving the visual inhaler spacer usage guidelines, in particular, will increase the correct usage rate and decrease the number of usage errors.

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

01-10-2019 – 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.

Olfactory cleft mucus proteins associated with olfactory dysfunction in a cohort without chronic rhinosinusitis

01-10-2019 – Frederick Yoo, Zachary M. Soler, Jennifer K. Mulligan, Kristina A. Storck, Jensine M. Lamira, Whitney N. Pasquini, Jonathan B. Hill, Tegan E. Noonan, Brandon J. Washington, Rodney J. Schlosser

Journal Article

Background
Olfactory dysfunction (OD) is a common problem, affecting up to 20% of the general population. Previous studies identified olfactory cleft mucus proteins associated with OD in chronic rhinosinusitis (CRS) but not in a healthy population. In this study we aimed to identify olfactory cleft mucus proteins associated with olfaction in individuals without sinus disease.
Methods
Subjects free of sinus disease completed medical history questionnaires that collected data regarding demographics, comorbidities, and past exposures. Olfactory testing was performed using Sniffin’ Sticks, evaluating threshold, discrimination, and identification. Olfactory cleft mucus (OC) and, in select cases, inferior turbinate mucus (IT) were collected with Leukosorb paper and assays performed for 17 proteins, including growth factors, cytokines/chemokines, cell‐cycle regulators, and odorant‐binding protein (OBP).
Results
Fifty‐six subjects were enrolled in the study, with an average age of 47.8 (standard deviation SD, 17.6) years, including 33 females (58.9%). The average threshold/discrimination/identification (TDI) score was 30.3 (SD, 6.4). In localization studies, OBP concentrations were significantly higher in OC than IT mucus (p = 0.006). Cyclin‐dependent kinase inhibitor 2A (CDKN2A/p16INK4a), basic fibroblast growth factor (b
FGF), chemokine ligand 2 (CCL2/MCP‐1), granulocyte macrophage colony‐stimulating factor (GM‐CSF), and chemokine ligand 20 (CCL20/MIP‐3a) all inversely correlated with overall TDI (all rho ≥ ‐0.479, p ≤ 0.004). Stem cell factor (SCF) correlated positively with overall TDI (rho = 0.510, p = 0.002).
Conclusion
Placement of Leukosorb paper is relatively site‐specific for olfactory proteins and it is feasible to collect a variety of olfactory cleft proteins that correlate with olfactory function. Further study is required to determine mechanisms of OD in non‐CRS subjects.

Antibiotic prophylaxis in anterior skull‐base surgery: a survey of the North American Skull Base Society

01-10-2019 – Christina H. Fang, Vivian S. Hawn, Vijay Agarwal, Howard S. Moskowitz, Varun R. Kshettry, Erin L. McKean, Emily Bellile, Nadeem A. Akbar, Waleed M. Abuzeid

Journal Article

Background
There is a paucity of data evaluating antibiotic use in anterior skull‐base surgery (ASBS). The goal of this study was to determine antibiotic prescribing patterns and factors that influence antibiotic use in ASBS.
Methods
An online‐based survey was distributed to the membership of the North American Skull Base Society in 2018. Outcomes included practitioner preference regarding intraoperative and postoperative antibiotic use, practice location and environment, surgeon experience, and patient factors influencing antibiotic use.
Results
There were 208 respondents (25.6% response rate) of which 182 (87.5%) performed ASBS; 60.4% were in academic institutions. Respondents were neurosurgeons (59.3%) or otolaryngologists (40.7%), and 75.3% were fellowship‐trained in ASBS. Most surgeons (95.0%) gave intraoperative antibiotics. Academic surgeons were 4 times more likely to prescribe intraoperative antibiotics than private practitioners (odds ratio OR 3.98; 95% confidence interval CI, 1.53 to 10.36; p = 0.005). Among surgeons who did not routinely prescribe intraoperative antibiotics, regression analysis indicated that the presence of actively infected sinuses, transplantation, diabetes, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and pulmonary disease influenced decision‐making (p < 0.03). Postoperative antibiotics were prescribed by 73.6% of respondents. European surgeons were 3 times less likely to prescribe postoperative antibiotics (OR 0.34; 95% CI, 0.15 to 0.80; p = 0.01). Regression modeling indicated that HIV/AIDS, cystic fibrosis, diabetes, transplantation, and pulmonary disease, as well as the use of absorbable packing influenced the decision to use postoperative antibiotics (p < 0.003).
Conclusion
This study demonstrates the significant variation in intra‐ and postoperative antibiotic use among surgeons performing ASBS. Prospective randomized studies are necessary to establish evidence‐based practice guidelines for perioperative antibiotic use in ASBS.

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

01-10-2019 – 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.

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

01-10-2019 – 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.

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

01-10-2019 – 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.

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

01-10-2019 – 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.

Advanced age adversely affects chronic rhinosinusitis surgical outcomes

01-10-2019 – Kristen L. Yancey, Anne S. Lowery, Rakesh K. Chandra, Naweed I. Chowdhury, Justin H. Turner

Journal Article

Background
Patient‐specific and disease‐specific factors shape the course of chronic rhinosinusitis (CRS) and its response to treatment, with optimal management involving interventions tailored to these factors. Recent evidence suggests CRS inflammatory signatures depend on age. The objective of this study was to determine whether age also influences quality‐of‐life (QOL) and postoperative outcomes.
Methods
Retrospective analysis of prospectively collected QOL data from 403 adults with medically refractory CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary care medical center between 2014 and 2018 was undertaken. Total and subdomain scores from the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and the Short Form 8 Health Survey (SF‐8) measure of general health completed at preoperative and postoperative visits were reviewed.
Results
Patients were divided into young (18 to 39 years, n = 100), middle‐aged (40 to 59 years, n = 172), and elderly (≥60 years, n = 131) groups. Baseline total SNOT‐22 scores differed between groups (p = 0.01), with middle‐aged patients having the highest symptom burden and elderly patients having the lowest. Similar patterns were observed for SNOT‐22 subdomains. Elderly patients reported smaller improvements and were less likely to achieve a minimally important clinical difference. CRS patients had worse SF‐8 scores compared to the general population, and elderly patients were the least likely to match population norms following surgery. Age was an independent predictor of QOL outcomes after FESS.
Conclusion
Age may play a significant role in CRS pathophysiology, symptom burden, and surgical outcomes. Elderly patients report smaller improvements in disease‐specific and general health QOL after surgery. CRS management in the elderly population should incorporate age‐dependent differences in symptom burden and expectations into treatment algorithms.

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

01-10-2019 – 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.

Effects of endoscopic sinus surgery on objective and subjective measures of cognitive dysfunction in chronic rhinosinusitis

01-10-2019 – Frederick Yoo, Rodney J. Schlosser, Kristina A. Storck, Kimia G. Ganjaei, Nicholas R. Rowan, Zachary M. Soler

Journal Article

Background
Chronic rhinosinusitis (CRS) is a common condition that has been associated with cognitive dysfunction. The purpose of this study was to evaluate the effect of endoscopic sinus surgery (ESS) on the subjective and objective measures of cognitive dysfunction and related quality‐of‐life measures in CRS.
Methods
Thirty‐five adults with CRS refractory to medical therapy were prospectively enrolled. Preoperatively and postoperatively (≥4 months), subjects completed objective neurocognitive evaluation with the Automated Neuropsychological Assessment Metrics (ANAM) platform and multiple questionnaires, including the Cognitive Failures Questionnaire (CFQ), a modified World Health Organization Health and Work Performance Questionnaire (ct
HPQ), 22‐item Sino‐Nasal Outcomes Test (SNOT‐22), Sinus Control Test (SCT), Questionnaire of Olfactory Disorders (QOD), Beck Depression Inventory―second edition (BDI‐II), Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS).
Results
Thirty‐three of 35 patients satisfactorily completed the study. Postsurgical improvement in the CFQ was 46.7 ± 18.4 to 31.9 ± 17.8 (p < 0.001). Neurocognitive testing revealed significant improvements in mathematical processing (p = 0.003) and matching to sample (p = 0.023), as well as a significant decline in simple reaction time (p = 0.026). In addition, improvements were noted for SNOT‐22 (54.8 ± 21.4 to 24.8 ± 21.1, p < 0.001), SCT (9.3 ± 2.6 to 3.9 ± 3.8, p < 0.001), PSQI (10.7 ± 4.5 to 6.9 ± 4.0, p < 0.001), BDI‐II (14.0 ± 9.9 to 8.9 ± 9.0, p < 0.001), QOD (17.6 ± 13.4 to 9.9 ± 12.3, p = 0.001), and FSS (4.6 ± 1.4 to 3.1 ± 1.5, p < 0.001). There was significant improvement in overall presenteeism (7.3 ± 1.4 to 8.4 ± 1.3, p = 0.029). Analysis by polyp status revealed significant improvement in mathematical processing and matching to sample in only CRS patients without polyps.
Conclusion
ESS is associated with improvement in subjective and some aspects of objective cognition.

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

01-10-2019 – 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

01-10-2019 – 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.

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

01-10-2019 – 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.
Conclusion
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.

Rhinologic and skull‐base surgery: an evidence‐based reevaluation

01-10-2019 – David W. Kennedy

Editorial

Issue Information

01-10-2019 –

Erratum for “Scientific abstracts for RhinoWorld 2019”

01-10-2019 –

Published Erratum

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

01-10-2019 – 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.

Calmodulin and protein kinases A/G mediate ciliary beat response in the human nasal epithelium

01-10-2019 – Ba Hung Do, Thi Nga Nguyen, Ryoko Baba, Toyoaki Ohbuchi, Jun‐ichi Ohkubo, Takuro Kitamura, Tetsuro Wakasugi, Hiroyuki Morimoto, Hideaki Suzuki

Journal Article

Background
Mucociliary clearance of the airway epithelium is an essential function for mucosal defense. We recently proposed a hypothetical mechanism of ciliary beat regulation, in which the pannexin‐1 (Panx1)‐P2X7 unit serves as an oscillator generating a periodic increase in intracellular Ca2+ (Ca2+i). In the present study, we examined the localization of Panx1 and P2X7 at the ultrastructural level, and investigated the regulatory pathway subsequent to Ca2+i increase.
Methods
The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic sinonasal surgery. The mucosa was examined by transmission immunoelectron microscopy for Panx1 and P2X7. Alternatively, the mucosa was cut into thin strips, and ciliary beat frequency (CBF) was measured under a phase‐contrast light microscope with a high‐speed digital video camera.
Results
In immunoelectron microscopy, immunoreactivities for Panx1 and P2X7 were localized along the plasma membrane of the entire length of the cilia. CBF was significantly increased by stimulation with 100 µM acetylcholine (Ach). The Ach‐induced CBF increase was significantly inhibited by calmidazolium (calmodulin antagonist), SQ22536 (adenylate cyclase inhibitor), ODQ (guanylate cyclase inhibitor), KT5720 (protein kinase A inhibitor), and KT5823 (protein kinase G inhibitor). Fluorodinitrobenzene (creatine kinase inhibitor) completely inhibited the ciliary beat in a time‐ and dose‐dependent manner.
Conclusion
These results indicate that Panx1 and P2X7 coexist at the cilia of the human nasal epithelial cells and that the ciliary beat is regulated by calmodulin, adenylate/guanylate cyclases and protein kinases A/G, and crucially depends on creatine kinase.

Development and validation of a preclinical model for training and assessment of cerebrospinal fluid leak repair in endoscopic skull base surgery

01-10-2019 – Davide Mattavelli, Marco Ferrari, Vittorio Rampinelli, Alberto Schreiber, Barbara Buffoli, Alberto Deganello, Luigi F. Rodella, Marco M. Fontanella, Piero Nicolai, Francesco Doglietto

Journal Article

Background
Achieving an effective endoscopic skull base reconstruction in case of large dural defects requires specific training and can be extremely challenging. The aim of this study was to describe the development and validation of a preclinical model for cerebrospinal fluid (CSF) leak repair, which can be used for training and to test the mechanical efficacy of endoscopic skull base reconstruction.
Methods
Eleven fresh‐frozen cadaver heads were dissected. A catheter was inserted in the subdural space via a cervical access, which was sealed with mastic; a vertical graduated tube connected to the catheter measured intracranial pressure (ICP), while stained water was injected intracranially. After endoscopic skull base reconstruction was performed, an expert surgeon assessed its efficacy. ICP was then gradually increased until a leak was evident and CSF leak pressure value was recorded. The correlation between subjective and quantitative evaluations was investigated through Pearson and Spearman correlation tests.
Results
The model was successfully tested in 11 specimens. A single, large dural defect was created in each model (transplanum‐transtuberculum = 4; transplanum‐transtuberculum‐transsellar = 3; transclival = 3; transcribriform‐transplanum = 1). Skull base reconstruction always comprised a rigid buttress with temporal fascia and/or fat. The CSF leak pressure ranged from 4 to 110 cm
H2O. The correlation between expert subjective and quantitative assessment of skull base reconstruction mechanical efficacy was high (r = 0.7; rs = 0.7; p = 0.010 and p = 0.006, respectively).
Conclusion
This preclinical model is simple, easily reproducible, and effective in simulating an intraoperative leak and objectively measures the CSF leak pressure point of a skull base reconstruction.

Endoscopic sinus surgery improves aspirin treatment response in aspirin‐exacerbated respiratory disease patients

30-09-2019 – Sharan J. Shah, Waleed M. Abuzeid, Anusha Ponduri, Teresa Pelletier, Zhen Ren, Taha Keskin, Gigia Roizen, David Rosenstreich, Denisa Ferastraoaru, Elina Jerschow

Journal Article

Background
Aspirin desensitization and treatment benefits most patients with aspirin‐exacerbated respiratory disease (AERD), although some patients fail therapy. Our objective was to assess whether recent endoscopic sinus surgery (ESS) improved aspirin treatment outcomes in AERD patients who initially failed aspirin therapy.
Methods
Outcomes of aspirin desensitization and treatment in AERD patients prospectively enrolled were assessed preoperatively and at 4, 12, and 24 weeks after ESS by determining changes in Asthma Control Test (ACT) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and respiratory function. Biomarkers, including fractional excretion of nitric oxide (Fe
NO), spirometry, nasal inspiratory peak flow (NPF), immunoglobulin E (Ig
E), and eosinophil count, were measured.
Results
Nineteen patients who benefited (responders) and 21 patients who failed (nonresponders) preoperative aspirin treatment with a distant history of ESS (mean, 48 months) were identified. Nonresponders were more likely to be African American (71%, p < 0.01) and have higher baseline Ig
E levels (252 k
U/L vs 87 k
U/L in responders, p < 0.01). 24 of the 40 patients (nine responders and 15 non‐responders) required subsequent ESS and underwent another aspirin desensitization 3‐4 weeks after ESS. All 24 patients tolerated a second round of aspirin desensitization and treatment. The primary aspirin therapy was associated with a significant increase in Ig
E in nonresponders, but there was no significant increase in Ig
E after the second aspirin desensitization and treatment.
Conclusion
Antecedent ESS enhances aspirin treatment responses in AERD patients and may convert patients who failed aspirin treatment before surgery to a more responsive phenotype after ESS. Patients with higher baseline serum Ig
E levels may benefit from ESS performed shortly before aspirin desensitization and therapy.

Impact of age on outcomes following endoscopic sinus surgery for chronic rhinosinusitis

26-09-2019 – Dana L. Crosby, Jeb Jones, James N. Palmer, Noam A. Cohen, Michael A. Kohanski, Nithin D. Adappa

Journal Article

Background
Chronic rhinosinusitis (CRS) is a common condition that affects people of all ages and negatively impacts quality of life. The goal of this study was to identify differences in outcomes by age following endoscopic sinus surgery (ESS) for CRS utilizing 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores.
Methods
Data from 1252 adult CRS patients electing to undergo ESS (2007‐2018) were collected retrospectively. The median age of 50 years was used to divide the data into 2 groups for comparison of the impact of age on SNOT‐22 scores at 0, 3, and 6 months after surgery. Changes in SNOT‐22 scores were analyzed using a mixed models analysis.
Results
After adjusting for gender, race, polyp status, and number of prior ESSs, patients younger than 50 years had a higher mean pre‐ESS SNOT‐22 score (44.0) compared to those of at least 50 years of age (38.9). Among patients younger than 50 years, SNOT‐22 scores declined by 20.7 points at 3 months post‐ESS and 16.1 points at 6 months post‐ESS. The rate of change between the dichotomized age groups was not significantly different at 3 and 6 months post‐ESS (p = 0.7952 and p = 0.1057, respectively).
Conclusion
Both age groups showed significant and durable improvement in SNOT‐22 scores after ESS. Patients younger than 50 years of age have higher pre‐ESS SNOT‐22 scores, but converge to the same SNOT‐22 scores by 3 months post‐ESS. The rate of change of SNOT‐22 scores is not different between those younger than 50 years and those of at least 50 years.

Free mucosal grafts and anterior pedicled flaps to prevent ostium restenosis after endoscopic modified Lothrop (frontal drillout) procedure: a randomized, controlled study

24-09-2019 – Ying‐Piao Wang, Ping‐Hung Shen, Li‐Chun Hsieh, Peter‐John Wormald

Journal Article

Background
The endoscopic modified Lothrop procedure (EMLP) is used to manage ongoing refractory frontal sinusitis after failed previous endoscopic sinus surgery (ESS), but this approach has a significant restenosis rate. We evaluated the potential benefits of mucosal grafts and pedicled flaps on the opening of the newly formed frontal ostium.
Methods
Fifty patients with refractory frontal sinusitis or mucoceles after ESS were randomized to undergo EMLP, either with (n = 27) or without (n = 23) mucosal grafts and pedicled flap reconstruction of the neo‐ostium. The frontal neo‐ostium was measured with Lindholm distending forceps, and anteroposterior (A‐P) and lateral dimensions were measured intraoperatively, and then again at 6 weeks, 6 months, and 12 months postoperatively. Olfaction outcomes were assessed using the Taiwan Smell Identification Test (TWSIT) and a smell visual analog scale (VAS) score preoperatively and at 6 months postsurgery.
Results
The initial intraoperative mean lateral and A‐P dimensions were 23.2 ± 2.7 mm and 14.8 ± 2.3 mm and were significantly decreased at all time‐points postoperatively. The mucosal grafts and pedicled flaps had greater lateral and A‐P dimensions, and a greater percentage of intraoperative frontal neo‐ostium area at all time‐points postoperatively (all p < 0.05). At 6 months postoperatively, TWSIT (p = 0.027), but not the smell VAS score (p = 0.063), was significantly improved compared with baseline. TWSIT and smell VAS score changes did not differ between groups (p = 0.92 and p = 0.85, respectively).
Conclusion
The use of mucosal grafts and pedicled flaps reduces stenosis of the frontal neo‐ostium postsurgery and should be considered after EMLP.

Infiltration pattern of gammadelta T cells and its association with local inflammatory response in the nasal mucosa of patients with allergic rhinitis

23-09-2019 – Qintai Yang, Chunwei Li, Weihao Wang, Rui Zheng, Xuekun Huang, Huiyi Deng, Peng Jin, Kaisen Tan, Yan Yan, Deyun Wang

Journal Article

Backgroundgammadelta (γδ) T cells play important roles in allergic lower airway inflammation. However, little is known about their infiltration pattern in the nasal mucosa during upper airway inflammation. This study investigated γδ T cell distribution in nasal tissues of allergic rhinitis (AR) patients and the relationship between γδ T cells and other inflammatory cell types.
Methods
A total of 30 patients with septal deviation were examined, including 22 with and 8 without AR. The localization of γδ T cells and other cells (eosinophils, neutrophils, mast cells, macrophages, B cells, cluster of differentiation CD4+ T cells, CD8+ T cells, regulatory T cells Tregs, interferon IFN‐γ+ cells, interleukin IL17+ cells, and IL10+ cells) was evaluated by histological analysis and immunohistochemistry. T helper cell (Th)1/Th2/Th17 and Treg gene expression was analyzed by quantitative polymerase chain reaction (PCR).
Resultsγδ T cells were localized in the epithelium or subepithelial region of nasal mucosa, and their infiltration was higher in AR patients relative to control subjects. The number of γδ T cells was associated with the presence of eosinophils, macrophages, mast cells, B cells, CD8+ T cells, Forkhead box (Fox)p3+ Tregs, IL17+ cells, and IL10+ cells but not of neutrophils or IFN‐γ+ cells. The messenger RNA (m
RNA) level of a γδ T cell subunit was positively correlated with those of Th1 genes (T‐bet and IFN‐γ), Th2 cytokine (C‐C motif chemokine ligand 18), and Treg genes (Foxp3 and IL10).
Conclusionγδ T cells play multiple roles in mucosal inflammation in AR including immune surveillance and adaptive and innate immune responses.

Hemokinin‐1 stimulates C‐C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps

23-09-2019 – Yi‐Ke Deng, Jin Ma, Zhi‐Chao Wang, Xiao‐Bo Long, Cai‐Ling Chen, Qi‐Miao Feng, Xin‐Hao Zhang, Ming Zeng, Heng Wang, Xiang Lu, Zheng Liu

Journal Article

Background
The mechanisms underlying mucosal eosinophilia in chronic rhinosinusitis with nasal polyps (CRSw
NP) remain poorly clarified. The nervous system and neuropeptides play an important role in the regulation of immune response. Herein we explore the expression and function of hemokinin‐1 (HK‐1), a newly identified tachykinin, along with its receptor neurokinin 1 receptor (NK1R) in CRSw
NP.
Methods
HK‐1, NK1R, and C‐C motif chemokine ligand 24 (CCL24) expression in nasal tissues (53 eosinophilic CRSw
NP, 32 non‐eosinophilic CRSw
NP, and 33 controls) was investigated by quantitative reverse transcript polymerase chain reaction (RT‐PCR) and immunofluorescence staining. THP‐1, a human monocytic leukemia cell line, and eosinophilic polyp tissues were stimulated with HK‐1. Cells, tissues, and culture supernatants were subsequently collected for detection of the production of various inflammatory cytokines and chemokines by quantitative RT‐PCR and enzyme‐linked immunoassay.
Results
HK‐1 and NK1R m
RNA and protein expression were upregulated in eosinophilic and non‐eosinophilic nasal polyps compared with control tissues, with eosinophilic polyps demonstrating a higher upregulation compared with that of non‐eosinophilic polyps. Eosinophils constituted the major source of HK‐1, whereas macrophages were the predominant cell type exhibiting NK1R in eosinophilic polyps. HK‐1 induced CCL24 production from macrophages differentiated from THP‐1 cells; this was abolished by an NK1R antagonist. HK‐1 also induced CCL24 production from ex vivo‒cultured eosinophilic nasal polyps. CCL24 was expressed by macrophages in eosinophilic but not non‐eosinophilic polyps. The expression level of HK‐1 correlated with CCL24 expression and tissue eosinophilia in eosinophilic nasal polyps.
Conclusion
Eosinophil‐derived HK‐1 induces CCL24 production from macrophages and therefore exaggerates eosinophilic inflammation in CRSw
NP.

Impact of palliative treatment on survival in sinonasal malignancies

20-09-2019 – Nicole I. Farber, Roman Povolotskiy, Richard D. Bavier, Julia Riccardi, Jean Anderson Eloy, Wayne D. Hsueh

Journal Article

Background
Although palliative care treatment modalities have been shown to improve functional outcomes and provide symptom alleviation in sinonasal cancer, its impact on survival still remains unclear. In this study we aimed to elicit the impact of different palliative therapy options on survival in a nationally representative sample of sinonasal cancer patients.
Methods
National Cancer Database 2004‐2015 data sets were queried for cases of primary sinonasal cancer (N = 380). Kaplan‐Meier analysis was utilized to determine median overall survival (M‐OS) and overall survival (OS) among the different treatment cohorts (pain management, palliative radiation therapy, palliative chemotherapy, palliative surgery, and combination therapy). Prognostic factors were elicited by comparing OS by log‐rank tests and subsequent multivariate Cox regression analysis.
Results
Of the total patients of sinonasal malignancy treated with palliative therapy, most were <70 years old, had stage 4 cancer, and histology indicating squamous cell carcinoma (p < 0.05). On Kaplan‐Meier survival analysis, the 1‐year OS (1Y‐OS) and M‐OS were 43.6% and 10.1 months, respectively. The 1Y‐OS and M‐OS for pain management alone were 35.3% and 4.56 months, respectively. Surgery had the highest 1Y‐OS and M‐OS, at 74.7% and 22.8 months, respectively (p = 0.002). All treatment modalities had increased 1Y‐OS compared with pain management alone. Multivariant analysis demonstrated palliative surgery to be associated with decreased risk of death (hazard ratio, 0.33; 95% confidence interval, 0.17‐0.63).
Conclusion
In this study we identify the impact of palliative treatment modalities on survival in sinonasal cancer. Palliative surgery was shown to have the highest 1Y‐OS and M‐OS compared with other palliative treatment modalities.

Efficacy of steroid‐eluting stents in management of chronic rhinosinusitis after endoscopic sinus surgery: updated meta‐analysis

20-09-2019 – Khodayar Goshtasbi, Mehdi Abouzari, Arash Abiri, Tyler Yasaka, Ronald Sahyouni, Benjamin Bitner, Bobby A. Tajudeen, Edward C. Kuan

Journal Article, Review

Background
Recently, there has been mounting evidence suggesting the efficacy of steroid‐eluting stents (SES) for management of chronic rhinosinusitis after endoscopic sinus surgery (ESS). This meta‐analysis serves to evaluate the efficacy of SES in improving postoperative outcomes after ESS.
Methods
A systematic literature search was performed of PubMed for articles published between 1985 and 2018. The outcome variables were reported at, on average, 30 days postintervention.
Results
Seven of the 76 published studies, all of which were industry‐sponsored, were included for a collective cohort of 444 SES and 444 control sinuses. In patients who received SES vs controls, collective odds ratios (ORs) for postoperative need for intervention, surgery, and oral steroid were 0.45 (95% confidence interval CI, 0.33‐0.62; p < 0.001), 0.30 (95% CI, 0.18‐0.52; p < 0.001), and 0.58 (95% CI, 0.40‐0.84; p = 0.004), respectively. In addition, collective ORs for frontal sinus ostia (FSO) patency, moderate‐to‐severe adhesion/scarring, and increase in polyp score were 2.53 (95% CI, 1.61‐3.97; p < 0.001), 0.28 (95% CI, 0.13‐0.59; p < 0.001), and 0.42 (95% CI, 0.25‐0.74; p = 0.002), respectively. Collective mean differences for FSO/ethmoid inflammation and FSO diameter were −10.86 mm (p < 0.001) and +1.34 mm (p < 0.001), respectively.
Conclusion
Aggregate evidence suggests that SES can improve ESS outcomes by reducing rates of postoperative intervention and recurrent polyposis and inflammation, while promoting FSO patency. All included and analyzed studies were industry‐sponsored and ruling‐out publication bias was not possible. Future independent and nonsponsored studies to further evaluate SESs long‐term efficacy are warranted.

Autophagy is involved in allergic rhinitis by inducing airway remodeling

19-09-2019 – Jing Li, Yong Li

Journal Article

Background
Allergic rhinitis (AR) is an allergic disorder affecting 10‐40% of the population worldwide. Autophagy has been implicated in numerous biological processes, including aging, immunity, development, and differentiation, and has been shown to affect the pathogenesis of allergic disease and airway remodeling. In this study we attempted to determine the association between autophagy and AR pathogenesis.
Methods
The severity of nasal and extranasal symptoms was measured with visual analog scale (VAS) scores. Autophagosome formation was detected in the nasal epithelium by transmission electron microscopy (TEM). Western blots and quantitative polymerase chain reaction were used to examine expression levels of autophagic markers. Collagen deposition was detected via Masson trichrome staining and collagen III expression was measured by enzyme‐linked immunosorbent assay. Spearmans correlation coefficient was used to assess the relationship between autophagy, AR symptoms, and collagen levels.
Results
Patients with AR had more autophagosomes, increased levels of Beclin‐1 m
RNA, and higher Beclin‐1 and LC3‐II protein expression. Collagen III protein expression was also higher in patients with AR than in the controls. Higher expression of Beclin‐1 was associated with higher VAS scores (Spearmans rho = 0.905, p < 0.01), higher collagen deposition (Spearmans rho = 0.862, p < 0.01), and higher collagen III protein (Spearmans rho = 0.849, p < 0.01).
Conclusion
The autophagosome and autophagic markers are highly expressed in the upper airways of patients with AR and are associated with corresponding changes in airway remodeling markers. Our data suggest a link between autophagy and airway remodeling in AR.

Diamine oxidase enzyme: a novel biomarker in respiratory allergy

18-09-2019 – Maged M. Refaat, Asmaa S. Abdel‐Rehim, Amira R. Elmahdi, Nesrine A. Mohamed, Sara S. Ghonaim

Journal Article

Background
Well‐known allergy tests are used to evaluate and diagnose allergic diseases. The aim of this study was to assess the role of serum level diamine oxidase (DAO) enzyme as a diagnostic marker in respiratory allergy.
Methods
This case‐control study included 40 patients with respiratory allergies (atopic asthma and allergic rhinitis) as well as 40 age‐ and sex‐matched controls. A detailed past medical history of allergy was collected from each participant including family history of allergy. Physical examination, pulmonary function test (PFT) and measurement of serum levels of total immunoglobulin E (Ig
E) and DAO were performed. Skin‐prick test and specific Ig
E to common aeroallergens were also carried out.
Results
DAO levels were higher in patients than controls. There was a positive correlation between severity of disease and DAO. No significant association was found between DAO level and age, type of respiratory allergy, duration of disease, PFT, eosinophilia, and total Ig
E. DAO had a high negative predictive value (94.7%) and high sensitivity (97.5%).
Conclusion
DAO may be helpful in the assessment of severity and in ruling out respiratory allergy.

Odontogenic sinusitis is a common cause of unilateral sinus disease with maxillary sinus opacification

17-09-2019 – Zaahir Turfe, Abid Ahmad, Edward I. Peterson, John R. Craig

Journal Article

Background
Unilateral sinus disease (USD) carries a broader differential diagnosis than bilateral sinus disease, including various inflammatory and neoplastic conditions. Odontogenic sinusitis (ODS) is a common cause of unilateral maxillary sinusitis, but few studies have examined its incidence among all USD etiologies. The main purposes of this prospective study were to determine the incidences of ODS and other etiologies causing USD with complete maxillary sinus opacification on computed tomography (CT), and to compare CT features of ODS and non‐odontogenic USD patients. In addition, clinical features of the ODS cohort are described.
Methods
A prospective case series of 134 patients with USD with complete maxillary sinus opacification on CT was conducted from August 2015 to November 2018. Based on nasal endoscopy, sinus CT, and dental examination and imaging, patients were categorized as having unilateral ODS or non‐odontogenic USD. Patients with non‐odontogenic USD were categorized as inflammatory or neoplastic. Demographic and clinical data were reported for ODS patients.
Results
Of the 134 patients, 45% had ODS, 36% had non‐odontogenic inflammatory conditions, 17% had inverted papilloma, and 2% had malignancies. Of the 60 ODS cases, 86.7% were associated with middle meatal purulence on nasal endoscopy. On CT, 88.3% had extramaxillary sinus disease extension, and 65.5% of CT reports made no mention of dental pathology.
Conclusion
ODS caused nearly 50% of all USD cases with maxillary sinus opacification on CT, and was the most common individual etiology. ODS was frequently associated with anterior ethmoid and frontal sinus disease on CT, and middle meatal purulence on nasal endoscopy.

Benefits and harms of aspirin desensitization for aspirin‐exacerbated respiratory disease: a systematic review and meta‐analysis

13-09-2019 – Derek K. Chu, Daniel J. Lee, Keith M. Lee, Holger J. Schünemann, Wojciech Szczeklik, John M. Lee

Journal Article, Review

Background
Aspirin desensitization is increasingly recommended for the treatment of aspirin‐exacerbated respiratory disease (AERD). The objective of this study is to systematically review the efficacy and safety of aspirin desensitization in patients with AERD.
Methods
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to January 5, 2019. We included randomized trials and comparative observational studies in any language. Data extraction and risk of bias assessment were performed in duplicate independently.
Results
Five randomized controlled trials (RCTs) enrolled 233 patients with AERD. Compared to placebo, aspirin desensitization (mean daily dose 800 mg) improved quality of life (risk ratio RR 2.00; 95% confidence interval CI, 1.31 to 3.06; heterogeneity measure I2 = 0%; risk difference RD +24%; 22‐item Sino‐Nasal Outcome Test SNOT‐22 scale 0 to 110, higher worse; mean difference MD −10.27 95% CI, −6.39 to −14.15; moderate‐certainty); and respiratory symptoms (RR 2.20 95% CI, 1.55 to 2.73, I2 = 34%, RD +36%; American Academy of Otolaryngology (AAO) scale 0 to 20, higher worse; MD −2.56 95% CI,−1.12 to −3.92; high‐certainty). Aspirin desensitization increased adverse events severe enough to cause treatment discontinuation (major bleeding, gastritis, asthma exacerbation, or rash causing drug discontinuation, RR 4.39 95% CI, 1.43 to 13.50, I2 = 0%, RD +11%, moderate‐certainty), and gastritis (RR 3.84 95% CI, 1.12 to 13.19, I2 = 0%, RD +9%, low‐certainty). Findings were robust to sensitivity analyses. Two available observational studies were not informative because they lacked adjustment for confounders and/or contemporaneous controls.
Conclusion
In patients with AERD, moderate‐certainty and high‐certainty evidence shows that aspirin desensitization meaningfully reduces symptoms of rhinosinusitis and improves quality of life, but results in a significant increase in adverse events.

Associations among air pollutants, grass pollens, and daily number of grass pollen allergen‐positive patients: a longitudinal study from 2012 to 2016

12-09-2019 – Yuhui Ouyang, Zhaoyin Yin, Ying Li, Erzhong Fan, Luo Zhang

Journal Article

Background
Grass pollen is the most prevalent sensitizing aeroallergen to cause respiratory allergies in northern China. Air pollutants have a substantial effect on respiratory health and some pollens. This study aimed to investigate relationships among airborne grass pollen, air pollutants and allergic diseases, in order to determine their effects on patients with grass pollen allergies in Beijing, China, during the period from 2013 to 2016.
Methods
Data regarding autumnal grass pollens and air pollutants measured in Beijing from 2012 to 2016 were obtained from local governmental agencies. Patient data regarding specific immunoglobulin E (Ig
E) analyses from 2013 to 2016 were obtained from the Department of Allergy in Beijing Tongren Hospital. Spearmans rank correlation analysis was used to assess associations between the daily number of grass pollen allergen–positive patients and the following parameters: 3 clinically‐relevant grass pollen genera (Artemisia, Humulus, and Chenopodium) and inhalable pollutants.
Results
Correlation analysis indicated that the daily number of grass pollen‐positive patients was significantly associated with the peak period of grass pollens, as well as pollutants SO2 and NOx. Moreover, concentrations of air pollutants (eg, ozone, oxides of nitrogen NOx, and SO2) were consistently and significantly associated with concentrations of grass pollens; particulate matter 2.5 µm in diameter was negatively associated with Artemisia and Chenopodium pollens.
Conclusion
Grass pollens exhibited substantial impact on allergic disease morbidity. Air pollutants impacted allergic disease and grass pollen. Thus, public health and clinical approaches to anticipate and reduce allergic disease morbidity from pollen and pollutants are needed.

The effectiveness of endoscopic sphenopalatine ganglion block in management of postoperative pain after septal surgery

05-09-2019 – Nur Yücel Ekici, Sedat Alagöz

Journal Article

Background
This study evaluated the effect of bilateral endoscopic sphenopalatine ganglion block (SPGB) for management of postoperative pain in patients undergoing septoplasty.
Methods
Sixty septoplasty patients (51.7% male, 48.3% female, aged 18 to 45 years) were randomly assigned to general anesthesia (GA) alone (control) (n = 30) or GA plus endoscopic SPGB (n = 30). Demographic data, duration of surgery, blood loss, postoperative visual analogue scale (VAS) pain scores (upon arrival at the postanesthesia care unit PACU and 2, 6, 12, and 24 hours after surgery), overall analgesic usage (end of 24 and 168 hours after surgery), overall satisfaction with the pain control (end of 24 and 168 hours after surgery), and complications (bleeding, nausea and vomiting, and visual disturbance) were recorded.
Results
Pain scores upon arrival to the PACU and 2, 6, 12, and 24 hours after surgery were significantly lower in the SPGB group compared to the control group (p < 0.001). Moreover, the SPGB group had significantly lower analgesic requirements and higher satisfaction scores with their pain control at the end of 24 and 168 hours after surgery compared to the control group (p < 0.001). The 2 groups significantly differed in terms of intraoperative blood loss (p = 0.024), and surgery time was longer in the SPGB group compared to the control group (p < 0.001).
Conclusion
SPGB with bupivacaine is a safe and effective method to reduce pain after septoplasty, and it is a cost‐effective alternative to high doses of analgesics.

Detection and quantification of Staphylococcus in chronic rhinosinusitis

04-09-2019 – Brett Wagner Mackenzie, Jesse Baker, Richard G. Douglas, Michael W. Taylor, Kristi Biswas

Journal Article

Background
The sinonasal microbiota has been implicated in chronic rhinosinusitis (CRS) pathogenesis, particularly related to the presence of Staphylococcus aureus. Staphylococcus epidermidis is also prevalent within the sinonasal microbiota and may inhibit S. aureus colonization. We investigated polymerase chain reaction (PCR) primer pairs for measuring absolute abundances of S. aureus and S. epidermidis, then compared bacterial community composition and absolute abundances of these species between CRS patients and controls.
Methods
Six candidate Staphylococcus species‐specific primer pairs were tested in silico and in vitro against pure bacterial isolates. Quantitative PCR (q
PCR) for absolute quantification of S. aureus, S. epidermidis, and overall bacterial load were assessed in 40 CRS (CRS without nasal polyposis CRSs
NP = 22, CRS with nasal polyposis CRSw
NP = 18) patients and 14 controls. Amplicon sequencing of the V3‐V4 hypervariable regions of the 16S ribosomal RNA (r
RNA) bacterial gene were conducted to investigate community composition.
Results
Primer pairs targeting the gmk gene of S. aureus and nrd gene from S. epidermidis were the most specific and sensitive primers. S. aureus (CRSs
NP = 81.8% occurrence, CRSw
NP = 83%, control = 92.9%) and S. epidermidis (CRSs
NP = 95.5%, CRSw
NP = 100%, control = 92.9%) were very prevalent, as indicated by q
PCR results. Both CRSs
NP and CRSw
NP had significantly (p < 0.05) higher bacterial load when compared with controls (p < 0.05 for both). No significant correlation was observed between S. aureus and S. epidermidis abundances (p > 0.05).
Conclusion
Bacterial community sequencing detected Staphylococcus‐assigned sequences in nearly all patients; however, it could not differentiate between S. aureus and S. epidermidis. Here, we present primer pairs that can distinguish between these species. We report a very high prevalence of S. aureus in both CRS patients and controls.

Manuka honey sinus irrigations in recalcitrant chronic rhinosinusitis: phase 1 randomized, single‐blinded, placebo‐controlled trial

28-08-2019 – Mian Li Ooi, Arvind Jothin, Catherine Bennett, Eng H. Ooi, Sarah Vreugde, Alkis J. Psaltis, Peter‐John Wormald

Journal Article

Background
Manuka honey (MH) has significant antibiofilm activity in vitro and in vivo against Staphylococcus aureus, methicillin‐resistant S aureus (MRSA), and Pseudomonas aeruginosa. This is the first randomized, single‐blinded, placebo‐controlled phase 1 clinical trial investigating the safety and preliminary efficacy of MH with augmented methylglyoxal (MGO) rinses in recalcitrant chronic rhinosinusitis (CRS).
Methods
Patients were included after previously undergoing endoscopic sinus surgery and presenting with signs and symptoms of sinus infection with positive bacterial cultures on sinus swabs. Patients were randomized to receive 14 days of twice‐daily 16.5% MH + 1.3 mg/m
L MGO sinonasal rinses and concurrent 10 days of placebo tablets (MH), or 14 days of twice‐daily saline sinonasal rinses and concurrent 10 days of culture‐directed antibiotic therapy (CON). Safety observations included the University of Pennsylvania Smell Identification Test (UPSIT) and adverse‐event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund‐Kennedy scores (LKSs), and symptom scores using the visual analog scale (VAS) and 22‐item Sino‐Nasal Outcome Test (SNOT‐22).
Results
Twenty‐five patients completed the study. MH demonstrated a good safety profile with no major AEs and no changes in UPSIT. Six of 10 (60%) MH patients had a reduction in bacterial culture rate with 1 of 10 of those having negative cultures, compared with 12 of 15 (80%) in the control group with 7 of 15 having negative cultures upon completion of the study.
Conclusion
This study concludes that twice‐daily 16.5% MH augmented with 1.3 mg/m
L MGO sinonasal rinses alone for 14 days is safe but not superior to culture‐directed oral antibiotics and twice‐daily saline rinses.

Radiofrequency ablation of turbinates after septoplasty has no effect on allergic rhinitis symptoms other than nasal obstruction

26-08-2019 – Taegu Kang, Chung Man Sung, Hyung Chae Yang

Journal Article

Background
In this study we evaluated the effects of inferior turbinate radiofrequency ablation (RFA), performed after septoplasty, on patients with allergic rhinitis (AR) symptoms.
Methods
This was a prospective, randomized, controlled study involving 60 patients with both a deviated nasal septum (DNS) and AR. Those who underwent septoplasty/sham surgery constituted the Septo‐Sham group and those who underwent septoplasty/RFA formed the Septo‐RFA group. Demographic factors, pre‐ and postoperative symptom scores for allergic rhinitis (SFARs), and Nasal Obstruction and Septoplasty Effectiveness Scale (NOSE) scores were calculated. We subdivided the total SFAR (t
SFAR) scores into scores for nasal obstruction (SFAR‐NO) and scores for symptoms other than nasal obstruction (SFAR‐SONO); the latter included rhinorrhea, itching, and sneezing.
Results
The baseline characteristics were similar between the groups. The 2 types of surgery improved both the NOSE and SFAR scores. In subgroup analysis according to the type of symptoms, both types of surgery showed improvement in SFAR‐NO and SFAR‐SONO scores. However, the extent of improvement did not differ between the groups, regardless of the type of symptoms.
Conclusion
For patients with both DNS and AR, both types of surgery afford postoperative symptomatic improvement. Both types of surgery yielded improvement in both nasal obstruction and symptoms other than nasal obstruction. However, performing RFA after septoplasty did not afford further short‐term symptomatic improvements. Thus, septoplasty without RFA may be optimal for patients with both DNS and AR.

Triangular excision and submucosal rejoining to correct horizontally folded caudal nasal septum

23-08-2019 – Yung Jin Jeon, Jin Hyun Seo, Yeon‐Hee Joo, Hyun‐Jin Cho, Sea‐Yuong Jeon, Sang‐Wook Kim

Journal Article

Background
Surgical correction of severe caudal deviation of nasal septum using an endonasal approach is challenging for surgeons. Among cases of severe caudal septal deflection, fracture lines along the horizontal direction are occasionally encountered during the surgery. We devised a simple and efficient technique called “triangular excision and submucosal rejoining” to address this kind of deformity.
Methods
A total of 9 patients with severe caudal septal deflection underwent “triangular excision and submucosal rejoining.” After the removal of the deformed posteroinferior portion of the quadrangular cartilage, 2 incision lines were made on the remaining caudal septum, starting from a point at the most anterior portion of the fracture line and diverging posteriorly above and below the fracture line. After removing a triangular cartilaginous piece, the upper and lower remaining cartilage segments were approximated using a single or 2 simple interrupted sutures. Sutures exiting the mucosa were re‐entered from the exit point so that all the sutures were buried underneath the mucosa while the mucosal flap was elevated only unilaterally.
Results
This technique was effective in all cases. Septal batten grafts were applied in 3 patients, in whom the remaining quadrangular cartilage was weak and thin. One patient showed a mildly recurred septal deviation, but the nasal cavities remained patent with no symptoms. Serious complications such as dorsal saddling or tip ptosis did not occur in any cases.
Conclusion“Triangular excision and submucosal rejoining” may be a safe and efficient septoplasty technique to correct a horizontally folded caudal septum.

Transnasal endoscopic resection of orbital cavernous hemangiomas: our experience with 23 cases

23-08-2019 – Jingying Ma, Bing Zhou, Huang Qian, Zhenxiao Huang, Shi Jitong

Journal Article

Background
The aim of this work was to present our single‐center experience on orbital cavernous hemangiomas managed using an endonasal endoscopic approach.
Methods
The study design used was one‐institutional retrospective review. Twenty‐three cases of orbital cavernous hemangioma were analyzed and followed up.
Results
There were 10 males and 13 females, with an average age of 46.1 years, included in our study. Seven cases were extraconal, 16 cases were intraconal, and in 10 of the patients the optic nerve was involved and compressed. Total resection of the tumor was achieved in 16 cases; of the remaining 7 cases, partial tumor resection and orbital decompression were conducted, orbital decompression was conducted in 2 cases, and orbital decompression and optic nerve decompression were conducted in 3 cases. Visual acuity in 9 patients improved significantly, as 16 of the 20 patients with a preoperative visual field defect had a smaller defect after surgery.
Conclusion
This study adds to the literature showing that endoscopic transnasal surgery is likely a reasonable option for patients with the orbital cavernous hemangiomas medial of the optic nerve. With greater experience, skilled surgical technique, and careful operation, better clinical efficacy can be achieved.

Longitudinal progression of aspirin‐exacerbated respiratory disease: analysis of a national insurance claims database

23-08-2019 – Lauren T. Roland, Heqiong Wang, C. Christina Mehta, Katherine N. Cahill, Tanya M. Laidlaw, John M. DelGaudio, Sarah K. Wise, Joshua M. Levy

Journal Article

Background
Aspirin‐exacerbated respiratory disease (AERD) is a recalcitrant inflammatory disorder defined by asthma, nasal polyposis, and sensitivity to cyclooxygenase‐1 inhibitors. The timeline and course of disease progression is unclear.
Methods
The Truven Market
Scan Database, a large American health insurance claims repository, was queried to identify patients meeting criteria for AERD from 2009 to 2015. Included patients had associated International Classification of Diseases, 9th edition (ICD‐9) codes consistent with all 3 components of AERD: asthma, nasal polyposis, and drug allergy. Patterns of disease onset and time to progression were analyzed.
Results
A total of 5628 patients were identified for study inclusion. Of the 3 components of AERD, 3303 patients (59%) were initially diagnosed with asthma, 1408 (25%) were initially diagnosed with nasal polyps, and 917 (16%) were first diagnosed with drug sensitivity. The most common (36%) sequence of diagnoses was asthma, followed by nasal polyps, followed by drug allergy. The median interval between diagnosis of upper or lower airway involvement (ie, nasal polyps and/or asthma) to recognition of drug sensitivity was 259 days (quartiles Q1 to Q3: 92 to 603 days). In patients with both asthma and nasal polyps diagnoses, the risk of developing drug sensitivity during the study time period was 6%.
Conclusion
Upper and lower airway disease is often initially recognized in patients with AERD, whereas drug sensitivity presents month to years later. This delay may be due to the pathophysiology of AERD and disease progression or due to practice patterns in diagnostic testing and coding. Further work is warranted to identify these patients at early stages in their disease progression.

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.

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.

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.

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.

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.

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.

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.

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