International Forum of Allergy and Rhinology

Factors impacting revision surgery in patients with chronic rhinosinusitis with nasal polyposis

14-01-2020 – Catherine A. Loftus, Zachary M. Soler, Vincent M. Desiato, Sina Koochakzadeh, Frederick Yoo, Kristina A. Storck, Rodney J. Schlosser

Background
Surgical treatment of chronic rhinosinusitis with nasal polyposis (CRSw
NP) has evolved over the last decade as rhinologists have increasingly used topical steroid therapies and altered surgical techniques. It is important to understand the changes in success rates of surgery and frequency of revision endoscopic sinus surgery (ESS) in CRSw
NP. The aim of this study was to retrospectively review the revision surgical rate of CRSw
NP patients by evaluating outcomes in a cohort from the Medical University of South Carolina (MUSC).
Methods
Retrospective review of CRSw
NP patients operated upon at the MUSC between 2002 and 2019 by a single surgeon was performed. Assessed factors included demographics, comorbidities, CRSw
NP subtype, extent of surgery, and steroid rinse compliance. Logistic regression was performed to identify factors associated with revision surgery.
Results
Among 338 patients with at least 6 months of follow‐up, 24.9% had revision surgery, with a mean follow‐up of 52.6 months. In patients with any person‐time measure, the revision rate was 5.58 per 100 person‐years. Independent risk factors associated with increased odds ratio (OR) for revision surgery were: younger age (OR, 1.1); prior surgery (OR, 3.3); longer follow‐up (OR, 1.1); and surgery before 2009 (OR, 2.4) (p < 0.05 for all).
Conclusion
The revision surgery rate for CRSw
NP was 24.9% among those with at least 6 months of follow‐up. Risk factors for higher revision rates included younger age, previous surgery, longer follow‐up, and surgery at the MUSC prior to 2009. As we enter an era of personalized medicine, it is important to consider patient‐ and surgeon‐specific factors, which impact revision surgery rates.

Significant polyomic and functional upregulation of the PAPP‐A/IGFBP‐4/5/IGF‐1 axis in chronic rhinosinusitis with nasal polyps

12-01-2020 – Sarina K. Mueller, Angela L. Nocera, Alan Workman, Towia Libermann, Simon T. Dillon, Achim Stegmann, Jochen Wurm, Heinrich Iro, Olaf Wendler, Benjamin S. Bleier

Journal Article

Background
Chronic rhinosinusitis with nasal polyps (CRSw
NP) is associated with epithelial expansion and polyp survival. However, the molecular mechanism of this aberrant proliferation is unclear. The purpose of this study was to interrogate derangements of the pappalysin‐A/insulin‐like growth factor binding protein/insulin‐like growth factor‐1 (PAPP‐A/IGFBP‐4/5/IGF‐1 axis) as a major contributing factor to polyp growth in CRSw
NP.
Methods
Matched tissue and exosomal proteomic arrays including PAPP‐A, IGFBP‐4, IGFBP‐5, and IGF‐1 were quantified using aptamer‐based methods/Western blots for proteomic analysis and whole‐transcriptome sequencing/quantitative polymerase chain reaction (q
PCR) for transcriptomic analysis in CRSw
NP and control patients. Functional PAPP‐A assays were then performed in both tissue and exosomes (set 1: n = 20 per group; validation set 2: n = 26 per group).
Results
Tissue and exosomal PAPP‐A was significantly overexpressed in CRSw
NP compared to controls on both a transcriptomic and proteomic level (p < 0.0001). Known inhibitors of PAPP‐A (stanniocalcin‐1/‐2) were significantly downregulated (p < 0.0001) as were PAPP‐A cleavage products (IGFBP‐5 p < 0.0001). PAPP‐A function was shown to be increased 5‐fold to 6‐fold in tissue and exosomes.
Conclusion
Upregulated tissue and exosomal PAPP‐A signaling is significantly associated with CRSw
NP and may be an important factor in the promotion of epithelial proliferation and polyp growth. These data lend further support to the emerging concept of exosomal functional and polyomic analyses as a method to study sinonasal pathology.

Use of mucosal eosinophil count as a guide in the management of chronic rhinosinusitis

12-01-2020 – Daniel Sharbel, Mingsi Li, Aykut A. Unsal, Sandra Y. Tadros, Jason Lee, Paul Biddinger, Thomas Holmes, Stilianos E. Kountakis

Journal Article

Background
Chronic rhinosinusitis (CRS) is a local inflammatory process driven by eosinophils. Mucosal eosinophil count (MEC) has previously been demonstrated to be a reliable indicator of disease severity. We aim to evaluate use of MEC in guiding medical management of CRS after functional endoscopic sinus surgery (FESS).
Methods
We retrospectively reviewed patients with CRS who underwent FESS from 2004 to 2017. Tissue MEC per high‐power field (HPF) was determined by pathologic examination. MECs were compared by polyp status, postoperative medication requirements, and revision surgery. Patients received normal saline (NS) nasal irrigations with additional treatment as needed for disease control: 1‐drug therapy (1‐DT) intranasal steroid spray (ISS), 2‐drug therapy (2‐DT) ISS plus budesonide nasal irrigations (BNI) or leukotriene receptor antagonist (LRA), or 3‐drug therapy (3‐DT) ISS plus BNI and LRA. Correlations between MEC and 22‐item Sino‐Nasal Outcome Test (SNOT‐22), preoperative computed tomography (CT), and nasal endoscopy scores were evaluated.
Results
A total of 156 patients were included. Fifty‐seven were managed with 1‐DT, 35 with 2‐DT, and 62 with 3‐DT. Across all patients, mean postoperative 6‐month and 1‐year SNOT‐22 (18.1 ± 17.0, 18.1 ± 20.2, respectively) and nasal endoscopy (3.6 ± 3.8, 3.6 ± 4.1, respectively) scores were significantly lower than preoperative scores (37.4 ± 22.8, 6.5 ± 4, respectively). With increasing MEC, odds of requiring 2‐DT (odds ratio OR = 1.1, p = 0.0002), 3‐DT (OR = 1.12, p < 0.0001), and revision surgery (OR = 1.11, p < 0.0001) were significantly increased. Preoperative endoscopy (ρ = 0.44, p < 0.0001) and CT scores (ρ = 0.51, p < 0.0001) and postoperative 6‐month (ρ = 0.55, p < 0.0001) and 1‐year (ρ = 0.4, p < 0.0001) endoscopy scores demonstrated good correlation with MEC.
Conclusion
MEC correlates with objective clinical disease severity and may guide aggressiveness of management for the individual patient.

Understandability and actionability of audiovisual patient education materials on sinusitis

12-01-2020 – Kolin E. Rubel, Mohamedkazim M. Alwani, Obi I. Nwosu, Elhaam H. Bandali, Taha Z. Shipchandler, Elisa A. Illing, Jonathan Y. Ting

Journal Article

Background
Acute and chronic rhinosinusitis are debilitating diseases that affect from 5% to 16% of the population. You
Tube is the second most commonly used search engine and is often utilized by patients to garner health information regarding various disease processes and their respective management options. An evaluation of these information resources for quality and reliability is warranted, especially in an era in which patients are increasingly turning to audiovisual (A/V) media to educate themselves regarding their ailments.
Methods
The You
Tube video database was searched using the term “sinusitis” from its inception through to November 2018. The first 50 videos populated under the relevance‐based ranking option were collected and parsed by time and language. Of the 50 videos, 10 were eliminated either for length (≤1 minute or ≥20 minutes), language (any language other than English), and/or for later being removed by You
Tube for copyright violations. The videos were then assessed using the Patient Education Materials Assessment Tool―Audio/Visual (PEMAT‐A/V) by 2 independent reviewers for understandability and actionability.
Results
A total of 40 videos were examined using the PEMAT‐A/V tool. The average understandability score was 57.7%, whereas the average actionability score was 46.3%. Eleven videos (28%) had actionability scores of 0%. Videos most commonly addressed disease management options (38%). The second largest category was case presentations regarding surgical techniques (30%). There were only 6 videos focused primarily on education about the definition and common traits of sinusitis (15%).
Conclusion
Our results show a paucity of high‐quality online A/V educational material pertaining to sinusitis, with a majority of videos being neither understandable nor actionable. As patients increasingly turn to internet video databases like You
Tube for medical information, it is critical that physicians and institutions create A/V material that is accurate, understandable, and actionable.

Treatment‐related morbidity in patients treated for sinonasal malignancy

12-01-2020 – Jena Patel, Chandala Chitguppi, Swar Vimawala, Gregory Epps, Judd Fastenberg, James Evans, Mindy Rabinowitz, Marc Rosen, Gurston Nyquist

Journal Article

Background
Sinonasal malignancies are a rare, heterogeneous group of tumors that often present at an advanced stage and require multimodal therapy. The presence of high‐grade toxicity and sinonasal complications after treatment can negatively impact quality of life. In this study we aim to describe posttreatment morbidity in patients with sinonasal malignancy.
Methods
A retrospective analysis of all patients treated for sinonasal malignancy was conducted from 2005 to 2018 at a tertiary referral institution. A total of 129 patients met the inclusion criteria. Primary outcomes were treatment details, pathology, posttreatment complications, and radiation toxicity. Fishers exact test, chi‐square test, and Student t test were used for statistical analysis.
Results
Mean age was 58.4 (median, 61; range, 19‐94) years. After diagnosis, 24 patients had surgery alone, 46 had surgery with radiation alone, 47 had surgery with chemoradiation, and 14 received definitive chemoradiation. Overall, 10.4% (n = 12) of patients had postoperative complications, and 21.0% (n = 22) had high‐grade (grade 3‐5) radiation toxicity. After radiation, 20% (n = 21) of patients had chronic sinusitis requiring functional endoscopic sinus surgery and 20% (n = 21) had symptomatic nasal obstruction requiring operative debridement.
Conclusion
Sinonasal complications, including nasal obstruction and chronic sinusitis, occur frequently after definitive treatment of sinonasal malignancy and should be addressed when considering quality of life in survivors. These complications occur more frequently in patients who undergo chemoradiation as opposed to surgery alone.

The impact of Lactococcus lactis (probiotic nasal rinse) co‐culture on growth of patient‐derived strains of Pseudomonas aeruginosa

10-01-2020 – Do‐Yeon Cho, Daniel Skinner, Dong Jin Lim, John G. Mclemore, Connor G Koch, Shaoyan Zhang, William E. Swords, Ryan Hunter, David K Crossman, Michael R. Crowley, Jessica W. Grayson, Steven M. Rowe, Bradford A. Woodworth

Journal Article

Background
The Lactococcus strain of bacteria has been introduced as a probiotic nasal rinse for alleged salubrious effects on the sinonasal bacterial microbiome. However, data regarding interactions with pathogenic bacteria within the sinuses are lacking. The purpose of this study is to assess the interaction between L. lactis and patient‐derived Pseudomonas aeruginosa, an opportunistic pathogen in recalcitrant chronic rhinosinusitis (CRS).
Methods
Commercially available probiotic suspension containing L. lactis W136 was grown in an anaerobic chamber and colonies were isolated. Colonies were co‐cultured with patient‐derived P. aeruginosa strains in the presence of porcine gastric mucin (mimicking human mucus) for 72 hours. P. aeruginosa cultures without L. lactis served as controls. Colony forming units (CFUs) were compared.
Results
Six P. aeruginosa isolates collected from 5 CRS patients (3 isolates from cystic fibrosis CF, 1 mucoid strain) and laboratory strain PAO1 were co‐cultured with L. lactis. There was no statistical difference in CFUs of 5 P. aeruginosa isolates grown with L. lactis compared to CFUs without presence of L. lactis. CFU counts were much higher when the mucoid strain was co‐cultured with L. lactis (CFU +L.lactis = 1.9 × 108 ± 1.44 × 107, CFU –L.lactis = 1.3 × 108 ± 8.9 × 106, p = 0.01, n = 7). L. lactis suppressed the growth of 1 P. aeruginosa strain (CFU +L.lactis = 2.15 × 108 ± 2.9 × 107, CFU –L.lactis = 3.95 × 108 ± 4.8 × 106, p = 0.03, n = 7).
Conclusion
L. lactis suppressed the growth of 1 patient P. aeruginosa isolate and induced growth of another (a mucoid strain) in in vitro co‐culture setting in the presence of mucin. Further experiments are required to assess the underlying interactions between L. lactis and P. aeruginosa.

Synergistic relationship between TSLP and IL‐33/ST2 signaling pathways in allergic rhinitis and the effects of hypoxia

10-01-2020 – Ruofei Huang, Wei Mao, Guoliang Wang, Jian Ding, Ying Sun, Gang Gao, Ping Dong, Zhenfeng Sun

Journal Article

Background
The World Health Organization (WHO) has noted that allergic diseases are a major health problem of the 21st century. Allergic rhinitis (AR) is a type I allergic disease characterized by nasal mucosa and immune system abnormalities. AR is mediated by various inflammatory cells and is mainly characterized by altered secretion of cytokines. Thymic stromal lymphopoietin (TSLP) and the interleukin‐33/stimulation‐expressed gene 2 (IL‐33/ST2) signaling pathway are cytokines that play pivotal roles in many inflammatory responses and allergic reactions. There have been reports of interactions between the 2 pathways in many diseases. Hypoxia is a common pathologic manifestation of AR. The aim of this study was to explore the relationship and expressions and biologic functions of TSLP and IL‐33/ST2 in AR, and also to determine the effects of hypoxia on these cytokines.
Methods
The rat nasal mucosal epithelium was obtained from Wistar rats. Cells were cultured in groups under hypoxia and normoxia conditions. Identification of rat nasal epithelial cell (RNEp
C) and protein expressions was done by immunohistochemistry and immunofluorescence methods. Cell proliferation and migration were examined using the cell counting kit‐8 (CCK‐8) and Transwell kit. Detection of apoptosis was tested using a fluorescence apoptosis kit. Enzyme‐linked immunoassay (ELISA) and Western blot analysis ELISA were used to measure cell secretion and protein expressions. For these experiments, TSLP was knocked down by lentivirus transfection and IL‐33 blocked with its antagonist.
Results
TSLP, IL‐33, and ST2 expressions were significantly higher in nasal mucosa epithelial cells from AR rats than in those from control rats. Hypoxia further promoted their expression. Increased TSLP and IL‐33/ST2 promoted cell proliferation, inhibited cell apoptosis, and enhanced cell migration. In addition, the downregulation of TSLP expression effectively attenuated expression of the IL‐33/ST2 axis and, through use of IL‐33 antagonists, could also reduce TSLP expression, a synergistic effect more obvious under hypoxia.
Conclusion
Our data indicate that TSLP and IL‐33/ST2 signaling pathways interact with each other in the pathogenesis and pathologic development of AR. TSLP inhibition is a key factor in AR treatment. Inhibiting hypoxia‐induced pathologic processes could represent a therapeutic effect by inhibiting IL‐33/ST2 expression via downregulating TSLP.

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

03-01-2020 – 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.

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

03-01-2020 – 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.

Endoscopic prelacrimal approach to lateral recess of sphenoid sinus: feasibility study

03-01-2020 – Lifeng Li, Nyall R. London, Daniel M. Prevedello, Ricardo L. Carrau

Journal Article

Background
Various pathologies, including cerebrospinal fluid leaks and meningoencephaloceles, may arise in the lateral recess of the sphenoid sinus (LRSS), which may be accessed via an endonasal transpterygoid approach. The objective of this study was to evaluate the feasibility of accessing the LRSS via an endoscopic prelacrimal approach. Furthermore, we hypothesized that this approach may protect the pterygopalatine ganglion and vidian nerve.
Methods
Five cadaveric heads (9 sides) with a well‐pneumatized LRSS were identified and an endonasal prelacrimal approach was performed. The infraorbital nerve, at the orbital floor, served as a critical landmark. After identification of the foramen rotundum at the pterygoid base, the vascular compartment of the pterygopalatine fossa and the pterygopalatine ganglion were displaced inferomedially and superomedially, respectively. Drilling of the bone inferomedial to the foramen rotundum allowed entry into the LRSS.
Results
The average distances from the prelacrimal window to the pterygoid base and the posterior wall of the LRSS were 6.22 ± 0.39 cm and 7.16 ± 0.50 cm, respectively. The average areas of the bony prelacrimal window and pterygoid base window were 4.33 ± 0.32 cm2 and 0.73 ± 0.10 cm2, respectively. The LRSS could be accessed using a 0‐degree endoscope, and pterygopalatine neurovascular structures, including the pterygopalatine ganglion and vidian nerve, could be preserved on all 9 sides.
Conclusion
Our findings suggest that an endonasal prelacrimal approach provides a reasonable alternative to access the LRSS while preserving the vidian nerve and pterygopalatine ganglion.

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

03-01-2020 – 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.

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

03-01-2020 – 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.

In‐vitro evaluation of a ciprofloxacin and azithromycin sinus stent for Pseudomonas aeruginosa biofilms

03-01-2020 – Dong‐Jin Lim, Daniel Skinner, John Mclemore, Nick Rivers, Jeffrey Brent Elder, Mark Allen, Connor Koch, John West, Shaoyan Zhang, Harrison M. Thompson, Justin P. McCormick, Jessica W. Grayson, Do‐Yeon Cho, Bradford A. Woodworth

Journal Article

Background
Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin‐azithromycin sinus stent (CASS) in vitro.
Methods
The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly‐l‐lactic acid (PLLA) stent. In‐vitro evaluation included: (1) assessment of drug‐coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti‐biofilm activities against Pseudomonas aeruginosa.
Results
The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reduced P aeruginosa biofilm mass compared with bare stents and controls (relative optical density units at 590‐nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000; p < 0.001; n = 3).
Conclusion
The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti‐biofilm activities against P aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.

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

03-01-2020 – 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.

Impact of Draf III, Draf IIb, and Draf IIa frontal sinus surgery on nasal irrigation distribution

03-01-2020 – Henry P. Barham, Christian A. Hall, Stephen C. Hernandez, Harry E. Zylicz, Megan M. Stevenson, Brittany A. Zito, Richard J. Harvey

Journal Article

Background
Delivery of topical pharmacotherapy to the paranasal sinuses remains integral to the management of chronic rhinosinusitis. The frontal sinus remains a difficult access site for irrigations, often limited by its position relative to the nostril and ethmoid sinus. In view of the previous demonstration of improved frontal sinus irrigation with Draf III vs Draf IIa, in this work we sought to evaluate topical access of Draf IIb relative to Draf IIa and Draf III modification of the frontal sinus outflow tract.
Methods
Unfixed human cadaver heads were dissected using Draf IIa, Draf IIb, and Draf III frontal sinusotomies. Draf IIa, Draf IIb, and Draf III frontal sinusotomies were performed in progressive sequence on each cadaver head. Nasal irrigation fluid access to the frontal sinus was tested after each successive frontal sinus intervention. Irrigations were performed using Frankfort horizontal and vertex positioning. Blinded reviewers were then asked to evaluate nasal irrigation access based on an ordinal scale.
Results
Eight cadaveric specimens (age, 78 ± 12.3 years; 62.5% female) were assessed. The greatest distribution scores were recorded by Draf III, then IIb, and then IIa (90.7% vs 81.3% vs 50.1%; p < 0.001). Similarly, the rate of lavage was greatest with Draf III (50% vs 12.5% vs 12.5%). Vertex positioning and increasing volume trended toward improved distribution but did not reach statistical significance.
Conclusion
Adequate delivery of topical therapy to the paranasal sinuses by nasal irrigation remains critical in the postoperative state. Although increasing the dimensions of the frontal recess improves nasal irrigation delivery, the Draf III procedure provides the optimal delivery of pharmacotherapy in those with frontal sinus disease.

Cranial nerve V2 and Vidian nerve trauma secondary to lateral pterygoid recess encephalocele repair

03-01-2020 – Sean P. Chislett, Alexander P. Limjuco, Alla Y. Solyar, Donald C. Lanza

Journal Article

Background
The incidence of adverse sequelae related to trauma of cranial nerve V2 (V2) and the Vidian nerve (VN) during endoscopic pterygoid recess repair (PRR) of lateral sphenoid encephalocele is insufficiently reported in the medical literature. As part of our quality assessment and improvement program we sought to analyze the incidence and severity of V2 and VN injury during a 9‐year experience (2010‐2018) with PRR.
Methods
Hypoesthesia, paresthesia, and dry eye and their impact on patient quality of life were sought through chart review and a self‐reported 0 to 5 Likert scale for each symptom.
Results
Thirty‐five patients underwent repair of spontaneous cerebrospinal‐fluid (CSF) rhinorrhea, with 11 consecutive patients undergoing endoscopic PRR. Mean follow‐up for PRR was 32.5 months (range, 2.4 to 103.3 months). Although definitive management resulted in 100% success, 1 required secondary treatment. Eight patients were available for long‐term follow‐up (72.7%) and completed a symptom severity questionnaire using a Likert‐scale. All patients observed either hypoesthesia, paresthesia, or dry eye of varying gradation (scale, 0 to 5). None described disabling symptoms, and some reported gradual improvement. Numbness, paresthesia, and dry eye were reported by 6 of 8 (75%), 5 of 8 (62.5%), and 4 of 8 (50%) patients, respectively. The mean Likert score among the 8 patients who completed this questionnaire noticing hypoesthesia, paresthesia, and dry eye was 2.6, 1.3, and 1.8, respectively.
Conclusion
Meticulous surgical technique is paramount for successful PRR and minimizing nerve injury, yet the anatomic variation of the lateral pterygoid recess can be challenging, and neural injury is a real risk. Preoperatively, patients should be counseled that although V2 or VN injury is common, most patients describe resulting symptoms to be rarely bothersome.

Baseline mucus cytokines predict 22‐item Sino‐Nasal Outcome Test results after endoscopic sinus surgery

03-01-2020 – Naweed I. Chowdhury, Ping Li, Rakesh K. Chandra, Justin H. Turner

Journal Article

Background
Mucus cytokines have been linked to baseline metrics of quality of life and olfactory function in patients with chronic rhinosinusitis (CRS). However, their potential utility in predicting postoperative outcomes has not been assessed. Therefore, in this study we evaluated the role of mucus cytokines in predicting 22‐item Sino‐Nasal Outcomes Test (SNOT‐22) scores after endoscopic sinus surgery (ESS) in a prospective cohort of CRS patients.
Methods
One hundred forty‐seven patients with CRS electing surgical therapy were enrolled in a longitudinal cohort study. Mucus was collected intraoperatively from the middle meatus and tested for interleukin (IL)‐1β, IL‐2, ‐4, ‐5, ‐6, ‐7,‐ 8, ‐9, ‐10, ‐12, ‐13, ‐17A, and ‐21; tumor necrosis factor (TNF)‐α; interferon‐γ; eotaxin; and RANTES (regulated‐on‐activation, normal T‐cell expressed and secreted) expression using a multiplex flow‐cytometric bead assay. Sixty‐two patients were followed postoperatively (average, 10.2 months) with baseline and follow‐up SNOT‐22 surveys. Stepwise multivariate linear regression was used to model relationships between baseline cytokines, phenotype, and average postoperative SNOT‐22 total and domain scores. A machine learning approach using a random forest algorithm was also used to investigate potential nonlinear relationships.
Results
IL‐5 was an independent predictor of postoperative total SNOT‐22 improvement (β = −8.8, p < 0.0001), whereas IL‐2 levels predicted postoperative worsening (β = 6.97, p = 0.0015). Similar relationships were also seen for postoperative SNOT‐22 domain scores. The overall model was also noted to be significant fit for the data (adjusted R2 = 0.398, p < 0.0001). The random forest model similarly identified IL‐5, TNF‐α, IL‐13, and IL‐2 as major predictors of postoperative SNOT‐22 scores.
Conclusion
Mucus cytokine profiles may help identify CRS patients who are likely to obtain postoperative improvement after ESS.

Hemodynamic changes in patients undergoing office‐based sinus procedures under local anesthesia

03-01-2020 – Michael T. Chang, Kawinyarat Jitaroon, Teresa Nguyen, Carol H. Yan, Jonathan B. Overdevest, Jayakar V. Nayak, Peter H. Hwang, Zara M. Patel

Journal Article

Background
The objective of this study is to characterize changes in hemodynamics, pain, and anxiety during office‐based endoscopic sinus procedures performed under local anesthesia.
Methods
We conducted a prospective study of adults undergoing in‐office endoscopic sinus procedures under local anesthesia. Patients with American Society of Anesthesiologists (ASA) Physical Status Classification System class 1 or 2 were included. Anesthesia was administered by topical 4% lidocaine/oxymetazoline and submucosal injection of 1% lidocaine/1:200,000 epinephrine. Vital signs and pain were measured at baseline, postinjection, and 5‐minute intervals throughout the procedure. Anxiety levels were scored using the State‐Trait Anxiety Inventory (STAI). Univariate and multivariate regression analyses were performed to identify factors significantly associated with changes in each hemodynamic metric.
Results
Twenty‐five patients were studied. This cohort was 52% male, mean age of 57.8 ± 14.4 years, and Charlson Comorbidity Index (CCI) median of 2. Mean procedure duration was 25.0 ± 10.3 minutes. Mean maximal increase in systolic blood pressure (SBP) was 24.6 ± 17.8 mm
Hg from baseline. Mean maximal heart rate increase was 22.8 ± 10.8 beats per minute (bpm) from baseline. In multivariate regression analysis, when accounting for patient age, cardiac comorbidity, CCI, and ASA, older age was significantly associated with an increase of >20 mm
Hg in SBP (p = 0.043). Mean pain score during procedures was 1.5 ± 1.3 with a mean maximum of 4.0 ± 2.6. STAI anxiety scores did not change significantly from preprocedure to postprocedure (32.8 ± 11.6 to 31.0 ± 12.6, p = 0.46). No medical complications occurred.
Conclusion
Although patients appear to tolerate office procedures well, providers should recognize the potential for significant fluctuations in blood pressure during the procedure, especially in older patients.

Chronic rhinosinusitis precipitated by tumor necrosis factor alpha inhibitors is the phenotype of chronic rhinosinusitis without nasal polyps

03-01-2020 – Peter Papagiannopoulos, Kyle Devins, Charles Ching Lick Tong, Christina Yver, Neil N. Patel, Hannah N. Kuhar, John V. Bosso, Michael A. Kohanski, Bobby A. Tajudeen, Edward C. Kuan, Pete S. Batra, Noam A. Cohen, David W. Kennedy, James N. Palmer, Kathy Montone, Nithin D. Adappa

Journal Article

Background
Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process.
Methods
A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSs
NP) patients, and CRS with nasal polyps (CRSw
NP) patients.
Results
Eighteen CRSαi, 91 CRSw
NP, and 113 CRSs
NP patients undergoing FESS were analyzed. Compared to CRSs
NP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot‐Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSw
NP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high‐power field (44.4% vs 73.6%, p < 0.017).
Conclusion
CRSαi exhibits structured histopathology more similar to CRSs
NP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide‐based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management.

Worldwide asthma epidemiology: insights from the Global Health Data Exchange database

03-01-2020 – Camilla Mattiuzzi, Giuseppe Lippi

Journal Article

Background
Enhanced focus on primary care provision is essential for lowering the risk of asthma exacerbation and complications, as well as for decreasing asthma‐related hospitalizations and deaths. This article provides an update on current worldwide epidemiology of asthma.
Methods
Worldwide epidemiologic information on asthma was obtained through electronic searches in the Global Health Data Exchange (GHDx) database.
Results
In 2017, the incidence of asthma was 43.12 million new cases/year (0.56%), while in that same year, prevalence and mortality accounted for 272.68 million cases (3.57%) and 0.49 million deaths (0.006%), respectively. Although the number of asthma cases significantly increased during the last 25 years, disability‐adjusted life years (DALYs) and deaths constantly declined. After adjustment of asthma incidence, prevalence, and DALYs for worldwide demographic variation, no significant changes could be seen during the last 25 years, while asthma mortality significantly declined during the same period. Asthma incidence peaks before the age of 5 years, whereas prevalence and DALYs peaks are observed between 0 and 14 years. DALYs also display a second peak, between 45 and 74 years. Asthma mortality increases with aging, reaching the peak after 80 years. The epidemiologic burden and mortality of asthma are constantly higher in women than in men. An inverse, highly significant correlation can be found between sociodemographic index and asthma incidence (r = −0.98) or mortality (r = −0.96).
Conclusion
Although the worldwide burden of asthma remains high, incidence and prevalence are not apparently translating into an escalating clinical and economic burden in terms of health loss and deaths.

Virtual coach: the next tool in functional endoscopic sinus surgery education

03-01-2020 – John P. Richards, Aaron J. Done, Samuel R. Barber, Saurabh Jain, Young‐Jun Son, Eugene H. Chang

Journal Article

Backgound
Functional endoscopic sinus surgery (FESS) can be challenging as novices become accustomed to handling endoscopes and instruments while navigating complex sinonasal anatomy. Experts demonstrate fluid and efficient motions when addressing pathology. The training process from novice to expert relies on hands‐on experience in cadaveric laboratories and preceptorship models that require significant time and expense. This study aims to validate the use of a virtual coach to guide users step‐by‐step through a basic FESS.
Methods
Seventeen surgeons were grouped into novice (n = 10) and expert (n = 7) based on self‐reported levels of surgical experience. Users were trained using the maxillary antrostomy module in the Neurorhinological Surgery (NRS) simulator combining the physical craniofacial model with virtual reality (VR)‐tracked surgical instruments in the VR operating room. The virtual coach guided the user using surgical videos, auditory, and visual cues. The coach recorded data for each subject including the number of times borders of the nasal cavity were encountered and time to completion. Users graded the usefulness of the virtual coach on a Likert questionnaire.
Results
Face validity of our NRS simulator was replicated by user questionnaires, and construct validity replicated by differentiation between novice and expert level surgeons (p < 0.01). Novices contacted a significantly higher number of anatomic borders (n = 17) and had a longer operative time (t = 370 seconds). All users reported high scores on the benefit and usefulness of the virtual coach.
Conclusion
The virtual coach provides a useful tool to enhance FESS education by providing objective real‐time data in a novel mixed‐reality surgical environment.

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

03-01-2020 – 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.

Characterization of nasal irrigation flow from a squeeze bottle using computational fluid dynamics

03-01-2020 – Kiao Inthavong, Yidan Shang, Eugene Wong, Narinder Singh

Journal Article

Background
Nasal saline irrigation has become standard of care in various sinonasal conditions, including allergic and nonallergic rhinitis, chronic rhinosinusitis, and in the postoperative patient. Evidence regarding the mechanisms and dynamics of liquid flow through the sinonasal cavity remains limited due to inadequate experimental models (cadaveric, 3‐dimensional 3D printed, imaging of labeled dyes and radioisotopes). We aimed to develop a computational fluid dynamics (CFD) model of nasal irrigation to demonstrate sinonasal surface coverage, residence times across the mucosal surfaces, and shearing force of irrigation.
Methods
A nasal cavity geometry derived from high‐resolution paranasal sinus computed tomography (CT) scans of a healthy, unoperated, 25‐year‐old patient was created. CFD analysis was performed to assess the distribution of nasal irrigation from a tapered nozzle bottle at a forward head‐tilt position of 45 degrees with a 2‐second burst at 35 m
L/second.
Results
The model demonstrates nasal irrigation from ipsilateral to contralateral with precise measures of velocity, pressure, wall shear stress, and mapping of surface coverage and residence times at specific locations and times. The nasal cavity experiences almost complete coverage of irrigation, while overflow from the nasal cavity facilitates moderate coverage of the ipsilateral maxillary (40%) and anterior ethmoid sinuses (30%). Negligible coverage of the sphenoid and frontal sinuses was noted.
Conclusion
Detailed physical mechanisms of liquid irrigation injected from a commonly used squeeze bottle were shown. Ipsilateral maxillary and ethmoid sinus penetration are primarily due to overflow rather than direct jet entry, confirming the recommendation of larger volumes of irrigation to “flood” the sinus ostia.

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

03-01-2020 – “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.

Successful endoscopic dacryocystorhinostomy: how high should the superior osteotomy be?

03-01-2020 – Swati Singh, David S. Curragh, Dinesh Selva

Letter

The spectrum of chronic rhinosinusitis therapy: from irrigation to the off‐target effects of biologics

03-01-2020 – Noam A. Cohen

Editorial

Issue Information

03-01-2020 –

Factors driving olfactory loss in patients with chronic rhinosinusitis: a case control study

03-01-2020 – Rodney J. Schlosser, Timothy L. Smith, Jess C. Mace, Jeremiah Alt, Daniel M. Beswick, Jose L. Mattos, Spencer Payne, Vijay R. Ramakrishnan, Zachary M Soler

Journal Article

Background
Olfactory dysfunction (OD) in chronic rhinosinusitis (CRS) is common. It is likely that numerous factors such as sex, race, age, allergies, asthma, smoking, and other comorbidities play a role in CRS‐related OD. In order to determine which aspects of OD are due solely to CRS and which are associated with other confounders, control populations are needed to allow appropriate risk assessments.
Methods
Prospective, multi‐institutional enrollment of patients with CRS and control subjects without CRS was performed. Demographic information, comorbidities, and olfactory testing (Sniffin’ Sticks) of threshold (T), discrimination (D), and identification (I) scores (TDI) was collected.
Results
A total of 224 patients with CRS and 164 control subjects were enrolled. Olfaction was worse in CRS patients compared to controls (mean ± standard deviation (SD) TDI = 22.4 ± 9.5 vs 28.8 ± 7.0, respectively, p < 0.001). Only 27% of CRS patients were normosmic compared to 49% of controls (p < 0.001). When stratifying by nasal polyp (NP) status, CRSw
NP patients had significant impairments in TDI, T, D, and I compared to controls with mean differences of 11.2, 3.3, 3.5, and 4.4 points, respectively (all p < 0.001). In contrast, CRSs
NP patients only had impaired T when compared to controls with a mean difference of 2.2 points (p < 0.001). Multivariate modeling of TDI scoring showed that OD was driven by polyps, asthma, diabetes, and age. CRSs
NP was not independently associated with worse TDI scores.
Conclusion
OD in CRS patients is multifactorial. Independent drivers appear to be polyp status, asthma, diabetes, and age. OD in patients with CRSs
NP is similar to controls with the exception of impaired thresholds.

Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis

23-12-2019 – Dong‐Jin Lim, Justin McCormick, Daniel Skinner, Shaoyan Zhang, Jeffrey B. Elder, John G. McLemore, Mark Allen, John Martin West, Jessica W. Grayson, Steven M. Rowe, Bradford A. Woodworth, Do‐Yeon Cho

Journal Article

Background
Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor‒releasing biodegradable sinus stent (CISS)―a drug‐delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis.
Methods
Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly‐D/L‐lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in‐vivo sinus potential difference (SPD) assay.
Results
Rabbits treated with CISS had significant reductions in computed tomography (∆ Kerschner scale: control, 0.55 ± 0.92; CISS, −5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores. A 2‐log reduction of PAO1 was observed (control, −2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl− transport in the CISS group compared with the control group (Cl−‐free + forskolin ΔPD: control, −4.23 ± 1.04 m
V; CISS, −18.36 ± 6.31 m
V; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals.
Conclusion
The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double‐layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis.

Predictive methods for efficacy of house dust mite subcutaneous immunotherapy in allergic rhinitis patients: a prospective study in a Chinese population

23-12-2019 – Zhuofu Liu, Hanyu Lu, Xian Feng, Li Hu, Jingjing Wang, Hongmeng Yu

Journal Article

Background
Allergen‐specific immunotherapy (AIT) is the only available treatment that can induce specific immune tolerance to allergens. However, the treatment course lasts >3 years, and there is no reliable method to predict treatment response. Therefore, in this study we aimed to establish a method that can predict treatment response to AIT in the second year.
Methods
This prospective study enrolled 119 patients who had undergone 2‐years of standard‐quality house dust mite subcutaneous immunotherapy. Clinical characteristics, skin‐prick test response, and treatment response were evaluated at months 4, 6, 12, and 18. Effective AIT was defined as a 25% reduction in average adjusted symptom score (AAd
SS) from baseline at the end of the second year of immunotherapy.
Results
The overall efficacy rate at the end of year 2 of the AIT was 67.4%. Age, sex, asthma, body mass index, smoking history, and aeroallergen categories were not associated with efficacy of AIT. Meanwhile, efficacy data at month 4 (odds ratio OR, 4.250; p = 0.004), month 6 (OR, 10.476; p < 0.000), month 12 (OR, 18.000; p < 0.000), and month 18 (OR, 9.716; p < 0.000) were associated with month 24 efficacy. The area under the curve for improvement at 4, 6, 12, and 18 months was 0.805, 0.834, 0.837, and 0.854, respectively.
Conclusion
Efficacy of AIT at months 4, 6, 12, and 18 is strongly associated with efficacy at month 24. Efficacy as early as month 4 can predict efficacy at the second year, and this may help to determine the need for long‐term treatment. Our findings may be useful for identifying novel treatment strategies for AIT.

The role of biologics in chronic rhinosinusitis: a systematic review

23-12-2019 – Isma Z. Iqbal, Stephen Shih‐Teng Kao, Eng Hooi Ooi

Journal Article, Review

Background
Chronic rhinosinusitis (CRS) refractory to medical and surgical treatment is challenging. It impacts patients’ quality of life significantly. The pathophysiology of CRS has some similarities to allergic asthma and allergic rhinitis (AR) and includes eosinophilia, T‐helper cell 2 cytokines, and local immunoglobilin E formation. Monoclonal antibody therapy has been used successfully in asthma and AR and more recently in CRS. Our was aim to systematically review the literature and identify the role of monoclonal antibodies (MAbs) in the treatment of CRS with polyps (CRSw
NP) and without polyps (CRSs
NP), especially with regard to comparability with current medical treatment, efficacy, and risk of complications. In addition, the role of surgery and biologics was evaluated.
Methods
We identified at total of 5341 relevant studies after a comprehensive database search. Six studies met the inclusion criteria, all 6 randomized, controlled trials.
Results
Treatment with omalizumab and mepolizumab demonstrated improvements in endoscopic nasal polyp score (EPS) and symptoms score in patients with CRSw
NP when compared with placebo. Reslizumab reduced nasal polyp size in patients with raised intranasal interleukin‐5 levels. Dupilumab treatment resulted in a 70% reduction in EPS compared with 20% in the placebo group (p < 0.001). These MAbs target different inflammatory markers involved in the pathophysiology of CRSw
NP. None of the studies reported on CRSs
NP or combined surgery with biologics. No severe adverse events were reported.
Conclusion
Evidence demonstrates that use of MAbs leads to clinical improvement in CRSw
NP. However, further research is required to determine their long‐term effects, comparability to other medical treatments, and potential side effects.

Influence of vitamin D receptor gene FokI and ApaI polymorphisms on glucocorticoid response in patients with asthma

20-12-2019 – Nesrine A. Mohamed, Asmaa S. Abdel‐Rehim

Journal Article

Background
Glucocorticoid (GC)‐resistant asthma, a complex disease phenotype, has a high morbidity and mortality and takes up a disproportionate share of healthcare costs. The aim of this work was to assess serum 25‐hydroxyvitamin D (25(OH)VD) levels in steroid‐resistant, steroid‐sensitive patients with asthma and in healthy controls, and to investigate the association between the vitamin D receptor gene (VDR) Fok
I and Apa
I polymorphisms and GC resistance in patients with asthma.
Methods
This case‐control study included 70 patients with severe bronchial asthma and 30 apparently healthy controls. Atopic status was determined by skin‐prick test reaction to the most common locally‐encountered allergens. A GC reversibility test was performed to differentiate between GC‐sensitive and GC‐resistant asthma. For all subjects, analysis of the VDR Fok
I and Apa
I polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) and measurement of serum 25(OH)VD levels by enzyme‐linked immunosorbent assay (ELISA) were performed.
Results
The frequencies of Fok
I polymorphism genotypes and alleles differed significantly between patients with asthma and controls. The frequencies of the TT genotype and T allele carriers were significantly higher among patients with asthma than among controls, and also among GC‐resistant patients with asthma than among GC‐sensitive patients with asthma. Additionally, serum 25(OH)VD levels differed significantly among the 3 VDR Fok
I polymorphic genotypes in GC‐resistant patients with asthma; the highest level was detected in the TT genotype. No significant differences in Apa
I were found.
Conclusion
We found a possible association between the Fok
I T allele and GC resistance in patients with asthma. Variations in VDR Fok
I might also play a role in 25(OH)VD levels.

Effect of oxidized cellulose on human respiratory mucosa and submucosa and its implications for endoscopic skull‐base approaches

19-12-2019 – Ezequiel Goldschmidt, Meghan Schneck, David M. Gau, Lauren Carey, Jorge Rasmussen, Bruno Ferreyro, Pablo Ajler, Carl Snyderman, Eric Wang, Juan Fernandez‐Miranda, Paul A. Gardner

Journal Article

Background
Regenerated oxidized cellulose (ROC) sheets have gained popularity as an adjunct to a vascularized nasoseptal flap for closure of dural defects after endoscopic endonasal skull‐base approaches (EESBS). However, evidence supporting its impact on the healing process is uncertain. This study was performed to evaluate the impact of ROC on the nasal mucosa and assess its effects on tissue p
H, structure, and cell viability.
Methods
In 5 patients, a 1‐cm2 piece of ROC gauze was placed on the surface of the middle turbinate before it was resected as part of a standard EESBS. Mucosa treated with ROC was separated from untreated mucosa and a histologic examination of structural changes in the respiratory epithelium was performed. To assess the effect of ROC on p
H, increasing amounts of ROC were added to culture medium. Nasal fibroblasts viability was assessed in the presence of ROC before and after the p
H was neutralized.
Results
Compared with unexposed controls, treated mucosa exhibited a higher incidence of cell necrosis and epithelial cell detachment. When added to Dulbeccos modified Eagle medium, ROC caused a dose‐dependent decrease in p
H of the medium. Only 1 ± 0.8% of cultured fibroblasts exposed to the ROC‐induced acidic medium were alive, whereas 98.25 ± 0.5% of the cells were viable when the p
H was neutralized (p < 0.001).
Conclusion
ROC applied in vivo to nasal mucosa induced epithelial necrosis likely by diminishing the medium p
H, because p
H neutralization prevents its effect. The ultimate effect of this material on the healing process is yet to be determined.

Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis

19-12-2019 – Zachary M. Soler, Frederick Yoo, Rodney J. Schlosser, Jennifer Mulligan, Vijay R. Ramakrishnan, Daniel M. Beswick, Jeremiah A. Alt, Jose L. Mattos, Spencer C. Payne, Kristina A. Storck, Timothy L. Smith

Journal Article

Background
Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi‐institutional cohort.
Methods
Adults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin’ Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification.
Results
Sixty‐two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSw
NP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSw
NP group, C‐C motif ligand 2 (CCL2), interleukin‐5 (IL‐5), IL‐6, IL‐13, IL‐10, IL‐9, tumor necrosis factor‐α (TNF‐α), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSs
NP), only C‐X‐C ligand 5 (CXCL5) showed a correlation. In CRSw
NP, IL‐6, IL‐10, vascular endothelial growth factor‐A, and immunoglobulin E (Ig
E) correlated with OC opacification, whereas, in CRSs
NP, only CXCL5 showed a correlation. OC mucus proteins and Lund‐Mackay score correlated only in the CRSs
NP group (CXCL5, IL‐5, IL‐13, Ig
E).
Conclusion
Several OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSs
NP and CRSw
NP subgroups, suggesting different mechanisms between groups, but further study is required.

Risk factors for neo‐osteogenesis in cystic fibrosis and non‒cystic fibrosis chronic rhinosinusitis

19-12-2019 – Peter Karempelis, Emily Karp, Nathan Rubin, Ryan Hunter, Jordan Dunitz, Holly Boyer

Journal Article

Background
The purpose of this retrospective review was to determine how patient‐related factors and culture data affect neo‐osteogenesis in patients with chronic rhinosinusitis (CRS) and patients with cystic fibrosis (CF) with CRS.
Methods
Information from a database associated with a large tertiary medical center was used to assess adult patients with CF CRS and non‐CF CRS (total, n = 102; CF CRS, n = 31; non‐CF CRS, n = 71). Radiologic evidence of neo‐osteogenesis was measured using the Global Osteitis Scoring Scale (GOSS), and mucosal disease was assessed using the Lund‐Mackay score (LMS) by 2 independent reviewers who were blinded to the patients disease state. Bacterial cultures were obtained endoscopically. Multiple logistic regression models were used to evaluate the effect of age, sex, number of previous surgeries, CF, and culture species on the odds of neo‐osteogenesis.
Results
Fifty‐one of the 102 patients (50%) met radiologic criteria for neo‐osteogenesis. Sixty‐nine patients (67.6%) with CF CRS and non‐CF CRS had culture data. In the multiple logistic regression model, male gender was significantly associated with neo‐osteogenesis (odds ratio OR, 5.2; 95% confidence interval CI, 1.68‐17.86; p = 0.006). Pseudomonas aeruginosa was not associated with neo‐osteogenesis (OR, 3.12; 95% CI, 0.84‐12.80; p = 0.097). Age, number of surgeries, CF, Staphylococcus aureus, and coagulase‐negative Staphylococcus were not statistically significant.
Conclusion
To our knowledge, this is the first study to assess risk factors associated with neo‐osteogenesis and patients with CF CRS. Interestingly, male gender was the only significant predictor of neo‐osteogenesis.

Sample collection for laboratory‐based study of the nasal airway and sinuses: a research compendium

17-12-2019 – Conner J. Massey, Fernando Diaz Del Valle, Waleed M. Abuzeid, Joshua M. Levy, Sarina Mueller, Corrina G. Levine, Stephanie S. Smith, Benjamin S. Bleier, Vijay R. Ramakrishnan

Journal Article

Background
Collection of biologic samples from the nasal cavity and paranasal sinuses is of critical importance to the study of infectious or inflammatory conditions that affect both upper and lower airways. Numerous techniques for the study of ex‐vivo samples exist, with specific applications, strengths, and weaknesses associated with each of them. In this compendium we summarize the available methods for collection of primary human samples and incorporate expert discussion of the pros, cons, and applications associated with each technique.
Methods
An expert panel containing members of the American Rhinologic Societys Research and Grants Committee compiled this educational reference. Rationale for use and the potential advantages and disadvantages are discussed. Research protocols and key references are enumerated.
Results
Sampling of the nasal cavity and paranasal sinuses can be achieved through a number of methods. Nonspecific sinonasal secretions may be collected via forced exhalation, nasal lavage, and nasal spray aspiration. Targeted collection of sinonasal secretions may be achieved via endoscopic placement of absorbent matrices. Nasal cytology or collection of superficial epithelium may be completed via brushing or scraping of endonasal structures. Collection of mucosal biopsies may be completed via sinonasal explant or full‐thickness biopsy.
Conclusion
Multiple sampling techniques are available to collect biologic samples from the sinonasal cavity. These techniques differ in their ease of application, reproducibility, sample yield, and utility for different sinonasal pathologies or research goals. An appreciation of the benefits and drawbacks of each approach will allow investigators to select the techniques most appropriate for achieving research objectives.

Sinonasal quality‐of‐life declines in cystic fibrosis patients with pulmonary exacerbations

13-12-2019 – Chetan Safi, Emily DiMango, Claire Keating, Zian Zhou, David A. Gudis

Journal Article

Background
In cystic fibrosis (CF), the relationship between chronic rhinosinusitis (CRS) and pulmonary disease is poorly understood. The purpose of this study was to evaluate the relationship between scores on the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and CF Questionnaire―revised for adolescents and adults over 14 (CFQ‐R 14+), and pulmonary function tests in 2 cohorts of CF patients: those at their baseline health and those with a pulmonary exacerbation.
Methods
Patients >18 years old seen in a Cystic Fibrosis Foundation‒accredited clinic completed the SNOT‐22 and CFQ‐R 14+ instruments. Patients presenting for routine care represented the baseline cohort. Patients diagnosed with a pulmonary exacerbation represented the exacerbation cohort. Average SNOT‐22 and CFQ‐R 14+ scores for both groups were compared using a 2‐sample t test, and correlation coefficient was calculated.
Results
One hundred three patients were enrolled over 3 months (30 exacerbations and 73 baseline). Patients’ mean age was 32 years (56% female and 44% male). Average SNOT‐22 and CFQ‐R 14+ scores were significantly worse for exacerbation patients (p = 0.001 and p = 0.0003, respectively). Percent predicted forced expiratory volume in 1 second and forced vital capacity were both higher for baseline patients (p = 0.002 and p = 0.001, respectively). Average SNOT‐22 score for all patients was worse than the average score for non‐CF, non‐CRS patients.
Conclusion
CF patients with pulmonary exacerbations have worse SNOT‐22 and CFQ‐R 14+ scores than CF patients at their baseline health. This finding suggests a temporal relationship between sinonasal and pulmonary quality of life, and that worsening of both is associated with reduced pulmonary function.

Multicenter study on the effect of nonsteroidal anti‐inflammatory drugs on postoperative pain after endoscopic sinus and nasal surgery

13-12-2019 – Arthur W. Wu, Evan S. Walgama, Ege Genç, Jonathan Y. Ting, Elisa A. Illing, Taha Z. Shipchandler, Thomas S. Higgins

Journal Article

Background
The taboo of avoiding nonsteroidal anti‐inflammatory drugs (NSAIDs) after functional endoscopic sinus surgery (FESS) has been waning. The impetus to reduce opioid prescriptions in view of the opioid epidemic led the authors to change their practices to include NSAIDs after sinus surgery. This studys aim was to analyze the differences between patients before and after we began recommending NSAIDs after FESS.
Methods
A prospective cohort study was performed on patients undergoing FESS or other endoscopic nasal surgeries at 3 institutions, by 5 rhinologists and 1 facial plastic surgeon. Before introducing NSAIDs, all patients were given a prescription for hydrocodone‐acetaminophen 5/325 mg and also recommended preferentially to use acetaminophen 325 mg. After the addition of NSAIDs, ibuprofen 200 mg and acetaminophen 325 mg were recommended preferentially, using the narcotic as a rescue medication. Patients kept a pain diary and medication log, and gave a visual analog scale (VAS) score for overall pain. Demographics, surgical variables, and comorbidities were also analyzed.
Results
One hundred sixty‐six total patients were recruited and had data that could be analyzed (65 without NSAIDs, 101 with NSAIDs). Overall, mean pain VAS score was 3.12 ± 1.95 for the non‐NSAID group and 2.33 ± 2.30 for the NSAID group (p value = 0.006). The day with the highest mean pain was the first postoperative day. The mean number of total opioid pills taken was 6.94 ± 6.85 without NSAIDs vs 3.77 ± 4.56 with NSAIDs (p = 0.018). Age and gender were found to be the only consistently significant patient variables to affect pain. There were no bleeding complications.
Conclusion
NSAID use was introduced into the practices of 5 practicing rhinologists and 1 facial plastic surgeon. No bleeding complications were seen. Both pain and overall opioid usage were reduced significantly.

Novel nitric oxide‒generating platform using manuka honey as an anti‐biofilm strategy in chronic rhinosinusitis

13-12-2019 – Catherina Yang, Girish Vallerinteavide Mavelli, Parimala Nacharaju, Kevin Li, Levi G. Cleare, Joshua D. Nosanchuk, Joel M. Friedman, Waleed M. Abuzeid

Journal Article

Background
Bacterial biofilms are implicated in the pathogenesis of chronic rhinosinusitis. Nitric oxide (NO) is a key immune effector with potent antimicrobial effects, but a short half‐life limits achievement of therapeutic concentrations. We hypothesized that manuka honey (MH) could induce sustained reduction of nitrite to NO causing biofilm disruption and that this effect would be enhanced with the addition of a NO‐releasing microparticle.
Methods
Porous organosilica microparticles containing nitrosylated thiol groups were formulated (SNO‐MP). MH was combined with serial dilutions of nitrite. NO release was evaluated using a NO analyzer. The susceptibility of 2 strains of Pseudomonas aeruginosa biofilms to these NO‐releasing platforms was evaluated using confocal microscopy. Cell viability and biofilm volume were quantified. Statistical analysis was performed using the Mann‐Whitney U test with SPSS software.
Results
MH with nitrite generated a linear increase in NO formation. SNO‐MP induced a bolus release of NO within 5 minutes, followed by a sustained plateau phase. MH with nitrite combined with SNO‐MP enhanced NO release during the plateau phase. MH with nitrite reduced biofilm live cells and volume by 88.5% to 96.9% and 95.1% to 95.6%, respectively, vs control (p < 0.0001). SNO‐MP reduced live cells and volume by 61.0% to 98.5% and 74.7% to 85.7%, respectively, vs control (p < 0.0001). MH with nitrite combined with SNO‐MP nearly eradicated biofilm, with a 98.3% to 99.8% (log 1.8‐2.6) reduction in viability and a 91.4% to 97.7% decrease in volume (p < 0.0001 vs control).
Conclusion
A novel platform that generates NO using MH and nitrite produces a potent anti‐biofilm effect, which can be further enhanced with the addition of SNO‐MP.

Economic implications of localization strategies for cerebrospinal fluid rhinorrhea

12-12-2019 – Christopher D. Pool, Vijay A. Patel, Amber Schilling, Christopher Hollenbeak, Neerav Goyal

Journal Article

Background
The direct costs associated with different diagnostic algorithms to localize cerebrospinal fluid (CSF) rhinorrhea have not been described.
Methods
A decision‐tree analysis of imaging modalities used to localize CSF rhinorrhea was performed to compare associated direct costs. The primary outcome was cost, which was determined based on reimbursement data published by the Centers for Medicare and Medicaid Services in 2018. The model was parameterized after a literature review of published studies was performed from 1990 to 2018 to estimate the sensitivity CSF rhinorrhea localization of the following radiographic modalities: high‐resolution computed tomography (HRCT), magnetic resonance cisternography (MRC), and CT cisternography (CTC). In addition to base case analysis, 1‐way sensitivity analyses were also performed to evaluate the robustness of results to changes in model parameters.
Results
Among patients with a high suspicion for CSF rhinorrhea, use of HRCT followed by exploration in the operating room if preliminary HRCT was negative was found to be the optimal localization modality from a cost perspective ($172.25). The next least costly algorithm was HRCT followed by MRC ($294.10). Imaging algorithms beginning with CTC were the next least costly modality ($727.37). Sensitivity analyses generally supported HRCT to be the optimal initial radiographic strategy over a wide range of parameter values.
Conclusion
This work advocates HRCT as first‐line modality to localize CSF rhinorrhea from a cost perspective. Although algorithms beginning with MRC were on average $35 more expensive than those starting with CTC, associated risks of CTC were not modeled and may play a role in decision making.

Real‐time hemodynamic effects of 1:100,000 and 1:200,000 injectable epinephrine and placement of topical 1:1000 epinephrine pledgets in patients undergoing endoscopic sinus and skull‐base surgery: a randomized, prospective study

09-12-2019 – Omar G. Ahmed, Justin Yu, Jonathan S. Choi, Michael T. Yim, Daniel Yoshor, Masayoshi Takashima

Journal Article

Background
Intranasal injection of epinephrine and placement of topical epinephrine pledgets are methods to improve visualization during endoscopic sinonasal surgery. Studies comparing the hemodynamic effects of these vasoconstrictors using intraoperative arterial line monitoring are lacking.
Methods
Twenty‐eight patients undergoing endoscopic skull‐base surgery were enrolled in a prospective, randomized study. Patients were randomized to have either 2 m
L of 1:100,000 or 2 m
L of 1:200,000 epinephrine injected intranasally. Hemodynamic parameters, including pulse, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), were collected using intraoperative arterial line monitoring for 5 minutes. Afterward, 1:1000 topical epinephrine‐soaked pledgets were placed in both groups, and the same parameters were collected for another 5 minutes.
Results
There was no statistical difference in change in pulse, SBP, DBP, and MAP between the 1:100,000 and 1:200,000 epinephrine groups. However, epinephrine injections did cause an increase in all hemodynamic parameters when compared with baseline (p < 0.05). Topical epinephrine pledgets placed after injection of epinephrine did not have any significant hemodynamic effects, except for 2 of 28 patients who had a >75‐mm
Hg increase in SBP. No preoperative characteristics were identified that predicted sensitivity to epinephrine.
Conclusion
There is no statistical difference in changes in hemodynamic parameters between injecting epinephrine 1:100,000 compared with 1:200,000 during endoscopic sinonasal surgery. In a subset of patients, placement of topical 1:1000 epinephrine pledgets had significant hemodynamic elevation requiring intervention and thus should be used judiciously depending on patient comorbidities.

Chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis: clinical presentation and antineutrophil cytoplasmic antibodies

02-12-2019 – “Christopher M. Low, Karina A. Keogh, Elias S. Saba, Nelson R. Gruszczynski, Alvise Berti, Ulrich Specks, Misbah Baqir, Byron M Smith, Garret Choby, Janalee K. Stokken, Erin K. OBrien”

Journal Article

Background
In this study we aim to describe presenting characteristics and identify prognostic factors for disease resolution in patients with chronic rhinosinusitis (CRS) in the setting of eosinophilic granulomatosis with polyangiitis (EGPA).
Methods
Patients evaluated at a tertiary care center with diagnoses of EGPA and CRS were identified. Descriptive statistics were obtained. Univariate analysis was used to search for prognostic factors associated with higher Lund‐Mackay score at presentation and disease resolution.
Results
Forty‐four patients were included with a mean age of 52.7 (standard deviation, 14) years. Twenty‐one patients (47.7%) were female, all had a diagnosis of asthma, and 36 (83.7%) had eosinophils >10%. Common presenting symptoms for CRS included nasal discharge (87.9%) followed by nasal congestion (83.9%) and facial pain and pressure (83.8%). Medical management of CRS included systemic corticosteroids (93.2%) and systemic antibiotics (75%). Surgical intervention occurred in 29 patients (67%). Nine patients (20.5%) had resolution of sinus symptoms, including 4 with imaging confirmation. Fourteen patients (31.8%) had continued CRS, but with improved symptoms, whereas 9 patients (20.5%) had continued CRS with no improvement in symptoms. Eleven patients (25%) were lost to follow‐up and 4 (9.1%) died. Univariate analysis did not show antineutrophil cytoplasmic antibody positivity, presence of peripheral eosinophilia, gender, age, or absence of systemic therapy to be predictive of higher Lund‐Mackay score at presentation or predictive of disease resolution.
Conclusion
CRS in patients with EGPA is often refractory to medical and surgical management. Treatment of these patients should occur in a multidisciplinary setting.

Survey of anesthesiologists on anesthetic maintenance techniques and total intravenous anesthesia for endoscopic sinus surgery

02-12-2019 – Yuki Yoshiyasu, Veronica F. Lao, Samuel Schechtman, Douglas A. Colquhoun, Sabrina Dhillon, Philip G. Chen

Journal Article

Background
Inhalational anesthesia and total intravenous anesthesia (TIVA) are techniques used for maintenance of general anesthesia for endoscopic sinus surgery (ESS). Growing evidence exists that TIVA may be associated with decreased bleeding and improved surgical fields, yet data suggest it is used in a minority of sinus surgery cases. The objective of this study was to investigate perceptions and approaches to anesthetic maintenance techniques in ESS among anesthesia providers.
Methods
A total of 719 anesthesiology residents, faculty, and certified registered nurse anesthetists (CRNAs) at 3 tertiary academic centers in the United States were invited to participate in a survey of considerations and practice patterns for inhalational anesthesia and TIVA for ESS.
Results
Responses were received from 200 participants (28%). Sixty‐five percent of respondents reported a lack of familiarity with current literature on TIVA for ESS. Many considered factors other than surgical field visualization when choosing a maintenance technique. Most were comfortable with performing TIVA but stated they would participate in additional training.
Conclusion
The majority of anesthesiology providers were unaware of the existing literature demonstrating advantage in improved surgical visualization with TIVA. Many used a combination of inhaled and intravenous anesthetics for maintenance. These findings suggest that future opportunities may exist to develop education, training, and practice approaches specific to anesthetic techniques for ESS.

Development of a novel simulation‐based task trainer for management of retrobulbar hematoma

27-11-2019 – Christopher J. Chin, Alexander Clark, Kathryn Roth, Kevin Fung

Journal Article

Background
Retrobulbar hematoma (RH) is a rare but devastating complication of sinus surgery. It is treated initially with a lateral canthotomy and cantholysis at the bedside. Due to the high stakes and urgency of this complication, teaching this in the clinical setting is difficult. The objective of this study was to develop a cadaveric model for addressing this problem.
Methods
A fresh‐frozen human cadaveric model of RH was created using a Foley catheter to simulate elevated intraocular pressure. Residents who participated in an emergencies in otolaryngology–head & neck surgery “boot camp” were included in the study. A survey measuring confidence levels in performing lateral canthotomy and cantholysis was administered. After completing the skill station, a postintervention survey was administered to assess the confidence of the learner as well as fidelity and usefulness of the task trainer.
Results
Thirty‐three residents participated in the boot camp. Residents rated their confidence preintervention at 1.3/5, which suggests the majority were unable to perform the procedure. After using the model, residents rated their confidence at 3.5/5, which falls between basic knowledge and reasonably confident; this improvement achieved statistical significance (p < 0.0001). The fidelity of the model was rated 3.9/5; a score of 4 is defined as realistic. The residents rated the usefulness of the model as 4.7; a score of 5 is defined as very useful.
Conclusion
A cadaveric model of RH was successfully developed. This novel simulator was perceived to be useful, realistic, and effective by junior residents.

Recurrent anaphylaxis in the United States: time of onset and risk factors

27-11-2019 – Mohamad R. Chaaban, Jared Stuart, Duncan Watley, Gwen Baillargeon, Yong‐Fang Kuo

Journal Article

Background
Studies have not yet examined the trends and risk factors of biphasic and recurrent anaphylaxis in the United States using International Classification of Diseases, tenth revision (ICD‐10) CM codes. The goal of this study is to examine the trends of biphasic and recurrent anaphylaxis in all patient care settings (inpatient, outpatient, emergency department, and observation).
Methods
We used the Clinformatics database from 2015 to 2017. Our main outcome measure was recurrent anaphylactic events occurring within 1 year after the initial event. We used Cox proportional hazards modeling to assess the factors associated with recurrent anaphylaxis and the Kaplan‐Meier method to estimate time to recurrence.
Results
There were a total of 19,039 patients with incident anaphylaxis in 2016 and, of these, 2017 had a recurrent anaphylaxis event in the 12‐month period after the index date (10.6%). The most common trigger for recurrent anaphylaxis is venom followed by food allergens. Pediatric patients aged <18 years were more likely to develop recurrent anaphylaxis compared with patients aged 18 to 64 years (hazard ratio HR, 1.53). Patients with allergic rhinitis and asthma were more likely to develop recurrent anaphylaxis compared to those without these comorbidities (HR, 1.15 and 1.27, respectively).
Conclusion
This is the first national study using ICD‐10 CM codes looking at rates of biphasic and recurrent anaphylaxis in all patient care settings. Recurrent anaphylaxis is more common in the first 3 days after the initial event, in younger patients (<18 years), and in patients with allergic rhinitis and/or asthma. Physicians need to prescribe epinephrine auto‐injectors and educate their patients about the risk of recurrence.

Rate of rhinosinusitis and sinus surgery following a minimally destructive approach to endoscopic transsphenoidal hypophysectomy

25-11-2019 – Ryan A. Rimmer, Swar Vimawala, Chandala Chitguppi, Erin K. Reilly, Alexander E. Graf, Judd H. Fastenberg, James J. Evans, Marc R. Rosen, Mindy R. Rabinowitz, Gurston G. Nyquist

Journal Article

Background
There remains considerable variation in the extent of sinonasal preservation during the approach for endoscopic transsphenoidal hypophysectomy (TSH). We advocate for a minimally destructive approach utilizing turbinate lateralization, small posterior septectomy, no ethmoidectomy, and preservation of nasoseptal flap (NSF) pedicles bilaterally. Due to these factors, this approach may affect the rates of postoperative rhinosinusitis. The objective of this study is to define the rates of postoperative rhinosinusitis in patients undergoing this approach.
Methods
Single institution, retrospective chart review of patients undergoing TSH from 2005 to 2018.
Results
A total of 415 patients were identified and 14% developed an episode of postoperative rhinosinusitis within 3 months. These patients were significantly more likely to have had a history of recurrent acute or chronic rhinosinusitis. Most cases were sphenoethmoidal sinusitis managed with 1 to 2 courses of antibiotics. Of patients with postoperative rhinosinusitis, most did not undergo NSF. Average follow‐up was 38 months. Six patients (1.4%) underwent post‐TSH functional endoscopic sinus surgery (FESS). Average time from TSH to FESS was 26.3 months. Two of these patients had a history of prior chronic rhinosinusitis without polyposis. Two patients underwent revision TSH for recurrent tumor as the primary indication for surgery at time of FESS. Twenty‐two–item Sino‐Nasal Outcome Test (SNOT‐22) scores generally increased immediately postoperatively, but frequently decreased below preoperative level by the time of last follow‐up, regardless of whether patients developed rhinosinusitis.
Conclusion
Sinonasal preservation during TSH is associated with a low rate of postoperative rhinosinusitis requiring FESS and excellent long‐term patient reported outcomes. We continue to advocate for sinonasal preservation during pituitary surgery.

Management of orbital invasion in sinonasal squamous cell carcinoma: 15 years’ experience

22-11-2019 – Ruichen Li, Shu Tian, Yi Zhu, Wenjia Zhu, Shengzi Wang

Journal Article

Background
This study was intended to review our management strategy for sinonasal squamous cell carcinomas (SNSCCs) with orbital invasion and to explore the role of radiotherapy in orbital preservation.
Methods
We retrospectively analyzed 93 SNSCC patients with orbital invasion who underwent radiotherapy with or without surgery over the past 15 years. The degree of orbital invasion was classified into 3 grades.
Results
Eighty‐eight patients presented with T4 tumors and 36 had grade III orbital invasion. Seventy‐two patients received surgery plus radiation and 67 received platinum‐based chemotherapy. The median follow‐up for surviving patients was 60 months. Five‐year overall survival (OS) for the whole group was 57.4%. The patients treated with surgery plus radiation had a 5‐year survival rate of 62.2% and orbital preservation was feasible in 90.3% of cases. Twenty‐one patients with SNSCCs that extended into the extraocular muscles or eye globe also underwent orbital preservation. Five‐year locoregional relapse‐free survival (LRFS) was 69.5% for patients treated with orbital preservation and 57.1% for those treated with orbital exenteration, indicating no statistical difference. Five‐year survival, 5‐year progression‐free survival (PFS), and 5‐year distant metastasis‐free survival (DMFS) were similar between groups. Grade III orbital invasion was independently associated with shorter OS, LRFS, PFS, and DMFS.
Conclusion
Orbital invasion in grade III was associated with the worst survival outcomes. Invasion of either the extraocular muscles or eye globe is not a contraindication for eye‐sparing surgery. Preoperative chemoradiation continues to offer hope to patients with a strong desire to preserve their eyes.

Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta‐analysis of risk factors

21-11-2019 – Catherine A. Loftus, Zachary M. Soler, Sina Koochakzadeh, Vincent M. Desiato, Frederick Yoo, Shaun A. Nguyen, Rodney J. Schlosser

Journal Article

Background
Wide variations in revision endoscopic sinus surgery (ESS) rates for chronic rhinosinusitis with nasal polyposis (CRSw
NP) have been reported. It is important to understand expected revision rates and factors that impact the need for revision.
Methods
A literature search was conducted on PubMed, Scopus, and the Cochrane Database of Systematic Reviews. Following PRISMA guidelines, a systematic review and meta‐analysis was performed on studies that reported revision surgery data for CRSw
NP patients.
Results
Forty‐five studies with 34,220 subjects were meta‐analyzed, with an overall revision rate of 18.6% (95% confidence interval, 14.1%‐23.6%). Studies with extractable follow‐up data reported a mean revision rate of 16.2% over a weighted mean follow‐up of 89.6 months. Factors associated with increased revision rates included allergic fungal rhinosinusitis (28.7%), aspirin‐exacerbated respiratory disease (27.2%), asthma (22.6%), prior polypectomy (26.0%), and publication prior to 2008 (22.7%) (p < 0.05 for all).
Conclusion
Although polyps can recur after ESS, reported long‐term ESS revision rates are approximately 14% to 24%. Identifying risk factors for revision surgery can help manage patient expectations and determine optimal personalized treatments.

Short‐term outcomes of olfaction in patients with eosinophilic chronic rhinosinusitis after endoscopic sinus surgery and an assessment of prognostic factors

21-11-2019 – Kosuke Akiyama, Yasushi Samukawa, Hiroshi Hoshikawa

Journal Article

Background
Olfactory dysfunction is one of the common symptoms of eosinophilic chronic rhinosinusitis (ECRS), for which endoscopic sinus surgery (ESS) is the standard treatment. Although the success rates of ESS for restoring olfaction in CRS have been reported, those for ECRS, as defined by new Japanese diagnostic criteria, remain unclear and the parameters affecting improvement rates have not yet been identified.
Methods
Eighty‐four patients with ECRS who underwent full‐house ESS were retrospectively investigated. Olfactory function was examined using T&T recognition thresholds before and 3 months after surgery.
Results
The total positive improvement rate in olfaction was 76.2% (64 of 84) and the mean T&T recognition threshold decreased significantly from 5.2 ± 1.1 to 3.0 ± 1.8 after surgery (p < 0.001). Some factors, including negative intravenous olfaction test, presence of olfactory cleft (OC) lesions, a history of sinus surgery, age ≥ 45 years, and being male, were more frequent in the olfaction refractory group. Furthermore, improvement of the T&T recognition threshold was significantly lower for factors of negative intravenous olfaction testing, the presence of OC lesions, and being male. Age and the proportion of blood eosinophils correlated with improvement.
Conclusion
Herein we examined prognostic factors for olfactory outcomes in ECRS treated with ESS. The intravenous olfaction test, presence of OC lesions, sex differences, and age (the cut‐off value was 45 years) were identified as independent prognostic factors for olfactory outcomes 3 months after surgery.

Comparison of steroid‐releasing stents vs nonabsorbable packing as middle meatal spacers

19-11-2019 – Jordan W. Rawl, Robert A. McQuitty, Mashfee H. Khan, Lara K. Reichert, Yong‐Fang Kuo, Mohamad R. Chaaban

Journal Article

Background
A randomized controlled trial was held to compare nonabsorbable packs to steroid‐eluting absorbable stents as middle meatal spacers after endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS).
Methods
CRS patients were randomly assigned to receive either nonabsorbable Merocel packs wrapped in non‐latex glove material (packing type A) or Propel steroid eluting stents (packing type B). Twenty‐two–item Sino‐Nasal Outcome Test (SNOT‐22) scores were collected preoperatively and postoperatively during the initial 4 debridements up to 3 months. Recording of the nasal endoscopy was also collected during all postoperative visits. In addition, Lund‐Kennedy scores and middle turbinate lateralization scores, using a new visual analogue scale, were compared between the 2 types of packing.
Results
Forty CRS patients were prospectively enrolled in this institutional review board (IRB)‐approved study. Patients with packing type A had significantly lower middle turbinate lateralization scores at their first (∼10 days) postoperative visit (p = 0.02 and p = 0.04, for left and right sides, respectively). This difference disappeared by later postoperative visits (from 20 days to 3 months). Overall, patients receiving packing type A had significant lower SNOT‐22 scores at 20 days postsurgery (p = 0.05). This difference also disappeared at 1 and 3 months postoperation. There were no statistically significant differences in Lund‐Kennedy scores.
Conclusion
In this study, nonabsorbable packing materials showed significant superior middle meatal spacing capacities as evidenced by greater middle turbinate medialization capability at the first postoperative visit. Additionally, patients with this type of packing saw improvements in their SNOT‐22 scores at the 20‐day postoperative visit. This study showed that there was no significant improvement in postoperative outcomes with drug‐eluting stents when compared to nonabsorbable packing.

Predictors of long‐term success and failure in primary and revision endoscopic dacryocystorhinostomy

15-11-2019 – Ashton E. Lehmann, George A. Scangas, Aria Jafari, Catherine G. Banks, Zoe H. Fullerton, Ralph Metson

Journal Article

Background
Although endoscopic dacryocystorhinostomy (endo‐DCR) is a common treatment of nasolacrimal duct obstruction, little is known about the determinants of surgical success and failure. The purpose of this study was to identify patient‐ and technique‐specific factors that may influence surgical outcomes of primary and revision endo‐DCR.
Methods
A retrospective review was conducted of 596 patients who underwent endo‐DCR over a 30‐year period (1989‐2018). Patients’ demographics and surgical techniques were assessed.
Results
Among the cohort of patients (n = 478) who underwent primary endo‐DCR, 10% (n = 48) required revision surgery. Patients who failed primary DCR tended to be younger (p = 0.015) and were less likely to have chronic sinonasal inflammation on histopathology (p = 0.047) than the successful surgery group. After adjusting for patient demographics and comorbidities, the occurrence of a postoperative complication was significantly associated with primary DCR failure (odds ratio OR, 2.2; p = 0.032). Among the cohort of patients (n = 118) who underwent revision endo‐DCR, 8.5% (n = 10) required additional revision surgery. Patients who failed revision DCR tended to be younger (p = 0.022), more likely to have had intraoperative laser usage (p = 0.031), and more likely to have had an intraoperative complication (p = 0.013) than the successful revision surgery group. Endo‐DCR failure was not associated with smoking status, middle turbinate resection, or intraoperative visualization of the internal common punctum (p > 0.05).
Conclusion
An understanding of factors associated with primary and revision endo‐DCR failure can help to inform preoperative counseling, intraoperative surgical technique, and postoperative care in the treatment of patients with nasolacrimal duct obstruction.

New landmarks in endonasal surgery: from nasal bone to anterior cribriform plate including branches of anterior ethmoidal artery and nerve and terminal nerve

13-11-2019 – Lise‐Marie Roussel, Vincent Patron, Eric Maubert, Clément Escalard, Didier Goux, Vincent Beaudouin, Emmanuèle Lechapt, Sylvain Moreau, Martin Hitier

Journal Article

Background
Despite the development of anterior skull base surgery, the anatomy of the nasal bone and anterior cribriform plate remains unclear. A recent study confirmed 2 distinct foramina in the anterior part of cribriform plate: the ethmoidal slit (ES) and the cribroethmoidal foramen (CF). The aim of this study was to specify their content, their anatomic relationship to the frontal sinus and skull base, and their potential value in skull base surgery.
Methods
Dissections were performed on 36 cadaver heads. Macro‐ and microscopic examinations were carried out. Microcomputed tomography scans contrasted with osmium were performed to identify vessels and nerves. Histology with neural, meningeal, or luteinizing hormone‒releasing hormone immunomarkers was performed on the content of the foramina. Finally, endonasal surgical dissections were carried out.
Results
The ES and the CF were observed in all cases. They measured a mean of 4.2 and 1.6 mm, respectively. The ES contained dura mater, arachnoid tissues, lymphatics, and the terminal nerve. The CF contained the anterior ethmoidal nerve and artery. This foramen continued forward with the cribroethmoidal groove, which measured a mean of 2.5 mm. This groove was under the frontal sinus and in front of the skull base. We also described a “cribroethmoidal canal” and a “nasal bone foramen.”Conclusion
The clinical applications of this new anatomic description concern both cribriform plate and frontal sinus surgeries. Identifying the terminal nerve passing through the ES is a step forward in understanding pheromone recognition in humans.

Cigarette smoke extract inhibits cell migration and contraction via the reactive oxygen species/adenosine monophosphate–activated protein kinase pathway in nasal fibroblasts

06-11-2019 – Jae‐Min Shin, Joo‐Hoo Park, Hyun‐Woo Yang, Heung‐Man Lee, Il‐Ho Park

Journal Article

Background
Fibroblast migration plays a significant role in wound healing after endoscopic sinonasal surgery. Cigarette smoke extract (CSE) is a potent inhibitor of fibroblast functions including cell proliferation and migration. The purpose of the study was to determine the influence of CSE on migration and collagen gel contraction in nasal fibroblasts and investigate its underlying mechanisms.
Methods
Fibroblast migration was evaluated using wound healing assay and transwell migration assay. Contractile activity was assessed by collagen gel contraction assay. Reactive oxygen species (ROS) were quantified by 2′,7′‐dichlorofluorescein diacetate. Fibroblasts were treated with CSE and N‐acetylcysteine (NAC), metformin, compound C, or transfected with small interfering RNA (si
RNA) to suppress adenosine monophosphate–activated protein kinase (AMPK) expression. AMPK activation was determined by Western blot.
Results
CSE and metformin were found to significantly reduce the migration and collagen gel contraction activity of nasal fibroblasts. Conversely, pretreatment with NAC and compound C significantly enhanced the migration and collagen gel contraction activity of fibroblasts. ROS production and AMPK phosphorylation were found to be significantly induced by CSE treatment, whereas the activity was inhibited on treatment with NAC, metformin, compound C, or AMPK si
RNA. Silencing of AMPK expression was found to significantly reverse the suppressive effect of CSE in nasal fibroblasts.
Conclusion
CSE has an inhibitory effect on cell migration and collagen gel contraction activity via the ROS/AMPK signaling pathway in nasal fibroblasts.

Prescription patterns and opioid usage in sinonasal surgery

06-11-2019 – Christopher I. Newberry, Geoffrey C. Casazza, Liese C. Pruitt, Jeremy D. Meier, David E. Skarda, Jeremiah A. Alt

Journal Article

Background
Excess opioid use after surgery contributes to opiate misuse and diversion. Understanding opioid prescribing and utilization patterns after sinonasal surgery is critical in designing effective practice protocols. In this study we aim to identify factors associated with variable opioid usage and further delineate optimal prescription patterns for sinonasal surgery.
Methods
All patients undergoing sinonasal surgery within a single health‐care system from March 2017 to August 2018 were sent electronic postoperative surveys. Data were collected on the amount of opioid required, pain control, presurgical opiate use, and narcotic disposal. Additional data collected from the electronic medical record included demographics, type of surgery performed, and total amount of opioid prescribed, including refills.
Results
Three‐hundred sixty four patients were included. A mean number of 25.3 tablets were prescribed per patient, yet the mean taken was just 11.8 tablets. Excess opioids were prescribed 84.9% of the time with a mean excess narcotic in oral morphine equivalents of 152.5. Among patients, 11.8% reported using no opioids, whereas 52.1% used <50% and 36.1% used >50% of their narcotic prescription. Patients used 9.3% of their full prescription and only 2.6% required a refill. The amount used was not associated with complexity of endoscopic sinus surgery, type of opiate prescribed, gender, distance living from hospital, or current opioid usage before surgery (p > 0.05). The addition of septoplasty and/or turbinoplasty was associated with variation in opioid usage (p < 0.001). A total of 76.1% of patients incorrectly discarded/stored excess opiates.
Conclusion
Opioids are overprescribed after sinonasal surgery. The amount of postoperative opiate prescribed should be greatly reduced and may be based on the specific procedures performed. Improved patient education regarding disposal of excess narcotics may help to curtail future opioid diversion.

Receptor activator of nuclear factor κB ligand is a biomarker for osteitis of chronic rhinosinusitis

06-11-2019 – Il Gyu Kong, Dong‐Kyu Kim, Kyoung Mi Eun, Seung Koo Yang, Minju Kim, Heonjeong Oh, Dae Woo Kim

Journal Article

Background
Evidence of osteitis is frequently observed in patients with chronic rhinosinusitis (CRS), especially in recalcitrant cases. However, studies focusing on biological markers of osteitis are limited and it remains unclear whether osteitis is associated with different phenotypes of CRS. This study aimed to analyze the expression and assess the roles of receptor activator of nuclear factor κB ligand (RANKL) in patients with CRS and osteitis.
Methods
CRS patients with nasal polyps (CRSw
NP, n = 63), CRS patients without nasal polyps (CRSs
NP, n = 8), and control subjects (n = 12) were enrolled. Histologic phenotypes, clinical information, and computed tomography (CT) scores were investigated. The Global Osteitis Scoring Scale (GOSS) and RANKL, a molecular marker of bone remodeling, were analyzed in each type of CRS. CRS mouse models were treated with anti‐RANKL.
Results
GOSS values were significantly higher in all CRS patients than in the control group. The GOSS value in non‐eosinophilic CRSw
NP was higher than in eosinophilic CRSw
NP. RANKL was upregulated whereas decoy receptor osteoprotegerin (OPG) was downregulated in CRS. RANKL messenger RNA (m
RNA) and protein levels were positively correlated with GOSS. RANKL/OPG was increased in recurrent cases compared with primary cases. Multiple inflammatory mediators were positively correlated with the protein level of RANKL in CRS tissues. In the mouse CRSw
NP model, anti‐RANKL treatment abrogated mucosal inflammation and bone remodeling.
Conclusion
RANKL expression is associated with clinical osteitis and disease severity in CRSw
NP. These findings shed light on the importance of RANKL as a potential biomarker of CRS and a key player in CRS pathogenesis.

Treatment practices for aspirin‐exacerbated respiratory disease: analysis of a national insurance claims database

06-11-2019 – Lauren T. Roland, Celeste Nagy, Heqiong Wang, Renee Moore, Katherine N. Cahill, Tanya M. Laidlaw, Sarah K. Wise, John M. DelGaudio, Merin Kuruvilla, Joshua M. Levy

Journal Article

Background
Aspirin‐exacerbated respiratory disease (AERD) is the triad of asthma, nasal polyposis, and sensitivity to cyclooxygenase‐1 inhibitors. Treatment options include medical management, surgical intervention, and aspirin desensitization (Asa
D).
Methods
AERD patients were identified using the Market
Scan Database from 2009 to 2015. Patients were included using International Classification of Diseases, 9th edition (ICD‐9) codes for asthma, nasal polyposis, and drug allergy. Treatments were determined by Current Procedural Terminology (CPT) codes for drug desensitization and endonasal procedures. Geographic trends and timing of interventions between those exposed and not exposed to desensitization were explored.
Results
A total of 5628 patients met inclusion criteria for AERD, with mean age 46 years, 60% female; 395 (7%) underwent Asa
D and 2171 (39%) underwent sinus surgery. Among patients who were desensitized, 229 (58%) underwent surgery, of whom 201 (88%) had surgery prior to Asa
D (median quartile 1, quartile 3; 61 days 30, 208 prior to desensitization). For patients undergoing surgery following Asa
D (n = 46), surgery was performed a median of 302 (163, 758) days after Asa
D. Nineteen patients had multiple surgeries post‐Asa
D with median time between surgeries being 734 days (312, 1484); 261 patients were not desensitized to aspirin but did undergo multiple surgeries, with the median of the median time between surgeries being 287 days (15, 617), which is shorter than for patients post‐Asa
D (p < 0.001).
Conclusion
A very small percentage of AERD patients undergo Asa
D. Patients who had Asa
D underwent surgery approximately 2 months prior to Asa
D. Patients who underwent Asa
D experienced an increased time between surgeries compared to patients who did not undergo Asa
D.

The effect of topical epinephrine 1:1000 with and without infiltration of 1% lidocaine with epinephrine 1:100,000 on endoscopic surgical field visualization: a double‐blind randomized controlled study

31-10-2019 – Navarat Tangbumrungtham, Peter H. Hwang, Ximena Maul, Nicole A. Borchard, Sachi S. Dholakia, Zara M. Patel, Jayakar V. Nayak, Garret Choby

Journal Article

Background
The objective of this study is to determine whether the infiltration of 1% lidocaine with 1:100,000 epinephrine in addition to topical application of 1:1000 epinephrine significantly improves surgical field grading scale score over topical 1:1000 epinephrine alone.
Methods
A prospective, double‐blind, randomized, controlled study was performed of 40 patients undergoing bilateral endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Patients were enrolled and randomly assigned to receive infiltration with 1% lidocaine with 1:100,000 epinephrine on 1 side of the nasal cavity vs plain saline on the other side in preparation for ESS. Both groups received topical application of 1:1000 epinephrine. Surgical videos were recorded and Wormald surgical field grading scale was assigned by 2 blinded reviewers. The number of extra 1:1000 epinephrine pledgets used during the surgery, estimated blood loss, and surgical duration were also recorded.
Results
There were no statistically significant differences in Wormald surgical field grading scale, number of extra pledgets used, or estimated blood loss between the nasal cavity side infiltrated with 1% lidocaine with 1:100,000 epinephrine in comparison to infiltration with saline. The side infiltrated with 1% lidocaine with 1:100,000 epinephrine had a reduced operative time compared to the side infiltrated with saline (p = 0.002). There were no differences in postoperative bleeding from questionnaire completed by patient at the first postoperative visit.
Conclusion
Addition of infiltration of 1% lidocaine with epinephrine 1:100,000 to topical application of epinephrine 1:1000 for preparation of ESS does not significantly improve surgical field of view compared to topical epinephrine alone.

Prospective characterization of postoperative nasal deformities in patients undergoing endoscopic endonasal skull‐base surgery

30-10-2019 – Nicholas R. Rowan, Benita Valappil, Jonlin Chen, Eric W. Wang, Paul A. Gardner, Carl H. Snyderman

Journal Article

Background
Surgeons have become increasingly aware of the impact of endoscopic endonasal surgery (EES) of the skull base on sinonasal‐related quality of life. Prior retrospective investigation described a correlation between nasoseptal flap (NSF) reconstruction in EES with postoperative nasal deformities, such as nasal dorsum collapse. The primary objective of this study was to prospectively evaluate the incidence of, and contributing factors to, postoperative changes in nasal structure following EES. Secondary goals included assessing subjective changes in nasal appearance as well as objective nasal analysis.
Methods
Clinical demographics and detailed perioperative information was prospectively collected for patients undergoing transsellar/suprasellar EES for skull‐base tumors. Preoperatively, 1‐month and 6‐month photographs were completed for objective photographic nasal analysis and blinded assessment by surgeons. Subjective patient feedback was also solicited.
Results
Overall, 14.7% (5/34) of patients subjectively reported postoperative nasal deformities, whereas both blinded‐surgeon and objective nasal measurements identified deformities in 12.9% (4/31) of patients. Patients with postoperative deformities were more likely to have skull‐base reconstruction with an NSF (p = 0.01) and trended toward an increased incidence in patients with nonpituitary neoplasms (p = 0.07). There were no other associations between clinical or operative characteristics and external deformities. No patients planned to undergo corrective repair.
Conclusion
External nasal deformities following EES are more frequent than previously acknowledged. Postoperative deformities appear to be associated with NSF reconstruction and may be associated with surgery for nonpituitary neoplasms. Patients should be counseled on this potential outcome, and future studies should investigate how to minimize postoperative sequela.

Association of air pollutants, airborne occupational exposures, and chronic rhinosinusitis disease severity

29-10-2019 – Nathalia Velasquez, John A. Moore, Robert M. Boudreau, Leila J. Mady, Stella E. Lee

Journal Article

Background
Previous work has shown that chronic rhinosinusitis (CRS) severity may be associated with particulate matter 2.5 (PM2.5) and black carbon (BC) in CRS patients without nasal polyps (CRSs
NP). Data regarding occupational exposures, however, are lacking. We assessed the impact of PM2.5, BC, as well as occupational airborne exposure on CRS disease severity.
Methods
Patients with CRS with nasal polyps (CRSw
NP), CRSs
NP, and aspirin‐exacerbated respiratory disease (AERD) were identified from an institutionwide database. Spatial modeling from 37 pollutant monitoring sites in Allegheny County was used to estimate exposures. Patient occupations using the 2010 Standard Occupation Classification (SOC10) and airborne occupation exposures to vapors, gases, dusts, fumes, fibers and mists (VGDFFi
M) or diesel fumes were recorded. Disease severity was measured by modified Lund‐Mackay score (LMS), systemic corticosteroid therapy, and incidence of functional endoscopic sinus surgery (FESS).
Results
Two hundred thirty‐four patients were included (CRSw
NP, n = 113; CRSs
NP, n = 96; AERD, n = 25). The prevalence of AERD among those with CRSw
NP was 18%. Patients exposed to VGDFFi
M or diesel fumes required higher steroid doses vs nonexposed patients (p = 0.015 and p = 0.03, respectively); patients with VGDFFi
M levels >5% were more likely to undergo FESS vs nonexposed patients (p = 0.0378). There was no difference in PM2.5 and BC with regard to disease severity and FESS between CRSw
NP, CRSs
NP, and AERD patients. Steroid use was significantly higher in CRSw
NP and AERD vs CRSs
NP (p = 0.001). LMS was significantly higher in AERD as compared with CRSw
NP and CRSs
NP (p = 0.001).
Conclusion
Occupational airborne exposure to VGDFFi
M correlated with increased prevalence of FESS and need for corticosteroids in CRS patients. There was no difference in PM2.5 and BC levels and disease severity outcome measures between CRS subtypes in this subset.

Cholinergic neuron‐like D‐U87 cells promote polarization of allergic rhinitis T‐helper 2 cells

28-10-2019 – Honghui Liu, Tiansheng Wang, Jinye Xia, Jingang Ai, Wei Li, Yexun Song, Yang Shen, Xiaowei Zhang, Guolin Tan

Journal Article

Background
Parasympathetic nerve hypersensitivity contributes to the severity of allergic rhinitis (AR), but the precise mechanism underlying neuroimmune regulation in patients with AR remains unclear. This study investigated the effect of cholinergic nerve inhibition on AR CD4+ T‐helper (Th)2‐cell polarization and the underlying regulatory mechanism in vitro.
Methods
An in‐vitro neuroimmune coculture model of D‐U87 cells and CD4+ T cells was established. D‐U87 cells with cholinergic neuron characteristics were used as cholinergic neuron models. CD4+ T cells were derived from peripheral blood monocytes from AR patients (n = 60) and control subjects (n = 40). Th1‐ and Th2‐cell percentages were measured by flow cytometry. Proteins involved in related signaling pathways were analyzed by protein chip assay and Western blotting.
Results
The Th2‐cell percentage among CD4+ T cells from AR patients was significantly increased after coculture with D‐U87 cells and was decreased by ipratropium bromide (IB) treatment. In contrast, the Th1‐cell percentage among control CD4+ T cells was significantly increased after coculture with D‐U87 cells, but was unaltered by IB treatment. Furthermore, phosphorylated Akt (p‐Akt) protein levels increased in CD4+ T cells from both controls and AR patients after coculture with D‐U87 cells and decreased after IB treatment. However, higher p‐Akt levels were observed in cells from AR patients than in cells from control subjects. Moreover, Akt inhibition decreased Th2‐cell percentage in AR patients.
Conclusion
In‐vitro cholinergic nerve inhibition with IB decreased AR CD4+ T‐cell polarization into Th2 cells partially through an Akt‐dependent mechanism.

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.

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.