International Forum of Allergy and Rhinology

International Forum of Allergy and Rhinology

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

03-12-2019 – 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

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.

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”

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

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.

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

27-11-2019 – 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.

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.

Comparing endoscopic resection and open resection for management of sinonasal mucosal melanoma

22-11-2019 – Nicole I. Farber, Richard D. Bavier, Meghan M. Crippen, Nishant Vatsa, Wayne D. Hsueh, Jean Anderson Eloy

Journal Article

Background
Sinonasal mucosal melanoma (SMM) is a rare, aggressive cancer, optimally managed with complete surgical resection. This study aimed to assess the impact of surgical approach on outcomes by comparison of cases managed with open vs endoscopic resection.
Methods
The National Cancer Database 2010–2015 datasets were queried for all cases of non‐metastatic SMM initially managed with definitive surgery. Patients were grouped according to surgical approach (open vs endoscopic) and compared for patient, tumor, and treatment variables using chi‐square analyses. Case‐control matching was used to generate subgroups of cases paired 1:1 between groups, matched for significantly distributed variables. Subgroups were compared for perioperative outcomes and overall survival (OS) using Kaplan‐Meier analyses.
Results
Of the 686 cases of SMM managed with definitive surgery, 46.2% were treated endoscopically. Open and endoscopic groups did not differ significantly by T‐stage, primary site, or rates of adjuvant therapies. Case‐control matching for these variables generated a subpopulation of 240 paired cases. Comparison of matched groups found no significant differences in 30‐day or 90‐day mortality. Endoscopically managed patients had higher rates of unplanned readmission whereas open resection patients had longer length of stay (LOS). There was no significant difference in OS between groups.
Conclusion
In surgically managed SMM, open resection patients have significantly longer LOS, whereas endoscopic patients have higher rates of unplanned readmission. Surgical approach does not appear to influence OS.

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.

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

19-11-2019 – Swati Singh, David S. Curragh, Dinesh Selva

Letter

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.

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

06-11-2019 – 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.

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.

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

06-11-2019 – 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.

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

05-11-2019 – Michael T. Chang, Kawinyarat Jitaroon, Teresa Nguyen, Carol H. Yan, Jonathan B. Overdevest, Jayakar V. Nayak, Peter H. Hwang, Zara M. Patel

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.

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

04-11-2019 – Yung Jin Jeon, Jin Hyun Seo, Yeon‐Hee Joo, Hyun‐Jin Cho, Sea‐Yuong Jeon, Sang‐Wook Kim

Journal Article

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

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

04-11-2019 – Ba Hung Do, Thi Nga Nguyen, Ryoko Baba, Toyoaki Ohbuchi, Jun‐ichi Ohkubo, Takuro Kitamura, Tetsuro Wakasugi, Hiroyuki Morimoto, Hideaki Suzuki

Journal Article

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

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

04-11-2019 – Hideaki Shiga, Koichi Okuda, Junichi Taki, Naoto Watanabe, Hisao Tonami, Seigo Kinuya, Takaki Miwa

Journal Article

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

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

04-11-2019 – Yuan Zhang, Feng Lan, Ying Li, Chengshuo Wang, Luo Zhang

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

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

04-11-2019 – Dong‐Kyu Kim, Young Chan Wi, Su‐Jin Shin, Kyung Rae Kim, Dae Woo Kim, Seok Hyun Cho

Journal Article

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

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

04-11-2019 – Wanpeng Li, Huan Wang, Huapeng Yu, Jingjing Wang, Xiaole Song, Zhuofu Liu, Juan Liu, Li Hu, Han Li, Dehui Wang, Xicai Sun

Journal Article

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

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

04-11-2019 – Ying‐Piao Wang, Ping‐Hung Shen, Li‐Chun Hsieh, Peter‐John Wormald

Journal Article

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

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

04-11-2019 – Juan Liu, Xicai Sun, Quan Liu, Yurong Gu, Houyong Li, Chunquan Zheng, Dehui Wang, Juan C. Fernandez‐Miranda, Carl H. Snyderman, Hongmeng Yu

Journal Article

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

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

04-11-2019 – Wei Wei Wang, Kai Zhu, Hong Wei Yu, Yong Liang Pan

Journal Article

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

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

04-11-2019 – Jingying Ma, Bing Zhou, Huang Qian, Zhenxiao Huang, Shi Jitong

Journal Article

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

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

04-11-2019 – Yuhui Ouyang, Zhaoyin Yin, Ying Li, Erzhong Fan, Luo Zhang

Journal Article

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

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

04-11-2019 – Yunxia Li, Chengshuo Wang, Ru Wang, Shizhi He, Ling Feng, Hongzhi Ma, Meng Lian, Qian Shi, Qi Zhong, Xiaohong Chen, Jugao Fang, Luo Zhang

Journal Article

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

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

04-11-2019 – Rong‐San Jiang, Chih‐Wen Twu, Kai‐Li Liang

Journal Article

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

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

04-11-2019 – Yifan Meng, Luo Zhang, Hongfei Lou, Chengshuo Wang

Journal Article

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

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

04-11-2019 – Taegu Kang, Chung Man Sung, Hyung Chae Yang

Journal Article

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

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

04-11-2019 – Qintai Yang, Chunwei Li, Weihao Wang, Rui Zheng, Xuekun Huang, Huiyi Deng, Peng Jin, Kaisen Tan, Yan Yan, Deyun Wang

Journal Article

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

Autophagy is involved in allergic rhinitis by inducing airway remodeling

04-11-2019 – Jing Li, Yong Li

Journal Article

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

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

04-11-2019 – Yi‐Ke Deng, Jin Ma, Zhi‐Chao Wang, Xiao‐Bo Long, Cai‐Ling Chen, Qi‐Miao Feng, Xin‐Hao Zhang, Ming Zeng, Heng Wang, Xiang Lu, Zheng Liu

Journal Article

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

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

04-11-2019 – Jin‐Mei Xue, Fei Ma, Yun‐Fang An, Li‐Min Suo, Xiao‐Rui Geng, Yan‐Nan Song, Li‐Hua Mo, Xiang‐Qian Luo, Xiao‐Wen Zhang, Da‐Bo liu, Chang‐Qing Zhao, Ping‐Chang Yang

Journal Article

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

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

04-11-2019 – Yanming Zhao, Yali Zhao, Yuan Zhang, Luo Zhang

Journal Article

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

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

04-11-2019 – So Young Kim, Chanyang Min, Dong Jun Oh, Hyo Geun Choi

Journal Article

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

Evolving management of upper airway diseases: focus on Asia

04-11-2019 – Luo Zhang

Editorial

Issue Information

04-11-2019 –

Morbidity and mortality associated with ventral skull base surgery: analysis of the National Surgical Quality Improvement Program

31-10-2019 – Roshansa Singh, Sana H. Siddiqui, Yonghee Choi, Monica C. Azmy, Nirali M. Patel, Jordon G. Grube, Wayne D. Hsueh, Soly Baredes, Jean Anderson Eloy

Journal Article

Background
Ventral skull base (VSB) surgery has associated morbidity and mortality that is poorly defined. In this study we aim to identify factors associated with adverse events in VSB surgery.
Methods
We queried the database of the American College of Surgeons National Surgical Quality Improvement Program for cases of VSB surgery during the period 2005‐2014. Patients with complications, readmissions, reoperations, or mortality were compared to those without adverse events.
Results
Nine hundred patients were included; 253 (28.1%) had complications, underwent reoperation, were readmitted, or died. These patients were older (42.6% vs 32.8, p = 0.032) and had higher rates of congestive heart failure (CHF) (3.2% vs 0.2%, p < 0.0001), disseminated cancer (8.3% vs 4.6%, p = 0.032), and preoperative sepsis (8.7% vs 2.2%, p < 0.0001). Other comorbidities included long‐term steroid use (13.4% vs 9.0%, p = 0.046) and higher rates of preoperative transfusion (2.4% vs 0%, p < 0.0001). The most common complication was bleeding (13.7%). Preoperative systemic sepsis (odds ratio OR, 2.6; 95% confidence interval CI, 1.0‐6.6) and lower hematocrit (OR, 2.1; 95% CI, 1.4‐3.4) were more likely to be associated with a complication. Those with disseminated cancer (OR, 12.0; 95% CI, 2.9‐50.5) were more likely to experience 30‐day mortality. Black patients had lower rates of reoperation (OR, 0.3; 95% CI, 0.1‐0.8), whereas patients with CHF (OR, 12.6; 95% CI, 1.7‐94.4) and hypertension (OR, 2.1; 95% CI, 1.1‐4.0) had higher rates of reoperation. Predictors of extended length of stay were Hispanic ethnicity (OR, 2.2; 95% CI, 1.2‐4.1) and lower hematocrit (OR, 2.3; 95% CI, 1.5‐3.6).
Conclusion
VSB surgery can involve significant morbidity and mortality, and thus identifying risk factors allows for better prognostication and delivery of care in these patients.

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.

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

23-10-2019 – 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.

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

23-10-2019 – 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.

Mometasone absorption in cultured airway epithelium

21-10-2019 – Tuong T. Nguyen, Paul S. Soma, Teresa Mascenik, Catherine A. Lewis, Rhianna E. Lee, Brian D. Thorp, Adam M. Zanation, Charles S. Ebert, Brent A. Senior, Scott H. Randell, Brandie M. Ehrmann, Adam J. Kimple

Journal Article

Background
Topical mometasone is frequently used as an intranasal spray, on drug‐eluting stents, and compounded by specialty pharmacies as a sinus rinse. A typical sinus rinse contains 1.2 mg of mometasone dissolved in 240 m
L of buffered saline and is flushed through the sinonasal cavity. The mometasone irrigation rapidly flows to the contralateral sinonasal cavity or the nasopharynx with a contact time on the order of 5 to 10 seconds. However, no information is available on the absorption rate of topical mometasone on the sinonasal surface.
Methods
To determine the absorption characteristics of mometasone, we harvested nasal epithelium from 2 healthy donors and differentiated them into a mature ciliated epithelium on Millicell membranes. We applied mometasone to the apical surface for various time intervals and then rinsed off non‐absorbed mometasone with phosphate‐buffered saline. Millicell membranes with the adherent epithelial cells were then harvested and stored in guanidine hydrochloride for quantification using high‐performance liquid chromatography–mass spectrometry.
Results
Fifty percent of the maximal absorption occurred after an average of 38 minutes after application, and maximal absorption occurred after an average of 114 minutes.
Conclusion
Our data provide an estimate for rates of absorption of mometasone applied to the sinonasal cavity and suggest that the absorption rates poorly match contact time during saline lavage.

Robotic surgery of the anterior skull base

21-10-2019 – Raewyn G. Campbell

Journal Article, Review

Background
Significant advances have been made in transoral robotic surgery (TORS), yet its application in anterior skull‐base surgery has yet to be defined. This work explores the history of endoscopic sinus and anterior skull‐base surgery, and its advantages and disadvantages. The development of robotic surgery is then discussed as well as the advantages and disadvantages of TORS as it relates to the anterior skull base. The current applications for robotic surgery to the anterior skull base are presented with details of future applications.
Methods
A structured search of the current literature using MEDLINE, PubMed, and EMBASE was performed from inception to May 2019. Search terms related to topics of robotic skull‐base surgery were identified and queried to identify relevant articles.
Results
Fifty‐four papers were identified from the literature search and a hand search of the references. Twenty‐one other references were discovered from personal communication, websites, and books relevant to the topic.
Conclusion
Anterior skull‐base surgery has the potential for significant morbidity compared to head and neck surgery, yet the application of the robot in sinus and anterior skull‐base surgery has yet to be formally defined. Currently, there are certain limitations that need to be overcome; however, research to address these barriers is currently underway and promises an exciting future for robotic sinus and anterior skull‐base surgery.

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

Impact of palliative treatment on survival in sinonasal malignancies

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

Journal Article

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

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

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

Journal Article, Review

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

Diamine oxidase enzyme: a novel biomarker in respiratory allergy

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article, Review

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

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

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

Journal Article

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

Detection and quantification of Staphylococcus in chronic rhinosinusitis

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

Journal Article

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

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

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

Journal Article

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

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

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

Journal Article

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

Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia

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

Journal Article

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

Fusarium: A potential cause of chronic rhinosinusitis?

28-02-2012 – Bradley Marple