Publications by authors named "Spencer C Payne"

68 Publications

Psychometric properties of the brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis.

Int Forum Allergy Rhinol 2021 Apr 17. Epub 2021 Apr 17.

Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.

Background: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample.

Methods: Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey.

Results: EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD.

Conclusion: The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS.
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http://dx.doi.org/10.1002/alr.22800DOI Listing
April 2021

Elevated Urine Leukotriene E4 Is Associated With Worse Objective Markers in Nasal Polyposis Patients.

Laryngoscope 2021 05 1;131(5):961-966. Epub 2020 Oct 1.

Division of Allergic Diseases, Mayo Clinic, Rochester, Minnesota, U.S.A.

Objectives: Urine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP.

Methods: A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected.

Results: Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P < .001), aspirin sensitivity (P < .001), worse Lund-Mackay CT scores (P = .002) and other objective markers of disease severity including serum IgE (P = .05), presenting blood eosinophil level (P < .001), and the highest recorded eosinophil level (P < .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (R range 0.31-0.52) than the aspirin tolerant CRSwNP group (R range -0.30-0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores).

Conclusion: Elevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient-reported symptom measures.

Level Of Evidence: 3 Laryngoscope, 131:961-966, 2021.
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http://dx.doi.org/10.1002/lary.29137DOI Listing
May 2021

Olfactory Function After Surgical Treatment of CRS: A Comparison of CRS Patients to Healthy Controls.

Am J Rhinol Allergy 2021 May 20;35(3):391-398. Epub 2020 Sep 20.

Department of Otolaryngology, Head and Neck Surgery, University of Colorado-Anschutz Medical Campus, Aurora, Colorado.

Background: Many patients with chronic rhinosinusitis (CRS) have persistent olfactory dysfunction (OD) following endoscopic sinus surgery (ESS). Few studies compare outcomes to control subjects so it is unknown if residual OD is due to persistent CRS.

Objective: Compare postoperative measures of OD in case patients with CRS to healthy controls without sinonasal disease.

Methods: Prospective, observational, multicenter cohort study between October, 2016 and May, 2019. Case participants were selected from referred adult patients diagnosed with CRS, with or without nasal polyposis (NP), electing ESS as subsequent treatment modality. Controls voluntarily enrolled from a community-based sample without a history of CRS. Primary outcomes included measures of preoperative and postoperative OD using "Sniffin' Stick" pens which summarize odorant threshold (T), discrimination (D), and identification (I) scores. Secondary outcomes included the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) survey and olfactory cleft endoscopy scores (OCES).

Results: Outcomes were compared between 113 cases and 164 controls of similar average age and gender. Cases reported significantly worse baseline Sniffin' Sticks TDI total scores (-6.8[SE ± 1.0]; 95% CI: -4.9 to -8.7), QOD-NS (8.9[SE ± 1.1]; 95% CI: 6.8-10.9), and OCES (3.5[SE ± 0.4]; 95% CI: 2.9-4.2) on average. Cases reported significant postoperative improvement in TDI total score (3.7[SD ± 8.2]; 95% CI: 2.2-5.2), QOD-NS (-5.9[SD ± 8.7]; 95% CI: -7.6 to -4.3), and OCES (-1.7[SD ± 3.8]; 95% CI: -2.7 to -0.8) on average, while 63% of anosmics reported improved postoperative olfaction. Multivariate regression identified that NP (OR = 0.4; 95% CI: 0.2-1.0) and previous ESS (OR = 0.3; 95% CI: 0.1-0.8) decreased the odds of postoperative improvement equal to mean TDI scores of controls, while septoplasty increased those odds (OR = 4.5; 95% CI: 1.5-13.7).

Conclusion: ESS improved olfactory metrics and restored olfactory function in approximately 50% of patients with CRS to that of healthy controls. Concurrent septoplasty increased the likelihood of achieving normal olfaction, while NP and previous ESS decreased those odds.
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http://dx.doi.org/10.1177/1945892420960671DOI Listing
May 2021

Efficacy of corticosteroid solution administration via Mygind's position for the management of chronic rhinosinusitis with nasal polyps.

Laryngoscope Investig Otolaryngol 2020 Aug 7;5(4):608-612. Epub 2020 Aug 7.

Department of Otolaryngology-Head and Neck Surgery University of Virginia School of Medicine Charlottesville Virginia USA.

Objective: To investigate whether direct steroid application via Mygind's position improved objective and subjective measures of chronic rhinosinusitis with nasal polyposis (CRSwNP).

Methods: A retrospective chart review was performed on patients seen by the senior author in a Rhinology Clinic of a tertiary academic center over a 2 year period. Patients whose only change in medical regimen was initiation of corticosteroid administration via Mygind's position were included for this analysis. The main subjective and objective outcome measures were Sino-nasal Outcome Test-22 (SNOT-22) and endoscopy scores, respectively. Patient scores before and after the change in treatment were compared and analyzed using Student's test and Wilcoxon signed-rank test.

Results: Twenty-two patients were identified for inclusion. There was a statistically significant decrease in overall nasal endoscopy scores for both the right ( = .001) and left ( = .001) sides. A statistically significant and clinically meaningful decrease in total SNOT-22 scores (12.7 points, = .008) was also seen. Intolerance to the regimen was observed in 5/48 patients reviewed for inclusion (10.4%), with issues including neck pain, burning, pressure, and thrush.

Conclusion: The direct application of topical corticosteroids, specifically via Mygind's position, may improve both objective exam findings and clinical symptomatology in patients with CRSwNP compared to indirect application. Intolerance to the regimen can be observed.

Level Of Evidence: 4-Case series (with or without comparison).
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http://dx.doi.org/10.1002/lio2.424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444766PMC
August 2020

Pilot Investigation: Prospective Needs Assessment of Knowledge, Attitude, and Insight About Mental Health Treatment Options in Patients With Chronic Rhinosinusitis.

Am J Rhinol Allergy 2020 Jul 18;34(4):537-542. Epub 2020 Mar 18.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Utah, Salt Lake City, Utah.

Introduction: Mood disorders frequently coexist with chronic rhinosinusitis (CRS), yet patient views of how mental health impacts their disease, and their willingness to engage in treatment is not well understood.

Methods: Subjects with CRS were enrolled regardless of their mental health status and completed a needs questionnaire on mental health as it related to CRS. In addition, demographic and disease-specific data were collected.

Results: We enrolled 55 subjects. In addition, 29.1% of them had polyps, with mean endoscopy/computed tomography (CT)/Sino-Nasal Outcome Test (SNOT-22) scores of 3.9/9.7/41.2, respectively and 45% thought depression was common in CRS patients. In total, 78.2% were open to taking a depression screener and would be comfortable discussing mental health with their Ear Nose and Throat provider, 76.4% of patients felt that treating mental health problems could improve sinus-related quality of life (QOL), and 87.3% were open to meeting with a mental health professional or participating in a course on managing stress/anxiety/mental health issues. The multivariate regression model of whether patients felt that treating the mind would improve sinus-related QOL as predicted by age, gender, SNOT-22, CT scores, and endoscopy scores was statistically significant ( = .027) and explained 42% of the variance in answers, but only age and gender approached statistical significance ( = .06 and .04).

Conclusions: CRS patients acknowledged the high prevalence of comorbid mood disorders and were willing to discuss and be treated for mental health issues. Many patients felt that treating their mental health would improve their disease-specific QOL. These findings warrant further study of how to incorporate the management of metal health into CRS treatment algorithms.
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http://dx.doi.org/10.1177/1945892420912369DOI Listing
July 2020

Perivascular epithelioid cell tumor (PEComa) of the pterygopalatine fossa.

Clin Case Rep 2020 Mar 5;8(3):553-558. Epub 2020 Feb 5.

Department of Otolaryngology- Head and Neck Surgery University of Virginia School of Medicine Charlottesville Virginia.

Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal tumors associated with tuberous sclerosis. These tumors are typically treated with resection and rarely recur or exhibit malignant behavior. A 78-year-old woman presented with an incidentally discovered pterygopalatine fossa/retroantral mass. Excisional biopsy was performed and revealed pathology consistent with PEComa. Upon review of the literature, there have been 43 reported cases of PEComa of the head and neck. There is only one previously reported case of PEComa in the skull base, and none reported in the pterygopalatine fossa. Of note, the previously reported case of skull base PEComa involved an aggressive tumor with widespread metastasis. Here, we report the first case of a PEComa of the pterygopalatine fossa/retroantral region, which was treated conservatively. This rare pathology should be considered in the differential diagnosis for atypical skull base tumors.
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http://dx.doi.org/10.1002/ccr3.2676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069881PMC
March 2020

The Rationale for Multidisciplinary Management of Chronic Rhinosinusitis with Nasal Polyposis.

J Allergy Clin Immunol Pract 2020 05 12;8(5):1565-1566. Epub 2020 Mar 12.

Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, AZ. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.03.001DOI Listing
May 2020

T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection.

Cell Rep 2020 01;30(2):351-366.e7

Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. Electronic address:

Human rhinoviruses cause the common cold and exacerbate chronic respiratory diseases. Although infection elicits neutralizing antibodies, these do not persist or cross-protect across multiple rhinovirus strains. To analyze rhinovirus-specific B cell responses in humans, we developed techniques using intact RV-A16 and RV-A39 for high-throughput high-dimensional single-cell analysis, with parallel assessment of antibody isotypes in an experimental infection model. Our approach identified T-bet+ B cells binding both viruses that account for ∼5% of CXCR5- memory B cells. These B cells infiltrate nasal tissue and expand in the blood after infection. Their rapid secretion of heterotypic immunoglobulin G (IgG) in vitro, but not IgA, matches the nasal antibody profile post-infection. By contrast, CXCR5+ memory B cells binding a single virus are clonally distinct, absent in nasal tissue, and secrete homotypic IgG and IgA, mirroring the systemic response. Temporal and spatial functions of dichotomous memory B cells might explain the ability to resolve infection while rendering the host susceptible to re-infection.
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http://dx.doi.org/10.1016/j.celrep.2019.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994188PMC
January 2020

Hypertension and Epistaxis: Why Is There Limited Guidance in the Nosebleed Clinical Practice Guidelines?

Otolaryngol Head Neck Surg 2020 01;162(1):33-34

Department of Otolaryngology-Head & Neck Surgery, School of Medicine, Johns Hopkins, Baltimore, Maryland, USA.

Hypertension has long been thought to influence the risk and severity of epistaxis. However, evaluation of the relevant literature reveals articles with methodologic concerns or limited quality. In many instances, these studies are not adequately controlled, and lack of multivariate analyses calls into question any noted association between epistaxis and hypertension. The goal of this commentary is to explain why there is limited guidance about the management of hypertension and the possible association with nosebleed in the 2020 American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline for nosebleeds. Background on the literature that describes the association between hypertension and nosebleeds is provided.
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http://dx.doi.org/10.1177/0194599819889972DOI Listing
January 2020

Clinical Practice Guideline: Nosebleed (Epistaxis) Executive Summary.

Otolaryngol Head Neck Surg 2020 01;162(1):8-25

American Academy of Otolaryngology-Head and Neck Surgery Foundation, Alexandria, Virginia, USA.

Objective: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the great majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds.

Purpose: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It will focus on nosebleeds that commonly present to clinicians with phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients, patients with hemorrhagic telangiectasia syndrome (HHT) and patients taking medications that inhibit coagulation and/or platelet function, are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the working group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based upon their experience and assessment of individual patients.

Action Statements: The guideline development group made for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include 1 or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome (HHT). (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation about examination of the nasal cavity and nasopharynx using nasal endoscopy was an (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.
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http://dx.doi.org/10.1177/0194599819889955DOI Listing
January 2020

Clinical Practice Guideline: Nosebleed (Epistaxis).

Otolaryngol Head Neck Surg 2020 01;162(1_suppl):S1-S38

American Academy of Otolaryngology-Head and Neck Surgery Foundation, Alexandria, Virginia, USA.

Objective: , also known as , is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as . Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds.

Purpose: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients.

Action Statements: The guideline development group made for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include one or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome. (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation, about examination of the nasal cavity and nasopharynx using nasal endoscopy, was an (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.
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http://dx.doi.org/10.1177/0194599819890327DOI Listing
January 2020

Association Between Smell, Taste, and Depression in Nationally Representative Sample of Older Adults in the United States.

Am J Rhinol Allergy 2020 May 2;34(3):369-374. Epub 2020 Jan 2.

School of Medicine, University of Virginia, Charlottesville, Virginia.

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http://dx.doi.org/10.1177/1945892419897217DOI Listing
May 2020

Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis.

Int Forum Allergy Rhinol 2020 03 19;10(3):343-355. Epub 2019 Dec 19.

Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health Sciences University, Portland, OR.

Background: Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi-institutional cohort.

Methods: Adults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin' Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification.

Results: Sixty-two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSwNP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSwNP group, C-C motif ligand 2 (CCL2), interleukin-5 (IL-5), IL-6, IL-13, IL-10, IL-9, tumor necrosis factor-α (TNF-α), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSsNP), only C-X-C ligand 5 (CXCL5) showed a correlation. In CRSwNP, IL-6, IL-10, vascular endothelial growth factor-A, and immunoglobulin E (IgE) correlated with OC opacification, whereas, in CRSsNP, only CXCL5 showed a correlation. OC mucus proteins and Lund-Mackay score correlated only in the CRSsNP group (CXCL5, IL-5, IL-13, IgE).

Conclusion: Several OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSsNP and CRSwNP subgroups, suggesting different mechanisms between groups, but further study is required.
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http://dx.doi.org/10.1002/alr.22499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145735PMC
March 2020

Suppression of aspirin-mediated eosinophil activation by prostaglandin E: Relevance to aspirin and nonsteroidal anti-inflammatory drug hypersensitivity.

Ann Allergy Asthma Immunol 2019 11 9;123(5):503-506. Epub 2019 Sep 9.

Departments of Medicine, University of Virginia Health System, Charlottesville, Virginia.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by severe, sometimes life-threatening reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Mechanisms driving the disease include overproduction of leukotrienes and loss of anti-inflammatory prostaglandin E (PGE) production. Many cell types contribute to the disease; however, eosinophils are markedly elevated and are important drivers of pathologic findings.

Objective: To investigate the capacity of aspirin and NSAIDs to drive eosinophil activation and the ability of PGE to inhibit this activation.

Methods: Eosinophils were purified from blood of healthy individuals without AERD and stimulated with lysine aspirin, ketorolac, or sodium salicylate. The role of PGE in altering activation was determined by incubating eosinophils with increasing doses of PGE before lysine aspirin stimulation. Specific PGE receptor use was determined by incubating eosinophils with receptor agonists and antagonists before aspirin stimulation. Cysteinyl leukotrienes (CysLTs), leukotriene B (LTB), and eosinophil-derived neurotoxin (EDN) were quantified by enzyme-linked immunosorbent assay.

Results: Stimulation of eosinophils with lysine aspirin, ketorolac, or sodium salicylate resulted in secretion of CysLTs and LTB in the absence of EDN release. Low doses of PGE inhibited LTB and CysLT release, an effect lost at higher PGE concentrations. Use of butaprost, an EP receptor agonist, suppressed lysine aspirin stimulation. This mechanism was supported by blocking activity of the EP and EP receptors.

Conclusion: Eosinophils can be directly activated by NSAIDs via cyclooxygenase-independent pathways to produce CysLTs and LTB. This effect can be inhibited by PGE acting through the EP receptor. The recognized loss of EP receptor expression combined with low PGE levels explains in part the sensitivity to NSAIDs.
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http://dx.doi.org/10.1016/j.anai.2019.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825585PMC
November 2019

Differential Expression of Extracellular Matrix Components in Nasal Polyp Endotypes.

Am J Rhinol Allergy 2019 Nov 25;33(6):665-670. Epub 2019 Jun 25.

Asthma and Allergic Disease Center, University of Virginia Health System, Charlottesville, Virginia.

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http://dx.doi.org/10.1177/1945892419860634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843742PMC
November 2019

Statin use protective for chronic rhinosinusitis in a nationally representative sample of the United States.

Laryngoscope 2020 04 31;130(4):848-851. Epub 2019 May 31.

Department of Otolaryngology, University of Virginia School of Medicine, Charlottesville, Virginia, U.S.A.

Objectives/hypothesis: Statins have long been used in the management of cardiovascular disease for their lipid-lowering properties. However, recent research suggests that statins may also have anti-inflammatory effects via modulation of lipid-containing enzymes and mediators, and therefore may have therapeutic value in the treatment of chronic rhinosinusitis (CRS).

Study Design: Retrospective database review.

Methods: The 2006 to 2015 National Ambulatory Medical Care Survey (NAMCS) data were queried to analyze the relationship between statin use and rates of CRS. CRS was indicated by the presence of an International Classification of Diseases, Ninth Revision code for CRS in one of the five diagnosis variables. Statin use was indicated by the presence of a statin medication in any of the 30 medication variables using the Multum Lexicon Drug Database, with newly prescribed medications excluded. Relevant demographic, socioeconomic, and comorbid factors were included in a multivariate logistic regression model, which accounted for the complex, stratified, multistage survey design of the NAMCS.

Results: There were 390,538 unweighted visit records used in the weighted analysis dataset, corresponding to 9,612,613,668 weighted visits. Statin use was associated with a decreased rate of CRS in both a univariate analysis (odds ratio [OR] = 0.53, P < .001) and the multivariate logistic regression accounting for comorbid, socioeconomic, and demographic factors (OR = 0.79, P = .030).

Conclusions: Statin use is associated with decreased rates of CRS based on a nationally representative sample of outpatient visits in the United States. This supports research that suggests statin medications may have protective properties against CRS, and further research is warranted into their potential therapeutic value for this indication.

Level Of Evidence: NA Laryngoscope, 130:848-851, 2020.
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http://dx.doi.org/10.1002/lary.28085DOI Listing
April 2020

Tumor to Cerebellar Peduncle T2-Weighted Imaging Intensity Ratio Fails to Predict Pituitary Adenoma Consistency.

J Neurol Surg B Skull Base 2019 Jun 24;80(3):252-257. Epub 2018 Aug 24.

Department of Neurological Surgery, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia, United States.

 The consistency of pituitary macroadenomas affects the complexity of surgical resection. On T2-weighted (T2W) imaging, the intensity ratio of the tumor to the cerebellar peduncle (tumor to cerebellar peduncle T2-weighted imaging intensity [TCTI] ratio) correlates with meningioma consistency. We aimed to determine the correlation of this radiographic finding with pituitary macroadenoma consistency and to determine whether it can be used for preoperative planning.  We performed a retrospective evaluation of 196 patients with macroadenomas who underwent endoscopic transsphenoidal resection from January 2012 to June 2017. Macroadenoma consistency was determined by one senior neurosurgeon at the time of surgery. Axial and coronal T2W magnetic resonance imaging images were evaluated retrospectively, and adenoma size, Knosp grade, suprasellar extension and TCTI were calculated.  The mean TCTI ratio was 1.70 (95% confidence interval [CI]: 1.65-1.75). Intraoperatively, 140 (71.4%) adenomas were classified as soft and 48 (24.5%) as fibrous. Gross total resection was achieved in 66.7% of fibrous adenomas and in 86.4% of soft adenomas (  = 0.007). The mean ratio was 1.68 (95% CI: 1.62-1.74) for soft tumors and 1.76 (95%CI: 1.67-1.84) for fibrous tumors. There was no difference in the mean TCTI ratio between groups. Lactotroph and somatotroph adenomas had a lower mean TCTI ratio compared with other functioning and nonfunctioning adenomas with a mean TCTI of 1.52 compared with 1.77.  In this retrospective cohort study, we found that the TCTI ratio does not correlate with tumor consistency. We also noted that the TCTI ratio is increased in prolactin and growth hormone-secreting adenomas.
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http://dx.doi.org/10.1055/s-0038-1668516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534739PMC
June 2019

Re: Management of spontaneous cerebrospinal fluid leaks.

Int Forum Allergy Rhinol 2019 03 18;9(3):332. Epub 2019 Feb 18.

Department of Otolaryngology-Head & Neck Surgery, University of Virginia, Charlottesville, VA.

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http://dx.doi.org/10.1002/alr.22317DOI Listing
March 2019

Association Between Olfactory and Gustatory Dysfunction and Cognition in Older Adults.

Am J Rhinol Allergy 2019 Mar 11;33(2):170-177. Epub 2019 Jan 11.

1 Department of Otolaryngology - Head & Neck Surgery, University of Virginia, Charlottesville, Virginia.

Background: The association between olfactory dysfunction (OD) and cognitive decline is becoming apparent in the emerging literature. However, the literature demonstrating a similar effect between gustatory dysfunction (GD) and cognition is not well established.

Objective: To determine whether OD and GD are independently associated with cognitive impairment.

Methods: The 2013-2014 National Health and Nutrition Examination Survey was queried for 1376 older adults, corresponding to a weighted population sample of 50 816 529, to assess olfactory and gustatory status and cognition using univariate and multivariate regression analyses. OD and GD were determined using objective measurements with validated protocols. Participants were stratified as normal or abnormal cognition status using accepted cutoff values as indicated for the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST).

Results: OD was associated with both mild cognitive impairment (odds ratio [OR] 1.809, P = .004) and dementia (OR 3.173, P < .001) with CERAD testing, abnormal AFT (OR 2.424, P < .001), and abnormal DSST (OR 4.028, P < .001). GD based on 1M NaCl whole mouth taste testing was associated with dementia on CERAD testing (OR 2.217, P = .004). When smell and taste parameters were included together in the regression model, both OD and GD remained significant independent predictors of dementia status based on CERAD testing (OR 3.133, P < .001, OR 1.904, P = .015).

Conclusions: OD and severe GD represent independent predictors of cognitive impairment in a nationally representative sample of older adults.
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http://dx.doi.org/10.1177/1945892418824451DOI Listing
March 2019

Preoperative management of spontaneous cerebrospinal fluid rhinorrhea with acetazolamide.

Int Forum Allergy Rhinol 2019 03 15;9(3):265-269. Epub 2018 Nov 15.

University of Virginia School of Medicine, Charlottesville, VA.

Background: Spontaneous cerebrospinal fluid (CSF) rhinorrhea has been associated with elevated intracranial pressure (ICP). As such, ICP reducing measures are commonly employed to optimize repair. Although postoperative acetazolamide use has been described, no data currently exists on the potential for preoperative use.

Methods: A retrospective review was performed including patients treated for anterior spontaneous CSF leaks by a single surgeon over a 6-year period during which acetazolamide therapy (250 mg twice daily) was employed before considering surgical repair. The primary endpoint was whether the patient went on to require surgical repair.

Results: A total of 16 patients were identified who were pretreated with acetazolamide. Leak sites were noted as cribriform (5/16), sphenoid (8/16), ethmoid (1/16), multiple (1/16), and indeterminate (1/16). Five patients had resolution of their rhinorrhea without surgery (31.3%). Mean follow-up for these nonsurgical patients was 470 days (range, 64 to 857 days). There were no differences in the patients' age or site of leak between surgical and nonsurgical patients (p = 0.65, p = 0.52, respectively). Nonsurgical patients had a lower body mass index (BMI) than surgical patients (p = 0.04).

Conclusion: This is the first study to report the use of acetazolamide therapy as a primary treatment option for spontaneous CSF rhinorrhea. This therapy enabled surgery to be avoided in 31.3% of patients. This would indicate that in the absence of other contraindications for delaying repair, a trial of acetazolamide therapy could be considered as an initial option in the management of isolated spontaneous CSF rhinorrhea.
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http://dx.doi.org/10.1002/alr.22245DOI Listing
March 2019

Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID).

J Clin Immunol 2018 04 17;38(3):225-233. Epub 2018 Feb 17.

Department of Medicine, University of Virginia, Box 801355, Charlottesville, VA, 22908, USA.

Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6-85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.
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http://dx.doi.org/10.1007/s10875-018-0476-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934300PMC
April 2018

Nasopharyngeal angiofibroma in a 32-year-old man.

BMJ Case Rep 2018 Feb 8;2018. Epub 2018 Feb 8.

Department of Otolaryngology - Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.

Nasopharyngeal angiofibroma (NA) is a benign, highly vascularised tumour of the nasopharynx, which typically occurs in young males aged 14-25 years. We report an interesting case of an NA arising de novo in a 32-year-old male. He was referred to our facility for severe nasal haemorrhage after biopsy of a left nasopharyngeal mass. In the operating room, extensive bleeding was noted, and an endoscopic medial maxillectomy was performed, and the left internal maxillary artery was ligated allowing for near total resection of the lesion. The pathological specimen confirmed the diagnosis of NA. To our knowledge, this is one of the oldest patients presenting with a de novo NA, in his fourth decade of life, confirming that this diagnosis must be considered in all those with large nasopharyngeal masses.
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http://dx.doi.org/10.1136/bcr-2017-222763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836611PMC
February 2018

Clinical Consensus Statement: Balloon Dilation of the Sinuses.

Otolaryngol Head Neck Surg 2018 02;158(2):203-214

14 American Academy of Otolaryngology-Head and Neck Surgery Founda-tion, Alexandria, Virginia, USA.

Objective To develop a clinical consensus statement on the use of sinus ostial dilation (SOD) of the paranasal sinuses. Methods An expert panel of otolaryngologists was assembled to represent general otolaryngology and relevant subspecialty societies. The target population is adults 18 years or older with chronic or recurrent rhinosinusitis (with or without nasal polyps, with or without prior sinus surgery) for whom SOD is being recommended, defined as endoscopic use of a balloon device to enlarge or open the outflow tracts of the maxillary, frontal, or sphenoid sinuses, as a standalone procedure or with endoscopic surgery. A modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus. Results After 3 iterative Delphi method surveys, 13 statements met the standardized definition of consensus while 45 statements did not. The clinical statements were grouped into 3 categories for presentation and discussion: (1) patient criteria, (2) perioperative considerations, and (3) outcomes. Strong consensus was obtained for not performing SOD in patients without sinonasal symptoms or positive findings on computed tomography (CT) in patients with symptoms only of headache or sleep apnea without criteria for sinusitis. In addition, strong consensus was met that CT scan of the sinuses was necessary before performing SOD and that surgeons need to understand and abide by regulations set forth by the US Food and Drug Administration if they choose to reuse/reprocess devices. Conclusion Expert panel consensus may provide helpful information for the otolaryngologist considering the use of SOD for the management of patients with a diagnosis of rhinosinusitis. This panel reached consensus on a number of statements that defined the use of SOD as inappropriate in the management of a variety of symptoms or diseases in the absence of underlying sinusitis. When patients meet the definition of chronic sinusitis as confirmed by CT scan, SOD of the sinuses can be indicated and/or effective in certain scenarios. Additional consensus statements regarding proper setting and safeguards for performing the procedure are described.
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http://dx.doi.org/10.1177/0194599817750086DOI Listing
February 2018

Presentation and outcomes in surgically and conservatively managed pediatric Rathke cleft cysts.

J Neurosurg Pediatr 2018 03 22;21(3):308-314. Epub 2017 Dec 22.

Departments of1Neurosurgery and.

OBJECTIVE Rathke cleft cysts (RCCs) are sellar lesions that are commonly encountered in adults but infrequently diagnosed in the pediatric population. As a result, the optimal management of pediatric RCCs remains a subject of controversy. Only 2 prior surgical series have been published on pediatric RCCs and no study has compared the presentation and outcomes of surgically versus conservatively managed cases. The authors therefore performed a comparative analysis of pediatric cases of RCC in which patients were treated with surgery or managed in a conservative manner. METHODS All cases involving pediatric patients diagnosed with an RCC at the University of Virginia between 2000 and 2016 were included in this study. Patient medical records, operative notes, and neuroimaging findings were reviewed. Patients who developed visual field deficits, radiographic evidence of chiasmal compression, or medically refractory headaches were considered candidates for surgical intervention. All patients who were selected for surgery underwent an endoscopic endonasal approach with cyst fenestration. RESULTS A total of 24 pediatric patients were diagnosed with an RCC over a 16-year period. Seven patients ultimately underwent transsphenoidal cyst fenestration, and 17 were managed conservatively. The patients' age at diagnosis, cyst size, and pituitary function at the time of RCC diagnosis were similar in the conservatively and surgically managed cohorts. At diagnosis, 19 of 24 patients endorsed headaches that led to neuroimaging. All patients in the surgical cohort endorsed severe headaches at diagnosis compared with 71% in the conservative group. For the 7 patients treated with surgery, complete cyst evacuation was achieved in 86% of cases. Transient postoperative endocrinopathy occurred in 4 (57%) of 7 surgically treated individuals and resolved in all cases. In the conservative cohort, 1 patient developed a delayed pituitary-related endocrinopathy. Headache resolution occurred in 5 (71%) of the 7 patients who underwent surgery and 7 (58%) of the 12 who were treated without surgery. Cyst recurrence was documented in 1 individual in the surgical cohort who underwent a subtotal cyst fenestration that ultimately required re-intervention. In the conservative cohort, spontaneous cyst shrinkage occurred in 35% of patients with a median time to regression of 23.5 months. CONCLUSIONS Pediatric RCCs are benign sellar lesions that often present with headaches. While cyst fenestration mitigates headaches in most patients, the majority of conservatively managed pediatric patients with RCCs will have spontaneous headache resolution. Furthermore, spontaneous RCC regression occurs in a substantial number of individuals. Thus, in the absence of optic compression, visual field deficit, or diagnostic uncertainty, many pediatric cases of RCC can be managed conservatively.
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http://dx.doi.org/10.3171/2017.9.PEDS17400DOI Listing
March 2018

Lack of Efficacy of Symptoms and Medical History in Distinguishing the Degree of Eosinophilia in Nasal Polyps.

J Allergy Clin Immunol Pract 2017 Nov - Dec;5(6):1582-1588.e3. Epub 2017 May 10.

Department of Medicine, University of Virginia Health Systems, Charlottesville, Va; Department of Microbiology, University of Virginia Health Systems, Charlottesville, Va. Electronic address:

Background: Distinguishing eosinophilic nasal polyps (NP) from noneosinophilic NP will impact prognosis and therapeutic responsiveness.

Objective: To investigate the ability of clinical history and biomarkers to distinguish these conditions.

Methods: A total of 74 consecutive patients undergoing surgery for NP were enrolled. Clinical presentations were evaluated using the 22-item sinonasal outcome test (SNOT-22). Biomarkers included absolute eosinophil count, IgE, and extent of tissue hyperplasia on sinus computed tomography scan. Tissue eosinophilia was quantified in 10 random hpf and data analyzed addressing both peak and average results.

Results: No component of the SNOT-22 was predictive of tissue eosinophilia. Similarly, a medical history of allergic rhinitis, asthma, or aspirin-exacerbated respiratory disease was not predictive. An absolute eosinophil count of more than 300 was associated with NP tissue eosinophilia. In contrast, neither IgE nor extent of sinus computed tomography hyperplasia was predictive.

Conclusions: The ability to individualize therapies for NP is dependent on identifying clinical features or biomarkers of eosinophilia. However, with the exception of circulating eosinophilia, we could not identify a clinical feature or biomarker that robustly predicted the presence of tissue eosinophilia. Even more problematic, even the seeming "criterion standard" determination of tissue pathology was of limited value, as our cohort displayed a continuous spectrum of tissue eosinophil expression, making arbitrary any definitive cutoff distinguishing these conditions.
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http://dx.doi.org/10.1016/j.jaip.2017.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784826PMC
June 2018

Failure of itraconazole to prevent T-helper type 2 cell immune deviation: Implications for chronic rhinosinusitis.

Am J Rhinol Allergy 2016 Nov;30(6):379-384

Department of Pediatrics and Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Background: T-helper (Th) type 2 cell inflammation is the hallmark of several disease processes, including asthma, atopic dermatitis, and some forms of chronic rhinosinusitis. Itraconazole has been used as both an antifungal and an anti-inflammatory agent, with some success in many of these diseases, in part, by altering Th2 cytokine expression by T cells. It is not known whether this merely reflects inhibition of established Th2-like cells or the inhibition of differentiation of naive T cells into Th2-like cells.

Objective: To evaluate the role of itraconazole in the differentiation of naive T cells during activation.

Methods: Naive CD45RA+ T cells were isolated from peripheral blood mononuclear cells from healthy volunteers. Th1 and Th2 type cells were differentiated in the presence of varying concentrations of itraconazole. After stimulation with anti-CD3 and anti-CD28 beads, carboxyfluorescein succinimidyl ester dilution was performed to evaluate proliferation and intracellular cytokine staining for interleukin (IL) 4 and interferon (IFN) gamma within proliferating T cells was measured along with enzyme-linked immunosorbent assay for secreted IL-5, IL-13, and IFN gamma.

Results: Itraconazole had no effect on proliferation of unbiased, Th1, or Th2 cells. Similarly, there was no effect of itraconazole on either intracellular cytokine staining of IL-4 and IFN gamma or secreted cytokine expression of IFN gamma, IL-5, and IL-13 in any of the cell populations.

Conclusion: Itraconazole did not alter the ability of naive T cells to proliferate or secrete cytokines under Th1 or Th2 deviating conditions in vitro. As such, reported inhibition of Th2-like lymphocyte function by itraconazole reflected action on mature effector cells and may have underscored why antifungal treatment failed in many clinical trials of eosinophilic chronic rhinosinusitis.
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http://dx.doi.org/10.2500/ajra.2016.30.4362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108838PMC
November 2016

Eosinophils and Mast Cells in Aspirin-Exacerbated Respiratory Disease.

Immunol Allergy Clin North Am 2016 11 13;36(4):719-734. Epub 2016 Sep 13.

Department of Medicine, Asthma and Allergic Disease Center, Carter Center for Immunology Research, University of Virginia Health System, 409 Lane Rd, Charlottesville, VA 22908, USA; Department of Microbiology, Asthma and Allergic Disease Center, Carter Center for Immunology Research, University of Virginia Health System, 409 Lane Rd, Charlottesville, VA 22908, USA. Electronic address:

Aspirin-exacerbated respiratory disease (AERD) involves overexpression of proinflammatory mediators, including 5-lipoxygenase and leukotriene C synthase (LTCS), resulting in constitutive overproduction of cysteinyl leukotrienes. Mast cells and eosinophils have roles in mediating many of the observed effects. Increased levels of both interleukin-4 (IL-4) and interferon (IFN)-γ are present in the tissue of patients with AERD. Previous studies showed that IL-4 is primarily responsible for the upregulation of LTCS by mast cells. Our studies show that IFN-γ, but not IL-4, drives this process in eosinophils. This article examines the overall role that eosinophils and mast cells contribute to the pathophysiology of AERD.
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http://dx.doi.org/10.1016/j.iac.2016.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116300PMC
November 2016

Eosinophil production of prostaglandin D in patients with aspirin-exacerbated respiratory disease.

J Allergy Clin Immunol 2016 10 14;138(4):1089-1097.e3. Epub 2016 Jun 14.

Asthma and Allergic Disease Center, University of Virginia Health System, Charlottesville, Va; Carter Immunology Center, University of Virginia Health System, Charlottesville, Va; Department of Medicine, University of Virginia Health System, Charlottesville, Va. Electronic address:

Background: Aspirin-exacerbated respiratory disease (AERD) differs from aspirin-tolerant disease in part because of eosinophilic tissue infiltration and overexpression of arachidonic acid metabolic pathway components that lead to enhanced secretion of cysteinyl leukotrienes and prostaglandin (PG) D observed constitutively and paradoxically in response to aspirin and other COX inhibitors. We have previously demonstrated the capacity of IFN-γ to drive cysteinyl leukotriene expression and response.

Objective: We investigated eosinophils as a source of PGD production in patients with AERD.

Methods: Eosinophils were enriched from tissue and peripheral blood obtained from control subjects, patients with aspirin-tolerant disease, and patients with AERD. mRNA was extracted and evaluated for expression of hematopoietic prostaglandin D synthase (hPGDS). Expression of hPGDS protein was confirmed with Western hybridization and immunofluorescence staining. Cells were stimulated with aspirin, and secretion of PGD was quantified. CD34 progenitor cells were isolated and matured into eosinophils in the presence or absence of IFN-γ and hPGDS mRNA, and PGD release was measured.

Results: Gene expression analysis revealed that eosinophils from tissue and blood of patients with AERD display increased levels of hPGDS compared with asthmatic and control samples. Western hybridization confirmed the increase in hPGDS mRNA translated to increased protein expression. Immunofluorescence confirmed mast cells and eosinophils from tissue of patients with AERD and asthma demonstrated hPGDS expression, with higher levels in eosinophils from patients with AERD. Incubation of eosinophils from blood and tissue with aspirin stimulated PGD release. IFN-γ-matured eosinophil progenitors showed enhanced hPGDS expression and increased levels of PGD release at baseline and after aspirin stimulation.

Conclusions: In addition to mast cells, eosinophils represent an important source of PGD in patients with AERD and identify a new target for therapeutic intervention.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056805PMC
http://dx.doi.org/10.1016/j.jaci.2016.04.042DOI Listing
October 2016

Medical therapy versus sinus surgery by using balloon sinus dilation technology: A prospective multicenter study.

Am J Rhinol Allergy 2016 Jul 17;30(4):279-86. Epub 2016 Jun 17.

Department of Otolaryngology-Head & Neck Surgery, University of Virginia, Charlottesville, Virginia, USA.

Background: Although previous studies of sinus surgery that used balloon catheter dilation technology for the paranasal sinuses (balloon sinus dilation [BSD]) demonstrated safety and efficacy, data that compare BSD with continued medical management (MM) are lacking.

Objective: To evaluate the outcomes of sinus surgery when using BSD instruments versus MM for patients with chronic rhinosinusitis for whom MM failed.

Methods: Adult patients with chronic rhinosinusitis for whom a minimum of 3 weeks of oral antibiotics, 4 weeks of daily saline solution therapy, and 4 weeks of daily nasal corticosteroids failed were included. Qualifying participants were allowed to self-select sinus surgery with BSD (either an office or operating room setting) or continued MM. The primary end point was the comparison of change in the Chronic Sinusitis Survey score from baseline to 24 weeks. Secondary end points included comparisons of change for the Rhinosinusitis Disability Index (RSDI) and the Sino-Nasal Outcome Test (SNOT-20).

Results: A total of 198 patients were enrolled (146 surgery and 52 MM). Of the patients who chose BSD, 72% (105/146) had their procedures completed in an office setting. Overall, BSD instruments were successful in dilating 97.6% of targeted sinuses (561/575). Patients who chose BSD showed a significantly greater improvement in the Chronic Sinusitis Survey score versus MM (42.0 versus 27.0, p < 0.001). Results from the RSDI and SNOT-20 surveys showed similar improvements for surgery versus MM (RSDI, 36.0 versus 18.1, p < 0.001; SNOT-20, 1.7 versus 1.0, p < 0.002).

Conclusion: Patients who selected sinus surgery in which BSD instruments were used on the peripheral sinuses demonstrated significantly greater improvements in quality of life compared with those who elected ongoing MM. These results were achieved through office-based procedures with the patient under local anesthesia in the majority of patients.
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http://dx.doi.org/10.2500/ajra.2016.30.4346DOI Listing
July 2016