Activation of platelet-adherent basophils in chronic rhinosinusitis with alcohol hypersensitivity.

BACKGROUND: Alcohol hypersensitivity (AH), an exacerbation of respiratory symptoms in response to alcohol consumption, is common in aspirin-exacerbated respiratory disease and other forms of chronic rhinosinusitis (CRS). We speculated that these reactions relate to the activation of innate immune cells including basophils and, in particular, platelet-adherent basophils by polyphenolic compounds contained within eliciting alcoholic beverages. OBJECTIVE: We investigated the absolute numbers of these cells in patients with AH and the ability of relevant polyphenolic compounds to cause cellular activation. METHODS: Data were collected from 412 consecutive adults presenting to a tertiary care sinonasal clinic in whom the presence of AH was elicited. The CRS phenotype was determined and results from complete blood cell count and differential were analyzed. A subset of patients was invited to donate blood samples that were used to explore the ability of relevant compounds associated with alcohol consumption to activate platelet-nonadherent and platelet-adherent basophils. Activation was quantified by flow cytometry as up-regulated expression of CD63 and as secretion of lipid metabolites. RESULTS: Of the 412 patients enrolled, 69 (16.7%) endorsed having AH. Significantly higher platelet counts were seen in patients reporting AH. Red wine extract and several polyphenolic compounds produced basophil activation and this was primarily observed among platelet-adherent basophils. Platelet activation was further established as the release of thromboxane B2. CONCLUSION: The presence of AH is associated with significantly higher platelet levels and compounds present in alcoholic beverages can directly mediate both their activation and the activation of platelet-adherent basophils.

Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity.

BACKGROUND: Viral infections, especially those caused by rhinovirus, are the most common cause of asthma exacerbations. Previous studies have argued that impaired innate antiviral immunity and, as a consequence, more severe infections contribute to these exacerbations. OBJECTIVE: These studies explored the innate immune response in the upper airway of volunteers with allergic rhinitis and asthma in comparison to healthy controls and interrogated how these differences corresponded to severity of infection. METHODS: Volunteers with allergic rhinitis, those with asthma, and those who are healthy were inoculated with rhinovirus A16 and monitored for clinical symptoms. Tissue and nasal wash samples were evaluated for antiviral signature and viral load. RESULTS: Both subjects with allergic rhinitis and asthma were found to have more severe cold symptoms. Subjects with asthma had worsened asthma control and increased bronchial hyperreactivity in the setting of higher fractional exhaled breath nitric oxide and blood eosinophils. These studies confirmed reduced expression of interferons and virus-specific pattern recognition receptors in both cohorts with atopy. Nevertheless, despite this defect in innate immunity, volunteers with allergic rhinitis/asthma had reduced rhinovirus concentrations in comparison to the controls. CONCLUSION: These results confirm that the presence of an allergic inflammatory disorder of the airway is associated with reduced innate immune responsive to rhinovirus infection. Despite this, these volunteers with allergy have reduced viral loads, arguing for the presence of a compensatory mechanism to clear the infection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02910401.

Nasal IgE production in allergic rhinitis: Impact of rhinovirus infection.

BACKGROUND: Rhinovirus (RV) infections exacerbate asthma in part by enhancing an allergic state, and these exacerbations can be mitigated via administration of anti-IgE. OBJECTIVE: We investigated the presence of local IgE production in the nose of allergic and non-allergic subjects and assessed whether this was enhanced by RV. METHODS: Local production of specific IgE was determined by comparing ratios of specific to total IgE concentrations between nasal and serum samples. Our initial studies were performed in subjects presenting to the emergency department for allergic and non-allergic respiratory complaints. Subsequently, we investigated influences of experimental RV infection on nasal sIgE production in an allergic cohort. RESULTS: We found evidence of local sIgE production to Dermatophagoides pteronyssinus in 30.3% and to Blomia tropicalis in 14.6% of allergic subjects. None of the non-allergic subjects demonstrated local IgE. Subjects with active RV infection were more than twice as likely to have local sIgE (45% vs 14%), and subjects with local sIgE being produced were ~3 times more likely to be having an asthma exacerbation. Experimental RV infection was able to induce local sIgE production. CONCLUSION: These studies confirm local IgE production in a large subset of allergic subjects and demonstrate that allergic asthmatics with local IgE are more likely to develop an asthma exacerbation when infected with RV. Our RV challenge studies demonstrate that at least some allergic asthmatics can be induced to secrete locally generated IgE in their nasal airway after RV infection.

Suppression of aspirin-mediated eosinophil activation by prostaglandin E2: Relevance to aspirin and nonsteroidal anti-inflammatory drug hypersensitivity.

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 E2 (PGE2) 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 PGE2 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 PGE2 in altering activation was determined by incubating eosinophils with increasing doses of PGE2 before lysine aspirin stimulation. Specific PGE2 receptor use was determined by incubating eosinophils with receptor agonists and antagonists before aspirin stimulation. Cysteinyl leukotrienes (CysLTs), leukotriene B4 (LTB4), 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 LTB4 in the absence of EDN release. Low doses of PGE2 inhibited LTB4 and CysLT release, an effect lost at higher PGE2 concentrations. Use of butaprost, an EP2 receptor agonist, suppressed lysine aspirin stimulation. This mechanism was supported by blocking activity of the EP1 and EP3 receptors. CONCLUSION: Eosinophils can be directly activated by NSAIDs via cyclooxygenase-independent pathways to produce CysLTs and LTB4. This effect can be inhibited by PGE2 acting through the EP2 receptor. The recognized loss of EP2 receptor expression combined with low PGE2 levels explains in part the sensitivity to NSAIDs.

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

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.

Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease.

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) D2 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 PGD2 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 PGD2 was quantified. CD34+ progenitor cells were isolated and matured into eosinophils in the presence or absence of IFN-γ and hPGDS mRNA, and PGD2 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 PGD2 release. IFN-γ-matured eosinophil progenitors showed enhanced hPGDS expression and increased levels of PGD2 release at baseline and after aspirin stimulation. CONCLUSIONS: In addition to mast cells, eosinophils represent an important source of PGD2 in patients with AERD and identify a new target for therapeutic intervention.

Aspirin activation of eosinophils and mast cells: implications in the pathogenesis of aspirin-exacerbated respiratory disease.

Reactions to aspirin and nonsteroidal anti-inflammatory drugs in patients with aspirin-exacerbated respiratory disease (AERD) are triggered when constraints upon activated eosinophils, normally supplied by PGE2, are removed secondary to cyclooxygenase-1 inhibition. However, the mechanism driving the concomitant cellular activation is unknown. We investigated the capacity of aspirin itself to provide this activation signal. Eosinophils were enriched from peripheral blood samples and activated with lysine ASA (LysASA). Parallel samples were stimulated with related nonsteroidal anti-inflammatory drugs. Activation was evaluated as Ca2+ flux, secretion of cysteinyl leukotrienes (CysLT), and eosinophil-derived neurotoxin (EDN) release. CD34+ progenitor-derived mast cells were also used to test the influence of aspirin on human mast cells with measurements of Ca2+ flux and PGD2 release. LysASA induced Ca2+ fluxes and EDN release, but not CysLT secretion from circulating eosinophils. There was no difference in the sensitivity or extent of activation between AERD and control subjects, and sodium salicylate was without effect. Like eosinophils, aspirin was able to activate human mast cells directly through Ca2+ flux and PGD2 release. AERD is associated with eosinophils maturing locally in a high IFN-γ milieu. As such, in additional studies, eosinophil progenitors were differentiated in the presence of IFN-γ prior to activation with aspirin. Eosinophils matured in the presence of IFN-γ displayed robust secretion of both EDN and CysLTs. These studies identify aspirin as the trigger of eosinophil and mast cell activation in AERD, acting in synergy with its ability to release cells from the anti-inflammatory constraints of PGE2.

Prominent role of IFN-γ in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is distinguished from aspirin-tolerant asthma/chronic sinusitis in large part by an exuberant infiltration of eosinophils that are characterized by their overexpression of metabolic pathways that drive the constitutive and aspirin-induced secretion of cysteinyl leukotrienes (CysLTs). OBJECTIVE: We defined the inflammatory milieu that in part drives CysLT overproduction and, in particular, the role of IFN-γ in the differentiation of eosinophils. METHODS: Quantitative real-time PCR was performed for TH1 and TH2 signature cytokines on tissue from control subjects, patients with chronic hyperplastic eosinophilic sinusitis, and patients with AERD, and their cellular source was determined. The influence of IFN-γ on maturation, differentiation, and functionality of eosinophils derived from hematopoietic stem cells was determined. RESULTS: Gene expression analysis revealed that tissue from both aspirin-tolerant subjects and patients with AERD display a TH2 cytokine signature; however, AERD was distinguished from chronic hyperplastic eosinophilic sinusitis by the prominent expression of IFN-γ. Intracellular and immunohistochemical cytokine staining revealed that the major sources of these cytokines were the eosinophils themselves. IFN-γ promoted the maturation of eosinophil progenitors, as measured by increased mRNA and surface expression of CCR3 and sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8). Additionally, IFN-γ increased the expression of genes involved in leukotriene synthesis that led to increased secretion of CysLTs. IFN-γ-matured eosinophil progenitors were also primed, as demonstrated by their enhanced degranulation. CONCLUSIONS: High IFN-γ levels distinguish AERD from aspirin-tolerant asthma and underlie the robust constitutive and aspirin-induced secretion of CysLTs that characterize this disorder.

Sino-nasal outcome test (SNOT-22): a predictor of postsurgical improvement in patients with chronic sinusitis.

BACKGROUND: A number of factors are critical when considering the expected benefit of surgical intervention in patients with chronic rhinosinusitis (CRS) who have failed medical therapy. OBJECTIVE: To evaluate the Sino-nasal Outcome Test (SNOT-22) and other patient demographic characteristics as predictors of postsurgical improvement in patients with CRS. METHODS: Consecutive adult subjects presenting to the Otolaryngology Clinics at the University of Virginia with refractory CRS that required surgery were included. Patients were excluded if they had not completed both preoperative and postoperative SNOT-22 evaluations. Demographic and baseline measures, including asthma and smoking status, total immunuglobulin E (IgE), absolute eosinophil counts, and Lund-Mackay computed tomography (CT) scoring were also obtained for each subject. Regression analyses were performed. RESULTS: One hundred four subjects met criteria and were included. These subjects showed a 51% overall improvement in postsurgical SNOT-22 evaluations (95% confidence interval [CI]: [45, 57%], P < .001). Multivariate regression analysis revealed that SNOT-22 items related to "runny nose," "cough," and "sadness" were independent predictors of postsurgical SNOT-22 improvement (P < .05, for all). Although "runny nose" had a direct correlation with improvement, more severe "sadness" and "cough" scores had a negative impact on degree of improvement. Similarly, analyses indicated that questions categorized as pertaining to nasal or ear symptoms were uniquely associated with postsurgical improvement in SNOT-22 scores (P < .001 and P = .015, respectively). Neither Lund-Mackay CT scoring, total IgE, nor absolute eosinophil counts correlated with improvement in postsurgical SNOT-22 scores. CONCLUSION: Physicians can use components of the SNOT-22 to predict likelihood of symptom improvement after surgical intervention in subjects with CRS.

Balloon Sinus Dilation Versus Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis: Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the efficacy of balloon sinus dilation (BSD) compared to functional endoscopic sinus surgery (FESS) or medical management for chronic rhinosinusitis (CRS). METHODS: A qualified medical librarian conducted a literature search for relevant publications that evaluate efficacy of BSD. Studies were assessed independently by 2 reviewers for inclusion in the systematic review and meta-analysis. RESULTS: From 315 abstracts reviewed, 18 studies were included in qualitative review, and 7 were included in meta-analysis. Quantitative analysis included 4 randomized clinical trials (RCTs) and 3 cohort studies comparing baseline and post-operative Sinonasal Outcome Test (SNOT)-20 scores in BSD and FESS. A meta-analysis restricted to the studies reporting SD for changes from baseline (2 RCTs, 1 cohort) showed the pooled difference in means to be 0.435, less than a clinically meaningful difference of 0.8. A separate sensitivity analysis of the studies including 4 additional studies with imputed values of SD for changes from baseline showed the pooled difference of means to be 0.237 assuming the highest level of correlation (Corr .8) between the pre- and post-intervention scores. CONCLUSIONS: There is limited high-quality evidence that assesses the efficacy of BSD versus FESS in the management of CRS patients. To better inform CRS management, future studies should compare BSD with endoscopic sinus surgery, hybrid procedures, and/or medical management alone using validated objective and patient-reported outcome measures.

Evaluation and workup of immunodeficiencies in recurrent acute rhinosinusitis: A scoping review.

BACKGROUND: Primary immunodeficiency disorders (PIDDs) may be a risk factor for development of recurrent acute rhinosinusitis (RARS). There are currently no clear guidelines for the timing and methodology of PIDD testing in patients with RARS. The aim of this scoping review is to identify and analyze existing literature on this topic. METHODS: A scoping review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Articles addressing recurrent acute sinusitis and immunodeficiencies were collected from PubMed, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and systematically evaluated for eligibility by two reviewers. RESULTS: Of the 209 unique articles identified, 11 met criteria for review and analysis. Articles consisted of historical cohort, case-control, and cross-sectional studies, in addition to case series and nonsystematic reviews. The majority (10) recommended immunodeficiency testing, consisting of general immunologic screening (3), quantitative immunoglobulins (6), and postvaccination antibody titers (5). There was an emphasis on immunoglobulin G (IgG) subclass testing (6). Of the eight articles providing timing recommendations, the majority recommended testing after recurrent infections or diagnosis (6); however, criteria for diagnosis of RARS and populations targeted by recommendations varied greatly by article. CONCLUSION: Current literature on RARS emphasizes immunoglobulin quantification and postvaccination antibody titers to evaluate for PIDD after diagnosis, but recommendations are limited by wide-ranging populations of interest and inconsistent definitions. This scoping review identified a lack of evidence-based articles specific to diagnostic workup for PIDD in patients with RARS, and additional research with standardized definitions and focus on RARS is necessary to guide clinical practice.

The association of gustatory dysfunction, olfactory dysfunction, and cognition in older adults.

BACKGROUND: The association of gustatory dysfunction (GD) with quality of life (QOL) and cognition in older adults is understudied. Our objective was to study the prevalence of GD in the community and explore impacts and associated factors. METHODS: A prospective, multi-institutional, pre-corona virus disease (COVID) cohort of adults aged 50 years and older had smell and taste testing using "Sniffin' Sticks" (TDI) and "Taste Strips." The impact of GD on mood, QOL, and social interaction was assessed through visual analog scales. Subjects completed the Questionnaire of Olfactory Disorders, Patient Health Questionnaire 9, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and the DeJong scale of loneliness. RESULTS: A total of 48 patients, average age of 54.7 years, were enrolled. Thirty-two percent experienced GD on taste strips, and 62% experienced olfactory dysfunction (OD) on TDI. Almost 30% (29.5%) had both GD and OD. GD and OD correlated with worsened cognitive function on MMSE (r = 0.392 and 0.05, p = 0.018 and 0.003). Subjects with both GD and OD had worse MMSE than either alone (p = 0.003). Dry mouth and difficult chewing correlated with GD (r = -0.37 and -0.31, p = 0.10 and 0.37). Self-reported GD and OD were correlated (r = 0.46, p = 0.001), as were psychophysical GD and OD (r = 0.394, p = 0.008). GD did not correlate with other metrics. CONCLUSION: Thirty-two percent of subjects experienced GD on psychophysical testing, yet most are unaware without impacts on daily life. However, GD correlates with worsened cognitive function. Taste testing may play a role in screening of neurocognitive decline, and multisensory dysfunction may indicate of worsened cognitive states.

Etiology of nasal polyps in cystic fibrosis: not a unimodal disease.

OBJECTIVES: The objective was to determine whether the polyp subtypes observed in cystic fibrosis (CF)-related sinusitis were similar to those observed in non-CF-related sinusitis. METHODS: Polyp and mucus samples were collected from CF patients who presented for sinus surgery. The polyps underwent histologic and cytochemical evaluation for the presence of lymphocyte cell populations and their respective cytokine markers. The mucus samples were evaluated for DNA content. RESULTS: Of the polyps, 42% had an eosinophilic infiltrate, of which 80% had an additional mixed neutrophilic infiltrate. Of the remaining polyp samples, 42% did not have a granulocytic infiltrate, consistent with non-eosinophilic polyps. All samples had CD138-positive plasma cells. The mucus samples from the patients with CF showed higher extracellular DNA concentrations than did the mucus samples from patients with non-CF sinus disease. CONCLUSIONS: Cystic fibrosis-related polyps demonstrated an eosinophil-based dichotomy similar to that of idiopathic non-CF-related polyps. Many also demonstrated neutrophilic infiltrate, indicating that chronic mucus stasis and infection complicate the disease. Agents capable of reducing extracellular DNA may help manage sinusitis in CF patients.

Genetics and phenotyping in chronic sinusitis.

Chronic sinusitis with nasal polyposis historically has been treated as a single monolithic clinical disorder. Just as asthma is now accepted as numerous heterogeneous diseases, chronic sinusitis should also be viewed as comprising several diseases with varying causes, with each one characterized by distinct histologic and gene and protein expression patterns. This includes recognition of the need to define these diseases based on the presence or absence of an eosinophilic infiltrate but also on additional distinctions based on unique agents that drive their development and perpetuation. As a collection of heterogeneous diseases, proper differential diagnosis is required to delineate appropriate therapeutic intervention. This review will focus on recognized distinct presentations of chronic sinus disease, including distinguishing the clinical presentations, cellular and molecular characteristics, genetic differences, and current treatment options for each.

Giant pituitary macroadenoma of stem cell origin: illustrative case.

BACKGROUND: Giant pituitary macroadenomas with a diameter >4 cm are rare tumors, accounting for only about 5% of pituitary adenomas. They are more difficult to maximally resect safely owing to limited access as well as encasement of adjacent structures. Acidophil stem cell adenomas are rare immature neoplasms proposed to derive from common progenitor cells of somatotroph and lactotroph cells. These adenomas comprise about 4.3% of surgically removed pituitary adenomas. No previous reports have described acidophil stem cell adenomas that grow to the size of giant macroadenomas. This rare entity poses special challenges given the need for maximal safe resection in an immature neoplasm. OBSERVATIONS: The authors report a 21-year-old female who presented with 3 years of progressive visual decline and a giant macroadenoma. She underwent endoscopic transsphenoidal surgery for decompression. Given the tumor size and involvement of adjacent critical structures, gross-total resection was not achieved. The authors review the literature on giant pituitary adenomas and provide a discussion on clinical management for this rare entity. LESSONS: The authors present a very rare case of a giant pituitary adenoma of acidophil stem cell origin and discuss the technical and management challenges in this rare entity.

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

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.

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

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.

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

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.

Early outcomes of endoscopic transsphenoidal surgery for adult craniopharyngiomas.

OBJECT: Although the transsphenoidal approach for subdiaphragmatic craniopharyngiomas has been performed for many years, there are few reports describing the role of the endoscopic transsphenoidal technique for suprasellar craniopharyngiomas. The purpose of this study was to report the outcomes of the endoscopic transsphenoidal approach for adults with craniopharyngiomas in whom the goal was gross-total resection. METHODS: Twelve patients were identified who were older than 18 years at the time of their pure endoscopic transsphenoidal surgery. Their medical records and imaging studies were retrospectively reviewed. RESULTS: Gross-total resection was achieved in 42% of cases when assessed by intraoperative impression alone and in 75% when assessed by the first postoperative MR imaging study. However, 83% of patients achieved at least a 95% resection when assessed by both intraoperative impression and the first postoperative MR imaging study. Permanent diabetes insipidus occurred postoperatively in 44% of patients. Six (67%) of 9 patients who had a functioning hypothalamic-pituitary axis preoperatively developed panhypopituitarism after surgery. Visual improvement or normalization occurred in 78% of patients with preoperative visual deficits. Although no patient experienced a postoperative CSF leak, 1 patient was treated for meningitis. CONCLUSIONS: The authors have achieved a high rate of radical resection and symptomatic improvement with the endoscopic transsphenoidal technique for both subdiaphragmatic (sellar/suprasellar) and supradiaphragmatic (suprasellar) craniopharyngiomas. However, this is also associated with a high incidence of new endocrinopathy. Endoscopic assessment of tumor resection may be more sensitive for residual tumor than the first postoperative MR imaging study.

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

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 t 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 (P = .001) and left (P = .001) sides. A statistically significant and clinically meaningful decrease in total SNOT-22 scores (12.7 points, P = .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).