An eosinophil peroxidase activity assay predicts acute exacerbations in post-operative chronic rhinosinusitis.

KEY POINTS: EPX activity has been correlated with eCRS diagnosis and baseline disease severity. Herein, EPX activity is shown to correlate with post-operative antibiotic and steroid use in CRS. EPX activity has potential to act as a prognostic biomarker of CRS disease severity and control.

An eosinophil peroxidase activity assay accurately predicts eosinophilic chronic rhinosinusitis.

BACKGROUND: A definitive diagnosis of eosinophilic chronic rhinosinusitis (eCRS) requires invasive surgical tissue sampling and histologic enumeration of intact eosinophils. Eosinophil peroxidase (EPX) is an accurate biomarker of sinonasal tissue eosinophilia in CRS regardless of polyp status. A less invasive and rapid method that accurately identifies tissue eosinophilia would be of great benefit to patients. OBJECTIVE: We sought to evaluate a new clinical tool that uses a nasal swab and colorimetric EPX activity assay to predict a diagnosis of eCRS. METHODS: A prospective, observational cohort study was conducted using nasal swabs and sinonasal tissue biopsies obtained from patients with CRS electing endoscopic sinus surgery. Patients were classified as non-eCRS (n = 19) and eCRS (n = 35) on the basis of pathologically determined eosinophil counts of less than 10 or greater than or equal to 10 eosinophils/HPF, respectively. Swab-deposited EPX activity was measured and compared with tissue eosinophil counts, EPX levels, and CRS-specific disease metrics. RESULTS: EPX activity was significantly increased in patients with eCRS than in patients without eCRS (P < .0001). With a relative absorbance unit cutoff value of greater than or equal to 0.80, the assay demonstrated high sensitivity (85.7%) and moderate specificity (79.0%) for confirming eCRS. Spearman correlations between EPX activity and tissue eosinophil counts (rs = 0.424), EPX levels (rs = 0.503), and Lund-Kennedy endoscopy scores (rs = 0.440) in eCRS were significant (P < .05). CONCLUSIONS: This investigation evaluates a nasal swab sampling method and EPX activity assay that accurately confirms eCRS. This method could potentially address the unmet need to identify sinonasal tissue eosinophilia at the point-of-care, as well as to longitudinally monitor eosinophil activity and treatment response.

Pharmacokinetics of intranasal amiloride in healthy volunteers.

Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single-center, open-label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non-nasal pathways. Intranasal amiloride exhibited a dose-proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.

Evaluating Distance Bias in Chronic Rhinosinusitis Outcomes.

Importance: The distance traveled by patients for medical care is associated with patient outcomes (ie, distance bias) and is a limitation in outcomes research. However, to date, distance bias has not been examined in rhinologic studies. Objective: To evaluate the association of distance traveled by a cohort of patients with chronic rhinosinusitis with baseline disease severity and treatment outcomes. Design, Setting, and Participants: A total of 505 patients with chronic rhinosinusitis were prospectively enrolled in a multi-institutional, cross-sectional study in academic tertiary care centers between April 2011 and January 2020. Participants self-selected continued appropriate medical therapy or endoscopic sinus surgery. The 22-item Sinonasal Outcome Test (SNOT-22) and Medical Outcomes Study Short Form 6-D (SF-6D) health utility value scores were recorded at enrollment and follow-up. Data on the distances traveled by patients to the medical centers, based on residence zip codes, and medical comorbid conditions were collected. Exposures: Distance traveled by patient to obtain rhinologic care. Main Outcomes and Measures: SNOT-22 and SF-6D scores. Scores for SNOT-22 range from 0 to 110; and for SF-6D, from 0.0 to 1.0. Higher SNOT-22 total scores indicate worse overall symptom severity. Higher SF-6D scores indicate better overall health utility; 1.0 represents perfect health and 0.0 represents death. Results: The median age for the 505 participants was 56.0 years (IQR, 41.0-64.0 years), 261 were men (51.7%), 457 were White (90.5%), and 13 were Hispanic or Latino (2.6%). These categories were collected according to criteria described and required by the National Institutes of Health and therefore do not equal the entire cohort. Patients traveled a median distance of 31.6 miles (50.6 km) (IQR, 12.2-114.5 miles [19.5-183.2 km]). Baseline (r = 0.00; 95% CI, 0.00-0.18) and posttreatment (r = 0.01; 95% CI, -0.07 to 0.10) SNOT-22 scores, as well as baseline (r = -0.12; 95% CI, -0.21 to -0.04) and posttreatment (r = 0.07; 95% CI, -0.02 to 0.16) SF-6D scores, were not associated with distance. There was no clinically meaningful correlation between distance traveled and mean comorbidity burden. Nevertheless, patients with a history of endoscopic sinus surgery were more likely to travel longer distances to obtain care (Cliff delta = 0.28; 95% CI, 0.19-0.38). Conclusions and Relevance: Although this cross-sectional study found that some patients appear more willing to travel longer distances for chronic rhinosinusitis care, results suggest that distance traveled to academic tertiary care centers was not associated with disease severity, outcomes, or comorbidity burden. These findings argue for greater generalizability of study results across various cohorts independent of distance traveled to obtain rhinologic care. Trial Registration: ClinicalTrials.gov Identifier: NCT02720653.

Comorbidities Known to Affect Physical Function Negatively Impact Baseline Health-Related Quality-of-Life in Patients With Chronic Rhinosinusitis.

BACKGROUND: Medical comorbidities are commonly encountered in chronic rhinosinusitis (CRS) and may impact both physical function and patient reported health-related quality-of-life (HRQOL). The functional comorbidity index (FCI) is designed to elucidate the role of comorbidities on functional prognosis. The objective of this study was to understand the impact of comorbidities known to impact physical function on baseline HRQOL using the FCI.Methodology: Patients meeting diagnostic criteria for CRS were prospectively enrolled in a cross-sectional study. Responses from the Sinonasal Outcomes Test-22 (SNOT-22), a measure of patient HRQOL, as well as the Lund-Kennedy and Lund-Mackay scores were recorded at enrollment. FCI was calculated retrospectively using the electronic medical record. Information was collected and compared for patients without (CRSsNP) and with nasal polyps (CRSwNP) using chi-square and t-tests. Spearman's correlations, followed by multivariate regression analysis, were used to assess the association between FCI and SNOT-22 scores. RESULTS: One hundred and three patients met inclusion criteria for analysis. There were no significant differences in age, gender, and SNOT-22 scores between patients with CRSsNP and those with CRSwNP. FCI was significantly and independently associated with worse SNOT-22 scores (P = .012). FCI did not correlate with endoscopy and computed tomography scores. The mean FCI for patients with CRSsNP and CRSwNP was 2.02 and 2.24, respectively, and did not differ significantly between the two cohorts (P = .565). CONCLUSIONS: Major medical comorbidities known to affect physical function are associated with worse SNOT-22 scores in patients with CRS as measured by the FCI.

Cell Adhesion Molecules are Upregulated and May Drive Inflammation in Chronic Rhinosinusitis with Nasal Polyposis.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly characterized by eosinophil- and T helper 2 cell (Th2)-biased inflammation. Integrins and intercellular adhesion molecules (ICAMs) are superfamilies of cell adhesion molecules (CAMs) that facilitate the recruitment and trafficking of immune cells and have been implicated in coordinating eosinophil and Th2 cell adhesion and signaling in asthma. The roles of CAMs in CRSwNP, however, remain poorly understood. The purpose of this study was to characterize the systemic and local expression of CAMs and identify which CAMs are potentially involved in CRSwNP pathology. MATERIALS AND METHODS: A prospective observational study was conducted using peripheral blood and anterior ethmoid tissues of patients with CRSwNP (n=32) and controls (n=15). Multiplex gene analysis and Pearson correlations were performed to identify associations between systemically and locally expressed CAMs. Based on the gene expression results, immunohistochemical evaluation and quantification of cells expressing integrins ITGAM, ITGAX, and ITGB2, as well as ICAM-3 in sinonasal tissues were conducted to compare local protein expression patterns. RESULTS: Integrin and ICAM genes were significantly elevated in the blood (p<0.001 to p<0.05) and sinuses (p<0.0003 to p<0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood (p<0.01 to p<0.05) and sinuses (p<0.01) were observed between ITGAM, ITGAX, ITGB2, and ICAM3. ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls (p<0.0001 to p<0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed (p<0.02). CONCLUSION: The systemic and local expression of ITGAM, ITGB2, and ICAM-3 is significantly upregulated in CRSwNP, suggesting that integrin complex ITGAM/ITGB2 and ICAM-3 serve a potential role in inflammation-mediated signaling in CRSwNP.

Sleep Dysfunction is an Independent Predictor of Productivity Losses in Patients with Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is known to have a significant impact on economic productivity. Sleep dysfunction is associated with staggering productivity losses and is highly prevalent in patients with CRS. The effect of sleep dysfunction on productivity in CRS has not been elucidated. The objective of this study was to determine the relationship between sleep dysfunction and lost productivity in patients with CRS. METHODS: Eighty-two adult patients with CRS were prospectively enrolled into a cross-sectional cohort study. Patients with obstructive sleep apnea were excluded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Presenteeism (reduced work efficiency), absenteeism (missed work days), and lost work, household, and overall productivity were analyzed. The primary aim was assessing the correlation between PSQI and productivity. Regression analyses were performed to account for disease severity, pain, and depression. RESULTS: Sleep dysfunction is significantly correlated with overall lost productivity (R2 = 0.397, P < .05). Presenteeism is the most strongly affected by sleep dysfunction (R2 = -0.441, P < .001). Higher PSQI scores were significantly associated with productivity losses, whereas lower scores were not. Sleep remained an independent predictor of productivity when regression analysis accounted for disease severity, depression, and pain. CONCLUSION: Sleep dysfunction has a significant association with lost productivity in patients with CRS, particularly with worsening PSQI scores. More clearly defining those components of CRS that most impact a patient's daily function will allow clinicians to more optimally manage and counsel patients with CRS.

Inflammation-driven vascular dysregulation in chronic rhinosinusitis.

BACKGROUND: Altered neovascularity is typically observed in chronic inflammatory diseases with overlapping pathophysiology to that observed in chronic rhinosinusitis (CRS). However, characterization of these inflammatory-induced vascular-mediated changes in CRS is limited. Understanding the underlying vascular changes in CRS will allow for strategic design and development of new drug-delivery technologies that exploit vascular permeability for increased extravasation into the target sinonasal tissues. METHODS: Patients with CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and non-CRS controls were enrolled in this prospective, observational study. The extent of angiogenesis in tissue was characterized using immunohistochemical and multiplex gene expression analyses. Vascular permeability, interendothelial junction structures, and endothelial barrier morphology were evaluated using transmission electron microscopy. RESULTS: Sinonasal vascularity was increased significantly in CRSsNP and CRSwNP (p < 0.05) when compared with controls, as assessed by enumerating the platelet endothelial cell adhesion molecule (PECAM-1)-positive blood vessels. Pro-angiogenic gene expression, including PECAM1 and platelet-activating factor receptor, was elevated significantly in patients with CRSwNP when compared with controls (p < 0.05). The fenestration sizes between endothelial cells (17-280 nm) were larger in CRSwNP compared with CRSsNP (10-33 nm) patients and controls (4-12 nm). Global thinning of the endothelial cell lining was observed in CRS patients but not in controls. CONCLUSION: Significant increases in vascularity, the pro-angiogenic gene, and protein expression and blood vessel morphogenesis were observed in CRS patients compared with controls. In addition, fenestration sizes between interendothelial junction structures were larger in CRS patients than in controls, suggesting inflammation-driven vascular dysregulation in CRS pathology.

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

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 (P = .027) and explained 42% of the variance in answers, but only age and gender approached statistical significance (P = .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.

Correlation between systemic inflammatory response and quality of life in patients with chronic rhinosinusitis.

BACKGROUND: Local sinonasal inflammation resulting from altered T-cell immune signaling is a contributor to the pathogenesis of chronic rhinosinusitis (CRS). CRS patients experience negative impacts on quality of life (QOL) and suffer from comorbidities linked to systemic inflammation. However, systemic inflammatory profiling to evaluate the association between systemic inflammation and QOL in CRS has not been performed. Our objectives were to compare local and systemic inflammatory gene expression in patients with CRS to determine if systemic markers of inflammation associate with disease severity and disease-specific QOL. METHODS: A prospective observational study was conducted comparing 16 patients with CRS to 10 controls. Inflammatory gene expression in the anterior ethmoid tissues and peripheral blood of patients was measured using multiplex gene expression analysis and correlated to disease severity (computed tomography and nasal endoscopy) and disease-specific QOL (22-item Sino-Nasal Outcome Test [SNOT-22] and Rhinosinusitis Disability Index) using linear regression analyses. RESULTS: Patients with CRS showed significant increases in the expression of ctla4 and jak1 in sinonasal tissue and blood (p < 0.05), whereas the gene expression of hla-dqa1, hla-dqb1, and dusp4 was significantly decreased in patients with CRS compared to controls (p < 0.05). Soluble and local ctla4 and jak1 showed a significant positive correlation with clinical markers of disease severity and disease-specific QOL (p < 0.05). CONCLUSION: Local and systemic gene expression involved in T-cell immune signaling was found to be significantly altered in the blood and sinonasal tissues of patients with CRS compared to controls and significantly correlated to disease severity and QOL in patients with CRS.

The effects of nasal closure on quality of life in patients with hereditary hemorrhagic telangiectasia.

INTRODUCTION: Epistaxis is the most common symptom of hereditary hemorrhagic telangiectasia (HHT). Complete nasal closure is one of the treatment options for patients with severe, intractable epistaxis. In our experience, this surgery can be life changing in a positive sense; but many patients as well as their physicians understandably fear that such a procedure will diminish certain aspects of quality of life (QOL). METHODS: Case-control study of HHT patients treated at the University of Utah HHT Center of Excellence with and without nasal closure from January 2005 to January 2016. Patients were matched according to epistaxis severity. Each included patient was issued three surveys: Epistaxis Severity Score (ESS), the Pittsburg Sleep Quality Index (PSQI), and the Nasal Obstruction Symptom Evaluation (NOSE). RESULTS: After treatment, the mean PSQI and NOSE scores were not significantly different between the two groups. However, the mean ESS score in the nasal closure group was significantly lower at 1.10 compared to the severe epistaxis group with a mean score of 3.99 (P = .027). CONCLUSION: The results of this study demonstrate that nasal closure significantly improves epistaxis severity without having a significant effect on sleep or nasal obstruction as they relate to QOL. These findings suggest that nasal closure should be considered for HHT patients with chronic severe epistaxis. LEVEL OF EVIDENCE: 4.

Calgranulin C (S100A12) Is Differentially Expressed in Subtypes of Chronic Rhinosinusitis.

Background Calgranulin C (S100A12) is an innate immune peptide at the air-mucosal interface associated with neutrophil involvement, which when overexpressed has been implicated as a biomarker of inflammatory diseases. Decreased epithelial expression of certain innate immune peptides has been reported in chronic rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in the sinonasal mucosa of patients with CRS compared to controls and that S100A12 is a potential biomarker of CRS-specific quality of life (QOL) and disease severity. Methods A prospective observational study was conducted which included 70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP) nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was assessed in the anterior ethmoid tissues from all patients using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease-specific QOL (Rhinosinusitis Disability Index) and disease severity (computed tomography [CT] and endoscopy) were evaluated and correlated to the expression levels of S100A12. Results S100A12 and HNE were significantly elevated in patients with CRSsNP compared to normal controls ( P < .05 and P < .001, respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS-specific disease severity compared to normal controls ( P < .05), and the increased protein levels of S100A12 were significantly correlated to disease severity, represented by CT scores ( P < .05). Conclusions S100A12 is differentially expressed in CRS subtypes and is significantly elevated in patients with CRSsNP and associated with CRS-specific disease severity.

The price of pain in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with productivity losses exceeding US$13 billion annually. Although pain is well known to significantly affect patient productivity in other diseases, its economic impact on CRS-related lost productivity has not been examined. The objective of this study was to determine whether CRS-related facial pain correlates with lost productivity in patients with CRS. METHODS: Seventy patients with CRS were enrolled in a cross-sectional investigation. Patients with a history of systemic inflammatory disease, ciliary dysfunction, chronic pain syndromes, migraines, and fibromyalgia were excluded. Pain was measured using the Brief Pain Inventory Short Form (BPI-SF) and the Short-Form McGill Pain Questionnaire (SF-MPQ). Presenteeism, absenteeism and lost work, and household and overall productivity were assessed. Regression analysis was performed to assess potential confounders, including depression. RESULTS: Pain as measured with BPI-SF and SF-MPQ total scores correlated with all domains of productivity losses. Overall, lost productivity was significantly correlated with pain (R range, 0.354-0.485; p < 0.001). Presenteeism (reduced work efficiency) had the highest correlation with all of the overall pain scores (R range, -0.366 to -0.515; p < 0.001). Lost household productivity time was the least affected by pain (R range, 0.267-0.389; p < 0.05). These correlations remained statistically significant after regression analysis, which accounted for depression (p < 0.05). CONCLUSION: A significant correlation exists between CRS-related facial pain and productivity losses in patients with CRS that is independent of depression. Facial pain has the strongest correlation with presenteeism, which is the main driver of productivity losses and indirect costs associated with CRS.

Time, Resident Involvement, and Supply Drive Cost Variability in Septoplasty with Turbinate Reduction.

Objective To determine factors that influence cost variability in septoplasty with inferior turbinate reduction. Study Design Case series with chart review. Setting Tertiary care hospital and affiliated ambulatory surgical center. Subjects and Methods Surgical costs were reviewed for adult patients undergoing septoplasty with inferior turbinate reduction between December 2014 and September 2017. Cases where additional procedures were performed were excluded. Operative supply costs, operative time, room time, and resident involvement were determined. Contribution of these factors to total costs and variability were analyzed. Results The study included 116 patients (mean age, 38 years) and 4 faculty surgeons. Total cost was primarily driven by operative time (74%), with a smaller portion of total cost arising from supplies (26%). Time cost ( P < .0001) and supply cost ( P = .006) varied significantly among surgeons. A resident was involved in 46.6% of cases. When subanalyzed by resident year, no-resident and senior resident (postgraduate years 4 and 5) cases had nearly identical mean times, while junior resident (postgraduate years 1-3) cases had mean times and operative time costs that were 39% greater ( P < .001). Conclusion For septoplasty with inferior turbinate reduction, the greatest driver of cost variation was operative time. Resident involvement correlated with increased time and cost. Supply costs had a much smaller impact. When subanalyzed by resident year, junior resident-involved cases were significantly longer than no-resident cases.

Single-Blinded Prospective Implementation of a Preoperative Imaging Checklist for Endoscopic Sinus Surgery.

Objective To determine if the introduction of a systematic preoperative sinus computed tomography (CT) checklist improves identification of critical anatomic variations in sinus anatomy among patients undergoing endoscopic sinus surgery. Study Design Single-blinded prospective cohort study. Setting Tertiary care hospital. Subjects and Methods Otolaryngology residents were asked to identify critical surgical sinus anatomy on preoperative CT scans before and after introduction of a systematic approach to reviewing sinus CT scans. The percentage of correctly identified structures was documented and compared with a 2-sample t test. Results A total of 57 scans were reviewed: 28 preimplementation and 29 postimplementation. Implementation of the sinus CT checklist improved identification of critical sinus anatomy from 24% to 84% correct ( P < .001). All residents, junior and senior, demonstrated significant improvement in identification of sinus anatomic variants, including those not directly included in the systematic review implemented. Conclusion The implementation of a preoperative endoscopic sinus surgery radiographic checklist improves identification of critical anatomic sinus variations in a training population.

International Frontal Sinus Anatomy Classification and anatomic predictors of low-lying anterior ethmoidal arteries.

BACKGROUND: The International Frontal Sinus Anatomy Classification (IFAC) was introduced to more accurately characterize ethmoid and frontal sinus pneumatization patterns. The prevalence of IFAC cells and their anatomic associations have not been described. OBJECTIVE: The goal was to examine the prevalence of IFAC cells and determine radiologic features associated with a low-lying anterior ethmoidal artery (LAEA). METHODS: Imaging of adult patients who underwent computed tomographies from January 2015 to March 2016 were retrospectively reviewed by using the IFAC classification. We also measured the distance from the skull base to the anterior ethmoidal artery (AEA), the height of the lateral lamella of the cribriform plate, and anterior-posterior diameter from the anterior wall of the frontal sinus to the skull base (APF). Patients with a history of sinus surgery, trauma, malignancy, or congenital anomaly were excluded. Statistical analysis was performed by using Pearson correlation coefficients and χ2 tests. RESULTS: A total of 95 patients met the inclusion criteria. There was a significant association between supraorbital ethmoid cells and an LAEA (p < 0.001), with a significant effect size (φ = 0.276, p = 0.007). An inverse relationship was observed between Keros type I classification I and an LAEA (p < 0.001), with a significant effect size (φ = -0.414, p = 0.000). Significant associations were found between the AEA distance from the skull base and the cribriform lateral lamella height (R = 0.576, p < 0.001). In addition, there was a significant association between the AEA distance from the skull base and the APF (R = 0.497, p < 0.001). CONCLUSION: The presence of a supraorbital ethmoid cell and a wide APF were associated with an LAEA. There was a significant relationship between Keros type I classification and the AEA adjacent to the skull base. Delineation of these anatomic relationships may be helpful during endoscopic sinus surgery to avoid complications.

The pain-depression dyad and the association with sleep dysfunction in chronic rhinosinusitis.

BACKGROUND: Depression, pain, and sleep disturbance is a symptom cluster often found in patients with chronic illness, exerting a large impact on quality of life (QOL). A wealth of literature exists demonstrating a significant association between depression, pain, and sleep dysfunction in other chronic diseases. This relationship has not been described in patients with chronic rhinosinusitis (CRS). METHODS: Sixty-eight adult patients with CRS were prospectively enrolled. Patients at risk for depression were identified using the Patient Health Questionnaire-2 (PHQ-2) using a cut-off score of ≥1. Pain experience was measured using the Brief Pain Inventory Short Form (BPI-SF) and the Short Form McGill Pain Questionnaire (SF-MPQ). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Forty-seven patients were at risk for depression. Significant positive correlations were found between total PSQI scores and all pain measures (R = 0.38-0.61, p ≤ 0.05) and between total PSQI scores and PHQ-2 scores (R = 0.46, p < 0.05). For patients at risk for depression, significant, positive correlations were found between pain measures, the total PSQI score, and the 3 PSQI subdomains (sleep latency, sleep quality, and daytime dysfunction; R = 0.31-0.61, p < 0.05). The relationship between pain and sleep dysfunction scores was not seen in the absence of depression. CONCLUSION: Depression, pain, and sleep dysfunction are interrelated in patients with CRS. In the absence of depression, significant correlations between pain and sleep are not observed, suggesting that depression plays a key role in this interaction. Further research is needed to investigate the complex relationship between depression, pain, and sleep dysfunction in CRS.

Lack of correlation between patient reported location and severity of facial pain and radiographic burden of disease in chronic rhinosinusitis.

BACKGROUND: Facial pain is a cardinal symptom of chronic rhinosinusitis (CRS) with significant impacts on patient treatment selection, quality of life, and outcomes. The association between facial pain and CRS disease severity has not been systematically evaluated with validated, facial pain-specific questionnaires. Our objective was to measure pain location, severity, and interference in patients with CRS, and correlate these to the location and severity of radiographic evidence of disease. METHODS: Patients with CRS were enrolled into a prospective, cross-sectional study. Patients completed the Brief Pain Inventory Short Form, which is a validated and widely used tool that measures pain location, severity, and interference with daily activities of living. The Lund-Mackay (L-M) computed tomography (CT) scoring system was used to operationalize the radiographic location and severity of inflammation. Facial pain location, severity, and interference scores were correlated to paranasal sinus opacification scores. RESULTS: Consecutive patients with CRS with nasal polyps (CRSwNP; n = 37) and CRS without nasal polyps (CRSsNP; n = 46) were enrolled. No significant relationship was found between the location and severity of reported facial pain and radiographic findings of disease for patients with either CRSwNP or CRSsNP. There was no difference in pain location between patients with and without radiographic disease in a given sinus. CONCLUSION: Facial pain in CRS is not predicted by the radiographic extent of disease. The location and severity of facial pain reported by the patient is not a reliable marker of the anatomic location and severity of sinonasal inflammation. Pain location should not necessarily be relied upon for guiding targeted therapy.

Nasal obstruction has a limited impact on sleep quality and quality of life in patients with chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: Nasal obstruction is a cardinal symptom in diagnosing chronic rhinosinusitis (CRS), and decreased sleep quality (SQ) and quality of life (QOL) are commonly reported in CRS. It is, however, unclear what role nasal obstruction severity plays in this decreased SQ and QOL. Using validated instruments, we evaluated the relationship between nasal obstruction severity, SQ, and QOL. STUDY DESIGN: Prospective case series. METHODS: Patients with CRS refractory to standard medical therapy (n = 28) were prospectively enrolled and completed the Nasal Obstruction Symptom Evaluation (NOSE), Pittsburg Sleep Quality Index (PSQI), Rhinosinusitis Disability Index, and the 22-item Sinonasal Outcome Test. CRS disease severity was evaluated with computed tomography and endoscopy. NOSE scores were compared to SQ, QOL, and disease severity measures. Spearman correlations were used to identify significant associations between measures. RESULTS: All patients reported symptomatic nasal obstruction (NOSE score ≥ 30), whereas poor sleep (PSQI ≥ 5) was reported by 82%. The NOSE sleeping subdomain correlated strongly with the PSQI total score, whereas other elements of the NOSE instrument correlated weakly or not at all with this measurement of SQ. Nasal obstruction correlated weakly with disease-specific QOL and had no correlation with the PSQI total. CONCLUSIONS: Nasal obstruction appears to have a limited association with CRS-specific QOL and CRS-associated decrease in SQ. Further, the NOSE instrument, because it contains a question about sleep, may have overlap with the PSQI as a measure of SQ. The total NOSE score in CRS patients does not appear to be purely a measure of nasal obstruction. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1971-1976, 2016.

Dyad of pain and depression in chronic rhinosinusitis.

BACKGROUND: Pain and depression often coexist as comorbidities in patients with chronic disease and exert a major impact on quality of life (QOL). Little is known about the relationship between pain and depression in chronic rhinosinusitis (CRS). Our objective was to investigate this relationship and to analyze the effect of pain and depression on QOL in CRS. METHODS: Patients with CRS were prospectively recruited as part of an observational cohort study. A total of 70 participants provided pain scores using both the Brief Pain Inventory Short Form (BPI-SF) and the Short Form McGill Pain Questionnaire (SF-MPQ). Patients at risk for depression were identified using the Patient Health Questionnaire-2 (PHQ-2). CRS-specific QOL was determined using the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: Significant positive correlations were found between depression scores and all pain measures (R = 0.475 to 0.644, p < 0.001). Patients with a PHQ-2 score ≥1 had significantly higher scores on all reported pain measures. Significant positive correlations were found between all pain measures, the total SNOT-22 score, and 3 SNOT-22 subdomains (sleep, psychological dysfunction, and ear/facial symptoms; R = 0.323 to 0.608, p < 0.05). CONCLUSION: Adult patients with CRS at risk for depression experience more pain and have overall worse disease-specific QOL. Further research investigating the complex interactions between depression and pain and the role it plays in CRS disease-specific QOL is warranted.