IL-13 and IL-13-induced periostin levels are specifically decreased in patients following endoscopic sinus surgery for chronic rhinosinusitis.

BACKGROUND: Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. OBJECTIVE: The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. METHODS: MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. RESULTS: A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP level was higher in patients undergoing extensive surgery. CONCLUSION: ESS decreased levels of IL-13 and periostin in the middle meatus. T2 inflammation after ESS was correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes.

Persistent discharge or edema after endoscopic sinus surgery in patients with chronic rhinosinusitis is associated with a type 1 or 3 endotype.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) may have persistence of polyps, discharge, or edema after endoscopic sinus surgery (ESS). Inflammation in CRS can be classified into three endotypes, with the presence of polyps associated with the type 2 endotype. Here, we evaluate the endotypic underpinnings of discharge or edema without polyps after ESS. METHODS: At a visit 6-12 months post ESS, patients underwent endoscopy and completed the CRS-PRO and SNOT-22. Luminex analysis of middle meatal mucus obtained at that visit was performed for IFN-γ, ECP, and IL-17a. Type 1, 2, and 3 endotypes were defined as greater than the 90th percentile expression of each marker, respectively, in controls. Wilcoxon rank-sum and chi-squared tests were used to compare cytokine levels and endotype prevalence between those with and without endoscopic findings. RESULTS: A total of 122 CRS patients completed a clinical exam (median: 8.2 months post ESS). Of the 122 patients, 107 did not have polyps on endoscopy. Of these 107 patients, 48 had discharge, 44 had edema, and 46 had neither discharge nor edema. Compared with those patients without any findings, patients with discharge or edema reported significantly worse severity as measured by CRS-PRO (10.5 vs. 7.0, p = 0.009; 12.0 vs. 7.0, p < 0.001; respectively), and had higher post-ESS IFN-γ, ECP, and IL-17a. Patients with discharge had higher prevalence of only T1 and T3 endotypes, while patients with edema had higher prevalence of only the T3 endotype. CONCLUSIONS: Post-ESS discharge or edema in the absence of polyps was associated with higher patient-reported outcome severity and was more strongly associated with type 1 or 3 inflammation.

Efficacy of an oral CRTH2 antagonist (AZD1981) in the treatment of chronic rhinosinusitis with nasal polyps in adults: A randomized controlled clinical trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils. OBJECTIVE: To evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP. METHODS: Eighty-one subjects (18-70 years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double-blind fashion to receive either AZD1981 (n = 22) or placebo (n = 21) orally three times a day for 12 weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12 weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test-22, and the Brief Smell Identification Test. RESULTS: Forty-three patients met the inclusion criteria and were enrolled. At 12 weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n = 15) compared with placebo (mean 0.20, standard error 0.36, n = 17); mean difference -0.20 (95% confidence interval: -1.21, 0.81; p = .69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction. CONCLUSION: In patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease-specific quality of life.

Use of intraoperative frontal sinus mometasone-eluting stents decreased interleukin 5 and interleukin 13 in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Mometasone-eluting stents (MES) have demonstrated improvement in short-term endoscopic outcomes and reduce short- to medium-term rescue interventions. Their effect on the local inflammatory environment, longer-term patient-reported outcomes, and radiographic severity have not been studied. METHODS: Middle meatal mucus and validated measures of disease severity were collected before and 6 to 12 months after endoscopic surgery in 52 patients with chronic rhinosinusitis with nasal polyps (CRSwNPs). Operative findings, type 2 mediator concentrations, intraoperative variables, and disease severity measures were compared between those who did and those who did not receive intraoperative frontal MES. RESULTS: A total of 52 patients with CRSwNPs were studied; 33 received frontal MES and were compared with 19 who did not. Pre-endoscopic sinus surgery (ESS) middle meatus (MM) interleukin (IL) 13 and eosinophil cationic protein (ECP) were higher in the stented group (p < 0.05), but pre-ESS clinical measures of disease severity were similar as were surgical extent and post-ESS medical management. Intraoperative eosinophilic mucin was more frequent in the stented group (58% vs 11%, p = 0.001). IL-5 (p < 0.05) and IL-13 (p < 0.001) decreased post-ESS in the stented group, but this was not observed in the nonstented group. Post-ESS IL-4 and IL-13 were higher in the nonstented vs stented group (p < 0.05 for both). CONCLUSION: Although patients who received intraoperative frontal MES had significantly higher pre-ESS MM IL-13 and ECP, patients who received frontal MES had lower concentrations of IL-4 and IL-13 than those who did not at a median of 8 months post-ESS. However, these changes did not correspond to significantly different measures of symptomatic or radiographic disease severity.

CRS-PRO and SNOT-22 correlations with type 2 inflammatory mediators in chronic rhinosinusitis.

The 22-item Sino-Nasal Outcome Test (SNOT-22) and 12-item Patient Reported Outcomes in Chronic Rhinosinusitis (CRS-PRO) instrument are validated patient-reported outcomes measures in CRS. In this study we assess the correlation of these with type 2 (T2) biomarkers before and after endoscopic sinus surgery (ESS). METHODS: Middle meatal mucus data were collected and the SNOT-22 and CRS-PRO were administered to 123 patients (71 CRS without nasal polyps [CRSsNP], 52 CRS with nasal polyps [CRSwNP]) with CRS before and 6 to 12 months after undergoing ESS. Interleukin (IL)-4, IL-5, IL-13, and eosinophilic cationic protein (ECP) were measured using a multiplexed bead assay and enzyme-linked immunoassay. Pre- and post-ESS SNOT-22 and CRS-PRO were compared with T2 biomarkers. RESULTS: Before ESS neither PROM correlated with any biomarker. After ESS, CRS-PRO showed a correlation with 2 mediators (IL-5 and IL-13: p = 0.012 and 0.003, respectively) compared with none for the SNOT-22. For CRSwNP patients, pre-ESS CRS-PRO and SNOT-22 correlated with IL-4 (p = 0.04 for both). However, after ESS, CRS-PRO correlated with 3 biomarkers (IL-5, IL-13, and ECP: p = 0.02, 0.024, and 0.04, respectively) and SNOT-22 with 2 biomarkers (IL-5 and IL-13: p = 0.038 and 0.02, respectively). There were no significant relationships between any of the T2 biomarkers pre- or post-ESS among patients with CRSsNP. Exploratory analyses of the subdomains showed the SNOT-22 rhinologic and CRS-PRO rhinopsychologic subdomains correlated better with the T2 biomarkers. On individual item analysis, IL-13 correlated significantly post-ESS with 8 of 12 items on the CRS-PRO vs 6 of 22 items on the SNOT-22. CONCLUSION: The CRS-PRO total score showed a significant correlation with T2 biomarkers especially when assessed post-ESS and among CRSwNP patients.

Prognostic factors for polyp recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is frequently managed with endoscopic sinus surgery (ESS). Prior studies describe individual clinical variables and eosinophil density measures as prognostic for polyp recurrence (PR). However, the relative prognostic significance of these have not been extensively investigated. OBJECTIVES: We sought to evaluate the impact of PR on measures of disease severity post-ESS and quantify the prognostic value of various clinical variables and biomarkers. METHODS: Ninety-four patients with chronic rhinosinusitis with nasal polyps and prospectively biobanked polyp homogenates at the time of ESS were recruited 2 to 5 years post-ESS. Patients were evaluated with patient-reported outcome measures and endoscopic and radiographic scoring pre- and post-ESS. Biomarkers in polyp homogenates were measured with ELISA and Luminex. Relaxed least absolute shrinkage and selection operator regression optimized predictive clinical, biomarker, and combined models. Model performance was assessed using receiver-operating characteristic curve and random forest analysis. RESULTS: PR was found in 39.4% of patients, despite significant improvements in modified Lund-Mackay (MLM) radiographic and 22-item Sinonasal Outcomes Test scores (both P < .0001). PR was significantly associated with worse post-ESS MLM, modified Lund-Kennedy, and 22-item Sinonasal Outcomes Test scores. Relaxed least absolute shrinkage and selection operator identified 2 clinical predictors (area under the curve = 0.79) and 3 biomarkers (area under the curve = 0.78) that were prognostic for PR. When combined, the model incorporating these pre-ESS factors: MLM, asthma, eosinophil cationic protein, anti-double-stranded DNA IgG, and IL-5 improved PR predictive accuracy to area under the curve of 0.89. Random forest analysis identified and validated each of the 5 variables as the strongest predictors of PR. CONCLUSIONS: PR had strong associations with patient-reported outcome measures, endoscopic and radiographic severity. A combined model comprised of eosinophil cationic protein, IL-5, pre-ESS MLM, asthma, and anti-double-stranded DNA IgG could accurately predict PR.

Radiographic disease severity in chronic rhinosinusitis patients and health care utilization.

OBJECTIVES: Chronic rhinosinusitis (CRS) affects approximately 12% of the population and leads to increased health care utilization and indirect costs exceeding $20 billion annually in the United States. The Lund-Mackay score (LMS) measures radiographic disease severity for CRS but poorly correlates with symptom scores. The association between LMS and health care utilization in CRS patients has not yet been investigated. The study aimed to assess the association between health care utilization and CRS radiographic severity using LMS. METHODS: CRS patients enrolled in a clinical registry were evaluated. Nasal endoscopy findings and LMS were recorded for patients with sinus CT imaging. Patient symptom scores, demographic characteristics, and health care utilization measures were collected. The relationship between these factors and LMS was examined. RESULTS: A total of 556 patients met inclusion criteria. Mean age was 45.3 years, 53.4% were male, and 41.7% had nasal polyps. There was no difference in sex, smoking history, 22-item Sino-nasal Outcome Test scores, or past medical history factors between patients with high (≥8, n = 410) and low (<8, n = 146) LMS. Among high LMS patients, 73.7% underwent endoscopic sinus surgery (ESS) compared to 55.5% with low LMS (P < .01), and a greater percentage of patients had nasal polyps (49.3% vs 20.5%, P < .01). On multivariable logistic regression, high LMS patients used fewer antibiotic courses (OR: 0.68 [0.51-0.91]), but were more likely to be managed with ESS (OR: 2.28 [1.41-3.73]), and have nasal polyps (OR: 2.11 [1.16-3.93]) compared to low LMS patients. There was no significant difference in the number of steroid courses, over the counter pill use, provider visits, work/school days missed, or symptom duration between the two LMS groups. CONCLUSION: CRS patients with severe radiographic disease are more likely to have nasal polyps, undergo ESS, and take fewer antibiotic courses. However, there is no association between radiographic disease severity and other measures of health care utilization. LEVEL OF EVIDENCE: 2b, individual retrospective cohort study.

Impact of type 2 targeting biologics on acute exacerbations of chronic rhinosinusitis.

Background: Acute exacerbations of chronic rhinosinusitis (AECRS) are associated with significant morbidity and decreased quality of life. There are sparse data assessing the real-world impact of biologics on AECRS. Objectives: We sought to determine the impact of type 2-targeting biologics on the frequency of medication use for AECRS episodes. Methods: Antibiotic and/or systemic corticosteroid courses for AECRS were identified in a retrospective study from November 2015 to February 2020, at a single academic health system. The estimated yearly rates for antibiotic and corticosteroid courses were evaluated before and after initiation of type 2 biologics. Results: One-hundred and sixty-five patients with chronic rhinosinusitis (CRS) had received either omalizumab (n = 12), mepolizumab (n = 42), benralizumab (n = 44), dupilumab (n = 61), or reslizumab (n = 6). Seventy percent had CRS with nasal polyps, and 30% had CRS without nasal polyps. All the patients had asthma. When all the biologics were combined, the estimated yearly rate for antibiotics for AECRS decreased from 1.34 (95% confidence interval [CI], 1.12-1.59) to 0.68 (95% CI, 0.52-0.88) with biologic use (49% reduction, p < 0.001). Those with frequent AECRS (three or more courses of antibiotics in the 1 year before biologic use) had a larger degree of reduction, with an estimated yearly rate of 4.15 (95% CI, 3.79-4.55) to 1.58 (95% CI, 1.06-2.35) with biologic use (n = 27; 62% reduction; p < 0.001). Within the total cohort, the estimated yearly rate for systemic corticosteroids for AECRS decreased from 1.69 (95% CI, 1.42-2.02) to 0.68 (95% CI, 0.53-0.88) with biologic use (60% reduction; p < 0.001). Conclusion: Type 2-targeting biologics reduced medication use for AECRS. This suggested that biologics may be a therapeutic option for patients with frequent AECRS.

Responsiveness and convergent validity of the chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure in CRS patients undergoing endoscopic sinus surgery.

BACKGROUND: The chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure is a 12-item measure with previously demonstrated validity in chronic rhinosinusitis (CRS) patients receiving medical therapy. This study establishes the factor structure, responsiveness, and convergent validity of the CRS-PRO following endoscopic sinus surgery (ESS). METHODS: Northwestern CRS Subject Registry patients had pre-ESS, 3-month (n = 111; CRS without nasal polyps [CRSsNP] = 60, CRS with nasal polyps [CRSwNP] = 51), and 6-month (n = 86; CRSsNP = 47, CRSwNP = 39) post-ESS assessments where patients completed the CRS-PRO, 22-item Sino-Nasal Outcome Test (SNOT-22), and four Patient-Reported Outcomes Measurement (PROM) Information System (PROMIS) short forms (general health measures). Patients had pre-ESS objective testing (endoscopic and radiographic assessment). Factor analysis was conducted using principal axis factoring with varimax rotation on the baseline CRS-PRO. The clinically important difference (CID) was estimated using both distribution-based and anchor-based methods. RESULTS: Factor analysis found the CRS-PRO comprised the "rhino-psychologic," "facial discomfort," and "cough" factors, which were responsive to ESS and correlated with the other PROMs. The changes observed in the CRS-PRO at 3 months had strong correlation with the corresponding changes in SNOT-22 (r = 0.792, p < 0.0001) and moderate correlations with changes in PROMIS fatigue and sleep domains. These changes had a very large effect size (Cohen's d 1.44) comparable to the longer SNOT-22 (Cohen's d 1.41) with slightly larger effect sizes observed in CRSwNP compared to CRSsNP patients. Similar convergent validity and responsiveness were observed in the 6-month data. The CRS-PRO CID was estimated to be between 5.0 and 7.5 (midpoint 6.0) using distribution-based and anchor-based methods. CONCLUSION: This study demonstrates the validity and responsiveness of the CRS-PRO in subjects receiving ESS.

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD. OBJECTIVE: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD. METHODS: Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence. RESULTS: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO+ epithelium in NPs from patients with AERD. CONCLUSIONS: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.

Responsiveness and Convergent Validity of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

BACKGROUND: The CRS-PRO is a new patient-reported outcome measure (PROM) for chronic rhinosinusitis (CRS) that was developed using extensive patient input per Food and Drug Administration guidance on PROMs acceptable for use as end points in clinical trials. OBJECTIVE: To assess the responsiveness and convergent validity of the CRS-PRO following standard-of-care medical therapy. METHODS: This was a prospective study of 51 patients (21 with nasal polyps and 30 without) with newly diagnosed CRS or having an acute CRS exacerbation who were initiated on appropriate medical therapy. At the baseline visit each patient completed the CRS-PRO questionnaire, the 22-item Sino-Nasal Outcome Test, the EuroQol 5-dimensional questionnaire, and 4 Patient-Reported Outcome Measure Information System short forms along with objective testing including endoscopic and radiographic scores, smell discrimination, and nasal inspiratory flow testing. This same battery of questionnaires and testing was administered at a follow-up visit 4 to 8 weeks later. RESULTS: We verified that shortening the 21-item CRS-PRO to 12 items as previously described maintains its psychometric properties. The 12-item CRS-PRO was responsive with a large effect size (Cohen's d, 0.94) comparable to the longer 22-item Sino-Nasal Outcome Test (Cohen's d, 0.93). The instrument was slightly more responsive to medically treated patients with CRS without nasal polyps compared with patients with CRS with nasal polyps (Cohen's d, 1.1 vs 0.89, respectively). The change in 12-item CRS-PRO total score has moderate correlation with change in Lund-Mackay computed tomography scores. CONCLUSIONS: The CRS-PRO is a 12-item rigorously developed, responsive, and valid PROM that was developed using extensive input from patients with current definitions of CRS, including its 2 major phenotypes.

Factors Associated With Intubation and Prolonged Intubation in Hospitalized Patients With COVID-19.

OBJECTIVE: To identify risk factors associated with intubation and time to extubation in hospitalized patients with coronavirus disease 2019 (COVID-19). STUDY DESIGN: Retrospective observational study. SETTING: Ten hospitals in the Chicago metropolitan area. SUBJECTS AND METHODS: Patients with laboratory-confirmed COVID-19 admitted between March 1 and April 8, 2020, were included. We evaluated sociodemographic and clinical characteristics associated with intubation and prolonged intubation for acute respiratory failure secondary to COVID-19 infection. RESULTS: Of the 486 hospitalized patients included in the study, the median age was 59 years (interquartile range, 47-69); 271 (55.8%) were male; and the median body mass index was 30.6 (interquartile range, 26.5-35.6). During the hospitalization, 138 (28.4%) patients were intubated; 78 (56.5%) were eventually extubated; 21 (15.2%) died; and 39 (28.3%) remained intubated at a mean ± SD follow-up of 19.6 ± 6.7 days. Intubated patients had a significantly higher median age (65 vs 57 years, P < .001) and rate of diabetes (56 [40.6%] vs 104 [29.9%], P = .031) as compared with nonintubated patients. Multivariable logistic regression analysis identified age, sex, respiratory rate, oxygen saturation, history of diabetes, and shortness of breath as factors predictive of intubation. Age and body mass index were the only factors independently associated with time to extubation. CONCLUSION: In addition to clinical signs of respiratory distress, patients with COVID-19 who are older, male, or diabetic are at higher risk of requiring intubation. Among intubated patients, older and more obese patients are at higher risk for prolonged intubation. Otolaryngologists consulted for airway management should consider these factors in their decision making.

Development and Preliminary Validation of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

BACKGROUND: Patient-reported outcome (PRO) measures developed and validated on patients with the currently defined phenotypes of chronic rhinosinusitis (CRS) are needed to support clinical trials in CRS. OBJECTIVE: This study developed and examined the initial reliability and validity of the CRS-PRO, a new PRO measure of CRS. METHODS: Instrument development was performed through structured interviews and focus groups with clinical experts and 45 patients with CRS meeting current definitions of disease, 21 patients with CRS without nasal polyps (CRSsNP), and 24 patients with CRS with nasal polyps (CRSwNP) to identify items important to patients. Then another 50 patients (32 with CRSsNP and 18 with CRSwNP) with stable CRS symptoms were enrolled to evaluate the reliability of the instrument. Each patient completed the CRS-PRO, Sinonasal Outcome Test-22 (SNOT-22), and 4 Patient-Reported Outcome Measurement Information System short forms at the baseline visit and then at least 7 days later. RESULTS: After the development process, 21 items were identified from the conceptual domains of physical symptoms, sensory impairment, psychosocial effects, and life impact. Using the responses of the 50 patients with CRS, 21 draft items were further refined to 12 items by eliminating conceptually similar or highly correlated items or those with low mean symptom severity. The 12-item questionnaire was shown to have excellent internal consistency (Cronbach α, 0.86) and test-retest reliability with a high intraclass correlation coefficient (0.89) and Pearson's correlation (r = 0.82, P < .0001). The 12-item CRS-PRO correlated highly with the longer SNOT-22 (r = 0.83, P < .0001) demonstrating its concurrent validity. We also demonstrated validity and reliability in a separate analysis for patients with CRSsNP and CRSwNP. CONCLUSION: The CRS-PRO is a concise, valid, and reliable measure that was developed with extensive input from patients with CRS with current disease definitions.

Predicting Obstructive Sleep Apnea Status With the Reflux Symptom Index in a Sleep Study Population.

OBJECTIVES/HYPOTHESIS: Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status. STUDY DESIGN: Cross-sectional. METHODS: We recruited 101 adults presenting for ambulatory polysomnograms to the Northwestern Sleep Disorders Center from July 2017 to July 2018. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Leicester Cough Questionnaire (LCQ), RSI, Gastroesophageal Reflux Disease Questionnaire, Sino-Nasal Outcome Test-22, Nasal Obstruction Symptom Evaluation, Eustachian Tube Dysfunction Questionnaire 7, and Headache Impact Test were administered. Polysomnogram results were subsequently obtained. Patients with OSA (apnea-hypopnea index ≥ 5) and without OSA were compared. RESULTS: Of the 101 participants, 98 had valid sleep study results. Of those, 72 were diagnosed with OSA and 26 were not. The two groups differed significantly in age and body mass index (BMI). Of the questionnaires, only the RSI and LCQ means differed significantly, with worse symptoms in the OSA group (P = .003 and .014, respectively). Upon univariate regression, age, BMI, and RSI were associated with OSA status. Using regression coefficients, a clinical score of 2 (RSI) + 1.5 (BMI) + age yielded a diagnostic model (C-statistic = 0.807, P < .001). A threshold score of 104.21 was 76.4% sensitive and 73.1% specific. CONCLUSIONS: Patients with OSA have worse symptoms of laryngopharyngeal reflux as measured by the RSI. The addition of the RSI to the recognized factors of age and BMI improves diagnostic utility for OSA. LEVEL OF EVIDENCE: 2 Laryngoscope, 2020.

Measuring the health utility of chronic eustachian tube dysfunction.

OBJECTIVE: To assess the health utility of chronic Eustachian tube dysfunction (ETD). METHODS: This is a prospective study of 53 patients with chronic ETD recruited from a tertiary clinic from April 2017 to July 2018. The 7-Item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was administered, and health utility was evaluated using the EuroQol-5 Dimensions-3 Level Instrument (EQ-5D-3L), the visual analogue scale (VAS), time tradeoff (TTO), and standard gamble (SG). Participants were grouped into medical or procedural management groups. One-week follow-up included repeated health utility measures and ETDQ-7. RESULTS: Fifty-three patients were included in the final analysis. Of those, 34 were managed medically, and 19 received myringotomies ± PE tubes. The mean baseline ETDQ-7 was 4.26 ± 1.31; whereas health utility measures were different depending on the method utilized: EQ-5D-3L 0.90 ± 0.11; VAS 0.76 ± 0.21; TTO 0.85 ± 0.23; and SG 0.94 ± 0.11 (P < .001). There was a significant change in ETDQ-7 (P = .001) and TTO (P = .011) scores posttreatment. On the ETDQ-7, question 2 (pain in the ears) was significantly associated with VAS (P = .032), and question 4 (ear symptoms during a cold or sinusitis) was significantly associated with TTO (P = .006). CONCLUSION: Chronic ETD has a significant burden on quality of life, with a health utility similar to gastroesophageal reflux disease and moderate asthma. Although treatment-related changes are measurable using disease-specific quality-of-life measures, only TTO was significantly changed after treatment. Health utility seemed to depend on the method of measurement but provided a benchmark for evaluating cost-effectiveness of innovations to manage ETD. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:E39-E44, 2020.

Risk factors for auricular hematoma and recurrence after drainage.

OBJECTIVES/HYPOTHESIS: To review an institutional experience with auricular hematoma across all clinical settings including the emergency department (ED) and outpatient clinics at an urban tertiary care academic hospital, characterize practice patterns across setting and specialty, and assess for factors predictive of treatment success. METHODS: Patients presenting to the ED, admitted to an inpatient ward, or seen in the outpatient setting between 2000 and 2017 with a diagnosis of auricular hematoma were reviewed. A number of relevant patient features including demographic factors, medications, and social risk factors were analyzed, as were several factors related to the presentation and management of the hematoma to identify variables of clinical significance. RESULTS: A total of 87 individual cases were identified. Auricular hematomas most commonly occurred in males after sports-related trauma (e.g., martial arts, wrestling, boxing). Factors associated with lower rates of recurrence included initial treatment by or in consultation with an otolaryngologist and application of a bolster dressing. CONCLUSIONS: In our cohort, initial management of auricular hematoma by an otolaryngologist or with an otolaryngology consultation and placement of a bolster dressing was associated with lower rates of hematoma recurrence. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:628-631, 2020.

Are chronic cough and laryngopharyngeal reflux more common in obstructive sleep apnea patients?

OBJECTIVES/HYPOTHESIS: To assess if there is a significant difference in the prevalence and severity of chronic cough symptoms in obstructive sleep apnea (OSA) patients versus non-OSA patients and examine this relationship in regard to laryngopharyngeal reflux (LPR) symptoms. STUDY DESIGN: Prospective cohort study. METHODS: Patients referred to Northwestern Medicine Sleep Lab for home sleep testing were enrolled. Patients filled out the Leicester Cough Questionnaire (LCQ) and Reflux Symptom Index (RSI) before completing sleep testing. Home sleep testing results were reviewed, and patients were separated into non-OSA and OSA groups by standard Apnea-Hypopnea Index (AHI) criteria. Demographic characteristics and questionnaire scores of the two groups were compared. The relationship between OSA severity, as determined by AHI, and LCQ and RSI scores was assessed. RESULTS: Of the 52 patients enrolled, 33 patients met criteria for OSA and 19 patients did not. Comparing patients without OSA versus those with OSA, there was a significant difference in mean LCQ score (129.9 vs. 120.0, respectively; P = .02), implying worse cough symptoms among OSA patients, and mean RSI score (3.2 vs. 11.2, respectively; P = .0013), implying worse upper-airway reflux symptoms among OSA patients. There was a significant correlation between LCQ score and AHI (r = -0.39, P = .0061) and between RSI score and AHI (r = 0.37, P = .0078). CONCLUSIONS: OSA patients demonstrate worse chronic cough and LPR-related quality of life versus non-OSA patients. Furthermore, the severity of these quality-of-life measures was correlated with the severity of the AHI. Chronic cough and particularly the pharyngeal LPR symptoms may be associated with the presence and severity of OSA. LEVEL OF EVIDENCE: 2 . Laryngoscope, 129:1244-1249, 2019.

Asthma onset pattern and patient outcomes in a chronic rhinosinusitis population.

BACKGROUND: Chronic rhinosinusitis (CRS) is strongly associated with comorbid asthma. This study compares early-onset and late-onset asthma in a CRS population using patient-reported and clinical characteristics. METHODS: At enrollment into a clinical registry, CRS patients completed the 22-item Sino-Nasal Outcome Test (SNOT-22), Asthma Control Test (ACT), mini-Asthma Quality of Life Questionnaire (miniAQLQ), the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), and medication use questionnaires. Patients also reported comorbid asthma and age at first asthma diagnosis. Early-onset (<18 years) and late-onset (>18 years) asthma groups were defined. Analysis of variance (ANOVA), chi-square, and Kruskal-Wallis tests were used to compare patient responses. RESULTS: A total of 199 non-asthmatic (56.1%), 71 early-onset asthmatic (20.0%), and 85 late-onset asthmatic (23.9%) CRS patients completed the survey. Body mass index (BMI) was significantly higher in late-onset asthmatic (p = 0.046) while age, gender, race, and smoking history did not differ with time of asthma onset. SNOT-22, ACT, and miniAQLQ were not different between asthma groups, but late-onset asthmatics had significantly lower physical function than non-asthmatics (p = 0.008). Compared to non-asthmatics, late-onset asthmatics showed increased rates of nasal polyps (p < 0.001), higher Lund-Mackay scores (p = 0.005), and had received more oral steroid courses (p < 0.001) and endoscopic surgeries (p = 0.008) for CRS management. Late-onset asthmatics compared to early-onset asthmatics showed increased nasal polyposis (p = 0.011) and oral steroid courses for CRS (p = 0.003). CONCLUSION: While CRS-specific and asthma-specific patient-reported outcome measures (PROMs) were not significantly different among groups, CRS patients with late-onset asthma had poorer physical function, more frequent nasal polyposis, and required increased treatment for CRS. Late-onset asthma may predict more severe disease in CRS.

A prospective analysis evaluating tissue biopsy location and its clinical relevance in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high propensity for recurrence. Studies suggest that eosinophilia influences disease severity and surgical outcomes, but the selection of sinonasal site for measuring eosinophilia has not been examined. The aim of this study was to investigate how region-specific tissue eosinophilia affects radiographic severity, comorbidity prevalence, and polyp recurrence risk following sinus surgery. METHODS: Eosinophil cationic protein (ECP) levels in uncinate tissue (UT) and nasal polyp (NP) homogenates from 116 CRSwNP patients were measured using enzyme-linked immunosorbent assay (ELISA). Clinical history, radiographic severity, and time to polyp recurrence were obtained from electronic health records. The correlations between baseline Lund-Mackay scores and comorbidities were compared between UT and NP ECP levels. Cox regression and Kaplan-Meier analysis were then performed to assess whether UT or NP ECP better predicted recurrence. Censoring occurred at 4 years or at last follow-up if there was no endoscopic diagnosis of recurrent polyps. RESULTS: Lund-Mackay scores were significantly correlated with UT and NP ECP (r = 0.46 and 0.26 respectively, p < 0.05). UT but not NP ECP was significantly higher in patients with asthma (p < 0.01) and aspirin-exacerbated respiratory disease (AERD) (p < 0.05). Polyp recurrence risk was only significantly higher for patients with eosinophilic UT tissue (hazard ratio [HR] = 2.84, p = 0.025). When measured in NP, eosinophilia did not predict recurrence. CONCLUSION: Although ECP in NP was higher than in UT tissue, eosinophilia in UT tissue was a more clinically coherent biomarker of baseline radiographic severity, comorbid asthma and AERD, and prospective polyp recurrence risk than NP eosinophilia.