Search

INTRODUCTION: While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. METHODS: COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. RESULTS: Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. CONCLUSION: IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. OBJECTIVE: We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. METHODS: Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. RESULTS: Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). CONCLUSION: Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

ObjectivesAnti-obesity bias is pervasive among medical professionals, students, and trainees. Stigmatization of patients leads to suboptimal care and clinical outcomes. Educational strategies in medical training are needed to reverse these attitudes. The aim of this study was to evaluate the effect of an innovative didactic intervention and a standardized patient (SP) exercise on attitudes towards patients with obesity among medical students.MethodsIn 2016, a quasi-experimental study design was used at a US medical school. The class was divided into 2 groups according to a pre-determined protocol based on their clinical schedule, one assessed after exposure to a SP group and the other after exposure to the SP and an interactive lecture (IL + SP group) with real patients. The Attitudes about Treating Patients with Obesity and The Perceived Causes of Obesity questionnaires measured changes in several domains. A generalized estimating equations model was used to estimate the effect of the interventions both within and between groups.ResultsBoth groups showed improvements in negative and positive attitudes, although the reduction in scores for the negative attitude domain did not reach statistical significance in the IL + SP group (for the SP group, P = .01 and

BackgroundObesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine-topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports.Case presentationA 35-year-old Caucasian male with a body mass index of 41.7 kg/m2 presented for obesity treatment. History revealed nocturnal episodes of hyperphagia associated with amnesia of overeating and other features of sleep-related eating disorder. Treatment was initiated with phentermine-topiramate extended release. Five months later he lost 5% of his body weight and demonstrated resolution of sleep-related eating disorder behaviors. He reported no adverse side effects. Upon self-discontinuation of the medication, his eating disorder recurred.ConclusionsClinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine-topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population.

Introduction  Race, ethnicity, and socioeconomic status (SES) are complex, interconnected social determinants of health outcomes. This study uses multivariable analysis on a combination of large national datasets to examine the effects of these factors on 5-year disease-specific survival (DSS) and conditional DSS (CDSS) for nasopharyngeal carcinoma (NPC). Methods  A retrospective study of adults with NPC between 2000 and 2017 from the Surveillance, Epidemiology, End Results (SEER) registry was performed, using the National Cancer Institute Yost Index, a census tract-level composite score of SES to categorize patients. Kaplan-Meier analysis and Coxs regression for DSS and CDSS were stratified by SES. Logistic regression was conducted to identify risk factors for advanced cancer stage at time of diagnosis and receiving multimodal therapy. Results  Our analysis included 5,632 patients. DSS was significantly associated with race and SES ( p

BackgroundPatients with persistent COVID-19 olfactory dysfunction (OD) commonly report parosmia. Understanding the impact of COVID-19 OD and parosmia is critical to prioritizing research and interventions. In this study we investigate the impact of parosmia and other clinical and disease characteristics on health state utility values (HUVs) for those with persistent COVID-19 OD.MethodsPatients with a history of COVID-19 diagnosis and persistent OD were recruited from a tertiary medical center and a social media support forum for chemosensory dysfunction. Clinical characteristics and disease-specific symptoms were obtained along with self-reported history of smell function and presence of parosmia. HUVs were calculated using indirect (EuroQol 5-Dimension [EQ-5D]) and direct (VAS) measures.ResultsOur study included 286 subjects (75.52% women) with persistent COVID-19-related OD. Results (mean ± standard deviation) of HUVs based on EQ-5D and VAS were 0.81 ± 0.14 and 0.73 ± 0.21, respectively. Mean self-reported smell function (on a 0-10 scale) was 9.67 ± 1.25 pre-COVID-19, 0.93 ± 2.34 at diagnosis, and 3.39 ± 2.32 at most current assessment. A total of 89.16% of the subjects reported parosmia and 24.13% sought medical care for anosmia. Seeing an MD for OD (p

BACKGROUND: Olfactory dysfunction (OD) is associated with both post-viral and inflammatory etiologies such as COVID-19 and chronic rhinosinusitis/rhinitis (CRS/R) respectively, to result in reduced quality of life (QoL). However, the former typically induces a sudden-onset OD while the latter has a gradual presentation. This study aims to establish and compare health utility values (HUVs) and olfactory-specific QoL measurements between patients with COVID-19 and CRS/R related OD. METHODS: This prospective study surveyed COVID-19 and CRS/R patients with self-reported OD using HUV assessments (EuroQol-visual analog scale [EQ-VAS], EuroQol-5 dimension [EQ-5D], time trade-off [TTO]) and olfactory and sinonasal QoL measures (questionnaire of olfactory disorders -negative and positive statements [QOD-NS + PS] and sino-nasal outcome test [SNOT-22]). A subgroup of subjects completed objective olfactory testing. Intergroup mean scores were compared using Mann-Whitney U tests. RESULTS: One hundred eleven subjects were enrolled: mean age ± SD (43.0 ± 15.4 years), 55.9% female. CRS/R was associated with lower HUVs as measured by EQ-VAS (CRS/R: 0.67 ± 0.18 vs. COVID-19: 0.74 ± 0.19, p = .03) and worse SNOT-22 scores in both overall (CRS/R: 49.03 ± 21.04 vs. COVID-19: 27.58 ± 18.45, p

Viral infections have already been implicated with otitis media and sudden sensorineural hearing loss. However, the pathophysiology of COVID-19 as it relates to otologic disorders is not well-defined. With the spread of SARS-CoV-2, it is important to evaluate its colonization of middle ear mucosa. Middle ear and nasal tissue samples for quantitative RT-PCR and histologic evaluations were obtained from post-mortem COVID-19 patients and non-diseased control patients. Here we present evidence that SARS-CoV-2 colonizes the middle ear epithelium and co-localizes with the primary viral receptor, angiotensin-converting enzyme 2 (ACE2). Both middle ear and nasal epithelial cells show relatively high expression of ACE2, required for SARS-CoV-2 entry. The epithelial cell adhesion molecule (EpCAM) was use as a biomarker of epithelia. Furthermore, we found that the viral load in the middle ear is lower than that present in the nasal cavity.

BACKGROUND: The clinical course of coronavirus disease 2019 (COVID-19) olfactory dysfunction remains poorly characterized, often limited by self-reported measures. Given the logistical challenges of psychophysical testing, understanding the longitudinal relationship between self-reported and quantitative measures can help accurately identify patients with persistent olfactory dysfunction. This study aimed to longitudinally correlate measured and subjective olfactory function in COVID-19 subjects. METHODS: A prospective, longitudinal study evaluating subjective and measured olfaction was conducted on ambulatory COVID-19 subjects. Olfaction scores were obtained using a visual analogue scale (VAS) (0 = anosmia, 10 = normosmia) and the validated 12-item Brief Smell Identification Test (BSIT). Weekly testing was performed until recovery (BSIT ≥ 9/12 and/or VAS = 10/10) or study completion. RESULTS: Eighty-six polymerase chain reaction (PCR)-positive COVID-19 subjects were recruited ≤3 days from diagnosis and 52 completed longitudinal testing. Among those with self-reported smell loss at recruitment, similar levels (75.8%) of objective (BSIT ≥ 9/12) and subjective recovery were obtained using a VAS cutoff ≥8, yet only 30.3% reported complete subjective recovery (VAS = 10). Median times to objective and complete subjective olfactory recovery were 12 ± 2.3 and 24 ± 3.5 days, respectively. Although both measures showed chemosensory improvement, the distributions of objective and full subjective olfactory recovery differed significantly (log rank test χ2 = 6.46, degrees of freedom [df] = 1, p = 0.011). Overall correlation between BSIT and VAS scores was moderate to strong across longitudinal follow-up (rs = 0.41-0.65). CONCLUSION: Self-reported and psychophysically measured COVID-19 olfactory dysfunction improve at similar levels and are moderately correlated longitudinally, yet there is a significant delay in complete subjective recovery. Psychophysical testing in conjunction with qualitative assessments may be considered for counseling and follow-up of patients with COVID-19 smell loss.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.

IntroductionNasal chondromesenchymal tumors (NCMT) are rare benign neoplasms that usually present in children

OBJECTIVES Anti-obesity bias is pervasive among medical professionals, students, and trainees. Stigmatization of patients leads to suboptimal care and clinical outcomes. Educational strategies in medical training are needed to reverse these attitudes. The aim of this study was to evaluate the effect of an innovative didactic intervention and a standardized patient (SP) exercise on attitudes towards patients with obesity among medical students. METHODS In 2016, a quasi-experimental study design was used at a US medical school. The class was divided into 2 groups according to a pre-determined protocol based on their clinical schedule, one assessed after exposure to a SP group and the other after exposure to the SP and an interactive lecture (IL + SP group) with real patients. The Attitudes about Treating Patients with Obesity and The Perceived Causes of Obesity questionnaires measured changes in several domains. A generalized estimating equations model was used to estimate the effect of the interventions both within and between groups. RESULTS Both groups showed improvements in negative and positive attitudes, although the reduction in scores for the negative attitude domain did not reach statistical significance in the IL + SP group (for the SP group, P = .01 and

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.MethodsA single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.ResultsA total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.ConclusionIn ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for coronavirus disease 2019 (COVID-19) patients early in the disease course could aid the efficient allocation of medical interventions. Self-reported olfactory impairment has recently been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome.MethodsA retrospective review of all patients presenting to a San Diego Hospital system with laboratory-confirmed positive COVID-19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia.ResultsA total of 169 patients tested positive for COVID-19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128 (75.7%) of 169 subjects, of which 26 (20.1%) of 128 required hospitalization. Admission for COVID-19 was associated with intact sense of smell and taste, increased age, diabetes, and subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (adjusted odds ratio [aOR] 0.09; 95% CI, 0.01-0.74), whereas positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01; 95% CI, 1.12-57.49) was strongly and independently associated with admission.ConclusionNormosmia is an independent predictor of admission in COVID-19 cases. Smell loss in COVID-19 may be associated with a milder clinical course.

Abstract Background Olfactory dysfunction (OD) is associated with both post‐viral and inflammatory etiologies such as COVID‐19 and chronic rhinosinusitis/rhinitis (CRS/R) respectively, to result in reduced quality of life (QoL). However, the former typically induces a sudden‐onset OD while the latter has a gradual presentation. This study aims to establish and compare health utility values (HUVs) and olfactory‐specific QoL measurements between patients with COVID‐19 and CRS/R related OD. Methods This prospective study surveyed COVID‐19 and CRS/R patients with self‐reported OD using HUV assessments (EuroQol‐visual analog scale [EQ‐VAS], EuroQol‐5 dimension [EQ‐5D], time trade‐off [TTO]) and olfactory and sinonasal QoL measures (questionnaire of olfactory disorders –negative and positive statements [QOD‐NS + PS] and sino‐nasal outcome test [SNOT‐22]). A subgroup of subjects completed objective olfactory testing. Intergroup mean scores were compared using Mann–Whitney U tests. Results One hundred eleven subjects were enrolled: mean age ± SD (43.0 ± 15.4 years), 55.9% female. CRS/R was associated with lower HUVs as measured by EQ‐VAS (CRS/R: 0.67 ± 0.18 vs. COVID‐19: 0.74 ± 0.19, p = .03) and worse SNOT‐22 scores in both overall (CRS/R: 49.03 ± 21.04 vs. COVID‐19: 27.58 ± 18.45, p

Abstract Background Obesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine–topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports. Case presentation A 35-year-old Caucasian male with a body mass index of 41.7 kg/m2 presented for obesity treatment. History revealed nocturnal episodes of hyperphagia associated with amnesia of overeating and other features of sleep-related eating disorder. Treatment was initiated with phentermine–topiramate extended release. Five months later he lost 5% of his body weight and demonstrated resolution of sleep-related eating disorder behaviors. He reported no adverse side effects. Upon self-discontinuation of the medication, his eating disorder recurred. Conclusions Clinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine–topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population.

Introduction  The fully endoscopic expanded endonasal approach (EEA) has been shown to be safe and efficacious in pediatric patients. However, in the very young patient (ages six and under), the anatomical challenge of working through a small nasal corridor is problematic. The ability to repair the skull base and use a nasoseptal flap (NSF) has also been called into question. Here, we review skull base resections using EEA in patients aged 6 years and younger. Methods  A retrospective chart review was conducted on pediatric patients age 6 years and younger who underwent EEA skull base resections over a 3-year period (June 2014 through June 2017). Results  Eight children aged 6 and under with seven tumor pathologies underwent an EEA for the resection of their skull base tumors, with a mean follow-up of 1.45 years. Only chordoma cases required multiple-staged resections. There are no tumor recurrences to date. A high-flow intraoperative cerebrospinal fluid (CSF) leak was encountered in three cases, and there were no postoperative CSF leaks. CSF leaks were effectively repaired with NSFs. One patient suffered from postoperative hypopituitarism, one patient experienced recurrent epistaxis secondary to turbinate destruction by the tumor, and one patient expired 8 months postresection secondary to metastatic disease. Conclusion  In our case series, EEA for skull base tumors in children aged 6 and under was a safe and effective surgical approach. Skull base defects are able to be effectively addressed with typical repairs including NSFs. Larger studies are warranted to further investigate this technique in this pediatric population.

ObjectiveThis is the first report of multifocal inflammatory pseudotumor (IPT) involving the temporal bone, orbit and paranasal sinus, and the use of rituximab as adjunctive therapy in multifocal temporal bone IPT.PatientWe describe a 46-year-old man with orbital and maxillary sinus IPT, whose disease progressed despite radiation and steroid burst. He then developed contralateral mastoid disease, otalgia, aural fullness, and hearing loss.InterventionHe was initiated on rituximab and prednisone therapy. Mastoidectomy with near-total tumor removal was accomplished and histopathology confirmed IPT. A literature review was also performed.Main outcome measureTumor regression or recurrence.ResultDespite disease progression after radiation and steroids, his orbital, sinus, and mastoid disease improved after surgery, steroids, and rituximab. A review of four other previously reported cases of multifocal disease involving the temporal bone suggest that multifocal disease may be a more aggressive entity with higher recurrence rate compared with solitary disease. Although surgery and steroids are typically recommended, there is currently no consensus treatment recommendation.ConclusionsMultifocal IPT of the temporal bone is a rare but aggressive entity for which surgery and steroid combination therapy should be first line treatment. We suggest rituximab may be an effective adjunctive treatment particularly for recurrent disease or where systemic therapy may be favored.

BackgroundCritical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).MethodsUsing previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.ResultsThe ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.ConclusionThis critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

BackgroundAspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD.ObjectiveWe sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD.MethodsBlood and nasal scrapings were collected at baseline, during reactions, and after completion of ketorolac/aspirin challenge/desensitization in 12 patients with AERD. ILC2s and eosinophils were quantitated by means of flow cytometry. Urine was also collected, and quantification of PGD2 metabolite and leukotriene E4 levels was done by using ELISA. Baseline and nonsteroidal anti-inflammatory drug reaction clinical data were correlated with cell changes.ResultsILC2 numbers significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in 2 patients without AERD. Furthermore, eosinophil numbers decreased in blood concurrently with significant increases in urinary PGD2 metabolite and leukotriene E4 levels. The magnitude of increases in nasal mucosal ILC2 numbers positively correlated with maximum symptom scores during challenges. Furthermore, blood ILC2 numbers during the reaction correlated with time for the reaction to resolve, possibly reflecting reaction severity.ConclusionsILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.

BackgroundPsychological dysfunction is highly prevalent among patients with chronic rhinosinusitis (CRS). Previous study has identified various measures of anxiety and depression as predictors of quality-of-life outcomes following endoscopic sinus surgery (ESS). Psychological dysfunction scores, as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22), have been found to influence treatment decision making in CRS. This study aims to further elucidate improvement in discrete psychological symptoms following ESS for CRS.MethodsAdult patients with medically recalcitrant CRS electing to undergo ESS were prospectively enrolled into a multi-institutional, observational cohort. Psychological-related symptom severity and postoperative outcomes were assessed using psychological domain items of the SNOT-22, including subgroup analysis of patients with and without comorbid depression.ResultsA total of 374 participants met inclusion criteria and were followed postoperatively for a mean ± standard deviation (SD) of 14.6 ± 5.0 months. Total mean psychological domain scores improved from 15.9 ± 8.2 to 8.5 ± 8.4 (p < 0.001). Significant relative mean improvements were reported in "waking up tired" (23%; p < 0.001), "fatigue" (25%; p < 0.001), "reduced productivity" (28%; p < 0.001), "reduced concentration" (27%; p < 0.001), " frustrated/restless/irritable" (27%; p < 0.001), "sad" (15%; p < 0.001), and "embarrassed" (8%; p < 0.001) scores. A total of 64% to 66% of participants reported improvement in "reduced productivity," "waking up tired," "fatigue," and "frustrated/restless/irritable," compared to 46% and 38% reporting improvement in "sad" and "embarrassed," respectively.ConclusionPatients with CRS report significant improvement in common mental health-related symptoms following ESS. Despite these improvements, some degree of persistent postoperative psychological dysfunction was reported. Further study is necessary to determine which factors are associated with persistent psychological dysfunction after ESS in order to optimize treatment outcomes.

BackgroundFor patients with chronic rhinosinusitis (CRS), the decision to elect continued medical management vs surgery is complex and involves tradeoffs between benefits, risks, and overall effectiveness of each therapy. The purpose of this study is to investigate whether baseline disease-specific quality of life (QOL) can assist in predicting outcomes in patients with refractory CRS who elect continued medical management.MethodsCRS patients electing medical management were enrolled in a prospective, multi-institutional cohort study. Patients were stratified into pretreatment 22-item Sino-Nasal Outcome Test (SNOT-22) subgroups based on 10-point score increments (eg, 10 to 19, 20 to 29, 30 to 39, etc.) to capture potential outcome differences by baseline SNOT-22 disease burden. The proportion of patients achieving minimal clinically important difference (MCID≥9 points) and relative improvement (%) for each score category were calculated.ResultsSeventy-five CRS patients with a mean ± standard deviation pretreatment SNOT-22 score of 45.2 ± 16.6 were followed for a mean of 14.9 months. The majority of participants electing medical therapy failed to improve 1 MCID (57%) with a mean relative score improvement of 16%. Overall, 37% of patients maintained baseline SNOT-22 QOL status, whereas 20% of patients deteriorated >1 MCID. When treatment crossover patients (to endoscopic sinus surgery [ESS]) were included (n = 117), approximately 1 in 4 (27%) patients achieved an MCID.ConclusionResults from this study suggest that the majority of CRS patients electing ongoing medical management with low baseline disease-specific QOL impairment maintain stable QOL with continued medical management. Furthermore, of CRS patients electing ongoing medical therapy, approximately 1 in 4 patients achieved MCID, whereas 1 in 5 experienced deterioration by >1 MCID.

BackgroundThe Rhinosinusitis Disability Index (RSDI) consists of multiple subdomains shown to be useful in studying chronic rhinosinusitis (CRS). The objective of this study was to determine if RSDI subdomain scores are associated with selection of treatment modality (endoscopic sinus surgery [ESS] or continued medical management [CMM]) in subjects with CRS.MethodsPatients with CRS were prospectively enrolled into a multi-institutional cohort study. Following an initial period of medical management, patients elected to undergo treatment with either ESS or CMM. Baseline RSDI total and subdomain scores were compared between patients electing different treatment modalities.ResultsA total of 684 subjects were enrolled with 122 (17.8%) electing CMM and 562 (82.2%) electing ESS. When compared to patients undergoing CMM, patients electing ESS exhibited significantly higher mean baseline RSDI total scores (mean ± standard deviation [SD]: 48.1 ± 24.9 vs 40.1 ± 24.1; p = 0.001) and subdomain scores (emotional: 13.2 ± 9.1 vs 10.4 ± 8.3; p = 0.001; functional: 15.3 ± 8.9 vs 12.6 ± 8.4; p = 0.002; and physical: 19.6 ± 9.3 vs 17.1 ± 9.6; p = 0.007). Emotional subdomain scores were found to be the most associated with choice of treatment modality.ConclusionPatients with CRS electing ESS had worse baseline RSDI total and subdomain scores compared to those electing CMM. Although both rhinologic and nonrhinologic symptoms contributed to the selection of treatment modality, emotional symptoms appeared to exhibit the greatest influence on patient-centered treatment decisions.

BackgroundBoth obesity and chronic rhinosinusitis (CRS) are characterized by inflammation. Furthermore, both disease processes are independently associated with decreases in quality-of-life (QOL). We sought to investigate the role of comorbid obesity in QOL outcomes in CRS patients undergoing endoscopic sinus surgery (ESS).MethodsAdult patients with medically refractory CRS (n = 241) were prospectively enrolled into a multi-institutional treatment outcomes investigation. Body mass index (BMI) calculations were used to differentiate patient weight groups (normal weight: 18.5 to 24.9, overweight: 25.0 to 29.9; and obese: ≥30.0). Preoperative and postoperative QOL (Rhinosinusitis Disability Index [RSDI] and the 22-item Sino-Nasal Outcome Test [SNOT-22]) were evaluated compared across BMI groups and obesity subclasses.ResultsThe prevalence of comorbid obesity was 41% (n = 99). Higher prevalence of comorbid disease was found across increasing BMI groups including diabetes mellitus, asthma, and depression. No significant differences were found in mean preoperative QOL measures between any BMI groups. Significant improvement between preoperative and postoperative QOL mean scores (p ≤ 0.050) was found for all BMI groups. Despite no significant difference in mean QOL improvement between BMI groups (p ≥ 0.142), overweight and obese patients reported reduced relative mean percentage (%) improvement compared to normal weight participants on the RSDI total score (33% and 37% vs 55%, respectively) and SNOT-22 total score (29% and 40% vs 48%, respectively).ConclusionPatients with comorbid obesity experience significant improvement in average QOL gains following ESS though the percentage of relative improvement in QOL may be decreased in patients with comorbid obesity and CRS as compared to those without.

Summary: Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.