The Inflation Reduction Act: Implications for Medicare spending and access to biologic therapies for chronic rhinosinusitis with nasal polyposis and asthma.

KEY POINTS: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA). Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%. Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%-60%.

Aerosolized Particulate Matter and Blunting of Ciliary Dynamic Responses: Implications for Veterans and Active Duty Military in Southwest Asia.

INTRODUCTION: Respiratory diseases such as chronic rhinosinusitis and asthma are observed at increased rates in active duty and veteran military members, and they are especially prevalent in individuals who have been deployed in Southwest Asia during Operation Iraqi Freedom and Operation Enduring Freedom. Particulate matter, specifically the fine-grain desert sand found in the Middle East, may be a key source of this pathology because of deleterious effects on mucociliary clearance. MATERIALS AND METHODS: With IRB approval, human sinonasal tissue was grown at an air-liquid interface and cultures were exposed to different types and sizes of particulate matter, including sand from Afghanistan and Kuwait. Ciliary dynamic responses to mechanical stimulation and ATP application were assessed following particulate exposure. RESULTS: Particle size of the commercial sand was substantially larger than that of the sand of Afghan or Kuwaiti origin. Following exposure to particulate matter, normal dynamic ciliary responses to mechanical stimulation and ATP application were significantly decreased (P < .01), with corresponding decreases in ATP-induced calcium flux (P < .05). These changes were partially reversible with apical washing after a 16-h period of exposure. After 36 h of exposure to Middle Eastern sand, ciliary responses to purinergic stimulation were completely abolished. CONCLUSIONS: There is a neutralization of the dynamic ciliary response following chronic particulate matter exposure, similar to ciliary pathologies observed in patients with chronic rhinosinusitis. Aerosolized particulate matter endured by military personnel in the Southwest Asia may cause dysfunctional mucociliary clearance; these data help to explain the increased prevalence of respiratory pathology in individuals who are or have been deployed in this region.

Utilizing Histopathology to Predict Success with Macrolide Therapy in CRS Patients.

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022.

KEYPOINTS: Between 2007 and 2022, the FDA received 119 US-based reports mentioning budesonide nasal irrigation. Most reports were submitted by patients and alerted FDA to off-label usage of budesonide. Notable adverse events reported to the FDA included headache, dyspnea, and blurred vision.

Utility of a LangChain and OpenAI GPT-powered chatbot based on the international consensus statement on allergy and rhinology: Rhinosinusitis.

KEY POINTS: We created a LangChain/OpenAI API-powered chatbot based solely on International Consensus Statement of Allergy and Rhinology: Rhinosinusitis (ICAR-RS). The ICAR-RS chatbot is able to provide direct and actionable recommendations. Utilization of consensus statements provides an opportunity for AI applications in healthcare.

Risk of inpatient epistaxis admission related to oral anticoagulation medication use.

We utilized a case control study to determine if novel oral anticoagulants were associated with a higher risk of inpatient epistaxis admission. Adult patients admitted with a principal diagnosis of epistaxis in 2019-2021 were identified as well as a control group of patients matched 1:1 for age, sex, race, and medical comorbidities. For both cohorts, the presence or absence of an oral anticoagulant, classified as vitamin K inhibitors, direct oral anticoagulants (DOAC) or platelet inhibitors, was identified. 158 adult unique inpatient admissions with a principal diagnosis of epistaxis were identified. Vitamin K inhibition was present in 5.7% of cases versus 0.6% of controls (p = 0.02; OR 9.48, range 1.19-75.77), DOACs in 4.4% of cases versus 5.1% of controls (p = 1.0) and platelet inhibitors in 2.5% of cases versus 3.8% of controls (p = 0.75). We concluded vitamin K inhibitors, compared to DOACs and platelet inhibitors, may be associated with higher likelihood of epistaxis admission.

Smell and Taste Loss Associated with COVID-19 Infection.

OBJECTIVE: The aim of this study was to quantify the impact of COVID-19 on olfactory and gustatory function in US adults. METHODS: From the 2021 Adult National Health Interview Survey, demographic and survey-specific module data concerning COVID-19 diagnoses, testing and disease severity, and data quantifying disturbances and eventual recovery of smell and taste were extracted. Sample weights were applied to obtain nationally representative statistics. The overall rate of COVID-19 infection was determined, and those diagnosed with COVID-19 were analyzed with respect to disease severity, smell and taste disturbance, and respective recoveries. RESULTS: In 2021, 35.8 million or 14% of the adult population (95% CI 13.5-14.7%; mean age, 43.9 years; 53.8% female) had been diagnosed with COVID-19. Among those, 60.5% (58.6-62.5%) and 58.2% (56.2-60.1%) reported accompanying losses  in smell or taste, respectively; there was a significant association between overall COVID-19 symptom severity and smell (p < 0.001) and taste disturbance (p < 0.001). Following infection, 72.2% (69.9-74.3%), 24.1% (22.2-26.2%), and 3.7% (3.0-4.6%) of the patients experienced complete, partial, and no smell recovery, respectively. Recovery rates for gustatory function paralleled olfaction, with 76.8% (74.6-78.9%), 20.6% (18.7-22.7%), and 2.6 (1.9-3.4%) reporting complete, partial, and no recovery of taste, respectively. When sensory disturbance was present, severity of overall symptomatology was negatively associated with smell and taste recovery (p < 0.001 for each). CONCLUSION: The majority of adults infected with COVID-19 in 2021 experienced olfactory or gustatory dysfunction with a non-negligible population reporting incomplete or no near-term sensory recovery. Our results are useful for providers counseling patients and suggest that interventions lessening overall COVID-19 symptom burden may prevent prolonged sensory dysfunction. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2357-2361, 2023.

Rates of Antidepressant, Anxiolytic, and ADHD Medication Use Among Patients Undergoing ESS.

Patients with chronic rhinosinusitis (CRS) are estimated to have psychiatric comorbidity at a higher rate than the general population; however, self-report of depression diagnoses or symptoms often underestimates true prevalence in many populations. In the present study, a cohort of 2279 patients undergoing endoscopic sinus surgery (ESS) were matched to an equal number of non-CRS control subjects by age, sex, race and health status. Overall, the rate of antidepressant/anxiolytic utilization among ESS patients was 22.1%versus 11.3% for controls (P < .001, OR = 2.23, 95% CI 1.90-2.63). The rate of ADHD medication utilization among ESS patients was 3.6%versus 2.0% for controls (P = .001, OR = 1.85, 95% CI 1.28-2.68). This study suggests that patients undergoing ESS exhibit significantly higher rates of antidepressant and ADHD medication utilization relative to a matched control population.

Trends in price, spending, and utilization of omalizumab among Medicare beneficiaries.

KEY POINTS: Between January 2005 and January 2023, the average selling price of omalizumab increased by nearly 60%. Between 2016 and 2021, Medicare Part B and D spending on omalizumab totaled over $3.7 billion. Between 2016 and 2021, Medicare Part B and D utilization of omalizumab increased by approximately 30%.

Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors.

BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.

Clinically meaningful changes in efficacy outcomes in chronic rhinosinusitis with nasal polyposis.

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) carries a high disease burden, and many studies have been done investigating the efficacy of various medical and surgical therapies. However, outcome metrics have varied across these studies, making it difficult to compare therapeutic efficacy on a large scale. In this article, we discuss various outcome metrics used across prior studies as well as the relationship between these measures. RECENT FINDINGS: Outcome metrics in CRSwNP studies include both clinically assessed and patient-reported outcome measures (PROMs). The former includes olfaction testing, scoring systems based on imaging and endoscopic evaluation, and histopathological and immunohistochemical evaluation of sinus tissue, and the latter includes quality-of-life instruments, symptom severity scales, and disease-control instruments. Recent studies evaluating the efficacy of new biologics have used a combination of both types of metrics. SUMMARY: Both clinical metrics and patient-reported outcomes provide utility in evaluating disease severity and control in patients with CRSwNP, although there are nuances when comparing therapies in this population as patients with CRSwNP are heterogeneous and may have symptoms across several domains. However, PROMs in conjunction with clinical metrics provide useful information to assess patient symptoms and response to interventions.

Cold exposure impairs extracellular vesicle swarm-mediated nasal antiviral immunity.

BACKGROUND: The human upper respiratory tract is the first site of contact for inhaled respiratory viruses and elaborates an array of innate immune responses. Seasonal variation in respiratory viral infections and the importance of ambient temperature in modulating immune responses to infections have been well recognized; however, the underlying biological mechanisms remain understudied. OBJECTIVE: We investigated the role of nasal epithelium-derived extracellular vesicles (EVs) in innate Toll-like receptor 3 (TLR3)-dependent antiviral immunity. METHODS: We evaluated the secretion and composition of nasal epithelial EVs after TLR3 stimulation in human autologous cells and fresh human nasal mucosal surgical specimens. We also explored the antiviral activity and mechanisms of TLR3-stimulated EVs against respiratory viruses as well as the effect of cool ambient temperature on TLR3-dependent antiviral immunity. RESULTS: We found that polyinosinic:polycytidylic acid, aka poly(I:C), exposure induced a swarm-like increase in the secretion of nasal epithelial EVs via the TLR3 signaling. EVs participated in TLR3-dependent antiviral immunity, protecting the host from viral infections through both EV-mediated functional delivery of miR-17 and direct virion neutralization after binding to virus ligands via surface receptors, including LDLR and ICAM-1. These potent antiviral immune defense functions mediated by TLR3-stimulated EVs were impaired by cold exposure via a decrease in total EV secretion as well as diminished microRNA packaging and antiviral binding affinity of individual EV. CONCLUSION: TLR3-dependent nasal epithelial EVs exhibit multiple innate antiviral mechanisms to suppress respiratory viral infections. Furthermore, our study provides a direct quantitative mechanistic explanation for seasonal variation in upper respiratory tract infection prevalence.

Aerosol Generation During Nasal Airway Instrumentation.

OBJECTIVE: Airborne aerosol transmission, an established mechanism of SARS-CoV-2 spread, has been successfully mitigated in the health care setting through the adoption of universal masking. Upper airway endoscopy, however, requires direct access to the face, thereby potentially exposing the clinic environment to infectious particles. This study quantifies aerosol production during rigid nasal endoscopy (RNE) and RNE with debridement (RNED) as compared with intubation, a posited gold standard aerosol-generating procedure. STUDY DESIGN: Prospective cross-sectional study. SETTING: Subspecialty single-center clinic and surgical study. METHOD: Three aerosol detectors (NANOSCAN-3910, OPS-3330, and APS-3321) with a particle size sensitivity of 10 to 20,000 nm were utilized to detect particulate production during the clinical care of 209 patients undergoing RNE/RNED and 25 patients undergoing intubation. RESULTS: RNE and RNED produced statistically significant particles over baseline in 29.3% and 51.0% of subjects (P = .003-.049 and .002-.047, respectively). Intubation produced statistically significant particles in 31.2% (P = .001-.015). The mean ± SD particle diameter in all tests was 69.9 ± 10.5 nm with 99.7% <300 nm. There were no statistical differences in particle production among RNE, RNED, and intubation. The presence of concomitant cough, sneeze, or prolonged speech similarly did not significantly affect particle production during any procedure. CONCLUSIONS: Instrumentation of nasal airway produces airborne aerosols to a similar degree of those seen during intubation, independent of reactive patient behaviors such as cough or sneeze. These data suggest that an improved understanding is necessary of both the definition of an aerosol-generating procedure and the functional consequences of procedural aerosol generation in clinical settings.

Cystatin SN is a potent upstream initiator of epithelial-derived type 2 inflammation in chronic rhinosinusitis.

BACKGROUND: Cystatin SN (CST1) and cystatin SA (CST2) are cysteine protease inhibitors that protect against allergen, viral, and bacterial proteases. Cystatins are overexpressed in the setting of allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP); however, their role in promoting type 2 inflammation remains poorly characterized. OBJECTIVE: The purpose of this study was to use integrated poly-omics and a murine exposure model to explore the link between cystatin overexpression in CRSwNP and type 2 inflammation. METHODS: In this institutional review board- and institutional animal care and use committee-approved study, we compared tissue, exosome, and mucus CST1 and CST2 between CRSwNP and controls (n = 10 per group) by using matched whole exome sequencing, transcriptomic, proteomic, posttranslational modification, histologic, functional, and bioinformatic analyses. C57/BL6 mice were dosed with 3.9 µg/mL of CST1 or PBS intranasally for 5 to 18 days in the presence or absence of epithelial ABCB1a knockdown. Inflammatory cytokines were quantified by using Quansys multiplex assays or ELISAs. RESULTS: Of the 1305 proteins quantified, CST1 and CST2 were among the most overexpressed protease inhibitors in tissue, exosome, and mucus samples; they were localized to the epithelial layer. Multiple posttranslational modifications were identified in the polyp tissue. Exosomal CST1 and CST2 were strongly and significantly correlated with eosinophils and Lund-Mackay scores. Murine type 2 cytokine secretion and TH2 cell infiltration increased in a time-dependent manner following CST1 exposure and was abrogated by epithelial knockdown of ABCB1a, a regulator of epithelial cytokine secretion. CONCLUSION: CST1 is a potent upstream initiator of epithelial-derived type 2 inflammation in CRSwNP. Therapeutic strategies targeting CST activity and its associated posttranslational modifications deserve further interrogation.

Surgical Considerations in Endoscopic Pituitary Approaches for the Otolaryngologist.

Advances in endoscopic surgical technique have ushered in a new era of pituitary surgery with improved rates of resection and minimized operative morbidity and burden. Anatomically, endoscopic transnasal transsphenoidal pituitary surgery is split into nasal, sphenoidal, and sellar stages, each with unique considerations. Recent developments in knowledge and technology seek to build on the success of the endoscope in pituitary surgery, while expanding its capabilities.

Spending and Utilization on Drugs Prescribed by Otolaryngologists to Medicare Beneficiaries, 2013 to 2017.

OBJECTIVES: The significant and rising cost of prescription drugs is a pressing concern for patients and payers. However, little is known about spending on and utilization of drugs prescribed by otolaryngologists. METHODS: Utilizing publicly available Medicare Part D Prescriber Public Use data, we conducted a retrospective cross-sectional analysis of 34 small-molecule drugs commonly prescribed by otolaryngologists (defined as 2017 Medicare Part D spending ≥$500 000) to Medicare beneficiaries. Prescription data was characterized by drug type (brand name vs generic). Primary outcomes for each prescription drug included the total annual cost and the total annual number of days supplied. RESULTS: From 2013 to 2017, spending on drugs prescribed by otolaryngologists to Medicare beneficiaries decreased by $32.1 million ($131.7-$99.5 million; relative decrease 24.4%; compound annual growth rate [CAGR] -5.4%), while total utilization increased by 24.9 million days supplied (74.6-99.5 million; relative increase 33.3%; CAGR 5.9%). For brand name drugs, there was a decrease in spending ($71.1-$26.7 million; relative decrease -62.4%; CAGR -17.8%) and utilization (11.2-3.1 million days supplied; relative decrease -72.5%; CAGR -22.8%). In contrast, generic drugs demonstrated increased spending ($60.6-$72.8 million; relative increase 20.2%; CAGR 3.7%) and utilization (63.5-96.4 million days supplied; relative increase 51.9%; CAGR 8.7%). CONCLUSIONS: Spending on drugs prescribed by otolaryngologists to Medicare Part D beneficiaries declined between 2013 and 2017 in part due to a transition from brand name drugs to lower-cost generic equivalents.

Chronic Rhinosinusitis and the Risk of Erectile Dysfunction.

Chronic rhinosinusitis is a common disease associated with reductions in quality of life across a range of measures, including sexual health. We conducted a case-control study assessing chronic rhinosinusitis prevalence among men with and without clinically significant erectile dysfunction. We found that chronic rhinosinusitis was significantly associated with erectile dysfunction (odds ratio = 2.0, 95% CI = 1.8-2.4, P < .001) and that this association remained significant even when the interval between chronic rhinosinusitis diagnosis and erectile dysfunction treatment was restricted. This study adds to a growing body of literature demonstrating an association between chronic rhinosinusitis and sexual dysfunction.

Rate of COVID-19 Infection in Patients Following Otolaryngology vs Non-otolaryngology Outpatient Encounters.

Routine outpatient otolaryngology visits have been identified as potential vectors for increased transmission of COVID-19 relative to other medical encounters. This is in part due to the inability of patients to mask during comprehensive otolaryngology examination and potential propensity for aerosolization during upper airway procedures, including endoscopy and nasopharyngoscopy. Using a matched-cohort sampling of >20,000 patients seen between April 2020 and January 2021, we found no increased rate of postvisit COVID-19 positivity following an in-office otolaryngology encounter relative to other non-otolaryngology outpatient encounters. This suggests that the perceived elevated risk of provider-to-patient and patient-to-patient transmission during outpatient otolaryngologic care may be unfounded.