Biologics versus endoscopic sinus surgery: Acute rhinosinusitis episodes and antibiotic use in chronic rhinosinusitis.

BACKGROUND: We sought to determine if chronic rhinosinusitis patients treated with endoscopic sinus surgery have fewer episodes of acute rhinosinusitis (ARS) post treatment compared to CRS patients treated with biologics alone. METHODS: We analyzed the electronic medical records of 213 adults with CRS who initiated treatment with either dupilumab or mepolizumab in calendar years 2016-2021 (CRS-biologics) group and a matched group with tissue eosinophilia who had undergone endoscopic sinus surgery (CRS-ESS) group. For each cohort, the medical record was reviewed to determine the number of ARS episodes for 12 months before and after treatment. Similarly, the number of antibiotic prescriptions was determined for each cohort in the 12 months after initiation of biologic therapy or ESS. RESULTS: There was no statistically significant difference in ARS episodes before initiation of between the CRS-biologic and CRS-ESS cohorts (0.38 versus 0.44 episodes per year, respectively; p = 0.323). In contrast, after initiation of therapy, the CRS-biologics group had a significantly reduced frequency of acute rhinosinusitis episodes versus the CRS-ESS group (0.11 versus 0.25 episodes per year; p = 0.001). Finally, the utilization of oral antibiotics in the 12 months after among those treated with biologics versus those treated with ESS was not significantly different (0.04 versus 0.08, respectively; p = 0.109). CONCLUSION: For CRS patients, treatment with dupilumab or mepolizumab significantly reduced the number of ARS episodes compared to CRS treated with ESS. Biologics appear to work as well as ESS in the control of ARS episodes after treatment for CRS.

TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

Diagnostic Yield of Patients Undergoing Evaluation of Possible Superior Canal Dehiscence.

OBJECTIVE: To characterize the diagnostic yield of patients undergoing evaluation for superior canal dehiscence syndrome (SCDS), and identify alternative conditions diagnosed in patients suspected of, but not ultimately diagnosed with, SCDS. METHODS: Diagnostically undifferentiated adult patients suspected of having SCDS were identified between 2016 and 2021 at a tertiary academic medical system. Patients were categorized by diagnostic testing, radiographic superior semicircular canal (SSC) abnormality, symptoms, evaluating clinician specialty, operative intervention, and diagnosis. Differences among groups were assessed for statistical significance. RESULTS: Of 1242 candidate patients, 477 met inclusion criteria-evaluation by a clinician with SCDS on their differential diagnosis prior to diagnostic imaging. The mean (SD) age was 53.0 (15.0) years and 70.6% were female. A total of 364 patients underwent subsequent diagnostic imaging, and among these, 164 (45.1%) had a radiographic SSC abnormality with 99 (27.2%) receiving a diagnosis of SCDS (two cases of "near dehiscence syndrome"). One third (33.3%) of patients with SCDS underwent operative repair. Most clinicians with the initial suspicion for SCDS were otolaryngologists (90.6%), who had greater diagnostic yield than clinicians from other specialties (22.2% vs. 6.7%, p = 0.012). Patients not diagnosed with SCDS alternatively received 21 unique diagnoses and 52.1% (138/265) were not definitively diagnosed with any condition. CONCLUSIONS: This study characterizes the diagnostic incidence, or yield, of newly identified radiographic SSC abnormalities (45.1%) and SCDS (27.2%) among people suspected of having SCDS. Considerable overlap in presentation between SCDS and other conditions exists, and there is need for improvement in efficiently diagnosing patients with SCDS and audio-vestibular complaints in general. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Evolving Utilization of Topical Budesonide Following Endoscopic Sinus Surgery.

Topical budesonide irrigations are frequently prescribed after endoscopic sinus surgery (ESS) to manage mucosal inflammation. However, this off-label indication may conflict with health insurance formularies. We sought to quantify the relative frequency of postoperative budesonide prescriptions to determine if this could be considered common practice after ESS. We extracted and analyzed postoperative prescription data for patients undergoing ESS from 2016 to 2022 within our health care system. Overall, among 8157 ESS patients, 15.9% and 22.1% received topical budesonide prescriptions within 30 or 180 days postoperatively, respectively. On a year-over-year basis, budesonide prescription frequency increased significantly over time, culminating at 20.3% and 24.9% in 2022. Conversely, postoperative oral corticosteroid (OCS) prescriptions showed a decreasing frequency over the same time period (P < .001). Our results show topical budesonide irrigations are increasingly frequently prescribed after ESS and may offset postoperative OCS requirements. This argues for coverage of topical budesonide as a formulary medication after ESS.

Increasing Prevalence of Voice Disorders in the USA: Updates in the COVID Era.

OBJECTIVE: To estimate the current prevalence of voice disorders among adults in the United States; to determine the association of individual factors with voice disorders. METHODS: The 2022 National Health Interview Survey (NHIS) was analyzed to identify adults reporting voice problems in the past 12 months. Demographics were assessed, as well as the duration, severity, and resolution of the voice problem. The relationship between voice problems, gender, lost workdays, and long COVID was investigated. A comparison to the 2012 NHIS was made to determine changes in voice disorder prevalence. RESULTS: 29.9 million Americans (95%CI[28.3-31.5]) annually report a voice problem, representing 12.2% of the population (95%CI[11.7-12.8%]). Overall, 26.8% and 13.2% reported the severity of their voice problem as moderate or severe, respectively. Only 5.1% (95%CI[4.3-6.0%]) of respondents sought treatment. Most voice problems were resolved within 1 week (53.0%,95%CI[50.9-55.1%]). Females were more likely than males to report a voice problem (14.4% vs. 10.0%,95%CI[13.7-15.1] and [9.3-10.7], respectively). The 17.6 million Americans with long COVID symptoms were more likely to have voice complaints than those without (21.1% vs. 11.6%,95%CI[18.9-23.5%] and [11.1-12.1%], respectively). Lost workdays were not significantly higher for those with voice disorders compared to those without (17.1 vs. 12.9 days,95%CI[12.0-22.1] and [11.0-14.8], respectively). CONCLUSIONS: Voice problems affect approximately 1 in 8 adults in the U.S. annually, demonstrating an alarming increased prevalence since 2012 using the same survey methodology. Relatively few individuals seek care for their voice problem, despite significant self-reported impact. Further study is required regarding the impact of COVID and changes in voice use patterns on voice disorders. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Real-world effectiveness of mepolizumab in severe asthma and chronic rhinosinusitis in the United States: Impact of comorbidity and sinus surgery.

BACKGROUND: Trial data demonstrate that mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, is effective for patients with severe asthma and comorbid chronic rhinosinusitis (CRS) with nasal polyps. This real-world, retrospective cohort study investigated mepolizumab for US patients with severe asthma and CRS with/without sinus surgery. METHODS: IQVIA PharMetrics Plus claims data from baseline and follow-up (12 months before and after mepolizumab initiation) were used to analyze three patient cohorts: cohort 1 (severe asthma only); cohort 2 (severe asthma + comorbid CRS without sinus surgery); and cohort 3 (severe asthma+comorbid CRS+sinus surgery), allowing for cross-cohort comparisons. RESULTS: The analysis included 495, 370, and 85 patients in cohort 1, cohort 2, and cohort 3, respectively. Systemic and oral corticosteroid use was lower for all cohorts after mepolizumab initiation. In cohort 3, asthma rescue inhaler and antibiotic use were lower during follow-up than baseline. Asthma exacerbations were reduced by 28% to 44% comparing follow-up versus baseline, with the largest reduction in cohort 3 (ratio of incidence rate ratio [RR] vs cohort 1: 0.76; p = 0.036). Reductions in oral corticosteroid claims were greater following mepolizumab initiation for cohort 3 versus cohort 1 (RR, 0.72; p = 0.011) and cohort 2 (RR, 0.70; p < 0.01). In cohorts 1 through 3, outpatient and emergency department visits were reduced by 1 to 2 and 0.4 to 0.6 visits annually, asthma-related and asthma exacerbation-related total costs were reduced by $387 to $2580 USD, and medical costs were reduced by $383 to $2438 USD during follow-up. CONCLUSIONS: Consistent with trial data, mepolizumab use in real-world practice shows benefits across comorbid patient cohorts with more a pronounced impact in those with severe asthma+comorbid CRS + sinus surgery.

Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis. OBJECTIVE: We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP. METHODS: NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing. RESULTS: Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes. CONCLUSION: NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP.

Increased epithelial mTORC1 activity in chronic rhinosinusitis with nasal polyps.

Background: The airway epithelium plays a central role in the pathogenesis of chronic respiratory diseases such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), but the mechanisms by which airway epithelial cells (EpCs) maintain inflammation are poorly understood. Objective: We hypothesized that transcriptomic assessment of sorted airway EpCs across the spectrum of differentiation would allow us to define mechanisms by which EpCs perpetuate airway inflammation. Methods: Ethmoid sinus EpCs from adult patients with CRS were sorted into 3 subsets, bulk RNA sequenced, and analyzed for differentially expressed genes and pathways. Single cell RNA-seq (scRNA-seq) datasets from eosinophilic and non-eosinophilic CRSwNP and bulk RNA-seq of EpCs from mild/moderate and severe asthma were assessed. Immunofluorescent staining and ex vivo functional analysis of sinus EpCs were used to validate our findings. Results: Analysis within and across purified EpC subsets revealed an enrichment in glycolytic programming in CRSwNP vs CRSsNP. Correlation analysis identified mammalian target of rapamycin complex 1 (mTORC1) as a potential regulator of the glycolytic program and identified EpC expression of cytokines and wound healing genes as potential sequelae. mTORC1 activity was upregulated in CRSwNP, and ex vivo inhibition demonstrated that mTOR is critical for EpC generation of CXCL8, IL-33, and CXCL2. Across patient samples, the degree of glycolytic activity was associated with T2 inflammation in CRSwNP, and with both T2 and non-T2 inflammation in severe asthma. Conclusions: Together, these findings highlight a metabolic axis required to support epithelial generation of cytokines critical to both chronic T2 and non-T2 inflammation in CRSwNP and asthma.

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.

Balance Disorder Trends in US Adults 2008-2016: Epidemiology and Functional Impact.

Objective: To quantify the changes in prevalence and impact of dizziness and balance disorders in adults from 2008 to 2016. Study Design: Epidemiological survey analysis. Setting: United States. Methods: The balance modules of the adult 2008 and 2016 National Health Interview Surveys were examined, and persons reporting dizziness or balance problems identified. The prevalence of balance problems was determined and compared over time, adjusting for age and sex. Among those with balance problems, associated symptoms and self-reported functional limitations were quantified and compared over time. Results: In 2016, 36.8 ± 1.0 million (15.5% ± 0.3%) adults reported a balance problem in the past year, versus 24.2 ± 0.7 million (11.% ± 0.3%) in 2008 (p < .001). After adjustment for age and sex, this percentage increase remained significant (odds ratio 1.435 [1.332-1.546], p < .001). Among those with balance problems, significantly more patients reported specific issues with feeling: off-balance (69.4% vs. 65.4%; p = .005), faint (48.5% vs. 40.3%; p < .001), or vertiginous (45.9% vs. 39.3%; p < .001) in 2016 than 2008. More adults experienced anxiety (29.4% vs. 19.4%; p < .001) and depression (16.3% vs. 12.9%; p = .002) with their balance problems in 2016 than in 2008. In 2016, adults with balance problems were limited in ability to drive motor vehicles (13.0%), exercise (14.4%), or walk downstairs (12.8%). These rates were not significantly different from 2008 (all p > .05). Conclusion: In this nationally representative analysis, we found a significantly increasing prevalence of balance problems and associated psychiatric symptom burden. This merits attention with respect to present and future health care resource allocation.

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.

Associations between chronic pain, anxiety, and depression among adults in the United States.

OBJECTIVE: The objective of the study was to determine the associations of depression and anxiety with chronic pain among U.S. adults. SETTING: Nationally representative cross-sectional survey analysis. METHODS: The National Health Interview Survey for 2019 was analyzed with respect to the chronic pain module and embedded depression and anxiety scales (PHQ-8 and GAD-7). Univariate associations between the presence of chronic pain and depression and anxiety scores were determined. Similarly, associations between the presence of chronic pain and the adults' treating with medications for depression and anxiety were also determined. Odds ratios, adjusted for age and sex, were computed for these associations. RESULTS: Among 244.6 million sampled U.S. adults, 50.2 million (95% confidence interval, 48.2-52.2 million) reported chronic pain (20.5%, [19.9%-21.2%] of the population). Adults with chronic pain had elevated severity of depressive symptoms (PHQ-8 categories: none/minimal: 57.6%, mild: 22.3%, moderate: 11.4%, and severe: 8.7%) versus those without chronic pain (87.6%, 8.8%, 2.3%, and 1.2%; p < 0.001). Adults with chronic pain had elevated severity of anxiety symptoms (GAD-7 categories: none/minimal: 66.4%, mild: 17.1%, moderate: 8.5%, severe: 8.0%) versus those without chronic pain (89.0%, 7.5%, 2.1%, and 1.4%; p < 0.001). 22.4% and 24.5% of chronic pain sufferers were taking medication for depression and anxiety versus 6.6% and 8.5% of those without chronic pain, respectively (both p < 0.001). Adjusted odds ratios for the association of chronic pain with increasing severity of depression or anxiety and taking a depression or anxiety medication were 6.32 (5.82-6.85), 5.63 (5.15-6.15), 3.98 (3.63-4.37), and 3.42 (3.12-3.75), respectively. CONCLUSIONS: The presence of chronic pain in adults associated with significantly higher severity scores for both anxiety and depression as measured by validated surveys in a nationally representative sample. The same is true for the association between chronic pain and an adult taking medication for depression and/or anxiety. These data highlight the impact of chronic pain has on psychological well-being within the general population.

Rethinking the relationships between chronic rhinosinusitis and asthma severity.

BACKGROUND: Previous authors have endorsed the need for prospective studies on the effect of treatment of chronic rhinosinusitis on asthma outcomes. Although common pathophysiology for asthma and chronic rhinosinusitis (CRS) has been suggested with the unified airway theory, there is limited data to support the claim and our study does not support the theory. METHODS: This case-control study involved adult patients with a primary diagnosis of asthma in 2019 who were identified from the electronic medical records and divided into those with and without an associated CRS diagnosis. For each asthma encounter, the asthma severity classification, oral corticosteroid (OCS) use and oxygen saturation scores were tabulated and compared between asthma patients with CRS versus control patients after 1:1 matching on age and sex. We determined the association between asthma and chronic rhinosinusitis when evaluating proxies for disease severity: oral corticosteroid use, average oxygen saturation and minimum oxygen saturation. We identified 1321 clinical encounters for asthma associated with CRS and 1321 control encounters for asthma without CRS. RESULTS: OCS prescription rates at the asthma encounter were not statistically different between the groups (15.3 % and 14.6 %, respectively; p = 0.623). Asthma severity classification was higher in those with CRS versus those without (38.9 % and 25.7 % classified as severe, respectively; p < 0.001). We identified 637 asthma with CRS and 637 matched control patients. There was no significant difference in mean recorded O2 saturations between asthma patients with CRS versus control patients (mean O2 saturations, 97.2 % and 97.3 %, respectively; p = 0.816) nor in minimum oxygen saturation (96.8 % and 97.0 %, respectively; p = 0.115). CONCLUSION: Among patients with a primary diagnosis of asthma an increasing severity of asthma classification was significantly associated with an associated diagnosis of CRS. In contradistinction, the presence of CRS comorbidity in asthma patients was not associated with increased OCS use for asthma. Similarly, average oxygen saturation and minimum oxygen saturation did not seem differ according to CRS comorbidity. Our study does not support the unified airway theory that suggests a causative relationship between the upper and lower airway.

Voice Disorders Associated With the Use of Inhaled Corticosteroids.

OBJECTIVE: Inhaled corticosteroids (ICS) have been demonstrated to be associated with voice changes. The goal was to determine the strength of the association between ICS use and a diagnosis of dysphonia made by an otolaryngologist and to determine whether inhaler particle type or medication type influenced this risk. STUDY DESIGN: A case-control study from 2018 to 2020. SETTING: Urban academic medical system. METHODS: Adult patients with dysphonia diagnosed by an otolaryngologist, and control patients matched on age, gender, race, and health status, were included. Exposure to ICS was assessed, and the odds ratio (OR) of the association of ICS with dysphonia was calculated. RESULTS: A total of 6551 cases and 6551 matched controls were included. We found that ICS use was significantly associated with dysphonia (OR: 5.11, 95% confidence interval: 4.23-6.17, p < .001). Subset analyses demonstrated no significant differences between inhaler particle types or specific active medications. CONCLUSION: This study emphasizes the importance of identifying ICS use in the evaluation and treatment of patients with dysphonia.

Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal cells (BCs). Recent studies have identified transcriptionally distinct BCs, but the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown. OBJECTIVE: We sought to determine the role of T2 cytokines in regulating airway BCs. METHODS: Single-cell and bulk RNA sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of inhibitors of IL-4R signaling. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and regeneration. RESULTS: Two subsets of BCs were found in human and murine respiratory mucosa distinguished by the expression of basal cell adhesion molecule (BCAM). BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. In the sinonasal mucosa, BCAMhi BCs expressing TSLP, IL33, CCL26, and the canonical BC transcription factor TP63 are increased in patients with CRSwNP. In cultured BCs, IL-4/IL-13 increases the expression of BCAM and TP63 through an insulin receptor substrate-dependent signaling pathway that is increased in CRSwNP. CONCLUSIONS: These findings establish BCAM as a marker of airway stem cells among the BC pool and demonstrate that airway epithelial remodeling in T2 inflammation extends beyond goblet cell metaplasia to the support of a BC stem state poised to perpetuate inflammation.

The prevalence of opioid medication use among adults in the United States.

OBJECTIVE: More than one in five American adults experiences chronic pain, and numerous approaches can be used to treat chronic pain. Opioid analgesics are commonly used to treat pain though precise estimates of the prevalence of opi-oid analgesic use vary widely. This study sought to determine the prevalence of opioid use for pain among adults in the United States. METHODS: We performed a retrospective analysis of the National Health Interview Survey, a national-level house-hold-based annual survey of self-reported health status of US adults, using a chronic pain module introduced in the 2019 edition. We examined overall rates of opioid medication use for pain and correlates of opioid use using survey-weighted analyses. RESULTS: We found 30.8 million adults (95 percent CI: 29.3-32.3 million), or 12.3 percent (11.8-12.8) of the population, had used opioids for pain in the preceding 12 months, while 9.3 million (8.6-10.0 million), or 3.7 percent (3.5-4.0), had used opioids for chronic pain in the preceding 3 months. Individuals reporting pain every day were more likely to have used opi-oids than those experiencing pain less frequently. Individuals who had tried other methods such as physical therapy and self-management programs were more likely to have used opioids. Individuals who used opioids for pain were more likely to report poorly controlled pain, with 38.0 percent (31.5-45.0) reporting their pain management was "not at all effective." CONCLUSIONS: Opioid use for chronic pain is common and frequently part of a multimodal and multidisciplinary approach.

Profiling Disease and Economic Burden in CRSwNP Using Machine Learning.

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with high healthcare resource utilization (HRU) and economic cost; however, heterogeneity of clinical burden among patients with differing clinical characteristics has not been fully elucidated. Here, an unsupervised machine learning approach supported by clinical validation identified distinct clusters of patients with CRSwNP and compared healthcare burden. Patients and Methods: This retrospective analysis identified adult patients with ≥2 claims for CRSwNP and date of first diagnosis (index date) between January 2015 and June 2019 from a healthcare database. Patients were required to have enrollment in the database 6-months pre- and 12-months post-index. Patients were assigned to clusters using latent class analysis. All-cause and nasal polyp (NP)-related HRU and costs were compared between clusters. Results: Among 12,807 patients, 5 clusters were identified: cluster 1: no surgery/low comorbidity/low medication use (n = 4076); cluster 2: no surgery/low comorbidity/high medication use (n = 2201); cluster 3: no surgery/high comorbidity/high medication use (n = 2093); cluster 4: surgery/low comorbidity/moderate medication use (n = 3168); cluster 5: surgery/high comorbidity/high medication use (n = 1269). All-cause HRU was similar across clusters. NP-related HRU was highest in the surgical clusters (clusters 4 and 5). All-cause costs were similar in clusters 1-3 ($15,833-$17,461) and highest in clusters 4 ($31,083) and 5 ($31,103), driven by outpatient costs. Total NP-related costs were also highest for clusters 4 and 5 ($14,193 and $16,100, respectively). Conclusion: Substantial heterogeneity exists in clinical and economic burden among patients with CRSwNP. Machine learning offers a novel approach to better understand the diverse, complex burden of illness in CRSwNP.

The association between sleep disorders, employment, and income among adults in the United States.

STUDY OBJECTIVES: To examine the association between sleep disorders, employment status, and income among US adults aged 18-64 years. METHODS: The 2018-2019 Medical Expenditure Panel Survey medical conditions file was queried for adults aged 18-64 years with a diagnosis of a sleep disorder (International Classification of Diseases, 10th Revision, code G47.x) and linked to the household dataset. Comparisons in rates of wage, supplemental, and social security income as well as mean wage income were made between those with and without sleep disorders. Multivariate analyses, adjusting for demographics and comorbidities, were conducted. RESULTS: A sleep disorder was diagnosed in 4.4% ± 0.2% of the study population (approximately 8.8 ± 0.4 million adults aged 18-64 years in the United States; mean age 46.9 years, 55.8% female). Adults with sleep disorders were less likely to have wage income from employment (adjusted odds ratio 0.5, 95% confidence interval 0.4-0.6, P < .001) and more likely to have Supplemental Security (1.8, 1.4-2.4, P < .001) and Social Security income (2.0, 1.6-2.4, P < .001) compared with those without sleep disorders. Among wage-earning adults, those with sleep disorders had $2,496 less mean annual wage income compared with those without a sleep disorder ($20,445 vs $22,941, P = .007), adjusting for demographics and comorbidities. CONCLUSIONS: There are significantly higher indirect costs associated with sleep disorders. This study specifically demonstrates lower employment rates, lower wages, and higher welfare income utilization among those with sleep disorders despite using a very conservative estimate of sleep disorder prevalence. CITATION: Huyett P, Bhattacharyya N. The association between sleep disorders, employment, and income among adults in the United States. J Clin Sleep Med. 2022;18(8):1967-1972.