RESUMEN
In patients with chronic rhinosinusitis with nasal polyps, primary human sinonasal epithelial cell (HSNEC) 1α-hydroxylase levels are reduced, as is their ability to metabolize 25-hydroxycholecalciferol [25(OH)D3] to its active metabolite, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In this study, we sought to identify the factor responsible for the regulation of HSNEC metabolism of 25(OH)D3, focusing on C3 and C3a. Multiple inhaled irritants trigger the release of complement components, C3 and C3a, leading to suppression of 1α-hydroxylase levels in HSNECs. Recombinant C3a was able to decrease 1α-hydroxylase and impair 25(OH)D3 to 1,25(OH)2D3 metabolism, while addition of a C3a receptor antagonist restored conversion. Conversely, 1,25(OH)2D3 suppressed Aspergillus fumigatus-induced C3 and C3a levels in HSNEC supernatant. Given the ability of 1,25(OH)2D3 to modulate LL37 in other cell types, we examined its regulation in HSNECs and relationship to C3a. 1,25(OH)2D3 stimulated the secretion of LL37, whereas A. fumigatus and C3a suppressed it. Conversely, LL37 reduced the release of C3/C3a by HSNECs. Lastly, oral steroid use and in vitro dexamethasone application both failed to increase 1α-hydroxylase or reduce C3a levels. In summary, in this article, we describe for the first time a novel relationship between complement activation and local vitamin D metabolism in airway epithelial cells. The presence of elevated C3/C3a in patients with asthma and/or chronic rhinosinusitis with nasal polyps may account for their impaired HSNEC 25(OH)D3 to 1,25(OH)2D3 metabolism and explain why they receive limited therapeutic benefit from oral vitamin D3 supplementation.
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Calcitriol , Pólipos Nasales , Calcitriol/farmacología , Células Epiteliales/metabolismo , Humanos , Oxigenasas de Función Mixta , Vitamina D/análogos & derivados , Vitamina D/metabolismoRESUMEN
BACKGROUND: In the phase III SYNAPSE study, mepolizumab reduced nasal polyp (NP) size and nasal obstruction in chronic rhinosinusitis with NP. OBJECTIVE: We sought to assess the efficacy of mepolizumab in patients from SYNAPSE grouped by comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and baseline blood eosinophil count (BEC). METHODS: SYNAPSE, a randomized, double-blind, 52-week study (NCT03085797), included patients with severe bilateral chronic rhinosinusitis with NP eligible for surgery despite intranasal corticosteroid treatment. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care for 52 weeks. Coprimary end points were change in total endoscopic NP score (week 52) and nasal obstruction visual analog scale score (weeks 49-52). Subgroup analyses by comorbid asthma and AERD status, and post hoc by BEC, were exploratory. RESULTS: Analyses included 407 patients (289 with asthma; 108 with AERD; 371 and 278 with BEC counts ≥150 or ≥300 cells/µL, respectively). The proportion of patients with greater than or equal to 1-point improvement from baseline in NP score was higher with mepolizumab versus placebo across comorbid diseases (asthma: 52.9% vs 29.5%; AERD: 51.1% vs 20.6%) and baseline BEC subgroups (<150 cells/µL: 55.0% vs 31.3%; ≥150 cells/µL: 49.5% vs 28.1%; <300 cells/µL: 50.7% vs 29.0%; ≥300 cells/µL: 50.4% vs 28.1%). A similar trend was observed in patients without comorbid asthma or AERD. More patients had more than 3-point improvement in nasal obstruction VAS score with mepolizumab versus placebo across comorbid subgroups. CONCLUSIONS: Mepolizumab reduced polyp size and nasal obstruction in chronic rhinosinusitis with NP regardless of the presence of comorbid asthma or AERD.
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Asma Inducida por Aspirina , Asma , Obstrucción Nasal , Pólipos Nasales , Sinusitis , Anticuerpos Monoclonales Humanizados , Asma/tratamiento farmacológico , Enfermedad Crónica , Comorbilidad , Eosinófilos , Humanos , Obstrucción Nasal/tratamiento farmacológico , Pólipos Nasales/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss. OBJECTIVES: The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach. METHODS: Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters. RESULTS: A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/Th17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test, χ182=178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all). CONCLUSIONS: Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes.
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Citocinas/inmunología , Moco/inmunología , Trastornos del Olfato/inmunología , Rinitis/inmunología , Sinusitis/inmunología , Adulto , Anciano , Biomarcadores , Enfermedad Crónica , Análisis por Conglomerados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cavidad Nasal , Trastornos del Olfato/diagnóstico , Rinitis/diagnóstico , Sinusitis/diagnóstico , Olfato , Adulto JovenRESUMEN
The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.
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Microbiota , Senos Paranasales , Sinusitis , Bacterias/genética , Enfermedad Crónica , Humanos , ARN Ribosómico 16S/genética , Sinusitis/epidemiologíaRESUMEN
OBJECTIVE: Enhanced odor sensitivity, particularly toward threat-related cues, may be adaptive during periods of danger. Research also suggests that chronic psychological distress may lead to functional changes in the olfactory system that cause heightened sensitivity to odors. Yet, the association between self-reported odor sensitivity, objective odor detection, and affective psychopathology is currently unclear, and research suggests that persons with affective problems may only be sensitive to specific, threat-related odors. METHODS: The current study compared adults with self-reported odor sensitivity that was described as functionally impairing (OSI; n = 32) to those who reported odor sensitivity that was non-impairing (OS; n = 17) on affective variables as well as quantitative odor detection. RESULTS: Increased anxiety sensitivity, trait anxiety, depression, and life stress, even while controlling for comorbid anxiety and depressive disorders, was found for OSI compared to OS. While OSI, compared to OS, demonstrated only a trend increase in objective odor detection of a smoke-like, but not rose-like, odor, further analysis revealed that increased detection of that smoke-like odor was positively correlated with anxiety sensitivity. CONCLUSION: These findings suggest that persons with various forms of psychological distress may find themselves significantly impaired by an intolerance of odors, but that self-reported odor sensitivity does not necessarily relate to enhanced odor detection ability. However, increased sensitivity to a smoke-like odor appears to be associated with sensitivity to aversive anxiogenic stimuli. Implications for the pathophysiology of fear- and anxiety-related disorders are discussed.
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Ansiedad/diagnóstico , Trastorno Depresivo/diagnóstico , Percepción Olfatoria , Distrés Psicológico , Olfato , Adulto , Anciano , Ansiedad/psicología , Trastorno Depresivo/psicología , Autoevaluación Diagnóstica , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: With an aging population, it is important to understand age-related anatomic changes in the nasal cavity and cribriform plate (CP) that may have clinical implications. METHODOLOGY: Computed tomography (CT) scans obtained for non-rhinologic conditions were divided into a young cohort (N=35, 18-34 years old) and an older adult cohort (N=32, 80-99 years old). Intranasal airspace volumes and bony anatomy of the CP were manually segmented using OsiriX software. The CP was assessed for mean Hounsfield Units (HU) and percentage of olfactory foramina. Deformation based morphometry (DBM) was then performed on the same cohort and correlated with manual measurements. RESULTS: Individual nasal cavity volumes increased 17-75% with age. Regression analysis of all scans revealed age to be the predominant variable influencing intranasal volume differences when controlling for sex and head size. Mean HU of the CP negatively correlated with age. No age-related differences in bone stenosis of olfactory foramina were identified. Automated DBM measurements of intranasal volumes, as well as CP and zygoma mean HU correlated with manual measurements. CONCLUSION: Older subjects have a global increase in intranasal volumes and diffuse bone density loss in the CP. The clinical impact of age-related anatomic changes in the nasal cavity and CP requires further investigation.
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Envejecimiento , Hueso Etmoides , Cavidad Nasal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Hueso Etmoides/diagnóstico por imagen , Hueso Etmoides/crecimiento & desarrollo , Femenino , Humanos , Masculino , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/crecimiento & desarrollo , Olfato , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Current clinical classifications of chronic rhinosinusitis (CRS) have weak prognostic utility regarding treatment outcomes. Simplified discriminant analysis based on unsupervised clustering has identified novel phenotypic subgroups of CRS, but prognostic utility is unknown. OBJECTIVE: We sought to determine whether discriminant analysis allows prognostication in patients choosing surgery versus continued medical management. METHODS: A multi-institutional prospective study of patients with CRS in whom initial medical therapy failed who then self-selected continued medical management or surgical treatment was used to separate patients into 5 clusters based on a previously described discriminant analysis using total Sino-Nasal Outcome Test-22 (SNOT-22) score, age, and missed productivity. Patients completed the SNOT-22 at baseline and for 18 months of follow-up. Baseline demographic and objective measures included olfactory testing, computed tomography, and endoscopy scoring. SNOT-22 outcomes for surgical versus continued medical treatment were compared across clusters. RESULTS: Data were available on 690 patients. Baseline differences in demographics, comorbidities, objective disease measures, and patient-reported outcomes were similar to previous clustering reports. Three of 5 clusters identified by means of discriminant analysis had improved SNOT-22 outcomes with surgical intervention when compared with continued medical management (surgery was a mean of 21.2 points better across these 3 clusters at 6 months, P < .05). These differences were sustained at 18 months of follow-up. Two of 5 clusters had similar outcomes when comparing surgery with continued medical management. CONCLUSION: A simplified discriminant analysis based on 3 common clinical variables is able to cluster patients and provide prognostic information regarding surgical treatment versus continued medical management in patients with CRS.
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Toma de Decisiones Clínicas/métodos , Técnicas de Apoyo para la Decisión , Fármacos del Sistema Respiratorio/uso terapéutico , Rinitis/tratamiento farmacológico , Rinitis/cirugía , Sinusitis/tratamiento farmacológico , Sinusitis/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Enfermedad Crónica , Análisis por Conglomerados , Análisis Discriminante , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
Differences in testing modalities and cut-points used to define olfactory dysfunction contribute to the wide variability in estimating the prevalence of olfactory dysfunction in chronic rhinosinusitis (CRS). The aim of this study is to report the prevalence of olfactory impairment using each component of the Sniffin' Sticks test (threshold, discrimination, identification, and total score) with age-adjusted and ideal cut-points from normative populations. Patients meeting diagnostic criteria for CRS were enrolled from rhinology clinics at a tertiary academic center. Olfaction was assessed using the Sniffin' Sticks test. The study population consisted of 110 patients. The prevalence of normosmia, hyposmia, and anosmia using total Sniffin' Sticks score was 41.8%, 20.0%, and 38.2% using age-appropriate cut-points and 20.9%, 40.9%, and 38.2% using ideal cut-points. Olfactory impairment estimates for each dimension mirrored these findings, with threshold yielding the highest values. Threshold, discrimination, and identification were also found to be significantly correlated to each other ( P < 0.001). In addition, computed tomography scores, asthma, allergy, and diabetes were found to be associated with olfactory dysfunction. In conclusion, the prevalence of olfactory dysfunction is dependent upon olfactory dimension and if age-adjusted cut-points are used. The method of olfactory testing should be chosen based upon specific clinical and research goals.
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Previous studies on the relationship between olfaction and depression have revealed mixed results. In addition, few have focused on the reciprocity of this association. The aim of this study is to combine depression and olfactory data in two separate patient populations to further understand their association. A systematic literature review was conducted using 3 online databases to identify studies correlating olfaction and depression in patients presenting with either primary depression or primary olfactory dysfunction. For the depressed population, weighted means and standard deviations for the Sniffin' Sticks Test and the 40-item Smell Identification Test were combined using 10 studies. For the olfactory dysfunction population, weighted means of Beck's Depression Inventory were combined using 3 studies. Independent t-tests were used to compare differences between groups. Comparing primary depressed patients with controls, depressed patients showed decreased scores in olfactory threshold (6.31±1.38 vs. 6.78±0.88, P = 0.0005), discrimination (12.05±1.44 vs. 12.66±1.36, P = 0.0073), identification (12.57±0.74 vs. 12.98±0.90, P < 0.0001), and 40-Item Smell Identification Test (35.31±1.91 vs. 37.41±1.45, P < 0.0001). In patients with primary olfactory dysfunction, Beck's Depression Inventory scores were significantly different between patients classified as normosmics, hyposmics and anosmics (5.21±4.73 vs. 10.93±9.25 vs. 14.15±5.39, P ≤ 0.0274 for all 3 comparisons). In conclusion, patients with depression have reduced olfactory performance when compared with the healthy controls and conversely, patients with olfactory dysfunction, have symptoms of depression that worsen with severity of smell loss.
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Trastorno Depresivo/complicaciones , Trastornos del Olfato/complicaciones , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Humanos , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/psicología , Umbral Sensorial , OlfatoRESUMEN
INTRODUCTION: Appropriate indications for endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) are currently poorly defined. The lack of clear surgical indications for ESS likely contributes to the large geographic variation in surgical rates and contributes to reduced quality of care. The objective of this study was to define appropriateness criteria for ESS during management of adult patients with uncomplicated CRS. METHODS: The RAND/UCLA appropriateness methodology was performed. An international, multi-disciplinary panel of 10 experts in CRS was formed and completed two rounds of a modified Delphi ranking process along with a face-to-face meeting. RESULTS: A total of 624 clinical scenarios were ranked, 312 scenarios each for CRS with and CRS without nasal polyps. For adult patients with uncomplicated CRS with nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is ≥ 1 and there has been a minimum trial of a topical intranasal corticosteroid plus a short-course of systemic corticosteroid with a post-treatment total SNOT-22 score ≥ 20. For adult patients with uncomplicated CRS without nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is ≥ 1 and there has been a minimum trial of a topical intranasal corticosteroid plus either a short-course of a broad spectrum/culture-directed systemic antibiotic or the use of a prolonged course of systemic low-dose anti-inflammatory antibiotic with a post-treatment total SNOT-22 score ≥ 20. CONCLUSION: This study has developed and reported of list of appropriateness criteria to offer ESS as a treatment option during management of uncomplicated adult CRS. The extent or technique of ESS was not addressed in this study and will depend on surgeon and patient factors. Furthermore, these criteria are the minimal threshold to make ESS a treatment option and do not imply that all patients meeting these criteria require surgery. The decision to perform ESS should be made after an informed patient makes a preference-sensitive decision to proceed with surgery. Applying these appropriateness criteria for ESS may optimize patient selection, reduce the incidence of unwarranted surgery, and assist clinicians in providing high quality, patient-centered care to patients with CRS.
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Endoscopía/métodos , Pólipos Nasales/cirugía , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Senos Paranasales/cirugía , Selección de Paciente , Rinitis/cirugía , Sinusitis/cirugía , Adulto , Antibacterianos/uso terapéutico , Enfermedad Crónica , Técnica Delphi , Humanos , Guías de Práctica Clínica como Asunto , Regionalización , Rinitis/diagnóstico , Rinitis/tratamiento farmacológico , Sinusitis/diagnóstico , Sinusitis/tratamiento farmacológicoRESUMEN
BACKGROUND: With a focus on patient-centered care, there is increasing policy interest in patient-reported outcome measures (PROMs) to inform improvements in health care delivery. Given the importance of understanding patient-reported outcomes during the management of chronic rhinosinusitis (CRS), PROMs will play an essential role in informing and tailoring the right intervention to the right patient. OBJECTIVE: The objective of this systematic review was to identify and assess the quality of PROMs being used for adults with CRS. METHODS: A systematic review of Ovid MEDLINE (R) (1947-May 2015), Embase, and the Cochrane databases was performed using the following key terms: ["chronic" AND "*sinusitis"] AND [PROM OR patient reported outcome measure* OR quality of life OR questionnaire OR survey OR valid* OR develop*]. An unlimited truncation strategy (placement of *) was used to capture all variations of terms used. The quality of each PROM was assessed and reported using standardized criteria from the COnsensus-based Standards for the selection of health status Measurement INstruments checklist. RESULTS: A total of 15 PROMs validated for use in adult patients with CRS were identified. Fourteen instruments were specific to adults with CRS, and one was a generic quality-of-life instrument (EuroQol five-dimensional questionnaire [EQ-5D]). There was significant variation in the quality of development and reporting of psychometric properties. Overall, the highest quality validated PROMs for adults with CRS were (1) the 22-item Sinonasal Outcome Test (19 points), (2) the Questionnaire of Olfactory Disorders (14 points), (3) the Sinusitis Control Test (14 points), and (4) the EQ-5D (13 points). Most of the PROMs were developed for research purposes such as determining changes in health-related quality of life or symptoms after an intervention as opposed to improving clinical decision making. CONCLUSIONS: Based on quality assessment, the 22-item Sinonasal Outcome Test, the Questionnaire of Olfactory Disorders, and the Sinusitis Control Test provided the highest quality CRS-specific PROMs, whereas the EQ-5D provided the highest quality generic quality-of-life instrument. Future CRS PROMs will need to incorporate clinical domains that assess common comorbid diseases along with patient values and preferences to improve clinical decision making.
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Rinitis/terapia , Sinusitis/terapia , Enfermedad Crónica , Humanos , Evaluación del Resultado de la Atención al Paciente , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Surface plasmon resonance (SPR) was used in this research to investigate the targeting efficacy (i.e., the binding affinity) of antibody-modified liposomes. The results indicated that liposomes modified by targeting antibodies exhibited an increase in apparent binding affinity, a result attributed to the avidity effect. More specifically, the targeting effect improved as the surface density of the targeting antibody increased, an increase primarily attributed to the decrease of the dissociation rate. However, this trend stopped when the surface density reached a threshold of approximately 1.5 × 10(8) antibody/mm(2). This surface density was found to be quite consistent regardless of the liposome size and the type of targeting antibody. In addition, a traditional cell binding experiment was conducted to confirm the saturation point obtained from SPR.
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Anticuerpos/inmunología , Liposomas , Relación Dosis-Respuesta Inmunológica , Resonancia por Plasmón de SuperficieRESUMEN
BACKGROUND: Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH)D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. OBJECTIVE: We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. METHODS: Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. RESULTS: CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. CONCLUSIONS: Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects.
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Calcitriol/deficiencia , Nicotiana/química , Rinitis/metabolismo , Sinusitis/metabolismo , Humo , Deficiencia de Vitamina D/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Adulto , Anciano , Calcifediol/metabolismo , Calcitriol/farmacología , Estudios de Casos y Controles , Enfermedad Crónica , Mezclas Complejas/aislamiento & purificación , Mezclas Complejas/farmacología , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Pólipos Nasales/metabolismo , Pólipos Nasales/patología , Cultivo Primario de Células , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Rinitis/complicaciones , Rinitis/patología , Sinusitis/complicaciones , Sinusitis/patología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/patologíaRESUMEN
Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) presents a significant challenge in clinical management owing to recalcitrant disease with accompanying profound impacts on patient quality of life. Although asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal problems, olfactory dysfunction, and the associated psychosocial and dietary implications. This review delves into specific quality of life metrics used to assess NSAID-ERD and the associated health care burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps when available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. Although some of these emerging treatment approaches show promise, they also present numerous unanswered questions, reflecting the dynamic nature of this field. As the landscape of NSAID-ERD management continues to evolve, this review provides insights into the challenges faced by clinicians and underscores the need for further research to optimize patient care and quality of life outcomes.
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Nasal obstruction is the subjective perception and objective state of insufficient airflow through the nose. Nasal congestion, conversely, describes a state of not just inadequate airflow or obstructive phenomena but also pressure- and mucus-related states to the patient. Nasal receptors belonging to the transient receptor potential (TRP) protein family mediate the sense of nasal patency via the trigeminal nerve. The transient receptor potential melastatin-8 (TRPM8) responds to temperatures around 8°C to 22°C, and is stimulated by menthol and other cooling agents. The radiant effects of airflow create heat loss to activate these receptors and humans perceive this as nasal patency rather than the direct detection of airflow. The thermovascular state of the mucosa, in conditions such as rhinitis, influence TRPM8 activation. Nasal endoscopy can show signs of rhinitis and should be considered an essential part of the workup of nasal congestion. Efforts to relieve nasal congestion need to manage the mucosal state and surgery needs to ensures that the nasal cavity mucosa is exposed to the cooling effects of airflow rather than simply creating a passage to the nasopharynx.
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Mucosa Nasal , Obstrucción Nasal , Humanos , Obstrucción Nasal/diagnóstico , Mucosa Nasal/metabolismo , Canales Catiónicos TRPM/metabolismo , Endoscopía , Rinitis/diagnóstico , Rinitis/fisiopatologíaRESUMEN
KEY POINTS: CRSwNP-specific mean total annual spending ranged from $5,837 (EDS-FLU) to $28,058 (dupilumab). Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery. While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS-FLU.
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OBJECTIVE: The purpose of this study was to analyze barriers to medical care and follow-up in patients with allergic fungal rhinosinusitis (AFRS). STUDY DESIGN: Cross-sectional questionnaire-based study with retrospective chart review. SETTING: Tertiary Medical Center. METHODS: Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review. RESULTS: Fifty-nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow-up within 6 months of surgery (35.6% vs 17.7%, P = 0.04) and no-show at least 1 appointment (20.3% vs 5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow-up visit (37.0% vs 3.1%, P < 0.001) and be lost to follow-up (66.7% vs 9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs 35.1%, P = 0.034), lost to follow-up (77.3% vs 10.8%, P < 0.0001), and have a single follow-up visit (40.9% vs 5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow-up visit (odds ratio 1.143, 95% CI 1.022-1.276). CONCLUSION: Young, male AFRS patients are more frequently lost to follow-up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow-up in these at-risk groups.
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Micosis , Pólipos Nasales , Rinosinusitis , Sinusitis , Humanos , Masculino , Femenino , Estudios Retrospectivos , Sinusitis/complicaciones , Sinusitis/terapia , Sinusitis/microbiología , Cuidados Posteriores , Estudios Transversales , Enfermedad Crónica , Micosis/terapia , Micosis/cirugía , Pólipos Nasales/complicacionesRESUMEN
KEY POINTS: The pandemic caused an increase in computed tomography imaging in patients with sinusitis, which persisted post-COVID. Nasal endoscopies significantly decreased during COVID but returned to pre-COVID levels in 2022. The management of cerebrospinal fluid leaks, tumors, and orbital pathology was not impacted by the pandemic.
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COVID-19 , Sinusitis , Humanos , COVID-19/epidemiología , Pandemias , Endoscopía , Tomografía Computarizada por Rayos X , Sinusitis/diagnóstico por imagen , Sinusitis/epidemiología , Sinusitis/terapiaRESUMEN
BACKGROUND: The purpose of this study was to investigate real-world adherence to intranasal corticosteroid irrigations using pharmacy data and assess factors associated with low adherence. METHODS: Patients undergoing treatment with corticosteroid irrigations for any diagnosis during a 2-year period were prospectively recruited. Subjects completed a one-time set of questionnaires including the Barriers to Care Questionnaire (BCQ), 22-item Sino-Nasal Outcome Test (SNOT-22), and a questionnaire assessing their experience with corticosteroid irrigations. Pharmacy data was used to calculate the medication possession ratio (MPR), a measure of medication adherence graded from 0 to 1. RESULTS: Seventy-one patients were enrolled. Patient diagnoses included chronic rhinosinusitis (CRS) without nasal polyps (n = 37), CRS with nasal polyps (n = 24), or a non-CRS diagnosis, most commonly chronic rhinitis (n = 10). The MPR for the overall group was 0.44 ± 0.33. Just 9.9% of patients had a perfect MPR of 1. Despite low MPR, only 19.7% of patients reported problems taking the medication when directly asked. Lower education resulted in lower MPR (unstandardized B = 0.065, p = 0.046). Increasing BCQ score, indicating higher barriers to care, was associated with lower MPR (unstandardized B = -0.010, p = 0.033). The lower the MPR, the worse the patient SNOT-22 scores (unstandardized B = -15.980, p = 0.036). CONCLUSION: Adherence to corticosteroid irrigations was low and patients underreported issues with their medication. Education and barriers to care were associated with lower adherence, which, in turn, was associated with worse sinonasal quality of life.
Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/tratamiento farmacológico , Calidad de Vida , Corticoesteroides/uso terapéutico , Administración Intranasal , Sinusitis/tratamiento farmacológico , Rinitis/tratamiento farmacológico , Enfermedad Crónica , Cumplimiento de la MedicaciónRESUMEN
KEY POINTS: Utilization of orbital decompressions (ODS) increased (CAGR: +3.2%) from 2000 to 2019. FDA approved teprotumumab in January 2020; ODS utilization decreased (CAGR: -14.9%) from 2019 to 2022. In 2022, total spending was substantially higher for teprotumumab ($325 million) than surgery ($580,000).