Structures and functions of the normal and injured human olfactory epithelium.

The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through the proliferation and differentiation of progenitor basal cells that are subsequently incorporated into olfactory neural circuits. Although normal olfactory function returns after injury in most cases, prolonged olfactory impairment and lack of improvement in olfactory function in some cases poses a major clinical problem. Persistent inflammation or severe injury in the OE results in morphological changes in the OE and respiratory epithelium and decreases the number of mature OSNs, resulting in irreversible loss of olfactory function. In this review, we discuss the histological structure and distribution of the human OE, and the pathogenesis of olfactory dysfunction associated with CRS and viral infection.

Lack of association of impaired upper airway sensation with the presence or absence of obstructive sleep apnoea or chronic rhinosinusitis in World Trade Center responders.

OBJECTIVE: Examine sensory function of the upper airway in four groups of subjects recruited from the World Trade Centre General Responder Cohort (WTCGRC), with/without obstructive sleep apnoea (OSA), and with/without chronic rhinosinusitis (CRS). METHODS: Upper airway sensory function was determined using 2-point discrimination (2-PD) and vibration threshold (VT) in 163 WTCGRC subjects with both OSA and CRS (cases), OSA or CRS alone and without OSA or CRS (controls). Presence of OSA was determined from clinical sleep studies or home sleep testing. Presence of CRS was determined by nasal symptom questionnaire. The relationship between the presence of OSA and CRS and upper airway sensory impairment was assessed using linear regression analysis with each of 2PD and VT sensory threshold values as the dependent variable; OSA, CRS and their interaction were the independent variables. Age, gender and body mass index were covariates in the statistical model. The primary analysis was comparison of OSA+CRS versus controls (no OSA and no CRS) evaluated by linear contrasts. RESULTS: There were no differences in 2-PD or VT in those with OSA+CRS, OSA and CRS alone or controls. However, both 2-PD and VT were significantly higher in the WTCGRC controls compared with values seen in historical controls using the same methodology (median 2-PD 13.0; CI (11.0 to 13.5) vs 10.5; CI (8 to 11); VT: mean±SEM (9.3±0.6 vs 2.2±0.1)). CONCLUSION: While no differences were found in upper airway sensation between cases of OSA and CRS versus controls in the WTGRC population, there was evidence of impaired upper airway sensation in the WTGRC overall.

Cognition and saccadic eye movement performance are impaired in chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) can experience cognitive dysfunction. The literature on this topic mostly reflects patient-reported measurements. Our goal was to assess cognitive function in patients with CRS using objective measures, including saccadic eye movements-a behavioral response reflecting cognitive and sensory information integration that is often compromised in conditions with impaired cognition. METHODS: Participants (N = 24 with CRS, N = 23 non-CRS healthy controls) enrolled from rhinology clinic underwent sinonasal evaluation, quality of life assessment (Sino-nasal Outcome Test 22 [SNOT-22]), and cognitive assessment with the Neuro-QOL Cognitive Function-Short Form, the Montreal Cognitive Assessment (MoCA), and recording of eye movements using video-oculography. RESULTS: Participants with CRS were more likely to report cognitive dysfunction (Neuro-QOL; 45.8% vs. 8.7%; p = 0.005) and demonstrate mild or greater cognitive impairment (MoCA; 41.7% vs. 8.7%; p = 0.005) than controls. Additionally, participants with CRS performed worse on the MoCA overall and within the executive functioning and memory domains (all p < 0.05) and on the anti-saccade (p = 0.014) and delay saccade (p = 0.044) eye movement tasks. Poorer performance on the MoCA (r = -0.422; p = 0.003) and the anti-saccade (r = -0.347; p = 0.017) and delay saccade (r = -0.419; p = 0.004) eye movement tasks correlated with worse CRS severity according to SNOT-22 scores. CONCLUSION: This study is the first to utilize objective eye movement assessments in addition to researcher-administered cognitive testing in patients with CRS. These patients demonstrated a high prevalence of cognitive dysfunction, most notably within executive functioning and memory domains, with the degree of dysfunction correlating with the severity of CRS.

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.

Vía aérea unificada: asociación entre rinosinusitis crónica y asma bronquial / Unified airway: association between chronic rhinosinusitis and bronchial asthma

Bajo la teoría de vía aérea unificada, se ha observado que el asma y la rinosinusitis crónica (RSC) tienen una estrecha relación, con efectos importantes de una enfermedad sobre el control de la otra. El objetivo de esta revisión bibliográfica es clarificar cómo ambas enfermedades se relacionan desde su origen, epidemiología, fisiopatología y tratamiento. Sabemos que la presencia de RSC se asocia con peores resultados del asma, mayor frecuencia de exacerbaciones, hospitalizaciones y mayor uso de corticoides sistémicos. Varios mecanismos parecen tener un rol en la disfunción de la vía aérea inferior en pacientes con RSC, dentro de los cuales se plantea que la respuesta inflamatoria en común de tipo Th2 juega un papel principal. Existe amplia literatura respecto al efecto que tiene el tratamiento de la RSC en el control del asma, en esta revisión se expondrá la evidencia disponible del tratamiento médico con corticoides nasales, montelukast y macrólidos, así como también del tratamiento quirúrgico de la RSC y el uso de biológicos.

Under the unified airway theory, asthma and chronic rhinosinusitis (CRS) have a close relationship, with significant effects of one disease on the control of the other. This bibliographic review aims to clarify how both diseases relate to each other from their origin, epidemiology, pathophysiology, and treatment. CRS is associated with worse asthma outcomes, higher frequency of exacerbations, hospitalizations, and increased use of systemic corticosteroids. Several mechanisms play a role in lower airway dysfunction in patients with CRS, among which the common Th2-type inflammatory response plays a substantial role. There is extensive literature regarding the effect of the treatment of CRS in the control of asthma. We present the available evidence regarding the effect of medical treatment with nasal corticosteroids, montelukast, and macrolides, as well as the surgical treatment and use of biologics.

Detection of maxillary sinus fungal ball via 3-D CNN-based artificial intelligence: Fully automated system and clinical validation.

BACKGROUND: This study aims to develop artificial intelligence (AI) system to automatically classify patients with maxillary sinus fungal ball (MFB), chronic rhinosinusitis (CRS), and healthy controls (HCs). METHODS: We collected 512 coronal image sets from ostiomeatal unit computed tomography (OMU CT) performed on subjects who visited a single tertiary hospital. These data included 254 MFB, 128 CRS, and 130 HC subjects and were used for training the proposed AI system. The AI system takes these 1024 sets of half CT images as input and classifies these as MFB, CRS, or HC. To optimize the classification performance, we adopted a 3-D convolutional neural network of ResNet 18. We also collected 64 coronal OMU CT image sets for external validation, including 26 MFB, 18 CRS, and 20 HCs from subjects from another referral hospital. Finally, the performance of the developed AI system was compared with that of the otolaryngology resident physicians. RESULTS: Classification performance was evaluated using internal 5-fold cross-validation (818 training and 206 internal validation data) and external validation (128 data). The area under the receiver operating characteristic over the internal 5-fold cross-validation and the external validation was 0.96 ±0.006 and 0.97 ±0.006, respectively. The accuracy of the internal 5-fold cross-validation and the external validation was 87.5 ±2.3% and 88.4 ±3.1%, respectively. As a result of performing a classification test on external validation data from six otolaryngology resident physicians, the accuracy was obtained as 84.6 ±11.3%. CONCLUSIONS: This AI system is the first study to classify MFB, CRS, and HC using deep neural networks to the best of our knowledge. The proposed system is fully automatic but performs similarly to or better than otolaryngology resident physicians. Therefore, we believe that in regions where otolaryngology specialists are scarce, the proposed AI will perform sufficiently effective diagnosis on behalf of doctors.

The enlargement of the maxillary ostium after balloon sinuplasty evaluated by a novel measuring technique from 3D CBCT images.

Our aim was to evaluate the effects of balloon sinuplasty on the size of the ostium in the maxillary sinuses in patients with chronic rhinosinusitis from cone beam computer tomography (CBCT) scans of the sinus. This is a blinded retrospective trial in patients who had undergone balloon sinuplasty of the maxillary sinus. CBCT scans were taken and SNOT-22 Quality of Life questionnaire completed before and 12 months after the operation. The size of the maxillary ostium was measured from the CBCT scans three-dimensionally. The association of changes in the SNOT-22 scores of the ostium was analysed. We discovered that the balloon sinuplasty increased the size of the maxillary ostium in all dimensions. The changes were statistically significant (p<0.05) in the axial diameter and the ostium area. The number of patent ostia increased after the intervention. The association between SNOT-22 score and ostium patency were statistically significant before the operation. Our conclusion is that the threedimensional measuring technique provides a reliable method to evaluate ostium dimensions. Balloon sinuplasty increased the size of the maxillary ostium and the result was maintained for 12 months after the operation.

A 70-Year-Old Man With Cough and Recurrent Respiratory Infections.

CASE PRESENTATION: A 70-year-old man was referred for evaluation of recurrent respiratory infections requiring antibiotics and chronic cough over 3 years. Two months prior to presentation, he started to develop blood-tinged sputum but not frank hemoptysis. He otherwise denied any fever, chills, night sweats, or weight loss. He had dyspnea during the respiratory infections but not otherwise. His medical history was significant for chronic rhinitis without sinusitis and a low serum IgM level. He was a never smoker and a farmer but otherwise had no significant or specific exposures or travel history. His family history was significant for alpha-1 antitrypsin deficiency in his mother.

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis.

The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders' pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.

The Effect of Aspirin on Moderate to Severe Asthmatic Patients with Aspirin Hypersensitivity, Chronic Rhinosinusitis, and Nasal Polyposis.

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.

Sleep Dysfunction is an Independent Predictor of Productivity Losses in Patients with Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is known to have a significant impact on economic productivity. Sleep dysfunction is associated with staggering productivity losses and is highly prevalent in patients with CRS. The effect of sleep dysfunction on productivity in CRS has not been elucidated. The objective of this study was to determine the relationship between sleep dysfunction and lost productivity in patients with CRS. METHODS: Eighty-two adult patients with CRS were prospectively enrolled into a cross-sectional cohort study. Patients with obstructive sleep apnea were excluded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Presenteeism (reduced work efficiency), absenteeism (missed work days), and lost work, household, and overall productivity were analyzed. The primary aim was assessing the correlation between PSQI and productivity. Regression analyses were performed to account for disease severity, pain, and depression. RESULTS: Sleep dysfunction is significantly correlated with overall lost productivity (R2 = 0.397, P < .05). Presenteeism is the most strongly affected by sleep dysfunction (R2 = -0.441, P < .001). Higher PSQI scores were significantly associated with productivity losses, whereas lower scores were not. Sleep remained an independent predictor of productivity when regression analysis accounted for disease severity, depression, and pain. CONCLUSION: Sleep dysfunction has a significant association with lost productivity in patients with CRS, particularly with worsening PSQI scores. More clearly defining those components of CRS that most impact a patient's daily function will allow clinicians to more optimally manage and counsel patients with CRS.

Association of Sinonasal Inflammation With Functional Brain Connectivity.

Importance: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of chronic rhinosinusitis. However, an investigation exploring the potential link between the underlying inflammatory disease and higher-order neural processing has not yet been performed. Objective: To describe the association of sinonasal inflammation with functional brain connectivity (Fc), which may underlie chronic rhinosinusitis-related cognitive changes. Design, Setting, and Participants: This is a case-control study using the Human Connectome Project (Washington University-University of Minnesota Consortium of the Human Connectome Project 1200 release), an open-access and publicly available data set that includes demographic, imaging, and behavioral data for 1206 healthy adults aged 22 to 35 years. Twenty-two participants demonstrated sinonasal inflammation (Lund-Mackay score [LMS] ≥ 10) and were compared with age-matched and sex-matched healthy controls (LMS = 0). These participants were further stratified into moderate (LMS < 14, n = 13) and severe (LMS ≥ 14, n = 9) inflammation groups. Participants were screened and excluded if they had a history of psychiatric disorder and/or neurological or genetic diseases. Participants with diabetes or cardiovascular disease were also excluded, as these conditions may affect neuroimaging quality. The data were accessed between October 2019 and August 2020. Data analysis was performed between May 2020 and August 2020. Main Outcomes and Measures: The primary outcome was the difference in resting state Fc within and between the default mode, frontoparietal, salience, and dorsal attention brain networks. Secondary outcomes included assessments of cognitive function using the National Institutes of Health Toolbox Cognition Battery. Results: A total of 22 patients with chronic rhinosinusitis and 22 healthy controls (2 [5%] were aged 22-25 years, 26 [59%] were aged 26-30 years, and 16 [36%] were aged 31-35 years; 30 [68%] were men) were included in the analysis. Participants with sinonasal inflammation showed decreased Fc within the frontoparietal network, in a region involving bilateral frontal medial cortices. This region demonstrated increased Fc to 2 nodes within the default-mode network and decreased Fc to 1 node within the salience network. The magnitude of these differences increased with inflammation severity (dose dependent). There were no significant associations seen on cognitive testing. Conclusions and Relevance: In this case-control study, participants with sinonasal inflammation showed decreased brain connectivity within a major functional hub with a central role in modulating cognition. This region also shows increased connectivity to areas that are activated during introspective and self-referential processing and decreased connectivity to areas involved in detection and response to stimuli. Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population.

A Young Girl With Bronchiectasis and Elevated Sweat Chloride.

CASE PRESENTATION: A 14-year old girl presented with history of productive cough since the age of 3 years. For the past 6 years, she complained of chest tightness and wheezing. There was also nasal stuffiness and discharge for the past 6 years. She denied history of hemoptysis, ear discharge, or chest pain. There was no history of respiratory distress at the time of birth. Her brother also suffered from productive cough and wheezing since the age of 3 years. However, both her parents were asymptomatic.

The Sinonasal Outcome Test (SNOT-22) Is a Poor Diagnostic Tool for Chronic Rhinosinusitis.

BACKGROUND: The SNOT-22 is a validated and widely used outcomes tool in chronic rhinosinusitis (CRS). We hypothesized that SNOT-22 scores and response patterns could be used as a diagnostic tool to differentiate between patients with CRS and those who present with CRS-like symptoms but prove not to have CRS. METHODOLOGY/PRINCIPAL: SNOT-22 measurements were collected from 311 patients who presented with a chief complaint of sinusitis to a tertiary rhinology practice. Following a full diagnostic evaluation, patients were diagnosed with CRS or determined to have non-CRS diagnoses. A response pattern "heatmap" of the SNOT-22 scores for each group was compared. An optimal cutoff point for total SNOT-22 score in predicting CRS was sought using a receiver operating characteristic (ROC) curve. RESULTS: A total of 109 patients were diagnosed with CRS and 202 patients were assigned to non-CRS. The non-CRS SNOT-22 total score histogram had lower overall scores compared to the CRS group, although there was substantial overlap. The CRS SNOT-22 heatmaps had a distinctive pattern compared to the non-CRS group. As individual measures, 3 of the 4 cardinal symptoms of CRS (nasal congestion, loss of smell, and rhinorrhea) were found to be significantly different between the 2 groups (P < .002). However, the ROC analysis showed the total SNOT-22 score to be a poor instrument to differentiate CRS from non-CRS patients. CONCLUSIONS: Our results cause us to reject our hypothesis and conclude that, while an effective outcomes tool, the SNOT-22 (using total score and response pattern) is a poor differentiator between CRS and non-CRS patients.

Invasive fungal disease misdiagnosed as tumour in association with orbital apex syndrome.

Invasive sino-orbital aspergillosis is a rare cause of orbital apex syndrome (OAS) in immunocompetent patients and often misdiagnosed as tumour because of its aggressive nature and invasive patterns. We report a 23-year-old immunocompetent man presenting with painful progressive loss of vision, ophthalmoplegia and proptosis of the right eye suggestive of OAS. MRI with gadolinium contrast showed an enhancing heterogeneous mass filling the paranasal sinuses, extraconal space and extending up to the right orbital apex. A functional endoscopic biopsy reported as invasive sino-orbital aspergillosis. He was started on intravenous voriconazole and maximal surgical debridement was done. He gradually regained his vision to 20/30 in the right eye. A review of literature reported several such cases which were managed medically or surgically but with poor visual recovery. This case highlights the need for awareness among clinicians for early diagnosis and treatment to prevent vision loss and better survival.

No difference in omalizumab efficacy in patients with asthma by number of asthma-related and allergic comorbidities.

BACKGROUND: Comorbidities are common in asthma and may complicate treatment response. OBJECTIVE: To examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities. METHODS: Patients aged 12 years or more from placebo-controlled 008/009 (n = 1071), EXTRA (n = 848), and INNOVATE (n = 419), and single-armed PROSPERO (n = 801) omalizumab studies were included. Poisson regression/analysis of covariance models were used to estimate adjusted exacerbation rates and forced expiratory volume in 1 second (FEV1) change from baseline after omalizumab initiation for subgroups by number of comorbidities (0, 1 [008/009]; 0, 1, ≥2 [EXTRA and INNOVATE]; 0, 1, 2, ≥3 [PROSPERO]). Self-reported comorbidities included allergic rhinoconjunctivitis, chronic rhinosinusitis, recurrent acute sinusitis, nasal polyps, atopic and contact dermatitis, urticaria, food allergy, anaphylaxis, other allergies, gastroesophageal reflux disease, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis. RESULTS: In the EXTRA and INNOVATE studies, no consistent pattern was observed for placebo-corrected relative rate reduction in normalized asthma exacerbations among omalizumab-treated comorbidity subgroups. In PROSPERO, on-study exacerbation rates in the comorbidity subgroups were similar (0, 0.68; 1, 0.70; 2, 0.77; ≥3, 0.80). FEV1 improvements were observed throughout the study for omalizumab vs placebo for all comorbidity subgroups. There were no consistent differences in FEV1 improvements among comorbidity subgroups in 008/009, EXTRA, or INNOVATE. Similarly, no among-group differences were observed for FEV1 change from baseline at month 12 in PROSPERO (0, 0.05 L; 1, 0.08 L; 2, 0.00 L; ≥3, 0.04 L). The 95% confidence intervals overlapped substantially in all instances. CONCLUSION: In these analyses of placebo-controlled/single-armed studies, on-study exacerbation rates and FEV1 improvements with omalizumab treatment were similar irrespective of comorbidity burden. TRIAL REGISTRATION: ClinicalTrials.gov identifiers are as follows: EXTRA, NCT00314574 (https://clinicaltrials.gov/ct2/show/NCT00314574); INNOVATE, NCT00046748 (https://clinicaltrials.gov/ct2/show/NCT00046748); and PROSPERO, NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037).

Can computational fluid dynamic models help us in the treatment of chronic rhinosinusitis.

PURPOSE OF REVIEW: The aim of this study was to review the recent literature (January 2017-July 2020) on computational fluid dynamics (CFD) studies relating to chronic rhinosinusitis (CRS), including airflow within the pre and postoperative sinonasal cavity, virtual surgery, topical drug and saline delivery (sprays, nebulizers and rinses) and olfaction. RECENT FINDINGS: Novel CFD-specific parameters (heat flux and wall shear stress) are highly correlated with patient perception of nasal patency. Increased ostial size markedly improves sinus ventilation and drug delivery. New virtual surgery tools allow surgeons to optimize interventions. Sinus deposition of nasal sprays is more effective with smaller, low-inertia particles, outside of the range produced by many commercially available products. Saline irrigation effectiveness is improved using greater volume, with liquid entering sinuses via 'flooding' of ostia rather than direct jet entry. SUMMARY: CFD has provided new insights into sinonasal airflow, air-conditioning function, the nasal cycle, novel measures of nasal patency and the impact of polyps and sinus surgery on olfaction. The deposition efficiency of topical medications on sinus mucosa can be markedly improved through parametric CFD experiments by optimising nasal spray particle size and velocity, nozzle angle and insertion location, while saline irrigation effectiveness can be optimized by modelling squeeze bottle volume and head position. More sophisticated CFD models (inhalation and exhalation, spray particle and saline irrigation) will increasingly provide translational benefits in the clinical management of CRS.

Long-Term Clinical Follow-Up of Patients With Chronic Rhinosinusitis.

OBJECTIVE: This study comprised a long-term follow-up of a cohort of patients with chronic rhinosinusitis (CRS) regarding clinical features and symptomatology. METHODS: Data from 42 patients with CRS were available from a previous study. Forty of these patients were alive and were contacted for inclusion after approximately 10 years. Patients completed a questionnaire about disease and symptoms, and underwent a clinical examination. RESULTS: Thirty-four patients (85%) responded and could be included and evaluated. For the participants in this follow-up study median length of time between initial inclusion (C1) and follow-up (C2) was 11 years (range: 8-15). In some patients the CRS shifted phenotype over time, from CRS with nasal polyposis to CRS without nasal polyposis or vice versa. The median total visual analogue score for combined sinonasal symptoms for all patients was statistically significantly reduced at follow-up. For individual patients, scores for nasal congestion, nasal discharge, facial pressure, and hyposmia were also statistically significantly reduced. The most frequently reported symptom-relieving treatments were nasal steroids and saline rinsing of the nose. Self-reported general quality of life was statistically significantly improved at C2 compared to C1. CONCLUSION: At long-term follow-up, symptoms were generally reduced and patients reported an improved quality of life. Patients can be given hope for eventual symptom relief. CRS is a chronic condition that seems to harbor the ability to alter its phenotype after several years. Topical corticosteroids and saline rinsing of the nose should be emphasized, since patients consider these treatments to be of high value.

A Systematic Review and Meta-Analysis of Taste Dysfunction in Chronic Rhinosinusitis.

OBJECTIVES: Patients with chronic rhinosinusitis (CRS) often describe alterations in sense of taste. These complaints have historically been attributed to olfactory dysfunction; however, there is evidence of direct, objective, gustatory disturbances in the setting of CRS that are not thoroughly characterized. This study sought to investigate and summarize gustatory dysfunction experienced by patients with CRS. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were reviewed following PRISMA guidelines. English language, original studies investigating objective taste in adult patients with CRS were included. A meta-analysis with inverse variance, random-effects model was performed. RESULTS: Of 2750 studies screened, 11 articles with 471 unique patients were included. Patients with CRS exhibit worse gustatory function compared to healthy controls (standardized mean difference 0.94 [95% CI, 0.44-1.45]). Hypogeusia was identified in 32/95 (33.7%) patients from three studies that used methods with a validated definition of hypogeusia. Older age, male gender, and smoking history were associated with taste dysfunction, while objective gustatory and olfactory dysfunction were not correlated. Subjective taste and quality of life measures were also not associated with objective taste. The impact of sinus surgery on objective taste is unclear. CONCLUSION: Approximately 34% of patients with CRS experience hypogeusia. Neither olfactory function nor subjective taste were associated with objective gustatory function. Given the substantial prevalence of taste dysfunction patients with CRS, there is significant potential for growth in understanding of pathogenesis, impact on quality of life, and potential treatment strategies of taste impairment in the CRS patient population. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:482-489, 2021.

Exosomal miR-22-3p Derived from Chronic Rhinosinusitis with Nasal Polyps Regulates Vascular Permeability by Targeting VE-Cadherin.

BACKGROUND: The abnormal vascular permeability is associated with the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). Previously, our study demonstrated that the nasal lavage fluid- (NLF-) derived exosomes from CRSwNP can promote the vascular permeability of human umbilical vein endothelial cells (HUVECs). miR-22-3p, a specific differentiated miRNA, is reported to regulate microvessels in some diseases. This study is purposed to explore the impact of exosomal miR-22-3p derived from CRSwNP on vascular permeability and identify the underlying targets. METHODS: Exosomes were extracted from NLF of 26 CRSwNP patients and 10 control patients. Quantitative real-time PCR (qRT- PCR) was applied to evaluate the relative level of exosomal miR-22-3p. The impact of exosomal miR-22-3p on HUVECs was assessed by permeability assays in vitro. The potential molecular targets of miR-22-3p were investigated by applying such technologies as dual-luciferase reporter assay and western blot. RESULTS: miR-22-3p was upregulated in NLF-derived exosomes from CRSwNP. Exosomal miR-22-3p derived from CRSwNP enhanced the tubule permeability of HUVECs. Vascular endothelial- (VE-) cadherin (CDH5) was identified as a direct target of miR-22-3p. miR-22-3p regulated the vascular permeability by targeting VE-cadherin in HUVECs. CONCLUSIONS: Exosomal miR-22-3p derived from NLF of CRSwNP plays an important role in regulating vascular permeability by targeting VE-cadherin.