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Abstract To identify the differences between COVID-19-associated and non-COVID-19-associated olfactory dysfunction (OD), we analyzed demographic and clinical characteristics based on the causative virus (COVID versus non-COVID groups) in patients with post-infectious olfactory dysfunction (PIOD) who underwent the olfactory questionnaire and olfactory function test. Out of 169 patients with PIOD, 99 were diagnosed with COVID-19 (COVID group), while 70 were not (non-COVID group). The COVID group was younger and had a higher percentage of male patients as well as patients with parosmia than the non-COVID group. In the initial olfactory function tests, the TDI, discrimination and identification scores were significantly higher in the COVID group than in the non-COVID group. TDI scores were significantly increased in patients with PIOD after treatment, regardless of the group. The threshold score was significantly increased by 1.38 in the COVID group while the identification score was significantly increased by 2.67 in the non-COVID group. Patients with COVID-19-associated OD were younger in age, tended to be male, had a higher incidence of parosmia, and had better initial olfactory function test results compared to those with non-COVID-19-associated OD. Following treatment, odor detection threshold improved in the COVID group, whereas odor identification improved in the non-COVID group.

Abstract The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.

Abstract Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8+ T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8+ T cells. We detect multimer+CD8+ T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+ T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer+CD8+ T cells–particularly the CD49a+ subset–exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+ T cells confirms the enhanced effector function of the CD49a+ subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+ memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.

Abstract Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air–liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air–liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment.

Abstract Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.

Background and Objectives This retrospective study, conducted at a single tertiary medical center, aimed to investigate the correlation between the severity of allergic rhinitis (AR) based on subjective symptoms and the severity assessed through laboratory data. Methods In total, 584 patients who were diagnosed with AR by a multiple-allergen simultaneous test were included. Patients were classified into four groups according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification guideline. The visual analog scale (VAS) score for overall discomfort and laboratory parameters, including the serum total immunoglobulin E (IgE) level and peripheral blood eosinophil count, were evaluated in all patients. An analysis was conducted to examine the differences in VAS scores and laboratory findings among the four groups. Additionally, the correlations between the laboratory findings and VAS score were analyzed. Results The serum total IgE level and the percentage and count of peripheral blood eosinophils showed no significant differences among the groups. However, the VAS score for overall discomfort exhibited notable between-group differences. The average VAS score was 6.14 (95% confidence interval 5.94–6.34) in the overall group. The mean scores of each group showed a noticeable increasing trend from the mild intermittent group to the mild persistent, moderate to severe intermittent, and moderate to severe persistent groups (p

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway obstruction during sleep. To reduce the morbidity of OSA, sleep specialists have explored various methods of managing the condition, including manifold positive airway pressure (PAP) techniques and surgical procedures. Nasal obstruction can cause significant discomfort during sleep, and it is likely that improving nasal obstruction would enhance the quality of life and PAP compliance of OSA patients. Many reliable studies have offered evidence to support this assumption. However, few comprehensive guidelines for managing OSA through nasal surgery encompass all this evidence. In order to address this gap, the Korean Society of Otorhinolaryngology-Head and Neck Surgery (KORL-HNS) and the Korean Society of Sleep and Breathing designated a guideline development group (GDG) to develop recommendations for nasal surgery in OSA patients. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. The types of nasal surgery included septoplasty, turbinate surgery, nasal valve surgery, septorhinoplasty, and endoscopic sinus surgery. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians’ grading system. The GDG developed 10 key action statements with supporting text to support them. Three statements are ranked as strong recommendations, three are only recommendations, and four can be considered options. The GDG hopes that this clinical practice guideline will help physicians make optimal decisions when caring for OSA patients. Conversely, the statements in this guideline are not intended to limit or restrict physicians’ care based on their experience and assessment of individual patients.

The automotive industry has experienced remarkable growth in recent decades, with a significant focus on advancements in autonomous driving technology. While still in its early stages, the field of autonomous driving has generated substantial research interest, fueled by the promise of achieving fully automated vehicles in the foreseeable future. High-definition (HD) maps are central to this endeavor, offering centimeter-level accuracy in mapping the environment and enabling precise localization. Unlike conventional maps, these highly detailed HD maps are critical for autonomous vehicle decision-making, ensuring safe and accurate navigation. Compiled before testing and regularly updated, HD maps meticulously capture environmental data through various methods. This study explores the vital role of HD maps in autonomous driving, delving into their creation, updating processes, and the challenges and future directions in this rapidly evolving field.

Abstract Interpreting the relationship between different taste function tests of different stimuli, such as chemical and electrical stimulation, is still poorly understood. This study aims to analyze visually as well as quantitatively how to interpret the relationship of results between taste function tests using different stimuli. Patients who underwent the whole mouth test and Electrogustometry (EGM) at a tertiary medical center between August 2018 and December 2018 were reviewed retrospectively with electronic medical records. Of the 110 patients, a total of 86 adults who self-reported that their taste function was normal through a questionnaire were enrolled. EGM measured the thresholds of the chorda tympani (CT) and glossopharyngeal nerve (GL) area of the tongue. The whole mouth test measured detection and recognition thresholds for sweet, salty, bitter, sour, and umami taste. Statistical analyses of Pearson’s, Spearman’s rank and polyserial correlation and multidimensional scaling (MDS) was performed. The EGM threshold for the average value of both CT regions and the recognition threshold of the whole mouth test were significantly correlated in sweet, salty, bitter, and sour taste (r = 0.244–0.398, P

Obstructive sleep apnea (OSA) is characterized by cyclic normoxic and hypoxic conditions (intermittent hypoxia, IH) induced by the repeated closure of the upper-airway respiratory tract. As a pathomechanism of OSA, IH results in various comorbidities via chronic inflammation and related pathways. However, the role of other inflammatory cells, such as lymphocytes, has not been well-explored. This study aimed to examine the effects of IH on the distribution and balance of T cell subsets and other related cytokines, and mechanisms in the immune system. We modified OSA mouse model (male C57BL/6N male) using our customized chamber that controls specific sleep and oxygenic cycles. To induce hypoxia, the IH group was repeatedly exposed to 5% O2 and 21% O2 lasting for 120 s each for 7 h daily for 4 weeks. Mice were then subjected to a recovery period of 4 weeks, in which IH stimulation was ceased. T cells and related cytokines were analyzed using flow cytometry and immunohistochemistry. Compared with the control group, the IH group had significantly lower levels of CD4+CD25+Foxp3+ regulatory T cells but higher levels of Th 17, IL-4, HIF-1, and inflammatory cytokines. After the recovery period, these altered changes in the immune cells were recovered, and we found no significant difference in their levels between the control and recovery groups. This study revealed that the Th17/Treg ratio is increased by intermittent hypoxia, and this imbalance can explain immune-related diseases, including recently reported allergies, autoimmune, and even cancer diseases, arising from OSA.

The proliferation of current and next-generation mobile and sensing devices has increased at an alarming rate. With these state-of-the-art devices, the global positioning system (GPS) has made remote sensing and location tracking more viable. One such query is the All Nearest Neighbor (ANN) query, which extracts and returns all data objects that are in close vicinity to all query objects. An ANN is a combination of $k$ -nearest neighbors (kNN), and join queries. Hence, ANN has useful for applications in different domains such as transportation optimization, locating safe zones, and ride-sharing. An example of its applications is, “find the nearest gas station for each car parking lot”. Because these applications are responsible for generating a massive number of query requests, a large amount of computation is required to return these query requests. As a single machine cannot meet this demand in this study, we propose a distributed query processing framework to process ANN queries using the Apache Spark framework. In an empirical study, our proposed framework achieved superior query efficiency and scalability compared to other methods and design alternatives.

Introduction: Serum level of high-mobility group box 1 protein is reportedly correlated with the severity of obstructive sleep apnea. Objective: We tried to evaluate the possibility of using the serum high-mobility group box 1 protein level as a biologic marker in obstructive sleep apnea patients. Methods: We generated a chronic intermittent hypoxia murine model that reflected human obstructive sleep apnea. Obstructive sleep apnea patients who underwent polysomnography were prospectively enrolled. Serum samples were obtained from mice and obstructive sleep apnea patients, and the serum high-mobility group box1 protein level was measured by enzyme-linked immunosorbent assay. Results: Serum high-mobility group box 1 protein level was 56.16 ± 30.33 ng/mL in chronic intermittent hypoxia and 18.63 ± 6.20 ng/mL in control mice (p 0.05). Instead, this protein level was significantly correlated with lowest arterial oxygen concentration (SaO2) (p

Gossypiboma, an infrequent surgical complication, describes a mass of cotton material inadvertently left in the body cavity after an operation. It is an extremely rare iatrogenic complication of nasal surgery, with only a few cases reported in literature to date. Here we present a case of gossypiboma in the nasal septum of a 35-year-old male patient who previously underwent septorhinoplasty fourteen years prior. He was treated by endoscopic endonasal surgery to remove the lesion. Pathologic findings showed a foreign body (gauze filament) with a giant cell reaction. This report will be helpful for treating patients with similar histories in the future.

Olfaction is an important aspect of quality of life, beyond simply smelling food and recognizing danger. Recently, research has focused on its association with various diseases, such as neurodegenerative diseases or viral infections. The evaluation of olfactory function must take into consideration the cultural experience of the target group. A new Korean culturefriendly olfactory function test, the YSK olfactory function test (YOF test, Kimex Co.), uses safe odorants, such as phenyl-ethyl alcohol (PEA) (not n-butanol), for the threshold test. Furthermore, odorants in the YOF identification test reflect each of eight major chemical functional groups. The diagnostic cut-off for anosmia was a Threshold Discrimination Identification (TDI) score of ≤14.5 and that for hyposmia was 14.5

IntroductionThe olfactory epithelium (OE) and olfactory bulb (OB) are the major components of the olfactory system and play critical roles in olfactory perception. However, the embryonic development of OE and OB by using the olfactory specific genes has not been comprehensively investigated yet. Most previous studies were limited to a specific embryonic stage, and very little is known, till date, about the development of OE.MethodsThe current study aimed to explore the development of mouse olfactory system by spatiotemporal analysis of the histological features by using the olfactory specific genes of olfactory system from the prenatal to postnatal period.ResultsWe found that OE is divided into endo-turbinate, ecto-turbinate, and vomeronasal organs, and that putative OB with putative main and accessory OB is formed in the early developmental stage. The OE and OB became multilayered in the later developmental stages, accompanied by the differentiation of olfactory neurons. Remarkably, we found the development of layers of olfactory cilia and differentiation of OE to progress dramatically after birth, suggesting that the exposure to air may facilitate the final development of OE.DiscussionOverall, the present study laid the groundwork for a better understanding of the spatial and temporal developmental events of the olfactory system.

Abstract Objective The aim of this systematic review and meta‐analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis. Methods The PubMed, Web of Science, and Cochrane Library databases were searched for articles examining hematocrit values in patients with OSA and control individuals published till September 1, 2021. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated, and subgroup analyses were performed. Results Eleven eligible studies with a total of 4608 patients with OSA were included in this meta‐analysis. Pooled outcomes revealed that hematocrit values were significantly higher in patients with OSA than in controls (SMD, 0.19; 95% CI, 0.08–0.29; p

Background and Objectives Osteomas are the most common benign tumors of the nasal cavity and paranasal sinuses (PNSs). In this study, clinical features and imaging findings were analyzed in patients with osteoma confirmed by ostiomeatal unit (OMU) computed tomography (CT) and PNS CT, and the surgical treatment performed at our hospital was introduced. Methods The Severance Clinical Research Analysis Portal (SCRAP) service of Severance Hospital was used to collect research data. A total of 128 cases of osteomas of the nasal cavity or PNSs confirmed by OMU CT or PNS CT was retrospectively reviewed, including the location and size of the osteoma, clinical features, accompanying findings on imaging tests, and cases of surgical treatment. Results In this study, osteomas were found in about 0.55% of patients who underwent computed tomography. Osteomas were most frequently found in the ethmoid sinus, followed by the frontal sinus, fronto-ethmoid sinus, maxillary sinus, intranasal sphenoid sinus, and maxillary sinus-ethmoid sinus. Patients with osteomas complained of symptoms such as rhinorrhea, postnasal drip, nasal congestion, hyposmia, headache, visual disturbance, and lacrimal duct obstruction. Conclusion Surgical treatment was considered for patients presenting with severe headache, visual field symptoms, or accompanying rhinosinusitis. Surgery was performed by endoscopic or external approaches depending on location and size of the osteoma.

The pathophysiology of CRS is multifactorial and complex yet needs to be completed. Recent evidence emphasizes the crucial part played by epithelial cells in the development of CRS. The epithelial cells act as physical barriers and play crucial roles in host defense, including initiating and shaping innate and adaptive immune responses. This review aims to present a comprehensive understanding of the significance of nasal epithelial cells in CRS. New research suggests that epithelial dysfunction plays a role in developing CRS through multiple mechanisms. This refers to issues with a weakened barrier function, disrupted mucociliary clearance, and irregular immune responses. When the epithelial barrier is compromised, it can lead to the passage of pathogens and allergens, triggering inflammation in the body. Furthermore, impaired mucociliary clearance can accumulate pathogens and secretions of inflammatory mediators, promoting chronic inflammation. Epithelial cells can release cytokines and chemokines, which attract and activate immune cells. This can result in an imbalanced immune response that continues to cause inflammation. The interaction between nasal epithelial cells and various immune cells leads to the production of cytokines and chemokines, which can either increase or decrease inflammation. By comprehending the role of epithelial cells in CRS, we can enhance our understanding of the disease’s pathogenesis and explore new therapeutics.

Abstract Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na+ absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.

Central sleep apnea (CSA) is defined as an absence of breathing without respiratory drive during sleep. It can occur after treatment of obstructive sleep apnea (OSA), a phenomenon known as treatment-emergent central sleep apnea (TECSA). We present a case of a 23-year-old male who developed CSA after pharyngeal and nasal surgery for severe OSA. High loop gain and increased ventilations from frequent arousal are likely explanations for our patient’s central apnea, which resolved with positive airway pressure therapy that possibly alleviated residual airway obstruction and ventilatory instability. This case suggests that effectiveness of treatment for OSA should be based on careful long-term observation with multiple follow-up polysomnography tests, especially in patients at high risk of TECSA.

Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)−/− mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3−/− mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3−/− mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3−/− mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3−/− mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3−/− mice without notable changes in pulmonary vasculature under CIH conditions.

Deep learning techniques have been widely applied to classify tree species and segment tree structures. However, most recent studies have focused on the canopy and trunk segmentation, neglecting the branch segmentation. In this study, we proposed a new approach involving the use of the PointNet++ model for segmenting the canopy, trunk, and branches of trees. We introduced a preprocessing method for training LiDAR point cloud data specific to trees and identified an optimal learning environment for the PointNet++ model. We created two learning environments with varying numbers of representative points (between 2048 and 8192) for the PointNet++ model. To validate the performance of our approach, we empirically evaluated the model using LiDAR point cloud data obtained from 435 tree samples scanned by terrestrial LiDAR. These tree samples comprised Korean red pine, Korean pine, and Japanese larch species. When segmenting the canopy, trunk, and branches using the PointNet++ model, we found that resampling 25,000–30,000 points was suitable. The best performance was achieved when the number of representative points was set to 4096.

Objectives Cultural familiarity and safety must be considered when assessing olfactory ability. The YSK olfactory function (YOF) test is a new olfactory function test using culturally familiar odorants to Koreans. Methods The YOF test comprises three subtests for threshold (T), discrimination (D), and identification (I). The identification test included eight universal and four Korean culture-friendly odorants, which were selected considering eight major functional groups. Data were obtained from 1,127 subjects over 19 years old. Subjects were classified as having normosmia (n=542), hyposmia (n=472), and anosmia (n=113) by self-reported olfactory function. The YOF test and the Korean version of the Sniffin’ stick test (KVSS-II) were performed on the same day in random order. Diagnostic cutoffs for anosmia and hyposmia were calculated using the Youden index (J). Results The mean values for each T/D/I subtest and the total TDI score were as follows: normosmia (T, 4.6±2.3; D, 8.6±2.1; I, 11.1±1.7; TDI score, 24.2±4.5); hyposmia (T, 3.3±2.2; D, 7.1±2.5; I, 9.2±3.1; TDI score, 19.5±6.4); and anosmia (T, 1.7±1.2; D, 5.1±2.5; I, 5.0±3.2; TDI score, 11.8±5.6). The correlation coefficients between the YOF test and KVSS-II were 0.57, 0.65, 0.80, and 0.86 for T, D, I, and the TDI score, respectively (P

Abstract Background The purpose of this study was to determine the therapeutic value of drug-induced sleep endoscopy (DISE) by comparing the outcomes of tongue base surgery based on Muller’s maneuver (MM) and those based on DISE in obstructive sleep apnea (OSA) patients. Methods Ninety-five patients who underwent the tongue base surgery in combination with palatal surgery for OSA at a tertiary referral hospital between March 2012 and March 2019 were enrolled in this retrospective comparative study. Forty-seven patients underwent MM for surgical decision and 48 patients underwent DISE in addition to MM for surgical decision. Surgical success was defined according to the Sher criteria (postoperative apnea-hypopnea index [AHI]

Advances in mobile technologies and map-based applications enables users to utilize sophisticated spatial queries, including k-nearest neighbor and shortest path queries. Often, location-based servers are used to handle multiple simultaneous queries because of the popularity of map-based applications. This study focuses on the efficient processing of multiple concurrent k-farthest neighbor (kFN) queries in road networks. For a positive integer k, query point q, and set of data points P, a kFN query returns k data points farthest from the query point q. For addressing multiple concurrent spatial queries, traditional location-based servers based on one-query-at-a-time processing are unsuitable owing to high redundant computation costs. Therefore, we propose a group processing of multiple kFN (GMP) algorithm to process multiple kFN queries in road networks. The proposed GMP algorithm uses group computation to avoid the redundant computation of network distances between the query and data points. The experiments using real-world roadmaps demonstrate the proposed solution's effectiveness and efficiency.

Objectives We performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).Design Retrospective cross-sectional analysis of health survey data.Setting Voluntary survey of representative South Korean populations.Participants In total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.Primary and secondary outcome measures Diagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.Methods A multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.Results The prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p

Background: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. Methods: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. Results: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. Conclusions: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases. Key words: Allergen, Epidemiology, House dust mite, Pollen, Sensitization

Given a set of facilities F and a query point q, a k-farthest neighbor (kFN) query returns the k farthest facilities f1,f1,⋯,fk from q. This study considers the moving k-farthest neighbor (MkFN) query that constantly retrieves the k facilities farthest from a moving query point q in a road network. The main challenge in processing MkFN queries in road networks is avoiding the repeated retrieval of candidate facilities as the query point arbitrarily moves along the road network. To this end, this study proposes a moving farthest search algorithm (MOFA) to compute valid segments for the query segment in which the query point is located. Each valid segment has the same k facilities farthest from the query locations in the valid segment. Therefore, MOFA retrieves candidate facilities only once for the query segment and computes valid segments using these candidate facilities, thereby avoiding the repeated retrieval of candidate facilities when the query point moves. An empirical study using real-world road networks demonstrates the superiority and scalability of MOFA compared to a conventional solution.

This paper considers k-farthest neighbor (kFN) join queries in spatial networks where the distance between two points is the length of the shortest path connecting them. Given a positive integer k, a set of query points Q, and a set of data points P, the kFN join query retrieves the k data points farthest from each query point in Q. There are many real-life applications using kFN join queries, including artificial intelligence, computational geometry, information retrieval, and pattern recognition. However, the solutions based on the Euclidean distance or nearest neighbor search are not suitable for our purpose due to the difference in the problem definition. Therefore, this paper proposes a cluster nested loop join (CNLJ) algorithm, which clusters query points (data points) into query clusters (data clusters) and reduces the number of kFN queries required to perform the kFN join. An empirical study was performed using real-life roadmaps to confirm the superiority and scalability of the CNLJ algorithm compared to the conventional solutions in various conditions.

Nearest neighbor (NN) and range (RN) queries are basic query types in spatial databases. In this study, we refer to collections of NN and RN queries as spatial proximity (SP) queries. At peak times, location-based services (LBS) need to quickly process SP queries that arrive simultaneously. Timely processing can be achieved by increasing the number of LBS servers; however, this also increases service costs. Existing solutions evaluate SP queries sequentially; thus, such solutions involve unnecessary distance calculations. This study proposes a unified batch algorithm (UBA) that can effectively process SP queries in dynamic spatial networks. With the proposed UBA, the distance between two points is indicated by the travel time on the shortest path connecting them. The shortest travel time changes frequently depending on traffic conditions. The goal of the proposed UBA is to avoid unnecessary distance calculations for nearby SP queries. Thus, the UBA clusters nearby SP queries and exploits shared distance calculations for query clusters. Extensive evaluations using real-world roadmaps demonstrated the superiority and scalability of UBA compared with state-of-the-art sequential solutions.

The increasing trend of GPS-enabled smartphones has led to the tremendous usage of Location-Based Service applications. In the past few years, a significant amount of studies have been conducted to process All nearest neighbor (ANN) queries. An ANN query on a road network extracts and returns all the closest data objects for all query objects. Most of the existing studies on ANN queries are performed either in Euclidean space or static road networks. Moreover, combining the nearest neighbor query and join operation is an expensive procedure because it requires computing the distance between each pair of query objects and data objects. This study considers the problem of processing the ANN queries on a dynamic road network where the weight, i.e., the traveling distance and time varies due to various traffic conditions. To address this problem, a shared execution-based approach called standard clustered loop (SCL) is proposed that allows efficient processing of ANN queries on a dynamic road network. The key concept behind the shared execution technique is to exploit the coherence property of road networks by clustering objects that share common paths and processing the cluster as a single path. In an empirical study, the SCL method achieves significantly better performance than competitive methods and efficiently reduces the computational cost to process ANN queries in various problem settings.

Recent brain connectome studies have evidenced distinct and overlapping brain regions involved in processing olfactory perception. However, neural correlates of hypo- or anosmia in olfactory disorder patients are poorly known. Furthermore, the bottom-up and top-down processing of olfactory perception have not been well-documented, resulting in difficulty in locating the disease foci of olfactory disorder patients. The primary aim of this study is to characterize the bottom-up process of the neural dynamics across peripheral and central brain regions in anesthetized mice. We particularly focused on the neural oscillations of local field potential (LFP) in olfactory epithelium (OE), olfactory blub (OB), prefrontal cortex (PFC), and hippocampus (HC) during an olfactory oddball paradigm in urethane anesthetized mice. Odorant presentations evoked neural oscillations across slow and fast frequency bands including delta (1–4 Hz), theta (6–10 Hz), beta (15–30 Hz), low gamma (30–50 Hz), and high gamma (70–100 Hz) in both peripheral and central nervous systems, and the increases were more prominent in the infrequently presented odorant. During 5 s odorant exposures, the oscillatory responses in power were persistent in OE, OB, and PFC, whereas neural oscillations of HC increased only for short time at stimulus onset. These oscillatory responses in power were insignificant in both peripheral and central regions of the ZnSO4-treated anosmia model. These results suggest that olfactory stimulation induce LFP oscillations both in the peripheral and central nervous systems and suggest the possibility of linkage of LFP oscillations in the brain to the oscillations in the peripheral olfactory system.

The rapid growth of GPS-enabled mobile devices has popularized many location-based applications. Spatial keyword search which finds objects of interest by considering both spatial locations and textual descriptions has become very useful in these applications. The recent integration of social data with spatial keyword search opens a new service horizon for users. Few previous studies have proposed methods to combine spatial keyword queries with social data in Euclidean space. However, most real-world applications constrain the distance between query location and data objects by a road network, where distance between two points is defined by the shortest connecting path. This paper proposes geo-social top-k keyword queries and geo-social skyline keyword queries on road networks. Both queries enrich traditional spatial keyword query semantics by incorporating social relevance component. We formalize the proposed query types and appropriate indexing frameworks and algorithms to efficiently process them. The effectiveness and efficiency of the proposed approaches are evaluated using real datasets.

Purpose. We hypothesized that CIH may affect the upper airway immune system and aimed to verify whether CIH can induce airway inflammation in a murine obstructive sleep apnea (OSA) model. Methods. C57BL6 male mice were exposed to intermittent hypoxia (CIH group; 5 ~ 21% FiO2, 120 sec cycles, 12 h/d, n=6) or room air (Sham group, n=6) for up to 4 weeks in identical chambers. Nasal and lung tissues and lavage fluid were collected and analyzed by multiplex assay. Lung lavage fluid was also utilized for FACS analysis to determine eosinophil count. Results. We determined the protein level of 24 different cytokines, chemokines, and inflammatory mediators. Among various cytokines, levels of IL-1α, IL-1β, IL-4, IL-6, and IL-13 were significantly elevated in nose or lung tissue from the CIH group. In addition, MCP-1 and periostin were elevated in nose and lung tissue and lavage fluid from the CIH group. Conclusions. CIH for 4 weeks altered the levels of inflammatory mediators in both the nose and lungs of mouse model. We suggest that the airway immune system may be deteriorated by CIH and allergic inflammation in the upper or lower airway could be worsened by sleep apnea.

Given a threshold distance ε and two object sets R and S in a road network, an ε-distance join query finds object pairs from R × S that are within the threshold distance ε (e.g., find passenger and taxicab pairs within a five-minute driving distance). Although this is a well-studied problem in the Euclidean space, little attention has been paid to dynamic road networks where the weights of road segments (e.g., travel times) are frequently updated and the distance between two objects is the length of the shortest path connecting them. In this work, we address the problem of ε-distance join queries in dynamic road networks by proposing an optimized ε-distance join algorithm called EDISON, the key concept of which is to cluster adjacent objects of the same type into a group, and then to optimize shared execution for the group to avoid redundant network traversal. The proposed method is intuitive and easy to implement, thereby allowing its simple integration with existing range query algorithms in road networks. We conduct an extensive experimental study using real-world roadmaps to show the efficiency and scalability of our shared execution approach.

Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269-319 proteins per subject). We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38%) had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican). A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment.

The aim of this study was to identify correlations between sleep apnea severity and tongue volume or posterior airway space measured via three-dimensional reconstruction of volumetric computerized tomography (CT) images in patients with obstructive sleep apnea (OSA) for use in predicting OSA severity and in surgical treatment. We also assessed associations between tongue volume and Mallampati score.Snoring/OSA male patients (n = 64) who underwent polysomnography, cephalometry, and CT scans were enrolled in this retrospective study. OSA was diagnosed when the apnea-hypopnea index (AHI) was greater than 5 (mild 5-14; moderate 15-29; severe>30). The patients were also categorized into the normal-mild group (n = 22) and the moderate-severe group (n = 42). Using volumetric CT images with the three-dimensional reconstruction technique, the volume of the tongue, posterior airway space volume, and intra-mandibular space were measured. The volumes, polysomnographic parameters, and physical examination findings were compared, and independent factors that are related to OSA were analysed.No associations between tongue volume or posterior airway space and the AHI were observed. However, multivariate linear analyses showed that tongue volume had significantly negative association with lowest O2 saturation (r = 0.365, p = 0.027). High BMI was related to an increase in tongue volume. Modified Mallampati scores showed borderline significant positive correlations with absolute tongue volume (r = 0.251, p = 0.046) and standardized tongue volume (absolute tongue volume / intramandibular area; r = 0.266, p = 0.034). Between the normal-mild and moderate-severe groups, absolute tongue volumes were not different, although the standardized tongue volume in the moderate-severe group was significantly higher.Absolute tongue volume showed stronger associations with lowest O2 saturation during sleep than with the severity of AHI. We also found that high BMI was a relevant factor for an increase in absolute tongue volume and modified Mallampati grading was a useful physical examination to predict tongue size.

To determine if oral dosing with the CFTR-potentiator ivacaftor (VX-770, Kalydeco) improves CFTR-dependent sweating in CF subjects carrying G551D or R117H-5T mutations, we optically measured sweat secretion from 32-143 individually identified glands in each of 8 CF subjects; 6 F508del/G551D, one G551D/R117H-5T, and one I507del/R117H-5T. Two subjects were tested only (-) ivacaftor, 3 only (+) ivacaftor and 3 (+/-) ivacaftor (1-5 tests per condition). The total number of gland measurements was 852 (-) ivacaftor and 906 (+) ivacaftor. A healthy control was tested 4 times (51 glands). For each gland we measured both CFTR-independent (M-sweat) and CFTR-dependent (C-sweat); C-sweat was stimulated with a β-adrenergic cocktail that elevated [cAMP]i while blocking muscarinic receptors. Absent ivacaftor, almost all CF glands produced M-sweat on all tests, but only 1/593 glands produced C-sweat (10 tests, 5 subjects). By contrast, 6/6 subjects (113/342 glands) produced C-sweat in the (+) ivacaftor condition, but with large inter-subject differences; 3-74% of glands responded with C/M sweat ratios 0.04%-2.57% of the average WT ratio of 0.265. Sweat volume losses cause proportionally larger underestimates of CFTR function at lower sweat rates. The losses were reduced by measuring C/M ratios in 12 glands from each subject that had the highest M-sweat rates. Remaining losses were estimated from single channel data and used to correct the C/M ratios, giving estimates of CFTR function (+) ivacaftor = 1.6%-7.7% of the WT average. These estimates are in accord with single channel data and transcript analysis, and suggest that significant clinical benefit can be produced by low levels of CFTR function.

Von-Willebrand disease (VWD) is one of the platelet dysfunction disorders that results from a deficiency of Von-Willebrand factor, which is essential for hemostasis. VWD patients typically have normal laboratory results on screening for bleeding disorders. To suspect and diagnose VWD, a careful review of past medical history and laboratory tests is critical. A 59-year-old male patient presented with intractable nasal bleeding after nasal polypectomy. The bleeding was controlled by platelet transfusion, and he was later diagnosed with VWD.

Excessive mucus production is typical in various upper airway diseases. In sinusitis, the expression of MUC5AC, a major respiratory mucin gene, increases. However, the mechanisms leading to mucus hypersecretion in sinusitis have not been characterized. Hypoxia due to occlusion of the sinus ostium is one of the major pathologic mechanisms of sinusitis, but there have been no reports regarding the mechanism of hypoxia-induced mucus hypersecretion.This study aims to identify whether hypoxia may induce mucus hypersecretion and elucidate its mechanism. Normal human nasal epithelial (NHNE) cells and human lung mucoepidermoid carcinoma cell line (NCI-H292) were used. Sinus mucosa from patients was also tested. Anoxic condition was in an anaerobic chamber with a 95% N2/5% CO2 atmosphere. The regulatory mechanism of MUC5AC by anoxia was investigated using RT-PCR, real-time PCR, western blot, ChIP, electrophoretic mobility shift, and luciferase assay. We show that levels of MUC5AC mRNA and the corresponding secreted protein increase in anoxic cultured NHNE cells. The major transcription factor for hypoxia-related signaling, HIF-1α, is induced during hypoxia, and transfection of a mammalian expression vector encoding HIF-1α results in increased MUC5AC mRNA levels under normoxic conditions. Moreover, hypoxia-induced expression of MUC5AC mRNA is down-regulated by transfected HIF-1α siRNA. We found increased MUC5AC promoter activity under anoxic conditions, as indicated by a luciferase reporter assay, and mutation of the putative hypoxia-response element in MUC5AC promoter attenuated this activity. Binding of over-expressed HIF-1α to the hypoxia-response element in the MUC5AC promoter was confirmed. In human sinusitis mucosa, which is supposed to be hypoxic, expression of MUC5AC and HIF-1α is higher than in control mucosa.The results indicate that anoxia up-regulates MUC5AC by the HIF-1α signaling pathway in human nasal epithelia and suggest that hypoxia might be a pathogenic mechanism of mucus hypersecretion in sinusitis.

A reverse k nearest neighbor (RkNN) query retrieves all the data points that have q as one of their k closest points. In recent years, considerable research has been conducted into monitoring reverse k nearest neighbor queries. In this paper, we study the problem of continuous reverse nearest neighbor queries where both the query object q and data objects are moving. Existing state-of-the-art techniques are sensitive towards the movement of data objects, e.g., a candidate object must be verified whenever it changes its location. Further, insufficient attention has been given to the monitoring of RNN queries in dynamic road networks where the network weight changes depending on the traffic conditions. In this paper, we address these problems by proposing a new safe exit-based algorithm called CORE-X for efficiently computing the safe exit points of both query and data objects. The safe exit point of an object indicates the point at which its safe region and non-safe region meet, thus a set of safe exit points represents the border of the safe region. Within the safe region, the query result remains unchanged provided the query and data objects remain inside their respective safe regions. The results of extensive experiments conducted using real road maps indicate that the proposed algorithm significantly reduces communication and computation costs compared to the state-of-the-art algorithm.

To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a β-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.

INTRODUCTION: We hypothesized that the size of the hyoid bone itself may affect the severity of sleep apnea. The aim of this study was to identify the relationship between hyoid bone dimensions and the severity of sleep apnea using computerized tomography (CT) axial images. METHODS: We retrospectively measured the hyoid bone in axial images of neck CTs and correlated these measurements with results of polysomnography in a total of 106 male patients. The new hyoid bone parameters studied in this study were as follows: distance between bilateral lesser horns (LH-d), distance between bilateral greater horns (GH-d), distance from the most anterior end of the hyoid arch to GH-d (AP), distance from the greater to the lesser horn on right and left sides (GH-LH), and the anterior angle between bilateral extensive lines from the greater to the lesser horn (H-angle). Data was analyzed using univariate and multivariate logistic regression, and Pearson correlation tests. RESULTS: We found a significant inverse correlation between the apnea-hypopnea index (AHI) and GH-d or AP. Neither the LH-d, GH-LH, nor H-angle were associated with the AHI. The patient group that met the criteria of both GH-d

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm that mainly arises from the lymphoid tissues of the immune system. Although this neoplasm typically occurs anywhere along the lymph nodes, it can also be found at extranodal sites, especially in the head and neck. We experienced a rare case of extranodal IDCS in the nasal cavity, a location that has not been previously reported. A 73-year-old woman presented with a polyp-like mass in the nasal cavity and underwent endoscopic sinus surgery. A histologic study confirmed the mass as IDCS by immunohistochemistry with S-100 antibody, and postoperative adjuvant radiotherapy was administered. Although the incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of nasal cavity masses.

Top-k spatial preference queries rank objects based on the score of feature objects in their spatial neighborhood. Top-k preference queries are crucial for a wide range of location based services such as hotel browsing and apartment searching. In recent years, a lot of research has been conducted on processing of top-k spatial preference queries in Euclidean space. While few algorithms study top-k preference queries in road networks, they all focus on undirected road networks. In this paper, we investigate the problem of processing the top-k spatial preference queries in directed road networks where each road segment has a particular orientation. Computation of data object scores requires examining the scores of each feature object in its spatial neighborhood. This may cause the computational delay, thus resulting in a high query processing time. In this paper, we address this problem by proposing a pruning and grouping of feature objects to reduce the number of feature objects. Furthermore, we present an efficient algorithm called TOPS that can process top-k spatial preference queries in directed road networks. Experimental results indicate that our algorithm significantly reduces the query processing time compared to period solution for a wide range of problem settings.

Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca(2+)-sensitive dye Fura2-AM was used to determine intracellular Ca(2+) concentration ([Ca(2+)](i)) by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP) elevated intracellular Ca(2+) and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca(2+) and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca(2+)-dependent and cystic fibrosis transmembrane conductance regulator-independent.

Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion.Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CF(ΔF508/ΔF508) with CFTR(-/-) piglets and found significantly greater forskolin-stimulated secretion rates in the ΔF508 vs. the null piglets (1.4±0.8, n = 4 vs. 0.2±0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ∼4 times greater in adult than in neonatal nasal glands.These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ΔF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections.

Background and Objectives: The serum galactomannan test (GM test) and the (1,3)-β-D-glucan test (G test) are utilized in diagnosing invasive fungal sinusitis. However, their effectiveness in detecting paranasal sinus fungus balls (FBs) has not been established. This study aimed to explore their diagnostic value in patients with FBs. Methods: We retrospectively reviewed the medical records of 105 patients (42 with FBs and 63 with chronic rhinosinusitis [CRS]) who underwent serum GM and G tests between June 2020 and May 2021. Olfactory test results and demographics were also analyzed. Results: There were 42 FB patients (10 men, 32 women) and 63 CRS patients (27 men, 36 women). The positivity rates for serum GM (7.1% in the FB group vs. 3.2% in the CRS group, p=0.640) and G test (9.5% in the FB group vs. 11.1% in the CRS group, p=0.482) did not differ significantly between groups. The sensitivities of the GM and G tests were 7.1% and 9.5%, respectively, and their specificities were 96.8% and 88.9%, respectively. The positive predictive values were 60.0% for the GM test and 36.3% for the G test, and the negative predictive values were 61.0% for the GM test and 59.6% for the G test. Conclusion: Serum GM and G tests demonstrated low sensitivity and high specificity, indicating limited effectiveness in differentiating between patients with FBs and those with CRS. Histological examination remains the gold standard for the definitive diagnosis of FBs. [ABSTRACT FROM AUTHOR]