Associations Between Systemic Inflammatory Markers Based on Blood Cells and Polysomnographic Factors in Obstructive Sleep Apnea

Objectives@#. Systemic inflammation plays a key role in the pathogenesis of obstructive sleep apnea (OSA); however, easy-to-use methods to evaluate the severity of systemic inflammation have yet to be developed. This study investigated the association between systemic inflammation markers that could be derived from the complete blood count (CBC) profile and sleep parameters in a large number of patients with OSA. @*Methods@#. Patients who visited our hospital’s Otorhinolaryngology Sleep Clinic between January 2017 and April 2022 underwent polysomnography and routine laboratory tests, including a CBC. Associations between three systemic inflammatory markers—the systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR)—and polysomnographic and demographic factors including age, sex, body mass index, the apnea-hypopnea index (AHI), the hypopnea index (HI), lowest oxygen saturation (%), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, and percentages of non-rapid eye movement (REM) sleep stage 3, REM sleep, and snoring time were analyzed. The inflammation markers were compared among OSA subgroups, and associations were also analyzed in subgroups with different OSA severities. @*Results@#. In total, 1,102 patients (968 men and 134 women) were included, and their mean AHI was 33.0±24.3. PSQI was significantly associated with SII (P=0.027). No independent significant factors were identified for the NLR or PLR. Within the simple snoring and mild OSA subgroups, no significant association was found between sleep parameters and the SII. In the severe OSA subgroup, the AHI (P=0.004) and PSQI (P=0.012) were independently associated with the SII. @*Conclusion@#. Our study analyzed systemic inflammatory markers based on the CBC, a simple, relatively cost-effective test, and showed that the AHI and SII were significantly correlated only in the severe OSA subgroup.

Prevalence and Clinical Implications of Lateral Wall Dehiscence in the Sphenoid Sinus: Sternberg’s Canal

Background and Objectives@#Sternberg’s canal is known to result from incomplete fusion of bony compartments constituting the sphenoid bone during the developmental process. This study aimed to evaluate the prevalence and clinical implications of Sternberg’s canal. @*Methods@#A retrospective review of patients over the age of 18 years who had undergone endoscopic sinus surgery from 2014 to 2019 at a single institution was performed. Patients (n=98) were categorized into those with sphenoid fungal ball (SFB) (n=39), those with primary chronic rhinosinusitis (CRS) (n=39), and controls (n=20) and were evaluated radiologically. A small pit in the lateral wall, located medial to the maxillary division of the trigeminal nerve (V2), in front of the opticocarotid recess was regarded as Sternberg’s canal. Children under the age of 12 years (n=39) without any sinus disease were also evaluated to determine the prevalence of Sternberg’s canal in the pediatric population. @*Results@#Patients with SFB showed the highest prevalence of Sternberg’s canal (56.4%), followed by those with CRS (20.5%) and controls (10.0%) (p<0.001). Logistic regression revealed that Sternberg’s canal was associated with osteitis of the sphenoid wall, and not with age, sex, or sphenoid sinus pathology. Children under the age of 12 years showed a significantly higher prevalence of the defect than adult controls (46.2%, p<0.001). @*Conclusion@#Sternberg’s canal was frequently identified in children under the age of 12 years. Sphenoid sinus pathology was often accompanied by osteitis. However, the presence of the canal alone did not predict skull base involvement in patients with SFB. A comprehensive evaluation should hence be performed if skull base involvement is suspected in such patients. Additionally, other clinical implications of Sternberg’s canal should be further evaluated.

Differences in Clinical and Immunological Characteristics According to the Various Criteria for Tissue Eosinophilia in Chronic Rhinosinusitis With Nasal Polyps

Objectives@#Several criteria exist for classifying chronic rhinosinusitis with nasal polyps (CRSwNP) as eosinophilic or non-eosinophilic. This study attempted to evaluate several criteria for defining eosinophilic CRSwNP from clinical and immunological perspectives. @*Methods@#A cohort of 84 patients (73 patients with CRSwNP and 11 control patients) was retrospectively analyzed. Patients were divided into eosinophilic and non-eosinophilic CRSwNP based on four different criteria: eosinophils (EOS) accounting for more than 20% of the total inflammatory cells; ≥70 EOS per high-power field (HPF); >55 EOS/HPF; and ≥10 EOS/HPF. Preoperative clinical characteristics, the immunological profiles of 14 cytokines from nasal tissue, and postoperative outcomes were compared between eosinophilic and non-eosinophilic CRSwNP based on each criterion. These criteria were immunologically validated by using 14 cytokines to predict the performance of tissue eosinophilia with a random forest model. @*Results@#Patients with eosinophilic CRSwNP were significantly older when the criterion of ≥10 EOS/HPF or EOS >20% was used. The number of patients with aspirin intolerance was significantly higher in eosinophilic CRSwNP based on the criterion of EOS >20%. From an immunological perspective, non-type 2 inflammatory cytokines were significantly higher in non-eosinophilic CRSwNP with the criterion of EOS >20% of the total inflammatory cells. In addition, the criterion of EOS >20% of the total inflammatory cells resulted in the best prediction of eosinophilic CRSwNP, with an accuracy of 88.10% and area under the curve of 0.94. @*Conclusion@#Clinical and immunological characteristics were different between eosinophilic and non-eosinophilic CRSwNP depending on a variety of criteria, and the results of this study should be taken into account when choosing the criterion for defining eosinophilic CRSwNP and interpreting the data accordingly.

The Olfactory System: Basic Anatomy and Physiology for General Otorhinolaryngologists

Olfaction is one of the five basic human senses, and it is known to be one of the most primitive senses. The sense of olfaction may have been critical for human survival in prehistoric society, and although many believe its importance has diminished over time, it continues to have an impact on human interaction, bonding, and propagation of the species. Even if we are unaware of it, the sense of smell greatly affects our lives and is closely related to overall quality of life and health. Nonetheless, olfaction has been neglected from a scientific perspective compared to other senses. However, olfaction has recently received substantial attention since the loss of smell and taste has been noted as a key symptom of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Studies investigating olfaction loss in association with coronavirus disease 2019 (COVID-19) have revealed that olfactory dysfunction can be both conductive and sensorineural, possibly causing structural changes in the brain. Olfactory training is an effective treatment for olfactory dysfunction, suggesting the reorganization of neural associations. A reduced ability to smell may also alert suspicion for neurodegenerative or psychiatric disorders. Here, we summarize the basic knowledge that we, as otorhinolaryngologists, should have about the sense of smell and the peripheral and central olfactory pathways for managing and helping patients with olfactory dysfunction.

Simultaneous Reconstruction of a Subtotal Maxillectomy and Columella Deficit using Radial Forearm and Preauricular Free Flaps / 대한두경부종양학회지

Reconstruction of subtotal maxillectomy defects with columella deficit is challenging. We report a unique case of facial reconstruction using a free radial forearm flap and a free preauricular flap for the maxillectomy and columella deficit. A 73-year-old woman was diagnosed with recurrent sebaceous carcinoma of the nose. We performed wide excision, including areas of the right cheek, nose, upper lip, maxilla, and columella. The resultant subtotal maxillectomy defect was reconstructed using a three-dimensional flap. First, a free radial forearm flap was transfered to resurface the nasal, oral, and external facial side. Second, a preauricular flap was positioned into the columella defect and anastomosed with the distal portion of the radial forearm flap pedicle. The two flaps survived, and the patient recovered uneventfully. We believe the radial forearm and preauricular double free flaps with the pedicle connection method were effective in reconstructing the present case of subtotal maxillectomy defect.

Development of High-Intensity Focused Ultrasound Therapy for Inferior Turbinate Hypertrophy

Objectives@#. Inferior turbinate (IT) hypertrophy is the main cause of chronic nasal obstruction. We developed a high-intensity focused ultrasound (HIFU) ablation device to treat patients with IT hypertrophy. @*Methods@#. First, computed tomography images of patients with no evidence of sinonasal disease were evaluated to measure and compare the IT, medial mucosal thickness (MT), and space between the nasal septum and IT according to clinical characteristics such as septal deviation. A HIFU prototype was developed based on the above human anatomical studies. The experimental study was performed in five pigs; the nasal volume and histological changes at 1 and 4 weeks postoperatively were evaluated to compare the efficacy of HIFU turbinoplasty with that of radiofrequency turbinoplasty and a control group. @*Results@#. The mean medial MT of the anterior, middle, and posterior portions of the IT were 4.66±1.14, 4.23±0.97, and 6.17±1.29 mm, respectively. The mean medial space was 2.65±0.79 mm. The diameter and focal depth of the prototype were 4 mm and 3 mm, respectively. HIFU showed no postoperative complications, including bleeding or scar formation. After HIFU treatment, the nasal volume increased by 196.62 mm3 (7.8%) and 193.74 mm3 (8.3%) at 1 week and 4 weeks, compared with the increase of 87.20 mm3 (3.1%) and 213.81 mm3 (9.0%), respectively,after radiofrequency therapy. A qualitative histological analysis after radiofrequency turbinoplasty showed epithelial layer disruption at 1 week and increased fibrosis, along with decreased glandular structure, at 4 weeks. The HIFU group had an intact epithelial layer at 1 week postoperatively. However, significant differences were observed at 4 weeks, including increased fibrosis and decreased glandular structure. @*Conclusion@#. The efficacy and safety of HIFU turbinoplasty were demonstrated in an animal study. Our results warrant further human clinical trials.

Human Rhinovirus Infection Enhances the Th2 Environment in Allergic and Non-allergic Patients with Chronic Rhinosinusitis

Objectives@#. This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). @*Methods@#. Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. @*Results@#. The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). @*Conclusion@#. This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

Human Rhinovirus Infection Enhances the Th2 Environment in Allergic and Non-allergic Patients with Chronic Rhinosinusitis

Objectives@#. This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). @*Methods@#. Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. @*Results@#. The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). @*Conclusion@#. This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

Characteristics of Obstructive Sleep Apnea Patients With a Low Body Mass Index: Emphasis on the Obstruction Site Determined by Drug-Induced Sleep Endoscopy

Objectives@#. This study aimed to elucidate the patterns of upper airway collapse in obstructive sleep apnea (OSA) patients with a low body mass index (BMI). @*Methods@#. We designed and conducted a retrospective cohort study. Consecutive patients diagnosed with OSA who underwent drug-induced sleep endoscopy (DISE) were included. Patients were classified into four groups according to their BMI. Age, sex, and polysomnography data were investigated. The patterns of upper airway collapse were characterized by the structures involved (soft palate, tongue base, lateral pharyngeal wall, and epiglottis). We compared the patterns of upper airway collapse in the supine and lateral decubitus position among the four BMI groups using the chi-square test and multivariate binary logistic regression analysis. @*Results@#. A total of 627 patients (male, 517; mean age, 47.6±12.8 years) were included, consisting of 45, 79, 151, and 352 patients who were underweight or lower normal-weight (defined as the low BMI group), upper normal-weight, overweight, and obese, respectively. Severity indicators of OSA, such as the overall apnea-hypopnea index and duration of SaO2 below 90%, were significantly lower in patients with a low BMI than in obese patients, while their average oxygen saturation was significantly higher. The most common obstruction site in the supine position was the tongue base in patients with a low BMI (100%), whereas this obstruction site was significantly less common in obese patients (54.8%). Tongue base obstruction was mostly relieved in the lateral position, with no discernible obstruction in 86.7% of the low BMI patients. @*Conclusion@#. Airway obstruction in OSA patients with a low BMI is mostly due to tongue base obstruction, which improves in the lateral position. These characteristics should be kept in mind when considering treatment options for this subgroup of OSA patients.

Clinical Characteristics Other Than Intralesional Hyperdensity May Increase the Preoperative Diagnostic Accuracy of Maxillary Sinus Fungal Ball

Objectives@#. This study aimed to evaluate the clinical characteristics of maxillary sinus fungus ball (MFB) to increase the preoperative diagnostic accuracy. @*Methods@#. A retrospective review of 247 patients who underwent endoscopic sinus surgery for unilateral maxillary sinusitis from January 2015 to December 2017 at a single institution was performed. Patients with pathologically proven MFB were compared to those with unilateral chronic maxillary sinusitis (CMS). Patient demographics and computed tomography (CT) findings were evaluated. The CT features were categorized as intralesional hyperdensity (calcification), the irregular lobulated protruding lesion (fuzzy appearance), maxillary sinus full haziness without mass effect, maxillary sinus full haziness with mass effect, and others. A regression tree analysis was performed. @*Results@#. In total, 247 patients were analyzed; among them, 179 (72.5%) had MFB and 68 (27.5%) had CMS. MFB showed predominance in older individuals. Among the radiological features, intralesional hyperdensity was most commonly associated with MFB. The presence of a fuzzy appearance or full opacity with mass effect was also associated with MFB. The highest area under the curve was noted with the regression tree analysis based on the model, which included the presence of intralesional hyperdensity, demographic data (age), and presence of fuzzy appearance or maxillary sinus full haziness with mass effect in case of absence of intralesional hyperdensity (0.904). @*Conclusion@#. A simple algorithm to optimize the preoperative diagnosis of MFB was developed. Physicians should be aware of such findings in the management of patients presenting with unilateral CMS.

Intranasal Treatment With 1, 25-Dihydroxyvitamin D3 Alleviates Allergic Rhinitis Symptoms in a Mouse Model

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.

Prediction of Obstructive Sleep Apnea Based on Respiratory Sounds Recorded Between Sleep Onset and Sleep Offset

OBJECTIVES: To develop a simple algorithm for prescreening of obstructive sleep apnea (OSA) on the basis of respiratorysounds recorded during polysomnography during all sleep stages between sleep onset and offset. METHODS: Patients who underwent attended, in-laboratory, full-night polysomnography were included. For all patients, audiorecordings were performed with an air-conduction microphone during polysomnography. Analyses included allsleep stages (i.e., N1, N2, N3, rapid eye movement, and waking). After noise reduction preprocessing, data were segmentedinto 5-s windows and sound features were extracted. Prediction models were established and validated with10-fold cross-validation by using simple logistic regression. Binary classifications were separately conducted for threedifferent threshold criteria at apnea hypopnea index (AHI) of 5, 15, or 30. Prediction model characteristics, includingaccuracy, sensitivity, specificity, positive predictive value (precision), negative predictive value, and area under thecurve (AUC) of the receiver operating characteristic were computed. RESULTS: A total of 116 subjects were included; their mean age, body mass index, and AHI were 50.4 years, 25.5 kg/m2, and23.0/hr, respectively. A total of 508 sound features were extracted from respiratory sounds recorded throughoutsleep. Accuracies of binary classifiers at AHIs of 5, 15, and 30 were 82.7%, 84.4%, and 85.3%, respectively. Predictionperformances for the classifiers at AHIs of 5, 15, and 30 were AUC, 0.83, 0.901, and 0.91; sensitivity, 87.5%,81.6%, and 60%; and specificity, 67.8%, 87.5%, and 94.1%. Respective precision values of the classifiers were89.5%, 87.5%, and 78.2% for AHIs of 5, 15, and 30. CONCLUSION: This study showed that our binary classifier predicted patients with AHI of ≥15 with sensitivity and specificityof >80% by using respiratory sounds during sleep. Since our prediction model included all sleep stage data, algorithmsbased on respiratory sounds may have a high value for prescreening OSA with mobile devices.

Early-Life Environmental Factors Can Increase the Risk of Allergic Rhinitis

No abstract available.

Long-term Breastfeeding in the Prevention of Allergic Rhinitis: Allergic Rhinitis Cohort Study for Kids (ARCO-Kids Study)

OBJECTIVES: There is a great deal of interest in the possibility that environmental factors may influence the risk of developing allergic rhinitis (AR) in early life. We investigated the simultaneous effects of mode of delivery and duration of breastfeeding on the development of AR in children. METHODS: Data from 1,374 children participating in the Allergic Rhinitis Cohort Study for kids (ARCO-kids study) was analyzed. All subjects were divided into AR or non-allergic rhinitis (NAR) groups. Data on environmental factors, mode of delivery and duration of breastfeeding were collected using a questionnaire. RESULTS: Compared with short-term breastfeeding (<6 months), long-term breastfeeding (≥12 months) was significantly associated with a lower prevalence of AR (adjusted odds ratio [aOR], 0.54; 95% confidence interval [CI], 0.34 to 0.88). Children in the AR group also had a higher cesarean delivery rate than those in the NAR group (39.1% vs. 32.8%, P=0.05). Regarding the combined effects of mode of delivery and duration of breastfeeding, long-term breastfeeding with a vaginal delivery strongly suppressed the development of AR, compared to short-term breastfeeding with a cesarean delivery (aOR, 0.47; 95% CI, 0.30 to 0.73). CONCLUSION: Long-term breastfeeding (≥12 months) and a vaginal delivery are associated with a lower risk of developing childhood AR.

The Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio before Radical Radiotherapy in Patients with Non-metastatic Nasopharyngeal Carcinoma: A Propensity Score Matching Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed. RESULTS: The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse–free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively). CONCLUSION: The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.

The Role of NF-κB in Chronic Rhinosinusitis With Nasal Polyps

PURPOSE: Whereas the majority of nasal polyps observed in Western populations are eosinophilic, non-eosinophilic nasal polyps are significantly more frequent in Asian countries. Given the importance of nuclear factor-kappa B (NF-κB) in inflammation, this study focused on the role of NF-κB in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs) in Asian patients. METHODS: A total of 46 patients were enrolled in this study (22 diagnosed with CRSwNPs, 10 with chronic rhinosinusitis without nasal polyps [CRSsNP], and 14 control subjects). Nasal polyps and uncinate tissues (UTs) were collected and the tissues prepared for hematoxylin-eosin staining and immunohistochemistric (IHC) analysis. Total RNA was isolated for real-time polymerase chain reaction for p65, interleukin (IL)-6, IL-8, intracellular adhesion molecule (ICAM)-1, IL-1β, tumor necrosis factor (TNF)-α, and eotaxin. RESULTS: In the CRSwNPs group, 50% of nasal polyps were non-eosinophilic. IHC revealed a significantly higher fraction of NF-κB p65-positive cells in nasal polyps of the CRSwNPs group than in the UTs of control and CRSsNP groups. No difference in NF-κB p65-positive cell fraction was observed between eosinophilic and non-eosinophilic nasal polyps. The mRNA expression of p65, IL-6, IL-8, and eotaxin was significantly higher in nasal polyps of the CRSwNPs than in the UTs of control and CRSsNP group. However, no difference in expression was observed between eosinophilic and non-eosinophilic nasal polyps, with the exception of IL-1β expression. CONCLUSIONS: Elevated expression of NF-κB- and NF-κB-associated inflammatory cytokines suggests NF-κB as the key factor for CRSwNPs pathogenesis in Asian patients. Understanding NF-κB-associated mechanisms will provide a deeper insight into CRSwNPs pathogenesis and ultimately improve therapeutic strategies for CRSwNPs.

Immunological Characteristics in Refractory Chronic Rhinosinusitis with Nasal Polyps Undergoing Revision Surgeries

PURPOSE: Despite medical and surgical treatments, some cases of nasal polyps (NP) exhibit recidivism. However, the endotype of refractory chronic rhinosinusitis with NP (CRSwNP) remains unclear. Therefore, the objective of this study was to characterize the immunological profile of refractory CRSwNP. METHODS: The control (n =23), primary NP group (pNP, n =70) and refractory NP group (rNP, n =86) were enrolled in this study. Patients who underwent revision surgeries due to failed maximal medical treatment after primary surgery were defined as the rNP group. A total of 18 inflammatory markers were investigated in nasal tissues using multiplex cytokine assay or enzyme-linked immunosorbent assay. RESULTS: The clinical characteristics of rNP included more extensive disease and worse clinical course after surgery. Additionally, rNP subjects showed higher infection rate (mucopurulence and culture-positive rate), more frequent use of antibiotics and suffered from symptomatic bacterial infection, increased asthma morbidity compared to pNP. Cytokine profile analysis showed that levels of Th17-associated mediators (myeloperoxidase, interleukin (IL)-8, IL-17A and IL-23), B-cell activating factor (BAFF) and Th1 cytokine (interferon-γ) were up-regulated in rNP compared to controls and pNP. Human neutrophil elastase-positive cells were also enhanced in rNP compared with pNP. Upregulation of Th17/Th1mediators and BAFF were observed in rNP, regardless of tissue eosinophilia or asthmatic comorbidity. Interestingly, eosinophilic markers, such as eosinophil cationic protein and C-C motif chemokine ligand 24, were up-regulated in asthmatic rNP compared to pNP and controls. Levels of anti-dsDNA immunoglobulin (Ig) G and IgA were up-regulated in rNP and highest in asthmatic eosinophilic rNP among subtypes of rNP. CONCLUSIONS: Our results suggest that Th17/Th1-associated mediators and BAFF may play a role and be a potential therapeutic target in refractory CRSwNP. Additionally, eosinophilic markers and autoantibodies may contribute to refractoriness in asthmatic rNP.

Optimization of Allergen Panels for Diagnosis of Allergic Rhinitis / 대한이비인후과학회지

The selection of allergen panel is very important to test for innumerable allergens throughout the Korea. However, the allergens studied are heterogeneous depending on the area the patient live and there is no methodological unification. Although, testing panel of allergens should be tailored according to the geographical areas, considering the relatively small Korean Peninsula, common inhalant allergens for test could be retrieved from the published data. Hence, this study is aimed to review the longitudinal variance of allergens in patients with allergic rhinitis live in several regional provinces of Korea, figure out the similarity and differences of sensitized allergens results derived from each study and finally make a guideline for physician in selecting the offending allergens to test. From the inception, studies which analyzing the offending allergens by either ImmunoCAP®, Multiple Allergen Simultaneous Test or Skin testing were reviewed and we found that the common sensitized allergens are house dust mites, pollen and mold plus 1–2 notable different allergens according to the specific regions. Especially, a total of 10±3 allergens adequately detected most of the sensitization of the major regions of Korea according to each age groups and special regional features. This study suggest that physicians should perform the screening of allergic rhinitis with minimally selected allergen in the light of age categories and special regional features. Standardization of allergens selection process would be predicted to have enormous benefits in establishing an insurance policy, giving sound scientific evidence and monitoring the antigenic variations of the Korean Peninsula.

Classification of chronic rhinosinusitis according to a nasal polyp and tissue eosinophilia: limitation of current classification system for Asian population

Chronic rhinosinusitis (CRS) can be classified according to the presence of a nasal polyp (NP): CRS with NP (CRSwNP) and CRS without NP (CRSsNP). CRSwNP has characteristics with high infiltration of tissue eosinophilia with a burst of Th2 inflammatory cytokine. However recent findings in Eastern Asia countries suggest that CRSwNP can be divided according to the presence of tissue eosinophilia. Thus, CRSwNP can be classified into eosinophilic and noneosinophilic. Eosinophilic CRSwNP seems to have different immunological and clinical feature compared to noneosinophilic CRSwNP. From the same point of view, CRSsNP can also be divided according to tissue eosinophilia. However, the meaning of this dichotomous categorization in CRS seems to be not quite clear. This review focus on the limitations in current subclassification of CRS according to the presence of NP and tissue eosinophilia and discuss other factors related to tissue remodeling and NP generation which may provide clues for the further understanding of CRS pathogenesis.

Inhibition of Allergic Response by Intranasal Selective NF-κB Decoy Oligodeoxynucleotides in a Murine Model of Allergic Rhinitis

PURPOSE: It remains unknown whether local inhibition of Nuclear factor-kappa B (NF-κB) could have therapeutic value in the treatment of allergic rhinitis (AR). This study aimed to evaluate the effect of selective NF-κB inhibition using NF-κB decoy oligodeoxynucleotides (ODNs) for the local treatment of AR in ovalbumin (OVA)-sensitized wild-type mice. METHODS: BALB/c mice were sensitized with OVA and alum, and then challenged intranasally with OVA. NF-κB decoy ODNs were given intranasally to the treatment group, and NF-κB scrambled ODNs were given to the sham treatment group. Allergic symptom scores, eosinophil infiltration, cytokine levels in the nasal mucosa, nasal lavage fluid, and spleen cell culture, serum total and OVA-specific immunoglobulins, as well as intercellular adhesion molecure-1 (ICAM-1) in the nasal mucosa, were analyzed. RESULTS: NF-κB decoy ODNs significantly reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. They also suppressed serum levels of total IgE, OVA-specific IgE, and IgG1. IL-5 and TNF-α levels and the expression of ICAM-1 were decreased in the nasal mucosa of the treatment group compared to the positive control and sham treatment groups. In addition, IL-6 levels were significantly decreased in the nasal lavage fluid of the treatment group. Furthermore, NF-κB decoy ODNs significantly reduced expression of the systemic Th2 cytokines, IL-4 and IL-5 in spleen cell culture. CONCLUSIONS: This study demonstrates for the first time that local NF-κB inhibition using NF-κB decoy ODNs suppressed the allergic response in a murine AR model. This shows the therapeutic potential of local NF-κB inhibition in the control of AR.