The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.

Differences in Nasal Shapes and the Degree of Changes Over a Decade or More: A Paired Analysis.

OBJECTIVES: This study investigated age-related differences in nasal morphometry and the degree of changes within an individual over at least a 10-year period by pairing previous and recent three-dimensional reconstructed computed tomography (CT) images. METHODS: Forty-eight adult Korean patients who underwent at least two CT scans of the nasal region with an interval of at least 10 years were selected. Patients were categorized into six subgroups according to sex and age (20-39 years, 40-49 years, and ≥50 years) at the time of initial imaging. Eight nasal parameters were measured on the initial and recent images, and paired comparisons between the two images were performed based on the data. The differences in the degree of change by age were also analyzed. RESULTS: Over an average image interval of 12 years, men exhibited an increase in the nasofrontal angle (3.2°±5.4°, P=0.041), profile nasal length (1.7±1.7 mm, P=0.002), and nasal bridge height (1.2±1.6 mm, P=0.002). Conversely, they showed a decrease in the nasofacial angle (-2.3°±2.9°, P=0.010). Women also demonstrated an increase in the nasofrontal angle (2.5°±5.2°, P=0.010), profile nasal length (1.4±1.9 mm, P<0.001), and nasal bridge height (1.3±1.6 mm, P<0.001). However, they exhibited a decrease in the nasofacial angle (-2.0°±2.1°, P<0.001), glabella angle (-9.1°±9.8°, P<0.001), and pyriform angle (-8.5°±10.1°, P<0.001). With the exception of the nasal bridge height (P=0.036) and pyriform angle (P=0.022), the degree of changes in most parameters did not show significant differences across age groups. CONCLUSION: Our findings indicate that the aging nose exhibits a greater nasal length with inferior angulation of the nasal tip, with an increase in the nasofrontal angle, profile nasal length, and nasal bridge height, along with a decrease in the nasofacial angle. The degree of most nasal morphologic changes demonstrated no significant differences by specific age group.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Symptomatic Differences between Influenza A/H3N2 and A/H1N1 in Korea.

BACKGROUND: Limited understanding exists regarding clinical distinctions between influenza A/H3N2 and A/H1N1 subtypes, particularly in primary health care. We conducted a comparative analysis of symptomatic characteristics of influenza subtypes in Korea. This retrospective study analyzed medical records of patients who presented with positive test results for influenza-like illness (rapid influenza diagnostic test; RIDT) during the H3N2-dominant 2016-2017 and H1N1-dominant 2018-2019 seasons. Symptomatic manifestations, contact history, vaccination history, and clinical course were analyzed between the two seasons. The most frequent symptom in the RIDT-positive patients was fever (80.1% and 79.1%, respectively). The average body temperature was higher, and the number of patients with high fever was greater in the H3N2-dominant season than in the H1N1-dominant season (p < 0.001). Conversely, other symptoms, such as myalgia, cough, and sore throat, were significantly more common in the H1N1-dominant season than in the H3N2-dominant season (p < 0.001). Antiviral drugs were prescribed to most febrile RIDT-positive patients (82.2% and 81.3%, respectively, p = 0.516). Analyzing primary care data revealed different clinical manifestations according to the subtype. Therefore, physicians should consider these variable hallmarks and employ tailored therapeutic strategies to reduce the complication rate.

The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis.

Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1ß, tumor necrosis factor-α, transforming growth factor-ß, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation.

PURPOSE: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. METHODS: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1ß, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-ß1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. RESULTS: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. CONCLUSIONS: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

Obstructive Sleep Apnea Is Associated With Late-Onset Preeclampsia in Overweight Pregnant Women in Korea.

BACKGROUND: Obstructive sleep apnea (OSA) is closely related to maternal obesity in pregnant women, and the association increases with later pregnancy. Obesity and OSA are risk factors of pregnancy-related complications, including gestational hypertension, gestational diabetes mellitus (GDM), and fetal morbidities. We aimed to determine the prevalence of OSA and to assess the impact of OSA on pregnancy-related disorders in overweight pregnant women. METHODS: Eligible participants who were overweight [body mass index (BMI) ≥ 23 kg/m²] in gestational age 30 weeks or more, assessed OSA using a portable polysomnography at home. Clinical data were collected from pregnant women and their babies. RESULTS: The average age of 51 participants was 34.5 years (27-44 years). The number of primipara was 25 (49%) and that of multipara was 26 (51%). Eight cases of GDM (15.7%) and five cases of preeclampsia (9.8%) were reported, and six patients (11.8%) experienced preterm delivery. In results of polysomnography, 14 patients (27.5%) were diagnosed as OSA. Apnea-hypopnea index moderately correlated with BMI (r = 0.515, P < 0.001). The BMI (P < 0.005) and preeclampsia rate (P < 0.017) were higher in the OSA group compared to the control group. Odds ratios (ORs) adjusting age, BMI, parity, and abortion history were calculated. The presence of OSA increased OR of preeclampsia (OR, 13.1; 95% confidence interval, 1.1-171.3). The majority of preeclampsia patients (4/5, 80%) underwent preterm delivery. CONCLUSION: OSA is an important risk factor for preeclampsia, resulting in preterm delivery. For overweight pregnant women, an OSA evaluation should be mandatory.

KAAACI Allergic Rhinitis Guidelines: Part 1. Update in Pharmacotherapy.

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

Obstructive Sleep Apnea and Its Influence on Intracranial Aneurysm.

Obstructive sleep apnea syndrome (OSAS) is associated with cerebrovascular disease, which can lead to life-threatening outcomes. The purpose of the study was to investigate the relationship between OSAS and comorbid intracranial aneurysms. We retrospectively reviewed 564 patients who underwent a polysomnography and brain magnetic resonance angiography as part of their health checkup. We calculated the prevalence of an intracranial aneurysm and OSAS in patients and measured the size of the intracranial aneurysm if present. The mean patient age was 55.6 ± 8.5 years, and 82.3% of them were men. The prevalence of an intracranial aneurysm in patients with OSAS was 12.1%, which is significantly higher than patients with non-OSAS (5.9%, p = 0.031). Patients with OSAS had a much higher prevalence of intracranial aneurysms, after adjusting all possible confounding factors such as age, sex, smoking status, alcohol drinking, and body mass index (odds ratio: 2.32; 95% confidence interval: 1.07-5.04). Additionally, the OSAS group had noticeably larger aneurysms compared with those of the non-OSAS group (3.2 ± 2.0 mm vs. 2.0 ± 0.4 mm, p = 0.013). We found a significant association between OSAS and intracranial aneurysms. OSAS could be another risk factor for the development of intracranial aneurysms.

Influence of Lingual Tonsillar Volume in Patients with Obstructive Sleep Apnea.

This study aimed to evaluate the influence of lingual tonsil (LT) volume measured using a three-dimensional (3D) reconstruction volume rendering program on clinical parameters and polysomnography (PSG) results. A total of 100 patients who underwent PSG, computed tomography (CT), and allergy test from April 2016 to April 2020 were randomly selected. LT volume was measured using an imaging software program that enables 3D reconstruction of CT images. PSG parameters were analyzed by dividing the subjects into two groups according to LT volume (each 50 people). Based on the medial volume of 0.863 cm3, the upper half LT volume group and the lower half LT volume group were analyzed. Clinical factors such as body weight, neck circumference, body mass index (BMI), and age showed no difference between the two groups. Among PSG parameters, supine arousal index and non-rapid eye movement (NREM) arousal index were significantly higher in the upper half LT volume group (p = 0.012, 0.037). However, there was no significant difference in apnea-hypopnea index (AHI) between the upper and lower half LT volume groups (p = 0.749). Arousal snoring index and REM arousal index also showed no difference between the two groups. The prevalence of allergic rhinitis was not different in the two groups. High LT volume is associated with NREM arousal and arousal in the supine position, but it is not related to AHI.

Internal Nasal Valve Modification via Correction of High Dorsal Deviation Using a Modified Mattress Suture Technique.

High dorsal deviation of the septum can cause nasal obstruction due to internal nasal valve (INV) stenosis. We have developed a new technique using a modified mattress suture on the bony-cartilaginous junction to correct high dorsal septal deviation. This study focused on the effect of this suturing technique on the modification of the INV. We enrolled 40 patients who underwent septoplasty using a modified mattress suture technique. We retrospectively analyzed the data of the preoperative and postoperative INV angles and cross-sectional areas (CSAs), which were measured using computed tomography. In addition, we compared the patients' subjective nasal symptoms, which were measured with the preoperative and postoperative Nasal Obstruction Symptom Evaluation (NOSE) instrument. Postoperative increases in the narrow side INV angle and CSA were achieved. Additionally, the wide side INV angle and CSA were significantly decreased postoperatively. The INV and CSA ratio (wide/narrow) were also decreased postoperatively and were brought closer to 1. The subjective nasal symptoms also exhibited significantly reduced NOSE values. In this study, we confirmed the effects of septoplasty using a modified mattress suture technique for INV modification through the comparison of the preoperative and postoperative INV angles and CSAs.

Therapeutic Effect of Multilevel Surgery on Laryngopharyngeal Reflux in Obstructive Sleep Apnea Patients: Impact on the Reflux Symptom Index and Reflux Finding Score.

OBJECTIVES: Our previous study found that multilevel obstructive sleep apnea (OSA) surgery mitigated laryngopharyngeal reflux (LPR) symptoms in terms of the reflux symptom index (RSI), but no studies have investigated the impact of OSA surgery on laryngoscopic parameters. The aim of this study was to examine the clinical outcome of LPR improvement following OSA surgery, with a focus on both the RSI and the reflux finding score (RFS). METHODS: Prospectively collected data from 28 patients who underwent multilevel OSA surgery from 2017 to 2021 were retrospectively analyzed. Patients were asked to complete the RSI questionnaire and underwent a laryngoscopic examination to evaluate the RFS before and after surgery. Age, height, weight, body mass index (BMI), and polysomnography data before and after surgery were also reviewed. RESULTS: After surgery, the total RSI and RFS decreased significantly from 11.96±8.40 to 7.68±6.82 (P=0.003) and from 6.57±3.49 to 3.21±1.87 (P<0.001). The positive rates of RSI and RFS decreased from 28.6% to 17.9% and 32.1% to 0%, respectively. Significant improvements were found in the RSI subdomains of throat clearing, throat mucus, breathing difficulty, troublesome cough, and heartburn sensation, while all RFS subdomains except granuloma improved significantly. In subgroup analyses, no significant differences were found between subgroups based on age, OSA severity, or BMI. CONCLUSION: OSA surgery has the potential to alleviate both LPR symptoms and laryngoscopic. RESULTS: Additional research integrating more objective techniques and novel treatment strategies is required to better comprehend the clinical impact of OSA surgery on LPR.

Associations of respiratory mechanic instability with respiratory parameters in pediatric patients with obstructive sleep apnea syndrome.

OBJECTIVES: This study aimed to identify the effectiveness of respiratory mechanic instability (RMI) in the diagnosis of pediatric obstructive sleep apnea syndrome (OSAS). We sought to evaluate the correlations of RMI with sleep-related parameters and determine the effectiveness of using RMI for diagnosing OSAS in children. METHODS: Children who underwent polysomnography (PSG) for various reasons were enrolled in this study. Patients' clinical and PSG data at two university hospitals were reviewed retrospectively. During PSG, RMI parameters were automatically calculated according to the phase relationship between thoracic and abdominal movement signals. RESULTS: Among 263 children who underwent PSG, 183 (70.4%) were diagnosed with OSAS (apnea-hypopnea index [AHI] ≥ 1). RMI parameters were higher in the OSAS group than in the control group. They also tended to increase with disease severity. RMI scores were well correlated with respiratory parameters, showing a stronger correlation in those with moderate or severe OSAS without central apnea. Areas under the receiver operating characteristics curves (AUROCs) of RMI indicators were over 0.65. The percentage of RMI in stage duration showed the highest value of the AUROCs. CONCLUSION: Paradoxical thoraco-abdominal movement assessed by RMI provides additional information. It may be useful in diagnosing OSAS in children.

SARS-CoV-2 Infection of Airway Epithelial Cells.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide since its outbreak in December 2019, and World Health Organization declared it as a pandemic on March 11, 2020. SARS-CoV-2 is highly contagious and is transmitted through airway epithelial cells as the first gateway. SARS-CoV-2 is detected by nasopharyngeal or oropharyngeal swab samples, and the viral load is significantly high in the upper respiratory tract. The host cellular receptors in airway epithelial cells, including angiotensin-converting enzyme 2 and transmembrane serine protease 2, have been identified by single-cell RNA sequencing or immunostaining. The expression levels of these molecules vary by type, function, and location of airway epithelial cells, such as ciliated cells, secretory cells, olfactory epithelial cells, and alveolar epithelial cells, as well as differ from host to host depending on age, sex, or comorbid diseases. Infected airway epithelial cells by SARS-CoV-2 in ex vivo experiments produce chemokines and cytokines to recruit inflammatory cells to target organs. Same as other viral infections, IFN signaling is a critical pathway for host defense. Various studies are underway to confirm the pathophysiological mechanisms of SARS-CoV-2 infection. Herein, we review cellular entry, host-viral interactions, immune responses to SARS-CoV-2 in airway epithelial cells. We also discuss therapeutic options related to epithelial immune reactions to SARS-CoV-2.

Long-Term Clinical Course of Benign Fibro-Osseous Lesions in the Paranasal Sinuses.

OBJECTIVES: Fibro-osseous lesions of the paranasal sinuses can present various clinical manifestations. This study aimed to report the long-term clinical course of benign fibro-osseous lesions (BFOLs) in the paranasal sinuses, including clinical and radiologic features. METHODS: Radiologically confirmed BFOLs between 1994 and 2016, with the exclusion of osteoma cases, were retrospectively reviewed. We compared demographic characteristics between the surgery and observation groups. The reasons for the imaging study, radiographic features, histopathology, and clinical course based on serial image scans were analyzed. RESULTS: In total, 183 subjects were selected from a thorough review of head and neck radiologic tests (n=606,068) at a tertiary referral hospital over 22 years. Patients' mean age was 28.6±18.1 years, and 56.3% were males. A diagnostic imaging workup was performed in 55.7% of patients due to facial asymmetry, headache, skull mass, or other symptoms related to BFOLs. In other patients (37.7%), BFOLs were found incidentally on computed tomography or magnetic resonance imaging. The most common diagnosis was fibrous dysplasia, followed by ossifying fibroma, based on both radiologic exams and histopathologic results. In total, 42.6% of the patients underwent surgery because of subjective symptoms or esthetic concerns. The patients who underwent surgery were younger (P<0.001) and had a longer follow-up duration (P<0.001) than those who underwent observation. Patients who experienced lesion growth (11.5%) were younger (P<0.001) and had more lesion sites (P=0.018) than those who did not, regardless of surgical treatment. Five patients underwent optic nerve decompression, and one patient experienced malignant transformation. CONCLUSION: BFOL in the paranasal sinuses is a rare disease, and most cases were observed without specific treatment. Surgical treatment should be considered in symptomatic patients with aggressive clinical features. Regular observation and management are needed, particularly in younger patients in their teens.

Epithelial-to-mesenchymal transition in neutrophilic chronic rhinosinusitis.

PURPOSE OF REVIEW: Barrier dysfunction, tissue fibrosis, and remodeling are essential processes of the pathophysiology of chronic rhinosinusitis (CRS). The role of epithelial-to-mesenchymal transition (EMT) has been assessed in various studies in CRS. In this review, we summarized the pathophysiologic mechanisms of EMT related to CRS, particularly neutrophilic CRS. RECENT FINDINGS: Loss of epithelial characteristics due to EMT makes leaky epithelium, and transformed mesenchymal cells cause fibrosis and remodeling. Hypoxia, allergens (house dust mites), infections, and air pollutants were related to the pathogenesis of neutrophilic CRS, and these factors are known to induce barrier dysfunction and EMT in sinonasal epithelia. Some molecular pathways related to EMT have been recognized in CRS, including interferon-γ/p38/extracellular signal-regulated kinase, high-mobility group box 1/receptor of advanced glycosylation end-products, TGF-ß1/SMAD, and Wnt/ß-catenin-signaling pathways. Apart from, several microRNAs (miR-21, miR-761, and miR-30a-5p) have been identified to regulate EMT in CRS. SUMMARY: EMT is considered to be an important pathogenesis mechanism for CRS. The factors cause EMT in CRS, and the associated molecular mechanisms are related to neutrophilic inflammation. Further studies on CRS endotype and/or phenotype are needed to clarify the implication of EMT on CRS pathogenesis.

Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.

Bidirectional association between asthma and chronic rhinosinusitis: Two longitudinal follow-up studies using a national sample cohort.

The aim of this study was to evaluate an epidemiologic association of asthma and chronic rhinosinusitis (CRS) using a national sample cohort of the Korean population. We collected data from the Korean Health Insurance Review and Assessment Service-National Sample Cohort between 2002 and 2013, and two different case-control cohorts were designed (1st: asthmatic patients matched in a 1:1 ratio with 204,119 non-asthmatics as control I, 2nd: CRS patients matched in a 1:4 ratio with 124,020 non-CRS patients as control II). Bidirectional association was examined using Cox proportional hazard models stratified by age, sex, income, and region of residence. Patients with asthma had an increased risk of developing CRS [adjusted hazard ratio (95% confidence interval) = 1.74 (1.67-1.80)], both with nasal polyps [1.55 (1.36-1.78)], without nasal polyps [1.74 (1.67-1.81)]. In the second cohort, patients with CRS had increased risk of developing asthma [1.85 (1.80-1.91)] with similar results for those with and without nasal polyps. The strongest association for risk of CRS was in 20-39 years old men with asthma [2.41 (1.97-2.96)], while the strongest association for increased risk of asthma in those with CRS group was also seen in this same subgroup [2.40 (2.18-2.63)]. CRS and asthma had a bidirectional influence on each other. CRS increased the risk of asthma, and asthma increased the risk of CRS, especially in young men.