Chang-Hoon Kim

Background: Dendritic cells (DCs) are antigen-presenting cells that play a critical role in airway diseases by initiating and regulating immune responses. DCs are classified into plasmacytoid DCs (pDCs) and conventional DCs (cDCs), with the cDC lineage further divided into cDC1 and cDC2 subsets. Each subset exhibits distinct functions in immune regulation and disease pathogenesis. Thus, analyzing DC subsets is crucial for understanding the pathogenesis of airway diseases with diverse endotypes. Objective: Allergic rhinitis (AR) and chronic rhinosinusitis (CRS), further divided into eosinophilic CRS (ECRS) and non-eosinophilic CRS (NECRS), are typical upper airway diseases with diverse endotypes. AR and CRS often occur simultaneously, and their severity tends to increase when they are comorbid. To understand the endotypes of AR and CRS, we classified the presence or absence of AR and CRS, analyzed the changes in DC subsets in the nasal mucosa, and compared these results with clinical features. Methods: Nasal polyp tissues and ethmoid mucosa were collected from 42 patients who underwent endoscopic sinus surgery. DC were analyzed by flow cytometry to detect the expression of blood DC antigen (BDCA)-1, BDCA-2, and BDCA-3. Results: BDCA-3 ⁺ cDC levels were significantly reduced in patients with both AR and CRS, compared to those with AR alone or CRS alone. This reduction was especially prominent in patients with ECRS, polysensitization, and total serum IgE ≥ 200 IU/mL. BDCA-3 ⁺ cDC levels were also inversely correlated with preoperative computed tomography scores and serum eosinophil and immunoglobulin E levels. Conclusion: BDCA-3 ⁺ cDC levels may be involved in mucosal immune regulation and are associated with increased disease burden in patients with comorbid AR and ECRS.

Background: Chronic rhinosinusitis (CRS) exhibits marked symptom heterogeneity that is not fully explained by anatomy or endotypes. Although allergen types shape symptom patterns in allergic rhinitis, largescale systematic analyses linking allergen sensitization profiles to patient-reported outcome measures in patients with CRS are limited. Methods: We conducted a multicenter, retrospective surgical cohort study (n = 1880) including patients with CRS who underwent preoperative specific IgE testing for 35 inhalant allergens and completed the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire within 1 year. Using a previously validated nonnegative matrix factorization model, we deconvolved each patient’s IgE profile into four allergen signatures (Mite, Grass/Weed, Pet, and Tree) and defined a dominant group. Associations between signature contributions and SNOT-22 items, domain subscores, and total score were estimated by ordinary least squares, adjusting for age, sex, nasal polyps, and asthma, with coefficients scaled per 10-percentage-point increase. Item-level multiplicity was controlled for using the false discovery rate. Seasonality was assessed using monthly means and the coefficient of variation of the dominant group. Results: Dominant groups were nonallergic (50%), mite (26%), grass/weed (9%), pet (9%), and tree (5%). Symptoms varied by age and sex, characterized by notably low nasal scores with aging and a high female burden for several items, motivating covariate adjustment. Signature–symptom associations were domain-specific: the pet signature showed the strongest and most consistent associations with nasal domain (such as rhinorrhea and nasal obstruction) and emotion domain (feelings of embarrassment); mite and grass/weed signatures were linked to the function domain (daytime fatigue/productivity); whereas the tree signature showed no significant associations. Seasonal patterns aligned with exposure ecology: grass/weed and tree groups had the largest relative variation (high coefficient of variations), the pet group showed the highest absolute burden year-round, and the mite group varied modestly with winter–spring predominance. Conclusions: Allergen signatures distilled from routine IgE panels explained meaningful variations in CRS patient-reported outcome measures, mapping to distinct symptom domains and seasonal profiles. Incorporating signature information into clinical assessments may support personalized counseling, anticipatory management around exposure windows, and targeted evaluation of environmental or immunologic interventions.

Objectives: This study aimed to evaluate the olfactory and gustatory functions of patients with nasal septal deviation (NSD) and identify the factors associated with olfactory loss (OL) and gustatory loss (GL). Design and Setting: Retrospective data analysis of cohort group. Participants: Two‐hundred fourteen adult patients with NSD at a tertiary hospital. Main Outcome Measures: Olfactory and gustatory functions were assessed using the psychophysical olfactory and gustatory function tests. The association of various demographic and clinical factors, including age, sex, NSD type, allergic sensitization status, presence of concha bullosa (CB), total serum immunoglobulin E (IgE) level, blood eosinophil count, and acoustic rhinometry parameters, with OL and GL was analysed. Results: Among the patients, 20.6% (44/214) and 16.4% (35/213) had OL and GL , respectively. Patients with CB showed a significantly lower threshold, discrimination, and identification ( TDI ) score than those without CB ( p = 0.012). Conversely, the TDI score did not differ according to age group, sex, NSD type, or allergic sensitization status. Blood eosinophil count was inversely correlated with the TDI score ( p = 0.003), whereas nasal cavity volume, minimal cross‐sectional area, and serum IgE level were not correlated with the TDI score. In the multivariable analysis, the presence of CB ( p = 0.029, odds ratio [ OR ] = 2.281) and a blood eosinophil count ≥ 190 ( p = 0.030, OR = 2.155) were identified as significant factors associated with OL . No factors were significantly associated with GL . Conclusion: The presence of CB and a high blood eosinophil count are significant predictors of OL in patients with NSD.

Purpose This study aimed to evaluate the clinical characteristics associated with post-operative recurrence in patients with sinonasal inverted papilloma (IP), focusing on the prognostic factors influencing recurrence-free survival (RFS). Methods We retrospectively reviewed clinical records from patients who underwent surgery for IP between January 1, 2007, and August 31, 2023. RFS was analyzed using Kaplan–Meier method and Cox proportional hazard regression analyses to identify the prognostic factors for recurrence. Variables, including age, sex, symptoms, timing of diagnosis, radiological findings, Krouse staging, previous surgery history, surgical method, and tumor origin site, were analyzed. Results Among the 315 patients with IP, 48 experienced recurrences. The survival analysis revealed 1-, 3-, and 5-year RFS rates of 88.88%, 82.84%, and 69.47%, respectively, and indicated that headache, diagnosis during or following surgery, high Krouse staging, intracranial extension, and frontal sinus origin reduce median RFS or the 5-year RFS rate. Multivariate Cox regression showed that headache, diagnoses made during or after surgery, intracranial extension, and frontal sinus origin significantly increased recurrence risk. Conclusions If IP is suspected, a biopsy should be performed, and an appropriate surgical approach should be planned. To select the appropriate surgical method, determining the tumor origin site using radiological imaging is crucial, particularly in cases involving the frontal sinus or intracranial extension. Additionally, vigilant monitoring is essential for identifying recurrences early in patients with significant risk factors.

Introduction: Olfaction is important for the quality of life; however, in Kallmann syndrome (KS), defective development results in olfactory dysfunction. Notably, the mechanism underlying olfactory development, especially in the olfactory epithelium (OE), which detects olfactory signals, remains unclear. Mutations in PROK2, which encodes prokineticin-2, have been identified in approximately 9% of the KS patients with olfactory defects.Methods: We examined olfactory function and analyzed the causes of olfactory dysfunction based on spatiotemporal development and gene expression changes in Prok2 knockout (KO) model mice with KS.Results: The ability of the OE to detect olfactory signals was diminished in adult Prok2 KO mice. Maturation of olfactory sensory neurons (OSNs) in the OE and formation of glomeruli in the olfactory bulb (OB) in adult Prok2 KO mice were disrupted, thus causing olfactory dysfunction. Furthermore, molecular analysis of Prok2 KO mice during embryonic development revealed abnormal development of OB layers and diminished differentiation to mature OSNs in the OE at the later stage, which caused defects in the entire olfactory system. Remarkably, downstream signaling genes of Prok2, including intermediate filament genes and genes expressed in the putative OB, were found to mediate olfactory system organization.Discussion: Overall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function.

Background: As treatment responses differ according to the inflammatory endotype of chronic rhinosinusitis (CRS), identifying the endotype could facilitate personalized treatment. We aimed to identify a noninvasive epithelial lining fluid (ELF) biomarker for the type 2 (T2) endotype of CRS.Methods: Nasal tissue and ELF samples were obtained from patients with CRS and control individuals. Single‐cell RNA sequencing (scRNA‐seq) data were analyzed. The expression of inflammatory mediators was measured using Luminex multiplex assays and enzyme‐linked immunosorbent assays.Results: Analysis of the scRNA‐seq data revealed that CST1 was exclusively expressed in epithelial cells of T2 CRS, but not in those of non‐T2 CRS, and this was confirmed by immunofluorescence staining. Cystatin SN expression was detected in ELF, and its levels were significantly higher in T2 CRS than in non‐T2 CRS and controls. The expression level of cystatin SN in the ELF was positively correlated with the Lund‐Mackay CT, SNOT‐22, and JESREC scores, whereas it was inversely correlated with olfactory function. Furthermore, ELF cystatin SN levels correlated with the tissue/blood eosinophil count and nasal tissue expression of T2 inflammatory mediators, indicating that ELF cystatin SN is a reliable marker of nasal T2 inflammation. In the receiver operating characteristics curve analysis evaluating the predictive efficacy for T2 CRS, the AUC for ELF cystatin SN was 0.894 (0.936 in the validation cohort), which was higher than that of other markers, including blood eosinophil count, serum total IgE level, and the JESREC score. With a cut‐off value of 112.5 ng/mg, ELF cystatin SN yielded a 75.0% sensitivity and 92.0% specificity.Conclusions: ELF cystatin SN is a clinically feasible, noninvasive biomarker with superior accuracy for predicting T2 CRS.

Background: Allergic rhinitis (AR) and asthma are involved in complex interactions between Th1 and Th2 inflammatory pathways. House dust mite (HDM) activates protease‐activated receptor 2 (PAR2) to trigger inflammatory responses, but current treatments often provide inadequate control. Objective: This study aimed to investigate the effects of selective PAR2 inhibition on Th1 and Th2 responses in human nasal epithelial (HNE) cells and murine models of AR and asthma. Methods: We examined the effects of selective PAR2 inhibition using primary HNE cells and HDM‐induced mouse models (PAR2‐wild‐type [PAR2‐wt] and knockout [PAR2‐ko]). Analyses included inflammatory signaling pathways, cytokine profiles, airway responses, histopathology, and transcriptomics. Results: In HNE cells, PAR2 inhibition suppressed Th2 (interleukin [IL]‐33, TSLP) and Th1 (TNF‐α, IL‐6) inflammatory cytokines while inhibiting calcium mobilization and ERK/NF‐κB signaling cascades. In PAR2‐wt mice, treatment with the PAR2 inhibitor reduced HDM‐specific Immunoglobulin E (IgE), airway hyperresponsiveness, and allergic inflammation in both nasal and bronchial tissues, matching the anti‐inflammatory profile of PAR2‐ko mice. Bulk RNA sequencing confirmed comprehensive suppression of inflammatory gene expression. Conclusions: Selective PAR2 inhibition effectively attenuates HDM‐induced allergic inflammation by modulation of Th1 and Th2 pathways in human airway epithelium and murine models. We suggest that PAR2 can be a possible target for AR and asthma.

Introduction: Eosinophilic chronic rhinosinusitis (ECRS) is a severe form of chronic rhinosinusitis characterized by type 2 inflammation, tissue remodeling, and bone thickening, known as osteitis. Periostin, a matricellular protein involved in extracellular matrix (ECM) regulation and T helper 2 (Th2)-mediated inflammation, is markedly elevated in patients with ECRS; however, its pathophysiological role remains unclear.Methods: We investigated the role of periostin in inflammation and tissue remodeling in ECRS using samples from ECRS patients, human nasal epithelial cells and fibroblasts, as well as an ECRS mouse model including periostin knockout mice.Results: Periostin levels were elevated in ECRS tissues and modestly correlated with osteitis scores. Th2 cytokines increased periostin expression, particularly in nasal fibroblasts. Conditioned medium containing periostin promoted osteogenic differentiation in vitro, whereas neutralizing antibodies reduced the expression of osteogenic markers. In an ECRS mouse model, periostin deficiency led to reduced bone thickening and lower expression of osteogenic markers despite similar eosinophil infiltration. Furthermore, periostin-deficient mice exhibited greater epithelial collapse and reduced fibronectin levels, indicating compromised ECM integrity.Discussion: These findings demonstrate that periostin contributes to osteogenesis and maintenance of structural stability in the inflamed sinonasal mucosa. Periostin may be a potential therapeutic target for controlling chronic inflammation and tissue remodeling in ECRS.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent condition that significantly impacts quality of life and places a burden on healthcare systems. The advent of biologics targeting type 2 immune pathways offers new therapeutic options for severe and/or uncontrolled CRSwNP. Initially, biologic use was guided by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) guidelines, despite limited data on clinical indications, response measures, and treatment duration. Since then, numerous studies and the EPOS/EUFOREA 2023 update have refined these guidelines. The update defines clinical indications for biologics based on type 2 inflammation markers by lowering the blood eosinophil threshold from 250 to 150 cells/μL. The response to biologics is now more simply categorized into three levels based on reductions in nasal polyp size, improvements in quality of life, and enhancement of smell. Treatment evaluation is recommended at 6 months with annual follow-up. Longer administration intervals, such as every four weeks, have also proven effective in well-controlled patients. Although specific guidelines for discontinuation or switching biologics remain lacking, clinical judgment is essential in determining when treatment should be stopped or adjusted. Additionally, regulatory updates support the use of biologics for CRSwNP, and novel agents such as tezepelumab (an anti-thymic stromal lymphopoietin monoclonal antibody) continue to show promise. Finally, in Korea, biologics for CRSwNP are not covered by national health insurance, leading to extended dosing intervals due to high costs. Despite this limitation, studies have shown that adjusted dosing can maintain subjective quality of life. Recent studies by Korean authors have also explored practical considerations such as dosing intervals and comparisons to surgery. Further research is needed to optimize treatment strategies, particularly regarding cost-effectiveness and prospective studies tailored to the Korean healthcare system.