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.

Pathogenesis of Recalcitrant Chronic Rhinosinusitis: The Emerging Role of Innate Immune Cells

Chronic rhinosinusitis (CRS) is a major part of the recalcitrant inflammatory diseases of the upper airway that needs enormous socioeconomic burden. T helper (Th) 2 type immune responses recruiting eosinophils were the most well-known immune players in CRS pathogenesis especially in western countries. By the piling up of a vast amount of researches to elucidate the pathogenic mechanism of CRS recently, heterogeneous inflammatory processes were found to be related to the phenotypes of CRS. Recently more cells other than T cells were in the focus of CRS pathogenesis, such as the epithelial cell, macrophage, innate lymphoid cells, and neutrophils. Here, we reviewed the recent research focusing on the innate immune cells related to CRS pathogenesis.

Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

PURPOSE: The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application. METHODS: A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators. RESULTS: The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses. CONCLUSIONS: The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.

Immediate and Sustained Improvement in Behavior and Life Quality by Adenotonsillectomy in Children With Sleep-Disordered Breathing

OBJECTIVES: To investigate longitudinal changes in behavior and quality-of-life (QoL) in children with sleep disordered breathing (SDB) after adenotonsillectomy (AT). METHODS: This study prospectively enrolled 148 children who underwent AT for SDB. Caregivers filled out Korean attention deficit hyperactivity disorder (ADHD) rating scale (K-ARS) and Korean version of the obstructive sleep apnea-18 (KOSA-18) at preoperative 1 day, postoperative 1 month, and postoperative 6 months. Longitudinal changes in K-ARS and KOSA-18 were evaluated and compared among subgroups. RESULTS: Both K-ARS and KOSA-18 scores improved immediately at postoperative 1 month and were maintained at postoperative 6 months. The mean preoperative K-ARS scores of the non-ADHD, ADHD-trait, and overt-ADHD groups showed uniformly immediate and sustained improvements. Also, the mean preoperative KOSA-18 scores of the small, moderate, and large impact groups were significantly improved both at postoperative 1 month and 6 months. The changes in behavior and QoL showed no significant differences with regard to the aforementioned factors. CONCLUSION: After AT, we may expect immediate and sustained improvements in behavior and QoL in children with SDB regardless of preoperative symptom severity. Moreover, by performing AT, improvements in behavior and QoL are expected regardless of sex, age, allergic trait, or concurrent coblation-assisted turbinoplasty. These findings may help our colleague physicians counselling pediatric SDB patients and their caregivers.

Clinical Experiences of Diagnosis and Treatment for Wegener's Granulomatosis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Because most patients with Wegener's granulomatosis (WG) visit otolaryngologists complaining of head and neck symptoms, otolaryngologists may play an important role in early diagnosis. In this study, we investigated clinical features, laboratory findings and treatment outcomes of 33 patients with WG, and propose a new algorithm for the diagnosis of WG. SUBJECTS AND METHOD: Thirty-three patients with WG who visited the clinic between January 1980 and December 2007 were included. The medical records of 13 male and 20 female patients were retrospectively reviewed. The mean follow-up duration was 68 months. RESULTS: Most WG patients had ENT symptoms such as nasal obstruction, rhinorrhea, otorrhea, hearing loss, dyspnea and hoarseness. The mean duration from ENT examination to diagnosis was 6.7 months (3 days- 102 months) and tissue biopsy was performed on an average of 2.1 times to confirm the diagnosis. While 16 patients could be diagnosed by the first biopsy, the others were required to repeat the biopsy. ANCA was positive in 17 patients (50%). Twentysix patients (78.7%) had multiple organ involvements such as lung, kidney, joint and skin. Twenty-eight patients received a combination of prednisolone and cyclophosphamide with the remission rate of 87%. CONCLUSION: Based on this study, we propose a better algorithm for the diagnosis of WG to avoid unnecessary delay in the diagnosis and treatment of WG.

Continuous Measurement of Suspension Force during Suspension Laryngoscopy: Preliminary Report / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Although suspension laryngoscopy is a very common procedure in the otolaryngoloical field and suspension force (Fs) is suspected to be related with the complications or laryngeal exposure, Fs has not been objectively measured yet. The objective of this study is to measure suspension force continuously during suspension laryngoscopy. SUBJECTS AND METHOD: Sixteen patients who had undergone laryngoscopic surgery were evaluated. The value measured with a load cell during the procedure was converted to Fs with calculation. The maximum force (Fsmax) and the mean force (Fsmean) were evaluated. The angle between the laryngoscope and the chest holder(angle alpha), and the angle between the chest holder and the horizontal plane (angle beta) were gauged. RESULTS: The mean values of Fsmax and Fsmean were 14.2 and 25.5 kgf, respectively. The mean values of angle alpha and angle beta were 124.0+/-4.3 degrees, and 19.0+/-2.6 degrees, respectively. CONCLUSION: The continuous measurement of the suspension force was executed successfully and quantitatively with a simple method.

Analysis of the Correct-Answer Rate of the Odor Identification Test in KVSS(Korean Version of Sniffin'Sticks) Test / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: KVSS (Korean Version of Sniffin' Sticks) identification test using 16 odorants familiar to Koreans is used for evaluation of olfactory function. We analyzed the correct-answer rate of the odor identification test among KVSS test to validate the reliability of these odorants. SUBJECTS AND METHOD: From April 2004 through August 2006, 720 patients underwent an odor identification test and from these, 441 patients who scored more than 9 were included. The score groups were divided into 4 groups: more than 9, 10, 11 and 12 score group. The age groups were divided into 4 groups: 0-19, 20-39, 40-59, 60 and more than 60 year-olds. The differences in the correct-answer rates of the odorant were investigated according to the score groups, age groups and sex were calculated using SPSS software. RESULTS: The odorant 6 (lemon), 7 (licorice), 8 (pine resin), and 11 (apple) showed low correct-answer rates than other odorants. Especially the correct-answer rates of odorant 7 and 11 were significantly lower than other odorants except odorant 6 and 8 in all score groups, in all age groups and both sex (p< or =.001). CONCLUSION: In the odor identification test, odorants 7 and 11 had low reliabililty for evaluation of the olfactory function, maybe due to unfamiliar odorants to Koreans or test pen failure and they had better be changed into more reliable odorants. For that, we need further investigations about KVSS test before widely used.

Comparison of Polysomnographic Findings according to Obstruction Sites in Obstructive Sleep Apnea Patients / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The aim of this study is to identify differences in polysomnographic findings according to the upper airway obstruction level in patients with obstructive sleep apnea (OSA). SUBJECTS AND METHOD: Eighty-four patients with OSA were included in this study. Every patient underwent polysomnography (PSG) and upper airway pressure measurement using a four-sensor catheter simultaneously. The catheter was positioned at the posterior nasal cavity, uvula tip, tip of the epiglottis, and mid-esophagus level, which was inserted through the nasal cavity down to the esophagus. The patients were categorized into two groups of single site obstruction and multi-site obstruction. RESULTS: Twenty-one patients showed single site obstruction and sixtythree patients showed multi-site obstruction. Apnea-hypopnea index, apnea index, and minimal oxygen saturation showed statistically significant differences between two groups. There was no difference in bony mass index (BMI). CONCLUSION: Upper airway pressure measurement can be a method to evaluate the upper airway obstruction site. This study shows that OSA patients with multisite obstruction have severer sleep apnea than those with single site obstruction.