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.

Successful Management of Naso-Oropharyngeal Stenosis Using Nasal Pedicled Flaps: Report of Two Cases / 대한이비인후과학회지

Naso-oropharyngeal stenosis is an uncommon but serious complication after naso-oropharyngeal surgery. Surgical failure and re-stenosis are common. We report two cases of severe naso-oropharyngeal stenosis, which were successfully treated with the use of nasal pedicled flaps.

Clinical assessment for obstructive sleep apnea and national health insurance criteria for polysomnography

Sleep apnea is a sleep disorder that includes symptoms such as snoring and apnea during sleep and daytime drowsiness. This disorder reduces a person’s quality of life and can also cause serious problems that interfere with one’s social life. Both non-surgical, such as positive pressure treatment, and surgical treatments can be performed to improve sleep apnea. Polysomnography is first needed to confirm the degree of sleep apnea before surgery and should be conducted in certified facilities according to strict regulations. While appropriate treatment for sleep apnea can be implemented based on polysomnography results, it is burdensome for patients to obtain a polysomnography examination because of the high cost. To increase the accessibility of polysomnography to patients, the government has implemented an insurance program for patients who meet certain criteria. Recently, these criteria have been revised. The purpose of this paper is to provide information on the latest health insurance criteria for polysomnography.

COVID-19 and Smell Loss / 대한이비인후과학회지

The world has been facing a tremendous threat for more than 1 year by coronavirus disease 2019 (COVID-19). Because of the ongoing pandemic of COVID-19, it is necessary to be aware of the characteristics and symptoms of COVID-19 in order to prevent the COVID-19 spread. Common symptoms of COVID-19 include fever, cough, shortness of breath, headache and various types of pneumonia. Recently, smell loss has been extensively reported in COVID-19 patients. They experience this before other general symptoms or smell loss can be their only symptom. These types of patients may be neglected and a potential source for viral spread. Thus, screening tests of COVID-19 should be considered if patients have smell loss without any other nasal symptoms. Even though the recovery rate of smell loss in COVID-19 is relatively high, there are unmet needs for further studies including the mechanism of olfactory dysfunction, proper treatment and long-term recovery in COVID-19.

Elastase-Positive Neutrophils Are Associated With Refractoriness of Chronic Rhinosinusitis With Nasal Polyps in an Asian Population

PURPOSE: Various immune cells, including eosinophils and neutrophils, are known to contribute to the development of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the current understanding of the role of neutrophils in the development of CRSwNP still remains unclear. Therefore, we investigated risk factors for refractoriness of CRSwNP in an Asian population. METHODS: Protein levels of 17 neutrophil-related mediators in nasal polyps (NPs) were determined by multiplex immunoassay, and exploratory factor analysis using principal component analysis was performed. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE) or myeloperoxidase (MPO)-positive cells. Tissue eosinophilic nasal polyp (ENP) and tissue neutrophilia (Neu(high)) were defined as greater than 70 eosinophils and 20 HNE-positive cells, otherwise was classified into non-eosinophilic nasal polyp (NENP) and absence of tissue neutrophilia (Neu(low)). RESULTS: In terms of disease control status, NENP-Neu(low) patients showed the higher rate of disease control than NENP-Neu(high) and ENP-Neu(high) patients. Linear by linear association demonstrated the trend in refractoriness from NENP-Neu(low) to NENP-Neu(high) or ENP-Neu(low) to ENP-Neu(high). When multiple logistic regression was performed, tissue neutrophilia (hazard ratio, 4.38; 95% confidence interval, 1.76-10.85) was found as the strongest risk factor for CRSwNP refractoriness. Additionally, exploratory factor analysis revealed that interleukin (IL)-18, interferon-γ, IL-1Ra, tumor necrosis factor-α, oncostatin M, and MPO were associated with good disease control status, whereas IL-36α and IL-1α were associated with refractory disease control status. In subgroup analysis, HNE-positive cells and IL-36α were significantly upregulated in the refractory group (P = 0.0132 and P = 0.0395, respectively), whereas MPO and IL-18 showed higher expression in the controlled group (P = 0.0002 and P = 0.0009, respectively). Moreover, immunofluorescence analysis revealed that IL-36R⁺HNE⁺-double positive cells were significantly increased in the refractory group compared to the control group. We also found that the ratio of HNE-positive cells to α1 anti-trypsin was increased in the refractory group. CONCLUSIONS: Tissue neutrophilia had an influence on treatment outcomes in the Asian CRSwNP patients. HNE-positive cells and IL-36α may be biomarkers for predicting refractoriness in Asians with CRSwNP. Additionally, imbalances in HNE and α1 anti-trypsin may be associated with pathophysiology of neutrophilic chronic rhinosinusitis.

Development of Airway Allergic Diseases and Immunotherapy in Children / 대한이비인후과학회지

Allergic march is a part of a phase that occurs in a series of continuous steps in disease of pediatric patients, which proceeds from atopic dermatitis to asthma, and from asthma to allergic rhinitis. Recently, several hypotheses have been raised to explain the allergic march. Among them, the study of the hygiene theory related to microbiota, and the study on the role of innate cytokines which occurs in skin barrier damage are attracting attentions. If the interaction between the microbiota and the immune system occurs improperly, the activity of the regulatory T cell becomes insufficient and the immune-regulatory function is reduced, resulting in allergic diseases. Because of the skin barrier disruption, the innate cytokines are activated, thus resulting in Th2 inflammation reaction being increased. Considering this pathogenesis, blocking the linkage to pathogens is regarded to play an important role in preventing and treating allergic march.

Development of Airway Allergic Diseases and Immunotherapy in Children / 대한이비인후과학회지

Allergic march is a part of a phase that occurs in a series of continuous steps in disease of pediatric patients, which proceeds from atopic dermatitis to asthma, and from asthma to allergic rhinitis. Recently, several hypotheses have been raised to explain the allergic march. Among them, the study of the hygiene theory related to microbiota, and the study on the role of innate cytokines which occurs in skin barrier damage are attracting attentions. If the interaction between the microbiota and the immune system occurs improperly, the activity of the regulatory T cell becomes insufficient and the immune-regulatory function is reduced, resulting in allergic diseases. Because of the skin barrier disruption, the innate cytokines are activated, thus resulting in Th2 inflammation reaction being increased. Considering this pathogenesis, blocking the linkage to pathogens is regarded to play an important role in preventing and treating allergic march.

Roflumilast Attenuates MUC5AC and MUC5B Expression in Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Roflumilast, a selective inhibitor of phosphodiesterase type 4, has an anti-inflammatory property. It has been used in the treatment of chronic inflammatory airway diseases such as chronic obstructive pulmonary disease and asthma. However, the effect of roflumilast on mucus secretion in inflammatory airway epithelial cells has not been reported. Therefore, this study was aimed at investigating the effects of roflumilast on the inflammatory mediator-induced MUC5AC and MUC5B expression in human airway epithelial cells. MATERIALS AND METHOD: In human mucin-producing NCI-H292 airway epithelial cells and primary cultures of nasal epithelial cells, the effects of roflumilast on lipopolysaccharide (LPS)- and phorbl-12-myrsitate-13-acetate (PMA)-induced MUC5AC and MUC5B expression were analyzed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Roflumilast attenuated LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression in NCI-H292 cells. And roflumilast attenuated PMA-induced MUC5AC and MUC5B mRNA and glycoprotein expression in NCI-H292 cells. In addition, roflumilast attenuated LPS and PMA-induced MUC5AC and MUC5B mRNA expression in the primary cultures of nasal epithelial cells. CONCLUSION: These results suggest that roflumilast attenuates MUC5AC and MUC5B expressions in airway epithelial cells. Roflumilast may be a potentially ideal therapeutic agent for the control of mucus-hypersecretion in treating chronic inflammatory airway diseases.

Effect of Udenafil on MUC5B Expression in Human Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mucus hypersecretion in the airway may lead to increased frequency and duration of infection, declined lung function, and increased morbidity and mortality in inflammatory respiratory diseases. Udenafil, a phosphodiesterase (PDE) 5 inhibitor, is an oral medication for erectile dysfunction. Recent studies show that PDE5 inhibitor has various anti-inflammatory properties. However, the effect of udenafil on mucus secretion in human airway epithelial cells is unclear. Therefore, the effect and brief signaling pathway of udenafil on MUC5B expression were investigated in human airway epithelial cells. MATERIALS AND METHOD: We analyzed the effects and brief signaling pathway of udenafil on the lipopolysaccharide (LPS) induced MUC5B expression in mucin-producing NCI-H292 epithelial cells using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblot analysis. RESULTS: Udenafil attenuated the LPS-induced MUC5B mRNA expressions and glycoprotein production in NCI-H292 epithelial cells. It also attenuated LPS-induced toll like receptor 4 (TLR4) mRNA expression and phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and p38 in NCI-H292 epithelial cells. CONCLUSION: These results suggest that udenafil attenuates the LPS induced MUC5B expression via TLR4, ERK1/2 and p38 mitogen activated protein kinase (MAPK) pathway in human airway epithelial cells, and that it could be a novel therapeutic agent for controlling chronic airway disease.

Effect of Anthocyanidin on MUC5AC and MUC5B Expression in Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Naringenin and delphinidin are types of anthocyanidin, which are flavonoids and thus have anti-inflammatory property. Moderate consumption of natural dietary naringenin and delphinidin is believed to do anti-inflammatory action, but the action mechanism is unclear. Therefore, this study aimed to investigate the effects of naringenin and delphinidin on interleukin-1beta (IL-1beta)- and lipopolysaccharide (LPS)-induced MUC5AC and MUC5B expressions in airway epithelial cells. MATERIALS AND METHOD: In NCI-H292 cells and cultured nasal polyp epithelial cells, the effects of naringenin and delphinidin on IL-1beta- and LPS-induced MUC5AC and MUC5B expressions were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Delphinidin attenuated IL-1beta- and LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression in a dose-dependent pattern in NCI-H292 cells and in cultured nasal polyp epithelial cells. Naringenin partially attenuated IL-1beta- and LPS-induced MUC5AC and MUC5B mRNA and glycoprotein expression at a high dose. CONCLUSION: These results suggest that delphinidin attenuates MUC5AC and MUC5B expressions in the airway epithelial cells. Between anthocyanidin and delphinidin, delphinidin exhibits greater potential as an ideal therapeutic agent for the control of mucus-hypersecretion in the treatment of airway inflammatory diseases.