The Impact of Spontaneous Aerobic Exercise on Allergen Sensitization and Allergic Reactions in an Allergic Rhinitis- Induced Mouse Model

배경 및 목적: 알레르기 비염 (Allergic Rhinitis, AR)은 특정 알레르겐에 감작된 개인의 비강 점막에서 유발되는 대표적인 제2형 면역 반응 질환이다. 알러지 비염의 유병률 및 질환 조절 정도에 신체적 운동이나 활동운동이 어린이의 알러지비염 또는 천식 조절을 개선할 수 있다는 연구 결과가 있는 반면, 일부에서는 운동이 기도 염증을 악화시킬 수 있다고 보고된 바 있지만, 운동이 알러지 비염의 병태생리 및 알러지 조절 정도에 대하여 기존 연구는 없는 실정이다. 따라서, 본 연구는 자발적 신체 운동이 알레르겐 감작 및 알레르기 반응에 미치는 영향을 알러지비염 유도 생쥐 모델에서 분석하여 알레르기 비염 조절에 있어 운동의 역할을 규명하고자 계획하였다. 방법: 4주령 BALB/c 암컷 생쥐를 사용하여 주사와 비강 도전을 통해 AR 유도 모델을 개발하였다. 감작군에는 매주 Dermatophagoides pteronyssinus (Der-p1; Dp) 25 µg과 수산화알루미늄 겔 1 mg을 복강 주사하고 매일 Der-p1 20 µg을 비강에 투여하였으며, 대조군은 PBS를 주사 및 투여하였다. 총 96마리의 생쥐를 4개의 그룹으로 나누어 1부와 2부로 나누어 실험을 진행하였다. 생쥐는 회전 횟수를 측정할 수 있는 설치류 전용 운동 휠에서 운동하였으며, 1부에서는 알레르겐 감작 및 비강 도전과 동시에 4주간 운동을 수행하였고, 2부에서는 감작 후 4주 후부터 4주간 운동을 진행하였다. 체중과 운동량은 매일 기록하였고, 생쥐는 8주와 12주에 희생되었다. 혈청 총 IgE 및 알레르겐 특이 IgE, IgG1은 ELISA로, IL-4, IL-5, eotaxin-1 MBAA법으로 분석하였다. 비강 조직은 전비중격의 비강 상피를 대상으로 조직학적 분석을 수행하였으며, 비강점막 조직의 염증성 사이토카인 유전자 발현은 RT-qPCR로 평가하였다. IL-6의 mRNA 발현은 비강점막, 대퇴사두근, 백색 지방조직(WAT)에서 분석하였으며, 그룹 간 차이는 t-검정을 통해 평가하였다. 결과: 운동은 체중에 유의미한 영향을 미치지 않았지만, 알레르기 감작 생쥐는 체중이 유의미하게 감소하였다 (p<0.05). 1부에서는 알레르기 및 비-알레르기 그룹 간 운동량 차이가 없었으나, 2부에서는 알레르기 생쥐의 운동량이 비-알레르기 생쥐보다 유의미하게 적었다 (10,607회 대 16,765회, p<0.05). 알레르겐 감작은 혈청 총 IgE, Dp-특이 IgE, IgG1 수치를 유의미하게 증가시켰으며 (p<0.05), 운동은 비-알레르기 모델에서 이러한 수치에 영향을 미치지 않았다. 알레르기 모델에서는 1부에서 운동이 혈청 총 IgE, Dp-특이 IgE, IgG1 수치를 비-알레르기 수준으로 유의미하게 감소시켰으나 (p<0.001), 2부에서는 이러한 감소가 관찰되지 않았다. 조직학적 분석 결과, 비강 상피에서 운동 및 알레르겐 도전에 의해 조직 내 호산구 침윤이 유의미하게 증가하였으나, 운동을 통해 Part 1과 Part 2 모두에서 감소가 관찰되었다(p<0.05). 그러나 상피 두께와 술잔세포 수와 같은 조직 재형성은 Part 1에서만 상피 두께가 유의미하게 감소하였고, Part 2에서는 감소가 관찰되지 않았다. RT-qPCR 분석에서는 비강 IL-4 mRNA 발현이 Part 1과 Part 2 모두에서 유의미하게 감소하였으며(p<0.001), eotaxin-1 발현 감소는 Part 1에서만(p<0.001), IL-17 감소는 Part 2에서만 관찰되었다. 운동으로 유도된 IL-6는 대퇴사두근과 비강점막에서 mRNA 발현이 유의미하게 증가하였으며, 알레르기군의 비강에서도 IL-6 발현이 상승함이 관찰되었으며, 운동을 실시한 알레르기 모델에서는 비강점막과 백색지방조직에서 IL-6 발현이 유의미하게 감소하였고, 이는 운동으로 인해 근육에서 분비된 IL-6가 지방조직의 Th2 염증을 억제하고, 알러젠 감작 단계에서의 감소 및 비강 점막 내 알러지 염증 반응을 억제하는 데 관여하는 매개체 중 하나가 될 수 있음을 시사한다. 결론 : 자발적 신체 운동은 알러지 비염 유도 생쥐 모델에서 알레르기 감작 정도 및 알러젠에 노출 시 전신 및 비강 알러지 반응을 완화시킬 수 있으며, 이러한 효과는 알레르겐에 감작되기 이전 또는 감작 초기부터 운동을 시작했을 때 더 강하게 나타난다.|Background: Allergic rhinitis (AR) is a type 2 immune response in the nasal mucosa triggered by allergen exposure in sensitized individuals. While increased physical activity or exercise may improve AR or asthma control in children, some evidence suggests it could worsen allergic inflammation in the airway. This study investigates the impact of spontaneous exercise on allergen sensitization and allergic responses in an AR-induced mouse model to clarify its role in modulating allergic rhinitis. Materials and Methods: An AR-induced mouse model was developed using 4-week-old BALB/c female mice sensitized with weekly intraperitoneal injections of 25 µg Dermatophagoides pteronyssinus (Der-p1; Dp) and 1 mg aluminum hydroxide gel, followed by daily nasal challenges with 20 µg Der-p1. Control mice received PBS injections and challenges. The study comprised two parts, each with four groups of 12 mice, making total of 96 mice. Mice exercised on a rodent-specific wheel with a revolution counter. Part 1 involved simultaneous exercise during sensitization and nasal provocation for 4 weeks, while Part 2 began exercise 4 weeks post-sensitization with continued nasal provocation for 4 weeks. Body weight and wheel revolutions were recorded daily, and mice were sacrificed at 8 and 12 weeks. Systemic sensitization was evaluated using ELISA for serum total and specific IgE and multiplex bead assay array for IL-4, IL-5, and eotaxin-1. Local AR responses were assessed via nasal histology at the nasal epithelium at the anterior part of the septum, and nasal mucosa tissue RT-qPCR for inflammatory cytokine gene expression levels. The mRNA expression of IL-6 was quantified in the nasal mucosa, quadriceps muscle, and white adipose tissue (WAT) to assess changes induced by physical exercise. Group differences were analyzed using t-tests. Results: Physical exercise did not significantly affect body weight, but allergy-sensitized mice showed a significant reduction in weight (p<0.05). In Part 1, no significant differences in wheel revolutions were observed between allergy and non-allergy groups. In Part 2, allergy mice had significantly fewer revolutions (10,607 vs. 16,765, p<0.05). Allergen sensitization significantly elevated serum total IgE, Dp-specific IgE, and Dp-specific IgG1 levels in allergy models (p<0.05), while physical exercise had no effect on these markers in non-allergy models. In allergy models, physical exercise significantly reduced serum total IgE, Dp-specific IgE, and Dp-specific IgG1 levels in Part 1 (p<0.001) to non-allergy levels, but no such reductions were observed in Part 2, where Dp-specific IgE remained elevated. Histological examination showed a significant increase in tissue eosinophils in the nasal respiratory mucosa with exercise and allergen challenge, with reductions observed in both Part 1 and Part 2 (p<0.05). However, tissue remodeling, indicated by increased epithelial thickness and goblet cell counts, showed a significant reduction in epithelial thickness only in Part 1, but not in Part 2. RT- qPCR analysis showed a significant decrease in nasal IL-4 mRNA expression with exercise in allergy models in both Part 1 and Part 2 (p<0.001), while reductions in nasal eotaxin-1 were observed only in Part 1 (p<0.001) and IL-17 only in Part 2. IL-6, induced by physical exercise in skeletal muscles and known for reducing inflammation, showed increased mRNA expression in the quadriceps and nasal tissue in exercise-only groups. In allergy-only groups, IL-6 also rose in nasal tissue and WAT. However, when the exercise was combined with allergy induction, IL-6 expression significantly increased in the quadriceps muscle, but showed significant decrease in nasal tissue and WAT. Conclusion: Spontaneous exercise may mitigate allergic responses in AR-induced mice, with stronger effects on systemic allergies than local nasal allergies, particularly when the physical exercised is initiated with or prior to allergen sensitization. Allergic response attenuation with exercise was highlighted only in acute nasal allergy reaction, but did not reverse chronically remodeled nasal mucosa. The increased release of IL-6 from skeletal muscle during physical exercise may cautiously suggest that IL-6 may play a role in attenuating systemic allergen sensitization and nasal allergic inflammation, potentially explaining our results.Docto

Incidence of Nasal Floor Tilting and its Relationship with Nasofacial Structures

Background and Objectives : The nasal floor tilting (NFT) is an incidental finding shown on the ostiomeatal computed tomography (OMU CT) image, created by an asymmetry in the levels of both nasal floors. Despite its frequent appearance, this finding has never been properly defined, and its correlation with asymmetry of the adjacent nasofacial structures was never investigated. This study aimed to reveal the incidence of nasal floor tilting in patients with sinonasal symptoms and find out its correlation with structures of the nasofacial skeleton. Materials and Methods : From January 2008 to July 2017, patients who had taken preoperative OMU CT as well as facial photograph were investigated. Patients under age of 20, with a history of craniofacial anomaly, prior nasofacial trauma or surgery, neoplasm in the head and neck area were excluded. The incidence of NFT and the degree of NFT angle was measured in 265 patients. Asymmetries shown on the adjacent nasofacial skeleton as well as in the external face were evaluated. Analysis on the incidental difference of adjacent nasofacial asymmetry upon the presence of the NFT was performed. The NFT, asymmetry in the orbital level, maxillary sinus level, and maxillary sinus size was evaluated along with bony nasal septal deviation (NSD) shown on the OMU CT was measured. In the frontal facial photograph, perceived overall facial asymmetry in addition to the anthropometric measurement of the each upper, middle, lower facial asymmetry was measured. Results : The incidence of nasal floor tilting (NFT) was shown as 51 % (136 in 265 patients), defined as the tilted group. The mean NFT angle in the tiled group showed 7.7°with a standard deviation (SD) of 4.4°, ranging from 2.4° to 22.4°. The tilted group showed a higher incidence of NSD, asymmetrical orbit levels, asymmetrical maxillary sinus levels along with the size (P &lt; .001) than the non-tilted group. The perceived facial asymmetry and perceived horizontal level asymmetry of the face were associated with a higher incidence in the tilted group (P &lt; .01), whereas the external nasal deviation and asymmetry in each upper, middle, and lower face showed no difference in between two groups. Conclusions : The tilting of the nasal floor can be seen in half of the patients complaining nasal symptoms. The incidence of asymmetry in the nasal skeleton as well as the in the face were shown to be higher in the NFT patients compared to patients not presenting a NFT. In addition, a higher nasofacial structures corresponded with the higher side of the nasal floor.Maste

한국 남성 수면무호흡 환자에서 설동맥과 혀의 위치관계 분석을 통한혀 기저부 기능 수술 시 안전 영역에 대한 연구

Background and Objectives Upon operation of the tongue base for obstructive sleep apneasyndrome (OSAS), the lingual artery and the hypoglossal nerve are put at risk of injury,resulting in fatal complications such as massive bleeding upon damage. We studied the courseof lingual artery in its relation with the tongue in OSAS patients and compared it with the ageand-gender-matched normal population. Subjects and Method Korean male patients confirmed with OSAS by polysomnography,including those who had contrast-enhanced computed tomography (ceCT) of the head andneck, were defined as “OSAS group.” Patients who had their ceCT image during the samestudy period were defined as the “control group.” The control group was paired with the OSASgroup by age and sex. By using foramen cecum (FC) as the main reference point, four referencemarks were defined. For each reference point, the distance between both lingual arteriesand the depth of the lingual artery from the lingual surface of the tongue were evaluated. Results The depth of the lingual artery from the lingual surface of the tongue in the OSASgroup (25.1±8.6 mm) was significantly different from the control (29.5±5.9 mm) at 1 cm anteriorto the FC level (p&lt;0.014). The width of both lingual arteries was narrower in the OSASgroup (20.9±2.9) than in the control (24.3±6.1) at the FC level (p&lt;0.003). Conclusion The course of lingual artery and its spatial relation with the tongue in Koreanmale OSAS patients differs from the matched normal population

비 기저부 비대칭과 비-안면구조물과의 관계 분석

Background and Objectives Nasal floor slanting (NFS) is an incidental radiographic finding of asymmetry in the nasal floor level. Despite its frequent appearance, however, NFS has never been properly defined, neither has its correlation with the asymmetry of the adjacent nasofacial structures been investigated. We evaluated the incidence of NFS in patients with sinonasal symptoms and its correlation with the nasofacial skeletal structures. Subjects and Method We investigated patients who underwent preoperative ostiomeatal unit (OMU) CT and facial photography. We measured the incidence of NFS and its angle in the 265 patient images, and analyzed the relationships between NFS and radiologically detected asymmetries of the adjacent nasofacial skeleton and facial asymmetry visible on a photograph. Results NFS was found in 51% of the study subjects (136/265), who were defined as the slanted group. The mean NFS angle in the slanted group was 7.7° with a standard deviation (SD) of 4.4°, ranging from 2.4° to 22.4°. The slanted group showed a higher incidence of nasal septal deviation, asymmetry in the orbit and maxillary sinus, and a larger maxillary cavity (p&lt;0.001) than the non-slanted group. Asymmetry of the face showed a higher incidence in the slanted group (p&lt;0.01), whereas an external nasal deviation did not show an association with NFS. Conclusion NFS is evident in about 50% of patients complaining of nasal symptoms and is associated with nasofacial skeletal asymmetry as well as asymmetry in the face