記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Dysfunctional breathing (DB) is a major asthma comorbidity; however, it is not well recognized in Japan. Moreover, it has rarely been reported in the asthma population, and its clinical characteristics are unclear. We aimed to clarify the clinical characteristics of DB as a comorbidity in patients with asthma in Japan. Questionnaire surveys were conducted among patients with asthma at medical facilities in three regions of Japan (Niigata, Kumamoto, and Tokyo). METHODS: This cross-sectional questionnaire survey targeting patients with asthma who had regularly visited medical institutions and their doctors was conducted from September to November 2021. The questionnaire addressed the control status and method of treatment. The diagnosis of DB was evaluated using the Nijmegen questionnaire (NQ). RESULTS: There were 2087 eligible participants. Based on their NQ scores, 217 patients were classified into the DB group (NQ ≥ 19). There were significant differences with respect to sex, disease duration, Asthma Control Test (ACT) scores, Patient Health Questionnaire-9 (PHQ-9) scores, type-2 biomarkers, pulmonary function indices, treatment methods, severity, and asthma exacerbations in the previous year between the DB and non-DB groups. In the multivariate analysis, there were significant differences in sex, disease duration (≥15 y), ACT scores (<20), and PHQ-9 scores (≥10). The cluster analysis of cases with DB classified the population into four clusters. CONCLUSIONS: The asthma population with DB exhibited several characteristics, including depression and poorly controlled asthma. Further large-scale interventional investigations with longer follow-up periods are necessary to verify these findings.

DOI： 10.1016/j.resinv.2024.08.004

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Benralizumab, an anti-interleukin-5 receptor chain monoclonal antibody, is used to treat severe asthma and control asthma symptoms or exacerbations. The aim of this study was to examine the changes in airway morphology using computed tomography (CT) images in accordance with clinical efficacy following the administration of benralizumab. METHODS: The clinical efficacy of benralizumab was evaluated in 11 patients with severe asthma by analyzing the changes in parameters, such as the asthma control test, asthma quality of life questionnaire, pulmonary function, and exacerbation count. We also investigated the airway wall thickness of the right bronchus (B1) and the total airway count (TAC) using CT images. RESULTS: Most patients treated with benralizumab showed improvements in asthma symptoms and exacerbations. CT imaging analyses showed a decrease in the right B1 airway wall thickness and an increase in the TAC. Correlations between blood eosinophil count and changes in CT imaging were observed. DISCUSSION/CONCLUSION: The data suggested that benralizumab has the potential to improve airway wall thickening and ventilation by alleviating the obstruction and clearing an obstructed airway.

DOI： 10.1159/000525846

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Mucus plugs are associated with airway obstruction in severe asthma and are involved in the formation of activated eosinophils. Benralizumab, an anti-interleukin-5 receptor antibody, markedly reduces not only peripheral blood eosinophils but also airway eosinophils; however, its effects on mucus plugs have not been clarified. In this study, we examined the efficacy of benralizumab on mucus plugs using computed tomography (CT) imaging. METHODS: Twelve patients who were administered benralizumab and underwent CT before and approximately 4 months after the introduction of benralizumab were included in this study, and the number of mucus plugs before and after benralizumab administration was compared. The correlation between the clinical background and treatment effect was also examined. RESULTS: The number of mucus plugs significantly decreased after the introduction of benralizumab. The number of mucus plugs was correlated with sputum eosinophil percentage and eosinophil cationic protein in the sputum supernatants and inversely correlated with forced expiratory volume in 1 s (FEV1). Benralizumab induction resulted in a marked decrease in blood and sputum eosinophil levels and a significant improvement in asthma symptoms, quality of life scores, FEV1, and exacerbation frequency. Furthermore, there was a significant correlation between the reduction in mucus plugs and changes in the symptom score or FEV1. DISCUSSION/CONCLUSION: These data suggest that benralizumab may have the potential to improve symptoms and respiratory function in patients with severe eosinophilic asthma by reducing mucus plugs.

DOI： 10.1159/000530392

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report a 45-year-old-man with multiple foreign body granulomas in the lungs caused by polytetrafluoroethylene (PTFE). A mass in the right lower lobe of the lung and bilateral centrilobular lung nodules were found unexpectedly during the patient's visit to a hospital for a respiratory infection. The patient's occupation for 26 years involved spraying PTFE. A lung biopsy using bronchoscopy revealed granulomatous lesions and giant cells. The presence of fluorine in the granulomatous lesions was confirmed using an electron probe microanalyzer with wavelength dispersive spectrometer. Fluorine is a component of PTFE and is not found in normal lung tissue.

DOI： 10.2169/internalmedicine.9008-21

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記述言語：英語  

DOI： 10.1016/j.alit.2022.03.005

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

背景.気管支静脈瘤は稀な疾患であり,その治療法は確立されていない.症例.78歳,女性.小児期より気管支拡張症を罹患し,膿胸の既往があった.6年前から喀血を繰り返し,計3回の気管支動脈塞栓術が行われていた.今回,喀血を契機に入院し,止血薬投与を受けたが大量喀血を来したため,気管挿管の上で人工呼吸管理となった.左下横隔動脈と左気管支動脈をゼラチンスポンジで塞栓し,止血を得た.その際の選択的動脈造影で左下横隔動脈と肺静脈との動静脈シャントを認めた.気管支鏡で観察すると,左上下葉支分岐部に気管支静脈瘤がみられ,出血源と考えられた.動脈塞栓術の2週後の気管支鏡では同部位の瘤は退縮していた.その後,再喀血なく自宅退院した.結論.気管支静脈瘤は気管支拡張症や動脈塞栓に関連して発症する可能性があり,喀血時は気管支鏡による確認が必要である.治療として異常シャントの塞栓術が有効と考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00298&link_issn=&doc_id=20211216270004&doc_link_id=%2Fcf0brond%2F2021%2F004306%2F005%2F0589-0594%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2021%2F004306%2F005%2F0589-0594%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00298&link_issn=&doc_id=20211216270004&doc_link_id=10.18907%2Fjjsre.43.6_589&url=https%3A%2F%2Fdoi.org%2F10.18907%2Fjjsre.43.6_589&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. &lt;b&gt;&lt;i&gt;Discussion/Conclusion:&lt;/i&gt;&lt;/b&gt; Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

DOI： 10.1159/000519296

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is a significant cause of mortality among patients with dermatomyositis (DM) or polymyositis (PM). There are two subtypes of PM and DM often complicated with ILD: those with anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies and those with anti-MDA-5-associated amyopathic DM (ADM). Our aim is to clarify the inflammatory and immunological differences between the disorders. METHODS: We retrospectively collected consecutive patients with anti-ARS-ILD and those with anti-MDA-5 antibody-positive ADM-ILD. The serum concentration of 38 cytokines was measured using a cytokine panel. The relative risks for anti-MDA-5 antibody-positive ADM-ILD were examined with univariate and multivariate logistic regression models. Spearman's rank correlation coefficient was calculated between cytokine levels and clinical parameters in the disease. Levels of cytokines were compared between anti-ARS-ILD and anti-MDA-5-positive ADM-ILD patients (alive or dead) using Dunnett's test. RESULTS: Twenty-three patients with anti-ARS-ILD and the same number of patients with anti-MDA-5-positive ADM-ILD were enrolled. The anti-MDA-5 group had poor survival (p = 0.025). Univariate logistic regression models showed that eotaxin, IL-10, IP-10, and MCP-1 were associated with the diagnosis of anti-MDA-5-positive ADM-ILD. Multivariate logistic regression models revealed that IP-10 was the most significantly associated (p = 0.001). Relationship analyses showed that IL-10 had significant positive correlations with CK (r = 0.5267, p = 0.009) and ferritin (r = 0.4528, p = 0.045). A comparison of the cytokine levels found that IP-10 was elevated in both patients who were alive and patients who had died with ADM-ILD compared with the levels in those with ARS-ILD (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Anti-MDA-5-positive ADM-ILD had poorer survival than anti-ARS-ILD. IP-10 seems to be most deeply involved in the pathophysiology of anti-MDA-5-associated ADM-ILD.Key Points• To clarify differences in the inflammatory and immunological features of anti-MDA-5-positive ADM-ILD and anti-ARS-ILD, we performed an observational study to measure serum cytokine concentrations before treatment using a multiplex immunoassay system.• Multivariate logistic regression models revealed that IP-10 was associated with the most significant relative risk for ADM-ILD with anti-MDA-5 antibodies.• Levels of IP-10 were elevated considerably in anti-MDA-5-positive survivors and nonsurvivors compared with the levels in anti-ARS patients.• These results suggest that IP-10 is the most deeply involved in the pathophysiology of anti-MDA-5-positive ADM-ILD.

DOI： 10.1007/s10067-020-04984-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It is well known that the prevalence of asthma is higher in athletes, including Olympic athletes, than in the general population. In this study, we analyzed the mechanism of exercise-induced bronchoconstriction by using animal models of athlete asthma. Mice were made to exercise on a treadmill for a total duration of 1 week, 3 weeks, or 5 weeks. We analyzed airway responsiveness, BAL fluid, lung homogenates, and tissue histology for each period. In mice that were treated (i.e., the treatment model), treatments were administered from the fourth to the fifth week. We also collected induced sputum from human athletes with asthma and analyzed the supernatants. Airway responsiveness to methacholine was enhanced with repeated exercise stimulation, although the cell composition in BAL fluid did not change. Exercise induced hypertrophy of airway smooth muscle and subepithelial collagen deposition. Cysteinyl-leukotriene (Cys-LT) levels were significantly increased with exercise duration. Montelukast treatment significantly reduced airway hyperresponsiveness (AHR) and airway remodeling. Expression of PLA2G4 (phospholipase A2 group IV) and leukotriene C4 synthase in the airway epithelium was upregulated in the exercise model, and inhibition of PLA2 ameliorated AHR and airway remodeling, with associated lower levels of Cys-LTs. The levels of Cys-LTs in sputum from athletes did not differ between those with and without sputum eosinophilia. These data suggest that AHR and airway remodeling were caused by repeated and strenuous exercise. Cys-LTs from the airway epithelium, but not inflammatory cells, may play an important role in this mouse model.

DOI： 10.1165/rcmb.2019-0325OC

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担当区分：責任著者   記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

オラパリブ(olaparib)は、進行卵巣癌・乳癌に対する新規の分子標的薬(poly ADP-ribose polymerase阻害薬)である。オラパリブによる薬剤性肺障害の発症頻度は低いとされているが、当院ではオラパリブによる薬剤性肺障害と思われる症例を2例経験した。発症時期、症状、経過、検査所見など多くの共通点がみられた一方、画像パターンには一定の傾向はみられなかった。原疾患が悪性腫瘍の場合、再投与の可否が問題となるが、本例では2例とも再燃を認めずに再投与し得た。今後オラパリブは適応が広まっていくことが予想されており、薬剤性肺障害にも留意する必要がある。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Objective: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naive cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, the immunological characteristics of these cases are not known and it is unclear if this situation contributes to asthma control. This study was performed to determine the answer of these questions. Methods: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n = 22) and healthy controls (n = 10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry. Results: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5 versus 36.6%; p&lt;0.01). The fraction of helper T (Th)17 lymphocytes as well as the ratio of Th17 to regulatory T cells (Treg) in the peripheral blood was higher in the NEA than in the EA group (0.24 versus 0.13; p&lt;0.05). Conclusions: Th17 were more prevalent than Treg cells in the peripheral blood of NEA patients under ICS treatment, corresponding to neutrophil-dominant airway inflammation and a severe asthmatic phenotype. Thus, an imbalance in Th17/Treg may be associated with the pathogenesis of NEA in patients undergoing ICS treatment.

DOI： 10.3109/02770903.2014.975357

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: Active suppression induced by regulatory T (Treg) cells is reported to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid (ATRA) has been reported to affect Treg cell differentiation. The present study examined the effects of ATRA on the induction of oral tolerance in a murine model of bronchial asthma. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups ATRA was orally administered concomitantly with OVA feeding either in the presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4(+) T cells were isolated from mice exposed to ATRA and/or OVA, and transferred to control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. Results: Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia, elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of Treg cells in the lungs was increased in mice treated with OVA and ATRA, as compared to those treated with OVA only. Transfer of lung CD4(+) T cells from mice treated with OVA and ATRA induced suppression of AHR and airway inflammation. LE135 completely reversed the effects of ATRA on AHR, airway allergic inflammation and the number of Treg cells in the lungs. Conclusion: These data suggested that oral administration of ATRA with OVA had the potential to enhance oral tolerance in this murine model of bronchial asthma. These effects were mediated, at least in part, by Treg cell expansion. (C) 2015 S. Karger AG, Basel

DOI： 10.1159/000437326

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記述言語：日本語   出版者・発行元：新潟医学会  

症例は54歳、男性。非小細胞肺癌(腺癌)、stage IV、上皮成長受容体遺伝子変異陽性と診断された。3次化学療法目的に入院した際、発熱、嘔気、低ナトリウム血症などの症状を認められた。血中コルチゾル低値、血中ACTH高値などから、急性副腎不全と診断した。両側副腎に巨大な肺癌の転移巣を認めており、副腎不全の原因と考えられた。ヒドロコルチゾン投与で症状は速やかに軽快した。肺癌は高率に副腎転移を来すが、両側副腎転移により副腎不全に至った報告例は少ない。我々は肺癌の両側副腎転移により副腎不全を来し、ステロイドホルモン補充により化学療法を再開しえた症例を経験したため、文献的考察を加え報告する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

症例は44歳男で、5ヵ月前頃より続く咳嗽・喀痰、呼吸苦、食欲低下を主訴に近医を受診し、胸部X線・CTで両上葉背側部を中心に比較的壁の厚い空洞性病変を伴う広範なconsolidationおよび右大量胸水を認め、喀痰抗酸菌塗抹検査でGaffky 5号が判明した。Quanti FERON TB-2Gは陽性、胸水中Adenosine deaminaseは高値で、肺結核+結核性胸膜炎を強く疑い、標準的抗結核化学療法であるrifampicin(RFP)など3剤で治療を開始したが、喀痰抗酸菌PCRは結核菌、Mycobacterium avium complexとも陰性で、薬剤性肝障害もありいったん中止した。その後複数回の異なる喀痰培養で非結核性抗酸菌が検出され、DNA-DNA hybridization methodでM.kansasiiが同定されたことより、最終的に肺M.kansasii症と診断した。RFPを含む3剤併用療法を再開し、副作用や胸水再貯留は認めず、経過良好である。

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記述言語：日本語   出版者・発行元：新潟医学会  

症例は79歳、男性。右背部痛と血痰を主訴に当科を受診した。胸部CT検査で右下葉末梢に不整な浸潤影と少量の胸水を認めた。造影CT検査で浸潤影の領域を支配する右肺動脈区域枝と右膝窩静脈に造影欠損を認めたため、急性肺血栓塞栓症、肺梗塞および深部静脈血栓症と診断した。抗凝固療法の開始により、肺動脈および下肢静脈内の血栓は消失し、右下葉胸膜下の浸潤影も縮小した。肺梗塞の早期診断・治療には、造影CT検査を積極的に行うことが重要と考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：新潟医学会  

症例は38歳, 男性. 右頸部腫瘤を主訴に近医を受診した際, 低酸素血症と胸部異常陰影を指摘された. CT検査で頸部リンパ節腫脹や肝硬変の所見に加えて, 肺内血管の拡張を認めた. 頸部リンパ節生検および肺血流シンチグラフィ検査で右左肺内シャントが確認されたことより, 悪性リンパ腫(びまん性大細胞型B細胞リンパ腫)および肝肺症候群と診断した. 家族歴の聴取により, 原因不明の肝硬変から肝肺症候群に至り, 在宅酸素療法を導入している兄の存在が判明した. これまで同胞内で肝肺症候群を発症した症例の報告はなく, 極めて稀な症例と考えられた.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Objective: While the majority of individuals with asthma retain normal lung function over time, some exhibit accelerated lung function decline. Preservation of lung function is an important aspect of asthma management. Whether the asthma guidelines can prevent lung function decline remains controversial. This study was performed to determine the distribution of asthmatic subjects with greater lung function decline and to identify characteristic clinical features of such subjects treated in accordance with clinical guidelines by using hierarchical cluster analysis. Methods: Eighty-six asthmatic subjects without a history of smoking were assessed with respect to eight variables selected from clinical phenotypes by using step-wise multiple regression analysis. Hierarchical cluster analysis using Ward's method generated a dendrogram for estimation of the number of clusters within the population and the differences between them. Results: Three distinct clusters were identified. Cluster 1 (n = 40) comprised women with late-onset asthma. Cluster 2 (n = 17) comprised subjects with early-onset asthma, atopy and long disease duration. Cluster 3 (n = 29) predominantly comprised older men who had late-onset asthma, a lower prevalence of exacerbation and a lower predicted % forced expiratory volume in 1 s (FEV1) at baseline. Subjects in cluster 3 showed a mean decline in FEV1 of 69 mL/year, which was the greatest lung function decline among the three clusters. Conclusion: We identified a subgroup of patients with accelerated lung function decline despite appropriate asthma treatment based on guidelines constructed by using subjective symptoms.

DOI： 10.3109/02770903.2013.852201

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記述言語：日本語   出版者・発行元：(株)医薬情報研究所  

喘息治療薬についての喘息患者の関心・要望について、新潟喘息治療研究会2010年アンケート調査より検討した。参加施設は新潟県内の医療機関で、200床以上の24病院、200床未満の16病院と56の診療所であった。アンケート回収率は58.0%(4662例中2706例)であった。喘息治療薬の効果、易使用性、コスト・安全性の中では、患者は喘息治療薬の効果を最も重要視した。更に、喘息治療薬の効果に関する項目では、効果発現の早さ、効果の持続の2つともに重要視しているが、喘息症状の完全寛解については理解が乏しかった。易使用性では使用回数に関した要望が高いものの、内服・吸入といった使用経路についての関心が低かった。コスト・安全性では副作用についての要望が高かったものの、予想されたコスト面での要望は低かった。

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記述言語：日本語   出版者・発行元：新潟県医師会  

Balb/cマウスにコナヒョウダニ抗原を5週間連日点鼻投与して気管支喘息モデルを作成し、その後ダニ抗原舌下投与500μg/日投与群、5mg/日投与群、生理食塩水投与群に分けて2週間行い、再度抗原を1週間点鼻投与して舌下免疫療法モデルを作成してその有効性について検討した。ダニ抗原を舌下投与した群では、生理食塩水投与群に比べ気道過敏性と気管支肺胞洗浄液(BALF)中の好酸球が抑制され、抗原500μg投与群に比べ5mg投与群でより顕著であった。また、抗原舌下投与群ではBALF中のTh2サイトカインも抑制され、粘液産生細胞や細胞浸潤の減少が認められた。本モデルにおける舌下免疫療法は有効と考えられた。

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER THORACIC SOC  

Airway remodeling in bronchial asthma results from chronic, persistent airway inflammation. The effects of the reversal of airway remodeling by drug interventions remain to be elucidated. We investigated the effects of ONO-1301, a novel prostacyclin agonist with thromboxane inhibitory activity, on the prevention and reversibility of airway remodeling in an experimental chronic asthma model. Mice sensitized and challenged to ovalbumin (OVA) three times a week for 5 consecutive weeks were administered ONO-1301 or vehicle twice a day from the fourth week of OVA challenges. Twenty-four hours after the final OVA challenge, airway hyperresponsiveness (AHR) was assessed, and bronchoalveolar lavage was performed. Lung specimens were excised for staining to detect goblet-cell metaplasia, airway smooth muscle, and submucosal fibrosis. Mice administered ONO-1301 showed limited increases in AHR compared with mice administered the vehicle. The histological findings of airway remodeling were improved in ONO-1301-treated mice compared with vehicle-treated mice. Presumably, these therapeutic effects of ONO-1301 are attributable to the up-regulation of production of hepatocyte growth factor (HGF) in lung tissue, because the neutralization of HGF by antibodies prevented the effects of ONO-1301 on AHR and airway remodeling. Mice administered ONO-1301 showed similar levels of AHR and airway remodeling as mice administered montelukast, a cysteinyl-leukotriene-1 receptor antagonist, and lower levels were observed in mice administered dexamethasone. These data suggest that ONO-1301 exerts the effect of reversing airway remodeling, at least in part through an elevation of HGF in the lungs, and may be effective as an anti-remodeling drug in the treatment of asthma.

DOI： 10.1165/rcmb.2011-0350OC

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background Oral tolerance is a classically used strategy for antigen-specific systemic immunotherapy. However, the roles of IL-17 in modification of oral tolerance are not yet understood.
Objective To define the effects of IL-17 on the modification of oral tolerance, the effects of transfer of Th17 cells, administration of IL-17 or anti-IL-17 antibody (alpha IL-17Ab) to a murine allergic airway inflammation model were investigated.
Methods Mice sensitized to and challenged with OVA, received OVA feeding, followed by OVA challenges. Transfer of Th17 cells, administration of IL-17 or alpha IL-17Ab were executed during OVA feeding. Airway hyperresponsiveness (AHR), airway inflammation, Th2 cytokine response and lung pathology were assessed.
Results Administration of IL-17 as well as transfer of Th17 cells aggravated AHR and airway allergic inflammation as compared with the findings in mice subjected to OVA feeding alone, whereas administration of aIL-17Ab ameliorated AHR and airway eosinophilia. The effects of Th17 transfer were presumably attributable to augmentation of endogenous IL-6 production in gut. The number of Foxp3-positive regulatory T (Treg) cells in lungs and Payer's patches was increased in the OVA fed mice, whereas the number of these cells was decreased in the mice subjected to OVA feeding + Th17 cell transfer. Neutralization of IL-6 by monoclonal antibody in the mice subjected to OVA feeding + transfer of Th17 cells restored the effects of oral tolerance.
Conclusions and Clinical Relevance These data suggest that IL-17 may inhibit the induction of tolerance to antigen through, at least in part augmenting IL-6 production, thereby suppressing the expansion of Treg cells.

DOI： 10.1111/j.1365-2222.2012.04006.x

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00009&link_issn=&doc_id=20121105180578&doc_link_id=%2Fcw4aller%2F2012%2F006109%2F246%2F1526-1526%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2012%2F006109%2F246%2F1526-1526%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00009&link_issn=&doc_id=20121105180577&doc_link_id=%2Fcw4aller%2F2012%2F006109%2F245%2F1526-1526%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2012%2F006109%2F245%2F1526-1526%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00009&link_issn=&doc_id=20121105180244&doc_link_id=%2Fcw4aller%2F2012%2F006109%2F0f8%2F1441-1441%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2012%2F006109%2F0f8%2F1441-1441%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

Web of Science

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.60.1433_4

CiNii Article

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER THORACIC SOC  

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.60.1373_4

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.60.1361_3

CiNii Article

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.59.1394_1

CiNii Article

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.59.1430_2

CiNii Article

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.59.1429_2

CiNii Article

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.59.1383_1

CiNii Article

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.59.1324_2

CiNii Article

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記述言語：日本語   出版者・発行元：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.59.392_2

CiNii Article

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記述言語：日本語  

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記述言語：日本語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：ポスター発表  

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記述言語：英語   会議種別：口頭発表（一般）  

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