研究者詳細 - 牧原　靖一郎

論文 - 牧原　靖一郎

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Impact of Preoperative Systemic Corticosteroids on the Histology and Diagnosis of Eosinophilic Chronic Rhinosinusitis. 査読国際誌

Kosuke Akiyama, Seiichiro Makihara, Kensuke Uraguchi, Yasushi Samukawa, Aiko Oka, Hiroshi Hoshikawa

International archives of allergy and immunology 179 ( 2 ) 81 - 88 2019年

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: The histological changes corticosteroids induce in nasal polyps, and whether these changes have an impact on the diagnosis of eosinophilic chronic rhinosinusitis (ECRS), currently remain unclear. OBJECTIVES: A prospective controlled multicenter trial was conducted to evaluate the efficacy of the low-dose and short-term oral prednisolone (oPSL) treatment for tissue eosinophil infiltrations in ECRS. METHODS: Subjects with ECRS diagnosed by previous biopsies received a low dose of oPSL for 3 days (PSL 3) or 7 days (PSL 7) before surgery. Changes in the tissue eosinophil count after these treatments were evaluated. Furthermore, the percent change of tissue eosinophil count from baseline and its impact on the diagnosis defined by the JESREC study were examined. RESULTS: There were 23 and 21 subjects in the PSL 3 and PSL 7 groups, respectively. Polyp scores, clinical symptom scores, and the proportion of blood eosinophils significantly decreased after the treatment, and no significant differences were observed between the groups. The entire tissue eosinophil count tended to be slightly decreased in both groups without reaching a statistically significant value. The median percent change of tissue eo-sinophil count from baseline was 83.6%, and only the posttreatment proportion of blood eosinophil showed a mild correlation with it. Seven out of 44 nasal polyp specimens collected from the superficial part of the middle meatus showed < 70 eosinophils/high-power field; therefore, the false negative rate was 15.9%, but decreased to 11.4% when other parts were included in the histological evaluation. CONCLUSIONS: Low-dose and short-term oPSL did not appear to markedly affect the tissue eosinophil count in ECRS patients; however, the potential for misdiagnoses due to the effects of oPSL cannot be rejected. The diagnosis of ECRS prior to the administration of corticosteroids or tissue evaluations using multiple tissue parts is desirable.

DOI： 10.1159/000496437

Baker's rhinitis症例における小麦粉抗原に対するIgEおよび末梢血単核細胞応答の解析の試み査読

春名威範, 岡野光博, 藤原田鶴子, 檜垣貴哉, 假谷伸, 牧原靖一郎, 金井健吾, 橘智靖, 松山祐子, 小松原靖聡, 直井勇人, 西崎和則

アレルギー 68 ( 1 ) 35 - 42 2019年

NLRP3 inflammasome expression in lipopolysaccharide-induced otitis media. 査読国際誌

Shin Kariya, Mitsuhiro Okano, Pengfei Zhao, Yukihide Maeda, Yuko Kataoka, Takaya Higaki, Yohei Noda, Seiichiro Makihara, Kazunori Nishizaki

Acta oto-laryngologica 138 ( 12 ) 1061 - 1065 2018年12月

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

BACKGROUND: The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a critical molecule mediating interleukin-1β (IL-1β) responses. However, the role of the NLRP3 inflammasome in otitis media has not been fully examined. AIMS/OBJECTIVES: The purpose of this study is to assess the expression of NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in lipopolysaccharide-induced otitis media. MATERIALS AND METHODS: BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 h after injection. Concentrations of IL-1β, NLRP3, ASC, and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. RESULTS: The transtympanic injection of lipopolysaccharide significantly upregulated levels of IL-1β, NLRP3, ASC, and caspase-1 in the middle ear as compared with the control mice. The proteins of NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear cavity. CONCLUSIONS AND SIGNIFICANCE: Lipopolysaccharide induces NLRP3 inflammasome components in the middle ear. The NLRP3 inflammasome may play an important role in the pathogenesis of otitis media. Modulation of inflammasome-mediated inflammation may be a novel therapeutic strategy for otitis media.

DOI： 10.1080/00016489.2018.1515499

【私はこうしている-鼻科手術編】鼻科手術全般鼻科手術のための局所解剖鼻副鼻腔

岡野光博, 牧原靖一郎

JOHNS 34 ( 9 ) 1083 - 1085 2018年9月

【私はこうしている-鼻科手術編】各種疾患に対する手術副鼻腔真菌症

牧原靖一郎, 岡野光博

JOHNS 34 ( 9 ) 1269 - 1272 2018年9月

Glottic cancer in patients without complaints of hoarseness. 国際誌

Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Seiichiro Makihara, Misato Hirai, Kentaro Miki, Yuya Ogawara, Hisashi Ishihara, Yuko Matsuyama, Iku Abe-Fujisawa, Aiko Shimizu, Yasuharu Sato, Kazunori Nishizaki

Head & neck 40 ( 7 ) 1608 - 1608 2018年7月

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

The authors have brought to our attention that an incorrect affiliation was supplied for Yorihisa Orita, Kentaro Miki, Iku Abe–Fujisawa, and Kazunori Nishizaki. All authors and their corrected affiliations appear below. Tomoyasu Tachibana, MD, 1 Yorihisa Orita, MD, PhD, 2 Hidenori Marunaka, MD, 3 Seiichiro Makihara, MD, PhD, 4 Misato Hirai, MD, PhD, 5 Kentaro Miki, MD, 2 Yuya Ogawara, MD, 1 Hisashi Ishihara, MD, 4 Yuko Matsuyama, MD, 1 Iku Abe–Fujisawa, MD, 2 Aiko Shimizu, MD, 1 Yasuharu Sato, MD, PhD, 6 Kazunori Nishizaki, MD, PhD 21 Department of Otolaryngology, Himeji Red Cross Hospital, Hyogo, Japan, 2 Department of Otolaryngology Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, 3 Department of Otolaryngology, Okayama Medical Center, Okayama, Japan, 4 Department of Otolaryngology, Kagawa Rosai Hospital, Kagawa, Japan, 5 Department of Otolaryngology, Okayama Saiseikai General Hospital, Okayama, Japan, 6 Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

DOI： 10.1002/hed.25196

Association between impaired IL-10 production following exposure to Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic rhinosinusitis. 査読国際誌

Takenori Haruna, Shin Kariya, Tazuko Fujiwara, Takaya Higaki, Seiichiro Makihara, Kengo Kanai, Rumi Fujiwara, Satoshi Iwasaki, Yoshihiro Noguchi, Kazunori Nishizaki, Mitsuhiro Okano

Allergology international : official journal of the Japanese Society of Allergology 67 ( 3 ) 392 - 398 2018年7月

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

BACKGROUND: IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). METHODS: Dispersed nasal polyp (NP) cells and uncinate tissue (UT) cells were prepared from patients with CRS with and without NP, respectively. Cells were incubated with SEB, and then the levels of IL-10 in the cell supernatants were determined. The effect of neutralizing IL-10 on SEB-induced IL-5, IL-13, IFN-γ, and IL-17A production was examined. Expression of IL-10 in NPs was also determined. RESULTS: IL-10 was expressed in infiltrating inflammatory cells in NPs. NP cells, especially non-adherent NP cells, produced substantial amounts of IL-10 in response to SEB. Although baseline production of IL-10 was significantly higher in NP cells than UT cells, the degree of IL-10 response to SEB was not significantly different between the cell types. The degree of IL-10 production was negatively correlated with the degree of eosinophilia both in tissues and peripheral blood whereas positively correlated with the 1-s forced expiratory volume/forced vital capacity ratio. Patients with severe ECRS displayed a significant decrease in IL-10 production compared with those with non-ECRS. IL-10 neutralization significantly augmented SEB-induced IL-13 and IFN-γ production by NP cells. CONCLUSIONS: Impaired IL-10 production in response to SEB in NP may exacerbate the pathophysiology of ECRS including eosinophilia and lower airway obstruction.

DOI： 10.1016/j.alit.2018.02.001

内視鏡手術で摘出した蝶形骨洞線維性骨異形成症例査読

浦口健介, 牧原靖一郎, 内藤智之, 假谷伸, 中川隆之, 岡野光博, 西崎和則

日本鼻科学会会誌 57 ( 2 ) 138 - 144 2018年7月

記述言語：日本語出版者・発行元：(一社)日本鼻科学会

線維性骨異形成症は非腫瘍性の線維性骨病変であり、頭蓋顔面領域に発生することが多い。今回、蝶形骨洞線維性骨異形成症に対して内視鏡手術で摘出した症例を経験したので報告する。症例は26歳男性。前医で頭痛の精査のためCTを撮影したところ蝶形骨洞に陰影が認められ当科紹介となった。初回の内視鏡下生検手術時の病理組織検査は化骨性線維腫の疑いという診断であった。その後、経鼻内視鏡下に腫瘤摘出術を行い、最終的には線維性骨異形成症の診断となった。術後1年半経過しているが再発はなく無症状で経過観察中である。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01675&link_issn=&doc_id=20180724360004&doc_link_id=10.7248%2Fjjrhi.57.138&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.57.138&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Neck metastasis in patients with T1-2 supraglottic cancer 査読

Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Sei ichiro Makihara, Misato Hirai, Yuka Gion, Kana Ikegami, Kentaro Miki, Takuma Makino, Yasuyuki Noyama, Yasutoshi Komatsubara, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Auris Nasus Larynx 45 ( 3 ) 540 - 545 2018年6月

掲載種別：研究論文（学術雑誌）

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer. Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015. Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p = 0.004). In multivariate analysis, age <70 years (p = 0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p = 0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer. Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis.

DOI： 10.1016/j.anl.2017.06.002

Pulmonary function in patients with eosinophilic chronic rhinosinusitis. 査読国際誌

Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Mitsuhiro Okano, Takenori Haruna, Aiko Oka, Rumi Fujiwara, Yohei Noda, Kazunori Nishizaki

Auris, nasus, larynx 45 ( 3 ) 476 - 481 2018年6月

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

OBJECTIVE: There is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients. METHODS: Pulmonary function was measured in 53 patients with eosinophilic chronic rhinosinusitis with asthma, 58 patients with eosinophilic chronic rhinosinusitis without asthma, and 30 patients with non-eosinophilic chronic rhinosinusitis. The diagnosis of chronic rhinosinusitis was based on the definition in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012. Eosinophilic chronic rhinosinusitis was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system. The relationship between pulmonary function and clinical parameters was assessed. These parameters included radiographic severity of chronic rhinosinusitis, peripheral blood eosinophil percentage, serum total immunoglobulin E level, and eosinophilic infiltration in nasal polyps. RESULTS: The pulmonary function of the patients with eosinophilic chronic rhinosinusitis was significantly affected. The eosinophilic chronic rhinosinusitis patients had more peripheral airway obstruction as compared to the patients with non-eosinophilic chronic rhinosinusitis. CONCLUSION: Our findings indicated latent obstructive lung function changes in the eosinophilic chronic rhinosinusitis patients. The patients with eosinophilic chronic rhinosinusitis should be carefully monitored in order to detect lung diseases.

DOI： 10.1016/j.anl.2017.07.020

Laryngeal squamous cell papilloma is highly associated with human papillomavirus. 査読国際誌

Yorihisa Orita, Yuka Gion, Tomoyasu Tachibana, Kana Ikegami, Hidenori Marunaka, Seiichiro Makihara, Yasuhiko Yamashita, Kentaro Miki, Takuma Makino, Naoki Akisada, Yusuke Akagi, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Japanese journal of clinical oncology 48 ( 4 ) 350 - 355 2018年4月

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

OBJECTIVE: To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. METHODS: Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody. RESULTS: In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (<60 years) showed a higher rate of HPV infection than older patients. Among the 34 cases with laryngeal papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other. CONCLUSIONS: HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma.

DOI： 10.1093/jjco/hyy009

前頭洞・蝶形骨洞に同時に発見された副鼻腔真菌症例査読

浦口健介, 牧原靖一郎, 内藤智之, 岡愛子, 假谷伸, 岡野光博, 西崎和則

日本鼻科学会会誌 56 ( 4 ) 625 - 631 2017年12月

記述言語：日本語出版者・発行元：(一社)日本鼻科学会

副鼻腔真菌症は一般には上顎洞へ片側に発症するとされており、前頭洞や両側に副鼻腔真菌症が発症することは極めて稀である。今回、前頭洞真菌症と対側の蝶形骨洞へ同時に発見された副鼻腔真菌症の1例を経験したため、文献的考察を加えて報告する。症例は71歳女性。頭痛により他院で頭部CTを撮影したところ前頭洞陰影を認めたため当科紹介された。CT上は左の前頭洞真菌症であり全身麻酔下にEndoscopic modified Lothrop procedureで真菌塊を摘出した。術後、CTで再評価したところ対側の右蝶形骨洞側窩のみに限局する陰影を認めた。初回CTを見直したところ蝶形骨洞には以前から陰影あり、蝶形骨洞真菌症に対して全身麻酔下で右蝶形骨洞開窓しハイドロデブリッダーシステムR(日本メドトロニック、東京)を用いて洗浄した。術後1年間経過したが真菌の再発を認めず、外来で経過観察中である。副鼻腔真菌症は複数洞や両側罹患の可能性もあるため、術前のCT読影を厳密にするべきと考えた。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01675&link_issn=&doc_id=20180122310012&doc_link_id=10.7248%2Fjjrhi.56.625&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.56.625&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

意識障害を契機に発見された前頭洞型髄膜脳瘤例査読

假谷伸, 岡野光博, 檜垣貴哉, 春名威範, 牧原靖一郎, 大道亮太郎, 西崎和則

日本鼻科学会会誌 56 ( 4 ) 564 - 569 2017年12月

記述言語：日本語出版者・発行元：(一社)日本鼻科学会

髄膜脳瘤は頭蓋骨の欠損孔から頭蓋内容が頭蓋外に脱出する疾患である。先天性の骨欠損による髄膜脳瘤は後頭部に多く発生し、頭蓋底に発生することは稀である。今回、前頭洞後壁の骨欠損部から鼻腔へと脱出した前頭洞型頭蓋底髄膜脳瘤症例に対して、前頭開頭術と経鼻内視鏡下鼻副鼻腔手術を併用した切除術を施行し、良好な経過を得たので報告する。症例は40歳、男性。感冒薬を内服後に意識障害を認め、近医総合病院へ救急搬送された。横紋筋融解症を認め、透析などの加療が施行された。また、頭部MRIで左篩骨洞・前頭洞陰影と脳室拡大を認めた。髄液鼻漏所見を認めたため同院耳鼻咽喉科へ紹介され、左鼻腔内腫瘤の生検を行ったところ脳組織とのことであった。横紋筋融解症が改善したのちも意識障害が遷延するため、精査加療目的で当院脳神経外科へ転院となった。意識障害はフェノバルビタールナトリウムなどの点滴静注治療により軽快した。髄膜脳瘤に対して前頭開頭術と内視鏡下鼻副鼻腔手術を併用した切除手術と前頭蓋底再建術を施行した。術後2年を経過して髄膜脳瘤の再発は認められない。近年、頭蓋底髄膜脳瘤に対しては内視鏡による経鼻的アプローチのみで切除術を行う報告が増加している。本症例は前頭洞後壁に骨欠損部があり、内視鏡下操作のみでは硬膜再建が困難と判断した。髄膜脳瘤は比較的まれな疾患であり、症例によって適切なアプローチ法を検討することが必要と思われた。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01675&link_issn=&doc_id=20180122310003&doc_link_id=10.7248%2Fjjrhi.56.564&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.56.564&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

扁桃周囲膿瘍のCT所見と臨床経過査読

岡愛子, 牧原靖一郎

日本気管食道科学会会報 68 ( 3 ) 217 - 221 2017年6月

記述言語：日本語出版者・発行元：(NPO)日本気管食道科学会

扁桃周囲膿瘍の治療として抗菌薬などによる保存的治療、穿刺もしくは切開排膿、全身麻酔下での即時膿瘍扁桃摘出術(膿瘍扁摘)がある。治療が有効でない場合には深頸部膿瘍や縦隔炎などで致死的となることがあり注意が必要である。今回、造影CT所見と治療法の選択、臨床経過について検討を行った。対象は2013年1月から2016年4月に当院を受診し、造影CTで扁桃周囲膿瘍を認めた100例とした。CT軸位断で膿瘍腔の最大径を計測し、計測部位が口蓋垂末端よりも頭側にあるものを上極型、尾側にあるものを下極型とし、膿瘍径、喉頭浮腫の有無、治療法、治療期間を検討した。上極型の方が膿瘍径は大きかったが、喉頭浮腫は下極型で多かった。保存的治療とした症例は全例膿瘍径16mm以下であり、膿瘍扁摘や穿刺・切開の症例と比較して小さかった。上極型では穿刺・切開で十分排膿可能であり、膿瘍扁摘により治療した症例と比較して治療期間が短く、最も多く選択された治療法であった。下極型では膿瘍扁摘と穿刺・切開で入院期間に差がなく、膿瘍径の大きな症例では確実な排膿が可能で再発防止になる膿瘍扁摘を選択した症例が多かった。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01054&link_issn=&doc_id=20170622400001&doc_link_id=%2Fea4broes%2F2017%2F006803%2F001%2F0217-0221%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2017%2F006803%2F001%2F0217-0221%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Delayed esophageal perforation 17 years after anterior cervical fusion surgery with plating. 査読

Hisanori Ikuma, Katsuhiko Ishibashi, Kazuta Yamashita, Ryoji Joko, Seiichiro Makihara, Masahiko Kobayashi, Yoshiki Yokoyama

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 22 ( 3 ) 566 - 570 2017年5月

【花粉症研究の進歩】鼻噴霧ステロイドの効果的な使い方の研究

春名威範, 岡野光博, 檜垣貴哉, 牧原靖一郎

アレルギー・免疫 24 ( 3 ) 328 - 333 2017年2月

記述言語：日本語出版者・発行元：(株)医薬ジャーナル社

鼻噴霧用ステロイド薬はアレルギー性鼻炎に対して強力な抗炎症作用を示す。花粉症の本格発症前の最小持続炎症の制御という観点から,これまで,鼻噴霧用ステロイド薬は花粉症初期治療薬としての有用性が議論されていたが,最新版の鼻アレルギー診療ガイドライン(2016年版)からは,鼻噴霧用ステロイド薬は初期療法の1つとして記載されるようになった。自験例も含めいくつかのプラセボ対照二重盲検比較試験において,鼻噴霧用ステロイド薬によるスギ・ヒノキ花粉症に対する初期治療は,プラセボと比較して症状およびQOLの増悪を有意に抑制した。一方,安全性に関しては実薬とプラセボとの間に有意な差を認めなかった。さらに発症後治療と比較しても花粉の本格飛散後の鼻眼症状の増悪を有意に抑制した。以上の結果からは鼻噴霧用ステロイド薬による初期治療は有効かつ安全な治療法であることが明らかとなった。しかし,初期治療の適切な開始時期や飛散花粉数による効果の変化など今後の検討も必要である。(著者抄録)

IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression 査読

Yasuyuki Noyama, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takaya Higaki, Takenori Haruna, Sei ichiro Makihara, Kengo Kanai, Takahisa Koyama, Masami Taniguchi, Jun ichi Ishitoya, Akira Kanda, Yoshiki Kobayashi, Mikiya Asako, Koichi Tomoda, Kazunori Nishizaki

Allergology International 66 ( 1 ) 42 - 51 2017年1月

掲載種別：研究論文（学術雑誌）

Background IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined. Results IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs. Conclusions These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.

DOI： 10.1016/j.alit.2016.04.017

Evaluation of a New and Simple Classification for Endoscopic Sinus Surgery 査読

Kengo Kanai, Mitsuhiro Okano, Takenori Haruna, Takaya Higaki, Ryotaro Omichi, Sei Ichiro Makihara, Munechika Tsumura, Shin Kariya, Yuji Hirata, Kazunori Nishizaki

Allergy and Rhinology 8 ( 3 ) 2017年

掲載種別：研究論文（学術雑誌）

Objective: In 2013, the Japanese Rhinologic Society proposed a simple classification for endoscopic sinus surgery (ESS). This classification consists of five procedures (type I, fenestration of the ostiomeatal complex, with uncinectomy and widening of the natural ostium; type II, single-sinus procedure, with manipulating the inside of the sinus; type III, polysinus procedure; type IV, pansinus procedure; type V, extended procedure beyond the sinus wall). The clinical relevance of this classification in chronic rhinosinusitis (CRS) and paranasal sinus cyst was evaluated. Study Design: A retrospective validation study. Methods: A total of 122 patients (195 sinuses) who underwent ESS in Okayama University Hospital in 2012 were enrolled. The relationships between the ESS classification and the clinical course, including the operation time, bleeding amounts during surgery and postoperative changes of olfaction, the computed tomography (CT) score, and nasal airway resistance were analyzed. Results: A total of 195 ESS procedures were classified into type I (n = 3), type II (n = 17), type III (n = 91), type IV (n = 82), and type V (n = 2). The major phenotypes of type II, III, and IV ESS were paranasal sinus cyst (68%), CRS without nasal polyps (77%), and CRS with nasal polyps (55%), respectively, and the difference was significant. The degree of ESS based on this classification was positively and significantly correlated with the operation time and bleeding amounts. As a whole, olfaction, CT score, and nasal airway resistance were significantly improved after surgery. The degree of improvement was similar between type III and type IV ESS. Conclusion: This simple classification for ESS reflected the perioperative burden of the disease.

DOI： 10.2500/ar.2017.8.0208

眼窩骨膜下膿瘍を合併したビスフォスフォネート関連顎骨壊死症例査読

牧原靖一郎, 岡野光博, 浦口健介, 岡愛子, 假谷伸, 西崎和則

日本鼻科学会会誌 55 ( 4 ) 515 - 523 2016年12月

担当区分：筆頭著者記述言語：日本語出版者・発行元：(一社)日本鼻科学会

ビスフォスフォネート(Bisphosphonate:BP)製剤は癌の骨転移の治療や,骨粗鬆症の予防に対して広く使用されている。一方,2003年に米国で初めて報告されたビスフォスフォネート関連顎骨壊死(Bisphosphonate-Related Osteonecrosis of the Jaw:BRONJ)はわが国においても少なからぬ発生を認め,その予防法や対処法の確立は急務である。今回我々は,副鼻腔炎から眼窩骨膜下膿瘍を続発したBRONJ症例を経験したので報告する。症例は86歳,女性。1ヵ月前から続く右側上歯肉部からの膿汁排出を主訴に近医歯科を受診し,当院歯科口腔外科へ紹介となった。約10年前より骨粗鬆症に対してBP製剤であるアレンドロネートを,慢性関節リウマチに対してメチルプレドニゾロンやメトトレキサートを内服していた。CTにて右側副鼻腔陰影を認め,当科を紹介され慢性副鼻腔炎と診断した。歯科にてBRONJと診断され,アレンドロネート休薬から3ヵ月後に腐骨除去と右内視鏡下副鼻腔手術(以下ESS)を予定し,抗生剤での保存的加療を開始した。休薬から2.5ヵ月後に右眼瞼発赤が生じ,造影CTにて右眼窩骨膜下膿瘍の所見を認めた。同日,眼窩紙様板除去を含むESSと腐骨除去,周囲骨削除の緊急手術を施行した。術後,骨膜下膿瘍,骨壊死の再増悪もなく,経過良好である。BRONJ症例への腐骨除去など外科治療の際にはBP製剤の休薬が望まれるが,BRONJを伴う慢性副鼻腔炎に対しては,全身状態が許せば通常上顎骨に対して侵襲は少ないと考えられるESSを腐骨除去より先行させることも選択肢となりうる可能性が示唆された。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01675&link_issn=&doc_id=20170323260002&doc_link_id=10.7248%2Fjjrhi.55.515&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.55.515&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts 査読

Kengo Kanai, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takenori Haruna, Ryotaro Omichi, Sei ichiro Makihara, Yuji Hirata, Kazunori Nishizaki

Allergology International 65 ( 4 ) 414 - 419 2016年10月

掲載種別：研究論文（学術雑誌）

Background Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E2 induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD2 metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production. In the present study, we sought to determine whether PGD2 regulates VEGF release by nasal polyp fibroblasts. Methods Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD2 or PGD2 receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. The concentration of VEGF in the culture supernatants was determined using ELISA. Results 5 μM of PGD2 significantly induced VEGF release by nasal polyp fibroblasts. VEGF release was also obtained by stimulation with a DP receptor-selective, but not with a CRTH2 receptor-selective agonist. In addition, PGD2-induced VEGF release was significantly inhibited by pre-treatment with DP receptor-selective antagonists. In contrast, pre-treatment with a CRTH2 receptor-selective antagonist significantly enhanced PGD2-induced VEGF release. Conclusions PGD2 stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts.

DOI： 10.1016/j.alit.2016.03.003

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