Relationship between the severity of adult RSV infection and plasma LL-37 levels

• Project/Area Number: 15K09190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyorin University
• Principal Investigator: Kurai Daisuke 杏林大学, 医学部, 准教授 (60530665)
• Co-Investigator(Kenkyū-buntansha): 木村 博一 群馬パース大学, 保健科学部, 教授 (20391807) ; 石井 晴之 杏林大学, 医学部, 教授 (30406970) ; 皿谷 健 杏林大学, 医学部, 講師 (40549185)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: RSウイルス / 呼吸器ウイルス / 肺炎 / LL-37 / ＲＳＶ / インフルエンザウイルス / RSV

Outline of Final Research Achievements

Serum LL-37 levels were measured in 59 adult patients with lower respiratory tract infections. We examined whether plasma LL-37 levels were associated with severity and causative organisms. The organisms were detected in 66% (39 cases) of patients. In 19 of the 59 patients (32%), respiratory viruses were detected using nucleic acid amplification methods. Rhinovirus (n=8) was the most frequently detected virus and RSV was detected in 5% (3 cases) in total. No significant differences in plasma LL-37 levels were found between the etiological groups (virus alone, virus+bacteria and bacteria alone). LL-37 levels (mean±SD) did not differ significantly among the 3 groups (mild:67.9±33.6 , moderate:77.0±53.9 and severe:46.9±18.4 ng/ml).

Academic Significance and Societal Importance of the Research Achievements

成人下気道感染患者の約2/3で原因微生物が検出された. 呼吸器ウイルスは, 細菌との混合感染を含め, 全体の約32%で検出された. 入院患者に限定してもその頻度は約30%であった. RSVは全体の約5%に検出された.
血漿LL-37値は, 重症度や原因微生物の種類（ウイルス、ウイルスと細菌、細菌）では有意な差は認めなかった.
RSVを含む呼吸器ウイルスは, 我が国の成人でも肺炎やCOPD増悪時には, 高頻度に検出され, 入院の原因となっている可能性が示唆された. これらの呼吸器ウイルス感染症の治療薬はインフルエンザを除くと存在せず, 治療薬・予防法の開発が必要であることが認識された.

Research Products

• [Journal Article] Clinical significance of respiratory virus detection in patients with acute exacerbation of interstitial lung diseases. (2018)
  • Author(s): Saraya T, Kimura H, Kurai D, Tamura M, Ogawa Y, Mikura S, Sada M, Oda M, Watanabe T, Ohkuma K, Inoue M, Honda K, Watanabe M, Yokoyama T, Fujiwara M, Ishii H, Takizawa H.
  • Journal Title: Respir Med. Volume: 136 Pages: 88-92
  • DOI: 10.1016/j.rmed.2018.02.003
  • Peer Reviewed
• [Journal Article] The molecular epidemiology of respiratory viruses associated with asthma attacks: A single-center observational study in Japan. (2017)
  • Author(s): Saraya T, Kimura H, Kurai D, Ishii H, Takizawa H.
  • Journal Title: Medicine (Baltimore). Volume: 96 Issue: 42 Pages: 1-7
  • DOI: 10.1097/md.0000000000008204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathogen profiles and molecular epidemiology of respiratory viruses in Japanese inpatients with community-acquired pneumonia (2016)
  • Author(s): Daisuke Kurai, Yoshiko Sasaki, Takeshi Saraya, Haruyuki Ishii, Hiroyuki Tsukagoshi, Kunihisa Kozawa, Akihide Ryo, Taisei Ishioka, Makoto Kuroda, Kazunori Oishi, Hajime Takizawa, Hirokazu Kimura
  • Journal Title: Respiratory Investigation Volume: in press Issue: 4 Pages: 255-263
  • DOI: 10.1016/j.resinv.2016.01.001
  • Peer Reviewed
• [Presentation] 呼吸器ウイルス感染症のマネージメント～成人例を中心に：RSウイルス感染症について (2019)
  • Author(s): 倉井大輔
  • Organizer: 第68回日本感染症学会東日本地方会学術集会・第66回日本化学療法学会東日本支部総会 合同学会
• [Presentation] 成人・高齢者におけるRSウイルス感染症の重要性 (2018)
  • Author(s): 倉井大輔
  • Organizer: 第81回日本呼吸器学会・日本結核病学会 日本サルコイドーシス／肉芽腫性疾患学会 九州支部 秋季学術講演会
  • Invited
• [Presentation] Comparison of the patients affected with respiratory syncytial virus and influenza virus: A single center prospective observational study in japan. (2017)
  • Author(s): Kurai Daisuke, Saraya Takeshi, Ishii Haruyuki, Kimura Hirokzu, Takizawa Hajime
  • Organizer: The 22nd Congress of the APSR
  • Int'l Joint Research
• [Presentation] A new criterion in predicting 30-day mortality in hospitalized adult patients with infectious diseases: a retrospective single center study (2017)
  • Author(s): Masafumi Shimoda, Daisuke Kurai, Takeshi Saraya, Keitaro Nakamoto, Takuma Yokoyama, Yuka Sasaki ,Haruyuki Ishii ,Hajime Goto ,Hajime Takizawa
  • Organizer: Asian Pacific Society of Respirology congrees 2017
  • Int'l Joint Research
• [Presentation] Pathogen Profiles and Molecular Epidemiology of Respiratory Viruses in Japanese Inpatients with Community-acquired pneumonia (2016)
  • Author(s): Daisuke Kurai, Takeshi Saraya, Haruyuki Ishii, Yoshiko Sasaki, Hiroyuki Tukagoshi, Hirokazu Kimura, Hajime Takizawa
  • Organizer: ATS International Conference
  • Place of Presentation: San Francisco,USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] 大学病院におけるRespiratory syncytial virus感染患者の予後と背景：Influenza virus感染患者との比較 (2016)
  • Author(s): 倉井大輔、皿谷健、石井晴之、木村博一、滝澤始
  • Organizer: 第91回日本感染症学会総会・学術講演会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-15
• [Presentation] 第20回症例から学ぶ感染症セミナー 症例１）発熱と急速に進行する呼吸不全を呈した1例 (2016)
  • Author(s): 皿谷健、倉井大輔、 南宮湖
  • Organizer: 第91回日本感染症学会総会・学術講演会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-15
• [Presentation] 成人下気道感染と呼吸器ウイルス：HRV・HMPV・RSV 検出患者の比較 (2016)
  • Author(s): 倉井大輔、佐々木佳子、 皿谷 健、石井晴之、 塚越博之、木村博一、滝澤 始
  • Organizer: 日本感染学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-15