環境中多環芳香族炭化水素によるアトピー咳嗽とその予防のための新しいバイオマーカー

2022 Fiscal Year Research-status Report

• Project/Area Number: 22K19686
• Research Institution: Kanazawa University
• Principal Investigator: 中村 裕之 金沢大学, 医学系, 教授 (30231476)
• Co-Investigator(Kenkyū-buntansha): 原 丈介 金沢大学, 医薬保健学総合研究科, 特任准教授 (30710199) ; 大倉 徳幸 金沢大学, 附属病院, 助教 (80397215) ; 早川 和一 金沢大学, 環日本海域環境研究センター, 連携研究員 (40115267) ; 原 章規 金沢大学, 医学系, 准教授 (70507045) ; 神林 康弘 岡山理科大学, 獣医学部, 教授 (20345630) ; 辻口 博聖 金沢大学, 医学系, 特任助教 (00723090)
• Project Period (FY): 2022-06-30 – 2025-03-31
• Keywords: 多環芳香族炭化水素 / アトピー咳嗽 / 疫学 / 大気汚染 / 酸化ストレス

Outline of Annual Research Achievements

持続する咳嗽を主訴とするアトピー咳嗽は、近年、急速に増加している。その基本病態は病理学的には中枢から末梢気道全体の好酸球性気道炎症であり、生理学的には気道過敏性亢進と気管支平滑筋トーヌス亢進であるが、その抜本的な原因はほとんど不明である。本研究では、新しい大気汚染物質として呼吸器疾患の原因の候補物質である多環芳香族炭化水素（PAH）とそのニトロ体（NPAH）とアトピー咳嗽の関係を明らかにするために、医療機関に外来受診しているアトピー性咳嗽、咳喘息、あるいは気管支喘息の慢性咳嗽（8週間以上の持続する咳）を呈する患者98人に対して、日々の患者の呼吸器疾患に関する咳や鼻水などの症状を日記方式で調査し、一方、集団サンプリングによってPAHやNPAH金属などの環境中化学物資の曝露を評価した。この症状と曝露量との関係を一般化推定方程式によって解析した結果、TSPとPAH濃度と咳の頻度との関係をlag0-4のGEEモデルにおいて解析したところ、BaP/BghiPとIcdP/(IcdP+BghiP)が咳の頻度と有意な負の相関を示し、ベンズ[a]アントラセン（BaA）およびピレン（Pyr）が有意なあるいはその傾向を示す正の相関を認めた。このことは、ローカルな交通車両由来のPAHが咳の発症と関係することが示唆している。アトピー咳嗽の病態をさらに解明するために、アトピー性咳嗽を有さない患者との比較などの疫学を次年度以降、実施する予定である。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

アトピー性咳嗽、咳喘息あるいは気管支喘息患者98人をリクルートし、症状をモニタリングし、個々のPAHごとに、咳症状のリスクを推定できたことから、「おおむね順調に進展している。」とした。

Strategy for Future Research Activity

アトピー性咳嗽、咳喘息あるいは気管支喘息患者をさらにリクルートし、アトピー性咳嗽と非アトピー性咳嗽の患者を比較可能にすることによって、アトピー性咳嗽独自の病態がさらに明らかになると考えられる。個々のPAHごとにリスクを、アトピー性咳嗽の他の症状を目的変数、アレルギー性疾患の合併の有無やBMIなどの体格あるいは生活習慣などを共変量とした一般化推定方程式によって評価する予定である。

Causes of Carryover

検査予定のアレルギーのバイオマーカーの試薬の一式の納品がアメリカからの仕入れのため、品不足が生じており、予定より時間がかかることがわかり、次年度に発注することにした。次年度には納品し、検査を終える予定としている。

Research Products

• [Journal Article] Acceptability of transdermal antipsychotic patches by patients who refuse oral medication and their effectiveness in preventing recurrence of delirium: a retrospective observational study (2023)
  • Author(s): Kotaro Hatta, Chie Usui, Hiroyuki Nakamura
  • Journal Title: International Clinical Psychopharmacology Publish Ahead of Print Volume: 38(1) Pages: 23-27
  • DOI: 10.1097/yic.0000000000000428
  • Peer Reviewed / Open Access
• [Journal Article] Genetic factors associated with serum amylase in a Japanese population: combined analysis of copy-number and single-nucleotide variants (2023)
  • Author(s): Zannatun Nayema, Takehiro Sato, Takayuki Kannon, Hiromasa Tsujiguchi, Kazuyoshi Hosomichi, Hiroyuki Nakamura, Atsushi Tajima
  • Journal Title: Journal of Human Genetics Volume: 68 Pages: 313-319
  • DOI: 10.1038/s10038-022-01111-3
  • Peer Reviewed / Open Access
• [Journal Article] Relationships among Depressive Symptoms, Body Weight, and Chronic Pain: A Cross-Sectional Analysis of the Shika Study (2023)
  • Author(s): Shinobu Fukushima, Hiroyuki Nakamura（20人中20番目）
  • Journal Title: Behavioral Sciences Volume: 13(2) Pages: 86-86
  • DOI: 10.3390/bs13020086
  • Peer Reviewed / Open Access
• [Journal Article] Association between Bone Mineral Density and Oral Frailty on Renal Function: Findings from the Shika Study (2023)
  • Author(s): Shingo Nakai, Fumihiko Suzuki, Shigefumi Okamoto, Hiromasa Tsujiguchi, Akinori Hara, Yukari Shimizu, Koichiro Hayashi, Keita Suzuki, Tomoko Kasahara, Masaharu Nakamura, Chie Takazawa, Takayuki Kannon, Atsushi Tajima, Hirohito Tsuboi, Noriyoshi Ogino, Tadashi Konoshita, Toshinari Takamura, Hiroyuki Nakamura
  • Journal Title: Healthcare Volume: 11(3) Pages: 314-314
  • DOI: 10.3390/healthcare11030314
  • Peer Reviewed / Open Access
• [Journal Article] Higher Intake of Vegetable Protein and Lower Intake of Animal Fats Reduce the Incidence of Diabetes in Non-Drinking Males: A Prospective Epidemiological Analysis of the Shika Study (2023)
  • Author(s): Aya Ogawa, Hiromasa Tsujiguchi, Masaharu Nakamura, Koichi Hayashi, Akinori Hara, Keita Suzuki, Sakae Miyagi, Takayuki Kannon, Chie Takazawa, Jiaye Zhao, Yasuhiro Kambayashi, Yukari Shimizu, Aki Shibata, Tadashi Konoshita, Fumihiko Suzuki, Hirohito Tsuboi, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 15(4) Pages: 1040-1040
  • DOI: 10.3390/nu15041040
  • Peer Reviewed / Open Access
• [Journal Article] Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study (2023)
  • Author(s): Yoshika Tsuji , Tomohiro Koga , Fumiaki Nonaka , Kenichi Nobusue , Shin-Ya Kawashiri , Hirotomo Yamanashi , Takahiro Maeda , Kazuhiko Arima , Kiyoshi Aoyagi , Meiko Takahashi , Shuji Kawaguchi , Fumihiko Matsuda , Hiroshi Fujii , Mitsuhiro Kawano , Hiroyuki Nakamura , Atsushi Kawakami , Mami Tamai
  • Journal Title: Front Immunol Volume: 14 Pages: 1124417
  • DOI: 10.3389/fimmu.2023.1124417
  • Peer Reviewed / Open Access
• [Journal Article] Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study (2023)
  • Author(s): Megumi Oshima, Hiroyuki Nakamura（23人中22番目）
  • Journal Title: J Diabetes Volume: 15(3) Pages: 246-254
  • DOI: 10.1111/1753-0407.13367
  • Peer Reviewed / Open Access
• [Journal Article] Acceptability of transdermal antipsychotic patches by patients who refuse oral medication and their effectiveness in preventing recurrence of delirium: a retrospective observational study (2023)
  • Author(s): Kotaro Hatta , Chie Usui , Hiroyuki Nakamura
  • Journal Title: Int Clin Psychopharmacol Volume: 38(1) Pages: 23-27
  • DOI: 10.1097/YIC.0000000000000428
  • Peer Reviewed / Open Access
• [Journal Article] Association between vitamin intake and chronic kidney disease according to a variant located upstream of the PTGS1 gene: A cross-sectional analysis of Shika study (2022)
  • Author(s): Kim-Oanh Pham, Hiroyuki Nakamura（21人中21番目）
  • Journal Title: Nutrients Volume: 14(10) Pages: 2082
  • DOI: 10.3390/nu14102082
  • Peer Reviewed / Open Access
• [Journal Article] Association between serum 25-hydroxyvitamin D concentrations, CDX2 polymorphism in promoter region of vitamin D receptor gene, and chronic pain in rural Japanese residents (2022)
  • Author(s): Keita Suzuki, Hiroyuki Nakamura（19人中19番目）
  • Journal Title: Journal of Pain Research Volume: 15 Pages: 1475-1485
  • DOI: 10.2147/JPR.S356630
  • Peer Reviewed / Open Access
• [Journal Article] Association between dietary fat intake and hyperuricemia in men with chronic kidney disease (2022)
  • Author(s): Fumika Oku, Akinori Hara, Hiromasa Tsujiguchi, Keita Suzuki, Kim-Oanh Pham, Fumihiko Suzuki, Sakae Miyagi, Masaharu Nakamura, Chie Takazawa, Kuniko Sato, Toru Yanagisawa, Takayuki Kannon, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 14(13) Pages: 2637-2637
  • DOI: 10.3390/nu14132637
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between fatty acid intake and chronic neck/shoulder/upper limb pain without elevated CRP in a Japanese population: A cross-sectional analysis of the Shika study (2022)
  • Author(s): Atsushi Asai, Hiroyuki Nakamura（21人中21番目）
  • Journal Title: Journal of Nutritional Science Volume: 11 Pages: -
  • DOI: 10.1017/jns.2022.37
  • Peer Reviewed / Open Access
• [Journal Article] Different Transport Behaviors between Asian Dust and Polycyclic Aromatic Hydrocarbons in Urban Areas: Monitoring in Fukuoka and Kanazawa, Japan (2022)
  • Author(s): Kim-Oanh Pham, Akinori Hara, Jiaye Zhao, Keita Suzuki, Atsushi Matsuki, Yayoi Inomata, Hiroshi Matsuzaki, Hiroshi Odajima, Kazuichi Hayakawa, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(11) Pages: 5404-5404
  • DOI: 10.3390/app12115404
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of Chemical Components of Fine Particulate Matter Observed at Fukuoka, Japan, in Spring 2020 and Their Transport Paths (2022)
  • Author(s): Ayako Yoshino, Akinori Takami, Atsushi Shimizu, Kei Sato, Kazuichi Hayakawa, Ning Tang, Kim-Oanh Pham, Akinori Hara, Hiroyuki Nakamura, Hiroshi Odajima
  • Journal Title: Applied Sciences Volume: 12(22) Pages: 11400-11400
  • DOI: 10.3390/app122211400
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of Mask Wearing in Preventing the Deleterious Health Effects of the Ionic Components of PM25-Possibility Seen in Allergic Patients (2022)
  • Author(s): Hiroshi Odajima, Hiroshi Matsuzaki, Yuko Akamine, Kaoru Kojima, Yoko Murakami, Ayako Yoshino, Akinori Takami, Kazuichi Hayakawa, Akinori Hara, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(21) Pages: 11185-11185
  • DOI: 10.3390/app122111185
  • Peer Reviewed / Open Access
• [Journal Article] Impact of gut microbiome on dyslipidemia in japanese adults: Assessment of the Shika-machi super preventive health examination results for causal inference (2022)
  • Author(s): Yuna Miyajima, Shigehiro Karashima, Kazuhiro Ogai, Kouki Taniguchi, Kohei Ogura, Masaki Kawakami, Hidetaka Nambo, Mitsuhiro Kometani, Daisuke Aono, Masashi Demura, Takashi Yoneda, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura, Shigefumi Okamoto
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 12(3) Pages: 145-153
  • DOI: 10.3389/fcimb.2022.908997
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between vitamin intake and resilience based on sex in middle-aged and older Japanese adults: Results of the Shika study (2022)
  • Author(s): Kuniko Sato, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Takayuki Kannon, Sakae Miyagi, Keita Suzuki, Masaharu Nakamura, Chie Takazawa, Aki Shibata, Hirohito Tsuboi, Yukari Shimizu, Thao Thi Thu Nguyen, Tadashi Konoshita, Yasuki Ono, Koichi Hayashi, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 14(23) Pages: 5042-5042
  • DOI: 10.3390/nu14235042
  • Peer Reviewed / Open Access
• [Journal Article] Bone strength of the calcaneus Is associated with dietary calcium intake in older Japanese men, but not women (2022)
  • Author(s): Keita Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Thao Thi Thu Nguyen, Yasuhiro Kambayashi, Yukari Shimizu, Fumihiko Suzuki, Chie Takazawa, Masaharu Nakamura, Hirohito Tsuboi, Takayuki Kannon, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Nutrients Volume: 14(24) Pages: 5225-5225
  • DOI: 10.3390/nu14245225
  • Peer Reviewed / Open Access
• [Journal Article] Cystatin C-based eGFR predicts cardiovascular disease in patients with overweight/obesity and hyperglycemia (2022)
  • Author(s): Keita Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura, Kazuhiko Kotani, Mitsuhiko Noda, Hajime Yamakage, Noriko Satoh-Asahara, Toshinari Takamura
  • Journal Title: Obesity Science and Practice Volume: 9(1) Pages: 4-14
  • DOI: 10.1002/osp4.630
  • Peer Reviewed / Open Access
• [Journal Article] Elevated ratio of serum anandamide to arachidonic acid intake in community-dwelling women with high depressive symptoms (2022)
  • Author(s): Hirohito Tsuboi, Masahiro Matsunaga, Hiromasa Tsujiguchi, Takayuki Kannon, Kazuyoshi Hosomichi, Takehiro Sato, Atsushi Tajima, Naoko Yoshida, Akinori Hara, Hiroyuki Nakamura
  • Journal Title: Neuro endocrinology letters Volume: 43(3) Pages: 145-153
  • Peer Reviewed / Open Access
• [Journal Article] Association between cough and ambient polycyclic aromatic hydrocarbons in patients with chronic cough: an observational study in two regions of Japan (2022)
  • Author(s): Akinori Hara, Hiroshi Odajima, Hiroshi Matsuzaki, Masaki Fujimura, Tomoko Toma, Taizo Wada, Noriyuki Ohkura, JiaYe Zhao, Kim-Oanh Pham, Keita Suzuki, Hiromasa Tsujiguchi, Akinori Takami, Kazuichi Hayakawa, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(24) Pages: 12505
  • DOI: 10.3390/app122412505
  • Peer Reviewed / Open Access
• [Journal Article] Prospective relationship between autistic traits and nutrient intakes among Japanese children: Results of the Shika study (2022)
  • Author(s): Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Kim Oanh Pham, Keita Suzuki, Thao Thi Thu Nguyen, Yasuki Ono, Yasuhiro Kambayashi, Yukari Shimizu, Haruki Nakamura, Fumihiko Suzuki, Aki Shibata, Koichi Hayashi, Hirohito Tsuboi, Hiroyuki Nakamura
  • Journal Title: Autism Volume: 27(2) Pages: 389-401
  • DOI: 10.1177/136236132210974
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Polygenic Susceptibility on Air Pollution-Associated Asthma between German and Japanese Elderly Women (2022)
  • Author(s): Sara Kress, Akinori Hara, Claudia Wigmann, Takehiro Sato, Keita Suzuki, Kim-Oanh Pham, Qi Zhao, Ashtyn Areal, Atsushi Tajima, Holger Schwender, Hiroyuki Nakamura, Tamara Schikowski
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 19(16) Pages: 9869-9869
  • DOI: 10.3390/ijerph19169869
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Social Capital and Depressive Symptoms: Differences According to Resilience and Gender in the Shika Study (2022)
  • Author(s): Kuniko Sato, Hiromasa Tsujiguchi, Fumihiko Suzuki, Akinori Hara, Takayuki Kannon, Go Muto, Daisuke Hori, Sakae Miyagi, Keita Suzuki, Masaharu Nakamura, Chie Takazawa, Tomoko Kasahara, Hirohito Tsuboi, Mie Matsui, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Journal of Affective Disorders Reports Volume: 10 Pages: 100421-100421
  • DOI: 10.1016/j.jadr.2022.100421
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Tofogliflozin and Glimepiride Effects on Nonalcoholic Fatty Liver Disease in Participants With Type 2 Diabetes: A Randomized, 48-Week, Open-Label, Active-Controlled Trial (2022)
  • Author(s): Yumie Takeshita, Masao Honda, Kenichi Harada, Yuki Kita, Noboru Takata, Hiromasa Tsujiguchi, Takeo Tanaka, Hisanori Goto, Yujiro Nakano, Noriho Iida, Kuniaki Arai, Tatsuya Yamashita, Eishiro Mizukoshi, Hiroyuki Nakamura, Shuichi Kaneko, Toshinari Takamura
  • Journal Title: Diabetes care Volume: 45(9) Pages: 2064-2075
  • DOI: 10.2337/dc21-2049
  • Peer Reviewed / Open Access
• [Journal Article] Seasonal Variability and Risk Assessment of Atmospheric Polycyclic Aromatic Hydrocarbons and Hydroxylated Polycyclic Aromatic Hydrocarbons in Kanazawa, Japan (2022)
  • Author(s): Masato Honda, Kazuichi Hayakawa, Lulu Zhang, Ning Tang, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(19) Pages: 9469-9469
  • DOI: 10.3390/app12199469
  • Peer Reviewed / Open Access
• [Journal Article] The Ionic Component of PM25 May Be Associated with Respiratory Symptoms and Peak Expiratory Flow Rate (2022)
  • Author(s): Hiroshi Odajima, Hiroshi Matsuzaki, Yuko Akamine, Kaoru Kojima, Yoko Murakami, Ayako Yoshino, Akinori Takami, Kazuichi Hayakawa, Akinori Hara, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(19) Pages: 10082-10082
  • DOI: 10.3390/app121910082
  • Peer Reviewed / Open Access
• [Journal Article] Hypertension and Low Body Weight Are Associated with Depressive Symptoms Only in Females: Findings from the Shika Study (2022)
  • Author(s): Toru Yanagisawa, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Takayuki Kannon, Keita Suzuki, Yukari Shimizu, Thao Thi Thu Nguyen, Fumika Oku, Kuniko Sato, Masaharu Nakamura, Koichiro Hayashi, Aki Shibata, Tadashi Konoshita, Yasuhiro Kambayashi, Hirohito Tsuboi, Atsushi Tajima, Hiroyuki Nakamura
  • Journal Title: Behavioral Sciences Volume: 12(11) Pages: 413-413
  • DOI: 10.3390/bs12110413
  • Peer Reviewed / Open Access
• [Journal Article] Neutralizing-antibody response to SARS-CoV-2 for 12 months after the COVID-19 workplace outbreaks in Japan (2022)
  • Author(s): Azumi Ishizaki, Xiuqiong Bi, Quynh Thi Nguyen, Tomomi Maeno, Akinori Hara, Hiroyuki Nakamura, Sanae Kuramoto, Koichi Nishi, Hiroyasu Ooe, Hiroshi Ichimura
  • Journal Title: PLOS ONE Volume: 17(8) Pages: -
  • DOI: 10.1371/journal.pone.0273712
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal Study on the Association between Ambient Polycyclic Aromatic Hydrocarbons and Nasal Symptoms in Adult Japanese (2022)
  • Author(s): Jiaye Zhao, Akinori Hara, Kazuichi Hayakawa, Kim-Oanh Pham, Keita Suzuki, Hiromasa Tsujiguchi, Hiroshi Matsuzaki, Hiroshi Odajima, Akinori Takami, Hiroyuki Nakamura
  • Journal Title: Applied Sciences Volume: 12(24) Pages: 12544-12544
  • DOI: 10.3390/app122412544
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial (2022)
  • Author(s): Moeko Noguchi-Shinohara, Tsuyoshi Hamaguchi, Kenji Sakai, Junji Komatsu, Kazuo Iwasa, Mai Horimoto, Hiroyuki Nakamura, Masahito Yamada, Kenjiro Ono
  • Journal Title: Journal of Alzheimer's disease Volume: 91(2) Pages: 805-814
  • DOI: 10.3233/JAD-220953
  • Peer Reviewed / Open Access
• [Journal Article] Selenoprotein P-mediated reductive stress impairs cold-induced thermogenesis in brown fat (2022)
  • Author(s): Swe Mar Oo , Hein Ko Oo , Hiroaki Takayama , Kiyo-Aki Ishii , Yumie Takeshita , Hisanori Goto , Yujiro Nakano , Susumu Kohno , Chiaki Takahashi , Hiroyuki Nakamura , Yoshiro Saito , Mami Matsushita , Yuko Okamatsu-Ogura , Masayuki Saito , Toshinari Takamura
  • Journal Title: Cell Rep Volume: 38(13) Pages: 110566
  • DOI: 10.1016/j.celrep.2022.110566
  • Peer Reviewed / Open Access
• [Journal Article] Diabetes Mellitus, Elevated Hemoglobin A1c, and Glycated Albumin Are Associated with the Presence of All-Cause Dementia and Alzheimer's Disease: The JPSC-AD Study (2022)
  • Author(s): Moeko Noguchi-Shinohara , Sohshi Yuki-Nozaki, Chiemi Abe , Ayaka Mori, Mai Horimoto, Masami Yokogawa, Natsuko Ishida, Yukio Suga, Junko Ishizaki, Mai Ishimiya, Hiroyuki Nakamura , Kiyonobu Komai, Hiroyuki Nakamura, Mao Shibata, Tomoyuki Ohara, Jun Hata, Toshiharu Ninomiya, Masahito Yamada
  • Journal Title: J Alzheimers Dis Volume: 85(1) Pages: 235-247
  • DOI: 10.3233/JAD-215153
  • Peer Reviewed / Open Access
• [Presentation] The role of polygenic susceptibility on air pollution-associated asthma between Caucasian and Asian elderly women (2022)
  • Author(s): Sara Kress, Akinori Hara, Claudia Wigmann, Keita Suzuki, Qi Zhao, Atsushi Tajima, Hiroyuki Nakamura, Tamara Schikowski
  • Organizer: 34th Annual Conferenceof the International Societyfor Environmental Epidemiology
  • Int'l Joint Research