The decreases in hypoxic ventilatory response affect acute exacerbation in patients with respiratory failure and/or obesity hypoventilation syndrome

• Project/Area Number: 23591158
• 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: Nara Medical University
• Principal Investigator: KIMURA Hiroshi 奈良県立医科大学, 医学部, 教授 (20195374)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Masanori 奈良県立医科大学, 医学部, 准教授 (80271203) ; HAMADA Kaoru 奈良県立医科大学, 医学部, 教授 (80228535) ; YAMAUCHI Motoo 奈良県立医科大学, 医学部, 学内講師 (30405378) ; FUJITA Yukio 奈良県立医科大学, 医学部, 助教 (60571023)
• Co-Investigator(Renkei-kenkyūsha): FUKUOKA Atsuhiko 奈良県立医科大学, 医学部, 博士研究員 (10336852)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 換気応答 / 低酸素 / 増悪 / 慢性閉塞性肺疾患 / 睡眠時無呼吸症候群 / 呼吸調節 / 呼吸不全 / 呼吸困難感 / 化学感受性

Outline of Final Research Achievements

We evaluated the hypoxic ventilatory response (HVR) in terms of the withdrawal test developed by Dejours in patients with chronic obstructive pulmonary disease (COPD), sleep apnea syndrome (SAS) and healthy controls. Findings included that there exist the individual differences in HVR for all subjects and HVR was gradually decreased in accordance with the order of healthy control and COPD and SAS. In patients with COPD, an acute exacerbation was not associated with HVR. In patients with SAS, there was no association between severity of sleep disordered breathing and their HVR. On the other hand, there was positive correlation between sleep efficiency and HVR. In addition, animal studies were performed to investigate the effects of aging on HVR and hypercapnic ventilatory response (HCVR). Both HVR and HCVR in C57BL/6J male mice were significantly lower at the age of 12 months than of 3 months, implying aging decreases the chemosensitivity.

Research Products

• [Journal Article] An important role of endothelial hairy-related transcription factors in mouse vascular development. (2014)
  • Author(s): Morioka T, Sakabe M, Ioka T, Iguchi T, Mizuta K, Hattammaru M, Sakai C, Itoh M, Sato GE, Hashimoto A, Fujita M, Okumura K, Araki M, Xin M, Pedersen RA, Utset MF, Kimura H, Nakagawa O
  • Journal Title: Genesis Volume: 52 Pages: 897-906
• [Journal Article] Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats. (2014)
  • Author(s): Tomoda K, Kubo K, Hino K, Kondoh Y, Nishii Y, Koyama N, Yamamoto Y, Yoshikawa M, Kimura H
  • Journal Title: J Toxicol Sci Volume: 39 Pages: 331-337
  • NAID: 130004903995
• [Journal Article] The Mini Nutritional Assessment Short-form predicts exacerbation frequency in patients with chronic obstructive pulmonary disease. (2014)
  • Author(s): Yoshikawa M, Fujita Y, Yamamoto Y, Yamauchi M, Tomoda K, Koyama N, Kimura H
  • Journal Title: Respirology Volume: 19 Pages: 1198-1203
• [Journal Article] Distribution of bone mineral content is associated with body weight and exercise capacity in patients with COPD. (2014)
  • Author(s): Yamamoto Y, Yoshikawa M, Tomoda K, Fujita Y, Yamauchi M, Fukuoka A, Tamaki S, Koyama N, Kimura H
  • Journal Title: Respiration Volume: 87 Pages: 158-164
• [Journal Article] Effects of environment light during sleep on autonomic functions of heart rate and breathing. (2014)
  • Author(s): Yamauchi M, Jacono FJ, Fujita Y, Kumamoto M, Yoshikawa M, Campanaro CK, Loparo KA, Strohl KP, Kimura H
  • Journal Title: Sleep And Breathing Volume: 18 Pages: 829-835
• [Journal Article] The Impact of Obstructive Sleep Apnea and Nasal CPAP on Circulating Adiponectin Levels. (2014)
  • Author(s): Yoshikawa M, Yamauchi M, Fujita Y, Koyama N, Fukuoka A, Tamaki S, Yamamoto Y, Tomoda K, Kimura H
  • Journal Title: Lung Volume: 192 Pages: 289-295
• [Presentation] Determinants of bone mineral density in the lumbar spine instable patients with COPD. (2014)
  • Author(s): Yamamoto Y, Yoshikawa M, Tomoda K, Fujita Y, Yamauchi M, Koyama N, Kimura H
  • Organizer: European Respiratory Society Annual Congress 2014
  • Place of Presentation: ミュンヘン
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] The possibility of breathing irregularity as an objective marker for dyspnea in patient with COPD. (2014)
  • Author(s): Fujita Y, Yamauchi M, Tomoda K, Yoshikawa M, Kimura H
  • Organizer: American Thoracic Society International Conference 2014
  • Place of Presentation: サンディエゴ
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] The proportion of accompanying arousal to apneic event affects systemic blood pressure but not sympathetic nerve activity. (2014)
  • Author(s): Yamauchi M, Fujita Y, Yoshikawa M, Kimura H
  • Organizer: American Thoracic Society International Conference 2014
  • Place of Presentation: サンディエゴ
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 慢性閉塞性肺疾患（COPD)患者の呼吸波形解析を活用した呼吸困難評価法 (2014)
  • Author(s): 藤田幸男、山内基雄、熊本牧子、山本佳史、本津茂人、児山紀子、須崎康恵、友田恒一、吉川雅則、木村 弘
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪府
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] COPDと全身併存症 (2014)
  • Author(s): 木村 弘
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪府
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] Withdrawal法を用いた低酸素化学感受性の評価 (2013)
  • Author(s): 藤田幸男、山内基雄、中村篤宏、大屋貴広、熊本牧子、山本佳史、本津茂人、児山紀子、須崎康恵、福岡篤彦、友田恒一、吉川雅則、木村 弘
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 肥満低換気症候群は稀少疾患として位置づけるべきか？ ―肥満度と呼吸調節機構からみたOSASとの差異―
  • Author(s): 山内基雄、吉川雅則、牧之段 潔、福岡篤彦、藤田幸男、児山紀子、玉置伸二、山本佳史、友田恒一、木村 弘
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸市