Graduate School of Medicine Human Science
Medicine (Respirology・Infectious Disease)

Professor: Keishi KUBO 
Associate Professor: Masayuki HANAOKA
Senior Assistant Professor: Hiroshi YAMAMOTO
Assistant Professor: Kazuhisa URUSHIHATA

◎Summary of Activity

Introduction of the department
Our department has made efforts to elucidate the basic and clinical problems in the field of internal medicine, particularly focusing on the respiratory medicine, by means of various research techniques such as case study, epidemiology, molecular and cellular biology, genetic study and also animal studies. The major diseases studied in our department include asthma/COPD (chronic obstructive pulmonary disease), lung cancer/chest malignant tumors, respiratory infectious diseases, interstitial lung diseases, drug-induced lung disease, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pulmonary hypertension, sleep apnea syndrome as well as mountain sickness (MS). MS including high-altitude pulmonary edema (HAPE) mainly occurs in the highland of Shinshu area in Japan.


◎Research Projects


Asthma/COPD
➢ The pathophysiology of transition in asthma from childhood to adult.
➢ The pathophysiology of respiratory airway inflammation in asthma and COPD by using method of inducing sputum from patients.
➢ The pathophysiology of the airway remolding in chronic asthma and the COPD phenotypes by using HRCT image and IOS method (respiratory airway resistance measurement) and, subsequently, further setup the guideline of treatment therapy.
➢ The associations of development of COPD with candidate genes.
➢ The susceptibility to early onset COPD.
➢ The clinical characteristics and the genetic pathogenesis of pulmonary fibrosis combined with pulmonary emphysema.
➢ Pulmonary circulation dynamics during COPD exacerbation.
➢ The pathophysiology for the development and progression of COPD.
➢ The effects of different drugs on prevention of COPD by using pulmonary emphysema rat model.
➢ The mechanisms of mucus production, research of the new drugs, and investigation of the mechanisms in controlling respiratory airway inflammation by using human respiratory airway epithelial cells.

Lung cancer/chest malignant tumors
➢ Clinical application of ablation catheter under bronchoscope for the treatment of early peripheral lung cancer.
➢ The research of the new combination therapy with chemotherapy and radiotherapy in the treatment of local advanced non-small-cell lung cancer.
➢ Participation in national multi-central collaboration in research of advanced thymoma (thymus tumor).
➢ Investigation of the biochemical characteristics and the treatment effects with respect of thymus tumor and lung cancer.
➢ Participation in national multi-central cooperation studies.

Bronchoscopy
➢ Clinical studies of interventional pulmonology.

Respiratory infection
➢ Seeking the optimal diagnosis criteria and the treatment guideline for pulmonary atypical mycobacteriosis, especially M. avium complex (MAC) disease.
➢ Epidemiological investigation of time-dependent alterations of resistant bacterium in the field of respiratory infection.

Interstitial lung diseases
➢ Elucidation of the pathogenesis of hypersensitivity pneumonia caused by Japanese mushrooms, and discussion of the quick diagnosis criteria for this disorder.
➢ Epidemiological study of drug-induced lung injure and investigation of the molecular genetics of the disorder.
➢ Investigation of the clinical characteristics of interstitial pneumonia complicated with collagen diseases, especially amyopathic dermatomyositis.
➢ Establishment of the treatment strategy for lung involvements in collagen diseases.
➢ Clinical application of 123I-metaiodobenzylguanidine (MIBG).

ALI/ ARDS
➢ The research of potential roles for alveolar macrophages in lung injury produced by LPS priming.
➢ The usefulness of hemodiafiltration and adsorption therapies in the treatment of ALI/ARDS.
➢ Early intervention of non-invasive ventilation (NIV).

Sleep apnea syndrome (SAS)
➢ The research of various novel sensors for early diagnosis of SAS.
➢ Pathophysiology of sleep disorder in high altitude.
➢ Epidemiological study of the association of obesity-hypoventilation syndrome with metabolic syndrome.
➢ Elucidation of the associations of development of SAS with candidate genes.

High-altitude medicine
➢ The molecular genetics in high-altitude pulmonary edema (HAPE).
➢ The individual susceptibility to HAPE and the mechanisms of development of HAPE.
➢ The mechanisms regarding genetic adaptation to high altitude in Sherpas.
➢ The research collaborated with high-altitude medicine institute of Qinghai University, China.

Drug-induced lung injury
➢ As principal investigator of “Genetic study with respect to genetic markers in drug-induced lung injury” that is supervised by Ministry of Health, Labour and Welfare of Japan, we are studying the epidemiological investigation of drug-induced lung injure.

References
  1. Tanabe T,Koizumi T,Tsushima K,Ito M,Kanda S,Kobayashi T,Yasuo M,Yamazaki Y,Kubo K,Honda T,Kondo R,Yoshida K: Comparative study of three different catheters for CT-Bronchoscopy-guided radiofrequency ablation as a potential and novel intervention therapy for lung cancer. Chest 2009

  2. Nakamura M,Koizumi T,Hayasaka M,Yasuo M,Tsushima K,Kubo K,Gomi K,Shikama N: Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally advanced stage III non-small-cell lung cancer. Cancer Chemother Pharmacol 63: 1091-6, 2009

  3. Komatsu Y,Fujimoto K,Yasuo M,Urushihata K,Hanaoka M,Koizumi T,Kubo K: Airway hyper-responsiveness in young adults with asthma that remitted either during or before adolescence. Respirology 14: 217-23, 2009

  4. Ito M,Yasuo M,Yamamoto H,Tsushima K,Tanabe T,Yokoyama T,Hamano H,Kawa S,Uehara T,Honda T,Kawakami S,Kubo K: Central airway stenosis in a patient with autoimmune pancreatitis. Eur Respir J 33: 680-3, 2009

  5. Chen Y,Hanaoka M,Droma Y,Chen P,Voelkel NF,Kubo K: Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats. Eur Respir J 2009

  6. Chen Y,Hanaoka M,Chen P,Droma Y,Voelkel NF,Kubo K: Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. Am J Physiol Lung Cell Mol Physiol 296: L648-56, 2009

  7. Hanaoka M,Yu X,Urushihata K,Ota M,Fujimoto K,Kubo K: Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea syndrome. Chest 133: 79-85, 2008

  8. Yoshikawa S,Tsushima K,Yasuo M,Fujimoto K,Kubo K,Kumagai T,Yamazaki Y: Hypersensitivity pneumonitis caused by Penicillium citrinum, not enoki spores. Am J Ind Med 50:1010-1017, 2007

  9. Tsushima K,Kubo K,Yoshikawa S,Koizumi T,Yasuo M,Furuya S,Hora K: Effects of PMX-DHP treatment for patients with directly induced acute respiratory distress syndrome. Ther Apher Dial 11: 138-45, 2007

  10. Sasabayashi M,Yamazaki Y,Tsushima K,Hatayama O,Okabe T: Usefulness of bronchoscopic microsampling to detect the pathogenic bacteria of respiratory infection. Chest 131: 474-9, 2007