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Kazuki Furuhashi,1,2 Tomoyuki Fujisawa,1 Dai Hashimoto,3 Yousuke Kamiya,1 Hideki Yasui,1 Masato Karayama,1 Yuzo Suzuki,1 Hironao Hozumi,1 Noriyuki Enomoto,1 Yutaro Nakamura,1 Naoki Inui,1,4 Takafumi Suda1 1Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; 2Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; 3Department of Respiratory Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan; 4Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, JapanCorrespondence: Kazuki FuruhashiSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, JapanTel +81 53 435 2870Fax +81 53 435 2096Email k.furu@hama-med.ac.jpIntroduction: Fluticasone furoate (FF)/vilanterol (VI) dry powder inhaler (DPI) is the only once-daily maintenance inhaled corticosteroid (ICS)/long-acting β2 adrenergic agonist (LABA) combination for asthma. We aimed to compare the clinical effects of once-daily FF/VI and twice-daily budesonide (BUD)/formoterol (FM) DPI in patients with controlled stable asthma.Methods: We performed a randomized crossover trial in which stable asthmatic patients controlled on ICS/LABA received 8 weeks of FF/VI (100/25 μg 1 puff once-daily) or BUD/FM (160/4.5 μg 2 puffs twice-daily) DPI treatment. After a 4–8-week washout period, patients received another crossover treatment for 8 weeks. We assessed pulmonary function, the 5-item version asthma control questionnaire (ACQ5), the asthma control test (ACT), and fractional exhaled nitric oxide (FeNO) at baseline and after 8 weeks of treatment (week 8). As the primary outcome was change in force expiratory volume in 1 s (FEV1) between baseline and week 8, we evaluated the incidence of asthma exacerbation and adherence barrier questionnaire (Ask-12) at week 8.Results: Twenty-three patients were initially enrolled in this study; however, one patient had to be excluded. The FF/VI DPI treatment group showed a similar magnitude of change in FEV1 between baseline and week 8 as the BUD/FM DPI treatment group. In addition, there were no significant differences in pulmonary function tests, ACQ5 scores, ACT scores, and FeNO between baseline and week 8 in both groups. Although the incidence of exacerbation did not differ between groups, the Ask-12 score in the FF/VI DPI group was significantly lower than that in the BUD/FM DPI group.Conclusions: The present study indicates that once-daily FF/VI DPI is not inferior to twice-daily BUD/FM DPI in clinical effect and more likely to improve inconvenience and forgetfulness in inhalation adherence barriers for stable asthma control therapy. Once-daily FF/VI DPI may be an effective alternative for asthma maintenance treatment.Keywords: fluticasone furoate/vilanterol, budesonide/formoterol, stable asthma, randomized crossover trial, inhalation adherence barriers

Yuzo Suzuki,1 Naoki Inui,1 Masato Karayama,1 Shiro Imokawa,2 Takashi Yamada,3 Koushi Yokomura,4 Kazuhiro Asada,5 Hideki Kusagaya,6 Yusuke Kaida,7 Hiroyuki Matsuda,8 Naoki Koshimizu,9 Mikio Toyoshima,10 Masafumi Masuda,11 Hiroshi Hayakawa,12 Hironao Hozumi,1 Kazuki Furuhashi,1 Noriyuki Enomoto,1 Tomoyuki Fujisawa,1 Yutaro Nakamura,1 Takafumi Suda11Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; 2Department of Respiratory Medicine, Iwata City Hospital, Iwata, Japan; 3Department of Respiratory Medicine, Shizuoka City Shizuoka Hospital, Shizuoka, Japan; 4Department of Respiratory Medicine, Seirei-Mikatahara Hospital, Hamamatsu, Japan; 5Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan; 6Department of Respiratory Medicine, Shizuoka Saiseikai Hospital, Shizuoka, Japan; 7Department of Respiratory Medicine, JA Shizuoka Kohseiren Enshu Hospital, Hamamatsu, Japan; 8Department of Respiratory Medicine, Shizuoka Red Cross Hospital, Shizuoka, Japan; 9Department of Respiratory Medicine, Fujieda City Hospital, Fujieda, Japan; 10Department of Respiratory Medicine, Hamamatsu Rosai Hospital, Hamamatsu, Japan; 11Department of Respiratory Medicine, Shizuoka City Shimizu Hospital, Shizuoka, Japan; 12Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, JapanCorrespondence: Yuzo SuzukiSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka 431-3192, JapanTel +81 53 435 2263Fax +81 53 435 2354Email yuzosuzu@hama-med.ac.jpBackground: Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor, has been shown to improve survival in non-small cell lung cancer (NSCLC). The possible involvement of PD-1 axis in the pathogenesis of inflammatory lung disease, such as chronic obstructive pulmonary disease (COPD) has also been reported. However, effects of PD-1 blockade on the respiratory system remain unknown.Objectives: This prospective study aimed to investigate whether inhibition of the PD-1 axis altered lung inflammation and pulmonary function in NSCLC patients with and without COPD.Method: This was a prospective multi-center study. Measurements of fractioned exhaled nitric oxide (FeNO) and pulmonary function were performed before and after 4 cycles of nivolumab therapy.Results: A total of 137 patients with NSCLC were initially enrolled, and subsequently 95 patients (41 COPD and 54 non-COPD) receiving 4 cycles of nivolumab administration were included. After anti-PD-1 therapy, FeNO levels were significantly elevated together with increase in peripheral eosinophils. Interestingly, significant FeNO elevation was only found in COPD patients without increased peripheral eosinophils, but this was not the case in non-COPD patients. Additionally, COPD patients exhibited significant increases in FVC and FEV1 but no changes in dyspnea scales, and acute exacerbation did not occur during the therapy.Conclusion: Our observations suggest that anti-PD-1 therapy changed FeNO levels and pulmonary function in NSCLC patients. This therapy does not worsen COPD in terms of symptoms, pulmonary function, or acute exacerbation.Keywords: immune checkpoint inhibitor, programmed death 1, PD-1, non-small cell lung cancer, NSCLC, chronic obstructive pulmonary disease, COPD

Masato Karayama,1 Naoki Inui,1,2 Hideki Yasui,1 Masato Kono,1 Hironao Hozumi,1 Yuzo Suzuki,1 Kazuki Furuhashi,1 Dai Hashimoto,1 Noriyuki Enomoto,1 Tomoyuki Fujisawa,1 Yutaro Nakamura,1 Hiroshi Watanabe,2 Takafumi Suda11Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan; 2Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanPurpose: The diagnosis and severity of chronic obstructive pulmonary disease (COPD) are defined by airflow limitation using spirometry. However, COPD has diverse clinical features, and several phenotypes based on non-spirometric data have been investigated. To identify novel phenotypes of COPD using radiologic data obtained by three-dimensional computed tomography (3D-CT).Patients and methods: The inner luminal area and wall thickness of third- to sixth-generation bronchi and the percentage of the low-attenuation area (less than −950 HU) of the lungs were measured using 3D-CT in patients with COPD. Using the radiologic data, hierarchical clustering was performed. Respiratory reactance and resistance were measured to evaluate functional differences among the clusters.Results: Four clusters were identified among 167 patients with COPD: Cluster I, mild emphysema with severe airway changes, severe airflow limitation, and high exacerbation risk; Cluster II, mild emphysema with moderate airway changes, mild airflow limitation, and mild dyspnea; Cluster III, severe emphysema with moderate airway changes, severe airflow limitation, and increased dyspnea; and Cluster IV, moderate emphysema with mild airway changes, mild airflow limitation, low exacerbation risk, and mild dyspnea. Cluster I had the highest respiratory resistance among the four clusters. Clusters I and III had higher respiratory reactance than Clusters II and IV.Conclusions: The 3D-CT-based radiologic phenotypes were associated with the clinical features of COPD. Measurement of respiratory resistance and reactance may help to identify phenotypic differences.Keywords: airway, chronic obstructive pulmonary disease, clustering analysis, emphysema, phenotype, three-dimensional computed tomography

Naoki Inui,1,2 Sayomi Matsushima,1 Shinpei Kato,1 Hideki Yasui,1 Masato Kohno,1 Tomoyuki Fujisawa,1 Noriyuki Enomoto,1 Yutaro Nakamura,1 Mikio Toyoshima,3 Takafumi Suda1 1Second Division, Department of Internal Medicine, 2Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan; 3Department of Respiratory Medicine, Hamamatsu Rosai Hospital, Shougen-cho, Hamamatsu, JapanAbstract: The forced oscillation technique (FOT) can measure respiratory mechanics and has attracted attention in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of only indacaterol and tiotropium monotherapies on airflow limitation and respiratory impedance. Pulmonary function tests, COPD assessment test (CAT), and multifrequency FOT with MostGraph-01 were performed at the beginning and after 8 weeks of treatment with indacaterol or tiotropium. The resistance index, resistance at 5 Hz (R5), resistance at 20 Hz (R20), reactance index, reactance at 5 Hz (X5), resonant frequency (Fres), and low-frequency reactance area (ALX) were determined at whole-breath, inspiratory, and expiratory phases. Eighty-two patients (mean age: 73 years; mean forced expiratory volume in 1 second (FEV1): 61.6%±19.0% predicted) were randomized to indacaterol or tiotropium treatment. Both bronchodilators improved airflow limitation, with mean trough improvements in FEV1 of 165 mL and 80 mL in the indacaterol and tiotropium groups, respectively. The CAT score decreased in the indacaterol group (P

Yasuo Sekine, Ryoko Yanagibori, Kiminori Suzuki, Sonomi Sugiyama, Haruko Yamaji, Michiko Ishibashi, Takehiko Fujisawa Chiba Foundation for Health Promotion and Disease Prevention, Chiba, Japan Background and objective: Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. Materials and methods: A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). Results: The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. Conclusion: COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD. Keywords: chronic obstructive pulmonary disease, lung neoplasms, mass screening, respiratory function tests

The design and construction of a permanent cyclotron magnet of variable magnetic field from 2.3 Tesla peak field to practically zero field and associated devices such as model magnet and accurate rapid field mapper are described. The studies have shown that the small field adjustment is possible along with the wide field range of variation such as ON and OFF.

Author(s): C. W. Lai (corresponding author) [1, 2, 3]; N. Y. Kim [1, 2]; S. Utsunomiya [3, 4]; G. Roumpos [1]; H. Deng [1]; M. D. Fraser [1]; T. Byrnes [...]

Magnetite (Fe3O4) was doped with radioactive 111mCd and 111In ions as impurities, and their residence sites and thermal stability were investigated by means of time-differential perturbed angular correlation (TDPAC) spectroscopy. Well-defined TDPAC spectra unequivocally show their sites: Cd ions are stably located only in the tetrahedral A site in all the temperature range of the present observation (77 K-873 K); In ions also specifically occupy the A site at low temperature, but at high temperature part of them select the B site in a reversible fashion. The energy difference between the A and B sites for the accommodation of In was experimentally determined to be 0.119 (9) eV by assuming a Boltzmann distribution for the populations of the 111In probe in the respective sites. The element-dependent thermal stabilities observed for Cd and In were well corroborated by density functional theory calculations. The successful observation of thermally activated site-tosite displacement of impurity In ions in Fe3O4 is reported. [ABSTRACT FROM AUTHOR]