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Tasuku Yamamoto,1,2 Keiji Oishi,1 Syuichiro Ohata,1 Yoriyuki Murata,1 Yoshikazu Yamaji,1 Maki Asami-Noyama,1 Nobutaka Edakuni,1 Tomoyuki Kakugawa,3 Tsunahiko Hirano,1 Kazuto Matsunaga1 1Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 2Department of Respiratory Medicine, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi, Japan; 3Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanCorrespondence: Keiji Oishi, Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan, Tel +81 836 85 3123, Fax +81 836 85 3124, Email ohishk@yamaguchi-u.ac.jpBackground: Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan.Patients and Methods: We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study.Results: Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p< 0.01). Although there was no difference in age or forced expiratory volume in one second (FEV1) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥ 2: p< 0.01; number of exacerbations≥ 2: p=0.011). The mean forced vital capacity and FEV1 values in females were lower than those in males (p< 0.0001 and p< 0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p< 0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males.Conclusion: The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV1, respiratory failure, and asthma-like conditions.Keywords: chronic obstructive pulmonary disease, exacerbation, subjective symptoms, gender difference, observational study

Kazuki Hamada,1 Keiji Oishi,2 Yoriyuki Murata,2 Tsunahiko Hirano,1 Kazuto Matsunaga1 1Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 2Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanCorrespondence: Kazuto MatsunagaDepartment of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, JapanTel/Fax +81-836-85-3123Email kazmatsu@yamaguchi-u.ac.jpAbstract: In severe asthma with type 2 (T2) inflammation, biologics targeting key mediators of T2 inflammation, including interleukin (IL)-5, IL-4/IL-13, and immunoglobulin (Ig)E, remarkably improve the management of severe asthma, providing new insights into the clinical course of asthma such as disease modification and broad modulation of T2 inflammation. Once severe asthma has become a “controllable” condition, the question of discontinuation of biologics arises due to cost and side effects. The studies on discontinuing biologics in asthma demonstrate that some of patients successfully discontinue biologics, indicating that it is a feasible option in a subset of patients. Incorporating the evidence of discontinuation, we propose the criteria for the discontinuation of biologics. Our proposed criteria for the discontinuation of biologics consist of an absence of asthma symptoms (asthma control questionnaire [ACQ] score < 1.5 or asthma control test [ACT] score > 19), no asthma exacerbations, no use of oral corticosteroids, normalized spirometry (forced exhaled volume in 1 second [FEV1] ≥ 80%), suppressed T2 inflammation (blood eosinophil counts < 300 μL and fractional exhaled nitric oxide [FeNO] < 50 ppb), and control of asthma comorbidities. Real-world evidence verified a subset of patients achieving highly well-controlled conditions after use of biologics, namely super-responders, who are candidates for the discontinuation of biologics. If super-responders meet all of the criteria, they are allowed to discontinue biological therapies. Our proposed algorithm may support physicians’ treatment decisions for patients receiving biologics.Keywords: biologics, discontinuation, severe asthma, super-responder

Kazuto Matsunaga,1 Keiji Oishi,2 Marc Miravitlles,3 Antonio Anzueto4,5 1Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 2Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 3Department of Pneumology, Hospital Universitari Vall d’Hebron/Vall d’Hebron Research Institute (VHIR), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 4Division of Pulmonary Diseases and Critical Care Medicine, School of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA; 5Pulmonary Diseases Section, Audie L. Murphy Memorial VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USACorrespondence: Kazuto MatsunagaDepartment of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, JapanTel +81 836 85 3123Fax +81 836 85 3124Email kazmatsu@yamaguchi-u.ac.jpAbstract: In 2017, a new two-step algorithm for the treatment of COPD was proposed. This algorithm was based on the severity of symptoms and phenotypes or treatable traits, and patient-specialised assessment targeting eosinophilic inflammation, chronic bronchitis, and frequent infections is recommended after exacerbation occurs despite maximal bronchodilation therapy. However, recent studies have revealed the clinical characteristics of patients who should have second controllers added, such as ICS. We again realized that treatable traits should be assessed and intervened for as early as possible. Moreover, the treatment algorithm is necessary to be adapted to the situation of clinical practice, taking into account the characteristics of the patients. The time to revise COPD treatment algorithm has come and we propose a new 3-step parallel approach for initial COPD treatment. After the diagnosis of COPD, the first assessment is to divide into two categories based on the usual clinical characteristics for patients with COPD and the specific clinical characteristics for each patient with concomitant disease. In the former, the assessment should be based on the level of dyspnea and the frequency of exacerbations. After the assessment, mono- or dual bronchodilator should be selected. In the latter, the assessment should be based on asthma characteristics, chronic bronchitis, and chronic heart failure. After the assessment, patients with asthmatic characteristics may consider treatment with ICS, while patients with chronic bronchitis may consider treatment with roflumilast and/or macrolide, while patients with chronic heart failure may consider treatment with selective β1-blocker. The 3-step parallel approach is completed by adding an additional therapy for patients with concomitant disease to essential therapy for patients with COPD. In addition, it is important to review the response around 4 weeks after the initial therapy. This COPD management proposal might be considered as an approach based on patients’ clinical characteristics and on personalized therapy.Keywords: parallel approach, treatable traits, ICS, personalized therapy

Keiji Oishi,1 Tsunahiko Hirano,2 Kazuki Hamada,2 Sho Uehara,2 Ryo Suetake,2 Yoshikazu Yamaji,2 Kosuke Ito,2 Maki Asami-Noyama,2 Nobutaka Edakuni,2 Kazuto Matsunaga2 1Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan; 2Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan Purpose: The 2017 GOLD ABCD classification shifts patients from groups C–D to A–B. Group A was the most widely distributed group in several studies. It would be useful to understand the characteristics for group A patients, but little has been reported concerning these issues. Patients and methods: This was a multicenter cross-sectional study using the COPD Assessment in Practice study database from 15 primary or secondary care facilities in Japan. We investigated the clinical characteristics of group A by stratification according to a mMRC grade 0 or 1. Results: In 1,168 COPD patients, group A patients accounted for approximately half of the patients. Compared with the groups B–D, group A was younger and had a higher proportion of males, higher pulmonary function, and higher proportion of monotherapy with long-acting muscarinic antagonist or long-acting β-agonist. The prevalence of mMRC grade 1 patients was about two-thirds of group A. Compared with the mMRC 0 patients, mMRC 1 patients showed a tendency to have a higher proportion of exacerbations (P=0.054) and had a significantly lower pulmonary function. Regardless of the mMRC grade, 60% of group A patients were treated with monotherapy of long-acting muscarinic antagonist or long-acting β-agonist. Conclusion: Group A patients accounted for approximately half of the patients, and they were younger, had higher pulmonary function, and had lower pharmacotherapy intensity compared with groups B–D. By stratifying according to the mMRC grade 0 or 1 in group A patients, there were differences in the exacerbation risk and airflow limitation. Keywords: COPD, GOLD, mMRC, exacerbation

We studied Nd3-XBiXFe4GaO12 films to obtain perpendicular magnetic anisotropy as well as large Faraday effect. NdBi2Fe4GaO12 (Bi2:NIGG) and Nd0.5Bi2.5Fe4GaO12 (Bi2.5:NIGG) films were obtained on Nd2BiFe4GaO12 (Bi1:NIGG) layer prepared on glass substrates by metal-organic decomposition (MOD) method. Bi2:NIGG and Bi2.5:NIGG films showed large Faraday rotation angles of 7.5 and 10.5 degree/µm, at a wavelength of 520 nm, respectively. Those films have perpendicular magnetic anisotropy with a coercivity of 350 Oe and a saturation magnetic field of 730 Oe.