Search

Takanori Numata, Jun Araya, Keitaro Okuda, Hanae Miyagawa, Shunsuke Minagawa, Takeo Ishikawa, Hiromichi Hara, Kazuyoshi Kuwano Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, JapanCorrespondence: Takanori Numata, Email t-numata@jikei.ac.jpBackground: Few studies on the long-term efficacy of benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, have been conducted for patients with severe eosinophilic asthma (SEA), especially regarding the improvement of pulmonary function and clinical remission in a real-world setting.Objective: To elucidate the long-term efficacy and clinical remission rate (CRR) in patients with SEA.Methods: From July 2018 to July 2022, 23 Japanese patients with SEA received benralizumab for two years or more at Jikei University Hospital. We retrospectively evaluated the patients’ characteristics, biomarkers, number of exacerbations, pulmonary function, asthma symptoms, maintenance oral corticosteroid (OCS) dose and CRR.Results: The mean observation period was 38.3 (24– 49) months. Among the 23 patients, 10 patients switched from mepolizumab to benralizumab. After administration of benralizumab, the forced expiratory volume in one second (FEV1) increased and was maintained for two years in the biologic-naïve group and in the switching group (177 ± 404 and 151 ± 236 [mL], respectively, P = 0.80). In all patients, the %FEV1 improved from 76.7 ± 22.9% to 84.3 ± 18.4% (P = 0.016), and the number of annual exacerbations decreased from 2.5 ± 3.3 to 0.74 ± 1.7 (P = 0.014). Furthermore, the Asthma Control Test score significantly improved, and the reduction in OCS dose was maintained for three years. Ultimately, five patients met the clinical remission criteria and exhibited stabilization of pulmonary function, no exacerbation, no OCS use and well-controlled symptoms. The CRR was significantly higher in patients with a blood basophil count (BBC) ≥ 22 than in those with a BBC < 22 (/μL) (38.5% vs 0%, respectively, P = 0.046).Conclusion: Long-term treatment with benralizumab significantly improved pulmonary function, alleviated asthma symptoms and decreased the number of exacerbations at two years in a real-world setting. The CRR may be associated with the BBC at baseline.Keywords: benralizumab, severe asthma, clinical remission, pulmonary function, blood basophil count

Takanori Numata, Jun Araya, Hanae Miyagawa, Keitaro Okuda, Daisuke Takekoshi, Mitsuo Hashimoto, Shunsuke Minagawa, Takeo Ishikawa, Hiromichi Hara, Kazuyoshi Kuwano Department of Respiratory Diseases, The Jikei University School of Medicine, Tokyo, JapanCorrespondence: Takanori Numata, Department of Respiratory Diseases, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku Tokyo, 105-8461, Japan, Tel +81-3-3433-1111 (ext. 3271), Fax +81-3-3433-1020, Email t-numata@Jikei.ac.jpBackground: Treatment with dupilumab, an anti-interleukin (IL)-4 receptor α monoclonal antibody that blocks both the IL-4 and IL-13 pathways, has demonstrated efficacy for the treatment of severe asthma (SA) with type 2 inflammation. However, few studies have focused on the efficacy of this biologic for the treatment of SA in a real-world setting.Methods: From April 2019 to December 2021, 26 Japanese patients with SA received dupilumab at Jikei University Hospital. We retrospectively evaluated the number of moderate-to-severe exacerbations, pulmonary function, maintenance dose of corticosteroids, biomarkers, and adverse events.Results: During a mean follow-up period of 12.6 months, 10 patients received dupilumab as the first biologic, and 16 switched to dupilumab from other biologics. Dupilumab treatment significantly reduced the number of annual exacerbations from 3.4 ± 4.1 to 1.6 ± 2.7 (/person-year, p < 0.01) at the last follow-up regardless of previous biologic use. The Asthma Control Test score significantly improved in all patients by six months after administration but tended to worsen by 24 months in patients with previous biologic use. On the other hand, blood eosinophil counts (BECs) transiently increased and peaked three to six months after administration. The peak timing can be affected by previous biologic use. Adverse events included wheezing immediately after injection, hypereosinophilia, mild conjunctivitis, and relapse of chronic eosinophilic pneumonia in the patient switched from benralizumab.Conclusion: Dupilumab treatment was useful for patients with SA in a real-world setting. However, the BEC should be monitored carefully, especially in patients who previously received anti-IL-5/IL-5 receptor antibody.Keywords: dupilumab, severe asthma, exacerbation, transient eosinophilia, real-world

Takanori Numata, Jun Araya, Hanae Miyagawa, Keitaro Okuda, Yu Fujita, Hirofumi Utsumi, Daisuke Takekoshi, Mitsuo Hashimoto, Shunsuke Minagawa, Takeo Ishikawa, Hiromichi Hara, Kazuyoshi Kuwano Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanCorrespondence: Takanori Numata Tel +81-3-3433-1111 (ex 3271)Fax +81-3-3433-1020Email t-numata@jikei.ac.jpBackground: In Japan, biologic therapy was initiated for patients with severe asthma in 2009. In recent years, four biologics with different mechanisms of action have become available in the clinical setting. However, the efficacy of switching between biologics remains uncertain.Methods: To elucidate the efficacy of switching between biologics, 97 patients were enrolled who had received any biologic therapy for severe asthma at Jikei University Hospital, Tokyo, Japan, from July 2009 to December 2020. We retrospectively examined the patient characteristics, biomarkers, pulmonary function test results, selected biologics, and efficacy.Results: Thirty-one males and 66 females received any biologics. The mean age was 53.3 years at the initiation of biologic therapy. Initially, 33, 41, 15 and eight patients received omalizumab, mepolizumab, benralizumab, and dupilumab, respectively. Among three representative indicators for biologics administration, the peripheral blood eosinophil count, serum IgE levels and fractional exhaled nitric oxide, 64% of the patients had two indicators, and 28% had three indicators. Thirty-four patients (35%) switched from the initial biologic to another, and the reasons for switching included persistent asthmatic symptoms (n=22), schedule of hospital visits (n=5), and other reasons. Thus, the treatment was effective in 11 patients after switching. In addition, two patients received combination therapy with different biologics. Eighteen patients (19%) interrupted treatment for various reasons. Regardless of whether the biologic was the initial therapy, the overall efficacy of the four biologics was 60% based on the global evaluation of treatment effectiveness.Conclusion: Switching between biologics can be a promising option for severe asthma patients in whom treatment with an initial biologic is ineffective.Keywords: benralizumab, dupilumab, mepolizumab, omalizumab, switching

Recently, outdoor-constructed solar panels have a problem such as power generation efficiency is reduced by the face plate dirt. On the other hand, electronic touch panels have a problem such as deterioration of visibility of the screen by finger grease stain. To solve these problems, we need to fabricate the anti-stain surfaces which have superhydrophobic and oil-repellent abilities without spoiling the transparency of the transparent substrate. In this study, we fabricated lotus leaves like surface on a glass substrate. Firstly, SiO2 particles of ca. 100 nm diameter were arranged on the glass substrates. Secondly, to obtain the fractal-like structure (ultra-micro-rough structure) on the surface, ZnO thin film having a columnar structure was fabricated on the SiO2 particles by using an atmospheric pressure cold plasma deposition system. By using these processes, the ZnO columns formed radiantly on the spherical surface of the SiO2 particles. Furthermore, without spoiling the ultra-micro-rough structure, a transparent anti-stain monolayer with low surface energy was prepared by using a chemical adsorption technique onto the surface. Average value of the water droplet contact angles of the samples fabricated was 151.8 deg. Field emission scanning electron microscope (FE-SEM) observation reviled that this sample has a raspberry structure in which columnar structure has grown radially on the SiO2 particles.

We studied dynamic interactions between CdSe/ZnS quantum dots (QDs) and cyclic solvents probed by femtosecond four-wave mixing. We found that the dynamic interactions of QDs strongly depend on the existence of π-bonds in solvent molecules.

Three very long runs of constant temperature molecular dynamics (MD) simulations, extending over typically 2×105 time steps, have been carried out for a state just above the glass transition of equimolar soft-sphere mixtures, with 500 atoms interacting through vαβ(r) =ε(σαβ /r)12 , where σαβ =(σα +σβ )/2 , and α,β (species indices)=1, 2. The ratio of diameters σ2/σ1 was chosen to be 1.2. Jump-type atomic motions are clearly found to occur in the glassy states. A coordinated (strongly correlated) jump motion was observed, where a cluster of several atoms dynamically linked at nearest-neighbor distances jump at successive close times. These simulations demonstrate that the characteristic time scale of structural relaxation becomes very long near the glass transition, and calculated mean square displacements exhibit complicated behaviors. Thermodynamic quantities, however, such as the mean pressure, energy, and pair distribution functions, appear to behave normaly, with no significant observable relaxations for increasing time, so that their averages are well defined. [ABSTRACT FROM AUTHOR]