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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

The reducing emissions from deforestation and forest degradation (REDD+) framework has been implemented over the past decade, and has led to a restructuring of forest governance systems in host countries. In the case of Lao People’s Democratic Republic, which is promoting REDD+, activities have been implemented at project, sub-national, and national scales. Project-scale REDD+ is assumed to be compatible with small-scale forestry, and usually targets local people to enhance participatory forest management through technology transfer. Such projects were also supported by foreign governments under bilateral cooperation or by private funding. In the case of sub-national- or national-scale REDD+, the Lao People’s Democratic Republic government aims to develop a system of forest monitoring, as well as related structures required by international REDD+ entities. These activities are supported by substantial funding from multilateral organizations. Lessons learned from project-scale REDD+ in northern Lao People’s Democratic Republic showed a gap in expectations among different donors and recipients regarding how to implement REDD+, in particular how to reduce dependency on forest resources in rural areas, and how to estimate and account for greenhouse gas emissions reductions with consistent methodologies at different scales. Such differences are related to the attitudes of local people toward participation, and those of the private entities that fund projects and ground-based activities. In future REDD+ schemes, the structural network or structural social capital among project-, sub- national-, and national-scale activities should be reconsidered to enhance the continued participation of stakeholders and make use of their accumulated experience and knowledge of small-scale forestry management.

BackgroundRecently, the use of telehealth for patient treatment under the COVID-19 pandemic has gained interest around the world. As a result, many infodemiology and infoveillance studies using web-based sources such as Google Trends were reported, focusing on the first wave of the COVID-19 pandemic. Although public interest in telehealth has increased in many countries during this time, the long-term interest has remained unknown among people living in Japan. Moreover, various mobile telehealth apps have become available for remote areas in the COVID-19 era, but the accessibility of these apps in epidemic versus nonepidemic regions is unknown. ObjectiveWe aimed to investigate the public interest in telehealth during the first pandemic wave and after the wave in the first part of this study, and the accessibility of medical institutions using telehealth in the epidemic and nonepidemic regions, in the second part. MethodsWe examined and compared the first wave and after the wave with regards to severe cases, number of deaths, relative search volume (RSV) of telehealth and COVID-19, and the correlation between RSV and COVID-19 cases, using open sources such as Google Trends and the Japanese Ministry of Health, Labour and Welfare (JMHLW) data. The weekly mean and the week-over-week change rates of RSV and COVID-19 cases were used to examine the correlation coefficients. In the second part, the prevalence of COVID-19 cases, severe cases, number of deaths, and the telehealth accessibility rate were compared between epidemic regions and nonepidemic regions, using the JMHLW data. We also examined the regional correlation between telehealth accessibility and the prevalence of COVID-19 cases. ResultsAmong the 83 weeks with 5 pandemic waves, the overall mean for the RSV of telehealth and COVID-19 was 11.3 (95% CI 8.0-14.6) and 30.7 (95% CI 27.2-34.2), respectively. The proportion of severe cases (26.54% vs 18.16%; P

Cross sectional echocardiography combined with Doppler echocardiography was used to record either ductal morphology or the flow profile within the ductus arteriosus before and after infusion of prostaglandin E1 in 25 newborn infants with cyanotic and acyanotic congenital heart disease with ductus dependent blood flow. The ultrasound results were compared with changes in arterial oxygen tension and the overall clinical response to prostaglandin E1 seen during the same period in 24 of the 25 patients in whom the degree of ductal narrowing could be determined with the ultrasound method. At the time of the study, the ductus was widely patent or slightly narrowed in 12 patients and was closed in two patients. These patients did not respond to prostaglandin E1. There was prominent localised narrowing of the ductus in seven patients and generalised narrowing in three. After the infusion of prostaglandin E1 there was no ductal narrowing in these patients, except for one patient who had slight residual localised narrowing. There was also a considerable change in the ductal flow profiles in each patient. In these 10 patients infusion of prostaglandin E1 resulted in an increase in arterial oxygen tension, clinical improvement, or both. The present study indicates that prostaglandin E1 is effective in patients with prominent narrowing of the ductus but is not in patients in whom the ductus is widely patent or closed. Cross sectional echocardiography combined with Doppler echocardiography was useful for predicting the responsiveness of the ductus arteriosus to the infusion. [ABSTRACT FROM PUBLISHER]