Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

Comparison of User Satisfaction and Preference with Inhalant Devices Between a Pressurized Metered-Dose Inhaler and Ellipta in Stable Asthma Patients: A Randomized, Crossover Study.

INTRODUCTION: Inhalation therapy involves two types of adherence: adherence to the drug and adherence to the procedures for the inhalation device. User satisfaction and preference are key factors for maintaining good adherence of both types, and they should be evaluated based on three conditions being well maintained: asthma control level (ACL), adherence, and adequate device operability during usage duration. We compared user satisfaction and preference between a pressurized metered-dose inhaler (pMDI) and a dry powder inhaler (Ellipta), while maintaining the three conditions during usage in stable asthma patients. METHODS: In this open-label, randomized, two-way crossover study, patients with stable asthma [Asthma Control Questionnaire (ACQ) scores < 0.75] were classified into a 20-64-year age group (G1) and a ≥ 65-year age group (G2) and randomly assigned to either a formoterol/fluticasone combination (FFC) as the pMDI group or a vilanterol/fluticasone combination (VFC) as the Ellipta group. Satisfaction and preference levels were evaluated at week 4. ACL was measured using the ACQ and Japan Asthma Control Survey questionnaires at weeks 0 and 4. Device operability and respiratory resistance were also examined. RESULTS: Forty-four patients (23 G1, age 45.8 ± 1.9 years; 21 G2, 74.1 ± 1.3 years) were enrolled and maintained good ACL during the study. Adherence to FFC pMDI and VFC Ellipta was > 97% in all groups. Device operability did not differ significantly between FFC pMDI and VFC Ellipta in the G1 (p = 0.189) or G2 (p = 0.506) group. Overall satisfaction was marginally higher with the FFC pMDI than with the VFC Ellipta in G2 (p = 0.012) but non-significantly different in G1 (p = 0.733). Factors affecting overall satisfaction in G2 were difference of inhalation device and body mass index. Respiratory resistance did not change significantly over the study in G2. CONCLUSION: Based on maintaining good ACL, adherence, and device operability, FFC pMDI showed significantly higher satisfaction and preference levels than VFC Ellipta in elderly persons. TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier, jRCTs041180001 (registered 21 August 2018).

Serum periostin reflects dynamic hyperinflation in patients with asthma.

INTRODUCTION: Dynamic hyperinflation (DH) is sometimes observed and is associated with impaired daily life activities of asthma. We assessed the relationship between DH and asthma biomarkers (blood eosinophil, fractional exhaled nitric oxide (F eNO) and serum periostin) in patients with asthma. METHODS: Fifty patients with stable asthma were prospectively recruited and underwent blood test, F eNO measurement, spirometry and metronome-paced tachypnoea (MPT) test to assess DH. In MPT tests, inspiratory capacity (IC) was measured at baseline and after 30 s of MPT with breathing frequencies of 20, 30 and 40 breaths·min-1. DH was assessed by the decline of IC from baseline, and maximal IC reduction ≥10% was considered as positive DH. RESULTS: Thirty patients (60%) showed positive DH. Patients with positive DH showed higher serum periostin levels (107.0±30.7 ng·mL-1) than patients with negative DH (89.7±23.7) (p=0.04). Patients in Global Initiative for Asthma treatment steps 4-5 (n=19) showed higher serum periostin levels (p=0.01) and more severe IC reduction after MPT (p<0.0001) than patients in steps 1-3 (n=31). Maximal IC reduction after MPT was significantly correlated with asthma control test score (r=-0.28, p=0.05), forced expiratory volume in 1 s (r=-0.56, p<0.0001), and serum periostin levels (r=0.41, p=0.003). CONCLUSION: Serum periostin may have the possibility to reflect DH in patients with stable asthma.

Evaluation of Rapid Onset of Action of ICS/LABA Combination Therapies on Respiratory Function in Asthma Patients: A Single-Center, Open-Label, Randomized, Crossover Trial.

INTRODUCTION: Products based on inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) combinations may provide different clinical benefits. This study was conducted to compare the rapid effects of three such combination products: formoterol/fluticasone (FFC) aerosol (pMDI), formoterol/budesonide (FBC) dry powder inhaler (DPI), and vilanterol/fluticasone furoate (VFC) DPI. METHODS: The study design was a three-armed, randomized, crossover study. Patients included in the study had stable moderate asthma, defined as an Asthma Control Questionnaire (ACQ) score ≤ 0.75, and were undergoing step 2 or 3 asthma treatment as defined by JGL2015. Subjects were treated with fluticasone propionate inhaled via Diskus® during a 2-week washout period before randomization. At visit 2, subjects were randomly assigned in a 1:1:1 ratio to FFC, FBC, or VFC, and evaluated for changes in pulmonary function over time. At visits 3 and 4, the treatment was switched to another ICS/LABA combination in a crossover manner after a 1-week washout period. Spirometry was performed pre-dose and at 3, 10, and 30 min post-dose, and forced oscillation was implemented pre-dose and at 1, 7, 15, and 60 min post-dose. RESULTS: Fifteen outpatients (63.3 ± 9.5 years, ACQ: 0.13 ± 0.19) completed the study. ∆FEV1 at 3 min did not significantly differ among the three groups. Significant increases in FEV1 and %FEV1 from baseline were observed in the FFC (p = 0.004, 0.003), FBC (p = 0.014, 0.011), and VFC (p = 0.032, 0.023) groups at 30 min. Improvements in respiratory resistance at 5-20 Hz from baseline at 60 min, resonant frequency, respiratory system reactance at 5 Hz, and low-frequency reactance area from baseline were observed at 1 min in the FFC group (p = 0.014, 0.002, 0.027, 0.018, respectively). CONCLUSION: FFC administered using a pMDI showed favorable delivery to peripheral airways and significantly more rapid action promptly after inhalation as compared with other ICS/LABA preparations inhaled using a DPI, thus broadening the potential therapeutic options for asthma. TRIAL REGISTRATION NUMBER: UMIN000029379. FUNDING: Kyorin Pharmaceutical Co., Ltd.