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BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness, with severe outcomes in older adults. Information on the prevalence, hospitalization rate, and impact on the health-related quality of life (HRQoL) of RSV in older adults with acute respiratory infections (ARI) in outpatient settings in Japan is limited. METHODS: This multi-center epidemiological study included outpatients aged ≥60 years presenting with ARI between August 2021 and February 2023. Nasal and throat swabs were collected and tested by reverse transcription polymerase chain reaction (RT-PCR). The prevalence of RT-PCR-confirmed RSV (cRSV)-ARI, cRSV-lower respiratory tract disease (LRTD), and other respiratory viruses was calculated by season, region, age group, and RSV subtype. HRQoL was assessed via patient-reported outcomes. RESULTS: The study included 923 ARI episodes (cRSV-ARI: N = 24; non-cRSV-ARI: N = 899). In years 1 and 2 (August 2021-July 2022 and August 2022-February 2023), the prevalence of cRSV-ARI was 2.5% and 2.8%, respectively. There was a predominance of RSV-B and RSV-A subtypes in years 1 and 2, respectively. In years 1 and 2 combined, 37.5% of cRSV-ARI cases had lower respiratory tract infection; all cRSV-LRTD cases occurred in those aged 60-74 years. RSV-ARI cases reported throat, chest, and respiratory symptoms, leading to impaired functioning and HRQoL. CONCLUSIONS: During the observed study period, RSV was circulating among older adults in Japan. RSV was a leading cause of ARI and LRTD. More data are needed to fully clarify the burden of RSV among older adults in Japan.
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Pacientes Ambulatoriais , Qualidade de Vida , Infecções por Vírus Respiratório Sincicial , Infecções Respiratórias , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Idoso , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Japão/epidemiologia , Doença Aguda , Pessoa de Meia-Idade , Feminino , Masculino , Prevalência , Pacientes Ambulatoriais/estatística & dados numéricos , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Hospitalização/estatística & dados numéricos , Vírus Sincicial Respiratório Humano/isolamento & purificaçãoRESUMO
The EXCITE-HT study aimed to evaluate the efficacy and safety of esaxerenone versus thiazide diuretics (trichlormethiazide) as second-line treatment for Japanese patients with uncontrolled essential hypertension. This was a 12-week, multicenter, randomized, open-label, parallel-group study. The non-inferiority of esaxerenone to trichlormethiazide was confirmed if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic blood pressure (SBP)/diastolic blood pressure (DBP) change between groups was below 3.9/2.1 mmHg. A total of 295 and 290 patients were included in the esaxerenone and trichlormethiazide groups, respectively. The non-inferiority of esaxerenone to trichlormethiazide was demonstrated: least squares mean change differences in morning home SBP/DBP at end of treatment (EOT) were -2.2 (95% CI, -3.6, -0.8) mmHg for SBP/-0.6 (-1.4, 0.2) mmHg for DBP. Morning home, bedtime home, and office BP significantly decreased (all p < 0.001) from baseline to EOT in both groups. The urinary albumin-to-creatinine ratio and N-terminal pro-brain natriuretic peptide level decreased from baseline to Week 12 in both groups, with no notable intergroup difference. Serum potassium elevations occurred more frequently with esaxerenone, while serum potassium reductions occurred more with trichlormethiazide. Uric acid elevations were observed in both groups, but more frequently with trichlormethiazide than esaxerenone. No cases of gout occurred in this study. Reductions in estimated glomerular filtration rate were similarly observed in both groups. EXCITE-HT is the first randomized controlled study to demonstrate evidence that esaxerenone is non-inferior to trichlormethiazide as second-line treatment for Japanese patients with uncontrolled essential hypertension, with no new safety concerns. The EXCITE-HT study demonstrated the non-inferiority of esaxerenone to trichlormethiazide in its morning home blood pressure lowering effect and safety profile in Japanese patients with uncontrolled essential hypertension who were previously treated with an angiotensin II receptor blocker or calcium channel blocker.
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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.
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Medicamentos de Ervas Chinesas , Tolerância ao Exercício , Fragilidade , Pulmão , Força Muscular , Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Humanos , Sarcopenia/fisiopatologia , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Masculino , Feminino , Idoso , Resultado do Tratamento , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/efeitos dos fármacos , Fatores de Tempo , Tolerância ao Exercício/efeitos dos fármacos , Fragilidade/diagnóstico , Fragilidade/fisiopatologia , Fragilidade/epidemiologia , Comorbidade , Fadiga/fisiopatologia , Fadiga/tratamento farmacológico , Fadiga/diagnóstico , Recuperação de Função Fisiológica , Estado Funcional , Idoso Fragilizado , Velocidade de CaminhadaRESUMO
BACKGROUND: Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option. METHODS: This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3-0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration. RESULTS: A total of 1030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p = 0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p = 0.97, p = 0.59). CONCLUSIONS: The results show that ivermectin (0.3-0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, including minor participants of 12 years or older (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.).
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COVID-19 , Humanos , COVID-19/epidemiologia , Ivermectina/efeitos adversos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Japão/epidemiologia , Tailândia/epidemiologia , Método Duplo-Cego , Resultado do TratamentoRESUMO
INTRODUCTION: Evidence on the prevalence of uncontrolled asthma upon the standard of care in Japan is scarce and inconsistent. We report the prevalence of uncontrolled asthma using the Japanese Guidelines for Asthma (JGL) 2018 and Global Initiative for Asthma (GINA) 2019 classifications in patients who are currently receiving standard-of-care treatment in a real-life setting. METHODS: In this prospective, 12-week, noninterventional study, patients with asthma aged 20-75 years and continuously treated with medium- or high-dose inhaled corticosteroid (ICS)/LABA, with or without other controller(s), were assessed for their asthma control status. The demographics, clinical characteristics, treatment patterns, health care resource utilization, patient-reported outcomes (PROs), and adherence to prescribed treatments were assessed for patients classified as either controlled or uncontrolled. RESULTS: Of 454 patients, 53.7% and 36.3% of the patients reported their asthma as uncontrolled based on the JGL and GINA criteria, respectively. Uncontrolled asthma was even higher (JGL, 75.0%; GINA, 63.5%) within the subpopulation of 52 patients receiving long-acting muscarinic antagonists (LAMAs; i.e., ICS/LABA/LAMA subpopulation). Sensitivity analysis by propensity matching identified significant odds ratios of controlled versus uncontrolled asthma for several demographics and clinical characteristics: male; sensitization to animals, fungi, or birch; comorbidities including food allergy or diabetes; and history of exacerbation were associated with the risk of uncontrolled asthma. No significant changes in PROs were observed. CONCLUSION: The frequency of uncontrolled asthma in the study population was high, as per JGL and GINA guidelines, despite good adherence to ICS/LABA treatment and other prescribed treatments over 12 weeks.
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Agonistas de Receptores Adrenérgicos beta 2 , Asma , Humanos , Masculino , Japão/epidemiologia , Prevalência , Estudos Prospectivos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Corticosteroides/uso terapêutico , Quimioterapia Combinada , Medidas de Resultados Relatados pelo Paciente , Administração por InalaçãoRESUMO
OBJECTIVE: To compare outcomes between two doses of lubiprostone in patients with chronic constipation (CC), to assess whether dose reduction affects efficacy. METHODS: This open-label exploratory study involved 146 patients with CC treated initially with lubiprostone 24 mcg twice daily for a planned duration of 4 weeks. Patients who experienced adverse events (AEs) had their dose reduced to 12 mcg twice daily (for 4 weeks). RESULTS: Lubiprostone dose was unchanged in 104 patients and reduced due to AEs in 42 patients. Significant differences in the mean number of bowel movements per week favored the dose-reduced group at Week 1 and end of follow-up. No between-group differences were observed over time for mean number of days per week with bowel movements or mean Bristol Stool Form Scale scores. Symptoms of abdominal bloating, strained defecation, and sensation of incomplete evacuation improved in both groups. Before dose reduction, nausea was reported by 64.3% and diarrhea by 45.2% of patients in the dose-reduced group; after dose reduction, no patients reported nausea and one patient reported diarrhea. CONCLUSION: Dose reduction of lubiprostone reduced the incidence of AEs, with no compromise to efficacy, and may be a suitable approach for patients who develop AEs during treatment.
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Alprostadil , Redução da Medicação , Alprostadil/efeitos adversos , Constipação Intestinal/diagnóstico , Constipação Intestinal/tratamento farmacológico , Diarreia/tratamento farmacológico , Método Duplo-Cego , Humanos , Japão , Lubiprostona/efeitos adversos , Náusea/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Recently, BudeForu® (BF), a generic of Symbicort Turbuhaler® (SMB), is widely used in Japan. Although appearance of BF resembles to SMB, several differences in length, weight, and side-hole sizes are seen with precise inspection. As particle releases from the inhalation device is strongly influenced by its mechanical characteristics, we compared their particle release patterns. METHODS: An inhalation simulator generated either ramp-up or triangular (time to reach peak inhaling flow (PIF) = 0.42 s) inhalation pattern. Time trajectories of inhaled flow and released particles from either device were depicted with a photo-reflection method. Internal resistances of them were also measured. RESULTS: Particle release patterns of both dry powder inhalers resembled each other. Immediately after release from the inhaler, they reached the peak value and then completed in 0.5 s. In either ramp-up or triangular inspiration pattern, a single burst developed at early inhalation. There were linear relationships between PIFs and emitted doses. The regression lines using ramp-up patters were: Y = 0.00241 X - 0.039, r2 = 0.700, p ï¼ 0.0001 (BF), Y = 0.00210 X - 0.038, r2 = 0.654, p ï¼ 0.0001 (SMB), and those using triangular patterns were: Y = 0.00223X ï¼ 0.0015, r2 = 0.445, p ï¼ 0.0001 (BF), and Y = 0.00229X ï¼ 0.0023, r2 = 0.687, p ï¼ 0.0001 (SMB). Internal resistances of the BF and SMB were 0.105±0.004 and 0.119±0.105 cmH2O0.5/L/min respectively. CONCLUSIONS: Present experimental study suggested that aerodynamic characteristics of BF were quite similar to those of SMB.
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Combinação Budesonida e Fumarato de Formoterol , Budesonida , Administração por Inalação , Broncodilatadores/uso terapêutico , Inaladores de Pó Seco , Fumarato de Formoterol , HumanosRESUMO
PURPOSE: The pivotal CAPTAIN study reported a favorable safety profile with once-daily inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in patients with inadequately controlled asthma, some of whom were Japanese. Here, we evaluate the long-term (52 weeks) safety of FF/UMEC/VI in Japanese patients with asthma. PATIENTS AND METHODS: This was a Phase III, 52-week, multicenter, non-comparator, non-randomized, open-label study (NCT03184987) in Japanese adults receiving maintenance therapy with ICS/LABA, with or without LAMA. At enrollment, patients were allocated to either FF/UMEC/VI 100/62.5/25mcg (Group 1) or 200/62.5/25mcg (Group 2). Patients in Group 1 could have their treatment stepped up to 200/62.5/25mcg at Week 24 if their Asthma Control Questionnaire (ACQ)-7 score was >0.75. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Secondary endpoints included vital signs, electrocardiogram measurements, and clinical laboratory tests (biochemistry, hematology, urinalysis). Efficacy was assessed as "other" endpoints. RESULTS: A total of 111 Japanese patients were included in the intention-to-treat (ITT) population. Overall, 77 (69%) patients reported ≥1 AE (Group 1: n=30 [64%]; step-up group: n=7 [78%]; Group 2: n=40 [73%]). SAEs were reported for 1 (2.1%) and 2 (3.6%) patients in Groups 1 and 2, respectively. All SAEs were considered unrelated to study treatment. One AE and one SAE led to study withdrawal: oropharyngeal discomfort (Group 1); eosinophilic granulomatosis with polyangiitis (Group 2). No new safety concerns were identified throughout the 52-week treatment period. CONCLUSION: In this uncontrolled open-label study, no new safety concerns were observed with long-term (52 weeks) treatment with once-daily FF/UMEC/VI among 111 Japanese patients with asthma.
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OBJECTIVE: In CAPTAIN, a double-blind, parallel-group, Phase IIIA study, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) improved lung function, symptoms and asthma control versus FF/VI in patients with inadequately controlled asthma. Here, we report efficacy and safety from a Japanese cohort in CAPTAIN. METHODS: Adults with inadequately controlled asthma despite inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) were randomized (1:1:1:1:1:1) to once-daily FF/VI (100/25 mcg or 200/25 mcg) or FF/UMEC/VI (100/31.25/25 mcg, 100/62.5/25 mcg, 200/31.25/25 mcg, or 200/62.5/25 mcg) for ≥24 weeks. Endpoints included change from baseline in clinic trough FEV1 (primary), annualized rate of moderate/severe asthma exacerbations (key secondary), clinic FEV1 3 h post-dose, and Asthma Control Questionnaire (ACQ)-7, St George's Respiratory Questionnaire (SGRQ) (all Week 24), Evaluating Respiratory Symptoms (E-RS): Asthma total scores (Weeks 21-24) (all secondary). Adverse events and adverse events of special interest were monitored. Clinical trials.gov registry no: NCT02924688. RESULTS: Overall, 229 of 2436 patients in the intention-to-treat (ITT) population were from Japan. In this cohort, change from baseline in trough FEV1 for FF/UMEC/VI 100/62.5/25 mcg versus FF/VI 100/25 mcg was 105 mL (95% confidence interval -5, 216) and 69 mL (-42, 179) for 200/62.5/25 mcg versus 200/25 mcg. These observations were supported by clinic FEV1 at 3 h post-dose. Moderate/severe exacerbation incidence was low and similar across pooled treatment groups (FF/VI, FF/UMEC 31.25 mcg/VI, FF/UMEC 62.5 mcg/VI). All pooled groups demonstrated clinically important improvements from baseline in ACQ-7, SGRQ and E-RS: Asthma total scores. Safety profiles were consistent with the overall ITT population, with no new safety concerns. CONCLUSION: FF/UMEC/VI is an effective option with a favorable risk-benefit profile in Japanese patients with uncontrolled moderate or severe asthma on ICS/LABA.
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Asma , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Androstadienos , Asma/tratamento farmacológico , Álcoois Benzílicos , Broncodilatadores , Clorobenzenos/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Humanos , Japão , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas , Resultado do TratamentoRESUMO
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).
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OBJECTIVE: To investigate the continuation rate with a reduced lubiprostone dose (12 mcg twice daily, BD) after the onset of adverse events (AEs) in patients with chronic constipation (CC). METHODS: In this exploratory, open-label, multicenter study, patients with CC received lubiprostone 24 mcg BD and the dose was reduced to 12 mcg BD in subjects experiencing AEs. The primary objective was the continuation rate after dose reduction due to nausea/vomiting. Secondary objectives included the continuation rate after dose reduction due to diarrhea/any AE and efficacy, including changes in number of weekly bowel movements and Bristol Stool Form Scale. RESULTS: Of the 146 patients included in the study, 42 (28.8%) received lubiprostone 12 mcg BD (dose-reduced group) due to any AE. Thirty-six (85.7%) subjects in the dose-reduced group continued treatment and completed the study. 22/27 (81.5%) and 17/19 (89.5%) patients in whom the dose was reduced due to nausea/vomiting or diarrhea, respectively, continued treatment. There was no clinically relevant difference in efficacy after dose reduction. CONCLUSION: These results suggest that treatment withdrawal due to AEs associated with lubiprostone 24 mcg BD could be minimized in patients with CC after dose reduction to 12 mcg BD, thus resulting in improved long-term outcomes. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (https://jrct.niph.go.jp/latest-detail/jRCTs031180069).
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Agonistas dos Canais de Cloreto/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Lubiprostona/efeitos adversos , Adulto , Idoso , Agonistas dos Canais de Cloreto/uso terapêutico , Doença Crônica , Diarreia/induzido quimicamente , Redução da Medicação , Feminino , Humanos , Lubiprostona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Vômito/induzido quimicamente , Suspensão de TratamentoRESUMO
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 30â s of MPT with breathing frequencies of 20, 30 and 40â 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±30.7â 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 1â 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.
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BACKGROUND: In use of Ellipta (EPT), Diskus (DKS) or Turbuhaler (TBH), an instruction not to close side holes is sometimes given, but validity of such instruction has not been proved. METHOD: Using an inhalation simulator we measured peak inhaled flow (PIF), peak inhaled pressure (PIP) and amount of the drug release from these DPIs before and after closure of side holes (SHC). In the case of EPT, incomplete obstruction was also assessed. RESULTS: SHC increased internal resistance by 2.8 times in TBH, 1.0 in DKS, and 1.28 (incomplete obstruction) and 1.86 (complete) in EPT. Inhaled flows at pressure of -15cmH2O were 14L/min in TBH, 47 in DKS and 34 in EPT (incomplete obstruction). SHC suppressed drug release from TBH but statistical significance was not obtained. Drug release was not suppressed by SHC in DKS, while it was almost half during SHC in EPT. The level of PIF decreased by SHC was serious since fine particles generation is not expected. Such severe decreases were not found in DKS and EPT. CONCLUSION: SHC severely inhibited drug release from TBH, but almost no effects on DKS. Such negative effect was limited in usual use of EPT.
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Administração por Inalação , Asma , Inaladores de Pó Seco/normasRESUMO
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on several cardiometabolic biomarkers, but this is not sufficient to fully explain the significant reduction in cardiovascular risk and mortality reported with SGLT2 inhibitor treatment in patients with diabetes mellitus. The 8-week, randomized, open-label SHIFT-J study investigated the effects of adding canagliflozin vs intensified antihyperglycemic therapy on nocturnal home blood pressure (BP) in patients with poorly controlled type 2 diabetes and nocturnal BP on existing therapy. Patients were randomized to oral canagliflozin 100 mg/d or control (increased hypoglycemic dosage/addition of another hypoglycemic agent). The efficacy analysis included 78 patients (mean 69 years; 59% male). Nocturnal home systolic BP [HSBP] decreased by 5.23 mm Hg in the canagliflozin group and by 1.04 mm Hg in the control group (P = 0.078 for between-group difference in change from baseline to week 8 [primary endpoint]); corresponding decreases in HSBP from baseline to week 4 were 5.08 and 1.38 mm Hg, respectively (P = 0.054). Reductions in morning HSBP from baseline to week 4 (-6.82 mm Hg vs -1.26 mm Hg, P = 0.038) and evening HSBP from baseline to week 8 (-8.74 mm Hg vs -2.36 mm Hg, P = 0.012) were greater in the canagliflozin group than in the control group. Body mass index (P < 0.001) and N-terminal pro B-type natriuretic peptide level (NT-proBNP; P = 0.023) decreased more in the canagliflozin group than in the control group. Glycemic control improved comparably in both groups. Reduction of HSBP and NT-proBNP level may be potential mechanism by which SGLT2 inhibitors reduce cardiovascular event risk.
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Pressão Sanguínea/efeitos dos fármacos , Canagliflozina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Idoso , Determinação da Pressão Arterial/métodos , Canagliflozina/administração & dosagem , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/efeitos dos fármacos , Fragmentos de Peptídeos/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
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.
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BACKGROUND: This study aimed to compare rapid improvements in respiratory function and symptoms following single inhalation of formoterol (FOM) dry power inhaler (DPI) or tiotropium bromide (TIO) DPI in patients with chronic obstructive pulmonary disease (COPD). METHODS: Fifty-two outpatients with COPD (GOLD stage 2 or 3) received either a single inhalation of FOM DPI (9 µg via a Turbuhaler®) or TIO DPI (18µg via a HandiHaler®) in a randomized crossover manner. Respiratory function testing was performed before, and 15, 60, and 120min after drug administration. Indices of respiratory resistance (assessed with a Mostgraph®) were measured before, and 3, 7, 10, 15, 30, 60, and 120min after treatment.Visual analogue scale (VAS) (range 0-10cm) and modified Borg scale scores (CR10) were compared before and after treatment. RESULTS: Forced expiratory volume in 1 second (FEV1) significantly improved 15min after both FOM (p=0.002) and TIO (p=0.026). Respiratory resistance at 5Hz (R5) and resonant frequency indices significantly decreased 10min (p=0.007) and 3min (p=0.034) after inhaling FOM and remained reduced at 120min. Low frequency reactant indices at 5Hz (X5) significantly increased at 30min (p=0.012) VAS significantly correlated with FEV1 (r=-0.371, p=0.007), X5 (r=-0.304, p=0.029), and low-frequency reactance area (AX; r=0.305, p=0.028) in FOM, but not in TIO. Borg scale scores significantly correlated with FEV1% (r=-0.398, p=0.004), R5 (r=-0.379, p=0.006), respiratory resistance at 20Hz (R20; r=0.321, p=0.020), and R5-R20 (r=0.377, p=0.006) in FOM, but not in TIO. CONCLUSIONS: FOM is more effective than TIO at rapidly improving pulmonary function and symptoms in patients with COPD.
Assuntos
Broncodilatadores/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Respiração , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Formas de Dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA); the treatment ameliorates dyspnea and improves quality of life (QOL). AIM: Efficacy and safety of lysozyme hydrochloride (LYS), an oral mucolytic enzyme preparation, for patients with COPD or BA were investigated. PATIENTS AND METHODS: This study was a placebo-controlled, double-blind, randomized, cross-over design. Twenty-four patients with COPD and twenty-four patients with BA were enrolled. LYS or placebo was administered for 28 days in each treatment period, with a 28-day washout between the first and second treatment periods. The results of spirometry, impulse oscillometry system (IOS) examination, fractional exhaled nitric oxide (FeNO) measurement, as well as the changes in the subjective symptoms, were evaluated after the treatment period. RESULTS: On spirometry, airway function (FEV1) improved in patients with COPD after administration of LYS (LYS vs placebo: 0.08 L vs 0.029 L, p = 0.030). Similar trends were also found in %FEV1 in COPD patients. On IOS examination, resistance of the respiratory system at 5 Hz levels was significantly improved only in patients with COPD (LYS vs placebo: -0.455 cm H2O/L/s vs 0.095 cmH2O/L/s, p = 0.012). Similar trends were found in terms of the resistance of the respiratory system at 20 Hz, and of the reactance area. In the COPD assessment test, subjective symptoms also significantly improved in patients with COPD during the LYS treatment period (improvement rates-LYS vs. placebo: 69.6% vs. 39.1%; p = 0.022). A similar effect of LYS was not seen in BA patients. CONCLUSION: LYS, a mucolytic agent, has capability to improve the function of peripheral airways in patients with COPD, which leads to improvements of the patients' symptoms and QOL.
Assuntos
Asma/tratamento farmacológico , Expectorantes/administração & dosagem , Muramidase/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Asma/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Dispneia/tratamento farmacológico , Dispneia/etiologia , Expectorantes/efeitos adversos , Expectorantes/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Muramidase/efeitos adversos , Muramidase/farmacologia , Óxido Nítrico/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Espirometria , Escarro/metabolismo , Resultado do TratamentoAssuntos
Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Asma/complicações , Diagnóstico Diferencial , Humanos , Terapia de Alvo Molecular/métodos , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoRESUMO
OBJECTIVE: Persistent cough is a frequent cause of doctor and hospital visits, and its incidence may be increasing. However, diagnosis of the cause of cough remains difficult. Because different causes of cough have different treatments, accurate diagnosis of the cause of cough is critical. To gain a better understanding of the causes of cough in Japan, we performed a multicenter epidemiological study of Japanese patients. METHODS: The study involved seven institutions in five different areas of Japan, and was conducted over 1 year from March 2009. Patients aged ≥16 years attending the participating centers for the first time complaining of cough persisting for ≥3 weeks were eligible. Patients with chest X-ray abnormalities responsible for cough, fever or blood-stained sputum were excluded, while those with wheeze or shortness of breath were included. Frequency and severity of cough were assessed using questionnaires, and laboratory tests were performed to enable differential diagnoses. RESULTS: Among the 313 patients evaluated, mean duration of cough symptoms was 192.1 ± 558.4 days. Cough variant asthma (CVA) was the most common cause of prolonged/chronic cough (42.2%), followed by cough-predominant asthma (CPA) (28.4%), atopic cough (7.3%) and chronic obstructive pulmonary disease (6.7%). Patients with an unclear diagnosis were treated with tulobuterol, a transdermal ß2-agonist preparation, for 1-2 weeks. Transdermal tulobuterol improved assessments of cough in patients with CVA or CPA, enabling rapid diagnosis of these diseases. CONCLUSIONS: These findings show that CVA and CPA are the main causes of cough persisting for ≥3 weeks.
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Agonistas Adrenérgicos beta/administração & dosagem , Asma/imunologia , Tosse/etiologia , Terbutalina/análogos & derivados , Adulto , Asma/diagnóstico , Asma/tratamento farmacológico , Tosse/diagnóstico , Tosse/tratamento farmacológico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não Paramétricas , Terbutalina/administração & dosagemRESUMO
BACKGROUND: The influence of dentures on residual inhaled corticosteroids (ICSs) in the mouths of elderly asthmatic patients and the appropriate time for gargling after inhaling ICSs are unclear. METHODS: Twenty elderly patients in whom moderate persistent asthma was stably controlled using fluticasone propionate Diskus (FP, n = 10) or hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP, n = 10) for more than 3 months and who wore dentures daily were switched to the other type of ICS for 4 weeks in a crossover manner. The residual amount of each ICS in their mouths after inhalation was measured along with determination of peak inspiratory flow (PIF) and pharyngeal culture for detecting Candida albicans. RESULTS: The total amounts of residual ICSs in gargling fluids (µg) with HFA-BDP were significantly greater than those with FP (15.6 ± 14.6 vs. 11.5 ± 13.8, p = 0.028). The residual amounts of HFA-BDP were significantly greater in the patients with complete dentures than in those with partial dentures. The residual amounts of FP were significantly correlated with the PIF values in the FP treatment (p = 0.013) but not in the HFA-BDP treatment (p = 0.202). No residual ICSs remained after the third gargling in either treatment. The occurrence of candidiasis during the HFA-BDP period was significantly higher than that during the FP treatment (p = 0.046). CONCLUSION: The dentures of elderly asthmatics affect the oral residues of ICSs and occurrence of candidiasis in HFA-BDP treatment; meanwhile, the PIF values affected these factors in FP treatment. Three times gargling after inhaling ICSs is required.