RESUMO
Emphysema is a significant feature of chronic obstructive pulmonary disease (COPD). Studies involving an emphysematous mouse model require optimal lung fixation to produce reliable histological specimens of the lung. Due to the nature of the lung's structural composition, which consists largely of air and tissue, there is a risk that it collapses or deflates during the fixation process. Various lung fixation methods exist, each of which has its own advantages and disadvantages. The lung fixation method presented here utilizes constant pressure to enable optimal tissue evaluation for studies using an emphysematous mouse lung model. The main advantage is that it can fix many lungs with the same condition at one time. Lung specimens are obtained from chronic cigarette smoke-exposed mice. Lung fixation is performed using specialized equipment that enables the production of constant pressure. This constant pressure maintains the lung in a reasonably inflated state. Thus, this method generates a histological specimen of the lung that is suitable to evaluate cigarette smoke-induced mild emphysema.
Assuntos
Pulmão/patologia , Enfisema Pulmonar/diagnóstico , Fixação de Tecidos , Animais , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Enfisema Pulmonar/patologia , VácuoRESUMO
Pulmonary hypertension (PH) due to lung diseases is classified as group 3 by the Dana Point classification. Given the basic pathophysiological conditions of group 3 lung diseases and the previously well-known concept of hypercapnic pulmonary vasoconstriction, chronic hypercapnia besides alveolar hypoxia might be another causative factor to increase mean pulmonary arterial pressure (PAm). Two hundred twenty-five subjects with chronic pulmonary diseases were assessed by a right heart catheterization and blood gas parameters. The subjects were classified into the following 4 groups: Hypercapnic Hypoxia (HCHX), Hypercapnic Normoxia (HCnx), Normocapnic Hypoxia (ncHX), and Normocapnic Normoxia (ncnx). Compared with ncnx, the HCHX, HCnx and ncHX groups all showed significantly higher PAm and met the criteria of borderline PH. Multiple regression analysis showed that PaCO2, as well as SaO2, was an independent variable for PAm. Given the poor prognosis with borderline PH, the elimination of excess pulmonary carbon dioxide in hypercapnia could be a considerable treatment strategy in chronic pulmonary disease.
Assuntos
Hipercapnia/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Adolescente , Adulto , Idoso , Pressão Arterial , Gasometria , Doença Crônica , Feminino , Humanos , Hidrocarbonetos Clorados/metabolismo , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: In patients with overlap syndrome (OVS), the pathophysiologies of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease can interact with one another. Focusing on low arousal threshold, the authors evaluated polysomnographic features of OVS patients. METHODS: This retrospective, multicenter study was conducted at three hospitals in Japan. Patients aged ≥ 60 years who underwent polysomnography and pulmonary function testing were reviewed. Severity of airflow limitation (AFL) was classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Low arousal threshold was predicted based on the following polysomnography features: lower apnea-hypopnea index (AHI); higher nadir oxygen saturation, and larger hypopnea fraction of total respiratory events. These features were compared among patients with only OSA (n = 126), OVS with mild AFL (n = 16), and OVS with moderate/severe AFL (n = 22). RESULTS: A low arousal threshold was more frequently exhibited by OVS patients with moderate/severe AFL than by those with OSA only (p = 0.016) and OVS with mild AFL (p = 0.026). As forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decreased in OVS patients, the mean length of apnea decreased (r = 0.388, p = 0.016), hypopnea fractions increased (r = - 0.337, p = 0.039), and AHI decreased (r = 0.424, p = 0.008). FEV1/FVC contributed to low arousal threshold independent of age, sex, smoking history, hospital, or body mass index in all subjects (OR 0.946 [95% CI 0.909-0.984]) and in OVS patients (OR 0.799 [95% CI 0.679-0.940]). CONCLUSIONS: This study first described peculiar polysomnographic features in OVS patients with moderate/severe AFL, suggesting a high prevalence of low arousal threshold.
Assuntos
Nível de Alerta , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/diagnóstico , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Idoso , Nível de Alerta/fisiologia , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Retrospectivos , Limiar Sensorial/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , EspirometriaRESUMO
Background: COPD remains a major health problem in Japan. Patients with COPD experience a reduced quality of life (QoL) and have a higher chance of work impairment and productivity loss. However, there is a lack of data on the impact of COPD in terms of QoL and work activity impairment in Japan. This study assessed the socioeconomic burden of COPD in Japan and the impact it may have on the working age population. Patients and methods: This was a 2-year retrospective chart review in COPD patients aged ≥40 years, with at least one health care visit to clinic or hospital in the previous 12 months. Patients were required to have available medical charts for at least the previous 24 months. Symptoms were assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L) and work productivity and activity impairment general health questionnaires were used to evaluate health-related QoL and work productivity, and health care resource utilization data were obtained from clinical charts. Results: In total, 71 patients aged <65 years, and 151 patients aged ≥65 years were included; the majority of patients had moderate or severe airflow limitation. Exacerbations (moderate or severe) were reported by ~35% of patients in both age groups; 52.1% and 62.9% of patients in the <65-year and ≥65-year age groups had COPD assessment test scores ≥10. EQ-5D-5L index scores in the <65-year and ≥65-year age groups were 0.79 and 0.77, respectively. Work productivity and activity impairment scores were higher in <65-year age group. Annual costs of health care resource use per patient in the <65-year and ≥65-year age groups were ¥438,975 (US$4,389) and ¥467,871 (US$4,678), respectively. Costs due to productivity loss were estimated to be ¥5,287,024 (US$52,870) in the <65-year age group and ¥3,018,974 (US$30,187) in the ≥65-year age group. Conclusion: COPD represents a significant socioeconomic burden in Japan. Patients with COPD report significant use of health care resources. Higher impact on work impairment and productivity loss was observed frequently in the working age population.
Assuntos
Doença Pulmonar Obstrutiva Crônica/economia , Qualidade de Vida , Fatores Socioeconômicos , Desempenho Profissional , Adulto , Idoso , Estudos Transversais , Progressão da Doença , Eficiência , Ex-Fumantes , Feminino , Custos de Cuidados de Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fumantes , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: The efficacy and safety of once-daily tiotropium+olodaterol (T+O) (2.5/5µg or 5/5µg) for treating chronic obstructive pulmonary disease (COPD) have been demonstrated in the large, multinational, randomized, Phase III studies TONADO® 1 and 2, which included 413 Japanese patients (~80 in each group). This study was conducted to supplement the TONADO® study data to assess long-term safety in ≥100 Japanese patients treated for 1 year in compliance with International Conference on Harmonisation guidelines. Efficacy was evaluated descriptively as a secondary end point. METHODS: Patients were randomized to 52 weeks of double-blind treatment with once-daily T+O (2.5/5 or 5/5µg) or O (5µg) monotherapy via the Respimat® inhaler. We report the safety and efficacy data descriptively. RESULTS: The incidence of adverse events (AEs) was comparable in the T+O 2.5/5µg (75.0%), T+O 5/5µg (85.4%), and O 5µg (80.5%) groups, with drug-related AEs being reported in 5.0%, 7.3%, and 4.9% of patients, respectively. Serious AEs were reported in 14 patients (11.5%). The change from baseline in forced expiratory volume in 1s (FEV1) area under the curve from 0 to 3h and trough FEV1 were numerically higher in the T+O treatment groups than in the O monotherapy group throughout the study period. Overall safety of T+O was comparable to that in the TONADO® studies. CONCLUSIONS: No safety concerns for long-term T+O treatment were identified in Japanese patients with COPD. A numerical improvement in lung function was observed with T+O treatment compared to O monotherapy.
Assuntos
Benzoxazinas/administração & dosagem , Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Adulto , Idoso , Povo Asiático , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: To better evaluate the efficacy and safety of the indacaterol/glycopyrronium (IND/GLY) fixed-dose combination versus tiotropium in Japanese patients, a pooled data analysis was conducted from the SHINE and ARISE studies, which were part of the IND/GLY clinical trial program. METHODS: Japanese patients with moderate-to-severe COPD were included in the analysis. Efficacy in terms of pre-dose forced expiratory volume in one second (FEV1) at Week 12 and Week 24/26 (ARISE/SHINE) and FEV1 at 30min and 60min post-dose at Day 1, Week 12, and Week 24/26 was evaluated. Health status using the St. George׳s Respiratory Questionnaire (SGRQ) score, rescue medication use (number of puffs/day), safety, and tolerability were also assessed. RESULTS: In total, 340 patients (IND/GLY, n=161; IND, n=41; GLY, n=40; tiotropium, n=79; and placebo, n=19) were included in the analysis that focused on comparing IND/GLY versus tiotropium since they were included in both studies. At Week 12 and Week 24/26, pre-dose FEV1 was significantly improved with IND/GLY compared with tiotropium (treatment differences=70mL and 80mL, respectively; both P≤0.001). FEV1 at 30min and 60min post-dose, the SGRQ total score, and rescue medication use were more statistically significant with IND/GLY than with tiotropium for all assessed time-points. The overall incidence of adverse events (AEs) and serious AEs was similar between the IND/GLY- and tiotropium-treated groups. CONCLUSIONS: Compared to tiotropium, IND/GLY provided significant improvements in lung function, health status, and rescue medication use, while having a good safety profile in Japanese patients with moderate-to-severe COPD.
Assuntos
Glicopirrolato/uso terapêutico , Indanos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/uso terapêutico , Estatística como Assunto/métodos , Idoso , Povo Asiático , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Volume Expiratório Forçado , Glicopirrolato/administração & dosagem , Glicopirrolato/efeitos adversos , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Masculino , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Índice de Gravidade de Doença , Brometo de Tiotrópio/administração & dosagem , Brometo de Tiotrópio/efeitos adversos , Brometo de Tiotrópio/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado(®) 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD. However, there may be racial differences in the effects of T+O on lung function in patients with COPD. METHODS: In this Tonado(®) subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants. RESULTS: Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George's Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history. A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting ß-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher. At Week 24, mean improvements with T+O 5/5 µg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 µg; mean improvements with T+O 2.5/5 µg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 µg. Mean improvements with T+O 5/5 µg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 µg; mean improvements with T+O 2.5/5 µg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 µg. SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies. Responses were similar in the overall population. Adverse-event incidence was generally balanced across treatment groups. CONCLUSION: Consistent with results from the overall population, T+O 5/5 µg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado(®).
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Benzoxazinas/administração & dosagem , Broncodilatadores/administração & dosagem , Antagonistas Colinérgicos/administração & dosagem , Pulmão/efeitos dos fármacos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Benzoxazinas/efeitos adversos , Broncodilatadores/efeitos adversos , Antagonistas Colinérgicos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Desenho de Equipamento , Feminino , Volume Expiratório Forçado , Humanos , Japão , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Brometo de Tiotrópio/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. METHODS: In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate. RESULTS: A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study. CONCLUSION: The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation.
Assuntos
Muramidase/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Idoso , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
PURPOSE: To assess the frequency of airflow limitation (AFL), and the relationship between AFL and preoperative comorbidities or postoperative complications in patients who had undergone thoracic surgery. METHODS: The medical records of patients who underwent non-cardiac thoracic surgery at our institution between August 1996 and January 2013 were retrospectively reviewed. On the basis of preoperative pulmonary function tests, patients were classified with those with FEV1/FVC <70% [AFL(+) group] or with FEV1/FVC ≥70% [AFL(-) group]. Patient characteristics, preoperative comorbidities and postoperative complications were compared between the groups. RESULTS: Of the 3667 patients assessed, 738 (20.1%) were allocated to the AFL(+) group. AFL was an independent risk factor for three preoperative comorbidities: chronic obstructive pulmonary disease (odds ratio [OR]: 4.65), bronchial asthma (OR 4.30) and cardiac diseases (OR 1.41). Airflow limitation was also an independent risk factor for postoperative respiratory failure including long-term oxygen therapy (OR 2.14) and atelectasis (OR 1.90) in the patients who underwent lobectomy or partial resection of the lung. CONCLUSIONS: Our retrospective study revealed that careful attention needs to be paid to airflow limitation in patients who undergo non-cardiac thoracic surgery since it appears to be an important feature of preoperative comorbidities and to increase postoperative complications.
Assuntos
Pulmão/fisiopatologia , Complicações Pós-Operatórias/etiologia , Doenças Respiratórias/complicações , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Idoso , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Volume Expiratório Forçado , Humanos , Modelos Logísticos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/terapia , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Capacidade VitalRESUMO
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 TratamentoRESUMO
BACKGROUND: Olodaterol is a novel long-acting ß2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies. OBJECTIVE: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD) olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD). METHODS: All eligible patients were randomized to receive 2 µg, 5 µg, or 10 µg of olodaterol or placebo for 4 weeks via the Respimat Soft Mist inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1 second (FEV1) after 4 weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1 week and 2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC(0-3)), peak FEV1 from 0 hour to 3 hours (peak FEV1), and corresponding forced vital capacity (FVC) responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed. RESULTS: A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P<0.0001). Mean increases in peak FEV1 and FEV1 AUC(0-3) compared to placebo were also significant (P<0.0001). A clear dose-response relationship was observed across all treatment groups. FVC responses (trough and FVC AUC(0-3)) supported FEV1 outcomes. All doses of olodaterol were well tolerated, and no safety concerns were identified. CONCLUSION: QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00824382.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Benzoxazinas/administração & dosagem , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/sangue , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Idoso , Área Sob a Curva , Benzoxazinas/efeitos adversos , Benzoxazinas/sangue , Benzoxazinas/farmacocinética , Broncodilatadores/efeitos adversos , Broncodilatadores/sangue , Broncodilatadores/farmacocinética , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado , Humanos , Japão , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento , Capacidade VitalRESUMO
BACKGROUND: Poor exercise tolerability is a major barrier to improving the quality of life of patients with chronic obstructive pulmonary disease (COPD). Although COPD is often treated with long-acting ß2 adrenergic agonists, few studies have examined their effects on exercise tolerability. METHODS: In this study, Japanese COPD patients were treated with 2 mg transdermal tulobuterol, a long-acting ß2 agonist, once daily for 4 weeks. Spirometry and exercise tests were conducted at baseline and at the end of treatment. The patients conducted constant load (30 W for 5 min) and incremental load (starting at 10 W and increasing by 10 W every 1 min for 5 min to a maximum load of 50 W) exercise tests on a cycle ergometer. RESULTS: Thirteen patients with stable COPD participated in this study (mean age ± standard deviation (SD), 69.5±9.7 years; smoking history 55.9±27.8 pack-years). Resting spirometric parameters were unchanged at the end of treatment. The maximum Borg scale for dyspnea and the Borg scale slope (BSS) decreased significantly from baseline to the end of treatment. The threshold load of dyspnea (TLD) increased slightly, although not significantly, in the constant load test but not in the incremental load test. There were no changes in respiratory parameters during exercise after treatment. CONCLUSIONS: In conclusion, we found that treatment with transdermal tulobuterol for 4 weeks improved self-assessed dyspnea in Japanese COPD patients during constant and incremental exercise tests. This improvement in dyspnea may encourage patients to perform daily life activities or regular physical activity.
RESUMO
BACKGROUND: We see patients who present with spirometry airflow limitation despite their forced expiratory volume in one second (FEV1) as well as forced vital capacity (FVC) to be supernormal (FEV1/FVC < 70%, both the %FEV1 and the %FVC ⧠100%) in asymptomatic healthy non-smokers. Based on previous studies, we hypothesized these spirometry conditions (results measured with spirometry) could be suitably used as a practical surrogate marker of pulmonary dysanapsis: the condition of disproportionate but physiologically normal growth between airways and lung parenchyma. METHODS: We compared the conventional surrogate marker of dysanapsis, maximum mid-expiratory flow to FVC (MMF/FVC), in SUBJECTS (FEV1/FVC < 70%, both the %FEV1 and the %FVC ⧠100% in healthy non-smokers) (n = 25), in EMPHYSEMA (CT confirmed pulmonary emphysema, same spirometry results with SUBJECTS) (n = 55), and in CONTROLS (age- and height- matched, normal spirometry results) (n = 25). Next we added imaging analysis to evaluate the relationship between the cross sectional airway luminal area (X-Ai) and the lung volume results among the three groups. RESULTS: The MMF/FVC was significantly lower in SUBJECTS and in EMPHYSEMA compared to CONTROLS. However, percent predicted peak expiratory flow (%PEFR) was significantly lower only in SUBJECTS and not in EMPHYSEMA compared to CONTROLS. The ratio of the X-Ai of the trachea and right apical bronchus to lung volume was significantly lower in SUBJECTS compared to CONTROLS. CONCLUSION: The simple spirometry conditions in SUBJECTS are highly suggestive of practical surrogate marker of pulmonary dysanapsis. Awareness of this concept would help to attenuate the risk of overdiagnosis of obstructive pulmonary disease.
Assuntos
Pneumopatias Obstrutivas/diagnóstico , Pneumopatias Obstrutivas/fisiopatologia , Espirometria , Idoso , Doenças Assintomáticas , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Enfisema Pulmonar/epidemiologia , Estudos Retrospectivos , Capacidade VitalRESUMO
Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.
Assuntos
Ácido Ascórbico/farmacologia , Proteínas de Ligação ao Cálcio/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Enfisema Pulmonar/prevenção & controle , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/fisiopatologia , Fumaça , NicotianaRESUMO
BACKGROUND AND OBJECTIVE: The efficacy and tolerability of budesonide/formoterol versus formoterol in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was evaluated. METHODS: In this randomized, double-blind, parallel-group, phase III study (NCT01069289), patients with moderate to severe COPD for ≥2 years received either budesonide/formoterol 160/4.5 µg two inhalations twice daily via Turbuhaler® or formoterol 4.5 µg two inhalations twice daily via Turbuhaler® for 12 weeks. Salbutamol was available as reliever medication. Primary outcome variable: change from baseline to average during treatment in pre-dose forced expiratory volume in 1 s (FEV1 ). RESULTS: One thousand two hundred ninety-three patients were randomized (budesonide/formoterol n = 636; formoterol n = 657). Both budesonide/formoterol and formoterol increased pre-dose FEV1 versus baseline (improvements of 4.6% and 1.5% over baseline, respectively), with the increase from baseline being significantly greater with budesonide/formoterol versus formoterol (budesonide/formoterol:formoterol ratio 1.032; 95% confidence interval: 1.013-1.052; P = 0.0011). The budesonide/formoterol group had a significantly prolonged time to first exacerbation versus the formoterol group (hazard ratio: 0.679; 95% confidence interval: 0.507-0.909; P = 0.0094) and significantly greater improvements in many secondary outcome measures. Both treatments were well tolerated; the incidence and type of adverse events were similar: most commonly reported (budesonide/formoterol vs formoterol): COPD (8.0% vs 9.4%) and nasopharyngitis (5.5% vs 4.9%). CONCLUSIONS: Budesonide/formoterol 160/4.5 µg two inhalations twice daily was effective and well tolerated in patients with moderate to severe COPD, offering benefits over formoterol alone in terms of improved lung function and reduced risk of exacerbation.
Assuntos
Budesonida/uso terapêutico , Etanolaminas/uso terapêutico , Nebulizadores e Vaporizadores/classificação , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Índice de Gravidade de Doença , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Etanolaminas/efeitos adversos , Feminino , Volume Expiratório Forçado/fisiologia , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do TratamentoRESUMO
INTRODUCTION: This post hoc analysis evaluated the efficacy of indacaterol, a novel inhaled once-daily long-acting ß(2)-agonist, by disease severity (GOLD 2005) in patients with moderate-to-severe COPD from six Asian countries/areas (Hong Kong, India, Japan, Korea, Singapore, Taiwan). METHODS: Data from a 12-week, double-blind, placebo-controlled, parallel-group study in patients randomized to indacaterol 150 µg, indacaterol 300 µg or placebo once daily were analyzed based on baseline disease severity (moderate or severe). Endpoints were: trough FEV(1) (average of 23 h 10 min and 23 h 45 min post-dose values), transition dyspnoea index (TDI) and St George's Respiratory Questionnaire (SGRQ) at Week 12. Safety data were collected. RESULTS: Of 347 patients randomized, 59.7% had moderate, and 40.3% had severe COPD. Least squares means (LSMs) indacaterol-placebo differences in trough FEV(1) at Week 12 exceeded the pre-specified minimal clinically important difference (MCID) of 0.12L and were statistically superior (p < 0.001) for indacaterol (150 µg, 300 µg) versus placebo in the two subgroups [0.19L, 0.20L (moderate); 0.15L, 0.19L (severe) respectively]. LSM TDI scores for both indacaterol doses versus placebo in both subgroups were statistically superior (p < 0.05) and clinically meaningful (≥1 unit). Both indacaterol doses showed improvements in LSM SGRQ total scores at Week 12 which exceeded the MCID (4 units) versus placebo in both subgroups, with indacaterol 300 µg-placebo difference in the severe subgroup being statistically significant (p < 0.01). Overall incidence of adverse events was lower with indacaterol than with placebo across both subgroups. CONCLUSIONS: Indacaterol demonstrated clinically relevant improvements versus placebo in lung function, dyspnea and health status in Asian COPD patients irrespective of disease severity. CLINICAL TRIALS IDENTIFIER: NCT00794157.
Assuntos
Broncodilatadores/administração & dosagem , Indanos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Adulto , Idoso , Ásia/etnologia , Broncodilatadores/efeitos adversos , Método Duplo-Cego , Dispneia/prevenção & controle , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Nível de Saúde , Humanos , Indanos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etnologia , Quinolonas/efeitos adversos , Transtornos do Sono-Vigília/prevenção & controle , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacosRESUMO
BACKGROUND: Pulmonary rehabilitation has generally relieved symptoms, strengthened exercise endurance and improved health-related quality of life (QOL) in patients with COPD, but recovery of pulmonary function remains questionable. This analysis of our innovative rehabilitation program is directed at documenting changes in patients' expiratory airflow limitation, pulmonary symptoms and QOL. This program is designed to provide "respiratory conditioning", a physical therapist-assisted intensive flexibility training that focuses on stretching and rib cage mobilization. METHODS: Thirty-one patients with COPD who attended rehabilitation sessions at Juntendo University Hospital from 1999 to 2006 were analyzed. Pulmonary function, expiratory flow limitation during tidal breathing, six minute walk distance (6MWD), respiratory muscle strength, and St. George Respiratory Questionnaire (SGRQ) were measured before and after pulmonary rehabilitation. RESULTS: In participants ages 68±7 years, the FEV(1)% predicted was 39.3±15.7%. 6MWD, SGRQ and respiratory muscle strength were significantly improved after pulmonary rehabilitation. Although neither FEV(1)% predicted nor FEV(1)/FVC was affected to a significant extent, indicating little effect on airflow limitation, expiratory flow limitation in supine as well as seated during tidal breathing improved significantly. Moreover, rehabilitation significantly diminished TLC% predicted, FRC% predicted, RV% predicted and RV/TLC values, thus indicating a reduction of hyperinflation of the lungs at rest. CONCLUSIONS: The present results suggest that our rehabilitation program with respiratory conditioning significantly lowered the hyperinflation of lungs at rest as well as the expiratory flow limitation during tidal breathing. In patients with COPD, overall pulmonary function improved, exercise endurance increased and health-related QOL was enhanced.
RESUMO
Tulobuterol patch (HokunalinTM Tape), which contains a ß(2)-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. This drug delivery system ensures that the time at which the peak drug concentration in the blood is reached coincides with the morning dip in respiratory function. The use of the patch also prevents excessive increase in blood drug concentrations, thereby reducing the incidence of systemic adverse reactions. Since 1998, when it was first approved in Japan and worldwide, the tulobuterol patch has been used widely in the treatment of bronchial asthma and chronic obstructive pulmonary disease (COPD), and evidence collected since it was approved has confirmed its clinical efficacy and safety. Because the patch is easy to use and requires only once-daily application, treatment adherence of patients using the patch is good. In this article, we discuss the rationale behind the development of the tulobuterol patch, evaluate data on its clinical efficacy and safety in the treatment of asthma and COPD, and examine the treatment adherence in individuals using the patch.