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Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it. Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers. Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence. Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence. [ABSTRACT FROM AUTHOR]

• Smoking and chronic obstructive pulmonary disease are known risk factors of severe COVID-19. • Cumulative smoking exposure was positively associated with COVID-19 outcomes. • In patients aged <65 years, chronic obstructive pulmonary disease affected disease severity in those with >30 pack-years. Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers. [ABSTRACT FROM AUTHOR]

BACKGROUND: COPD is characterized by progressive and irreversible air flow limitations. Single-inhaler therapies (SITTs) incorporating an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β2-agonist have been shown to effectively alleviate symptoms and improve lung function. Fluticasone-furoate/umeclidinium/vilanterol (F/U/V) and budesonide/glyco-pyrronium/formoterol (B/G/F) are available as SITT in Japan. However, the clinical differences between these 2 combinations and the predictors of their proper use have not been established. This study aimed to identify the subject characteristics that could predict the effectiveness of inhaler therapy. METHODS: We assessed the pulmonary function test results of subjects with COPD before and one month after using F/U/V and B/G/F as SITT. Subjects with a difference of 100 mL or more in the FEV1 after treatment with pre-SITT were extracted and divided into the F/U/V effect and no-effect group and B/G/F effect and no-effect group to examine the factors associated with positive outcomes with each inhaler. RESULTS: F/U/V and B/G/F significantly improved the inspiratory capacity (IC), %IC, FVC, and %FEV1 when compared to pre-inter-vention values (P < .001, P = .001, P = .007, P = .009, respectively, for F/U/V; and P = .006, P = .008, P = .038, P = .005, respectively, for B/G/F). Factors associated with FEV1 improvement in F/U/V included lower %IC (odds ratio 0.97 [95% CI 0.94-0.99], P = .03) and a higher modified Medical Research Council (mMRC) dyspnea score (2.36 [1.27-4.70], P < .01). In addition, a higher %IC (1.03 [1.00-1.06], P = .02) and lower mMRC dyspnea score (0.55 [0.28-0.99], P = .041) were predictors for the effectiveness of B/G/F. CONCLUSIONS: Our results showed that SITT significantly improved the IC, %IC, FVC, and %FEV1 when compared to pre-inter-vention and that F/U/V was more effective in subjects with severe symptoms, whereas B/G/F was more effective in subjects with mild symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Symptom status and treatment changes among patients with chronic obstructive pulmonary disease (COPD) using inhaler treatment in real-world clinical settings are not well understood, particularly according to class of treatment. We investigated the proportion of symptomatic patients among those with COPD using inhaler treatment, based on COPD Assessment Test (CAT) scores in clinical practice, and changes in inhaler treatments and symptoms at 1-year follow-up., Methods: This was a retrospective analysis of data from a multicenter, prospective cohort study conducted at medical institutions with respiratory specialists in Japan. The primary endpoint was the proportion of patients with CAT scores ≥ 10 or < 10 in each inhaler treatment group at registration., Results: Of 414 patients in the full analysis set, 76 (18.4%), 261 (63.0%), and 77 (18.6%) were using long-acting muscarinic antagonist (LAMA), LAMA + long-acting β 2 -agonist (LABA), and inhaled corticosteroids (ICS) + LABA, respectively, at registration. The proportions of patients with CAT scores ≥ 10 or < 10 per inhaler treatment group at registration, respectively, were 32.9% and 67.1% in the LAMA group, 55.0% and 45.0% in the LAMA + LABA group, and 50.0% and 50.0% in the ICS + LABA group. Most patients (> 75%) in each inhaler treatment group showed no change in inhaler treatment at 1 year, regardless of their CAT score at registration. Approximately 70-80% of patients with CAT scores ≥ 10 at registration still had CAT scores ≥ 10 at 1 year; 10-30% of patients with CAT scores < 10 at registration had CAT scores ≥ 10 at 1 year., Conclusion: In real-world Japanese clinical practice, a considerable proportion of patients have persistent symptoms (CAT score ≥ 10) despite using mono or dual inhaler treatment; > 75% of symptomatic patients with COPD using inhaler treatment did not undergo treatment escalation at 1-year follow-up and remained symptomatic., Trial Registration: ClinicalTrials.gov identifier, NCT05903989., (© 2024. The Author(s).)

Pulmonary emphysema is predominantly caused by chronic exposure to cigarette smoke (CS). Novel tobacco substitutes, such as heated tobacco products (HTPs), have emerged as healthier alternatives to cigarettes. IQOS, the most popular HTP in Japan, is advertised as harmless compared with conventional cigarettes. Although some studies have reported its toxicity, few in vivo studies have been conducted. Here, 12-wk-old C57BL6/J male mice were divided into three groups and exposed to air (as control), IQOS aerosol, or CS for 6 mo. After exposure, the weight gain was significantly suppressed in the IQOS and CS groups compared with the control ( –4.93 g; IQOS vs. air and –5.504 g; CS vs. air). The serum cotinine level was significantly higher in the IQOS group than in the control group. The neutrophils and lymphocyte count increased in the bronchoalveolar lavage fluid of the IQOS and CS groups compared with those in the control group. Chronic IQOS exposure induced pulmonary emphysema similar to that observed in the CS group. Furthermore, expression levels of the genes involved in the apoptosis-related pathways were significantly upregulated in the lungs of the IQOS-exposed mice. Cytochrome c, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase-1 were overexpressed in the IQOS group compared with the control. Single-stranded DNA and TdT-mediated dUTP nick-end labeling-positive alveolar septal cell count significantly increased in the IQOS group compared with the control. In conclusion, chronic exposure to IQOS aerosol induces pulmonary emphysema predominantly via apoptosis-related pathways. This suggests that HTPs are not completely safe tobacco products. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of airflow obstruction in Japan is 3.8%-16.9%. This epidemiological study based on a large database aimed to reassess the prevalence of airflow obstruction in Japan and the diagnosis rate of chronic obstructive pulmonary disease (COPD)., Patients and Methods: We used data regarding claims from the health insurance union and health checkups provided by JMDC. The present study included a subgroup of individuals aged ≥40 years who underwent health checkups involving spirometry between January and December 2019. The study endpoints were the prevalence of airflow obstruction, COPD diagnosis rate, disease stage, and respiratory function test results., Results: Among 102,190 participants, 4113 (4.0%) had airflow obstruction. The prevalence of airflow obstruction was 5.3% in men and 2.1% in women. Among the study population, 6.8% were current smokers, while 3.4% were never or former smokers. Additionally, the prevalence of COPD increased with age. Approximately 8.4% of participants with airflow obstruction were diagnosed with COPD. Regarding the COPD diagnosis status, participants with airflow obstruction who were diagnosed with COPD were at a more advanced stage than those not diagnosed. Finally, patients diagnosed with COPD had significantly lower FEV 1 /FVC and FEV 1 (p < 0.0001; Wilcoxon rank sum test)., Conclusion: The epidemiological study based on a large database determined the COPD diagnosis rate related to airflow obstruction. The COPD diagnosis rate was extremely low among individuals who underwent health checkups, indicating the need for increased awareness about this medical condition. Moreover, primary care physicians should identify patients with suspected COPD and collaborate with pulmonologists to facilitate the early detection of COPD and enhance the COPD diagnosis rate., Competing Interests: YK, SD, TM, and AS are employees of Kracie, Ltd. GT and TT are affiliated with JMDC Inc. YS and HS received personal fees from Kracie, Ltd. The authors report no other conflicts of interest in this work., (© 2024 Koga et al.)

BACKGROUND: Dyspnea is a common symptom in patients with COPD. It causes physical inactivity and impaired health-related quality of life. Although optimal breathing methods alleviate dyspnea, it is unclear whether breathing instability has a clinical impact on patients with COPD. This study aimed to investigate whether resting breathing instability during wakefulness was associated with dyspnea assessed by the modified Medical Research Council (mMRC) dsypnea scale and whether breathing instability can be a novel predictor of clinical outcomes. METHODS: Forty-four subjects with stable COPD were enrolled (mean age, 71.0 y). Resting breathing was monitored for 15 min by using respiratory inductance plethysmography. Breathing instability was evaluated with the coefficient of variation for breath-by-breath respiratory duration and tidal volume (Embedded Image) by using an artifact-free respiratory signal for 5 min. Pulmonary function testing and blood gas analysis were performed (mean FEV1 percent of predicted, 68.5%). Questionnaires with regard to dyspnea and health-related quality of life were also completed. Exacerbations were recorded prospectively for 1 year after the initial assessment. RESULTS: The coefficients of variation for Embedded Image were significantly higher in the subjects with an mMRC dyspnea scale score ≥ 2 versus those with an mMRC dyspnea scale score < 2 (26.4 ± 7.4% vs 20.3 ± 6.4%, P = .006) . The coefficients of variation for respiratory duration and VT were not associated with age, body mass index, and pulmonary function variables. In multivariate analysis, FEV1 percent of predicted and coefficient of variation for Embedded Image remained significant predictors for an mMRC dyspnea scale score ≥ 2 (P = .004 and P = .01, respectively). Coefficient of variation values were also correlated with several health-related quality of life domains. The exacerbation frequency was associated with the coefficient of variation for Embedded Image. CONCLUSIONS: Resting breathing pattern during wakefulness is a novel assessment tool for severity of dyspnea, which can be one of the predictors for exacerbation in patients with COPD. [ABSTRACT FROM AUTHOR]

BACKGROUND: A recent paper reported that low muscle mass in the erector spinae muscles (ESM) was strongly associated with poor prognosis and declining muscle mass over time in subjects with COPD. However, effects of pulmonary rehabilitation (PR), if any, on ESM mass have not been reported. We hypothesized that PR reduces the annual decline in ESM mass. METHODS: This was a retrospective cohort study. Thirty-nine subjects with COPD who received PR and underwent chest computed tomography before and after PR were evaluated (rehabilitation group). We also evaluated 39 age-matched subjects with COPD who did not receive PR (nonrehabilitation group). Data were collected from August 2010 until March 2020 in both groups. The ESM cross-sectional area (ESMCSA) was measured using axial computed tomography images, and annual changes were calculated. The 6-min walk distance (6MWD) was measured before and after PR; the minimum clinically important difference was defined as 30 m. RESULTS: ESMCSA declined in the nonrehabilitation group over time (-116.0 ± 141.2 mm²/y) but increased in the PR group (51.0 ± 95.3 mm2/y; P < .001). The annual increase in ESMCSA was significantly higher among subjects with an increase in 6MWD that exceeded the minimum clinically important difference compared with nonresponders in the rehabilitation group. The annual change in ESMCSA was negatively correlated with comorbidity index, and triple therapy (long-acting β2-agonist/long-acting muscarinic antagonist/inhaled corticosteroid) had a favorable effect on annual change in ESMCSA. Multiple regression analysis revealed that only PR was an independent factor for annual change in ESMCSA. CONCLUSIONS: ESM mass was shown to decline yearly in subjects with COPD. The annual decline in muscle mass was reduced by PR. [ABSTRACT FROM AUTHOR]

Background: Assistive use of short-acting ß2 agonists (SABAs) reportedly improves exercise tolerance, activities of daily living, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). However, the effect of SABA on physical activity (PA) is unclear. Objective: This study aimed to determine whether assistive use of SABA increases PA and whether additional pulmonary rehabilitation (PR) can aid further improvement. Methods: Twelve outpatients with COPD and dyspnea during daily activities despite regular use of long-acting bronchodilators were enrolled. This study comprised a 2-week pre-intervention investigation, a 12-week investigation of SABA effects, and an 8-week investigation of the additional effects of PR. Assistive use of SABA was allowed up to 4 times per day after the pre-intervention period. PA was measured for 14 consecutive days using an accelerometer sensor. Dyspnea, exercise tolerance, and HRQOL were evaluated at entry, at 4 and 12 weeks after initiating SABA use, and after completing PR. Results: Assistive use of SABA improved breathlessness during daily activities and increased PA (p < .001). PA and HRQOL were also improved following PR (p < .001 and p = .013, respectively). Conclusions: Combined therapy of SABA and PR can increase PA and HRQOL in COPD patients. [ABSTRACT FROM AUTHOR]

Primary palliative care is essential for the continuity of care in severe COPD. This study aimed to identify essential factors and aspects to enhance the quality of primary palliative care for adults with severe COPD living in the community. Interviews with medical professionals from six institutions located in two major metropolitan areas in Japan were conducted, and these interviews were analyzed by using a qualitative content analysis approach. Results indicate that effective collaborative communication among team members, long-term care insurance system and related services, and palliative care techniques were the primary themes. [ABSTRACT FROM AUTHOR]

Background: Navafenterol (AZD8871) is a novel, long-acting, dual-pharmacology (muscarinic receptor antagonist and β2-adrenoceptor agonist) molecule in development for chronic obstructive pulmonary disease and asthma.Methods: These two phase I, randomised, single-blind, multiple-ascending-dose studies evaluated inhaled navafenterol and placebo (3:1 ratio) in healthy, male, non-Japanese (study A; NCT02814656) and Japanese (study B; NCT03159442) volunteers. In each study, volunteers were dosed in three cohorts, allowing gradual dose escalation from 300 μg to 600 μg to 900 μg. The primary objective was to investigate the safety and tolerability of navafenterol at steady state. Pharmacokinetics were also assessed.Results: Twenty-four volunteers completed each study (navafenterol, n = 6; placebo, n = 2 in each cohort). There were no deaths, serious adverse events (AEs) or treatment-emergent AEs (TEAEs) leading to discontinuation of navafenterol. The most frequent TEAEs were vessel puncture-site bruise (placebo, n = 2; navafenterol 900 μg; n = 3) in study A and diarrhoea (placebo, n = 1; navafenterol 300 μg, n = 2; navafenterol 900 μg, n = 3) in study B. No dose-response relationship was observed for TEAEs. There was a dose-dependent increase in mean heart rate on day 16 in both studies. The pharmacokinetics of navafenterol were similar between non-Japanese and Japanese volunteers.Conclusions: Multiple ascending doses of navafenterol were well-tolerated and the safety and pharmacokinetics of navafenterol were similar in non-Japanese and Japanese volunteers. The findings support navafenterol clinical development.Trial Registration: ClinicalTrials.gov ; Nos.: NCT02814656 and NCT03159442; URL: www.clinicaltrials.gov . [ABSTRACT FROM AUTHOR]

While machine learning approaches can enhance prediction ability, little is known about their ability to predict 30-day readmission after hospitalization for Chronic Obstructive Pulmonary Disease (COPD). We identified patients aged ≥40 years with unplanned hospitalization due to COPD in the Diagnosis Procedure Combination database, an administrative claims database in Japan, from 2011 through 2016 (index hospitalizations). COPD was defined by ICD-10-CM diagnostic codes, according to Centers for Medicare and Medicaid Services (CMS) readmission measures. The primary outcome was any readmission within 30 days after index hospitalization. In the training set (randomly-selected 70% of sample), patient characteristics and inpatient care data were used as predictors to derive a conventional logistic regression model and two machine learning models (lasso regression and deep neural network). In the test set (remaining 30% of sample), the prediction performances of the machine learning models were examined by comparison with the reference model based on CMS readmission measures. Among 44,929 index hospitalizations for COPD, 3413 (7%) were readmitted within 30 days after discharge. The reference model had the lowest discrimination ability (C-statistic: 0.57 [95% confidence interval (CI) 0.56–0.59]). The two machine learning models had moderate, significantly higher discrimination ability (C-statistic: lasso regression, 0.61 [95% CI 0.59–0.61], p = 0.004; deep neural network, 0.61 [95% CI 0.59–0.63], p = 0.007). Tube feeding duration, blood transfusion, thoracentesis use, and male sex were important predictors. In this study using nationwide administrative data in Japan, machine learning models improved the prediction of 30-day readmission after COPD hospitalization compared with a conventional model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spiritual care for patients with COPD has rarely been discussed, and thus much remains unknown about their needs. The aims of this study were to identify the factors associated with spiritual well-being and to compare the levels of spiritual well-being between subjects with advanced COPD and those with inoperable lung cancer. METHODS: A total of 96 subjects with COPD or lung cancer participated in this study, which was conducted between December 2014 and April 2016. Measures included the Japanese version of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, the McGill Quality of Life Questionnaire (MQOL), the modified Medical Research Council (mMRC) dyspnea scale, and various other medico-social factors. RESULTS: No significant differences were found between subjects with COPD and those with lung cancer in median FACIT-Sp-12 scores (COPD, 27; lung cancer, 26; P = .81). However, significant differences were found in the 2 MQOL domains, suggesting that subjects with COPD had a better psychological state (P = .01) and that subjects with lung cancer had a better support state (P = .002). Multiple regression analysis revealed that mMRC was significantly associated with FACIT-Sp-12 scores in subjects with COPD. CONCLUSIONS: These results suggest that subjects with advanced COPD experience spiritual well-being similar to that of subjects with inoperable lung cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the course of therapy of patients with COPD, non-pharmacologic treatment, such as rehabilitation, plays an important role. Although some studies have provided concrete evidence of the effectiveness of rehabilitation in improving functional outcomes in subjects with COPD, evidence of its mortality-reducing effect has been insufficient. In the present study, we examined whether rehabilitation had positive effects on in-hospital mortality of subjects with COPD. METHODS: We used the Japanese Diagnosis Procedure Combination nationwide administrative claims database. This was a retrospective cohort study, and there were 18,037 eligible subjects with COPD from 1,055 hospitals. The main outcome was in-hospital mortality rates. A one-to-one propensity score matching method was used to compare hospital mortality rates after admission between rehabilitation and non-rehabilitation groups. RESULTS: A total of 3,356 pairs of subjects were selected from the rehabilitation and non-rehabilitation groups (n = 6,712). Subjects in the rehabilitation program showed a reduction in the odds of mortality (odds ratio = 0.80, 95% CI 0.65-1.00, P = .045). In the subgroup analyses, the rehabilitation group had a lower in-hospital mortality in the pre-obese subgroup (body mass index 25.0-29.9) than the non-rehabilitation group (P = .02). Although not significant, the rehabilitation group showed a relatively low in-hospital mortality in the Hugh-Jones dyspnea scale class 5 subgroup (P - .066). CONCLUSIONS: This large nationwide cohort study showed that rehabilitation indeed contributed to a reduction of in-hospital mortality. These findings underscore the importance of adopting rehabilitation as part of the treatment of COPD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Advanced air-flow limitation in patients with COPD leads to a reduction in vital capacity, respiratory muscle strength, and exercise capacity. However, its impact on chest and abdominal wall mobility is unknown. This study aimed to ascertain the prevalence of patients with COPD with reduced chest and abdominal wall mobility and to investigate the effect of reduced chest and abdominal wall mobility on pulmonary function, respiratory muscle strength, and exercise capacity. METHODS: In 51 elderly male subjects with COPD, chest and abdominal wall mobility, FVC, FEV1, FEV1/FVC, maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the 6-min walk distance (6MWD) were assessed. Chest and abdominal wall mobility were measured using the breathing movement scale (0-8) at the 3 regions (upper chest, lower chest, and abdomen). Reduced mobility was defined as a value lower than the lower limit of the normal scale. The unpaired t test, Mann-Whitney test, and multiple regression analysis were performed. RESULTS : The percentages of subjects with reduced mobility were 78% for the upper chest, 76% for the lower chest, and 53% for the abdomen. The subjects with reduced mobility had significantly low FVC, FEV1 and 6MWD in each region and significantly low FEV1/FVC, PImax, and PEmax in the abdominal region compared with those with nonreduced mobility. FVC and 6MWD were independently associated with the scale values in each region and with the abdominal scale value, respectively. CONCLUSIONS: The majority of subjects with COPD had reduced chest and abdominal wall mobility, which was independently associated with FVC. Even though abdominal wall mobility was relatively preserved compared with chest wall mobility, it was also independently associated with 6MWD. [ABSTRACT FROM AUTHOR]

• Mortality risk of chronic obstructive pulmonary disease (COPD) was examined. • Older adults with screened COPD had an increased three-year mortality risk. • The mortality risk of COPD was found even after adjusting for socioeconomic factors. • The risk was higher among those with lower education and less social relationship. : Chronic obstructive pulmonary disease (COPD) is a common disease among older adults, leading to mortality. Although COPD is also associated with socioeconomic factors, little is known about the impact of COPD on mortality accounting for them. We examined the association between COPD and mortality among older male adults, adjusting for socioeconomic factors. : This study recruited functionally independent male older adults from the Japan Gerontological Evaluation Study. Participants answered self-reported questionnaires mailed in 2013, followed up to 2016. Participants with COPD were screened as those with higher scores than the upper quantile of the modified International Primary Care Airway Group questionnaire. Regarding individual socioeconomic factors, educational attainment, household equivalized income, living arrangements, and social participation was assessed. The Cox proportional hazards model was applied to examine the association between screened COPD and mortality. : Data of 6,662 male older adults were analyzed (mean age [standard deviation]: 73.0 [5.8] years). During the observation periods, 394 deaths (5.9%) occurred. Screened COPD was associated with an increased mortality risk, even after adjusting for socioeconomic factors (hazard ratio, 1.56; 95% confidence interval, 1.25–1.94). In the stratified analysis among current smokers, the mortality risk of screened COPD was high in those with lower education, higher income, living alone, and less social participation. : Those with screened COPD had an increased mortality risk, even after adjusting for socioeconomic factors. The risk was higher among those with lower education and less social relationships. Detection and treatment of COPD should be performed considering individual socioeconomic backgrounds. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although it is useful for COPD patients to relieve their dyspnea by bracing their arms, the relationships between the arm bracing posture and expiratory flow limitation (EFL) and lung volume are unknown. Whether arm bracing affects dyspnea, EFL, and lung volume in elderly COPD patients was investigated. METHODS: Sixteen elderly subjects (median [interquartile range] age 81 [77-85] y) with stable COPD (percent-of-predicted FEV, 50.9 [31.3-64.9] %) and 16 age-matched healthy subjects were studied. Breathing patterns, EFL, lung volume, ..., and heart rate during quiet breathing were randomly evaluated in 3 standing postures: erect, leaning forward, and arm bracing. Dyspnea was also assessed for each posture with a Borg dyspnea score at the end of the test. RESULTS: Lung volume was significantly higher with arm bracing than with the other postures in both groups (P < .05). Breathing patterns, ..., and pulse rate were not significantly different among the 3 postures in both groups. However, EFL and Borg dyspnea scores were significantly lower with arm bracing than with the other postures in COPD subjects (P < .01). CONCLUSIONS: The decreased EFL in the arm bracing position may be caused by breathing at a higher lung volume than in the erect position, which may be one of the factors relieving dyspnea in elderly COPD patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although recent studies have shown that distractive auditory stimuli (DAS) in the form of music increase adherence to exercise in subjects with COPD, the effect of DAS on dyspnea induced by low-intensity, constant-load exercise in elderly patients with COPD has not been elucidated. Therefore, the purpose of this study was to investigate the effect of DAS on the perception of dyspnea induced by low-intensity, constant-load exercise in elderly subjects with COPD. METHODS: We enrolled 16 male out-patients with COPD. Subjects completed cycling exercises with and without DAS at 40% maximum oxygen consumption. They were asked to rate their perception of dyspnea using the modified Borg scale every 3 min during exercise and every 1 min during the recovery period. RESULTS: Dyspnea perception during low-intensity exercise showed a significant correlation between the exercise condition (DAS and control) and exercise duration (P = .04). Exercise-induced dyspnea perception under the DAS condition was significantly lower than that under the control condition from 18 min after the start of exercise to 3 min after the end of exercise (18, 20, 21, 22, and 23 min, P = .01, P < .001, P = .009, P = .006, and P = .006, respectively). However, oxygen consumption and ventilation in response to low-intensity exercise did not significantly differ in the DAS and control conditions (P = .39 and .14, respectively) CONCLUSIONS: Our results suggest that DAS is a non-pharmacologic therapy that can be used to reduce the dyspneic sensation in elderly patients with COPD. [ABSTRACT FROM AUTHOR]

Background:A close relationship between upper and lower respiratory tract diseases has been reported. However, little is known about pulmonary function in patients with upper respiratory tract diseases.Methods:Pulmonary function was measured in: 68 patients with chronic rhinosinusitis without nasal polyps, 135 patients with chronic rhinosinusitis with nasal polyps, 89 patients with allergic rhinitis and 100 normal control subjects. The relationships between pulmonary function and clinical parameters were assessed. These parameters included radiographic severity of chronic rhinosinusitis, serum total immunoglobulin E levels, concentrations of cytokines in nasal secretions and exhaled nitric oxide levels.Results:The pulmonary function of patients with chronic rhinosinusitis was significantly affected. The level of interleukin-5 in nasal secretions was significantly correlated with pulmonary function in patients with chronic rhinosinusitis.Conclusion:The findings indicated latent obstructive lung function changes in chronic rhinosinusitis patients. The cytokines in nasal secretions might be related to obstructive lung function changes in chronic rhinosinusitis. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Assessment of the degree of air-flow obstruction is important for determining the treatment strategy in COPD patients. However, in some elderly COPD patients, measuring FVC is impossible because of cognitive dysfunction or severe dyspnea. In such patients a simple test of airways obstruction requiring only a short run of tidal breathing would be useful. We studied whether the spontaneous expiratory flow-volume (SEFV) curve pattern reflects the degree of airflow obstruction in elderly COPD patients. METHODS: In 34 elderly subjects (mean ± SD age 80 ± 7 y) with stable COPD (percent-of-predicted FEV1 39.0 ± 18.5%), and 12 age-matched healthy subjects, we measured FVC and recorded flow-volume curves during quiet breathing. We studied the SEFV curve patterns (concavity/convexity), spirometry results, breathing patterns, and demographics. The SEFV curve concavity/convexity prediction accuracy was examined by calculating the receiver operating characteristic curves, cutoff values, area under the curve, sensitivity, and specificity. RESULTS: Fourteen subjects with COPD had a concave SEFV curve. All the healthy subjects had convex SEFV curves. The COPD subjects who had concave SEFV curves often had very severe airway obstruction. The percent-of-predicted FEV1% (32.4%) was the most powerful SEFV curve concavity predictor (area under the curve 0.92, 95% CI 0.83-1.00), and had the highest sensitivity (0.93) and specificity (0.88). CONCLUSIONS: Concavity of the SEFV curve obtained during tidal breathing may be a useful test for determining the presence of very severe obstruction in elderly patients unable to perform a satisfactory FVC maneuver. [ABSTRACT FROM AUTHOR]

To substantiate the beneficial effects of switching from cigarette smoking to heated tobacco products (HTP), this study conducted a time-trend analysis using data from the Japanese Medical Data Center (JMDC) database. Specifically, we assessed hospitalization numbers for chronic obstructive pulmonary disease (COPD) exacerbations and acute ischemic heart disease (IHD) before and after the introduction of HTPs in the Japanese market. This study replicated a previous study using a different Japanese real-world data source (Medical Data Vision). We retrieved the number of hospitalizations associated with the International Classification of Diseases-10 codes for COPD and IHD from 2010 to 2019-5 years before to 4 years after introducing HTPs in the Japanese market-from the JMDC database. Then, we used interrupted time-series analyses to test the hypothesis that the introduction of HTPs is associated with a reduction in hospitalizations for COPD (all codes), COPD exacerbation, COPD exacerbation plus lower respiratory tract infections (LRTI), and IHD, adjusting for age, sex, seasonality, and flu vaccination rates. Analysis of all available data from the JMDC database revealed a significant reduction in the number of hospitalizations for COPD (all codes; P = 0.0001) and IHD using Diagnosis Procedure Combination data on causative disease flags ( P < 0.00001). We also observed a non-significant reduction in hospitalizations for COPD plus LRTI as well as IHD after HTP introduction in Japan. This study confirmed the findings of our previous study where a decrease in hospitalizations due to COPD exacerbation after the introduction of HTPs in Japan was also shown. Nevertheless, these findings warrant further research to evaluate the impact of HTPs on the health of populations in other countries where these products have been introduced., Competing Interests: AP, MA, AR-K, MH, and AH are employees of Philip Morris International., (Copyright © 2022 van der Plas, Antunes, Romero-Kauss, Hankins and Heremans.)

BACKGROUND: In patients with COPD, early detection and rapid treatment are essential to prevent its progression and exacerbations. OBJECTIVE: To identify factors that delay COPD detection. METHODS: We conducted a cross-sectional study of elderly COPD patients and healthy subjects in rural Japan. We measured respiratory and physical function (hand grip force, maximum inspiratory pressure, maximum expiratory pressure, total trace length, and toe grasp force), walking ability, and quality of life (QOL, measured with a visual analog scale). We conducted spirometry in 408 subjects, whom we divided into 2 groups: those whose ratio of FEV1 to forced vital capacity (FVC) was < 70% (the airway-obstruction group, n = 60), and those whose FEV1/FVC was ≥ 70% (the healthy-subjects group, n = 348). To avoid confounding, we then matched 60 subjects from the healthy-subjects group to the 60 in the airway-obstruction group for age, sex, height, and smoking history, so both groups had 60 subjects. RESULTS: Physical function was significantly inferior in the airway-obstruction group. Variables reflecting instantaneous walking ability (maximum walking speed and walking time in the 10-m hurdle walk) were significantly inferior in the airway-obstruction group, but there were no significant differences in 6-min-walk test, which reflects walking endurance, or in QOL. CONCLUSIONS: Walking endurance, QOL, and proximal muscle strength in the extremities of patients with COPD were well preserved, which prevented detection of COPD and hampered the subjects' motive for seeking medical care. In consequence, lack of awareness impeded the early detection of COPD. In primary healthcare for the general elderly population, spirometry is much easier to conduct than physical function tests, so we recommend that spirometry screening programs for early-stage COPD detection and staging. [ABSTRACT FROM AUTHOR]

Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days). Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 µg) or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h) and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years), 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 µg, respectively (P < 0.001). The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points). All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 µg) provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. [ABSTRACT FROM AUTHOR]

Background and objective: Symptom-based questionnaires may be helpful in diagnosing patients with COPD. The aim of this study was to determine whether two COPD questionnaires designed in Western countries were applicable to Japanese and other Asian patients. Methods: The participants were Japanese people aged 40 years and over. Each subject answered questions on demographics and symptoms and underwent spirometry before and after administration of a bronchodilator. Questionnaire A was designed to identify previously undiagnosed COPD and questionnaire B was designed to differentiate between COPD and asthma. Results: The numbers of COPD patients who answered questionnaires A and B were 33 of 169 (19.5%) and 112 of 168 (66.7%), respectively. Comparison of the COPD group with the non-COPD group revealed a significant difference in total score in both questionnaire A and questionnaire B (both P < 0.001). The area under the receiver operating characteristic curve (AUC-ROC) for questionnaire A was 0.791. With a cut-off value of 16.5 points, the sensitivity and specificity were 0.939 and 0.404, and with a 19.5-point cut-off, sensitivity and specificity were 0.848 and 0.647, respectively. The AUC-ROC for questionnaire B was 0.765. With cut-off values of 18.5 and 24.5 points, the respective sensitivities and specificities were 0.946 and 0.393, and 0.741 and 0.607. Conclusions: A simple self-administered questionnaire can help to diagnose COPD in Japanese subjects. When these questionnaires are used in Japan, cut-off values should be set somewhat higher than in Western countries. [ABSTRACT FROM AUTHOR]

Background: Injectable methylxanthines are useful drugs in the treatment of asthma. The Asthma Prevention and Management Guidelines (JGL) that are followed in Japan recommend the use of sustained-release theophylline to control the disease and use of injectable methylxanthines to alleviate symptoms. In contrast, the guidelines followed in the west do not promote theophylline use due to safety concerns, and the use of injectable methylxanthines in particular are not recommended. We thus conducted a study on adult patients with bronchial asthma or chronic obstructive pulmonary disease treated with theophylline and injectable methylxanthines in Japan in order to assess the safety of these drugs. Methods: 876 patients were surveyed at 55 medical institutions by the Committee on the Safety of Sustained-Release Theophylline and Injectable Methylxanthines (CST) of the Committee for Asthma Prevention and Management Guidelines of the Japanese Society of Allergology (JSA). 682 of the patients were evaluated for safety. Results: Adverse reactions including facial flushing, palpitations, headache, tinnitus, diaphoresis, nausea, vomiting and tachycardia were reported by only 2 (0.29%) of the 682 patients, but none of these were serious. Conclusions: The results confirm that injectable methylxanthines are safe, when used in accordance with the JGL. [ABSTRACT FROM AUTHOR]

Objective To evaluate the long-term safety and efficacy of indacaterol/glycopyrronium (IND/GLY) in patients with chronic obstructive pulmorary disease (COPD) in a real-world setting in Japan. Methods This 52-week, multicentre, post-marketing surveillance conducted in Japan between December 2013 and August 2019 included patients using IND/GLY for the first time to relieve airway obstructive disorder-related symptoms. Safety outcomes included the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), and serious ADRs during the 52-week period. The incidence of priority variables, including cardiovascular/cerebrovascular (CCV) AEs, β-adrenergic-related or anticholinergic AEs and cough, was also assessed. Safety outcomes were also evaluated in elderly patients. Efficacy outcomes included a physician's global assessment, COPD assessment test (CAT) and lung function test. Results Of the 1,167 patients registered, 1,108 were included in the safety and efficacy analysis. In the safety analysis population, the incidence of AEs was 13.54%, that of SAEs was 4.69%, that of ADR was 3.61%, and that of serious ADRs was 0.36% over 52 weeks. CCV AEs, β-adrenergic-related and anticholinergic AEs and cough were reported as 2.62%, 1.99% and 0.63%, respectively. The physician's global assessment showed that the overall response rate at the last assessment was 74.19%. The mean (95% confidence interval) CAT scores decreased from the start of treatment to Week 52 with IND/GLY [-6.9 (-7.8 to -6.1)]. The lung function (FEV 1 and FVC) improved over time from the start of IND/GLY to Week 52. Conclusion IND/GLY demonstrated a good long-term safety profile in a real-world setting in Japanese patients with COPD, with beneficial effects in terms of the lung function and symptoms in clinical use.

Background: To improve physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD), providing a target PA value based on the individual patient's condition may be a useful interventional strategy. However, to determine the target value, a predictive PA value for each patient is required., Research Question: What is the reference equation consisting of PA-related factors to determine the predictive PA value for each patient with COPD?, Material and Methods: In this prospective cross-sectional observational study, we measured the PA with a triaxial accelerometer and several other factors including demographic factors, pulmonary function, dyspnea, exercise capacity, muscle strength, nutrition, and indicators of several comorbidities in stable Japanese outpatients with COPD aged ≥40 years old and detected PA-related factors by a multiple regression analysis and stepwise method. We created reference equations for four indices of PA using multiple linear regression equations., Results: Two hundred and twenty-seven patients were registered. The equations of duration at ≥2.0 metabolic equivalents (METs) and step count consisted of 4 factors: 6-minute walk distance, modified Medical Research Council dyspnea scale, anxiety score of the Hospital Anxiety and Depression Scale, and the forced expiratory volume in 1 second % of predicted value. Those of duration at ≥3.0 METs and total activity at ≥3.0 METs consisted of 5 factors: the above 4 factors and age or brain natriuretic peptide. There was no fixed bias or proportional bias between the measured and predictive values in patients with non-high measured PA values., Conclusion: We determined reference equations for four indicators of PA using PA-related factors in Japanese patients with COPD. The predictive values calculated using the equations could be useful for deciding target PA values for each patient., Clinical Trial Registration: UMIN-CTR; No.: UMIN000025459; URL: https://www.umin.ac.jp/ctr/index.htm., Competing Interests: YM received lecture fee from Nippon Boehringer Ingelheim. Other authors have no conflicts of interest., (© 2021 Minakata et al.)

There is a concern that persons with underlying respiratory disease may have increased susceptibility to COVID-19 and/or increased severity/mortality if infected. However, information regarding such patients during the first wave of the epidemic is lacking in Japan. We surveyed chest physicians nationwide, and collected anonymous data concerning 1444 patients. Among COVID-19 patients, the prevalence of asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILD) was 3.4%, 4.8%, and 1.5%, respectively. Among COVID-19 patients with these 3 comorbidities, exacerbation of the comorbidity occurred in 12.2%, 18.8%, and 36.4%, respectively, and mortality (6.2% overall) was 4.1%, 13.0%, and 31.8%, respectively. The prevalence of asthma among COVID-19 patients was not higher than that for the general population, and mortality in COVID-19 patients with asthma was not higher than mortality in COVID-19 patients without underlying respiratory disease. COVID-19 patients having COPD or ILD had relatively high mortality, especially for ILD., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objective Evidence concerning the safety and efficacy of indacaterol maleate in a real-life setting is limited. The objective of this post-marketing surveillance was to evaluate the real-life safety and efficacy of indacaterol maleate in Japanese patients with chronic obstructive pulmonary disease (COPD). Methods This was a 52-week post-marketing surveillance conducted between April 2012 and December 2018. The safety endpoints included the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs). The efficacy endpoints included the physician-reported global evaluation of treatment effectiveness (GETE), change from baseline in the COPD assessment test (CAT) results, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), and %FEV 1 following 4, 12, 26, and 52 weeks of indacaterol administration. Results Of the 1,846 enrolled patients, 1,726 were included in the safety and efficacy analyses. The mean age of the patients was 72.5 years old. Cough, pneumonia and COPD worsening were the most common AEs reported, while pneumonia (1.04%) was the most common SAE, and cough (1.68%) was the most common ADR. GETE showed that 69.70% of patients achieved an excellent/good/moderate response following indacaterol treatment. The CAT score decreased, and lung function parameters (FVC, FEV 1 and %FEV 1 ) improved across all the COPD stages following treatment with indacaterol. Conclusion Indacaterol showed a favorable safety and tolerability profile in Japanese patients with COPD without new safety signals observed in real-life settings. These findings demonstrated that indacaterol is an effective maintenance treatment in real-life practice for Japanese patients with COPD.

The Japanese Respiratory Society (JRS) has recommended spirometry for the diagnosis of respiratory diseases. It is indispensable for the confirmation of airflow obstruction by spirometry in chronic obstructive pulmonary disease (COPD) diagnosis. However, the coronavirus disease 2019 (COVID-19) pandemic has made it difficult for many clinics to perform spirometry as it may lead to possible aerosol infections. Thus, the diagnosis of COPD, especially in the early stage, has become difficult. To overcome this situation, JRS issued a "Flowchart of Working Diagnosis and Management of COPD during the COVID-19 Pandemic". This flowchart may help physicians provisionally diagnose COPD patients without performing spirometry, offering them appropriate intervention even in epidemic and pandemic situations., Competing Interests: Conflict of Interest Yoko Shibata: Lecture fees; GSK Japan, Boehringer Ingelheim Japan, AstraZeneca Japan, and Novartis Japan. Advisory Board: GSK Japan. Shigeo Muro: Honorarium from Boehringer Ingelheim Japan, AstraZeneca Japan, and Novartis Japan. Advisory Board: GSK Japan and AstraZeneca Japan. Akihito Yokoyama: Honorarium from Boehringer Ingelheim Japan, AstraZeneca Japan, GSK Japan, Sanofi Japan, and Novartis Japan. Shu Hashimoto: Lecture fees; AstraZeneca Japan, Boehringer Ingelheim Japan., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) are complex and heterogeneous diseases that share clinical characteristics (phenotypes) and molecular mechanisms (endotypes). Whilst physicians make clinical decisions on diagnostic groups, for some such as ACO there is no commonly accepted criteria. An alternative approach is to evaluate phenotypes and endotypes that are considered to respond well to a specific type of treatment ("treatable traits") rather than diagnostic labels., Purpose: The prospective, longitudinal, and observational TRAIT study will evaluate disease characteristics, including both phenotypes and endotypes, in relation to the presentation of obstructive respiratory disease characteristics in patients diagnosed with asthma, COPD, or ACO in Japan, with the aim of further understanding the clinical benefit of a treatable traits-based approach., Patients and Methods: A total of 1500 participants will be enrolled into three cohorts according to their treating physician's diagnosis of asthma, COPD, or ACO at screening. Part 1 of the study will involve cross-sectional phenotyping and endotyping at study enrollment. Part 2 of the study will evaluate the progression of clinical characteristics, biomarker profiles, and treatment over a 3-year follow-up period. The follow-up will involve three annual study visits and three telephone calls scheduled at 6-month intervals. A substudy involving 50 participants from the asthma cohort (in which the ratio will be approximately 1:1 including 25 participants with a smoking history of ≥10 pack-years and 25 participants with no smoking history), 100 participants from the ACO cohort, and 100 participants from the COPD cohort will evaluate disease phenotypes using inspiratory and expiratory computed tomography scans., Conclusion: TRAIT will describe clinical characteristics of patients with obstructive respiratory diseases to better understand potential differences and similarities between clinical diagnoses, which will support the improvement of personalized treatment strategies., Competing Interests: This is a prospective, three-group cohort study with no study treatment intervention administered to participants. Nobuyuki Hizawa received scholarship donation (research grant) from GSK in 2018 and lecture fees from GSK, AstraZeneca, and Novartis. Koichi Fukunaga received personal fees from AstraZeneca and Boehringer Ingelheim. Hisatoshi Sugiura received lecture fees from GSK, AstraZeneca, Novartis, and Boehringer Ingelheim. Yasutaka Nakano received personal fees from Nippon Boehringer Ingelheim, GSK, Novartis, Shionogi, Kyorin Pharmaceutical, Daiichi Sankyo, Chugai Pharmaceutical, Eli Lilly Japan, Sumitomo Dainippon Pharma, Eisai, Olympus, and AstraZeneca. Motokazu Kato received lecture fees from GSK. Yutaro Sugiyama and Tomohiro Hanazawa are GSK employees. Toshihiko Kaise, Paul W Jones, Neil Barnes, Chris Compton, and Takeo Ishii are GSK employees and hold stocks/shares in GSK. Ruth Tal-Singer was a GSK employee at the time of the study, holds stocks/shares in GSK, and received personal fees from Immunomet, Vocalis Health, Teva, and Ena Respiratory and Ena Therapeutics. The authors report no other conflicts of interest in this work., (© 2021 Hizawa et al.)

Purpose: A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed and untreated even though they may have a burden of respiratory symptoms that impact quality of life. The OCEAN study assessed the ability of screening questionnaires to identify individuals with, or at risk of, COPD by comparing questionnaire outcomes with spirometric measures of lung function., Methods: This observational study included participants ≥40 years of age presenting for their annual health examination at a single medical center in Okinawa, Japan. Participants completed COPD screening questionnaires (CAPTURE and COPD-Q), the Chronic Airways Assessment Test (CAAT), and general demographic and health-related questionnaires. The performance characteristics of CAPTURE and COPD-Q were compared with spirometry-based airflow limitation by calculating the area under the receiver operating characteristic (ROC-AUC) curve., Results: A total of 2518 participants were included in the study; 79% of whom were <60 years of age (mean 52.0 years). A total of 52 (2.1%) participants had airflow limitation defined as forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) <0.7, and 420 (16.7%) participants were classified as Preserved Ratio Impaired Spirometry (PRISm). Among participants with PRISm, 75 (17.9%) had a CAAT total score ≥10. Airflow limitation and PRISm were more prevalent in current smokers versus past smokers. For the CAPTURE questionnaire, ROC-AUC for screening airflow limitation, PRISm, and PRISm with a CAAT total score ≥10 were 0.59, 0.55, and 0.69, respectively; for COPD-Q, these three clinical features were 0.67, 0.58 and 0.68, respectively., Conclusion: This study demonstrated that CAPTURE and COPD-Q appear to be effective screening tools for identifying symptomatic individuals with undiagnosed, or at risk of developing COPD in adults ≥40 years of age in Okinawa. Furthermore, early diagnosis and management of PRISm is important to improve future outcomes and the societal burden of disease., Competing Interests: Kentaro Tamaki, Eishin Sakihara, Hiroaki Miyata, and Norimichi Hirahara belong to the association/institution that received funding for this study from GSK. Takeo Ishii, Shoko Akiyama, Toshihiko Kaise, Masayuki Katsumata and Ryosuke Tawara are employees of GSK and hold shares in GSK. Mei Haruya, Oksana Kirichek and Edgar P. Simard are former employees of GSK. Bruce E. Miller and Ruth Tal-Singer are former employees of GSK and hold shares in GSK. Ruth Tal-Singer reports personal fees from Ena Respiratory, Immunomet, Vocalis Health, and Teva. The authors report no other conflicts of interest in this work., (© 2021 Tamaki et al.)

Introduction: Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) present with chronic respiratory symptoms with features of both asthma and COPD. New ACO diagnostic criteria (2018) were suggested by the Japanese Respiratory Society (JRS). This prospective, multicenter, observational cohort study was conducted to investigate the proportion of patients who meet the JRS ACO diagnostic criteria among COPD patients in clinical practice., Methods: This 2-year ongoing study enrolled consecutive outpatients aged ≥ 40 years with COPD who visited one of 27 Japanese centers at which the medical examinations/tests required for ACO diagnosis were routinely conducted. At registration, the proportion of ACO or non-ACO patients was determined using the JRS diagnostic criteria, and the characteristics of the two groups were compared using analysis of variance and chi-square test., Results: Of 708 COPD patients analyzed at registration, 396 (55.9%) had the data necessary for ACO diagnosis to be conducted, and 312 (44.1%) were lacking these data. Of the 396 patients who had the data necessary for ACO diagnosis, 101 (25.5%) met the diagnostic criteria for ACO, and 295 (74.5%) did not (non-ACO patients). ACO patients were younger, had a greater rate of asthma based on a physician's diagnosis, and used more medications, including inhaled corticosteroids (p < 0.05), compared with non-ACO patients., Conclusions: We have determined the proportion of patients with the data necessary to diagnose ACO using the JRS criteria, and the proportion of these who met the ACO criteria among the COPD population at the time of registration. Patients, including those lacking necessary examination/test data at registration, will continue to undergo follow-up to explore changes in their testing and ACO diagnostic status over time. Analyses of study data over 2 years will provide relevant information on the ACO symptoms, clinical course, and real-world treatment patterns., Trial Registration: ClinicalTrials.gov identifier, NCT03577795.

Background: In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting β2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs-glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)-in patients with COPD., Methods: We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC)., Results: No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported., Conclusions: The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported. Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).

Purpose: Patients with chronic obstructive pulmonary disease (COPD) have decreased physical activity (PA) compared with healthy adults. As lower PA is associated with increased mortality, improving PA is an important objective for COPD management. This large-scale, multicenter, non-interventional, cross-sectional study examined the activity status of COPD patients in Japan and explored factors related to PA., Patients and Methods: Outpatients aged ≥40 years with confirmed COPD diagnosis and pulmonary function test data were enrolled. Primary study outcomes were measurement of daily steps (over 14 consecutive days, using an activity monitor), assessment of activity time by activity intensity (using metabolic equivalents [METs]), and evaluation of correlation between PA and patient characteristics. Secondary outcomes included further investigation of the influence of patient characteristics on PA., Results: Data from 417 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I (29.5%), II (43.9%), III (23.5%), and IV (3.1%) were evaluated. Median (Q1, Q3) daily step count was 3440.8 (1831.3, 5709.3). Median (Q1, Q3) durations of PA at ≥3 (moderate-to-vigorous) and ≥2 METs (light-to-vigorous) were 18.7 (6.5, 41.3) and 186.9 (126.9, 259.2) minutes, respectively. For >30% of patients, time spent in ≥3 METs activity was ≤10 minutes. Unemployment was significantly correlated with reduced activity time (≥3 and ≥2 METs) and step count. Severe GOLD stage was significantly correlated with reduced activity time (≥3 and ≥2 METs). High modified Medical Research Council (mMRC) dyspnea score was significantly correlated with reduced activity time (≥3 METs) and step count. Patients tended to overestimate the time spent in activities requiring ≥2 METs in their subjective reports compared with activity monitor measurements., Conclusion: Reduced PA was observed in the Japanese COPD patients with the majority of them being GOLD stage I/II. Employment status, GOLD stage, and mMRC dyspnea score could help identify patients at risk of reduced PA., Clinical Trial Registration: NCT03642613 (ClinicalTrials.gov); UMIN000032962 (UMIN-CTR, umin.ac.jp)., Competing Interests: Masakazu Ichinose has received honoraria for speaking from AstraZeneca, GSK, and Nippon Boehringer Ingelheim. Yoshiaki Minakata has received personal fees from AstraZeneca K.K. and Nippon Boehringer Ingelheim outside the submitted work. Takashi Motegi has received personal fees from AstraZeneca K.K. for the submitted work, and personal fees from Nippon Boehringer Ingelheim outside the submitted work. Ichiro Kuwahira has received honoraria for speaking from AstraZeneca, GSK, Nippon Boehringer Ingelheim, and Meiji Seika Pharma. Munehiro Seki, Satoko Sugaya, and Nobuya Hayashi are employees of AstraZeneca K.K. The authors report no other conflicts of interest in this work., (© 2020 Ichinose et al.)

Purpose: Inhaler therapy is the mainstay of chronic obstructive pulmonary disease (COPD) management. Poor adherence causes disease exacerbation and affects patient mortality. Although the Adherence Starts with Knowledge-20 (ASK-20) questionnaire is a reliable tool for assessing medication adherence, the relationship between the ASK-20 and clinical factors in patients with COPD remains unknown. We investigated the relationship between the ASK-20 and clinical factors, and assessed real-world inhaler therapy use., Patients and Methods: A multicenter, cross-sectional study of outpatients with COPD undergoing inhaler treatment who completed the ASK-20 questionnaire was performed. We investigated COPD-related health status using the COPD Assessment Test (CAT), psychological status using the Hospital Anxiety and Depression Scale (HADS-anxiety and HADS-depression), respiratory function, patient satisfaction levels, and real-world inhaler therapy use., Results: Of the total 319 patients, 87% were male with a median age of 74 years. Most patients had mild or moderate COPD, according to Global Initiative for Chronic Obstructive Lung Disease stage. The total ASK-20 scores correlated significantly with the CAT, HADS-anxiety, and HADS-depression scores (r = 0.27, 0.33, and 0.29, respectively, p < 0.01). Multivariable analysis showed that CAT and HADS-anxiety scores had an independent and significant impact on the ASK-20 scores [β, standardized regression coefficient: 0.18 (95% CI, 0.03-0.35; p = 0.02), and 0.29 (95% CI, 0.17-0.42; p < 0.01), respectively]; however, the ASK-20 scores were not correlated with age, sex, body mass index, cohabitation, modified Medical Research Council Dyspnea Scale score, pulmonary function, disease duration, number of COPD exacerbations per year, comorbidities, inhaler numbers, nor inhaler components., Conclusion: The ASK-20 scores in patients with COPD were significantly associated with CAT and HADS scores. In Japan, Respimat was prescribed to younger patients and patients with lower CAT scores. The ASK-20, a simple evaluation method, is useful for identifying clinical factors affecting adherence in patients with COPD., Competing Interests: Shintaro Suzuki reports a grant from KAKENHI (20K03161) and a sponsored research grant from MylanEPD (JAPAN), outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2020 Akimoto et al.)

Purpose: Asthma-COPD overlap (ACO) has been reported as an association with a lower quality of life, frequent exacerbations, and higher mortality than those with COPD alone. However, clinical characteristics and outcomes of ACO remain controversial., Patients and Methods: We conducted a prospective observational study analyzing data of patients with stable COPD enrolled from the Ishinomaki COPD Network Registry. Patients with features of asthma who had a history of respiratory symptoms that vary over time and intensity, together with documented variable expiratory airflow limitation, were identified, and then defined as having ACO. The characteristics, frequency of exacerbations, and mortality during the 3-year follow-up were compared between patients with ACO and patients with COPD alone., Results: Among 387 patients with COPD, 41 (10.6%) were identified as having ACO. Patients with ACO tended to be younger, have higher BMI, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids. Inflammatory biomarkers including fractional exhaled nitric oxide, blood eosinophil count, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were significantly higher in patients with ACO than in those with COPD alone. Lung function, mMRC score, CAT score, and comorbidity index were not different between the groups. The annual rate of all exacerbations and severe exacerbations required hospital admission were not different between ACO and COPD alone (0.20 vs 0.14, 0.12 vs 0.10, events per person, respectively). Mortality was significantly higher in patients with COPD alone compared with those with ACO during the study period (P=0.037)., Conclusion: The results of our study indicate that ACO is not associated with poor clinical features nor outcomes in an outpatient COPD cohort receiving appropriate treatment., Competing Interests: Dr Seiichi Kobayashi reports personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, TEIJIN PHARMA LIMITED., and Kyowa Kirin Co., Ltd., grants from GlaxoSmithKline, and grants and personal fees from AstraZeneca and Novartis, outside the submitted work. The authors report no other potential conflicts of interest in this work., (© 2020 Kobayashi et al.)

Purpose: To date, no consensus exists on the effects of systemic steroid use on pneumonic chronic obstructive pulmonary disease (COPD) exacerbation owing to trial design issues in previous trials involving these conditions. This multicenter study aimed to evaluate more precisely the effectiveness of the use of systemic steroids in treating pneumonic COPD exacerbation in a larger sample by adjusting for confounding factors., Patients and Methods: This multicenter, retrospective, observational study was conducted across five acute general hospitals in Japan. We analyzed the association between parenteral/oral steroid therapy and time to clinical stability in pneumonic COPD exacerbation. We used a validated algorithm derived from the 10th revision of the International Classification of Diseases and Related Health Problems (ICD-10) to include patients with pneumonic COPD exacerbation. We excluded patients with other hypoxia causes (asthma exacerbation, pneumothorax, heart failure) and complicated pneumonia (obstructive pneumonia, empyema), those who required tracheal intubation/vasopressors, and those who were clinically stable on day of admission. The primary outcome was the time to clinical stability. Multiple imputation was used for missing data. Propensity scores within each imputed dataset were calculated using potential confounding factors. The Fine and Gray model was used within each dataset to account for the competing risk of death and hospital discharge without clinical stability, and we combined the results., Results: Altogether, 1237 patients were included. Systemic steroid therapy was administered to 658 patients (53%). The pooled estimated subdistribution hazard ratio of time to clinical stability in steroid vs non-steroid users was 0.89 (95% confidence interval, 0.78 to 1.0)., Conclusion: This study revealed that systemic steroid therapy may not improve the time to clinical stability in patients with pneumonic COPD exacerbation of mild to moderate severity. Further randomized controlled trials including more severe patients will be needed to evaluate the effectiveness of systemic steroid therapy accurately., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Shiroshita et al.)

Background: Pulmonary hypertension (PH) is a major comorbidity of chronic obstructive pulmonary disease (COPD). However, the association of PH detected by echocardiography and COPD-related outcome in longitudinal follow-up has not been elucidated. In this study, we aimed to investigate the relationship between clinical characteristics of COPD patients with PH detected by echocardiography and various outcome parameters such as COPD exacerbation and health status over a three-year observation period., Methods: In this observational study, we analyzed patients with COPD who underwent chest computed tomography and echocardiography at baseline (n = 183)., Results: The prevalence of PH was 21.9% (40 patients). The median estimated systolic pulmonary artery pressure in patients with PH was 38.8 mmHg. COPD patients with PH were older, had a lower body mass index, scored worse in the COPD Assessment Test and St. George's Respiratory Questionnaire, and exhibited a lower diffusing capacity of the lung for carbon monoxide in comparison to patients without PH. In computed tomography images, the percentages of low-attenuation areas (LAA%) and interstitial abnormalities were higher in COPD patients with PH than in those without PH. Higher values for LAA% (LAA ≥ 30%) and interstitial abnormalities independently increased the risk of PH. The ratio of main pulmonary diameter to aortic artery diameter was significantly correlated with estimated systolic pulmonary artery pressure. In the follow-up analysis, the frequency of exacerbations in three years was significantly higher in patients with PH compared to patients without PH., Conclusion: In this study, we identified the clinical characteristics of COPD patients with PH detected by echocardiography. The presence of PH assessed by echocardiography was related to future COPD exacerbations and closely related to radiographical emphysema., Competing Interests: Dr Koichiro Asano reports personal fees from Teijin Pharma Ltd, Novartis Pharma, Sanofi, Astellas Pharma, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Kyorin Pharma, and MSD, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Nakayama et al.)

Introduction: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood., Methods: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined., Results: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers., Conclusion: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.

Purpose: The improvement of physical activity in patients with COPD is an important issue. However, no standard for the recommended number of steps for patients with COPD has been determined. We conducted a retrospective observational study to create a simple standard equation for the daily step count, which makes it easier to determine whether each subject is attaining his/her predicted value or not., Patients and Methods: Stable outpatients diagnosed with COPD whose physical activities had been measured using a triaxial accelerometer for more than 2 weeks were recruited from 5 institutes in Japan. Factors associated with the step count were detected by multivariate regression analysis. After the data were transformed to a normalized distribution, a multivariate linear regression equation was created using stepwise regression., Results: One hundred sixty-two patients aged 72.3 (7.2) years and of FEV1 %pred 59.2 (22.8) % were recruited. Among the parameters, age, mMRC dyspnea scale and inspiratory capacity (IC) were detected by the stepwise method. The created standard equation was "Step count = (-0.079×[age]-1.595×[mMRC]+2.078×[IC]+18.149) 3 ". The correlations between the calculated values and the measured values were observed, and fixed, and proportional biases between them were also observed. When patients with <6500 steps/day were selected, no systematic bias between them could be detected., Conclusion: A simple standard equation for Japanese patients with COPD was created using age, mMRC and IC, and could provide an individual-predicted value, especially for patients with <6500 steps/day., Competing Interests: YM received lecturer fee from Nippon Boehringer Ingelheim. The authors report no other conflicts of interest in this work., (© 2019 Nakanishi et al.)

Objective This multicenter, cross-sectional, non-interventional trial aimed to investigate adherence barriers to inhaled medicines when compared with oral medicines in Japanese patients with chronic obstructive pulmonary disease (COPD) and asthma. Methods The self-reporting "Adherence Starts with Knowledge 20" (ASK-20) questionnaire was administered for adherence barriers of inhaled and oral medicines to outpatients with regular clinic attendance. Results Patients with COPD and asthma reported different adherence barriers to inhaled medicines. Independent adherence barriers [odds ratio (95% confidence interval)] to inhaled medicines relative to those for oral medicines among patients with COPD and asthma were those related to item Q8 [ "I know if I am reaching my health goals"; 2.49 (1.39-4.47); p=0.0022] and item Q2 [ "I run out of my medicine because I do not get refills on time"; 2.69 (1.26-5.75); p=0.0127], respectively. Among patients with poor adherence to only inhaled medicines, those with COPD and asthma recognized item Q3 [ "consuming alcohol and taking medicines"; 6.63 (1.27-34.7); p<0.05] and item Q1 [ "forget to take medicines only sometimes"; 4.29 (1.83-10.0); p<0.05], respectively, were recognized as independent adherence barriers to inhaled medicines. The total ASK-20 scores and total barrier counts in patients with poor adherence to inhaled medicines were significantly higher than in those without poor adherence among patients with asthma (p=0.0057) but not those with COPD (p>0.05). Conclusion These results will aid in personalizing education on adherence to inhaled medicines among patients with COPD and asthma.

Purpose: The 2017 GOLD ABCD classification shifts patients from groups C-D to A-B. Group A was the most widely distributed group in several studies. It would be useful to understand the characteristics for group A patients, but little has been reported concerning these issues., Patients and Methods: This was a multicenter cross-sectional study using the COPD Assessment in Practice study database from 15 primary or secondary care facilities in Japan. We investigated the clinical characteristics of group A by stratification according to a mMRC grade 0 or 1., Results: In 1,168 COPD patients, group A patients accounted for approximately half of the patients. Compared with the groups B-D, group A was younger and had a higher proportion of males, higher pulmonary function, and higher proportion of monotherapy with long-acting muscarinic antagonist or long-acting β-agonist. The prevalence of mMRC grade 1 patients was about two-thirds of group A. Compared with the mMRC 0 patients, mMRC 1 patients showed a tendency to have a higher proportion of exacerbations ( P =0.054) and had a significantly lower pulmonary function. Regardless of the mMRC grade, 60% of group A patients were treated with monotherapy of long-acting muscarinic antagonist or long-acting β-agonist., Conclusion: Group A patients accounted for approximately half of the patients, and they were younger, had higher pulmonary function, and had lower pharmacotherapy intensity compared with groups B-D. By stratifying according to the mMRC grade 0 or 1 in group A patients, there were differences in the exacerbation risk and airflow limitation., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

COPD is associated with significant morbidity and is one of the leading causes of death worldwide. Periods of exacerbation, the acute worsening of symptoms, are interspersed throughout the disease's natural history and can result in increased treatment burden and hospitalization for patients with COPD. The frequency of exacerbations varies between countries, with both epidemiological studies and randomized controlled trials (RCTs) showing significant differences in observed prevalence rates. Differences in study design and the healthcare setting are likely to contribute to differences in exacerbation frequency, however the perceived rate of exacerbations in Japan is currently lower then the rest of the world. This review identified nine cohort studies and five RCTs that reported COPD annual exacerbation rates in Japan in the ranges of 0.1-2.1 and 0.33-1.79, respectively. The difference in exacerbation rate between studies appeared greater than the difference between Japan and Western countries, likely because of disparities between settings, design, and inclusion criteria. Of these, only one (Understanding the Long-Term Impacts of Tiotropium) had uniform inclusion criteria across different regions. This study found that the annual rate of exacerbation events per patient in Japan was 0.61, compared with 0.85 worldwide in the placebo groups. This review summarizes the published rates of COPD exacerbations in Japan and the rest of the world and explores the hypotheses as to why rates in Japan might be lower than other countries. These include access to medical care, variance in the associated morbidity profile, environmental factors, diagnostic crossover with related diseases, and differences in study design (including the underreporting of COPD exacerbations in Japan). Understanding the reasons why COPD exacerbation rates appear lower in Japan could help clinicians to recognize and modify treatment behaviors, which may lead to improved patient outcomes in all populations., Competing Interests: Disclosure TI, AA, MJ, and PJ are employees of GlaxoSmithKline (GSK) and hold stock/shares in GSK. MN has received research grants from Nippon Boehringer Ingelheim, AstraZeneca, and Novartis Japan, as well as personal fees from Nippon Boehringer Ingelheim. The authors report no other conflicts of interest in this work.

Background: The use of inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD) decreases the frequency of COPD exacerbations. Recently, pneumonia was reported as a complication of ICS in patients with COPD. However, there have been few reports concerning the relationship between ICS and pneumonia in Japan. Moreover, there is little information on the types of ICS., Patients and Methods: To clarify these issues, we investigated the occurrence of pneumonia in Japanese patients with COPD. We retrospectively investigated the occurrence of pneumonia in patients with COPD in our hospital from January 2009 to August 2013. Morbidity and mortality, ICS use, age, sex, and COPD classification were investigated. A group of patients with COPD who received ICS and a group of patients with COPD who did not receive ICS were compared each other., Results: Fifty-one patients developed pneumonia among 639 (7.98%) patients with COPD. Among 252 ICS-treated patients with COPD, 13 (5.16%) developed pneumonia, and among 387 ICS-untreated patients with COPD, 38 (9.82%) developed pneumonia. The mortality rate in ICS-treated patients with COPD was 7.7%, while that in ICS-untreated patients was 10.5% ( P =0.767). Fluticasone/salmeterol use tended to show a higher risk of pneumonia than budesonide/formoterol use. The use of ICS did not increase the risk of pneumonia or mortality due to pneumonia in Japanese patients with COPD., Conclusion: ICS might not increase the risk of pneumonia in Japanese patients with COPD. In regard to pneumonia, ICS can be safely used in Japanese patients with COPD. Because there are apparent differences in lung diseases among races, appropriate treatment should be investigated in each country., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: A large body of evidence suggests that long-acting β2-adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) combinations induce a strong synergistic bronchodilatory effect in human isolated airways. Moreover, a recent post hoc analysis demonstrated clinical synergism between LABAs and LAMAs, which induces a synergistic improvement not only in lung function but also in dyspnea in COPD patients., Aim: The aim of this study is to examine the baseline factors related to improvement in lung function or clinical symptoms that results from the administration of LAMA or LAMA/LABA and to compare the differences in improvement in lung function or clinical symptoms between LAMA and LAMA/LABA., Methods: Among 829 patients with COPD who were treated with LAMA or LAMA/LABA in our hospital, 112 patients (aged 40-89 years) matched the criteria. Of these 112 patients, 71 received LAMA (LAMA group) and 41 received LAMA/LABA (LAMA/LABA group) as the initial treatment. Various examination results such as lung function test values, symptom change, and frequency of exacerbations were compared between the two groups., Results: Compared with the monotherapy, the combination therapy significantly improved the FEV 1 , inspiratory capacity (IC), and total COPD assessment test (CAT) scores. Comparing the improvement in each domain of the CAT produced by the combination therapy with that of the monotherapy, larger improvements were found for the domains of going out and sleeping. The frequency of exacerbations during the 24 weeks was significantly lower in the combination therapy group than in the LAMA monotherapy group ( P =0.034). Although no relationship was found between improvement in FEV 1 and any pretreatment factors in the LAMA/LABA group, the improvement in the CAT score was strongly related to the baseline CAT score, smoking index, and air trapping index ( P -value <1×10 -4 )., Conclusion: In this study of clinical practice, we found that LAMA/LABA combination therapy improved the clinical symptoms of COPD and IC and that the effects of the combination therapy were consistent with those observed in previous clinical trials., Competing Interests: Disclosure HY has received lecture fees from Boehringer Ingelheim. NHiz has received lecture fees from AstraZeneca, Astellas Pharma, and Boehringer Ingelheim. NHid has no conflicts of interest in this work.

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

Purpose: Skeletal muscle wasting is an independent predictor of health-related quality of life and survival in patients with COPD, but the complexity of molecular mechanisms associated with this process has not been fully elucidated. We aimed to determine whether an impaired ability to repair DNA damage contributes to muscle wasting and the accelerated aging phenotype in patients with COPD., Patients and Methods: The levels of phosphorylated H2AX (γH2AX), a molecule that promotes DNA repair, were assessed in vastus lateralis biopsies from 10 COPD patients with low fat-free mass index (FFMI; COPD L ), 10 with preserved FFMI and 10 age- and gender-matched healthy controls. A panel of selected markers for cellular aging processes (CDKN2A/p16 ink4a , SIRT1, SIRT6, and telomere length) were also assessed. Markers of oxidative stress and cell damage and a panel of pro-inflammatory and anti-inflammatory cytokines were evaluated. Markers of muscle regeneration and apoptosis were also measured., Results: We observed a decrease in γH2AX expression in COPD L , which occurred in association with a tendency to increase in CDKN2A/p16 ink4a , and a significant decrease in SIRT1 and SIRT6 protein levels. Cellular damage and muscle inflammatory markers were also increased in COPD L ., Conclusion: These data are in keeping with an accelerated aging phenotype as a result of impaired DNA repair and dysregulation of cellular homeostasis in the muscle of COPD L . These data indicate cellular degeneration via stress-induced premature senescence and associated inflammatory responses abetted by the senescence-associated secretory phenotype and reflect an increased expression of markers of oxidative stress and inflammation., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker of inflammation in chronic obstructive pulmonary disease (COPD) patients. But, a meaningful threshold and the longitudinal changes are unknown. We aimed to investigate the association between NLR and the clinical characteristics of COPD patients and to determine a meaningful threshold and the longitudinal changes for NLR., Methods: Keio University and its affiliate hospitals conducted an observational COPD cohort study over 3 years. We performed a blood examination and a pulmonary function test. Blood examination was completed at baseline and annually thereafter, at a time when the disease was stable. Two hundred seventy-four patients who had at least 3 blood examinations over 3 years were included., Results: Baseline NLR was correlated with baseline C-reactive protein (CRP) (r = 0.18, p = 0.003) and SAA (r = 0.34, p <  0.001). We defined an NLR score of 2.7 as the arbitrary cut-off value based on upper quartile points. COPD patients with NLR ≥ 2.7 were older (p = 0.037), had a lower BMI (p = 0.005) and a lower %FEV1 (p = 0.0003) compared to patients with NLR < 2.7. Receiver-operating-characteristic (ROC) curves showed the optimal cutoff for the baseline NLR in the predicting moderate/severe exacerbation to be 2.7, which was same as the upper quartile points. Follow-up analysis over 3 years revealed that the differences in the trends of NLR among the three groups based on the categories of exacerbations (moderate or severe, mild, no exacerbation) were significant (p = 0.006)., Conclusions: NLR is associated with COPD severity and exacerbations. For predicting exacerbations, we estimated the threshold of NLR to be 2.7 at baseline., Trial Registration: Clinical trial registered with the University Hospital Medication Information Network ( UMIN000003470 , April 10, 2010).

Background:  To present up-to-date meta-analyses of evidence from Japan relating smoking to major smoking-related diseases.  Methods:  We restricted attention to lung cancer, chronic obstructive pulmonary disease (COPD), ischemic heart disease (IHD) and stroke, considering relative risks (RRs) for current and ex-smokers relative to never smokers.  Evidence by amount smoked and time quit was also considered.  For IHD and stroke only, studies had to provide age-adjusted RRs, with age-specific results considered.  For each disease we extended earlier published databases to include more recent studies.  Meta-analyses were conducted, with random-effects RRs and tests of heterogeneity presented.  Results:   Of 40 studies, 26 reported results for lung cancer and 7 to 9 for each other disease.  For current smoking, RRs (95%CIs) were lung cancer 3.59 (3.25-3.96), COPD 3.57 (2.72-4.70), IHD 2.21 (1.96-2.50) and stroke 1.40 (1.25-1.57).  Ex-smoking RRs were lower.  Data for lung cancer and IHD showed a clear tendency for RRs to rise with increasing amount smoked and decrease with increasing time quit.  Dose-response data were unavailable for COPD and unclear for stroke, where the association was weaker.  Conclusions:  Compared to studies in other Asian and Western countries, current smoking RRs were quite similar for IHD and stroke.  The comparison is not clear for COPD, where the Japanese data, mainly from cross-sectional studies, is limited.  For lung cancer, the RRs are similar to those in other Asian countries, but substantially lower than in Western countries.  Explanations for this are unclear, but less accurate reporting of smoking by Japanese may contribute to the difference., Competing Interests: Competing interests: P N Lee Statistics and Computing Ltd, for whom PNL and KJC are directors, and BAF and AJT are consultants, have for many years carried out work for many different tobacco companies and organizations, including Philip Morris International, the sponsors of this study. The work described here has been carried out independently of the sponsors.