Determinants of Activity Phenotype in Patients with Chronic Obstructive Pulmonary Disease.

Introduction: Physical activity (PA) and sedentary behavior (SB) have attracted attention in chronic obstructive pulmonary disease (COPD), and there have been efforts to evaluate PA and SB separately. The factors associated with the characteristics of the four activity phenotypes defined by the durations of PA and SB are largely unknown. The aim of this study was to clarify the factors that could differentiate each activity phenotype. Materials and Methods: Study subjects were outpatients with stable COPD who were ≥40 years of age. We investigated the influence of 26 different factors on the activity phenotypes of COPD and extracted the factors that showed significant differences among the four activity phenotypes. Results: Two hundred sixteen patients were included in the analysis. Exercise capacity and dyspnea were determinants that distinguished the low PA groups from the high PA groups. The pulmonary function and desaturation during exercise were factors that distinguished the high PA with low SB group from the low PA with high SB group. BMI, grip strength, upper arm circumference and HbA1c were higher in the low PA and low SB group than in the low PA and high SB group. Conclusion: These factors could be the determinants discriminating activity phenotypes of patients with COPD.

Objective Measurement of Physical Activity and Sedentary Behavior in Patients with Chronic Obstructive Pulmonary Disease: Points to Keep in Mind during Evaluations.

Objective measurement methods using accelerometers have become the mainstream approach for evaluating physical activity (PA) and sedentary behavior (SB). However, several problems face the objective evaluation of PA and SB in patients with chronic obstructive pulmonary disease (COPD). For example, indicators of PA differ depending on whether the accelerometer detects the kind of activity on the one hand, or its intensity on the other. Measured data are also strongly influenced by environmental factors (weather, season, employment status, etc.) and methodological factors (days with uncommon activities, non-wearing time, minimum required wearing time per day, minimum number of valid days required, etc.). Therefore, adjusting for these factors is required when evaluating PA or SB, especially when evaluating the effects of intervention. The exclusion of sleeping time, unification of total measurement time, and minimization of the required wearing time per day might be more important for the evaluation of ST than for evaluating PA. The lying-down-time-to-sitting-time ratio was shown to be larger in COPD patients than in healthy subjects. In this review, we clarified the problems encountered during objective evaluations of PA and SB in patients with COPD and encouraged investigators to recognize the presence of these problems and the importance of adjusting for them.

Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

Validation of Simple Prediction Equations for Step Count in Japanese Patients with Chronic Obstructive Pulmonary Disease.

Physical activity is decreased in patients with chronic obstructive pulmonary disease, and decreased physical activity leads to a poor prognosis. To determine an individual's target step count from the measured step counts and predicted step counts, simple and detailed prediction equations for step count were developed. To verify the validity of the simple prediction equation, the validity of the simple equation was evaluated in a different cohort and the correlation between the step counts calculated by the simple equation and those by the detailed prediction equation were evaluated. When the step counts calculated by the simple prediction equation for all participants were compared with the measured step counts, a significant correlation was obtained among them, and the calculated values were found to be reproducible with the measured values in patients with a measured step count of <6500 by Bland−Altman plots. Furthermore, the values calculated by the simple prediction equation and those calculated by the detailed prediction equation showed a significant correlation. In conclusion, the simple prediction equation was considered reasonable.

Effects of individualized target setting on step count in Japanese patients with chronic obstructive pulmonary disease: a pilot study.

INTRODUCTION: Improving physical activity in patients with chronic obstructive pulmonary disease (COPD) is a very important issue; however, effective recommended targets for individual patients remain to be determined. MATERIAL AND METHODS: We developed a method for setting a target value for the step count for each patient using a measured value and the predicted step count. We then evaluated the effect of providing a pedometer or a pedometer with this target value for eight weeks on the step count in patients with COPD. RESULTS: Sixteen stable COPD patients were included in the analysis. Overall, no significant increase in the step count was obtained by providing the target value; however, when the patients were divided into two groups based on the median step count at baseline, a significant increase in the step count was observed in the low step-count group. In both the overall population and the low step-count group, there was a significant increase in the target achievement rate in patients who received a pedometer with a target value in comparison to patients who were given a pedometer without a target value. CONCLUSIONS: Physical activity may be improved by providing a newly developed individual target step count to COPD patients with a low step count at baseline.

Reference Equations for Assessing the Physical Activity of Japanese Patients with Chronic Obstructive Pulmonary Disease.

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.

A case of primary racemose hemangioma in which the disappearance of an endobronchial lesion was confirmed after bronchial artery embolization.

The confirmation of the improvement of endobronchial lesions in addition to that of vascular lesions after bronchial artery embolization of primary racemose hemangioma could be important.

Longitudinal Relationship Between Growth Differentiation Factor 11 and Physical Activity in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Daily physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD) and a reduced level of physical activity has been shown to be an important predictor for the prognosis, such as increased risk of exacerbation and mortality. However, there has not yet been a useful biomarker of the physical activity. In our previous cross-sectional study, we showed that the level of one of the possible myokines, which is an anti-aging factor, growth differentiation factor 11 (GDF11), was decreased in the plasma from patients with COPD and correlated with the physical activity. To clarify this relationship, we conducted a longitudinal evaluation of such factors. PATIENTS AND METHODS: Twenty-four COPD patients were enrolled and prospectively followed. We measured the levels of plasma GDF11 and systemic inflammatory markers with immunoblotting or ELISA, respectively. We also evaluated lung function and daily physical activity using a triaxial accelerometer and the incidence of exacerbation. RESULTS: The change in the plasma level of GDF11, but not systemic inflammatory markers, was positively correlated with the change in the physical activity in an intensity-dependent manner (between the change in the number of steps and GDF11; r = 0.41, p = 0.047). In the multiple regression analysis, the relationship was confirmed (ß = 0.93, p < 0.001). In addition, patients who maintained their plasma level of GDF11 showed a significantly lower incidence in exacerbations of COPD than those with decreased levels of GDF11 (p = 0.041). CONCLUSION: The longitudinal change in the plasma level of GDF11 was positively correlated with the change in the daily physical activity in COPD. GDF11 could be a useful humoral factor that reflects the physical activity in COPD.

A Non-Interventional, Cross-Sectional Study to Evaluate Factors Relating to Daily Step Counts and Physical Activity in Japanese Patients with Chronic Obstructive Pulmonary Disease: STEP COPD.

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).

Data Reproducibility and Effectiveness of Bronchodilators for Improving Physical Activity in COPD Patients.

Increasing physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is an important issue, however, the effect of bronchodilators on PA is still controversial. The indicators of PA, as measured by an accelerometer, can easily fluctuate based on several factors, which might cause inconsistent results. In this review, we listed the indicators of PA and the factors influencing the reproducibility of indicators of PA, and reviewed reports in which the effects of bronchodilators on PA were evaluated by an accelerometer. Then, we investigated the association between the processing of influencing factors and the effectiveness of bronchodilators for improving the PA of COPD patients. Fifteen reports were extracted using the PubMed database. In all seven reports in which adjustment was performed for at least two of four influencing factors (non-wear time, data from days with special behavior, environmental factors, and number of valid days required to obtain reproducible data), bronchodilators showed beneficial effects on PA. No adjustment was made for any of these factors in any of the four bronchodilator-ineffective reports. This suggests that the processing of influencing factors to secure reproducibility might affect the results regarding the effectiveness of bronchodilators for improving PA in COPD patients.

Simple standard equation for daily step count in Japanese patients with chronic obstructive pulmonary disease.

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.

Effect of tiotropium/olodaterol on sedentary and active time in patients with COPD: post hoc analysis of the VESUTO® study.

Background: Patients with COPD are less physically active. This post hoc analysis of a randomized, double-blind, active-controlled, crossover trial assessed the efficacy of once-daily tiotropium/olodaterol combination therapy versus tiotropium monotherapy in Japanese patients with COPD. Patients and methods: Patients were provided with a three-axis accelerometer to measure sedentary and active behavior defined as 1.0-1.5 metabolic equivalents (METs), ≥2.0 METs, and ≥3.0 METs, respectively. Of the 182 patients enrolled, 131 satisfied the conditions for the present analysis and were randomized to tiotropium monotherapy (n=62) or tiotropium/olodaterol combination therapy (n=69). Results: Tiotropium/olodaterol combination therapy significantly reduced the duration of 1.0-1.5 MET activity by 8.64 mins (p=0.040) and significantly increased the duration of ≥2.0 MET and ≥3.0 MET activity by 6.51 mins (p=0.017) and 2.60 mins (p=0.008), respectively, compared with tiotropium alone. Subgroup analyses showed that better lung function, milder dyspnea, and higher levels of physical activity at baseline were associated with reduced sedentary time and increased duration of physical activity. Conclusion: Tiotropium/olodaterol combination therapy significantly reduced sedentary time and improved physical activity compared with tiotropium monotherapy. This trial was registered in ClinicalTrials.gov (NCT02629965).

Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is mainly treated pharmaceutically with bronchodilators. The purpose of this study was to evaluate the clinical benefits of two-times-per-day aclidinium bromide (Acli-BID) compared with once-a-day tiotropium bromide hydrate (Tio-QD) in patients with COPD. DESIGN: This study was a multicentre, open-label, randomised study. SETTING: Fourcentres in Kagawa prefecture, Japan. PARTICIPANT: Patients who were diagnosed to have COPD Grade 2-3 according to the Global Initiative for Chronic Obstructive Lung Disease 2015 criteria were enrolled. INTERVENTIONS: Patients were randomly assigned to receive Acli-BID or Tio-QD at a 1:1 ratio, and followed for 8 weeks. Acli-BID was administered in the morning and night, and Tio-QD was administered in the night. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was forced expiratory volume in one second area under the curve (FEV1AUC0-3), and secondary outcomes were pulmonary function, physical activity, St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC), the 8-item Short-Form Health Survey (SF-8) and COPD exacerbations. Adverse events were evaluated during the study. RESULTS: 44 patients were included in this study. FEV1AUC0-3 at week 8 was 4.62±1.43 L·hour in Acli-BID and 4.73±1.60 L·hour in Tio-QD (mean difference (MD) -0.11 L·hour; 95% CI), -1.04 to 0.83). Significant improvement was observed in activity-related subscales of SGRQ (MD -7.78; 95% CI -14.61 to -0.94) and SF-8 (MD 4.01; 95% CI 0.37 to 7.65), mMRC (MD -0.66; 95% CI -1.19 to -0.13) and rate ratio (0.52, 95% CI 0.27 to 0.99) of exacerbations in the Acli-BID compared with the Tio-QD. Acli-BID and Tio-QD significantly improved sedentary behaviour (MD -35.20 min; 95% CI -67.41 to -2.94 and MD -55.40 min; 95% CI -98.15 to -12.77) within each group, but there was no significant difference between the two groups. CONCLUSION: Acli-BID as with Tio-QD could be one of the therapeutic options for patients with COPD to improve pulmonary function. Also, our results suggest that intervention with bronchodilators enhanced physical activity in patients with COPD. TRIAL REGISTRATION NUMBER: UMIN 000020020.

Verification of a Motion Sensor for Evaluating Physical Activity in COPD Patients.

Background: Objective evaluation of the physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is important. We validated a triaxial accelerometer, Active Style Pro HJA-750C® (HJA), and evaluated the necessary conditions for obtaining reproducible data. Methods: The PA measured by HJA was compared with that measured by two already validated accelerometers in 11 patients with COPD (age: 76.6 ± 6.9, FEV1% predicted: 57.6 ± 18.6). Then, the influence of weather and holidays on the PA and the required number of days to obtain repeatability were examined in 21 patients with COPD (age: 73.0 ± 8.0, FEV1% predicted: 58.7 ± 19.0). Results: The PA values measured by HJA and those by DynaPort Move Monitor® (DMM) or Actimarker® (AM) were significantly correlated at all intensities (p=0.024 at ≥4.0 METs by DMM and p < 0.0001 at the rest) except at ≥4.0 METs by AM, though the values measured by HJA were higher than those by AM which was reported to underestimate PA. The durations of PA on rainy days were significantly shorter than those on nonrainy days, but those on holidays were not different from those on weekdays. The values of ICC for 3, 4, or 5 days were higher than 0.8 at all intensities. The PA measured by HJA was correlated with the dyspnea scale FVC and age and tended to correlate with FEV1. Conclusions: The HJA was validated for evaluating the PA in patients with COPD. This trial is registered with UMIN000016363.

Efficacy of tiotropium/olodaterol on lung volume, exercise capacity, and physical activity.

Purpose: This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD. Patients and methods: A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose. Results: Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001). Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001). Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254). In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337). Conclusion: Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients. A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol.

Study Design of VESUTO®: Efficacy of Tiotropium/Olodaterol on Lung Hyperinflation, Exercise Capacity, and Physical Activity in Japanese Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD. METHODS: A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD. RESULTS: A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints. CONCLUSION: The VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting ß2-agonist (LABA) combination therapy on patients' physical activities as well as lung function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015). FUNDING: The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.

Improved quality of life in asthma patients under long-term therapy: Assessed by AHQ-Japan.

BACKGROUND AND OBJECTIVES: Assessment of the effects of long-term management on patient quality of life (QOL) would be extremely useful for determining asthma treatment strategies. However, no studies have evaluated QOL over an extended period of time. This study evaluated the changes in QOL, drug management and disease severity in the same asthma patients at an interval of approximately 9 years. METHODS: We re-surveyed asthma patients enrolled in a survey conducted in 2004 to evaluate the effects of approximately a decade of treatment on disease severity and QOL assessed by the Japanese Asthma Health Questionnaire (AHQ-JAPAN). RESULTS: A total of 2179 patients were enrolled in the study from 93 centres, and 1332 patients were included in the per-protocol analysis. Usage rates of inhaled corticosteroids (ICS) for treatment of stable asthma were over 90% at both time points. The AHQ-JAPAN total score improved significantly from 22.2±19.7 in 2004 to 19.7±19.9 in 2013 (P<.001). Significant improvements were also observed in 5 of 6 subscales of AHQ-JAPAN, with Social Activity constituting the sole exception. CONCLUSIONS: Asthma severity declined and QOL assessed by AHQ-JAPAN improved, which is considered as a reflection of improved asthma control at least partly attributable to widespread use of anti-inflammatory drugs as represented by ICS. The study also revealed the presence of those with poor QOL, especially in patients with concomitant respiratory diseases, and an increase in severe persistent asthma cases, warranting further long-term efforts at improving QOL. TRIAL REGISTRATION NUMBER: UMIN 000010483.

Chylothorax Associated with Chronic Lymphocytic Leukemia.

An 80-year-old man who had suffered from chronic lymphocytic leukemia (CLL) and achieved complete remission was admitted to our hospital due to right pleural effusion. Thoracentesis revealed that the effusion was chyle. Lymphoscintigraphy showed an obstruction of the thoracic duct below the sternum. CD45-gated flow cytometry of the pleural effusion showed elevated numbers of CD5- and CD23-positive lymphocytes and a high serum level of soluble interleukin-2 receptor. These results suggested that the chylothorax was caused by the obstruction of the thoracic duct by the sludging of either abnormal lymphocytes of CLL or transformed malignant lymphoma cells.

Differences in physical activity according to mMRC grade in patients with COPD.

BACKGROUND: Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness. The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD. OBJECTIVES: We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD. METHODS: A cross-sectional study was performed on stable outpatients with COPD. PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale. RESULTS: Ninety-eight patients were recruited. Significant differences in PA duration were observed at all intensities according to the mMRC grade. Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day. COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4). CONCLUSION: PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL. Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD.