Search

Masakazu Ichinose,1 Yoshiaki Minakata,2 Takashi Motegi,3 Tsuneyuki Takahashi,4 Munehiro Seki,5 Satoko Sugaya,5 Nobuya Hayashi,6 Ichiro Kuwahira7 1Academic Center of Osaki Citizen Hospital, Osaki 989-6183, Japan; 2Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama 644-0044, Japan; 3Respiratory Care Clinic Tokyo, Institute of Clinical Respirology, Tokyo 104-0031, Japan; 4Department of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Sendai 984-8560, Japan; 5Medical Department, AstraZeneca K.K., Osaka 530-0011, Japan; 6Biometrics Department, AstraZeneca K.K., Osaka 530-0011, Japan; 7Department of Pulmonary Medicine, Tokai University Tokyo Hospital, Tokyo 151-0053, JapanCorrespondence: Masakazu Ichinose Email ichinose@h-osaki.jpPurpose: 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).Keywords: COPD, physical activity, pulmonary function, activity monitor, step counts

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).

In patients with COPD, self-management plays an important role in disease management. Recently, self-management programmes have expanded patient education practices to include a variety of disease management techniques. We hypothesised that COPD patients have insufficient and/or different self-management needs according to institution. We compared information needs of patients between specialised clinics in Canada (SCC) and Japan and a hospital outpatient clinic in Japan (HCJ), all employing different self-management interventions. This cross-sectional study evaluated patients’ information needs for disease management using the Lung Information Needs Questionnaire (LINQ). Furthermore, we assessed pulmonary function tests, modified Medical Research Council (mMRC) dyspnoea scale and frequencies of hospitalisations and emergency visits. The total number of patients was 183. Those attending SCC were younger (p=0.047), with lower forced expiratory volume in 1 s % predicted (p, This study compared patients’ information needs from three institutions, highlighting real-world differences in information needs and the importance of assessing individual needs for self-management in COPD https://bit.ly/3jlPbse

AIM To determine whether home-based exercise can improve clinical outcomes in older patients with advanced chronic obstructive pulmonary disease using long-term oxygen therapy. METHODS Information was provided to improve chronic obstructive pulmonary disease self-management before the onset of the present prospective 3-year cohort study. Patients selected either home-based exercise using a lower-limb cycle machine (ergo-bicycle; group E), or usual exercise (group U). To assess self-management, the Lung Information Needs Questionnaire was evaluated every 6 months. Clinical outcomes included the 6-min walk test, pulmonary function tests, the body mass index, airflow obstruction, dyspnea and exercise index, St. George's respiratory questionnaire, and the number of exacerbations and hospitalizations. RESULTS A total of 136 patients (group E = 72; group U = 64), with a mean age of 74.2 years were enrolled. Total Lung Information Needs Questionnaire scores improved over 3 years for group E (P = 0.003). The distance of the 6-min walk test was well maintained in group E, but significantly decreased in group U (P < 0.001). The percentage of forced expiratory volume in 1 s at baseline was lower in group E (P = 0.016), but was maintained over 3 years, whereas a significant reduction was seen in group U (P = 0.001). The body mass index, airflow obstruction, dyspnea and exercise index significantly worsened in both groups over 3 years (group E: P = 0.011; group U: P < 0.001), whereas a significant decrease in the number of exacerbations was noted in group E (P = 0.009). CONCLUSIONS Patients who undertook home-based exercise using an ergo-bicycle were able to maintain clinical outcomes including 6-min walk test distance and percentage of forced expiratory volume in 1 s predicted, and recorded fewer exacerbations over 3 years. Geriatr Gerontol Int 2018; 18: 42-49.

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 β2-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. Electronic supplementary material The online version of this article (doi:10.1007/s12325-017-0554-3) contains supplementary material, which is available to authorized users.

Background and objective The exacerbation-prone phenotype of COPD is particularly important, as exacerbations lead to poor quality of life and disease progression. We previously found that COPD patients who lack Siglec-14, a myeloid cell protein that recognizes bacteria and triggers inflammatory responses, are less prone to exacerbation. We hypothesized that the variations in other SIGLEC genes could also influence COPD exacerbation frequency, and investigated the association between SIGLEC9 polymorphisms and the exacerbation-prone phenotype of COPD. Methods We examined whether SIGLEC9 polymorphisms affect the frequency of COPD exacerbation in 135 subjects within our study population, and also analysed the correlation between the genotypes and the severity of airflow obstruction and emphysema in 362 Japanese smokers including 244 COPD patients. The association between these single nucleotide polymorphisms (SNPs) and COPD phenotypes were also assessed in a Caucasian population of ECLIPSE study. The effects of these coding SNPs (cSNPs) on Siglec-9 protein functions were analysed using in vitro assays. Results The G allele of rs2075803 and rs2075803 G/rs2258983 A(GA) haplotype in SIGLEC9 was associated with higher frequency of exacerbations and the extent of emphysema in COPD. These results did not replicate in the ECLIPSE study. A myeloid cell line expressing the Siglec-9 variant corresponding to GA haplotype produced more TNF-α than the one expressing the variant corresponding to the other major haplotype. Conclusion The SIGLEC9 rs2075803 G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less effective at suppressing inflammatory response, may be a risk factor for the development of emphysema.

Masakazu Ichinose,1 Yoshiaki Minakata,2 Takashi Motegi,3 Jun Ueki,4 Yasuhiro Gon,5 Tetsuo Seki,6 Tatsuhiko Anzai,7 Shuhei Nakamura,6 Kazuto Hirata8 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, 2Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama, 3Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, 4Clinical Research Unit of Respiratory Pathophysiology, Juntendo University Graduate School of Health Care and Nursing, Chiba, 5Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 6Medical Division, Nippon Boehringer Ingelheim Co., Ltd, 7Clinical Information Division Data Science Center, Statistics Analysis Department 1, EPS Corporation, Tokyo, 8Osaka City University, Osaka, Japan 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

Objective Although chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, the association between the neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) and the clinical status of COPD has not been well studied. We hypothesized that the NLR is associated with disease severity and exacerbation in COPD patients. Methods We performed blood testing, pulmonary function testing, chest computed tomography, a body composition analysis, and a 6-minute walk test and applied the modified Medical Research Council (MMRC) dyspnea scale for 141 stable COPD patients. In addition, we calculated the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index to evaluate the disease severity. Finally, we examined the association between the NLR and clinical parameters in stable COPD patients, and we further investigated changes in the NLR between exacerbation and the stable state. Results The NLR was positively correlated with the BODE index, extent of emphysema, and MMRC score (p

Background: Supraventricular and ventricular premature complexes (SVPC and VPC, respectively) are associated with chronic obstructive pulmonary disease (COPD) and with increased mortality in COPD patients. However, there are few reports on the causes of arrhythmia in COPD patients. Objectives: This study explores the associations between cardiopulmonary dysfunction and COPD by comparing patients with defined arrhythmias (>100 beats per 24 h) and those without, based on 24-hour electrocardiogram (ECG) recordings. Methods: Patients with arrhythmia underwent a 24-hour ECG and subsequent pulmonary function tests, computed tomography, ECG, 6-min walk test (6MWT), and BODE (body mass index, airflow obstruction, modified Medical Research Council Dyspnoea Scale, exercise capacity) index calculation. Results: Of 103 study patients (71 COPD patients and 32 at-risk patients), 36 had VPC, 45 had SVPC, 20 had both, and 42 had neither. The predicted post-bronchodilator forced expiratory volume in 1 s, the proportion of low-attenuation area on computed tomography, and BODE index values were significantly worse in the SVPC and VPC groups compared with the corresponding reference groups. Patients in the VPC group showed significantly increased right ventricular pressure and increased desaturation in the 6MWT compared with the reference group. In the multivariate analyses, bronchodilator use was a significant risk factor in the SVPC group, whereas in the VPC group, all parameters of the BODE index except for the dyspnoea score were identified as risk factors. Conclusions: Increased SVPC might be caused by bronchodilator use, whereas increased VPC is likely related to the peculiar pathophysiology of COPD.

Background and objective Vitamin D supplementation can decrease the vulnerability to pulmonary infections. Therefore, it is speculated that the genes related to vitamin D metabolism are associated with an exacerbation-prone phenotype in chronic obstructive pulmonary disease (COPD). Because genetic variations of group component (GC) affect immunological capacity and serum vitamin D concentration, they could also affect the susceptibility to COPD exacerbation and the disease progression. We investigated the association between GC genetic variations and COPD and its exacerbation frequency in a Japanese population. Methods We performed genotype analysis of 361 COPD patients and 219 controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and rs7041. We examined whether these polymorphisms were associated with the frequency of COPD exacerbation and analysed the correlation between the genotypes, COPD, emphysema severity and COPD progression, namely, the annual decline in airflow obstruction and diffusing capacity. Results Subjects with a C allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048), greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction (P = 0.0927). Conclusions GC variations may affect exacerbation susceptibility, possibly leading to COPD worsening and its progression.

Exercise training is the most common form of non-pharmacologic therapy prescribed to chronic obstructive pulmonary disease (COPD) patients. In the pathogenesis of COPD, only ventilation limitation is not a problem, and many patients have also caused muscle dysfunction. Therefore, the treatment for the muscle dysfunction is required. Pulmonary rehabilitation has been shown to be as highly effective as pharmacotherapy for improving lung function as evidenced by contributing to improvements in shortness of breath, quality of life, exercise capacity, depression, and rates of hospitalization. In addition, it has also been recommended that the patients who fail to clinically improve solely with pharmacotherapy undergo pulmonary rehabilitation.

The exacerbation-prone phenotype of COPD is particularly important, as exacerbations lead to poor quality of life and disease progression. We previously found that COPD patients who lack Siglec-14, a myeloid cell protein that recognizes bacteria and triggers inflammatory responses, are less prone to exacerbation. We hypothesized that the variations in other SIGLEC genes could also influence COPD exacerbation frequency, and investigated the association between SIGLEC9 polymorphisms and the exacerbation-prone phenotype of COPD.We examined whether SIGLEC9 polymorphisms affect the frequency of COPD exacerbation in 135 subjects within our study population, and also analysed the correlation between the genotypes and the severity of airflow obstruction and emphysema in 362 Japanese smokers including 244 COPD patients. The association between these single nucleotide polymorphisms (SNPs) and COPD phenotypes were also assessed in a Caucasian population of ECLIPSE study. The effects of these coding SNPs (cSNPs) on Siglec-9 protein functions were analysed using in vitro assays.The G allele of rs2075803 and rs2075803 G/rs2258983 A(GA) haplotype in SIGLEC9 was associated with higher frequency of exacerbations and the extent of emphysema in COPD. These results did not replicate in the ECLIPSE study. A myeloid cell line expressing the Siglec-9 variant corresponding to GA haplotype produced more TNF-α than the one expressing the variant corresponding to the other major haplotype.The SIGLEC9 rs2075803 G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less effective at suppressing inflammatory response, may be a risk factor for the development of emphysema.

Background This study evaluated the implementation of pulmonary rehabilitation (PR), and the extent of the collaboration between primary care and chest physicians involved in the management of chronic obstructive pulmonary disease (COPD) in Japan. Methods The survey was conducted in 2006 via post and facsimile and included all medical institutions approved by the Japan Respiratory Society. Results In total, 176 institutions responded (response rate, 27%); a PR program was conducted at 55.1% of these institutions throughout Japan, but with regional differences. The mean duration of each session in an outpatient setting was 30 min with 2 sessions per week, and the mean length of hospitalization was 2–3 weeks. Although 33% of the hospitals adopted PR programs, on a scale from none (0) to maximum achievement (100), the accomplishment score was 48. Similarly, the mean satisfaction level score for collaboration was 44. The main problem arising with regards to chest physicians’ referral to general physicians was the reluctance of patients or family members (88%). Chest physicians believed that general physicians should perform early screening of patients and manage early exacerbations, including educating patients of the need to discontinue smoking. Conclusions Most chest physicians in Japan were not satisfied with the status of long-term COPD management. PR for COPD patients and collaboration between primary care physicians and specialists remain problematic in Japan. Moreover, there are widespread regional differences in terms of implementation. Sharing and implementing appropriate clinical information with primary care physicians according to current clinical guidelines should be emphasized.

Fut8 (α1,6-Fucosyltransferase) heterozygous knock-out (Fut8+/−) mice had an increased influx of inflammatory cells into the lungs, and this was associated with an up-regulation of matrix metalloproteinases, MMP-2 and MMP-9, after treatment with porcine pancreatic elastase (PPE), exhibiting an emphysema-prone phenotype as compared with wild type mice (Fut8+/+). The present data as well as our previous data on cigarette-smoke-induced emphysema [8] led us to hypothesize that reduced Fut8 levels leads to COPD with increased inflammatory response in humans and is associated with disease progression. To test this hypothesis, symptomatic current or ex-smokers with stable COPD or at risk outpatients were recruited. We investigated the association between serum Fut8 activity and disease severity, including the extent of emphysema (percentage of low-attenuation area; LAA%), airflow limitation, and the annual rate of decline in forced expiratory volume in 1 s (FEV1). Association with the exacerbation of COPD was also evaluated over a 3-year period. Serum Fut8 and MMP-9 activity were measured. Fut8 activity significantly increased with age among the at risk patients. In the case of COPD patients, however, the association was not clearly observed. A faster annual decline of FEV1 was significantly associated with lower Fut8 activity. Patients with lower Fut8 activity experienced exacerbations more frequently. These data suggest that reduced Fut8 activity is associated with the progression of COPD and serum Fut8 activity is a non-invasive predictive biomarker candidate for progression and exacerbation of COPD.

Aim: Education is a key issue for the long-term management of chronic obstructive pulmonary disease in older patients. We tested the hypothesis that integrated care focusing on patient information needs for self-management can improve patient information needs and health outcomes. Methods: Patients with chronic obstructive pulmonary disease (n = 102) were randomized into integrated care (group I) and usual care (group U) groups. Group I underwent a program of educational sessions for 6 months (integrated education period), and then repeatedly received an individually tailored education according to the Lung Information Needs Questionnaire score. Both groups were followed up monthly for 6 months. Results: A total of 85 patients (mean age: 71.7 years) were followed up for 12 months. The total Lung Information Needs Questionnaire score was significantly better in group I than in group U at 12 months (P

OBJECTIVES: To determine whether the presence of in-home caregivers is associated with changes in the health outcomes of older adults with chronic obstructive pulmonary disease (COPD). DESIGN: Cross-sectional study. SETTING: Geriatric medical center and academic respiratory clinic in Japan. PARTICIPANTS: Community-dwelling adults with COPD and their caregivers. MEASUREMENTS: Outcome measures (pulmonary function tests, distance on the 6-minute walking test (6MWT), activities of daily living (ADLs), quality of life (Medical Outcomes Study 36-item Short Form Survey and St. George's Respiratory Questionnaire), and frequencies of emergency visits and hospitalizations of those living alone (group A), those living with one caregiver (group B), and those living with two or more caregivers (group C) were compared. RESULTS: Three hundred eighty-nine participants (315 men and 74 women; mean age 73.3) were enrolled. Mean predicted forced expiratory volume in 1 second was 57.5%. The numbers of participants allocated into the global initiative for chronic obstructive lung disease stages I, II, III, and IV were 105, 107, 122, and 55, respectively. Group A had 87 participants; group B, 125; and group C, 177. Instrumental ADL scores were highest in group A (P

Objective Early diagnosis is a key factor in the management of chronic obstructive pulmonary disease (COPD). Although mass screening is widely used, little is known about its accuracy and efficacy. This study investigated whether using spirometry during mass screening to detect COPD among community residents might be ineffective because of variability in the training and experience of examiners. Participants and Methods Both spirometry and a self-written questionnaire-based survey, including questions designed to detect respiratory symptoms, were conducted on community residents. Two separate studies were conducted on islanders living in similar environments. Study I was performed from 2004 to 2007 on Hachijyo Island residents, while study II, with a similar study design, was performed in 2003 on Inno Island residents. Results In study I, 3,592 subjects underwent examination over the 4-year study period; of these, 378 subjects underwent repeated examinations. Approximately 25% of the subjects had respiratory symptoms. Acceptable spirometry recordings were obtained for 62.0% (2004) to 84.1% (2006) of the subjects. In study II, 167 of the 254 subjects (65.7%) had respiratory symptoms. Acceptable assessment recordings were achieved in 254 subjects (95.5%). The suitability of the recordings was influenced by the extent/level of training of the examiners and the accompanying thoracic specialists. Conclusion We concluded that the effectiveness of health check-ups for COPD evaluation using spirometry was greatly influenced by the quality of the examiners, even when the subjects had respiratory symptoms. Thus, we recommend caution when screening for early signs of COPD during health check-ups.

Background Although muscle loss is thought to be a prognostic factor in chronic obstructive pulmonary disease (COPD), its determinants remain unclear. Aim To verify the hypothesis that fat-free mass (FFM) and fat mass (FM) are associated with the extent of emphysema in COPD patients. Patients and Methods A total of 112 stable, male current or ex-smokers with or without COPD attending a secondary care specialist COPD clinic were studied. FFM and FM were measured by bioelectrical impedance analysis. We also assessed the nutrition status, muscle strength by the handgrip test, exercise tolerance by the 6-minute walking test, airflow limitation and diffusion capacity, the extent of emphysema by high-resolution CT scan, systemic inflammation status using C-reactive protein, and a lipid-related hormone (adiponectin). Results The FFM index (FFMI), which was defined as the FFM divided by the square of the body height, was significantly correlated with age, the total number of lymphocytes, handgrip strength, distance on 6-minute walking, airflow limitation, diffusion capacity, extent of emphysema, and C-reactive protein. On multivariate analysis, the FFMI was associated with handgrip strength and inversely correlated with the extent of emphysema. The FM index (FMI) was positively correlated with pack-years, and was inversely correlated with the extent of emphysema and concentrations of adiponectin. Conclusion The extent of emphysema was correlated with skeletal muscle loss and also the FM.

Introduction: Measuring exhaled nitric oxide (eNO is a noninvasive and useful method for evaluating the correlation between airway inflammation and air pollution. The method is being used in studies; however the effects of polluted air on eNO values are poorly understood. If polluted air significantly affects eNO concentrations then it would be hard to evaluate the concentration of eNO particularly in epidemiological measurements to detect the effects of airway inflammation such as that in bronchial asthma. Thus we hypothesized that short‑term exposure to air pollution affects eNO values. Purpose: To study the effects of environmental nitrogen oxides on the measurement of eNO concentration. Subjects and Methods: A total of 19 school children who lived on a large street with heavy traffic with random allocation were studied. Subjects with bronchial asthma were identified with a questionnaire. Suspended particulate matter. including particulate matter with an aerodynamic diameter 2.5 µ m( PM 2.5 optical black carbon nitric oxide (NO nitric dioxide (NO2 and nitrogen oxides (NOX were measured at a fixed place along the street every hour for 11 consecutive days. The concentrations of NO and NO2 for each subject were measured by an individual 2‑pyenyl‑4455‑tetramethylimidazoline‑3‑oxide‑1‑oxyl sampler and the concentration of eNO was measured with the off‑line method. Results: Of 19 subjects 3 were found to have bronchial asthma. The level of each pollutant for 11 days peaked during the mornings (6～9 a.m. and evenings (6～9 p.m. due to traffic jams; average eNO values in healthy subjects and those with asthma were 27.1 � 9.7 and 57.7 � 18.6 ppb (p＝0.098 respectively. It was found that the eNO value remained high when the mean values of various pollutants remained high for 8 hours before the measurements. It was estimated that the mean eNO values increased by 1.08 ppb (95% CI: 0.72～1.45 when the mean NOX value for the previous 8 hours reached approximately 10 ppb. Conclusion: We conclude that short‑term exposure to polluted air of at least 8 hours before measurement affects eNO values. Therefore caution should be exercised when measuring eNO value in epidemiological studies. (J Nippon Med Sch 2007; 74: 30―36

Background: In general, the clinical features of chronic obstructive pulmonary disease in the elderly are complicated, frequently resulting in undiagnosed disorders. It would be convenient if simple parameters to screen for the disease were developed. The present study investigated the pathological–clinical inter-relationships in emphysema. Methods: A total of 121 cases were graded by severity of emphysema into five groups according to the panel grid system. Grades were then compared with various clinical parameters including the severity of respiratory symptoms, characteristics of physical examination, measurements on chest radiographs and airflow obstruction on pulmonary function tests. Results: The mean age of patients was 77.1, and 71 cases (58.7%) were male. The severity distribution was as follows: no emphysema 20 (16.5%), and the four grades, ranging from mild to severe, were 65 (53.7%) grade I, 16 (13.2%) grade II, 13 (10.7%) grade III and seven (5.9%) cases were grade IV. Both smoking history (pack-year) and body mass index were significantly correlated with emphysema severity. In addition, both respiratory symptoms and airflow obstruction were sharply and significantly increased in groups III + IV compared with groups I + II. On plain chest radiograph, the ratio of lung length to body height was significantly correlated with the severity of emphysema (P

Objective: To evaluate the long-term effects of pulmonary rehabilitation in elderly COPD patients, we monitored patients for 1 year after they completed a 2-week inpatient pulmonary rehabilitation program. We also compared the effects of pulmonary rehabilitation on young-elderly (age 65–74 years) and old-elderly (age 75 years or over) COPD patients. Methodology: Fifty-nine elderly COPD patients (mean age 72.8 years) were studied. They underwent a comprehensive 2-week inpatient pulmonary rehabilitation program incorporating 10 exercise sessions, each of which included endurance training of the lower extremities, peripheral muscle conditioning training of the upper and lower extremities, and stretching, along with various education sessions. The effects of pulmonary rehabilitation were evaluated at 3, 6, and 12 months after completion of the program. Results: Overall, patient health-related quality of life (HRQoL) as assessed by a QoL scale, and dyspnoea as assessed by an oxygen cost diagram, improved significantly over the 12-month period. Exercise capacity assessed by a 6-min walking distance test (6MWD) was similarly significantly improved. However, there was some fall-off in terms of the distance walked 12 months after pulmonary rehabilitation. The improvements in exercise capacity, dyspnoea, and HRQoL did not differ between the two groups, with the exception that the 6MWD (P

Sweet's syndrome occurring during the course of interstitial pneumonitis in a 70-year-old woman was encountered. She was admitted because of dyspnea on exercise, dry cough and interstitial shadow on chest x-ray. Lung biopsy, together with other findings confirmed interstitial pneumonitis. Five days after admission, genital ulcer and aphtha on the oral mucosa were detected and exudative erythema appeared on her right shoulder, chest and back. Histological examination of the skin lesions demonstrated numerous nutrophilic infiltration in the upper dermis, indicating Sweet's syndrome. The skin eruption rapidly disappeared on treatment with colchicine. Although six months after admission interstitial pneumonitis caused respiratory failure, treatment with prednisolone and cyclophosphamide was effective. Serological and immunological tests demonstrated hyper-gammaglobulinemia and positive reaction for anti SS-A antibody. Pathological examination of the lip revealed numerous lymphocyte infiltrates around the duct of the minor salivary gland, suggesting Sjögren's syndrome as the background disease of Sweet's syndrome and interstitial pneumonitis. This evidence indicating that even in elderly patients, skin lesions of Sweet's syndrome may reveal the background disease.

Vitamin D supplementation can decrease the vulnerability to pulmonary infections. Therefore, it is speculated that the genes related to vitamin D metabolism are associated with an exacerbation-prone phenotype in chronic obstructive pulmonary disease (COPD). Because genetic variations of group component (GC) affect immunological capacity and serum vitamin D concentration, they could also affect the susceptibility to COPD exacerbation and the disease progression. We investigated the association between GC genetic variations and COPD and its exacerbation frequency in a Japanese population.We performed genotype analysis of 361 COPD patients and 219 controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and rs7041. We examined whether these polymorphisms were associated with the frequency of COPD exacerbation and analysed the correlation between the genotypes, COPD, emphysema severity and COPD progression, namely, the annual decline in airflow obstruction and diffusing capacity.Subjects with a C allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048), greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction (P = 0.0927).GC variations may affect exacerbation susceptibility, possibly leading to COPD worsening and its progression.

Age-associated changes of the lung might increase pathogenetic susceptibility to chronic obstructive pulmonary disease (COPD). Decrement in serum transforming growth factor (TGF)-β1 concentration is reported in elderly people. As impaired TGF-β1 signaling could cause emphysema-like changes, we hypothesized that decreased TGF-β1 with aging is correlated with emphysema.Symptomatic patients with or without COPD and healthy normal subjects without COPD were recruited (COPD, n = 182; smoking controls, n = 73; normal, n = 26). We investigated the correlation between TGF-β1 and extent of emphysema and airway wall thickness, which were defined as the percentage of low-attenuation area (LAA%) and large airway wall area (WA%) on pulmonary high-resolution computed tomography, respectively. The correlation of pulmonary function test parameters and TGF-β1 was evaluated. TGF-β1 was determined by enzyme-linked immunosorbent assay.TGF-β1 significantly decreased with age (P = 0.0009). When the correlation between age and TGF-β1 was analyzed in each group, a significant inverse correlation was found in COPD patients and smoking controls (P = 0.0095 and 0.0132, respectively), whereas no correlation was observed in healthy older adults. Among COPD patients with severe emphysema, LAA% was inversely correlated with TGF-β1 (n = 89, P = 0.0104), whereas WA% and pulmonary function test parameters were not.Although no correlation was found between TGF-β1 and the severity of COPD, TGF-β1 significantly decreased as emphysema became more severe. Age-related decrease of TGF-β1 in COPD might be associated with emphysematous alterations of the lungs in elderly subjects.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.

Education is a key issue for the long-term management of chronic obstructive pulmonary disease in older patients. We tested the hypothesis that integrated care focusing on patient information needs for self-management can improve patient information needs and health outcomes. Patients with chronic obstructive pulmonary disease (n=102) were randomized into integrated care (group I) and usual care (group U) groups. Group I underwent a program of educational sessions for 6months (integrated education period), and then repeatedly received an individually tailored education according to the Lung Information Needs Questionnaire score. Both groups were followed up monthly for 6months. A total of 85 patients (mean age: 71.7years) were followed up for 12months. The total Lung Information Needs Questionnaire score was significantly better in group I than in group U at 12months (P0.03). Activities of daily living scores were significantly improved in group I at 6months (P0.03). The dyspnea score and the BODE index (body mass index, dyspnea, airflow obstruction and exercise capacity) were significantly improved in group I at 12months (P0.01 and P0.02, respectively). During the integrated education period, the frequency of hospitalization was significantly lower in group I than in group U (P=0.033).Integrated education for older patients with chronic obstructive pulmonary disease effectively improved patients' information needs, activities of daily living, dyspnea score, BODE index and reduced hospitalizations during the observed period. Geriatr Gerontol Int 2011; 11: 422-430.

To determine whether the presence of in-home caregivers is associated with changes in the health outcomes of older adults with chronic obstructive pulmonary disease (COPD).Cross-sectional study.Geriatric medical center and academic respiratory clinic in Japan.Community-dwelling adults with COPD and their caregivers.Outcome measures (pulmonary function tests, distance on the 6-minute walking test (6MWT), activities of daily living (ADLs), quality of life (Medical Outcomes Study 36-item Short Form Survey and St. George's Respiratory Questionnaire), and frequencies of emergency visits and hospitalizations of those living alone (group A), those living with one caregiver (group B), and those living with two or more caregivers (group C) were compared.Three hundred eighty-nine participants (315 men and 74 women; mean age 73.3) were enrolled. Mean predicted forced expiratory volume in 1 second was 57.5%. The numbers of participants allocated into the global initiative for chronic obstructive lung disease stages I, II, III, and IV were 105, 107, 122, and 55, respectively. Group A had 87 participants; group B, 125; and group C, 177. Instrumental ADL scores were highest in group A (P.001), whereas 6MWT distance was longest in group B and shortest in group A. The frequency of emergency visits was highest in group A (P.001).Participants with COPD living alone were higher functioning in terms of instrumental ADLs, but they had less exercise capacity and more-frequent emergency visits than participants in the in-home caregiver groups and no difference in hospitalizations.

Background: Limited data are available on the association between the severity of emphysema or airway narrowing, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD), which has been seen to be more prevalent among elderly subjects. The aim of this study was to examine the association between HRQOL, physical parameters and structural alterations in lung of COPD patients. Methods: Stable COPD patients (n = 125; mean age 71.0) were studied. Both the severity of emphysema, which was expressed as the extent of the low-attenuation area (LAA%), and percentage of the large airway wall area (WA%) on high-resolution computed tomography (HRCT) were compared with various parameters of the generic and HRQOL, respectively, together with pulmonary function tests and exercise capacity. Results: The predicted value of forced expiratory volume in 1 s was significantly associated with both LAA% and WA%, but the diffusion capacity was strongly correlated with LAA% alone. Parameters of the generic and HRQOL, and almost all other parameters appeared to be significantly associated with LAA% alone, whereas no association was observed between WA% and QOL. Conclusion: We concluded that the severity of emphysema, but not that of large airway narrowing on HRCT, is associated with both generic and health-related QOL and reduced diffusion capacity. This notion might provide useful information in practice among elderly subjects who are unable to perform a spirometry.

Objective Low-dose, long-term macrolide therapy has been shown to be effective for the treatment of diffuse panbronchiolitis (DPB) and similar disorders in terms of the presence of airway mucus hypersecretion such as bronchiectasis, chronic bronchitis and sinobronchial syndrome. However, there are some patients, especially advanced cases, whose volume of sputum does not decrease sufficiently with macrolide therapy. These patients suffer from copious expectoration. There is currently no effective treatment, and an effective therapy is therefore urgently required. The aim of this study was to clarify whether or not the inhalation of tiotropium improves the symptoms in these cases. Methods Tiotropium (18 μg/day) was administered to patients with DPB and similar disorders with airway mucus hypersecretion who did not respond to macrolide. The symptoms were evaluated by a visual analog scale (VAS) prior to and at 1 and 3 months after tiotropium administration. Radiological and pulmonary function tests were also performed to evaluate the effects of tiotropium. Results Thirteen patients (DPB 5, sinobronchial syndrome 5, bronchiectasis 3) were enrolled. The VAS scores were dramatically improved after the introduction of tiotropium. FEV1 was significantly improved after 3 months of treatment with tiotropium. In contrast, the radiological findings remained unchanged. Conclusion Tiotropium improved the symptoms of cough, sputum and breathlessness in the macrolide-resistant cases of DPB or similar disorders. These beneficial effects might be due to the suppression of airway secretion through the anticholinergic effect of tiotropium on the submucosal gland, however, the long-term efficiency of this treatment still needs to be further assessed.

Acute exacerbation of COPD (AE-COPD) is a major problem influencing patient outcome, increasing both economic burden and mortality. We investigated: 1) the direct medical cost for inpatients with AE-COPD, and 2) factors that contribute to the higher cost of AE-COPD. A total of 131 episodes in 99 patients (mean age: 77.9 yr) with AE-COPD (79 men and 20 women) were investigated. Mean FEV1 and FEV1% pred were 0.97L and 42.7%, respectively. Mean length of stay (LOS) was 23.9 days and longer LOS was correlated with poorer basic activities of daily living (ADL). Mortality during admission and one month after discharge was 4.8%, however, it reached 20.2% one year later. The mean total cost for each admission was 690,000 yen (median 613,000 yen). Univariate analysis indicated that advanced age, hypoxemia, hypercapnea, systemic steroid use and reduction of ADL significantly correlated with increased total cost over the median cost. Multivariate analysis showed that factors significantly correlated with high medical cost over the median cost were observed in patients with a reduction of ADL (p0.001), hypoxemia OR 4.13 (95% CI: 1.54-11.05), systemic steroid use OR 3.14 (95% CI: 1.07-9.26), and reduced ADL OR 2.76 (95% CI: 1.04-7.30). However, neither advanced age nor severity of COPD, body mass index, or comorbidity significantly correlated with the total cost. We concluded that reduction of ADL in elderly COPD patients closely correlated with increased cost due to acute exacerbation. Therefore, pulmonary rehabilitation should be implemented from the perspective of reducing economic health burden.

A 31-year-old woman was admitted to our hospital because of progressive dyspnea and chest X-ray abnormality. She was given a diagnosis of bronchial asthma 3 years previously. She had received medical treatment, but her dyspnea did not improve. Chest CT showed multiple thin-walled cysts and centrilobular nodules throughout both lungs. Video-assisted thoracoscopic lung biopsy revealed remarkable plasmacytic infiltration in the bronchioles and its surrounding interstitium. Small cystic lesions were detected and with remarkable mural plasmacytic infiltration. The immunohistochemistry showed infiltrated plasmacytes with polyconal characteristics. Her biochemical examinations showed polyclonal hyperimmunoglobulinemia and a high range of serum IL-6. In addition, CT scans showed multiple mediastinal and intraperitoneal lymphadenopathy. From these examinations, she was given a diagnosis of multicentric Castleman disease (MCD) with pulmonary involvement showing diffuse cystic change. This case showed an unusual pattern of MCD with pulmonary involvement. However, we suggest that MCD also should be considered as a differential diagnosis in cases with diffuse lung cystic changes.

A 67-year-old female presented with diffuse edema, generalized telangiectasia, and indurated skin plaques. Histopathological findings of the skin lesion included CD45+/CD79+/CD20+ large lymphoma cells that filled the vascular lumina and infiltrated the subcutaneous tissues with panniculitic formations. Three cycles of a CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) chemotherapy regimen resolved the skin manifestations. After five cycles of CHOP, however, she developed dementia-like symptoms. Three cycles of additional intrathecal chemotherapy (methotrexate, cytarabine and prednisolone) did not improve the neurological symptoms.

A 65-year-old man was admitted to Tokyo Metropolitan Geriatric Medical Center because of dyspnea on effort, loss of appetite and general fatigue. Chest radiography on admission showed niveau formation in, and infiltration around, the bulla. Percutaneous drainage of the intrabullous fluid was performed and Mycobacterium gordonae was repeatedly cultured from it. The patient was treated with RFP, INH and CAM and the intrabullous fluid and infiltration around the bulla was markedly improved. Seven cases of pulmonary infection by M. gordonae have been reported in Japan, but this is the first case of bulla infected by this organism.

Two elderly patients with sarcoidosis complicated with Sjogren's syndrome are described. Case 1: A 70-year-old woman was admitted due to dry eyes. Histological examination of a minor salivary gland specimen revealed lymphocytic infiltration, which was compatible with Sjogren's syndrome. Because uveitis was demonstrated, transbronchial lung biopsy (TBLB) was performed, to confirm a diagnosis of lung sarcoidosis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Case 2: A 70-year-old woman was admitted due to dyspnea on exercise and blurred vision. Two years previously, Sjogren's syndrome was diagnosed because of a positive Shirmer test and positive SS-A antibody. Result of ophthalmic examination were compatible with uveitis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Certain similarities between sarcoidosis and Sjogren's syndrome in terms of immunological aspects have attracted attention. In the present manuscript, a possible relationship between the two diseases as well as the characteristics of elderly sarcoidosis are discussed.

To elucidate the involvement of NO in pain transmission in humans, we measured NO metabolites (nitrite/nitrate) in the CSF of patients with painful diseases using an NO analyzer based on the Griess method. The nitrite/nitrate levels in patients with degenerative lumbar disease (DLD), but not those with fracture or appendicitis, were significantly higher than those in an age-matched control group. The duration of pain in the DLD group was much longer than that in the fracture or appendicitis group. The nitrite/nitrate levels in the middle-aged and elderly DLD patients depended on the duration of pain. These data probably suggest that the duration of pain is critical for the elevation in nitrite/nitrate levels.

Takashi Motegi,1,2 Rupert C Jones,3 Takeo Ishii,1,2 Kumiko Hattori,1,2 Yuji Kusunoki,1,2 Ryuko Furutate,2 Kouich Yamada,1,2 Akihiko Gemma,1 Kozui Kida1,2 1Divisions of Pulmonary Medicine, Infectious Disease, and Oncology, Department of Internal Medicine, 2Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan; 3Respiratory Research Unit, Peninsula Medical School, Plymouth, UK Background: Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease. Aim: To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations. Methods: This was a 2-year prospective cohort study of COPD patients. Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared. Results: Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002). For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001). Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation. Conclusion: In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices. Keywords: frequency of exacerbation, multidimensional assessment systems, DOSE index, BODE index A Letter to the Editor has been received and published for this article.