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Hongxia Duan, Long Liang, Xinyang Liu, Shuanshuan Xie, Changhui Wang Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Shuanshuan Xie; Changhui WangDepartment of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, #301, Mid Yanchang Road, Shanghai, People’s Republic of ChinaTel/Fax +86-21-66301685Email xieshuanshuan@aliyun.com; wang-chang-hui@hotmail.comBackground: Pulmonary and activation-regulated chemokine (PARC) also named CC-chemokine ligand 18 (CCL18) is a lung-predominant inflammatory protein that is found in serum. The relationship of PARC/CCL18 with the chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC/CCL18 in COPD.Methods: Ninety-eight hospitalized COPD patients and 60 healthy volunteers from January 2019 to December 2019 were recruited in this retrospective study. Gender, age, height, weight, disease duration, smoking status, blood cell classification and count, length of hospital stay (LOS), symptom score, including COPD Assessment Test (CAT) score, modified British Medical Research Council (mMRC) score, lung function and therapy were recorded and serum PARC/CCL18 was analyzed by ELISA. The correlation between symptom score, blood cell classification and count, CRP, lung function parameters and serum levels of PARC/CCL18 and ROC curves of PARC/CCL18 levels and inhaled corticosteroids (ICS) were accessed.Results: It was found that serum PARC/CCL18 level in hospitalized COPD population was significantly higher than that in healthy people (p=0.003). COPD patients with emphysema had significantly higher serum level of PARC/CCL18 than those without emphysema (p=0.049). Total lung capacity (TLC) and residual volume (RV)/TLC had positive correlation with serum level of PARC/CCL18 (p=0.001, 0.020, respectively). Furthermore, serum PARC/CCL18 level was predictive for the application ICS (p=0.003) and related to C-reactive protein (p < 0.0001) in hospitalized COPD patients.Conclusion: PARC/CCL18 is associated with the severity of inflammation and emphysema in COPD. Furthermore, PARC/CCL18 is a predictor of ICS application in the treatment of hospitalized COPD patients.Keywords: PARC/CCL18, COPD, inflammation, pulmonary function, inhaled corticosteroids

Qing Song,1– 3 Yi-Yang Zhao,1– 3 Yu-Qin Zeng,1– 3 Cong Liu,1– 3 Wei Cheng,1– 3 Min-Hua Deng,4 Xin Li,5 Li-Bing Ma,6 Yan Chen,1– 3 Shan Cai,1– 3 Ping Chen1– 3 1Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4Department of Respiratory, PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 5Division 4 of Occupational Disease, Hunan Occupational Disease Prevention and Treatment Hospital, Changsha, Hunan, 410000, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541000, People’s Republic of ChinaCorrespondence: Ping ChenDepartment of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86 731 8529 5248Fax +86 731 8529 5848Email pingchen0731@csu.edu.cnBackground: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 separated pulmonary function from combined assessment. We aimed to analyze the characteristics of airflow limitation and future exacerbations in different GOLD groups of chronic obstructive pulmonary disease (COPD) patients.Methods: For this prospective observational study, stable COPD outpatients were enrolled and divided into Groups A, B, C and D based on GOLD 2017, and followed-up for 18 months. Data on demographics, pulmonary function, COPD assessment test (CAT), Clinical COPD Questionnaire (CCQ), modified Medical Research Council (mMRC), exacerbations, mortality and treatments were collected. A post-bronchodilator ratio of forced expiratory volume in one second to forced vital capacity < 0.70 confirms the presence of airflow limitation.Results: A total of 993 subjects were classified into Groups A (n = 170, 17.1%), B (n = 360, 36.3%), C (n = 122, 12.3%), and D (n = 341, 34.3%). There were significant differences in mMRC, CAT, CCQ, exacerbations and hospitalizations rates among the different groups (P < 0.001). Groups B and D had more severe airflow limitation than Groups A and C (P < 0.05). In the same groups with different severity of airflow limitation, the differences were mainly observed in body mass index, CAT, CCQ and treatment with long-acting muscarinic antagonist (LAMA) and LAMA + long-acting β 2-agonist + inhaled corticosteroid (P < 0.05). After 18 months of follow-up, the exacerbations and hospitalizations rates were significantly different among different groups (P < 0.05). However, in the same groups with different airflow limitation severity, the mortality rates and number of exacerbations, hospitalizations and frequent exacerbators showed no differences.Conclusion: In the GOLD groups, different severity of airflow limitation had no impact on future exacerbations and mortality rate. It implies that pulmonary function is not a good indicator for predicting exacerbation.Keywords: chronic obstructive pulmonary disease, Global Initiative for Chronic Obstructive Lung Disease, pulmonary function, exacerbation

Yiben Huang,1,* Bingqian Jiang,1,2,* Xiaqi Miao,1,2,* Jiedong Ma,1,2 Jianing Wang,1,2 Keke Ding,1,2 Xianjing Chen,1 Qiaoming Hu,1,2 Fangyi Fu,1,2 Tian Zeng,1,2 Jingyu Hu,1,2 Binbin Hu,1,2 Dehao Yang,3 Xiaodiao Zhang1 1Department of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehao YangDepartment of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009 Zhejiang, People’s Republic of ChinaTel +8613566209652Email dehao_yang@zju.edu.cnXiaodiao ZhangDepartment of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou 325000 Zhejiang, People’s Republic of ChinaTel +86-577-65866223Fax +86-577-65866586Email xiaodiao_zhang@126.comPurpose: This study aimed to explore the relation between lymphocyte to high-density lipoprotein ratio (LHR) and pulmonary function of chronic obstructive pulmonary disease (COPD) patients compared with neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR).Patients and Methods: In total, 154 participants (n = 77 with COPD and n = 77 without COPD) were recruited. LHR, NLR, PLR, lung function and other data were collected and compared. Pearson’s correlation test and the receiver operating characteristics curves were used to compare the utility of LHR, NLR and PLR. Besides, univariate and multivariate logistic regression analyses were conducted.Results: COPD patients with poorer lung function had a lower LHR level (P < 0.001). In low LHR group, more patients underwent greater airflow limitation than the other group (P = 0.006). LHR positively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV1%) (r = 0.333, P = 0.003). At a cut-off value of 2.08, the sensitivity and specificity of LHR in predicting FEV1% < 50 were 93.2% and 55.6%, respectively, with an AUC of 0.770 (P = 0.001) better than NLR and PLR. Based on logistic regression analyses, it was proved that LHR was associated with decreased risk of FEV1 < 50% predicted in COPD patients (odds ratio = 0.198, 95% CI: 0.048– 0.811, P = 0.024).Conclusion: In contrast with NLR and PLR, LHR has higher accuracy for predicting pulmonary function in COPD; lower LHR level is independently associated with poorer pulmonary function.Keywords: COPD, pulmonary function, lymphocytes, high-density lipoprotein

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

Jinglong Chen,1,2,&ast; Changbin Jiang,1,&ast; Youlan Zheng,1,&ast; Dongxing Zhao,1,&ast; Fan Wu,1 Zhuxiang Zhao,3 Jun Zhao,2 Qing Li,2 Bing Li,4 Gongyong Peng,1 Yumin Zhou,1 Pixin Ran1 1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Geriatrics, National Clinical Key Specialty, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3The Pulmonary Medicine, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 4GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin RanNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of ChinaEmail pxran@gzhmu.edu.cnBackground and Objective: To determine the effects of BSE (biomass smoke exposure) on pulmonary and non-pulmonary changes in patients with COPD compared with normal individuals.Methods: Using a cohort, we recruited 16 healthy individuals with BSE (BSE normal), 19 patients with BSE+COPD, 13 healthy individuals with cigarette smoke exposure (CSE normal), 25 patients with CSE+COPD, and 25 healthy controls. Patients with GOLD stage I and II COPD were included. Baseline data (demographic data, BSE or CSE, lung function, and CT findings) and follow-up lung function data were collected. CT parameters of emphysema, pulmonary small vessels, airway remodeling, pectoralis muscles, and erector spinae muscle were measured.Results: Individuals with BSE were mainly women (32/35, 91.43%). Compared with the CSE+COPD group, the BSE+COPD group demonstrated slower lung function decline, increased lower lung emphysema, narrower airway lumen dimensions and increased airway wall thickening in the moderate and small airways (all P< 0.05). Compared with healthy controls, the CSE normal and BSE normal groups exhibited significant reductions in pulmonary small vessel area and obvious airway remodeling in small airways (P< 0.05). Compared with the BSE normal group, the BSE+COPD group showed significantly more severe emphysema and airway remodeling, as well as reduced left pectoralis major muscle area (all P< 0.05).Conclusion: Healthy individuals with BSE had reduced pulmonary small vessel area and evidence of airway remodeling; patients with BSE and COPD showed more severe emphysema, airway remodeling, and reductions in pectoralis major muscle area.Clinical Trial Registration: ChiCTR-OO-14004264.Keywords: biomass smoke, chronic obstructive pulmonary disease, computed tomography, pulmonary function

Yuanlong Hu,1,&ast; Xiaomeng Cheng,1,&ast; Zhanjun Qiu,2 Xianhai Chen2 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanjun Qiu; Xianhai Chen Email qiuzhj227@163.com; chenxianhai18@163.comPurpose: This study aimed to identify the COPD molecular subtypes reflecting pulmonary function damage on the basis of metabolism-related gene expression, which provided the opportunity to study the metabolic heterogeneity and the association of metabolic pathways with pulmonary function damage.Methods: Univariate linear regression and the Boruta algorithm were used to select metabolism-related genes associated with forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) in the Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. COPD subtypes were further identified by consensus clustering with best-fit. Then, we analyzed the differences in the clinical characteristics, metabolic pathways, immune cell characteristics, and transcription features among the subtypes.Results: This study identified two subtypes (C1 and C2). C1 exhibited higher levels of lower pulmonary function and innate immunity than C2. Ten metabolic pathways were confirmed as key metabolic pathways. The pathways related to N-glycan, hexosamine, purine, alanine, aspartate and glutamate tended to be positively associated with the abundance of adaptive immune cells and negatively associated with the abundance of innate immune cells. In addition, other pathways had opposite trends. All results were verified in Genetic Epidemiology of COPD (COPDGene) datasets.Conclusion: The two subtypes reflect the pulmonary function damage and help to further understand the metabolic mechanism of pulmonary function in COPD. Further studies are needed to prove the prognostic and therapeutic value of the subtypes.Keywords: chronic obstructive pulmonary disease, molecular subtype, metabolic pathway, pulmonary function

Kai Liu,1,* Xinjuan Yu,2,* Xuefen Cui,2 Yi Su,2 Lixin Sun,3 Jiulong Yang,4 Wei Han2 1Department of Rehabilitation, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Anesthesia, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 4Hospital Office, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnJiulong YangHospital Office, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 88905509Email qdyxkp@163.comBackground: The proprioceptive neuromuscular facilitation (PNF) stretching could improve the contractile capacity of respiratory muscles, but the effect on pulmonary function, when it is combined with aerobic training, remains unknown.Objective: To evaluate the effect of PNF combined with aerobic training on respiratory symptoms, pulmonary function and neck/shoulder mobility in patients with COPD.Design: Randomized controlled trial.Participants: Fifty-five COPD patients were randomly divided into PNF group (n=28) and control group (n=27).Intervention: On the basis of conventional treatment, the control group performed 30 min aerobic training on a treadmill, while the PNF group added 10-minute PNF stretching 3 times every training day. Both groups did their training in 5 days per week for 6 weeks.Measures: Measures were taken before and after 6 weeks of training. COPD Assessment Test (CAT), dyspnea Visual Analog Scale (VAS), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), inspiratory capacity (IC), inspiratory reserve volume (IRV), 6-minute walk test (6MWT), the range of motion (ROM) of head protraction, shoulder flexion, and the non-dominant pectoralis minor muscle (PmM) length were measured.Results: All the indicators of both groups were significantly improved after 6 weeks of intervention except for FVC, FEV1 and PmM length. Compared to the control group, the PNF group showed significant improvement in the CAT score, dyspnea VAS score, IC, IRV, 6MWT, as well as head protraction ROM and shoulder flexion ROM. Furthermore, IC was positively correlated with the head protraction ROM and PmM length (r=0.415, 0.579, P=0.028, 0.001); IRV was positively correlated with the shoulder flexion ROM (r=0.405, P=0.032) in the PNF group.Conclusion: PNF stretching combined with aerobic training reduces dyspnea and improves some pulmonary function measures, which is associated with neck/shoulder mobility, in COPD patients.Keywords: chronic obstructive pulmonary disease, proprioceptive neuromuscular facilitation stretching, aerobic training, pulmonary function

Yiben Huang,1,* Jianing Wang,1,2,* Jiamin Shen,1,2,* Jiedong Ma,1,2 Xiaqi Miao,1,2 Keke Ding,1,2 Bingqian Jiang,1,2 Binbin Hu,1,2 Fangyi Fu,1,2 Lingzhi Huang,1 Meiying Cao,3 Xiaodiao Zhang1 1Department of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Cardiology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodiao ZhangDepartment of Respiratory Medicine, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaTel +86-577-65866223Fax +86-577-65866586Email xiaodiao_zhang@126.comMeiying CaoDepartment of Cardiology, The Third Affiliated Hospital of Wenzhou Medical University Email 519243591@qq.comBackground: We aimed to investigate the association between red cell index (RCI) and the severity of Chronic Obstructive Pulmonary Disease (COPD), and compare predictive value of RCI, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) for the severity of COPD.Methods: A total of 207 participants were recruited (100 COPD patients and 107 healthy controls). COPD patients were divided into two groups according to the optimal cut-off value of RCI determined by the receiver operating characteristic (ROC) curve. Pearson’s correlation test, logistic regression analysis and other tests were performed.Results: Compared with low RCI group, the forced expiration volume in 1 second (FEV1) and FEV1 in percent of the predicted value (FEV1%) in high RCI group were lower (p = 0.016, p = 0.001). There was a negative correlation between RCI and FEV1% (r = − 0.302, p = 0.004), while no correlation between FEV1% and NLR as well as PLR were found. RCI showed higher predictive value than NLR and PLR for predicting Global Initiative for Chronic Obstructive Lung Disease classification (GOLD), with a cut-off value of 1.75 and area under the curve (AUC) of 0.729 (p = 0.001). Multivariate logistic regression analysis proved that RCI was an independent factor for lung function in COPD patients (odds ratio [OR] = 4.27, 95% CI: 1.57– 11.63, p = 0.004).Conclusion: RCI is a novel biomarker that can better assess pulmonary function and severity of COPD than NLR and PLR. Higher RCI is related to deterioration of pulmonary function.Keywords: COPD, pulmonary function, RCI, biomarker

David M Mannino,1 Emmanuelle M Clerisme-Beaty,2 Joanne Franceschina,2 Naitee Ting,2 Nancy K Leidy3 1Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY, USA; 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 3Evidera, Bethesda, MD, USA Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI). Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care for AECOPD and RTI. Due to under-recruitment, the trial ended early and hence was underpowered to detect treatment differences. Data were pooled and exacerbation recovery patterns examined by using the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), forced expiratory volume in 1 second, rescue medication use, COPD Assessment Test™, Functional Assessment of Chronic Illness Therapy–Short Form, and Work Productivity and Activity Impairment Questionnaire: Respiratory Symptoms. Results: Of 140 patients, 73.6% had a prior COPD diagnosis without maintenance therapy; 80.0% had moderate-to-severe airflow obstruction. In addition to study drug, 40.0% were prescribed pharmacologic therapy (corticosteroids [34.3%], antibiotics [16.4%], and short-acting β2-adrenergic agonists [5.0%]) within ±7 days of randomization. Over 12 weeks, 78.6% exhibited symptomatic recovery (EXACT score) in a median of 5.0 days. Across all patients, 49.3% recovered without relapse, 29.3% recovered and then relapsed, and 21.4% had persistent symptoms (recovery criteria unmet). Conclusion: A substantial portion of newly diagnosed or maintenance treatment-naïve patients with COPD experience relapse or persistent symptoms following a clinic visit for AECOPD with symptoms of RTI. Whether initiating maintenance therapy could improve outcomes and reduce exacerbation risk requires further study. Keywords: acute respiratory tract infection symptoms, acute exacerbation of chronic obstructive pulmonary disease, AECOPD, COPD Assessment Test™, EXACT, maintenance therapy, pulmonary function, tiotropium

Background and purpose While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials. Materials and methods In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0–3) response and trough FEV1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication. Results In the East Asian population, 1,152 patients were randomized (5,163 overall). After 24 weeks, FEV1 AUC0–3 and trough FEV1 responses were greater (P, Video abstract

Rachida Rafiq,1 Hendrik J Prins,2 Wim G Boersma,2 Johannes MA Daniels,3 Martin den Heijer,1 Paul Lips,1 Renate T de Jongh1 1Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, 2Department of Pulmonary Diseases, Northwest Hospital group, Alkmaar, 3Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, the Netherlands Background: Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients. Objective: To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life. Methods: We performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms. Results: At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P

Shih-Lung Cheng,1,2 Hsu Hui Wang,1 Ching-Hsiung Lin3–5 1Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, 2Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan, 3Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, 4Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, 5School of Medicine, Chung Shan Medical University, Taichung, Taiwan Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder encompassing different phenotypes with different responses to treatment. The present 1-year, two-center hospital-based study investigated whether the plasma immunoglobulin E (IgE) level and/or eosinophil cell count could be used as biomarkers to stratify patients with COPD according to predicted responses to inhaled corticosteroids (ICS)-based therapy. Methods: A hospital-data based cohort study of COPD patients treated at two territory hospital centers was conducted for 1 year. Allergic biomarkers, including blood eosinophil counts and IgE levels, were assessed at baseline. Lung function parameters, including forced expiratory volume in 1second (FEV1), forced vital capacity (FVC), and the COPD Assessment Test (CAT), were also evaluated. The frequencies of acute exacerbation (AE) and pneumonia were also measured. Eosinophilia and a high IgE level were defined as >3% and 173 IU/mL, respectively. Results: A total of 304 patients were included. Among patients with eosinophilia and high IgE levels, ICS-based therapy was associated with significant improvements in FEV1, FVC, and CAT scores, compared with bronchodilator (BD) therapy (P≤0.042). ICS-based therapy was also associated with a significantly lower incidence of AE vs BD-based therapy (11.7% vs 24.1%; P

Background Clinical studies have suggested nebulized budesonide (NB) as an alternative to systemic corticosteroids for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the optimal budesonide dose for AECOPD remains unclear. Objectives To compare the efficacy and safety of different doses of NB in the management of AECOPD. Patients and Methods A total of 321 AECOPD patients with moderate-to-severe exacerbation were randomly divided into three groups and treated with NB. The low dose group (L) was given 4 mg/day (n=95, 1 mg Q6h), while high-dose group 1 (H1, n=111, 2 mg Q6h) and high-dose group 2 (H2, n=115, 4 mg Q12h) were given 8 mg/day. Patients also received routine treatment including oxygen therapy, expectorant, nebulization bronchodilators, antibiotics, and fluid rehydration. The COPD assessment test (CAT), lung function, and artery blood gas were evaluated before and after 3 hrs and 5 days of treatment. In addition, hospital stay, frequency of acute exacerbations within 3 months of discharge, and adverse events during treatment were compared. Results H1 and H2 showed improved spirograms and CAT score faster than L. In H2, forced expiratory volume in 1 s (FEV1%) at 3 hrs and FEV1%, forced expiratory flow after 50% of the forced vital capacity has been exhaled (FEF50%), mean forced expiratory flow between 25% and 75% of forced vital capacity (FEF25–75%) and CAT score at 5 days were significantly improved compared to L. FEV1% improved most in H2, moderately in H1, and least in L, with significant differences between groups at 5 days. No differences between groups were observed in adverse effects, hospital stay, and frequency of exacerbations within 3 months of discharge. Conclusion Compared to the conventional dose (4 mg/day), a high dose (8 mg/day) of NB improved pulmonary function and symptoms more effectively in the early treatment of AECOPD, especially when given as 4 mg twice daily.

Kazuhiko Watanabe,1 Ayumi Onoue,1 Kenichi Kubota,2 Noritaka Higashi,2 Toshinari Hayashi,3 Tohru Tsuda,4 Hisamitsu Omori1 1Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan; 2Department of Respiratory Medicine, Japanese Red Cross Kumamoto Health Care, Kumamoto 861-8528, Japan; 3Tokorozawa Respiratory Clinic, Tokorozawa, Saitama, Japan; 4Kirigaoka Tsuda Hospital, Kitakyusyu, Fukuoka, JapanCorrespondence: Hisamitsu OmoriDepartment of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuo-ku Kumamoto, Kumamoto 862-0976, JapanTel +81 96 373 5462Fax +81 96 373 5462Email omorih@gpo.kumamoto-u.ac.jpIntroduction: This study aimed to assess the association between airflow limitation (AL) severity and reduced bone mineral density (BMD) in Japanese men.Subjects and methods: This cross-sectional study included 290 subjects aged over 40years (mean age 72.0, SD 11.6), who underwent a comprehensive health examination, including spirometry and measurement of BMD at the left femoral neck using dual-energy X-ray absorptiometry (DXA), between 2016 and 2017 at Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of −2.5 SD]), or osteoporosis (YAM ≦ 70% [≦ −2.5 SD]). Reduced BMD was defined as osteopenia, osteoporosis, or medication used for osteoporosis. Logistic regression analysis was used to assess the association between AL severity and the reduced BMD.Results: The prevalence of reduced BMD in subjects with moderate-to-severe AL (76.2%) was significantly higher than in those without AL (47.9%) (p=0.030). In logistic regression models adjusted for age, body mass index, pack-years, physical activity, and alcohol drinking, the risk of reduced BMD (odds ratio: 3.87; 95% confidence interval: 1.20–12.49; p=0.024) was significantly higher in subjects with moderate-to-severe AL than in those with normal pulmonary function.Conclusion: Present results suggest that reduced BMD is associated with AL severity in Japanese men.Keywords: chronic obstructive pulmonary disease, comorbidity, bone mineral density, osteoporosis, airflow limitation, pulmonary function

Purpose: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. Patients and methods: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. Results: In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. Conclusion: A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema., International Journal of Chronic Obstructive Pulmonary Disease, 11(1), pp.2287-2294; 2016

Jui-O Chen,1,2,* Jui-Fang Liu,1,3–5,* Yu-qi Liu,6 Yu-Mu Chen,7 Mei-Lien Tu,4 Hong-Ren Yu,8 Meng-Chih Lin,3,7 Chiu-Chu Lin,2 Shih-Feng Liu3,7 1Department of Nursing, Tajen University, Pingtung, Taiwan; 2College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Respiratory Care, Chang Gung University of Science and Technology, Taoyuan, Taiwan; 5Department of Education, National Kaohsiung Normal University, Kaohsiung, Taiwan; 6Department of Intensive Care unit, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 8Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan *These authors contributed equally to this work Purpose: It is unclear whether the effectiveness of pulmonary rehabilitation program (PRP) after cardiac surgery differs between patients with and without COPD. This study aimed to compare the effectiveness of PRP between patients with and without COPD undergoing coronary artery bypass graft (CABG) surgery. Patients and methods: We retrospectively included patients who underwent CABG surgery and received 3-week PRP from January 2009 to December 2013. We excluded patients who underwent emergency surgery, had an unstable hemodynamic status, were ventilator dependent or did not complete the PRP. Demographics, muscle strength, degree of dyspnea, pulmonary function and postoperative complications were compared. Results: Seventy-eight patients were enrolled (COPD group, n=40; non-COPD group, n=38). Maximal inspiratory pressure (MIP; −34.52 cmH2O vs −43.25 cmH2O, P

Ah Young Leem, Se Kyu Kim, Joon Chang, Young Ae Kang, Young Sam Kim, Moo Suk Park, Song Yee Kim, Eun Young Kim, Kyung Soo Chung, Ji Ye Jung Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Heavy metal exposure may contribute to inflammation in the lungs via increased oxidative stress, resulting in tissue destruction and obstructive lung function (OLF). In this study, we evaluated the relationship between lead and cadmium levels in blood, and lung function in the Korean population.Methods: Pooled cross-sectional data from 5,972 subjects who participated in the Korean National Health and Nutrition Examination Survey 2008–2012 were used for this study. OLF was defined as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)

Mariko Kitano,1 Shingo Iwano,1 Naozumi Hashimoto,2 Keiji Matsuo,3 Yoshinori Hasegawa,2 Shinji Naganawa1 1Department of Radiology, 2Department of Respiratory Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan; 3Department of Radiology, Ichinomiya Municipal Hospital, Ichinomiya, Aichi, Japan Background: We investigated correlations between lung volume collapsibility indices and pulmonary function test (PFT) results and assessed lobar differences in chronic obstructive pulmonary disease (COPD) patients, using paired inspiratory and expiratory three dimensional (3D) computed tomography (CT) images. Methods: We retrospectively assessed 28 COPD patients who underwent paired inspiratory and expiratory CT and PFT exams on the same day. A computer-aided diagnostic system calculated total lobar volume and emphysematous lobar volume (ELV). Normal lobar volume (NLV) was determined by subtracting ELV from total lobar volume, both for inspiratory phase (NLVI) and for expiratory phase (NLVE). We also determined lobar collapsibility indices: NLV collapsibility ratio (NLVCR) (%) = (1 - NLVE/NLVI) × 100%. Associations between lobar volumes and PFT results, and collapsibility indices and PFT results were determined by Pearson correlation analysis. Results: NLVCR values were significantly correlated with PFT results. Forced expiratory volume in 1 second, measured as percent of predicted results (FEV1%P) was significantly correlated with NLVCR values for the lower lobes (P

Masanari Watanabe,1 Hisashi Noma,2 Jun Kurai,1 Hiroyuki Sano,3 Yasuto Ueda,1 Masaaki Mikami,4 Hiroyuki Yamamoto,5 Hirokazu Tokuyasu,6 Kazuhiro Kato,7 Tatsuya Konishi,8 Toshiyuki Tatsukawa,8 Eiji Shimizu,1 Hiroya Kitano9 1Department of Respiratory Medicine and Rheumatology, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 2Department of Data Science, The Institute of Statistical Mathematics, 10-3 Midori-cho, Tachikawa, Tokyo, 3Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, 4Hosshoji Clinic, 286-4 Hosshoji, Saihaku, 5Saihaku Hospital, 397 Yamato, Saihaku, 6Department of Respiratory Medicine, Matsue Red Cross Hospital, 200 Horomachi, Matsue, 7Department of Respiratory Medicine, San-in Rosai Hospital, 1-8-1 Kaikeshinden, Yonago, 8Department of Respiratory Medicine, Matsue City Hospital, 32-1 Noshirachou, Matsue, 9The Board of Directors, Tottori University, 36-1 Nishi-cho, Yonago, Japan Background: Asian dust (AD) exposure exacerbates pulmonary dysfunction in patients with asthma. Asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS), characterized by coexisting symptoms of asthma and chronic obstructive pulmonary disease, is considered a separate disease entity. Previously, we investigated the effects of AD on pulmonary function in adult patients with asthma. Here, we present the findings of our further research on the differences in the effects of AD exposure on pulmonary function between patients with asthma alone and those with ACOS.Methods: Between March and May 2012, we conducted a panel study wherein we monitored daily peak expiratory flow (PEF) values in 231 adult patients with asthma. These patients were divided into 190 patients with asthma alone and 41 patients with ACOS in this study. Daily AD particle levels were measured using light detection and ranging systems. Two heavy AD days (April 23 and 24) were determined according to the Japan Meteorological Agency definition. Alinear mixed model was used to estimate the association between PEF and AD exposure.Results: Increments in the interquartile range of AD particles (0.018 km-1) led to PEF changes of–0.50 L/min (95% confidence interval, –0.98 to –0.02) in patients with asthma alone and–0.11 L/min (–0.11 to 0.85) in patients with ACOS. The PEF changes after exposure to heavy AD were –2.21 L/min (–4.28 to –0.15) in patients with asthma alone and –2.76 L/min (–6.86 to 1.35) in patients with ACOS. In patients with asthma alone, the highest decrease in PEF values was observed on the heavy AD day, with a subsequent gradual increase over time.Conclusion: Our results suggest that the effects of AD exposure on pulmonary function differ between patients with asthma alone and ACOS, with the former exhibiting a greater likelihood of decreased pulmonary function after AD exposure. Keywords: Asian dust, asthma, asthma–chronic obstructive pulmonary disease overlap syndrome, peak expiratory flow, pulmonary function

Yoshiaki Minakata,1 Yukiko Morishita,2 Tomohiro Ichikawa,3 Keiichiro Akamatsu,3 Tsunahiko Hirano,3 Masanori Nakanishi,3 Kazuto Matsunaga,3 Masakazu Ichinose41Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Mihama-cho, Hidaka-gun, Wakayama, Japan; 2Department of Respiratory Medicine, Naga Municipal Hospital, Kinokawa, Wakayama, Japan; 3Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Wakayama, Japan; 4Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, JapanBackground: Improvement in the daily physical activity (PA) is important for the management of chronic obstructive pulmonary disease (COPD). However, the effects of pharmacologic treatment on PA are not well understood. We evaluated the effects of additional medications, including bronchodilator with or without inhaled corticosteroid, based on airflow limitation and breathlessness on the PA in COPD patients and the factors that could predict or affect the improvement in PA.Methods: A prospective non-randomized observational study was employed. Twenty-one COPD subjects without any other diseases that might reduce PA were recruited. The PA was measured with a triaxial accelerometer for 2 weeks, and pulmonary function tests and incremental shuttle walking tests were administered before and after 4-week treatment with an additional medication.Results: Bronchodilation was obtained by additional medication. The mean values of PA evaluated by metabolic equivalents (METs) at ≥3.0 METs and the duration of PA at ≥3.0 METs and ≥3.5 METs were improved by medication. The % change in the duration of PA at ≥3.5 METs was significantly correlated with the baseline functional residual capacity (FRC), residual volume, and inspiratory capacity/total lung capacity. However, the % change in the duration of PA at any intensity was not correlated with the % changes of any values of the pulmonary function tests or incremental shuttle walking test except the PA at ≥2.5 METs with FRC.Conclusion: Medication could improve the PA in patients with COPD, especially at a relatively high intensity of activity when medication was administered based on airflow limitation and breathlessness. The improvement was seen in the patients with better baseline lung volume, but was not correlated with the improvements in the pulmonary function tests or exercise capacity.Keywords: COPD, accelerometer, bronchodilator, pulmonary function, predictor

Soichiro Hanada,1 Shota Wada,1 Takeshi Ohno,1 Hirochiyo Sawaguchi,1 Masato Muraki,1 Yuji Tohda2 1Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, 2Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine, Osakasayama, Japan Background: Tiotropium (Spiriva) is an inhaled muscarinic antagonist for patients with chronic obstructive pulmonary disease (COPD), and is available in two forms: the HandiHaler and the Respimat inhaler. The aim of this study was to investigate the handling of and preference for each device immediately after switching from the HandiHaler to the Respimat and 2–3 years after the switch.Materials and methods: The study comprised two surveys. A questionnaire was first administered to 57 patients with COPD (male:female 52:5, mean age 73.6±7.1 years) 8 weeks after switching from the HandiHaler (18 µg) to the Respimat (5 µg). A second similar but simplified questionnaire was administered to 39 of these patients who continued to use the Respimat and were available for follow-up after more than 2 years. Pulmonary function was also measured during each period.Results: In the first survey, 17.5% of patients preferred the HandiHaler, and 45.6% preferred the Respimat. There were no significant changes in pulmonary function or in the incidence of adverse events after the switch. In the second survey, performed 2–3 years later, the self-assessed handling of the Respimat had significantly improved, and the number of patients who preferred the Respimat had increased to 79.5%.Conclusion: The efficacy of the Respimat was similar to that of the HandiHaler. This was clear immediately after the switch, even in elderly patients with COPD who were long-term users of the HandiHaler. The preference for the Respimat increased with continued use. Keywords: chronic obstructive pulmonary disease, tiotropium, HandiHaler, Respimat, questionnaire, pulmonary function

This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study. COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 microg, 2.5 microg, 5 microg, 10 microg, or 20 microg Respimat SMI (a novel, propellant-free device); tiotropium 18 microg HandiHaler; placebo Respimat; or placebo HandiHaler for 3 weeks. The primary endpoint was trough FEV1 on Day 21. Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics. In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo. Tiotropium 5 microg Respimat, 20 microg Respimat, and tiotropium 18 microg HandiHaler were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV1 was 150 mL (both Respimat doses) versus 20 mL (placebo Respimat); p0.05; and 230 mL (HandiHaler) versus -90 mL (placebo HandiHaler); por = 0.001). The urinary excretion (up to 2 hours post-dose) of tiotropium 5-10 microg Respimat was comparable with tiotropium 18 microg HandiHaler; the overall incidence of adverse events was comparable across treatment groups. Tiotropium 5 and 10 microg Respimat improve lung function in COPD patients and appear to be comparable with tiotropium 18 microg HandiHaler.

Masakazu Ichinose,1 Ayako Takizawa,2 Toshiyasu Izumoto,2 Yusuke Tadayasu,2 Alan L Hamilton,3 Christina Kunz,4 Yoshinosuke Fukuchi51Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany; 5Juntendo University School of Medicine, Tokyo, JapanBackground: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.Objective: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD) olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4weeks in Japanese patients with chronic obstructive pulmonary disease (COPD).Methods: All eligible patients were randomized to receive 2µg, 5µg, or 10µg of olodaterol or placebo for 4weeks via the Respimat® Soft Mist™ inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1second (FEV1) after 4weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1week and 2weeks of treatment, FEV1 area under the curve from 0hour to 3hours (AUC0–3), peak FEV1 from 0hour to 3hours (peak FEV1), and corresponding forced vital capacity (FVC) responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed.Results: A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P

Gianna Camiciottoli,1 Stefano Diciotti,2 Francesca Bigazzi,1 Simone Lombardo,3 Maurizio Bartolucci,4 Matteo Paoletti,1 Mario Mascalchi,3 Massimo Pistolesi1 1Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy; 2Department of Electrical, Electronic, and Information Engineering “Guglielmo Marconi,” University of Bologna, Cesena, Italy; 3Radiodiagnostic Section, Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy; 4Department of Diagnostic Imaging, Careggi University Hospital, Florence,Italy Abstract: A substantial proportion of patients with chronic obstructive pulmonary disease (COPD) develops various degree of intrathoracic tracheal collapsibility. We studied whether the magnitude of intrathoracic tracheal collapsibility could be different across clinical phenotypes and sex in COPD. Intrathoracic tracheal collapsibility measured at paired inspiratory–expiratory low dose computed tomography (CT) and its correlation with clinical, functional, and CT-densitometric data were investigated in 69 patients with COPD according to their predominant conductive airway or emphysema phenotypes and according to sex. Intrathoracic tracheal collapsibility was higher in patients with predominant conductive airway disease (n=28) and in females (n=27). Women with a predominant conductive airway phenotype (n=10) showed a significantly greater degree of collapsibility than women with predominant emphysema (28.9%±4% versus 11.6%±2%; P

Yan Zhang,* You-Hui Tu,* Guang-He FeiPulmonary Department, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally tothis workBackground: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a validated simple instrument to assess health status, and it correlates well with the severity of airway obstruction in COPD patients. However, little is known about the relationships between CAT scores and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness in COPD patients in the People’s Republic of China. Methods: One hundred and twelve participants including 63 COPD patients and 49 normal control subjects were recruited. All participants were examined with high-resolution CT to get the measurements of emphysema (percentage of pixels below -950 HU [%LAA–950]) and airway wall thickness (wall area percentage and the ratio of airway wall thickness to total diameter). Meanwhile, they completed the CAT and modified Medical Research Council questionnaire independently.Results: Significantly higher CAT scores and CT measurements were found in COPD patients compared with normal control subjects (P

Background: Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome). It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS). Methods: Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1], Article, INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. 7:283-289 (2012)