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Lian Wu,1,2 Jing Zhang,3 Jie Ming Qu,4 Chun-xue Bai,3 Mervyn J Merrilees5 1Department of Community and Health Services, Unitec, 2Department of Pharmacology & Clinical Pharmacology, University of Auckland, Auckland, New Zealand; 3Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 4Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand Abstract: A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA) against versican to determine if knockdown of versican could restore the deposition of insoluble elastin. Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients (P<0.01) and significantly increased deposition of insoluble elastin in the COPD cell cultures (P<0.05). The treatment, however, did not significantly affect production of soluble elastin (tropoelastin) in either the COPD or non-COPD cell cultures, supporting a role for versican in inhibiting assembly but not synthesis of tropoelastin. These results suggest that removal or knockdown of versican may be a possible therapeutic strategy for increasing deposition of insoluble elastin and stimulating repair of elastic fibers in COPD lung. Keywords: pulmonary fibroblasts, COPD, elastin, versican

Bai-qiang Cai,1 Shao-xi Cai,2 Rong-chang Chen,3 Li-ying Cui,4 Yu-lin Feng,5 Yu-tong Gu,6 Shao-guang Huang,7 Rong-yu Liu,8 Guang-nan Liu,9 Huan-zhong Shi,10 Yi Shi,11 Yuan-lin Song,6 Tie-ying Sun,12 Chang-zheng Wang,13 Jing-lan Wang,1 Fu-qiang Wen,5 Wei Xiao,14 Yong-jian Xu,15 Xi-xin Yan,16 Wan-zhen Yao,17 Qin Yu,18 Jing Zhang,6 Jin-ping Zheng,3 Jie Liu,6 Chun-xue Bai6 1Department of Pulmonary Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Southern Medical University South Hospital, Guangzhou, 3The First Affiliated Hospital of Guangzhou Medical College and Guangzhou Institute of Respiratory Diseases, Guangzhou, 4Affiliate Hospital of Inner Mongolia Medical University, Huhehaote, 5Huaxi Hospital of Sichuan University, Chendu, 6Zhongshan Hospital, Shanghai Medical College, Fudan University and Shanghai Respiratory Research Institute, Shanghai, 7Ruijing Hospital of Shanghai Jiaotong University, Shanghai, 8The First Affiliated University of Anhui Medical University, Hefei, 9The First Affiliated University of Guangxi Medical University, Nanning, 10Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 11General Hospital of Nanjing Military Region, Nanjing, 12Beijing Hospital of the Ministry of Health, Beijing, 13Xinqiao Hospital, Third Military Medical University, Chongqing, 14Qilu Hospital of Shandong University, Jinan, 15Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 16The Second Affiliated Hospital of Hebei Medical University and Hebei Research Institute of Respiratory Medicine, Shijiazhuang, 17The Third Affiliated Hospital of Beijing University, Beijing, 18The First Affiliated University of Lanzhou University, Lanzhou, People's Republic of China Abstract: Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease pro

Jing Zhang,* Xin-feng Lin,* Chun-xue Bai Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China *These authors contributed equally to this paper Background: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, the similarities and differences in clinical presentation between smokers and nonsmokers are not fully described in patients with COPD. This study was designed to address this issue in a general teaching hospital in the People’s Republic of China. Methods: The medical records of patients hospitalized with a lung mass for further evaluation at Zhongshan Hospital, Fudan University, from January 2006 to December 2010 were reviewed and the data of interest were collected. The definition of COPD was according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric criteria. Participants who had a previous exacerbation within 4 weeks of admission, airflow limitation due to abnormalities in the large airways, or with other pulmonary diseases were excluded. Included subjects were divided into nonsmokers with COPD and smokers with COPD by a cutoff of a 5 pack-year smoking history. Results: A total of 605 subjects were included in the final analysis. The average age was 64.8±8.5 years and 62.0% (375/605) were smokers. Eighty percent of the patients had mild to moderate disease (GOLD grade 1–2). Age and years with COPD were comparable between the two groups. Compared with smokers with COPD, nonsmokers with COPD were more likely to be female, reported less chronic cough and sputum, have less emphysema on radiologic examination, and higher measures of forced expiratory volume in the first second percent predicted (FEV1), forced expiratory volume in one second/forced vital capacity (FEV1/FVC%) percent predicted, maximal voluntary ventilation percent predicted, diffusing capacity of lung (DLCO) percen

Xiao-ru Wang,1,* Yong-pu Li,2,* Shui Gao,2 Wei Xia,2 Kun Gao,1 Qing-hua Kong,1 Hui Qi,1 Ling Wu,1 Jing Zhang,3 Jie-ming Qu,4 Chun-xue Bai3 1Department of Pulmonary Medicine, Dahua Hospital, Xuhui District, Shanghai, 2Department of Pulmonary Medicine, People's Hospital of Changshou, Chongqing, 3Department of Pulmonary Medicine, Zhongshan Hospital, 4Department of Pulmonary Medicine, Huadong Hospital, Fudan University, Shanghai, People's Republic of China *These two authors contributed to this paper equally Abstract: Despite a number of studies on biomarkers in chronic obstructive pulmonary disease (COPD), only a few disease-related markers have been identified, yet we still have no satisfactory markers specific to innate immune system and neutrophil activation, which is essential in airway inflammation in COPD. Recent biological studies indicated that lipocalins (LCNs) might be involved in airway inflammation and innate immunity; however, results from available studies on the association of LCNs with COPD are not consistent. We carried out a multicenter prospective observational cohort study to investigate the differences in serum levels of LCN1 and LCN2 between subjects with COPD (n=58) and healthy controls (n=29). Several validated inflammatory markers, including C-reactive protein, tumor necrosis factor-a, interleukin-6, and interleukin-8, were measured. The correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung function, symptoms, and disease category was also analyzed. When comparing with healthy controls, serum levels of LCN1 (66.35±20.26 ng/mL versus 41.16±24.19 ng/mL, P<0.001) and LCN2 (11.29±3.92 ng/mL versus 6.09±5.13 ng/mL, P<0.001) were both elevated in subjects with COPD after adjusting for age, sex, smoking habits, and inflammatory biomarkers. Smoking history and tobacco exposure, as quantified by pack-year, had no impact on systemic expressions of LCN1 an

Jing Zhang, Yuan-lin Song, Chun-xue Bai Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China Abstract: Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the ‘MIOTIC study’ to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. Keywords: Internet of Things, mobile phone, chronic obstructive pulmonary disease, efficacy