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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

Liu Y, Zhang C, Li C, Bai C, Shang H. Clin Interv Aging.2020;15:2109–2115. Page 2111, Results, third paragraph, second sentence, thetext “Elderly patients with XBJ had a significantly inferioroverall survival to those with placebo” should read“Elderly patients with placebo had a significantly inferior overall survival to those with XBJ”. Page 2114, Figure 1 caption, the text “elderly group:patients with XBJ had a significantly inferior overall survivalto those who with placebo” should read “elderlygroup: patients with placebo had a significantly inferioroverall survival to those with XBJ”. The authors apologize for these errors and advise they do notchange the scientific conclusions of the article in any way. Read the original article

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

Background Early diagnosis of COPD is often not achieved due to limited recognition and limited access to the pulmonary function test. Our hypothesis was that lung function decline may be different between populations with mild COPD and those who are at high risk and do not receive treatment. Patients and methods Subjects with mild COPD and those from a high-risk COPD population were recruited from a community-based COPD epidemiological study after obtaining consent. Baseline clinical characteristics, symptom questionnaire, spirometry, low-dose computed tomography (LDCT) chest scan, and blood plasma biomarker data were collected initially and then 1 year later. Results A total of 617 participants were recruited, and 438 eventually completed the first-year follow-up visit; 72 participants (46 males) were in the mild COPD group, and 225 participants (165 males) were in the high-risk group. The mean forced expiratory volume in the first second of expiration (FEV1) decline in the mild COPD group was 129 mL, which was significantly higher than the 30 mL decline in the high-risk population group (P=0.005). Group category (odds ratio [OR] =0.230) and COPD Assessment Test (CAT) score (OR =9.912) were independent risk factors for an FEV1% predicted decline of >15% for all participants. In the mild COPD group, patients with a higher CAT (OR =5.310) and Emphysema Index (OR =5.681) were associated with a FEV1% predicted decline of >15% at the first-year follow-up. No factor showed a significantly predictive effect on FEV1 decline in the high-risk COPD group. Conclusion Group category was an independent influential factor associated with FEV1 decline.

Chronic obstructive pulmonary disease (COPD) is a very common disease all around the world and has become an increasing public health concern to the Chinese medical community. In the past decades, telehealthcare technology has become a good way to manage COPD but current evidence makes it hard to determine the effectiveness of this technology. Internet of things (Iot) is a recent breakthrough in communication technology, which links the virtual world to the real world through connection between sensors and working devices. It relates people and items in any ways so that data collection and management become more flexible. Our review concentrates on the effectiveness and potential application of telehealthcare in COPD management and how IoT technology may stimulate COPD healthcare delivery through telehealthcare technology.

Multiple cells play critical roles in the pathogenesis of lung diseases, even though the exact mechanisms are still not clear. Telocytes are characterized by telopodes, which are thin and long prolongations, and a small amount of cytoplasm rich with mitochondria, as shown by immune-positive staining against CD34, c-kit and vimentin. Telocytes have been found in many organs of mammals, including the trachea and lung. This report summarizes the latest findings associated with telocytes, with a special focus on the lung, and demonstrates that telocytes exist in the smooth muscle layer under cartilage and bronchiole in the lung, and also in the interstitial space of alveoli. Telocytes have a mediate connection with epithelial cells and direct connection with smooth muscle cells both in blood vessels and bronchiole in the lung. Telocytes also have a close relationship with other cell types, such as immune cells and stem cells. Telopodes appear with dichotomous branching and alternation of podom and podomer, forming a 3D network structure with complex homo- and hetero-cellular junctions. All characteristics of telocytes in lung tissue indicate that telocytes may play a potential, but important, role in the pathogenesis of lung diseases.

Multiple genetic and environmental factors impact the pathogenesis of asthma. ADAM33 (a disintegrin and metalloproteinase domain 33) represents a novel susceptibility gene for asthma in several diverse populations. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of the ADAM33 gene associate with asthma susceptibility and severity in the Chinese Han population.A total of 224 subjects were enrolled, including 74 normal controls and 150 asthmatic patients. The asthmatic enrollees were further categorized into high- or low-severity groups according to the percentage of forced expiratory volume in 1 second of predicted value, symptoms, nighttime awakening, requirement for short-acting β2-agonist, and interference with normal activities. Six SNPs (F + 1, ST + 4, S1, S2, T1, and T2) in ADAM33 were genotyped using the polymerase chain restriction fragment length polymorphism method.Three SNPs (F + 1, T1, and T2) of ADAM33 were found to have significant associations with asthma in the study population (p = .0058-.0067). The allele frequencies of two SNPs (F + 1, T1) in both the low- and high-severity groups were significantly different from the allele frequency in the control group. The allelic frequency of the T2 SNP was significantly different from that of the control group only in the high-severity group (p = .0081). Haplotype analysis demonstrated that the frequency of 7575G, 12433T, and 12462C (GTC haplotype) is higher in healthy controls than amongst asthma patients (78.4% vs. 61.8%, p = .0004).Polymorphisms of the ADAM33 gene associate with asthma susceptibility in the east China Han population, and the genetic association is stronger in high-severity asthmatics.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an acute life-threatening form of hypoxemic respiratory failure with a high mortality rate, and there is still a great need for more effective therapies for such a severe and lethal disease. Dysfunction of endothelial and epithelial barriers is one of the most important mechanisms in hypoxia-associated ALI/ARDS. The acceleration of the epithelial repair process in the injured lung may provide an effective therapeutic target. KGF-2, a potent alveolar epithelial cell mitogen, plays an important role in organ morphogenesis and epithelial differentiation, and modulates a variety of mechanisms recognized to be important in alveolar repair and resolution in ALI/ARDS. Preclinical and clinical studies have suggested that KGF-2 may be the candidate of novel therapies for alveolar epithelial damage during ALI/ARDS.

5-Lipoxygenase (5-LO) is an important enzyme that dominates the metabolism of arachidonic acid and the synthesis of leukotrienes, of which leukotriene B4 (LTB4) is suggested to be one of the most potent chemoattractants and activators of leukocytes. 5-LO is normally limited to hematopoetic cells, e.g. granulocytes and macrophages, where LTB4 is produced. Leukotrienes play an important role in the innate defense system, in the antimicrobial defense system, and in intercellular signaling. Under pathophysiological conditions, overproduction of LTB4 was noted in multiple cells. It is known that 5-LO and its production of LTB4 are involved in the maintenance of normal host defense, initiation of inflammation, migration of leukocytes, development of endothelial barrier dysfunction, hyperresponsiveness of smooth muscle cells, stimulation of mucus secretion, reduction of mucociliary clearance, and tissue remodeling. In order to understand the role of 5-LO and its production in functions of the innate host defense...

Objective. Acute pancreatitis (AP) remains a severe disease responsible for the development of multiple organ dysfunction, and is associated with high mortality and morbidity. Early enteral nutrition has been suggested to have therapeutic potential for improving the outcome of AP patients. The aim of this study was to investigate whether supplementation of enteral nutrition with ebselen and ethylhydroxyethyl cellulose (EHEC) can attenuate the acute-phase responses and the severity of organ dysfunction in AP patients with either single- or multiple-organ dysfunction. Material and methods. AP patients with single-organ dysfunction (acute lung dysfunction) were treated with either vehicle (n=43) or the combination of ebselen and EHEC (n=48). AP patients with multiple-organ dysfunction (more than two organs) were treated with either vehicle (n=52) or the combination of ebselen and EHEC (n=55). Results. The combination of ebselen and EHEC significantly reduced the occurrence of infection (as indicated by a low...

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are common and important stages of both pulmonary and systemic critical illnesses. ALI/ARDS is categorized as primary or secondary based on the etiology of the disease. There is increasing evidence to suggest the involvement of airway epithelial cells in the pathogenesis of ALI/ARDS. The airway epithelial cell is a new candidate as a biological target responsible for development of the disease and the role of these cells in the pathogenesis of ALI/ARDS is under investigation. This review describes the importance of the airway epithelial cell in the development of ALI/ARDS, its role as the first line of lung defense facing local and primary challenges, its role as an important player in the development of airway inflammation and remodeling, as an inflammatory promoter for initiating both local and systemic inflammation and as an active producer of several inflammatory and anti-inflammatory mediators. It is hypothesized that airway epithelial cells may contribute to ALI/ARDS via Toll-like receptor-involved mediators, reactive oxygen species-involved reactions and an imbalance between protease and antiprotease activation. The airway epithelial cell may be a valuable therapeutic target for discovering and developing new drugs and/or new therapeutic strategies for ALI/ARDS.

In this article we review the current status of multiple-organ dysfunction syndrome (MODS) in China, with a focus on its epidemiology and pathogenesis and clinical treatment approaches. Current and future research directions are also reviewed with the overall goal of improving our understanding of this disorder so that optimal prevention and treatment strategies can be developed. Pathogenically, Chinese scholars hypothesize that MODS occurs in accordance with a “two-hit” model, which results in an overwhelming systemic inflammatory response within the host. Lipopolysaccharide or endotoxin activates several intracellular signaling pathways via cellular membrane receptors, thereby contributing to this inflammatory response. Supportive therapy of vital organs represents the main therapeutic approach for these patients, although nutritional support in the form of early enteral feeding is also important. Additional approaches include the administration of agents to increase the rate of protein synthesis and mo...

The incidence of the pulmonary complications in patients with acute pancreatitis is up to 60%, from mild hypoxaemia without clinical or radiological abnormalities to severe acute lung injury. Although a number of reviews has described clinical evidence of pancreatitis-associated lung injury (PALI), there is still a lack of information on potential interorgan signalling involved in the development of PALI. The present review discusses the potential factors that have been considered as candidates responsible for interorgan signalling coupling pancreatitis to lung injury. Inflammatory mediators produced from the pancreas, leucocyte system and extrapancreatic organs may directly or indirectly contribute to the high concentration in the circulation, activate circulating leucocytes, initiate the inflammatory responses of pulmonary resident cells or induce acute lung injury. Circulating leucocytes have been suggested to play an important role in interorgan signalling during the development of PALI, by producing ...

The objective of this study was to evaluate the cardiopulmonary effects of a dual-endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute lung injury with pulmonary arterial hypertension in dogs. Twelve pentobarbital-anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were divided into 2 groups. The control group (n=6) received saline treatment, whereas the treatment group (n=6) received the ET receptor antagonist, Tezosentan (1 mg/kg intravenous [i.v.]+1 mg/kg/h i.v. infusion). Cardiopulmonary parameters were monitored continuously for 1 hour. OA administration resulted in a significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) and a decrease in mean systemic arterial pressure (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all dogs. Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32% decrease in MPAP (from 23 +/- 2 mm Hg to 15 +/- 2 mm Hg; P.01) and a 22% decrease in PVR (from 860 +/- 105 dyn.s.cm(-5) to 670 +/- 96 dyn.s.cm(-5); P.01) at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and there was an increase in cardiac output and a decline in peak inspiratory pressure (PIP) in the Tezosentan group compared with the control group. These results indicate that the dual-ET receptor antagonist, Tezosentan, can attenuate the pulmonary hypertension induced by OA. Thus, dual-ET receptor antagonists such as Tezosentan may be useful in the management of acute pulmonary arterial hypertension, complicating the course of OA-induced lung injury.

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

WOS: 000319053100028, PubMed ID: 22563246, Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality. Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care. A web-based pilot survey was conducted to evaluate the primary care physician's, or general practitioner's (GP's), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory. The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant. This survey demonstrated that the GPs' understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management. A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa. Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%). Management of COPD was well below guideline-recommended levels in most of the regions investigated. The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied., GlaxoSmithKlineGlaxoSmithKline, The authors would like to thank GlaxoSmithKline for the financial support of the study and Dr Jagdish Devalia for assistance in the preparation and editing of this article.