Day 1 :
Albany Medical College, USA
Keynote: Promising molecular mechanisms and therapeutic options for chronic obstructive pulmonary disease (COPD)
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Dr. Yong-Xiao Wang has been a Full Professor in Albany Medical College (USA) since 2006. Dr. Wang has had extensive research experience in basic, translational and drug research concerning pulmonary hypertension, asthma, chronic obstructive pulmonary disease, diabetes, and cardiac arrhythmia for over 30 years. As the Principal Investigator, he has/had numerous NIH R01 research awards, AHA Established Investigator Award, and various other grants, for which he often holds/held NIH R01 grants with other awards each year. As the corresponding author, first author and key contributor, he has had numerous publications in highly peer-reviewed journals including Antioxid Redox Signal (impact factor: 8.209), Proc Natl Acad Sci USA (9.432), Nature (34.480), Circ Res (9.214), etc. Dr. Wang has been the editor of academic books in the field including one entitled by “Redox Signaling in Health and Disease Pulmonary Vasculature” that was published by Springer (New York) last fall. Dr. Wang has also served as the editorial board member and/or section editor for the Clinical and Translational Medicine, Pulmonary Circulation and several other journals.
COPD is the third leading cause of mortality in the world and will be the second leading cause of death by 2020. However, the molecular mechanisms for this devastating disease remain largely unknown; currently, the clinical therapeutic options are neither specific and nor always effective. A major characteristic of COPD is expiratory airflow limitation, which can be attributed to airway hyperresponsiveness. A very important player (VIP) in airway hyperresponsiveness is the increased contraction of airway smooth muscle cells (ASMCs). An increase in intracellular calcium ([Ca2+]i) is a key factor in the increased contraction in AMCs. Consistent with this view, bronchodilators including muscarinic receptor antagonists, β-adrenergic receptor agonists and corticosteroids are used as the first-line drugs in the clinical treatment of COPD, and the functional role of all these forefront drugs are associated with their inhibition of the increased [Ca2+]i and contraction in ASMCs. Multiple ion channels such as inositol trisphosphate receptor (IP3R)/Ca2+ release channel, ryanodine receptor (RyR)/Ca2+ release channel and canonical transient receptor potential-3 (TRPC3) channel, play a major role in initiation and maintenance of [Ca2+]i. Recent studies suggest that these channels are essential for airway hyperresponsiveness in COPD and other pulmonary diseases. Equally interestingly, IP3R, RyR and TRPC3 channels are highly sensitive to reactive oxygen species (ROS), and ROS are well known to mediate airway hyperresponsiveness and other unleashed cellular responses in COPD. ROS are primarily produced by mitochondria and NADPH oxidase (NOX). A number of antioxidants targeted at mitochondria and/or NOX are currently used in clinical trials and show potential effectiveness in the treatment of COPD. ROS may implement their role in COPD by causing of oxidation of IP3R, RyR and TRPC3 channels, leading to their hyperfunctions. Thus, it is reasonably believed that genetic and pharmacological inhibition of these channels, like antioxidants, may also be effective for therapies of COPD. In support, studies using animals have revealed their therapeutic for airway hyperresponsiveness and COPD.
University of Virginia
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Kun Qing is an MR scientist with more than nine years of experience working in the medical imaging research field. Currently, I am serving as an Assistant Professor of Radiology & Medical Imaging at University of Virginia (UVa). My research has primarily focused on development and optimization of MR and image processing techniques to provide better depiction of lung structure and function. Also I served as PI or Co-Investigator on multiple research projects and performed MR imaging studies to investigate patients with pulmonary diseases and their responses to treatments. The hyperpolarized xenon-129 dissolved-phase MRI [ref 1] that I developed is the first non-invasive imaging technique to measure regional gas exchange in the human lung. It showed its unique abilities to characterize lung disease and detect early changes of lung function in many primary lung diseases.
Purpose: Airway-predominant chronic bronchitis (CB) and alveolar-predominant emphysema (EM) were regarded as major phenotypes of smoke-induced COPD. Routine clinical tools, including pulmonary function tests (PFTs) and computed tomography (CT), have their limitations to characterize COPD. This study will characterize COPD phenotypes using a new imaging tool - hyperpolarized xenon-129 (Xe129) MRI .
Methods: Thirteen healthy and thirty-three COPD subjects were recruited and underwent PFT, CT. COPD patients were phenotyped into three groups by PFT percent diffusion capacity (%DLCO) and CT percent of EM lung tissue (%EM): 1) EM: low %DLCO and high %EM; 2) CB: high %DLCO and low %EM; and 3) mixed indeterminate (IND) phenotype: low %DLCO but low %EM. Xe129 MRI was subsequently administered to determine airflow limitation by measuring percent of ventilation dead space (%VD) and alveolar gas uptake by measuring Xe129 diffused into interstitial tissue [tissue/gas ratio, reflecting lung tissue integrity] or into red blood cells (RBCs) [RBC/tissue ratio, reflecting gas exchange and pulmonary perfusion].
Results and Discussion: Using the criteria described above, 18% of patients (6/33) were EM predominant; 21% (7/33) were CB phenotype; and surprisingly, 61% (20/33) were IND phenotype. The IND group had %FEV1 substantially overlapped the CB group (p>0.05, Figure 1a), and did not show significantly higher %VD than the control group (p>0.05, Figure 1b). Also, no statistical differences were found in Xe129 tissue/gas ratios among the control, CB and the IND groups (p>0.05). However, the RBC/tissue ratios, measuring gas transfer from the interstitium further to the blood stream, were much lower in the mixed group as compared to all other groups (p<0.05) (Figure 1d).
Conclusion: There seemed to be a new mixed phenotype of COPD identified in a majority of COPD patients, which had minimal emphysematous tissue destruction, but impaired gas exchange to the blood as indicated by Xe129 MRI.
Schoen Klinik Berchtesgadener Land , Germany
Vasileios Andrianopoulos is a clinical exercise physiologist / researcher working as postdoctoral research fellow at Schoen Klinik Berchtesgadener Land in Germany. He has his expertise in COPD pathophysiology, COPD-related cognitive impairment, clinical exercise assessment and Pulmonary Rehabilitation programs for COPD patients. Devoting himself to research, he acquired experience in designing research protocols, analyzing data and writing manuscripts as well as in operating several clinical devices. He has numerous scientific publications in healthy individuals and COPD patients. Since 2014, he is an active member of the European Respiratory Society (ERS) College of Experts and recently, in 2016, he has been awarded with a prestigious Marie Skłodowska-Curie fellowship co-funded by the European Union (EU) and the European Respiratory Society (ERS) for his project about cognitive dysfunction in patients with COPD
The beneficial effects of Pulmonary Rehabilitation (PR) are well established in COPD. However, data for the effectiveness of PR in patients with COPD and co-existing cognitive impairment are limited. We wish to compare the effect of a Pulmonary Rehabilitation program on cognitive function, health status, and exercise outcomes in cognitively normal (CN) and cognitively impaired (CI) patients with COPD. Methodology & Theoretical Orientation: Sixty COPD patients (FEV1: 47±15%; 42%women) referred to 3-week in-patient PR and classified as “CN” or “CI” according to the Montreal Cognitive Assessment (MoCA) cutoff-score (≤25points). Domain-specific cognitive function (MoCA, SMMSE, ACER, T-ICS), health status (CAT), health-related quality of life (SF-36), the six-minute walk test (6MWT) and cerebral oxygen availability during cycle endurance test (CET) at 75% of peak Work Rate, were assessed on admission and discharge of PR program. Findings: Twenty-five patients (42%) presented evidences of CI and low performance in cognitive tests. Compared to CN, CI patients improved visuospatial skills and fluency (Effect Size; ES: 0.44; 0.48), whilst similar improvements in memory (ES: 0.75), physical and social function (ES: 0.45; 0.47), vitality (ES: 0.56), general and mental health (ES: 0.47; 0.67) were observed, respectively. CI patients did not improve body pain and limitations from emotional problems as assessed by SF-36 but increased 6MWD (from 378 to 403m, p=0.052), CET (from 10.0 to 12.3min, p<0.001) and SpO2 nadir ([Δ]: +1.1%, p=0.047) in cycling, whilst CET cerebral oxygen availability remained unchanged. The proportion of CI and CN with clinically relevant improvements in 6MWT, CET and CAT was similar. Conclusion & Significance: CI patients gain significant benefits in cognitive function from PR but are not responsive to improvements in body pain and emotional limitations compared to CN. Persistent body pain may have limited the effectiveness of PR and improvements in the 6MWT in cognitively impaired patients with COPD.
FSBI Novosibirsk Tuberculosis Research Institute, Russia
Krasnov D.V. - Chief Researcher in the Novosibirsk Tuberculosis Research Institute, head of the surgical department for tuberculosis patients and he is the scientific leader of a number of research works on phthisiology and thoracic surgery.
Krasnov D.V. is a recognized expert in the field of tuberculosis surgery, has a degree of Doctor of Medicine. He is a high professional in all methods of surgical treatment in patients with pulmonary tuberculosis. In 2013, he participated in the development and drafting of international recommendations for the surgical treatment of multidrug-resistant tuberculosis for the WHO European Region.
Krasnov D.V. carried out a large amount of research work in the field of surgical treatment of patients with pulmonary tuberculosis and especially drug resistant tuberculosis. Results of his research work were repeatedly reported at international scientific and practical conferences, congresses and symposia.
The article presents a retrospective analysis of treatment results in patients with destructive pulmonary tuberculosis and concomitant chronic nonspecific lung diseases.
The aim of the study was to evaluate the effect of endobronchial valve (EBV) application on the respiratory function.
Materials and methods: 102 patients were included in an open comparative retrospective study. In 49 patients (main group), the EBV was used in the treatment, and 53 patients (comparison group) received standard anti-tuberculous chemotherapy. The parameters of the respiratory function (RF) were measured at three critical points during hospital stage of treatment and in the long-term period.
Results: the installation of EBV led to a slight decrease in the level of vital lungs capacity (VLC) and the forced expiration volume. After removal of the valve, these RF values came to the initial level. Standard anti-TB therapy of patients in the comparison group contributed to a 6% decrease in the VLC values below the baseline, while the level of bronchial patency was preserved. At the final measurement in the main group, the proportion of patients with normal volumetric RF values increased with a simultaneous decrease in the proportion of patients with moderate and significantly reduced rates. Also in the main group, there was an increase in the proportion of patients with normal indices of bronchial patency, and in the comparison group the proportion of patients with normal indices remained at the same level.
Conclusion: EBV application leads to a non-significant (less than 10% decrease in relation to the initial indices) and reversible disruption of both volume and bronchial patency of respiratory function. There is a significant irreversible decrease in the parameters of the respiratory function during the long treatment of patients with infiltrative pulmonary tuberculosis.
Department of Health & Family Welfare, India
Rakesh K Gupta is the Deputy Director, Non-Communicable Diseases, Department of Health & Family Welfare, Punjab. He has expertise in managing National Non-Communicable diseases Programs especially Blindness Control/Tobacco Control Programs and has professional experience of 33 years in service. He has represented MOHFW in WHO ENDS Consultation in Panama 2016 and WHO consultation on Plain packaging in Geneva 2017.
Background and challenges to implementation: Electronic Nicotine Delivery System (ENDS) popularly known as e-cigarettes are highly addicting and potentially lethal products. It is mostly being used by children and youth because these are glamorised by the tobacco industry. Though not generally available in stores, they are widely promoted and sold through E commerce sites with discount offers. Sales are increasing sharply all over the world. Punjab was the first state in India to declare Electronic Nicotine Delivery System (ENDS) as unapproved under Drugs and Cosmetics Act in 2013. Intervention or response: A circular was issued by Government of Punjab regarding declaration of manufacture and sale of ENDS as illegal. To counter the sale on the Ecommerce site, Punjab Government had issued a Demi-Official letter to Cyber Crime cell regarding the sale of E-cigarettes in 2016. Awareness notices were sent to various E commerce sites regarding the sale of E cigarette. District level Task Force effectively implements the ban through conducting raids at suspected point of sale, which is being monitored monthly by Deputy Commissioners of all Districts. Results and lessons learnt: Cyber Crime Cell identified the 26 E commerce sites that were selling the E cigarettes. Letter was sent to these sites regarding the Blocking/banning the sale of e cigarettes. After that No E commerce sites are selling e cigarettes in Punjab Conclusions and key recommendations: The declaration by the Government of Punjab opens the way for other states to follow suit, and prevent ENDS becoming an additional marketing strategy for tobacco companies.
Schoen Klinik Berchtesgadener Land, Germany
Vasileios Andrianopoulos is a clinical exercise physiologist / researcher working as postdoctoral research fellow at Schoen Klinik Berchtesgadener Land in Germany. He has his expertise in COPD pathophysiology, COPD-related cognitive impairment, clinical exercise assessment and Pulmonary Rehabilitation programs for COPD patients. Devoting himself to research, he acquired experience in designing research protocols, analyzing data and writing manuscripts as well as in operating several clinical devices. He has numerous scientific publications in healthy individuals and COPD patients. Since 2014, he is an active member of the European Respiratory Society (ERS) College of Experts and recently, in 2016, he has been awarded with a prestigious Marie Skłodowska-Curie fellowship co-funded by the European Union (EU) and the European Respiratory Society (ERS) for his project about cognitive dysfunction in patients with COPD.
Pulmonary Rehabilitation (PR) is widely recognized as an important therapeutic intervention that improves health status in patients with COPD. However, the extent of the improvements in cognitive function after PR in COPD patients with co-existing cognitive impairment has not yet been adequately investigated. We wish to compare changes in cognitive function after 3-week PR program and at 1-year follow-up in cognitive normal (CN) and cognitive impaired (CI) patients with COPD. Methodology & Theoretical Orientation: Thirty-two COPD patients (FEV1: 43±14%; 44% women) referred to 3-week in-patient PR and classified as “CN” or “CI” according to the Montreal Cognitive Assessment (MoCA) cutoff-score (≤25points). Face-to-face and telephone-based cognitive assessment was performed at admission and discharge of PR, and at 1-year follow-up, respectively. Overall cognitive performance was assessed by the “Telephone (T-) Interview for Cognitive Status” (T-ICS), whilst domain-specific cognitive evaluation also included T-MoCA and T-SMMSE. Changes in cognitive performance from admission to discharge and at follow-up were compared in CN and CI COPD. Findings: Thirteen patients (41%) showed evidences of CI and low performance in cognitive tests. From admission to discharge, CI patients had comparable increase on overall cognitive performance (Effect Size; ES: 0.53) compared to CN (ES: 0.65) improving memory (ES: 0.55), whilst had positive changes on attention (ES: 0.44), language/ executive (ES: 0.36), and fluency (ES: 0.32). From discharge to follow-up, CI patients had comparable deterioration on overall cognitive performance (ES: -1.26) compared to CN (ES: -1.59) decreasing attention (ES: -1.42), whilst had negative changes on memory (ES: -0.86), language/executive (ES: -0.34), fluency (ES: -0.10). Conclusion & Significance: Cognitively impaired patients with COPD improve to similar extent cognitive function after a 3-week PR program compared to CN and have comparable cognitive deterioration after 1-year. These changes in cognitive function may be dependent on the baseline levels of cognitive performance in COPD.