Day 1 :
Albany Medical College, USA
Keynote: Novel signaling mechanisms for airway remodeling and hyperresponsiveness in chronic obstructive pulmonary disease (COPD)
Time : 09:30-10:15
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 2 – 3 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 has been confirmed for publication by Springer (New York). 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.
Statement of the Problem: COPD is the fourth leading cause of mortality in the world and will be the second leading cause of death by 2020. However, the molecular processes for this devastating disease remain largely unknown, and current treatments are limited. Purposes: This study was to test a novel hypothesis that the reciprocal crosstalks between ion channel-mediated calcium signaling and transcriptional factor-dependent inflammatory signaling are essential for COPD. The current study also sought to determine whether specific genetic and pharmacological targets for these signaling molecules would become effective therapeutics for COPD. Methodology: Ion channel expression and activity were assayed using RT-PCR, Western blotting and patch clamp recordings; airway remodeling and hyperresponsiveness examined using in-situ immunohistological staining and both in-vivo and in-vitro muscle contraction measurements; and targeted molecule activities changed using virus-based genetic modifications. Findings: Among 7 known different gene-encoded classic transient receptor potential (TRPC) channel members, only shows the TRPC3 channel a predominant activity and expression in airway smooth muscle cells (ASMCs). This channel is significantly upregulated in COPD patient ASMCs. Mice with nicotine-induced COPD also show largely increased TRPC3 channel expression and activity in ASMCs. In-vivo lentiviral shRNA-mediated TRPC3 channel knockdown abolishes airway remodeling and hyperresponsiveness in COPD. The channel blocker Pyr3 produces similar effects. The TRPC3 channel promoter has binding sites for NFkB, an important inflammatory transcription factor. NFkB expression and activity are increased in COPD ASMCs. Genetic NFkB function gain and loss, respectively, increases and blocks, TRPC3 channel promoter activity and expression. Vise verse, TRPC3 channel gain and loss, downregulates and upregulates, NFkB activity and expression. Conclusion & Significance: Reciprocal crosstalks between TRPC3 channel-mediated calcium signaling and NFkB-dependent inflammatory signaling are essential for airway remodeling and hyperresponsiveness in COPD. Specific lentiviral TRPC3 channel shRNAs and channel blockers may become novel and effective treatments for COPD.
Okayama University, Japan
Time : 10:15-11:00
Nobuaki Miyahara graduated from Hiroshima University School of Medicine in 1988. He has completed his PhD in Department of Medicine II, Okayama University School of Medicine in 1994. He had done research on allergic airway inflammation at the National Jewish Health in Denver, CO, USA (Dr. Erwin Gelfand’s Lab) from 2001 to 2008. Currently, he works at Department of Medical Technology, Okayama University Graduate School of Health Sciences, and Department of Allergy and Respiratory Medicine, Okayama University Hospital. His research interest is pathogenesis of COPD and asthma.
Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. We have recently reported that IL-17A and Th17 cells play a critical role to the development of porcine pancreatic elastase (PPE)-induced emphysema. Differentiation of Th17 cells is shown to be induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23-/-) and wild type (WT) mice were compared. Intra-tracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared to WT mice, IL-23-/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses following PPE-instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage (BAL) fluid of WT mice was attenuated in IL-23-/- mice, and the reduction was associated with decreased levels of KC and MIP-2 in BAL fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23-IL-17 pathway. Targeting IL-23 in emphysema may be a potential therapeutic strategy for delaying disease progression.
- CO-Morbidities in COPD |Management of COPD | COPD Exacerbations | COPD Theraupetics
Pyunkang Korean Medicine Hospital, South Korea
Schoen Klinik Berchtesgadener Land, Germany
Schoen Klinik Berchtesgadener Land, Germany
Title: Prevalence and determinants of cognitive impairment in COPD patients enrolled for pulmonary rehabilitation: A preliminary analysis
Time : 11:20-11:55
Vasileios Andrianopoulos is a clinical exercise physiologist working as postdoctoral research fellow at Schoen Klinik Berchtesgadener Land in Germany. He has his expertise in COPD pathophysiology, 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 publications in healthy and patients with COPD and since 2014 is an active member of the European Respiratory Society (ERS) College of Experts. Recently (2016), he has been awarded with a prestigious Marie Skłodowska-Curie fellowship cofounded by the European Union and the European Respiratory Society (ERS) for his project about cognitive dysfunction in COPD.
Introduction:Cognitive impairment (CI) is a prevalent extra-pulmonary manifestation in COPD, which is associated with increased mortality. We assessed the prevalence and the determinants of CI in patients enrolled for Pulmonary Rehabilitation.
Method: 52 COPD patients (aged: 68±8yrs; FEV1: 45±14%; 40% women) underwent a comprehensive cognitive assessment in the beginning of PR using a detailed neuropsychological testing battery (Image). Patients were assigned to “CI” and “non-CI” groups according to Montreal Cognitive Assessment (MoCA) cutoff score ≤25points. Clinical data including medical history, respiratory function, health/mood status evaluation by Saint-George respiratory questionnaire (SGRQ) and hospital anxiety-depression scale (HADS) were collected. Patients performed six-minute walk test (6MWT) and cycle endurance test (CET) at 75% of peak work rate.
Results: 23 patients (44%) presented evidences of CI (MoCA≤25) with also lower scores in the other cognitive tests (all p <0.001). CI group had worse memory, attention, language/executive, fluency, visuospatial (all p≤0.001) and concentration performance (Stroop test - accuracy: 96.5% vs 89.8%, p<0.001), while was less educated (12.6 ±2.1yrs vs 11.3 ±2.1yrs, p=0.034). CI group had similar FEV1%, health and mood status (SGRQ, HADS), and exercise capacity (6MWD: 359 ±85m vs 380 ±116m, p=0.48; CET: 616 ±329sec vs 551 ±370sec, p=0.51) but greater oxygen desaturation during the CET (SpO2nadir: 92.3 ±2.9% vs 89.9 ±3.9%, p=0.014). Certain threshold of SpO2nadir (≤90%) increased the risk for CI after adjustment for oxygen-use (p=0.026).
Conclusion: CI is highly prevalent in patients with COPD and affects several cognitive domains. It is associated with the years of education and the oxygen desaturation during the CET, however, it seems that is not associated with exercise capacity in COPD patients.
Birjand University of Medical Sciences,Iran
Title: Comparing the effect of resistive inspiratory muscle training and incentive Spirometry on Respiratory Pattern of COPD Patients
Time : 11:55-12:30
Marjan Farzad is a member of cardiovascular diseases research center and faculty member of Birjand University of Medical Sciences in Iran at the moment. She had a Master’s degree in nursing and experiences of 16 years work as critical care nurse and supervisor. She has her expertise in intensive care unit.
Background: Resistive Inspiratory Muscle Training (RIMT) is a well-known technique for rehabilitation of patients with Chronic Obstructive Pulmonary Disease (COPD). Incentive spirometry is another technique with potential viability for this application, but there is limited evidence in support of its efficacy in the rehabilitation of COPD patients.
Aim: The objective of this study was to compare the effect of resistive inspiratory muscle training and incentive spirometry on respiratory pattern of COPD patients.
Method: This study was a randomized clinical trial on 30 patients with moderate COPD who were referred, in 2011, to the pulmonary clinic of Emamreza Hospital of Mashhad (Iran). The patients were randomly divided into the RIMT and the IS treatment group. In both groups, exercise regimen consisted of two 15-minute sessions of exercise per day, in the morning and evening, four days a week for 4 weeks. Respiratory pattern (respiratory rate and depth) and dyspnea (at rest and during activity) were measured before and after exercise. Data was analyzed with the Mann-Whitney and ratio difference tests using SPSS v.11.5.
Results: The average age was 50.8±10.7 in the IS group and 51±10.8 in the RIMT group. The statistical tests found no significant difference between the groups in terms of post-intervention exertional dyspnea, dyspnea at rest, tidal volume, and respiratory rate (P>0.05); but post-intervention maximal inspiratory pressure and maximal voluntary ventilation in the two groups were found to be significantly different (P <0.05).
Implications for Practice: despite statistically superior performance of resistive training in improving the maximal voluntary ventilation and maximal inspiratory pressure (the two effective factors for improving strength and endurance of respiratory muscles), the difference between its results and the results of incentive spirometry is not clinically important, therefore, positive clinical outcomes of incentive spirometry are sufficiently significant to encourage its use in COPD rehabilitation programs.
Tribhuvan University, Nepal
Title: Knowledge and practice of dry powder inhalation among the patients with chronic obstructive pulmonary disease in a regional hospital
Time : 12:30-13:05
Mira Adhikari has her expertise in clinical and teaching to the nursing students. She has a deep interest in working towards improving the practice of the nurses to achieve the optimum health of the patients. She has generated this concept after years of experience in the hospital, and after immense study in the field.
Inhaled aerosoled drug is the mainstay of treatment in patients with Chronic Obstructive Pulmonary Disease (COPD) as it allows the delivery of drugs directly to the lungs with minimal side effects. Effectiveness of the treatment by those drugs depend on how correctly a patient inhales the drug through the prescribed inhaler. It has been reported that incorrect inhalation technique results in recurrent exacerbations of COPD increasing the health care costs and socio economic burden to the patient and the family. Despite this serious result, very little consideration is given to the inhalation technique used by the patient. Among the various devices, rotahaler is a commonly used aerosol device used to deliver drug in the form of dry powder for the treatment of COPD. Therefore, this study was undertaken to assess the accuracy of knowledge and practice of rotahaler among COPD patients.
The current study was descriptive study conducted in Western Regional Hospital, Pokhara. Study was conducted among 204 COPD patients (aged 20 or over) and who had been using DPI through rotahaler and purposive sampling technique was used. A questionnaire was administered by the interviewer to assess the knowledge while an observation checklist was adopted from Dutch Asthma Foundation to evaluate the practice of DPI. Findings from the study showed that a very less proportion (3.9%) of the respondents had correct practice of inhalation technique even though nearly half of them(49.5%) possessed average knowledge of DPI.
This study has concluded that rotahaler users possessed poor practice of DPI. The most important modifiable factor for incorrect practice was lack of demonstration on inhalation technique by health care provider. So, health care providers (doctors, nurses and pharmacists) should provide comprehensive verbal instruction followed by demonstration and return demonstration by the patient to improve the efficacy and effectiveness of the treatment in COPD patients.
Hyo-seok Seo, the director of Pyunkang Korean Medicine Hospital, has his expertise in developing medicine for pulmonary diseases. Chronical tonsillitis from his childhood motivated him to become Korean Medicine doctor. During research, He found that main cause of asthma, COPD, rhinitis and tonsillitis are deeply related to health condition of one’s lungs. The result of research led him to focus the health of lungs. Pyunkang-Hwan, which is Korean medicine invented by Dr. Seo helps restoration lung health and function to strengthen immune ability of our body. Now he is known for “Patients’ most wish to meet” in South Korea. From 2014, He has been strived to globalize Korean medicine. In 2014, He placed 11 times of Health Campaign on New York Times and 31 times of column on Epoch Times. Moreover, he is a frequent speaker at conference across the globe.
For 44 years, Dr. Seo Hyo-seok has treated over 15.5 thousand of patients suffering from lung diseases through his professional and ingenious study on traditional Korean Medicine for modern environment. Dr. Seo will introduce how we can improve our lung health and its effect on prevention of flu and severe pulmonary diseases.
His study shows that improvement of pulmonary function, the key factor of healthy immune system, will strengthen tonsil which has the most important role of immune system in our body. Accordingly, Lymphocytes emitted from the strengthened tonsil will easily protect our body from harmful bacteria and viruses. With large numbers of cases and explicit principle of treatment, Dr. Seo will introduce how the advanced immune system can expel painful allergic diseases and COPD known for killer disease and how humanity can approach to the age of “homo-hundred”.
Tatyana Vlaykova is a professor in medical biochemistry in Medical Faculty, Trakia University, Stara Zagora and Medical University, Plovdiv. She obtained a PhD degree in Department of Oncology, Medical Faculty, Turku University, Turku, Finland, focusing on tumor agiogenesis, apoptosis and proliferation markers as predictive and prognostic factors of skin metastatic melanoma. Later she extended her interest and expertise in analyzing the risk and prognostic factors in colorectal cancer and of chronic inflammatory lung diseases as COPD and bronchial asthma. In those latter field she has been studying the genetic predisposition factors for COPD as polymorphisms in the genes encoding xenobiotic-metabolizing enzymes of GST family, cytokines (IL-6, IL-1B, TNF-a, IL-10, IL-1Ra) and several matrix metalloproteinases. She is a supervisor of six PhD students and tutor of the research work of many undergraduate students in medicine.
The main pathological features of COPD are abnormal chronic inflammation in the airways, development of extensive tissue remodeling and local and systemic oxidative stress. A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a pivotal role in remodeling of the small airways and particularly of the terminal bronchioles in lungs of COPD patients.
In the current review we aim to present our results concerning the possible role of several functional SNPs in promoter regions of MMPs (MMP-1607 1G>2G, [rs1799750], MMP2–1306C>T [rs243865], MMP3-1171 5A>6A, [rs3025058], MMP7-181A>G [rs11568818], and MMP12-82A>G [rs2276109]) and serum levels of those proteinases in development of COPD in Bulgarian population from the central region of the country.
The performed case-control studies showed that MMP2–1306C>T, MMP7-181A>G and MMP12-82 A>G may affect the risk for COPD, while the other promoter SNPs did not have any associations with COPD. The old carriers (≥65 years) of minor T allele genotypes (CT+TT) of MMP2–1306C>T SNP had higher risk than CC carriers (OR=4.54, 95%CI:1.20-17.24, gender and age adjusted, p=0.026). Concerning MMP7-181A>G SNP, we observed that the minor G allele genotypes (AG+GG) were more frequent in COPD than AA genotype among the younger individuals (OR=2.30, 95%CI:1.00-5.27, gender and age adjusted, p=0.050). Moreover, patients with minor G allele genotypes developed COPD significantly early that those with AA genotype (61.01±10.11 vs. 64.87±9.00 years, p=0.032). The minor G allele of MMP12-82 A>G SNP appeared to be a protective factor for COPD as the carriers of G allele genotypes had about 2-fold lower risk for the disease (OR=0.446, 95%CI:0.25-0.80, adjusted for gender and age, p=0.007).
The serum levels of MMP-1 and MMP-7 did not differ significantly between patients and controls, while the MMP-3 appeared to be higher in patients with COPD (p=0.020), and MMP-2 was higher in female COPD patients than healthy women (p=0.043)