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1.
Association of RAGE gene multiple variants with the risk for COPD and asthma in northern Han Chinese.
Niu, H, Niu, W, Yu, T, Dong, F, Huang, K, Duan, R, Qumu, S, Lu, M, Li, Y, Yang, T, et al
Aging. 2019;(10):3220-3237
Abstract
Clinical and experimental data have shown that the receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of respiratory disorders. In this study, we genotyped five widely-evaluated variants in RAGE gene, aiming to assess their association with the risk for chronic obstructive pulmonary disease (COPD) and asthma in northern Han Chinese. Genotypes were determined in 105 COPD patients, 242 asthma patients and 527 controls. In single-locus analysis, there was significant difference in the genotype distributions of rs1800624 between COPD patients and controls (p=0.022), and the genotype and allele distributions of rs1800625 differed significantly (p=0.040 and 0.016) between asthma patients and controls. Haplotype analysis revealed that haplotype T-A-G-T (allele order: rs1800625, rs1800624, rs2070600, rs184003) was significantly associated with a reduced COPD risk (OR=0.32, 95% CI: 0.06-0.60), and haplotype T-A-A-G was significantly associated with a reduced asthma risk (OR=0.19, 95% CI: 0.04-0.96). Further haplotype-phenotype analysis showed that high- and low-density lipoprotein cholesterol and blood urea nitrogen were significant mediators for COPD (psim=0.041, 0.043 and 0.030, respectively), and total cholesterol was a significant mediator for asthma (psim=0.009). Taken together, our findings indicate that RAGE gene is a promising candidate for COPD and asthma, and importantly both disorders are genetically heterogeneous.
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2.
Effects of Clinical Pathways for COPD on Patient, Professional, and Systems Outcomes: A Systematic Review.
Plishka, CT, Rotter, T, Penz, ED, Hansia, MR, Fraser, SA, Marciniuk, DD, ,
Chest. 2019;(5):864-877
Abstract
BACKGROUND COPD has a substantial burden seen in both patient quality of life and health-care costs. One method of minimizing this burden is the implementation of clinical pathways (CPWs). CPWs bring the best available evidence to a range of health-care professionals by adapting guidelines to a local context and detailing essential steps in care. METHODS A systematic review was conducted to address the following question: What are the effects of CPWs for COPD on patient-, professional-, and systems-level outcomes? The review used methods outlined by the Cochrane Collaboration. We included all studies that met our operational definition for CPWs and focused on COPD. All studies were evaluated for risk of bias, and all data regarding patient, professional, and systems outcomes were extracted. RESULTS The search strategy identified 497 potentially relevant titles. Of these, 13 studies were included in the review. These studies reported a total of 398 outcomes, with sufficient data for meta-analysis of five outcomes: complications, length of stay, mortality, readmissions, and quality of life. Results showed statistically significant reductions in complications, readmissions, and length of stay but did not show changes in mortality or quality of life. CONCLUSIONS This systematic review reveals evidence to suggest that CPWs for COPD have the potential to reduce complications, readmissions, and length of stay without negatively influencing mortality or quality of life. However, quality of evidence was generally low. The authors therefore acknowledge that results should be interpreted with caution and note the need for additional research in this area.
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Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry.
Callejón-Leblic, B, Pereira-Vega, A, Vázquez-Gandullo, E, Sánchez-Ramos, JL, Gómez-Ariza, JL, García-Barrera, T
Biochimie. 2019;:111-122
Abstract
The high prevalence of lung cancer (LC) has triggered the search of biomarkers for early diagnosis of this disease. For this purpose the study of metabolic changes related to the development of lung cancer could provide interesting information about its early diagnosis. In this sense, chronic obstructive pulmonary disease (COPD), a disease associated with tumor development, is a comorbidity that increases the risk of onset and progression of lung neoplasia and has also to be considered in the study of pathology related to lung cancer. This work develop a metabolomic approach based on direct infusion mass spectrometry using a hybrid triple quadrupole-time of flight mass spectrometer (DI-ESI-QqQ-TOF-MS) in order to identify altered metabolites from serum of LC and COPD patients and evaluate its relationship and implication in the progression of LC. This methodology has been applied to 30 serum samples from LC, 30 healthy patients used as controls (HC) and 30 serum samples from COPD to found altered metabolites from both LC and COPD diseases. In addition, some metabolic differences and similarities were found in Pulmonary Emphysema and Chronic Bronchitis patients. On the other hand, altered metabolites were studied in different stages of LC (II, III and IV) to evaluate the perturbation of them throughout the progression of disease. The sample treatment consisted of the extraction of polar and non-polar metabolites from serum that was later infused into the mass spectrometer using an electrospray ionization source in positive and negative mode. Partial least squares discriminant analysis (PLS-DA) allowed a classification between LC, HC and COPD groups in all acquisition modes. A total of 35 altered and common metabolites between LC and COPD, including amino acids, fatty acids, lysophospholipids, phospholipids and triacylglycerides were identified, being alanine, aspartate and glutamate metabolism the most altered. Finally, ROC curves were applied to the dataset and metabolites with AUC value higher than 0.70 were considered as relevant in the progression of LC.
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Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study.
Kamei, T, Nakamura, H, Nanki, N, Minakata, Y, Matsunaga, K, Mori, Y, ,
BMJ open. 2019;(7):e024114
Abstract
OBJECTIVE Chronic obstructive pulmonary disease (COPD) is mainly treated pharmaceutically with bronchodilators. The purpose of this study was to evaluate the clinical benefits of two-times-per-day aclidinium bromide (Acli-BID) compared with once-a-day tiotropium bromide hydrate (Tio-QD) in patients with COPD. DESIGN This study was a multicentre, open-label, randomised study. SETTING Fourcentres in Kagawa prefecture, Japan. PARTICIPANT Patients who were diagnosed to have COPD Grade 2-3 according to the Global Initiative for Chronic Obstructive Lung Disease 2015 criteria were enrolled. INTERVENTIONS Patients were randomly assigned to receive Acli-BID or Tio-QD at a 1:1 ratio, and followed for 8 weeks. Acli-BID was administered in the morning and night, and Tio-QD was administered in the night. PRIMARY AND SECONDARY OUTCOME MEASURES Primary outcome was forced expiratory volume in one second area under the curve (FEV1AUC0-3), and secondary outcomes were pulmonary function, physical activity, St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC), the 8-item Short-Form Health Survey (SF-8) and COPD exacerbations. Adverse events were evaluated during the study. RESULTS 44 patients were included in this study. FEV1AUC0-3 at week 8 was 4.62±1.43 L·hour in Acli-BID and 4.73±1.60 L·hour in Tio-QD (mean difference (MD) -0.11 L·hour; 95% CI), -1.04 to 0.83). Significant improvement was observed in activity-related subscales of SGRQ (MD -7.78; 95% CI -14.61 to -0.94) and SF-8 (MD 4.01; 95% CI 0.37 to 7.65), mMRC (MD -0.66; 95% CI -1.19 to -0.13) and rate ratio (0.52, 95% CI 0.27 to 0.99) of exacerbations in the Acli-BID compared with the Tio-QD. Acli-BID and Tio-QD significantly improved sedentary behaviour (MD -35.20 min; 95% CI -67.41 to -2.94 and MD -55.40 min; 95% CI -98.15 to -12.77) within each group, but there was no significant difference between the two groups. CONCLUSION Acli-BID as with Tio-QD could be one of the therapeutic options for patients with COPD to improve pulmonary function. Also, our results suggest that intervention with bronchodilators enhanced physical activity in patients with COPD. TRIAL REGISTRATION NUMBER UMIN 000020020.
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Concordant Evidence-Based Interventions in Cardiac and Pulmonary Rehabilitation Guidelines.
Smith, SMS, Chaudhary, K, Blackstock, F
Journal of cardiopulmonary rehabilitation and prevention. 2019;(1):9-18
Abstract
Chronic conditions such as chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) contribute to a significant burden to patients and many experience a reduction in physical functioning, psychological health, and quality of life. The sentinel symptom for COPD and CVD is breathlessness. Rehabilitation programs have been proven to reduce disease symptoms and increase levels of physical and psychological wellness. Pulmonary and cardiac rehabilitation programs have been recommended in international and national guidelines for managing COPD and CVD. Given that these programs seek to reduce breathlessness and improve the physical and psychological functioning of people with COPD and CVD, this review examines the concordant evidence-based interventions in rehabilitation guidelines. The findings of this review indicate that there was concordance in the program design, location of programs, types of health professionals involved in program delivery, assessments of patient at commencement and completion of program, and the delivery of educational topics with minor deviations that were related to disease-specific topics. Apart from disease-specific recommendations, the main divergence from rehabilitation guidelines was found to be dietary screening, inspiratory muscle training, and psychological assessments in evidence-based recommendations for cardiac and pulmonary programs.
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6.
The copper-zinc superoxide dismutase activity in selected diseases.
Lewandowski, Ł, Kepinska, M, Milnerowicz, H
European journal of clinical investigation. 2019;(1):e13036
Abstract
Copper-zinc superoxide dismutase (Cu,Zn-SOD) plays a protective role in various types of tissue protecting them from oxidative damage. Alterations in Cu,Zn-SOD (SOD1 and SOD3) activity and its expression have been observed in pathological occurrences most prevalent in modern society, including inflammatory bowel disease, obesity and its implications-diabetes and hypertension, and chronic obstructive pulmonary disease. Moreover, several SOD1 and SOD3 gene polymorphisms have been associated with the risk of developing a particular type of disease, or its exacerbation. This article features recent observations in this topic, aiming to show the importance of proper gene sequence and activity of Cu,Zn-SOD in the aforementioned diseases.
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Comparison of the Association between Circulating Vitamin D3 Levels and Clinical Outcomes in Patients with Asthma and Chronic Obstructive Pulmonary Disease: A Prospective Observational Study.
Hirai, K, Shirai, T, Suzuki, Y, Shimomura, T, Itoh, K
Biological & pharmaceutical bulletin. 2019;(11):1861-1866
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Abstract
Vitamin D has an immune-modulating effect, related to the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). However, few studies have focused on the difference between patients with asthma and COPD in the association of circulating vitamin D levels with clinical outcomes. We sought to investigate the associations of circulating vitamin D levels with health-related QOL (HR-QOL), severity, and exacerbations. Subjects included 152 asthma patients and 50 COPD patients. We measured plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3]. HR-QOL was assessed using the EuroQoL 5-Dimension (EQ-5D) and the 12-item Short Form Health Survey (SF-12) scales. Exacerbations were recorded during a one-year follow-up. Associations between plasma 25 (OH)D3 concentrations and outcome variables were evaluated using linear regression. Plasma concentrations of 25(OH)D3 were positively associated with the EQ-5D index value and the SF-12 physical component score in patients with asthma; however, such associations were not observed in patients with COPD. A significant association between severity and plasma concentrations of 25(OH)D3 was found only in patients with COPD. The hazard ratios (95% confidence interval) of plasma 25(OH)D3 concentrations (per 1 ng/mL decrease) for time to first exacerbation was 1.38 (1.10-1.75; p = 0.006) and 0.95 (0.87-1.03; p = 0.179) in patients with COPD and asthma, respectively. Lower concentrations of plasma 25(OH)D3 contributed to lower HR-QOL in patients with asthma, and were associated with severity and risk of future exacerbations in patients with COPD.
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A phase II, open-label clinical trial on the combination therapy with medium-chain triglycerides and ghrelin in patients with chronic obstructive pulmonary disease.
Miki, K, Kitada, S, Miki, M, Hui, SP, Shrestha, R, Yoshimura, K, Tsujino, K, Kagawa, H, Oshitani, Y, Kida, H, et al
The journal of physiological sciences : JPS. 2019;(6):969-979
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Abstract
The aim of this study was to investigate the effect of activated ghrelin with dietary octanoic acids or medium-chain triglyceride (MCT) administration to underweight patient with chronic obstructive pulmonary disease (COPD). Eleven severe and very severe COPD patients received a 5-day treatment with edible MCT. Sequentially, 10 patients received a 3-week combination treatment with MCT and intravenous acyl ghrelin. Five-day MCT treatment increased endogenous acyl ghrelin (p = 0.0049), but the total ghrelin level was unchanged. MCT-ghrelin combination treatment improved the peak oxygen uptake (p = 0.0120) during whole treatment course. This effect was attributed to the resultant improvements in cardiac function by O2 pulse, and to the difference between inspired and expired oxygen concentration rather than minute ventilation. Addition of dietary MCT to ghrelin treatment improved the aerobic capacity of underweight COPD patients, likely by mechanisms of increased O2 delivery through improvements in primary cardiocirculatory and muscular crosstalk.
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The Pulmonary Rehabilitation Adapted Index of Self-Efficacy (PRAISE) tool predicts reduction in sedentary time following pulmonary rehabilitation in people with chronic obstructive pulmonary disease (COPD).
Liacos, A, McDonald, CF, Mahal, A, Hill, CJ, Lee, AL, Burge, AT, Moore, R, Nicolson, C, O'Halloran, P, Cox, NS, et al
Physiotherapy. 2019;(1):90-97
Abstract
OBJECTIVES To examine the predictive validity, minimal important difference (MID) and responsiveness of the PRAISE tool. DESIGN Retrospective data analysis from HomeBase trial of home vs centre-based pulmonary rehabilitation. SETTING Tertiary health service. PARTICIPANTS One hundred and sixty-six participants with COPD (100 men) with mean age 69 (SD 9) years, FEV1% predicted 50% (19). INTERVENTIONS Eight-week pulmonary rehabilitation program, conducted at the hospital or at home. MAIN OUTCOME MEASURES The 15-item PRAISE tool comprising 10 general and five pulmonary rehabilitation-specific self-efficacy questions. Predictive validity was examined by exploring the relationship between baseline PRAISE score and objective change in physical activity following pulmonary rehabilitation using the SenseWear Armband. The MID was evaluated using anchor-based and distribution-based methods. Responsiveness was assessed with effect sizes. RESULTS A higher baseline PRAISE score (indicating better self-efficacy) was an independent predictor of reduced sedentary time following pulmonary rehabilitation (P=0.03). A one point increase in PRAISE was associated with a decrease in sedentary time of 4minutes/day (95% confidence interval -7.8 to -0.4minutes/day). Anchor-based estimates of the MID were 0.5 to 1.5 points; however sensitivity and specificity were modest (area under the curve <0.70). Change in PRAISE score following pulmonary rehabilitation had an effect size of 0.21. CONCLUSIONS The PRAISE tool has predictive validity and may be useful to identify those with high self-efficacy who are more likely to achieve important health behaviour changes with pulmonary rehabilitation. The small effect size suggests that the PRAISE tool was not responsive to changes following pulmonary rehabilitation. TRIAL REGISTRATION NUMBER NCT01423227, clinicaltrials.gov.
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The added value of ultrasound muscle measurements in patients with COPD: An exploratory study.
Nijholt, W, Beek, LT, Hobbelen, JSM, van der Vaart, H, Wempe, JB, van der Schans, CP, Jager-Wittenaar, H
Clinical nutrition ESPEN. 2019;:152-158
Abstract
BACKGROUND AND AIMS Malnutrition and sarcopenia are common nutrition (-related) disorders in patients with COPD and are associated with negative health outcomes and mortality. This study aims to correlate ultrasound measured rectus femoris size with fat-free mass and muscle function in patients with COPD. METHODS Patients with COPD, at the start of a pulmonary rehabilitation program, were asked to participate in this study. Rectus femoris (RF) size (thickness in cm, cross-sectional area [CSA] in cm2) was determined by ultrasound. Fat-free mass index (FFMI in kg/m2) was estimated with bioelectrical impedance analyses, using a disease-specific equation. Handgrip strength (HGS) was measured in kilograms and the five times sit to stand test (in seconds, higher scores indicating decreased strength) was performed to assess leg muscle power. The Incremental Shuttle Walk Test (ISWT, in m) was used to assess maximal exercise capacity. RESULTS In total, 44 patients with COPD (mean age 59.8 ± 8.6 years, 43% male, median FEV1%pred 37 [IQR = 23-52]) were included. Greater RF-CSA and thickness were associated with higher FFMI (r = 0.57, p < 0.001; r = 0.53, p = 0.003, respectively) and HGS (CSA r = 0.58, p < 0.001, thickness r = 0.48, p = 0.009). No significant correlations between RF-thickness, CSA, and leg muscle power were found (r = -0.33, p = 0.091; r = -0.35, p = 0.073, respectively). Furthermore, no correlation between RF size and maximal exercise capacity was observed (thickness r = 0.21, p = 0.297, CSA r = 0.22, p = 0.274). CONCLUSIONS This exploratory study shows that in patients with COPD, rectus femoris size is moderately correlated with FFMI and HGS. Future studies should focus on the role of ultrasound in evaluating nutritional status.