Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD?

Dynamic hyperinflation (DH) during exercise occurs in most but not all patients with advanced chronic obstructive pulmonary disease (COPD). It is not known whether the presence or absence of DH has implications for dyspnoea and exercise tolerance. Therefore, we compared detailed ventilatory and sensory responses to exercise in hyperinflators and nonhyperinflators with moderate-to-severe COPD. Nonhyperinflators (n=65) were retrospectively identified from a sample of 427 patients and case-matched to a group of hyperinflators (n=65) based on sex, age, body mass index and % predicted forced expiratory volume in 1 s. Resting pulmonary function and constant work rate cycle exercise responses were compared. Hyperinflators decreased inspiratory capacity (IC) from rest to peak exercise by 0.46±0.24 L whereas the nonhyperinflators increased IC by 0.10±0.15 L (p<0.0001). There were no significant group differences in endurance time (9.11±5.98 versus 8.87±5.24 min) or dyspnoea intensity for any given time or ventilation. An inflection in tidal volume versus ventilation occurred in the majority of nonhyperinflators (n=61) and hyperinflators (n=62) at a similar time and ventilation. Mechanical constraints on tidal volume expansion and the attendant rise in dyspnoea intensity were similar in both groups. Dyspnoea intensity during exercise was associated with progressive mechanical constraints on tidal volume expansion regardless of the presence of DH.     

Can targeting ANGPTL proteins improve glucose tolerance?

Three members of the angiopoietin-like (ANGPTL) family of proteins, ANGPTL3, ANGPTL4 and ANGPTL8, are known regulators of plasma triacylglycerol levels. Recently, these three proteins have garnered considerable interest as potential targets for therapeutically reducing plasma triacylglycerol levels and improving cardiovascular outcomes. In this issue of Diabetologia, Janssen et al ( https://doi.org/10.1007/s00125-018-4583-5) and Vatner et al ( https://doi.org/10.1007/s00125-018-4579-1) show that reducing levels of ANGPTL4 and ANGPTL8, respectively, could have the added benefit of improving glucose tolerance. Interestingly, the improvements in glucose tolerance observed in both studies, both done in rodents, were coupled with increased fat mass. These findings suggest that funnelling lipids to adipose tissue and away from ectopic sites could be beneficial and strengthen the argument for pursuing the therapeutic targeting of ANGPTL proteins.     

Can individualized rehabilitation improve functional independence in elderly patients with COPD?

STUDY OBJECTIVES: The aims of this study were to establish whether pulmonary rehabilitation (PR) improves domestic function and daily activity levels in COPD and whether individually targeted exercise is more effective than general exercise. DESIGN: Prospective randomized, controlled trial. SETTING: Outpatient PR program in secondary care. PARTICIPANTS: One-hundred eighty patients (mean [+/-SD] age, 68.3 +/- 8.6 years; FEV1, 0.95 +/- 0.4 L; FEV1/FVC ratio, 0.51 +/- 0.15; 111 male patients; 69 female patients) with stable COPD. One hundred twenty-one patients completed the study. INTERVENTIONS: Patients were randomized to a conventional 7-week general exercise program ([GEP] n = 90) or an individually targeted exercise program ([ITEP] n = 90). MEASUREMENT AND RESULTS: Daily activity was measured using ambulatory activity monitors (Z80 -32k V1 Int; Gaehwiler Electronics; Hombrechtikon, Switzerland). These were lightweight devices, which contained a uniaxial accelerometer. Domestic function was assessed by the Canadian Occupational Performance Measure (COPM). Exercise performance was assessed by the incremental shuttle walk test (ISWT) and the endurance shuttle walk test and health status by the chronic respiratory questionnaire-self-reported. Activity monitor counts increased by 29.18% (95% confidence interval [CI], 3.19 to 55.17; p = 0.03) for the GEP and 40.63% (95% CI, 7.42 to 73.83; p = 0.02) for the ITEP. Mean COPM performance scores increased by 1.71 (95% CI, 1.37 to 2.05; p = 0.0001) for the GEP and 1.46 (95% CI, 1.05 to 1.87; p = 0.0001) for the ITEP. Mean COPM satisfaction scores increased by 2.27 (95% CI, 1.74 to 2.81; p = 0.0001) for the GEP and 2.04 (95% CI, 1.56 to 2.52; p = 0.0001) for the ITEP. ISWT scores increased by 81.72 m (range, 63.83 to 99.62) for the GEP and by 85.52 m (range, 67.62 to 103.42) for the ITEP. No statistically significant difference was found between the general exercise group and the individually targeted exercise group for any outcome measure. CONCLUSIONS: Pulmonary rehabilitation improves domestic function and physical activity. This study also demonstrates that general exercise training is as effective as individually targeted training.     

Can bisphosphonates improve outcomes in patients with newly diagnosed multiple myeloma?

Preclinical and clinical evidence suggests that bisphosphonates have anticancer activities both within and outside bone. Early clinical trials of bisphosphonates provided evidence for antimyeloma effects in exploratory analyses in high-risk subsets, and recent trials of zoledronic acid (ZOL) have provided further support of antimyeloma activity The MRC Myeloma IX trial is an innovative 2 x 2 factorial trial comparing ZOL and clodronate (CLO) in patients with newly diagnosed multiple myeloma receiving either intensive or non-intensive therapy regimens. Results showed that ZOL significantly reduced skeletal morbidity and significantly improved both progression-free and overall survival versus CLO. Notably, the survival benefit with ZOL remained significant after adjustment for skeletal-related events, consistent with clinically meaningful antimyeloma activity. Further analyses of these data will provide greater insight into ZOL interactions with primary treatment regimens for multiple myeloma.     

Can exercise minimize postprandial oxidative stress in patients with type 2 diabetes?

It has recently been estimated by the American Diabetes Association that 21 million Americans, or about 7% of the U.S. population, have diabetes, while an additional 54 million Americans have pre-diabetes. The onset and progression of these disorders and related complications are linked to impairments in glucose and lipid metabolism, both of which are associated with increased production of reactive oxygen and nitrogen species (RONS). Increased RONS production coupled with impaired antioxidant defense (a common finding among patients with diabetes) promotes oxidation of specific biomolecules (lipid, protein, DNA), which can lead to an exacerbation of diabetic complications. While bloodborne variables related to these disorders have traditionally been measured in a fasted state, increasing evidence suggests that measurement of postprandial glycemia, lipemia, and oxidative stress may provide more important clinical information concerning an individual's susceptibility to diabetes onset and disease progression. While drugs to treat hyperglycemia and hyperlipidemia have been reported in some studies to promote favorable outcomes related to attenuating the postprandial rise in blood glucose and triglycerides, one non-pharmaceutical approach which may have promise is the performance of regular exercise. Both acute and chronic exercise may aid in attenuating postprandial oxidative stress in three distinct ways. First, exercise stimulates an increase in endogenous antioxidant enzyme activity. Second, exercise improves blood glucose clearance via enhanced GLUT 4 translocation and protein content, as well as enhanced insulin-insulin receptor binding and post-receptor signaling. Third, exercise improves blood triglyceride clearance via a reduced chylomicron-triglyceride half-life and enhanced lipoprotein lipase activity. In this article we provide evidence for the potential role of exercise in modulating postprandial oxidative stress in diabetic and pre-diabetic individuals. It is certainly possible that exercise may prove beneficial in this regard. If so, and in accordance with the recent joint initiative of the American College of Sports Medicine and the American Medical Association, exercise may be viewed as "medicine" for individuals who are at increased risk for postprandial oxidative stress.     

Can we induce tolerance in rheumatoid arthritis?

Oral tolerance (OT) has worked well in numerous laboratory animal models of autoimmune diseases. Humans have been orally tolerized to keyhole limpet hemocyanin (KLH); patients with systemic sclerosis (SSc, scleroderma) have been orally tolerized to oral type I collagen (CI). However, clinical trials of oral type II collagen (CII) therapy in rheumatoid arthritis (RA) have had mixed results. Clinical studies show that compounds (such as nonsteroidal antiinflammatory drugs [NSAID] and prednisone) that inhibit generation of PGE₂block OT induction. In murine OT models, the PGE₁analog, misoprostol, reverses the NSAID OT block. These animal studies suggest that OT to CII or other antigens in patients with RA should be inducible if measures are taken to maintain normal prostaglandin function in the gut-associated lymphoid tissue (GALT). A clinical trial is underway in patients with RA to assess whether withholding NSAIDs and prednisone will allow OT to to be induced, and whether oral CII has meaningful clinical efficacy in this disease.     

Can the exercise test with nitroglycerin be useful for differentiation of patients with and without changes in coronary arteries--syndrome X?

The aim of this study was to compare the results of ECG exercise test performed before and after oral administration of nitroglycerine (NTG) in patients with coronary artery disease (CAD), and patients with typical chest pain without any changes in coronary arteriography--syndrome X. We examined 98 patients with typical chest pain, positive result of ECG exercise test, then accordingly to results of coronary arteries assessed with coronary arteriography, patients (pts.) were divided into two groups: group 1--35 pts. without any changes in coronary arteriography--syndrome X, and group 2--48 pts. with significant stenosis present in one or more coronary vessels. Each patient underwent two ECG exercise tests: first without any medication and second performed average 30 minutes after first test, and 5 min after oral administration of 1 table of nitroglycerine. During both tests the following parameters were evaluated: test duration, presence of chest pain, max. ST-T changes, heart rate (HR), and systolic blood pressure (SBP). RESULTS: In group 1 after NTG time of test duration had shortened from 5.9 +/- 0.4 min to 5.7 +/- 0.6 min. We also observed an increase in max. ST-T complex depression (2.2 +/- 0.5 mm vs 2.4 +/- 0.4 mm) but these differences were not statistically significant. In CAD group, duration of test after NTG was longer (6.2 +/- 1 vs 7.4 +/- 1.2), and normalization of max. ST-T complex depressions (2.7 +/- 0.5 vs 2.0 +/- 0.3 mm) was observed p < 0.01. CONCLUSION: Our study suggests that ECG exercise test with NTG may be useful in differentiation of patients with syndrome X and patients with typical coronary artery disease.     

Can exogenously administered hyaluronan improve respiratory function in patients with pulmonary emphysema?

While most attempts at developing a treatment for pulmonary emphysema have focused on the use of elastase inhibitors to reduce elastic fiber damage and the loss of alveoli, this laboratory has developed a method of preventing such injury by the intratracheal administration of hyaluronan (HA). Animals treated with HA prior to the induction of experimental emphysema develop significantly less disease than untreated controls. The protective effect of HA may be related to its ability to bind to lung elastic fibers, thereby preventing their breakdown by elastases. Although clinical trials involving nebulized HA are not expected to yield a measurable treatment effect for at least several years, it is proposed that the special ability of this polysaccharide to retain water may increase the elasticity of lung elastic fibers, producing a relatively rapid improvement in pulmonary mechanics. Such an outcome might speed the development of this potential treatment for pulmonary emphysema.     

Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction?

OBJECTIVE: The objective of the present study was to determine whetherappropriate endurance exercise training improves cardiac functionin patients with prior myocardial infarction. METHODS: Methods Twenty-nine patients with prior myocardial infarctionwere divided into three groups (Group 1: control, Group 2: low-intensitytraining, Group 3: high-intensity training). Low and high trainingintensities were determined according to the gas exchange thresholdof each patient. The patients in Groups 2 and 3 performed 15min of home-based physical training safely, twice a day, 5 daysa week for 2 months. Prior to and following this training, eachpatient performed two constant work rate tests (moderate andheavy intensity) and a symptom-limited incremental exercisetest. RESULTS: Heart rates at rest and during exercise were decreased significantlyafter 2 months in all three groups. Stroke volume at rest increasedsignificantly after 2 months only in Group 3. Stroke volumeafter 6 min of heavy intensity exercise increased significantlyin Groups 2 and 3. However, the ejection fraction at 6 min ofheavy-intensity exercise increased significantly only in Group3. The maximal work rate attained during incremental exercisetesting increased significantly in Groups 2 and 3. This parameterdid not significantly change in the control group. CONCLUSIONS: Effects of physical training on maximal exercise capacity werenoted in both exercise training groups. However, improvementin cardiac function (such as stroke volume), both at rest andduring exercise, was noted only in the high-intensity traininggroup. Our results suggest that relatively high-intensity trainingmay improve exercise capacity and cardiac function of patientswith prior myocardial infarction. (Eur Heart J 1996; 17: 1511–1521)     

Does correction of exercise-induced desaturation by O2 always improve exercise tolerance in COPD? A preliminary study

BACKGROUND: This study sought to investigate whether correction of exercise-induced desaturation by oxygen supply (O(2)) systematically improves exercise tolerance and cardiorespiratory adaptations in COPD patients. METHODOLOGY: Twenty-five COPD patients [FEV(1)=52+/-2.5% pred] exhibiting exercise-induced desaturation performed cyclo-ergometer endurance exercise at 60%of their maximal workload in two randomized conditions: air vs. O(2). O(2) was adjusted to ensure 90相似文献