Background. Endurance training improves cardiopulmonary fitness in maintenance haemodialysis (MHD). Because many MHD patients are profoundly deconditioned and exhibit significant muscle weakness, ...endurance training may also improve muscle strength and physical performance in these patients. This study assessed this possibility. Methods. Twelve MHD patients performed incremental and constant work rate cycle exercise tests to determine peak work rate, VO2peak and endurance time (ET). Lower extremity strength, power and fatigability, stair-climbing time, 10 m walk time and a timed up-and-go were assessed before and after 8.6±2.3 weeks of thrice weekly, progressive, semi-recumbent, leg-cycle training during haemodialysis. Initial training intensity and duration targets were set at 50% peak work rate (WR) and 20 min, respectively, with a goal of progressing to 40 min at the highest WR tolerable. Non-exercising MHD patients and healthy volunteers with similar age, gender and race/ethnicity served as comparison groups. Results. None of the subjects tolerated the initial target intensity. Therefore, WR was reduced to 19±9 watts (30% of peak WR) for 19.9 min/session. At end of training, subjects cycled at 29±25 watts (46% initial peak WR; P = 0.01) for 38±8 min (P<0.001). VO2peak and ET improved 22% (P = 0.018) and 144% (P = 0.001), respectively. Quadriceps strength, power and fatigability improved 16% (P = 0.002), 15% (P = 0.115) and 43% (P = 0.029), respectively. The three measures of physical performance improved by 14–17% (P<0.031). Total work performed in training increased by 5.5±21.1 kJ/week (17%); a 165% increase during the study period. Conclusions. Nine weeks of leg-cycling during haemodialysis in MHD patients improves not only cardiopulmonary fitness and endurance but also muscle strength, power, fatigability and physical function. These data underscore the value of endurance training in MHD.
Chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging and is associated with comorbid conditions including osteoporosis and sarcopenia. These extrapulmonary conditions are ...highly prevalent yet frequently underdiagnosed and overlooked by pulmonologists in COPD treatment and management. There is evidence supporting a role for bone-muscle crosstalk which may compound osteoporosis and sarcopenia risk in COPD. Chest CT is commonly utilized in COPD management, and we evaluated its utility to identify low bone mineral density (BMD) and reduced pectoralis muscle area (PMA) as surrogates for osteoporosis and sarcopenia. We then tested whether BMD and PMA were associated with morbidity and mortality in COPD.
BMD and PMA were analyzed from chest CT scans of 8468 COPDGene participants with COPD and controls (smoking and non-smoking). Multivariable regression models tested the relationship of BMD and PMA with measures of function (6-min walk distance (6MWD), handgrip strength) and disease severity (percent emphysema and lung function). Multivariable Cox proportional hazards models were used to evaluate the relationship between sex-specific quartiles of BMD and/or PMA derived from non-smoking controls with all-cause mortality.
COPD subjects had significantly lower BMD and PMA compared with controls. Higher BMD and PMA were associated with increased physical function and less disease severity. Participants with the highest BMD and PMA quartiles had a significantly reduced mortality risk (36% and 46%) compared to the lowest quartiles.
These findings highlight the potential for CT-derived BMD and PMA to characterize osteoporosis and sarcopenia using equipment available in the pulmonary setting.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pulmonary rehabilitation has been established as the standard of care for patients with symptomatic chronic obstructive pulmonary disease (COPD). Benefits include improvements in exercise tolerance, ...dyspnoea and quality of life; magnitude of benefit is generally greater than for any other COPD therapy. A wide range of professional organizations and standards documents have recommended pulmonary rehabilitation; benefits accrue across the spectrum of disease severity.
However, pulmonary rehabilitation is provided to only a tiny fraction of those chronic obstructive pulmonary disease (COPD) patients who would benefit. International estimates posit that only 1-2% of COPD patients receive pulmonary rehabilitation. In contrast, other COPD therapies, bronchodilators and oxygen therapy in particular, are much more widely available. The costs of pulmonary rehabilitation should not be a major barrier, as costs are comparable to other therapies.
In seeking strategies to increase pulmonary rehabilitation availability, it can be argued that a demonstration of a life prolongation benefit would be of great help. Therapies that improve survival have a high priority for patients, for their health care providers and for payers. A well-designed survival study has never been performed. Although efforts are underway to organize such a trial, even in a best-case scenario it will be a number of years before the results are available.
Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and ...DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1-2 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease. TRIAL REGISTRATION: NCT00608764. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bronchodilator therapy represents a potentially valuable therapeutic option to increase exercise tolerance and enhance lung function in mild to moderate chronic obstructive pulmonary disease (COPD).
...To determine effects of tiotropium on pulmonary hyperinflation and exercise tolerance in patients with symptomatic Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and 2 COPD who experienced inspiratory capacity decrease greater than or equal to 100 ml during incremental and constant work rate treadmill exercise.
This 22-week, randomized, double-blind, two-period crossover study evaluated the efficacy of once-daily tiotropium bromide (18 μg) versus placebo in patients with GOLD 1 and 2 COPD. Primary endpoint was between-group (tiotropium vs. placebo) difference in inspiratory capacity at isotime (i.e., at the time the shortest test ended) during constant work rate treadmill exercise from baseline to the end of a 6-week treatment period. Key secondary endpoints included differences in exercise duration and exertional dyspnea. Safety was assessed by recording adverse events.
Study population comprised 48 patients with GOLD 1 COPD and 78 patients with GOLD 2 COPD. Resting inspiratory capacity significantly improved with tiotropium versus placebo in the overall (P < 0.0001), GOLD 1 (P = 0.0183), and GOLD 2 (P < 0.0001) groups. Isotime inspiratory capacity was significantly enhanced during exercise in the overall (P = 0.0087) and GOLD 2 (P = 0.0494) groups after tiotropium versus placebo. Tiotropium versus placebo significantly enhanced exercise duration in the GOLD 2 group (P = 0.0070) but not in the GOLD 1 or overall patient groups. In the overall group, increase in exercise duration seen with tiotropium was well correlated with the increase in isotime inspiratory capacity (r = 0.463, P < 0.0001).
Resting and exercise hyperinflation were ameliorated by bronchodilator therapy with tiotropium in the overall GOLD 1 plus 2 COPD group. Exercise tolerance was enhanced in GOLD 2, but not GOLD 1, COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01072396).
1 Division of Endocrinology, Metabolism, and Molecular
Medicine, Charles R. Drew University of Medicine and Science, Los
Angeles 90059; 2 Laboratory for Exercise Sciences, El Camino
College, and 3 ... Harbor-University of California Los Angeles
Medical Center, Torrance, California 90502; and 4 Biomedical
Mass Spectrometric Research Resource, Department of Internal
Medicine, Washington University, School of Medicine, St. Louis,
Missouri 63110
Testosterone increases muscle mass and strength and regulates
other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for
maintaining various androgen-dependent processes are similar. To
determine the effects of graded doses of testosterone on body
composition, muscle size, strength, power, sexual and cognitive
functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin,
and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for
20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean
nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively.
Fat-free mass increased dose dependently in men receiving 125, 300, or
600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg,
respectively). The changes in fat-free mass were highly dependent on
testosterone dose ( P = 0.0001) and correlated with log
testosterone concentrations ( r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps
muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did
not change significantly at any dose. We conclude that changes in
circulating testosterone concentrations, induced by GnRH agonist and
testosterone administration, are associated with testosterone dose- and
concentration-dependent changes in fat-free mass, muscle size, strength
and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in
conformity with a single linear dose-response relationship. However,
different androgen-dependent processes have different testosterone
dose-response relationships.
sexual function; testosterone effects on muscle; cognitive
function; plasma lipids; prostate-specific antigen; testosterone
effects on insulin-like growth factor I; testosterone and hemoglobin
Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to ...concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts.
We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use.
Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time.
We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with ...reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.
Methods
Forty‐six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre‐type distribution and cross‐sectional area via immunofluorescence microscopy and RNA‐sequenced to generate transcriptome‐wide gene expression data. Sex‐stratified k‐means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co‐expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype.
Results
Abnormal myofibre proportion was defined in males with COPD (n = 29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n = 17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6‐min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s‐to‐forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty‐nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co‐expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co‐expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density.
Conclusions
Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co‐expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.
Muscle weakness and effort intolerance are common in maintenance hemodialysis (MHD) patients. This study characterized morphometric, histochemical, and biochemical properties of limb muscle in MHD ...patients compared with controls (CTL) with similar age, gender, and ethnicity. Vastus lateralis muscle biopsies were obtained from 60 MHD patients, 1 day after dialysis, and from 21 CTL. Muscle fiber types and capillaries were identified immunohistochemically. Individual muscle fiber cross-sectional areas (CSA) were quantified. Individual fiber oxidative capacities were determined (microdensitometric assay) to measure succinate dehydrogenase (SDH) activity. Mean CSAs of type I, IIA, and IIX fibers were 33, 26, and 28% larger in MHD patients compared with CTL. SDH activities for type I, IIA, and IIX fibers were reduced by 29, 40, and 47%, respectively, in MHD. Capillary to fiber ratio was increased by 11% in MHD. The number of capillaries surrounding individual fiber types were also increased (type I: 9%; IIA: 10%; IIX: 23%) in MHD patients. However, capillary density (capillaries per unit muscle fiber area) was reduced by 34% in MHD patients, compared with CTL. Ultrastuctural analysis revealed swollen mitochondria with dense matrix in MHD patients. These results highlight impaired oxidative capacity and capillarity in MHD patients. This would be expected to impair energy production as well as substrate and oxygen delivery and exchange and contribute to exercise intolerance. The enlarged CSA of muscle fibers may, in part, be accounted for by edema. We speculate that these changes contribute to reduce limb strength in MHD patients by reducing specific force.
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