Ulrik Winning Iepsen

Effectiveness of pulmonary rehabilitation in COPD with mild symptoms: a systematic review with meta-analyses

Purpose Most guidelines recommend pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) and modified Medical Research Council dyspnea scale (mMRC) levels ≥2, but the effectiveness of PR in patients with less advanced disease is not well established. Our aim was to investigate the effects of PR in patients with COPD and mMRC ≤1. Methods The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. We identified randomized controlled trials (RCTs) through a systematic, multidatabase literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC ≤1. Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and dropouts were important outcomes. Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence. Meta-analyses were performed when deemed feasible. Results Four RCTs (489 participants) were included. On the basis of moderate-quality evidence, we found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [−4.51 to −3.89]) on St George’s Respiratory Questionnaire, but not at the longest follow-up. We also found a statistically significant improvement of 25.71 m (95% CI: [15.76–35.65]) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant. No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity. No adverse effects were reported. Conclusion We found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically nonsignificant improvement in walking distance following PR in patients with COPD and mild symptoms. This resulted in a weak recommendation of routine PR in these patients using the GRADE approach.

A combination of resistance and endurance training increases leg muscle strength in COPD An evidence-based recommendation based on systematic review with meta-analyses

Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD). Our objectives were to assess the efficiency of combining RT with ET compared with ET alone. We identified eligible studies through a systematic multi-database search. One author checked titles and abstracts for relevance using broad inclusion criteria, whilst two independent authors checked the full-text copies for eligibility. Two authors independently extracted data, and we assessed the risk of bias and quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation guidelines. We included 11 randomized controlled trials (331 participants) and 2 previous systematic reviews. The meta-analyses showed equal improvements in HRQoL, walking distance and exercise capacity. However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39–0.98). In conclusion, we found significantly increased leg muscle strength favouring a combination of RT with ET compared with ET alone. Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET.

A Systematic Review of Resistance Training Versus Endurance Training in COPD

PURPOSE: Endurance training (ET) as part of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) has been shown to improve exercise capacity and health-related quality of life, but dyspnea limits the exercise intensity. Therefore, resistance training (RT), which may cause less dyspnea, could be an alternative. The purpose of this review was to formulate evidence-based recommendations on the use of RT in pulmonary rehabilitation of patients with COPD. Our primary outcomes were health-related quality of life, activities of daily living, dyspnea, possible harm, and total mortality. Our secondary outcomes were walking distance, lean body mass, muscle strength, and exercise capacity. METHODS: We identified randomized controlled trials through a systematic multidatabase search. One author checked titles and abstracts for relevance using broad inclusion criteria, whereas 2 authors independently checked the full-text articles for eligibility. Two authors independently extracted data and assessed the risk of bias and quality of evidence. Meta-analyses were performed when deemed feasible based on the quality and amount of data. RESULTS: We included 8 randomized controlled trials (328 participants). On the basis of moderate- to very low-quality evidence, we found no clinically important difference between RT and ET. We did not find sufficient data for a meta-analysis of total mortality, adverse events, dyspnea, or lean body mass. CONCLUSIONS: We found that in patients with COPD, RT seems to induce the same beneficial effects as ET. Therefore, we recommend that RT should be considered according to patient preferences when designing a pulmonary rehabilitation program for patients with COPD.

Effect of endurance versus resistance training on quadriceps muscle dysfunction in COPD: a pilot study

Introduction Exercise is an important countermeasure to limb muscle dysfunction in COPD. The two major training modalities in COPD rehabilitation, endurance training (ET) and resistance training (RT), may both be efficient in improving muscle strength, exercise capacity, and health-related quality of life, but the effects on quadriceps muscle characteristics have not been thoroughly described. Methods Thirty COPD patients (forced expiratory volume in 1 second: 56% of predicted, standard deviation [SD] 14) were randomized to 8 weeks of ET or RT. Vastus lateralis muscle biopsies were obtained before and after the training intervention to assess muscle morphology and metabolic and angiogenic factors. Symptom burden, exercise capacity (6-minute walking and cycle ergometer tests), and vascular function were also assessed. Results Both training modalities improved symptom burden and exercise capacity with no difference between the two groups. The mean (SD) proportion of glycolytic type IIa muscle fibers was reduced after ET (from 48% [SD 11] to 42% [SD 10], P<0.05), whereas there was no significant change in muscle fiber distribution with RT. There was no effect of either training modality on muscle capillarization, angiogenic factors, or vascular function. After ET the muscle protein content of phosphofructokinase was reduced (P<0.05) and the citrate synthase content tended increase (P=0.08) but no change was observed after RT. Conclusion Although both ET and RT improve symptoms and exercise capacity, ET induces a more oxidative quadriceps muscle phenotype, counteracting muscle dysfunction in COPD.

The effect of low-volume high-intensity interval training versus endurance training on glycemic control in individuals with type 2 diabetes

To evaluate whether high‐intensity interval training (HIIT) with a lower time commitment can be as effective as endurance training (END) on glycaemic control, physical fitness and body composition in individuals with type 2 diabetes.

Leg blood flow is impaired during small muscle mass exercise in patients with COPD

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex-matched healthy controls were studied. During knee-extensor exercise (10 W), leg blood flow was lower in the patients compared with the controls (1.82 ± 0.11 vs. 2.36 ± 0.14 l/min, respectively; P < 0.05), which compromised leg oxygen delivery (372 ± 26 vs. 453 ± 32 ml O2/min, respectively; P < 0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the patients with COPD (P < 0.05) and also tended to be higher during exercise (P = 0.07), whereas the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggest that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1.NEW & NOTEWORTHY This study demonstrates that chronic obstructive pulmonary disease (COPD) is associated with a reduced blood flow to skeletal muscle during small muscle mass exercise. In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD.

Effect of 6 weeks of high-intensity one-legged cycling on functional sympatholysis and ATP signaling in patients with heart failure

Breathlessness during daily activities is the primary symptom in patients with heart failure (HF). Poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors, such as skeletal muscle function, play a role in determining exercise capacity. We investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 × 4 at 90% one-legged cycling max) on 1) the ability to override sympathetic vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6). Arterial tyramine infusion lowered leg blood flow and leg vascular conductance at rest and during KEE before the training intervention in both groups ( P < 0.05) but not during KEE after the training intervention. There was no difference between groups. The peak vasodilatory response to ATP was blunted in HF patients ( P < 0.05), whereas there was no difference in ACh- and sodium nitroprusside-induced vasodilation between HF patients and healthy individuals. ACh-induced vasodilation increased in HF patients after the training intervention ( P < 0.05). HIC improved aerobic capacity in both groups ( P < 0.05), whereas only HF patients made improvements in the 6-min walking distance ( P < 0.05). These results suggest that exercise hyperemia and functional sympatholysis are not altered in HF patients and that functional sympatholysis is improved with HIC in both HF patients and healthy individuals. Moreover, these results suggest that the peak vasodilatory response to ATP is blunted in HF. NEW & NOTEWORTHY The ability to override sympathetic vasoconstrictor activity (by arterial tyramine infusion) during exercise is not different between heart failure patients and healthy individuals and is improved by high-intensity, one-legged cycling training. The peak vasodilatory response to ATP is reduced in heart failure patients.

Alpha adrenergic receptor blockade increases capillarization and fractional O2 extraction and lowers blood flow in contracting human skeletal muscle

To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction.

Effect of endurance versus resistance training on local muscle and systemic inflammation and oxidative stress in COPD

Limb muscle dysfunction in patients with COPD may be associated with local muscle and/or systemic inflammation, and therefore we investigated whether exercise training altered markers of inflammation and oxidative stress. We obtained vastus lateralis muscle biopsies and venous blood samples from patients with COPD (n = 30) before and after 8 weeks of resistance training (RT) (n = 15) or endurance training (ET) (n = 15). Healthy age‐matched subjects were included as baseline controls (n = 8). Inflammatory markers in muscle and systemically were determined by interleukins (IL), tumour necrosis factor alfa (TNF‐α), leukocyte concentration together with immunohistochemical staining for macrophages. Muscle oxidative stress and antioxidant capacity were determined by NADPH oxidase (NOX) and superoxide dismutase 2 (SOD2), respectively. Before exercise training, COPD patients had a higher muscular NOX protein content and circulating IL‐8, IL‐18, CRP, and leukocyte levels but a similar number of muscle‐infiltrating macrophages compared with controls. Eight weeks of ET or RT increased muscle SOD2 content with no difference between groups. Plasma TNF‐α, increased (P < .05) after ET and tended to (P = .06) increase after RT, but had no effect on muscular NOX protein content, number of muscle‐infiltrating macrophages, or systemic levels of other pro‐inflammatory cytokines or leukocytes. In patients with COPD, we found no evidence for muscular inflammation and no effect of exercise training. However, systemic inflammation was elevated in COPD and both training modalities induced an upregulation of muscle antioxidant capacity.

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure

Purpose: Cardiorespiratory fitness is positively related to heart failure (HF) prognosis, but lack of time and low energy are barriers for adherence to exercise. We, therefore, compared the effect of low-volume time-based resistance exercise training (TRE) with aerobic moderate-intensity cycling (AMC) on maximal and submaximal exercise capacity, health-related quality of life, and vascular function. Methods: Twenty-eight HF patients (New York Heart Association class I-II) performed AMC (n = 14) or TRE (n = 14). Maximal and submaximal exercise capacity, health-related quality of life, and vascular function were evaluated before and after a 6-wk training intervention with 3 training sessions per week. The AMC group and the TRE group trained for 45 and 25 min per training session, respectively. During the training sessions, the TRE and AMC groups trained at 60 ± 4% and 59 ± 2% (mean ± standard deviation) of O2peak, respectively. Results: The energy expenditure was significantly greater in AMC than in TRE (P < .05). The O2peak and Wattpeak increased in AMC group (P < .001) and TRE group (P = .001), with no differences between groups. Six-minute walk distance also increased in both groups (AMC, P = .006 and TRE, P = .036), with no difference between groups. Health-related quality of life improved equally in the 2 groups, whereas vascular function did not change in either group. Conclusion: These results demonstrate that AMC and TRE equally improved exercise capacity and health-related quality of life in lower New York Heart Association–stage HF patients, despite less time required as well as lower energy expenditure during TRE than during AMC. Therefore, TRE might represent a time-efficient exercise modality for improving adherence to exercise in patients with class I-II HF.