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New Findings: What is the topic of this review? Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID-19). What advances does it highlight? Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID-19 exhibit near-normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. Abstract: In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen ‘debt’ and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high-intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis-induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus dis

New Findings: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its ‘natural’ posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure. Abstract: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ((Formula presented.)) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) (Formula presented.) ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical (Formula presented.) ratio gradient is present in both postures, but with better (Formula presented.) matching in the prone position. In ARDS and CARDS, the vertical (Formula presented.) ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still

Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes were allocated (randomized controlled trial) to 11 weeks of aerobic exercise training consisting of either moderate-intensity endurance training (END; n=10), or low-volume high-intensity interval training (HIIT; n=11). Skeletal muscle biopsies (m vastus lateralis) were obtained before and after the training intervention. At baseline, there was no difference in capillarization, capillary structure and exercise hyperaemia between the two groups. After the training intervention, capillary-to-fiber ratio increased by 8±3% in the END group (P<0.05) and was unchanged in the HIIT group with no difference between groups. Endothelium thickness increased (P<0.05), basement membrane thickness decreased (P<0.05) and the capillary lumen tended (P=0.07) to increase in the END group, whereas these structural indicators were unchanged after HIIT. In contrast, skeletal muscle endothelial nitric oxide synthase (eNOS) increased after HIIT (P<0.05), but not END, whereas there was no change in vascular endothelial growth factor (VEGF), superoxide dismutase (SOD)-2 or NADPH oxidase after both training protocols. In contrast to END training, HIIT did not alter capillarization or capillary structure in individuals with type 2 diabetes. In conclusion, HIIT appears to be a less effective strategy to treat capillary rarefaction and reduce basement thickening in type 2 diabetes.

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 (Equation is included in full-text article.)O2peak, respectively.RESULTS: The energy expenditure was significantly greater in AMC than in TRE (P < .05). The (Equation is included in full-text article.)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.

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with 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 versus 2.36±0.14 L/min, respectively, P<0.05) which compromised leg oxygen delivery (372±26 versus 453±32 mLO2/min, respectively, P<0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the COPD patients (P<0.05) and also tended to be higher during exercise (p=0.07), while 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 suggests 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.

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.

High physical activity is important in chronic obstructive pulmonary disease treatment Patients with chronic obstructive pulmonary disease (COPD) have lower activity levels than healthy controls. Loss of skeletal muscle affects COPD negatively, and strengthening of the musculature is probably part of the explanation for the positive effects of physical activity. This review de­scribes the recent literature on restoring and maintaining physical activity in COPD and the importance of maintaining high physical activity levels. Furthermore, the future per­spectives for research in COPD, physical activity, and the possible mechanisms for the beneficial effects are discussed., Patients with chronic obstructive pulmonary disease (COPD) have lower activity levels than healthy controls. Loss of skeletal muscle affects COPD negatively, and strengthening of the musculature is probably part of the explanation for the positive effects of physical activity. This review describes the recent literature on restoring and maintaining physical activity in COPD and the importance of maintaining high physical activity levels. Furthermore, the future perspectives for research in COPD, physical activity, and the possible mechanisms for the beneficial effects are discussed.

Ulrik Winning Iepsen,1 Gregers Druedal Wibe Munch,1 Mette Rugbjerg,1 Anders Rasmussen Rinnov,1 Morten Zacho,1 Stefan Peter Mortensen,1,2 Niels H Secher,3 Thomas Ringbaek,4 Bente Klarlund Pedersen,1 Ylva Hellsten,5 Peter Lange,1,4,6 Pia Thaning1,4 1The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark, 2Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, 3Department of Anesthesiology, University of Copenhagen, Rigshospitalet, Copenhagen, 4Department of Respiratory Medicine, University Hospital Hvidovre, Hvidovre, 5Department of Nutrition, Exercise and Sports, University of Copenhagen, 6Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark 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. Th

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 clinica

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.

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.

Mette Rugbjerg,1 Ulrik Winning Iepsen,1 Karsten Juhl Jørgensen,2 Peter Lange1,3,4 1The Centre of Inflammation and Metabolism and The Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2The Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark; 3Department of Respiratory Medicine, University Hospital Hvidovre, Copenhagen, Denmark; 4Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark 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&rsq

IntroductIon: Pneumothorax is a common problem in Denmark. Guidelines recommend insertion of small-bore (≤ 14 Fr) chest tubes or simple needle aspiration in spontaneous pneumothorax. Our objective was to investigate the management of pneumothorax in Danish hospitals. Material and Methods: We undertook a questionnaire survey at all Danish acute hospitals enquiring about current practice in the management of pneumothorax. A questionnaire was sent to 35 hospitals in May 2013. After follow-up in September 2013, a total of 32 completed questionnaires were assessed. results: We found that three hospitals (10.7%) used simple needle aspiration in primary spontaneous pneumothorax. The majority of the hospitals treated all types of pneumothorax by inserting chest tubes with a traditional small thoracotomy (75%), and most hospitals used large-bore (> 14 Fr) chest tubes (85.7%). There were no regional differ-ences in the management of pneumothorax among the five regions in Denmark (p > 0.05), but we found a trend towards use of less invasive techniques in hospitals with departments of either Respiratory Medicine or Thoracic Surgery. conclusIon: Management of pneumothorax in Denmark is mainly based on insertion of a large-bore (> 14 Fr) chest tube by a traditional small thoracotomy. Only a few hospitals in Denmark use minimally invasive techniques in the management of spontaneous pneumothorax. We speculate that implementation of these techniques may reduce hospital admission time for patients with spontaneous pneumothorax in Denmark.