Maurice Hayot

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

BACKGROUND Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. PURPOSE The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. METHODS An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. RESULTS We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. CONCLUSIONS Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.

An official European Respiratory Society statement on physical activity in COPD

This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 “Rehabilitation and Chronic Care” determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5–8 years). An official ERS statement providing a comprehensive overview on physical activity in patients with COPD http://ow.ly/C6v78

Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease

Background: Because oxidative stress affects muscle function, the underlying mechanism to explain exercise induced peripheral muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD) is clinically relevant. This study investigated whether chronic hypoxaemia in COPD worsens peripheral muscle oxidative stress and whether an abnormal muscle inflammatory process is associated with it. Methods: Nine chronically hypoxaemic and nine non-hypoxaemic patients performed repeated knee extensions until exhaustion. Biopsy specimens were taken from the vastus lateralis muscle before and 48 hours after exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin and thiobarbituric acid reactive substances (TBARs)) and oxidised proteins. Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis factor (TNF)-α levels. Results: When both groups were taken together, arterial oxygen pressure was positively correlated with quadriceps endurance time (n = 18, r = 0.57; p<0.05). At rest, quadriceps lipofuscin inclusions were significantly greater in hypoxaemic patients than in non-hypoxaemic patients (2.9 (0.2) v 2.0 (0.3) inclusions/fibre; p<0.05). Exercise induced a greater increase in muscle TBARs and oxidised proteins in hypoxaemic patients than in non-hypoxaemic patients (40.6 (9.1)% v 10.1 (5.8)% and 51.2 (11.9)% v 3.7 (12.2)%, respectively, both p = 0.01). Neutrophil levels were significantly higher in hypoxaemic patients than in non-hypoxaemic patients (53.1 (11.6) v 21.5 (11.2) counts per fibre × 10−3; p<0.05). Exercise did not alter muscle neutrophil levels in either group. Muscle TNF-α was not detected at baseline or after exercise. Conclusion: Chronic hypoxaemia was associated with lower quadriceps endurance time and worsened muscle oxidative stress at rest and after exercise. Increased muscle neutrophil levels could be a source of the increased baseline oxidative damage. The involvement of a muscle inflammatory process in the exercise induced oxidative stress of patients with COPD remains to be shown.

Skeletal muscle microbiopsy: a validation study of a minimally invasive technique

The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease (COPD) is of growing interest, but often requires biopsies, usually with the Bergström technique. The current study was designed to test the validity of a minimally invasive technique: the microbiopsy. In 17 patients with COPD and four normal subjects, two specimens of the vastus lateralis were taken percutaneously under local anaesthesia, one with a 16-gauge needle (microbiopsy) and the other with the Bergström needle. The enzymatic activity of citrate synthase (CS) and phosphofructokinase (PFK), and the myosin heavy chain (MyoHC) composition were measured for both techniques. The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy. The microbiopsy sample weight reached 55±17 mg. The two techniques showed excellent agreement for CS activity and MyoHC composition. The PFK activity did not differ statistically between the techniques, but the agreement was moderate. The agreement between both biopsy techniques was stable over time. The median (range) fibre number within the microbiopsy specimens was 144 (38–286). In conclusion, the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects, compared with the Bergström technique.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes. ATS/ERS statement highlighting research areas that will have the greatest impact on patient-centred outcomes in COPD http://ow.ly/LXW2J

Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study

Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7–11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125–203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.

Does systemic inflammation trigger local exercise-induced oxidative stress in COPD?

Inflammatory abnormalities may be involved in the inadequate basal oxidant/antioxidant balance and local exercise-induced oxidative stress in chronic obstructive pulmonary disease (COPD) patients. The time course of oxidative stress and inflammation was investigated in 10 COPD patients and seven healthy subjects before and after local dynamic quadriceps endurance exercise at 40% of maximal strength. Venous samples were collected before, immediately after and up to 48 h after exercise. At rest, levels of an oxidant released by stimulated phagocytes, the superoxide anion, were significantly higher in patients, as were plasma levels of C‐reactive protein, tumour necrosis factor‐α and interleukin‐6, inflammatory markers. An inverse relationship was found between baseline C‐reactive protein levels and endurance time in patients. Six hours after exercise, superoxide anion release and levels of protein oxidation products, an index of oxidative stress, increased similarly in both groups, whereas thiobarbituric acid reactive substance levels, another index of oxidative stress, increased significantly only in patients. Plasma nonenzymatic antioxidant and inflammatory cytokine levels were unchanged by the exercise protocol. The increased baseline systemic inflammation in chronic obstructive pulmonary disease patients could be related to disturbed oxidant/antioxidant balance, and, together, these may have triggered the exercise-induced oxidative stress. The absence, however, of local exercise-induced systemic inflammation suggests that additional mechanisms explain local exercise-induced oxidative stress.

An Official American Thoracic Society/European Respiratory Society Statement: Research questions in chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. METHODS Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified. RESULTS Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. CONCLUSIONS Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes. ATS/ERS statement: which types of research will have the greatest future impact on patient-centred outcomes in COPD? http://ow.ly/I54Hb

Skeletal muscle abnormalities in patients with COPD : contribution to exercise intolerance

Exercise intolerance in COPD patients appears to be in part because of skeletal muscle dysfunction. Studies using biopsy techniques and magnetic resonance spectroscopy have demonstrated changes in enzyme activities and metabolism that indicate reduced oxidative capacity in the peripheral muscles of these patients. Regarding the respiratory muscles, the biochemical characteristics have been studied in only a few works and the results seem to depend on the specific muscle group studied. Several factors, such as hypoxemia, nutritional status, pharmacological treatment, and deconditioning, may be responsible for these skeletal muscle abnormalities. This brief review describes the changes in peripheral and respiratory muscles in COPD patients based on data from the literature. The causes of these muscle abnormalities, their contribution to exercise intolerance, and the effects of training are then discussed. We conclude with suggested directions for future investigation using contemporary noninvasive technologies.