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.

Quadriceps strength relates to exercise capacity and prognosis in chronic obstructive pulmonary disease (COPD). We wanted to quantify the prevalence of quadriceps weakness in COPD and hypothesised that it would not be restricted to patients with severe airflow obstruction or dyspnoea.Predicted quadriceps strength was calculated using a regression equation (incorporating age, sex, height and fat-free mass), based on measurements from 212 healthy subjects. The prevalence of weakness (defined as observed values 1.645 standardised residuals below predicted) was related to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and Medical Research Council (MRC) dyspnoea score in two cohorts of stable COPD outpatients recruited from the UK (n = 240) and the Netherlands (n = 351).32% and 33% of UK and Dutch COPD patients had quadriceps weakness. A significant proportion of patients in GOLD stages 1 and 2, or with an MRC dyspnoea score of 1 or 2, had quadriceps weakness (28 and 26%, respectively). These values rose to 38% in GOLD stage 4, and 43% in patients with an MRC Score of 4 or 5.Quadriceps weakness was demonstrable in one-third of COPD patients attending hospital respiratory outpatient services. Quadriceps weakness exists in the absence of severe airflow obstruction or breathlessness.

Nutrition and metabolism have been the topic of extensive scientific research in chronic obstructive pulmonary disease (COPD) but clinical awareness of the impact dietary habits, nutritional status and nutritional interventions may have on COPD incidence, progression and outcome is limited. A multidisciplinary Task Force was created by the European Respiratory Society to deliver a summary of the evidence and description of current practice in nutritional assessment and therapy in COPD, and to provide directions for future research. Task Force members conducted focused reviews of the literature on relevant topics, advised by a methodologist. It is well established that nutritional status, and in particular abnormal body composition, is an important independent determinant of COPD outcome. The Task Force identified different metabolic phenotypes of COPD as a basis for nutritional risk profile assessment that is useful in clinical trial design and patient counselling. Nutritional intervention is probably effective in undernourished patients and probably most when combined with an exercise programme. Providing evidence of cost-effectiveness of nutritional intervention is required to support reimbursement and thus increase access to nutritional intervention. Overall, the evidence indicates that a well-balanced diet is beneficial to all COPD patients, not only for its potential pulmonary benefits, but also for its proven benefits in metabolic and cardiovascular risk.

Low exercise tolerance has a large influence on health status in chronic obstructive pulmonary disease and chronic heart failure. In addition to primary organ dysfunction, impaired skeletal muscle performance is a strong predictor of low exercise capacity. There are striking similarities between both disorders with respect to the muscular alterations underlying the impairment. However, different alterations occur in different muscle types. Histologic and metabolic data show that peripheral muscles undergo a shift from oxidative to glycolytic energy metabolism, whereas the opposite is observed in the diaphragm. These findings are in line with the notion that peripheral and diaphragm muscle are limited mainly by endurance and strength capacity, respectively. In both diseases, muscular impairment is multifactorially determined; hypoxia, oxidative stress, disuse, medication, nutritional depletion, and systemic inflammation may contribute to the observed muscle abnormalities and each factor has its own potential for innovative treatment approaches.

Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.

Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease (COPD) which is associated with intrinsic muscular abnormalities. One of the most consistently reported alterations is a shift from fibre type I to II in the vastus lateralis of these patients. Surprisingly, the relationship between this shift and the severity and phenotype of COPD remains unclear. A study was conducted to determine whether vastus lateralis muscle fibre type proportions are associated with COPD disease severity and to provide reference values for the proportions of fibre types in the vastus lateralis in COPD. A systematic review and a meta-analysis were conducted in which muscle fibre type data and markers of disease severity were collected from the literature. The forced expiratory volume in 1 s (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC) and body mass index were positively associated with the proportion of type I fibres in COPD. A proportion of 51% for vastus lateralis fibre type I and 13% for fibre type IIX were calculated from the combined data as normal values for patients with typical GOLD stage 3-4 COPD aged 60-70 years. Based on these reference values, a proportion of fibre type I 29% were defined as pathologically abnormal. This review sheds new light on the relationship between skeletal muscle abnormalities and important hallmarks of the disease in severe COPD, and identifies absence of data in GOLD stages 1-2. This review also provides reference values on fibre type composition for diagnostic purposes in COPD.