Sex differences in COPD-related quadriceps muscle dysfunction and fibre abnormalities

In chronic obstructive pulmonary disease (COPD), lower limb dysfunction is associated with reduced exercise capacity, increased hospitalizations and mortality. We investigated sex differences in the prevalence of quadriceps dysfunction and fibre abnormalities in a large COPD cohort, controlling for the normal sex differences in health. We compared existing data from 76 male and 38 female COPD patients where each variable was expressed as a function of gender-specific normal values (obtained from 16 male and 14 female controls). Female COPD patients had lower quadriceps muscle strength and peak workload on a maximal incremental cycle ergometry protocol compared to male patients. Female patients had a smaller type II fibre cross-sectional area (CSA) compared to male patients, suggesting a greater female preponderance to fibre atrophy, although this result was largely driven by a few male patients with a large type II fibre CSA. Female patients had significantly higher concentrations of a number of plasma pro-inflammatory cytokines including tumour necrosis factor alpha and interleukin 8 (IL8), but not lower levels of physical activity or arterial oxygenation, compared to males. Our data confirm results from a previous small study and suggest that female COPD patients have a greater prevalence of muscle wasting and weakness. Larger studies investigating sex differences in COPD-related muscle atrophy and weakness are needed, as the results will have implications for monitoring in clinical practice and for design of clinical trials evaluating novel muscle anabolic agents.

[1]  E. Barreiro,et al.  Sex differences in function and structure of the quadriceps muscle in chronic obstructive pulmonary disease patients , 2017, Chronic respiratory disease.

[2]  T. Jorgensen,et al.  Suppressive effects of androgens on the immune system. , 2015, Cellular immunology.

[3]  F. Maltais,et al.  Vastus lateralis fiber shift is an independent predictor of mortality in chronic obstructive pulmonary disease. , 2014, American journal of respiratory and critical care medicine.

[4]  A. Agustí,et al.  Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect , 2014, PloS one.

[5]  M. Polkey,et al.  Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine? , 2013, Muscle & nerve.

[6]  M. Velders,et al.  How Sex Hormones Promote Skeletal Muscle Regeneration , 2013, Sports Medicine.

[7]  Virginia M Miller,et al.  Sex differences and sex steroids in lung health and disease. , 2012, Endocrine reviews.

[8]  D. Sin,et al.  The role of female hormones on lung function in chronic lung diseases , 2011, BMC women's health.

[9]  C. Iribarren,et al.  Respiratory and Skeletal Muscle Strength in Chronic Obstructive Pulmonary Disease: IMPACT ON EXERCISE CAPACITY AND LOWER EXTREMITY FUNCTION , 2011, Journal of cardiopulmonary rehabilitation and prevention.

[10]  E. Volpi,et al.  Protein metabolism in women and men: similarities and disparities , 2011, Current opinion in clinical nutrition and metabolic care.

[11]  M. Polkey,et al.  The prevalence of quadriceps weakness in COPD and the relationship with disease severity , 2009, European Respiratory Journal.

[12]  J. Soriano,et al.  COPD as a Systemic Disease , 2008, COPD.

[13]  M. Polkey,et al.  A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans. , 2007, Journal of applied physiology.

[14]  Huating Wang,et al.  NF-κB Regulation of YY1 Inhibits Skeletal Myogenesis through Transcriptional Silencing of Myofibrillar Genes , 2007, Molecular and Cellular Biology.

[15]  R. Porcher,et al.  Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease , 2006, Thorax.

[16]  G. Manier,et al.  Peak anaerobic power in patients with COPD: gender related differences , 2006, European Journal of Applied Physiology.

[17]  Thierry Troosters,et al.  Activity monitoring for assessment of physical activities in daily life in patients with chronic obstructive pulmonary disease. , 2005, Archives of physical medicine and rehabilitation.

[18]  J. Hankinson,et al.  Standardisation of the single-breath determination of carbon monoxide uptake in the lung , 2005, European Respiratory Journal.

[19]  G. Viegi,et al.  Standardisation of the measurement of lung volumes , 2005, European Respiratory Journal.

[20]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[21]  Susan C Kandarian,et al.  Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. , 2004, The Journal of clinical investigation.

[22]  M. Polkey,et al.  Acute effect of oral steroids on muscle function in chronic obstructive pulmonary disease , 2004, European Respiratory Journal.

[23]  S. Kandarian,et al.  Disruption of either the Nfkb 1 or the Bcl 3 gene inhibits skeletal muscle atrophy , 2004 .

[24]  Y. Lacasse,et al.  Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. , 2002, American journal of respiratory and critical care medicine.

[25]  Sally J. Singh,et al.  Bedside methods versus dual energy X‐ray absorptiometry for body composition measurement in COPD , 2002, European Respiratory Journal.

[26]  ATS Statement , 2002 .

[27]  ATS statement: guidelines for the six-minute walk test. , 2002, American journal of respiratory and critical care medicine.

[28]  D J Glass,et al.  Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy , 2001, Science.

[29]  D. Hostler,et al.  Fiber Type Composition of the Vastus Lateralis Muscle of Young Men and Women , 2000 .

[30]  D L Sherrill,et al.  Reference equations for the six-minute walk in healthy adults. , 1998, American journal of respiratory and critical care medicine.

[31]  E. Wouters,et al.  Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. , 1993, The American review of respiratory disease.

[32]  S. Heymsfield,et al.  Height-normalized indices of the body's fat-free mass and fat mass: potentially useful indicators of nutritional status. , 1990, The American journal of clinical nutrition.

[33]  J. E. Hansen,et al.  Predicted values for clinical exercise testing. , 2015, The American review of respiratory disease.

[34]  D. Jones,et al.  Human skeletal muscle function: description of tests and normal values. , 1977, Clinical science and molecular medicine.

[35]  J. Bergstrom Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. , 1975, Scandinavian journal of clinical and laboratory investigation.