Skeletal muscle inflammation and nitric oxide in patients with COPD

de, María Montes; Torres, Sonia H.; Sanctis, Juan B. De; Mata, Abdón; Hernández, Noelina; Tálamo, Carlos

doi:10.1183/09031936.05.00107404

Cited by 108 publications

(83 citation statements)

References 35 publications

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“…However, it is also possible that the decline results from the development of more advanced systemic involvement of COPD [28]. This hypothesis is further supported by the observations of AGUSTI et al [29], who showed worsening apoptosis in muscle biopsies of patients with COPD, and by MONTES DE OCA et al [30] who described increased levels of markers of oxidative stress and infiltration by macrophages in patients with severe COPD compared with controls. In addition, worsening Charlson comorbidity scores over time in the present study suggest a possible role for increasing comorbidity as the population aged.…”

Section: Discussionsupporting

confidence: 74%

The 6-min walking distance: long-term follow up in patients with COPD

Casanova¹,

Côté²,

Marı́n³

et al. 2006

Eur Respir J

156

105

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The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter.The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored.At baseline, the median 6MWD was 380 m (range 160-600 m). It declined by 19% (16 m?yr -1 ) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30-50% predicted) and by 26% (15 m?yr -1 ) in patients with stage IV COPD (FEV1 ,30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values.In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.KEYWORDS: Chronic obstructive pulmonary disease, 6-min walking distance T he 6-min walking distance (6MWD) test has gained importance in the assessment of functional exercise capacity in patients with chronic obstructive pulmonary disease (COPD) [1,2] Introduced in 1976 as a 12-min walk test to measure the exercise capacity of patients with COPD, the abbreviated 6MWD has proved to be reliable, inexpensive, safe and easy to apply [7][8][9][10]. Furthermore, it correlates well with other important outcomes in COPD patients such as dyspnoea, airway obstruction and lung hyperinflation [11]. The test has been shown to be an important prognostic factor for outcome independent of the forced expiratory volume in one second (FEV1) [12]. The 6MWD is a submaximal excercise test, but it correlates well with the maximal cardiopulmonary exercise test [13][14][15], and appears to be better tolerated and more reflective of the activities of daily living than other walk tests [16,17].While there is plenty of data concerning the natural history of FEV1 over time, little information has been published regarding the temporal behaviour of the 6MWD. This is a significant omission, as the 6MWD test is frequently used to evaluate the long-term impact of interventions. Changes in 6MWD over time have been addressed in one published study [12], but it was limited to patients with severe COPD, the follow-up time was relatively short (1 yr) and the decline trend was established with only two measurements.As part of the large body mass index, degree of obstruction, dyspnoea and exercise capacity (BODE) cohort, the present authors have evaluated the 6MWD systematically as one of several variables included in the evaluation of pati...

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Section: Discussionsupporting

confidence: 74%

The 6-min walking distance: long-term follow up in patients with COPD

Casanova¹,

Côté²,

Marı́n³

et al. 2006

Eur Respir J

156

105

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“…In resting quadriceps muscles of patients with severe COPD, total glutathione concentrations are lower whereas the levels of HNE and lipofuscin (products of lipid peroxidation) are signifi cantly higher than those detected in control subjects (Engelen et al 2000a;Allaire et al 2002;Barreiro et al 2003). In addition, resting limb muscles of COPD patients have increased protein tyrosine nitration and elevated levels of iNOS protein, suggesting the development of nitrosative stress (Barreiro et al 2003;Montes de Oca et al 2005). With respect to exercise, patients with moderate to severe COPD have elevated ROS-induced DNA damage in peripheral blood mononuclear cells, plasma uric acid, blood oxidized glutathione and lipid peroxides levels at the end of whole body exercise indicating that these patients experience systemic oxidative stress, even during normal daily activity (Vina et al 1996;Heunks et al 1999;Mercken et al 2005).…”

Section: Oxidative and Nitrosative Stressmentioning

confidence: 97%

“…Few studies have as yet explored whether or not NO production and NOS expression are altered in skeletal muscles of COPD patients. Several studies have reported that the levels of nNOS and eNOS proteins in quadriceps of patients with severe and moderate COPD are similar or even lower than that those of control subjects (Barreiro et al 2003(Barreiro et al , 2008aMontes de Oca et al 2005). In comparison, others described induction of the iNOS isoform in quadriceps of patients with severe COPD patients, particularly those with low BMI ( .…”

Section: Nitric Oxide Synthasesmentioning

confidence: 99%

“…In comparison, others described induction of the iNOS isoform in quadriceps of patients with severe COPD patients, particularly those with low BMI ( . In addition, elevated protein tyrosine nitration in quadriceps muscles of COPD patients has been documented by many authors thereby confi rming an increase in peroxynitrite formation in these patients (Barreiro et al 2003;Agusti et al 2004;Montes de Oca et al 2005). It is worth noting that not all skeletal muscles of COPD patients show evidence of nitrosative stress and peroxynitrite formation.…”

Section: Nitric Oxide Synthasesmentioning

confidence: 99%

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Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

2010

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Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by infl ammation-induced airfl ow limitation and parenchymal destruction. In addition to pulmonary manifestations, patients with COPD develop systemic problems, including skeletal muscle and other organ-specifi c dysfunctions, nutritional abnormalities, weight loss, and adverse psychological responses. Patients with COPD often complain of dyspnea on exertion, reduced exercise capacity, and develop a progressive decline in lung function with increasing age. These symptoms have been attributed to increases in the work of breathing and in impairments in gas exchange that result from airfl ow limitation and dynamic hyperinfl ation. However, there is mounting evidence to suggest that skeletal muscle dysfunction, independent of lung function, contributes signifi cantly to reduced exercise capacity and poor quality of life in these patients. Limb and ventilatory skeletal muscle dysfunction in COPD patients has been attributed to a myriad of factors, including the presence of low grade systemic infl ammatory processes, nutritional depletion, corticosteroid medications, chronic inactivity, age, hypoxemia, smoking, oxidative and nitrosative stresses, protein degradation and changes in vascular density. This review briefl y summarizes the contribution of these factors to overall skeletal muscle dysfunction in patients with COPD, with particular attention paid to the latest advances in the fi eld. Keywords: skeletal muscles, chronic obstructive pulmonary disease, diaphragm, quadriceps, fatigue, disuse, atrophy, smoking, exercise It has long been recognized that COPD is a systemic disease in which several extrapulmonary manifestations, including cachexia and skeletal muscle dysfunction, contribute to morbidity and mortality. Functionally, skeletal muscle dysfunction in COPD patients is characterized by signifi cant reduction in muscle strength and endurance. It is structurally characterized by loss of muscle mass and cross-sectional area (muscle atrophy), fi ber type distribution (reduction in the proportion of oxidative fi bers and increases in the proportion of glycolytic fi bers), oxidative metabolic capacity (attenuation of mitochondrial enzyme activities and expression) and capillary distribution (signifi cant loss of capillary density). Although disuse and inactivity are important contributors to the pathogenesis of skeletal muscle dysfunction in COPD patients, several other systemic and local factors are also involved. These include systemic infl ammation, malnutrition, corticosteroid usage, hypoxemia, aging, smoking and local factors such as the production of reactive oxygen (ROS) and nitrogen species (RNS) and enhanced protein degradation inside muscle fi bers, a result of increased activities of the proteasomal and lysosomal pathways and activation of calpains and caspases. Evidence of skeletal muscle dysfunction in patients with COPDIt has been well established that skeletal muscle function (strength and endurance) and s...

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“…Impaired insulin sensitivity in skeletal muscle is a major feature of type 2 diabetes [12]. An increased amount of TNF-α protein in skeletal muscle has been found in patients with insulin resistance [13] and chronic obstructive pulmonary disease [14]. Regular exercise improves insulin sensitivity [15] and the amount of TNF-α protein is reduced by resistance exercise in frail elderly patients [16].…”

mentioning

confidence: 99%

Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

et al. 2007

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Aims/hypothesis Clear evidence exists that TNF-α inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-α in type 2 diabetes. Methods We obtained blood and biopsy samples from skeletal muscle and subcutaneous adipose tissue in patients with type 2 diabetes (n=96) and healthy controls matched for age, sex and BMI (n=103). Results Patients with type 2 diabetes had higher plasma levels of fasting insulin (p<0.0001) and glucose (p<0.0001) compared with controls, but there was no difference between groups with regard to fat mass. Plasma levels of TNF-α (p=0.0009) and soluble TNF receptor 2 (sTNFR2; p = 0.002) were elevated in diabetic patients. Insulin sensitivity was correlated with quartiles of plasma TNF-α after adjustment for age, sex, obesity, WHR, neutrophils,

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Skeletal muscle inflammation and nitric oxide in patients with COPD

Cited by 108 publications

References 35 publications

The 6-min walking distance: long-term follow up in patients with COPD

The 6-min walking distance: long-term follow up in patients with COPD

Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

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