Diaphragm Injury in Individuals with Airflow Obstruction

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition.Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin-proteasome system, redoxsignalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls.Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2 14k , atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced.In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.

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“…The area fraction of normal and abnormal muscle was also evaluated following previously published methodologies [35].…”

Section: Detection Of Superoxide Anion Within Myonucleimentioning

confidence: 99%

Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

et al. 2012

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“…In a cross-sectional study, MACGOWAN et al [88] recently showed that the degree of airflow obstruction (i.e. per cent predicted FEV1) is inversely related to the abnormal muscle and directly related to the area fraction of normal muscle.…”

Section: Loading and Respiratory Muscle Injurymentioning

confidence: 99%

Structure and function of the respiratory muscles in patients with COPD: impairment or adaptation?: Fig. 1.—

Orozco-Levi¹

2003

Eur Respir J

131

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Structure and function of the respiratory muscles in patients with COPD: impairment or adaptation?. M. Orozco-Levi. #ERS Journals Ltd 2003. ABSTRACT: Respiratory muscles are essential to alveolar ventilation. These muscles work against increased mechanical loads due to airflow limitation and geometrical changes of the thorax derived from pulmonary hyperinflation. Respiratory muscle fibres show several degrees of impairment in cellular and subcellular structures which, in many cases, are proportional to the severity of the disease and accompanying conditions (ageing, deconditioning, starvation, comorbidity). This structural impairment translates, from the functional point of view, to a loss of strength (capacity to generate tension) and an increased susceptibility to failure in the face of a particular load (early onset of fatigue).On the other hand, there is accumulating evidence that the diaphragm and other respiratory muscles are also able to express adaptive changes in response to the chronic mechanical load imposed by the disease. In most cases, impairment and adaptation of the respiratory muscles reaches a balance that permits enough ventilation for patients9 survival. However, this balance can be altered for additional increments of the mechanical or metabolic load on the muscles (e.g. abdominal or thoracic surgeries, pneumonia, pulmonary embolism, etc.). Moreover, loss of balance is not always associated with extreme situations. Many patients develop ventilatory failure and require hospital admission even if the cause of the exacerbation is less dramatic (bronchial infections, pain of any nature, electrolyte disturbances, etc.).Although the physiopathology of chronic obstructive pulmonary disease exacerbations is multifactorial, the above-mentioned fragility suggests the existence of a "fragile balance" between respiratory muscle overload and respiratory muscle adaptations. Assessment of respiratory muscle function through specific tests evaluating the strength and endurance could offer valuable information about this particular susceptibility to muscle imbalance. Identification of patients possessing a fragile respiratory muscle balance could have important implications for the application of specific strategies such as respiratory muscle training, nutrition, or anabolic treatment. Dyspnoea, decrease of exercise capacity and impairment of quality of life are common in patients with chronic obstructive pulmonary disease (COPD). Recently, it has been demonstrated that the decrease in exercise capacity is associated with mortality of these patients. Depending on the individual, the imbalance between the functional capacity of the respiratory muscles and the load they are chronically facing plays an important role in the genesis of dyspnoea [1] and hypercapnia [2,3]. It has also been described that respiratory muscle dysfunction could be an important determinant of increased use of health resources and survival in hospitalised patients with severe COPD [4][5][6][7][8][9].Respiratory muscles are skeletal musc...

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“…Labelled intramyofibre and interstitial leukocytes were counted using a rectangular unbiased counting frame superimposed on the image as described previously [16]. Labelled cells inside the blood vessels were excluded.…”

Section: Histological and Immunohistochemical Studiesmentioning

confidence: 99%

Granulocytosis and increased adhesion molecules after resistive loading of the diaphragm

Wang¹

2005

Eur Respir J

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Upregulation of endothelial cell adhesion molecules, followed by an influx of granulocytes and macrophages, can contribute to exertion-induced skeletal muscle injury. The purpose of this study was to quantify circulating leukocyte subsets, diaphragm injury and infiltrating leukocyte subsets, and surface expression of vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 in the diaphragm after inspiratory resistive loading (IRL).Eight New Zealand white rabbits underwent 1.5 h of IRL and seven control rabbits underwent a sham procedure. Blood samples, taken at baseline and 2, 6, 12, 24, 48 and 72 h after the onset of IRL or sham, showed that band cell counts had increased at 6 h post-IRL. Point counting of haematoxylin and eosin-stained cross-sections, sampled at 72 h post-IRL, showed greater injury in diaphragms from IRL rabbits compared with controls. Immunohistochemical processing showed increased expression of ICAM-1 and VCAM-1, and higher granulocyte and macrophage counts in IRL diaphragms than control diaphragms. Macrophages were the predominant inflammatory cells.Increased intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, and infiltration of granulocytes and macrophages may contribute to inspiratory resistive loadinginduced diaphragm injury.

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Diaphragm Injury in Individuals with Airflow Obstruction

Cited by 49 publications

References 26 publications

Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

Structure and function of the respiratory muscles in patients with COPD: impairment or adaptation?: Fig. 1.—

Granulocytosis and increased adhesion molecules after resistive loading of the diaphragm

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