Diaphragm Muscle Fiber Dysfunction in Chronic Obstructive Pulmonary Disease

Abstract

Inspiratory muscle weakness in patients with chronic obstructive pulmonary disease (COPD) is of major clinical relevance; maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered of pathologic nature. Although the fiber-type shift toward oxidative type I fibers in COPD diaphragm is regarded as beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single-fiber level is associated with loss of myosin content. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. The current Pulmonary Perspective postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force-generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients do not appear to be limited in their daily-life activities. Therefore, investigating in vivo diaphragm function in mild to moderate COPD should be the focus of future research. Treatment of diaphragm dysfunction in COPD is complex because its etiology is unclear, but recent findings show promise for the use of proteasome inhibitors in syndromes associated with muscle wasting, such as the diaphragm in COPD.

Oxidised proteins and superoxide anion production in the diaphragm of severe COPD patients

“…Importantly, our observations were consistent with previous reports, where in vivo respiratory muscle and diaphragm strength were also shown to be compromised [14,21,22]. In keeping with this, it has recently been proposed [23] that in severe COPD, several molecular mechanisms contribute to the aetiology of this respiratory muscle dysfunction, such as myosin loss [10,11], sarcomeric injury [24], oxidative stress [14] and alterations in cross-bridge cycling kinetics [8], resulting in reduced diaphragm isometric force. This raises serious questions concerning whether the adaptive mechanisms encountered in the diaphragms of severe COPD patients [4][5][6][7][8] are sufficient to make this muscle more efficient, since impaired contractile properties of the diaphragm muscle fibres have been clearly demonstrated [9][10][11].…”

Depression, anxiety and chronic pain in patients with chronic obstructive pulmonary disease: the influence of breath

“…The contractile force is decreased, with electrical and metabolic alterations. The muscle thickness is increased, especially on the left side, with decreased mechanical excursion, probably due to fibers' shortening [5,6]. There is a decrease of anaerobic type fibers (type II) and an increase in aerobic fibers (type I); this process progressively increases with the pathology worsening [6].…”

Effects of Inspiratory Muscle Training and Calisthenics-and-Breathing Exercises in COPD With and Without Respiratory Muscle Weakness

“…5 This occurs due to changes in the rib cage geometry caused by lung hyperinflation, which alters the length-tension curve of the diaphragm muscle. It also occurs due to systemic factors and structural changes in those muscles, 6,7 since strength mainly depends on muscle mass, and endurance is related to muscle fiber aerobic properties. 5 In the literature, the forms of therapeutic approach to respiratory muscles are inspiratory muscle training, 8 which uses overload for such training, and calisthenics-andbreathing exercises, which are characterized by breathing exercises and stretching of respiratory muscles and/or by exercises involving the trunk and upper limbs to improve mobility of the rib cage muscles.…”