Effects of Respiratory Muscle Training on Physiological and Psychological Aspects of Dyspnea Perception and Exercise Tolerance in Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic health condition leading to increased disability, morbidity and mortality. COPD is a treatable and preventable disease but the significant health care costs related to the medical treatment of the condition constitute a global financial burden (1, 2). Dyspnea or breathlessness is the main symptom in many COPD patients and contributes to limitations in daily activities including exercise. Respiratory muscle weakness contributes to symptoms of dyspnea in patients with COPD (3-5). Due to dynamic hyperinflation COPD patients are forced to breathe at higher lung volumes during activities. The diaphragm (main inspiratory muscle) is adapted to chronic increases of resting lung volume (static hyperinflation) but not to the acute changes in lung volume during activities (dynamic hyperinflation) which puts it at a mechanical disadvantage. The increased elastic loading at higher lung volumes forces the inspiratory muscles to generate higher inspiratory pressures (i.e. perform more work for a given volume change) while the pressure generating capacity of the diaphragm and the other muscles of inspiration is reduced (because of muscle shortening). Simultaneously contraction velocity is increased when higher inspiratory flow rates are generated with increased ventilatory needs resulting in further functional weakening (6-11). During exercise the somatosensory cortex calibrates and interprets an appropriate muscular-mechanical response to the central respiratory motor drive. It has been shown that dyspnea varies directly with an awareness of the magnitude of central motor command output (12). When the load on the diaphragm is increased and force generating capacity is reduced during exercise induced dynamic hyperinflation an imbalance between drive and response occurs, which has been shown to intensify the sensation of breathlessness or dyspnea (13, 14). Improving inspiratory muscle strength could potentially reduce respiratory neural drive, perceived effort of breathing and dyspnea during exercise (10). Indeed, in previous studies significant improvements in inspiratory muscle function (strength and endurance) dyspnea and exercise capacity have been observed after inspiratory muscle training (IMT) (15, 16). Ventilatory muscle recruitment (VMR) in COPD patients is altered in comparison with healthy subjects. Due to both static and dynamic hyperinflation the inspiratory muscles of the ribcage are recruited more while the diaphragm contribution is reduced (17-19). Also at rest the motor unit recruitment of intercostal muscles, scalenes and diaphragm is higher in COPD patients compared to normal subjects, the neural drive to the sternomastoids is higher and for expiration the transversus abdominis is activated (20). These changes are all related to the mechanical disadvantage of the diaphragm. Potential changes of the VMR pattern in COPD patients in response to inspiratory muscle training have not yet been studied. Previous studies have mostly focused on diaphragmatic activity. It has been shown that during periods of increased respiratory muscle work, a so called 'metaboreflex' leads to sympathetically induced vasoconstriction of limb locomotor muscles (less blood and oxygen supply to active limbs muscle) resulting in locomotor muscle fatigue and reduced endurance performance (21). Previous studies applying both loading and unloading of respiratory muscles in COPD patients have shown effects of these procedures on limb blood flow (peripheral muscle oxygenation) (22, 23) and locomotor fatigue (24) during exercise. The effects of IMT on these mechanisms have however not yet been studied. Within this PhD project both physiological and psychological mechanisms of dyspnea reduction in response to inspiratory muscle training will be studied in COPD patients with pronounced inspiratory muscle weakness. The sensory aspects of dyspnea (intensity and quality) and affective perception of dyspnea (unpleasantness of the sensation for a given intensity) will be assessed and compared between patients who participated in either a sham-training or in an active IMT intervention. Also the changes in respiratory muscle recruitment patterns and changes of electromyogram of diaphragm and accessory inspiratory muscles (reflecting neural drive) will be compared between shame and IMT. The inter-relationships between the post-intervention changes in dyspnea (intensity and unpleasantness) and changes in relevant measures of respiratory muscle performance will be explored as well as the activation/connectivity patterns of regions of the central nervous system in response to a standardized dyspnea provoking stimulus (EEG measurements will be conducted to evaluate the affective perception). Moreover an evaluation of the impact of IMT on blood flow distribution and locomotor muscle function during exercise will be performed. A better understanding of the underlying mechanisms of dyspnea in response to inspiratory muscle training will provide better insights on the potential of this intervention to improve, exercise performance, participation in physical activities, and quality of life in patients with COPD 1. Halpin DM, Miravitlles M. Chronic obstructive pulmonary disease: the disease and its burden to society. 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Publication year:2019

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