Chest
Opinions and HypothesesNeurohumoral Activation as a Link to Systemic Manifestations of Chronic Lung Disease
Section snippets
Peripheral Sympathetic Activation
Using microneurography of the peroneal nerve, direct evidence of marked peripheral sympathetic activation in patients with COPD and hypoxemia has recently been obtained.6 As compared with age- and sex-matched healthy control subjects, muscle sympathetic nerve activity was twice as high in the patients as compared to the control subjects. These results could not be explained by concomitant medication.6
Cardiac Sympathetic Activation
Volterrani and colleagues7 were the first to study heart rate variability in the time domain
METHODOLOGIC AND HISTORICAL NOTES
The importance of neurohumoral activation in COPD is not well recognized and is relatively neglected from an investigative perspective. Initially, the altered heart rate response in COPD patients to various maneuvers was explained by autonomic polyneuropathy.11 Stein et al10 were among the first to interpret altered heart rate variability in their patients with obstructive lung disease as evidence of sympathetic activation. That the concept of neurohumoral activation in COPD has not been
POSSIBLE MECHANISMS OF NEUROHUMORAL ACTIVATION IN COPD
Dyspnea, respiratory motor drive, and autonomic control are anatomically and functionally tightly coupled in the brainstem. Specifically the perception of respiratory discomfort is represented in the sensorimotor integration area of the limbic system that governs autonomic control,28 and central respiratory motor drive is linked with central sympathetic outflow in the brainstem.29 These central interactions speak to the construct that dyspnea and increased respiratory drive in COPD may be
CONSEQUENCES OF NEUROHUMORAL ACTIVATION: PRECEDENTS FROM CHRONIC HEART FAILURE AND OTHER DISEASES CHARACTERIZED BY NEUROHUMORAL ACTIVATION
In patients with chronic heart failure, sympathetic overactivity plays a central role in disease progression and poor prognostic outcomes. Sympathetic activation is associated with increased breathing frequency, increased dead space ventilation and exertional dyspnea,46, 47 impaired endothelial function with decreased exercise-induced vasodilatation in skeletal muscle, a decrease in the number of type 1 (slow, endurance) muscle fibers, cardiomyocyte injury and apoptosis, and catabolic/anabolic
POTENTIAL IMPLICATIONS OF NEUROHUMORAL ACTIVATION IN COPD
Symptoms such as shortness of breath and fatigue are remarkably similar in chronic heart failure and COPD patients.52 The undesired accompaniments of neurohumoral activation described in heart failure may also be relevant to the shortness of breath, fatigue, cachexia, and other stigmata that characterize the pathophysiology of COPD.52
The proposed concept does not replace well-established concepts of disease progression in COPD, such as airway inflammation due to inhaled noxious agents, lung
CONCLUSION
We have presented evidence supporting neurohumoral activation in patients with COPD. By precedents derived from chronic heart failure and other diseases characterized by neurohumoral activation, we propose that the well-established negative consequences of neurohumoral activation, namely inflammation, cachexia, effects on ventilation, and skeletal muscle dysfunction, give rise to a self-perpetuating cycle that contributes to the pathogenesis of COPD, which involves respiratory muscle
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