S. Andreas asks two questions about dysfunction of the autonomic nervous system in chronic obstructive pulmonary disease (COPD). Does it occur? And if it does, why? To clarify our response, we add a third question: what are the clinical implications of autonomic dysfunction in COPD?
Regarding the question whether autonomic dysfunction occurs in COPD, there is accumulating evidence for sympathetic activation and sympathovagal imbalance in COPD 1, 2. There is also growing support for the presence of sympathetic 3, 4 and parasympathetic neuropathy 5 in COPD.
Why does sympathetic activation occur 1, 2? Potential mechanisms include activation of the limbic system by the perception of respiratory discomfort, muscle metaboreflexes and altered lung inflation reflexes 1, 2, 6. Another possible mechanism is right atrial distension 6.
Why does autonomic neuropathy occur? In the most severe cases of COPD, we agree with S. Andreas that autonomic neuropathy might be caused by intraneural hypoxaemia 5. We also agree that it is difficult to postulate a mechanistic role of hypoxaemia in the development of autonomic imbalance in patients who are normoxic 1, 3, unless decreased oxygenation during exercise and sleep 2 are sufficient to cause critical levels of intraneural hypoxaemia. If not hypoxaemia, what other factors could cause autonomic neuropathy? In patients with cardiac disease 7, type 1 diabetes mellitus 8 and cirrhosis-hepatic encephalopathy 9, a link between low-grade inflammation and autonomic neuropathy has been proposed. These observations raise the possibility that low-grade inflammation 10 could be linked to autonomic neuropathy in COPD.
What are the implications of autonomic dysfunction in COPD? Parasympathetic neuropathy can increase vasopressin and thus increase tubular reabsorption of solute-free water 10. Sympathetic neuropathy could explain why hypercapnia can cause a (direct) decrease in peripheral vascular resistance rather than an (indirect) increase secondary to sympathetic stimulation 10. Autonomic dysfunction may thus contribute to the fluid retention seen in patients with COPD and associated with a poor prognosis 10. In addition, heightened sympathetic activity, through the stimulation of the renin–angiotensin–aldosterone system, can participate in sodium reabsorption 11. Heightened sympathetic activity might also contribute to dyspnoea, exercise intolerance and increased cardiovascular morbidity and mortality 2. Autonomic neuropathy has been suggested as an independent risk factor for sudden cardiac death in diabetic patients 12. Whether the same is true for patients with COPD is unknown. Should attempts to modulate autonomic tone be a goal of therapy in COPD? The current understanding of autonomic dysfunction is not sufficient to formulate any recommendation.
Statement of interest
None declared.
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