Ayaka Ando, Stuart B. Mazzone, Michael J. Farrell
European Respiratory Journal 2019 54: 1900362; DOI: 10.1183/13993003.00362-2019
Cough is important for airway defence, and studies in healthy animals and humans have revealed multiple brain networks intimately involved in the perception of airway irritation, cough induction and cough suppression. Changes in cough sensitivity and/or the ability to suppress cough accompany pulmonary pathologies, suggesting a level of plasticity is possible in these central neural circuits. However, little is known about how persistent inputs from the lung might modify the brain processes regulating cough.
In the present study, we used human functional brain imaging to investigate the central neural responses that accompany an altered cough sensitivity in cigarette smokers.
In nonsmokers, inhalation of the airway irritant capsaicin induced a transient urge-to-cough associated with the activation of a distributed brain network that included sensory, prefrontal and motor cortical regions. Cigarette smokers demonstrated significantly higher thresholds for capsaicin-induced urge-to-cough, consistent with a reduced sensitivity to airway irritation. Intriguingly, this was accompanied by increased activation in brain regions known to be involved in both cough sensory processing (primary sensorimotor cortex) and cough suppression (dorsolateral prefrontal cortex and the midbrain nucleus cuneiformis). Activations in the prefrontal cortex were highest among participants with the least severe smoking behaviour, whereas those in the midbrain correlated with more severe smoking behaviour.
These outcomes suggest that smoking-induced sensitisation of central cough neural circuits is offset by concurrently enhanced central suppression. Furthermore, central suppression mechanisms may evolve with the severity of smoke exposure, changing from initial prefrontal inhibition to more primitive midbrain processes as exposure increases.
Smokers are less sensitive to inhaled cough-evoking stimuli due to increased activity in brain circuits that inhibit coughing. Smoking history influences the nature of the inhibitory process engaged to reduce sensitivity to cough stimuli.
This article has supplementary material available from erj.ersjournals.com
Support statement: This research was supported by grants to S.B. Mazzone and M.J. Farrell from the National Health and Medical Research Council (NHMRC) of Australia (grant 1078943). Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: A. Ando has nothing to disclose.
Conflict of interest: S.B. Mazzone reports grants from The University of Melbourne (NHMRC grant 1078943), during the conduct of the study; grants and personal fees from Merck Sharpe & Dohme, outside the submitted work.
Conflict of interest: M.J. Farrell reports grants from The University of Melbourne (NHMRC grant 1078943), during the conduct of the study.