Introduction: Study of guinea pig airways has shown that vagal stimulation alters airway calibre, and so change in bronchial responsiveness, in response to a given dose of methacholine. We hypothesised that spinal neural outflow influences the sensitivity of airways to methacholine in humans. Patients with neuromodulators for various indications, offered the opportunity to test this physiological response.

Methods: Patients with spinal cord stimulators for chronic pain were recruited into the study; therapeutic stimulation is around 60Hz. Testing was conducted on two separate occasions, at the same time of day, within one week. Methacholine challenge testing was carried out as per standard protocol and oscillometric testing was conducted at baseline and after each dose. Spirometry was also performed, pre and post testing. Testing was terminated either once threshold changes in resistance had been reached, by patient choice, or if maximum dose was reached. Ethics was obtained for this study. Lower, and total, airways resistance for each dose was compared for each subject when on and off stimulation, using paired t-tests. In addition, ANOVA testing was conducted comparing spinal level of stimulation, and response to methacholine. Patients were grouped into cervical, thoracic and lumbar stimulation depending on vertebral level of electrode, on XRay

Results: Stimulation led to an alteration in the responsiveness of the airways to methacholine with patients having increased total and lower airways resistance, for a given methacholine dose, when stimulation was on. This did not correlate with clinical symptoms. In addition stimulation at different spinal levels had differing degree of effects on the change in airways resistance detected in response to methacholine challenge.

Conclusions: We conclude that reactivity of the airways is increased when the spinal cord is stimulated. This is a novel and unexpected finding and suggests there is active modulation of the airways by the spinal neuronal outflow. In addition the effects differed by level of stimulation suggesting a localised differentiation of modulation.

Patient Care: Understanding the effects that neuromodulation have on the autonomic system gives greater depth of appreciation for central neural control of physiological parameters. We have begun to characterise the effect that spinal cord outflow has on the reactivity of the airways. Respiratory disease is a major cause of worldwide morbidity and this research opens up avenues for future therapeutic interventions to be developed for novel targets

Learning Objectives: Stimulation of the spinal cord increases airway responsiveness to methacholine challenge, suggesting there is modulatory outflow.

References: Zhuang J, Bailet D, Curtis R, Xu F. High-Frequency stimulation of cervical vagi reduces airway response to methacholine. World J Respirol 2013; 3(2): 11-19