Lack of patients

The treatment we are studying is Transcranial Magnetic Stimulation (TMS). In TMS, an electromagnetic pulse is passed into the brain through a coil placed on the head. Previous studies have shown TMS to be capable of altering brain activity in specific areas; for example it has been used to improve mood in clinical depression. In this study we will assess if, by targeting TMS to the brain area responsible for feeling breathless, participants' breathlessness will be improved

This protocol describes an exploratory crossover pilot study to assess whether targeted repetitive pulse Transcranial Magnetic Stimulation (TMS) i.e. targeted at the anterior cingulate cortex (ACC), affords relief of 'air hunger' in patients with breathlessness refractory to maximal medical therapy, compared to 'control' TMS directed at a remote site independent of the area of interest (within the lateral right parietal region of the brain).

12 right-handed patients suffering from refractory dyspnoea will receive pulses of targeted TMS or control TMS (crossover design), in a random order. The order will be random and use a minimisation procedure for baseline dyspnoea severity and sex. Repetitive targeted TMS (or control) pulses at 110% motor threshold at a frequency of 1Hz will be given for a 15 minute period1.

On a second, later, day the same subjects will perform the same protocol after receiving inhaled menthol or control (normal, non odorous air), in random order.

Outcomes will be assessed during the 10 minutes after targeted TMS/control TMS during which post stimulation inhibition of neural activity is expected.

Inclusion Criteria:

1. Refractory dyspnoea (persisting sensation of air hunger despite optimisation of medical treatment)
2. Histocytologically proven thoracic malignancy
3. Written informed consent

Exclusion Criteria:

1. Age <18 years
2. Left-handed
3. Structural brain disease (including cerebral metastasis)
4. Personal or family history of seizures
5. Implantable metallic objects e.g. a pacemaker, or other contraindication to transcranial magnetic stimulation
6. Pregnant or breast feeding
7. Previous electroconvulsive therapy (ECT)
8. Poor mobility
9. Visual impairment
10. Lack of social support / home to go to after the study treatment
11. Alcohol dependency
12. PaCO2 >6kPa at rest
13. Inability to provide informed consent

Patients attending out-patient clinic