Neurophysiology of Cough Reflex Hypersensitivity

Pilot Study Investigating Central Sensitisation of the Cough Reflex in Subjects With Chronic Cough and Healthy Volunteers

Central sensitisation is an increase in the excitability of nerves within the central nervous system, which can lead to heightened sensitivity to certain stimuli. This process is involved in some chronic pain conditions e.g. migraines and non-cardiac chest pain. Recent work by our group suggests central sensitisation may be an important mechanism leading to chronic cough.

The main questions in this study include:

1. Can the investigators induce temporary central sensitisation of the cough reflex in healthy volunteers for testing of new medications?
2. Can the investigators demonstrate exaggerated sensitisation in patients with chronic cough (indicating these patients are already centrally sensitised)?

In animal studies, acid infusion into the gullet (oesophagus) is able to induce central sensitisation of the cough reflex. Acid infusion into the oesophagus has also been shown to induce central sensitisation in human healthy volunteers, increasing the sensitivity to pain on the front of the chest but this study did not test the the cough reflex. Using human participants, the investigators plan to test whether acid infusion into the oesophagus increases the sensitivity of the cough reflex in healthy volunteers and also patients complaining of chronic cough.

Inclusion Criteria:

Healthy volunteers inclusion:

• Over 18 years
• Measurable cough reflex sensitivity - required as is the primary end-point
• No current or past history of chronic cough or chronic respiratory disease

Chronic Cough Patients inclusion:

• Over 18 years
• Chronic persistent cough (> 8 weeks) despite investigation and/or treatment trials for cough variant asthma/post-nasal drip and gastro-oesophageal reflux
• Normal chest radiograph - primary respiratory cause for cough excluded
• Normal lung function - primary respiratory cause for cough excluded Measurable cough reflex sensitivity - required as primary end-point

Exclusion Criteria:

• Recent upper respiratory tract infection (<4 weeks) - this can lead to increased sensitivity of the cough reflex which resolves as the infection settles
• Pregnancy/breast-feeding - unknown effects of oesophageal acid infusion
• Current smokers or ex-smokers with < 6 month abstinence or history > 20 pack years - smoking can alter the sensitivity of the cough reflex
• Opiate or ACE inhibitor use or centrally acting medication - can alter the cough reflex sensitivity
• Symptomatic gastro-oesophageal reflux, post-nasal drip or asthma (chronic cough cohort may have been treated for these in the past but cough did not resolve) - these conditions are known to cause cough and alter cough reflex sensitivity
• Significant ongoing chronic respiratory/cardiovascular/gastro-intestinal/haematological/ neurological/psychiatric illness. We are aiming to recruit healthy volunteers and chronic cough patients who are otherwise healthy