Specificity of Dyspnoea Relief With Inhaled Furosemide

This is a double-blind, placebo-controlled trial. 16 healthy volunteers will attend 4 sessions. After 2 practice sessions subjects will undergo 2 test days where they will be made to feel 'air hunger' (hypercapnia with constrained ventilation) before and after mist inhalations on one day and sense of breathing 'effort' (raised ventilation with external resistive load) before and after mist inhalations on the second test day. The mist will either be furosemide or a placebo (saline) mist.

The urge to urinate from systemic absorption from the lungs will be accounted for by a concomitant administration of intravenous furosemide when saline is inhaled.

Furosemide is a prescription drug which makes kidneys produce more urine. When administered by inhalation as an aerosol it has direct action in the lungs which sensitises slowly adapting stretch receptors which is believed to account for the relief of dyspnoea previously reported with inhaled furosemide.

Vagal afferents from the pulmonary stretch receptors are known to be involved in relief of air hunger but it is not known if they will also relieve the sense of breathing effort. Relief of breathlessness will be measured and compared between the two trial days to see if furosemide specifically relieves the 'air hunger' type of breathlessness and not the 'effort' type of breathlessness.

Inclusion criteria

• Healthy individuals

Exclusion criteria

• On any medication, including herbal medication (other than mild analgesics, vitamins and mineral supplements or, for females, oral contraceptives), whether prescribed or over-the-counter, in the two weeks prior to test sessions involving administration of furosemide or saline.
• Female participants who are pregnant, lactating or planning pregnancy over the course of trial
• A medical history of heart, kidney or liver disease/electrolyte disturbances/ immunosuppression/frequent fainting episodes/COPD/nasal polyps/Addison's/acute porphyria/significant prostatic symptoms/acute gout attack/life expectancy <6months or history of allergic reaction to furosemide and/or any of the other ingredients of furosemide or amiloride, sulfonamides or sulphonamide derivatives, such as sulfadiazine or co-trimoxazole
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Have participated in another research trial involving an investigational product in the past 4 weeks.