Specificity of Dyspnoea Relief With Inhaled Furosemide

Study Overview
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Brief Summary
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This study evaluates the effect of inhaled furosemide on different types of breathlessness relief in healthy volunteers. Each volunteer inhaled mists of either furosemide or a control substance on 3 occasions per day on 2 separate days. On one day they performed one breathlessness test which creates an 'urge to breathe' known as air hunger (AH) and the other day they performed a breathlessness test which increases the sense of work/effort (WE) of breathing. The study is double blinded so neither the volunteer or the research knows which mist is being inhaled.

Detailed Description
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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.

Official Title
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Specificity of Dyspnoea Relief With Inhaled Furosemide

Conditions
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Dyspnea

Intervention / Treatment
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* Drug: Furosemide
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Air Hunger<br>Previous studies have shown that inhaled furosemide relieves 'air hunger'. Each volunteer has 3 mists per visit. The mists are either in the order of Furosemide-Saline-Furosemide or Saline-Furosemide-Saline. The furosemide mist is 40mg (10mg/ml) nebulised and the saline mist is 4ml nebulised. Induced air hunger (hypercapnia with constrained ventilation) is the active comparator and will be the type of breathlessness induced, before and after each mist inhalation on one day. . | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> * Other names: 0.9% sodium chloride;|
| Experimental: Work Effort<br>Induced sense of breathing effort (raised ventilation with external resistive load) is the 'experimental arm' and will be the type of breathlessness induced, before and after each mist inhalation on the other day. . | Drug: Furosemide<br> <br> * Other names: Lasix;Drug: Saline<br> <br> * Other names: 0.9% sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analogue scale for breathlessness type | The visual analogue scale (VAS) is from 0 (no breathlessness) to 100 (maximal breathlessness willing to tolerate). The VAS is measure every 15-20 seconds during each experimentally induced breathing test. Each breathing test is performed before and after each mist inhalation. Total of 6 breathing tests. The final minute of a 4 minute steady state breathing test is analysed. | 20minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Air hunger, Work/effort, Aerosolized, Hypercapnia, Resistive load, Nebulised