Vagal Nerve Stimulation Assessed by the Diving Reflex: An Investigation Into Mechanisms of Asthma Death

Study Overview
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Brief Summary
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The investigators' hypothesis is that dysregulation of autonomic function, as revealed during a simulated dive reflex, may result in an attenuation of the heart rate response to a greater degree in asthmatics who collapse during exacerbations of asthma than that seen in healthy individuals and in asthmatics without a history of syncope. The investigators will test this by assessing autonomic function through a dive reflex protocol.

Detailed Description
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Tests of autonomic function are notoriously difficult to evaluate. Here the investigators required a well validated test of the dynamic cardiovascular response to an abrupt stimulus and considered the diving reflex the most reliable and practical. In man, the diving reflex acts as a vestigial reflex aimed at conserving oxygen storage during apnoeic facial immersion. Facial immersion activates a vagally-induced bradycardia and a sympathetically activated alpha-adrenergic peripheral vasoconstriction and hypertension. There are two triggers of the diving reflex, facial immersion in water and breath hold, both of which can impact on heart rate attenuation. Facial immersion can be further delineated into exposure to cold, wetness and pressure.

Official Title
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Vagal Nerve Stimulation Assessed by the Diving Reflex: An Investigation Into Mechanisms of Asthma Death

Conditions
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Asthma, Syncope

Intervention / Treatment
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* Procedure: Simulated dive reflex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Syncopal Asthmatics: Asthmatic patients with a history of syncope during asthma exacerbations Normal Asthmatics: Asthmatic patients on BTS Step 3 treatment (LABA/ICS) with no history of syncope during exacerbations Normal volunteers: no history of airways disease or syncope Exclusion Criteria: • Subjects who are pregnant, or have pacemakers in situ are excluded from this study. Subjects with significant cardiovascular disease are excluded from this study. Those who are non-English speakers and special groups (i.e. mentally ill, children under 16 years of age, and those suffering from dementia) will be excluded. No test will be performed on any subject during an acute worsening of asthma or upper airway infection. If the subject has had an upper airway infection in the last three weeks. Another appointment should be made unless the subject is unwilling to come back, in which case testing should continue. The number of days elapsed since the end of the airway infection should be recorded. If the subject smokes: citric acid or capsaicin challenges must be performed at least one hour after the last cigarette has been smoked. Subjects taking beta-blockers and calcium antagonists will be excluded from this study. No beta agonists should be taken within 6 hours of starting this study. If the subject has taken any over the counter (OTC) cough mixture within the last twelve hours: If the subject is willing to come back another time for challenge testing, another appointment should be made. If the subject is unwilling to return another time, testing should proceed and the medication used recorded. If the subject has had any food or drink products containing caffeine or menthol within the last hour. If the subject is unwilling to wait for 1 hour before starting the test, the subject should return another time. If the subject is unwilling to return another time, testing should proceed and the medication used recorded. If the participant is currently involved in research, or within 3 months of participation in any type of research, they will be excluded from this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Syncopal Asthmatic<br>All subject undergo simulated dive reflex, with 30s facial immersion and continuous HR and BP monitoring with Nexfin over a period of 6 minutes. | Procedure: Simulated dive reflex<br>* All subjects undergo simulated dive reflex, with 30s facial immersion and continuous HR and BP monitoring with Nexfin over a period of 6 minutes.<br>|
| Experimental: Non Syncopal Asthmatic<br>All subject undergo simulated dive reflex, with 30s facial immersion and continuous HR and BP monitoring with Nexfin over a period of 6 minutes. | Procedure: Simulated dive reflex<br>* All subjects undergo simulated dive reflex, with 30s facial immersion and continuous HR and BP monitoring with Nexfin over a period of 6 minutes.<br>|
| Experimental: Normal Volunteers<br>All subject undergo simulated dive reflex, with 30s facial immersion and continuous HR and BP monitoring with Nexfin over a period of 6 minutes. | Procedure: Simulated dive reflex<br>* All subjects undergo simulated dive reflex, with 30s facial immersion and continuous HR and BP monitoring with Nexfin over a period of 6 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in heart rate from baseline | Nexfin and ECG monitoring continuously measuring subject heart rate during dive protocol, over a period of 6 minutes. Beat to beat data is converted into mean HR per 10-second epoch and compared to a baseline value for each subject. | 2 minutes prior to facial immersion in water and in 10 second epochs continuously until 3 minutes after facial immersion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure from baseline | Nexfin monitoring continuously measuring subject blood pressure (systolic, diastolic and mean arterial pressure) during dive protocol, over a period of 6 minutes. Beat to beat data is converted into mean blood pressure values per 10-second epoch and compared to a baseline value for each subject | 2 minutes before facial immersion and continuously throughout dive protocol, over a period of 6 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Death, Mechanism, Syncope, Dive reflex