Atelectasis Formation: Role of Positive Pressure Breathing, Hyperoxia, and Hypobaria

Study Overview
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Brief Summary
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The primary aim of this project is to get further knowledge of the physiology of flight atelectasis and its prevention. We seek to: 1) assess whether low levels of positive pressure breathing can prevent atelectasis formation in humans during exposure to hyperoxia and +Gz-accelerations. 2) get further knowledge on the effects of hypobaria on regional ventilation and perfusion. A secondary aim is to evaluate the effect of anti G-trouser inflation on ventilation and regional perfusion.

Detailed Description
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The effect of positive pressure breathing on lung function is being studied, when applied during exposure to hyperoxia and +Gz-accelerations. Focus is on lung tissue compression, ventilation and regional perfusion. In addition, the influence of hypobaria on these parameters is assessed. This study is conducted in accordance with the amended Declaration of Helsinki. The Ethics Committee Ile-de-France III (ref. 3274) and the French National Agency for Drug Safety ANSM have approved the protocol (ref. ID RCB 2015-A00485-44 and ANSM 151046B-32). Primary aim, item 1: Experiments are conducted in a human centrifuge. The protocol mimics a routine peacetime flight in combat aircraft, and includes 1hr05 min at +1Gz followed by 10-min exposure to +1.4 to +3.5Gz . Subjects are exposed three times to this sequence, breathing at positive pressure levels of 0, 5 or 10 hPa. Two groups of sixteen healthy male non-smoking volunteers, wearing anti-G trousers, are studied and compared: group 1 breathes air, group 2 100% O2. Primary aim, item 2: Experiments are conducted in a hypobaric chamber. Sixteen healthy male non-smoking volunteers are exposed to four conditions: 0 or 15,000 ft altitude, breathing air or 100%O2. Protocol duration is 1h15min. Positive breathing pressure can be applied depending on the results of the experiments of item 1. Secondary aim: Experiments are conducted in a human centrifuge. Sixteen healthy male non-smoking volunteers are exposed to four conditions: uninflated or inflated anti-G trousers (175 hPa), +1 or +3.5 Gz for 3 min.

Official Title
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Influence of Hyperoxia and Hypobaria on Atelectasis Occurrence and Mitigation of Atelectasis Formation

Conditions
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Pulmonary Atelectasis

Intervention / Treatment
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* Other: +Gz accelerations and positive pressure breathing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normal lung function checked by pulmonary function tests. normal ECG normal clinical examination Aim 1 exclusion criteria: smoking myopia past medical history of heart or lung disease current medical treatment for heart or lung disease past medical history of back pain or spine trauma or disease otitis bad tolerance to +Gz accelerations (G-induced loss of consciousness, motion sickness) claustrophobia in the centrifuge gondola Aim 2 exclusion criteria: smoking past medical history of heart or lung disease current medical treatment for heart or lung disease otitis bad tolerance to the altitude chamber (15,000 ft): ear pain, claustrophobia

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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
Interventional Model Description: Two arms are studied, breathing air or 100%O2. In each arm, subjects are studied at two occasions: with and without positive pressure breathing. These occasions are randomized.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100%O2 breathing<br>Primary aim, item 1 | Other: +Gz accelerations and positive pressure breathing<br> <br> |
| Experimental: Air breathing<br>Primary aim, item 1 | Other: +Gz accelerations and positive pressure breathing<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| atelectasis formation (change between pre and post-protocol) | computerized tomography: 0-5 scale for size and localization | pre-protocol (baseline) and 1h30 min after centrifuge stop | 
| change in pulmonary ventilation between 1 Gz, 1.6 Gz and 3.5 Gz | electrical impedance tomography: deltaZ on regions of interest | pre-protocol (baseline), baseline + 1hr, baseline +1h10 min, baseline +1h15 min | 
| change in pulmonary tissue density from baseline at centrifuge stop and 1h30 min after stop | ultrasound: number of lung comets + localization | pre protocol (baseline), at centrifuge stop (baseline + 1h15 min) and 1h30 min after centrifuge stop | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary ultrasound, hypergravity, human physiology, oxygen, lung ventilation, lung perfusion, computed tomography, electrical impedance tomography, altitude chamber