Effect of Smoking on Ventilation-Perfusion Ratio

Study Overview
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Brief Summary
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Smoking is one of the world's leading health hazards. Besides being a major risk factor in the etiology of COPD and lung cancer, cigarette smoke is also a causative agent lung diseases characterized by bronchiolar and interstitial inflammation. However, the associated lung pathology of smoking is not only a risk in the development of lung diseases, but also widely recognized as a major risk factor associated with perioperative respiratory and cardiovascular complications. Apart from the long term effects of cigarette smoke, acute effects of the inhalation of cigarettes smoke may influence the course of lung pathology. The inhalation of smoke causes inflammation in the lung by inducing chemotaxis and activation of neutrophils and macrophages and induces oxidative stress. As the acute inflammatory response to smoke inhalation seems to be the underlying mechanism for chronic diseases of smokers, exploring the field of the acute pulmonary changes after exposure to cigarette smoke is highly relevant. One reason for acute hypoxia and injury during smoking might be a severe mismatch of ventilation and perfusion of the lung. Using the multiple inert gas elimination technique (MIGET), a distribution of ventilation-perfusion ratios in the lung can be calculated by analyzing data on the retention and excretion of six infused inert gases. A saline solution containing the gases is infused intravenously. When passing through the lung the gases are either eliminated from the blood or retained depending on their partition coefficient and local V/Q ratio. The concentrations of the gases are measured in the mixed venous blood or the mixed expired gas and the arterial blood allowing for the calculation of retention and excretion and the derivation of V/Q distribution. MIGET is the experimental gold standard to determine the Ventilation-Perfusion ratio of the lung. The aim of this study is to show the acute effect of smoking on ventilation/perfusion ratio distribution in the lung in otherwise healthy smokers.

Official Title
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Acute Effect of Smoking Cigarettes on Ventilation-Perfusion Ratio: A Pilot Study in Healthy Volunteers

Conditions
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Lung Disease

Intervention / Treatment
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* Procedure: cigarette
* Procedure: dummy cigarette


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normal body mass index (BMI) Exclusion Criteria: Medical history of pulmonary or cardiovascular disease Family history of malignant hyperthermia, neuro-muscular disorders Known hypersensitivity to any of the inert gases or substances administered History of post operative nausea and vomiting Pregnancy (pregnancy test will be performed on study day)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy Volunteers - non-smokers<br>control group: After baseline measurements V/Q will be measured by MIGET. After a 2 hour wash out period, the Volunteers will smoke a dummy cigarette. Then V/Q will be measured again after 15 minutes. | Procedure: dummy cigarette<br>* smoking a dummy cigarette<br>* Other names: smoking;|
| Other: Healthy Volunteers - occasional smokers<br>intervention: After baseline measurements V/Q will be measured by MIGET. After a 2 hour wash out period, the Volunteers will smoke 4 conventional cigarettes. Thereafter, V/Q will be measured again after 15, 30, 45, 60 and 120 minutes. | Procedure: cigarette<br>* smoking 4 conventional cigarettes<br>* Other names: smoking;|
| Other: Healthy Volunteers - heavy-smokers<br>intervention: After baseline measurements V/Q will be measured by MIGET. After a 2 hour wash out period, the Volunteers will smoke 4 conventional cigarettes. Thereafter, V/Q will be measured again after 15, 30, 45, 60 and 120 minutes. | Procedure: cigarette<br>* smoking 4 conventional cigarettes<br>* Other names: smoking;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ventilation-perfusion ratio by MMIMS-MIGET | V/Q-ratio as well as shunt, low V/Q, normal V/Q and high V/Q i.e. deadspace will be assessed by micropore-membrane inlet mass-spectrometry multiple inert gas elimination technique (MMIMS-MIGET) | within a time-frame of 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum nicotine by blood sampling | the serum nicotine level will be assessed by clinical chemistry | within a time-frame of 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple inert gas elimination technique, smoking, pulmonary disorder