Effect of Smoking on Ventilation-Perfusion Ratio

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Disease
• Intervention / Treatment: Procedure: "dummy cigarette"; Procedure: cigarette

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Bernd Jilma, Ao.Univ.-Prof.Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Healthy Volunteers - non-smokers; 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"; smoking a "dummy cigarette"; Other Names: smoking
OTHER: Healthy Volunteers - occasional smokers; 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; smoking 4 conventional cigarettes; Other Names: smoking
OTHER: Healthy Volunteers - heavy-smokers; 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; smoking 4 conventional cigarettes; Other Names: smoking

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2018
• Primary Completion (ANTICIPATED): August 1, 2019
• Study Completion (ANTICIPATED): September 1, 2019

Study Registration Dates

• First Submitted: November 4, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (ESTIMATE): November 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: smoking; multiple inert gas elimination technique; pulmonary disorder
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: 1133/2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No