Longitudinal Acute Air Pollution Systemic Effects

Study Overview
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Brief Summary
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Air pollution continues to be a key global issue with many governments focusing great attention on air quality legislation because of its harmful environmental and health impacts. Whilst there is much that remains unknown about the mechanisms underlying the negative health effects of air pollution, it is generally acknowledged that air pollution exposure leads to an increase in cardiovascular, cerebrovascular and respiratory mortality and morbidity. The current study will investigate systemic effects during a 72 hour period after a controlled diesel exhaust exposure.

Detailed Description
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Exposure to air pollution (both indoor and outdoor sources) contributes to the premature deaths of 7 million people each year, primarily linked to cardiovascular and respiratory conditions. Within the complex mixture which air pollution comprises, combustion derived particulate matter (PM) has been suggested as one of the most harmful components to the cardiopulmonary system. In urban areas PM derived from combustion originates largely from diesel vehicles. Numerous experimental chamber studies have demonstrated respiratory as well as cardiovascular dysfunctions after the inhalation of diesel exhaust. Many of these dysfunctions are driven by inflammation and oxidative stress. There is much less knowledge concerning the systemic effects of diesel exhaust exposure, and especially over longer time courses than 24 hours. The investigators aim to investigate the time course of systemic effects (such as markers of inflammation, cardiovascular dysfunction, and oxidative stress) in blood and urine samples taken after a diesel exhaust exposure. The effects of exercise or rest in an experimental chamber exposure will also be investigated.

Official Title
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Longitudinal Acute Air Pollution Systemic Effects (LAPSE)

Conditions
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Healthy

Intervention / Treatment
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* Other: Diesel Exhaust
* Other: Filtered air


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal clinical examination Normal EKG Normal routine blood tests Normal lung function Normal skinprick test Exclusion Criteria: Cardiovascular disease Diabetes Mellitus Asthma and/or allergy Smoking

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Filtered air exposure<br>2 hour exposure to filtered air during intermittent exercise or rest. | Other: Filtered air<br>* Filtered air<br>|
| Experimental: Diesel exhaust exposure<br>2 hour exposure to dilute diesel exhaust (approximate PM10 (particulate matter<10um) concentration 300 mcg/m3) during intermittent exercise or rest. | Other: Diesel Exhaust<br>* Dilute diesel exhaust<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory biomarkers | In blood samples (total and differential counts | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress markers | In blood samples (ox-LDL, ROS) | 72 hours | 
| Cardiovascular biomarkers | In blood samples (sTM, hsCRP, syndecan-1) | 72 hours | 
| Metabolomics | Mass spectrometry based metabolomics in blood samples | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diesel exhaust, Oxidative stress, Systemic inflammation, Air pollution