London Underground Study - Health Effects of Particulate Matter

Study Overview
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Brief Summary
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An average of 4.8 million journeys are made on the London Underground every day and as the 'Tube' has elevated airborne particulate matter concentrations compared to ambient air, this raises concern about the potential health impact of this environment. This study explores the health effects of particulate matter from the London Underground on patients with COPD and healthy volunteers. Patients with COPD and healthy participants will be invited to undertake a set 90 min journey on the London Underground, and on a separate occasion (3-8 weeks apart), a 90 min journey on the London Overground (as a proxy for a clean air London area while maintaining other aspects of a train journey). A series of clinical, physiological and inflammatory data will be collected before, during and after (at different time points) each of the sessions in order to compare their response in relation to exposure and/or to disease status.

Official Title
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Exposure to Particulate Matter on the London Underground in Healthy Subjects and Patients With Chronic Respiratory Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Other: Exposure to London Underground ambient particulate matter
* Other: Exposure to London air ambient particulate matter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for both groups: Give informed consent London resident For participants with COPD: GOLD stage 2 COPD (FEV1/FVC<70%; 50%>FEV1<80% predicted), GOLD stage 3 COPD (FEV1/FVC<70%; 30%>FEV1<50%) and GOLD stage 4 (FEV1/FVC<70%;FEV1<30%) No history of ischaemic heart disease For healthy volunteers: No history of ischaemic heart disease. Normal lung function with no evidence of airflow obstruction. Exclusion Criteria for both participants with COPD and healthy volunteers: Those with unstable ischaemic heart disease or COPD. Current smokers and those who are ex-smokers of <12 months duration. Those who work in the London Underground or are occupationally exposed to - - high levels of vehicle traffic exposure on a frequent basis. Those who cannot walk for 30 mins. Involvement in another research study Those unable to give consent.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD patients<br>As per inclusion and exclusion criteria for COPD patients | Other: Exposure to London Underground ambient particulate matter<br>* Exposure to particulate matter on the London Underground<br>Other: Exposure to London air ambient particulate matter<br>* Exposure to ambient particulate matter on the London Overground (as a proxy as a proxy for a clean air London area while maintaining other aspects of a train journey)<br>|
| Experimental: Healthy volunteers<br>As per inclusion and exclusion criteria for healthy volunteers | Other: Exposure to London Underground ambient particulate matter<br>* Exposure to particulate matter on the London Underground<br>Other: Exposure to London air ambient particulate matter<br>* Exposure to ambient particulate matter on the London Overground (as a proxy as a proxy for a clean air London area while maintaining other aspects of a train journey)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference (London Underground vs control exposure) in post exposure pulse wave velocity in healthy vs COPD participants. | Measurement of arterial stiffness | -2 hours, +2 hours, +5 hours, +6 hours, +24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other clinical responses on the London Underground vs control exposure | Symptom questionnaire | -2 hours, 0 hours, +45 minutes +90 minutes, +4 hours, +5 hours, +6 hours, +24 hours | 
| Other clinical responses on the London Underground vs control exposure | Spirometry (FEV1) | -2 hours, 0 hours, +45 minutes, +90 minutes, +2 hours, +4 hours, +6 hours, +24 hours | 
| Other clinical responses on the London Underground vs control exposure | Spirometry (FVC) | -2 hours, 0 hours, +45 minutes, +90 minutes, +2 hours, +4 hours, +6 hours, +24 hours | 
| Other clinical responses on the London Underground vs control exposure | Spirometry (FEF 25-75) | -2 hours, 0 hours, +45 minutes, +90 minutes, +2 hours, +4 hours, +6 hours, +24 hours | 
| Other clinical responses on the London Underground vs control exposure | Single breath transfer factor for carbon monoxide (TLCO) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (IL8) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (High sensitivity CRP) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (FBC) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (TNFa) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (vWf antigen) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (Thrombin generation (systemic inflammatory response)) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (8-isoprostanes (ELISA)) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (Blood malondialdehyde (lipid peroxidation)) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Blood sample (Oxidation Reduction Potential (oxidative stress)) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (IL-8) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (IL-6) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (IL-33) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (Myeloperoxidase) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (Neutrophil lipocalin-2) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (Tryptases) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (Complement) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (vWf antigen) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (Thrombin generation) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasosorption (D-dimer activation) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Nasal curettage (mRNA levels to elucidate molecular mechanisms that may explain the toxic effects of particulate matter) | -2 hours, +7 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Urine (8-isoprostane) | -2 hours, +24 hours | 
| Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure | Urine (8-hydroxy 2-deoxyguanosine) | -2 hours, +24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Chronic Obstructive Pulmonary Disease, Particulate matter, London Underground