London Underground Study - Health Effects of Particulate Matter

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Other: Exposure to London Underground ambient particulate matter; Other: Exposure to London air ambient particulate matter

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPD patients; As per inclusion and exclusion criteria for COPD patients	Other: Exposure to London Underground ambient particulate matter; Exposure to particulate matter on the London Underground; Other: Exposure to London air ambient particulate matter; 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)
Experimental: Healthy volunteers; As per inclusion and exclusion criteria for healthy volunteers	Other: Exposure to London Underground ambient particulate matter; Exposure to particulate matter on the London Underground; Other: Exposure to London air ambient particulate matter; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Medical Research Council
• Investigators: Principal Investigator: Frank Kelly, Imperial College London

Publications and helpful links

General Publications

• Sinharay R, Gong J, Barratt B, Ohman-Strickland P, Ernst S, Kelly FJ, Zhang JJ, Collins P, Cullinan P, Chung KF. Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study. Lancet. 2018 Jan 27;391(10118):339-349. doi: 10.1016/S0140-6736(17)32643-0. Epub 2017 Dec 5. Erratum In: Lancet. 2018 Jan 27;391(10118):308.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Particulate matter; London Underground
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 20SM6236

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