Air Pollution and Allergens - Attenuation of Health Effects Particle Reduction (DE3)

September 27, 2017 updated by: Christopher Carlsten, University of British Columbia

Strengthening the Case for Ongoing Reduction of Exposure to Traffic-Related Air Pollution

The study probes the effects of combined exposures to diesel exhaust and allergens on lung function and on the immune system, specifically focusing on the ability of a particle depletion technique to attenuate effects we and others have seen previously. Individuals are exposed to either filtered air (FA), carefully controlled levels of diesel exhaust (DE) or particle-depleted diesel exhaust (PDDE) in our exposure chamber, after which the investigators will administer an inhaled allergen challenge. 48h later, a procedure called bronchoscopy is used to collect samples from the lungs. After 1 month, the entire procedure is to be repeated with one of the alternate exposures. This will be repeated 4 times (4 exposures; 2 filtered air, 1 diesel exhaust, 1 particle-depleted diesel exhaust)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  1. Purpose/Objective:

    The aim of this study is to investigate the ability of depletion of diesel exhaust particles to attenuate adverse effects of diesel exhaust on lung function and on allergic responses.

  2. Hypotheses:

    Hypothesis 1: Allergen-specific immune response (specific IgG4, etc; relevant responses in DNA methylation and proteomics) in allergen-challenged airways in sensitized individuals is increased by diesel exhaust "synergy".

    Hypothesis 2: Synergistic responses will be greater in asthmatics than in non-asthmatics.

    Hypotheses 3: Synergy is attributable to the particulate fraction of DE (i.e. is normalized by particle depletion).

  3. Justification:

    Diesel exhaust consists of both gaseous and particulate air pollutants. In recent studies, cardiovascular effects seem attenuated when the particulate portion is removed. We would like to know if that is true for respiratory and immunological endpoints. Understanding these changes may help us prevent health problems associated with air pollution in the future.

  4. Research Method:

Blinded crossover experiment between four conditions (DE and allergen, PDDE and allergen, FA and allergen, FA and saline), randomized and counter-balanced to order. Each condition will be separated by a 4-week washout period.

An inhaled allergen or saline challenge is delivered after each exposure (DE, PDDE, or FA). 24 h post challenge, airway reactivity will be assessed with a methacholine challenge. 48 h post challenge, bronchoalveolar lavage (BAL), airway brushes and tissue biopsies will be obtained for analysis of immune activation. Nasal lavage samples will also be collected to examine responses in the upper airways and blood and urine will be studied to examine systemic responses. Spirometry and methacholine challenge will be used to assess effects on airway function.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • University of British Columbia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 47 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age between 19 and 49 years
  • Non-smoking
  • Positive skin prick test for at least one of: birch, grass, or dust

Exclusion Criteria:

  • Using inhaled corticosteroids
  • Pregnant or planning to be pregnant in the next 12 months / Breastfeeding
  • Usage of bronchodilators more than three times per week.
  • Co-morbidities (as assessed by the primary investigator)
  • Taking part in other studies
  • Unwilling to withhold bronchodilator, aspirin, anti-coagulant, antihistamine or decongestant medications or caffeine prior to testing procedures.
  • FEV1(Forced expiratory volume in one second) < 70% predicted.
  • Allergy to lidocaine, fentanyl, midazolam or salbutamol.
  • Unstable asthma (i.e exacerbation in 2 weeks preceding testing)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Filtered air
Exposure for 2 hours to filtered air followed by subject specific inhaled allergen challenge
Other: Allergen
Subject specific allergen is inhaled on day 1 of the triad
Experimental: Diesel exhaust
Exposure for 2 hours to diesel exhaust followed by subject specific inhaled allergen challenge
Other: Allergen
Subject specific allergen is inhaled on day 1 of the triad
Active Comparator: Filtered air control
Exposure for 2 hours to filtered air followed by inhaled saline challenge
Other: Saline
Saline is inhaled on day 1 of the triad
Experimental: Particle depleted diesel exhaust
Exposure for 2 hours to particle depletion diesel exhaust followed by inhaled allergen challenge
Other: Allergen
Subject specific allergen is inhaled on day 1 of the triad
Other: Particle depleted diesel exhaust
High-efficiency particulate filtration of diesel exhaust

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune response to allergen +/- DE (BAL)
Time Frame: 48 hours
BAL cellular differential and activation,
48 hours
Immune response to allergen +/- DE (Th1/Th2/IgE/IgG4)
Time Frame: 48 hours
Th1/Th2 profile and IgE and IgG4 specific to the allergen used for allergen challenge will be assessed.
48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epithelial cell DNA methylation
Time Frame: 48 hours
Determine if allergen-induced changes in DNA methylation within epithelial cells is augmented by DE (300 µg/m3 inhaled for two hours) and attenuated by PDDE.
48 hours
Proteomic signature
Time Frame: 48 hours
Determine if allergen-induced changes in proteomic profile within epithelial cells is augmented by DE (300 µg/m3 inhaled for two hours) and attenuated by PDDE.
48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2014

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

April 1, 2017

Study Registration Dates

First Submitted

December 16, 2013

First Submitted That Met QC Criteria

December 16, 2013

First Posted (Estimate)

December 20, 2013

Study Record Updates

Last Update Posted (Actual)

September 29, 2017

Last Update Submitted That Met QC Criteria

September 27, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H11-01831/2013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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