NCT02017431

Brief Summary

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)

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2014

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 16, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 20, 2013

Completed
12 days until next milestone

Study Start

First participant enrolled

January 1, 2014

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
Last Updated

September 29, 2017

Status Verified

September 1, 2017

Enrollment Period

3.2 years

First QC Date

December 16, 2013

Last Update Submit

September 27, 2017

Conditions

Allergies

Keywords

Diesel exhaustParticle depleted diesel exhaustAir pollutionAirway responsivenessAllergies

Outcome Measures

Primary Outcomes (2)

  • Immune response to allergen +/- DE (BAL)

    BAL cellular differential and activation,

    48 hours

  • Immune response to allergen +/- DE (Th1/Th2/IgE/IgG4)

    Th1/Th2 profile and IgE and IgG4 specific to the allergen used for allergen challenge will be assessed.

    48 hours

Secondary Outcomes (2)

  • Epithelial cell DNA methylation

    48 hours

  • Proteomic signature

    48 hours

Study Arms (4)

Filtered air

ACTIVE COMPARATOR

Exposure for 2 hours to filtered air followed by subject specific inhaled allergen challenge

Other: Allergen

Diesel exhaust

EXPERIMENTAL

Exposure for 2 hours to diesel exhaust followed by subject specific inhaled allergen challenge

Other: Allergen

Filtered air control

ACTIVE COMPARATOR

Exposure for 2 hours to filtered air followed by inhaled saline challenge

Other: Saline

Particle depleted diesel exhaust

EXPERIMENTAL

Exposure for 2 hours to particle depletion diesel exhaust followed by inhaled allergen challenge

Other: AllergenOther: Particle depleted diesel exhaust

Interventions

AllergenOTHER

Subject specific allergen is inhaled on day 1 of the triad

Diesel exhaustFiltered airParticle depleted diesel exhaust
SalineOTHER

Saline is inhaled on day 1 of the triad

Filtered air control
Particle depleted diesel exhaustOTHER

High-efficiency particulate filtration of diesel exhaust

Particle depleted diesel exhaust

Eligibility Criteria

Age19 Years - 49 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (8)

  • Calhoun WJ, Jarjour NN, Gleich GJ, Stevens CA, Busse WW. Increased airway inflammation with segmental versus aerosol antigen challenge. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1465-71. doi: 10.1164/ajrccm/147.6_Pt_1.1465.

    PMID: 8389107BACKGROUND

  • Diaz-Sanchez D, Dotson AR, Takenaka H, Saxon A. Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms. J Clin Invest. 1994 Oct;94(4):1417-25. doi: 10.1172/JCI117478.

    PMID: 7523450BACKGROUND

  • Nordenhall C, Pourazar J, Ledin MC, Levin JO, Sandstrom T, Adelroth E. Diesel exhaust enhances airway responsiveness in asthmatic subjects. Eur Respir J. 2001 May;17(5):909-15. doi: 10.1183/09031936.01.17509090.

    PMID: 11488325BACKGROUND

  • Carlsten C, Melen E. Air pollution, genetics, and allergy: an update. Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):455-60. doi: 10.1097/ACI.0b013e328357cc55.

    PMID: 22885891RESULT

  • Riedl MA, Diaz-Sanchez D, Linn WS, Gong H Jr, Clark KW, Effros RM, Miller JW, Cocker DR, Berhane KT; HEI Health Review Committee. Allergic inflammation in the human lower respiratory tract affected by exposure to diesel exhaust. Res Rep Health Eff Inst. 2012 Feb;(165):5-43; discussion 45-64.

    PMID: 22852485RESULT

  • Robinson A, Huff RD, Ryu MH, Carlsten C. Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study. Respir Res. 2023 Sep 7;24(1):218. doi: 10.1186/s12931-023-02518-y.

    PMID: 37679687DERIVED

  • Ryu MH, Lau KS, Wooding DJ, Fan S, Sin DD, Carlsten C. Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs. Thorax. 2020 Aug;75(8):640-647. doi: 10.1136/thoraxjnl-2020-214561. Epub 2020 May 28.

    PMID: 32467339DERIVED

  • Wooding DJ, Ryu MH, Huls A, Lee AD, Lin DTS, Rider CF, Yuen ACY, Carlsten C. Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study. Am J Respir Crit Care Med. 2019 Sep 1;200(5):565-574. doi: 10.1164/rccm.201809-1657OC.

    PMID: 30974969DERIVED

MeSH Terms

Conditions

Hypersensitivity

Interventions

AllergensSodium Chloride

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

AntigensBiological FactorsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Christopher Carlsten, MD, MPH

    University of British Columbia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

December 16, 2013

First Posted

December 20, 2013

Study Start

January 1, 2014

Primary Completion

April 1, 2017

Study Completion

April 1, 2017

Last Updated

September 29, 2017

Record last verified: 2017-09

Locations

CA(1)