Air Pollution and Allergens - Attenuation of Health Effects Particle Reduction

NCT ID: NCT02017431

Last Updated: 2017-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2017-04-30

Brief Summary

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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)

Detailed Description

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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.

Conditions

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Allergies

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Filtered air

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

Group Type ACTIVE_COMPARATOR

Allergen

Intervention Type OTHER

Subject specific allergen is inhaled on day 1 of the triad

Diesel exhaust

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

Group Type EXPERIMENTAL

Allergen

Intervention Type OTHER

Subject specific allergen is inhaled on day 1 of the triad

Filtered air control

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

Group Type ACTIVE_COMPARATOR

Saline

Intervention Type OTHER

Saline is inhaled on day 1 of the triad

Particle depleted diesel exhaust

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

Group Type EXPERIMENTAL

Allergen

Intervention Type OTHER

Subject specific allergen is inhaled on day 1 of the triad

Particle depleted diesel exhaust

Intervention Type OTHER

High-efficiency particulate filtration of diesel exhaust

Interventions

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Allergen

Subject specific allergen is inhaled on day 1 of the triad

Intervention Type OTHER

Saline

Saline is inhaled on day 1 of the triad

Intervention Type OTHER

Particle depleted diesel exhaust

High-efficiency particulate filtration of diesel exhaust

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

19 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Christopher Carlsten

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher Carlsten, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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University of British Columbia

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 8389107 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7523450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11488325 (View on PubMed)

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.

Reference Type RESULT
PMID: 22885891 (View on PubMed)

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.

Reference Type RESULT
PMID: 22852485 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37679687 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32467339 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30974969 (View on PubMed)

Other Identifiers

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H11-01831/2013

Identifier Type: -

Identifier Source: org_study_id