Air Pollution and Allergens - Attenuation of Health Effects Particle Reduction

Allergies Clinical Trial

— DE3  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02017431
• Other study ID #: H11-01831/2013
• Status: Completed
• Phase: N/A
• First received: December 16, 2013
• Last updated: September 27, 2017
• Start date: January 2014
• Est. completion date: April 2017

Study information

• Verified date: September 2017
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 49 Years

Eligibility

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)

Related Conditions & MeSH terms

• Allergies

Intervention

Other:
• Allergen
Subject specific allergen is inhaled on day 1 of the triad
• Saline
Saline is inhaled on day 1 of the triad
• Particle depleted diesel exhaust
High-efficiency particulate filtration of diesel exhaust

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (5)

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. — View Citation

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

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. — View Citation

Nordenhäll C, Pourazar J, Ledin MC, Levin JO, Sandström T, Adelroth E. Diesel exhaust enhances airway responsiveness in asthmatic subjects. Eur Respir J. 2001 May;17(5):909-15. — View Citation

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. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune response to allergen +/- DE (BAL)	BAL cellular differential and activation,	48 hours
Primary	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	Epithelial cell DNA methylation	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
Secondary	Proteomic signature	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