Clinical Trial: Genetic Susceptibility to Ozone in Mild Asthmatic Volunteers

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Glutathione S Transferase M1 (GSTM1) Genotype Associated Susceptibility to Airway Response to Ozone in Mild Asthmatic Volunteers.

Brief Summary: Recent reports have shown that people with asthma who have a particular gene, known as the GSTM1 null gene, are more susceptible to the effect of air pollutants. The purpose of this research study is to learn if volunteers who have asthma and have a GSTM1 null gene have increased response (change in lung function and increase in lung cells collected from sputum) compared to volunteers with asthma who have the GSTM1 sufficient gene when challenged with 0.4 ppm ozone during intermittent exercise. The principal purpose of this study is to identify hyper-responsive, responsive and non-responsive groups of human subjects with mild asthma based on their airway neutrophilic response to ozone exposure, and to perform analyses on DNA from airway cells to explore possible differences in genetic profiles between the three groups. An additional pilot aim is to compare expression of a small number of specific genes of interest in a subset of ozone-responsive and ozone-non-responsive subjects with mild asthma.

Detailed Summary:

Fifty volunteers with mild asthma will be recruited to undergo ozone challenge in the controlled exposure facility of the US EPA Human Studies Division (104 Mason Farm Road, Chapel Hill, NC) with 0.4ppm for 2 hours with moderate exercise alternating with rest. Endpoints will include genetic analysis for the GSTM1 genotype, sputum and spirometry changes pre and post exposure, and blood endpoints pre and post exposure.

TRAINING DAY: (at least 3 days prior to the ozone challenge) Eligible subjects will report to the research lab for a 3 hour training session.

  • All female volunteers will undergo a urine pregnancy test.
  • After informed consent is obtained, Measurement of orally exhaled nitric oxide will be obtained
  • Subjects will perform spirometry.
  • Subjects will exercise on a treadmill to determine the workload for the actual exposure.
  • Finally the subject will undergo sputum induction following pretreatment with albuterol.

The sputum will be assessed for quality to determine continued eligibility. If a subject has provided an acceptable sputum sample within the prior 6 months this may be used as inclusion criteria rather than repeating the induction at this point. After subjects have demonstrated production of an adequate sputum sample, they will be scheduled for the ozone exposure visit.

24 HOURS PRIOR to the exposure day (Day 1): Subjects will be asked to refrain from smoking as well as drinking alcohol for 24 hours prior to Day 1 until after completion of Day 3.

  • Subjects w
    Sponsor: University of North Carolina, Chapel Hill

    Current Primary Outcome: Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects [ Time Frame: 6 hours post exposure ]

    Original Primary Outcome: The primary effect of ozone we will assess in this study are decrease is the FEV1 (% decrease from baseline value).

    Current Secondary Outcome:

    • Secondary Endpoints Include Post Ozone Airway PMN Influx Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects [ Time Frame: 6 hours post exposure ]
    • % Decrease in FVC in Asthmaticsbetween Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects [ Time Frame: 6 hours post exposure ]


    Original Secondary Outcome:

    • Secondary endpoints include post ozone airway PMN influx and
    • % decrease in FVC.


    Information By: University of North Carolina, Chapel Hill

    Dates:
    Date Received: February 3, 2006
    Date Started: January 2006
    Date Completion:
    Last Updated: May 12, 2017
    Last Verified: February 2017