Glutathione S Transferase M1 (GSTM1) Genotype Associated Susceptibility to Airway Response to Ozone in Mild Asthmatic Volunteers.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •healthy volunteers with mild asthma
- •Normal lung function,
- •Oxygen saturation of > 94 %
- •Normal blood pressure
排除标准
- •A history of significant chronic illnesses
- •Allergy to any medications which may be used or prescribed in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose, polyethylene glycol)
- •Positive pregnancy test within 48 hours of the time of challenge
- •Subjects currently taking medications which may impact the results of the ozone challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics).
- •Mega doses of vitamins and supplements, homeopathic/naturopathic medicines
- •Any acute, non-chronic, medical conditions occurring in the prior two weeks. Such illnesses must be totally resolved symptomatically for 2 weeks and documentation of normal lung function must be obtained.
- •Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with ozone inhalation challenge, will be a basis for exclusion.
- •Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
- •Use of systemic steroid therapy within the preceding 12 months.
- •> 0.5 pack year history of tobacco use
- •Use of inhaled steroids, cromolyn or leukotriene inhibitors initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy.
- •Use of daily theophylline within the past month.
- •Pregnancy or nursing a baby.
- •Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- •Exacerbation of asthma more than 2x/week which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- •Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
- •Dosing level of an inhaled steroid must be consistent with mild episodic asthma as outlined by the NHLBI NAEPP guidelines. Use of inhaled steroid at doses typically used for moderate or severe asthma will result in exclusion of that individual from the protocol.
- •Students or staff members who work directly for the PI, Dr David Peden, are excluded from study participation
研究组 & 干预措施
1-ozone
Mildly asthmatic subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects
干预措施: ozone (Drug)
结局指标
主要结局
Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects
时间窗: 6 hours post exposure
次要结局
- Secondary Endpoints Include Post Ozone Airway PMN Influx Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects(6 hours post exposure)
- % Decrease in FVC in Asthmatics Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects(6 hours post exposure)