Effects of Phthalate Inhalation on Airway Immunology: A Controlled Human Exposure Study
试验速览
- 阶段
- 不适用
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Recruitment of immune cells in airways
研究概览
简要总结
Phthalates are commonly used plasticizers that have been linked to asthma in epidemiological studies. The investigators are researching effects of phthalates on airway immunology and lung function, and on allergic responses by doing an inhaled allergen challenge. After exposing participants to either filtered air or carefully controlled levels of phthalate in our exposure chamber we will collect samples from the nose and the upper airways, by rinsing the nose with saltwater or performing small brushings. The investigators will also collect a bronchial samples by bronchoscopy after each exposure. After 2 weeks, the entire procedure will be repeated with the alternate exposure.
详细描述
- Purpose:
To study the effects of phthalates on airway immunology, lung function and nasal allergic responses. 2. Hypotheses:
Phthalate inhalation increases recruitment of immune cells to the upper airways and affects the functionality of immune and epithelial cells.
Hypothesis 2: Phthalate inhalation alters the cellular response to an inhalation allergen challenge. 3. Justification:
Phthalates are plasticizers or softeners, used in PVC and other plastics and a range of consumer products. Since phthalates are not chemically bound to the plastic they leak out from these products, causing routine human exposure through air, dust and food. Exposure to phthalates has been linked to worsening or development of airway diseases in epidemiological studies, but the effects of phthalates on our airways and immune responses are largely unknown. In this study we would like to investigate how one particular phthalate, dibutyl phthalate (DBP), can affect the human respiratory and immune systems. The investigators are not expecting that the responses will be noticeable to the subjects; they are expecting that any responses that may occur will only be detectable through careful examination of cells and tissues (e.g. nasal lavage and brushes (fluid from the nose), bronchial samples, blood, urine). Nasal samples will be used for measurement of nasal inflammatory responses in terms of cell recruitment and levels of inflammatory mediators. Bronchial samples will allow for a refined examination of an inflammatory responses in the lung and thus provide a much more detailed information concerning the phthalate-induced responses due to allergen challenge. Understanding these subtle changes will help us prevent health problems associated with phthalate exposure in the future. 4. Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 19 and 49 years.
- •Non-smoking.
- •Proficient in English
- •Positive skin prick test for at least one of: birch, grass, or dust.
- •Healthy, or diagnosed with mild asthma
- •Exclusion Criteria
- •pregnancy/breastfeeding
- •unstable asthma symptoms (eg: exacerbations in previous 2 weeks)
- •use of inhaled corticosteroids or bronchodilator medication more than 3 times a week
- •presence of co-existing medical conditions i.e. arrythmia (as assessed by the primary investigator)
- •participation in another study that involves taking medications
- •regular use of antihistamines, non-steroidal anti-inflammatories, anticoagulants, acetylsalicylic acid (ASA) or decongestants
- •allergy to salbutamol or lidocaine.
排除标准
- 未提供
结局指标
主要结局
Recruitment of immune cells in airways
时间窗: 3-24 hours
Recruitment will be identified by performing differential cell counts
Airway Inflammation
时间窗: 3-24 hours
Airway Inflammation will be measured by Fractional exhaled NO.
Airway responsiveness
时间窗: 3-24 hours
Airway responsiveness will be measured by spirometry.
Activation of immune cells in airways
时间窗: 3-24 hours
Cellular activation will be measured by cytokine expression in airway samples.
次要结局
- Allergen specific IgE(24 hours)
- Inflammatory markers in plasma and cell function after in vitro stimulation with inflammatory ligands (LPS & R848)(3-24h)
- Response of immune cells in blood(3-24 hours)
- Response of immune cells in airways(3-24 hours)
研究者
Christopher Carlsten
Principal Investigator
University of British Columbia