A Study of Inhalation of 20,000 EU Clinical Center Reference Endotoxin in Normal Volunteers Compared to Allergic Asthmatic Individuals
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers
研究概览
简要总结
This will be a single center, open label study comparing baseline characteristics of recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after inhalational challenge with 20,000 EU Clinical Center Reference Endotoxin (CCRE, a component of air pollution)) within each group as well as cross group comparisons between individuals with allergic asthma (AA's)and normal volunteers (NV's). The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers. Secondary objectives include post CCRE comparison between AA's and NV's with regard to changes in airway cells and blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000 EU CCRE.
详细描述
This will be a single center, open label study of allergic asthmatic and normal volunteers. The protocol will compare baseline characteristics of recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after inhalational challenge with CCRE within each group as well as cross group comparisons between AA's and NV's. The following information indicates procedures to be performed at each visit as well as the anticipated duration of visits. Subsequent to this description are details regarding specific study procedures.
Visit 1: Baseline Visit (5 hours)
- Consent will be obtained, review of subject's medical history, current medications and inclusion/exclusion criteria.
- Vital sign measurements (temperature, pulse, respiratory rate, blood pressure), oxygen saturation, and symptom scoring
- Urine pregnancy test for women of child bearing potential
- Spirometry
- Venipuncture for CBC with differential and baseline blood analyses
- Physical exam of the ears, nose, throat and chest
- Collection of exhaled breath for measurement of nitric oxide level
- Xenon equilibrium gas scan and MCC
- MCC scan
- Sputum induction
- After completion of the sputum induction, subjects will have brief MCC scan (< 10 minutes)
Visit 2: 24 hours post baseline subjects will return for the following 1 hour visit:
- Review any change in medical status over prior 24 hours, vital signs, O2 saturation and symptom score
- Follow up MCC scan
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- 是
入选标准
- •for healthy controls:
- •Normal lung function, defined as (Knudson 1976/1984 predicted set):
- •FVC of > 80 % of that predicted for gender, ethnicity, age and height FEV1 of > 80 % of that predicted for gender, ethnicity, age and height FEV1/FVC ratio of > .75
- •Oxygen saturation of > 94 % and normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
- •Symptom Score no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.
- •Negative methacholine inhalation challenge as performed in the screening protocol. (Less than a 20% decrease in FEV1 at a maximum methacholine concentration of 10 mg/ml)
- •-Negative pregnancy test for females
- •Negative allergy skin test (AST)
- •Inclusion criteria for allergic asthmatics also include:
- •History of episodic wheezing, chest tightness, or shortness of breath after age of 6 years consistent with asthma, or physician diagnosed asthma after age of 6 years.
- •Positive methacholine test.
- •FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .70 (without use of bronchodilating medications for 12 hours)
- •Allergic sensitization to at least one of the following allergen preparations: (House Dust Mite f, House dust mite p, Cockroach, Tree mix, Grass Mix, Weed Mix, Mold Mix 1, Mold Mix 2, Rat, Mouse, Guinea Pig, Rabbit, Cat or Dog) confirmed by positive AST.
- •Negative allergy skin test as performed in the screening protocol.
排除标准
- •Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.
- •Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
- •Use of systemic steroid therapy within the preceding 12 months for an asthma exacerbation. All use of systemic steroids in the last year will be reviewed by a study physician.
- •Use of inhaled steroids, cromolyn or leukotriene inhibitors (montelukast or zafirlukast) except for use of cromolyn exclusively prior to exercise.
- •Use of daily theophylline within the past month.
- •Use of tricyclics and MAO inhibitors
- •Pregnancy or nursing a baby.
- •Cigarette smoking > 1 pack per month.
- •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 of 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).
- •Viral upper respiratory tract infection within 2 weeks of challenge.
- •Any acute infection requiring antibiotics within 2 weeks of challenge
- •Receipt of LAIV (Live Attenuated Influenza Vaccine), also know as FluMist®, within the prior 14 days
研究组 & 干预措施
Allergic asthma
subjects with allergic asthma will undergo challenge with 20,000 EU CCRE
干预措施: Clinical Center Reference Endotoxin (CCRE) (Biological)
healthy control
Healthy volunteers will undergo challenge with 20,000 EU CCRE
干预措施: Clinical Center Reference Endotoxin (CCRE) (Biological)
结局指标
主要结局
The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers
时间窗: 6 hours post challenge
次要结局
- Secondary objectives include post CCRE comparison between AA's and NV's with regard to changes in airway cells and blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000 EU CCRE.(6-24 hours post challenge)