Biomarkers of Irritant-Induced and Allergic Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change in TSLP Gene Expression
研究概览
简要总结
Asthma is a heterogeneous disease, and although much is understood about mechanisms of inflammation in allergic asthma, less is known about mechanisms of irritant-induced asthma (IA). Understanding the underlying similarities and differences in mechanisms of these two types of asthma will help focus current treatments and lead to development of new therapies. There is a longstanding NYU/Bellevue Asthma registry (NYUBAR), with a large population (N = 900) of asthma cases and controls, a program that has been housed at the CTSI (formerly GCRC). The destruction of the World Trade Center (WTC) resulted in massive dust, gas and fume exposures to local residents, workers and cleanup workers and individuals involved in rescue and recovery and adverse respiratory health effects of this disaster are reported more than 7 years after 9/11. Many responders, as well as those exposed as residents or local workers, have developed IA, asthma that arises after a lag from an environmental exposure . The WTC Environmental Health Center (WTC EHC) is one of the three New York City (NYC) WTC Centers of Excellence and the only one that focuses on treatment and monitoring of local workers and residents. As such, it has a large population of individuals with irritant-induced asthma. It has been proposed to use participants from the NYUBAR and the WTC EHC to expand the knowledge of irritant and allergic asthma. Non-invasive studies allow for the assessment of airway inflammation, a non-specific response to environmental exposure and injury. Recent technologies also allow for assessment of microRNA (miRNA), small RNAs that regulate gene expression at the post-transcriptional level and thus serve as a pathway to regulation of inflammation. The hypothesis will be tested in that airway inflammation in irritant and allergic asthma may be similar, but result from divergent miRNA regulatory pathways expressed in sputum cells. These studies will provide preliminary data for future studies that will help identify biological pathways to categorize these asthma phenotypes and target future treatment interventions.
详细描述
This study will have two asthma phenotypes and one control population. Patients will be recruited from the WTC EHC = 30 with WTC dust cloud exposure, patients will be recruited from the NYUBAR (n=30) and have asthma as defined by NIH guidelines, and control patients will be recruited from the NYUBAR (n=30) and will have no respiratory sx, no asthma diagnosis, or no WTC dust exposure.
The study will entail two to three visits. On visit 1 (V1) all individuals will sign informed consent to participate in the study under an NYU IRB approved protocol. A questionnaire will be completed with standardized questions that include information on WTC exposures, demographics, presence and severity of respiratory symptoms, tobacco history and past medical history. Individuals will undergo spirometry with inhaled bronchodilator. Individuals will undergo methacholine challenge test (visit 1a) if they have normal spirometry or no bronchial hyperresponsiveness. On visit 2, individuals will return to undergo ENO, EBC and spirometry with pre and post bronchodilator maneuvers and induced sputum. Blood will be obtained for CBC with differential cell count, and assessment of total IgE and allergen-specific IgE. Blood will also be stored for future analysis of inflammatory markers. Based on experience, there have been individuals unable to produce enough sputum and thus yield too small a number of cells. These individuals are excluded from data analysis. In addition, there will also be subjects who are able to produce sputum and return for repeat sputum testing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For the WTC population with Irritant-Induced Asthma (IA):
- •> 18 years of age*
- •Current nonsmoker*
- •< 5 pack year (p-y) history of tobacco use*
- •Spirometry in the past 6 months or on day of evaluation with a bronchodilator* response of ≥ 12% and 200 ml improvement in FEV*
- •Positive methacholine challenge test (decrease in FEV1*
- •≥ 20% (PC20) after inhalation of < 16 mg/ml of methacholine)
- •Inhaled corticosteroid use in previous 1 month or more will be allowed*
- •Patients will be recruited from the WTC EHC and will have WTC dust cloud exposure
- •New symptoms after 9/11
- •Symptoms of wheeze and shortness of breath (> 2x / week) in the 4 weeks before inclusion (persistent symptoms).
- •Inclusion for Allergic Asthma Population (AA):
- •All of the above items with an asterisk (*)
- •Patients will be recruited from the NYUBAR or advertisement and will have asthma as defined by NIH guidelines, persistent symptoms, absence of WTC dust exposure.
- •Participants who will have completed the Phase I of the study and were able to produce adequate sputum samples.
- •Inclusion of Control Population:
- •Patients will be recruited from the NYUBAR and will have no respiratory symptoms, no asthma diagnosis, no WTC dust exposure, no current tobacco use, ≤ 5 p-y history of tobacco use, and normal spirometry with no bronchodilator response and negative methacholine challenge in past 6 months.
- •Inclusion Criteria for Phase II:
- •Successfully completed Phase I
- •Has asthma according to Phase I diagnostic criteria
- •Signed consent to be re-contacted
排除标准
- •Current Smoker
- •Pulmonary diseases such as Chronic Pulmonary Disease (COPD) or Interstitial Lung Disease
- •Cardiac Disease
- •Inability to perform lung function or other maneuvers
- •Upper respiratory tract infection within the last 4 weeks
- •FEV1 <60% predicted normal pre-bronchodilator
- •Oral corticosteroid treatment within the last 4 weeks.
- •No vulnerable subjects will be part of this study.
研究组 & 干预措施
Allergic Asthma (AA)
干预措施: Fluticasone propionate HFA 220 (Drug)
结局指标
主要结局
Change in TSLP Gene Expression
时间窗: Baseline and Two (2) weeks
The primary outcome is the change in TSLP gene expression in epithelial cells after 2 weeks of treatment of inhaled corticosteroid compared to no treatment.
次要结局
未报告次要终点