Biomarkers of Irritant-Induced and Allergic Asthma
| Status: | Recruiting |
|---|---|
| Conditions: | Asthma |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 4/17/2018 |
| Start Date: | December 2013 |
| End Date: | December 2018 |
| Contact: | Maria Cotrina-Vidal |
| Email: | maria.cotrina@nyumc.org |
Biomarkers of Irritant-Induced and Allergic Asthma: Phase I and Phase II
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.
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.
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.
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.
Inclusion Criteria for Phase I
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
Exclusion Criteria:
- 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.
We found this trial at
1
site
550 1st Ave
New York, New York 10016
New York, New York 10016
(212) 263-7300
Principal Investigator: Angeliki Kazeros, MD
New York University Langone Medical Center NYU NYU Langone Medical Center, a world-class, patient-centered, integrated,...
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