Biomarkers of Irritant-Induced and Allergic Asthma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Allergic Asthma (AA)
|
Drug: Fluticasone propionate HFA 220
Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day.
Other Names:
|
| No Intervention: Control
|
Outcome Measures
Primary Outcome Measures
- Change in TSLP Gene Expression [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York University Langone Medical Center | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
Investigators
- Principal Investigator: Angeliki Kazeros, MD, NYU Langone Health
Study Documents (Full-Text)
More Information
Publications
None provided.- 10-01191
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Allergic Asthma (AA) | Control |
|---|---|---|
| Arm/Group Description | Fluticasone propionate HFA 220: Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day. | No fluticasone propionate HFA was given to participants. |
| Period Title: Overall Study | ||
| STARTED | 9 | 9 |
| COMPLETED | 9 | 9 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Allergic Asthma (AA) | Control | Total |
|---|---|---|---|
| Arm/Group Description | Fluticasone propionate HFA 220: Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day. | No fluticasone propionate HFA was given to participants. | Total of all reporting groups |
| Overall Participants | 9 | 9 | 18 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
29
(7)
|
33
(8)
|
30
(8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
66.7%
|
6
66.7%
|
12
66.7%
|
| Male |
3
33.3%
|
3
33.3%
|
6
33.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
11.1%
|
2
22.2%
|
3
16.7%
|
| Not Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
8
88.9%
|
7
77.8%
|
15
83.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
11.1%
|
1
5.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
11.1%
|
1
11.1%
|
2
11.1%
|
| White |
7
77.8%
|
1
11.1%
|
8
44.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
11.1%
|
6
66.7%
|
7
38.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
9
100%
|
9
100%
|
18
100%
|
Outcome Measures
| Title | Change in TSLP Gene Expression |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Two (2) weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Allergic Asthma (AA) | Control |
|---|---|---|
| Arm/Group Description | Fluticasone propionate HFA 220: Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day. | No fluticasone propionate HFA was given to participants. |
| Measure Participants | 9 | 9 |
| Mean (Standard Deviation) [Fold Change] |
0.000197
(0.000134)
|
0.000035
(0.000023)
|
Adverse Events
| Time Frame | 2 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Allergic Asthma (AA) | Control | ||
| Arm/Group Description | Fluticasone propionate HFA 220: Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day. | Fluticasone propionate HFA was not given to participant | ||
All Cause Mortality |
||||
| Allergic Asthma (AA) | Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Serious Adverse Events |
||||
| Allergic Asthma (AA) | Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Allergic Asthma (AA) | Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Angeliki Kazeros, MD |
|---|---|
| Organization | NYU Langone Health - Bellevue Hospital |
| Phone | 212-263-6479 |
| Angeliki.Kazeros@nyulangone.org |
- 10-01191