Biomarkers of Irritant-Induced and Allergic Asthma

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone propionate HFA 220

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
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: Corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in TSLP Gene Expression	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.	Baseline and Two (2) weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Angeliki Kazeros, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): October 23, 2019
• Study Completion (Actual): October 23, 2019

Study Registration Dates

• First Submitted: April 8, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (Estimate): April 15, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Induced Sputum; Exhaled Breath Condensate; World Trade Center; WTC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 10-01191