Biomarkers of Irritant-Induced and Allergic Asthma

• Status: Completed
• Trial end date: 2019-10-23
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Treatments: Fluticasone; Xhance

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.