Biomarkers of Irritant-Induced and Allergic Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone propionate HFA 220
Intervention description: Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day.
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: World Trade Center; WTC; Induced Sputum; Exhaled Breath Condensate

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.
    

Eligibility 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.