Biomarkers of Irritant-Induced and Allergic Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Fluticasone propionate HFA 220
Intervention type(s): Drug
Intervention description(s): Subjects will take two (2) puffs of Fluticasone propionate HFA 220 twice a day.
Other intervention name(s): Corticosteroid
Intervention MeSH terms: Fluticasone; Xhance
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: World Trade Center; WTC; Induced Sputum; Exhaled Breath Condensate