Asthma Atopic Clinical Trial
Official title:
Identification of Allergic Asthmatics Reactive to Felis Catus (Cat Hair) Allergen Inhalation
This study is designed to identify Felis Catus, or cat hair, sensitive asthmatics who demonstrate a late phase asthmatic response after cat hair inhalation. These subjects may be invited to participate in a planned future study investigating novel asthma treatments.
Asthma is an increasingly common chronic illness among children and adults, and allergen exposure is among the most common triggers for asthma exacerbations. Exacerbations of allergic asthma are characterized by an early phase response (EPR), mediated by release of preformed mediators like histamine from mast cells, and a late phase response (LPR) 3-7 hours later mediated by chemokines and cytokines that attract leukocytes such as neutrophils and eosinophils to the airways, increase mucus production, trigger airway smooth muscle contraction, and result in airway constriction and airway hyperreactivity (AHR). The LPR does not occur in the absence of an EPR. The LPR is thought to be predominantly responsible for the symptoms associated with acute exacerbations of allergic asthma and is often used as the measure of efficacy in trials of asthma therapeutics. This group has taken a particular interest in targeting an inflammatory cytokine, Interleukin-1β, involved in both the early and late phase asthmatic responses to inhaled allergen in allergic asthmatics. In the lung, interleukin 1 beta (IL-1β) is produced by numerous cell types (including epithelial cells, macrophages, neutrophils, eosinophils, and mast cells), where it signals through its receptor to induce transcription of pro-inflammatory genes (17-19). IL-1β is increased in bronchoalveolar lavage fluid from persons with symptomatic asthma vs. those with asymptomatic asthma; likewise, immunohistochemistry of bronchial biopsies of allergic asthmatics reveal increased expression of IL-1β in both bronchial epithelial cells and macrophages. In order to better understand the role of IL-1β in allergen-induced airway inflammation, induced sputum will be obtained to determine if higher baseline sputum IL-1β concentrations or larger increases in IL-1β following allergen challenge impact non-specific airway hyperresponsiveness (via methacholine challenge), sputum granulocyte recruitment (neutrophil and eosinophil counts and exhaled nitric oxide (eNO), a marker of airway eosinophilia), or changes in expression of inflammatory or allergy-related genes. To this last point, little is known about the mechanisms contributing to response patterns in allergic asthmatics undergoing allergen challenge. Changes in gene expression occurring during the window of time between the EPR and LPR, as these expression changes may dictate whether or not a LPR occurs or to what extent it occurs. The goal of this screening protocol is to identify subjects who exhibit both an EPR and LPR and who will be eligible for enrollment in the yet to be developed IL-1β protocols. Subjects will undergo a baseline methacholine challenge to establish reactivity, then allergen exposure, followed 24 hours later by methacholine challenge. ;