Asthma Research Paper

Research Plan

(a) Significance

a.1 Allergic asthma. Asthma is characterized by airway inflammation, goblet cell hyperplasia with mucus secretion, increased IgE, airway hyper-responsiveness and airway remodeling. Asthma is a multi-factorial disease with strong genetic and environmental components (33-35). In the 2004 report from the Global Initiative for Asthma Worldwide, it was estimated that ~300 million people suffer from asthma (36). From 2001 - 2003 an average of 20 million people suffered annually from asthma the United States (2). Asthma affects all demographic groups but can disproportionately impact people based on age, sex, ethnicity, obesity and socioeconomic status and is increasing in prevalence in the United States and World-Wide

Historically, atropine-containing products--including asthma cigarettes made with herbs containing atropine and related compounds--were used to control asthma symptoms. In the 20th century, bronchodilators, including epinephrine, isoproterenol, albuterol, terbutaline and long acting adrenergic receptor agonists became available (38). Asthma inflammation was targedted by corticosteroids, with inhaled steroids coming into use over 40 years ago (39,40). Recently, leukotriene modifiers (41) IgE modifiers (42) and newer biological drugs have been used in subsets of asthmatics. Despite progress in defining mechanisms underlying asthma pathogenesis and novel biologicals that target them, clinical management of asthma for most patients has changed little (33). Current asthma guidelines rely strongly on inhaled corticosteroids and agonist receptor modulators, tying 21st century asthma management

Airway epithelial cells line the airway where they represent the first contact with inhaled insults including asthmagens (22). Airway epithelial cells express a variety of pattern recognition receptors (e.g., toll like receptors (TLRs) and protease activated receptors (PARs)) that interact with microbial components and initiate innate immune responses via cytokine, chemokine or small molecule release (21). Airway epithelial activation can lead to local activation of dendritic cells (DC; (20)) or group innate lymphoid cells (ILC2; (63)). Airway epithelial cells also can be triggered to release eicosanoids (e.g., PGE2) that can act on smooth muscle to favor bronchodilation (64,65), or dampen DC activity (66) to limit inflammation. The relationship between airway epithelium and asthma initiation/progression makes it an excellent target for drug-based asthma prevention and