Study of the Mechanisms of Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to identify the causes of asthma that were not previously
      suspected, to better understand the effects of inhaled steroids on asthma and to identify new
      way to treat asthma. In order to take advantage of the most current scientific expertise, we
      (scientists at UCSF) plan to work together with Genentech Inc. We believe that working with
      Genentech will provide the best chance of developing new treatments for asthma.
    

Detailed description: 
      Asthma is a common airway disease with persistent unmet needs on terms of treatment. Although
      many asthmatics enjoy good control of their disease by using regularly scheduled
      corticosteroid treatment, a significant minority do not achieve optimal control with steroids
      and suffer asthma exacerbations which can be severe and even fatal. Asthma pathophysiology is
      complex and involves multiple cell types and multiple signaling mechanisms. One approach to
      this complexity has been to study responses of isolated airway cells to experimental
      conditions which model asthmatic inflammation; another has been genetic manipulations of
      candidate mediators of asthma in inbred mice. These studies have yielded important insights
      about possible mechanisms of asthma in humans, but the relevance of these mechanisms to human
      disease has not always been proven, and it is possible that unsuspected mechanism have not
      yet been revealed by these approaches. In the studies proposed here we will take an
      experimental approach which takes advantage of the distinct clinical phenotype of human
      asthma, the ability to measure steroid response in asthma, the relative ease of collecting
      airway cells and tissues by bronchoscopy, and the availability of new technologies such as
      high density microarrays which have probes for all genes in the genome or proteomics which
      can identify all proteins present in a biologic sample. Using this approach, we will identify
      differential expression of genes and proteins in airway cells and tissues in asthma that can
      then be explored further in cell and animal model systems to determine their potential as
      drug targets in asthma. We further believe that our approach will identify previously
      unsuspected mechanisms of action of corticosteroids in airway cells and tissues in asthma.
      Presently, relatively little is known about why some asthmatics respond well and some poorly
      to steroids and closing this gap in knowledge will help identify candidate genes and proteins
      to target in order to address unmet therapeutic needs in asthmatics with steroid resistant
      asthma.
    

Intervention name(s): Pulmicort
Intervention type(s): Drug
Intervention description(s): inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Other intervention name(s): Budesonide
Intervention MeSH terms: Budesonide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science