Asthma is an inflammatory airways disease which is often characterized by reversible obstruction. In certain patients, however, this inflammation may lead to irreversible obstruction, secondary to structural changes. These airway changes include mucus cell hyperplasia/hypertrophy, increased thickness of the airway basement membrane by deposition of collagen and other extracellular proteins, increased vascularity, altered neuronal responses and hypertrophy of the airway smooth muscle. Current evidence suggests that these changes may not be prevented with anti-inflammatory treatment such as corticosteroids, but this is controversial. TNF-a is an important cytokine in asthma which has both proinflammatory and profibrotic properties and its role in promoting structural changes in the airway has been noted in animal models of asthma and in humans. Importantly, approaches to block the effects of TNF-a have proven to be quite effective in a number of other chronic inflammatory diseases. Given this background, it is my hypothesis that TNF-a is an important cytokine in asthma in the regulation of mucus-cell hyperplasia. Furthermore, modulation of TNF-a, using an anti-TNF-a antibody may be an appropriate adjunctive therapy in asthma, preventing or attenuating mucus-cell hyperplasia/hypertrophy (metaplasia in the murine system) and avoiding the consequences of long-term corticosteroid use. The overall goal of this proposal is to evaluate the effects of TNF-a on an important aspect of airway pathology in asthma, mucus-cell hyperplasia/hypertrophy. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI063932-03
Application #
7426352
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2006-07-01
Project End
2011-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
3
Fiscal Year
2008
Total Cost
$124,065
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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