Asthma persistence versus progression: Does airway smooth muscle function predict irreversible airflow obstruction?
Abstract:Asthma, a disease characterized by airway inflammation and reversible bronchoconstriction, manifests a variety of phenotypes, and in some, but not all, asthma leads to a persistent and/or progressive loss of lung function. Conceptually, asthma persistence is identified by a stable decrement in lung function over time, and asthma progression can be identified by a gradual loss in pulmonary function associated with increasing symptoms. Whether these phenotypes are determined by distinct cellular and molecular mechanisms or whether unique genotypes define asthma persistence versus progression remains unknown. Recent evidence suggests that airway remodeling in some is associated with asthma persistence and/or progression, although the direct link of airway remodeling to these phenotypes remains tenuous. The development of in vitro cell models using nontransformed human airway smooth muscle (ASM) cells has been a useful approach in defining corticosteroid sensitivity and bronchodilator response. New evidence suggests some, but not all, immunomodulatory function of ASM is modulated by corticosteroid treatment. Additionally, the combinations of interferon and TNF-α render ASM insensitive to corticosteroids. The further development of cellular and ex vivo systems that can predict corticosteroid sensitivity and bronchodilator unresponsiveness may be useful in identifying new biomarkers and therapeutic approaches to address asthma persistence and progression.
Document Type: Research Article
Affiliations: Pulmonary, Allergy and Critical Care Division, Airways Biology Initiative, University of Pennsylvania, Philadelphia, Pennsylvania
Publication date: 2009-03-01
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- Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.
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