Anti-remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling.
Abstract: 1. Airway wall remodelling (AWR), the structural change induced by acute and chronic inflammation in the airways, may be one of the most significant and difficult to reverse components of progressive asthma. 2. The mechanisms underlying the development of AWR are not known. Studies of only the most superficial wall structures of large airways can be conducted in living humans because of the degree of invasiveness required to measure airway structural changes. These studies reveal that currently available agents do not fully prevent or reverse AWR. Thus, animal models of asthma pathology may be used to assess the contribution of particular mediators and cells to the development of remodelling and may also prove to be useful in the initial screening of potential anti-remodelling agents. 3. Airway hyperresponsiveness and AWR stimulated by chronic antigen challenge in previously disease-free animals is the most popular of the currently used models of remodelling. Other animal models include the use of specially bred strains with intrinsic airway hyperresponsiveness or animals that have a naturally occurring asthma-like disease, such as cats with feline asthma or horses with heaves. The further development of animal models of AWR will facilitate the development of novel anti-asthma therapies.
Publication Date: 2001-07-28 PubMed ID: 11473527DOI: 10.1046/j.1440-1681.1999.03494.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Review
Summary
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This research article discusses the importance of using animal models to better understand airway wall remodelling (AWR) in asthma, and thereby develop potential anti-remodelling drugs for advanced asthma treatment.
Understanding Airway Wall Remodelling (AWR)
The main focus of the research is AWR, a significant structural change in the airways caused by acute and chronic inflammation, commonly linked with progressive asthma cases. The traits of AWR include:
- The mechanisms causing AWR are not fully understood yet due to the invasive procedures required to track these changes.
- Existing therapeutic agents do not completely prevent or reverse AWR, pointing towards the need for enhanced studies and new solutions.
The Role of Animal Models
Leading from the challenges faced in human studies, the authors propose the use of animal models to explore the pathology of asthma, focusing on:
- Exploring the role certain cells and mediators play in the development of AWR.
- Testing the potential effectiveness of anti-remodelling agents through initial screening.
Current Usage and Future Application of Animal Models
The research reveals that the most popular animal models currently used for studying remodelling are previously disease-free animals who undergo chronic antigen exposure to stimulate airway hyperresponsiveness alongside AWR. Additional models include:
- Special bred strains intrinsically susceptible to airway hyperresponsiveness.
- Animals with naturally occurring, asthma-like conditions such as feline asthma in cats or “heaves” in horses.
The researchers conclude by articulating their belief that further advancements in animal models of AWR can accelerate the development of innovative anti-asthma therapies.
Cite This Article
APA
Fernandes DJ, Xu KF, Stewart AG.
(2001).
Anti-remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling.
Clin Exp Pharmacol Physiol, 28(8), 619-629.
https://doi.org/10.1046/j.1440-1681.1999.03494.x Publication
Researcher Affiliations
- Department of Pharmacology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
MeSH Terms
- Airway Obstruction / etiology
- Animals
- Anti-Asthmatic Agents / pharmacology
- Anti-Asthmatic Agents / therapeutic use
- Asthma / drug therapy
- Asthma / physiopathology
- Bronchi / drug effects
- Bronchi / physiopathology
- Bronchial Hyperreactivity
- Disease Models, Animal
- Humans
Citations
This article has been cited 3 times.- Bright LA, Dittmar W, Nanduri B, McCarthy FM, Mujahid N, Costa LR, Burgess SC, Swiderski CE. Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.. Vet Med (Auckl) 2019;10:43-63.
- Hu R, Pan W, Fedulov AV, Jester W, Jones MR, Weiss ST, Panettieri RA Jr, Tantisira K, Lu Q. MicroRNA-10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway.. FASEB J 2014 May;28(5):2347-57.
- Gualano RC, Vlahos R, Anderson GP. What is the contribution of respiratory viruses and lung proteases to airway remodelling in asthma and chronic obstructive pulmonary disease?. Pulm Pharmacol Ther 2006;19(1):18-23.
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