Anti-remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling

• Published in: Clinical and experimental pharmacology & physiology Vol. 28; no. 8; pp. 619 - 629
• Main Authors: Fernandes, Darren J, Xu, Kai-Feng, Stewart, Alastair G
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01.08.2001
• Subjects: airway hyperresponsiveness; Airway Obstruction - etiology; airway wall remodelling; animal models; Animals; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; asthma; Asthma - drug therapy; Asthma - physiopathology; Bronchi - drug effects; Bronchi - physiopathology; Bronchial Hyperreactivity; chronic antigen challenge; Disease Models, Animal; drug therapy; Humans
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1046/j.1440-1681.1999.03494.x

SUMMARY 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.