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.

Airway goblet cell hyperplasia in asthma: hypersecretory and anti‐inflammatory?

“…Airway goblet cell hyperplasia can be readily induced in animal models of asthma [22]. As in the paper herein by Kasper and colleagues [5], systemic ovalbumin sensitization followed by repeated inhaled ovalbumin challenge in guinea‐pigs and rodents results in high blood IgE concentrations and induces inflammatory changes characteristic of asthma, including pulmonary eosinophilia and increased expression of Th2 cytokines [3, 4]. Remodelling includes increased smooth muscle mass, thickening of the sub‐basement membrane region and goblet cell hyperplasia.…”

“…For example, goblet cell hyperplasia is linked to chronic mucous hypersecretion and consequent airflow obstruction. The perceived impact of airway remodelling on morbidity and mortality in asthma has prompted the development of animal models to aid understanding of basic mechanisms underlying asthma pathophysiology and to rationalize development of therapeutic drugs [3, 4]. These models are beginning to define the pathways involved in airway remodelling.…”

The role of oxidative stress in an equine model of human asthma

“…4,[11][12][13][14] An obvious downside to studying horses is the cost of their management. 2 However, there are several advantages of using horses to study respiratory disease. For example, the horses' environment, diet and management can be closely regulated, and techniques such as broncho-alveolar lavage (BAL) are well-tolerated in horses, which can therefore be performed repeatedly to follow the time course of an inflammatory response.…”

An Experimental Model of Allergic Asthma in Cats Sensitized to House Dust Mite or Bermuda Grass Allergen

“…Characteristic histologic changes associated with chronic asthma in humans include epithelial cell hyperplasia and desquamation, subepithelial fibrosis, an inflammatory cell influx, smooth muscle hypertrophy and hyperplasia, submucosal gland hyperplasia, and an increased vascularity [36, 37]. In the cats of this study, histologic changes were seen both in the proximal and distal airways, similar to humans.…”