Models and approaches to understand the role of airway remodelling in disease

Airway remodelling is a collective term for changes in the amount or organisation of the cellular and molecular constituents of the airway wall. Remodelling occurs in and is associated with the pathophysiology of airways diseases including asthma and chronic obstructive pulmonary disease. The remodelling that occurs in these diseases exhibits both shared and distinct features. Remodelling is generally considered to be deleterious to airway function but recent studies also indicate potential protective effects. However, the true impact of different aspects of the remodelling process on lung function, both negative and positive, is poorly understood. In addition, the genetic susceptibility and processes by which environmental insults drive the cell and molecular events which result in airway remodelling and the potential for therapeutic reversibility are also incompletely understood. The last 10–15 years has seen the development of animal models of airway remodelling which have been refined and modified as new factors such as exacerbations and early life influences have been recognised as being of importance. In addition, invertebrate models have been put forward and complex in vitro culture systems and lung slice preparations developed. In parallel, imaging technology has developed to an extent where it is feasible using a combination of techniques to image structural components, cells and proteins in the airway wall as well as to analyse biological processes, cell and receptor activation non-invasively over time. The integration of data from in vivo and in vitro models together with use of imaging techniques in man and animals should allow validation of models, further our understanding of the pathophysiology of airway remodelling and potentially improve predictive accuracy for the translation of novel therapeutic agents into the clinic.

► Current and novel in vivo and in vitro models of airway remodelling are reviewed. ► Imaging techniques and their application to airway remodelling are highlighted. ► Using imaging techniques in man and animals may allow validation of models. ► An Integrated approach may give new insights into structure-function relationships. ► Improved models and approaches may more accurately predict efficacy of new drugs.