Novel concepts in airway inflammation and remodelling in asthma

Abstract

The hallmark pathological features of asthma include airway eosinophilic inflammation and structural changes (remodelling) which are associated with an irreversible loss in lung function that tracks from childhood to adulthood. In parallel with changes in function, pathological abnormalities occur early, during the pre-school years, are established by school age and subsequently remain (even though symptoms may remit for periods during adulthood). Given the equal importance of inflammation and remodelling in asthma pathogenesis, there is a significant disparity in studies undertaken to investigate the contribution of each. The majority focus on the role of inflammation, and although novel therapeutics such as those targeted against T-helper cell type 2 (Th2) mediators have arisen, it is apparent that targeting inflammation alone has not allowed disease modification. Therefore, unless airway remodelling is addressed for future therapeutic strategies, it is unlikely that we will progress towards a cure for asthma. Having acknowledged these limitations, the focus of this review is to highlight the gaps in our current knowledge about the mechanisms underlying airway remodelling, the relationships between remodelling, inflammation and function, remodelling and clinical phenotypes, and the importance of utilising innovative and realistic pre-clinical models to uncover effective, disease-modifying therapeutic strategies. @ERSpublications We discuss mechanisms of airway inflammation and remodelling in asthma to uncover effective therapeutic strategies http://ow.ly/SsXiO

Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

“…41 Individuals with severe asthma have increased tissue remodelling, compared to individuals with mild-to-moderate disease. [42][43][44] However, most animal models only assess acute lung inflammation and tissue responses over a relatively short time period.…”

Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma

“…In this review, we were invited to highlight experiments conducted primarily in our laboratories (in conjunction with many collaborators) that have focused on understanding the fundamental pathways underpinning the pathogenesis of asthma by employing a range of mouse models (see for excellent reviews with broader field focus). In the development of these models, we have utilized the clinical data of the “time” to shape the development of appropriate models to gain insights into pathogenic mechanisms.…”

The Role of Mnk-1, Eukaryotic Translation Initiation Factors and Translation Control in the Pathogenesis of Asthma

“…Recent studies indicated that asthma is caused by an inheritable epigenetic event which modifies protein expression [11,34]; thus, post-transcriptional control became focus of interest. Reflecting these new data on epigenetic events and airway wall remodelling in asthma, the American Thoracic Society stated that unless airway wall remodelling is understood, there will be no cure for asthma [4]. Thus, the search for new therapeutic targets in asthma has to be promoted.…”

“…Earlier it was thought that airway wall remodelling results from term chronic inflammation in asthma or COPD [1][2][3][4]. Recent clinical studies indicated that airway wall remodelling occurs before or without inflammation [1,5,6].…”