title: Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease.
abstract: Clinical asthma is very widely assumed to be the net result of excessive inflammation driven by aberrant T-helper-2 (Th2) immunity that leads to inflamed, remodelled airways and then functional derangement that, in turn, causes symptoms. This notion of disease is actually poorly supported by data, and there are substantial discrepancies and very poor correlation between inflammation, damage, functional impairment, and degree of symptoms. Furthermore, this problem is compounded by the poor understanding of the heterogeneity of clinical disease. Failure to recognise and discover the underlying mechanisms of these major variants or endotypes of asthma is, arguably, the major intellectual limitation to progress at present. Fortunately, both clinical research and animal models are very well suited to dissecting the cellular and molecular basis of disease endotypes. This approach is already suggesting entirely novel pathways to disease-eg, alternative macrophage specification, steroid refractory innate immunity, the interleukin-17-regulatory T-cell axis, epidermal growth factor receptor co-amplification, and Th2-mimicking but non-T-cell, interleukins 18 and 33 dependent processes that can offer unexpected therapeutic opportunities for specific patient endotypes.
authors.affiliation: Lung Disease Research Group, Departments of Medicine and Pharmacology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Anderson
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000402:Airway Obstruction / Q000209:etiology; D001249:Asthma / Q000145:classification / Q000276:immunology* / Q000628:therapy; D004804:Eosinophils / Q000276:immunology / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D018448:Models, Immunological; D012720:Severity of Illness Index; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones