A new identity for asthma.

  • Published 2015 in The Lancet. Respiratory medicine

Abstract

It has been 10 years since the Global Initiative for Asthma (GINA) released their inaugural report that defi ned a global strategy for the management and prevention of asthma. Since then, this annually updated reference has been an authority on asthma care despite the fact that the disease has changed in this time, almost beyond recognition. The latest GINA guidelines, released in July, 2015, nominally redefi ne asthma, although few experts will be surprised by the new defi nition of “the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airfl ow limitation”. The real showstopper from this update is that the GINA authors no longer believe that the four established asthma subtypes (intermittent, mild persistent, moderate persistent, and severe persistent) adequately defi ne the disease. They boldly declare that asthma should no longer be a fi nal diagnosis, but rather regarded as an “umbrella term”, akin to cancer or atopy. For this to be of use, the specialty must now use precision medicine to identify populations of patients with similar genotypes, phenotypes, and clinical features. For now, that simply means that treatment choices should be made with consideration of both population-level decisions (eg, treatment effi cacy, safety, and cost) as well as patient-level decisions (such as phenotype, risk profi le, and adherence history). To fully identify and defi ne all the subtypes of asthma, rigorous analysis of large, heterogeneous populations of people with the disease must be done. This need for a personalised approach to asthma management is now largely known and accepted, and has been reinforced by various global initiatives that aim to produce a bio-clinical handprint of asthma. The fi rst of these long-term initiatives are now beginning to bear fruit. The initial reference paper from the European Unbiased BIOmarkers in PREDiction of respiratory disease outcomes (U-BIOPRED) project was published in the European Respiratory Journal on Sept 10, 2015, and the US National Heart, Lung and Blood Institute’s Severe Asthma Research Program (SARP) reached its recruitment goal earlier this year, and the results are expected imminently. The U-BIOPRED cohort has collected unbiased data from nearly 900 people with asthma, recruited from 16 sites across 11 European countries. As expected, results in the reference paper (analysis of 610 adults) showed that adults with severe disease had more symptoms, exacerbations, anxiety, and depression, with lower lung function and quality of life. Data from the U-BIOPRED children’s cohort are due to be reported soon, and the community expects similarly predictable baseline fi ndings. Hopefully these data will off er answers to outstanding questions raised in the latest GINA update such as how best to diagnose asthma in children younger than 5 years. Personalised clinical and biological profi les of childhood asthma will be crucial for creating patient risk profi les and making treatment decisions in this clinically complicated population. Although the U-BIOPRED reference data are somewhat orthodox, they set the scene for promising future analyses. The assembled data use the newest technology, measuring not just the clinical characteristics, but also defi ning the lipidome, metabolome, proteome, and transcriptome of each patient. The hope is that interrogation of this microlevel data, using knowledge management platforms such as the not-for profi t TRANSMART tool, will allow experts to distinguish diff erent phenotypes of asthma that lead to new or more eff ective treatment approaches. In a welcome move, U-BIOPRED has a liberal approach to data sharing, with the omics data being provided in public databases and all clinical results set to be released for open access within 12 months of publication. Furthermore, this ideological project has seemingly succeeded where so many others have failed, challenging the culture of how science is done by systematically collecting and analysing data in a successful pan-European collaboration involving academia, industry, and patients. Initiatives like U-BIOPRED and SARP should be applauded, and as these long-term projects come to fruition, much excitement builds for the future management of asthma. While experts are right to be optimistic about the potential use of a disease mapped under a new asthma umbrella term, stakeholders must remember that disease sub-classifi cations are not the required endpoint. What are really needed are clinically relevant phenotypes, which will then facilitate optimum patient management and treatment. ■ The Lancet Respiratory Medicine For more on U-BIOPRED see http://www.europeanlung.org/ en/projects-and-research/ projects/u-biopred/home

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