Rationale-Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model.Objectives-To explore the application of a multivariate mathematical technique, k-means cluster analysis, for identifying distinct phenotypic groups.Methods-We performed k-means cluster analysis in three independent asthma populations. Clusters of a population managed in primary care (n = 184) with predominantly mild to moderate disease, were compared with a refractory asthma population managed in secondary care (n = 187). We then compared differences in asthma outcomes (exacerbation frequency and change in corticosteroid dose at 12 mo) between clusters in a third population of 68 subjects with predominantly refractory asthma, clustered at entry into a randomized trial comparing a strategy of minimizing eosinophilic inflammation (inflammation-guided strategy) with standard care.Measurements and Main Results-Two clusters (early-onset atopic and obese, noneosinophilic) were common to both asthma populations. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation (early-onset symptom predominant and late-onset inflammation predominant) were specific to refractoryCorrespondence and requests for reprints should be addressed to Dr. P. Haldar, M.R.C.P., Institute for Lung Health, Glenfield Hospital, Leicester, LE3 9QP, UK. ph62@le.ac.uk. Conflict of Interest Statement: P.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. I.D.P. received $2,000 for speaking at conferences organized by GlaxoSmithKline and $5,000 for speaking at conferences organized by AstraZeneca; he is in receipt of a $500,000 grant for a study of severe asthma from GlaxoSmithKline. D.E.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.A.B. has received lecture fees and conference support from AstraZeneca and GlaxoSmithKline. M.T. has received speaker's honoraria in the last 3 years for speaking at meetings sponsored by the following companies marketing respiratory products: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Schering-Plough, Teva; he has received honoraria for attending advisory panels with Altana, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MSD, Merck Respiratory, Schering-Plough, Teva; he has received sponsorships to attend international scientific meetings from GlaxoSmithKline, MSD, AstraZeneca; he has received funding for research projects from GlaxoSmithKline, MSD, AstraZeneca; he holds a research fellowship from Asthma UK. C.E.B. has received a total of $2.2 million in research funding over the last 3 years (or is pending) from AstraZeneca, Cambridge Antibody Technology, GlaxoSmithKline; he has received less than $10,000 per annum from consultancy fees from Cambridge Antibody Technology...

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control.''Asthma control'' refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline).The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) highintensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

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An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines. Clinical trial registered with www.controlled-trials.com (ISRCTN08067387).

On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often overlap and that both require individualised assessment and treatment. This paper summarises the presentations and discussions that took place during the seminar. Specifically, we discussed the need for a new taxonomy of human diseases, the role of different players in this scenario (exposome, genes, endotypes, phenotypes, biomarkers and treatable traits) and a number of unanswered key questions in the field. We also addressed how to deploy airway precision medicine in clinical practice today, both in primary and specialised care. Finally, we debated the type of research needed to move the field forward.