Cluster Analysis and Clinical Asthma Phenotypes

Abstract

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...

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

“…Phenotypes may be based on the presence and level of inflammation, which may be termed inflammatory phenotypes [16], or based on a combination of clinical characteristics, physiological, and inflammatory markers, which may be termed clinical phenotypes [17–22]. …”

Asthma-related comorbidities

“…Various asthma inflammatory phenotypes have been described and the identification of these last can be potentially useful in the assessment of the effect of comorbid conditions on asthma and the treatment requirements [201,202]. The presence of a mainly noneosinophilic type of asthma can predict a reduced response to inhaled corticosteroids (e.g., in smokers or obese patients), while a marked eosinophilia may suggest insufficient steroid therapy (or poor compliance).…”

Recommendations for the use of bronchial thermoplasty in the management of severe asthma

“…[34] Several subgroups of bronchial asthma have now been described, including those with high symptom counts but minimal eosinophilic inflammation, and those that are inflammation dominant but have fewer daily symptoms. [35] Phenotypes may also be categorised based on biomarker profiles, and some biomarkers (e.g. blood eosinophils, serum periostin, IgE levels, FeNO, etc.)…”