Cluster analysis and clinical asthma phenotypes
Open accessAbstract
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 refractory asthma. Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster (3.53 [SD, 1.18] vs. 0.38 [SD, 0.13] exacerbation/patient/yr, P = 0.002) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster (mean difference, 1,829 μg beclomethasone equivalent/d [95% confidence interval, 307–3,349 μg]; P = 0.02). Conclusions: Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms.
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Female obesity has been associated with a pauci-eosinophil and non-atopic asthma endotype that is symptom-predominant and less steroid-responsive.
“While this review did not find significant sex-related differences, female obesity has been associated with a pauci-eosinophil and non-atopic asthma endotype that is symptom-predominant and less steroid-responsive in previous cluster and LCA (16, 28).”
From Epidemiology of Asthma in Children and Adults (2019) · cites this paper as [16]
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- Authors
- Haldar, P., Pavord, I. D., Shaw, D. E., Berry, M. A., Thomas, M., Brightling, C. E., Wardlaw, A. J., & Green, R. H.
- Affiliations
- Institute for Lung Health, Glenfield Hospital, Leicester, United Kingdom
- Glenfield Hospital (GB)
- University of Aberdeen (GB)
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-08-01
- Volume
- 178
- Issue
- 3
- Pages
- 218-224
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- PMC
- PMC3992366
- OpenAlex
- W2106715003
- Cited by
- 1,987
- References
- 25
- Citations by year
- 2026: 49 · 2025: 63 · 2024: 87 · 2023: 105 · 2022: 104 · 2021: 128 · 2020: 133 · 2019: 138 · 2018: 155 · 2017: 167 · 2016: 140 · 2015: 133 · 2014: 134 · 2013: 133 · 2012: 110
- FWCI
- 45.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Funders
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Teva Pharmaceutical Industries
- Wellcome Trust (082265)
- Asthma and Lung UK
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Keywords
- asthma phenotypes, asthma heterogeneity, K-means clustering, refractory asthma, eosinophilic airway inflammation, asthma exacerbations, inhaled corticosteroid dose reduction, allergic asthma, obesity
- MeSH terms
- Adrenal Cortex Hormones, Adult, Aged, Asthma, Classification, Female, Humans, Inflammation, Male, Middle Aged, Phenotype, Prospective Studies, Cluster Analysis
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