Features of asthma which provide meaningful insights for understanding the disease heterogeneity.
Clin Exp Allergy
; 48(1): 39-47, 2018 01.
Article
in En
| MEDLINE
| ID: mdl-28833810
ABSTRACT
BACKGROUND:
Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results.OBJECTIVE:
To develop a framework for the discovery of stable and clinically meaningful asthma subtypes.METHODS:
We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process.RESULTS:
Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. CONCLUSIONS AND CLINICAL RELEVANCE An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asthma
/
Severity of Illness Index
/
Models, Immunological
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Clin Exp Allergy
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
United kingdom