Allergy Asthma Immunol Res.  2017 Nov;9(6):483-490. 10.4168/aair.2017.9.6.483.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis

• Kim MA
• Shin SW
• Park JS
• Uh ST
• Chang HS
• Bae DJ
• Cho YS
• Park HS
• Yoon HJ
• Choi BW
• Kim YH
• Park CS

• KMID: 2421658
• DOI: http://doi.org/10.4168/aair.2017.9.6.483

Abstract

PURPOSE
Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation.
METHODS
A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters.
RESULTS
Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation.
CONCLUSIONS
Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two.

Keyword

Asthma; cluster analysis; exacerbation

MeSH Terms

Adult*
Asthma
Clothing
Cluster Analysis*
Eosinophils
Follow-Up Studies
Humans
Inflammation
Lung
Methods
Phenotype

Figure

• 

  Fig. 1 A heap map. Hierarchical cluster analysis of 259 subjects using 12 parameters: age at enrollment, age at asthma onset, BMI, atopy, log total IgE, duration of asthma, ΔFEV1, FEV1 (% predicted), log bood eosinophils (%), sex, smoking history, and PC20. Red color indicates 100% and green color indicates 0%. The gradations of the 2 colors indicate the range from 0% to 100%. BMI, body mass index; IgE, immunoglobulin E; FEV1, forced expiratory volume in 1 second; ΔFEV1, short acting bronchodilator-induced percentage increase in FEV1; PC20, provocation concentration of methacholine inducing a 20% decrease in FEV1.

• 

  Fig. 2 Comparison of the corticosteroid dose and exacerbation frequency during follow-up. The dosages of inhaled corticosteroids (A) and systemic corticosteroids (B) are presented as fluticasone equivalents (µg/day) and prednisone equivalents (mg/year), respectively. The annual rate of exacerbation (C) was calculated as the total number of exacerbations divided by the follow-up duration (years). The subject numbers were 72 (C1), 48 (C2), 52 (C3), and 87 (C4). Box plots show the median values with interquartile ranges. P values were obtained using the Mann-Whitney U test. C1, cluster 1; C2, cluster 2; C3, cluster 3; C4, cluster 4.

• 

  Fig. 3 Kaplan-Meier plots of the accumulation risk of the first (A) and second (B) exacerbations. Y-axis, accumulation rate of exacerbation; X-axis, time to exacerbation. P values were obtained using the χ2 test.

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