Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.
BACKGROUND
Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking.


METHODS
Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles.


RESULTS
Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13.


CONCLUSION
We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.
['Seys|Sven F|SF|', 'Scheers|Hans|H|', 'Van den Brande|Paul|P|', 'Marijsse|Gudrun|G|', 'Dilissen|Ellen|E|', 'Van Den Bergh|Annelies|A|', 'Goeminne|Pieter C|PC|', 'Hellings|Peter W|PW|', 'Ceuppens|Jan L|JL|', 'Dupont|Lieven J|LJ|', 'Bullens|Dominique M A|DM|']
D000293:Adolescent D000328:Adult D000368:Aged D001249:Asthma D001530:Belgium D015415:Biomarkers D016000:Cluster Analysis D016207:Cytokines D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D015995:Prevalence D012307:Risk Factors D013183:Sputum D018418:Th2 Cells D055815:Young Adult
Airway inflammation Phenotype Endotype Precision medicine Type 2 inflammation