Abstract
BackgroundAsthma 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.MethodsPatients (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.ResultsHalf 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.ConclusionWe 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.
Highlights
Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation
We previously showed that sputum analysis can be used to identify different “cytokine-high” patterns and that these patterns are linked to lung function parameters, asthma control and BMI [11, 14]
Power analysis showed that 300 asthma patients and 100 healthy subjects were required, considering that 70% of individuals will produce a sample that is useful for cytokine analysis
Summary
Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Corticosteroids and bronchodilators are the first choice treatment for patients with asthma [2]. Several other T cell related and epithelial derived cytokines are found to be increased in patients with asthma [8,9,10,11]. How they are associated which each other is not fully understood. We previously showed that sputum analysis can be used to identify different “cytokine-high” patterns and that these patterns are linked to lung function parameters, asthma control and BMI [11, 14]
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