Sputum cytokine mapping reveals an ‘IL-5, IL-17A, IL-25-high’ pattern associated with poorly controlled asthma
Article first published online: 20 AUG 2013
© 2013 John Wiley & Sons Ltd
Clinical & Experimental Allergy
Volume 43, Issue 9, pages 1009–1017, September 2013
How to Cite
Clinical & Experimental Allergy, 2013 (43) 1009–1017., , , , , , , , .
- Issue published online: 20 AUG 2013
- Article first published online: 20 AUG 2013
- Accepted manuscript online: 15 APR 2013 10:59AM EST
- Manuscript Accepted: 4 APR 2013
- Manuscript Revised: 27 MAR 2013
- Manuscript Received: 11 SEP 2012
- airway inflammation;
- asthma control;
- asthma phenotyping;
- induced sputum
Background and objective
Asthma is a heterogeneous disease with various clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA expression patterns in an unselected group of adult asthma patients to characterize the underlying inflammatory process.
Differential cell counts and cytokine mRNA (quantified by real-time PCR) were analysed on sputum from 40 controls and 66 asthmatic adults. A ‘cytokine-high’ profile was defined if mRNA levels for that particular cytokine exceeded the 90th percentile value in the control population. Radar graphs were used to visualize cytokine profiles.
Sputum mRNA analysis confirmed heterogeneity of cytokine patterns among patients. Thirty-six patients (55%) had a Th2 cytokine pattern: ‘IL-5-high’ (n = 13), ‘IL-4-high’ (n = 17) or ‘IL-4- and IL-5-high’ (n = 6). The ‘IL-5-high’ asthma profile (n = 13) coincided with the ‘IL-25-high’ (10/13) and surprisingly also with the ‘IL-17A-high’ (11/13) profile. The ‘IL-5-/IL-25-/IL-17A-high profile was different from the ‘IL-4-high’ pattern. Patients with the ‘IL-5, IL-17A, IL-25-high’ pattern had significantly worse lung function parameters. Uncontrolled asthmatics [Asthma Control Test (ACT) < 20] had higher sputum IL-5, IL-17A and IL-25 mRNA levels compared to controlled asthmatics (P = 0.002; P = 0.002; P = 0.066) and uncontrolled asthma is more common among ‘IL-5- and IL-17A-high’ asthmatics compared to ‘IL-5-, IL-17A-low’ asthmatics (χ2 = 3.7, P = 0.027; relative risk (RR): 1.8, 95% CI = 1.1–3.1).
Conclusions and Clinical Relevance
Patients with the ‘IL-5, IL-17A, IL-25-high’ airway inflammatory pattern are often uncontrolled asthmatics, despite daily treatment. It seems worthwhile to evaluate whether measuring sputum cytokine levels might be used to assess the response to increased doses of steroids in patients with asthma.