Sputum cytokine mapping reveals an 'IL-5, IL-17A, IL-25-high' pattern associated with poorly controlled asthma

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. Methods 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. Results 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 ((2)=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.