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 (χ(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.
['Seys|S F|SF|', 'Grabowski|M|M|', 'Adriaensen|W|W|', 'Decraene|A|A|', 'Dilissen|E|E|', 'Vanoirbeek|J A|JA|', 'Dupont|L J|LJ|', 'Ceuppens|J L|JL|', 'Bullens|D M A|DM|']
D000328:Adult D001249:Asthma D016022:Case-Control Studies D016207:Cytokines D005260:Female D005786:Gene Expression Regulation D006801:Humans D020381:Interleukin-17 D015848:Interleukin-5 D008297:Male D008875:Middle Aged D012307:Risk Factors D013183:Sputum D018418:Th2 Cells D059467:Transcriptome D016896:Treatment Outcome D055815:Young Adult
cytokine asthma control airway inflammation asthma phenotyping induced sputum