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Clinical & Experimental Allergy

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

Authors

  • S. F. Seys,

    1. Pneumology, Department of Clinical and Experimental Medicine, Catholic University of Leuven (KU Leuven), Leuven, Belgium
    2. Pediatric Immunology, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • M. Grabowski,

    1. Clinical Immunology, Department of Microbiology and Immunology, Catholic University of Leuven (KU Leuven), Leuven, Belgium
    Current affiliation:
    1. Department of Physiology, Wroclaw Medical University, Wroclaw, Poland
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  • W. Adriaensen,

    1. Department of General Practice, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • A. Decraene,

    1. Pneumology, Department of Clinical and Experimental Medicine, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • E. Dilissen,

    1. Clinical Immunology, Department of Microbiology and Immunology, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • J. A. Vanoirbeek,

    1. Department of Public Health, Occupational, Environmental and Insurance Medicine, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • L. J. Dupont,

    1. Pneumology, Department of Clinical and Experimental Medicine, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • J. L. Ceuppens,

    1. Clinical Immunology, Department of Microbiology and Immunology, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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  • D. M. A. Bullens

    Corresponding author
    • Pediatric Immunology, Catholic University of Leuven (KU Leuven), Leuven, Belgium
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Correspondence:

Dominique Bullens, Clinical immunology, CDG 8th Floor, PB 811, Gasthuisberg, 3000 Leuven, Belgium.

E-mail: dominique.bullens@med.kuleuven.be

Summary

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 (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.

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