Kinetics of TH2 biomarkers in sputum of asthmatics following inhaled allergen

Rob G. J. A. Zuiker, Marcella K. Ruddy, Nicoletta Morelli, Robin Mogg, Veronica M. Rivas, Kristien van Dyck, Inge De Lepeleire, Michael R. L. Tanen, J. Diderik Boot, Ingrid M. C. Kamerling, Zuzana Diamant*

*Bijbehorende auteur voor dit werk

    Onderzoeksoutput: ArticleAcademicpeer review

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    Background: Allergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitolprocessed sputum.

    Objectives: To test whether allergen-induced TH2 inflammatory markers can be reproducibly quantified by sensitive detection techniques in ultracentrifuged sputum and the effect of fluticasone ( FP) on these endpoints.

    Methods: Thirteen allergic asthmatics with dual allergen-induced airway responses, documented during a single-blind placebo run-in period, participated in a double-blind, two-period crossover study. Each period consisted of three consecutive days, separated by] 3 weeks. Following randomization, subjects inhaled FP (500 mg bid, five doses total) or placebo. On Day 2 in each study period, allergen challenge was performed and airway response measured by forced expiratory volume in 1 sec (FEV1) until 7 h post-challenge. Sputum was induced 24 h pre-allergen and 7 and 24 h post-allergen. Sputum samples were split into two portions: TH2 biomarkers were quantified by Meso Scale multiplex platform following ultracentrifugation, and cell differentials were counted on Giemsa-May-Grunwald-stained cytospins. Allergen-induced changes in inflammatory endpoints were compared between FP and placebo using a mixed model ANCOVA.

    Results: Inhaled allergen induced dual airway responses in all subjects during both placebo periods with reproducible late asthmatic response (LAR) and increased sputum inflammatory biomarkers (IL-2, IL-4, IL-13, and eotaxin-1) and eosinophil counts. FP effectively blunted both the LAR and the inflammatory biomarkers.

    Conclusions: Combining novel, sensitive quantification methods with ultracentrifugation allows reproducible quantification of sputum biomarkers following allergen challenge, reversed by FP. This approach allows noninvasive identification of pharmacodynamic targets for anti-asthma therapies.

    Originele taal-2English
    Aantal pagina's11
    TijdschriftEuropean clinical respiratory journal
    Nummer van het tijdschrift1
    StatusPublished - 2015

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