• Linsey E S de Groot, Marianne A van de Pol, Niki Fens, Barbara S Dierdorp, Tamara Dekker, Wim Kulik, Christof J Majoor, Jörg Hamann, Peter J Sterk, and René Lutter.
• Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology (Amsterdam Infection & Immunity Institute), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: l.e.degroot@amsterdamumc.nl.
• Chest. 2020 Jan 1; 157 (1): 16-25.

BackgroundLoss of asthma control and asthma exacerbations are associated with increased sputum eosinophil counts. However, whether eosinophils, or the also present neutrophils, actively contribute to the accompanying inflammation has not been extensively investigated.MethodsTwenty-three patients with mild to moderate asthma were included in a standardized prospective inhaled corticosteroid (ICS) withdrawal study; 22 of the patients experienced loss of asthma control. The study assessed various immune, inflammatory, and oxidative stress parameters, as well as markers of eosinophil and neutrophil activity, in exhaled breath condensate, plasma, and sputum collected at three phases (baseline, during loss of control, and following recovery).ResultsLoss of asthma control was characterized by increased sputum eosinophils, whereas no differences were detected between the three phases for most inflammatory and oxidative stress responses. There were also no differences detected for markers of activated eosinophils (eosinophil cationic protein and bromotyrosine) and neutrophils (myeloperoxidase and chlorotyrosine). However, free eosinophilic granules and citrullinated histone H3, suggestive of eosinophil cytolysis and potentially eosinophil extracellular trap formation, were enhanced. Baseline blood eosinophils and changes in asymmetric dimethylarginine (an inhibitor of nitric oxide synthase) in plasma were found to correlate with the decrease in FEV1 percent predicted upon ICS withdrawal (both, rs = 0.46; P = .03).ConclusionsThe clinical effect in mild to moderate asthma upon interruption of ICS therapy is not related to the classic inflammatory activation of eosinophils and neutrophils. It may, however, reflect another pathway underlying the onset of loss of disease control and asthma exacerbations.Trial RegistryThe Netherlands Trial Register; No.: NTR3316; URL: trialregister.nl/trial/3172.Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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