Linsey E S de Groot1, Marianne A van de Pol2, Niki Fens2, Barbara S Dierdorp3, Tamara Dekker3, Wim Kulik4, Christof J Majoor2, Jörg Hamann3, Peter J Sterk2, René Lutter5. 1. 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. 2. Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 3. Department of Experimental Immunology (Amsterdam Infection & Immunity Institute), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 4. Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 5. 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.
Abstract
BACKGROUND: Loss 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. METHODS: Twenty-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). RESULTS: Loss 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). CONCLUSIONS: The 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 REGISTRY: The Netherlands Trial Register; No.: NTR3316; URL: trialregister.nl/trial/3172.
BACKGROUND:Loss 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. METHODS: Twenty-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). RESULTS:Loss 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). CONCLUSIONS: The 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 REGISTRY: The Netherlands Trial Register; No.: NTR3316; URL: trialregister.nl/trial/3172.
Authors: Abilash Ravi; Saheli Chowdhury; Annemiek Dijkhuis; Barbara S Dierdorp; Tamara Dekker; Rianne Kruize; Yanaika S Sabogal Piñeros; Christof J Majoor; Peter J Sterk; René Lutter Journal: ERJ Open Res Date: 2022-04-19
Authors: Linsey E S de Groot; Dingyu Liu; Barbara S Dierdorp; Niki Fens; Marianne A van de Pol; Peter J Sterk; Wim Kulik; Miriam E Gerlofs-Nijland; Flemming R Cassee; Elena Pinelli; René Lutter Journal: Environ Health Date: 2020-07-03 Impact factor: 5.984
Authors: Jasper H Kappen; Elisabeth F C van Rossum; Jan A Witte; Gert-Jan Braunstahl; Wouter J B Blox; Susan C van 't Westeinde; Johannes C C M In 't Veen Journal: BMC Pulm Med Date: 2022-02-05 Impact factor: 3.317