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Corticosteroid Withdrawal-Induced Loss of Control in Mild to Moderate Asthma Is Independent of Classic Granulocyte Activation
- Source :
- Chest, 157(1), 16-25. American College of Chest Physicians
- Publication Year :
- 2020
-
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.
- Subjects :
- Pulmonary and Respiratory Medicine
Adult
Male
Granulocyte activation
Inflammation
Critical Care and Intensive Care Medicine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
neutrophils
Adrenal Cortex Hormones
Surveys and Questionnaires
Administration, Inhalation
medicine
Humans
oxidative stress
Exhaled breath condensate
030212 general & internal medicine
Prospective Studies
Asthma
Eosinophil cationic protein
business.industry
Eosinophil
asthma
medicine.disease
Blood Cell Count
Respiratory Function Tests
medicine.anatomical_structure
030228 respiratory system
chemistry
inflammation
Immunology
Sputum
Female
eosinophils
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Asymmetric dimethylarginine
Biomarkers
Granulocytes
Subjects
Details
- Language :
- English
- ISSN :
- 00123692
- Volume :
- 157
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Chest
- Accession number :
- edsair.doi.dedup.....cce70fe588060eb1ae202e5e68edce8a