Corticosteroid Withdrawal-Induced Loss of Control in Mild to Moderate Asthma Is Independent of Classic Granulocyte Activation.
Chest
; 157(1): 16-25, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31622588
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Corticosteroides
/
Granulócitos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
/
Male
Idioma:
En
Revista:
Chest
Ano de publicação:
2020
Tipo de documento:
Article