Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2
Issued Date
2025-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-105010061117
Journal Title
Scientific Reports
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.15 No.1 (2025)
Suggested Citation
Maneechotesuwan K., Assawabhumi J., Chankham J., Kasetsinsombat K., Htwe K.S.S., Adcock I.M. Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2. Scientific Reports Vol.15 No.1 (2025). doi:10.1038/s41598-025-07102-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111225
Title
Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
TSLP-regulated Park2 and mitophagy may be critical underlying driver of asthma exacerbations, as well as eosinophil responses to oral corticosteroids (OCS). However, detailed molecular knowledge of the molecular mechanisms involved is lacking. In a prospective cohort study at ED Siriraj Hospital, 28 consecutive patients with an acute asthma exacerbation were administered OCS treatment for one week. Serum levels of TSLP, Park2, Mul1, related cytokines, mitochondrial DNA (mtDNA), and oxidative stress were measured. The effects of TSLP, inhaled corticosteroids, NLRP3 inflammasome inhibitor, and mitochondrial-targeted antioxidant on mitophagy, mtDNA release, Park2, and Mul1 were examined in blood monocytes and in a human bronchial epithelial cell line (HBEC). Two distinct eosinophil responses to OCS treatment were observed: reduced (RE) and increased absolute blood eosinophil levels (IE). Following OCS treatment, participants with IE demonstrated stable TSLP levels and a significant rise in Park2. The IE group exhibited markedly higher baseline oxidative stress levels than the RE group at an exacerbation episode and further increase in oxidative stress after OCS treatment. TSLP augmented the induction of Park2 while inhibiting mitophagy, resulting in increased release of mtDNA from blood monocytes and human bronchial epithelial cells and stimulating inflammasome activation. Corticosteroids did not effectively suppress oxidative stress-mediated TSLP effects. The present study demonstrated potential inflammatory mechanisms in acute asthmatics with rising eosinophil counts following OCS treatment including a possible role of TSLP in suppressing mitophagy and inducing mtDNA release with concomitant inflammasome activation, and Park2 expression.
