Creatine kinase is decreased in childhood asthma

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• dc.contributor.author Guerra, Stefano
• dc.contributor.author Lavi, Iris
• dc.contributor.author Carsin, Anne-Elie
• dc.contributor.author Vidal, Marta
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author García Aymerich, Judith
• dc.contributor.author Dobaño, Carlota
• dc.contributor.author Kogevinas, Manolis
• dc.contributor.author Sunyer Deu, Jordi
• dc.contributor.author Antó i Boqué, Josep Maria
• dc.date.accessioned 2023-10-25T06:28:29Z
• dc.date.issued 2023
• dc.description.abstract Rationale: The identification of novel molecules associated with asthma may provide insights into the mechanisms of disease and their potential clinical implications. Objectives: To conduct a screening of circulating proteins in childhood asthma and to study proteins that emerged from human studies in a mouse model of asthma. Methods: We included 2,264 children from eight birth cohorts from the Mechanisms of the Development of ALLergy project and the Tucson Children's Respiratory Study. In cross-sectional analyses, we tested 46 circulating proteins for association with asthma in the selection stage and carried significant signals forward to a validation and replication stage. As CK (creatine kinase) was the only protein consistently associated with asthma, we also compared whole blood CK gene expression between subjects with and without asthma (n = 249) and used a house dust mite (HDM)-challenged mouse model to gain insights into CK lung expression and its role in the resolution of asthma phenotypes. Measurements and Main Results: As compared with the lowest CK tertile, children in the highest tertile had significantly lower odds for asthma in selection (adjusted odds ratio, 95% confidence interval: 0.31; 0.15-0.65; P = 0.002), validation (0.63; 0.42-0.95; P = 0.03), and replication (0.40; 0.16-0.97; P = 0.04) stages. Both cytosolic CK forms (CKM and CKB) were underexpressed in blood from asthmatics compared with control subjects (P = 0.01 and 0.006, respectively). In the lungs of HDM-challenged mice, Ckb expression was reduced, and after the HDM challenge, a CKB inhibitor blocked the resolution of airway hyperresponsiveness and reduction of airway mucin. Conclusions: Circulating concentrations and gene expression of CK are inversely associated with childhood asthma. Mouse models support a possible direct involvement of CK in asthma protection via inhibition of airway hyperresponsiveness and reduction of airway mucin.
• dc.format.mimetype application/pdf
• dc.identifier.citation Guerra S, Ledford JG, Melén E, Lavi I, Carsin AE, Stern DA, et al. Creatine kinase is decreased in childhood asthma. Am J Respir Crit Care Med. 2023 Mar 1;207(5):544-52. DOI: 10.1164/rccm.202010-3746OC
• dc.identifier.doi http://dx.doi.org/10.1164/rccm.202010-3746OC
• dc.identifier.issn 1073-449X
• dc.identifier.uri http://hdl.handle.net/10230/58124
• dc.language.iso eng
• dc.publisher American Thoracic Society
• dc.relation.ispartof Am J Respir Crit Care Med. 2023 Mar 1;207(5):544-52
• dc.rights Originally Published in: Guerra S, Ledford JG, Melén E, Lavi I, Carsin AE, Stern DA, et al. Creatine kinase is decreased in childhood asthma. Am J Respir Crit Care Med. 2023 Mar 1;207(5):544-52. DOI: 10.1164/rccm.202010-3746OC. Copyright © 2023 by the American Thoracic Society. The final publication is available at http://dx.doi.org/10.1164/rccm.202010-3746OC.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Asthma
• dc.subject.keyword Biomarkers
• dc.subject.keyword Creatine kinase
• dc.title Creatine kinase is decreased in childhood asthma
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion