Creatine Kinase Is Decreased in Childhood Asthma.

Autor:	Guerra S; Asthma and Airway Disease Research Center.; ISGlobal, Barcelona, Spain., Ledford JG; Asthma and Airway Disease Research Center.; Department of Cellular and Molecular Medicine., Melén E; Department of Clinical Science and Education and.; Sachs' Children's and Youth Hospital, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden., Lavi I; ISGlobal, Barcelona, Spain., Carsin AE; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Hospital del Mar Medical Research Institute, Barcelona, Spain., Stern DA; Asthma and Airway Disease Research Center., Zhai J; Asthma and Airway Disease Research Center., Vidal M; ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Barcelona, Spain., Bustamante M; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain., Addison KJ; Asthma and Airway Disease Research Center., Vallecillo RG; Department of Molecular and Cellular Biology., Billheimer D; BIO5 Institute, and.; Department of Epidemiology and Biostatistics, University of Arizona Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona., Koppelman GH; Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Garcia-Aymerich J; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain., Lemonnier N; Institute for Advanced Biosciences, UGA-INSERM U1209-CNRS UMR5309, Site Santé, Allée des Alpes, 38700 La Tronche, France., Fitó M; Cardiovascular Risk and Nutrition Group and.; CIBER de Fisiopatología de la Obesidad y Nutricion (CIBEROBN), Institute of Health Carlos III, Madrid, Spain., Dobaño C; ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Barcelona, Spain., Kebede Merid S; Department of Clinical Science and Education and., Kull I; Department of Clinical Science and Education and.; Sachs' Children's and Youth Hospital, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden., McEachan RRC; Bradford Institute for Health Research, Bradford, United Kingdom., Wright J; Bradford Institute for Health Research, Bradford, United Kingdom., Chatzi L; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Kogevinas M; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Hospital del Mar Medical Research Institute, Barcelona, Spain., Porta D; Department of Epidemiology, Lazio Regional Health Service, Rome, Italy., Narduzzi S; Department of Epidemiology, Lazio Regional Health Service, Rome, Italy., Ballester F; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Nursing School, Universitat de València, Valencia, Spain.; FISABIO-Universitat Jaume I-Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain., Esplugues A; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Nursing School, Universitat de València, Valencia, Spain.; FISABIO-Universitat Jaume I-Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain., Zabaleta C; Pediatrics Service, Hospital de Zumárraga, Gipuzkoa, Spain.; Group of Environmental Epidemiology and Child Development, Biodonostia Health Research Institute, San Sebastian, Spain., Irizar A; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Group of Environmental Epidemiology and Child Development, Biodonostia Health Research Institute, San Sebastian, Spain., Sunyer J; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Hospital del Mar Medical Research Institute, Barcelona, Spain., Halonen M; Asthma and Airway Disease Research Center., Bousquet J; University Hospital Montpellier, France; and.; Respiratory and Environmental Epidemiology Team, INSERM 1018, CESP Centre, Villejuif, France., Martinez FD; Asthma and Airway Disease Research Center., Anto JM; ISGlobal, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Hospital del Mar Medical Research Institute, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2023 Mar 01; Vol. 207 (5), pp. 544-552.
DOI:	10.1164/rccm.202010-3746OC
Abstrakt:	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.
Databáze:	MEDLINE
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