Lower Creatine Kinase Levels Among Children with Asthma

A 2020 study aimed to explore novel molecules associated with asthma by analyzing the circulating proteins in childhood asthma. Identifying asthma-associated novel molecules could provide insights into the disease pathogenesis and its potential clinical implications. 

This experimental study investigated the role of circulating proteins (detected in asthmatic children) in a mouse model of asthma. The researchers selected 2,264 children from eight birth cohorts. A cross-sectional analysis was performed to test 46 circulating proteins for their association with asthma. Proteins showing significant associations were further validated and replicated. The researchers also compared the gene expression of CK in whole blood – between subjects with and without asthma. Additionally, they used a mouse model challenged with house dust mites (HDM) to examine CK expression in the lungs and its involvement in resolving asthma phenotypes.

Creatine kinase (CK) consistently emerged as the only asthma-associated protein among the circulating proteins. The findings suggested that children in the highest tertile of CK concentration had significantly lower odds of asthma compared to those in the lowest tertile in the selection, validation, and replication stages of the study.

Both cytosolic forms of CK (CKM and CKB) were under-expressed in the blood of asthmatic individuals compared to control subjects. In the HDM-challenged mouse model, the expression of CKB was reduced. Inhibiting CKB prevented the resolution of airway hyper-responsiveness and the reduction of airway mucin.

The results indicated an inverse association between the CK circulating concentrations and gene expression and childhood asthma. The results from the mouse model also suggested that CK may play a direct role in protecting against asthma by inhibiting airway hyperresponsiveness and reducing airway mucin.

Source: Guerra S, Ledford JG, Melén E, et al. Am J Respir Crit Care Med. 2023;207(5):544-552. doi:10.1164/rccm.202010-3746OC