Childhood asthma is associated with low levels of creatine kinase, according to a study with over 2,000 children from eight different cohorts. The study, co-led by ISGlobal, an institution supported by “la Caixa” Foundation, also used a mouse model to provide evidence that the enzyme may be directly involved in protecting against the disease by reducing inflammation and mucus in the airways.
Asthma is the most common chronic disease in children globally. “Identifying molecules associated with asthma may help us understand the mechanisms of disease and develop personalized interventions, but there are few studies that have explored multiple circulating proteins in a large number of children,” explains Josep M. Antó, ISGlobal researcher and last author of the study.
The team led by Antó set out to identify novel molecules associated with asthma using a multi-stage, multi-cohort approach. In a first stage, they used 2 cohorts from the MeDALL project to measure 46 proteins in serum samples from around 250 children with or without asthma. In a second stage, they used samples from over 1,500 children from five other MeDALL cohorts to test proteins selected in the previous stage. Within an international collaboration, investigators further confirmed findings from the previous stage in the independent cohort of the Tucson TCRS study. A total of 2,264 children from the eight cohorts were included.
Creatine kinase (an enzyme involved in energy production) was the only protein consistently associated with asthma in the three stages - children with asthma had lower levels of the enzyme circulating in blood, as compared to controls. Furthermore, expression of the creatine kinase gene was also reduced in blood from children with asthma.
Using an experimental model in which asthma is induced in mice by exposing them to house dust mites, the researchers found that expression of creatine kinase was reduced in the lung of exposed mice, and that the inflammation and mucus in airways did not resolve when the function of the enzyme was blocked by an inhibitor. “The results in mice are consistent with our findings in children, and support the idea that creatine kinase may be directly involved in protecting against asthma,” says Stefano Guerra, first author of the study.
However, the authors warn that more work is needed to confirm causality between low levels of creatine kinase and asthma in childhood and adult life, to understand the mechanisms involved, and to determine whether circulating levels of the enzyme are predictive of developing the disease.
Guerra S, Ledford JG, Melén E. et al. Creatine Kinase is Decreased in Childhood Asthma. Am J Respir Crit Care Med. 2022 Jul 23. doi: 10.1164/rccm.202010-3746O