Asthmatic children had significantly elevated levels of circadian clock proteins (BMAL1, CLOCK, CRY1, PER1, and PER2) compared to healthy controls, and these elevated levels correlated with poorer asthma control, reduced pulmonary function, and poor sleep quality, with PER2 and BMAL1 showing the highest individual diagnostic value (AUC ~0.75).
Key Findings
Results
Asthmatic children had significantly elevated levels of five circadian clock proteins compared to healthy controls.
Patients with asthma aged 8-17 years were compared to age-matched healthy controls.
BMAL1, CLOCK, CRY1, PER1, and PER2 were all significantly elevated in asthmatic children (p<0.01).
CRY2 levels were not significantly different between asthmatic children and controls.
Serum circadian protein levels were quantified using standardized measurement methods across both groups.
Results
Poor sleep quality in asthmatic children was associated with higher levels of specific circadian clock proteins.
Sleep quality was assessed using the Children's Sleep Habits Questionnaire (CSHQ).
Poor sleep quality was associated with higher levels of BMAL1, PER1, and PER2 (p<0.01).
Not all elevated circadian proteins were associated with poor sleep quality; CRY1 and CLOCK were not specifically highlighted in this association.
The study population included children aged 8-17 years with asthma.
Results
Elevated circadian protein levels correlated with poorer asthma control and reduced pulmonary function.
Asthma control was assessed via the Asthma Control Test (ACT).
Pulmonary function was assessed using spirometry, measuring FEV1, FEV1/FVC, and PEF.
Elevated circadian protein levels correlated with poorer asthma control and reduced pulmonary function parameters (FEV1, FEV1/FVC, PEF; p<0.05).
The direction of correlation indicated that higher protein levels corresponded with worse clinical outcomes.
Results
PER2 and BMAL1 individually showed the highest discriminative ability as biomarkers, while a combined model of all proteins provided complementary rather than singularly dominant contributions.
Individually, PER2 and BMAL1 showed the highest AUCs of approximately 0.75.
A combined model incorporating all circadian proteins yielded an AUC of approximately 0.76.
The marginal improvement from individual to combined model (~0.75 to ~0.76) indicated complementary rather than singularly dominant contributions among the proteins.
These AUC values characterize the proteins as having moderate discriminative ability as potential biomarkers.
Conclusions
The study characterized its findings as exploratory and concluded that circadian proteins warrant further investigation as biomarkers and for chronotherapy research rather than justifying specific dosing time recommendations at present.
Authors described the findings as 'exploratory' and stated they 'support further evaluation of circadian proteins as biomarkers in pediatric asthma.'
The authors stated the findings 'warrant investigation of chronotherapy in appropriately designed trials, rather than justifying a specific dosing time at present.'
The study enrolled children aged 8-17 years with asthma and age-matched healthy controls.
Six circadian clock proteins were quantified: BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2.
What This Means
This research suggests that children with asthma have higher blood levels of several proteins that control the body's internal 24-hour clock (circadian clock proteins) compared to healthy children. Specifically, five out of six proteins studied — BMAL1, CLOCK, CRY1, PER1, and PER2 — were significantly elevated in asthmatic children aged 8 to 17. Among these, BMAL1, PER1, and PER2 were also linked to poor sleep quality. Higher levels of these proteins were associated with worse asthma control and lower lung function measurements, suggesting a connection between the body's internal clock system and how well asthma is managed in children.
The study also tested whether these proteins could serve as diagnostic markers to distinguish asthmatic children from healthy ones. PER2 and BMAL1 individually performed moderately well (with an AUC of about 0.75, where 1.0 would be perfect), and combining all the proteins together produced a similar result (AUC ~0.76), suggesting each protein contributes somewhat independently rather than one protein dominating the others.
This research matters because it points to a biological link between the body clock system and childhood asthma that is not yet routinely considered in clinical care. The authors emphasize that these are early, exploratory findings and do not yet support changing when children take their asthma medications. However, the results suggest that future research into 'chronotherapy' — timing medical treatments to work with the body's internal clock — could be worthwhile. Circadian proteins, particularly PER2 and BMAL1, may eventually help doctors better understand and personalize asthma treatment in children.
Yaşar A, Çelik F, Aydın T, Büyükkayhan D. (2026). Circadian rhythms and asthma: exploring the impact of circadian clock proteins on childhood asthma management.. Allergologia et immunopathologia. https://doi.org/10.15586/aei.v54i1.1477