Circadian rhythms and asthma: exploring the impact of circadian clock proteins on childhood asthma management

Background: Asthma is a chronic inflammatory disorder characterized by airway inflammation and hyperresponsiveness, significantly impacting children’s quality of life. Despite optimal treatment, some children experience poor asthma control, partly attributed to circadian rhythm disturbances. Objectives: This study aimed to evaluate circadian clock protein levels and their relationship with asthma control and sleep quality in children. Methods: Patients with asthma aged 8–17 years and age-matched healthy controls were enrolled. Pulmonary function was assessed using spirometry, asthma control via the Asthma Control Test (ACT), and sleep quality using the Children’s Sleep Habits Questionnaire (CSHQ). Serum circadian protein levels (BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2) were quantified and compared between groups. Results: Asthmatic children had significantly elevated levels of BMAL1, CLOCK, CRY1, PER1, and PER2 compared to controls (p<0.01); however, CRY2 was not significantly different. Poor sleep quality was associated with higher levels of BMAL1, PER1, and PER2 (p<0.01). Elevated circadian protein levels correlated with poorer asthma control and reduced pulmonary function (FEV1, FEV1/FVC, PEF; p<0.05). Individually, PER2 and BMAL1 showed the highest AUCs (~0.75), while a combined model of all proteins yielded an AUC of ~0.76, indicating complementary rather than singularly dominant contributions. Conclusion: These exploratory findings support further evaluation of circadian proteins as biomarkers in pediatric asthma and warrant investigation of chronotherapy in appropriately designed trials, rather than justifying a specific dosing time at present. Circadian proteins, particularly PER2 and BMAL1, may serve as potential biomarkers and support precision-based chronotherapy in pediatric asthma management.