Association of beta-arrestin gene expression with corticosteroids -long-acting beta-agonist step-up therapy in children with asthma

Abstract

Background

Beta2-adrenergic receptors (β₂-ARs) mediate airway relaxation through cAMP-dependent and cAMP-independent pathways. Studies have shown the existence of alternative β-arrestin mediated pathways, downstream of β₂-AR that play a role in inflammation. The higher β-arrestin expression is linked to the attenuation of agonist induced broncho dilating signaling pathways in human airway smooth muscle cells. The Long-acting beta-agonists (LABAs) are the preferred approach to inhaled corticosteroids (ICS). LABAs act on β₂-ARs in bronchial smooth muscles and cause bronchodilation. The ICS/LABA therapy provides synergistic effects in asthma control that are not achieved by any of them alone. Despite this, a subset of patients remains symptomatic of the treatment. Deterioration of asthma control can be due to β-arrestin-dependent pathways and the effects of ICS/LABA therapy on β-arrestin expression have not been explored.

Methods

The study included 76 asthmatic children taking ICS-LABA therapy and 29 healthy children with no respiratory disease and family history of asthma. After excluding Children with ABPA, 70 asthmatic children were categorized into responders and non-responders. The gene expression of β-arrestin1 &2 gene was analyzed.

Results

Among the 70 subjects 34 were responders and 36 were non-responders. β-arrestin 1 mRNA expression was significantly higher in the non-responder's group as compared to healthy controls [3.3 (1.46–6.19) vs 0.72 (0.4–3.4); p = 0.002]. No significant difference was observed in β-arrestin2 mRNA expression among all groups.

Conclusions

β-arrestin-1 gene expression can be associated with symptomatic conditions in patients. Studies with large sample sizes are required in steroids-resistant asthma to explore the link between β-arrestin and asthma.