Circulating miRNA expression in asthmatics is age-related and associated with clinical asthma parameters, respiratory function and systemic inflammation

Abstract

Background: The course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA. Methods: Control and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry. Results: No difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs. Conclusion: Serum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.