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

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.

Circulating miRNA Expression in Asthmatics is Age-related and Associated with Clinical Asthma Parameters, Respiratory Function and Systemic Inflammation

Background: Asthma in elderly asthmatics (EA) may have a different course than in non-elderly asthmatics (nEA), which may be partially associated with age-dependent aberrant immune response. The aim of the study was to assess the association of serum miRNA expression with asthma characteristics and systemic inflammation markers in EA and nEA.Methods: In 28 EA and 31 nEA patients, control and severity of asthma, pulmonary function and FeNO were assessed. The control group included 59 age-matched non-asthmatics. Expression of selected miRNAs in serum was measured with RT-PCR, and proinflammatory cytokines were assayed by ELISA or flow cytometry. Results: EA had lower serum expression of miRNA -19b and -146a, while the nEA had a higher expression of miRNA -146a than controls. EA had a higher serum expression of miRNA -106a and -126a than nEA. In all asthmatics, miRNA -106a and -126a were correlated with age. Only in nEA, the expression of selected miRNAs was associated with the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO concentration. Elevated levels of systemic inflammation markers were associated with impaired respiratory function in all asthmatics and with worsened asthma control in the elderly patients. A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs.Conclusion: Serum miRNA expression was correlated 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.

A Single Institution Retrospective Study of the Clinical Efficacy of Tiotropium Respimat in Never-Smoking Elderly Asthmatics with Irreversible Airflow Limitation

Objective In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium RespimatⓇ (Tio-Res) in symptomatic, never-smoking, elderly asthmatics with irreversible airflow limitation despite the use of high-dose inhaled corticosteroids (ICS) plus long-acting β2-adrenoceptor agonists (LABA). Methods The Asthma Control Test™ (ACT), pulmonary function tests, morning and evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS® peak flow meter), and respiratory impedance (assessed with MostGraph®) were measured before and after a minimum of one year of Tio-Res 5 µg/day administration. Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA, were analyzed. Results All patients were female (mean age, 81.6 years). Tio-Res led to statistically significant improvements in the total ACT score (19.9 to 23.6), FVC and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also resulted in statistically significant improvements in respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). Conclusions Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.