MicroRNA-206, IL-4, IL-13, and INF-γ levels in lung tissue and plasma are increased by the stimulation of particulate matter with a diameter of ≤2.5μm, and are associated with the poor prognosis of asthma induced pulmonary arterial hypertension patients

This study aimed to explore the prognostic value of particulate matter with a diameter of ≤2.5 μm (PM2.5)-related microRNA-206 combined with interleukin (IL)-4, IL-13 and interferon-γ (INF-γ) in asthma induced pulmonary arterial hypertension (PAH). Fifty SPF BALB/c mice were divided into 5 groups: control group, asthma + PAH group, low-toxic asthma + PAH group, moderately-exposed asthma + PAH group, highly-exposed asthma + PAH group. Differences of microRNA-206, IL-4, IL-13, and INF-γ expression in lung tissue and plasma were detected. A total of 98 patients with asthma induced PAH and 98 healthy persons were collected. Patients were followed up for 12 months. Based on microarray analyses, we found that microRNA-206 may be involved in asthma induced PAH stimulated by PM2.5. Compared with healthy people, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in asthma induced PAH patients were significantly higher (<i>P</i>&lt; .05). Compared with survivors, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in non-survivors were significantly higher (<i>P</i>&lt; .05). Survival analyses showed that compared with low microRNA-206, low IL-4, low IL-13 and low INF-γ groups, survival rate of patients in high microRNA-206 (<i>χ² </i>= 4.864, <i>P</i>= .013), high IL-4 (<i>χ² </i>= 3.774, <i>P</i>= .038), high IL-13 (<i>χ² </i>= 8.375, <i>P</i>&lt; .001) and high INF-γ groups (<i>χ² </i>= 9.007, <i>P</i>&lt; .001) were significantly reduced. Established prognostic evaluation model was built and the estimated probability was 0.473. Compared with estimated probability ≤ 0.473, survival rate of patients in estimated probability&gt; 0.473 was significantly reduced (<i>χ² </i>= 17.377, <i>P</i>&lt; .001). Current model combining plasma microRNA-206, IL-4, IL-13, and INF-γ has potential significance for prognosis of asthma induced PAH.

本研究旨在探讨粒径≤2.5μm的细颗粒物（PM2.5）相关的微小RNA-206（microRNA-206）联合白细胞介素-4（IL-4）、白细胞介素-13（IL-13）及干扰素-γ（INF-γ）对哮喘诱导型肺动脉高压（PAH）的预后价值。将50只无特定病原体（SPF）级BALB/c小鼠分为5组：对照组、哮喘+PAH组、低毒性哮喘+PAH组、中暴露哮喘+PAH组、高暴露哮喘+PAH组。检测肺组织与血浆中微小RNA-206、IL-4、IL-13及INF-γ的表达差异。共收集98例哮喘诱导型PAH患者与98名健康受试者，对所有患者进行为期12个月的随访。通过微阵列分析（microarray analyses）发现，微小RNA-206可能参与PM2.5诱导的哮喘相关PAH进程。与健康受试者相比，哮喘诱导型PAH患者血浆中的微小RNA-206、IL-4、IL-13及INF-γ水平均显著升高（P<0.05）。与存活患者相比，非存活患者血浆中的微小RNA-206、IL-4、IL-13及INF-γ水平均显著升高（P<0.05）。生存分析结果显示，相较于低微小RNA-206组、低IL-4组、低IL-13组及低INF-γ组，高微小RNA-206组（χ²=4.864，P=0.013）、高IL-4组（χ²=3.774，P=0.038）、高IL-13组（χ²=8.375，P<0.001）及高INF-γ组患者的生存率均显著降低。构建的预后评估模型的预测临界概率为0.473。相较于预测概率≤0.473的患者，预测概率>0.473的患者生存率显著降低（χ²=17.377，P<0.001）。本研究构建的联合血浆微小RNA-206、IL-4、IL-13及INF-γ的预后模型，对哮喘诱导型PAH的预后评估具有潜在应用价值。