Department of Pediatrics and Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Physiol Rep. 2023 Feb;11(3):e15528. doi: 10.14814/phy2.15528.
Respiratory biomarkers have the potential to identify airway injury by revealing inflammatory processes within the respiratory tract. Currently, there are no respiratory biomarkers suitable for clinical use to identify patients that warrant further diagnostic work-up, counseling, and treatment for toxic inhalant exposures or chronic airway disease. Using a novel, noninvasive method of sampling the nasal epithelial lining fluid, we aimed to investigate if nasal biomarker patterns could distinguish healthy nonsmoking adults from active smokers and those with chronic upper and lower airway disease in this exploratory study. We compared 28 immune mediators from healthy nonsmoking adults (n = 32), former smokers with COPD (n = 22), chronic rhinosinusitis (CRS) (n = 22), and smoking adults without airway disease (n = 13). Using ANOVA, multinomial logistic regressions, and weighted gene co-expression network analysis (WGCNA), we determined associations between immune mediators and each cohort. Six mediators (IL-7, IL-10, IL-13, IL-12p70, IL-15, and MCP-1) were lower among disease groups compared to healthy controls. Participants with lower levels of IL-10, IL-12p70, IL-13, and MCP-1 in the nasal fluid had a higher odds of being in the COPD or CRS group. The cluster analysis identified groups of mediators that correlated with disease status. Specifically, the cluster of IL-10, IL-12p70, and IL-13, was positively correlated with healthy and negatively correlated with COPD groups, and two clusters were correlated with active smoking. In this exploratory study, we preliminarily identified groups of nasal mucosal mediators that differed by airway disease and smoking status. Future prospective, age-matched studies that control for medication use are needed to validate these patterns and determine if nasosorption has diagnostic utility for upper and lower airway disease or injury.
呼吸生物标志物有可能通过揭示呼吸道内的炎症过程来识别气道损伤。目前，尚无适合临床使用的呼吸生物标志物可用于识别需要进一步诊断、咨询和治疗毒性吸入物暴露或慢性气道疾病的患者。本研究采用一种新的、非侵入性的方法来采样鼻上皮衬液，旨在研究鼻生物标志物模式是否能区分健康的不吸烟成年人、慢性阻塞性肺疾病（COPD）的前吸烟者、慢性鼻-鼻窦炎（CRS）患者和无气道疾病的吸烟成年人。我们比较了 28 种免疫介质，包括健康不吸烟成年人（n=32）、有 COPD 的前吸烟者（n=22）、CRS 患者（n=22）和无气道疾病的吸烟成年人（n=13）。采用方差分析、多项逻辑回归和加权基因共表达网络分析（WGCNA），我们确定了免疫介质与各队列之间的关系。与健康对照组相比，疾病组中六种介质（IL-7、IL-10、IL-13、IL-12p70、IL-15 和 MCP-1）水平较低。鼻液中 IL-10、IL-12p70、IL-13 和 MCP-1 水平较低的参与者患 COPD 或 CRS 的几率较高。聚类分析确定了与疾病状态相关的介质组。具体来说，IL-10、IL-12p70 和 IL-13 这一组介质与健康相关，与 COPD 组呈负相关，而另外两组与主动吸烟相关。在这项探索性研究中，我们初步确定了与气道疾病和吸烟状态不同的鼻黏膜介质组。需要进行前瞻性、年龄匹配的研究来验证这些模式，并确定鼻吸是否对上下气道疾病或损伤具有诊断价值。
