Jena University Hospital, CF-Center, Jena, Germany.
Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
Pediatr Pulmonol. 2018 Jul;53(7):881-887. doi: 10.1002/ppul.24004. Epub 2018 Apr 6.
Previously, we found linkages of inflammatory mediator levels in CF upper airways (UAW) sampled by nasal lavage (NL) to disease severity and to chronic pathogen colonization such as Pseudomonas aeruginosa (PsA). Here, we assess UAW cytokine dynamics in CF patients with a new PsA colonization.
We measured cytokines in 149 longitudinally obtained NL samples from 34 CF patients. Cytokine concentrations determined prior to, at the time of de novo PsA detection in either UAW or lower airways (LAW), and in a subsequent PsA free period in newly colonized patients (PsA-new/n = 7) were compared to levels of not- (PsA-free/n = 13) and chronically colonized patients (PsA-chron/n = 14). Moreover, serological and clinical data were compiled.
Concentrations of IL-1ß, IL-6, and IL-8 in samples taken prior to new PsA detection were comparable with PsA-free patients. At the time of PsA detection and, most interestingly, irrespective of whether PsA occurred in the UAW or LAW, IL-8 increased (P = 0.009) and IL-6 tended to increase (P = 0.081). In these patients, detection of PsA was not related to elevated PsA antibody-titers. In comparison, NL of PsA-chron patients revealed generally lower IL-8 and IL-1β concentrations as in PsA-free patients, most likely due to a consequent antibiotic and anti-inflammatory therapy (eg, with azithromycin).
Monitoring cytokine dynamics in the UAW by serial NL sampling may be valuable in the early phase of PsA acquisition and, thus, increase the chance to adjust treatment options early and more specifically.
此前,我们发现通过鼻灌洗(NL)取样的 CF 上呼吸道(UAW)中炎症介质水平与疾病严重程度以及慢性病原体定植有关,如铜绿假单胞菌(PsA)。在这里,我们评估了 CF 患者新出现 PsA 定植时的 UAW 细胞因子动态。
我们对 34 例 CF 患者的 149 个纵向获得的 NL 样本进行了细胞因子测量。在 UAW 或下呼吸道(LAW)新发现 PsA 时以及新定植患者的后续无 PsA 期(PsA-new/n=7)时测定的细胞因子浓度与无 PsA(PsA-free/n=13)和慢性定植患者(PsA-chron/n=14)的浓度进行了比较。此外,还汇编了血清学和临床数据。
在新出现 PsA 检测之前采集的样本中,IL-1β、IL-6 和 IL-8 的浓度与无 PsA 患者相当。在 PsA 检测时,并且最有趣的是,无论 PsA 是在 UAW 还是 LAW 中发生,IL-8 增加(P=0.009),IL-6 呈上升趋势(P=0.081)。在这些患者中,PsA 的检测与升高的 PsA 抗体滴度无关。相比之下,PsA-chron 患者的 NL 显示通常较低的 IL-8 和 IL-1β浓度,与无 PsA 患者相似,这可能是由于随后的抗生素和抗炎治疗(例如,使用阿奇霉素)所致。
通过连续 NL 采样监测 UAW 中的细胞因子动态可能对 PsA 获得的早期阶段具有重要价值,从而增加了早期更具体地调整治疗方案的机会。