Wojewodka Gabriella, De Sanctis Juan B, Bernier Joanie, Bérubé Julie, Ahlgren Heather G, Gruber Jim, Landry Jennifer, Lands Larry C, Nguyen Dao, Rousseau Simon, Benedetti Andrea, Matouk Elias, Radzioch Danuta
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Institute of Immunology, Central University of Venezuela, Caracas, Venezuela.
PLoS One. 2014 Feb 12;9(2):e88567. doi: 10.1371/journal.pone.0088567. eCollection 2014.
Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.
We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.
Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.
Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.
肺部加重（PEs）会导致严重的发病情况，并可能严重影响囊性纤维化（CF）肺部疾病的疾病进展，尤其是对于那些反复发生PEs的患者。能够预测未来PE或反复发生PE的评估方法有限。我们假设，结合临床、分子和患者报告的数据可以识别出有PE风险的患者。
我们对53名成年CF患者进行了为期24个月的前瞻性随访。在疾病稳定期收集所有患者的肺活量测定基线值、使用马图克疾病评分的临床状态、生活质量（QOL）、炎症标志物（C反应蛋白（CRP）、白细胞介素（IL）-1β、-6、-8、-10、巨噬细胞炎性蛋白（MIP）-1β、肿瘤坏死因子（TNF）和血管内皮生长因子（VEGF））、血浆中的多不饱和脂肪酸和脂质过氧化情况，并对需要口服/静脉注射抗生素治疗的PE患者进行监测。此外，我们在PE期间密切跟踪了13名患者，收集了标志物相对于基线值变化的纵向数据。我们评估了在基线和抗生素治疗后，是否有任何标志物可预测未来的PE。
在我们的研究期间，53名患者中有37名发生了PEs。在基线时，我们发现肺功能低下、临床评分和QOL值与PE事件风险增加相关。在第1天，PEs与炎症标志物增加相关，并且这些生物标志物在治疗后有所改善。花生四烯酸和二十二碳六烯酸水平的失衡在治疗后得到改善，这与脂质过氧化的减少同时发生。高水平的炎症标志物CRP和IL-8与早期再次加重相关。
我们的结果表明，在疾病稳定期较差的临床和QOL评估是与未来发生PEs的较高风险相关的潜在标志物，而在抗生素治疗结束时较高水平的炎症标志物可能与早期再次加重相关。
