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骨髓增生异常综合征患者存在更严重的呼吸肌损伤和用力肺活量降低:炎症信号紊乱是罪魁祸首吗?

Myelodysplastic syndrome patients present more severe respiratory muscle impairment and reduced forced vital capacity: Is disordered inflammatory signaling the culprit?

作者信息

Okubo Bruno Memória, Matos Anacélia Gomes de, Ribeiro Junior Howard Lopes, Borges Daniela de Paula, Oliveira Roberta Taiane Germano de, de Castro Marilena Facundo, Martins Manoel Ricardo Alves, Gonçalves Romélia Pinheiro, Bruin Pedro Felipe Carvalhedo, Pinheiro Ronald Feitosa, Magalhães Silvia Maria Meira

机构信息

Cancer Cytogenomic Laboratory, Federal University of Ceará, Ceará, Brazil.

Post-Graduate Program in Medical Science, Federal University of Ceará, Ceará, Brazil.

出版信息

PLoS One. 2017 Sep 6;12(9):e0184079. doi: 10.1371/journal.pone.0184079. eCollection 2017.

Abstract

BACKGROUND/OBJECTIVES: The ageing process is associated with gradual decline in respiratory system performance. Anemia is highly prevalent among older adults and usually associated with adverse outcomes. Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies with increasing incidence with age and characterized by anemia and other cytopenias. The main objectives of this study were to evaluate respiratory muscle strength and lung function in elderly patients with anemia, compare data between myelodysplastic syndromes and non-clonal anemias and evaluate the influence of serum IL-8 level and NF-kB activity on deteriorate pulmonary function in this specific population.

PARTICIPANTS

Individuals aged 60 and older with anemia secondary to MDS, non-clonal anemia and healthy elderly individuals.

MEASUREMENTS

Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/ FVC ratio were measured by spirometry. Respiratory muscle strength was evaluated by maximal static respiratory pressures measurement. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay.

RESULTS

Mean Hb concentration was comparable between patients with anemia. Significant differences were detected between all patients with anemia and controls for maximum-effort inspiratory mouth pressure (PImax) and also for maximum-effort expiratory mouth pressure (PEmax). The MDS group recorded a significantly lower PImax and PEmax percent predicted when compared to non-clonal anemia group. For FVC and FEV1, a significant difference was found in anemic patients, with even significantly lower values for FVC and FEV1 in MDS group. No significant differences were detected for PImax and PEmax and spirometry parameters when anemic patients were stratified according to the degree of anemia. A significant negative impact in FVC (% pred), PImax (% pred) and PEmax (% pred) was observed in patients with MDS and higher levels of IL-8 or increased activity of NF-kB.

CONCLUSION

A negative impact of anemia, independent of its degree, was demonstrated in respiratory muscle strength and lung function particularly in MDS. The well known elevated proinflammatory cytokines in MDS patients were proposed to play a role as was demonstrated by detrimental effect of higher IL-8 and NF-kB in pulmonary function tests in this population.

摘要

背景/目的:衰老过程与呼吸系统功能的逐渐衰退相关。贫血在老年人中非常普遍,且通常与不良后果相关。骨髓增生异常综合征(MDS)是一组异质性血液系统恶性肿瘤,其发病率随年龄增长而增加,以贫血和其他血细胞减少为特征。本研究的主要目的是评估老年贫血患者的呼吸肌力量和肺功能,比较骨髓增生异常综合征和非克隆性贫血之间的数据,并评估血清白细胞介素-8(IL-8)水平和核因子-κB(NF-κB)活性对该特定人群肺功能恶化的影响。

参与者

60岁及以上继发于MDS的贫血患者、非克隆性贫血患者和健康老年人。

测量指标

通过肺量计测量1秒用力呼气量(FEV1)、用力肺活量(FVC)和FEV1/FVC比值。通过测量最大静态呼吸压力评估呼吸肌力量。采用酶联免疫吸附测定法(ELISA)进行IL-8分析,通过化学发光测定法检测NF-κB活性。

结果

贫血患者的平均血红蛋白浓度相当。所有贫血患者与对照组之间在最大用力吸气口腔压力(PImax)和最大用力呼气口腔压力(PEmax)方面均检测到显著差异。与非克隆性贫血组相比,MDS组记录的PImax和PEmax预测百分比显著更低。对于FVC和FEV1,贫血患者中发现存在显著差异,MDS组的FVC和FEV1值甚至显著更低。当根据贫血程度对贫血患者进行分层时,未检测到PImax、PEmax和肺量计参数的显著差异。在MDS患者中,IL-8水平较高或NF-κB活性增加时,观察到对FVC(预测值百分比)、PImax(预测值百分比)和PEmax(预测值百分比)有显著负面影响。

结论

贫血,无论其程度如何,对呼吸肌力量和肺功能均有负面影响,尤其是在MDS患者中。正如该人群肺功能测试中较高的IL-8和NF-κB的有害作用所表明的,MDS患者中众所周知的促炎细胞因子升高被认为起到了一定作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ef5/5587331/e0c287681514/pone.0184079.g001.jpg

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