慢性血栓栓塞性肺动脉高压患者SPECT/CT肺灌注体积及视觉评分与血流动力学参数的相关性研究

目的探讨慢性血栓栓塞性肺动脉高压(CTEPH)患者肺灌注SPECT/CT显像肺灌注体积及视觉评分与右心导管血流动力学参数的相关性。方法回顾性分析2015年3月至2019年7月间广州医科大学附属第一医院51例连续CTEPH患者的资料,其中男17例,女34例,年龄(59±12)岁。所有患者均行肺灌注SPECT/CT显像及右心导管检查。应用不同百分比阈值(15%~85%)分割法计算肺灌注体积。参照Begic三分法对肺灌注SPECT/CT图像进行视觉评分。收集右心导管检查血液动力学参数[肺动脉收缩压(PASP)、舒张压(PADP)及平均压(mPAP)、肺小动脉楔压(PAWP)、肺血管阻力(PVR)、心输出量(CO)、心指数(CI)等],并采用Spearman相关分析评价肺灌注体积、视觉评分和右心导管血流动力学参数间的相关性。结果在30%~70%阈值下,双肺灌注体积与mPAP间存在相关性(rs值:-0.414~-0.302,均P<0.05)。其中40%和45%阈值下双肺灌注体积与mPAP间呈中等负相关(rs值:-0.414和-0.412,均P<0.05)。40%阈值下双肺灌注体积与PASP、PADP呈中等负相关(rs值:-0.402和-0.440,均P<0.05),与PVR呈弱的负相关(rs=-0.352,P<0.05)。视觉评分与PADP间存在弱的正相关(rs=0.311,P<0.05),余右心导管参数与视觉评分间无相关性(rs值:-0.201~0.275,均P>0.05)。结论肺灌注SPECT/CT显像中基于阈值分割的肺灌注体积参数可较准确反映肺动脉压力等血流动力学状态,可用于评估CTEPH患者病情严重程度。     

Lipid-mediated innate lymphoid cell recruitment and activation in aspirin-exacerbated respiratory disease

ObjectiveTo synthesize investigations into the role of lipid-mediated recruitment and activation of group 2 innate lymphoid cells (ILC2s) in aspirin-exacerbated respiratory disease (AERD).Data SourcesA comprehensive literature review of reports pertaining to cellular mechanisms, cytokine, and lipid mediators in AERD, as well as ILC2 activation and recruitment, was performed using PubMed and Google Scholar.Study SelectionsSelections of studies were based on reports of lipid mediators in AERD, cytokine mediators in AERD, type 2 effector cells in AERD, platelets in AERD, AERD treatment, ILC2s in allergic airway disease, and ILC2 activation, inhibition, and trafficking.ResultsThe precise mechanisms of AERD pathogenesis are not well understood. Greater levels of proinflammatory lipid mediators and type 2 cytokines are found in tissues derived from patients with AERD relative to controls. After pathognomonic cyclooxygenase-1 inhibitor reactions, proinflammatory mediator concentrations (prostaglandin D2 and cysteinyl leukotrienes) are rapidly increased, as are ILC2 levels in the nasal mucosa. The ILC2s, which potently generate type 2 cytokines in response to lipid mediator stimulation, may play a key role in AERD pathogenesis.ConclusionAlthough the literature suggests that lipid-mediated ILC2 activation may occur in AERD, there is a dearth of definitive evidence. Future investigations leveraging novel next-generation single-cell sequencing approaches along with recently developed AERD murine models will better define lipid mediator–induced ILC2 trafficking in patients with AERD.     

呼吸训练器与缩唇呼气对AECOPD患者排痰效果的对比研究

目的比较呼吸训练器与缩唇呼气在慢性阻塞性肺疾病急性加重(AECOPD)患者中的排痰效果。方法于2018年3月至5月因急性加重住院的40例慢性阻塞性肺疾病(COPD)患者随机分为2组,观察和比较呼吸训练器和缩唇呼气的排痰效果。结果呼吸训练器和缩唇呼气干预期间,2组痰液总量和纯痰液容量均比干预前的显著增多(呼吸训练器组:P值均<0.01;缩唇呼气组:P值均<0.05),其中呼吸训练器增加痰液总量比缩唇呼气更显著(P<0.05);呼吸训练器组的痰液水成分容量/痰液总量比值比干预前明显增加(P<0.01),呼吸训练器组的咳嗽难度和痰液性状均比干预前的明显改善(P值均<0.05),呼吸训练器组的痰黏稠度较干预前提高(P<0.05),而缩唇呼气的咳嗽难度、痰液性状和痰黏稠度没有改变;排痰干预后期,2组痰液总量和纯痰液容量均低于干预前期的,2组痰黏稠度均比干预前期增加,其中呼吸训练器组的效果更显著,但咳嗽难度和痰液性状均比干预前期和干预期的明显改善;2组干预期和干预后期,BORG评分和外周氧饱和度均较干预前改善。结论呼吸训练器与缩唇呼气均能帮助AECOPD患者排痰,呼吸训练器更能促进痰水化、改善痰性状和加快排痰。     

改良Padua风险评估模型对评估内科住院患者静脉血栓栓塞症风险有效性研究

目的:回顾性验证改良Padua风险评估模型在内科住院患者中筛选静脉血栓栓塞症(VTE)的有效性。方法:采用回顾性病例对照研究设计,以2013年1月至2016年12月在广州医科大学附属第一医院内科住院患者中确诊为VTE的432例患者作为VTE组,以随机数字表法选取同时期同科室的出院诊断非VTE的864例内科住院患者为对照组,回顾性收集2组患者病史、实验室检查结果等临床资料,对所有患者进行Padua风险评估模型以及改良Padua风险评估模型评分,比较2种风险评估模型评分情况。结果:VTE组患者Padua风险评估模型评分高于对照组[(2.92±0.18)分比(1.25±0.10)分,t=16.241,P<0.05]。VTE组患者改良Padua风险评估模型评分高于对照组[(3.27±0.19)分比(1.64±0.11)分,t=14.245,P<0.05]。2组患者随着2种风险评估模型评分的升高,发生VTE的风险也相应增高,经Padua风险评估模型以及改良Padua风险评估模型判定为VTE高危患者(评分≥4分)发生VTE的风险分别是低危患者的12.72倍(95%CI:9.00~17.98,P<0.05)与8.17倍(95%CI:6.00~11.12,P<0.05)。VTE组患者经改良Padua风险评估模型判定为VTE高危患者占比高于Padua风险评估模型(48.61%比39.12%,P<0.05)。结论:改良Padua风险评估模型是基于个体危险因素对内科住院患者进行量化更加有效的VTE风险评估模型。     

慢性血栓栓塞性肺动脉高压的介入治疗

慢性血栓栓塞性肺动脉高压(CTEPH)是肺栓塞的潜在致命结果。目前肺动脉内膜剥脱术(PEA是首选的治疗方法,但多种因素限制了其临床应用和开展。对于不能行PEA治疗的CTEPH患者,经皮球囊肺动脉成形术是近年来发展迅速的一种能够改善患者临床症状、降低肺动脉压力和肺血管阻力并改善患者预后的新的介入治疗方法。     

Serum–Glucocorticoid Regulated Kinase 1 Regulates Macrophage Recruitment and Activation Contributing to Monocrotaline-Induced Pulmonary Arterial Hypertension

Sustained inflammation is associated with pulmonary vascular remodeling and arterial hypertension (PAH). Serum–glucocorticoid regulated kinase 1 (SGK1) has been shown to participate in vascular remodeling, but its role in inflammation-associated PAH remains unknown. In this study, the importance of SGK1 expression and activation was investigated on monocrotaline (MCT)-induced PAH, an inflammation-associated experimental model of PAH used in mice and rats. The expression of SGK1 in the lungs of rats with MCT-induced PAH was significantly increased. Furthermore, SGK1 knockout mice were resistant to MCT-induced PAH and showed less elevation of right ventricular systolic pressure and right ventricular hypertrophy and showed reduced pulmonary vascular remodeling in response to MCT injection. Administering the SGK1 inhibitor, EMD638683, to rats also prevented the development of MCT-induced PAH. The expression of SGK1 was shown to take place primarily in alveolar macrophages. EMD638683 treatment suppressed macrophage infiltration and inhibited the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in the lungs of rats with MCT-induced PAH. Co-culture of bone marrow-derived macrophages (BMDMs) from wild-type (WT) mice promoted proliferation of PASMC in vitro, whereas BMDMs from either SGK1 knockout mice or WT mice with EMD638683 treatment failed to induce this response. Collectively, the present results demonstrated that SGK1 is important to the regulation of macrophage activation that contributes to the development of PAH; thus, SGK1 may be a potential therapeutic target for the treatment of PAH.     

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF‐β superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)‐induced inflammation, and in airway epithelial cells treated with LPS or TNF‐α. BMP4 mutant (BMP4^+/?) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4^+/+ mice. Knockdown of BMP4 by siRNA increased LPS and TNF‐α‐induced IL‐8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4^+/? mice produced greater levels of TNF‐α and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4^+/+ mice. Administration of exogenous BMP4 attenuated the upregulation of TNF‐α, IL‐8, or KC induced by LPS and/or TNF‐α in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4^+/? mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti‐inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation.