Combined Cardiopulmonary Failure in COPD: SPIROMICS HF

2010年，慢性阻塞性肺疾病（COPD）的死亡率和住院率翻了一番。 过去50年。三分之一的COPD住院与心力衰竭重叠，大多数是保留射血 尽管HFpEF的研究结果表明，HFpEF与心功能相关，但没有大型COPD研究确定心脏功能。多种族研究 资助了动脉粥样硬化（梅萨）COPD研究，以检验肺气肿的内皮假说， 检查COPD中RV尺寸减小（“肺心病”）。在梅萨COPD研究II中，我们发现 肺微血管血流量减少与肺气肿的关系似乎并不 被缺氧性肺血管收缩所混淆，CT显示的肺气肿预测RV消退超过 5年我们还开发了进一步分型肺气肿和COPD的方法，并将其扩大到 COPD研究中的亚群和中间结局指标（SPIROMICS）。我们使用无人监督的 机器学习来发现新的肺气肿亚型，这些亚型是常见的，具有分子起源。 另外，我们发现26%的成年人有节段性气道变异，这与COPD有关， 发育基因FGF 10和RARA。这两种基因都会影响右心的发育。在试点工作中，我们 发现了一个显著改变的RV菌株，另一个与肺心病有关。最后我们 发现支气管炎的“症状性吸烟者”，由于气体滞留而过度膨胀， 左室舒张功能不全。因此，COPD的心脏改变是复杂的，但最近的进展， 分型可以允许他们的个性化诊断和治疗。SPIROMICS是一个由NHLBI资助的 这项研究招募了患有COPD的吸烟者和对照组，并重新检查了2,000名参与者， 包括全肺CT的标准肺表型。我们建议增加全面超声心动图（回声） 对1,000名SPIROMICS参与者进行心脏力学斑点追踪，700名参与者进行锻炼， 600例心肺MRI，以测试以下假设：1）机器学习的肺气肿亚型 CT与心脏结构和功能的特定改变有关，从肺心病到 LV舒张功能障碍; 2）具有节段性气道变异的参与者具有异常的RV结构， 3）有症状的吸烟者有左室后负荷增加和左室舒张功能障碍的迹象。 该应用的创新方面包括在一个大的，良好的， COPD患者的特征队列。这些假设的证实将确定 HFpEF在COPD中的应用，并确定心肺功能障碍靶向治疗的患者亚群。

The death rate and hospitalizations from chronic obstructive pulmonary disease (COPD) have doubled in the last 50 years. A third of COPD hospitalizations overlap with heart failure, mostly with preserved ejection fraction (HFpEF), yet no large COPD study has ascertained cardiac function. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study was funded to test the endothelial hypothesis of emphysema and examine reduced RV dimensions (“cor pulmonale parvus”) in COPD. In the MESA COPD Study II, we found that associations of reduced pulmonary microvascular blood flow with emphysema do not appear to be confounded by hypoxic pulmonary vasoconstriction and that emphysema on CT predicted RV regression over 5 years. We also developed methods to further subtype emphysema and COPD and scaled them up to the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). We used unsupervised machine learning to discover new emphysema subtypes that are common and have molecular origins. Separately, we found that 26% of adults have segmental airway variants, which are associated with COPD and the developmental genes FGF10 and RARA. Both genes affect right heart development. In pilot work, we found one dramatically altered RV strain and the other associated with cor pulmonale parvus. Finally, we found that bronchitic ‘symptomatic smokers,’ who have hyperinflation from gas trapping, may have increased LV diastolic dysfunction. Hence, cardiac alterations in COPD are complex but recent advances in COPD subtyping may allow their personalized diagnosis and treatment. SPIROMICS is an NHLBI-funded prospective study that recruited smokers with COPD and controls and is re-examining 2,000 participants with gold- standard lung phenotyping including full-lung CT. We propose to add comprehensive echocardiography (echo) with speckle-tracking for cardiac mechanics for 1,000 SPIROMICS participants, with exercise in 700 and cardiopulmonary MRI in 600, to test the following hypotheses: 1) machine-learned subtypes of emphysema on CT are associated with specific alterations in cardiac structure and function, which vary from cor pulmonale to LV diastolic dysfunction; 2) participants with segmental airway variants have abnormal RV structure and function; 3) symptomatic smokers have signs of increased LV afterload and LV diastolic dysfunction. Innovative aspects of the application include the use of novel echo and MRI measures in a large, well- characterized cohort of COPD patients. Confirmation of the hypotheses would define the mechanisms of HFpEF in COPD and identify subsets of patients for targeted treatment of cardiopulmonary dysfunction.