根据一项以人群为基础的前瞻性队列研究的结果，慢性阻塞性肺病(COPD)与脑微出血(脑内小血管疾病的一种标志物)风险增高相关，而与年龄、性别、吸烟状态和胆固醇水平等因素无关。
“抑郁症、体位不稳定性、认知和功能受损是已知的脑内小血管疾病的后果，同时也是COPD患者中常见的肺外表现，”比利时Ghent大学医院的Lies Lahousse医生及其同事说，“但尚不清楚COPD是否与脑内小血管疾病的发生相关。”
该研究纳入了参加鹿特丹扫描研究的165例COPD患者和645例非COPD患者。鹿特丹扫描研究是一项以人群为基础的队列研究，使用MRI评估年龄相关的脑变化。
结果显示，即使在校正年龄、性别、吸烟状态、动脉粥样硬化性大血管病变、抗血栓剂的使用、总胆固醇、甘油三酯和血清肌酐之后，COPD患者的脑微出血患病率仍显着高于肺功能正常患者[比值比(OR)，1.7；95%置信区间(CI)：1.15~2.47；P=0.007)。根据在线发表于7月19日的《美国呼吸与重症医学杂志》上的这篇文章的数据，COPD患者深部或小脑天幕下微出血的患病率也增加2倍以上(OR，3.3；95%CI：1.97~5.53；P＜0.001)。
对基线时无微出血的患者进行的纵向分析显示，在中位数为3.42年的时间段内，COPD可独立预测深部或小脑天幕下微出血风险增加6倍(OR，7.1；95%CI：2.1~24.5；P=0.002)。
“我们的结果与之前的两项横断面研究一致，显示COPD患者脑白质病变体积显着增加，这是脑内小血管疾病的另一标志物，并且已知与深部或小脑天幕下区域的微出血相关。”尽管COPD患者中微出血发生率增高与吸烟状态无关，但研究者发现，在吸烟者中，脑微出血的患病率显着增高。既往研究显示，COPD患者动脉粥样硬化性大血管病变患病率增高，在这项分析中也考虑了这一因素。
研究者认为，鉴于脑微出血可能造成认知和功能障碍，该研究结果有助于识别易感患者人群，并提示有必要开展更多关于预防策略的研究。（生物谷Bioon.com）
生物谷推荐英文摘要：
Am J Respir Crit Care Med http://www.atsjournals.org/doi/abs/10.1164/rccm.201210-1884OC
The Role of Soluble Guanylyl Cyclase in Chronic Obstructive Pulmonary Disease
Constantinos Glynos, Lisa L Dupont, Theodoros Vassilakopoulos, Andreas Papapetropoulos, Peter Brouckaert, Athanassios Giannis, Guy F Joos, Ken R Bracke, and Guy G Brusselle
Rationale: Soluble guanylyl cyclase (sGC), a cyclic guanosine 5′-monophosphate (cGMP) generating enzyme, regulates smooth muscle tone and exerts anti-inflammatory effects in animal models of asthma and acute lung injury. In Chronic Obstructive Pulmonary Disease (COPD), primarily caused by cigarette smoke (CS), lung inflammation persists and smooth muscle tone remains elevated, despite ample amounts of nitric oxide (NO) that could activate sGC. Objective: To determine the expression and function of sGC in patients with COPD and in a murine model of COPD. Methods: Expression of sGCα1, α2 and β1 subunits was examined in lungs of never smokers, smokers without airflow limitation and patients with COPD; and in C57BL/6 mice after 3 days, 4 and 24 weeks of CS exposure. The functional role of sGC was investigated in vivo by measuring bronchial responsiveness to serotonin (5-HT) in mice using genetic and pharmacological approaches. Measurements and Main Results: Pulmonary expression of sGC, both at mRNA and protein level, was decreased in smokers without airflow limitation and in patients with COPD, and correlated with disease severity (FEV1%). In mice, exposure to CS reduced sGC, cGMP levels and protein kinase G activity. sGCα1-/- mice exposed to CS exhibited bronchial hyperresponsiveness (BHR) to serotonin. Activation of sGC by BAY 58-2667 restored the sGC signaling and attenuated BHR in CS-exposed mice. Conclusions: Downregulation of soluble guanylyl cyclase due to cigarette smoke exposure might contribute to airflow limitation in COPD.
