Bristol Royal Infirmary, Bristol, United Kingdom.
Hammersmith Hospital, London, United Kingdom.
J Am Heart Assoc. 2018 Feb 14;7(4):e007249. doi: 10.1161/JAHA.117.007249.
Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls.
Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls. Spirometry, gas transfer, whole body plethysmography and lung clearance index, 6-minute walk distance, and medical research council dyspnea scoring were performed. Inflammatory markers and endothelin-1 levels were determined in blood and induced sputum. The CHD-APAH group had abnormal lung function with lung restriction, airway obstruction, and ventilation heterogeneity. Inverse correlations were shown for CHD-APAH between medical research council dyspnea score and percent predicted peak expiratory flow (=-0.5383, =0.0174), percent predicted forced expiratory flow rate at 50% of forced vital capacity (=-0.5316, =0.0192), as well as for percent predicted forced expiratory volume in 1 s (=-0.6662, =0.0018) and percent predicted forced vital capacity (=-0.5536, =0.0186). The CHD-APAH patients were more breathless with lower 6-minute walk distance (360 m versus 558 m versus 622 m, =0.00001). Endothelin-1, interleukin (IL)-β, IL-6, IL-8, tumor necrosis factor α, and vascular endothelial growth factor were significantly higher in CHD-APAH than controls. Serum endothelin-1 for CHD-APAH correlated with airflow obstruction with significant negative correlations with percent predicted forced expiratory flow rate at 75% of forced vital capacity (=-0.5858, =0.0135).
Raised biomarkers for inflammation were found in CHD-APAH. Significant abnormalities in airway physiology may contribute to the dyspnea but are not driven by inflammation as assessed by circulating and sputum cytokines. A relationship between increased serum endothelin-1 and airway dysfunction may relate to its bronchoconstrictive properties.
呼吸困难是肺动脉高压和先天性心脏病（CHD-APAH）患者最常见的症状，以前认为是由肺动脉高压恶化引起的，但也可能是由炎症和肺功能异常引起的。我们研究了 CHD-APAH 患者的肺功能和气道炎症，并将结果与对照组进行了比较。
共有 60 人入组研究：20 例 CHD-APAH、20 例 CHD 对照组和 20 例健康对照组。进行了肺量测定、气体转移、全身 plethysmography 和肺清除指数、6 分钟步行距离和医学研究委员会呼吸困难评分。在血液和诱导痰中测定了炎症标志物和内皮素-1 水平。CHD-APAH 组肺功能异常，表现为肺限制、气道阻塞和通气异质性。CHD-APAH 与医学研究委员会呼吸困难评分呈负相关，与预测最大呼气流量的百分比（=-0.5383，=0.0174）、预测用力肺活量 50%时的用力呼气流量率（=-0.5316，=0.0192）以及预测 1 秒用力呼气量的百分比（=-0.6662，=0.0018）和预测用力肺活量的百分比（=-0.5536，=0.0186）。CHD-APAH 患者呼吸困难更严重，6 分钟步行距离更短（360m 比 558m 比 622m，=0.00001）。CHD-APAH 患者的内皮素-1、白细胞介素（IL）-β、IL-6、IL-8、肿瘤坏死因子-α和血管内皮生长因子均显著高于对照组。CHD-APAH 患者的血清内皮素-1与气流阻塞相关，与预测用力肺活量 75%时的用力呼气流量率呈显著负相关（=-0.5858，=0.0135）。
CHD-APAH 患者发现炎症标志物升高。气道生理学的显著异常可能导致呼吸困难，但循环和痰细胞因子评估的炎症并非驱动因素。血清内皮素-1升高与气道功能障碍之间的关系可能与其支气管收缩特性有关。
