Milne Kathryn M, James Matthew D, Smyth Reginald M, Vincent Sandra G, Singh Namisha, D'Arsigny Christine L, de-Torres Juan P, de Wit Kerstin, Johri Amer, Neder J Alberto, O'Donnell Denis E, Phillips Devin B
Respiratory Investigation Unit, Department of Medicine, Queen's University and Kingston Health Sciences Centre Kingston General Hospital Campus, Kingston, Ontario, Canada.
Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia St. Paul's Hospital, Vancouver, British Columbia, Canada.
J Appl Physiol (1985). 2023 Mar 1;134(3):667-677. doi: 10.1152/japplphysiol.00677.2022. Epub 2023 Jan 26.
Following pulmonary embolism (PE), a third of patients develop persistent dyspnea, which is commonly termed the post-PE syndrome. The neurophysiological underpinnings of exertional dyspnea in patients with post-PE syndrome without pulmonary hypertension (PH) are unclear. Thus, the current study determined if abnormally high inspiratory neural drive (IND) due, in part, to residual pulmonary gas-exchange abnormalities, was linked to heightened exertional dyspnea and exercise limitation, in such patients. Fourteen participants with post-PE syndrome (without resting PH) and 14 age-, sex-, and body mass index-matched healthy controls undertook pulmonary function testing and a symptom-limited cycle cardiopulmonary exercise test with measurements of IND (diaphragmatic electromyography), ventilatory requirements for CO (V̇e/V̇co), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs. control) had a reduced resting transfer coefficient for carbon monoxide (: 84 ± 15 vs. 104 ± 14%pred, < 0.001) and peak oxygen uptake (V̇o) (76 ± 14 vs. 124 ± 28%pred, < 0.001). IND and V̇e/V̇co were higher in post-PE than controls at standardized submaximal work rates ( < 0.05). Dyspnea increased similarly in both groups as a function of increasing IND but was higher in post-PE at standardized submaximal work rates ( < 0.05). High IND was associated with low ( = -0.484, < 0.001), high V̇e/V̇co nadir ( = 0.453, < 0.001), and low V̇o ( = -0.523, < 0.001). In patients with post-PE syndrome, exercise IND was higher than controls and was associated with greater dyspnea intensity. The heightened IND and dyspnea in post-PE, in turn, were strongly associated with low resting and high exercise V̇e/V̇co, which suggest important pulmonary gas-exchange abnormalities in this patient population. This study is the first to show that increased exertional dyspnea in patients with post-pulmonary embolism (PE) syndrome, without overt pulmonary hypertension, was strongly associated with elevated inspiratory neural drive (IND) to the diaphragm during exercise, compared with healthy controls. The greater IND was associated with impairments in pulmonary gas exchange and significant deconditioning. Our results help to explain why many patients with post-PE syndrome report significant dyspnea at relatively low levels of physical activity.
肺栓塞（PE）后，三分之一的患者会出现持续性呼吸困难，这通常被称为PE后综合征。无肺动脉高压（PH）的PE后综合征患者运动性呼吸困难的神经生理学基础尚不清楚。因此，本研究确定在这类患者中，部分由于残留肺气体交换异常导致的吸气神经驱动（IND）异常升高是否与运动性呼吸困难加剧和运动受限有关。14名PE后综合征患者（无静息PH）和14名年龄、性别及体重指数匹配的健康对照者进行了肺功能测试和症状限制性心肺运动试验，测量了IND（膈肌肌电图）、CO的通气需求（V̇e/V̇co）和主观呼吸困难强度（改良Borg 0 - 10级）。PE后患者（与对照组相比）静息一氧化碳转运系数降低（：84±15 vs. 104±14%预计值，<0.001），峰值摄氧量（V̇o）降低（76±14 vs. 124±28%预计值，<0.001）。在标准化次最大运动强度下，PE后患者的IND和V̇e/V̇co高于对照组（<0.05）。两组的呼吸困难均随IND增加而相似地增加，但在标准化次最大运动强度下，PE后患者的呼吸困难更严重（<0.05）。高IND与低（= -0.484，<0.001）、高V̇e/V̇co最低点（= 0.453，<0.001）和低V̇o（= -0.523，<0.001）相关。在PE后综合征患者中，运动IND高于对照组，且与更严重的呼吸困难强度相关。PE后患者升高的IND和呼吸困难，反过来又与低静息和高运动V̇e/V̇co密切相关，这表明该患者群体存在重要的肺气体交换异常。本研究首次表明，与健康对照者相比，无明显肺动脉高压的肺栓塞（PE）后综合征患者运动性呼吸困难加剧与运动期间膈肌吸气神经驱动（IND）升高密切相关。更高的IND与肺气体交换受损和明显的身体机能下降有关。我们的结果有助于解释为什么许多PE后综合征患者在相对较低的体力活动水平时就报告有明显的呼吸困难。
