Faria-Urbina Mariana, Ung Keith T, Lawler Laurie, Zisman Lawrence S, Waxman Aaron B
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
iPharma, Ltd, San Francisco, CA.
Pulm Circ. 2021 May 13;11(2):20458940211012591. doi: 10.1177/20458940211012591. eCollection 2021 Apr-Jun.
Inhalation profiles to support use of dry powder inhalers for drug delivery in patients with pulmonary arterial hypertension have not been reported. We aimed to evaluate the inspiratory flow pattern associated with low and medium flow resistance dry powder inhaler devices (RS01-L and RS01-M, respectively) in patients with pulmonary arterial hypertension. This single-center study enrolled patients with pulmonary arterial hypertension associated with connective tissue disease ( = 10) and idiopathic pulmonary arterial hypertension ( = 10) to measure the following inhalation parameters: inspiratory effort (kPa), peak inspiratory flow rate (L/min), inhaled volume (L), and flow increase rate (L/s) using the two devices. We identified a trend toward higher mean pulmonary artery pressure in the idiopathic pulmonary arterial hypertension group (50 ± 13 mmHg vs. 40 ± 11 mmHg in pulmonary arterial hypertension associated with connective tissue disease; = 0.077). On average, peak inspiratory flow rate was higher with RS01-L vs. RS01-M (84 ± 19.7 L/min vs. 70.4 ± 13.2 L/min; = 0.015). In the overall group, no differences between RS01-L and RS01-M were observed for inhaled volume, inspiratory effort, or flow increase rate. Inhaled volume with RS01-L was higher in pulmonary arterial hypertension associated with connective tissue disease vs. idiopathic pulmonary arterial hypertension patients: 1.6 ± 0.4 L vs. 1.3 ± 0.2 L; = 0.042. For the RS01-L, inhaled volume correlated with forced expiratory volume in one second ( = 0.460, = 0.030) and forced vital capacity ( = 0.507, = 0.015). In patients with pulmonary arterial hypertension associated with connective tissue disease using RS01-L, both inspiratory effort and flow increase rate were highly correlated with pulmonary vascular compliance ( = 0.903, = 0.0001 and = 0.906, = 0.0001; respectively); while with RS01-M, inspiratory effort was highly correlated with pulmonary vascular compliance ( = 0.8, = 0.001). Our data suggest that the use of RS01-L and RS01-M dry powder inhaler devices allowed adequate inspiratory flow in pulmonary arterial hypertension patients. The correlation between flow increase rate and pulmonary vascular compliance in pulmonary arterial hypertension associated with connective tissue disease deserves further investigation.
尚未有关于支持肺动脉高压患者使用干粉吸入器进行药物递送的吸入概况的报道。我们旨在评估与低流量阻力和中流量阻力干粉吸入器装置（分别为RS01-L和RS01-M）相关的吸气气流模式在肺动脉高压患者中的情况。这项单中心研究纳入了患有结缔组织病相关肺动脉高压（n = 10）和特发性肺动脉高压（n = 10）的患者，以使用这两种装置测量以下吸入参数：吸气努力（kPa）、吸气峰值流速（L/min）、吸入量（L）和流速增加率（L/s）。我们发现特发性肺动脉高压组的平均肺动脉压有升高趋势（结缔组织病相关肺动脉高压为40±11 mmHg，特发性肺动脉高压为50±13 mmHg；P = 0.077）。平均而言，RS01-L的吸气峰值流速高于RS01-M（84±19.7 L/min对70.4±13.2 L/min；P = 0.015）。在总体组中，RS01-L和RS01-M在吸入量、吸气努力或流速增加率方面未观察到差异。与特发性肺动脉高压患者相比，结缔组织病相关肺动脉高压患者使用RS01-L时的吸入量更高：1.6±0.4 L对1.3±0.2 L；P = 0.042。对于RS01-L，吸入量与一秒用力呼气量（r = 0.460，P = 0.030）和用力肺活量（r = 0.507，P = 0.015）相关。在使用RS01-L的结缔组织病相关肺动脉高压患者中，吸气努力和流速增加率均与肺血管顺应性高度相关（分别为r = 0.903，P = 0.0001和r = 0.906，P = 0.0001）；而对于RS01-M，吸气努力与肺血管顺应性高度相关（r = 0.8，P = 0.001）。我们的数据表明，使用RS01-L和RS01-M干粉吸入器装置可使肺动脉高压患者获得足够的吸气气流。结缔组织病相关肺动脉高压中流速增加率与肺血管顺应性之间的相关性值得进一步研究。
