Inspiratory flow patterns with dry powder inhalers (DPIs) of low and medium flow resistance in subjects with pulmonary arterial hypertension (PAH)

Introduction: Inhalation profiles to support use of DPIs for drug delivery in PAH subjects have not been reported. Objective: Evaluate the inspiratory flow pattern associated with low and medium flow resistance DPI devices (RS01L, RS01M, respectively) in subjects with PAH. Methods: This single center study enrolled subjects with PAH associated with connective tissue disease (aPAH, n=10) and idiopathic PAH (iPAH, n=10) to measure the following inhalation parameters: inspiratory effort (kPa), peak inspiratory flow rate (L/min), inhaled volume (L), and flow increase rate (L/s2) using the two devices. Results: On average, peak inspiratory flow rate was higher with RS01L vs. RS01M (84 ± 19.73 L/min vs. 70.47 ± 13.26 L/min; p=0.015). In the overall group, no differences between RS01L and RS01M were observed for inhaled volume, inspiratory effort, or flow increase rate. Inhaled volume with RS01L was higher in aPAH vs iPAH subjects: 1.67 ± 0.43L vs. 1.31 ± 0.26L; p=0.042. For the RS01L, inhaled volume correlated with forced expiratory volume in one second (r=0.460, p=0.030) and forced vital capacity (r=0.507, p=0.015). In subjects with aPAH using RSO1L, inspiratory effort was highly correlated with pulmonary vascular compliance (PVC) (r=0.903), and flow increase rate with PVC (r=0.906). For RSO1M, inspiratory effort was highly correlated with PVC (r=0.81). Conclusions: Use of RS01L and RS01M DPI devices allowed adequate inspiratory flow in PAH subjects. The correlation between flow increase rate and PVC in aPAH deserves further investigation.