Impact of human behavior on inspiratory flow profiles in patients with pulmonary arterial hypertension using AOS™ dry powder inhaler device

Abstract

Relative to healthy subjects, patients with pulmonary arterial hypertension often present with decreased respiratory muscle strength, resulting in decreased maximum inspiratory pressure. Little is known about the impact of reduced respiratory muscle strength on the ability to achieve the peak inspiratory pressures needed for effective drug delivery when using portable dry powder inhalers (≥1.0 kPa). The objective of this study was to assess the impact of inhaler resistance and patient instruction on the inspiratory flow profiles of pulmonary arterial hypertension patients when using breath-actuated dry powder inhalers. The inspiratory flow profiles of 35 patients with pulmonary arterial hypertension were measured with variants of the RS01 dry powder inhaler. Profiles were determined with a custom inspiratory flow profile recorder. Results showed that going from the low resistance RS01 dry powder inhaler to the high resistance AOS® dry powder inhaler led to increases in mean peak inspiratory pressures for pulmonary arterial hypertension subjects from 3.7 kPa to 6.5 kPa. Instructions that ask pulmonary arterial hypertension subjects to inhale with maximal effort until their lungs are full led to a mean peak inspiratory pressures of 6.0 kPa versus 2.1 kPa when the same subjects are asked to inhale comfortably. Significant decreases in mean peak inspiratory pressures are also observed with decreases in lung function, with a mean peak inspiratory pressures of 7.2 kPa for subjects with FEV1 > 60% predicted, versus 3.3 kPa for those subjects with FEV1 < 50% predicted. In conclusion, despite having reduced respiratory muscle strength, subjects with pulmonary arterial hypertension can effectively use a breath-actuated dry powder inhaler. The probability of achieving effective dose delivery may be increased by using dry powder inhalers with increased device resistance, particularly when subjects do not follow the prescribed instructions and inhale comfortably.

Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler

“…Sahay et al [ 131 ] studied the inspiratory flow profiles of 35 adult patients with pulmonary arterial hypertension (PAH) using variants of the RS01 DPI that had resistance values between 0.017 and 0.051 kPa 0.5 L −1 min. Mean Vi values increased from 1.7 to 1.9 L as the resistance of the device decreased.…”

“…With the higher resistance DPI, the mean Vi decreased from 1.8 to 1.2 L when FEV 1 values were decreased from >60% predicted to <50% predicted. Adult patients with PAH have lower inhaled volumes than adults with asthma, COPD, CF, or Parkinson’s disease, due in part to most PAH patients being female [ 131 ].…”

Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler

“…Even the high 42 mg requires only two inhalations from two capsules. Sahay et al [132] studied the inspiratory flow profiles of 35 adult patients with pulmonary arterial hypertension (PAH) using variants of the RS01 DPI that had resistance values between 0.017 and 0.051 kPa 0.5 L -1 min. Mean Vi values increased from 1.7 L to 1.9 L as the resistance of the device decreased.…”

“…With the higher resistance DPI, the mean Vi decreased from 1.8 L to 1.2 L when FEV1 values were decreased from >60% predicted to <50% predicted. Adult patients with PAH have lower inhaled volumes than adults with asthma, COPD, CF, or Parkinson's disease, due in part to most PAH patients being female [132].…”

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

“…Indeed, most children ages six and above exceed a pressure drop of 1 kPa when using passive DPIs [51][52][53][54]. This is especially true for children using higher resistance DPIs, as subjects tend to provide greater inspiratory effort when using a higher resistance device [55][56][57][58][59].…”