Modeling of Inhalation Profiles Through Dry Powder Inhaler in Healthy Adults and Asthma Patients As a Prerequisite for Further In Vitro and In Silico Studies.

Background: The severity of airway obstruction may affect patient's ability to perform an effective drug inhalation from a dry powder inhaler (DPI). Also, an incorrect inhalation technique may negatively affect the efficacy of asthma treatment. The aims of the study were (1) to analyze and compare inhalation profiles recorded with the use of different inhalation techniques, and thus, (2) to establish model inhalation profiles representative for healthy subjects and subjects with mild and moderate-to-severe asthma. Methods: This study was performed in healthy volunteers, patients with mild and moderate-to-severe asthma. A modified flow-volume test to define two different expiratory levels (to residual volume and half-way to residual volume) was performed. Inspiratory flow parameters were extracted: peak inspiratory flow rate (PIFinh), time at which peak inspiratory flow rate occurs (tPIFinh), total inhalation time (T), and inhaled volume (V). Test of frequency for tPIFinh100% and tPIFinh50% by asthma severity was performed, to provide information about initial flow accelerations. The impact of two different expiratory levels preceding inhalation (with severity of asthma as a categorical factor) on inspiratory flow parameters was examined. Results: PIFinh was dependent upon asthma severity (p = 0.046). Type of exhalation before inhalation had no effect on PIFinh values. V value was significantly affected both by asthma severity (p = 0.024) and type of exhalation before inhalation (p < 0.0001). Mean T value was influenced by type of exhalation before inhalation (p = 0.0003), but not by asthma severity. Mean tPIFinh value was affected by the type of exhalation before inhalation only in healthy subjects (p = 0.01). Conclusions: Both asthma severity and type of exhalation before inhalation have little impact on the dynamics of inhalation through a DPI. An alternative form of equation describing inhalation profiles demonstrating a relationship between lung mechanics and dynamics of inspiratory profile has been proposed.