Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by four dry powder inhalers under realistic inhalation and exhalation conditions. To simulate patients undergoing inhalation therapy, the active respiratory system model (xPULM™) was used. A mechanical upper airway model was developed, manufactured, and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung, while particles with the size of (>0.5 μm) are least influenced by deposition mechanisms. The fraction of exhaled particles ranges from 2.13% (HandiHaler^®) over 2.94% (BreezHaler^®), and 6.22% (Turbohaler^®) to 10.24% (Ellipta^®). These values are comparable to previously published studies. Furthermore, the mechanical upper airway model increases the resistance of the overall system and acts as a filter for larger particles (>3 μm). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract regarding applicable deposition mechanisms. The model strives to support the reduction of animal experimentation in aerosol research and provides an alternative to experiments with human subjects.

During mechanical ventilation, a disparity between flow, pressure and volume demands of the patient and the assistance delivered by the mechanical ventilator often occurs. This paper introduces an alternative approach of simulating and evaluating patient–ventilator interactions with high fidelity using the electromechanical lung simulator xPULM™. The xPULM™ approximates respiratory activities of a patient during alternating phases of spontaneous breathing and apnea intervals while connected to a mechanical ventilator. Focusing on different triggering events, volume assist-control (V/A-C) and pressure support ventilation (PSV) modes were chosen to test patient–ventilator interactions. In V/A-C mode, a double-triggering was detected every third breathing cycle, leading to an asynchrony index of 16.67%, which is classified as severe. This asynchrony causes a significant increase of peak inspiratory pressure (7.96 ± 6.38 vs. 11.09 ± 0.49 cmH₂O, p < 0.01)) and peak expiratory flow (−25.57 ± 8.93 vs. 32.90 ± 0.54 L/min, p < 0.01) when compared to synchronous phases of the breathing simulation. Additionally, events of premature cycling were observed during PSV mode. In this mode, the peak delivered volume during simulated spontaneous breathing phases increased significantly (917.09 ± 45.74 vs. 468.40 ± 31.79 mL, p < 0.01) compared to apnea phases. Various dynamic clinical situations can be approximated using this approach and thereby could help to identify undesired patient–ventilation interactions in the future. Rapidly manufactured ventilator systems could also be tested using this approach.

During mechanical ventilation, a disparity between flow, pressure or volume demands of the patient and the assistance delivered by the mechanical ventilator often occurs. Asynchrony effect and ventilator performance are frequently studied from ICU datasets or using commercially available lung simulators and test lungs. This paper introduces an alternative approach of simulating and evaluating patient-ventilator interactions with high fidelity using the electro-mechanical lung simulator xPULM™ under selected conditions. The xPULM™ approximates respiratory activities of a patient during alternating phases of spontaneous breathing and apnoea intervals while connected to a mechanical ventilator. Focusing on different triggering events, volume assist-controlled (V/A-C) and pressure support ventilation (PSV) modes were chosen to test patient-ventilator interactions. In V/A-C mode a double-triggering was detected every third breathing cycle leading to an asynchrony index of 16.67%, being classified as severe. This asynchrony causes a major increase of Peak Inspiratory Pressure PIP = 12.80 ± 1.39 cmH2O and Peak Expiratory Flow PEF = -18.33 ± 1.13 L/min when compared to synchronous phases of the breathing simulation. Additionally, events of premature cycling were observed during PSV mode. In this mode, the peak delivered volume during simulated spontaneous breathing phases almost doubles compared to apnoea phases. The presented approach demonstrates the possibility of simulating and evaluating disparities in fundamental ventilation characteristics caused by double-triggering and premature cycling under V/A-C and PSV ventilation modes. Various dynamic clinical situations can be approximated and could help to identify undesired patient-ventilation interactions in the future. Rapidly manufactured ventilator systems could also be tested using this approach.

Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by five dry powder inhalers under realistic inhalation and exhalation conditions. The active respiratory system model (xPULM™) was used as a model of the human respiratory system and to simulate a patient undergoing inhalation therapy. A mechanical upper airway model was developed, manufactured and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that the upper airway model increases the resistance of the overall system and act as a filter for bigger particles (>3 µm). Furthermore, there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung. The minimum deposition is reached for particle size of 0.5 µm. The mean particle number concentrations exhaled are 2.94% (BreezHaler®), 2.66% (Diskus®), 10.24% (Ellipta®) 2.13% (HandiHaler®) and 6.22% (Turbohaler®). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract in terms of applicable deposition mechanisms. The model can support the reduction of animal experimentation in aerosol research and provide an alternative to experiments with human subjects.