Response to Letter to the Editor: Pulmonary Delivery of Dry Powders During Invasive Mechanical Ventilation: Innovations Are Required

To the Editor:

We thank Dr. Guillon and his co-workers for their feedback on our article.⁽¹⁾ They re-emphasized the need to develop new technologies for the delivery of dry powder to ventilated patients, providing clinicians more options in patient care. A major limitation of the dry powder delivery system that we proposed is the necessity to disconnect the intubated patients temporarily from the ventilator, which could be a risk factor for patients suffering from severe hypoxemic respiratory failure. Therefore, we suggested further study in incorporating the dry powder delivery system within a mechanical ventilator.

Guillon et al. has proposed an interesting system to introduced lactose powder (2.5 mg/kg) to ventilated Cynomolgus monkeys without disconnecting them from the mechanical ventilation. They employed a Dry Powder Insufflator^™ and Bodai valve, with the delivery tube directly inserted into the endotracheal tube and adjusted to the extremity position of the endotracheal tube to deliver the powder directly to the lungs. The DPI was placed inside a holding chamber and actuated by air puffs generated by a syringe. This system is relatively simple and major components are commercially available, making it an attractive candidate to be developed for human use.

In vitro results showed that more than 90% powder was released in four puffs of air, and a volume median diameter (VDM) of 63 μm was measured. In their in vivo experiment, a 100% powder delivery was achieved and no relevant histological modification and pulmonary damages were observed in the tested monkeys after a 14-day treatment period. These promising results demonstrate the potential of their system to be further developed to introduce carrier-based DPIs to ventilated patients.

Guillon et al. highlighted that the large VDM could limit alveolar deposition. It is worth pointing out that most commercially available carrier-based inhalers used coarse lactose particles (VDM = 40–73 μm) as carrier particles,⁽²⁾ which are mostly deposited in the throat and upper lung regions when inhaled through a carrier-based DPI.⁽³⁾ They also underlined another limitation of their proposed system, which is the tip of the device touching the trachea during insertion. It would be of interest to investigate the effects of tip position of the delivery tube on the deliver dose. Identifying a tip position away from the extremity of the endotracheal tube without significant reduction in the delivered dose can reduce the risk of touching the trachea.

Moreover, we believe the coordination between device actuation and breathing pattern of the ventilated monkey could have a crucial role in determining the delivered dose. This information is missing in the letter.

Lastly, we appreciate Dr. Guillon et al. for their comments on our publication and are delighted to learn more efforts are devoted to developing dry powder delivery system for mechanically ventilated patients.