The study demonstrates the high efficiency of a pulsating airflow in paranasal sinus ventilation and aerosolized drug delivery. This proves that topical drug delivery to the paranasal sinuses in relevant quantities is possible and indicates further clinical studies are necessary.

Our data support the hypothesis that topical drug delivery in relevant quantities to the nose and osteomeatal areas, including the paranasal sinuses, is possible using pulsating airflows. Furthermore, the frequency of drug applications may be reduced due to a delayed clearance and longer residence time.

Inhalation of aerosols is the preferred route of administration of pharmaceutical compounds to the lungs when treating various respiratory diseases. Inhaled antibiotics, hormones, peptides and proteins are potential candidates for direct targeting to the site of action, thus minimising systemic absorption, dilution and undesired side effects, as much lower doses (as low as a fiftieth) are sufficient to achieve a similar therapeutic effect, compared with oral administration. A quick relief from the symptoms and a good tolerance are the main advantages of aerosol therapy. A new class of electronic delivery device is now starting to enter the market. The eFlow electronic nebuliser (PARI GmbH, Germany) provides improved portability and, in some instances, cuts treatment time to only a fraction of what has been experienced with current nebulised therapy. Drug formulations and the device can be mutually adapted and matched for optimal characteristics to meet the desired therapeutic target. Reformulation of known and proven compounds in a liquid format are commercially attractive as they present a relatively low development risk for potential drug candidates and, thus, have become a preferred pathway for the development of new inhalation products.

Smart inhalers, connected to smartphones, can provide real-life objective information about the patterns of a patient's adherence and their inhaler technique during routine use. The e-modules contain the battery and measuring sensors. Many of these are add-on modules attached externally whilst others are integrated inside the inhaler. Smart inhalers that identify a dose has either been actuated or prepared do not confirm the dose was inhaled but they can send missed dose reminders and clinical studies have highlighted their potential to improve adherence and outcomes. The e-modules that measure an inhalation profile confirm a dose has been inhaled together with providing useful information about the inhaler technique. Studies confirm that the sensors are accurate and confirm their usefulness to provide information about real-life inhaler use. Add-on e-modules are generic whereas integrated smart inhalers can be approved containing active agents and, therefore, prescribed and instructed under healthcare guidance. Real-life studies need to be carried out to demonstrate their potential to improve disease control and prevent exacerbations to justifying their increased cost.

We investigated the in vitro influence of breathing patterns on lung dose (LD) and particle size distribution in an infant upper airway cast model in order to determine the optimal particle size for nebulized aerosol delivery to infants. Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200 mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm, respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8-30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p < 0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4 microm) through the upper airway cast showed a negative correlation with increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available as LD for all simulated breathing pattern showed a particle size distribution with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From our in vitro study, we conclude that the optimal particle size for nebulized aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.