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.

ObjectivesChronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery.Methods 99mTc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging.ResultsIn healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses.ConclusionIn contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways.

Innovative nebuliser systems bear the potential to greatly improve and expand the administration of therapeutic aerosols for the treatment of respiratory diseases. Exploiting the technology of a microperforated vibrating membrane offers a close control of the droplet size that is being generated and targeted to reach the lower airways, with little oropharyngeal deposition, thereby reducing undesired side effects. The greatly improved efficiency of such devices, as exemplified by the eFlow nebuliser (PARI), provides further advantages for the patient. A high respirable fraction due to the precisely defined perforations, low residual losses and the high liquid output rate combine to produce a highly efficient and fast administration of inhaled medications. Portability, ease of handling and noiseless operation have a positive effect on patient compliance, control of the therapy by the physician and the therapy costs.

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A special new device for diagnostic (bronchoprovocation) and therapeutic aerosol application is described. It consists of a high quality nebulizer system combined with a 10-liter storage bag which serves as an aerosol ‘conditioner’ (saturated ambient temperature and pressure conditions) and as a holding chamber to increase the respirable aerosol fraction and hence pulmonary deposition (Pari Provocation Test I). It allows ten times better standardized pulmonary aerosol deposition compared with the generally used nebulizers for calculation of dose-response curves especially for asthma provocation and dilatation tests. If slow inspiratory vital capacity maneuvers are used, pulmonary deposition of about 100 mg aerosol is achieved in children and adults. This device is especially important when exact dosing (also for therapeutic reasons) is required in the expanding field of topical and systemic aerosol application to or via the lung.