Sounding airflow enhances aerosol delivery into the paranasal sinuses.
BACKGROUND
The use of aerosol therapy is commonly suggested in the treatment of paranasal disorders but it is difficult to achieve an effective penetration of drugs into the sinuses. The authors have recently shown that an oscillating airflow produced by phonation (nasal humming) causes a large increase in the gas exchange between the nose and the paranasal sinuses. This is reflected by a high peak in nasally exhaled nitric oxide (NO) levels because NO accumulated in the sinuses is rapidly washed-out via the sinus ostia.


OBJECTIVE
This study was designed to test whether the increase in sinus gas exchange caused by an oscillating airflow could be used to enhance penetration of a drug into the sinuses.


METHODS
In six healthy subjects a nitric oxide-synthase inhibitor L-NAME was administrated into the nostrils by a jet nebulizer connected to a duck call, which could be modified to generate either a sounding airflow or a non-sounding airflow. The degree of L-NAME penetration into the sinuses was judged from the reduction in nasal NO during humming exhalations. Sinus drug deposition was also studied in a model of the nose and sinus.


RESULTS
In humans the delivery of L-NAME with the non-sounding airflow had no effect on the NO levels achieved during humming, whereas L-NAME administration with sound caused a significant 22-35% reduction in nasal NO. In the model the aerosol delivery with the sounding airflow caused a fourfold increase in sinus drug deposition as compared with an aerosol without sound.


CONCLUSIONS
A sounding airflow increases the delivery of an aerosolized drug into the paranasal sinuses.
Maniscalco
M
M
Department of Pharmacology and Physiology, Karolinska Institute, Stockholm, Sweden. mauromaniscalco@hotmail.com
Sofia
M
M
Weitzberg
E
E
Lundberg
J O
JO
D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009330:Nebulizers and Vaporizers; D009569:Nitric Oxide / Q000032:analysis*; D009666:Nose; D010256:Paranasal Sinuses / Q000378:metabolism*; D012123:Pulmonary Ventilation
D000336:Aerosols; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester