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PubMed1997

Magnetic resonance imaging of pulmonary ventilation. Initial experiences with a gadolinium-DTPA-based aerosol.

RATIONALE AND OBJECTIVES: The authors investigate whether a modified gadolinium (Gd)-DTPA formulation can be aerosolized and used as a contrast agent for magnetic resonance (MR) ventilation imaging of the lungs. METHODS: Gadolinium-DTPA (gadopentetate dimeglumine, Schering AG, Berlin, Germany, 100 mmol Gd/L) was modified by addition of mannitol (Sigma, Deisenhofen, Germany, 10 mg/mL) and the surface active detergent Lutrol F68 (BASF, Mannheim, Germany, 2 mg/mL). The imaging was performed in an anesthetized rat model after inhalation of the contrast agent aerosol (PulmoSonic, De Vilbiss, Germany, 10-minute nebulization). T1-weighted spin echo images (repetitive time [TR]/echo time [TE] = 40/3 mseconds) were acquired at 2 T (SIS 85; Sisco, Fremont, CA) before and as long as 120 minutes after administration of the contrast agent. RESULTS: The modified Gd-DTPA aerosol elicited high and relatively homogeneous enhancement of the lung directly after nebulization. The enhancement was more pronounced than that obtained with a Gd-DTPA formulation without additives. CONCLUSIONS: Gadolinium-DTPA-based aerosol appears to be a suitable contrast agent for MR ventilation imaging in an experimental animal model. Modification by mannitol (to increase proton density through a slight additional osmotic effect) and a detergent (to reduce droplet size by decreasing surface tension) is suitable and effective in increasing signal intensity compared with Gd-DTPA without modification.

Administration, Inhalation↗
PubMed2004

Otitis media: treatment with intranasal aerosolized surfactant.

OBJECTIVES/HYPOTHESIS: The objective was to determine the effect of intranasal surfactant alone and with other medications administered by metered dose inhaler aerosol on the function of the eustachian tube and on the resolution of experimentally induced otitis media with effusion (OME) and acute otitis media (AOM). STUDY DESIGN: Randomized, experimental, controlled animal studies. METHODS: Previously unreported (experiment 4) as well as published (experiments 1-3) data were detailed so that the reader could understand the continuum of information leading to the conclusions. In experiment 1, after a live-animal technique of measuring eustachian tube passive opening pressure was developed and validated, eustachian tube passive opening pressure was determined in 61 adult gerbils and 34 mice at baseline and 5 and 10 minutes after delivery of aerosolized intranasal metered dose inhaler surfactant. In experiments 2 and 3 (Klebsiella pneumoniae), lipopolysaccharide-induced OME was developed in gerbils. Thirty-five animals were randomly assigned to control, placebo, surfactant, surfactant with betamethasone, and surfactant with phenylephrine groups. Seventy animals were randomly assigned to control, placebo once daily (QD) and twice daily (BID), surfactant QD and BID, surfactant with betamethasone QD and BID, and surfactant with phenylephrine QD and BID groups. Intranasal aerosolized MDI medications were administered from postinfection day 2 until the effusion resolved. Otomicroscopy and tympanometry were performed on alternate days for 30 days. In experiment 4, AOM was developed in 39 chinchillas via transbullar injection of nontypeable Haemophilus influenzae on day 1. Thirteen animals each received placebo BID or surfactant BID, beginning on day 1. Thirteen animals received surfactant BID beginning on day 3. All administrations were continued for 10 days. Examinations were performed on seven occasions until day 27. Appropriate statistical measurements were employed, including one- and two-way ANOVA, strength-of-association measure (omega) calculation, chi, and Newman-Keuls post hoc multiple comparison tests. Significance was set as P value of less than.05. RESULTS: In experiment 1, a significant reduction in passive opening pressure was seen in both 5- and 10-minute postsurfactant measurements. Propellant alone was not effective. In experiments 2 and 3, OME resolved after an average period of 16 to 16.5 days in control, placebo QD and BID, and surfactant with phenylephrine QD groups. A significant decrease in OME days was seen in the surfactant QD (10.57 d) and BID (8.57 d), and surfactant with betamethasone QD (8.57 d) and BID (6.3 d) groups. A significant increase was seen in the phenylephrine BID group (18.67 d). In experiment 4, tympanometry was normal or near-normal in 62% and 48% of treated ears and in only 24% of placebo ears on day 12. Sixty-seven percent of placebo ears were culture positive at day 27, compared with 10% and 16% in surfactant groups 1 and 2. Seventy-five percent of untreated animals developed severe labyrinthitis, compared with 15% in groups 1 and 2. On day 27, 58% of placebo group middle ears had fluid, whereas 61% and 62% of ears in groups 1 and 2, respectively, were dry. These findings were significant. CONCLUSION: Intranasal application of aerosolized metered dose inhaler surfactant alone or with steroid reduced eustachian tube passive opening pressure in normal animals and duration of effusion in animals with experimental OME. Intranasal surfactant reduced the severity and duration of middle ear infection in AOM in this animal model.

Acute Disease↗
PubMed1986

The stability of 99Tcm-DTPA in an aerosol delivery system.

99Tcm-DTPA is now widely used in aerosol nebulizers for routine ventilation lung scanning. The stability of a commercially available DTPA kit has been measured when used in an aerosol delivery system and compared with the stability when stored in the parent vial according to the manufacturer's instructions. No significant breakdown was measured up to 8 h after reconstitution in the parent vial and up to 3 h when used as an aerosol. Values of the half time of clearance of DTPA aerosols in a group of 23 patients are compared with values given in the literature.

Adolescent↗
PubMed1988

Aerosol-perfusion lung scintigraphy: value of ventilation subtraction.

99Tcm-labelled aerosol ventilation and 99Tcm-macroaggregate albumin (99Tcm-MAA) perfusion can be performed in the diagnosis of pulmonary embolism (PE). If both examinations are performed on the same day, the superposition of activity from the first scintigraphic examination might mask defects in the second. In this study, 106 examinations were carried out for suspected PE. Aerosol ventilation was performed first with 20 to 30 mCi 99Tcm-labelled rhenium sulphur (four views, 200,000 counts). Immediately afterwards, with the patient remaining in the same position, 5 to 7 mCi of 99Tcm-MAA were injected (four views, 400,000 counts). After normalization, aerosol activity was subtracted from perfusion images and unprocessed perfusion (UP) and ventilation subtraction perfusion (SP) images were compared. Interobserver diagnostic reproducibility between three readers was calculated both for UP and SP images. Intraobserver reproducibility between UP and SP images was calculated for each reader. Interobserver reproducibility was comparable for SP and UP images. Intraobserver reproducibility was good. Thus, whether ventilation was subtracted or not from perfusion images, there was no appreciable effect on perfusion defect detection. However, some perfusion abnormalities showed up more clearly on SP images. Perfusion can be performed immediately after aerosol ventilation; the images thus obtained are reliable for interpretation, and subtraction of ventilation is not necessary.

Aerosols↗
PubMed1994

Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia in infants with human immunodeficiency virus infection.

Aerosolized pentamidine is widely used in adult patients with human immunodeficiency virus as both prophylaxis and therapy for Pneumocystis carinii pneumonia. The aim of this study was to evaluate the safety of a monthly regimen of aerosolized pentamidine in human immunodeficiency virus-infected infants. Seven human immunodeficiency virus-infected infants, ages 3.5 to 11 months, were given a total of 45 monthly treatments of aerosolized pentamidine. The infant's dose of pentamidine was based on an adult dosage of 300 to 600 mg/month, adjusted for minute ventilation and weight. There were no discernible clinical side effects in 62% (28 of 45) of the treatments. Observed toxicity included mild to moderate coughing, mild wheeze and transient arterial desaturation as measured by pulse oximetry. Pulmonary function data revealed an increased tidal volume (P < 0.005) and an increased pulmonary resistance (P < 0.02) post-pentamidine treatment. Urinary pentamidine concentrations were obtained and pentamidine was detected in all tested samples suggesting pulmonary deposition and systemic absorption. In conclusion aerosolized pentamidine appears to be a relatively safe, well-tolerated treatment in infants, with side effects similar to those seen in adults.

AIDS-Related Opportunistic Infections↗
PubMed1996

Aerosolized immunoglobulin treatment of respiratory syncytial virus infection in infants.

BACKGROUND: Recent studies in animals with experimental respiratory syncytial virus (RSV) infection indicate that passive immunization by intranasal or intratracheal application of gamma-globulins (immunoglobulins) may be beneficial for treatment of infants with lower respiratory tract infection caused by RSV. METHODS: We conducted a placebo-controlled, randomized multicenter study involving 68 infants with proven RSV infection admitted to 5 pediatric centers in Switzerland from November 1, 1992, through April 30, 1993. Treatment was carried out with aerosolized human IgG (Sandoglobulin) by assisted ventilation. On the day of hospital admission a single dose of 0.1 g of IgG per kg of body weight in a 5% solution or an identical amount of placebo, each delivered in 2 parts, was given. RESULTS: The two groups did not differ substantially in their response to the aerosol received. The rate of improvement for symptoms of respiratory tract infection, oxygen requirement and length of hospital stay were comparable for both groups. There was a significant reduction (P < 0.05) in the frequency of apneic spells observed in the treatment group by Day 3 posttreatment. Aerosol therapy was generally well-tolerated in nonintubated infants, but some severe side effects (increased oxygen requirements in two patients, pneumothorax in one patient) were observed in two of three intubated and ventilated infants treated with IgG. CONCLUSIONS: Aerosolized immunoglobulin in the dosage used had no substantial beneficial effect on RSV bronchiolitis. Despite these findings passive immunotherapy for treatment of RSV-induced lower respiratory tract infection deserves further evaluation before being discarded as ineffective.

Aerosols↗
PubMed2001

Safety of aerosolized amphotericin B lipid complex in lung transplant recipients.

BACKGROUND: Fungal infections remain an important cause of morbidity and mortality in lung transplant recipients. Aerosolized amphotericin B lipid complex (ABLC) may be more efficacious than conventional amphotericin B in the prevention of fungal infections in animal models, but experience with aerosolized ABLC in humans is lacking. METHODS: We conducted a prospective, noncomparative study designed to evaluate safety of aerosolized ABLC in lung or heart-lung transplant recipients. RESULTS: A total of 381 treatments were administered to 51 patients. Complete spirometry records were available for 335 treatments (69 in intubated patients, 266 in extubated patients). ABLC was subjectively well tolerated in 98% of patients. Pulmonary mechanics worsened by 20% or more posttreatment in less than 5% of all treatments. There were no significant adverse events related to study medication in any patient, and 1-year survival for all enrolled patients was 78%. CONCLUSION: Administration of nebulized ABLC is safe in the short-term and well-tolerated in lung transplant recipients. Additional prospective, randomized studies are needed to determine the efficacy of aerosolized ABLC alone or in conjunction with systemic therapies in the prevention of fungal infections in lung transplant recipients.

Adult↗
PubMed2000

Aerosol therapy for asthma.

Inhaled drugs play an important role in asthma management. The correct use of an appropriate delivery device is necessary to achieve the desired therapeutic effects of the drug. Currently, chlorofluorocarbon-propelled metered-dose inhalers, with or without spacers, are the most popular aerosol delivery devices. With the planned phase out of the chlorofluorocarbon metered-dose inhalers, the use of other delivery devices is being emphasized. To achieve optimal therapeutic effects, the drug and the delivery device should be considered a "couple". Aerosol delivery devices should provide an adequate "drug dose to the lung", be cost effective, simple to operate, minimize oropharyngeal deposition and systemic side effects, and match the patient's requirements. A new generation of aerosol delivery devices, incorporating the latest advances in aerosol technology, is likely to fulfill many of the goals mentioned above.

Administration, Inhalation↗
PubMed2004

Comparison of aerosol therapy with different perfluorocarbons in surfactant-depleted animals.

OBJECTIVE: The study investigates the effectiveness of aerosol treatment on gas exchange and pulmonary inflammatory reaction using perfluorocarbons with different molecular structure and vapor pressure. DESIGN: Experimental, prospective, randomized, controlled study. SETTING: Experimental laboratory at a university hospital. SUBJECTS: Twenty anesthetized neonatal piglets assigned to four groups. INTERVENTIONS: After establishment of lung injury by bronchoalveolar lavage, piglets either received aerosolized FC77 (n = 5), perfluorooctylbromide (n = 5), or FC43 (n = 5, 10 mL x kg(-1) x hr(-1) for 2 hrs) or intermittent mandatory ventilation (control, n = 5). Thereafter, animals were supported for another 6 hrs. MEASUREMENTS AND MAIN RESULTS: Pao2 significantly improved in the perfluorocarbon groups compared with control (p < .01). Final Pao2 (mean +/- SEM) was FC77, 406 +/- 27 mm Hg; perfluorooctylbromide, 332 +/- 32 mm Hg; FC43, 406 +/- 19 mm Hg; control, 68 +/- 8 mm Hg. Paco2 and mean pulmonary arterial pressure were lower in all perfluorocarbon groups compared with control. The ratio of terminal dynamic compliance to total compliance was significantly higher in the FC77 than in the FC43, perfluorooctylbromide, and control groups. Relative gene expression of interleukin-1beta, interleukin-8, P-selectin, E-selectin, and intercellular adhesion molecule-1 in lung tissue was determined by TaqMan real time polymerase chain reaction normalized to hypoxanthineguanine-phosphoribosyl-transferase and was shown to be reduced by all perfluorocarbons. CONCLUSIONS: Aerosol treatment with all the perfluorocarbons investigated improved gas exchange and reduced pulmonary inflammatory reaction independently from molecular structure and vapor pressure of the perfluorocarbons. Although differences in vapor pressure and molecular structure may account for varying optimal dosing strategies, several different perfluorocarbons were shown to be principally suitable for aerosol treatment.

Administration, Inhalation↗
PubMed2004

Characterization of plutonium aerosol collected during an accident.

This study determined the plutonium particle size distribution and dissolution rate of PuO2 aerosol collected during the 16 March 2000 release of an undetermined amount of PuO2 in a room within a plutonium facility at Los Alamos National Laboratory. The facility has been in operation since 1978 to support the development, fabrication, and testing of Pu heat sources for the U.S. Department of Energy. Several workers were in the room at the time of the release and in vivo study of five of the workers began the day after the exposure event. Four of the subjects subsequently received chelation therapy. Over 30 fixed air filter samplers (FASs) and four continuous air monitors (CAMs) were operating in the room during the radiological release. One 47-mm-diameter glass fiber FAS filter and one 25-cm-diameter mixed cellulose ester CAM filter containing Pu aerosol from the incident were examined in the study described here. Total alpha radioactivity on the filters was determined by gross alpha counting. Isotopic identification of the Pu was made by alpha spectrometry. Film autoradiography was used to characterize the spatial distribution of alpha-emitting particles on the filters. Track-etch autoradiography was used to estimate the distribution of alpha radioactivity in individual plutonium particles on the filters for particle size measurement. The glass fiber filter was then cut into six sections. Particles from two sections were resuspended in alcohol, dispersed as an aerosol using a Lovelace nebulizer, and characterized by aerodynamic diameter using a Lovelace Multi-jet cascade impactor. The measured activity median aerodynamic diameter from the cascade impactor was 4.8 mum with a geometric standard deviation of 1.5. That agreed with the size distribution obtained from the alpha track detection technique. The remaining four filter sections were used in an in vitro dissolution study with synthetic serum ultrafiltrate. The retention of undissolved Pu was consistent with a biphasic exponential function. The majority of the Pu dissolved with a half-time of 900 d. The information on particle size distribution and solubility from this study was useful in assigning a radiation dose to the exposed workers, supporting the decision to administer chelation therapy, and providing a model for characterizing accident-associated aerosols in the future.

Aerosols↗
PubMed2005

Aerosol transfer of bladder urothelial and smooth muscle cells onto demucosalized colonic segments for porcine bladder augmentation in vivo: a 6-week experimental study.

PURPOSE: In a pilot study we developed a cell transfer technology for populating demucosalized colonic segments with bladder urothelium. This process was achieved through aerosol transfer of a single cell suspension consisting of bladder urothelial cells, smooth muscle cells and fibrin glue onto demucosalized colonic segments. We further evaluate this new concept in a controlled study. MATERIALS AND METHODS: The study was performed on 20 piglets (20 kg). In all animals 50% of the bladder with excised, and a 10 cm segment of the sigmoid was isolated. Animals were then equally divided into 5 groups of 1) colocystoplasty only, 2) demucosalized colocystoplasty, 3) demucosalized colocystoplasty plus covering of the demucosalized sigmoid with fibrin glue only, 4) aerosol application of fibrin glue with single cell suspension of urothelial cells only to the demucosalized colon, and 5) aerosol application of fibrin glue with urothelial and smooth muscle cells to the demucosalized colon. The 4 corners of the augmented segments were marked with 5-zero polypropylene sutures. Animals were sacrificed 6 weeks later and the surface area of the augmented segment was measured. Segments were submitted to histological and immunohistochemical analysis. RESULTS: The surface area of the augmented segments showed an increase in group 1 animals, stabilization in groups 4 and 5, and marked reduction in groups 2 and 3. On hematoxylin and eosin, and Masson trichrome staining all group 1 animals showed normal colonic epithelium of the augment. All animals in groups 2 and 3 showed excessive scarring with urothelial coverage only at the augment periphery, while the central augment area showed no epithelium. Segments from groups 4 and 5 showed confluent epithelial covering with no fibrosis. There was no evidence of colonic epithelial re-growth in any animal in groups 2 to 5. Cytokeratin 7 and uroplakin III staining demonstrated complete coverage of the augmented segment with urothelium only in groups 4 and 5. CONCLUSIONS: The addition of aerosolized cells of urological origin is a viable augmentation approach that appears to achieve the much sought after inhibition of intrinsic fibrosis and contraction of colonic segments when incorporated into the urinary tract without this cellular component. Moreover, this technique appears to provide a histologically normal, confluent urothelium, which sets the stage for prevention of the well-documented biochemical aberrations inherent in augments containing gastrointestinal epithelium. While successful in this model regardless of the incorporation of urological smooth muscle cells, chronic studies are now warranted to validate the short-term results as well as determine whether the urological mesenchymal population (smooth muscle) will be required to sustain the uroepithelial phenotype in the long term.

Aerosols↗
PubMed2004

Administration of aerosolized terbutaline and budesonide reduces chlorine gas-induced acute lung injury.

BACKGROUND: The pathophysiology and treatment of chlorine gas-induced acute lung injury is poorly characterized and based on anecdotal data. This study aimed to assess the effects of aerosolized beta-2 adrenergic agonist and corticosteroid therapy on chlorine gas-induced lung injury. METHODS: Anesthetized, ventilated pigs were exposed to chlorine gas (400 parts per million for 20 minutes), then assigned randomly 30 minutes later to receive aerosolized terbutaline, budesonide, terbutaline followed by budesonide or placebo (6 pigs in each group). Hemodynamics, gas exchange, and lung mechanics were evaluated for another 5 hours. RESULTS: All the animals demonstrated an immediate increase in airway and pulmonary artery pressure as well as sharp drops in arterial oxygen tension (PaO2) and lung compliance (CL). Recovery of PaO2 and CL was greatest in the terbutaline plus budesonide group, but therapy with terbutaline and budesonide alone also was associated with significant improvement in PaO2 and CL, as compared with placebo. CONCLUSIONS: Treatment of acute chlorine gas lung injury with aerosolized terbutaline followed by aerosolized budesonide improved lung function. Combined treatment was more effective than treatment with either drug alone.

Adrenergic beta-Agonists↗
PubMed1980

Comparative efficacy of salbutamol by pressurized aerosol and wet nebulizer in acute asthma.

1 Cumulative dose-response curves (FEV1) to pressurized aerosol salbutamol were established in 17 patients admitted to hospital with acute severe asthma. After the maximal pressurized aerosol effect had been achieved, a further dose (5 mg) of salbutamol was given by wet nebulizer and any further increment recorded. 2 Baseline FEV1 was 1.16 +/- 0.55 (mean +/- s.d.), an average of 36% of predicted, and the maximal aerosol induced change in FEV1 was 0.435 +/- 0.330 1 (t = 5.72, P < 0.01). There was an additional, small increment in FEV1 after nebulizer of 0.043 +/- 0.085 1 (t = 2.26, P < 0.05). 3 Detailed analysis of the data according to a theoretical dose-response relationship showed that the nebulizer-aerosol increment was unrelated to asthma severity.

Acute Disease↗
PubMed1981

Sodium cromoglycate: spincaps or metered dose aerosol.

1 Sodium cromoglycate administered as a dry powder inhalation (20 mg/dose) via the Spinhaler was compared with a metered dose aerosol (2 mg/dose) in an eight week double dummy double blind crossover trial in 29 asthmatic children. 2 The powder formulation was associated with significantly less symptoms (night wheeze, night cough, day wheeze, day cough, activity) and bronchodilator intake; and significantly greater weight gain than aerosol therapy. There were no significant differences in morning or evening peak flow measurements on the two treatments. 3 The powder may be more effectively inhaled than the aerosol or the dose of the aerosol may not be large enough.

Adolescent↗
PubMed1977

Comparison of salbutamol Rotahaler with conventional pressurized aerosol.

Salbutamol in a powder aerosol from the Rotahaler insufflator was compared, with equal doses of the conventional pressurized aerosol by dose-response curves and in a 1 month open trial, in the treatment of asthma patients with good inhalation technique. Results were not significantly different in either study. A further group of asthma patients, who were known to be incapable of using pressurized aerosols effectively, were shown to benefit from treatment with the Rotahaler. This device should increase the value of the sympathomimetic drugs to the minority of asthma patients who cannot use conventional aerosols correctly.

Administration, Intranasal↗
PubMed1984

Delivery of sodium cromoglycate by pressurized aerosol.

Sodium cromoglycate (SCG) has recently been formulated as a pressurized aerosol. Twenty-five asthmatic outpatients taking SCG via the Spinhaler were studied in a double-dummy, double-blind cross-over trial in which subjects took Spincaps containing 20 mg of SCG for 2 months, and for the alternate 2 months were treated with SCG aerosol delivering 1 mg/actuation. There was no evidence of clinical deterioration occurring during the period on aerosol SCG. During this period however cough frequency was significantly lower and when data for the 8-13 and 14-46 year age groups were analysed separately, this decrease was seen to be confined to the younger group. Furthermore, this group but not the adults, showed a significant improvement in morning peak expiratory flow rate. We conclude that the aerosol preparation of SCG is a useful alternative to delivery by Spinhaler for patients who are able to coordinate, and that it may have special advantages for children.

Adolescent↗
PubMed1991

Bronchial hyperresponsiveness and cellular infiltration in the lung of guinea-pigs sensitized and challenged by aerosol.

We have studied the development of airway hyperresponsiveness and the pulmonary cell infiltration in a guinea-pig model in which both initial sensitization and subsequent exposure to the antigen were performed by aerosol. Enhanced bronchopulmonary response to aerosol administration of acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) was observed 3-4 hr and 18-24 hr after antigen exposure of sensitized animals. In contrast, when ACh and 5-HT were administered intravenously 3-4 hr after the challenge, no significant alteration of the dose-response curves was observed. However, 18-24 hr after antigen challenge, a marked leftward shift of the dose-response curve was observed on intravenous injection of ACh or 5-HT. The increased bronchial reactivity to aerosolized ACh in sensitized and challenged guinea-pigs reached a maximum by days 2-4, was still significantly increased at day 5 and returned to the basal value by day 8. No further alteration of the dose-related bronchopulmonary response to aerosol or intravenous administration of ACh was recorded 24 hr after a second antigen challenge, performed 8 days after the initial one. The analysis of bronchoalveolar lavage fluids showed a significant increase in the number of polymorphonuclear neutrophils 3-4 hr after the exposure of sensitized animals to the antigen, which was also associated with a significant eosinophilia at 18-24 hr. Histological examination of lung specimens obtained from animals 3-4 hr following challenge demonstrated eosinophil infiltration in the peribronchial regions and bronchial walls, as well as within the epithelium. Furthermore, as compared to time 3-4 hr, less eosinophils in the peribronchial area and submucosa were counted 24 hr after antigen challenge. However, a role of eosinophil-derived products in the development of bronchial hyperresponsivenss in this experimental model remains to be established.

Acetylcholine↗
PubMed2006

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. MATERIALS AND 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. CONCLUSION: A sounding airflow increases the delivery of an aerosolized drug into the paranasal sinuses.

Administration, Intranasal↗