Pari Respiratory Equipment Research Articles

NUMERICAL SIMULATION OF THE DISPERSION AND DEPOSITION OF A SPRAY CARRIED BY A PULSATING AIRFLOW IN A PATIENT-SPECIFIC HUMAN NASAL CAVITY

The authors thank Dr. H. Mentzel from PARI Respiratory Equipment, Inc. for intense discussions about the pulsating spray initial conditions. The current study is part of a project supported by the German Research Foundation (DFG) through a research fellowship of the HGS MathComp. Furthermore, high-performance computing time at the bwForCluster MLS&WISO Production which is funded by the state of Baden-Wurttemberg through bwHPC and DFG through grant INST 35/1134-1 FUGG.

Computerized Dead-Space Volume Measurement of Face Masks Applied to Simulated Faces.

The dead-space volume (VD) of face masks for metered-dose inhaler treatments is particularly important in infants and young children with asthma, who have relatively low tidal volumes. Data about VD have been traditionally obtained from water displacement measurements, in which masks are held against a flat surface. Because, in real life, masks are placed against the face, VD is likely to differ considerably between masks depending upon their contour and fit. The aim of this study was to develop an accurate and reliable way to measure VD electronically and to apply this technique by comparing the electronic VD of commonly available face masks. Average digital faces were obtained from 3-dimensional images of 270 infants and children. Commonly used face masks (small and medium) from various manufacturers (Monaghan Medical, Pari Respiratory Equipment, Philips Respironics, and InspiRx) were scanned and digitized by means of computed tomography. Each mask was electronically applied to its respective digital face, and the VD enclosed (mL) was computerized and precisely measured. VD varied between 22.6 mL (SootherMask, InspiRx) and 43.1 mL (Vortex, Pari) for small masks and between 41.7 mL (SootherMask) and 71.5 mL (AeroChamber, Monaghan Medical) for medium masks. These values were significantly lower and less variable than measurements obtained by water displacement. Computerized techniques provide an innovative and relatively simple way of accurately measuring the VD of face masks applied to digital faces. As determined by computerized measurement using average-size virtual faces, the InspiRx masks had a significantly smaller VD for both small and medium masks compared with the other masks. This is of considerable importance with respect to aerosol dose and delivery time, particularly in young children. (ClinicalTrials.gov registration NCT01274299.).

Tobramycin administered by the TOBI® Podhaler® for persons with cystic fibrosis: a review

From its introduction, the antibiotic tobramycin has been an important tool in the management of persons with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infections. Initially an intravenous rescue treatment for pulmonary exacerbations, tobramycin delivered by inhalation has become a mainstay of chronic suppressive CF infection management. Platforms for tobramycin aerosol delivery have steadily improved, with increased lung deposition complimented by decreased device complexities, loaded tobramycin doses, delivery times, and treatment burdens. Most recently, a unique tobramycin inhalation powder (TIP) formulation with a portable delivery system, the TOBI® Podhaler® (Novartis AG, Basel, Switzerland) has been developed and approved in Europe, Canada, and Chile. Four capsules, each containing 28 mg of TIP are successively pierced and inhaled via the T-326 Dry Powder Inhaler Device (Novartis AG, Basel, Switzerland). No external power source is required to deliver an efficacious tobramycin dose in minutes. By comparison, tobramycin inhalation solution (TIS) (TOBI®; Novartis), is delivered by LC® Plus (PARI Respiratory Equipment Inc, Midlothian, VA) jet nebulizer powered by an air compressor over 15–20 minutes. Comparative pharmacokinetics, safety, and efficacy studies of TIS and TIP in CF subjects with P. aeruginosa ≥ 6 years old demonstrate that: tobramycin lung deposition with 112 mg TIP is comparable to that attained with 300 mg TIS, TIP is more effective than placebo and not inferior to TIS with respect to pulmonary function benefit, and TIP has significantly faster treatment times and achieves higher patient satisfaction than TIS. TIP is associated with an increased frequency of mild to moderate local adverse events (cough, dysphonia, and dysgeusia) compared with TIS, however, these become less frequent as subjects gain TIP experience. These results suggest that the TOBI Podhaler may better meet the needs of many CF patients and families by reducing treatment time and complexity and improving patient satisfaction compared with TIS.

Facial and Ocular Deposition of Nebulized Budesonide: Effects of Face Mask Design

In vivo case reports and in vitro studies have indicated that aerosol therapy using face masks can result in drug deposition on the face and in the eyes, and that face mask design may affect drug delivery. To test different mask/nebulizer combinations for budesonide, a nebulized steroid used to treat pediatric patients with asthma. Using high-performance liquid chromatography, drug delivery (inhaled mass), facial, and ocular deposition of budesonide aerosols were studied in vitro using a ventilated face facsimile (tidal volume, 50 mL; rate, 25 breaths/min, duty cycle 0.4), a tight-fitting test mask, a standard commercial mask, and a prototype mask designed to optimize delivery by reducing particle inertia. Nebulizer insertion into the mask (front loaded vs bottom loaded) was also tested. Particle size was measured by cascade impaction. Pari LC Plus (PARI Respiratory Equipment; Midlothian, VA) and MistyNeb (Allegiance; McGaw Park, IL) nebulizers were tested. Inhaled mass for tight-fitting and prototype masks was similar (13.2 +/- 1.85% vs 14.4 +/- 0.67% [percentage of nebulizer charge], p = 0.58) and significantly greater than for the commercial mask (3.03 +/- 0.26%, p = 0.005). Mask insertion of nebulizer was a key factor (inhaled mass: front loaded vs bottom loaded, 8.23 +/- 0.18% vs 3.03 +/- 0.26%; p = 0.005). Ocular deposition varied by an order of magnitude and was a strong function of mask design (4.77 +/- 0.24% vs 0.35 +/- 0.05%, p = 0.002, tight fitting vs prototype). Particle sizes (7.3 to 9 microm) were larger than previously reported for budesonide. For pediatric breathing patterns, mask design is a key factor defining budesonide delivery to the lungs, face, and eyes. Front-loaded nebulizer mask combinations are more efficient than bottom-loaded systems.

Effect of High-Frequency Chest Wall Oscillation on the Central and Peripheral Distribution of Aerosolized Diethylene Triamine Penta-acetic Acid as Compared to Standard Chest Physiotherapy in Cystic Fibrosis

High-frequency chest wall oscillation (HFCWO) has been shown to be as effective as standard chest physiotherapy (SCPT) for removal of pulmonary secretions as well as increasing FEV(1) in cystic fibrosis (CF) patients. Patients using HFCWO often administer aerosolized medications simultaneously, reducing time required for daily care. While peripheral pulmonary distribution of tracer in normal subjects has been shown to be unaffected by HFCWO, this has not been studied in CF patients. We evaluated distribution of aerosolized (99m)Tc diethylene triamine penta-acetic acid (DTPA) administered simultaneously with HFCWO and compared this with DTPA aerosolized after SCPT. Ten CF patients, ages 22 to 38 years, with moderate-to-severe obstructive disease were studied in a crossover design after documentation of stable lung function. (133)Xe was administered to delineate total lung volume. DTPA was aerosolized (Pari LC Plus nebulizer and Pulmo-Aide compressor; Pari Respiratory Equipment Inc.; Richmond, VA) to delineate airway deposition. The central to peripheral deposition ratio (C/P ratio) of each lung was analyzed in each study group. Central regions were represented by the inner one third of the (133)Xe scan as demonstrated in previous research models. The mean C/P ratio (+/- SD) for both lungs was 1.45 +/- 0.31 with HFCWO and 1.46 +/- 0.28 following SCPT (p = not significant [NS]). Right lung mean C/P ratio was 1.74 +/- 0.43 with HFCWO and 1.85 +/- 0.63 after SCPT (p = NS). Left lung mean C/P ratio was 1.25 +/- 0.29 with HFCWO and 1.21 +/- 0.35 after SCPT (p = NS). There was no correlation between C/P ratio and FEV(1) or FVC. Use of HFCWO in combination with aerosolized DTPA did not result in increased central deposition as compared with aerosolized DTPA administered after SCPT. Further study is required to determine if combining HFCWO with aerosolized medications can be modified to improve peripheral deposition.

Suitability of Caspofungin for Aerosol Delivery: Physicochemical Profiling and Nebulizer Choice

Background: Aerosolized antifungal therapy is a promising route of drug delivery for pulmonary aspergillosis due to attainment of high localized concentrations. Caspofungin, a new antifungal agent with proven efficacy against invasive aspergillosis, has ideal potential for aerosolization. Study objective: To examinein vitro the suitability of caspofungin for aerosol administration by characterizing factors that influence efficacy and airway tolerance of aerosol delivery: physicochemical properties, aerodynamics of drug particles, and efficiency of nebulizing systems. Design: Physicochemical characteristics of caspofungin solutions (10 mg/mL and 30 mg/mL) were analyzed: osmolality, pH, viscosity, and surface tension. A time-of-flight aerosol spectrometer API Aerosizer was used to determine aerosol particle size and distribution. Drug output was quantified by high-performance liquid chromatography assay. Nebulizer efficiency was measured by drug output and respirable fraction (percentage of aerosolized particles with a 1 to 5 μm aerodynamic diameter) and compared among three jet nebulizer/compressor systems: device 1, Micromist (Hudson RCI; Temecula, CA)/Pulmo-Aide (model 5650D; DeVilbiss; Somerset, PA); device 2, Sidestream MS 2400/Envoy model IRC 1192 (Invacare; Elyria, OH); and device 3, Pari LC Star/Proneb Ultra (Pari Respiratory Equipment; Midlothian, VA). Measurements and results: Caspofungin requires 0.9% NaCl rather than sterile water as the diluent and addition of 0.3N NaOH buffer to adjust acidity of solutions (pH 6.17 to 6.26) in order to achieve optimal physicochemical properties for airway tolerability (osmolality, 150 to 550 milliosmol per kilogram; chloride ion, 31 to 300 mmol/L; and pH 7.4). The drug output rate increased with higher concentrations of drug solution: device 1, 4.0 mg/min vs 12.5 mg/min; device 2, 5.4 mg/min vs 14.7 mg/min; and device 3, 2.3 mg/min vs 12 mg/min, respectively. The percentage of particles within the respirable range varies depending on device and concentration of drug solutions (10 mg/mL vs 30 mg/mL): device 1, 85% vs 38%; device 2, 44% vs 57%; and device 3, 83% vs 93%, respectively. Conclusion: Caspofungin solution with adjustments appears to have physicochemical and aerodynamic characteristics suitable for aerosolization when used with either the Pari LC Star/Proneb Ultra or Micromist/Pulmo-Aide devices. Furtherin vivo testing is warranted. Background: Aerosolized antifungal therapy is a promising route of drug delivery for pulmonary aspergillosis due to attainment of high localized concentrations. Caspofungin, a new antifungal agent with proven efficacy against invasive aspergillosis, has ideal potential for aerosolization. Study objective: To examinein vitro the suitability of caspofungin for aerosol administration by characterizing factors that influence efficacy and airway tolerance of aerosol delivery: physicochemical properties, aerodynamics of drug particles, and efficiency of nebulizing systems. Design: Physicochemical characteristics of caspofungin solutions (10 mg/mL and 30 mg/mL) were analyzed: osmolality, pH, viscosity, and surface tension. A time-of-flight aerosol spectrometer API Aerosizer was used to determine aerosol particle size and distribution. Drug output was quantified by high-performance liquid chromatography assay. Nebulizer efficiency was measured by drug output and respirable fraction (percentage of aerosolized particles with a 1 to 5 μm aerodynamic diameter) and compared among three jet nebulizer/compressor systems: device 1, Micromist (Hudson RCI; Temecula, CA)/Pulmo-Aide (model 5650D; DeVilbiss; Somerset, PA); device 2, Sidestream MS 2400/Envoy model IRC 1192 (Invacare; Elyria, OH); and device 3, Pari LC Star/Proneb Ultra (Pari Respiratory Equipment; Midlothian, VA). Measurements and results: Caspofungin requires 0.9% NaCl rather than sterile water as the diluent and addition of 0.3N NaOH buffer to adjust acidity of solutions (pH 6.17 to 6.26) in order to achieve optimal physicochemical properties for airway tolerability (osmolality, 150 to 550 milliosmol per kilogram; chloride ion, 31 to 300 mmol/L; and pH 7.4). The drug output rate increased with higher concentrations of drug solution: device 1, 4.0 mg/min vs 12.5 mg/min; device 2, 5.4 mg/min vs 14.7 mg/min; and device 3, 2.3 mg/min vs 12 mg/min, respectively. The percentage of particles within the respirable range varies depending on device and concentration of drug solutions (10 mg/mL vs 30 mg/mL): device 1, 85% vs 38%; device 2, 44% vs 57%; and device 3, 83% vs 93%, respectively. Conclusion: Caspofungin solution with adjustments appears to have physicochemical and aerodynamic characteristics suitable for aerosolization when used with either the Pari LC Star/Proneb Ultra or Micromist/Pulmo-Aide devices. Furtherin vivo testing is warranted.

Evaluation of Nebulizer Performance under Various Humidity Conditions

Jet nebulizers are a drug delivery tool commonly used for treating respiratory diseases. When a nebulizer generates aerosols, the rate at which droplets evaporate depends on humidity conditions around the nebulizer outlet. Because the relative humidity (RH) of the air affects the evaporation rate, the aerosol distribution and drug delivery dose is also affected by RH. Four nebulizers were chosen for comparison in this study: PARI LC Plus (PARI Respiratory Equipment, Inc., Midlothian, VA), SideStream (Medic-Aid Ltd., UK), VixOne (Westmed, Inc., Tucson, AZ), and Micromist (Hudson Respiratory Care Inc., Temecula, CA). Two different formulations were used: albuterol (liquid solution) and budesonide (suspension). Particle distribution (mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD]), nebulizer efficiency (total efficiency and respirable fraction [RF] efficiency for particles less than 4.7 microm), and dead volume (the amount of solution remaining after nebulization) were compared at the RH of 5%, 50%, and 80%. Our results showed that the MMAD increased (p value varied from <0.001 to 0.016) with the increase in RH, except for with the VixOne unit with albuterol (p = 0.24). The MMAD from the budesonide always appeared higher than from the albuterol. The RF (and thus, the inhalation dose) was lower with a higher RH. Except for the PARI LC Plus with budesonide, the RF decreased approximately 15-27% when the RH rose from 5% to 50%. For the PARI LC Plus nebulizer, the lower dead volume (0.22 mL) with higher residual drugs (62.3% of total drug) was obtained at an RH of 5% comparing the RH of 50% and 80% because of the unit's unique design.

Pulmonary delivery of anti-contagion aerosol to diminish exhaled bioaerosols and airborne infectious disease

BACKGROUND/OBJECTIVES: Many contagious diseases are transmitted by exhalation of infectious droplets. Airborne infectious disease (AID) spread via exhaled bioaerosols (EBs) is a significant public health risk. Altering biophysical surface properties of airway lining fluid (ALF) through an inhaled, safe anticontagion aerosol (ACA) of isotonic saline provides a novel mechanism to diminish EB. In a recent study in normal volunteers (Edwards et al., PNAS 101:17383-388, 2004), half the study population was found to expire many more bioaerosol particles during quiet breathing and therefore bear the burden of production of EB. Administering nebulized isotonic saline (6 minutes) to these high producers diminished EB expired by 72.1 ± 8.2% for up to 6 hours. A subsequent study in Holstein bulls (a relevant animal model of AID) investigated the role of ACA dose on EB over time. METHODS: Seven Holstein bull calves (75-140 kg) were anesthetized, intubated, and maintained under general anesthesia following Defense Department and university-approved protocols on a custom-designed closed circle anesthesia system modified to evaluate pulmonary function and sample the number and size of EB using an Optical Particle Counter (Climet Instrument Company, Redlands, California). Every animal received four different ACA (0.9% isotonic saline) doses by nebulization (sham, 1.8, 6, or 12 minutes; Pari Respiratory Equipment, Starnberg, Germany) through the intubation tube; a minimum of 1week separated dosing in individual animals and doses were randomized throughout the study. EB were measured pre-ACA treatment and at 5, 15, 30, 60, 90, 120, and 180 minutes post-ACA treatment. RESULTS: Substantial inter-subject variability was found in baseline values, which revealed two distinct populations, low producers and high producers similar to the human trial. Delivery of ACA showed a dose-responsive effect on EB; 6 minutes of ACA treatment resulted in >50% decrement in EB for at least 120 minutes compared to pre-treatment. CONCLUSIONS: These results suggest individual variability in EB production may contribute to infectivity and ACA offers a dose-sensitive, ubiquitous measure to limit EB. A clinical trial assessing the role of AID (influenza) on EB production with a follow-up study evaluating the role of ACA in limiting EB is ongoing. These studies provide the foundation for a strategy to mitigate transmission of AID. This work was partially funded by the Technical Support Working Group (TSWG).

Comparison of Breath-Enhanced to Breath-Actuated Nebulizers for Rate, Consistency, and Efficiency

To evaluate differences between three new-generation nebulizers-Pari LC Star (Pari Respiratory Equipment; Mississauga, ON, Canada), AeroEclipse (Trudell Medical International, London, ON, Canada), and Halolite (Medic-Aid Limited, West Sussex, UK)-in terms of rate and amount of expected deposition as well as the consistency of the doses delivered. The in vitro performance characteristics were determined and then coupled to the respiratory pattern of seven patients with cystic fibrosis (age range, 4 to 18 years) in order to calculate expected deposition. The Pari LC Star and AeroEclipse were characterized while being driven by the Pari ProNeb Ultra compressor (Pari Respiratory Equipment) for home use, and by a 50-psi medical air hospital source. The Halolite has its own self-contained compressor. Algorithms for the rate of output for the inspiratory flow were developed for each device. Patient flow patterns were divided into 5-ms epochs, and the expected deposition for each epoch was calculated from the algorithms. Summed over a breath, this allowed the calculation of the estimated deposition for each patient's particular pattern of breathing. The rate of deposition was highest for the Pari LC Star and lowest for the Halolite. Rate of deposition was independent of respiratory pattern for the Pari LC Star and AeroEclipse, but proportional to respiratory rate for the Halolite. The differences between the Pari LC Star and AeroEclipse were less when driven by the 50-psi source. The AeroEclipse had the least amount of drug wastage. As designed, the Halolite delivered a predetermined amount of drug very accurately, whereas expected deposition when run to dryness of the other two devices had significant variations. To minimize treatment time, the Pari LC Star would be best. To minimize drug wastage, the AeroEclipse would be best. To accurately deliver a specific drug dose, the Halolite would be best.

In vitro comparison of an electronic micropump nebulizer with other high efficiency nebulizers

Rationale Nebulizers vary in available respirable mass and treatment times. The Aeroneb® Go Nebulizer (Aerogen, Inc.) has a novel design and generates aerosol using the OnQ™ electronic micropump. Its aerosol delivery characteristics were compared with those of the high efficiency MicroAir® (Omron, Inc.) and LC Star® (Pari Respiratory Equipment, Inc.) nebulizers using albuterol sulfate ampoules (2.5 mg in 3 mL). Methods Inhaled albuterol was collected on a filter placed between the nebulizer and breathing simulator (Hans Rudolph; adult pattern). Aerosol Mass Median Aerodynamic Diameter (MMAD) and fine particle fraction less than 5.8 μm (FPF) were determined by cascade impaction. The amount of drug deposited was determined by HPLC. Treatment time was measured to the end of aerosol generation or one minute past sputter. Results The MMAD of the Go (3.1 μm) fell between those of the MicroAir (5.2 μm) and LC Star (1.7 μm). Respirable mass (inhaled mass × FPF) trended greater for the LC Star (31 ± 6%) and the Go (31 ± 4%) vs. the MicroAir (27 ± 2%) (p=ns by ANOVA). Treatment time for the Go (6 min) was half that of the Micro Air (12 min) or the LC Star (14 min). Conclusion Aerosol delivery characteristics of the Aeroneb Go are consistent with those of the most efficient general-purpose nebulizers. The Aeroneb Go offers the advantage of a substantially shorter treatment time.

Efficiency of Pulmonary Administration of Tobramycin Solution for Inhalation in Cystic Fibrosis Using an Improved Drug Delivery System

To determine whether tobramycin solution for inhalation (TSI) can be administered safely and more efficiently with a new-generation aerosol device, the AeroDose 5.5 RP inhaler (Aerogen; Mountain View, CA) than with the approved PARI LC PLUS nebulizer (PARI Respiratory Equipment; Monterey, CA) with Pulmo-Aide compressor (DeVilbiss Corp; Somerset, PA). Second, we wanted to ascertain which AeroDose-delivered tobramycin dose is equivalent to the standard 300-mg dose administered with the PARI LC PLUS. Open-label, randomized, multicenter, single-dose, three-period, four-treatment, active- control, crossover trial. Nine US cystic fibrosis (CF) centers. Fifty-three patients >or= 12 years of age with a confirmed diagnosis of CF, the ability to expectorate sputum, and FEV(1) of >or= 40% of predicted. Subjects inhaled three single doses of TSI at 1-week intervals, as follows: conventional control treatment, 300 mg via the PARI LC PLUS; and two of three experimental treatments, 30, 60, or 90 mg via the AeroDose. FEV(1) was measured before and after dosing. After each dose, sputum and serum samples were collected at various intervals for 8 h, and urine was collected for 24 h to estimate lung and systemic tobramycin delivery. There were no significant differences between treatments in the change in FEV(1) 30 min after dosing or in the frequency of adverse events. Sputum and serum levels of tobramycin produced by the AeroDose 90-mg dose treatment approximated those achieved with the PARI LC PLUS 300-mg dose treatment. Nebulization times using the AeroDose inhaler were < 50% those of the PARI LC PLUS. Compared with the standard nebulizer, the AeroDose safely achieved an approximately threefold greater efficiency in the delivery of TSI to the lungs in less than half the time.

Nebulizer Choice for Inhaled Colistin Treatment in Cystic Fibrosis

To develop practical ways of nebulizing colistin by determining the rate of drug output, total drug output, and particle-size distribution of two commercially available jet nebulizers, the disposable Hudson 1730 Updraft II (Hudson Respiratory Care; Temecula, CA) and the reusable Pari LC Star breath-enhanced nebulizer (Pari Respiratory Equipment; Midlothian, VA). The nebulizers contained colistin, 75 mg, in 4 mL of isotonic solution. Particle-size distribution was measured by helium-neon laser diffraction, allowing calculation of the respirable fraction (RF), the mass of aerosol comprised of droplets < 5 microm. The mean (95% confidence interval [CI]) total rate of output of the Updraft II was 2.6 mg/min (2.0, 3.1; n = 4) with 1.3 mg/min (1.0, 1.5) mg/min within the RF. The rate of output of the LC Star increased in a quadratic relationship to the inspiratory flow, delivering 1.8 mg/min (0.7, 2.0; n = 4) with 1.4 mg/min (1.3, 1.6) within the RF, and 6.2 mg/min (5.6, 6.8) with 5.3 mg/min (4.8, 5.7) within the RF, at 0 L/min and 20 L/min inspiratory flows, respectively. Efficiency, as the rate of expected pulmonary deposition divided by rate of total output, was then calculated. The LC Star estimated 56% (51, 61) efficiency, with pulmonary delivery of 29% (26, 32) of the charge of the nebulizer, compared to the Updraft II at 22% (22, 23) efficiency and expected pulmonary deposition of 10% (10, 10) of the dose. Colistin can be successfully nebulized with both nebulizers tested. This study provides an estimate of in vivo efficiency and expected pulmonary deposition that may be used in future trials.

Accounting for radioactivity before and after nebulization of tobramycin to insure accuracy of quantification of lung deposition.

The ability to predict drug deposition of inhaled drugs used in cystic fibrosis (CF) is important if there is a need to target specific doses of drug to the lungs of individual patients. The gold standard of measuring pulmonary deposition is the quantification of an aerosolized radiolabel either mixed with the drug solution or tagged directly to the compound of interest. Accuracy of the quantification could be assured if there is agreement between the amount of radioactivity before and after administration. Before administration, the radiolabel is concentrated in the well of the nebulizer, whereas after administration, it is distributed throughout the nebulizer, the expiratory filter and connectors, and the upper airway, stomach, trachea, and lung. Not only is the geometry of the distribution that is presented to the gamma camera different, but there are different attenuation factors for the various body tissues. The primary aim of this study was to evaluate the accuracy of the quantification of deposition. Secondary goals were to compare in vitro nebulizer performance with that measured in vivo during the deposition study. Eighty milligrams of tobramycin and technetium bound to human serum albumin was administered to 10 normal adults using a Pari LC Jet Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebulizer. Techniques were developed that allowed for the accounting of 99 +/- 2% of the initial radioactivity. The fraction of the rate of lung deposition to total body deposition was the in vivo respirable fraction (0.62 +/- 0.07), which closely agreed with in vitro measurements of respirable fraction (0.62 +/- 0.04). Drug output measured from the change in weight and concentration in the nebulizer systematically overestimated drug output measured by the deposition study. The results indicate that 11.8 of the initial 80 mg would be deposited in the lungs. This technique could be adapted to accurately quantify the amount of deposition on any inhaled therapeutic agent, but caution must be used when extrapolating performance of a nebulizer on the bench to expected deposition in patients.

A Comparison of Peak Sputum Tobramycin Concentration in Patients With Cystic Fibrosis Using Jet and Ultrasonic Nebulizer Systems

To determine whether adequate concentrations of a new formulation of tobramycin could be delivered to the lower respiratory tract of patients with cystic fibrosis (CF) using a jet nebulizer delivery system. A multicenter, open-label, randomized, crossover study. Ten tertiary care, university-affiliated, teaching hospitals in the United States. Sixty-eight patients recruited from 10 CF Foundation centers and who were at least 8 years of age, had a diagnosis of CF, and expectorated daily sputum. No control subjects enrolled. Each patient received one administration of aerosolized tobramycin from each of the three nebulizer systems in random order. Each administration was separated by a minimum of 48 h. The two jet nebulizer systems tested were the Sidestream (Medic-Aid; Sussex, UK), and the Pari LC (Pari Respiratory Equipment; Richmond, Va), with a DeVilbiss Pulmoaide compressor (DeVilbiss Health Care; Somerset, Pa), both administering 300 mg tobramycin in 5 mL of 1/4 normal saline solution (NS). Patients were also administered 600 mg tobramycin in 30 mL of 1/2 NS with the UltraNeb 99/100 (DeVilbiss). Sputum and serum tobramycin concentration and pulmonary function were monitored. An adequate peak sputum tobramycin concentration was defined as > 128 microg/g sputum at any of three time points (10, 60, or 120 min) after completion of treatments. The peak tobramycin concentrations in expectorated sputum were 687+/-663 microg/g (mean+/-SD) with the Pari LC and 489+/-402 microg/g with the Sidestream. Adequate peak sputum tobramycin concentration was achieved in 93% of the patients with the Sidestream, and in 87% of the patients with the Pari LC. Peak sputum concentrations were found to be substantially higher when patients received tobramycin administered with the UltraNeb 99/100, 1,498+/-1,331 microg/g with 30% of patients having levels exceeding 2,000 microg/g. Serum tobramycin concentrations were < or = 4 microg/mL for all patients following administration with each nebulizer. Adequately high sputum tobramycin concentrations were documented in sputum in > 85% of patients following the administration of 300 mg/5 mL formulation of tobramycin aerosolized by the two jet nebulizer delivery systems, Sidestream and Pari LC. The single tobramycin administration delivered by these two systems is well-tolerated.