Clinical and endoscopic predictors of histological oesophagitis in infants

Therapeutic aerosols pay an increasing role in the treatment of equine respiratory disorders. This route of delivery permits concentration of significant amounts of drugs at the site of action without unwanted high systemic concentration and resultant side effects. The efficiency of such a topical therapy depends on the quantity of inhaled drugs deposited in the lungs and, for some drugs, on the proportion retained in specific parts of the lungs. The objective of this study was to define and to compare quantitative (dose deposited) and qualitative (regional distribution) deposition of an aerosol in the equine lungs, using either a ultrasonic nebuliser (UN) currently used in human medicine or a high pressure jet nebuliser (JN) especially developed for the equine species. This comparison was possible owing to gamma-scintigraphy, a noninvasive technique ideally suited to give information about both total and regional deposition of inhaled drugs in the respiratory tract. The quantitative study did not point out any difference between the 2 systems concerning the activity released from the nebuliser proportionally to the initial loaded dose (mean +/- s.d. 45.95 +/- 4.93% for the UN vs. 46.47 +/- 8.49% for the JN). By contrast, the percentage of the dose released reaching the lungs was significantly lower with the UN compared to the JN (5.09 +/- 0.66% vs. 7.35 +/- 1.96%). The qualitative analysis did not show any significant difference in size of aerosol deposition image between the 2 nebulisers. However peripheral deposition was significantly higher with JN compared to UN. In conclusion, both nebulisers may be used for aerosol therapy in the equine species. The ultrasonic and pneumatic nebulisation achieved drug deposition in the peripheral part of the lungs (i.e. small airways and lung parenchyma).     

Safety of a single aerosol administration of escalating doses of the cationic lipid GL-67/DOPE/DMPE-PEG5000 formulation to the lungs of normal volunteers

Several groups are assessing the use of cationic lipids for respiratory gene therapy. To date no human data are available regarding the safety of intra-pulmonary cationic lipid delivery. In preparation for a trial of pulmonary delivery of the CFTR gene, we have assessed the safety of nebulised lipid GL-67/DOPE/DMPE-PEG5000 (GL-67A), the cationic lipid formulation to be used in this study. Fifteen healthy volunteers were given incremental doses of GL-67A via a Pari LC Jet nebuliser; three volunteers in each of five dosing cohorts with a week interval between cohorts. Markers of safety included clinical assessment, measurement of lung function, chest CT scan, serological testing and analysis of induced sputum. Measurements were taken before administration and at intervals up to 21 days thereafter. No adverse clinical events were seen or any statistically significant changes in spirometry or gas transfer. There were no clinically significant changes in any of the blood parameters and no CT changes were seen. Comparisons of the cellular subpopulations (neutrophils, eosinophils, lymphocytes and macrophages) in induced sputum showed no significant alterations following administration of the GL-67A. This study suggests that a single application of aerosol formulation of GL-67A does not result in clinically detectable changes when given by nebulisation into the lungs of normal volunteers and provides an indication of a lipid dose tolerated in man.     

Treatment of subglottic laryngitis (pseudocroup): steroids instead of steam]

Traditionally, steaming with warm moist air was recommended for the treatment of subglottic laryngitis (pseudocroup). However, no favourable effect has ever been demonstrated. Consequently, steaming is no longer to be advised. Systemic corticosteroids, already of proven effectiveness in severe croup, were shown to be also effective when administered in a single oral dose in moderately severe disease. Besides, in various studies, nebulisation of budesonide (2000 micrograms) with a jet nebuliser had a good effect on the clinical course of croup. However, dose-effect studies are still lacking. A single dose of corticosteroids, either systemic or inhaled via a jet nebuliser, should be the first line therapy in moderate and severe croup syndrome. In milder cases no specific treatment is needed as the disease is self-limiting.     

Nebulisation of surfactants in an animal model of neonatal respiratory distress

AIMS: To evaluate pulmonary deposition and gas exchange following nebulisation of two surfactants by either a jet or an ultrasonic nebuliser. METHOD: After bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1 (n = 5) and A2 (n = 6) received Technetium-99m labelled Exosurf, and groups B1 (n = 4) and B2 (n = 4) received radiolabelled Survanta. Groups A1 and B1 received jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser. Pulmonary deposition, distribution, and blood gases were determined. RESULTS: Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or 0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)% or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2. Deposition in group A2 was greater than in other groups (p = 0.001). Group A2 showed a small improvement in blood gases. CONCLUSIONS: Even the highest deposition--ultrasonic nebuliser with Exosurf--achieved limited clinical effect. The aerosol route is currently not effective for surfactant treatment.     

On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a "particle growth factor" derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.     

A non-parametric method of reconstructing single-dose survival curves from multi-fraction experiments

Nebulisation is currently the most acceptable and practical delivery system for repeated applications of gene therapy to the lower airways of cystic fibrosis (CF) patients. We have assessed whether this route of administration offers other benefits with regard to respiratory gene transfer. A standard jet nebuliser (Acorn System 22, Medicaid) was used to transfer the reporter gene beta-galactosidase complexed with the cationic liposome DC-Chol/DOPE to three epithelial cell lines in vitro, two non-CF and one CF, using a novel collection system. In all three cell lines, nebulisation resulted in significantly (P < 0.05) improved transfection efficiency compared with instillation. At a constant DNA: liposome ratio of 1:5 (wt:wt), transfection efficiency was inversely related to increasing concentrations of DNA-liposomes before nebulisation. This effect was not related to the amount of DNA delivered and measurements of both zeta potential and mean aerodynamic particle size before and after nebulisation did not show concentration-related differences. The increased transfection efficiency did not relate either to the physical consequences of the nebulisation processes nor the effects of nebulisation on the complexes before instillation. Significantly increased transfection efficiency was seen following nebulisation with 95% O2/5% CO2 in comparison with 21% O2/78% N2 (air); this did not relate to changes in either the pH or temperature of the solution bathing the cells. The data confirm that nebulisation is appropriate for gene delivery to the lower airways in clinical practice and points to factors that may optimise gene transfer efficiency.     

Cellular mechanisms of adrenaline-stimulated anion secretion by the mouse endometrial epithelium

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.     

Aerosol therapy

Aerosol therapy plays a major role in the diagnosis and treatment of various lung diseases. The aim of inhalation therapy is to deposit a reproducible and adequate dose of a specific drug to the airways, in order to achieve a high, local, clinical effect while avoiding serious systemic side effects. To achieve this goal, it is therefore important to have an efficient inhalation device to deliver different medications. However, the currently available therapeutic inhalation devices (nebuliser, pressurised metered-dose inhaler and dry powder inhaler) are not very efficient in aerosol delivery and have several disadvantages. Inhalation devices can be assessed by in vitro studies, filter studies and radiolabelled deposition studies. Several radiolabelled deposition studies have shown that nebulisers and pressurised metered-dose inhalers are not very efficient in aerosol delivery. In children, before 1997, only 0.5% to 15% of the total nebulised or actuated dose from a nebuliser or pressurised metered-dose inhaler actually reached the lungs. These numbers were somewhat improved in adults, 30% of the total nebulised or actuated dose reaching the airways. Aerosol therapy with dry powder inhalers was the most efficient before 1997, 30% of the total dose being deposited in the lungs of adults and children. In 1997, new developments in pressurised metered-dose inhalers much improved their efficiency in aerosol delivery. Lung deposition can be increased by up to 60% with use of a non-electrostatic holding chamber and/or a pressurised metered-dose inhaler with a hydrofluoroalkane propellant possessing superior aerosol characteristics. Several studies comparing the clinical efficiency of different inhalation devices have shown that the choice of an optimal inhalation device is crucial. In addition to the aerosol characteristics, ventilation parameters and airway morphology have an important bearing on deposition patterns. These parameters may be greatly influenced by the patient's acceptance of a specific inhalation device and therefore determine the choice of the device used. It is important for the clinical impact to develop more efficient inhalation devices, which need to be assessed for use in different age groups. These devices should be cheap, easy to use, portable, usable with all medications and environmentally safe.     

The experience with berodual inhalation in emergency treatment of bronchial asthma

Of 56 patients with bronchial asthma demanding emergency care 27 had moderate exacerbation (group 1) and 29--a severe one (group 2). All the patients inhaled berodual (B) solution with a compressive pneumatic nebuliser Medic-Aide. The relief of the attack was achieved for 20 minutes of the inhalation in 22 and 19 patients of groups 1 and 2, respectively. Inhalation monotherapy with B solutions using a compressive nebuliser provides control of moderate and severe attacks of bronchial asthma.     

Personal thoracic CIP10-T sampler and its static version CATHIA-T

A specific version of the personal aerosol sampler CIP 10 was designed, named CIP10-T, for sampling the conventional CEN thoracic fraction. A static sampler, named CATHIA, was also designed. It uses the same sampling head, but the size selected particles are collected onto a filter. The combined particle efficiency of the aspiration slot and the selector was measured in a horizontal wind tunnel at low air velocity, close to 16 cm s-1. The flow rate of both samplers was fixed at its nominal value, i.e., 71 min-1. Two different methods were used: the former was based on the Aerodynamic Particle Sizer (TSI); the latter used the measurement of particle size distribution of the collected samples by the Coulter technique. For the CIP10-T sampler, the particle collection efficiency onto the rotating cup was also measured. For both samplers bias and accuracy maps have been calculated, following the recommendations of a new CEN standard about sampler performance. The bias does not exceed 10% in absolute value for both samplers, within a large range of particle size distribution of the total aerosol. For the CIP10-T sampler, the accuracy map exhibits a large area where the accuracy is better than 10%, corresponding for example to 4 microns < or = MMAD < or = 14 microns for GSD = 2. For the same geometric standard deviation, the accuracy is still better than 20% for 15 microns < or = MMAD < or = 21 microns. For the CATHIA-T sampler, the accuracy map can be roughly divided into two parts. The accuracy remains better than 10% for MMAD < or = 12 microns, and it remains between 10 and 20% for coarser aerosols, with 13 microns < or = MMAD < or = 20 microns, provided GSD > or = 2.     

Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.     

Ultrastructural changes in the rat phrenic nucleus developing within 2 h after cervical spinal cord hemisection

The present study was conducted to describe the ultrastructural changes which occur in the young adult rat phrenic nucleus within 2 h after an ipsilateral C2 spinal cord hemisection. The main objective was to determine if there is a temporal relationship between specific ultrastructural changes in the phrenic nucleus and a significant augmentation of crossed phrenic nerve activity which occurs as early as 2 h after hemisection. Phrenic motoneurons were identified at electron microscopic levels by retrograde HRP labeling. Ultrastructural features in the phrenic nucleus of control and experimental rats were qualitatively analyzed and then quantitated. At 2 h posthemisection, there was a significant increase in the mean percentage of phrenic dendrodendritic appositions. In the control rats, 4.73 +/- 0.18% of phrenic dendrites were in apposition, and this percentage increased significantly to 8.58 +/- 0.54% at 2 h after injury. Furthermore, the mean lengths of asymmetrical and symmetrical synaptic active zones increased significantly at 2 h posthemisection from control lengths of 0.372 +/- 0.009 microns and 0.404 +/- 0.007 microns to 0.410 +/- 0.011 microns and 0.513 +/- 0.032 microns, respectively, in experimental rats. The phrenic nucleus is therefore capable of morphological plasticity as early as 2 h after spinal cord hemisection and this plasticity coincides temporally with the physiological augmentation of crossed phrenic nerve activity at 2 h. The data further suggest that these morphological changes may be part of the substrate for the unmasking of ineffective synapses during the crossed phrenic phenomenon.     

Regional deposition of inhaled particles in human lungs: comparison between men and women

We measured detailed regional deposition patterns of inhaled particles in healthy adult male (n = 11; 25 +/- 4 yr of age) and female (n = 11; 25 +/- 3 yr of age) subjects by means of a serial bolus aerosol delivery technique for monodisperse fine [particle diameter (Dp) = 1 micron] and coarse aerosols (Dp = 3 and 5 micron). The bolus aerosol (40 ml half-width) was delivered to a specific volumetric depth (Vp) of the lung ranging from 100 to 500 ml with a 50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp, showing characteristic unimodal curves with respect to particle size and flow rate. However, the unevenness was more pronounced in women. LDF tended to be greater in all regions of the lung in women than in men for Dp = 1 micron. For Dp = 3 and 5 micron, LDF showed a marked enhancement in the shallow region of Vp 200 ml. Total lung deposition was comparable between men and women for fine particles but was consistently greater in women than men for coarse particles regardless of flow rates used: the difference ranged from 9 to 31% and was greater with higher flow rates (P < 0.05). The results indicate that 1) particle deposition characteristics differ between healthy men and women under controlled breathing conditions and 2) deposition in women is greater than that in men.     

Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants

AIMS: To compare the effects of a single dose of frusemide administered either intravenously or by nebulisation on pulmonary mechanics in premature infants with evolving chronic lung disease. METHODS: The effect of frusemide on pulmonary mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19 premature infants at 24 to 30 weeks gestational age, who had been dependent on mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was administered, in random order, intravenously and by nebulisation, on two separate occasions 24 hours apart. Pulmonary function studies were performed before and at 30, 60, and 120 minutes after administration of frusemide. Urine was collected for six hours immediately before and for six hours after administration of frusemide. RESULTS: Nebulised frusemide increased the tidal volume 31 (SE 11.5)% and compliance 34 (SE 12)% after two hours, whereas no change in either was noted for up to two hours after intravenous frusemide administration. Neither intravenous nor nebulised frusemide had any effect on airway resistance. Six hour urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8) ml/kg/hour following intravenous frusemide administration while nebulised frusemide had no effect on urine output. Urinary sodium, potassium, and chloride losses were also significantly higher after intravenous frusemide, whereas nebulised frusemide did not increase urinary electrolyte losses. CONCLUSION: Single dose nebulised frusemide improves pulmonary function in premature infants with evolving chronic lung disease without adverse effects on fluid and electrolyte balance.     

Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLPC), containing 118 micrograms of CsA/L of aerosol with a particle size of 1.6 to 1.7 micron diameter, was inhaled by 10 nonsmoking, normal volunteers each for 45 min. Aerosol was administered through an Aerotech II nebulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunteers had tracheal irritation and intermittent coughing following exposure. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteers later inhaled DLPC only, administered through the nebulizer mouthpiece. There was no change in FEV1 or FVC values, and there was no coughing or tracheal irritation. Subsequently, five of the volunteers who had previously had respiratory reactions inhaled CsA-DLPC liposome aerosol for 45-min, but through a mouth-only face mask. There was no tracheal irritation, coughing, or changes in spirometric measures. Blood concentrations of CsA at 15 min after the 45-min inhalation with a face mask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, CsA was undetectable in blood of the initial 10 volunteers. These studies indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.     

Scintiphotography of lungs with dry aerosol--generation and delivery system: concise communication

A compressed-air nebulizer with low holdup and high output was used to nebulize [99mTc] pertechnetate presented in normal saline. Generated droplets were dried in line and led to an inhalation chamber from which the dry aerosol was inhaled using a nose or mouth inhalation unit. The mass median diameter of the particles was 0.8 microns, with an associated geometric standard deviation of 2.0. The deep lung delivery efficiency--defined as the ratio of the activity deposited in the lung area to the activity nebulized--was found to be reproducible and consistent (15-22%) in all the subjects studied. A 3-5 min inhalation of aerosol, nebulized from 20 mCi, was sufficient to provide a lung image of good information density. No noticeable deposit was seen in the trachea or major brochi. The system is inexpensive, stable in performance, adaptable to other solutions or colloids, and is promising for routine use.     

Association between a history of childhood sexual abuse and subsequent, adolescent psychoactive substance use disorder in a sample of HIV seropositive men

As the number of inhaled drugs available for cystic fibrosis grows, there is increasing awareness of delivery device issues. Current jet and ultrasonic nebulizers are inefficient at delivering drugs to the lower respiratory tract. There are large differences in output characteristics between nebulizers and high intersubject variability in lung deposition. The clinical effects of inhaled drugs depend on adequate dosing to the lower airway, so we must choose a nebulizer and patient characteristics that will affect lung deposition positively. Aerosols with particle sizes at the smaller end of the respirable range (2 to 3 microns) may enhance the clinical benefit of some drugs, regardless of patient age or disease severity. Breath-enhanced (Venturi) jet nebulizers are less wasteful than constant-output nebulizers and perform better than conventional nebulizers with many drugs. Patient breathing patterns and degree of airway obstruction are important in determining the site of airway deposition. With increased attention to aerosol delivery issues by clinicians, industry, and regulatory agencies, improved technologies will evolve to target therapies to the lung.     

Loss and/or formation of antioxidants during food processing and storage

The functional parameters influence the ventilation of the airways and determine the amount of aerosol penetrating there and the speed of airflow. 100 observations were made, on ten healthy subjects (5 men, 5 women) and with two breathing patterns (tidal volume 500 ml, respiration rate 16 min-1, and tidal volume 2000 ml, respiration rate 8 min-1). Inhaled and exhaled air were sampled by a Royco 518 sampler and the number, concentrations and particle size distributions in five particle size ranges were determined. In all the measurements the fraction deposited was higher in higher tidal volumes, especially in the class of the size range 0.5-1.75 microns. For tidal volumes of 2000 ml the deposited fraction for the women was greater than that for the men.     

Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space

The fractional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the relative volume and size of an individual's airways. To evaluate the effect of variable anatomic dead space (ADS) on aerosol bolus delivery we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5 micron mean mondispersed aerosol diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at a lung volume of 70% total lung capacity end inhalation. By using filter techniques, aerosol photometry, and gamma camera analysis, we estimated the fraction of the inhaled boluses deposited in intrathoracic airways (IDF). ADS by single-breath N2 washout was also measured from 70% total lung capacity. Results showed that among all subjects IDF was variable (range = 0.04-0.43, coefficient of variation = 0.54) and increased with decreasing ADS (r = -0.76, P = 0.001, n = 16). We found significantly greater deposition in the left (L) vs. right (R) lungs; mean L/R (ratio of deposition in L lung to R lung, normalized to ratio of L-to-R lung volume) was 1.58 +/- 0.42 (SD; P < 0.001 for comparison with 1.0). Retention of deposited particles at 2 h was independent of ADS or IDF. There was significant retention of particles at 24 h postdeposition (0.27 +/- 0.05) and slow clearance of these particles continued through 48 h postdeposition. Finally, analysis of central-to-peripheral ratios of initial deposition and 24-h-retention gamma-camera images suggest significant retention of insoluble particles in large bronchial airways at 24 h postdeposition (i.e., 24 h central-to-peripheral ratio = 1.40 +/- 0. 44 and 1.82 +/- 0.54 in the R and L lung, respectively; P < 0.02 for comparison with 1.0). These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.     

Medication nebulizer performance. Effects of diluent volume, nebulizer flow, and nebulizer brand

BACKGROUND: Medication nebulizers are commonly used to delivery aerosolized medications to patients with respiratory disease. We evaluated output and respirable aerosol available to the patient (inhaled mass) for 17 medication nebulizers using a spontaneous breathing lung model. METHODS: Three nebulizer fill volumes (3, 4, and 5 mL containing 2.5 mg of albuterol) and 3 oxygen flows (6, 8, and 10 L/min) were evaluated using the 17 nebulizers. A cotton plug at the nebulizer mouthpiece was used to trap aerosol during simulated spontaneous breathing. Following each trial, the amount of albuterol remaining in the nebulizer and the amount deposited in the cotton plug were determined spectrophotometrically. Aerosol particle size was determined using an 11-stage cascade impactor. RESULTS: Increasing fill volume decreased the amount of albuterol trapped in the dead volume (p < 0.001) and increased the amount delivered to the patient (p < 0.001). Increasing flow increased the mass output of particles in the respirable range of 1 to 5 microns (p = 0.004), but the respirable mass delivered to the patient was affected to a greater extent by nebulizer brand (p < 0.001) than flow. Although 2.5 mg of albuterol was placed into the nebulizers, less than 0.5 mg in the respirable range of 1 to 5 microns was delivered to the mouthpiece. CONCLUSIONS: The performance of medication nebulizers is affected by fill volume, flow, and nebulizer brand. When they are used for research applications, the nebulizer characteristics must be evaluated and reported for the conditions used in the investigation.