Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine最新文献

An analytical algorithm has been recently described for converting planar scintigraphic images of aerosol distributions in the lungs to an equivalent three-dimensional (3D) representation. The recovery of the volumetric information has opened up to planar imaging the possibility of measuring aerosol deposition per airway generation. This paper investigates the accuracy and precision of the generation analysis achievable with planar imaging using simulation. Typical generation parameters--such as the bronchial and conducting airway deposition fractions (BADF and CADF)--have been derived. The accuracy of the technique has been measured by the coefficient of variation (COV) of the estimates from the known values used in the simulation. The results have also been compared to those obtained from 3D imaging (single photon emission computed tomography or SPECT). Finally, the technique has been applied to two aerosol studies conducted on a healthy volunteer, to demonstrate its implementation on clinical data. The accuracy of the BADF and CADF estimates from planar imaging were 42% and 41%, respectively; the corresponding values from SPECT were 32% and 22%. In conclusion, approximate estimates of airway distribution parameters can be derived from planar imaging. However, the errors are significantly higher than with SPECT.

Nebulizers are often interfaced to patients using facemasks, especially when the patient is sick and uncooperative. Tight-fitting masks are thought to improve drug delivery, but recent studies have indicated that facemask seal can impact facial and eye deposition of aerosol. The purpose of the present study was to define the factors that influence drug delivery to the lung in pediatric patients using nebulizers and facemasks; particularly the roles of facemask seal, mask vents and nebulizer flow. Using a pediatric face facsimile and radiolabeled saline aerosols front-loaded and bottom-loaded nebulizers were tested for aerosol delivery during a pediatric pattern of breathing. Gamma scintigraphy provided images of the face. Filters measured drug delivery to the patient (inhaled mass [IM]). All data were reported as percent (%) nebulizer charge. Nebulizer flows of 4 and 8 L/min were tested. Preliminary experiments suggested that inertial forces between the edge of the mask and the face were responsible for facial and eye deposition. Front-loaded nebulizers were more efficient than bottom-loaded systems in delivering drug to the patient but favored eye deposition. These observations led to the design of a mask prototype constructed to maximize aerosol delivery to the patient with reduced deposition on the face and in the eyes. Modifications included vents and specialized cutouts in the region of the eyes. A tight fitting front-loaded mask delivered an IM of 6.38 +/- 0.42% (mean +/- SE) with facial and eye deposition of 1.76 +/- 0.17% and 1.14 +/- 0.15% respectively. The presence of specialized eye cutouts minimized facial and eye deposition (0.72 +/- 0.07%, and 0.15 +/- 0.02% [P < 0.0001]), even in the presence of increased nebulizer flow. The prototype design at 4 L/min maximized IM to 8.78 +/- 0.98% and further reduced facial and eye deposition (0.66 +/- 0.07% and 0.09 +/- 0.01%). Commercial bottom loaded masks reduced IM to 2.33 +/- 0.22%, with significant deposition on the face (1.43 +/- 0.16%). For aerosol therapy with nebulizers in pediatric patients, facemask design is a key factor in maximizing aerosol delivery to the patient while minimizing deposition on the face and in the eyes.

There has been much clinical and academic interest in the use of noninvasive positive-pressure ventilation (NPPV) in patients with acute and chronic respiratory failure. The use of NPPV in appropriately selected patients improves survival and decreases the need for endotracheal intubation. The most commonly used interfaces for NPPV are nasal masks or oronasal masks, but nasal pillows, mouthpieces, total face masks, and helmets can also be used. Critical care ventilators, portable volume ventilators, and ventilators designed specifically for NPPV can be used. There are three options for aerosol delivery during NPPV. The patient can be removed from NPPV and the aerosol administered by nebulizer or MDI in the standard manner, the aerosol can be delivered by nebulizer placed in-line between the circuit and the mask, or a spacer chamber can be placed between the circuit and the mask. There is presently no commercially available system designed specifically for aerosol delivery during NPPV with a bilevel (BiPAP) ventilator. However, in vitro and in vivo studies have demonstrated that a significant amount of bronchodilator can be administered by in-line nebulizer or MDI during NPPV. The evidence base for aerosol delivery during NPPV is not nearly as mature as the evidence for aerosol delivery during invasive mechanical ventilation. With NPVV, issues related to the optimal interface, ventilator settings, and aerosol generator (nebulizer versus MDI) are largely unexplored.

In quantifying aerosol delivery, the drug is often mixed with a radiolabel such as (99m)Tc-DTPA whose deposition is used as a proxy for the drug. (99m)Tc-DTPA deposited in the lung is cleared by a combination of absorption into the pulmonary circulation and mucociliary clearance. If administration is not instantaneous, the image will not include that clearance during administration, a problem raised if comparing devices with different administration times. However, if rates of clearance are measured, it will be possible to "correct" the initial image for the clearance that occurred during administration and before counting. Five adult males inhaled a 5-mL solution containing (99m)Tc-DTPA from a breath enhanced jet nebulizer (LC Plus)over the course of 10 min and a 1.25-mL solution from a vibrating membrane device (eFlow), which was delivered in 2.5 min. Quality assurance was the radioactivity count balance (RCB) defined as the difference in the total radioactivity pre-nebulization less post, divided by pre, and expressed as a percentage. Attenuation calculations used a (57)Co flood source (Macey and Marshall). The "correction" for the clearance of (99m)Tc-DTPA was 0.91 +/- 0.04 (mean +/- SD) for the LC Plus) and 0.96 +/- 0.02 for the eFlow). RCB was -0.6 +/- 3.5% for the LC Plus and -4.7 +/- 6.4% for the eFlow, implying acceptable accuracy. For the LC Plus, lung deposition was 15.9(13.4, 18.4)% (mean and 95% CI) of the charge dose, and for the eFlow it was 32.0(29.0, 35.0)%. This technique gave an acceptable level of accuracy for quantitative planar imaging and allowed the comparison of delivery from devices with very different rates of delivery.

There are theoretical benefits of delivering drug aerosols to patients with asthma and chronic obstructive pulmonary disease (COPD) using Heliox as a carrier gas. The objective of this study was to develop systems to allow bronchodilators nebulized by a breath enhanced jet nebulizer and a vibrating mesh nebulizer to be delivered to patients in Heliox. This was achieved by attaching a reservoir to the nebulizers to ensure inhaled Heliox was not diluted by entrained air. For the vibrating mesh nebulizer, the total output was significantly higher after 5 min of nebulization when Heliox rather than air was used as the delivery gas (p < 0.001). The proportion of drug in particles <5 microm was 58.1% for Heliox and 50.1% when air was entrained. When the breath enhanced nebulizer was used a much higher driving flow of Heliox, compared to air, was required to deliver a similar dose of drug (p < 0.05). The total amount of drug likely to be inhaled was significantly higher when the vibrating mesh nebulizer (Aerogen) was used compared to the breath enhanced jet nebulizer (Pari LC plus) (p < 0.001). The amount of drug likely to be inhaled was also significantly greater for the adult as opposed to pediatric breathing pattern for all nebulizers and flows tested with the exception of the Aeroneb and Heliox entrainment. In this case, total amounts were similar for both patterns but for the pediatric pattern, the time taken to reach this output was longer. Such information is required to allow appropriate interpretation of clinical trials of drug delivery using Heliox.

This work investigated the size distribution of the droplet nuclei and coughed droplets by test subjects. The size distributions of droplet nuclei coughed by test subjects were determined with an aerodynamic particle sizer (APS) and scanning mobility particle sizer (SMPS) system (system 1). Coughed droplets were only sampled with the APS system (system 2). Two different schemes were employed in system 2. Furthermore, the size distribution of coughed droplets of different ages and gender was investigated to identify the effects of age and gender on droplet size distribution. Results indicated the total average size distribution of the droplet nuclei was 0.58-5.42 microm, and 82% of droplet nuclei centered in 0.74-2.12 microm. The entire average size distribution of the coughed droplets was 0.62-15.9 microm, and the average mode size was 8.35 microm. The size distribution of the coughed droplets was multimodal. The size distribution of coughed droplets showed three peaks at approximately 1 microm, 2 microm, and 8 microm. These analytical findings indicate that variation for average droplet size among the three age groups was insignificant (p > 0.1). Moreover, the variation in average droplet size between males and females was also insignificant (p > 0.1). Also, the variation in droplet concentration between males and females was significant (p > 0.1). Droplet nuclei concentrations from male subjects were considerably higher than that from females. Comparison of the droplet concentrations for subjects in different age groups demonstrated that subjects in the 30-50-year age group have the largest droplet concentrations.

It has been shown in vitro that even a small air leak in the facemask can drastically reduce the efficiency of drug delivery. In addition, it has been shown that drug deposition on the face does significantly add to overall drug loss and has the potential of local side effects. The aim of this study is therefore to verify these findings in vivo. Eight asymptomatic recurrently wheezy children, aged 18-36 months, inhaled a radiolabeled salbutamol formulation either from a pressurized metered-dose inhaler through a spacer with attached facemask or from a nebulizer with attached facemask. Drug deposition of radiolabeled salbutamol was assessed with a gamma camera and expressed as a percentage of the total dose. Lung deposition expressed as a percentage of the total dose (metered dose and nebulizer fill, respectively) was 0.2% and 0.3% in children who inhaled with a non-tightly fitted facemask. Lung deposition was 0.6% and 1.4% in screaming children with a tightly fitted facemask and between 4.8% and 8.2% in patients breathing normally. Overall mask deposition was between 0.8% and 5.2%. Overall face deposition was between 2.6% and 8.4%. The results from this pilot study support the results found in in vitro studies, where a facemask leak greatly reduces drug delivery to the patient.

Pulmonary gene therapy has the potential to treat or cure respiratory diseases such as cystic fibrosis. Much work has focused on the delivery of genes to the lung using viral vectors with varying degrees of success. Viral vectors are problematic and undesirable for use in the lung because they can provoke an acute immune response. This study has focused on the characterization of nonviral, polymer-based gene vectors for use with nebulizers. Calf thymus DNA has been used as a model, and was complexed with each of the three polycations; 22 kDa linear polyethyleneimine, 25 kDa branched polyethyleneimine, and 29.5 kDa polylysine using water, glucose solution, and phosphate-buffered saline (PBS) as carrier liquids. Fourier transform infrared spectroscopy has shown that the DNA retains the B form during the complex formation. The complexes prepared at N:P ratios of 10, have been nebulized using a vibrating plate nebulizer and the particle size and Zeta potentials measured before and after nebulization. The particle size distributions of the DNA complexes prepared in water and glucose solution were unimodal before and after nebulization with a small increase in particle size following nebulization. Choice of complexing polymer is shown to have only a small effect on particle size with the dominant effect coming from the ionic character of the dispersion fluid. Complexes prepared in PBS, although originally unimodal, showed pronounced agglomeration on nebulization. With all polymers in water or glucose solution, the Zeta potential increases after nebulization, but with PBS as the carrier liquid the potential falls and is clearly associated with the observed agglomeration. Gel electrophoresis shows that the complexing polymers protect the DNA through the nebulization process in all cases.

In vitro polydisperse aerosol deposition in three mouth-throat models, namely, the USP (United States Pharmacopeia) mouth-throat (induction port), idealized mouth-throat, and highly idealized mouth-throat, was investigated experimentally. Aerosol particles emitted from two commercial inhalers, Qvar (pMDI) and Turbuhaler (DPI), were used. The in vitro deposition results in these three mouth-throat models were compared with in vivo data available from the literature. For the DPI, mouth-throat deposition was 57.3 +/- 4.5% for the USP mouth-throat, 67.8 +/- 2.2% for the idealized mouth-throat, and 69.3 +/- 1.1% for the highly idealized mouth-throat, which are all relatively close to the in vivo value of 65.8 +/- 10.1%. In contrast, for the pMDI, aerosol deposition in the idealized mouth-throat (25.8 +/- 4.2%) and the highly idealized mouth-throat (24.9 +/- 2.8%) agrees with the in vivo data (29.0 +/- 18.0%) reported in the literature better than that for the USP mouth-throat (12.2 +/- 2.7%). In both cases, the USP mouth-throat gives the lowest deposition among the three mouth-throat models studied. In summary, both the idealized mouth-throat and highly idealized mouth-throat improve the accuracy of predicted mean in vivo deposition in the mouth-throat region. This result hints at the potential applicability of either the idealized mouth-throat or highly idealized mouth-throat as a future USP mouth-throat standard to provide mean value prediction of in vivo mouth-throat deposition.

The objective of this article was to show the role of cytokines in the pathogenesis of pulmonary fibrosis due to sulfur mustard gas inhalation. Eighteen veterans with mustard gas-induced pulmonary fibrosis and 18 normal patients were used as controls. Bronchoalveolar larvage (BAL) and analyses of BAL fluids for cellular and cytokine levels were performed. There was a significant difference in granulocyte colony stimulating factor (G-CSF) level in the BAL fluid of patients and the controls (p < 0.0001). Granulocyte-macrophage colony stimulating pulmonary fibrosis (GM-CSF) BAL levels were significantly increased in patients with pulmonary fibrosis (PF) in comparison with controls (p < 0.0001). Patients with PF have highly significant increases in IL-8 level compared to controls (87.94 +/- 59.63 vs. 8.66 +/- 6.97 g/mL(1); p < 0.0001) as well. IL-8 and G-CSF levels in BAL fluid correlate only with the percentage and the absolute number of neutrophils of the BAL fluid in patients with PF (p = 0.02/p = 0.01; p = 0.01/p = 0.01; respectively). A significant correlation was found between GM-CSF BAL fluid level and the percentage and the absolute number of the BAL fluid eosinophils (p = 0.04 and p = 0.03). Neutrophils alveolitis, the presence of eosinophils, and higher concentrations of interleukin-8, G-CSF, and GM-CSF in BAL fluid are associated with the development of fibrosis in sulfur mustard victims.