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PubMed1992

Blood-containing aerosols generated by surgical techniques: a possible infectious hazard.

The aerosols generated in an operating room during surgery were simulated in the laboratory by using a variety of common surgical power tools. A Stryker bone saw, a Hall drill, and a Shea drill were used on bone, and a Bovie electrocautery was used in both the cutting and coagulation modes on tendon, all in the presence of a thin film of blood. A 10-stage, low-pressure cascade impactor was used to determine the particle size distribution of each aerosol, and Hemastix was used to assess the hemoglobin content of each particle size fraction. The same assessment was done for another series of blood aerosols that had previously shown the ability to infect human T-cell cultures. All of the tools tested produced blood-containing aerosol particles in the respirable size range (less than 5 microns). Because surgical masks offer little protection against such particles, personal sampling is indicated to define the risk of exposure to bloodborne pathogens by this route.

Aerosols↗
PubMed1997

An experimental method for measuring aerosol deposition efficiency in the human oral airway.

An experimental technique was developed to measure the oral deposition of aerosols by successively drawing them passively through (1) the nasal and oral passage in series, and (2) the nose and an oral bypass "extension tube" inserted into the oral cavity just anterior to the uvula. To test this technique, a replicate human upper airway cast was challenged with monodisperse aerosols ranging in diameter from 3.6 to 150.0 nm at constant flow rates ranging from 7.5 to 30 L/min. For the inhalation study, test aerosols were drawn into the nasal cavity and directed either through the laryngeal-tracheal (L-T) section or the oral passage with/without the oral extension tube. The flow was reversed for the exhalation study. Deposition fractions of aerosols in the main oral cavity were found approximately equal to those in the L-T section for both inhalation and exhalation. Following this phase of the study, experimental measurements of total particle deposition fraction for the oral inlet-tracheal outlet path were performed. The results of these measurements agreed well with the calculated oral deposition fractions based on the initial measurements. This technique has application for measuring oral deposition of larger particles encountered in occupational environments.

Aerosols↗
PubMed2007

Chemical characteristics of aerosol mists in phosphate fertilizer manufacturing facilities.

Of the carcinogens listed by the National Toxicology Program (NTP), strong inorganic mists containing sulfuric acid were identified as a known human carcinogen. In this study, aerosol sampling was conducted at 24 locations in eight Florida phosphoric acid and concentrated fertilizer manufacturing plants and two locations as background in Winter Haven and Gainesville, Florida, using dichotomous samplers. The locations were selected where sulfuric acid mist may potentially exist, including sulfuric acid pump tank areas, belt or rotating table phosphoric acid filter floors, sulfuric acid truck loading/unloading stations, phosphoric acid production reactors (attack tanks), and a concentrated fertilizer granulator during scrubbing with a weak sulfuric acid mixture. An ion chromatography system was used to analyze sulfate and other water soluble ion species. In general, sulfate, fluoride, ammonium, and phosphate were the major species in the fertilizer facilities. For the rotating table/belt phosphoric acid filter floor, phosphate and fluoride were the dominant species for PM10, and the maximum concentrations were 170 and 106 microg/m3, respectively. For the attack tank, fluoride was the dominant species for PM10, and the maximum concentration was 462 microg/m3. At the sulfuric acid pump tank, sulfate was the dominant species, and the maximum PM10 sulfate concentration was 181 microg/m3. The concentration of PM10 sulfate including ammonium sulfate, calcium sulfate, and sulfuric acid were lower than 0.2 mg/m3 at all locations. The aerosols at the filter floor and the attack tank were acidic. The coarse mode aerosol at the sulfuric acid pump tank (an outdoor location) was acidic, whereas the fine mode aerosol was neutral to basic.

Aerosols↗
PubMed2004

Design of aerosolized amphotericin b formulations for prophylaxis trials among lung transplant recipients.

BACKGROUND: Emphasis has been placed on the need for antifungal prophylaxis when transplanted organs are directly exposed to the environment. In lung transplantation, one strategy for prevention has been aerosolization of polyenes into the lung. Despite widespread use of amphotericin B aerosols, there are still few studies on how to validate their effectiveness or optimize pharmacokinetics. METHODS: We compared results of several of our own studies of lung transplant recipients receiving formulations of amphotericin B with results of other studies. RESULTS: Recent aerosol studies suggest that aerosols of a lipid formulation of amphotericin B are safe and better tolerated than is amphotericin B deoxycholate. Their use in prophylaxis is associated with very few pulmonary fungal infections. CONCLUSION: This safe drug delivery at a local body site to directly protect the transplanted organ without systemic antifungal drug exposure is attractive from a cost and toxicity standpoint. However, careful multicenter, comparative studies are still needed to ensure that this strategy is consistently successful.

Aerosols↗
PubMed1986

Distributions of an ultra-fine 99Tcm aerosol and 81Krm gas in human lungs compared using a gamma camera.

A 99Tcm aerosol of particle size 0.12 micron and the gas 81Krm were administered to four normal subjects and to eleven patients with airway disease. Posterior-anterior gamma camera images of erect lungs were compared qualitatively and quantitatively, and 99Tcm clearance rates were measured. Qualitatively the two images were similar in normal subjects but differed in most patients owing to small regions of high count density in the 99Tcm images. In a few patients, regional variations in ventilation were defined more finely by the aerosol. In both groups a significant vertical gradient in 99Tcm count density relative to 81Krm count density was found. Penetration of 99Tcm to the lung periphery relative to the hilar region was similar to that of 81Krm in the normal subjects and less than that of 81Krm in the patients. Possible causes of the differing distributions are discussed. The images obtained with the aerosol in the two groups studied were similar to those reported for larger particle aerosols.

Adult↗
PubMed2001

Aerosols and anti-infectious agents.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides), and amphotericin B can be administered by aerosol. Apart from pentamidine and Tobi, this route of administration is not officially approved and it constitutes an empirical approach, which has benefited from recent research summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti-infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics also have to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Differentiating between good and bad nebulizers is not dependent upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent significant progress. Finally, administration of anti-infectious aerosols requires a new pharmacological approach to monitor treatment, and urinary assays are promising for this purpose.

Administration, Inhalation↗
PubMed2002

Changes in lung deposition of aerosols due to hygroscopic growth: a fast SPECT study.

Our objective was to use rapid dynamic SPECT to study the effect of hygroscopic growth on aerosol deposition in the lung. Six healthy volunteers inhaled radiolabeled ((99m)Tc-DTPA) saline aerosols of two different droplet sizes (MMAD Small 3.2 +/- 0.2 and Large 6.5 +/- 0.2 microm, span 1.8 and 1.7, respectively) and tonicities (normal saline, NS, 0.9% and hypertonic saline 'HS' 7.0% NaCl) reproducibly on 4 occasions. Simultaneous emission-transmission scanning with a triple detector gamma camera was used to collect the lung images. Regional lung deposition was quantified by the penetration index or PI. The results revealed significant differences of aerosol deposition in the lung, which follows precisely the expectation from particle size and hygroscopicity. The difference in the PI values between the aerosols increases in the order of: Large NS-Large HS < Small NS-Small HS < Small HS-Large NS < Small HS-Large HS < Small NS-Large NS < Small NS-Large HS.

Aerosols↗
PubMed2003

Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a (99m)Tc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 +/- 3.5% (mean +/- SD) after 10 min and 44.2 +/- 3.8% (mean +/- SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with (99m)Tc HSA should allow quantification of its deposition in CF patients.

Administration, Inhalation↗
PubMed2004

The development of a novel high-dose pressurized aerosol dry-powder device (PADD) for the delivery of pumactant for inhalation therapy.

The performance of a novel dry powder inhaler designed to deliver exceptionally high doses was investigated using pumactant as a model powder. Pumactant (a synthetic lung surfactant consisting of a phospholipid mixture), with a 90th percentile particle size of 2.92 microm is highly cohesive, has a high moisture affinity (6.2% w/w at 45% RH), and is predominantly amorphous. The device (pressurized aerosol dry-powder delivery [PADD]) utilizes pressurized gas to aerosolize a powder bed from a reservoir and delivers it through a conventional mouthpiece. The influence of loaded dose on dry powder delivery and can pressure on aerosolization efficiency was investigated. Analysis of the delivered dose studies suggested a linear relationship between loaded dose and delivered dose (R(2) = 0.96, for loaded doses of 0-250 mg), with a delivery efficiency of 70%. Analysis of the aerosolization efficiency using a Marple Miller type impactor suggested fine particle fractions (particles with an aerodynamic diameter of <5 microm) of approximately 30% using canister pressures of 8-14 bars. These results indicate that the PADD device may be a useful tool in delivering high-dose medicaments, as a carrier-free formulation, to the deep lung.

Administration, Inhalation↗
PubMed2004

Marburg and Ebola viruses as aerosol threats.

Ebola and Marburg viruses are the sole members of the genus Filovirus in the family Filoviridae. There has been considerable media attention and fear generated by outbreaks of filoviruses because they can cause a severe viral hemorrhagic fever (VHF) syndrome that has a rapid onset and high mortality. Although they are not naturally transmitted by aerosol, they are highly infectious as respirable particles under laboratory conditions. For these and other reasons, filoviruses are classified as category A biological weapons. However, there is very little data from animal studies with aerosolized filoviruses. Animal models of filovirus exposure are not well characterized, and there are discrepancies between these models and what has been observed in human outbreaks. Building on published results from aerosol studies, as well as a review of the history, epidemiology, and disease course of naturally occurring outbreaks, we offer an aerobiologist's perspective on the threat posed by aerosolized filoviruses.

Aerosols↗
PubMed2006

Improving performance of HVAC systems to reduce exposure to aerosolized infectious agents in buildings; recommendations to reduce risks posed by biological attacks.

The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon. The Working Group was composed of subject matter experts in air filtration, building ventilation and pressurization, air conditioning and air distribution, biosecurity, building design and operation, building decontamination and restoration, economics, medicine, public health, and public policy. The group focused on functions of the heating, ventilation, and air conditioning systems in commercial or public buildings that could reduce the risk of exposure to deleterious aerosols following biological attacks. The Working Group's recommendations for building owners are based on the use of currently available, off-the-shelf technologies. These recommendations are modest in expense and could be implemented immediately. It is also the Working Group's judgment that the commitment and stewardship of a lead government agency is essential to secure the necessary financial and human resources and to plan and build a comprehensive, effective program to reduce exposure to aerosolized infectious agents in buildings.

Advisory Committees↗
PubMed1996

Delivery of DNA-cationic liposome complexes by small-particle aerosol.

Aerosol delivery of gene therapy for treatment of lung diseases allows topical treatment of the airways with DNA concentrations not obtainable by systemic administration. We have investigated delivery of cationic liposomes complexed to plasmid DNA in a small particle aerosol. Plasmid cDNA-DMRIE/DOPE complexes were nebulized using either an Aerotech II or Puritan-Bennett 1600 (PB1600) nebulizer. Reservoir sampling showed that DNA-DMRIE/DOPE complexes were damaged to a significant degree during nebulization, such that activity of transfected gene was diminished. Of the nebulizers analyzed, DNA-DMRIE/DOPE complexes were more stable in the PB1600. The loss of effective transfection by DNA-DMRIE/DOPE, as detected by decreased reporter gene activity in A549 lung cells, was consistent with denaturation of the DMRIE/DOPE. In contrast, nebulized DNA-DOSPA/DOPE complexes retained complete ability to transfect. Adjustments to flow rate and reservoir volume of the PB1600 allowed a longer period of delivery of active DNA-DMRIE/DOPE particles. DNA-DMRIE/DOPE was radiolabeled with Technetium-99m (99mTc), nebulized, and the output captured in either an Andersen Sampler (AS) (Andersen, 1958) cascade impactor particle size analyzer or an all glass impinger. cDNA-cationic lipid complexes were detected in size ranges of 0.4-10 microns, with most particles found between 1-2 microns. Aerosol output was consistent from 0 to 5 min. These results show the feasibility of aerosol delivery of DNA-cationic lipids for the purposes of gene therapy to the lung.

Aerosols↗
PubMed1997

A concentrated and stable aerosol formulation of cationic lipid:DNA complexes giving high-level gene expression in mouse lung.

Advances in gene therapy vectors and techniques hold promise for treatment of many inherited and acquired diseases. For lung indications, especially those involving the epithelium, delivery of the gene therapy vehicle ideally will involve the use of an aerosol. Aerosol delivery of transgenes using cationic lipids is currently limited by the ability to generate highly concentrated formulations of lipid:DNA complexes that are stable and retain their activity following aerosolization. We have examined many of the variables inherent in aerosolizing cationic lipid gene delivery vehicles and have devised a new formulation that incorporates small amounts of a polyethylene glycol-containing lipid. This formulation has allowed the preparation of concentrated dispersions of cationic lipid:plasmid DNA (pDNA) complexes (> 20 mM pDNA) at approximately 10-fold higher concentrations than previously reported. Most of the pDNA in these formulations was bound to the lipid component and thereby protected from nebulizer-induced shearing; the pDNA also maintained full biological activity both in vitro and in vivo. This new formulation thus represents a significant improvement over current methods to prepare concentrated, active cationic lipid gene delivery vectors, and provides a new tool with which to test gene transfer to the lung.

Administration, Inhalation↗
PubMed1995

Measuring alveolar dimensions at total lung capacity by aerosol-derived airway morphometry.

A technique based on particle sedimentation, aerosol-derived airway morphometry (ADAM), was modified to investigate the morphometry of human lung airspaces at full inflation in 54 subjects with normal lung function, ages 18 to 69 years. The technique compares the recovered concentrations of monodisperse aerosol particles after gravitational settling during breath holds to determine effective airspace diameters (EADs) as a function of volumetric lung depth. The method is simple and non-invasive, requiring only several inhalations of aerosol to total lung capacity, breath holds at end inhalation and exhalation to residual volume (RV). The method is sensitive enough to detect differences in the smallest observed airspaces (EADmin) due to normal aging of healthy lungs when older subjects are compared to younger subjects. The average EADmin was larger (p = 0.009) for the oldest adults (293 +/- 54 um, s.d., 50-70 years, n = 13) at the deepest volumetric lung depth (near 40% of TLC into the lung) when compared to the youngest adults (250 +/- 38 um, s.d., 18-40 years, n = 22). The two groups had similar EADs at a depth of 5% of TLC. No gender difference in EADmin was found when comparing all males and females. No correlation was found between EADs and TLC implying number of alveolar airspaces rather than airspace size determines lung volume. The effects of changing the aerosol inhalation volume to TLC ratio was also investigated. Compared to the dichotomous Weibel morphometric model, the average EADs of 22 18-40 year old subjects were found to be equivalent near 1% TLC and 40% TLC, but were larger in size than the model between those extremes with a maximum difference occurring at approximately 3% TLC. This method appears to be extremely sensitive to in vivo changes in airspace dimensions and may prove useful in determining changes in these dimensions associated with normal lung development and early disease states.

Adolescent↗
PubMed1995

Delivery and retention of an insulin aerosol produced by a new jet nebulizer.

UNLABELLED: This study describes the delivery and distribution of an aerosol generated by a jet nebulizer (MAXIN) in an experimental animal model. Anesthetised, intubated and ventilated piglets inhaled radiolabeled technetium diethylene-triamine-penta-acetic acid (99mTc-DTPA) through the endotracheal tube. The lungs were excised en bloc and scintigraphed, using a computerized gamma camera to evaluate the pattern of distribution. By nebulizing radiolabeled 125I-insulin and comparing the activity deposited on inspiratory and expiratory electrostatic filters, delivery and retention of nebulized insulin was assessed. The distribution of aerosol in the lungs was very even and reached the most peripheral parts. The delivery of nebulized insulin was calculated to be 88.9 +/- 5.3% and 36.1 +/- 8.8% of the insulin delivered to the respiratory tract was retained. The immediate local effects of insulin aerosol administration on the lungs were evaluated using light microscopy. No adverse effects were observed at histopathologic examination of the lung tissue. CONCLUSION: This study shows a high penetration of aerosol to the peripheral parts of the lung and efficient delivery of nebulized insulin when using the MAXIN-nebulizer.

Aerosols↗
PubMed1996

Therapeutic aerosols and airway secretions.

Despite common misconceptions, airway mucus is not an impermeable barrier that entraps and clears all inhaled material. To be therapeutically effective, an aerosol medication must efficiently deposit in the airway and then diffuse or translocate across the mucous barrier while retaining bioactivity. Characteristics of aerosols that affect their ability to penetrate the mucous barrier include particle charge, solubility, and size. Aerosol medications can also change the biophysical properties of secretions and influence how rapidly mucus is cleared. Surfactant is probably responsible for the displacement of inhaled particles through the mucous layer (Schürch et al., 1990). As well, exogenous surfactant has been shown to increase tracheal mucociliary clearance in anesthetized dogs (de Sanctis et al., 1994) and to improve the mucociliary clearability of secretions from babies with neonatal respiratory distress syndrome (Rubin et al., 1992). Using measurements of sputum-substrate contact angle and interfacial tension, cystic fibrosis (CF) sputum had been shown to have an abnormally high adhesion tension, (Girod et al., 1992). We assessed the in vitro effects of synthetic surfactant (Exosurf, Burroughs-Wellcome, Research Triangle Park, NC) on the physical and transport properties of sputum from 15 patients with CF and 30 patients with stable chronic bronchitis (CB). The concentration of ExosurfTM used was 13.5 mg of DPPC/ml corresponding to the reconstituted concentration for aerosol administration. The sputum was divided so that aliquots each were treated with Exosurf and amphibian Ringer's solution layered on the sputum at a concentration of 1:5 v/v for 15 min at 24 degrees C. There was a reduction in spinnability (p < 0.0001) in CF sputum from baseline and a fall in adhesion tension (0.05 < p < 0.1) with Exosurf treatment. Potentially important increases in both mucociliary and cough clearability were noted without associated changes in sputum rheology. In bronchitis sputum, surfactant reduced adhesiveness (p < 0.01), but this was not associated with improved clearability. Adhesive forces are involved in ciliary coupling and cough transport. This raises the possibility of using surfactant as a mucokinetic agent in the therapy of chronic suppurative lung disease.

Aerosols↗
PubMed1997

Effect of nebulizer configuration on delivery of aerosolized tobramycin.

Differences in the reported efficacy of aerosolized aminoglycosides may be due, in part, to differences in aerosol delivery. Optimization of delivery systems of bench testing of nebulizers in a manner that simulates clinical conditions can lead to enhanced lung deposition in subsequent clinical studies. In the present study, we assessed the effects of varying nebulizer configuration on the performance of ultrasonic and jet nebulizers. Tobramycin was mixed with a radiotracer (99mTc) to facilitate measurement of nebulizer output and particle size. A piston ventilator provided a simulated breathing pattern, and the dose delivered to a filter corresponded to what would have been inhaled by a patient (percentage of nebulizer charge inhaled). Particle size was measured using a cascade impactor, sampling at 1 L/min. An ultrasonic nebulizer (Ultra-Neb; DeVilbiss, Somerset, PA), ventilated at 20 breaths per minute, charged with 600 mg of tobramycin (in 30-mL volume) and fitted with its standard tubing, was tested with and without the addition of one-way valves to the inspiratory and expiratory ports of the mouthpiece. In order to assess the degree of environmental contamination associated with jet nebulizer therapy, a filter was placed at the expiratory port of all jet nebulizer experiments. The addition of the valves reduced the percentage of charge inhaled from a mean +/- standard deviation (SD) of 29.2% +/- 1.4% to 7.6% +/- 2.3% and reduced mass median aerodynamic diameter [MMAD (sigma g) from 4.3 microns (2.1) to 1.45 microns (1.65)]. A Circulaire (Westmed, Tucson, AZ) jet nebulizer (7 L/min flow, 50 pounds per square inch gauge (psig), 20 breaths per minute, containing 160 mg of tobramycin in a 4-mL volume) was tested in two configurations: using a plain T-piece and using a valved inflatable aerosol chamber. The use of the holding chamber resulted in an almost twofold reduction in MMAD [MMAD (sigma g) = 2.45 microns (2.0); T-piece; 1.25 microns (2.0), holding chamber]. A slight reduction in the percentage of nebulizer charge inhaled using the holding chamber, compared to the plain T-piece, was not statistically significant (mean +/- SD of percentage inhaled with holding chamber = 20.8% +/- 1.6%; with T-piece = 23.6% +/- 0.5%). With both the jet and ultrasonic nebulizers, breathing frequency influenced percentage inhaled, with a higher percentage inhaled at 20 breaths per minute compared to 15 breaths per minute. The use of the plain T-piece at 20 breaths per minute was associated with more environmental contamination than the use of the holding chamber with the same breathing pattern (26.7% +/- 1.0%, T-piece; 4.5% +/- 0.3%, holding chamber, P < 0.0001). We conclude that nebulizer configuration can potentially affect both the amount of aerosol inhaled and the particle size, and needs to be specified precisely in treatment protocols.

Administration, Inhalation↗
PubMed1998

Aerosol bolus dispersion in patients with bronchiolitis obliterans after heart-lung and double-lung transplantation. The Munich Lung Transplantation Group.

Bronchiolitis obliterans (BO) is one of the main late complications in patients after lung transplantation. Because BO is located in small airways, conventional lung function tests are supposed to be rather insensitive to detect early stages of this disease. In this study, the capability of the aerosol bolus dispersion test to detect BO was tested in 12 subjects with heart-lung and double-lung transplantation. Four of these patients had histological evidence of BO. The broadening (dispersion) of inhaled boluses consisting of monodispersed inert test particles during respiration was repeatedly measured in each subject. Additional measurements of spirometric and bodyplethysmographic measurements were performed. Patients with evidence of BO showed significantly increased aerosol bolus dispersion and significantly reduced maximal airflow parameters. Calculation of receiver operating characteristics (ROCs) revealed that from all lung function parameters under consideration, aerosol bolus dispersion divided by the maximum expiratory flow rate at 50% of vital capacity (MEF50) and MEI50 had the highest sensitivity and specificity for the detection of BO. Both parameters showed a sensitivity and specificity of 100%. Therefore, it may be speculated that even in early stages of disease, the combination of MEF50 measurement with aerosol bolus dispersion measurements may be a powerful tool for the detection of BO in patients with lung transplantation.

Adolescent↗