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PubMed2004

Biogenically driven organic contribution to marine aerosol.

Marine aerosol contributes significantly to the global aerosol load and consequently has an important impact on both the Earth's albedo and climate. So far, much of the focus on marine aerosol has centred on the production of aerosol from sea-salt and non-sea-salt sulphates. Recent field experiments, however, have shown that known aerosol production processes for inorganic species cannot account for the entire aerosol mass that occurs in submicrometre sizes. Several experimental studies have pointed to the presence of significant concentrations of organic matter in marine aerosol. There is some information available about the composition of organic matter, but the contribution of organic matter to marine aerosol, as a function of aerosol size, as well as its characterization as hydrophilic or hydrophobic, has been lacking. Here we measure the physical and chemical characteristics of submicrometre marine aerosol over the North Atlantic Ocean during plankton blooms progressing from spring through to autumn. We find that during bloom periods, the organic fraction dominates and contributes 63% to the submicrometre aerosol mass (about 45% is water-insoluble and about 18% water-soluble). In winter, when biological activity is at its lowest, the organic fraction decreases to 15%. Our model simulations indicate that organic matter can enhance the cloud droplet concentration by 15% to more than 100% and is therefore an important component of the aerosol-cloud-climate feedback system involving marine biota.

Aerosols↗
PubMed2001

Airflow and device effects on aerosol delivery for large animals.

Aerosol delivery of medications has recently gained acceptance in large animal veterinary medicine. However, delivery of therapeutic aerosols currently relies on equipment modified from human use and delivery of medical aerosols may be adversely affected by the equipment design. In this study, we demonstrate the effect of typical large animal inspiratory flow rates on aerosol delivery characteristics. A benchtop system was assembled to simulate aerosol delivery to large animals. Phasic airflow was generated using a large animal anesthesia machine set to deliver 6 bpm (7 L/breath) at 100, 150 and 180 L/min mean inspiratory airflow. Aerosol from a DeVilbis ultrasonic nebulizer was delivered to a simulated facemask using standard 22 mm tubing and fittings. Total mass, delivery efficiency and mass median aerosol diameter (MMAD) was measured with and without an inspiratory one-way valve on the facemask. Delivered aerosol mass ranged from 0.26 to 0.08 g/min and delivery efficiency ranged from 30 to 6%. Both parameters were significantly reduced by both increasing flow rates and the presence of a one-way valve between the nebulizer and the facemask. Average MMAD was 0.7 microm and was not affected by any experimental variable. These results demonstrate that current aerosol equipment used on large animals has a substantial adverse effect on aerosol delivery. Elimination of one-way valves between the aerosol source and the patient is expected to improve delivery of the aerosol in these patients.

Administration, Inhalation↗
PubMed2002

Personal sampling for inhalable aerosol exposures of carbon black manufacturing industry workers.

The study was concerned with the measurement of inhalable aerosol exposures in the carbon black production industry. The primary goal of the study was to determine the extent to which inhalable aerosol exposure, as measured by the Institute of Occupational Medicine (IOM) personal inhalable sampling head, compared to "total" aerosol exposure, as measured by traditional methodology. A secondary objective was the evaluation of another inhalable aerosol sampler for carbon black aerosol measurement. In addition, an exploratory evaluation of the applicability of the National Institute for Occupational Safety and Health (NIOSH) analytical method (Method 5040) for the determination of carbon black, measured as elemental carbon, was conducted. A field study was carried out in a number of North American carbon black production plants using three samplers: the 2 Lpm IOM sampler as a reference sampler for the inhalable fraction, the 2 Lpm closed-face 37-mm plastic cassette that has been used for many years for total aerosol, and the 3.5 Lpm GSP sampler that has recently been identified by some as a possible candidate for inhalable aerosol. No such studies have previously been reported for the carbon black industry. Further, there have been no reports of the GSP performance in direct comparison to a reference instrument like the IOM sampler. The results showed that inhalable aerosol exposures for workers in carbon black production and packing areas were higher than the corresponding total aerosol exposures by a factor of nearly three, implying the presence of significantly coarser aerosol than previously thought based simply on knowledge of the carbon black production process. The fact that the aerosols collected in portions of the process comprised high proportions of non-elemental carbon particulate was thought likely to be responsible, underlining the need to consider whether gravimetric assessment for such exposure is the most appropriate metric. In addition, and somewhat surprisingly, the GSP sampler emerged clearly as a good alternative to the IOM sampler for collecting inhalable aerosol in carbon black industry workplaces like those studied (although this conclusion cannot yet be extended to other workplaces).

Aerosols↗
PubMed1999

Assessment of need for transport tubes when continuously monitoring for radioactive aerosols.

Aerosol transport tubes are often used to draw aerosol from desirable sampling locations to nearby air sampling equipment that cannot be placed at that location. In many plutonium laboratories at Los Alamos National Laboratory, aerosol transport tubes are used to transport aerosol from the front of room ventilation exhaust registers to continuous air monitors (CAMs) that are mounted on nearby walls. Transport tubes are used because past guidance suggests that extraction of aerosol samples from exhaust locations provides the most sensitive and reliable detection under conditions where the rooms have unpredictable release locations and significant spatial variability in aerosol concentrations after releases, and where CAMs cannot be located in front of exhaust registers without blocking worker walkways. Despite designs to minimize particle loss in tubes, aerosol transport model predictions suggest losses occur lowering the sensitivity of CAMs to accidentally released plutonium aerosol. The goal of this study was to test the hypotheses that the reliability, speed, and sensitivity of aerosol detection would be equal whether the sample was extracted from the front of the exhaust register or from the wall location of CAMs. Polydisperse oil aerosols were released from multiple locations in two plutonium laboratories to simulate plutonium aerosol releases. Networked laser particle counters (LPCs) were positioned to simultaneously measure time-resolved aerosol concentrations at each exhaust register (representative of sampling with transport tubes) and at each wall-mounted CAM location (representative of sampling without transport tubes). Results showed no significant differences in detection reliability, speed, or sensitivity for LPCs positioned at exhaust locations when compared to LPCs positioned at the CAM wall location. Therefore, elimination of transport tubes would likely improve CAM performance.

Aerosols↗
PubMed1987

Effect of nebulised aerosol size on lung deposition in patients with mild asthma.

A radioaerosol technique has been used to investigate whether the size distribution of aerosols released from a jet nebuliser affects the amount of aerosol delivered to the lungs. Six subjects with mild asthma (FEV1 81% of predicted) were studied on three occasions. On each visit they received one of three aerosols tagged with technetium-99m in 0.9% saline. The aerosols were generated by either (A) a Turret nebuliser operated at 8 l min-1 (mass median diameter (MMD) 1.8 micron); (B) an Upmist nebuliser operated at 6 l min-1 (MMD 4.6 microns); or (C) an Inspiron Mini-neb operated at 4 l min-1 (MMD 10.3 microns). The aerosols were given in a randomised single blind manner and inhaled under identical conditions of inspiratory volume and frequency. The mean (SD) percentage of aerosols A, B, C released from the nebulisers during inhalation that was recovered in an expiratory filter was 23 (6), 25 (4), and 24 (4) respectively. Of the aerosols released from the nebuliser and deposited in the body, the percentage deposited in the lung was 79 (3) for aerosol A, 59 (4) for aerosol B, and 44 (5) for aerosol C. The remaining aerosol was deposited in the oropharynx and swallowed. It is concluded that small nebulised aerosols (MMD less than 2 microns) deliver a larger dose to the lungs and should be used to maximise lung deposition.

Adult↗
PubMed1986

Effects of aerosol histamine and carbachol on central and peripheral airflow resistance in sheep.

Sixteen anesthetized artificially ventilated open-chest sheep were prepared with retrograde catheters to allow for measurement of dynamic compliance of the lungs (Cdyn), total airflow resistance of the lungs (RL), and central (Rc) and peripheral (Rp) airflow resistance. Twelve sheep received aerosol histamine and 12 sheep received aerosol carbachol. Eight sheep received and responded to both aerosol histamine and aerosol carbachol. Three sheep received both aerosol histamine and aerosol carbachol but failed to respond to both agents. Under base-line conditions, for the 16 sheep, 69% of total RL was located in the peripheral component, Rp, and 31% in the central component, Rc. Aerosol histamine caused only peripheral small airway changes while aerosol carbachol predominantly effected the central large airways. When aerosol histamine responsiveness, defined using Cdyn or Rp, was compared to aerosol carbachol responsiveness using Rc, a correlation was demonstrable (r = 0.84, n = 8, P less than 0.05). It is possible in sheep to cause relatively pure peripheral small airway and relatively pure central large airway changes by using different bronchoconstrictor agents. Aerosol histamine and aerosol carbachol responsiveness correlated with each other in these artificially ventilated anesthetized sheep.

Aerosols↗
PubMed1992

Aerosolized lidocaine reduces dose of topical anesthetic for bronchoscopy.

Conventional aerosol techniques were used to determine if inhalation of lidocaine can supplement topical anesthesia applied during bronchoscopy. Aerosols of either saline or lidocaine (50 mg at either 2 or 4% concentrations) were generated by jet nebulizer and administered with or without intermittent positive-pressure breathing. Patients (n = 38) after aerosol inhalation were administered 2% lidocaine (atomized and instilled) for suppression of the gag reflex, control of cough, and airway anesthesia. For five of the patients, prior to bronchoscopy, additional studies with radioaerosols and scintillation scans were accomplished with the same aerosol methodology to demonstrate lung distribution of deposited aerosol. For five patients who received 2% lidocaine aerosol prior to bronchoscopy, the subsequent topical dose of anesthetic required for the procedure was 186 +/- 34 (SEM) mg lidocaine. Nine patients in a control group received saline aerosol and required significantly more anesthetic, i.e., 308 +/- 26 mg; procedures were completed on average within 50 min. The largest difference was in the amount delivered to the upper airway (naris, pharynx, epiglottis, and larynx), i.e., 144 +/- 26 mg for saline control versus 48 +/- 16 mg for lidocaine aerosol protocol. Airways distal to the cords required less anesthesia also, on average, 77 mg for the saline control versus 46 mg for the lidocaine aerosol protocol (p < 0.05). Topical anesthetic dosage data were replicated in 12 additional patients studied by a different bronchoscopist. No additional benefit was afforded by premedication with 4% lidocaine aerosol rather than the 2% aerosol (n = 12). We conclude that aerosol modalities can supplement topical anesthesia during bronchoscopy, primarily by reducing the dose required to anesthetize the upper airway.

Administration, Inhalation↗
PubMedDate not supplied

Aerosol transmission of arthropathic and amyloidogenic Enterococcus faecalis.

One-day-old brown layer chicks were exposed to an aerosol of an arthropathic and amyloidogenic Enterococcus faecalis strain alone or after being subjected to treatment with formaldehyde gas (100-200 ppm). Four-day-old chicks were also treated with the same aerosol but after treatment with a Newcastle disease vaccine virus (NDVV) aerosol or intramuscular injection with methylprednisolon at day 1. The same E. faecalis strain was inoculated intramuscularly in day-old chicks as positive control. Bacteremia with time showed that 24 hr after the aerosol the day-old exposed chicks had the highest rate of positive blood cultures (70%-80%). Lower numbers of bacteremic birds at this point in time were found in the chicks treated with E. faecalis aerosol at day 4 (3/10 in the methylprednisolon-treated group and 0/10 in the NDVV-treated group) and the E. faecalis intramuscular-injected group at day 1 (2/10). Formaldehyde gas treatment did not favor the occurrence of bacteremia. NDVV aerosol exposure or injection with corticosteroids did not favor the occurrence of bacteremia 24 hr after E. faecalis aerosol exposure at day 4 either, although 66 days after aerosol, one bird (1/14) treated with NDVV showed bacteremia. A few bacteremic birds were found 10 days after aerosol in the NDVV- and methylprednisolon-treated groups, whereas at 14 days after aerosol, one bacteremic bird was seen in the group subjected to E. faecalis aerosol at day 1, indicating the occurrence of chronic bacteremia. In contrast to the E. faecalis intramuscular-inoculated birds, no joint pathology was seen in the aerosol-exposed groups in spite of the occurrence of chronic bacteremia.

Aerosols↗
PubMed2004

Validation of MODIS aerosol retrievals and evaluation of potential cloud contamination in East Asia.

MODIS aerosol retrievals onboard Terra/Aqua and ground truth data obtained from AERONET (Aerosol Robtic Network) solar direct radiance measurements are collocated to evaluate the quality of the former in East Asia. AERONET stations in East Asia are separated into two groups according to their locations and the preliminary validation results for each station. The validation results showed that the accuracy of MODIS aerosol retrievals in East Asia is a little worse than that obtained in other regions such as Eastern U.S., Western Europe, Brazil and so on. The primary reason is due to the improper aerosol model used in MODIS aerosol retrieval algorithm, so it is of significance to characterize aerosol properties properly according to long-term ground-based remote sensing or other relevant in situ observations in order to improve MODIS retrievals in East Asia. Cloud contamination is proved to be one of large errors, which is demonstrated by the significant relation between MODIS aerosol retrievals versus cloud fraction, as well as notable improvement of linear relation between satellite and ground aerosol data after potential cloud contamination screened. Hence, it is suggested that more stringent clear sky condition be set in use of MODIS aerosol data. It should be pointed out that the improvement might be offset by other error sources in some cases because of complex relation between different errors. Large seasonal variation of surface reflection and uncertainties associated with it result in large intercepts and random error in MODIS aerosol retrievals in northern inland of East Asia. It remains to be a big problem to retrieve aerosols accurately in inland characterized by relatively larger surface reflection than the requirement in MODIS aerosol retrieval algorithm.

Aerosols↗
PubMed1978

Pneumonia in calves produced with aerosols of bovine herpesvirus 1 and Pasteurella haemolytica.

In each of 11 experiments, four calves were exposed first to an aerosol of bovine herpesvirus 1 (BHV1, virus of infectious bovine rhinotracheitis) and second to an aerosol of Pasteurella haemolytica. The interval between aerosols was three to five days. In two other experiments, calves were exposed only to a bacterial aerosol. Climate was controlled for all experiments from the day of viral exposure and for eight of the experiments it was also controlled for four to six days before the first aerosol. The concentration of infectious doses of virus in the aerosols and the number of bacteria in the aerosols of each calf were determined. Macroscopically recognizable rhinitis, tonsillitis, laryngitis, tracheitis and pneumonia of lobar distribution in 42 lobes from 11 calves were seen in five experiments in which bacterial aerosol followed the viral aerosol by at least four days. One calf died with marked respiratory disease in each of four experiments within four days of exposure to the bacterial aerosol. Production of pneumonia was dependent on an interval between aerosols of at least four days but not on the condition of controlled climate on the environmental chamber either before or after the viral aerosol nor on the period of habituation allowed calves of some experiments.

Aerosols↗
PubMed2004

Observational evidence of a change in radiative forcing due to the indirect aerosol effect.

Anthropogenic aerosols enhance cloud reflectivity by increasing the number concentration of cloud droplets, leading to a cooling effect on climate known as the indirect aerosol effect. Observational support for this effect is based mainly on evidence that aerosol number concentrations are connected with droplet concentrations, but it has been difficult to determine the impact of these indirect effects on radiative forcing. Here we provide observational evidence for a substantial alteration of radiative fluxes due to the indirect aerosol effect. We examine the effect of aerosols on cloud optical properties using measurements of aerosol and cloud properties at two North American sites that span polluted and clean conditions-a continental site in Oklahoma with high aerosol concentrations, and an Arctic site in Alaska with low aerosol concentrations. We determine the cloud optical depth required to fit the observed shortwave downward surface radiation. We then use a cloud parcel model to simulate the cloud optical depth from observed aerosol properties due to the indirect aerosol effect. From the good agreement between the simulated indirect aerosol effect and observed surface radiation, we conclude that the indirect aerosol effect has a significant influence on radiative fluxes.

Journal Article↗
PubMed2005

The effect of smoke, dust, and pollution aerosol on shallow cloud development over the Atlantic Ocean.

Clouds developing in a polluted environment tend to have more numerous but smaller droplets. This property may lead to suppression of precipitation and longer cloud lifetime. Absorption of incoming solar radiation by aerosols, however, can reduce the cloud cover. The net aerosol effect on clouds is currently the largest uncertainty in evaluating climate forcing. Using large statistics of 1-km resolution MODIS (Moderate Resolution Imaging Spectroradiometer) satellite data, we study the aerosol effect on shallow water clouds, separately in four regions of the Atlantic Ocean, for June through August 2002: marine aerosol (30 degrees S-20 degrees S), smoke (20 degrees S-5 degrees N), mineral dust (5 degrees N-25 degrees N), and pollution aerosols (30 degrees N- 60 degrees N). All four aerosol types affect the cloud droplet size. We also find that the coverage of shallow clouds increases in all of the cases by 0.2-0.4 from clean to polluted, smoky, or dusty conditions. Covariability analysis with meteorological parameters associates most of this change to aerosol, for each of the four regions and 3 months studied. In our opinion, there is low probability that the net aerosol effect can be explained by coincidental, unresolved, changes in meteorological conditions that also accumulate aerosol, or errors in the data, although further in situ measurements and model developments are needed to fully understand the processes. The radiative effect at the top of the atmosphere incurred by the aerosol effect on the shallow clouds and solar radiation is -11 +/- 3 W/m2 for the 3 months studied; 2/3 of it is due to the aerosol-induced cloud changes, and 1/3 is due to aerosol direct radiative effect.

Air Pollutants↗
PubMed1996

Aerosol deposition in infants with cystic fibrosis.

Twenty asymptomatic infants with cystic fibrosis (CF) were studied to determine the amount of radiolabeled aerosol [99m technetium diethylenetriamine penta acetic acid (Tc99m DTPA)] deposited in the respiratory system and its distribution. Aerosols were generated by jet nebulization systems that were used in the wards and the laboratory. Subjects were studied in three groups: group A (n = 10) was sedated with chloral hydrate; children inhaled an aerosol of 7.7 microns mass median diameter (MMD); group B (n = 5) was not sedated, using the same nebulization system (same aerosol particle size as group A); and group C (n = 5) was not sedated; these children inhaled an aerosol with an MMD of 3.6 microns. Normal saline plus 4 mCi of Tc99m bound to DTPA was added to each nebulizer. A closed system was used to collect the expired aerosol. Radioactivity in each infant and in the equipment was measured with a gamma camera on completion of nebulization. In groups A and B, the percentages of the total dose deposited in the lung were 0.97 +/- 0.35% and 0.76 +/- 0.36%, respectively. In group C, 2.0 +/- 0.71% was deposited in the lung (P < 0.01). Deposition in the nose, mouth, and pharynx was least in group C (P < 0.01). In groups A and B, the intrathoracic deposition occurred predominantly in the trachea and main bronchi, whereas in group C, significantly more aerosol was deposited in the lung region. There was marked inter-subject variability in the percentage of aerosol deposition within the three groups. There was no correlation between percentage of aerosol deposited in the respiratory system and age, height, or weight. Sedation did not have a significant effect on deposition of aerosol in infants. This study indicates that only a small proportion of nebulized solution is deposited in the lungs of infants and that this proportion is influenced by the particle size of the aerosol. The smaller particle size (3.6 microns MMD) was deposited in the lung better than large particles.

Aerosols↗
PubMed1996

Antigen-driven peripheral immune tolerance: suppression of experimental autoimmmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type II collagen.

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously demonstrated that exposure of gut-associated lymphoid tissue to myelin basic protein (MBP) via oral administration suppresses experimental autoimmune encephalomyelitis (EAE). To further study presentation of antigen to the immune system by mucosal surfaces as a method of antigen-driven tolerance, the effect of inhalation of MBP was investigated. MBP was given as an aerosol to Lewis rats on Days -10, -7, -5, and -3 prior to immunization with MBP in Freund's adjuvant and on Days 0, 2, and 4 following immunization. Aerosolization of MBP completely abrogated clinical EAE in 100% of treated rats. Central nervous system inflammation and delayed-type hypersensitivity and antibody responses to MBP were also significantly reduced in aerosol-treated animals. Aerosolization of histone, a basic protein of similar weight and charge as MBP, had no effect. Disease was also suppressed with one aerosol treatment on Day -3 or by administering MBP nasally. Aerosolization was more effective than oral administration of MBP over a wide dose range (0.005-5 mg). Splenic T cells isolated from animals postaerosolization adoptively transferred protection to naive animals immunized with MBP. Aerosolization of MBP to animals with relapsing EAE after recovery from the first attack decreased the severity of a subsequent attack. Aerosol and oral MBP were equally effective at suppressing the in vitro immune response as measured by proliferation and interferon-gamma production. We then tested aerosolization of a different autoantigen in a different disease model and found that aerosolization of type II collagen was effective in suppressing collagen-induced arthritis. Thus, aerosolization of an autoantigen is a potent method to downregulate an experimental T cell-mediated autoimmune disease and suggests that exposure of antigen to lung mucosal surfaces preferentially generates immunologic tolerance.

Administration, Oral↗
PubMed2001

Effects of inhalation of perfluorocarbon aerosol on oxygenation and pulmonary function compared to PGI2 inhalation in a sheep model of oleic acid-induced lung injury.

OBJECTIVE: To evaluate the effects of PFC aerosol compared to PGI2 aerosol and NaCl aerosol on gas exchange and lung mechanics in oleic acid-induced acute lung injury. DESIGN: A prospective, controlled, randomised, in vivo animal laboratory study. SETTING: Research laboratory at an university hospital. SUBJECTS: Twenty one (n = 21) adult sheep of either gender weighing 26.8+/-6.4 kg. INTERVENTIONS: The animals were randomised to three groups: PFC aerosol (perfluorooctane), PFC group; prostacyclin aerosol (Flolan), PGI2 group; and NaCl aerosol (0.9% sodium chloride solution), control group. After induction of anaesthesia and placement of vascular catheters, lung injury was induced with 0.12 ml x kg(-1) oleic acid. Aerosols were continuously administered for 2 h using a jet nebuliser. Gas exchange, pulmonary mechanic, and haemodynamic parameters were obtained at regular intervals. MEASUREMENTS AND MAIN RESULTS: PFC aerosol increased oxygenation (PaO2) 15 min after the initiation of treatment up to 120 min (P < 0.05). Transpulmonary shunt improved in the PFC group (P < 0.05) while it did not change in the two other groups. PFC aerosol reduced maximum airway pressure (Pmax) (median) significantly from (median) 38 mbar to 32 mbar (P < 0.05). Static compliance improved significantly in the PFC group (P < 0.05). CONCLUSION: The inhalation of a PFC aerosol led to a significant improvement in pulmonary mechanics and gas exchange, which was not observed in the other two groups. These data suggest that a small dose of perfluorocarbon will have beneficial effects on gas exchange and respiratory mechanics. Therefore, the non-invasive aerosol application technique seems to be a reasonable alternative to administer perfluorocarbons in severe lung injury.

Aerosols↗
PubMed2004

Design of liposomal aerosols for improved delivery of rifampicin to alveolar macrophages.

The present study was aimed at preparation, characterization, and performance evaluation of rifampicin-loaded aerosolized liposomes for their selective presentation to alveolar macrophages, that being the most dense site of tuberculosis infection. Egg phosphatidylcholine (PC)- and cholesterol (Chol)-based liposomes were modified by imparting negative charge (using dicetylphosphate, DCP) or by coating them with alveolar macrophage-specific ligands (maleylated bovine serum albumin, MBSA; and O-steroyl amylopectin, O-SAP). The prepared formulations were characterized in vitro for vesicle morphology, mean vesicle size, and percent drug entrapment. Pressurized packed systems based on preformed liposomal formulations in chlorofluorocarbon aerosol propellants were prepared. In vitro airway penetration efficiency of the liposomal aerosols was determined by percent dose reaching the base of the lung, it was recorded 1.5-1.8 times higher as compared to plain drug solution-based aerosol. Percent viability of Mycobacterium smegmatis inside macrophages (in vitro) after administration of drug (in vivo) was in the range of 7-11% in the case of ligand-anchored liposomal aerosols, while it was recorded to be 45.7 and 31.6% in case of plain drug and plain neutral liposomal aerosol (based on PC:Chol)-treated macrophages. Results suggest the preferential accumulation of MBSA- and O-SAP-coated formulations in the lung macrophages, which was further reflected in the periodically monitored in vivo tissue distribution studies. Higher lung drug concentration was recorded in case of ligand-anchored liposomal aerosols and negatively charged liposomal aerosols (based on PC:Chol:DCP) as compared to plain drug and plain liposome-based aerosols. The drug was estimated in the lung in high concentration even after 24h. The drug localization index calculated after 6h was nearly 1.4- and 3.5-fold, respectively, for both ligand-appended liposome-based systems as compared to negatively charged and plain neutral liposome-based aerosolized systems. These results suggest that the ligand-anchored liposomal aerosols are not only effective in rapid attainment of high-drug concentration in lung with high population of alveolar macrophages but also maintain the same over prolonged period of time. The significance of targeting potential of the developed systems was established.

Administration, Inhalation↗
PubMed1998

Continuous nebulization therapy for asthma with aerosols of beta2 agonists.

BACKGROUND: Various studies have demonstrated the benefits of continuous nebulization therapy for delivering aerosols of the beta2 agonists such as terbutaline sulfate or albuterol sulfate to patients with severe asthma and/or impending respiratory failure. OBJECTIVE: The purpose of this investigation was to explicate the operational factors associated with the use of nebulizers for extended aerosol respiratory therapy including those factors that affect the prescribed aerosol dosages and the relationship to actual delivery of prescribed drugs to the respiratory airways of the lungs of a patient under treatment conditions. METHODS: Operational characteristics and methods have been investigated for use of long-running nebulizers for continuous nebulization therapy. Factors considered were particle size distribution, setup conditions, aerosolization concentrations and rates, delivery fraction of aerosol reaching patient, and changes in medication concentration during extended operation. With a large volume nebulizer, aerosols can be delivered to the patient without dilution via a standard open mask for up to eight hours without refill. The pneumatic HEART nebulizer with 240 mL reservoir was evaluated. RESULTS: The nebulizer was operated from a single compressed air or oxygen source and found to provide from 10 to 15 L/min of aerosol with 38 to 50 microL of aerosolized medicine per liter of air (or oxygen) and utilize from 30 to 56 mL/hour of medicinal liquid. The mass median aerodynamic diameter of the aerosol droplets was found to be about 2.0 microm (sigma(g) = 2.7). Delivery efficiency to the patient mask was about 90%. The aerosolized medicine delivered to the patient can be increased by adjusting the flow rate of the gas source or changing the solution concentration of medicine. Typically, several milligrams of drug can be delivered to the patient as inhaled aerosol per hour of treatment of which about one-quarter can be expected to be deposited in the lungs. During eight hours of operation the concentration of medicinal solution increased by about a factor of two because of water evaporation. CONCLUSIONS: Continuous nebulization therapy is an important means of treating patients with severe asthma. Dosage criteria can be established based on the operating characteristics of the nebulizer system, drug solution concentration, and patient respiration.

Adrenergic beta-2 Receptor Agonists↗
PubMed1995

The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF.

PURPOSE: The objective of this study was to highlight differences in the pulmonary absorption of a monoPEGylated rhG-CSF and rhG-CSF after intratracheal instillation and aerosol delivery. METHODS: Male Sprague Dawley rats (250 g) were anesthetized and intratracheally instilled (IT) with protein solution or were endotracheally intubated and administered aerosol for 20 min via a Harvard small animal ventilator. A DeVilbiss "Aerosonic" nebulizer containing 5 ml of protein solution at approximately 3 mg/ml was used to generate aerosol. The volume of protein solution deposited in the lung lobes was estimated to be approximately 13 microliters after delivery of Tc-99m HSA solutions. The PEGylated proteins consisted of a 6 kDa (P6) or 12 kDa PEG (P12) linked to the N-terminus of rhG-CSF. rhG-CSF also was administered IT in buffers at pH 4 and pH 7 and in dosing volumes ranging from 100 to 400 microliters. Blood samples were removed at intervals after dosing and the total white blood cell counts (WBC) were determined. Plasma was assayed for proteins by an enzyme immuno assay. RESULTS: The plasma protein concentration v. time profiles were strikingly different for aerosol v. IT delivery. The Cmax values for rhG-CSF and P12 after aerosol delivery were greater than found after IT (Aerosol: 598 +/- 135 (ng/ml) rhG-CSF; 182 +/- 14 P12 v. IT: 105 +/- 12 rhG-CSF; 65.9 +/- 5 P12). Similarly, Tmax was reached much earlier after aerosol administration (Aerosol: 21.7 +/- 4.8 (min) rhG-CSF; 168 +/- 31 P12 v. IT: 100 +/- 17 rhG-CSF; 310 +/- 121 P12). Estimated bioavailabilities (F(lung)%) were significantly greater via aerosol delivery than those obtained after IT (Aerosol: 66 +/- 14 rhG-CSF; 12.3 +/- 1.9 P12 v. IT: 11.9 +/- 1.5 rhG-CSF; 1.6 +/- 0.1 P12). An increase in circulating WBC counts was induced by all proteins delivered to the lungs. The rate and extent of absorption of rhG-CSF was not influenced by the pH employed nor the instilled volume. CONCLUSIONS: Estimates of bioavailability are dependent upon the technique employed to administer drug to the lungs. Aerosol administration provides a better estimate of the systemic absorption of macromolecules.

Absorption↗