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PubMed2002

Stronger constraints on the anthropogenic indirect aerosol effect.

The anthropogenic indirect aerosol effects of modifying cloud albedo and cloud lifetime cannot be deduced from observations alone but require a modeling component. Here we validate a climate model, with and without indirect aerosol effects, by using satellite observations. The model agrees better with observations when both indirect aerosol effects are included. However, the simulated clouds are more susceptible to aerosols than the observed clouds from the POLDER satellite, thus overestimating the indirect aerosol effect. By taking the difference in susceptibilities into account, the global mean total anthropogenic aerosol effect is reduced from -1.4 to -0.85 watts per square meter.

Journal Article↗
PubMed2003

Surface aerosol radiative forcing derived from collocated ground-based radiometric observations during PRIDE, SAFARI, and ACE-Asia.

An approach is presented to estimate the surface aerosol radiative forcing by use of collocated cloud-screened narrowband spectral and thermal-offset-corrected radiometric observations during the Puerto Rico Dust Experiment 2000, South African Fire Atmosphere Research Initiative (SAFARI) 2000, and Aerosol Characterization Experiment-Asia 2001. We show that aerosol optical depths from the Multiple-Filter Rotating Shadowband Radiometer data match closely with those from the Cimel sunphotometer data for two SAFARI-2000 dates. The observed aerosol radiative forcings were interpreted on the basis of results from the Fu-Liou radiative transfer model, and, in some cases, cross checked with satellite-derived forcing parameters. Values of the aerosol radiative forcing and forcing efficiency, which quantifies the sensitivity of the surface fluxes to the aerosol optical depth, were generated on the basis of a differential technique for all three campaigns, and their scientific significance is discussed.

Journal Article↗
PubMed2006

Simulations of the accuracy in retrieving stratospheric aerosol effective radius, composition, and loading from infrared spectral transmission measurements.

We examine the extent to which three physical aerosol parameters--effective radius, composition (sulfate weight percent), and total volume-can be determined from infrared transmission spectra. Using simulated transmission data over the range 800-4750 cm(-1) (12.5-2.1 microm) and errors taken from the infrared spectral measurements of the Atmospheric Trace Molecule Spectroscopy (ATMOS) instrument, we use optimal estimation to recover these aerosol parameters. Uncertainties in these are examined as a function of the size, composition, and loading of stratospheric aerosols and of the spectral range employed. Using the entire spectral range above, we retrieve all three parameters with a precision to within 3% if the size distribution form is known. Additional errors result, however, from an uncertainty in the size distribution width. These are small (only a few percent) for composition and total volume but are substantial (as much as 50%) for effective radius. Errors also increase substantially when the spectral range is reduced. The retrieved effective radius can have an error of 100% or greater for typical stratospheric aerosol sizes when the spectral range is restricted to the lower wavenumber part of the range. For good accuracy in effective radius, the spectral range must extend beyond approximately 3000 cm(-1). Composition and total volume are less sensitive to the spectral range than effective radius. These simulations were carried out with modeled data to test the potential accuracy of stratospheric sulfate aerosol retrievals from the Atmospheric Chemistry Experiment (ACE). Because of the limitations that result from the use of simulated data, we have tested our retrieval algorithm using ATMOS spectra in different filter regions and present here the aerosol parameters obtained.

Journal Article↗
PubMed2000

9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice.

The response rates of relapsed osteosarcoma and melanoma pulmonary metastases to traditional i.v. chemotherapeutic regimens have been disappointing. Direct drug delivery of chemotherapy to the lungs could increase the drug concentration in the tumor area and may offer a new therapeutic approach for these patients. Previous studies demonstrated that drugs delivered to the respiratory tract in liposomal formulation resulted in high pulmonary drug concentration, reduced systemic toxicity, and reduced dosage requirements compared with parenteral and oral administration. To determine whether this approach has utility against pulmonary metastases, the efficacy of aerosol therapy with liposome-encapsulated 9-nitrocamptothecin (L-9NC) was determined using two different experimental lung metastasis models. C57BL/6 mice were treated the day after the i.v. injection of B16 melanoma cells with aerosol L-9NC for 1 h (153 microg 9-nitrocamptothecin/kg) for 5 days per week for up to 3 weeks. Aerosol L-9NC treatment resulted in a reduction in lung weights (P = 0.005) and number of tumor foci (P < 0.001). Visible tumor nodules were fewer and smaller in the 9-nitrocamptothecin-treated group than in untreated control mice (P < 0.001). Using a newly developed human osteosarcoma experimental metastasis model in nude mice, we demonstrated that aerosol L-9NC was also effective against established lung metastases. Aerosol therapy initiated on the ninth week after i.v. tumor injection and continued for 8 or 10 weeks produced highly significant reductions in the number of animals with both visible and microscopic disease (P < 0.02), the total number of tumor foci in the lungs (P < 0.005), and the size of the individual tumor nodules (P < 0.02). These data suggest that L-9NC aerosol therapy may offer significant advantage over existing methods in the treatment of melanoma and osteosarcoma pulmonary metastases.

Animals↗
PubMed2004

[Distribution of hydroxycamptothecin after aerosol inhalation in rabbits].

AIM: To investigate the tissue distribution and pharmacokinetics of hydroxycamptothecin (HCPT) after aerosol inhalation in rabbits. METHODS: RP-HPLC was used to determine the concentration of HCPT in different tissues and plasma of rabbits. The tissue distribution of HCPT after aerosol inhalation or iv administration was compared. The plasma concentrations at different time after aerosol inhalation were compared with iv injection. RESULTS: The HCPT concentrations in lung after aerosol inhalation at 0.5, 1 and 2 h were 13.52, 27.81 and 20.82 times higher than that of iv administration group, respectively. At the same time, concentrations in other tissues were decreased obviously. The absolute bioavailability of HCPT after aerosol inhalation was 7.38%. CONCLUSION: After aerosol inhalation, HCPT is retained mostly in lung. So this administration route can raise the therapeutic index and reduce adverse effects.

Administration, Inhalation↗
PubMed1992

Aerosolized pentamidine: a well-tolerated mode of prophylaxis against Pneumocystis carinii pneumonia in older children with human immunodeficiency virus infection.

Aerosolized pentamidine has been recommended as an alternative mode of antipneumocystis prophylaxis in human immunodeficiency virus-infected children with trimethoprim-sulfamethoxazole intolerance. However, there have been no definitive data concerning the most appropriate dose and the tolerance of aerosolized pentamidine in children. In the present study, we assessed the tolerance of aerosolized pentamidine in older children using a regimen similar to the one recommended in adults. A 300-mg dose of pentamidine was administered to our human immunodeficiency virus-infected patients monthly using the Respirgard II nebulizer. Patients were assessed for their heart rate, respiratory rate, breath sounds and oxygen saturations during and after pentamidine aerosolization. During a 21-month period (August, 1989, to May, 1991), 22 patients (mean age, 9.8 +/- 0.6 years; range, 3 to 15 years) received a total of 185 treatments. Patients complained of either a bitter taste (16 of 22) or developed short periods of coughing (15 of 22) during the aerosol. Five patients developed reversible bronchospasm requiring bronchodilators; no patients developed oxygen desaturation. None of the patients developed Pneumocystis carinii pneumonia during the limited protocol follow-up (mean, 9.8 months). Thus aerosolized pentamidine for antipneumocystis prophylaxis is well-tolerated in older children. However, more comprehensive investigations of efficacy are indicated.

Administration, Inhalation↗
PubMed1990

Diagnostic and therapeutic technology assessment. Prophylactic treatment for opportunistic infections in HIV-positive patients: aerosolized pentamidine.

The DATTA panelists considered aerosolized pentamidine to be both safe and effective for primary and secondary prophylaxis of PCP. T4 helper cell counts offer guidance as to the best candidates for primary prophylaxis. Patients with a T4 helper cell count of fewer than 200/mm3 are the most appropriate group to receive primary prophylaxis with aerosolized pentamidine. However, T4 helper cell counts are not an exclusive criterion for aerosolized pentamidine prophylaxis. Some DATTA panelists suggested that certain patients, such as those with Kaposi's sarcoma and lymphomas and those with concomitant human T-cell lymphotropic virus type 1 infection, might be considered candidates for aerosolized pentamidine regardless of T4 helper cell counts. There is no current literature to support this, and this opinion is based solely on clinical experience. Perhaps the use of other markers of immune function (beta 2-microglobulin, neopterin) in conjunction with T4 helper cell counts will give a better indication of when to start primary prophylaxis. Aerosolized pentamidine is not the only potential prophylactic regimen for PCP. Other drugs, including pyrimethamine and sulfadoxine, sulfamethoxazole and trimethoprim, and dapsone, are currently being evaluated. Prior diagnosis and therapy for patients with M tuberculosis must occur before initiation of the use of aerosolized pentamidine. This and other appropriate environmental precautions should reduce transmission of M tuberculosis to health care workers and other patients. Whether any prophylactic treatment of an opportunistic infection will prolong survival in HIV-infected individuals has yet to be proved. The assumption is made, however, that a reduction in opportunistic infections should lower mortality and improve the quality of life.

American Medical Association↗
PubMed1996

Comparison of the pulmonary distribution and efficacy of antibodies given to mice by intratracheal instillation or aerosol inhalation.

The respiratory tract is the portal of entry and target organ of many aerosolized toxins and infective agents, and there is increasing need for testing the efficacy of potential therapeutic agents delivered directly into the lungs. Intratracheal instillation and aerosol inhalation are the two methods most often used to introduce drugs, toxins, or infective agents into the respiratory tract of experimental animals. In this study we compared the distribution and efficacy of antibodies given to mice by aerosol inhalation or intratracheal instillation. We determined the pulmonary distribution of these antibodies by immunohistochemistry and observed the distribution and severity of pulmonary lesions that developed after exposure to aerosolized ricin. Although antibodies administered by either method prevented death, we found that instilled antibodies tended to concentrate around terminal airways and often failed to reach peripheral lung fields. Sometimes entire lung lobes were missed by the instillation route. Acute and chronic pulmonary lesions developed in the unprotected areas of instillation-treated lungs. In contrast, aerosolized antibodies covered all pulmonary surfaces and effectively prevented ricin-induced lesions throughout the lungs. Our findings suggest that the aerosol inhalation method may be preferable for evaluating the efficacy of therapeutic agents in the respiratory tract because of the failure of instilled agents to reach and protect peripheral alveoli.

Administration, Inhalation↗
PubMed1999

Placebo-controlled, comparative study of the efficacy and safety of triamcinolone acetonide inhalation aerosol with the non-CFC propellant HFA-134a in patients with asthma. Azmacort HFA Clinical Study Group.

BACKGROUND: Triamcinolone acetonide (TAA) inhalation aerosol (Azmacort Inhalation Aerosol), a well-established corticosteroid treatment for bronchial asthma, utilizes the chlorofluorocarbon (CFC) propellant P-12, which will be phased out because of environmental concerns. Two TAA aerosol formulations have been developed using a non-chlorofluorocarbon propellant, HFA-134a (Azmacort HFA Inhalation Aerosol delivering TAA 75 microg/puff or 225 microg/puff). OBJECTIVE: This study compared the efficacy and safety of the new 225 microg/puff formulation (TAA-HFA 225) to the marketed TAA inhalation aerosol (TAA-CFC) and to placebo in adult patients with moderate-to-severe persistent asthma. METHODS: After a 5-day to 21-day baseline period during which all patients received TAA-CFC 150 microg/day, 538 patients were randomized to one of the following treatment schedules: TAA-HFA 450, 900, or 1800 microg/day; TAA-CFC 450 or 900 microg/day; or placebo for 12 weeks. RESULTS: All active treatment groups showed statistically significant improvement compared with placebo in pulmonary function (FEV1, FEF25-75%, morning and evening PEF), use of rescue albuterol, and asthma symptom scores. Improvements in all variables occurred within 1 week of treatment. CONCLUSIONS: The TAA-HFA 225 exhibited similar safety and efficacy profiles to the two equivalent doses of TAA-CFC studied. Our findings indicate that TAA-HFA is a safe and effective replacement for the currently marketed CFC-containing product. The higher strength 225 microg/puff formulation provides effective control of asthma with fewer inhalations.

Administration, Inhalation↗
PubMed1975

An improved aerosol generator.

An aerosolizer has been developed which automatically compensates for changes in the concentration and volume of a solution during aerosolization by adjustment of the temperature and pressure of the atomizing air jet. It represents the redesign of a generator previously used for short-term inhalation exposures (one-half to a few hours) where variability in solution concentration was not of great concern and solutions could be replenished daily. The stability of the original generator was quite inadequate, and it was not satisfactory for production of aerosols of constant physical characteristics over longer or repetitive time periods or where a minimum of manipulation is required--viz., for radioactive and other highly noxious materials. The redesigned aerosolizer should be valuable for long-term or repetitive use, since it requires no cleaning, merely refilling, and can 0e made as small or as large as experimental needs require. It should be particularly useful where correlations between the amount of deposition and aerosol characteristics are being studied.

Aerosol Propellants↗
PubMed1994

Generation of aerosolized drugs.

The expanding use of inhalation therapy has placed demands on current aerosol generation systems that are difficult to meet with current inhalers. The desire to deliver novel drug entities such as proteins and peptides, as well as complex formulations including liposomes and microspheres, requires delivery systems of improved efficiency that will target the lung in a reproducible manner. These efforts have also been spurred by the phase out of chlorofluorocarbons (CFCs) and this has included a directed search for alternative propellants. Consequently, a variety of new aerosol devices and methods of generating aerosols are being studied. This includes the use of freon replacement propellants, dry powder generation systems, aqueous unit spray systems and microprocessor controlled technologies. Each approach has advantages and disadvantages depending upon each principle of action and set of design variables. In addition, specific drugs may be better suited for one type of inhaler device vs. another. The extent to which aerosol generation systems achieve their goals is discussed together with a summary of selected papers presented at the recent International Congress of Aerosols in Medicine.

Administration, Inhalation↗
PubMed2005

Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers.

Apart from particle size distribution, spray velocity is one of the most important aerosol characteristics that influence lung deposition of inhaled drugs. The time period over which the aerosol is released (spray duration) is also important for coordination of inhalation. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that delivers drug to the lung much more efficiently than pressurised metered dose inhalers (pMDIs). The objective of this study was to compare the velocity and spray duration of aerosol clouds produced by Respimat SMI with those from a variety of chlorofluorocarbon (CFC) and hydrofluoroalkane (HFA) pMDIs. All inhalers contained solutions or suspensions of bronchodilators. A videorecording method was used to determine the aerosol velocity. For spray duration, the time for generation of the Soft Mist by Respimat SMI was initially determined using three different methods (videorecording [techniques A and B], laser light diffraction and rotating disc). Videorecording was then used to compare the spray duration of Respimat SMI with those from the other inhalers. The Soft Mist produced by Respimat SMI moved much more slowly and had a more prolonged duration than aerosol clouds from pMDIs (mean velocity at a 10-cm distance from the nozzle: Respimat SMI, 0.8 m/sec; pMDIs, 2.0-8.4 m/sec; mean duration: Respimat SMI, 1.5 sec; pMDIs, 0.15-0.36 sec). These characteristics should result in improved lung and reduced oropharyngeal deposition, and are likely to simplify coordination of inhaler actuation and inhalation compared with pMDIs.

Aerosol Propellants↗
PubMed1983

Factors influencing the size distribution of aerosols from jet nebulisers.

The size distribution of saline and bronchodilator (terbutaline) aerosol droplets generated from four widely used jet nebulisers (Acorn, Upmist, Turret, and Inspiron Mini-neb) has been measured with a Malvern 2200 Laser Particle Sizer. The mass median diameter of aerosol droplets generated by each nebuliser was strongly influenced by the driving flow rate of compressed air. By increasing the flow rate from 4 to 8 1 min-1 mass median diameters were halved (p less than 0.01) and there was an increase in the mass of aerosol within the optimum respirable range (less than 5 micron). To achieve this range the following individual flow rates were required: Turret 4 1 min-1, Acorn and Upmist 6 1 min-1, and Inspiron Mini-neb 8 1 min-1. A significant inverse relation (p less than 0.001) was found between mass median diameter and the geometric standard deviation, indicating that the aerosols were smaller but more heterodisperse at high flow rates. Changes in drug concentration had little effect on aerosol size. In 72% of the nebulisations followed to dryness there was no significant change in mass median diameter during the course of nebulisation and in the remainder it was less than 1.3 micron.

Aerosol Propellants↗
PubMed1997

Aerosol delivery to non-ventilated infants by metered dose inhaler: should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 micrograms/dose) of MDI albuterol through a neonatal Aerochamber 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber: 51.2 +/- 3.1% vs. 35.0 +/- 2.8%, P < 0.0001; Babyhaler: 38.8 +/- 2.3% vs. 19.2 +/- 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used.

Aerosols↗
PubMedDate not supplied

Gene transfer by guanidinium-cholesterol: dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol.

BACKGROUND: A major challenge of gene therapy is the efficient transfer of genes to cell sites where effective transfection can occur. The impact of jet nebulization on DNA structural and functional integrity has been problematic for the aerosol delivery of genes to pulmonary sites and remains a serious concern for this otherwise promising and noninvasive approach. METHODS: This study examined effects of cationic liposome-DNA formulation on both transfection efficiency (in vitro and in vivo) and jet nebulizer stability. The effects of nebulization and sonication on liposome-DNA particle size characteristics were examined. Electron microscopy of promising formulations was performed using several fixation methods. RESULTS: The cationic lipid bis-guanidinium-tren-cholesterol (BGTC), in combination with the neutral co-lipid dioleoylphosphatidylethanolamine (DOPE), was found to have a degree of stability adequate to permit effective gene delivery by the aerosol route. Optimal ratios of lipids and plasmid DNA were identified. Particle size analysis and ultrastructural studies revealed a remarkably homogeneous population of distinctly liposomal structures correlating with the highest levels of transfection efficiency and nebulizer stability. CONCLUSIONS: Optimizing gene delivery vectors for pulmonary aerosol delivery to respiratory sites must take into account factors other than transfection efficiency in vitro. Effects of liposome-DNA formulation on liposomal morphology (i.e. particle size, multilamellar structure) appear to be relevant to stability during aerosolization. These studies have allowed us to identify formulations that hold promise for successful clinical application of aerosol gene delivery.

Aerosols↗
PubMed2001

Note: dissolution of aerosol particles of budesonide in Survanta, a model lung surfactant.

The effect of a pulmonary surfactant extract from bovine lung, Survanta, on the dissolution rate of aerosol particles of budesonide was determined. Aerosol particles of budesonide were generated from an ethanol solution, dried, and collected by a cascade impactor for characterization or by a liquid impinger for dissolution experiments. Powder x-ray diffraction, differential scanning calorimetry, differential thermal analysis, and scanning electron microscopy were used to characterize the aerosol particles and starting material. No change in phase was detected, although the aerosol particles appeared to contain residual solvent. The dissolution rate of the aerosol particles in saline was low and variable. Survanta increased the extent of dissolution of budesonide in proportion to the added concentration, which was also verified by equilibrium solubilization studies. Survanta also increased rate of dissolution, in a manner similar to sodium dodecyl sulfate. Analysis of the concentration of budesonide following ultracentrifugation indicated that there is rapid equilibration of budesonide between the Survanta and aqueous phase. These results show that lung surfactant has the potential of enhancing the rate and extent of dissolution of drugs administered to the lung.

Aerosols↗
PubMed1994

Experimental grain dust atmospheres generated by wet and dry aerosolization techniques.

Properties of grain dust aerosols generated using wet and dry techniques were studied. Relative to the dry aerosol generation, the wet generation technique yielded a smaller particle size distribution (MMAED of 1.5 microns vs. 15.5 microns) but also reduced the viability of microorganisms. Analysis of dust mass and endotoxin activity on cascade impactor stages demonstrated equivalent partitioning of the airborne endotoxin with the dust mass for aerosols produced by either generation method. Comparison of laboratory-generated atmospheres to field sampling indicated a greater proportion of respirable microorganisms in soybean handling facilities than were generated using the dry aerosol system. Limitations of both aerosol generation systems were found that may affect the validity of inhalation toxicology studies in which these bioaerosols are artificially created.

Aerosols↗
PubMed2005

Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastases.

Osteosacarcoma (OS) lung metastases are often resistant to chemotherapy. Most anticancer drugs are administered systemically. In many cases this is followed by dose-dependent toxicity, which may not allow the achievement of therapeutic levels in lungs to eradicate metastases. We determined the efficacy of gemcitabine (GCB) by administering it directly to the lungs via aerosol and studied the role of the Fas pathway in response to the therapy. We used 2 osteosarcoma lung metastases animal models: human LM7 cells that form lung metastases in mice following intravenous injection and murine LM8 cells, which grows subcutaneously in mice and spontaneously metastasize to the lung. Treatment was initiated when the presence of lung metastases had been established. Aerosol GCB inhibited the growth of lung metastases in mice. Intraperitoneal GCB administration at similar dosage had no effect on lung metastases. Besides its direct effect on lung metastases, aerosol GCB suppressed the growth of subcutaneous LM8 tumor. Histopathological examination of mice receiving aerosol GCB showed no evidence of toxicity. Lungs are distinguished from other tissues by the constitutive expression of FasL. Since exposure of tumor cells to GCB upregulated Fas expression, we hypothesized that the susceptibility of the tumor cells to ligand-induced cell death by resident lung cells may be increased. Therefore, the Fas pathway may contribute to the therapeutic effect of aerosol GCB.

Aerosols↗