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PubMed1992

Resolution of Pneumocystis carinii pneumonia in CD4+ lymphocyte-depleted mice given aerosols of heat-treated Escherichia coli.

Mice were thymectomized and depleted of CD4+ lymphocytes by treatment with monoclonal antibody to induce Pneumocystis carinii (PC) pneumonia (PCP). These mice were then exposed to aerosols of heat-treated Escherichia coli three times a week. Aerosol treatment for 10 d caused a slight reduction in numbers of PC nuclei in the lungs of mice, and treatment for 22 d resulted in nearly complete resolution of PCP. Large numbers of macrophages, polymorphonuclear leukocytes, and lymphocytes accumulated in lungs of aerosol-treated mice. Depletion of either CD8+ lymphocytes or asialo GM1+ cells that remained in the mice after CD4+ cell depletion had no effect on the ability of the mice to resolve PCP after E. coli aerosol treatments. However, depletion of Thy-1+ lymphocytes in these mice abrogated their ability to resolve PCP and reduced the numbers of macrophages that accumulated in the lungs. In addition, it was found that resolution of PCP induced by heat-treated E. coli aerosol treatments was also abrogated when mice were treated with polyclonal antibodies against tumor necrosis factor alpha (TNF-alpha). Thus, resolution of PCP in CD4+ lymphocyte-depleted mice by heat-treated E. coli aerosols was not dependent on either CD8+ or asialo GM1+ cells but was dependent on Thy-1+CD4-CD8- lymphocytes and on the participation of TNF. These results indicate that heat-treated E. coli aerosols can act as an immune response modifier by inducing resolution of PCP in mice by a mechanism not dependent on the presence of CD4+ lymphocytes.

Aerosols↗
PubMed2002

Aerosolization of protein solutions using thermal inkjet technology.

Vapotronics Inc. is developing the thermal inkjet (TIJ) technology used extensively in the printer industry to create a digital aerosol inhaler for the inhalation of therapeutics for local and systemic delivery. The operation of thermal inkjet printers requires generation of high temperatures and vaporization of the liquid formulation to effect droplet ejection. A study was conducted to develop formulations that would permit the generation of aerosols of therapeutic proteins without damage to the inkjet system or degradation of the proteins. Two proteins, human growth hormone and insulin, were formulated and aerosolized. The aerosol was collected and subjected to assays to compare the physicochemical and biological activities of these proteins before and after aerosolization. In each case, there was no significant changes to the proteins as a result of the aerosolization, providing evidence that TIJ can be used for aerosolizing solutions of protein therapeutics.

Administration, Inhalation↗
PubMed1996

Liposomal aerosols in the management of pulmonary infections.

The combination of liposomes and aerosols has been utilized to directly target the lungs with chemotherapeutic agents that might not have been used because of low solubility or toxicity. There are a variety of antibacterials, antifungals, and antivirals that have good in vitro activity, but are not effective because of their systemic toxicity and/or poor penetration into the lungs. Incorporation of many lipophilic drugs into liposomes decreases their toxicity without affecting effectiveness, thus increasing the therapeutic index. We have focused on aerosol delivery of amphotericin B (ampB) for the treatment of pulmonary and systemic fungal diseases. We have tested a variety of ampB-lipid formulations for the optimal treatment regimen for Cryptococcus and Candida infections in mouse models. The AeroTech II nebulizer (MMADs of 1.8-2.2 microns) produced aerosols with the highest concentrations in the breathable range. Pharmacokinetic studies revealed that pulmonary drug was present for hours to weeks. AmBisome retained its anticryptococcal activity even when animals were challenged 14 days after aerosol treatment. Aerosols may also be effective in systemic diseases. In our Candida-mouse model, systemic candidiasis and mortality were reduced by aerosolized ampB-liposome treatment. The ability to utilize lipophilic drugs, to deliver high concentrations of drug directly to the site of infection, and to reduce toxicity makes aerosol liposomes an attractive, alternative route of administration.

Aerosols↗
PubMed1998

Characterization of the carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in cooking aerosols under domestic conditions.

Lung cancer in women is the leading cause of cancer death in Taiwan. Most Chinese women are non-smokers and 60% of female lung cancer patients have adenocarcinomas. Epidemiological data indicate that the incidence of lung cancer among Chinese women may be correlated with cooking fumes. However, the carcinogenic compound(s) in cooking fume aerosols is not defined. In the present study, the cooking aerosols from Chinese stir-frying of fish were prepared under domestic conditions. To determine the mutagenic compounds in the cooking aerosol, mutagens were purified by two steps of high-performance liquid chromatography (HPLC), and their mutagenicity was monitored with Salmonella typhimurium TA98. The mutagen was eluted as a single peak. The chemical structure of the mutagenic fraction of cooking aerosol from frying of fish was characterized by UV spectra and electrospray mass spectrometry. The bacterial indirect-acting mutagenic compound in the cooking aerosol extract was determined to be 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). An amount of 0.25 ng MeIQx/g of meat per min was estimated based on the mutagenic response. These data indicated that significant amounts of MeIQx (268.1 ng/Chinese dish of frying fish) were present in cooking aerosol in a short time. Chinese women spend approximately 1 h preparing meals everyday, thus, they may be exposed to significant amounts of MeIQx from cooking aerosols in the kitchen.

Aerosols↗
PubMed1999

Factors contributing to the acute and subchronic adverse respiratory effects of machining fluid aerosols in guinea pigs.

Several physical, chemical, and microbial factors are potential contributors to the adverse pulmonary effects associated with occupational exposure to machining fluid aerosols. The present study examined the relative toxicity of 3 major classes of machining fluids (soluble, semi-synthetic, and synthetic) as well as that of unused (fresh) versus used (grab samples taken from manufacturing sites) machining fluids. Pulmonary function and changes in cellular and biochemical indices in bronchoalveolar lavage fluid were examined during and 24 h after exposure, respectively. Statistically significant differences in toxicity were observed in guinea pigs exposed for 3 h to respirable aerosols of unused machining fluids (semi-synthetic > soluble >> synthetic). In addition, greater toxicity was observed in animals exposed to used, machining fluid aerosols compared to unused fluids. Moreover, within the used machining fluid types, significantly greater adverse effects were observed in animals exposed to poorly maintained fluids (i.e., heavy microbial contamination) versus well-maintained fluids. Changes in biochemical and cellular parameters in bronchoalveolar lavage fluid occurred after a single exposure to 5 mg/m3 of the poorly maintained used machining fluid aerosols. Changes in inflammation but not LDH and protein were observed in animals repeatedly exposed to semi-synthetic machining fluid aerosols. A statistically significant increase in lavage fluid neutrophils was observed in guinea pigs exposed to 5 mg/m3 used, semi-synthetic machining fluid aerosols for 4 weeks. In separate experiments, physicochemical properties of unused machining fluids were found to contribute to the production of adverse effects. Adjustment of the alkaline and hypotonic nature of the unused semi-synthetic machining fluid to isotonicity and pH 7 significantly reduced adverse effects. Together, these findings strongly suggest that multiple factors contribute to the adverse respiratory effects associated with occupational exposure to machining fluid aerosols.

Administration, Inhalation↗
PubMed1996

Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats.

OBJECTIVE: To compare the effects of surfactant replacement by aerosol inhalation and bolus instillation on acute lung injury caused by the intratracheal injection of endotoxin in rats. DESIGN: Prospective, randomized study. SETTING: University Laboratory. SUBJECTS: Male Wistar rats weighing 368 +/- 31 (SD) g. INTERVENTIONS: Escherichia coli endotoxin (57 +/- 20 mg/kg) was injected into the tracheas of 36 anesthetized and mechanically ventilated rats (FIO of 1.0). When the PaO2 had decreased to <200 torr (<26.7 kPa), the rats were randomly assigned to one of three groups: a control group (n=12)given no material; a bolus group (n=12) given a modified natural surfactant suspension (100 mg/kg in 2.0 mL/kg saline) by bolus instillation into the trachea; and an aerosol group (n=12) given surfactant aerosolized with an ultra-sonic nebulizer for 60 mins. MEASUREMENTS AND MAIN RESULTS: Bolus instillation transiently decreased the mean blood pressure by approximately 30%. However, aerosol inhalation did not. The PaO2 values of the control group remained <90 torr (<12.0 kPa) until the end of the experiment (180 mins). In contrast, the PaO2 of the bolus group increased to 387 +/- 134 torr (51.6 +/- 17.9 kPa; p<.05 vs. other groups) 15 mins after surfactant replacement, and remained at approximately 400 torr (approximately 53.3 kPa) throughout the experiment. The PaO2 values of the aerosol group increased slowly, peaked at 240 +/- 109 torr (32.0 +/- 14.5 kPa; p<.05 vs. the control group) 60 mins after the start of surfactant replacement, and remained at approximately 200 torr (approximately 26.7 kPa). CONCLUSIONS: Bolus instillation was superior to aerosol inhalation concerning maximum efficacy, the rapid onset of therapeutic effects, and the necessary dose of surfactant. However, aerosol that does not cause hypotension may be of use in the treatment of adult respiratory distress syndrome in patients with circulatory instability.

Aerosols↗
PubMed1996

An experimental study of aerosol penetration through horizontal tubes and Strom-type loops.

Because some designers of aerosol transport systems use the assumption that aerosol penetration through a system is maximized if the flow Reynolds number is 2,800, we have conducted tests to determine if such an assumption is appropriate. Although we do not believe that optimal performance of an aerosol sample transport system can be presented solely in terms of the Reynolds number, we have presented our results in terms of that parameter to compare our work with the results of an earlier study. Two types of experiments were performed. First, the penetration of liquid aerosol particles through horizontal tubes was experimentally investigated for a range of design and operational conditions. For a particle size of 10 microm aerodynamic diameter, the maximum penetration through a 6.7 mm diameter tube was associated with a Reynolds number of approximately 2,000; the maximum penetration through a tube of 15.9 mm occurred at a Reynolds number of about 3,000; and the maximum penetration through a 26.7 mm diameter tube occurred at about 4,000. It was also experimentally demonstrated that for a fixed flow rate through a horizontal tube, there is an optimum tube diameter for which the aerosol penetration is a maximum. An early study dealing with aerosol particle penetration through a 16.8 mm inside diameter loop of tubing (two vertical tubes, two horizontal tubes and three 90 degrees bends) suggested there was a fixed Reynolds number for optimal aerosol penetration independent of particle size. Those experiments were repeated here and the agreement with those tests is excellent; namely, the maximum penetration through a loop of 15.9 mm diameter tube occurs at a Reynolds number of approximately 2,800, independent of particle size. However, when the tube diameter of the transport system layout was changed to 26.7 mm, the Reynolds number associated with maximum penetration varied for different particle sizes, occurring at Reynolds numbers of approximately 5,600 for 8 microm AD particles, 3,800 for 10 microm particles and 3,000 for 15 microm particles.

Aerosols↗
PubMed2005

Feasibility of pulmonary ventilation visualization with aerosolized magnetic resonance contrast media.

OBJECTIVE: The objective of this study was to evaluate a new approach to noninvasive magnetic resonance assessment of human pulmonary ventilation with aerosolized Gd-DTPA. MATERIALS AND METHODS: Fifteen experimental procedures were carried out in 15 healthy volunteers on a 1.5-T imager. For a timespan of 10 minutes, the subjects spontaneously inhaled a commercially available Gd-DTPA magnetic resonance contrast agent in aerosolized form through an inflatable facemask. Gd-DTPA was aerosolized by means of a small-particle generator with integrated heater to increase aerosol production. Respiratory gated dynamic T1-weighted turbo spin echo images were obtained before and after contrast agent aerosol administration. After nebulization, homogeneity of aerosol distribution was graded by 2 experienced readers and pulmonary signal intensity (SI) changes were measured in corresponding regions of both lungs. RESULTS: Pulmonary ventilation visualization, and hence contrast agent delivery, was rated homogeneously distributed by both readers in 14 of 15 cases (93.3%) and slightly inhomogeneous in 1 case (6.7%). Pulmonary SI increased by an average of +37% +/- 8.5 (range, 10-48%). Allergic responses were not noted. CONCLUSIONS: Human ventilation imaging with aerosolized gadolinium-chelates is viable. The presented modality might evolve as an alternative to current nuclear medicine and magnetic resonance image ventilation imaging procedures, avoiding radiation exposure while offering functional ventilation assessment with an acceptable temporal and spatial resolution. Nevertheless, further evaluation is required to define the potential of gadolinium-based ventilation magnetic resonance imaging in illustrating lung disease.

Adult↗
PubMed2001

Aerosolization of epidermal cells with fibrin glue for the epithelialization of porcine wounds with unfavorable topography.

Aerosolized epidermal cell suspension was previously found to be effective for the epithelialization of full-thickness wounds. This suspension is less expensive than and requires a shorter preparation time than the currently used cultured epithelial autografts. Still, convex and irregular wounds present unfavorable conditions for homogenous dispersion of the aerosolized cell suspension. The authors hypothesized that the addition of fibrin glue to the aerosol of cells would reduce cell movement and ensure homogenous dispersion of the cells, thereby promoting wound epithelialization. The objectives of the study were to evaluate the healing of wounds with unfavorable topography after autotransplantation of an epidermal cell aerosol with and without fibrin glue. Six Yorkshire piglets were studied. An epidermal suspension was made from full-thickness groin skin. Dispase was used to separate the epidermis from the dermis, and trypsin was used to separate the epidermal cells from one another. Twenty-four hours later, full-thickness wounds with unfavorable topography were created adjacent to the vertebral column of six pigs. Twelve wounds were treated with an aerosol of epidermal cell suspension mixed with fibrin glue (study group), and 12 wounds were treated with the same suspension without the fibrin glue (control group). The percentages of total wound contraction and the epithelialized and nonepithelialized areas were evaluated 1, 2, 3, and 4 weeks after aerosolization. The histologic characteristics of the newly formed skin were examined by light microscopy using slides stained with hematoxylin and eosin. Study wounds were characterized by central epithelialization, whereas control wounds were characterized by peripheral epithelialization. Study wounds contracted at a slower rate than control wounds, but wound size was the same in both groups after 4 weeks. The addition of fibrin glue facilitated epithelialization: Study wounds showed 75.5 +/- 22.4 percent (mean +/- SD) and 94.2 +/- 8.8 percent epithelialization after 3 and 4 weeks, respectively, compared with 46.3 +/- 9.5 percent and 47.9 +/- 13.1 percent epithelialization of the control wounds at the same times. These differences between the study and control groups were statistically significant (p < 0.001, paired t test). The addition of fibrin glue to an aerosol of epidermal cells significantly enhances the epithelialization of wounds with unfavorable topography in pigs.

Administration, Topical↗
PubMed2005

Blockade of CTLA-4 promotes airway inflammation in naive mice exposed to aerosolized allergen but fails to prevent inhalation tolerance.

In subjects not developing allergy, inhalation of nonpathogenic protein antigens causes no harm and is associated with tolerance induction. Repeated exposure to aerosolized ovalbumin (OVA) likewise does not evoke airway inflammation and induces inhalation tolerance in experimental animals. The present study explored the role of the inhibitory T-cell receptor CTLA-4, in preventing inflammation and in establishing inhalation tolerance in response to a protein antigen. Naive BALB/c mice were injected intraperitoneally with anti-CTLA-4 monoclonal antibody or control immunoglobulin G (IgG) and exposed daily to aerosolized saline or OVA over 10 or 20 consecutive days. OVA-specific IgE levels and the inflammatory response in airway tissues were assessed 2 days after last exposure. The OVA-specific IgE response was also evaluated in mice subjected to a subsequent immunogenic OVA challenge 18 days after last aerosol exposure. Additional mice were made tolerant by 10 days of OVA aerosol exposure and were then subjected to an immunogenic OVA challenge combined with CTLA-4 blockade or control IgG treatment. Repeated inhalation of aerosolized OVA alone did not cause a pulmonary inflammatory response. In contrast, 10 days of OVA exposure combined with blockade of CTLA-4 led to development of eosinophilic lung infiltrates, BAL fluid eosinophilia, goblet cell hyperplasia and increased OVA-specific IgE. By 20 days of OVA exposure and blockade of CTLA-4, the inflammatory response remained. Mice exposed to aerosolized OVA for 10 days exhibited greatly reduced OVA-specific IgE responses to subsequent immunogenic OVA challenge. Blockade of CTLA-4 during the period of OVA aerosol exposure did not prevent this suppression of the OVA-specific IgE response. Neither did blockade of CTLA-4 during immunogenic OVA challenge alter the allergen-specific IgE response. Our results indicate that in vivo blockade of CTLA-4 modulates the initial immune response to a protein antigen allowing the development of allergen-induced airway inflammation in naive mice. However, this initial exaggerated immune response is followed by the induction of inhalation tolerance, demonstrating that CTLA-4 signalling is not decisive in this process. Our findings also show that once inhalation tolerance is established it may not be disrupted by blockade of CTLA-4.

Aerosols↗
PubMed1999

Future options for aerosol delivery to children.

There is an increasing awareness of the importance of reliable aerosol delivery, with emphasis on the dose delivered to the lungs, optimal clinical control, cost-effectiveness, and safety in children. Dose prescription should relate to the expected lung dose rather than the factory-dispensed dose, as at present. The device determines the lung dose. Clearly, therefore, the device should be considered an integral part of the prescription. Drug approval processes should clearly specify the device, and discourage the use of other devices. This would rationalize the choice of devices. Important new insights into factors essential for drug delivery to the airways have been acquired in recent years. Nasal inhalation increases systemic bioavailability, reduces lung dose, and adds to its variability; hence, face masks to prevent nasal breathing have been developed. Similarly, dead space in the inspiratory line causes a proportional reduction in lung dose; hence, attention should be paid to reducing such dead space. Plastics in spacers cause a rapid loss of drug due to electrostatic attraction of the aerosol. The residence time of the aerosol, i.e., the time available for inhalation, is increased in nonelectrostatic spacers, allowing less compliant children enough time to obtain a full dose. Eliminating the electrostatic charge can change the lung dose by several times; hence, nonelectrostatic materials should be used in future spacer devices. Compliance is the biggest problem in drug delivery to children. The inhaler design process should be reversed, adapting technology to the child. Interactive microchip technology should provide intelligent devices that react to correct handling and breathing maneuvers. An intelligent nebulizer has been developed that adapts nebulization to the child's breathing pattern, nebulizing only during inhalation and avoiding loss of aerosol during exhalation. An automatic device (AirPac) has been developed that transforms a dry-powder inhaler, Turbuhaler, into a spacer. In addition to the general advantages of spacer treatment, this device offers the advantage of a drug aerosol delivered without use of propellants or additives. The mechanical actuation ensures highly repeatable drug delivery. Finally, a nonelectrostatic, tower-shaped spacer provides a stable aerosol, which remains airborne for a prolonged period. The spacer is equipped with a face mask that prevents nasal breathing. Such features should improve our ability to treat young children with inhaled drug aerosols.

Aerosols↗
PubMed1979

Amantadine aerosols in normal volunteers: pharmacology and safety testing.

The acceptability and pharmacology of intermittent aerosol administration of amantadine was assessed in healthy volunteers. Amantadine solutions of 2.5, 1.5, or 1.0 g/100 ml were used for 12 30-min, twice-daily aerosol treatments in 15 subjects. Overall, the aerosol treatments were well tolerated. During and up to 1 h after aerosol exposures, nasal irritation, rhinorrhea, dysgeusia, or a combination of symptoms was experienced by some of the subjects receiving either of the two higher amantadine concentrations. Aerosol treatments were associated with small but statistically significant decreases in maximal expiratory flow rates. One hour after aerosol treatments with the 1.0-g/100 ml solution, amantadine levels in nasal wash samples (mean, 30.3 micrograms/ml; range, 1.7 to 108 micrograms/ml) greatly exceeded blood and nasal wash levels reported after oral administration. Amantadine can be administered safely by small-particle aerosol to humans in doses that could be expected to exert an antiviral effect in influenza A virus infections.

Adolescent↗
PubMed1990

Safety and pharmacokinetics of rimantadine small-particle aerosol.

The safety and pharmacokinetics of rimantadine administered by small-particle aerosol were assessed in healthy adults and adults with acute influenza virus infection. Aerosolized rimantadine delivered at a concentration of 40 micrograms/liter of air was associated with nasal burning and irritation in normal volunteers. A concentration of 20 micrograms/liter of air was well tolerated for up to 12 h by normal volunteers and was not associated with any changes in pulmonary function, as measured by routine spirometry, plethysmography, or diffusion capacity of carbon monoxide. Mean peak levels of drug in serum were approximately 10-fold lower after 12 h of aerosol administration than they were after oral administration of 200 mg (29.7 versus 255 ng/ml, respectively), while mean nasal wash levels were approximately 100-fold higher (6,650 versus 66.6 ng/ml, respectively). Elimination half-lives were similar after both aerosol and oral administration (24.1 and 25.2 h, respectively), and rimantadine urinary excretion was less than 1% per 24 h in both groups. Twenty micrograms of aerosolized rimantadine per liter of air given 12 h daily for 3 days to nine adults with acute influenza virus infection was well tolerated. Levels in plasma after 12 h of aerosol inhalation were similar to those in normal volunteers, but were higher at the end of the third treatment than they were at the end of the first treatment (88.3 versus 47.9 ng/ml, respectively). Thus, rimantadine delivered via small-particle aerosol at a dose of 20 micrograms/liter of air was well tolerated in normal volunteers and in those with acute influenza and was associated with high local concentrations.

Adult↗
PubMed1991

Aerosol and intraperitoneal administration of ribavirin and ribavirin triacetate: pharmacokinetics and protection of mice against intracerebral infection with influenza A/WSN virus.

Ribavirin is active in vitro but not in vivo against a number of viruses capable of causing encephalitis. Ribavirin triacetate (RTA), a lipophilic derivative, has been reported to be more effective than ribavirin in protecting animals from encephalitis. By using an influenza A/WSN virus encephalitis model, we demonstrated that RTA administered by small-particle aerosol was able to decrease the death rate and increase the time of survival. To determine if this beneficial effect was due to increased delivery of drug, the pharmacokinetic properties of ribavirin and RTA when administered as an aerosol or by intraperitoneal injection were examined. Aerosol administration of ribavirin or RTA gave significantly higher concentrations of ribavirin in the lungs and serum of mice than did intraperitoneal injection. There was no difference, however, in ribavirin levels when either ribavirin or RTA was administered by small-particle aerosol. In brain tissue, ribavirin concentrations increased with time and did not appear to decrease as rapidly as in lungs and serum. Mean peak ribavirin concentrations in the brain were higher following aerosol administration of ribavirin than RTA, and both were higher than that following intraperitoneal injection of either drug. Administration of ribavirin or RTA by intraperitoneal injection failed to protect mice from a lethal intracerebral inoculation of influenza A/WSN virus, while aerosolized RTA did protect mice. The pharmacokinetics of ribavirin in brain tissue following aerosol administration of either drug did not explain the advantage of RTA over ribavirin in protecting mice from intracerebral infection with influenza A/WSN virus.

Aerosols↗
PubMed2004

Paucibacillary tuberculosis in mice after prior aerosol immunization with Mycobacterium bovis BCG.

To develop a murine model of paucibacillary tuberculosis for experimental chemotherapy of latent tuberculosis infection, mice were immunized with viable Mycobacterium bovis BCG by the aerosol or intravenous route and then challenged six weeks later with virulent Mycobacterium tuberculosis. The day after immunization, the counts were 3.71 +/- 0.10 log(10) CFU in the lungs of aerosol-immunized mice and 3.65 +/- 0.11 and 4.93 +/- 0.07 log(10) CFU in the lungs and spleens of intravenously immunized mice, respectively. Six weeks later, the lungs of all BCG-immunized mice had many gross lung lesions and splenomegaly; the counts were 5.97 +/- 0.14 and 3.54 +/- 0.07 log(10) CFU in the lungs and spleens of aerosol-immunized mice, respectively, and 4.36 +/- 0.28 and 5.12 +/- 0.23 log(10) CFU in the lungs and spleens of intravenously immunized mice, respectively. Mice were then aerosol challenged with M. tuberculosis by implanting 2.37 +/- 0.13 log(10) CFU in the lungs. Six weeks after challenge, M. tuberculosis had multiplied so that the counts were 6.41 +/- 0.27 and 4.44 +/- 0.14 log(10) CFU in the lungs and spleens of control mice, respectively. Multiplication of M. tuberculosis was greatly limited in BCG-immunized mice. Six weeks after challenge, the counts were 4.76 +/- 0.24 and 3.73 +/- 0.34 log(10) CFU in the lungs of intravenously immunized and aerosol-immunized mice, respectively. In contrast to intravenously immunized mice, there was no detectable dissemination to the spleen in aerosol-immunized mice. Therefore, immunization of mice with BCG by the aerosol route prior to challenge with a low dose of M. tuberculosis resulted in improved containment of infection and a stable paucibacillary infection. This model may prove to be useful for evaluation of new treatments for latent tuberculosis infection in humans.

Aerosols↗
PubMed1988

Deposition of carbenicillin aerosols in cystic fibrosis: effects of nebuliser system and breathing pattern.

Antibiotic aerosol treatment is successful in treating Pseudomonas infection in some patients with cystic fibrosis, but the amount of drug reaching the lungs is unknown. The deposition patterns of carbenicillin aerosols delivered from two commercially available nebuliser systems (the Turret nebuliser plus Maxi compressor and the Inspiron nebuliser plus Traveller compressor) have been compared in six patients with cystic fibrosis during tidal breathing. The aerosol mass median diameters were 3.2 and 7.3 microns. In addition, the aerosol from the Turret-Maxi nebuliser system was inhaled by a combination of tidal and deep breathing. After two minutes' breathing via a mouthpiece the mean (SEM) deposition in the lungs was 15.60 (1.5) mg carbenicillin with the Turret nebuliser plus Maxi compressor, but only 6.54 (1.09) mg with the Inspiron nebuliser plus Traveller compressor; the distribution pattern within the lung was significantly more peripheral with the former nebuliser system. These differences may be ascribed partly to the smaller droplet size from the Turret system and partly to the higher nebulisation rate from the more powerful Maxi compressor. Tidal plus deep breathing produced a further small but non-significant increase in lung aerosol deposition. A seventh patient, who failed to complete the trial, had little aerosol deposited in his lungs because he inhaled through his nose. These results emphasise the importance of correct selection of nebuliser equipment for antibiotic aerosol treatment.

Adult↗
PubMed2006

The measurement of aerosolized endotoxin from land application of Class B biosolids in Southeast Arizona.

The purpose of this study was to determine aerosolized endotoxin concentrations downwind of a biosolids land application site. Aerosol samples were collected from biosolids land application sites, tractor operation, and an aeration basin located within an open-air wastewater treatment plant. Aerosolized endotoxin above background concentrations was detected from all sites, at levels ranging from below detection up to 1800 EU m-3 of air. Biosolids loading operations resulted in the greatest concentrations of endotoxin (mean 344 EU m-3). As downwind (perpendicular to wind vector) distance increased from sources (2-200 m), levels of endotoxin decreased to near background (without biosolids application) concentrations. Overall, the detected levels of aerosolized endotoxin were within past proposed aerosolized endotoxin limits (250-2000 EU m-3) by other occupational exposure studies. Occasionally, peak concentrations were found to be above these limits. Sites in which soil was being aerosolized resulted in greater concentrations of endotoxin with or without biosolids, which suggested that the majority of endotoxin may in fact be of soil origin. This study evaluated the presence of aerosolized endotoxin from the land application of biosolids and showed that these levels were within ranges for concern suggested by other studies and that this area of research needs further investigation.

Aerosols↗
PubMed1977

Canine pulmonary response to aerosol histamine: direct versus vagal effects.

Histamine, a potent bronchoconstrictor, has been shown to produce bronchoconstriction both directly and by a vagal reflex. To define the relative roles of direct and reflex effects, we studied the pulmonary response of dogs exposed to increasing doses of aerosol histamine before and after vagal blockade or vagotomy. In addition, the relative contributions of aerodynamically large and small airways to the overall response were determined by the measurement of pulmonary resistance on sulfur hexafluoride-oxygen and helium-oxygen mixtures. Histamine aerosol caused a similar dose-dependent increase in resistance of aerodynamically large and small airways and fall in dynamic compliance. The dose-response relationships were not consistently altered by either vagal blockade or vagotomy. The following variables were found not to alter the experimental results: anesthesia, type of aerosol generator, control of breathing during aerosol exposure, spontaneous breathing vs. controlled ventilation after aerosol exposure, cold block of vagi vs. vagotomy. We conclude that 1) histamine aerosol in dogs causes a local dose-dependent constriction of bronchial smooth muscle, and 2) the vagus nerve played a relatively minor role in the pulmonary response to aerosol histamine in these experiments.

Aerosols↗