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PubMed2005

A national study on the residential impact of biological aerosols from the land application of biosolids.

AIMS: The purpose of this study was to evaluate the community risk of infection from bioaerosols to residents living near biosolids land application sites. METHODS AND RESULTS: Approximately 350 aerosol samples from 10 sites located throughout the USA were collected via the use of six SKC Biosamplers. Downwind aerosol samples from biosolids loading, unloading, land application and background operations were collected from all sites. All samples were analysed for the presence of HPC bacteria, total coliform bacteria, Escherichia coli, Clostridium perfringens, coliphage, enteroviruses, hepatitis A virus and norovirus. Total coliforms, E. coli, C. perfringens and coliphage were not detected with great frequency from any sites, however, biosolids loading operations resulted in the largest concentrations of these aerosolized microbial indicators. Microbial risk analyses were conducted on loading and land application operations and their subsequent residential exposures determined. CONCLUSIONS: The greatest annual risks of infection occurred during loading operations, and resulted in a 4 x 10(-4) chance of infection from inhalation of coxsackievirus A21. Land application of biosolids resulted in risks that were <2 x 10(-4) from inhalation of coxsackievirus A21. Overall bioaerosol exposure from biosolids operations poses little community risk based on this study. SIGNIFICANCE AND IMPACT OF THE STUDY: This study evaluated the overall incidence of aerosolized micro-organisms from the land application of biosolids and subsequently determined that microbial risks of infection were low for residents close to biosolids application sites.

Aerosols↗
PubMed1986

A new inhalation technique for improved effect of aerosolized drugs in asthma. The shrug of the shoulder method.

A new, simple technique for inhalation of aerosolized drugs is described: During the breathholding period after inhalation from a pressurized aerosol the patient lifts his right and lowers his left shoulder and vice versa to "disperse" the drug as well as possible in the lungs. Twenty outpatients suffering from reversible bronchial obstruction inhaled two puffs from a pressurized terbutaline aerosol in the morning on two consecutive days using the new inhalation technique on one day and their ordinary technique on the other in this randomised, cross-over trial. Compared with the conventional method the new inhalation technique significantly improved bronchodilation as measured by forced expiratory volume in 1st s and forced vital capacity during a period of 6 h. The new method of inhalation may improve treatment with aerosolized drugs.

Adult↗
PubMed2006

Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk for invasive fungal infections (IFIs) over prolonged periods of time. Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung transplant recipients as a convenient means of delivering protective drug to the upper airways avoiding systemic toxicities. The safety and tolerability of aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively investigated in an open-labeled, non-comparative study. Subjects received aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks; fluconazole was administered daily as standard of care through post-transplant day 100. Pulmonary mechanics were measured before and after each dose of inhaled ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough, nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC administrations; 5.2% of inhaled ABLC administrations were associated with >or=20% decrease in pulmonary function measurements (forced expiratory volume in 1 second or forced vital capacity) and none required treatment with bronchodilators or withdrawal from study. Four mild AEs were considered possibly or probably related to study treatment; no deaths or withdrawals from treatment were attributed to study drug. Of 3 proven IFIs occurring during the study period, only 1, a catheter-related case of disseminated fusariosis, occurred while the subject was receiving study medication. Aerosolized ABLC was well tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing IFI while receiving treatment, the combination of fluconazole and inhaled ABLC warrants further study as antifungal prophylaxis following allogeneic HSCT.

Adolescent↗
PubMed1994

Aerosolized surfactant reverses respiratory failure in lung-lavaged rats.

The effects of surfactant replacement by aerosol inhalation and by bolus instillation were compared in rats with respiratory failure induced by repeated lung lavage. The rats were anesthetized with pentobarbital sodium and mechanically ventilated with 100% oxygen. The PaO2 of control rats not given surfactant (n = 9) remained below 13 kPa. A bolus instillation of a modified natural surfactant (75 mg.kg-1 b.w. in 1.5 ml.kg-1 b.w. saline) into the airways rapidly reversed the respiratory failure; the mean PaO2 value (n = 9) 15-180 min after instillation remained over 50 kPa (P < 0.05 vs. controls). Inhalation of the aerosolized surfactant for 60 min through an ultrasonic nebulizer delivering < or = 75 mg.kg-1 b.w. of the surfactant into the lungs gradually reversed the respiratory failure. The mean PaO2 value (n = 9) 15 min after initiation of inhalation was 19.6 kPa (NS vs. controls), but after 60 min it rose to above 43 kPa (P < 0.05 vs. controls; NS vs. bolus instillation). Treatment with surfactant either by continuous aerosol or by bolus led to significant increases of over 24% in the dynamic lung-thorax compliance. We conclude that aerosolized surfactant reverses respiratory failure induced by lung lavage, although the response is slower than after bolus instillation.

Aerosols↗
PubMed1977

The effects of sodium cromoglycate on histamine aerosol-induced reflex bronchoconstriction in the anaesthetized dog.

1 The effects have been studied of sodium cromoglycate (SCG), given by aerosol or intravenously, on reflex bronchoconstriction induced by histamine aerosol in the anaesthetized dog. 2 Four breaths of an aerosol generated from a 2% solution of SCG significantly inhibited the vagally mediated increase in total lung resistance (RL) produced by histamine. 3 SCG given intravenously as bolus injections (5-500 microgram/kg) produced a dose-dependent reversal of a sustained reflex bronchoconstriction induced by histamine aerosol. Propranolol (500 microgram/kg) did not prevent this reversal. 4 SCG did not inhibit the increase in RL produced by supramaximal electrical stimulation of a vagus nerve. 5 The possibility is discussed that SCG may reduce the activity of lung irritant receptors in the anaesthetized dog.

Aerosols↗
PubMed1990

Cigarette smoke, nicotine and capsaicin aerosol-induced vasodilatation in pig respiratory mucosa.

1. Anesthetized pigs were used to study vascular responses in the sphenopalatine artery (SPA), superior laryngeal artery (SLA) and bronchial artery (BA) upon exposure to cigarette smoke or aerosol of nicotine and capsaicin. Direct blood flow recordings were made with ultrasonic probes around the vessels. 2. Smoke from one cigarette was administered as inhalation for 2 min with or without a Cambridge filter which removes the particulate matter including nicotine from the smoke. Aerosols of nicotine (2.5 mg) or capsaicin (10 mg) were administered to the nose or the lower airways for 3 min. 3. Cigarette smoke exposure caused a reproducible reduction of the vascular resistance (VR) suggesting vasodilatation in the SPA, SLA, and especially the BA. The vasodilatation was not modified by the Cambridge filter, suggesting that it was caused by vapour phase components rather than nicotine. 4. The smoke effect was not changed after pretreatment with the cyclo-oxygenase inhibitor, diclofenac, or with atropine, guanethidine, H1- or H2-histamine receptor antagonists, nedocromil, or by vagotomy. The smoke-evoked decrease in VR was not modified by the nicotinic receptor antagonist chlorisondamine in the SLA or BA. 5. In pigs pretreated with increasing doses of capsaicin two days earlier, the decrease in VR upon smoke exposure in both the BA and SLA was unaffected while the change in VR was attenuated in the SPA. 6. Nicotine aerosol had no effect on VR in the peripheral airways supplied by the BA while a decrease in VR was observed in the SLA and SPA. The nicotine response was reduced after capsaicin pretreatment in the nasal and upper tracheal circulation. 7. Capsaicin aerosol reduced VR in the vascular beds supplied by the SPA, SLA and BA and this response was markedly reduced after capsaicin pretreatment. 8. The mechanisms underlying vasodilatation upon cigarette smoke exposure in the bronchial mucosa are at the moment unclear while both non-cholinergic parasympathetic and sensory components may be involved in the nose. Capsaicin induced a vasodilatation at all levels via sensory mechanisms, whereas nicotine-evoked vasodilatation is restricted to the upper airway mucosa and is at least partly dependent on parasympathetic reflexes involving capsaicin-sensitive sensory nerves.

Aerosols↗
PubMed1999

Aerosol route enhances the contamination of intact eggs and muscle of experimentally infected laying hens by Salmonella typhimurium DT104.

Commercial laying hens were infected with Salmonella typhimurium DT104 strain 16 alternatively via the crop (10(7) cfu per bird) or by an aerosol delivered directly to the beaks using a Collison nebuliser and Henderson apparatus (2 x 10(2) or 2 x 10(4) cfu per bird). Infection by both routes caused systemic infection and prolonged contamination of faeces. Contamination rates of eggs and muscle were much higher following the aerosol challenges despite the much lower doses given by this route. The frequency of Salmonella isolation from eggs rose from 1.7% following oral challenge to 14% and 25%, for each of the aerosol challenges respectively, and the frequency of isolation from muscle rose from 0% following the oral challenge to 27% following each of the aerosol challenges.

Aerosols↗
PubMedDate not supplied

Optimized delivery of skin keratinocytes by aerosolization and suspension in fibrin tissue adhesive.

Aerosolized suspensions of keratinocytes provide a potential therapy for wounds, but the effects of aerosolization on cell viability remain unclear. Likewise, little is known of the resulting cell distribution pattern and how this compares to the density required for epithelialization. The potential benefits of cospraying cells in the presence of fibrin adhesive are equally uncertain. Thus, in the present study we have optimized conditions for the aerosolization of cultured keratinocytes using a device (Tissomat) that supports the option for coapplication with fibrin (Tisseel). Cell viability was unaffected when sprayed at 10 psi, but a significant reduction in metabolic activity, as determined by the methylthiazoyldiphenol-tetrazolium assay, was observed at higher pressure. Bursts of 0.2 mL cell suspension (1.5x10(6)/mL) delivered from a height of 10 cm was sufficient to epithelialize an area of 10-15 cm2 within 7 days in vitro. Confluent areas corresponded to those with a density of 5,000-10,000 cells/cm2 at 24 hours. Optimal cell growth in Tisseel was achieved through dilution of fibrinogen (1-3 mg/mL) and thrombin (2-5 IU/mL). This optimized formulation eliminated fluid run-off postspraying and stimulated a twofold increase in cellular response. Therefore, our in vitro data supports the theory that aerosolized suspensions of keratinocytes in fibrin will benefit healing.

Aerosols↗
PubMed1990

Experimental infection of ponies with equine influenza (H3N8) viruses by intranasal inoculation or exposure to aerosols.

Infection of seronegative Welsh mountain ponies was established by intranasal instillation or exposure to nebulised aerosol of egg grown H3N8 viruses. Pyrexia and coughing were noted following intranasal instillation and high titres of virus were recovered from the nasopharynx. Exposure to aerosol resulted in more severe clinical signs characterised by high temperatures, dyspnoea, anorexia and coughing; lower levels of virus were recovered from the nasopharynx. The severity of clinical signs and the kinetics of virus shedding were dose-related with the minimal infectious dose being 10(2)EID50/ml when ponies were exposed to aerosols produced by nebulisation of 20ml allantoic fluid. Full clinical signs only developed when ponies were exposed to a dose of 10(6)EID50/ml. It was concluded that exposure to nebulised aerosols of egg grown H3N8 viruses was a more reliable method of inducing clinical influenza than intranasal inoculation and would be more suitable for challenge studies.

Administration, Intranasal↗
PubMed1981

A semi-empirical model of aerosol deposition in the human respiratory tract for mouth inhalation.

A mathematical model for regional deposition of aerosols following inhalations via mouth has been developed. The model is in the form of algebraic equations which make it particularly efficient for computation of deposition of polydisperse aerosols. The parameters of the model were derived from average experimental data for "head' and tracheobronchial deposition which were supplemented by results of previous theoretical calculations and mass balance considerations. An example is presented to illustrate an application of the model to a problem in formulation of inhalation aerosols. To make the calculations more reliable for particular patho-physiological groups of patients, some modifications of the parameters used in the model are necessary. The model may be suitable, e.g. for testing the changes in regional deposition which would be likely to result from modification of particle size and related formulation properties of inhalation aerosols.

Aerosols↗
PubMed1996

A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers.

A pharmacokinetic study was undertaken to compare the pharmacokinetics of morphine after an intravenous dose with the pharmacokinetics after a sublingual dose administered from an aerosol. Plasma levels of morphine, morphine-3-glucuronide and morphine-6-glucuronide were measured in five normal volunteers after morphine administration by the intravenous route and from a novel sublingual pressurized aerosol formulation. The mean (+/- s.d.) bioavailability of the sublingual aerosol morphine was 19.7 +/- 6.7%. The morphine-3-glucuronide/morphine and the morphine-6-glucuronide/morphine ratios were 5.1 +/- 1.6 and 1.2 +/- 0.4, respectively, for the intravenous route and 28.3 +/- 11.3 and 5.2 +/- 1.4, respectively, for the sublingual route. The combined total areas under the plots of systemic concentration against time (AUC) for the metabolites after the two routes was not significantly different. When compared with published data for oral administration the results demonstrate that the sublingual aerosol morphine might provide an alternative to conventional methods of morphine delivery, and has similar pharmacokinetics to a sublingual morphine tablet. It has no particular pharmacokinetic advantages over oral morphine, except a potential for a faster onset of analgesia. Bioavailability, maximum plasma concentration, Cpmax, and the time at which the maximum plasma concentration is reached, Tmax, are equivalent to those for orally administered morphine.

Administration, Sublingual↗
PubMed1992

[Evaluation of aerosol therapy of streptomycin for tracheobronchial and pulmonary tuberculosis].

The clinical features of tracheobronchial tuberculosis are distinct from those of pulmonary tuberculosis in some aspects. Streptomycin (SM) is claimed by some investigators that it has a tendency to promote the development of bronchial stenosis due to scarred healing of the involved endobronchial mucosa, and, for that reason, they recommend not to use it in treatment of bronchial tuberculosis. In some patients with pulmonary tuberculosis, who have renal or hearing disturbance, SM avoided. Yet unless SM is used improvement of tuberculosis could be delayed. It is the purpose of the present investigation to point out that aerosol therapy of SM is useful for patients with respiratory tuberculosis. Furthermore, we wish to demonstrate that we can safely treat the patients with respiratory tuberculosis who suffer from renal function or hearing disorder by use of aerosol therapy of SM. Prior to clinical application of the inhalation therapy, we confirmed that the therapy was not harmful. Serum concentration of SM, when inhaled, was measured in 9 volunteers. Before and after administration of SM aerosol, spirograms were examined in 4 volunteers, nevertheless, no special abnormality was recognized. It seemed that serum concentration of SM after the administration was two low to evoke adverse reactions (less than 3.0 gamma). In 6 patients with pulmonary tuberculosis, blood gases were measured and no obvious change was observed. As a result, it was demonstrated that the endobronchial tuberculous lesions improved faster when treated by inhalation of aerosolized SM as compared with the conventional injection therapy, without evoking any apparent adverse reactions. In some of the patients with pulmonary tuberculosis, it seemed that the therapy was useful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Duration of effect of interferon aerosol prophylaxis of vesicular stomatitis virus infection in mice.

Mice were exposed for 8 h to continuous small-particle aerosols containing natural mouse alpha interferon (estimated dosage 100 U per mouse) or one of two concentrations of hybrid recombinant alpha interferon A/D bgl (estimated dosages of 100 and 10,000 U per mouse, respectively). On days 1, 3, 5, 7, and 9 after exposure to these interferons, three mice from each group were inoculated intranasally with 100 PFU of vesicular stomatitis virus. Control mice were exposed to aerosols of saline or inoculated intraperitoneally with either natural mouse alpha interferon (350 U) or one of two doses of hybrid recombinant alpha interferon A/D bgl (350 or 35,000 U) and challenged similarly. Of mice injected intraperitoneally, only those given 35,000 U of hybrid recombinant alpha interferon A/D bgl 24 h before virus challenge were protected from pulmonary infection, compared with the saline-treated control mice. Of mice given 100 U of either interferon by small-particle aerosol, only those exposed 24 h before inoculation of vesicular stomatitis virus had reduced pulmonary titers of the virus. However, of mice given ca. 10,000 U of hybrid recombinant alpha interferon A/D bgl by small-particle aerosol, all groups except those exposed 9 days before virus inoculation had significantly reduced lung virus titers.

Aerosols↗
PubMed1987

Pentamidine aerosol in prophylaxis and treatment of murine Pneumocystis carinii pneumonia.

The efficacy and tolerance of pentamidine aerosol were evaluated in the prophylaxis and therapy of murine Pneumocystis carinii pneumonia. P. carinii pneumonia was induced in rats by corticosteroid immunosuppression. Pentamidine was administered three times weekly via a Bird micronebulizer. The actual amount of pentamidine inhaled was estimated by monitoring the ventilation of the rats during the aerosol administration. Pentamidine levels in blood, lung, liver and kidney samples were determined by high-pressure liquid chromatography after completion of the treatment. Efficacy was evaluated by examination of lung imprints. In the prophylactic treatment, 4.8- and 8.6-mg/kg doses of aerosolized pentamidine administered three times weekly for 7 weeks were effective in preventing P. carinii pneumonia in 80 and 100% of the rats, respectively. In the therapeutic studies, a 14.6-mg/kg dose of aerosolized pentamidine administered three times weekly for 3 weeks was effective both in curing the pneumonia and in clearing P. carinii cysts in 70% of the rats. In the remaining animals, although the pneumonia was cured, the cysts persisted. A dose-dependent effect of the drug was demonstrated in both prophylactic and therapeutic treatments. High lung/kidney and lung/liver ratios of pentamidine levels were demonstrated and were associated with good clinical, biological, and histologic tolerance.

Aerosols↗
PubMed1988

Activity against rhinoviruses, toxicity, and delivery in aerosol of enviroxime in liposomes.

Enviroxime has been shown to inhibit the replication of rhinoviruses and other enteroviruses in concentrations as low as nanograms per milliliter in in vitro assays but is markedly less effective in clinical trials. The marked hydrophobicity and water insolubility of this compound may be a factor for this disparity. To overcome this handicap, we incorporated enviroxime into liposomes and then tested the antirhinovirus activity and toxicity of the liposome-incorporated enviroxime (LE) in cell culture and studied its administration by small-particle aerosol. Free enviroxime and LE were found to have equivalent efficacies against rhinovirus strains 1A and 13 in in vitro assays; however, preparations of LE were 10- to greater than or equal to 50-fold less toxic to tissue culture cells than was free enviroxime. In contrast to free enviroxime, which could not be delivered by small-particle aerosol because of its water insolubility, LE (4 mg/ml) was readily and successfully delivered by small-particle aerosol to the upper and lower respiratory tracts of mice; after just 20 min, significant levels of enviroxime were detected in the lungs and noses of exposed mice. Moreover, mice exposed to aerosols of liposomes containing both enviroxime and fluorescein isothiophosphatidylethanolamine showed accumulations of the fluorescent marker in the lungs, particularly in or around the tall columnar epithelial cells lining the bronchi and bronchioles.

Aerosols↗
PubMed1992

Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice.

Cryptococcus infections of the lung and central nervous system have become major problems in immuno-compromised patients, leading to the need for additional treatment protocols. We have utilized a Cryptococcus-mouse model that mimics human cryptococcal disease to evaluate the efficacy of amphotericin B-liposomes (AmpB-Lip) when delivered by small-particle aerosol (SPA). In the model, initial intranasal inoculation leads to a pulmonary infection that spreads after 2 to 3 weeks to distant organs, including the brain. Aerosols of AmpB-Lip that were generated by a Collison nebulizer had mass median aerodynamic diameters of 1.8 microns and contained 10.3 micrograms of AmpB per liter. When AmpB-Lip SPA was begun at 24 h postinoculation, a single 2-h treatment (0.3 mg of AmpB per kg of body weight) was effective in reducing pulmonary Cryptococcus infection. This regimen was more effective than intravenous administration of AmpB-Lip given for 3 continuous days. This single 2-h exposure to AmpB-Lip also was effective in reducing pulmonary Cryptococcus infection when treatment was delayed for 7 or 14 days. At day 21, when organisms had spread to the brain in all animals, the single 2-h aerosol treatment reduced the number of cryptococci in the brain as well as in the lungs. AmpB-Lip SPA administered once for 2 h on days 7, 14, and 21 also was effective in increasing the duration of survival of infected animals. These results demonstrate that aerosolized AmpB-Lip can be effective in treating both local, pulmonary Cryptococcus disease and systemic disease.

Aerosols↗
PubMed1985

Effect of an activated sludge wastewater treatment plant on ambient air densities of aerosols containing bacteria and viruses.

Bacteria- and virus-containing aerosols were studied during the late summer and fall seasons in a midwestern suburb of the United States before and during the start-up and operation of an unenclosed activated sludge wastewater treatment plant. The study showed that the air in this suburban area contained low-level densities of indicator microorganisms. After the plant began operating, the densities of total aerobic bacteria-containing particles, standard plate count bacteria, total coliforms, fecal coliforms, fecal streptococci, and coliphages increased significantly in the air within the perimeter of the plant. Before plant operations, bacteria were detected from five genera, Klebsiella, Enterobacter, Serratia, Salmonella, and Aeromonas. During plant operations, the number of genera identified increased to 11. In addition to those genera found before plant operations, Escherichia, Providencia, Citrobacter, Acinetobacter, Pasteurella, and Proteus, were also identified. Enteric viruses were detected in low densities from the air emissions of this plant. Only standard plate count bacteria remained at significantly higher than base-line densities beyond 250 m downwind from the center of the aeration tanks. Fecal streptococci and coliphages appeared to be more stable in aerosols than the other indicator microorganisms studied. In general, the densities of microorganism-containing aerosols were higher at night than during the day. The techniques used in this study may be employed to establish microorganism-containing aerosol exposure during epidemiological investigations.

Aerosols↗
PubMed1985

Method for detecting viruses in aerosols.

A simple method with poliovirus as the model was developed for recovering human enteric viruses from aerosols. Filterite filters (pore size, 0.45 micron; Filterite Corp., Timonium, Md.) moistened with glycine buffer (pH 3.5) were used for adsorbing the aerosolized virus. No virus passed the filter, even with air flow rates of 100 liters/min. Virus recovery from the filter was achieved by rapid elution with 800 ml of glycine buffer, pH 10. The virus in the primary eluate was reconcentrated by adjusting the pH to 3.5, adding AlCl3 to 0.0005 M, collecting the virus on a 0.25-micron-pore Filerite disk (diameter, 25 mm) and and eluting with 6 ml of buffer, pH 10. With this method, virus could be detected regularly in aerosols produced by flushing when 3 X 10(8) PFU of poliovirus were present in the toilet bowl. Poliovirus-containing fecal material from two of four infants who had recently received oral polio vaccine also yielded virus in the aerosols when feces containing 2.4 X 10(7) to 4.5 X 10(7) PFU of virus had been added to the toilet bowl. Persons infected with a variety of natural enteric viruses are known to excrete this amount of virus in their daily stools.

Aerosols↗