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PubMed1992

Deposition of aerosolized pentamidine and failure of pneumocystis prophylaxis.

OBJECTIVE: To determine if outcome of Pneumocystis carinii prophylaxis is related to total lung dose of aerosolized pentamidine. SETTING: AIDS treatment centers at a VA and University Hospital. PATIENTS: Fifty-eight HIV-infected patients receiving P carinii prophylaxis with aerosolized pentamidine using a nebulizer (CIS-US AeroTech II) were followed up over a 90-week period. Treatment consisted of 60 to 90 mg every two weeks. MEASUREMENTS: In all patients, deposition of pentamidine aerosol was measured using a radioaerosol filter technique. Factors thought to be important in deposition, nebulizer output and breathing pattern were also measured. Six months later, repeated deposition studies were performed in 20 patients. Pentamidine dose to the lung was related to occurrence of P carinii pneumonia and correlated with nebulizer function and breathing parameters. Outcome was assessed in terms of pentamidine deposition and patient characteristics, including demographic, immunologic, physiologic, and medical variables. RESULTS: Ten patients (17.2 percent) had development of P carinii pneumonia. However, pentamidine deposited in the failures (8.18 +/- 4.74 mg) was no different than deposition in protected patients (6.39 +/- 3.07 mg, p = NS). Most of the variability in deposition was accounted for by variability in nebulizer output (r = 0.919, p less than 0.001). Deposition did not significantly correlate with any of the measured breathing parameters. Serial deposition measurements were not significantly different by paired analysis. The incidence of P carinii pneumonia did not correlate with any measured patient characteristic. CONCLUSIONS: Failure of aerosolized pentamidine prophylaxis is not related to total lung dose of pentamidine. Other factors such as inadequate microscopic deposition between alveoli, pentamidine clearance, or drug resistance may be important. In HIV-infected patients, interpatient variability in aerosol deposition can be reduced by reducing variability in nebulizer output rather than control of breathing pattern.

Aerosols↗
PubMed1993

Differential lobe lavage for diagnosis of acute Pneumocystis carinii pneumonia in patients receiving prophylactic aerosolized pentamidine therapy.

The diagnostic yield of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus has been reported to be 95 percent, but falls to 62 percent in patients receiving aerosolized pentamidine. Because aerosolized pentamidine appears to be preferentially deposited in the middle and lower lobes, we postulated that an upper lobe lavage would have a higher diagnostic yield than the standard middle/lower lobe lavage in patients receiving aerosolized pentamidine. Twenty-five patients receiving aerosolized pentamidine suspected of having acute PCP underwent separate BAL of an upper lobe and lower lobe as well as transbronchial biopsy. Fifteen of the 25 (60 percent) were diagnosed as having PCP. Of the 15, one had the samples inadvertently combined. In the remaining 14, BAL was positive for P carinii organisms in 12 lavages of the lower lobe and 14 of the upper lobe. Upper lobe lavage had statistically significantly more P carinii organisms by semiquantitative technique than the lower lobe. In patients receiving aerosolized pentamidine, who develop acute PCP, an upper lobe lavage may have a higher diagnostic yield than the standard middle/lower lobe lavage. In addition, the transbronchial biopsy specimen offered no treatable diagnosis that was not made by lavage alone in the 25 patients. This raises the question of the utility of transbronchial biopsies in these patients.

Acute Disease↗
PubMed1996

Determinants of aerosolized albuterol delivery to mechanically ventilated infants.

An in-vitro lung model and a volume ventilator were used to evaluate the delivery of aerosolized albuterol through an infant ventilator circuit. We compared the following: continuous nebulization (CNA) and intermittent nebulization (INA); various nebulizer gas flows, 5.0, 6.5,and 8.0 L/min; and duty cycle of 33% and 50%. The efficiency and consistency of aerosol delivery by metered-dose inhaler (MDI) with four different spacer devices and by nebulizer positioned at the manifold and at the same position as the MDI were also evaluated. A volume ventilator (Servo 900B) was used with settings selected to reflect those of a moderately to severely ill 4-kg infant. A 3.5-mm endotracheal tube was used in all experiments. A specific type of nebulizer used (Airlife Misty Neb; Baxter; Valencia, Calif) and several spacers were studied (Aerochamber and Aerovent, Monaghan Medical Corporation in Plattsburgh, NY [corrected]; ACE, Diemolding Healthcare Division in Canastota, NY [corrected]; and an in-line MDI adapter, Instrumentation Industries Inc, Pittsburgh). CNA delivered significantly more aerosol to the lung model (4.8 +/- 0.6% of the starting dose) than INA (3.8 +/- 0.3%; p<0.01). There was a significant stepwise decrease in aerosol delivery with increasing nebulizer flow (4.8 +/- 1.3% at 5.0 L/min; 3.7 +/- 1.1% at 6.5 L/min; and 2.7 +/- 1.1% at 8.0 L/min). Increasing duty cycle did not significantly affeet delivery. Overall the spacers with MDI were more efficient than the nebulizer in either position delivering about twice the percentage of the starting dose than the nebulizers. All modes of delivery, except the Aerochamber, demonstrated a marked degree of variability. Most of the starting dose of albuterol either remained in the nebulizer (30.4 +/- 6.0% at 5.0 L/min and 25.3 +/- 4.1% at 8.0 L/min) or was deposited in the inspiratory tubing (34.7 +/- 0.7% at 5.0 L/min and 43.7+/- 4.9% at 8.0 L/min) in our system. In conclusion, we have confirmed that aerosol delivery depends on the mode of delivery and the operating conditions. Although delivery with an MDI and spacer is more efficient than a nebulizer, both methods may produce high variability depending on the method or spacer used.

Aerosols↗
PubMed2003

Two aerosolized nitric oxide adducts as selective pulmonary vasodilators for acute pulmonary hypertension.

STUDY OBJECTIVES: To determine the selective vasodilatory effects of two inhaled "NONOate" aerosols in a closed chest pig model of acute pulmonary hypertension (APH). METHODS: APH was induced by IV infusion of the prostaglandin H(2)/thromboxane A(2) receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 micro mol each], or placebo (n = 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy. RESULTS: Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p < 0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p < 0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO. CONCLUSION: Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.

Aerosols↗
PubMed1981

An evaluation of the physical properties of monodisperse and heterodisperse aerosols used in the assessment of bronchial function.

Designing a therapeutic aerosol on the basis of its physical properties is a very important objective, but experience has also clearly demonstrated the value of controlling the breathing and drug administration patterns. Presently, the state of aerosol technology is well advanced of its use in medicine. The employment of more sophisticated aerosolization methods can undoubtedly be advocated on both intuitive and scientific grounds, but whether the benefit will justify their cost and complexities is far less evident. This report attempts to set the issue in perspective by reviewing the important properties of commonly-prepared heterodisperse aerosols with monodisperse aerosols of the research laboratory in the context of bronchial deposition and retention.

Aerosols↗
PubMed1984

Assessment of tachyphylaxis following prolonged therapy of asthma with inhaled albuterol aerosol.

Controversy exists concerning possible tachyphylaxis of the acute bronchodilating effect of albuterol, especially with regard to the duration of its acute bronchodilating action. We evaluated 140 patients with bronchial asthma in a prospective double-blind controlled study of possible tachyphylaxis to albuterol aerosol as compared to isoproterenol aerosol. We demonstrated statistically significant tachyphylaxis with regard to duration of acute bronchodilating effect. We believe that this tachyphylaxis is not clinically significant because there was no tachyphylaxis with regard to peak bronchodilating effect and because the duration of bronchodilating effect remains significantly greater, both quantitatively and statistically, when compared to isoproterenol aerosol. Moreover, it appeared that most of the tachyphylaxis was present at four weeks of therapy. There was a small increment of tachyphylaxis after eight weeks of therapy, but no further increase in tachyphylaxis was demonstrated after 13 weeks of inhaled albuterol therapy. We therefore feel that clinically significant tachyphylaxis to inhaled albuterol aerosol must be quite unusual and that chronic therapy with inhaled albuterol aerosol is probably both safe and efficacious for bronchospastic disorders.

Adolescent↗
PubMed2003

Aerosol gene therapy.

Gene therapy is a novel field of medicine that holds tremendous therapeutic potential for a variety of human diseases. Targeting of therapeutic gene delivery vectors to the lungs can be beneficial for treatment of various pulmonary diseases such as lung cancer, cystic fibrosis, pulmonary hypertension, alpha-1 antitrypsin deficiency, and asthma. Inhalation therapy using formulations delivered as aerosols targets the lungs through the pulmonary airways. The instant access and the high ratio of the drug deposited within the lungs noninvasively are the major advantages of aerosol delivery over other routes of administration. Delivery of gene formulations via aerosols is a relatively new field, which is less than a decade old. However, in this short period of time significant developments in aerosol delivery systems and vectors have resulted in major advances toward potential applications for various pulmonary diseases. This article will review these advances and the potential future applications of aerosol gene therapy technology.

Administration, Inhalation↗
PubMed2006

The 15th International Society of Aerosols in Medicine Congress. Perth, Australia, 14-18 March 2005.

This international meeting brought together approximately 250 delegates from the pharmaceutical industry, academia, hospitals and government agencies, to discuss the latest research and development on areas related to inhalation aerosols. Fundamental science and applied research encompassing both the biological and physicochemical aspects were presented. There was a wide range of topics covered, from immune modulation to pharmaceutical regulatory issues, including aerosol clearance; industry innovations; aerosols and in utero effects; technical advances in imaging; inhalation catastrophes; as well as recent advances and future directions in aerosol delivery systems. This biennial congress has provided an excellent forum for stimulating fruitful discussion of aerosols in medicine.

Aerosols↗
PubMed1996

Reduction of aerosols produced by ultrasonic scalers.

There is concern with decreased air quality and potential aerosol contamination in the dental operatory. This problem has been addressed by the Centers for Disease Control and Prevention, which recommends that all sources of blood-contaminated splatter and aerosols be minimized. One of the major sources of potential aerosol contamination in the dental setting is the ultrasonic scaler. This study looks at the use of a high volume evacuator attachment for the ultrasonic scaler handpiece. Artificial teeth were mock-scaled for 1 minute with and without the evacuator attachment. The mock scaling was performed within a plastic enclosure that had a 1 cm grid laid out on 4 sides. Scaling was performed 10 times each by 2 operators. An erythrosin solution was used for the ultrasonic scaler coolant with a coolant volume of 17.5 ml/min. The number of squares containing a red erythrosin spot were counted and considered to represent aerosol contamination. The high volume evacuator attachment produced a 93% reduction in the number of contaminated squares (chi squared significant at P < 0.05). There was no increase in heat transfer to a tooth analogue when the high volume evacuator attachment was used with the ultrasonic scaler as compared to the scaler without the evacuator attachment. It is felt that the high volume evacuator attachment is capable of significantly reducing the amount of aerosol contamination produced within the test system without increased heat transfer to the tooth.

Aerosols↗
PubMed2003

Aerosol therapy for malignancy involving the lungs.

The lungs are common sites of involvement by primary and metastatic malignant disease. Patients with malignancies in the lung have limited treatment options and are usually not curable. Numerous investigators have studied the potential of delivering various therapeutic agents directly to the lungs and pulmonary lymphatics by nebulization. Most of the research involves the use of immunomodulatory strategies; a few aerosol studies of chemotherapy and gene therapy have also been conducted. Most of these studies have been conducted in animal models. A few human trials have also been completed. Results suggest that aerosol therapies have the potential to shrink pulmonary metastases of selected histologies, and that survival in selected patients with metastatic renal cell cancer may be prolonged. The approach to therapy of cancer in the lungs holds promise as a means to avoid systemic toxicity and obtain an improved therapeutic effect. Research is currently underway to address issues of local versus systemic toxicity, optimal drug delivery and selection of optimal drugs and schedules including outpatient aerosol therapy. Future issues in design of aerosol cancer treatment include identifying effective combinations of agents, schedules, and use of aerosol therapy at home as adjuvant therapy.

Administration, Inhalation↗
PubMedDate not supplied

Air pollution and asthma: clinical studies with sulfuric acid aerosols.

Until recently, acid deposition has been widely considered a serious ecological problem but not a threat to human health. The controlled clinical study is an important approach in linking acidic aerosol inhalation with respiratory effects. Asthmatic patients represent a subpopulation most responsive to sulfuric acid aerosols. In a series of studies with asthmatic volunteers, several factors have been identified that may modulate the intensity of the bronchoconstrictor response to inhaled acidic aerosols. We found (1) enhancement of the bronchoconstrictor response during exercise, (2) the more acidic aerosols provoke the greatest changes in lung function, and (3) mitigation of airway responses during sulfuric acid aerosol inhalation caused by high respiratory ammonia concentrations. Additional factors influencing responsiveness await identification.

Adult↗
PubMed1986

Aerosolized 5 alpha-androst-16-en-3-one reduced agonistic behavior and temporarily improved performance of growing pigs.

Two experiments were conducted to determine the effect of aerosolized 5 alpha-androst-16-en-3-one (androstenone) on pig aggressive and submissive behaviors and on pig performance. In Exp. 1, twenty-four 5-wk-old pigs were randomly regrouped in a two-pig bioassay. A solution of either isopropyl alcohol or .5 mg androstenone in isopropyl alcohol per pig was aerosolized on both pigs in the observation pens. Summarization of video records from the 90-min bioassay showed that pens of pigs aerosolized with androstenone spent 58% less time engaged in aggressive behavior (P less than .05) and 96% less time engaged in submissive behavior (P less than .01). In Exp. 2, a performance trial was conducted with finishing pigs from 57 to 91 kg body weight. Factorially arranged treatments included aerosolized androstenone (.5 mg/pig) or the vehicle isopropyl alcohol and regrouping into uniform body weight blocks or no regrouping. Regrouping depressed average daily feed consumption (P less than .05) and average daily gain (P less than .05) for the first 7 d of the trial. Pigs reveiving the androstenone aerosol had improved average daily gain (P = .01) and gain:feed ratio (P less than .01) for the first 28 d of the trial. Performance of all treated pigs was similar for the entire finishing period. This olfactory stimulant reduced pig agonistic behavior and transiently improved performance of regrouped and non-regrouped finishing pigs.

Aerosols↗
PubMed1999

Aerosol deposition modeling using ACSL.

An aerosol deposition model has been written for inclusion into physiologically based pharmacokinetic (PBPK) models, allowing PBPK model based risk assessments to be performed for aerosolized materials. Previously, PBPK models could only treat inhaled gases and vapors. The deposition model employs a semi-empirical equation to describe extrathoracic deposition and employs data concerning the geometry of the thoracic conducting airways as well as that of the gas exchange regions of the lung to compute the deposited aerosol mass based on aerosol diffusion, sedimentation, and impaction. Provisions are made to allow calculations for polydisperse aerosols whose size distribution and mass vary with time. Variations in the model subject's respiration can be accommodated through selection of respiratory parameters at model startup as well as through consideration of carbon dioxide stimulation of respiration. The model is compared with other similar calculations and experimental data to validate the calculations. An example model application is presented in the form of a comparison of two inhalation atmospheres, one from an inhalation toxicity study and one from a similar atmosphere produced for fire extinguishing agent testing.

Administration, Inhalation↗
PubMed1984

A mechanism of synergistic lung damage by ozone and a respirable aerosol.

A hitherto unexpected synergism between the oxidant air pollutants ozone or nitrogen dioxide and a respirable-sized aerosol of ammonium sulfate was previously observed during controlled exposures of rats to these substances. In this paper we examine biochemical and morphometric changes in lungs of rats exposed for 3, 7, or 14 days to ozone (0.64-0.96 ppm), with or without an accompanying aerosol (approximately 1 micrometer mass median aerodynamic diameter) of ammonium sulfate (5 mg/m3). After 3 days of exposure to the mixture of pollutants, rat lung macrophage and macrophage precursors (monocytes) were increased 2- to 3-fold, fibroblasts were increased 2-fold, and apparent collagen synthesis rates were increased 2.5-fold, fibroblasts were increased 2-fold, and apparent collagen synthesis rates were increased 2.5-fold, as compared with values from animals exposed to ozone alone. Continued exposure to ozone alone for 7 or 14 days seemed to mimic changes seen at 3 days with the mixture of pollutants. Total number of lesions per lung was the same for ozone exposure with and without accompanying aerosol; lesions were larger in lungs of rats exposed to ozone plus ammonium sulfate. Based on these findings and a review of the literature, a mechanism for ozone-aerosol synergism is proposed. We suggest that the lifetime of free radicals arising from interaction of oxidants such as ozone or nitrogen dioxide with molecules within the lung is increased by either local pH changes or changes in the local sulfate concentration (or both) caused by inhalation of the respirable aerosol.

Aerosols↗
PubMedDate not supplied

Effect of heart rate on aerosol recovery and dispersion in human conducting airways after periods of breathholding.

With a newly developed aerosol inhalation device, small volumes of aerosols ("boluses") can be inspired predominantly into the conducting airways of the human lungs. The aerosol is injected by a fast-operating valve system using preselected volumes near the end of a clean air inhalation of 1000 cm3. Particle behavior in upper human airways was investigated by measuring particle recovery and bolus dispersion in exhaled air with a laser photometer positioned directly in front of the mouth after various periods of breathholding. The effect of physical motion of the heart on these measurements has been investigated by increasing the heart rate of a subject by more than a factor of 2. Monodisperse sebacate aerosols were used with droplets in the aerodynamic size (dac) range between 0.8 and 1.1 micron to minimize particle losses by diffusion and by inertial forces. It was shown that motion of the heart considerably influences both particle recovery and dispersion of such boluses during postinhalation periods of breathholding. For a twofold enhancement in heart frequency the standard deviation of the expired aerosol bolus was increased by up to 60% after certain breathholding periods. Particle recovery from shallow volumetric lung depths was significantly decreased.

Aerosols↗
PubMedDate not supplied

Accuracy and resolution power of aerosol-derived airway morphometry in a simple lung model.

Aerosol-derived airway morphometry (ADAM) uses sedimentational deposition of monodisperse aerosol particles during breathhold to estimate intrapulmonary air-space dimensions. To determine the accuracy and resolution power of this technique a simple physical lung model comprised of uniform glass beads was investigated. Using the chordlength model, aerosol recovery from this porous medium was calculated by computer simulation of the geometrical structure of air-spaces between glass beads. The results of this calculation were then compared with experimental data: Calculated and measured air-space dimensions differ less than 2% for particles with diameters above about 1 micron. The measured air-space dimension can be described geometrically by the mean chordlength of the porous medium. To estimate the resolution power of ADAM, a defined change in air-space dimensions represented by a horizontal air slit was introduced into the porous medium. This air slit induces a marked increase of measured air-space dimensions. The volumetric width of this increase is the higher the deeper the slit is situated within the medium. Intercomparison of these data with the results of aerosol bolus dispersion measurements suggests that the resolution power of ADAM is decreased by the same mechanisms that increase dispersion of aerosol boluses, demonstrating the close relationship between both methods.

Aerosols↗
PubMed1977

Application of the cell-free turkey herpesvirus vaccine by the aerosol route for the prevention of Marek's disease in chickens.

In field trials approximately 300,000 birds were vaccinated against Marek's disease (MD) by aerosol spray with 1,000 to 5,000 PFU of cell-free HVT vaccine per chick. Chicks were sprayed in the trays of the hatchers which still contained dust and down after hatching. Prior to spraying, the incoming and outgoing air ducts were closed. The chicks were sprayed for 12--15 min. with HVT in 250 to 300 ml. of diluent, and after completion of spraying the chicks remained in contact with the aerosol for approximately 10 minutes. In birds vaccinated by aerosol spray the incidence of MD ranged from 0.0% to 24.4%; while the incidence of MD in birds vaccinated by subcutaneous inoculation varied from 0.02 to 23.9%. In trial 1 the incidence of MD in birds vaccinated by aerosol spray was essentially the same as those vaccinated by subcutaneous inoculation; whereas, the incidence of MD (Trial 2 and 3) was higher in birds vaccinated by aerosol as compared to chickens vaccinated by subcutaneous inoculation.

Aerosols↗
PubMed2003

Aerosol exposure of white-tailed deer (Odocoileus virginianus) to Mycobacterium bovis.

Tuberculosis due to Mycobacterium bovis affects both captive and free-ranging Cervidae in the United States. Various animal models have been developed to study tuberculosis of both humans and animals. Generally, tuberculosis is transmitted by aerosol and oral routes. Models of aerosol exposure of large animals to M. bovis are uncommon. In order to develop a reliable method of aerosol exposure of white-tailed deer (Odocoileus virginianus) to M. bovis, 12 healthy white-tailed deer, aged 8-10 mo, were infected by aerosol exposure to 2 x 10(5) to 1 x 10(6) colony forming units (CFU) (high close, n = 4) of M. bovis or 6 x 10(2) to 1.6 x 10(3) CFU (low dose, n = 8) of M. bovis. Tuberculous lesions were more widely disseminated in (leer receiving the high dose, while lesions in deer receiving the low dose were more focused on the lungs and associated lymph nodes (tracheobronchial and mediastinal). Aerosol delivery of M. bovis to white-tailed deer results in a reliable manner of experimental infection that may be useful for studies of disease pathogenesis, immune response, mycobacterial shedding, and vaccine efficacy.

Aerosols↗