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PubMed1985

Aerosol deposition considerations in inhalation therapy.

Successful aerosol therapy generally depends on the small percentage (typically 10 percent) of the drug dose delivered to the lungs from metered-dose inhalers (MDIs), nebulizers, and dry powder inhalers. Deposition of therapeutic aerosols occurs by inertial impaction (in the oropharynx and large conducting airways) and by gravitational sedimentation (in the small conducting airways and alveoli) and is determined by the mode of inhalation, particle or droplet size, and the degree of airway obstruction. Deposition of metered-dose aerosols in the lungs can be enhanced by using MDIs correctly (aerosol release coordinated with slow, deep inhalation, followed by a period of breath-holding); many patients have poor inhaler technique. Extension devices (spacers and holding chambers) make MDIs easier to use and may increase lung deposition to levels achieved by a correctly used MDI while substantially reducing oropharyngeal deposition. Optimal use of air-driven (jet) nebulizers depends primarily on the choice of nebulizers with relatively small droplet size and on the volume fill and compressed gas flow rate.

Aerosol Propellants↗
PubMed1974

Blood fluorocarbon levels following exposure to household aerosols.

Measurement of blood fluorocarbon levels was carried out in subjects exposed to a number of household aerosol products containing fluorocarbon gases as propellants. All aerosols were used according to manufacturers' recommendations. The general purpose of the study was to determine whether with normal routine exposure to a wide variety of household aerosol products fluorocarbon could be found in the blood and if so, to check the potential toxicity of the levels reached. Daily exposure to aerosols according to the study regimen lasted four consecutive weeks; this period was preceded and followed by two weeks of abstention from exposure. At the end of each of the three periods a medical examination, including evaluation of cardiac function, respiratory function studies, and hematological and functional clinical biochemical tests was performed. All tests and assessments failed to show any indication of toxicity. No trace of fluorocarbon was found in any of the blood sampled at intervals during the study.

Adult↗
PubMed1982

Different techniques of aerosol administration to the lower respiratory tract.

Nebulizers, pressurized aerosols and powder aerosols are often used by asthmatic patients in order to obtain an immediate, local effect from a low dose of a drug in the lower respiratory tract. However, the aerosol delivery systems are not ideal for oral inhalation as the availability to the lower respiratory tract is low, the device is not always easy to use in an acute situation, and the constituents in the dosage form may cause side effects. The aerosol delivery systems for clinical practice are described and their limitations are emphasized. It is suggested that controlled comparative studies be performed concerning various systems for oral inhalation.

Aerosol Propellants↗
PubMed1985

Edetate sodium aerosol in Pseudomonas lung infection in cystic fibrosis.

In vitro and animal experimental data suggest the combination of edetate sodium (EDTA) by aerosol plus oral antimicrobials might be effective in the treatment of chronic Pseudomonas infection in patients with cystic fibrosis (CF). For six months we studied the effects of edetate sodium administered by ultrasonic nebulizer to ten children with CF and chronic Pseudomonas aeruginosa infection in a double-blind, placebo-controlled, crossover study. The children had evidence of mild to moderate disease at entry in the study, with a mean (+/- SD) forced expiratory volume in the first second of 85% (+/- 18%) of the predicted value and a mean (+/- SD) Shwachman-Kulczycki score of 83 (+/- 7)/100. Each child was on a three-month regimen of aerosolized edetate sodium plus oral tetracycline twice daily followed by three months of placebo aerosol plus tetracycline or vice versa. Progress was assessed by measurement of pulmonary function, physical examination, and sputum cultures at four weekly intervals, plus chest roentgenograms on entry and after each of the three-month treatment periods. Daily symptoms were assessed using a diary card system. Two patients could not complete the study, one because of severe respiratory relapse, the other because of antibiotic side effects. Of the remaining eight patients, none showed any improvement in pulmonary function, weight gain, or growth acceleration, and none was rendered free of Pseudomonas lung infection. Daily symptom scores and chest roentgenograms were unaltered by edetate sodium. We conclude that the combination of aerosol edetate sodium plus oral tetracycline over a three-month period does not modify the clinical course nor the pulmonary flora in patients with CF with chronic Pseudomonas lung infection.

Administration, Oral↗
PubMed1996

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Aerosols↗
PubMed1997

Repeatability of methacholine challenges in 2- to 4-year-old children with asthma, using a new technique for quantitative delivery of aerosol.

To determine the repeatability of bronchial responsiveness in awake young children, two methacholine challenge tests were performed on separate days in 16 children with stable asthma (mean age, 3 3/4 years). Methacholine was administered using a new method for quantitative delivery of aerosol that eliminates the effect of dilution of the aerosol by entrainment of air and enables quantitative delivery of aerosol according to body weight. Respiratory function was monitored by measurement of respiratory resistance by the interrupter technique (Rint), respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique, transcutaneous measurements of oxygen (PtcO2), and specific airway resistance (sRaw). Repeatability was evaluated by determining the provocative dose that caused a defined percentage of change relative to baseline (PD%: Rint PD30, Rrs5 PD30, Xrs5 PD80, PtcO2 PD10, and sRaw PD80. Repeatability was estimated from the difference between the PD% obtained at the time of the two tests. Using the numeric value of these differences, the repeatability of Xrs5 PD60, PtcO2 PD10, and sRaw PD50 was [mean (SD)]: [0.8 (0.5)] [0.5 (0.4)] and [0.7 (0.6)] doubling doses, respectively. Rint PD30 and Rrs5 PD30 proved to be less reproducible: [1.2 (1)] and [1.6 (0.9)] doubling doses, respectively. The new method of aerosol delivery offers a means of standardizing the bronchoconstrictor stimulus, and the results show that estimates of bronchial responsiveness in young children can be obtained reproducibly within one doubling dose of methacholine.

Aerosols↗
PubMed2004

Screening of urban aerosol particulate composites for selected metal distribution and their dependence on meteorological parameters.

Local atmospheric aerosol particulate samples, collected as composites on daily 6-12 hour basis, at Quaid-i-Azam University campus, Islamabad, Pakistan, using high volume sampling technique, were analysed for Pb, Na, K, Fe, Mn, Cd, Cr, Ni, Zn and Co by FAAS method. The monitoring period ran from October, 2001 through March, 2002, with a total of 105 samples collected on cellulose filters, treated in part with the HNO3-based wet digestion method for metal quantification, and for particle size distribution separately. The metal content of the aerosols was examined in relation to dependence on meteorological parameters, such as temperature, relative humidity, wind speed, sun shine and pan evaporation. Statistical correlation analysis was conducted for multiple metal pairs in aerosols, and the data were examined in relation to meteorological parameters and relevant aerosol particle size fractions. The study revealed no viable strong correlation between the meteorological parameters and metal levels; in general, however, a significant positive correlation was found for temperature. A strong positive correlation was observed for PM<25 and PM2.5-10. For coarse particles (PM10-100 and PM>100), however, a negative correlation was observed. The levels of Na, K, Fe and Zn were found in the range of 1-5 microg/m3 while those for the rest of the metals in the sub microg/m3 range. Principal component analysis and cluster analysis were performed on dataset for source identification and appointment. Largest contribution (33%) was shown by the industrial emissions followed by traffic/road dust (16.7%).

Aerosols↗
PubMed1993

Plasma concentrations and hemodynamic effects of intravenous, sublingual, and aerosolized nitroglycerin in patients undergoing cardiac catheterization.

Intravenous, sublingual, or aerosolized nitroglycerin was administered to 19 patients with coronary artery disease during clinically indicated cardiac catheterization. Eight blood samples were collected over 15 min from each patient, and analyzed for content of nitroglycerin, 1,2-glycerol dinitrate, and 1,3-glycerol dinitrate. Simultaneously, heart rate (HR), systolic blood pressure (SBP), and left ventricular end-diastolic pressure (LVEDP) were recorded. Plasma concentrations of nitroglycerin were highest after intravenous injection and lowest after sublingual tablets. Metabolite concentrations were highest after intravenous injection at early time-points; at later time-points, no between-group differences could be detected. SBP was minimally affected by intravenous nitroglycerin but was significantly reduced by sublingual and aerosolized formulations. Minor fluctuations in HR were observed in association with all three formulations. LVEDP was reduced by all three formulations of nitroglycerin but most rapidly by the intravenous form. Overall, no differences were detected in hemodynamic responses caused by sublingual and aerosolized nitroglycerin. Efficacy of sublingual and aerosolized nitroglycerin in patients undergoing cardiac catheterization is equivalent.

Administration, Inhalation↗
PubMed1981

Evaluation of selected aerosol-control measures on flow sorters.

Flow sorters produce microdroplets as part of their normal operation, and if these microdroplets escape into the room, they are potentially hazardous. We have tested several aerosol-control measures on a commercial flow sorter. To accomplish this, T-4 phages were introduced into the sorter's liquid jet through the sample injection tube, and culture plates containing lawns of T-4-sensitive Escherichia coli bacteria were exposed around the sorter for each operational configuration. After the exposure, the plates were incubated and then scored for plaques. A single phage-containing microdroplet landing on a plate was sufficient to cause a plaque of lysed bacteria to form. The number of plaques was thus an indicator of how much aerosol was released for each configuration. Aerosols were controlled most effectively by catching the central, undeflected stream in a vacuum-exhausted tube; this technique, coupled with the manufacturer's vacuum-exhaustion of the air around the sorting location, produced no plaques. Several failure modes were tested, including having the central stream hit the outside of the catch-tube or deflection plates, and loss the manufacturer's vacuum-exhaustion system. Many flow sorters allow the underflected stream to splash into a flask or beaker, an approach that produces the most plaques if instrument-failure modes are excluded. The simple addition of a catch-tube removed this major contributor to the aerosol production.

Accident Prevention↗
PubMed1975

Five fluorocarbons for administration of aerosol bronchodilators.

The exposure of the upper respiratory tract to aerosol propellants produces apnea, bradycardia, and biphasic fall and rise in aortic blood pressure in anesthetized dogs. This response represents the irritation of sensory receptors in the nasal and nasopharyngeal mucosa and is not elicited with aerosol propellants administered via a tracheal cannula bypassing the upper respiratory tract. When this is done, a different reflex is elicited, consisting of tachycardia that is mediated by the thoracic sympathetic nerves. There is either bronchodilation or bronchoconstriction depending on the type of propellant. The three propellants (11, 12, and 114) widely used in aerosols, when inspired in large doses, elicit both bradycardia and tachycardia and induce bronchoconstriction or bronchodilation. Two additional propellants (115 and C318), which are not ordinarily used to dispense bronchodilator drugs, do not elicit any change in heart rate and produce only bronchodilation. It is suggested that these two propellants merit further investigation and may replace the three widely used ones if these prove the use and abuse of aerosols.

Aerosol Propellants↗
PubMed2001

The usefulness of the modified extra-oral vacuum aspirator (EOVA) from household vacuum cleaner in reducing bacteria in dental aerosols.

AIMS AND OBJECTIVES: Currently, as a preventive measure against air contamination caused by dental procedures, dust-collecting aspirators such as an extra-oral vacuum aspirator (EOVA) are coming into general use. In this study, we tested the ability of a modified EOVA that uses a household vacuum machine. DESIGN AND SETTING: The study was conducted in two parts. First, the modified EOVA was tested for its ability to eliminate an Escherichia coli aerosol generated in a manikin. Second, the device was tested for its ability to remove the aerosol generated by dental treatment procedures, scaling and drilling a tooth, on human subjects. RESULTS: There was a statistically significant reduction in both the E. coli aerosol and the oral bacterial aerosol during dental treatment procedures. CONCLUSION: The modified EOVA machine is highly effective in preventing air contamination by dental procedures. Its main advantages are that it can easily be modified for use with any dental unit and it is relatively inexpensive.

Aerosols↗
PubMedDate not supplied

A review of the therapeutic efficacy of aerosolized and endotracheally instilled antibiotics.

Achievement of sufficient concentrations of aerosolized antibiotic at the site of infection is limited by technical problems in antibiotic delivery and by drug inactivation. Antibiotic delivery by aerosolization is generally associated with minimal systemic absorption, whereas systemic absorption may be significant after endotracheal instillation. Methodologic problems make correlations between clinical response and sputum antibiotic concentrations difficult. Studies suggest that aerosolized antibiotics are of little value in the treatment of chronic bronchopulmonary infections. Endotracheal instillation appears to be associated with favorable clinical responses, possibly due to enhanced antibiotic delivery to the site of infection. Prophylactic aerosolized antibiotics are effective in altering sputum flora; reduction in mortality from acquired pneumonia has not been demonstrated. The development of resistant organisms may occur as a result of prophylactic treatment.

Aerosols↗
PubMed2001

Characterization of novel di- and tricarboxylic acids in fine tropical aerosols.

Three unknown di- and tricarboxylic acids were characterized in the fine size fraction of aerosols which were collected during the wet season in the Amazon basin (Rondonia, Brazil). For the structural characterization of the methyl esters of these unknown compounds, mass spectrometry with electron ionization (EI) and tandem mass spectral techniques combined with gas chromatographic (GC) separation were employed. Fragment and parent ion spectra were recorded during elution of the GC peaks by linked scanning of the B and E sectors in combination with high-energy collision-induced dissociation. The fragmentation patterns of significant ions in the first-order EI spectra were also obtained for nonanedioic acid, which was examined as a model compound. The compounds were tentatively identified as 4-acetyloxyheptanedioic acid and cis and trans isomers of 5-hexene-1,1,6-tricarboxylic acid. Since there were indications of biomass burning during the aerosol sampling the di- and tricarboxylic acids characterized in the present work could be markers for biomass burning. Furthermore, the characterization of di- and tricarboxylic acids in the fine size fraction of atmospheric aerosols may be important for assessing the effects of organic aerosols in cloud formation.

Aerosols↗
PubMed2006

The use of colloid probe microscopy to predict aerosolization performance in dry powder inhalers: AFM and in vitro correlation.

The atomic force microscope (AFM) colloid probe technique was utilized to measure cohesion forces (separation energy) between three drug systems as a function of relative humidity (RH). The subsequent data was correlated with in vitro aerosolization data collected over the same RH range. Three drug-only systems were chosen for study; salbutamol sulphate (SS), triamcinolone acetonide (TAA), and di-sodium cromoglycate (DSCG). Analysis of the AFM and in vitro data suggested good correlations, with the separation energy being related inversely to the aerosolization performance (measured as fine particle fraction, FPF(LD)). In addition, the relationship between, cohesion, RH, and aerosolization performance was drug specific. For example, an increase in RH between 15% and 75% resulted in increased cohesion and decreased FPF(LD) for SS and DSCG. In comparison, for TAA, a decrease in cohesion and increased FPF(LD) was observed when RH was increased (15-75%). Linear regression analysis comparing AFM with in vitro data indicated R(2) values > 0.80, for all data sets, suggesting the AFM could be used to indicate in vitro aerosolization performance.

Administration, Inhalation↗
PubMed2006

Ultra-fast absorption of amorphous pure drug aerosols via deep lung inhalation.

A deficiency of most current drug products for treatment of acute conditions is slow onset of action. A promising means of accelerating drug action is through rapid systemic drug administration via deep lung inhalation. The speed of pulmonary drug absorption depends on the site of aerosol deposition within the lung and the dissolution rate and drug content of the deposited particles. Alveolar delivery of fast-dissolving, pure drug particles should in theory enable very rapid absorption. We have previously shown that heating of thin drug films generates vapor-phase drug that subsequently cools and condenses into pure drug particles of optimal size for alveolar delivery. Here we present a hand held, disposable, breath-actuated device incorporating this thermal aerosol technology, and its application to the delivery of alprazolam, an anti-panic agent, and prochlorperazine, an anti-emetic with recently discovered anti-migraine properties. Thermal aerosol particles of these drugs exist in an amorphous state, which results in remarkably rapid drug absorption from the lung into the systemic circulation, with peak left ventricular concentrations achieved within 20 s, even quicker than following rapid (5 s) intravenous infusion. Absorption of the thermal aerosol is nearly complete, with >80% absolute bioavailability found in both dogs and human normal volunteers.

Absorption↗
PubMed1989

Comparison of a new multidose powder inhaler with a pressurized aerosol in children with asthma.

Thirteen children with asthma were treated with cumulative doses of terbutaline delivered as a pressurized aerosol and from a new multidose powder inhaler (Turbuhaler) in a randomized cross-over dose-response study. The cumulative dose of terbutaline was 2 mg on each study day. All children used a correct aerosol inhalation technique. At no time was there any difference in forced expiratory volume in 1 s (FEV1), forced midexpiratory flow, forced vital capacity, peak expiratory flow rate, or percent increase in these parameters between the two inhalers. The mean total increases in FEV1 after 2 mg terbutaline were 60% (aerosol) and 62% (Turbuhaler); 90% of these increases were measured after a cumulative dose of 0.5 mg terbutaline. One milligram of terbutaline inhaled from a Nebuhaler at the end of each study day did not result in additional increase of pulmonary functions, indicating that maximal bronchodilation had been achieved with both inhalers. After a cumulative dose of 2 mg terbutaline from the aerosol seven children complained of tremor and one of restlessness. No side effects were reported when the Turbuhaler was used (P less than 0.02). 1989; 7:00-00.

Administration, Inhalation↗
PubMed2005

Aerosol treatment with MNEI suppresses bacterial proliferation in a model of chronic Pseudomonas aeruginosa lung infection.

Neutrophil elastase is present at high levels in airway fluid of patients with cystic fibrosis (CF), and is responsible for considerable inflammatory damage. Human monocyte/neutrophil elastase inhibitor (MNEI), a 42-kDa serpin protein, is an effective inhibitor of neutrophil elastase, cathepsin G, and proteinase-3, related proteases released from inflammatory neutrophils. We hypothesized that recombinant MNEI would reduce inflammatory damage and enhance bacterial clearance from the lung in an animal model of chronic Pseudomonas aeruginosa infection. In vitro studies showed that MNEI causes dose-dependent inhibition of the activity of rat neutrophil elastase. Recombinant MNEI was administered daily by aerosolization to rats previously inoculated with agar beads containing P. aeruginosa to initiate chronic infection. Administered MNEI was partially recovered in lavage fluid of treated rats as a 66-kDa complex with protease indicative of in vivo inhibition of elastase or a related protease. Aerosol treatment with MNEI significantly decreased the extent of inflammatory injury, quantified as the histopathology score. MNEI, which had no bactericidal effect on P. aeruginosa in vitro, significantly enhanced clearance of bacteria from infected rat lungs. The reduction of histopathology scores and enhancement of bacterial killing were evident 6 hr after a single aerosol treatment with MNEI. These findings indicate an important function of MNEI in protecting innate antimicrobial defense. Similar results were previously obtained for aerosolized prolastin (alpha1-antitrypsin), indicating that enhanced bacterial clearance by MNEI is due to inhibition of neutrophil protease. These findings demonstrate the value of this nonantibiotic protease inhibitor as an adjunct for the treatment and prevention of the infection component of CF lung disease.

Aerosols↗
PubMed2005

Randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer vs. jet nebulizer in young children with wheezing.

The jet nebulizer is a common device used for administering aerosol medication in young children. However, compared to a metered dose inhaler-spacer (MDI-spacer), it takes more time and personnel. This study aimed to compare the efficacy of salbutamol aerosol therapy given via these two devices in young wheezing children. A prospective randomized, double-blind, placebo-controlled trial was performed in children up to 5 years old who had acute wheezing and were admitted to the Department of Pediatrics, King Chulalongkorn Memorial Hospital. Patients were randomly divided into two groups. The first group received 2 puffs of placebo via MDI-spacer, followed by 0.15 mg/kg salbutamol respiratory solution via jet nebulizer. The second group received 2 puffs (100 microg/puff) of salbutamol via MDI-spacer, followed by placebo via jet nebulizer. Clinical scores and tidal breathing pulmonary function test were evaluated before and after treatment. Pulmonary function parameters included those derived from flow volume loops (volume to peak tidal expiratory flow over total expiratory volume, V(PTEF)/V(E); time to peak tidal expiratory flow over total expiratory time, T(PTEF)/T(E); and ratio of tidal expiratory flow at 25% remaining expiration to peak expiratory flow, 25/PF), compliance (Crs), and resistance (Rrs) of the respiratory system. The efficacy of both methods was compared by using analysis of covariance. Forty-seven wheezing children were studied (24 received salbutamol via MDI-spacer, and 23 received it via jet nebulizer). There was no statistical difference between the two groups regarding clinical scores and all pulmonary function parameters. However, heart rate was significantly increased after treatment in the jet nebulizer group when compared to those in the MDI-spacer group (P = 0.004). In conclusion, the efficacy of salbutamol aerosol therapy via MDI-spacer compared to jet nebulizer in young wheezing children was not different in terms of clinical score and postbronchodilator pulmonary function parameters. However, salbutamol aerosol therapy via jet nebulizer significantly increased the heart rate when compared to the MDI-spacer.

Aerosols↗