Scintiphotography of lungs with dry aerosol--generation and delivery system: concise communication

International Nuclear Information System (INIS)

Kotrappa, P.; Raghunath, B.; Subramanyam, P.S.S.; Raikar, U.R.; Sharma, S.M.

1977-01-01

A compressed-air nebulizer with low holdup and high output was used to nebulize [/sup 99m/Tc] pertechnetate presented in normal saline. Generated droplets were dried in line and led to an inhalation chamber from which the dry aerosol was inhaled using a nose or mouth inhalation unit. The mass median diameter of the particles was 0.8 microns, with an associated geometric standard deviation of 2.0. The deep lung delivery efficiency--defined as the ratio of the activity deposited in the lung area to the activity nebulized--was found to be reproducible and consistent (15 to 22%) in all the subjects studied. A 3 to 5 min inhalation of aerosol, nebulized from 20 mCi, was sufficient to provide a lung image of good information density. No noticeable deposit was seen in the trachea or major bronchi. The system is inexpensive, stable in performance, adaptable to other solutions or colloids, and is promising for routine use

Inhalation deposition and retention patterns of a U-Pu chain aggregate aerosol

International Nuclear Information System (INIS)

Briant, J.K.; Sanders, C.L.

1987-01-01

Chain aggregate aerosol particles are normally formed during many high-temperature combustion and vaporization processes. The shape of chain aggregate aerosol particles could have an effect on the pattern of inhalation deposition and retention of the particles in the respiratory tract. A chain aggregate aerosol of nuclear reactor fuel could be present as an inhalation hazard if it were released to the atmosphere after a meltdown, core-disruptive accident. Rats were exposed to a chain aggregate U-Pu aerosol made by laser vaporization of mixed-oxide, breeder reactor fuel (20% plutonium dioxide and 80% uranium dioxide), then sacrificed to measure the clearance and retention of the fuel aerosol particles. Deposition of the 0.7-micron (activity median aerodynamic equivalent diameter) aerosol particles resulted in an average initial lung burden of 4140 Bq alpha activity. The chain aggregate particle shape was not a major factor in the total deposition; however, it may have influenced the regional distribution of the activity deposited. Retention of the particles in the upper airways of the tracheobronchial tree was on the order of 1% of the concurrent lung burden, which is consistent with recent data of other investigations. This study indicates that insoluble chain aggregate particles are retained in the tracheobronchial airways to a degree similar to simple spherically shaped particles of equivalent volume diameter

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

Science.gov (United States)

Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

2017-11-01

Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Role of radio-aerosol and perfusion lung imaging in early detection of chronic obstructive lung disease

Energy Technology Data Exchange (ETDEWEB)

Garg, A; Pande, J N; Guleria, J S; Gopinath, P G

1983-04-01

The efficacy of radio-aerosol and perfusion lung imaging in the early detection of chronic obstructive lung disease was evaluated in 38 subjects. The subjects included 5 non-smokers, 21 smokers with minimal or no respiratory symptoms and 12 patients with chronic obstructive lung disease. Each subject consented to a respiratory questionaire, detailed physical examination, chest X-ray examinations, detailed pulmonary function tests and sup(99m)Tc-radioaerosol-inhalation lung imaging. Perfusion lung imaging with sup(99m)Tc-labelled macroaggregated albumin was performed in 22 subjects. A significant correlation (P<0.001) was observed between the degree of abnormalities on radio-aerosol imaging and pulmonary function tests (PFTs) including forced expiratory volume in 1 s, maximum midexpiratory flow rate and mean transit time analysis. Abnormal radio-aerosol patterns and deranged PFTs were observed in 21 subjects each. Of 21 subjects with abnormal radioaerosol pattern 8 had normal PFTs. Of 21 subjects with abnormal PFTs 8 had normal aerosol images. Aerosol lung images and PFTs were abnormal more frequently than perfusion lung images. The results suggest that radio-aerosol lung imaging is as sensitive an indicator as PFTs for early detection of chronic obstructive lung disease and can be usefully combined with PFTs for early detection of alteration in pulmonary physiology in smokers.

The removal of inhaled 239Pu and 238Pu from beagle dogs by lung lavage and chelation treatment

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Miglio, J.J.; Slauson, D.O.; McClellan, R.O.

1976-01-01

Studies were conducted in beagle dogs to determine the efficiency of treatment by lung lavage and injections of chelating agents in removing inhaled plutonium of varied chemical forms and particle sizes. Polydisperse aerosols of 239 Pu were produced at different temperatures from 325 0 C to 1150 0 C to evaluate the effect of the chemical form of the particles. Aerosols of 238 Pu were produced at 1150 0 C only but were of different particle size or size distributions. Three dogs that inhaled each different plutonium aerosol were treated by lung lavages starting two days after the exposure. Subsequent lavages were performed on days 7, 10, 14, 21, 28, 35, 42, and 49 after exposure. Intravenous injections of 100 mg of diethylenetriaminepentaacetic acid (DTPA) as the calcium salt were given on days 1, 2, 3 and 4 after exposure and twice weekly thereafter to the time of sacrifice, 56 days after exposure. The 10 lung lavages removed from 18 to 49% of the initial lung burden of plutonium. The recovery of plutonium by lavage was similar irrespective of the temperature at which the aerosol was produced, however, lavage recovery decreased somewhat with increasing particle size. The efficacy of DTPA treatment increased with decreasing production temperature of the 239 Pu. Treatment with DTPA was not affected by particle size of the 0.8- and 1.9-μm monodisperse 239 Pu aerosol. The effectiveness of lung lavage decreased as the solubility of the aerosol particles increased whereas the effectiveness of the DTPA treatment increased as the solubility of the inhaled aerosol increased as shown by the lowest temperature aerosol and the aerosol-containing soluble fraction. These findings correlated qualitatively with a 2-hour in-vitro solubility test on the exposure aerosols. (author)

Radiation dose to the lungs due to inhalation of alpha emitters

International Nuclear Information System (INIS)

Haque, A.K.M.M.; Al-Affan, I.A.M.

1987-01-01

The radiation dose to the lungs due to inhalation of radon daughters has been computed with improved data on lung models, aerosol parameters, deposition and clearance mechanisms. The dose corresponds to mean radon concentration of 23 Bq/m 3 indoors (recent NRPB Survey) for different living conditions. The dose rate to basal cells in gen. 5 is 12 mGy/WLM. (author)

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Science.gov (United States)

Zarogouldis, Paul; Karamanos, Nikos K.; Porpodis, Konstantinos; Domvri, Kalliopi; Huang, Haidong; Hohenforst-Schimdt, Wolfgang; Goldberg, Eugene P.; Zarogoulidis, Konstantinos

2012-01-01

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer. PMID:23109824

Evaluation of expectoration using aerosol inhalation cine-scintigraphy, 2

International Nuclear Information System (INIS)

Ohnuki, Masahiro

1986-01-01

Postural drainage and mechanical vibration have been evaluated in 16 patients of stable chronic obstructive pulmonary diseases with copious sputum (daily sputum volume > 50 ml) using aerosol cine-scintigraphy. After inhalation of a 99m Tc-Milli MISA aerosol, the removal of radioactivity from total lung field and selected peripheral lung region was measured during 40 min of (1) resting in the upright position (control), (2) postural drainage (PD), (3) postural drainage with mechanical vibration (PDWV). Compared with the control run, PD significantly improved of mucus clearance on the total lung field (p < 0.001 ∼ 0.01) and peripheral lung region (p < 0.001). However, there was no significant difference between PD and PDWV. Abnormal mucus movement was often recognized, such as stasis at the first carina, main bronchus and trachea, wandering to the lower lung (22.7 %) and regurgitation in the lower lung (50.0 %). The study indicated that postural drainage is an effective form, but mechanical vibration is of no value as an adjunct to postural drainage in the treatment of patients with stable chronic obstructive pulmonary diseases, and it was suggested that there is an adverse effect of postural drainage in the lower lung portion. (author)

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

Science.gov (United States)

Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

2017-05-01

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of

Removal of inhaled industrial mixed oxide aerosols from Beagle dogs by lung lavage and chelation therapy

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Eidson, A.F.; Guilmette, R.A.

1978-01-01

An experiment was conducted in 15 adult Beagle dogs to evaluate lung lavage and chelation therapy for the removal of inhaled particles of mixed actinide oxides. The dogs were divided into three groups of five dogs each. Each group was exposed to an aerosol from a different industrial process. Group 1 was exposed to mixed oxide material which had been calcined at 750 0 C collected from a ball milling process. Group 2 was exposed to mixed oxide material from a centerless grinding operation which had been previously heat treated to 1750 0 C. The third group was exposed to 239 PuO 2 not containing uranium from a V-blending procedure which had been heat treated at 850 0 C. After exposure, three dogs in each group were given ten lung lavages and 18 intravenous injections of calcium trisodium diethylenetriaminepentaacetate (DTPA). All dogs were sacrificed 64 days after inhalation exposure. The tissues were radioanalyzed for plutonium and americium. Fluorimetric analyses for uranium in the tissues are in progress. The urine, feces and lavage fluid are also being analyzed for plutonium, americium and uranium. The distribution of plutonium and americium expressed as percentages of the sacrifice body burden was similar in the tissues of the treated and unteated dogs. The lungs contained most of the radionuclides with a small amount in the liver, skeleton and tracheobronchial lymph nodes. The percentage of the sacrifice body burden of americium and plutonium that was present in the lung was less in the treated dogs and was higher in the TBLN's and skeleton than in the untreated dogs. The ratio of Pu/Am was higher in the lungs than in the original material obtained from the industrial sites suggesting a shorter retention time for americium than plutonium to 64 days in the dog

Radioaerosol inhalation lung scintigraphy in bronchial asthma

International Nuclear Information System (INIS)

Chiba, Takashi

1993-01-01

A study on obstructive changes in airways and mucociliary clearance in children and youth with bronchial asthma was performed. Radioaerosol inhalation lung scintigraphies using 99T c-human serum albumin (HSA) were applied to 50 children and youth with bronchial asthma. The deposition patterns of the radioaerosol and aerosol clearance curves were evaluated. Abnormal deposition patterns, which consisted of non-homogeneous distribution and/or hot spot formation, were likely to be seen in patients with asthmatic attacks at the time of measurements. However, a few asymptomatic patients also revealed abnormal deposition patterns. The deposition patterns were related to FEV 1.0 %, MMF, V 50 and V 25 , but especially to FEV 1.0 %. As an index of mucociliary clearance, β, the rate constant of the 99m Tc-HSA aerosol clearance curve, was introduced. β was significantly lower in patients with abnormal aerosol deposition patterns than in normal persons. β was also significantly lower in patients undergoing asthmatic attack at the time of the measurements than in asymptomatic patients. β correlated negatively with FEV 1.0 %, MMF, V 50 and V 25 , but especially with FEV 1.0 %. Although patients with long term affection or moderate-to-severe asthma tended to reveal abnormal deposition patterns and had low β values, these differences were not statistically significant. Radioaerosol inhalation lung scintigraphy with 99m Tc-HSA is useful for evaluating not only obstructive changes in the airways but also for evaluating mucociliary clearance in children with bronchial asthma. (author)

Radioaerosol inhalation lung imaging for the diagnosis of chronic obstructive pulmonary diseases in Thailand. Final report for the period 10 December 1987 - 15 December 1993

Energy Technology Data Exchange (ETDEWEB)

Buachum, V [Chulalongkorn Univ., Bangkok (Thailand). Nuclear Medicine Div.

1993-12-01

The radionuclide pulmonary function studies such as aerosol inhalation lung imaging, mucociliary clearance and pulmonary epithelial were developed and studied in normal and chronic obstructive pulmonary disease. The results of the aerosol inhalation lung imaging in 71 cases of COPD revealed that the aerosol inhalation lung scan was the most sensitive test for the diagnosis of early COPD as compared to the chest X-ray, vascular perfusion lung scan and spirometric test (% FEVI). The aerosol and perfusion lung scan were also performed in 21 cases of carcinoma of lung who had been treated with external radiation or chemotherapy. The result of study revealed 5 patients died during treatment, 5 patients were slightly improved, no significant change was detected in 10 cases and deterioration was found in one patient. The lung scintigraphy was studied in 15 cases of well differentiated carcinoma of thyroid with pulmonary metastasis who had I-131 treatment. The study showed that the radioactive iodine treatment dose had minimal effect on the post treatment lung imaging study. The perfusion and aerosol study in 15 cases of operated patients revealed no evidence of pulmonary embolism in post operative study. Abnormal vascular disease or pulmonary embolism was observed in one patient preoperatively. 12 refs, 13 figs, 13 tabs.

Radioaerosol inhalation lung imaging for the diagnosis of chronic obstructive pulmonary diseases in Thailand. Final report for the period 10 December 1987 - 15 December 1993

International Nuclear Information System (INIS)

Buachum, V.

1993-12-01

The radionuclide pulmonary function studies such as aerosol inhalation lung imaging, mucociliary clearance and pulmonary epithelial were developed and studied in normal and chronic obstructive pulmonary disease. The results of the aerosol inhalation lung imaging in 71 cases of COPD revealed that the aerosol inhalation lung scan was the most sensitive test for the diagnosis of early COPD as compared to the chest X-ray, vascular perfusion lung scan and spirometric test (% FEVI). The aerosol and perfusion lung scan were also performed in 21 cases of carcinoma of lung who had been treated with external radiation or chemotherapy. The result of study revealed 5 patients died during treatment, 5 patients were slightly improved, no significant change was detected in 10 cases and deterioration was found in one patient. The lung scintigraphy was studied in 15 cases of well differentiated carcinoma of thyroid with pulmonary metastasis who had I-131 treatment. The study showed that the radioactive iodine treatment dose had minimal effect on the post treatment lung imaging study. The perfusion and aerosol study in 15 cases of operated patients revealed no evidence of pulmonary embolism in post operative study. Abnormal vascular disease or pulmonary embolism was observed in one patient preoperatively. 12 refs, 13 figs, 13 tabs

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung.

Science.gov (United States)

Darquenne, Chantal; Fleming, John S; Katz, Ira; Martin, Andrew R; Schroeter, Jeffry; Usmani, Omar S; Venegas, Jose; Schmid, Otmar

2016-04-01

Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.

Whole-body nanoparticle aerosol inhalation exposures.

Science.gov (United States)

Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

2013-05-07

Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is sampling flowrate (m(3)/min), and t is the sampling

Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

Energy Technology Data Exchange (ETDEWEB)

Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

1987-01-01

Biological clearance half-lives (Tsub(b)) of different /sup 99/Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values.

Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

International Nuclear Information System (INIS)

Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

1987-01-01

Biological clearance half-lives (Tsub(b)) of different 99 Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values. (author)

Biological alterations resulting from chronic lung irradiation. II. Connective tissue alterations following inhalation of 144Ce fused clay aerosol in beagle dogs

International Nuclear Information System (INIS)

Pickrell, J.A.; Harris, D.V.; Pfleger, R.C.; Benjamin, S.A.; Belasich, J.J.; Jones, R.K.; McClellan, R.O.

1975-01-01

Beagle dogs were exposed by inhalation to an aerosol of 144 Ce clay to quantitate the relationship between pulmonary radiation dose and induced fibrosis. Collagen, elastin, glucosamine, and the ratios of elastin/collagen, hydroxyproline/hydroxylysine, and hydroxyproline/proline were determined to indicate changes in connective tissue constituents. Total lung collagen was partitioned into native collagen, soluble collagen, and ultrafilterable hydroxyproline peptides. Increased total lung collagen correlated best with increasing cumulative radiation dose and increasing time after inhalation exposure. The increase in total lung collagen was not seen until more than 4 mo after exposure and a cumulative dose of about 40,000 rad. Soluble collagen and low molecular weight hydroxyproline peptide quantities both increased at 2 mo after exposure and cumulative doses of 20,000 to 27,000 rad. A variable elastin response apparently was not related to either increasing time or increasing radiation dose after exposure. These results indicate that collagen accumulation is an important factor in pulmonary fibrosis. Although collagen synthesis and breakdown were both activated at a relatively early time after inhalation, a significant increase in native collagen (scarring) occurred only when the metabolic balance was altered by protracted time or irradiation after exposure. The interrelationships observed in this study provide insight into the mechanism of fibrosis induced by chronic pulmonary injury. (U.S.)

Tumor production in Syrian hamsters following inhalation of PuO2--ZrO2 aerosol

International Nuclear Information System (INIS)

Thomas, R.G.; Smith, D.M.

1978-01-01

Syrian golden hamsters of both sexes were exposed to aerosols of ZrO 2 containing PuO 2 . The starting material in the aerosol generator also had a small amount of 57 Co added as a tracer. The mixture of all three constituents was nebulized and the droplets passed through a heating column at 1000 0 C. Aerosol sampling was accomplished with a cascade impactor and electrostatic precipitator. The median aerodynamic diameters in all inhalation runs were approximately 2 μm with a geometric standard deviation of 2. One exposed group of 60 hamsters had 6-day lung burdens averaging 100 nCi. This group had a lung tumor incidence of 44% with an even distribution of adenomas and carcinomas. Two other groups had average 6-day lung burdens of 80 to 90 nCi plus 55 nCi of intravenously injected spheres localized in the lung. These animals had tumor incidences of approximately 30%

Administration of cyclosporine by inhalation: A feasibility study in Beagle dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Hoover, M.D.; Haley, P.J.; Snipes, M.B.; Wolff, R.K.; Yeh, H.C.; Griffith, B.P.; Burckart, J.; Mauderly, J.L.

1988-01-01

Oral cyclosporine inhibits the primary,but-not the secondary immune responses in the lung. These findings suggest that the local administration of cyclosporine by inhalation could be a useful tool for increasing our understanding of lung immunity. Five dogs were each treated with inhaled, oral and intravenous cyclosporine, aerosol vehicle (ethyl alcohol), and no treatment, over a 5-wk period. One treatment per week was given to each dog. A radiolabel, 99m Tc was included in the cyclosporine aerosol to allow visualization of lung distribution of the aerosol. Blood plasma concentrations of cyclosporine were approximately the same at 4 h and were essentially cleared by 24 h for all routes of administration. Aerosol distribution in the lung appeared uniform, based on 99m Tc scintigrams. In a second study, two dogs inhaled cyclosporine once a day for five days, two dogs inhaled the aerosol vehicle, and one dog was not treated. No evidence of acute lung injury, based on cell counts, total protein, alkaline phosphatase, or lactic dehydrogenase levels in the bronchoalveolar lavage fluid, was found at 24 h after one or five administrations of cyclosporine. These data indicate that cyclosporine administered by aerosol either once or five times was distributed throughout the lung and was absorbed into the blood without producing an acute inflammatory reaction in the lung. Our results suggest that cyclosporine may be safely given by inhalation for studies of local immune responses in the lung. (author)

Lung delivery of aerosolized dextran.

Science.gov (United States)

Finlay, W H; Lange, C F; King, M; Speert, D P

2000-01-01

The ability of nebulizers to deliver dextran (nominal molecular mass, 4,000 g/mol) to the lung as an inhaled aerosol is evaluated by in vitro experimental methods and mathematical models. Dextran in isotonic saline was aerosolized by four nebulizer types (Pari LC STAR, Hudson T-Updraft II, Acorn II, and Sonix 2000) at dextran concentrations phase Doppler anemometry, filter collection, osmometry, and gravimetry. Mathematical models were used to estimate amounts of the characterized aerosols depositing in the different regions of lung models, and mathematical models of mucous thickness were then developed to estimate initial concentrations of the depositing dextran in the mucus of each conducting airway generation. Models of three subjects (4 yr old, 8 yr old, and adult) were used. The high viscosity of the dextran solutions tested (up to seven times that of water) negatively impacts nebulization, and results in poor performance with most delivery systems tested. Our results suggest that airway mucosal dextran concentrations associated with efficacy in previous animal and in vitro models are achievable with reasonable delivery times (

Fatal accidental inhalation of brake cleaner aerosols.

Science.gov (United States)

Veit, F; Martz, W; Birngruber, C G; Dettmeyer, R B

2018-04-23

Brake cleaner liquid is commonly used for cleaning of engines and motor parts. The commercially available products usually contain mainly volatile organic compounds. As a consequence brake cleaner evaporates fast and almost completely from the cleaned surface. This case report presents a fatal accidental inhalation of brake cleaner liquid aerosols due to the attempted cleaning of a boat engine. A 16year old boy was found lifeless in the engine compartment of a boat engine. In close proximity to the body, the police found cleanings wipes soaked with brake cleaner as well as a pump spray bottle filled with brake cleaner. Essentially the autopsy revealed a cerebral oedema with encephalomalacia, no coagulated blood as well as increased blood and tissue fluid content of the lung. Toxicological analysis revealed brake cleaner fluid in the lung, gastric content and heart blood. Copyright © 2018 Elsevier B.V. All rights reserved.

Inhaler devices - from theory to practice

DEFF Research Database (Denmark)

Sanchis, Joaquin; Corrigan, Chris; Levy, Mark L

2013-01-01

This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...

Bio-mathematical models for radon daughters inhalation. The ModeLung software

International Nuclear Information System (INIS)

Tomulescu, Vlad C.; Rusu, Mircea

2002-01-01

Radon and its decay daughters are the most important sources for natural irradiation of population. ModeLung software is based on the human respiratory tract compartment model and is computing radiation doses on several internal organs and tissues for subjects inhaling radon daughters attached to aerosols. Radiation doses are presented for several subjects performing different types of activity under specific environmental conditions. (authors)

The effect of varying physical and chemical characteristics of inhaled plutonium aerosols on metabolism and excretion

International Nuclear Information System (INIS)

Mewhinney, J.A.; Muggenburg, B.A.; McClellan, R.O.; Miglio, J.J.

1976-01-01

The effects of different chemical and physical parameters of plutonium aerosols on lung retention, tissue distribution and excretion patterns were evaluated in beagle dogs. Polydisperse aerosols of 239 Pu of different chemical form were produced by heating droplets nebulized from a solution of 239 PuIV in 1M HC1 to temperatures ranging from 325 0 C to 1150 0 C. Droplets containing 238 Pu(OH) 4 were treated at 1150 0 C and the resultant polydisperse aerosol used or separated into monodisperse size groups. Beagle dogs were exposed by inhalation to provide initial lung burdens in the range of 0.75 to 1.0μCi. The aerosols were characterized as to particle size and size distribution, and an in-vitro solubility measurement was made on samples of the aerosol from each animal exposure. Different production temperatures for the 239 Pu aerosols resulted in lung retention half-times that increased as the production temperature increased. The 239 Pu tissue distribution and urinary excretion patterns were correlated with lung retention. Faecal excretion was greater for aerosols produced at lower temperatures. Lung retention half-times for 238 Pu monodisperse aerosols were not greatly different from particle sizes of 0.8 and 1.9μm activity median aerodynamic diameter (AMAD). The third monodisperse aerosol intended to be 3.0μm AMAD had a bimodal particle size distribution and contained a significant fraction of readily soluble material. The 238 Pu polydisperse aerosol had a slightly lower lung retention, increased urinary excretion and translocation to tissues than the comparable 239 Pu polydisperse material. This study serves to emphasize the importance of complete analysis of the aerosol material as well as early excretion data following accidental human exposure to aerosols containing plutonium. The role of chemical form and aerosol particle size in evaluation of such cases is discussed. (author)

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment

Energy Technology Data Exchange (ETDEWEB)

Winkler-Heil, R.; Hofmann, W. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Hussain, M. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Higher Education Commission of Pakistan, Islamabad (Pakistan)

2015-05-15

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM{sup -1}. If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas. (orig.)

Radioaerosol Inhalation Lung Scan in Pulmonary Emphysema

Energy Technology Data Exchange (ETDEWEB)

Jeon, Jeong Soo; Park, Yong Ha; Kyo, Chung Soo; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

1990-07-15

Perfusion and ventilation imagings of the lung are well established procedure for diagnosing pulmonary embolism, differentiation it from chronic obstructive lung disease, and making an early detection of chronic obstructive lung disease. To evaluate the usefulness of radioaerosol inhalation imaging (RII) in chronic obstructive lung disease, especially pulmonary emphysema, we analyzed RIIs of five normal adult non-smokers, five asymptomatic smokers (age 25-42 years with the mean 36), and 21 patients with pulmonary emphysema (age 59-78 years with the mean 67). Scintigrams were obtained with radioaerosol produced by a BARC nebuliser with 15 mCi of {sup 99m}Tc-phytate. Scanning was performed in the anterior, posterior, and lateral projections after five to 10-minute inhalation of the radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function studies and chest radiographs. Also lung perfusion scan with {sup 99m}Tc-MAA was performed in 12 patients. In five patients, we performed follow-up scans for the evaluation of the effects of a bronchodilator. Based on the X-ray findings and clinical symptoms, pulmonary emphysema was classified into four types: centrilobular (3 patients), panlobular (4 patients), intermediate (10 patients), and combined (4 patients). RII findings were patternized according to the type, extent, and intensity of the aerosol deposition in the central bronchial and bronchopulmonary system and lung parenchyma. 10 controls, normal five non-smokers and three asymptomatic smokers revealed homogeneous parenchymal deposition in the entire lung fields without central bronchial deposition. The remaining two of asymptomatic smokers revealed mild central airway deposition. The great majority of the patients showed either central (9/21) or combined type (10/21) of bronchopulmonary deposition and the remaining two patients peripheral bronchopulmonary deposition. Parenchymal aerosol deposition in pulmonary

Radioaerosol Inhalation Lung Scan in Pulmonary Emphysema

International Nuclear Information System (INIS)

Jeon, Jeong Soo; Park, Yong Ha; Chung Soo Kyo; Bahk, Yong Whee

1990-01-01

Perfusion and ventilation imagings of the lung are well established procedure for diagnosing pulmonary embolism, differentiation it from chronic obstructive lung disease, and making an early detection of chronic obstructive lung disease. To evaluate the usefulness of radioaerosol inhalation imaging (RII) in chronic obstructive lung disease, especially pulmonary emphysema, we analyzed RIIs of five normal adult non-smokers, five asymptomatic smokers (age 25-42 years with the mean 36), and 21 patients with pulmonary emphysema (age 59-78 years with the mean 67). Scintigrams were obtained with radioaerosol produced by a BARC nebuliser with 15 mCi of 99m Tc-phytate. Scanning was performed in the anterior, posterior, and lateral projections after five to 10-minute inhalation of the radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function studies and chest radiographs. Also lung perfusion scan with 99m Tc-MAA was performed in 12 patients. In five patients, we performed follow-up scans for the evaluation of the effects of a bronchodilator. Based on the X-ray findings and clinical symptoms, pulmonary emphysema was classified into four types: centrilobular (3 patients), panlobular (4 patients), intermediate (10 patients), and combined (4 patients). RII findings were patternized according to the type, extent, and intensity of the aerosol deposition in the central bronchial and bronchopulmonary system and lung parenchyma. 10 controls, normal five non-smokers and three asymptomatic smokers revealed homogeneous parenchymal deposition in the entire lung fields without central bronchial deposition. The remaining two of asymptomatic smokers revealed mild central airway deposition. The great majority of the patients showed either central (9/21) or combined type (10/21) of bronchopulmonary deposition and the remaining two patients peripheral bronchopulmonary deposition. Parenchymal aerosol deposition in pulmonary emphysema was

Quantification of inhaled aerosol particles composed of toxic household disinfectant using radioanalytical method.

Science.gov (United States)

Shim, Ha Eun; Lee, Jae Young; Lee, Chang Heon; Mushtaq, Sajid; Song, Ha Yeon; Song, Lee; Choi, Seong-Jin; Lee, Kyuhong; Jeon, Jongho

2018-05-25

To assess the risk posed by a toxic chemical to human health, it is essential to quantify its uptake in a living subject. This study aims to investigate the biological distribution of inhaled polyhexamethylene guanidine (PHMG) aerosol particle, which is known to cause severe pulmonary damage. By labeling with indium-111 ( 111 In), we quantified the uptake of PHMG for up to 7 days after inhalation exposure in rats. The data demonstrate that PHMG is only slowly cleared, with approximately 74% of inhaled particles persisting in the lungs after 168 h. Approximately 5.3% of inhaled particles were also translocated to the liver after 168 h, although the level of redistribution to other tissues, including the kidneys and spleen, was minimal. These observations suggest that large uptake and slow clearance may underlie the fatal inhalation toxicity of PHMG in humans. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lung epithelial permeability and inhaled furosemide. Added dimensions in asthmatics

International Nuclear Information System (INIS)

Bhure, U.N.; Bhure, S.U.; Bhatt, B.M.; Mistry, S.; Pednekar, S.J.; Chari, V.V.; Desai, S.A.; Joshi, J.M.; Paidhungat, A.J.

2009-01-01

Lung clearance rates of inhaled 99m Tc-diethylene-triamine-pentaacetic acid (DTPA) aerosols constitute a sensitive index to evaluate the permeability changes characteristic of airway epithelial damage. It was thought that edema of the airway wall which is reported in asthma could be relieved with a diuretic like furosemide, helping to relieve the symptoms. We intended to study the effect of inhaled furosemide on lung epithelial permeability in asthmatics and smokers with the help of 99m Tc-DTPA lung clearance test (LCT). The study included three groups (n=15), viz. normal healthy controls, asymptomatic chronic smokers, and chronic persistent asthmatics. Each subject underwent the LCT twice, baseline and post-furosemide (Lasix) study, within a week's interval. The post-furosemide study was carried out 15 min after inhalation of 10 mg of lasix. Lung epithelial permeability was determined in terms of clearance half-life (T 1/2 ). The baseline mean T 1/2 values for controls, smokers, and asthmatics were 50.95±16.58, 20.81±5.47, 24.06±6.19 min, respectively. Post-lasix T 1/2 values were 50.83±15.84, 20.70±5.65, 41.27±15.07 min, respectively. There was a significant difference (P<0.001) in baseline and post-lasix clearance values in asthmatics only. Baseline lung epithelial permeability was altered in smokers and asthmatics compared to the controls. Furosemide was effective only in asthmatics in reverting the permeability almost back to the normal range. Inhaled furosemide was effective even in moderate and severe asthmatics. Furosemide has multiple mechanisms of action. It possibly acts at bronchial level in view of the pathology in asthmatics lying in the airways. (author)

Deposition of inhaled LMFBR-fuel-sodium aerosols in beagle dogs

International Nuclear Information System (INIS)

Hackett, P.L.; Mahlum, D.D.; Briant, J.K.; Catt, D.L.; Peters, L.R.; Clary, A.J.

1980-01-01

Initial alveolar deposition of LMFBR-fuel aerosols in beagle dogs amounted to 30% of the inhaled activity, but only 5% of the total inhaled activity was deposited in dogs exposed to sodium-fuel aerosols. Aerosol deposition in the gastrointestinal tract amounted to 4% of the initial body burden of fuel-aerosol exposed dogs and 24% of the burden of animals receiving sodium-fuel aerosols. Preliminary analytical data for the dog exposures appear to agree with rodent data for deposition and distribution patterns of aerosols of similar sodium: fuel ratios

Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

Science.gov (United States)

Duan, Jinghua; Vogt, Frederick G; Li, Xiaojian; Hayes, Don; Mansour, Heidi M

2013-01-01

The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. PMID:24092972

Total and regional deposition of inhaled aerosols in supine healthy subjects and subjects with mild-to-moderate COPD

Energy Technology Data Exchange (ETDEWEB)

Darquenne, Chantal; Lamm, Wayne J.; Fine, Janelle M.; Corley, Richard A.; Glenny, Robb W.

2016-09-01

Despite substantial development of sophisticated subject-specific computational models of aerosol transport and deposition in human lungs, experimental validation of predic- tions from these new models is sparse. We collected aerosol retention and exhalation profiles in seven healthy volunteers and six subjects with mild-to-moderate COPD (FEV1 ¼ 50–80%predicted) in the supine posture. Total deposition was measured during continuous breathing of 1 and 2.9 mm-diameter particles (tidal volume of 1 L, flow rate of 0.3 L/s and 0.75 L/s). Bolus inhalations of 1 mm particles were performed to penetration volumes of 200, 500 and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and mode shift (MS) were calculated from these data. There was no significant difference in total deposition between healthy subjects and those with COPD. Total deposition increased with increasing particle size and also with increasing flow rate. Similarly, there was no significant difference in aerosol bolus deposition between subject groups. Yet, the rate of increase in dispersion and of decrease in MS with increasing penetration volume was higher in subjects with COPD than in healthy volunteers (H: 0.79870.205 vs. 0.52770.122 mL/mL, p¼ 0.01; MS: - 0.27170.129 vs. - 0.145 70.076 mL/mL, p¼ 0.05) indicating larger ventilation inhomogeneities (based on H) and increased flow sequencing (based on MS) in the COPD than in the healthy group. In conclusion, in the supine posture, deposition appears to lack sensitivity for assessing the effect of lung morphology and/or ventilation distribution alteration induced by mild-to- moderate lung disease on the fate of inhaled aerosols. However, other parameters such as aerosol bolus dispersion and mode shift may be more sensitive parameters for evaluating models of lungs with moderate disease.

Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials

Directory of Open Access Journals (Sweden)

Fischer A

2009-12-01

Full Text Available Abstract In the treatment of pulmonary diseases the inhalation of aerosols plays a key role - it is the preferred route of drug delivery in asthma, chronic obstructive pulmonary disease (COPD and cystic fibrosis. But, in contrast to oral and intravenous administration drug delivery to the lungs is controlled by additional parameters. Beside its pharmacology the active agent is furthermore determined by its aerosol characteristics as particle diameter, particle density, hygroscopicity and electrical charge. The patient related factors like age and stage of pulmonary disease will be additionally affected by the individual breathing pattern and morphometry of the lower airways. A number of these parameters with essential impact on the pulmonary drug deposition can be influenced by the performance of the inhalation system. Therefore, the optimization of nebulisation technology was a major part of aerosol science in the last decade. At this time the control of inspiration volume and air flow as well as the administration of a defined aerosol bolus was in the main focus. Up to date a more efficient and a more targeted pulmonary drug deposition - e.g., in the alveoli - will be provided by novel devices which also allow shorter treatment times and a better reproducibility of the administered lung doses. By such means of precise dosing and drug targeting the efficacy of inhalation therapy can be upgraded, e.g., the continuous inhalation of budesonide in asthma. From a patients' perspective an optimized inhalation manoeuvre means less side effects, e.g., in cystic fibrosis therapy the reduced oropharyngeal tobramycin exposure causes fewer bronchial irritations. Respecting to shorter treatment times also, this result in an improved quality of life and compliance. For clinical trials the scaling down of dose variability in combination with enhanced pulmonary deposition reduces the number of patients to be included and the requirement of pharmaceutical

Generation and characterization of cyclosporine aerosols for administration by inhalation

International Nuclear Information System (INIS)

Hoover, M.D.; Muggenburg, B.A.; Snipes, M.B.; Wolff, R.K.; Yeh, H.C.; Griffith, B.P.; Burckart, G.J.; Mauderly, J.L.

1988-01-01

A method was developed for generating aerosols of the immunosuppressive agent cyclosporine and a gamma-emitting radiolabel ( 99m Tc) for administration by inhalation. Cyclosporine was dissolved in ethyl alcohol (EtOH) and nebulized with a Love- lace nebulizer operated with 50 psi compressed air. For a cyclosporine concentration of 25 mg/mL, the particle size of the aerosol was 0.7 μm activity median aerodynamic diameter (AMAD), with 1.8 geometric standard deviation (GSD). The clear solution of EtOH and cyclosporine became a cloudy suspension when a limited amount of saline solution containing a 99m Tc radiolabel was added. This occurred because cyclosporine is hydrophobic. If saline concentrations as high as 6% in EtOH by volume were used, a gummy residue formed in the nebulizer and the particle aerodynamic diameter became unacceptably large (4.7 μm). When the saline concentration was only 3 % (the minimum radiolabel volume needed for gamma camera studies of lung deposition), the suspensions of cyclosporine could be nebulized to give a particle size of 2.2 μm AMAD with 2.1 GSD. The radiolabel was uniformly distributed with the spherical cyclosporine particles. Concentrations and particle size distributions remained constant over 1-h generation periods. These aerosols have been used in inhalation studies with Beagle dogs. (author)

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition.

Science.gov (United States)

Sørli, Jorid B; Huang, Yishi; Da Silva, Emilie; Hansen, Jitka S; Zuo, Yi Y; Frederiksen, Marie; Nørgaard, Asger W; Ebbehøj, Niels E; Larsen, Søren T; Hougaard, Karin S

2018-01-01

Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21 impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if the products inhibited surfactant function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e., the in vitro method predicted all the products that were toxic for mice to inhale. The specificity of the in vitro test was 63%, i.e., the in vitro method found three false positives in the 21 tested products. Six of the products had been involved in accidental human inhalation where they caused acute inhalation toxicity. All of these six products inhibited lung surfactant function in vitro and were toxic to mice.

Lung Deposition Calculations for Radioactive Aerosol Particles Originating from Caves and Uranium Mines

International Nuclear Information System (INIS)

Alfoldy, B.; Torok, Sz.; Winkler, R.

2001-01-01

Full text: The present study simulates lung deposition of radioactive aerosol particles originating from the atmosphere of a therapeutic cave (Szemlohegyi cave, Budapest) and several uranium mines. Particle deposition patterns and surface densities have been calculated by the stochastic lung model of Koblinger and Hofmann. In the model, deposition can be caused by the simultaneous effects of Brownian motion, inertial impaction and gravitational settling. The calculations were carried out by considering the aerosol particle size distribution and radon concentration of the atmosphere of the cave and mines. The deposition was computed in the whole lung, in characteristic parts of the respiratory system such as extrathoracic, tracheobronchial, acinar and alveolar regions and in the singe airway generations at different flow rates for adults. The adverse health effects of inhaled radionuclides strongly depend from the local deposition density values in cellular dimensions. Thus we will built in the results to a cellular effects model of Balashazy and Hofmann for the simulation of the pathological effects of inhaled radionuclides for risk assessment. (author)

A study of the behaviour of 0.5 μm aerosol particles in the human lung

International Nuclear Information System (INIS)

Subba Ramu, M.C.

1974-01-01

The evaluation of the tissue dose of inhaled aerosol particles (including radioactive particles) requires a study of the behaviour of particles in the human lung. Half-micron particles (unit density spheres) of di-2-ethyl hexyl subacate have been used for carrying out the study since their deposition is mostly in the pulmonary region and they are good tracers of air flow in the lung. The deposition measured is the lowest reported so far and is affected by physiological parameters like the tidal volume, the breathing frequency and the resting expiratory level. Steady-state and single-breath aerosol experiments show that the particles inhaled remain airborne in the lung during several breaths and support the view that mechanical mixing is completely absent in the alveolated airways of the lung. Studies of the effect of breath-holding on the deposition of 0.5 μm particles in the lung show that these particles may be used for the calculation of the diameter of the alveolar space in life. (author)

Improvements in lung lavage to increase its effectiveness in removing inhaled radionuclides

International Nuclear Information System (INIS)

Muggenburg, B.A.; Guilmette, R.A.; Romero, L.M.; Mewhinney, J.A.

1991-01-01

Lung lavage has been shown to be an effective method to remove insoluble radionuclides deposited and retained in the lung, but the treatment has been limited to the effective removal of only about 50% of the retained material. Reported here is change in lavage technique that slightly increases the effectiveness and the addition of high-frequency chest wall oscillation. The latter increased the effectiveness of the lavage procedure but also caused significant physiological complications. These studies were conducted in adult male and female beagles. The aerosol in the first study was 239 PuO 2 heat-treated at 850 degrees C, obtained as powder from a commercial V-blending process. The dogs briefly inhaled the aerosol per nasi. The tissue content at death and the amount of 239 Pu excreted and in the recovered lung lavage fluid was determined by radiochemical methods 5 . These values were used to reconstruct the initial pulmonary burden of 239 and the amount of 239 Pu removed by lavage. In the second study, with the HFCWO, the aerosol was 85 Sr fused in aluminosilicate particles. The IPB of 85 Sr was determined by whole-body counting. The excreta and recovered lung lavage fluids were also assayed for 85 Sr activity

Using 99mTc-DTPA radioaerosol inhalation lung scan as compared with computed tomography to detect lung injury in blunt chest trauma

International Nuclear Information System (INIS)

Esme, H.; Kaya, E.; Solak, O.; Yavuz, Y.; Yurumez, Y.; Sezer, M.

2007-01-01

Detection of pulmonary contusion in patients with blunt chest trauma is very important so as to commence therapy immediately to avoid irreversible damage. The purpose of our study was to evaluate the efficacy of technetium-99m diethylene triamine penta-acetic acid ( 99m Tc-DTPA) aerosol inhalation lung scintigraphy in comparison with chest computed tomography (CT) in the diagnosis of pulmonary contusion at acute blunt chest trauma. Twenty-nine patients with isolated blunt chest trauma were referred to the emergency department of our hospital, and nine healthy people participated in this study. Sixteen patients who had pulmonary contusion on CT scans were referred to as group 1, and 13 patients who had normal CT scans as group 2. Nine healthy people comprised a control group. 99m Tc-DTPA aerosol inhalation lung scintigraphy was performed on the first day in all patients. The mean half time (T 1/2 ) and penetration index values of 99m Tc-DTPA clearance were significantly lower in groups 1 and 2 compared with the control group. Among the three groups, there were no significant differences in arterial blood gas analysis except for PO 2 . The mean T 1/2 value of 99m Tc-DTPA clearance did correlate with PO 2 values but not with pH, PCO 2 , or HCO 3 values. 99m Tc-DTPA radioaerosol inhalation lung imaging may serve as a useful adjunct and supportive method to chest CT scanning for detecting mild pulmonary contusion. (author)

Inhalation toxicology of industrial plutonium and uranium oxide aerosols II. Deposition, retention and dosimetry

International Nuclear Information System (INIS)

Stanley, J.A.; Eidson, A.F.; Mewhinney, J.A.; Mo, T.

1978-01-01

A series of studies has been initiated in which powdered fuel materials obtained at industrial sites have been aerosolized in the dry state for the inhalation exposure of Fischer-344 rats, Beagle dogs and Cynomolgus monkeys to evaluate the potential biological hazard of such accidents. The materials chosen for study were 750 deg. C heat-treated mixed PuO 2 and UO 2 obtained from a ball milling process and 1750 deg. C heat-treated (U,Pu)O 1.97 powder obtained from the centerless grinding of fuel pellets. Care was taken to insure that the regenerated aerosols used in animal inhalation exposures had similar particle size and size distribution characteristics to those measured during glove box sampling at the industrial plant. The deposition, retention, distribution and excretion of these materials are being studied, using serial sacrifice of animals at times from 4 hours to several years after inhalation exposure. Periodic excreta samples are collected on all animals. Biological samples are analyzed to yield data on Pu, Am and U content. Data from animals sacrificed up to one year will be presented. The retention of 239 Pu and 241 Am in the lung and their subsequent clearance and translocation to other tissues such as liver, skeleton and tracheobronchial lymph nodes will be discussed in relation to the influence of species and of the physical chemical properties of the exposure aerosol. (author)

Late effects following inhalation of mixed oxide (U,PuO2) mox aerosol in the rat

International Nuclear Information System (INIS)

Griffiths, N.; Van Der Meeren, A.; Fritsch, P.; Maximilien, R.

2008-01-01

Exposure to alpha-emitting particles is a potential long-term health risk to workers in nuclear fuel fabrication plants. Mixed Oxide (MOX: U,PuO 2 ) fuels containing low percentages of plutonium obtained from spent nuclear fuels are increasingly employed and in the case of accidental contamination by inhalation or wounds may result in the development of late-occurring pathologies such as lung cancer. However the long term risks particularly with regard to lung cancer are to date unclear. In the case of MOX the risk may indeed be different from that assigned to the individual components, plutonium and uranium. Several factors are influential (i) the dissolution of Pu depends on the physico-chemical properties, for example risk of lung cancer is increased 10 fold after Pu(NO 3 ) 2 as compared with PuO 2 . (ii) The solubility of Pu is variable whether delivered as PuO 2 or contained within MOX. (iii) The risk of cancer appears to increase with spatial homogeneity of the lung alpha dose. The objective of this study was to investigate the long term effects in rat lungs following MOX aerosol inhalation of similar particle size containing 2.5 or 7.1% Pu. Conscious rats were exposed to MOX aerosols using a 'nose-only' system and kept for their entire life (2-3 years). Different Initial Lung Deposits (ILDs) were obtained using different concentrations of the MOX suspension. Lung total alpha activity was determined in vivo at intervals over the study period by external counting as well as at autopsy in order to estimate the total lung dose. Anatomo-pathological and immunohistochemical analyses were performed on fixed lung tissue after euthanasia. The frequencies of lung pathologies and tumours were determined on lung sections at several different levels. In addition, autoradiography of lung sections was performed in order to assess the spatial localisation of a activity. Inhalation of MOX at ILD ranging from 1-20 kBq resulted in lung pathologies (90% of exposed rats

Antagonist effect of interferon-γ aerosol inhalation on pulmonary remodeling after γ-ray irradiation

International Nuclear Information System (INIS)

Li Ming; Song Liangwen; Wang Shaoxia; Diao Ruiying; Xu Xinping; Luo Qingliang

2008-01-01

Objective: To observe the antagonistic effect of interferon-y aerosol inhalation on pulmonary remodeling after γ-ray irradiation, and explore its mechanisms. Methods: The Wistar rats were randomly divided into irradiation control group and irradiation + Interferon-γ antagonist group, which proceeded IFN-γ aerosol inhalation 3 days before 20 Gy 60 Co γ-ray irradiation, then were sacrificed at 10, 20, 30 days after irradiation. Conventional histopathological sections of lung tissue were prepared, which were stained immunohistochemically for α-SMA and Sirius red. The contents of collagen IV were determined by Western blot. The expression of MMP-2, MMP-9 and TIMP-1 in lung homogenate was detected by ELISA. Results: The widen degrees of interalveolar septum, the deposition of collagen I, III, and the expression of α-SMA decreased significantly in IFN-γ treatment group as compared with those in the irradiation control group. The expression of collagen IV appeared an elevation trend, but this phenomenon attenuated after IFN-γ was used. The levels of MMP-2 and TIMP-1 decreased 10 days after administration with IFN-γ but the opposite trend appeared for MMP- 9. The expression of MMP-2, MMP-9 and TIMP-1 decreased 30 days after administration with IFN-γ. Conclusion: IFN-γ is effective in alleviating pulmonary injuries induced by irradiation in rats, possibly by decreasing the expression of TIMP-1 to relieve the inhibition to MMP-9, then degrading collagen IV to antagonize remodeling after lung injury. (authors)

Aerosol generation and delivery in medical applications

International Nuclear Information System (INIS)

Soni, P.S.; Raghunath, B.

1998-01-01

It is well established that radioaerosol lung technique by inhalation is a very versatile technique in the evaluation of health effects and medical diagnostic applications, especially to detect chronic obstructive pulmonary diseases, their defence mechanism permeability and many others. Most important part of aerosol technology is to generate reproducibly stable diagnostic radioaerosols of known characteristics. Many compressed air atomisers are commercially available for generating aerosols but they have limited utility in aerosol inhalation, either because of large droplet size, low aerosol output or high airflow rates. There is clearly a need for a versatile and economical aerosol generation/inhalation system that can produce dry labelled aerosol particles with high deep lung delivery efficiency suitable for clinical studies. BARC (Bhabha Atomic Research Centre) has developed a dry aerosol generation/delivery system which operates on compressed air and generates dry polydisperse aerosols. This system is described along with an assessment of the aerosol characteristics and efficiency for diagnosis of various respiratory disorders

Experiment of aerosol-release time for a novel automatic metered dose inhaler

Directory of Open Access Journals (Sweden)

Mingrong Zhang

2016-05-01

Full Text Available The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-deep waveforms were matched within reasonable accuracy. Finally, with the help of dynamic image processing, the aerosol-release time (Tr was carefully measured and fully discussed, including the switch-on time (Ts, the mechatronics-hysteresis (Tm and the intentional-delay (Ti. Under slow-deep inhalation condition which is suitable for metered dose inhaler medicine delivery, the switch-on flow-rate could reach as low as 10 L/min, and the corresponding switch-on time was approximately 0.20 s. While the mechatronics-hysteresis depended on the brand of metered dose inhaler, assuming there was no intentional-delay, the aerosol-release time could be as low as 0.40 and 0.60 s, respectively, for two commercially available metered dose inhalers studied in this article. Therefore, this newly developed mechatronic adapter system could ensure aerosol-release time (Tr within satisfactory range for metered dose inhalers.

MRI contrast enhancement of the lung using a Gd-DTPA aerosol

International Nuclear Information System (INIS)

Bockisch, A.; Harvey, R.C.; Davis, M.A.; Kabalka, G.W.

1993-01-01

A MR imaging study was performed in anesthetized female beagle dogs to investigate the effectiveness of Gd-DTPA aerosol for contrast enhancement in ventilated lungs. Ventilation was performed using a commercially available atomizer to administer Gd-DTPA solution. MR imaging was performed with a 1.9 T whole body imager using respiratory gated acquisition. To define the amount of Gd-DTPA being trapped in the lungs identical experiments were performed with 99m Tc-DTPA. MR imaging confirmed at 70% contrast enhancement following inhalation of Gd-DTPA. Because of the inherently low signal intensity of lung parenchyma the degree of contrast enhancement is not sufficient for clinical application. (orig.) [de

Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung.

Science.gov (United States)

Dolovich, M A

2000-06-01

A number of studies in the literature support the use of fine aerosols of drug, inhaled at low IFRs to target peripheral airways, with the objective of improving clinical responses to inhaled therapy (Fig. 8). Attempts have been made to separate response due to changes in total administered dose or the surface concentration of the dose from response due to changes in site of deposition--both are affected by the particle size of the aerosol, with IFR additionally influencing the latter. The tools for measuring dose and distribution have improved over the last 10-15 years, and thus we should expect greater accuracy in these measurements for assessing drug delivery to the lung. There are still issues, though, in producing radiolabeled (99m)technetium aerosols that are precise markers for the pharmaceutical product being tested and in quantitating absolute doses deposited in the lung. PET isotopes may provide the means for directly labelling a drug and perhaps can offer an alternative for making these measurements in the future, but deposition measurements should not be used in isolation; protocols should incorporate clinical tests to provide parallel therapeutic data in response to inhalation of the drug by the various patient populations being studied.

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy

International Nuclear Information System (INIS)

Cayir, D.; Demirel, K.; Korkmaz, M.; Koca, G.

2011-01-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using technetium-99m-labeled diethylenetriamine pentaacetic acid (Tc-99m DTPA) aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T 1/2 ) of Tc-99m DTPA were calculated. T 1/2 of whole lung was calculated as a mean of the T 1/2 of left and right lung. The T 1/2 values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86±8.44, and 62.14±26.12 min (p=0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function. (author)

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

Science.gov (United States)

Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

2011-10-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

Directory of Open Access Journals (Sweden)

Tongtong Zhang

2018-05-01

Full Text Available Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency. Key words: Curcumin, Dry powder inhaler, Liposome, Primary lung cancer, Pulmonary delivery

Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung

NARCIS (Netherlands)

Wittgen, Bart P. H.; Kunst, Peter W. A.; van der Born, Kasper; van Wijk, Atie W.; Perkins, Walter; Pilkiewicz, Frank G.; Perez-Soler, Roman; Nicholson, Susan; Peters, Godefridus J.; Postmus, Pieter E.

2007-01-01

PURPOSE: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma. EXPERIMENTAL DESIGN: Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory

Influence of lavage therapy on the distribution patterns of inhaled, relatively insoluble particles in the lung

International Nuclear Information System (INIS)

Snipes, M.B.; Runkle, G.E.; Muggenburg, B.A.

1977-01-01

Four Beagle dogs were exposed by inhalation to a polydisperse fused aluminosilicate aerosol labeled with 147 Pm and 169 Yb. The left or right lung of each dog was lavaged one or five times to remove a portion of the lung burden. Autoradiographic and computer techniques were combined to determine the dispersion pattern of radioactive particles still in the lung after lavage therapy. For all four dogs the dispersion pattern of particles in the lung was the same for the lavaged and non-lavaged lung lobes. Examination of the autoradiograms indicated that lavage therapy did not preferentially remove particles from some areas of the lung. The similarity of particle dispersion patterns suggests that a minimal relocation of particles in lung results from lavage therapy

The inhalation of insoluble iron oxide particles in the sub-micron ranges. Part II - Plutonium-237 labelled aerosols

International Nuclear Information System (INIS)

Waite, D.A.; Ramsden, D.

1971-10-01

The results of a series of inhalation studies using iron oxide particles in the size range 0.1 to 0.3 um (count median diameter) are described. In this series the aerosols were labelled with plutonium 237. In vivo detection, excretion analysis and crude location studies were obtainable and the results compared to the earlier studies using chromium 51 labelled aerosols. Plutonium 237 can be considered as a simulator for plutonium 239 and attempts are made to extrapolate the results to the problem of the estimation of plutonium 239 in the human lung. (author)

Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity.

Science.gov (United States)

Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming

2012-05-01

3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer.

A nonhuman primate aerosol deposition model for toxicological and pharmaceutical studies

Energy Technology Data Exchange (ETDEWEB)

Martonen, T.B.; Katz, I.M.; Musante, C.J. [US EPA, Research Triangle Park, NC (USA)

2001-07-01

Nonhuman primates may be used as human surrogates in inhalation exposure studies to assess either the (1) adverse health effects of airborne particulate matter or (2) therapeutic effects of aerosolized drugs and proteins. Mathematical models describing the behavior and fate of inhaled aerosols may be used to complement such laboratory investigations. In this work a mathematical description of the rhesus monkey (Macaca mulatta) lung is presented for use with an aerosol deposition model. Deposition patterns of 0.01- to 5-{mu}m-diameter monodisperse aerosols within lungs were calculated for 3 monkey lung models (using different descriptions of alveolated regions) and compared to human lung results obtained using a previously validated mathematical model of deposition physics. The findings suggest that there are significant differences between deposition patterns in monkeys and humans. The nonhuman primates had greater exposures to inhaled substances, particularly on the basis of deposition per unit airway surface area. However, the different alveolar volumes in the rhesus monkey models had only minor effects on aerosol dosimetry within those lungs. By being aware of such quantitative differences, investigators can employ the respective primate models (human and nonhuman) to more effectively design and interpret the results of future inhalation exposure experiments.

Dosage of DTPA administration by inhalation

International Nuclear Information System (INIS)

Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

2000-01-01

The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

Dosimetry of 239Pu in dogs that inhaled monodisperse aerosols of 239PuO2

International Nuclear Information System (INIS)

Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Mewhinney, J.A.; Seiler, F.A.; Boecker, B.B.; McClellan, R.O.

1987-01-01

Existing data from human exposure cases and experimental animal studies on the fate and dosimetry of inhaled insoluble Pu particles are inadequate to provide a comprehensive description and evaluation of the tissues at risk from the alpha radiations of Pu. To improve our knowledge of the dosimetry of inhaled insoluble 239 PuO 2 , this paper describes the uptake and retention of 239 Pu in the tissues of dogs that received single inhalation exposures to monodisperse aerosols of 239 PuO 2 . These data include times through 3 years after exposure. Using analytical functions fitted to each tissue data set, 1100-day radiation doses were calculated for lung, liver, skeleton, kidney, spleen, and tracheobronchial, mediastinal, sternal, hepatic, mandibular, and retropharyngeal lymph nodes. The dosimetry results suggest that the lung and lymph nodes associated with lymphatic drainage of the respiratory tract are the principal sites of alpha irradiation. However, the doses for the different respiratory tract lymph nodes vary by a factor of 2000, suggesting that assuming equivalent doses to respiratory tract lymph nodes is not appropriate. Other tissues receive radiation doses also but at levels one to three orders of magnitude less than the lung. Particle size dependence on uptake and retention was noted for the skeleton, mediastinal lymph nodes, hepatic lymph nodes, retropharyngeal lymph nodes, and mandibular lymph nodes

Late effects following inhalation of mixed oxide (U,PuO{sub 2}) mox aerosol in the rat; Effets tardifs de l'inhalation d'aerosols de Mox 2,5% ou 7,1% Pu chez le rat

Energy Technology Data Exchange (ETDEWEB)

Griffiths, N.; Van Der Meeren, A.; Fritsch, P.; Maximilien, R

2008-07-01

Exposure to alpha-emitting particles is a potential long-term health risk to workers in nuclear fuel fabrication plants. Mixed Oxide (MOX: U,PuO{sub 2}) fuels containing low percentages of plutonium obtained from spent nuclear fuels are increasingly employed and in the case of accidental contamination by inhalation or wounds may result in the development of late-occurring pathologies such as lung cancer. However the long term risks particularly with regard to lung cancer are to date unclear. In the case of MOX the risk may indeed be different from that assigned to the individual components, plutonium and uranium. Several factors are influential (i) the dissolution of Pu depends on the physico-chemical properties, for example risk of lung cancer is increased 10 fold after Pu(NO{sub 3}){sub 2} as compared with PuO{sub 2}. (ii) The solubility of Pu is variable whether delivered as PuO{sub 2} or contained within MOX. (iii) The risk of cancer appears to increase with spatial homogeneity of the lung alpha dose. The objective of this study was to investigate the long term effects in rat lungs following MOX aerosol inhalation of similar particle size containing 2.5 or 7.1% Pu. Conscious rats were exposed to MOX aerosols using a 'nose-only' system and kept for their entire life (2-3 years). Different Initial Lung Deposits (ILDs) were obtained using different concentrations of the MOX suspension. Lung total alpha activity was determined in vivo at intervals over the study period by external counting as well as at autopsy in order to estimate the total lung dose. Anatomo-pathological and immunohistochemical analyses were performed on fixed lung tissue after euthanasia. The frequencies of lung pathologies and tumours were determined on lung sections at several different levels. In addition, autoradiography of lung sections was performed in order to assess the spatial localisation of a activity. Inhalation of MOX at ILD ranging from 1-20 kBq resulted in lung

Influence of inhaled Ca-DTPA on the long-term effects of inhaled Pu nitrate

International Nuclear Information System (INIS)

Ballou, J.E.; Dagle, G.E.; McDonald, K.E.; Buschbom, R.L.

1975-01-01

Inhaled Ca-DTPA administered to rats in 6 weekly, one-hour treatments of 3 mg/rat did not affect weight gain or life-span compared to Pu burdened animals (78 nCi ILB) or nontreated controls. In addition, the drug did not appear to promote the development of malignant lung tumors and bone tumors in Pu burdened rats although one rat exposed only to Ca-DTPA aerosols did develop a malignant lung tumor. This single lung tumor can not be considered significant although the normal incidence of this lesion is quite low. Inhaled Ca-DTPA therapy administered 20 days after Pu inhalation showed little effect in reducing the lung burden of plutonium. Skeletal deposition was decreased possibly because Ca-DTPA was administered during a time of active translocation of the inhaled Pu when Pu may have been available for chelation in the blood. Inhaled Ca-DTPA therapy did not appear to be beneficial in reducing the number of malignant lung tumors or bone tumors in plutonium burdened rats but on the other hand the chelate did not appear to promote these lesions. (U.S.)

The clearance of Pu and Am from the respiratory system of rodents after the inhalation of oxide aerosols of these actinides either alone or in combination with other metals

International Nuclear Information System (INIS)

Stather, J.W.; James, A.C.; Brightwell, J.; Rodwell, P.

1979-01-01

In this series of studies in rodents the lung clearance and tissue distribution of both plutonium and americium have been measured following their inhalation as mixed actinide oxides either alone or in combination with other metals. The aerosols used were materials to which workers in the nuclear industry may be occupationally exposed or which could be generated in the event of an accident in a reactor core or fuel fabrication plant. The studies showed that, at least for some PuO 2 aerosols, the lung model currently being used by ICRP for estimating tissue doses from inhaled actinides may overestimate, by about a factor of ten, the amount of plutonium translocated to the blood. The presence of oxides of other metals can, however, appreciably influence the clearance of plutonium from the lung. While in some mixtures plutonium dioxide behaves as an insoluble (Class Y) compound and in others as a soluble (Class W) compound, it may also have transportability characteristics between these two extremes. Americium-241 behaves as a soluble (Class W) compound when inhaled as the oxide. However, if it is present in trace quantities in mixed-oxide aerosols its behaviour depends upon that of the materials present in greatest mass. (author)

Influence of elastase-induced emphysema and the inhalation of an irritant aerosol on deposition and retention of an inhaled insoluble aerosol in Fischer-344 rats

International Nuclear Information System (INIS)

Damon, E.G.; Mokler, B.V.; Jones, R.K.

1983-01-01

The purpose of this study was to assess the effects of elastase-induced pulmonary emphysema and the inhalation of an irritant aerosol (Triton X-100, a nonionic surfactant similar to those used in a number of pressurized consumer products) on pulmonary deposition and retention of an insoluble test aerosol, 59 FE-labeled Fe 2 O 3 . Untreated rats or rats pretreated by intratracheal in stillation with elastase were exposed to an aerosol of 59 Fe-labeled Fe 2 O 3 either 18 hr or 7 days after exposure to aerosslized Triton X-100 which was administered in doses of 20, 100, or 200 μg/g of lung. Rats pretreated with elastase had significantly lower pulmonary deposition of 59 Fe than the untreated controls (p 2 O 3 was unaffected by pretreatment with Triton X-100. Elastase treatment alone had no effect on retention of Fe 2 O 3 . Triton X-100 administered 18 hr prior to exposure of rats to Fe 2 O 3 aerosol resulted in dose-related increases in whole-body retention of 59 Fe. When rats were exposed to Triton X-100 7 days before exposure to Fe 2 O 3 , increased retention of 59 Fe was noted only in those treated at the highest Triton X-100 dose level (200 μg/g). 20 references, 5 tables

Design and application of a new modular adapter for laser diffraction characterization of inhalation aerosols

NARCIS (Netherlands)

de Boer, Anne; Gjaltema, D; Hagedoorn, P; Schaller, M; Witt, W; Frijlink, H W

2002-01-01

An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles

Monitoring the Inhalation Flow Rate of Nebulized Aerosols Using an Ultrasonic Flow Meter: In Vitro Assessment.

Science.gov (United States)

Yang, Michael Y; Chan, Hak-Kim

2017-06-01

The measurement of aerosol flow rates without obscuration of the flow is of particular concern with in vivo lung deposition studies, where precise knowledge of aerosol particle size distributions is a necessary requirement for the development of predictive correlations. This study examines the utility of an ultrasonic flow meter for such measurements and determines if a valved system can be attached to the flow meter for sampling exhaled aerosols. The flow rate across a D-30 flow meter was compared with and without nebulization of 0.9% saline aerosols from a PARI LC Sprint nebulizer. Particle size distributions of the nebulized aerosol before and after adding the D-30 flow meter and duckbill valve were measured using a Spraytec laser diffraction system. Finally, the ability of the Thor D-30 to capture a realistic breathing profile was assessed. The mean ± standard error flow rates measured by the D-30 flow meter with and without nebulization were 10.4 ± 0.1 versus 10.4 ± 0.1 L/min, 66.4 ± 0.1 versus 67.2 ± 0.1 L/min, and 89.9 ± 0.1 versus 91.4 ± 0.1 L/min. The D-30 flow meter did not considerably affect the volumetric median diameter (VMD) of the aerosols, while the VMD reduced slightly by 0.65 μm at 10 L/min and 0.69 μm at 72 L/min upon the inclusion of a duckbill valve. Time-weighted average inhalation flow rates measured by D-30 flow meters placed upstream and downstream of the one-way valve agreed well, 31.9 versus 32.6 L/min, respectively. The D-30 flow meter can be used to accurately measure inhalation flow rates of nebulized aerosols without significantly impacting particle size distributions, and one-way duckbill valves can be used to isolate the inhalation portion of a breathing pattern to facilitate collection of exhaled doses.

CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization.

Science.gov (United States)

Yousefi, Morteza; Pourmehran, Oveis; Gorji-Bandpy, Mofid; Inthavong, Kiao; Yeo, Leslie; Tu, Jiyuan

2017-12-01

Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning. The particles generated by the SAW are released in different locations in a spacer chamber attached to a lung model extending from the mouth to the 6th generation of the lung bronchial tree. An Eulerian approach is used to solve the Navier-Stokes equations that govern the airflow within the respiratory tract, and a Lagrangian approach is adopted to track the particles, which are assumed to be spherical and inert. Due to the complexity of the lung geometry, the airflow patterns vary as it penetrates deeper into the lung. High inertia particles tend to deposit at locations where the geometry experiences a significant reduction in cross section. Our findings, nevertheless, show that the injection location can influence the delivery efficiency: Injection points close to the spacer centerline result in deeper penetration into the lung. Additionally, we found that the ratio of drug particles entering the right lung is significantly higher than the left lung, independent of the injection location. This is in good agreement with this fact that the most of airflow enters to the right lobes.

Experimental study of contamination by inhalation of radioactive iodine aerosols. Biological balance; Etude experimentale de la contamination par inhalation d'aerosols d'iode radioactif bilan biologique

Energy Technology Data Exchange (ETDEWEB)

Marble, G [Commissariat a l' Energie Atomique, 92 - Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1968-07-01

Several articles have been published concerning research into contamination produced by inhalation of radioactive iodine aerosols in monkeys. Results dealing with the biological balance of this contamination are presented and discussed in this report. (author) [French] L'etude experimentale de la contamination par inhalation d'aerosols d'iode radioactif effectuee chez le singe a fait l'objet de plusieurs publications. Les resultats concernant le bilan biologique de cette contamination sont presentes et discutes dans ce rapport. (auteur)

Inhalation of gas metal arc-stainless steel welding fume promotes lung tumorigenesis in A/J mice.

Science.gov (United States)

Falcone, Lauryn M; Erdely, Aaron; Meighan, Terence G; Battelli, Lori A; Salmen, Rebecca; McKinney, Walter; Stone, Samuel; Cumpston, Amy; Cumpston, Jared; Andrews, Ronnee N; Kashon, Michael; Antonini, James M; Zeidler-Erdely, Patti C

2017-08-01

Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas metal arc-stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m 3 . Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.

Lung dose and lung cancer risk by inhalation of radon daughters

International Nuclear Information System (INIS)

Jacobi, W.

1983-01-01

The inhalation of short-lived radon daughters constitutes the most important occupational radiation exposure in mines, particularly in uranium mines. Among some groups of miners exposed in the past to relatively high radon levels, an excess lung cancer incidence has been observed. In addition to this occupational hazard, the observed radon levels in domestic houses indicate that the inhalation of short-lived radon daughters seems to be the most important component of the radiation exposure of the population from natural sources. For the quantification and judgment of the radiological impact by inhalation of radon daughters in mines as well as in houses, it is necessary to estimate the relationships between the inhaled activity or potential alpha (α) energy of these radionuclides, the dose to target tissues in the lung, and the possible associated lung cancer (LC) risk. It is the purpose of this paper to give a condensed review of our present knowledge in this field and to indicate the main gaps and uncertainties where future research seems necessary

Physicochemical characteristics of chlorofluorohydrocarbon-based inhalation aerosols

Energy Technology Data Exchange (ETDEWEB)

Ashurst, I C

1985-01-01

The aim of this work was to gain a better understanding of the physicochemical factors which affect the formulation of suspension inhalation aerosols. The adsorption of six nonionic and cationic surfactants onto Spherisorb has been investigated. The results were analyzed by calculating the area occupied by one adsorbed molecule at the surface and by comparing these values for each surfactant. The amount of each surfactant adsorbed was correlated with the number of sites on that surfactant molecule which could interact with the surface. The stability of suspensions, produced by both the model colloid Spherisorb, and by the drug isoprenaline sulfate, after adsorption of the surfactants, has been assessed by measuring settling times and rising times. The most stable suspension were found to be those which had the greatest amounts of long chain fatty acid surfactant adsorbed on their surface. A comparison was made between the effective stabilizing properties of Span 85 and oleic acid on various drug suspension. It was found that Span 85 gave the most stable suspension. Inhalation aerosol suspensions of isoprenaline sulfate were manufactured using the same surfactants used in the adsorption and suspension stability studies and were analyzed by measuring the particle size distributions of the suspension and the emitted doses. The results were found to correlate with the adsorption and suspension stability studies and it was concluded that a deflocculated suspension was preferable to a flocculated suspension in inhalation aerosols provided that the drug density was less than the propellant density. The application of this work to preformulation studies was also discussed.

Higher lung deposition with Respimat® Soft Mist™ Inhaler than HFA-MDI in COPD patients with poor technique

Directory of Open Access Journals (Sweden)

Peter Brand

2008-08-01

Full Text Available Peter Brand1, Bettina Hederer2, George Austen3, Helen Dewberry3, Thomas Meyer41RWTH, Aachen, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Boehringer Ingelheim, Bracknell, UK; 4Inamed Research, Gauting, GermanyAbstract: Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs, improving the efficiency of pulmonary drug delivery to patients. In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 µg/ipratropium bromide 20 µg via Respimat® SMI or hydrofluoroalkane (HFA-MDI (randomized order on test days 1 and 2, with no inhaler technique training. The procedure was repeated on test days 3 and 4 after training. Deposition was measured by gamma scintigraphy. All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted inhaled too fast at screening (peak inspiratory flow rate [IF]: 69–161 L/min. Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose and trained patients (53% of delivered vs 21% of metered dose (pSign-Test = 0.15; pANOVA< 0.05. Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time. Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique. Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI.Keywords: chronic obstructive pulmonary disease, drug delivery, inhalation, metered-dose inhaler, poor inhalation technique, training

Particle-size dependent effects in the Balb/c murine model of inhalational melioidosis

Directory of Open Access Journals (Sweden)

Richard eThomas

2012-07-01

Full Text Available Deposition of Burkholderia pseudomallei within either the lungs or nasal passages of the Balb/c murine model resulted in different infection kinetics. The infection resulting from the inhalation of B. pseudomallei within a 12 um particle aerosol was prolonged compared to a 1 um particle aerosol with a mean time-to-death (MTD of 73.8 ± 11.3 h and 174.7 ± 14.9 h respectively. Inhalation of B. pseudomallei within 1 um or 12 um particle aerosols resulted in a median lethal dose (MLD of 4 and 12 cfu respectively. The 12 mm particle inhalational infection was characterised by involvement of the respiratory epithelium and inflammation of the neurological path leading from the olfactory epithelium to the olfactory bulb (100%, culminating in abscessation of the brain (33%. Initial involvement of the upper respiratory tract lymphoid tissues (nasal-associated lymphoid tissue and cervical lymph nodes was observed in both the 1 and 12 um particle inhalational infections (80-85%. Necrotising alveolitis and bronchiolitis were evident in both inhalational infections however lung pathology was greater after inhalation of the 1 mm particle aerosol with pronounced involvement of the mediastinal lymph node (50%. Terminal disease was characterised by bacteraemia in both inhalational infections with dissemination to the spleen, liver, kidneys and thymus. Treatment with co-trimoxazole was more effective than treatment with doxycycline irrespective of the size of the particles inhaled. Doxycycline was more effective against the 12 um particle inhalational infection as evidenced by increased time to death. However, both treatment regimes exhibited significant relapse when therapy was discontinued with massive enlargement and abscessation of the lungs, spleen and cervical lymph nodes observed.

Comments on the rat lung as a human surrogate in inhalation studies

International Nuclear Information System (INIS)

Koblinger, L.

1988-01-01

The laboratory rat is often used as a surrogate to estimate the hazard to human health following inhalation exposure to ambient aerosols. Extrapolation of rat deposition data to humans depends, however, on the similarities and differences between the morphometric structures of the two airway systems. The main structural difference between the lungs of the two species, aside from dimensions per se, is their respective airway branching pattern : while the human lung is a rather symmetrically, dichotomously dividing system, the rat network is a more monopodial branching structure. In our stochastic modelling approach to defining suitable morphologies for human and rat lung, we utilise measured morphometric dimensions as the data base upon which a rigorous statistical analysis is performed, instead of forcing them into a formalised, average pathway scheme. This stochastic approach allows us, therefore, to account for structural irregularities, such as asymmetric branching, monopodial structure, and inter and intra-subject variability

Validating CFD Predictions of Pharmaceutical Aerosol Deposition with In Vivo Data.

Science.gov (United States)

Tian, Geng; Hindle, Michael; Lee, Sau; Longest, P Worth

2015-10-01

CFD provides a powerful approach to evaluate the deposition of pharmaceutical aerosols; however, previous studies have not compared CFD results of deposition throughout the lungs with in vivo data. The in vivo datasets selected for comparison with CFD predictions included fast and slow clearance of monodisperse aerosols as well as 2D gamma scintigraphy measurements for a dry powder inhaler (DPI) and softmist inhaler (SMI). The CFD model included the inhaler, a characteristic model of the mouth-throat (MT) and upper tracheobronchial (TB) airways, stochastic individual pathways (SIPs) representing the remaining TB region, and recent CFD-based correlations to predict pharmaceutical aerosol deposition in the alveolar airways. For the monodisperse aerosol, CFD predictions of total lung deposition agreed with in vivo data providing a percent relative error of 6% averaged across aerosol sizes of 1-7 μm. With the DPI and SMI, deposition was evaluated in the MT, central airways (bifurcations B1-B7), and intermediate plus peripheral airways (B8 through alveoli). Across these regions, CFD predictions produced an average relative error <10% for each inhaler. CFD simulations with the SIP modeling approach were shown to accurately predict regional deposition throughout the lungs for multiple aerosol types and different in vivo assessment methods.

Aerosol Deposition in Health and Disease

Science.gov (United States)

2012-01-01

Abstract The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. This article reviews the main mechanisms affecting the transport and deposition of inhaled aerosol in the human lung. Aerosol deposition in both the healthy and diseased lung is described mainly based on the results of human studies using nonimaging techniques. This is followed by a discussion of the effect of flow regime on aerosol deposition. Finally, the link between therapeutic effects of inhaled drugs and their deposition pattern is briefly addressed. Data show that total lung deposition is a poor predictor of clinical outcome, and that regional deposition needs to be assessed to predict therapeutic effectiveness. Indeed, spatial distribution of deposited particles and, as a consequence, drug efficiency is strongly affected by particle size. Large particles (>6 μm) tend to mainly deposit in the upper airway, limiting the amount of drugs that can be delivered to the lung. Small particles (<2 μm) deposit mainly in the alveolar region and are probably the most apt to act systemically, whereas the particle in the size range 2–6 μm are be best suited to treat the central and small airways. PMID:22686623

Study on the deposition patterns of aerosol inhalation scintigraphy, 1; Comparison of the deposition patterns of aerosol inhalation scintigraphy with lung function tests in pulmonary diseases

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Hiroyuki [Nara Medical Univ., Kashihara (Japan)

1989-06-01

The deposition patterns of aerosol inhalation scintigraphies and lung function tests were studied in 102 cases; 64 cases of obstructive pulmonary diseases (19 pulmonary emphysema, 27 diffuse panbronchiolitis, 18 chronic bronchitis) and 38 restrictive pulmonary disease (15 idiopathic interstitial pneumonia, 16 pulmonary asbestosis, 7 interstitial pneumonia due to collagen vascular disease). The deposition patterns were classified into 5 patterns (Type A:normal homogenous distribution; Type B: mildly unhomogenous distribution; Type C: severely unhomogenous distribution mingled with hot spots; Type D: non-hilar hot spots; and Type E: hilar hot spots). The deposition patterns of restrictive pulmonary diseases were markedly abnormal as well as obstructive pulmonary diseases. The deposition patterns showed mainly Types C, D and E in obstructive pulmonary diseases, Type B in restrictive pulmonary diseases. The deposition patterns showed mainly Type E in pulmonary emphysema, Types C and D in diffuse panbronchiolitis, Types A, B and C in chronic bronchitis, Type B in idiopathic interstitial pneumonia interstitial pneumonia due to collagen vascular disease, Types B and C in pulmonary asbestosis. The deposition patterns correlated well with %FEV{sub 1.0} which was a good indicator of the severity of obstructive pulmonary diseases and restrictive pulmonary diseases. Furthermore, the mean %FEV{sub 1.0} in obstructive pulmonary diseases was nearly equal to the mean %FEV{sub 1.0} in restrictive pulmonary diseases in each type of the deposition patterns. (J.P.N.).

The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol.

Science.gov (United States)

Fleming, John; Conway, Joy; Majoral, Caroline; Tossici-Bolt, Livia; Katz, Ira; Caillibotte, Georges; Perchet, Diane; Pichelin, Marine; Muellinger, Bernhard; Martonen, Ted; Kroneberg, Philipp; Apiou-Sbirlea, Gabriela

2011-02-01

Gamma camera imaging is widely used to assess pulmonary aerosol deposition. Conventional planar imaging provides limited information on its regional distribution. In this study, single photon emission computed tomography (SPECT) was used to describe deposition in three dimensions (3D) and combined with X-ray computed tomography (CT) to relate this to lung anatomy. Its performance was compared to planar imaging. Ten SPECT/CT studies were performed on five healthy subjects following carefully controlled inhalation of radioaerosol from a nebulizer, using a variety of inhalation regimes. The 3D spatial distribution was assessed using a central-to-peripheral ratio (C/P) normalized to lung volume and for the right lung was compared to planar C/P analysis. The deposition by airway generation was calculated for each lung and the conducting airways deposition fraction compared to 24-h clearance. The 3D normalized C/P ratio correlated more closely with 24-h clearance than the 2D ratio for the right lung [coefficient of variation (COV), 9% compared to 15% p computer analysis is a useful approach for applications requiring regional information on deposition.

Repeated inhalation exposure of Beagle dogs to aerosols of 239PuO2. XII

International Nuclear Information System (INIS)

Diel, J.H.; Hahn, F.F.; Muggenburg, B.A.

1988-01-01

Beagle dogs were exposed once or semi-annually for 10 yr by inhalation to aerosols of 239 PuO 2 to study the relative doses and effects of these two types of exposures. All exposures have been completed. Dogs exposed at high levels died predominantly of radiation pneumonitis and pulmonary fibrosis. Dogs exposed at lower levels, either once or repeatedly, are dying of a variety of causes including lung cancer. Dogs have survived up to 11 yr after their first exposure. Preliminary results suggest that single and repeated exposures cause similar health effects for equal accumulated radiation doses. (author)

Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

Science.gov (United States)

Klonne, D R; Dodd, D E; Losco, P E; Troup, C M; Tyler, T R

1989-03-01

PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

Experimental study of contamination by inhalation of radioactive iodine aerosols. Biological balance; Etude experimentale de la contamination par inhalation d'aerosols d'iode radioactif bilan biologique

Energy Technology Data Exchange (ETDEWEB)

Marble, G. [Commissariat a l' Energie Atomique, 92 - Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1968-07-01

Several articles have been published concerning research into contamination produced by inhalation of radioactive iodine aerosols in monkeys. Results dealing with the biological balance of this contamination are presented and discussed in this report. (author) [French] L'etude experimentale de la contamination par inhalation d'aerosols d'iode radioactif effectuee chez le singe a fait l'objet de plusieurs publications. Les resultats concernant le bilan biologique de cette contamination sont presentes et discutes dans ce rapport. (auteur)

Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

Science.gov (United States)

Tehrani, A M; Hwang, S-K; Kim, T-H; Cho, C-S; Hua, J; Nah, W-S; Kwon, J-T; Kim, J-S; Chang, S-H; Yu, K-N; Park, S-J; Bhandari, D R; Lee, K-H; An, G-H; Beck, G R; Cho, M-H

2007-03-01

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

PHARMACEUTICAL AEROSOLS FOR THE TREATMENT AND PREVENTION OF TUBERCULOSIS

Directory of Open Access Journals (Sweden)

Shumaila N Muhammad Hanif

2012-09-01

Full Text Available Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers and dry powder inhalers. In addition to the advantages of providing more efficient delivery of the drug, low cost and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by

Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation.

Science.gov (United States)

Wang, S; Young, R S; Witten, M L

2001-02-01

Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.

Lung radiopharmaceuticals

International Nuclear Information System (INIS)

Gonzalez, B.M.

1994-01-01

Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP

Electrostatics in pharmaceutical aerosols for inhalation.

Science.gov (United States)

Wong, Jennifer; Chan, Hak-Kim; Kwok, Philip Chi Lip

2013-08-01

Electrostatics continues to play an important role in pharmaceutical aerosols for inhalation. Despite its ubiquitous nature, the charging process is complex and not well understood. Nonetheless, significant advances in the past few years continue to improve understanding and lead to better control of electrostatics. The purpose of this critical review is to present an overview of the literature, with an emphasis on how electrostatic charge can be useful in improving pulmonary drug delivery.

Experiment of aerosol-release time for a novel automatic metered dose inhaler

OpenAIRE

Mingrong Zhang; Songhao Wang; Yu-Ching Yang

2016-01-01

The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-de...

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Park, J.F.

1985-01-01

This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239 PuO 2 , during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238 PuO 2 , mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239 PuO 2 or 238 PuO 2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

Inhalation of antibiotics in cystic fibrosis

NARCIS (Netherlands)

Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of

Radioaerosol lung imaging in small airways disease

Energy Technology Data Exchange (ETDEWEB)

Weiss, T; Dorow, P; Felix, R

1981-06-01

Aerosol inhalation lung imaging was performed in 35 asymptomatic smokers who have been selected on the basis of abnormal findings in small airways pulmonary function tests. Qualitative (image inspection) and quantitative (aerosol distribution index = ADI) analysis of the radioaerosol lung patterns was accomplished. Compared to healthy subjects as well as to patients with chronic obstructive lung disease significant differences of mean aerosol distribution homogeneity were observed. A characteristic type of abnormal aerosol pattern, indicating peripheral airways obstruction, was found in 71% of the patients with small airways disease.

Detection of alveolar epithelial injury by 99mTc-DTPA radioaerosol inhalation lung scan following blunt chest trauma

International Nuclear Information System (INIS)

Okudan, B.; Han, S.; Baldemir, M.; Yildiz, M.

2004-01-01

DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99m Tc-DTPA aerosol inhalation scintigraphy was used to assess the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53±13 yrs) who were referred to the emergency department in our hospital participated in this study. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T 1/2 ) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T 1/2 value of the whole lung was 63±19 minutes (min), and thirtieth day mean T 1/2 value was 67±21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60±0.05, and 0.63 ±0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99m Tc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase. (author)

Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention

International Nuclear Information System (INIS)

Garbuzenko, Olga B.; Mainelis, Gediminas; Taratula, Oleh; Minko, Tamara

2014-01-01

Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs. The following nanocarriers were studied: micelles, liposomes, mesoporous silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All particles were characterized using the following methods: dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation of liposomes and micelles in lungs remained relatively high even 24 h after inhalation when compared with MSNs, QDs, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer. The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer

Development of high efficiency ventilation bag actuated dry powder inhalers.

Science.gov (United States)

Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R; Hindle, Michael

2014-04-25

New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70-80% with fine particle fractions <5 μm of 65-85% and mass median aerodynamic diameters of 1.5 μm, which were target conditions for controlled condensational growth aerosol delivery. Decreasing the size of the flow control orifice from 3.6 to 2.3mm reduced the flow rate through the system with manual bag actuations from an average of 35 to 15LPM, while improving ED and aerosolization performance. The new devices can be applied to improve aerosol delivery during mechanical ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of the effects of inhaled 239PuO2 and β- emitting radionuclides on the incidence of lung carcinomas in laboratory animals

International Nuclear Information System (INIS)

Hahn, F.F.; Griffith, W.C.; Boecker, B.B.; Muggenburg, B.A.; Lundgren, D.L.

1991-01-01

The health effects of inhaling radioactive particles when the lung is the primary organ irradiated were studied in rats and Beagle dogs. The animals were exposed to aerosols of 239 PuO 2 or fission-product radionuclides in insoluble forms and observed for their life span. Lung carcinomas were the primary late-occuring effect. The incidence rate for lung carcinomas was modeled using a proportional hazard rate model. Linear functions predominated below 5 Gy to the lung. The life-time risk for lung carcinomas per 10 4 Gy for beta emitters was 60 for rats and 65 for dogs, and for 239 PuO 2 it was 1500 for rats and 2300 for dogs

Comparison of the effects of inhaled 239PuO2 and β-emitting radionuclides of the incidence of lung carcinomas in laboratory animals

International Nuclear Information System (INIS)

Hahn, F.F.; Griffith, W.C.; Boecker, B.B.; Muggenburg, B.A.; Lundgren, D.L.

1992-01-01

The health effects of inhaling radioactive particles when the lung is the primary organ irradiated were studied in rats and dogs. The animals were exposed to aerosols of 239 PuO 2 or fission-product radionuclides in insoluble forms and observed for their life span. Lung carcinomas were the primary late-occurring effect. The incidence rate for lung carcinomas was modeled using a proportional hazard rate model. Linear functions predominated below 5 Gy to the lung. The life-time risk for lung carcinomas per 10 4 Gy for beta emitters was 60 for rats and 65 for dogs, and for 239 PuO 2 it was 1500 for rats and 2300 for dogs. (author)

Lung radiopharmaceuticals; Radioformacos pulmonares

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, B M [Instituto Nacional de Pediatroa (Mexico)

1994-12-31

Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP.

Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

Science.gov (United States)

Hwang, S-K; Jin, H; Kwon, J T; Chang, S-H; Kim, T H; Cho, C-S; Lee, K H; Young, M R; Colburn, N H; Beck, G R; Yang, H-S; Cho, M-H

2007-09-01

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

Development of Respimat® Soft Mist™ Inhaler and its clinical utility in respiratory disorders

Directory of Open Access Journals (Sweden)

Dalby RN

2011-09-01

Full Text Available Richard N Dalby1, Joachim Eicher2, Bernd Zierenberg21Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA; 2Boehringer Ingelheim, Ingelheim, GermanyAbstract: The Respimat® Soft Mist™ Inhaler (SMI (Boehringer Ingelheim International GmbH, Ingelheim, Germany was developed in response to the need for a pocket-sized device that can generate a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible, and environmentally friendly energy supply. This paper describes the design and evolution of this innovative device from a laboratory concept model and the challenges that were overcome during its development and scaleup to mass production. A key technical breakthrough was the uniblock, a component combining filters and nozzles and made of silicon and glass, through which drug solution is forced using mechanical power. This allows two converging jets of solution to collide at a controlled angle, generating a fine aerosol of inhalable droplets. The mechanical energy comes from a spring which is tensioned by twisting the base of the device before use. Additional features of the Respimat® SMI include a dose indicator and a lockout mechanism to avoid the problems of tailing-off of dose size seen with pressurized metered dose inhalers. The Respimat® SMI aerosol cloud has a unique range of technical properties. The high fine particle fraction allied with the low velocity and long generation time of the aerosol translate into a higher fraction of the emitted dose being deposited in the lungs compared with aerosols from pressurized metered dose inhalers and dry powder inhalers. These advantages are realized in clinical trials in adults and children with obstructive lung diseases, which have shown that the efficacy and safety of a pressurized metered dose inhaler formulation of a combination bronchodilator can be matched by a Respimat® SMI formulation containing only one half or one quarter

DTPA therapy of lung contaminations: testing a self contained aerosol generator

International Nuclear Information System (INIS)

Ducousso, R.; Pasquier, C.

1975-01-01

It has been shown how much the effectiveness of DTPA therapy of respiratory contamination decreased when the delay of administration of the product increased. Moreover, the effectiveness of local administration of the chelating agent as aerosol has been widely recognized. Owing to both the therapeutic urgency and the local administration, an individual pocket apparatus allowing emergency DTPA inhalation, on the spot of the accident was tried. A turbo-inhalator sold for the administration of an anti-asthmatic powder was tested, using DTPA powder inhaled by a volunteer previously contaminated by a 140 LaCl 3 aerosol [fr

Establishment and evaluation of a rat model of inhalation lung injury induced by ship smog

Directory of Open Access Journals (Sweden)

Xin-xin DUAN

2018-03-01

Full Text Available Objective To establish and evaluate a rat model of inhalation lung injury induced by ship smog. Methods A rat model of inhalation lung injury was established by analyzing the composition of ship materials after combustion. Forty- two healthy male Wistar rats were randomly divided into normal control group and 2, 6, 12, 24, 48 and 72h groups (6 eachafter inhalation, these rats were killed at each time point, and the changes of arterial blood gas, coagulation function, the lung water content (% were detected. Macroscopic and microscopic changes in lung tissues were observed to judge the degree of lung injury. Results The main components after combustion of 7 kinds of nonmetal materials on ship included CO, CO2, H2S, NOx and other harmful gases in this study, AIKE in one gas detector was used to monitor O2, CO, CO2 and H2S, and their concentrations remained relatively stable within 15 minutes, and the injury time was 15 minutes. The rats presented with shortness of breath and mouth breathing. Smoke inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 2h and the lung water content (% did 6h after inhalation (P<0.05. It is metabolic acidosis in the early stage after inhalation, but metabolic acidosis combined with respiratory acidosis in the later period. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in the lung tissue as manifestations of lung injury, and the injury did not recover at 72h after inhalation, the change of blood coagulation function was not statistically significant. Conclusion A rat model of inhalation lung injury induced by ship smog has been successfully established, and has the advantages of easy replication, stability and reliability, thus can be used to research and treat inhalation lung injury induced by ship smog in naval war environment and other cases. DOI: 10.11855/j.issn.0577-7402.2018.03.14

The toxicity of inhaled particles of 238PuO2 in dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Guilmette, R.A.; Griffith, W.C. Jr.; Hahn, F.F.; Boecker, B.B.

1991-01-01

This study was conducted to determine the toxicity of inhaled 238 PuO 2 in the dog. Inhalation was selected because it is the mostly likely route of human exposure in the event of an accidental airborne release. Of 166 dog in the study, 72 inhaled 1.5μm and 72 inhaled 3.0 μm activity median aerodynamic diameter particles of 238 PuO 2 . Another 24 dogs inhaled the aerosol vector without plutonium. The aerosol exposures resulted in initial pulmonary burdens ranging from 37 to 0.11 and 55.5 to 0.37 kBq of 238 Pu/kg body mass, of 1.5 μm and 3.0 μ, particles, respectively. The particles dissolved slowly resulting in translocation of the Pu to liver, bone and other sites. The dogs were observed for biological effects over their life span. Necropsies were performed at death, and tissues were examined microscopically. The principal late-occurring effects were tumors of the lung, skeleton, and liver. Risk factors estimated for these cancers were 2800 lung cancers/10 4 Gy, 800 liver cancers/10 4 Gy, and 6200 bone cancers/10 4 Gy for dogs. The potential hazard from 238 Pu to humans may include tumors of the lung, bone and liver because of the likelihood of similarity of the dose patterns for the two species. 10 refs., 1 fig., 3 tabs

The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

Science.gov (United States)

Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

2017-02-01

The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Prevention of radiation pneumonitis from inhaled 144Ce by lung lavage in beagle dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mauderly, J.L.; Boecker, B.B.; Hahn, F.F.; McClellan, R.O.

1975-01-01

This study was performed to evaluate bronchopulmonary lavage and chelation therapy as a treatment method to prevent the development of radiation pneumonitis after inhalation of a radioactive aerosol. Twelve beagle dogs were exposed to an aerosol of cerium-144 in fused clay particles resulting in initial lung burdens from 47 to 64 μCi of 144 Ce per kg of body weight. Eight of the dogs were treated with a series of 10 bronchopulmonary lavages and 10 intravenous injections of calcium diethylenetriamine pentaacetate acid during the first 56 days after exposure to remove the deposited 144 Ce; the remaining 4 exposed dogs received no treatment. An additional 4 dogs were exposed to stable cerium and were given the course of treatment as an additional control group. Three of the 4 untreated dogs and 2 of the 8 treated dogs died 171 to 246 days after exposure with radiation pneumonitis or pulmonary fibrosis, or both. All but one of the remaining dogs were alive and apparently in good clinical health 550 days after exposure; the one dog had radiographic indications of pulmonary fibrosis by 365 days after exposure. The relative distribution of 144 Ce in the lungs and other major organs was similar in the treated and untreated dogs that died

Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

Directory of Open Access Journals (Sweden)

Yi-fan LIU

2013-09-01

Full Text Available Objective　To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods　The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results　The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion　The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

Radioaerosol lung imaging - history and pharmaceuticals

International Nuclear Information System (INIS)

Isawa, Toyoharu

1994-01-01

The first use of a radioactive tracer to study lung function was made by Knipping and others in 1955. They used radioactive 133 Xe (xenon) gas as an inhalation agent in a patient with lung cancer and found that distal to a tumor no radioactivity was detected indicating no ventilation although chest x-rays appeared as if there was active ventilation. Subsequently with advance in technology a number of radioactive gases such as 81m Kr (krypton) and cyclotron produced 15 O 2 (oxygen), 11 C (carbon) and 13 N 2 (nitrogen) became available to assess regional lung function. The advantages of these gases are manifold, but their utility is mostly limited due to high cost. An alternative to the use of radioactive gases to study regional ventilation is the use of particulate radioactive aerosol. Radioaerosol inhalation lung imaging technique was developed in 1965 almost simultaneously by Taplin and others and Pircher and others just 2 years following Taplin's invention of 131 I-MAA for perfusion lung imaging. Their main aim was to use 131 I-human serum albumin (HSA), and 99m Tc-HSA, 131 I-rose bengal, 197 Hg-chlormerodrin and colloidal 198 Au as agents for radioaerosol generation, and Taplin himself preferred 198 Au colloids for serial studies from economical reasons. Already in 1965, however, Taplin said that the best agent would be 99m Tc-HSA. Pircher used 131 I-HSA aerosol. Taplin already noted at that time that the inhaled aerosol was removed from the lungs mainly by ciliary action and that it was not absorbed either from the lungs or the intestine. Anyway it is noteworthy that the idea of radioaerosol inhalation lung imaging was proposed soon after the advent of perfusion lung imaging. Besides 131 I-HSA and colloidal 198 Au, the following agents have been or are currently being used. The superiority of 99m TC over other radioisotopes used in the past is beyond dispute

Intermittent aerosol delivery to the lungs during high-flow nasal cannula therapy.

Science.gov (United States)

Golshahi, Laleh; Longest, P Worth; Azimi, Mandana; Syed, Aamer; Hindle, Michael

2014-10-01

Use of submicrometer particles combined with condensational growth techniques has been proposed to reduce drug losses within components of high-flow nasal cannula therapy systems and to enhance the dose reaching the lower respiratory tract. These methods have been evaluated using continuous inhalation flow rather than realistic inhalation/exhalation breathing cycles. The goal of this study was to evaluate in vitro aerosol drug delivery using condensational growth techniques during high-flow nasal cannula therapy using realistic breathing profiles and incorporating intermittent aerosol delivery techniques. A mixer-heater combined with a vibrating mesh nebulizer was used to generate a submicrometer aerosol using a formulation of 0.2% albuterol sulfate and 0.2% sodium chloride in water. Delivery efficiency of the aerosol for 1 min through a nasal cannula was considered using an intermittent delivery regime with aerosol being emitted for either the entire inhalation time (2 s) or half of the inhalation period (1 s) and compared with continuous delivery. The deposition of the aerosol was evaluated in the nasal delivery components (ventilator tubing and cannula) and an in vitro adult nose-mouth-throat (NMT) model using 3 realistic breathing profiles. Significant improvements in dose delivered to the exit of the NMT model (ex-NMT) were observed for both condensational growth methods using intermittent aerosol delivery compared with continuous delivery, and increasing the tidal volume was found useful. The combination of the largest tidal volume with the shortest intermittent delivery time resulted in the lowest respiration losses and the highest ex-NMT delivered dose. Intermittent aerosol delivery using realistic breathing profiles of submicrometer condensational growth aerosols was found to be efficient in delivering nasally administered drugs in an in vitro airway model. Copyright © 2014 by Daedalus Enterprises.

Nanotechnology-based inhalation treatments for lung cancer: state of the art

Directory of Open Access Journals (Sweden)

Ahmad J

2015-11-01

Full Text Available Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5 Moshahid Alam Rizvi,6 Mohammad A Kamal,7 Farhan Jalees Ahmad1,21Department of Pharmaceutics, 2Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India; 3Centre de Biophysique Moléculaire(CBM-CNRS UPR4301, University of Orléans, Orléans Cedex 2, France; 4Department of Pharmaceutics, Abhilashi College of Pharmacy, Mandi, HP, India; 5Department of Pharmaceutics, College of Pharmacy, Najran University, Saudi Arabia; 6Department of Biosciences, Jamia Millia Islamia, New Delhi, India; 7Metabolomics and Enzymology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia*These authors contributed equally to this workAbstract: Considering the challenges associated with conventional chemotherapy, targeted and local delivery of chemotherapeutics via nanoparticle (NP carriers to the lungs is an emerging area of interest. Recent studies and growing clinical application in cancer nanotechnology showed the huge potential of NPs as drug carriers in cancer therapy, including in lung carcinoma for diagnosis, imaging, and theranostics. Researchers have confirmed that nanotechnology-based inhalation chemotherapy is viable and more effective than conventional chemotherapy, with lesser side effects. Recently, many nanocarriers have been investigated, including liposomes, polymeric micelles, polymeric NPs, solid lipid NPs, and inorganic NPs for inhalation treatments of lung cancer. Yet, the toxicity of such nanomaterials to the lungs tissues and further distribution to other organs due to systemic absorption on inhalation delivery is a debatable concern. Here, prospect of NPs-based local lung cancer targeting through inhalation route as well as its associated challenges are discussed.Keywords: nanoparticles, lung cancer, inhalational chemotherapy, drug targeting, nanotoxicity

Experimental study of the effect of wearing dust-proof mask on inhaled aerosol particle size

International Nuclear Information System (INIS)

Lu Shunguang; Mei Chongsheng; Wu Yuangqing; Ren Liuan.

1985-01-01

This paper describes a method for measuring particle size of inhaled aerosol with a phantom of human head wearing dust-proof mask and a cascade impactor. The results showed that AMAD of inhaled aerosol was degraded and the size distribution of particles changed when the dust-proof mask was wearing. The leak rate of mask increased as the size of dust particles decreased. The results are applicable to estimate internal exposure dose and to evaluate the dust-proof capacity of mask

Proposed retention model for human inhalation exposure to 241AmO2

International Nuclear Information System (INIS)

Mewhinney, J.A.; Griffith, W.C.; Muggenburg, B.A.

1980-01-01

A dosimetry model based on a four-year study in Beagle dogs was developed to predict patterns of absorbed radiation doses for people exposed by inhalation to 241 AmO 2 . Following a single inhalation exposure to one of three sizes of monodisperse or a polydisperse aerosol of 241 AmO 2 , pairs of dogs were sacrificed at 8, 32, 64 and 256 days, and 2 and 4 years. For about 80% of the initial lung burden, the retention halftimes were 11, 18, 26 and 27 days for the 0.75, 1.5 and 3.0 μm aerodynamic diameter and the 1.8 μm activity median aerodynamic diameter aerosols, respectively. For the remaining 20% of the initial lung burden, the retention halftimes were between 200 to 300 days with no apparent particle size influence. Additional 241 Am metabolic studies reported in the literature using inhalation exposure or injection of the citrate complex were synthesized in the model as were eleven reported cases of human inhalation exposure. This model is compared to the ICRP II and TGLD lung models, both developed by analogy to Pu metabolism. The proposed model differs from these latter models in two important areas: (a) lung retention of 241 AmO 2 could not be adapted to the classifications used in these models, and (b) the fractional translocation from lung to other organs is 2 to 8 times larger. These factors considerably alter the predicted radiation dose distribution among organs and lead to the conclusion that derived radiation protection standards for 241 AmO 2 inhalation exposure should be modified. (author)

Advance in research on aerosol deposition simulation methods

International Nuclear Information System (INIS)

Liu Keyang; Li Jingsong

2011-01-01

A comprehensive analysis of the health effects of inhaled toxic aerosols requires exact data on airway deposition. A knowledge of the effect of inhaled drugs is essential to the optimization of aerosol drug delivery. Sophisticated analytical deposition models can be used for the computation of total, regional and generation specific deposition efficiencies. The continuously enhancing computer seem to allow us to study the particle transport and deposition in more and more realistic airway geometries with the help of computational fluid dynamics (CFD) simulation method. In this article, the trends in aerosol deposition models and lung models, and the methods for achievement of deposition simulations are also reviewed. (authors)

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC and dipalmitoylphosphatidylethanolamine poly(ethylene glycol (DPPE-PEG microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Directory of Open Access Journals (Sweden)

Meenach SA

2013-01-01

total-reflectance Fourier-transform infrared (ATR-FTIR spectroscopy and confocal Raman microscopy (CRM, and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™ coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved.Keywords: biocompatible biodegradable lipopolymers, lung surfactant, pulmonary delivery, self-assemblies, solid-state, lipospheres

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects

International Nuclear Information System (INIS)

Chan, H.K.; Eberl, S.; Bautovich, G.

1999-01-01

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AER x ) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AER x is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs ''fixed volume'' of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P x system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 μm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AER x system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs. (orig.)

The History of Therapeutic Aerosols: A Chronological Review.

Science.gov (United States)

Stein, Stephen W; Thiel, Charles G

2017-02-01

In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We

Assessment of anthropogen aerosols : influence on environment and human health

International Nuclear Information System (INIS)

Kwasny, F.

2010-01-01

The term aerosol describes a dispersion of liquid or solid particles in a gaseous medium, usually including particles at a size ranging from 0.001 to 100 μm. The size of an aerosol's particle is of special interest, as it influences its fate. Together with other physical properties like shape, density and mass of the particles, it defines the aerosol's possibilities of sedimentation, diffusion, dispersion, coagulation or impaction onto surfaces. As aerosols are by definition composed of a number of particles, this regime of constituent parts varies. Aerosols are well known with their common names such as dust, smoke, fume, fog, mist, spray or haze. The projects of this thesis deal with different aspects of anthropogenic aerosols. We investigated their influence on human health and environmental impact by looking at particle concentrations and size distributions of aerosols. Ultimately, we examined their fate in a human lung model to reveal a direct influence on humans. Our studies included brine inhalation at an open-air spa, exposure to ultrafine particles while driving a car through a heavy impacted environment, and the influence of aerosols on spectators while watching fireworks. In a project with the local environmental authorities we investigated the correlation of air quality, meteorological and traffic data with ultrafine particles. Resulting from our studies, we found beneficial effects of salt aerosols used for inhalation therapy, showing the positive influence in lung deposition, as well as, an effect on ultrafine particle inventory of the ambient air. Combustion aerosols and other man-made particulate matter proved to have adverse effects on human lung deposition, allowing ultrafine particles to reach deep into the human lung. This not only poses a threat to respiratory organs; particles can be translocated from the respiratory tract into the blood stream and from there to other organs, affecting the entire body. For the purpose of finding reasonable

Early diagnosis of morphologic-functional changes of the airways by a simple method of inhalation scintigraphy

International Nuclear Information System (INIS)

Flierdt, E. van de; Bauer, R.; Laubenbacher, C.; Didic, M.; Langhammer, H.R.; Pabst, H.W.

1992-01-01

In order to validate a method of inhalation scintigraphy with 99m Tc-labeled human serum albumin in the early diagnosis of morphologic-functional changes of the airways 35 volunteers and patients (12 healthy non-smokers and smokers each, 11 patients with bronchitis) were studied. Deposition of the aerosol immediately after inhalation was calculated quantitatively by a ROI technique and qualitatively (scoring of central deposition, homogeneity, and recognizability of lung outline). Additionally, the regional clearance of the inhaled aerosol was determined by continuous lung imaging up to 60 min (mainly regional mucociliary removal rates). Discrimination between healthy volunteers and patients with bronchitis was possible by means of deposition patterns immediately after inhalation. On the other hand, no differences could be recognized in this way between healthy non-smokers and smokers. Regional mucociliary removal was higher in non-smokers than in smokers, but there was no difference between smokers and patients with bronchitis. (orig.) [de

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis : A European consensus

NARCIS (Netherlands)

Heijerman, Harry; Westerman, Elsbeth; Conway, Steven; Touw, Daan; Döring, Gerd; Frijlink, Henderik

In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

Energy Technology Data Exchange (ETDEWEB)

Hanns-Rudolf, Paur; Cassee, Flemming R.; Teeguarden, Justin G.; Fissan, Heinz; Diabate, Silvia; Aufderheide, M.; Kreyling, Wolfgang G.; Hanninen, Otto; Kasper, G.; Riediker, Michael; Rothen-Rutishauser, Barbara; Schmid, Otmar

2011-10-01

The rapid introduction of engineered nanostructured materials into numerous industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of consumer products. The dynamic development of new nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety. In this consensus document from a workshop on in-vitro cell systems for nanotoxicity testing an overview is given of the main issues concerning inhalation exposure to nanoparticles, lung physiology, nanoparticle-related biological mechanisms, in-vitro cell exposure systems for nanoparticles and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanotoxicity. For the investigation of pulmonary nanotoxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

International Nuclear Information System (INIS)

Hanns-Rudolf, Paur; Cassee, Flemming R.; Teeguarden, Justin G.; Fissan, Heinz; Diabate, Silvia; Aufderheide, M.; Kreyling, Wolfgang G.; Hanninen, Otto; Kasper, G.; Riediker, Michael; Rothen-Rutishauser, Barbara; Schmid, Otmar

2011-01-01

The rapid introduction of engineered nanostructured materials into numerous industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of consumer products. The dynamic development of new nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety. In this consensus document from a workshop on in-vitro cell systems for nanotoxicity testing an overview is given of the main issues concerning inhalation exposure to nanoparticles, lung physiology, nanoparticle-related biological mechanisms, in-vitro cell exposure systems for nanoparticles and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanotoxicity. For the investigation of pulmonary nanotoxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

Tc-99m erythromycin lactobionate inhalation scintigraphy in parenchymal lung diseases

Energy Technology Data Exchange (ETDEWEB)

Durak, Hatice E-mail: hdurak@kordon.deu.edu.tr; Aktogu, Serir; Degirmenci, Berna; Sayit, Elvan; Ertay, Tuerkan; Dereli, Sevket

1999-08-01

We have investigated Technetium 99m erythromycin lactobionate (Tc 99m EL) clearance from the lungs after inhalation, in the presence of an alveolitis. Eighteen patients (6 sarcoidosis, 7 idiopathic fibrosis, and 5 miliary tuberculosis) were imaged after the patients inhaled 1,110 MBq of Tc 99m EL. Clearance half time for the first 45 min, for 24 h, and retention at 24 h correlated with percentage of lymphocytes in bronchoalveolar lavage fluid (BAL) (r=.729, r=.883, and r=.826, respectively). There was a positive correlation between peripheral penetration (PP) and forced expiratory volume in 1 s (FEV{sub 1}) (r=.806) and forced vital capacity (FVC) (r=.781). Retention was more marked in sarcoidosis compared with tuberculosis (0.025lung imaging may reflect the pulmonary function impairment in parenchymal lung diseases. Retention of Tc 99m EL may be related to number of BAL cells or presence of a lymphocytic alveolitis. Long residency time of Tc 99m EL in the lungs implies that erythromycin can also be administered by inhalation for therapeutic purposes.

Distribution, retention and early cytogenetic damage in Cynomolgus monkeys following inhalation of 239Pu(NO3)4

International Nuclear Information System (INIS)

Brooks, A.L.; Mewhinney, J.A.; Redman, H.C.; Guilmette, R.A.; McClellan, R.O.

1980-01-01

Sixteen Cynomolgus monkeys were exposed by inhalation to an aerosol of 239 Pu(NO 3 ) 4 which resulted in calculated initial lung burdens of 1.0, 0.3 and 0.1 μCi. Four animals were exposed to the carrier aerosol and served as controls. Animals were sacrificed at 4 days and 45 days after exposure to determine the distribution and retention of the aerosol. The amount of plutonium in the liver, skeleton and testes increased as a function of time after exposure. Two monkeys died 155 and 188 days after inhalation exposure from radiation pneumonitis and fibrosis. There was a doubling of the total chromosome aberration frequency in the blood lymphocytes and a significant increase in dicentric chromosomes in the animals exposed for 6 months to initial lung burdens of 1.0 μCi

History of aerosol therapy: liquid nebulization to MDIs to DPIs.

Science.gov (United States)

Anderson, Paula J

2005-09-01

Inhaled therapies have been used since ancient times and may have had their origins with the smoking of datura preparations in India 4,000 years ago. In the late 18th and in the 19th century, earthenware inhalers were popular for the inhalation of air drawn through infusions of plants and other ingredients. Atomizers and nebulizers were developed in the mid-1800s in France and were thought to be an outgrowth of the perfume industry as well as a response to the fashion of inhaling thermal waters at spas. Around the turn of the 20th century, combustible powders and cigarettes containing stramonium were popular for asthma and other lung complaints. Following the discovery of the utility of epinephrine for treating asthma, hand-bulb nebulizers were developed, as well as early compressor nebulizers. The marketing of the first pressurized metered-dose inhaler for epinephrine and isoproterenol, by Riker Laboratories in 1956, was a milestone in the development of inhaled drugs. There have been remarkable advances in the technology of devices and formulations for inhaled drugs in the past 50 years. These have been influenced greatly by scientific developments in several areas: theoretical modeling and indirect measures of lung deposition, particle sizing techniques and in vitro deposition studies, scintigraphic deposition studies, pharmacokinetics and pharmacodynamics, and the 1987 Montreal Protocol, which banned chlorofluorocarbon propellants. We are now in an era of rapid technologic progress in inhaled drug delivery and applications of aerosol science, with the use of the aerosolized route for drugs for systemic therapy and for gene replacement therapy, use of aerosolized antimicrobials and immunosuppressants, and interest in specific targeting of inhaled drugs.

Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges

Directory of Open Access Journals (Sweden)

Wing-Hin Lee

2015-12-01

Full Text Available Ever since the success of developing inhalable insulin, drug delivery via pulmonary administration has become an attractive route to treat chronic diseases. Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy. Nano-based systems such as liposome, polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability, stability and residency at targeted lung regions. Along with these benefits, nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening and drug tracking. Nevertheless, delivery of nano-based drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected. Pharmacology, immunology, toxicology and large-scale manufacturing (stability and activity of drugs are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs. This review will focus on the current inhalable nano-based drugs for lung cancer treatment.

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

DEFF Research Database (Denmark)

Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

2009-01-01

, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we...... review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics...

Optimal delivery of aerosols to infants during mechanical ventilation.

Science.gov (United States)

Longest, P Worth; Azimi, Mandana; Hindle, Michael

2014-10-01

The objective of this study was to determine optimal aerosol delivery conditions for a full-term (3.6 kg) infant receiving invasive mechanical ventilation by evaluating the effects of aerosol particle size, a new wye connector, and timing of aerosol delivery. In vitro experiments used a vibrating mesh nebulizer and evaluated drug deposition fraction and emitted dose through ventilation circuits containing either a commercial (CM) or new streamlined (SL) wye connector and 3-mm endotracheal tube (ETT) for aerosols with mass median aerodynamic diameters of 880 nm, 1.78 μm, and 4.9 μm. The aerosol was released into the circuit either over the full inhalation cycle (T1 delivery) or over the first half of inhalation (T2 delivery). Validated computational fluid dynamics (CFD) simulations and whole-lung model predictions were used to assess lung deposition and exhaled dose during cyclic ventilation. In vitro experiments at a steady-state tracheal flow rate of 5 L/min resulted in 80-90% transmission of the 880-nm and 1.78-μm aerosols from the ETT. Based on CFD simulations with cyclic ventilation, the SL wye design reduced depositional losses in the wye by a factor of approximately 2-4 and improved lung delivery efficiencies by a factor of approximately 2 compared with the CM device. Delivery of the aerosol over the first half of the inspiratory cycle (T2) reduced exhaled dose from the ventilation circuit by a factor of 4 compared with T1 delivery. Optimal lung deposition was achieved with the SL wye connector and T2 delivery, resulting in 45% and 60% lung deposition for optimal polydisperse (∼1.78 μm) and monodisperse (∼2.5 μm) particle sizes, respectively. Optimization of selected factors and use of a new SL wye connector can substantially increase the lung delivery efficiency of medical aerosols to infants from current values of <1-10% to a range of 45-60%.

Sidestream smoke inhalation decreases respiratory clearance of 99mTc-DTPA acutely

International Nuclear Information System (INIS)

Yates, D.H.; Havill, K.; Thompson, M.M.; Rittano, A.B.; Chu, J.; Glanville, A.R.

1996-01-01

The permeability of the alveolar-capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta-acetate ( 99m Tc-DTPA is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers. The aim of this study was to determine the effect of sidestream smoke inhalation on permeability as this has not been described previously. Lung clearance of inhaled 99m Tc-DTPA aerosol was measured in 20 normal non-smoking subjects before and after exposure to one hours sidestream smoke inhalation. Measured carbon monoxide (CO) levels rose to a maximum of 23.5 ±6.2 ppm from baseline values of 0.6±1.3 (p 99m Tc-DTPA clearance rose from baseline 69.1± 15.6 (mean ± to 77.4 ±17.8) after smoke exposure. No effect of 99m Tc-DTPA scanning of sidestream smoke was demonstrated on lung function. It was concluded that low level sidestream smoke inhalation decreases 99m Tc-DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response. 34 refs., 2 figs

Experimental study of contamination by inhalation of radioactive iodine aerosols. Biological balance

International Nuclear Information System (INIS)

Marble, G.

1968-01-01

Several articles have been published concerning research into contamination produced by inhalation of radioactive iodine aerosols in monkeys. Results dealing with the biological balance of this contamination are presented and discussed in this report. (author) [fr

Effects of inhaled insoluble 239PuO2 on immune responses following lung immunization

International Nuclear Information System (INIS)

Bice, D.E.; Harris, D.L.; Brooks, A.L.; Mewhinney, J.A.

1978-01-01

To determine if inhaled 239 PuO 2 suppresses immunity in lung-associated lymph nodes, Chinese hamsters were exposed to a polydisperse aerosol of 239 PuO 2 produced at 1150 0 C. The mean lung burden of these animals was estimated to be 10 nCi at 8 days after exposure. At 128, 256 and 400 days after exposure, sham exposed controls and experimental animals were immunized by intratracheal instillation of 1 x 10 8 sheep red blood cells (SRBC). Six days later, they were sacrificed and the number of antibody forming cells (AFC) in lung-associated lymph nodes, spleen and cervical lymph nodes was evaluated. Results of these studies indicated that the number of AFC in lung-associated lymph modes was significantly lower in animals exposed to 239 PuO 2 . Only a few AFC were found in spleen and cervical lymph nodes after intratracheal immunization and the number in exposed animals was not significantly different than in the controls. These data indicate that even though the 239 PuO 2 exposure had suppressed immune responses in lung-associated lymph nodes, their filtering capacity was unaffected and antigen did not translocate to the spleen. We conclude that, at the sacrifice intervals evaluated, the immune function of lung-associated lymph nodes was suppressed and that distant lymphoid tissue (e.g., spleen and cervical lymph nodes) did not replace the immune function of the lung-associated lymph nodes

Functional state of the bronchopulmonary system in Mayak nuclear workers inhaled plutonium-239 aerosols

International Nuclear Information System (INIS)

Belyaeva, Z.; Grigoryeva, E.; Khokhryakov, V.

2006-01-01

Full text of publication follows: The current system of the individual and collective protection facilities for nuclear personnel permits decreasing the radiation dose from internal emitters at the most. At the same time, specific production conditions do not exclude possible inhalation of plutonium-239 aerosols. As the lung is the critical organ for this isotope, the study of respiratory function is aimed at detecting of pre-clinical lung pathology. Early detection of internal exposure effects on functional state of respiratory apparatus is difficult due to a number of confounding actors of non-radiation nature, one of which is smoking. Functional state of bronchopulmonary system was studied in 386 males, workers of the first Russian nuclear facility. 1198 examinations were carried out during medical inspection as well as hospitalization for routine preventive inspection. Most of males (39.4%) started working at the age of 21-26 years and 27.2% at the age of 20 years. The main factors of occupational exposure were exposure to plutonium-239 aerosols and the external gamma -rays. The absorbed dose to lungs from incorporated plutonium-239 was 0-435.8 c Gy. Whole-body external gamma dose varied from 0 to 382 c Gy at the examination. Individual dosimetry data were provided by the Mayak Radiation Safety Department and Internal Dosimetry Laboratory of the Southern Urals Biophysics Institute. While studying respiratory function, the most informative indices characterizing the state of lung tissue and tracheobronchial system such as vital capacity inspiration, forced expiratory volume, forced inspiratory volume, test Tiffno, diffusion capacity, characteristics of the flow vs. volume of the forced vital capacity inspiration curve, and resistance were used. Analysis was done separately for smokers and nonsmokers. Smoking index, i.e. product of number of smoked cigarettes per day and number of years of smoking was considered an integral value. The study did not reveal the

Functional state of the bronchopulmonary system in Mayak nuclear workers inhaled plutonium-239 aerosols

Energy Technology Data Exchange (ETDEWEB)

Belyaeva, Z.; Grigoryeva, E.; Khokhryakov, V. [Southern Urals Biophysics Institute, Ozyorsk (Russian Federation)

2006-07-01

Full text of publication follows: The current system of the individual and collective protection facilities for nuclear personnel permits decreasing the radiation dose from internal emitters at the most. At the same time, specific production conditions do not exclude possible inhalation of plutonium-239 aerosols. As the lung is the critical organ for this isotope, the study of respiratory function is aimed at detecting of pre-clinical lung pathology. Early detection of internal exposure effects on functional state of respiratory apparatus is difficult due to a number of confounding actors of non-radiation nature, one of which is smoking. Functional state of bronchopulmonary system was studied in 386 males, workers of the first Russian nuclear facility. 1198 examinations were carried out during medical inspection as well as hospitalization for routine preventive inspection. Most of males (39.4%) started working at the age of 21-26 years and 27.2% at the age of 20 years. The main factors of occupational exposure were exposure to plutonium-239 aerosols and the external gamma -rays. The absorbed dose to lungs from incorporated plutonium-239 was 0-435.8 c Gy. Whole-body external gamma dose varied from 0 to 382 c Gy at the examination. Individual dosimetry data were provided by the Mayak Radiation Safety Department and Internal Dosimetry Laboratory of the Southern Urals Biophysics Institute. While studying respiratory function, the most informative indices characterizing the state of lung tissue and tracheobronchial system such as vital capacity inspiration, forced expiratory volume, forced inspiratory volume, test Tiffno, diffusion capacity, characteristics of the flow vs. volume of the forced vital capacity inspiration curve, and resistance were used. Analysis was done separately for smokers and nonsmokers. Smoking index, i.e. product of number of smoked cigarettes per day and number of years of smoking was considered an integral value. The study did not reveal the

Cigarettes, lung cancer, and coronary heart disease: the effects of inhalation and tar yield.

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Higenbottam, T; Shipley, M J; Rose, G

1982-06-01

Ten-year mortality rates for lung cancer and coronary heart disease have been related to cigarette smoking habits in 17 475 male civil servants aged 40-64 and in sample of 8089 male British residents aged 35-69. Both diseases were more frequent in smokers. Lung cancer rates were higher overall for "non-inhalers", particularly in heavy smokers. Tar yield correlated with the risk of lung cancer in non-inhalers but less so in inhalers. Conversely, coronary deaths were more common among inhalers, and the effect of tar/nicotine yield (such as it was) was confined to inhalers. It appears that there are subtle interactions between the amount smoked, the tar/nicotine yield of the cigarette, and the style of smoking. Thus the effects of a change in cigarette characteristics are hard to predict, and they may be different for respiratory and cardiovascular disease.

Removal of inhaled 241Am oxide of various particle sizes from beagle dogs by lung lavage and chelation treatment

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Mo, T.; Felicetti, S.A.

1976-01-01

The removal of 241 Am oxide aerosols of various particle sizes from the lung was studied in 24 Beagle dogs. There were four groups of dogs with six dogs per group and each group inhaled an aerosol of 241 Am oxide of a different particle size or particle size distribution. The four aerosols had sizes of: 0.75 μm AD, sigma/sub g/ 1.1; 1.5 μm AD, sigma/sub g/ 1.1; 3.0 μm AD, sigma/sub g/ 1.1; or 1.5 μm AMAD and sigma/sub g/ of 1.6. Three of the dogs in each group were treated with 10 lung lavages, the first lavage performed 2 days after exposure and the last lavage on day 49 after exposure. Each of these treated dogs was also given 100 mg diethylenetriaminepentaacetic acid (DTPA) intravenously daily for 4 days after 241 Am exposure and twice per week thereafter to the end of the study. Daily excreta collections were made on each of the dogs until sacrifice at 64 days after exposure. The sacrifice body burden (SBB) was much lower for all of the treated dogs compared to the untreated dogs. The 241 Am activity found in the recovered lavage fluid was two to four times greater than the sacrifice body burden. These results suggest that the treatment procedures were effective in reducing the lung and body burden of 241 Am

The removal of inhaled 239Pu from beagle dogs by bronchopulmonary lavage and chelation therapy

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Slauson, D.O.; Miglio, J.J.; Ruoff, L.; Mersch, S.; McClellan, R.O.

1976-01-01

The efficacy of bronchopulmonary lavage and chelatan therapy for removing 239 Pu from beagle dogs after inhalation of 239 Pu aerosols having different solubilities has been investigated. The four aerosols used were nebulized from a solution of 239 PuCl 4 and heat treated at temperatures of 325, 600, 900 and 1150 0 C. Groups of six beagle dogs were exposed to each of the aerosols. Subsequently, three dogs in each group were treated by lavage and intravenous injections of DTPA. The remaining three dogs in each group served as untreated controls. It was found that bronchopulmonary lavage treatment was effective in removing nearly half of the 239 Pu activity from the lung regardless of the aerosol production temperature. This early removal of 239 Pu activity resulted in a significant reduction in daily dose rate and therefore cumulative α dose to lung. The effectiveness of DTPA treatment depended on aerosol production temperature, and was effective in reducing accumulation of 239 Pu in liver and skeleton of the dogs that inhaled aerosols produced at 325 0 and 600 0 C by enhancing urinary excretion of 239 Pu. (U.K.)

In Vitro Tests for Aerosol Deposition. V: Using Realistic Testing to Estimate Variations in Aerosol Properties at the Trachea.

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Wei, Xiangyin; Hindle, Michael; Delvadia, Renishkumar R; Byron, Peter R

2017-10-01

The dose and aerodynamic particle size distribution (APSD) of drug aerosols' exiting models of the mouth and throat (MT) during a realistic inhalation profile (IP) may be estimated in vitro and designated Total Lung Dose, TLD in vitro , and APSD TLDin vitro , respectively. These aerosol characteristics likely define the drug's regional distribution in the lung. A general method was evaluated to enable the simultaneous determination of TLD in vitro and APSD TLDin vitro for budesonide aerosols' exiting small, medium and large VCU-MT models. Following calibration of the modified next generation pharmaceutical impactor (NGI) at 140 L/min, variations in aerosol dose and size exiting MT were determined from Budelin ® Novolizer ® across the IPs reported by Newman et al., who assessed drug deposition from this inhaler by scintigraphy. Values for TLD in vitro from the test inhaler determined by the general method were found to be statistically comparable to those using a filter capture method. Using new stage cutoffs determined by calibration of the modified NGI at 140 L/min, APSD TLDin vitro profiles and mass median aerodynamic diameters at the MT exit (MMAD TLDin vitro ) were determined as functions of MT geometric size across Newman's IPs. The range of mean values (n ≥ 5) for TLD in vitro and MMAD TLDin vitro for this inhaler extended from 6.2 to 103.0 μg (3.1%-51.5% of label claim) and from 1.7 to 3.6 μm, respectively. The method enables reliable determination of TLD in vitro and APSD TLDin vitro for aerosols likely to enter the trachea of test subjects in the clinic. By simulating realistic IPs and testing in different MT models, the effects of major variables on TLD in vitro and APSD TLDin vitro may be studied using the general method described in this study.

Recent advances in delivery mechanisms for aerosol therapy during pediatric respiratory diseases.

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Wu, Yue'E; Zhang, Chonglin; Zhen, Qing

2018-04-01

The treatment of pediatric surgery diseases via utilization of aerosol delivery mechanisms is in progress for the betterment of pediatric care. Over the years, aerosol therapy has come to play an integral role in the treatment of pediatric respiratory diseases. Inhaled aerosol agents such as bronchodilators, corticosteroids, antibiotics, and mucolytics are commonly delivered to spontaneously breathing pediatric patients with a tracheostomy. Administering therapeutic inhaled aerosols to pediatric patients is challenging. The pediatric population ranges in age, which means patients with different airway sizes, breathing patterns, and cooperation levels. These patient-related factors impact the deposition of aerosol drugs in the lungs. The present review article will discuss the recent advancements in the delivery mechanisms for aerosol therapy in pediatric patients with respiratory diseases.

Toxicity of inhaled 238PuO2 II

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Merickel, B.S.; Boecker, B.B.; Hahn, F.F.; Guilmette, R.A.; Mauderly, J.L.; McClellan, R.O.

1980-01-01

Studies are in progress to determine dose-response relationships for inhaled 238 PuO 2 . Beagle dogs were given a single, brief, nose-only inhalation exposure to aerosols of monodisperse particles of 238 PuO 2 . Aerosols of two sizes were used, 1.5 μm aerodynamic diameter (AD) and 3.0 μm AD. Dogs were exposed to achieve initial lung burdens of 0.56, 0.28, 0.14, 0.07, 0.03 or 0.01 μCi 238 PuO 2 /kg body weight. Twelve dogs were exposed at each activity level to each aerosol particle size. The local dose around each 3.0 μm AD particle was 10 times higher than the local dose around 1.5 μm AD particles, but the dose averaged over the whole lung was the same at each activity level for both particle sizes. The lung retention of 238 Pu was divided into two phases of clearance. During the first 100 days after exposure, the average retention half-time for 238 Pu in the lung was 310 days. When the solubility changed due to particle breakup, the retention half-time decreased to 180 days during the period from 1OO to 1,500 days after exposure. The first biological effects observed were lymphopenia and neutropenia in peripheral blood. To date, 28 Beagle dogs have died at times from 536 to 1683 days after exposure. Initial lung burdens for the dead dogs ranged from 0.18 to 2.2 μCi 238 Pu/kg body weight. Nine died with radiation pneumonitis and pulmonary fibrosis, 10 died with lung tumors and 19 dogs died with bone tumors. There are 116 exposed and 22 control dogs surviving and under observation. Current patterns of dose versus response are discussed. (author)

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1

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Sosna William A

2010-09-01

Full Text Available Abstract Background There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1 virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1 through intranasal verses inhalation routes was analyzed. Results Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1. The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret. Conclusions Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1 is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.

Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione.

Science.gov (United States)

Pauluhn, Jürgen; Hai, Chun Xue

2011-01-01

Phosgene is an important high-production-volume intermediate with widespread industrial use. Consistent with other lung irritants causing ALI (acute lung injury), mode-of-action-based countermeasures remain rudimentary. This study was conducted to analyze whether extremely short high-level exposure to phosgene gas could be mitigated using three different inhaled nucleophiles administered by inhalation instantly after exposure to phosgene. Groups of young adult male Wistar rats were acutely exposed to carbonyl chloride (phosgene) using a directed-flow nose-only mode of exposure of 600 mg/m³ for 1.5 min (225 ppm × min). Immediately after exposure to phosgene gas the rats were similarly exposed to three strong nucleophiles with and without antioxidant properties for 5 or 15 min. The following nucleophiles were used: hexamethylenetetramine (HMT), l-cysteine (Cys), and l-glutathione (GSH). The concentration of the aerosol (mass median aerodynamic diameter 1.7-2 µm) was targeted to be in the range of 1 mg/L. Cys and GSH have antioxidant properties in addition. The calculated alveolar molar dosage of phosgene was 9 µmol/kg. At 15-min exposure duration, the respective inhaled dose of HMT, Csy, and GSH were 111, 103, and 46 µmol/kg, respectively. The alveolar dose of drugs was ~10-times lower. The efficacy of treatment was judged by protein concentrations in bronchoalveolar lavage fluid (BALF) collected 1 day post-exposure. In spite of using optimized aerosolization techniques, none of the nucleophiles chosen had any mitigating effect on BALF-protein extravasation. This finding appear to suggest that inhaled phosgene gas acylates instantly nucleophilic moieties at the site of initial deposition and that the resultant reaction products can not be reactivated even following instant inhalation treatment with competing nucleophilic agents. In spite of using maximal technically attainable concentrations, it appears to be experimentally challenging to deliver

Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS).

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Leigh, Noel J; Lawton, Ralph I; Hershberger, Pamela A; Goniewicz, Maciej L

2016-11-01

E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled. Aerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air-liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines). Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic. Our data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Removal of inhaled 241Am oxide particles from beagle dogs by combined treatment with lung lavage and a chelating agent

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Mo, T.; Slauson, D.O.

1978-01-01

This experiment was performed to evaluate combined therapy of lung lavage and chelation treatments to remove inhaled particles of 241 Am oxide. Twenty-four Beagle dogs were divided into four groups of 6 dogs each. Each group was exposed to an aerosol of different-sized particles of 241 Am oxide: monodisperse particles with AD of 0.75, 1.5 or 3.0 μm; polydisperse particles with AMAD = 1.5 μm. Three dogs in each group were treated with 5 lung lavages of the right lung (day 2, 7, 14, 28 and 42), and 5 lavages of the left lung (days 2, 10, 21, 35, and 49). In addition, each of the treated dogs was given 22 μmoles of trisodium calcium diethylenetriaminepentaacetate (Na 3 Ca DTPA) by intravenous injection 18 times from day 1 to 52 after exposure. The remaining 3 dogs in each group were untreated control dogs. All of the dogs were sacrificed 64 days after exposure and tissues, excreta, and lavage fluids were analyzed for 241 Am activity. Tissue distribution of 241 Am activity at sacrifice varied with aerosol particle size. Less 241 Am activity was found in the lungs of the dogs exposed to 0.75 and 1.5 μm AD aerosols groups than in those exposed to 3.0 μm particles. Lung lavage removed from 24 to 58% of the initial lung burden (ILB). Particle size did not affect the usefulness of lung lavage but it did influence the effectiveness of Na 3 Ca DTPA treatment. Na 3 Ca DTPA enhanced urinary excretion of 241 Am; dogs exposed to 0.75 μm particles excreted 31% of the ILB, and those exposed to 3.0 μm particles excreted only 10%. This experiment showed the effectiveness of combined treatment with lung lavage and chelation therapy for the removal of 241 Am oxide in the first 64 days after exposure. (author)

Lung clearance of inhaled particles after exposure to carbon black generated from a resuspension system

International Nuclear Information System (INIS)

Lee, P.S.; Gorski, R.A.; Hering, W.E.; Chan, T.L.

1987-01-01

A system to resuspend carbon black particles for providing submicron aerosols for inhalation exposure studies has been developed. The effect of continuous exposure to carbonaceous material (as a surrogate for the carbonaceous particles in diesel exhaust) on the pulmonary clearance of inhaled diesel tracer particles was studied in male Fischer 344 rats. Submicron carbon black particles with a mass median aerodynamic diameter (MMAD) of 0.22 micron and a size distribution similar to that of exhaust particles from a GM 5.7-liter diesel engine were successfully generated and administered to test animals at a nominal concentration of 6 mg/m3 for 20 hr/day, 7 days/week, for periods lasting 1 to 11 weeks. Immediately after the carbon black exposure, test animals were administered 14 C-tagged diesel particles for 45 min in a nose-only chamber. The pulmonary retention of inhaled radioactive tracer particles was determined at preselected time intervals. Based upon the data collected up to 1 year postexposure, prolonged exposure to carbon black particles exhibits a similar inhibitory effect on pulmonary clearance as does prolonged exposure to diesel exhaust with a comparable particulate dose. This observation indicates that the excessive accumulation of carbonaceous material may be the predominant factor affecting lung clearance

ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED AMBIENT AEROSOLS FOR DIFFERENT DOSE METRICS

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ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED AMBIENT AEROSOLS FOR DIFFERENT DOSE METRICS.Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *South...

Effect of exercise on deposition and subsequent retention of inhaled particles

International Nuclear Information System (INIS)

Bennett, W.D.; Messina, M.S.; Smaldone, G.C.

1985-01-01

To investigate the effect of exercise and its associated increase in ventilation on the deposition and subsequent retention of inhaled particles, we measured the fractional and regional lung deposition of a radioactively tagged (/sup 99m/Tc) monodisperse aerosol (2.6 microns mass median aerodynamic diam) in normal human subjects at rest and while exercising on a bicycle ergometer. Breath-by-breath deposition fraction (DF) was measured throughout the aerosol exposures by Tyndallometry. Following each exposure gamma camera analysis was used to 1) determine the regional distribution of deposited particles and 2) monitor lung retention for 2.5 h and again at 24 h. We found that DF was unchanged between ventilation at rest (6-10 l/min) and exercise (32-46 l/min). Even though mouth deposition was enhanced with exercise, it was not large enough to produce a significant difference in the deposition fraction of the lung (DFL) between resting and exercise exposures. The central-to-peripheral distribution of deposited aerosol was larger for the exercise vs. resting exposure, reflecting a shift of particle deposition to more central bronchial airways. Apical-to-basal distribution was not different for the two exposures. Retention at 2.5 h and 24 h (R24) was reduced following the exercise vs. the resting exposure, consistent with greater bronchial deposition during exercise. The product of DFL and R24 gave a measure of fractional burden at 24 h (B24), i.e., the fraction of inhaled aerosol residing in the lungs 24 h after exposure. B24 was not significantly different between rest and exercise exposures

FACTORS AFFECTING THE DEPOSITION OF AEROSOLIZED INSULIN

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AbstractBackground The inhalation of insulin for absorption into the bloodstream via the lung seems to be a promising technique for the treatment of diabetes mellitus. A fundamental issue to be resolved in the development of such insulin aerosol delivery systems is their...

Modeling accumulations of particles in lung during chronic inhalation exposures that lead to impaired clearance

International Nuclear Information System (INIS)

Wolff, R.K.; Griffith, W.C. Jr.; Cuddihy, R.G.; Snipes, M.B.; Henderson, R.F.; Mauderly, J.L.; McClellan, R.O.

1989-01-01

Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people

Atmospheric aerosol sampling campaign in Budapest and K-puszta. Part 2. Application of Stochastic Lung Model

International Nuclear Information System (INIS)

Dobos, E.; Borbely-Kiss, I.; Kertesz, Zs.; Balashazy, I.

2004-01-01

Complete text of publication follows. The Stochastic Lung Model [1] is a new important tool for the investigation of the health impact of atmospheric aerosols. The obtained concentrations of urban and rural aerosols (see part 1) were applied for lung deposition calculations with this model. The health effects of the inhaled particles may strongly depend on the location of deposition within the lung. This model was applied in order to calculate the deposition efficiencies of the measured aerosols in the tracheobronchial and the acinar regions of human respiratory system. In the acinar regions takes place the gas-exchange. In this model a lot of parameters can be adjusted and changed. For example: tidal volume, aerosol diameter and density, time of breathing cycle, etc. So can be calculation some cases among others males, females or children, sleep, sitting, light or heavy exercise, etc. As example the Figure 1. demonstrates that the acinar deposition has a maximum at 1-3 μm aerosol size and above 10 μm the practically do not reach the acinar region at sitting breathing conditions for male person. In the part I. the elements have been grouped. The first group was composed of Fe, Si and Ca. These elements can be found in 2-8 m size range with the largest rate. The deposition of Fe, Si and Ca elements has the largest probability in acinar region. The elemental concentrations in Budapest are much larger than in K-puszta. Thus, the acinar deposition of aerosol containing Fe, Si and Ca is relatively more significant in Budapest than in K-puszta. The second group was composed of S, Pb and W. The majority of these elements was in the 0,25-1 μm size range. These elements also deposit in acinar region but with less probability. Because their particles have large concentration they can also deposit in large amount. This work was supported by the National Research and Development Program (NRDP 3/005/2001). (author)

Generation of aerosols: BARC nebulizer and others

International Nuclear Information System (INIS)

Soni, P.S.; Raghunath, B.

1994-01-01

The concern with atmospheric pollution in recent times has focused attention on aerosols, their distribution pattern after inhalation and the kinetics of their deposition and exclusion from bronchial passages. The technique of radioaerosols for lung imaging is of recent origin. The procedure was proposed as a means of estimating regional ventilation and localizing areas of airway narrowing. The technique is an alternative in the face of non-availability of radioactive gases, especially in developing countries where the cost is the major factor due to economic reasons. Now, it is beyond doubt that radioaerosol lung studies are a potentially valuable tool in the evaluation of respiratory function in health and disease, especially to detect chronic obstructive pulmonary diseases. Also, the administration of a drug by aerosol inhalation provides a convenient method for the treatment of conditions affecting the respiratory system. This write-up will brief us about radioaerosol, its generation and characterisation

Generation of aerosols: BARC nebulizer and others

Energy Technology Data Exchange (ETDEWEB)

Soni, P S; Raghunath, B

1994-07-01

The concern with atmospheric pollution in recent times has focused attention on aerosols, their distribution pattern after inhalation and the kinetics of their deposition and exclusion from bronchial passages. The technique of radioaerosols for lung imaging is of recent origin. The procedure was proposed as a means of estimating regional ventilation and localizing areas of airway narrowing. The technique is an alternative in the face of non-availability of radioactive gases, especially in developing countries where the cost is the major factor due to economic reasons. Now, it is beyond doubt that radioaerosol lung studies are a potentially valuable tool in the evaluation of respiratory function in health and disease, especially to detect chronic obstructive pulmonary diseases. Also, the administration of a drug by aerosol inhalation provides a convenient method for the treatment of conditions affecting the respiratory system. This write-up will brief us about radioaerosol, its generation and characterisation.

Evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.

Science.gov (United States)

Grinshpun, Sergey A; Weber, Angela M; Yermakov, Michael; Indugula, Reshmi; Elmashae, Yousef; Reponen, Tiina; Rose, Laura

2017-08-01

Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to (1) evaluate the performance of four filter types (one mixed cellulose ester, MCE (pore size = 3 µm), two polytetrafluoroethylene, PTFE (1 and 3 µm), and one polycarbonate, PC (3 µm)); and (2) evaluate the best performing filters in two commercially available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of the four tested collection filters-except MCE-were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 hr. The PC (3 µm) filter was identified as the best performing filter in this study. The PTFE (3 µm) demonstrated a comparable performance, but it is more expensive. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler's performance criterion when detecting a highly pathogenic agent with no established "safe" inhalation exposure level. Additional studies are needed to address the effects of

Lung dosimetry for inhaled radon progeny in smokers

International Nuclear Information System (INIS)

Baias, P. F.; Hofmann, W.; Winkler-Heil, R.; Cosma, C.; Duliu, O. G.

2010-01-01

Cigarette smoking may change the morphological and physiological parameters of the lung. Thus the primary objective of the present study was to investigate to what extent these smoke-induced changes can modify deposition, clearance and resulting doses of inhaled radon progeny relative to healthy non-smokers (NSs). Doses to sensitive bronchial target cells were computed for four categories of smokers: (1) Light, short-term (LST) smokers, (2) light, long-term (LLT) smokers, (3) heavy, short-term (HST) smokers and (4) heavy, long-term (HLT) smokers. Because of only small changes of morphological and physiological parameters, doses for the LST smokers hardly differed from those for NSs. For LLT and HST smokers, even a protective effect could be observed, caused by a thicker mucus layer and increased mucus velocities. Only in the case of HLT smokers were doses higher by about a factor of 2 than those for NSs, caused primarily by impaired mucociliary clearance, higher breathing frequency, reduced lung volume and airway obstructions. These higher doses suggest that the contribution of inhaled radon progeny to the risk of lung cancer in smokers may be higher than currently assumed on the basis of NS doses. (authors)

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds.

Science.gov (United States)

Fröhlich, Eleonore; Mercuri, Annalisa; Wu, Shengqian; Salar-Behzadi, Sharareh

2016-01-01

Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.

Nucleomedical diagnosis of lung cancer

Energy Technology Data Exchange (ETDEWEB)

Ito, Yasuhiko [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1982-06-01

/sup 67/Ga citrate is most often used in the diagnosis of lung cancer. As judged from reported cases, the accuracy rate was 90%, with a false negative rate being about 5%. Lung ventilation and blood flow scintigraphy are valuable in assessing the degree of damage to lung function and the therapeutic effect rather than in finding lung cancer. In aerosol scintigraphy, sup(99m)Tc labelled aerosols with different particle size depending on the purpose of diagnosis are used; the large particles deposit at the center of the trachea and small size aerosols on the periphery. Aerosol-inhaled scintigraphy is highly valuable for the diagnosis of hilus lung cancer. sup(99m)Tc methylene diphosphate is used in bone scintigraphy to detect bone metastasis. But it sometimes gives false positive results such as in the case of senile bone changes. Another valuable method of diagnosis is emission CT by which various substances having affinity for the tumor can be detected by labelling them with a proton emitting nuclear species such as 11 C, /sup 13/N, /sup 15/O and /sup 18/F. Some cases of lung cancer, and the radionuclide methods used in the diagnosis are shown.

Preliminary studies on the spatial-temporal microdistribution of inhaled soluble plutonium in the lungs of dogs

International Nuclear Information System (INIS)

Cho, M.W.; Dagle, G.E.

1987-01-01

The pulmonary microdistribution of inhaled soluble plutonium in four beagle dogs was studied in autoradiographs of histologic sections and transmission electron micrographs of lungs. Dogs were exposed to a single nose-only aerosol of 239 Pu nitrate with a post-exposure time ranging from 1 month to 42 months. At one month after the exposure, the plutonium was dispersed throughout the lung section, with a higher percentage of the activity found on alveolar macrophages and alveolar septa. However, a nonrandom localization of the plutonium was observed as time passed. The focal concentrations were primarily in nodular or diffuse interstitial fibrotic tissues typically contiguous with subpleural, peribronchial, or perivascular areas. More than 50% of the total activity was in the form of single-tracks at one month exposure, and this percentage increased with time. In summary, this preliminary study suggests an initial random dispersion of soluble plutonium with increased concentration of activity to nonrandom focal locations with time

Influence of 239Pu aerosol production temperature on biological responses in Chinese hamsters

International Nuclear Information System (INIS)

Brooks, A. L.; Peters, R.F.; Mewhinney, J.A.

1977-01-01

Studies on the retention, distribution and effects of inhaled 239 Pu particles produced at different temperatures are continuing in an effort to assess the consequences of accidental inhalation exposures under various conditions. Three groups of Chinese hamsters, 381 animals per group, were exposed to aerosols of 239 Pu which had been treated in a heating column at either 50, 600 or 1150 0 C. Retention and distribution of the plutonium through 600 days after exposure reflected the relative insolubility of the aerosols heated at 1150 and 600 0 C, and the relative solubility of the aerosol heated at 50 0 C. Animals exposed to either of the insoluble aerosols had 80 to 90 percent of the sacrifice body burden in the lung at 400 days after exposure whereas animals exposed to the aerosol heated at 50 0 C had only 10 percent of the sacrifice body burden in the lung at 400 days. Translocation was mainly to the liver. To date, survival of the animals seemed to depend primarily on activity level, with production temperature exerting an influence only at the highest activities

Inhaled Antibiotics for Ventilator-Associated Infections.

Science.gov (United States)

Palmer, Lucy B

2017-09-01

Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Xenon ventilation-perfusion lung scans. The early diagnosis of inhalation injury

International Nuclear Information System (INIS)

Schall, G.L.; McDonald, H.D.; Carr, L.B.; Capozzi, A.

1978-01-01

The use of xenon Xe-133 ventilation-perfusion lung scans for the early diagnosis of inhalation injury was evaluated in 67 patients with acute thermal burns. Study results were interpreted as normal if there was complete pulmonary clearance of the radioactive gas by 150 seconds. Thirty-two scans were normal, 32 abnormal, and three technically inadequate. There were three true false-positive study results and one false-negative study result. Good correlation was found between the scan results and various historical, physical, and laboratory values currently used to evaluate inhalation injury. The scans appeared to be the most sensitive method for the detection of early involvement, often being abnormal several days before the chest roentgenogram. Xenon lung scanning is a safe, easy, accurate, and sensitive method for the early diagnosis of inhalation injury and has important therapeutic and prognostic implications as well

Study on the deposition patterns of aerosol inhalation scintigraphy, 2

International Nuclear Information System (INIS)

Watanabe, Hiroyuki

1989-01-01

The superimposed images obtained by the SPECT of aeresol inhalation scintigraphy and chest CT were applied in 7 cases of diffuse panbronchiolitis. Aerosol deposition patterns were examined, and hot spots were compared with bronchial morphological abnormalities. The results were as follows: 1. Nevertheless, aerosol deposition patterns were characterized by defects of the depositions in the outer zone and hot spots in the inner zone, hot spots distributed from the inner zone to the outer zone. 2. Hot spots and bronchial morphological abnormalities were markedly matched in the inner zone; however, they were mismatched in the outer zone. I concluded that the mechanisms of hot spot formation in the inner zone were different from those in the outer zone. (author)

Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats.

Science.gov (United States)

Petitot, Fabrice; Lestaevel, Philippe; Tourlonias, Elie; Mazzucco, Charline; Jacquinot, Sébastien; Dhieux, Bernadette; Delissen, Olivia; Tournier, Benjamin B; Gensdarmes, François; Beaunier, Patricia; Dublineau, Isabelle

2013-03-13

Uranium nanoparticles (fuel cycle and during remediation and decommissioning of nuclear facilities. Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols. The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account. In order to address this issue, the absorption rate of inhaled uranium nanoparticles needs to be characterised experimentally. For this purpose, rats were exposed to an aerosol containing 10⁷ particles of uranium per cm³ (CMD=38 nm) for 1h in a nose-only inhalation exposure system. Uranium concentrations deposited in the respiratory tract, blood, brain, skeleton and kidneys were determined by ICP-MS. Twenty-seven percent of the inhaled mass of uranium nanoparticles was deposited in the respiratory tract. One-fifth of UO₂ nanoparticles were rapidly cleared from lung (T(½)=2.4 h) and translocated to extrathoracic organs. However, the majority of the particles were cleared slowly (T(½)=141.5 d). Future long-term experimental studies concerning uranium nanoparticles should focus on the potential lung toxicity of the large fraction of particles cleared slowly from the respiratory tract after inhalation exposure. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A new mask to prevent environmental contamination during radio aerosol mouth-piece inhalation procedures

International Nuclear Information System (INIS)

Braga, Francisco Jose Hossri Nogueira.

1994-01-01

Environmental contamination is frequent during labelled aerosol mouth-piece inhalation procedures. Previous personnel data showed that in 18/18 situations air background activity has increased after inhalation and this may create serious routine and economical problems. We have tested a new adherent mask made of 3 M's TEGADERM in sixty 99 m Tc-DTPA inhalation studies and the results indicates that the use of such a mask may eliminate the problem of environmental contamination. The device is useful but not entirely efficient in cases when good skin adherence cannot be obtained. 48 refs, 10 figs, 2 tabs

ANALYSIS OF RESPIRATORY DESPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS

Science.gov (United States)

ANALYSIS OF RESPIRATORY DEPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS. Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *S...

Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

Science.gov (United States)

Islam, Nazrul; Richard, Derek

2018-05-24

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical assessment of a commercial delivery system for aerosol ventilation scanning by comparison with Krypton-81m

International Nuclear Information System (INIS)

Wollmer, P.; Eriksson, L.; Andersson, A.

1985-01-01

A commercial aerosol delivery system for ventilation scanning was evaluated in 23 patients with lung disease involving regional disturbances of ventilation. Ventilation scans obtained after inhalation of an aerosol labeled with In-113m were compared with Kr-81m ventilation scans. An indirect comparison was also made with a settling bag technique. There was close agreement between the aerosol and the Kr-81m ventilation scans in all of the patients. The aerosol outlined the ventilated parts of the lung adequately, and central deposition of particles was minimal. The penetration of the aerosol into the lung was higher with the delivery system that with a settling bag system. The aerosol delivery system appears suitable for clinical pulmonary ventilation scintigraphy

Long-term clearance of inhaled magnetite and polystyrene latex from the lung: a comparison

Energy Technology Data Exchange (ETDEWEB)

Schlesinger, R.B.; Halpern, M.; Lippmann, M. (New York Univ., NY (USA). Inst. of Environmental Medicine)

1982-01-01

As part of a larger study evaluating the applicability of a magnetic detection technique for monitoring lung retention of inhaled particles, simultaneous radiological measurements of the retention of magnetite and polystyrene latex particles in four donkeys were performed. The radiometric measurements were performed using a scintillation detector series modified for separation of the higher energy ..gamma..-emissions of /sup 59/Fe and /sup 85/Sr. In all animals, after 24 hr post-exposure, both polystyrene and magnetite exhibited a relatively rapid phase for 80 days (Tsub(1/2) = 15-22 days) which, in three donkeys, was clearly followed by a slower phase (Tsub(1/2) = 42-173 days); activity levels after 80 days in the fourth donkey were too low to permit determination of clearance rate. During the second phase, a deviation in pattern was clearly observed between the two aerosols, the polystyrene being cleared consistently faster than the magnetite. It is suggested that this deviation implies that, beginning at this time, there were functional differences between the dominant clearance mechanisms for the two aerosols. Exactly what these mechanisms were, or whether the difference was attributable to specific differences in particle characteristics, could not be determined.

Long-term clearance of inhaled magnetite and polystyrene latex from the lung: a comparison

International Nuclear Information System (INIS)

Schlesinger, R.B.; Halpern, M.; Lippmann, M.

1982-01-01

As part of a larger study evaluating the applicability of a magnetic detection technique for monitoring lung retention of inhaled particles, simultaneous radiological measurements of the retention of magnetite and polystyrene latex particles in four donkeys were performed. The radiometric measurements were performed using a scintillation detector series modified for separation of the higher energy γ-emissions of 59 Fe and 85 Sr. In all animals, after 24 hr post-exposure, both polystyrene and magnetite exhibited a relatively rapid phase for 80 days (Tsub(1/2) = 15-22 days) which, in three donkeys, was clearly followed by a slower phase (Tsub(1/2) = 42-173 days); activity levels after 80 days in the fourth donkey were too low to permit determination of clearance rate. During the second phase, a deviation in pattern was clearly observed between the two aerosols, the polystyrene being cleared consistently faster than the magnetite. It is suggested that this deviation implies that, beginning at this time, there were functional differences between the dominant clearance mechanisms for the two aerosols. Exactly what these mechanisms were, or whether the difference was attributable to specific differences in particle characteristics, could not be determined. (U.K.)

Inhalation toxicology of diesel fuel obscurant aerosol in Sprague-Dawley rats. Final report, Phase 3, subchronic exposures

Energy Technology Data Exchange (ETDEWEB)

Lock, S.; Dalbey, W.; Schmoyer, R.; Griesemer, R.

1984-12-01

Inhalation exposures were performed twice per week, for 13 weeks, to determine whether there was any potential toxicity to rats of comparatively low concentrations of a condensation aerosol from diesel fuel. Changes in breathing frequency and the response of animals to a loud sharp sound (startle response) were measured in selected animals prior to the start of the exposures, at various time points during the thirteen week exposure period, and at monthly intervals during the recovery period. Assays were performed on selected animals at the end of the exposure period, and again after the two month recovery period. Endpoints included pulmonary function tests, numbers of alveolar free cells, clinical chemistry, hematology, organ weights and histopathology. No mortalities were recorded during the exposure or recovery periods. Slight toxicity occurred at these low aerosol concentrations with the loss in body weight of all treated animals during the exposure period. During the exposure period there were also some slight changes in startle reflex, however, these were apparently acute effects, and there appeared to be no permanent CNS involvement as measured by this endpoint. Immediately post-exposure, the numbers of lavaged alveolar macrophages were slightly elevated in all aerosol exposed animals. Pulmonary function tests, pulmonary gas exchange and dynamic lung tests were all apparently unaffected by these low diesel fuel aerosol exposures. Changes in tissue weights in aerosol exposed animals were minor and the few histopathological lesions were randomly scattered amongst all groups included in this study and were more attributable to the age of the animals than any specific treatment group. No significant cumulative toxicity may be attributed to these diesel fuel aerosol exposures. 14 references, 1 figure, 42 tables.

RECONSTRUCTION OF A HUMAN LUNG MORPHOLOGY MODEL FROM MAGNETIC RESONANCE IMAGES

Science.gov (United States)

RATIONALE A description of lung morphological structure is necessary for modeling the deposition and fate of inhaled therapeutic aerosols. A morphological model of the lung boundary was generated from magnetic resonance (MR) images with the goal of creating a framework for anato...

Lung inhalation scintigraphy with radioactive aerosols in several pulmonary diseases

International Nuclear Information System (INIS)

Martins, L.R.; Marioni Filho, H.; Romaldini, H.; Uehara, C.; Alonso, G.

1983-01-01

The pulmonary ventilation scintigraphy with 99m Tc diethylene-triamine-pentaacetate (99mTc-DTPA) delivered through a new nebulizer system when analyzed together with the classic lung perfusion scintigraphy with 99mTc-labeled albumin macroaggregates (99mTcMAA) is a very important diagnostic tool in several pulmonary diseases. Several aspects of the lung ventilation-perfusion scintigraphy are studied in 15 people with no lung disease, smokers and nonsmokers. The findings with the lung ventilation-perfusion scintigraphy are also discussed in 34 patients with several pulmonary diseases: lung cancer, chronic obstructive lung disease, policystic pulmonary disease, and pulmonary embolims. The authors concluded that the procedure is a valuable diagnostic tool in several pulmonary diseases, especially because good lung images are obtained, no side effects were detected, the technique is ease and low cost, and it brings new informations, not available with other diagnostic methods. (author)

Toxicity of inhaled 90Sr in fused aluminosilicate particles in beagle dogs. VIII

International Nuclear Information System (INIS)

Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1977-01-01

Studies on the metabolism, dosimetry and biological effects of 90 Sr inhaled in a relatively insoluble form by Beagle dogs have continued during the past year to define the biological consequences of inhaling this important radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol of fused aluminosilicate particles labeled with 90 Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90 Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. These 124 dogs were assigned to the longevity study. An additional 26 dogs were exposed similarly to achieve lung burdens of approximately 1.5 to 12 μCi/kg and assigned for sacrifice at intervals after exposure to define metabolism and dosimetry of this aerosol in Beagle dogs. Of the longevity dogs, 33 dogs having initial lung burdens of 16 to 94 μCi 90 Sr/kg and cumulative doses to lung of 40,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis from 159 to 2373 days after exposure. Thirty-one dogs with initial lung burdens of 3.7 to 36 μCi 90 Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung or heart between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with a hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. The remaining exposed dogs and controls of the longevity study are surviving at 1022 to 2803 days after exposure

Recent lung imaging studies

International Nuclear Information System (INIS)

Taplin, G.V.; Chopra, S.K.

1976-01-01

Radionuclide lung imaging procedures have been available for 11 years but only the perfusion examination has been used extensively and mainly for the diagnosis of pulmonary embolism (P.E.). Its ability to reveal localized ischemia makes it a valuable test of regional lung function as well as a useful diagnostic aid in P.E. Although it had been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as a means of distinguishing P.E. from COPD. In this review emphasis is placed on our recent experience with both of these inhalation procedures in comparison with pulmonary function tests and roentgenography for the early detection of COPD in population studies. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imaging for a functional diagnosis of P.E. Two new developments in regional lung diffusion imaging, performed after the inhalation of radioactive gases and/or rapidly absorbed radioaerosols are described. The experimental basis for their potential clinical application in pulmonary embolism detection is presented

Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma.

Science.gov (United States)

Phillips, Jonathan E; Renteria, Lorena; Burns, Lisa; Harris, Paul; Peng, Ruoqi; Bauer, Carla M T; Laine, Dramane; Stevenson, Christopher S

2016-06-01

In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR. Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation.

The deposition - a modern phenomenon in the evaluation of inhalation risk of mining aerosols

Directory of Open Access Journals (Sweden)

Ľubomír Legáth

2007-04-01

Full Text Available The deposition is defined as an array of processes causing a part of the inhaled aerosol to remain (after its expiration in the respiratory tract. The particles retained in the respiratory tract are called deposits. The deposition encompasses of three different mechanisms: impaction, sedimentation and Brown molecular movement combined with the diffusion. The impaction remains the most potential contribution to the deposition in the conductive zone of the respiratory tract. While the sedimentation and diffusion in conjunction with the Brown molecular movement have a major impact in the respiratory area with the zero flow movement. The above listed mechanisms participate with the different ratio to the deposition at respective parts of the respiratory tract.The deposition depends on physical and chemical properties of inhaled aerosols as well as on the susceptibility of each individual. The size, shape, mass, and electric charges are among the basic characteristics of aerosols. The individual susceptibility is mainly influenced by an anatomical arrangement of respiratory tract, tidal volume, frequency of breathing, and breath holding.

Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

Science.gov (United States)

Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

2016-12-01

Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

Research of transport and deposition of aerosol in human airway replica

Science.gov (United States)

Lizal, Frantisek; Jedelsky, Jan; Elcner, Jakub; Durdina, Lukas; Halasova, Tereza; Mravec, Filip; Jicha, Miroslav

2012-04-01

Growing concern about knowledge of aerosol transport in human lungs is caused by great potential of use of inhaled pharmaceuticals. Second substantial motive for the research is an effort to minimize adverse effects of particular matter emitted by traffic and industry on human health. We created model geometry of human lungs to 7th generation of branching. This model geometry was used for fabrication of two physical models. The first one is made from thin walled transparent silicone and it allows a measurement of velocity and size of aerosol particles by Phase Doppler Anemometry (PDA). The second one is fabricated by stereolithographic method and it is designed for aerosol deposition measurements. We provided a series of measurements of aerosol transport in the transparent model and we ascertained remarkable phenomena linked with lung flow. The results are presented in brief. To gather how this phenomena affects aerosol deposition in human lungs we used the second model and we developed a technique for deposition fraction and deposition efficiency assessment. The results confirmed that non-symmetric and complicated shape of human airways essentially affects transport and deposition of aerosol. The research will now focus on deeper insight in aerosol deposition.

Investigations of the tracheobronchial epithelium of rat after X-ray irradiation and inhalation of 212Pb aerosol

International Nuclear Information System (INIS)

Petri, P.

1981-01-01

Early reactions of the tracheobronchial epithelium of rats. Be up to 96 h after irradiation have been investigated. Detection of autoradiographically labelled DNA in the basal cells is a measure of the regenerative function of the epithelium. The labelling index is determined on the basis of histological preparations of trachea and bronchi. Each group of animals was exposed to partial irradiation of the thorax of 500 R, 1000 R and 1500 R. A dose-dependent reduction of the labelling index is found with a minimum after 24 h. A further group of animals inhaled 212 Pb aerosol while the control group was given inactive aerosol. The calculations of Hofmann (1969) yield a value of about 170 rad for the trachea and 480 rad for the upper part of the lungs. The labelling index after 12 h is lower than in the animals exposed to 500 R. It is significantly higher in the lobar bronchi. At the time of sacrificing, the labelling index is higher in all regions than the labelling index of 500 R animals. This labelling method enables quantitative determination of DNA synthesis and labelling index after radiation exposure. The study did not indicate the stage of development in which the so-called ''replacement cells'' of the bronchial epithelium are influenced by radiation exposure. Radionuclide inhalation does not affect the bronchial DNA synthesis index as strongly as assumed on the basis of dose estimates. Ater 12 h, the trachea shows a stronger reaction than the bronchi. Explanations are offered. (orig./MG) [de

Late effects of inhaled 253Es(NO3)3 in rats

International Nuclear Information System (INIS)

Ballou, J.E.; Dagle, G.E.; Gies, R.A.; Smith, L.G.

1979-01-01

Einsteinium-253 nitrate was administered as an aerosol to male Wistar rats and the long-term biological effects were followed for the animals' life span. Lung was the major target organ for absorbed radiation dose and tumor induction, in agreement with results for other inhaled transuranic nitrates. The earlier finding of a high incidence of bone tumors following intratracheal instillation of 253 EsCl 3 was not confirmed in the present study with inhaled 253 Es(NO 3 ) 3 . The reason for the difference in bone tumor production is believed to be related to the different acute toxicities of intratracheally instilled and inhaled 253 Es. Intratracheally instilled 253 EsCl 3 was less acutely toxic (only a single lobe or one-half the lung was irradiated); thus, a larger more tumorigenic dose could be translocated to bone without shortening the life span to the extent that bone tumors could not be expressed. The radiation dose from inhaled 253 Es(NO 3 ) 3 was uniformly spread throughout both lungs and early death due to a generalized radiation pneumonitis precluded the development of long-term effects in bone. (author)

Production of monodisperse respirable aerosols of 241AmO2 and evaluation of in vitro dissolution

International Nuclear Information System (INIS)

Boyd, H.A.; Raabe, O.G.; Peterson, P.K.

1974-01-01

A method is described for production of monodisperse (sigma//sub g/ less than 1.2) particles of 241 AmO 2 for use in inhalation experiments with dogs and rodents. The effects of physical and chemical factors on the production of polydisperse aerosols of 241 AmO 2 were studied and evaluated. The best aerosol was achieved when a suspension of americium hydroxide with 2.5 mg Am/ml at pH = 7.3 was aerosolized and passed through two heating columns in succession, the first at 300 0 C and the second at 1050 0 C. The particles were roughly spherical and had densities near 8 gm/cm 3 ; the aerosol AMAD and sigma/sub g/ were about 1.5 μm and 1.7, respectively. Monodisperse particles were separated and collected with the Lovelace Aerosol Particle Separator (LAPS) and subsequently suspended in deionized water with pH adjusted to 10.2 with NH 3 for nebulization to produce monodisperse aerosols for inhalation exposures. Particles collected on filters during inhalation experiments were used for evaluation of in vitro dissolution rates with two systems and various forms of a lung fluid simulant. The important role of phosphate ions in such dissolution systems was demonstrated, suggesting the potential for the equally important role of free phosphate in retarding dissolution of AmO 2 particles in the lung. (U.S.)

No correlation between initial arterial carboxyhemoglobin level and degree of lung injury following ovine burn and smoke inhalation.

Science.gov (United States)

Lange, Matthias; Cox, Robert A; Traber, Daniel L; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D; Enkhbaatar, Perenlei

2014-04-01

Fire victims often suffer from burn injury and concomitant inhalation trauma, the latter significantly contributing to the morbidity and mortality in these patients. Measurement of blood carboxyhemoglobin levels has been proposed as a diagnostic marker to verify and, perhaps, quantify the degree of lung injury following inhalation trauma. However, this correlation has not yet been sufficiently validated. A total of 77 chronically instrumented sheep received sham injury, smoke inhalation injury, or combined burn and inhalation trauma following an established protocol. Arterial carboxyhemoglobin concentrations were determined directly after injury and correlated to several clinical and histopathological determinants of lung injury that were detected 48 hours post-injury. The injury induced severe impairment of pulmonary gas exchange and increases in transvascular fluid flux, lung water content, and airway obstruction scores. No significant correlations were detected between initial carboxyhemoglobin levels and all measured clinical and histopathological determinants of lung injury. In conclusion, the amount of arterial carboxyhemoglobin concentration cannot predict the degree of lung injury at 48 hours after ovine burn and smoke inhalation trauma.

Lung deposition and systemic bioavailability of different aerosol devices with and without humidification in mechanically ventilated patients.

Science.gov (United States)

Moustafa, Islam O F; Ali, Mohammed R A-A; Al Hallag, Moataz; Rabea, Hoda; Fink, James B; Dailey, Patricia; Abdelrahim, Mohamed E A

During mechanical ventilation medical aerosol delivery has been reported to be upto two fold greater with dry inhaled gas than with heated humidity. Urine levels at 0.5 h post dose (URSAL0.5%) has been confirmed as an index of lung deposition and 24 h (URSAL24%) as index of systemic absorption. Our aim was to determine the effect of humidification and aerosol device type on drug delivery to ventilated patients using urine levels. In a randomized crossover design, 36 (18female) mechanically ventilated patients were assigned to one of three groups. Groups 1 and 2 received 5000 μg salbutamol using vibrating mesh (VM) and jet nebulizers (JN), respectively, while group 3 received 1600 μg (16 puffs) of salbutamol via metered dose inhaler with AeroChamber Vent (MDI-AV). All devices were placed in the inspiratory limb of ventilator downstream from the humidifier. Each subject received aerosol with and without humidity at >24 h intervals with >12 h washout periods between salbutamol doses. Patients voided urine 15 min before each study dose and urine samples were collected at 0.5 h post dosing and pooled for the next 24 h. The MDI-AV and VM resulted in a higher percentage of urinary salbutamol levels compared to the JN (p < 0.05). Urine levels were similar between humidity and dry conditions. Our findings suggest that in-vitro reports overestimate the impact of dry vs. heated humidified conditions on the delivery of aerosol during invasive mechanical ventilation. Copyright © 2017 Elsevier Inc. All rights reserved.

Exercise increases the lung clearance of inhaled Tc-99m DTPA

International Nuclear Information System (INIS)

Meignan, M.; Rosso, J.; Cinotti, L.; Galle, P.

1985-01-01

It has been suggested that blood flow have little effect on the lung clearance of Tc-99m DTPA which depends on the alveolar distension. However an increase of pulmonary blood flow, induces a recruitment of new vascular areas which can enhance this clearance. To assess this hypothesis the pulmonary apical and basal clearances of a sumicronic aerosol of Tc-99m DTPA were studied at rest and at exercise in seven non smoking volunteers in upright posture. As a matter of fact exercising upright is known to increase primarily the apical blood flow. After inhalation the subjects were seated on a bicycle their back against a gamma camera which was linked to a computer. The lung radioactivity was registered successively during a resting and an exercising period. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise (50 Watts, 60 c. min /sup -1/, 7 min.) this regional gradient was enhanced by a large and significant increase of the apical clearances (0.0340 min /sup -1/ +-0.0063 SD versus 0.00183 min /sup -1/ +- 0.074 SD at rest, n = 7, p < 0.01). By contrast the changes of the basal clearances were slight and unsignificant (0.0146 min /sup -1/ +- 0.0062 SD versus 0.0140 min /sup -1/ +- 0.0082 SD). Since exercise induces little distension of the apical alveoli but drastically enhances the apical blood flow, the observed increase of the apical lung clearance could be primarily attributed to the recruitment of new capillaries induced by exercise in the apices. This led to an increase of the surface area permeability product

Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

Directory of Open Access Journals (Sweden)

Pierre Ernst

1998-01-01

Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

Influence of initial lung deposit on pulmonary clearance after plutonium oxide inhalation in rat

International Nuclear Information System (INIS)

Van der Meeren, A.; Grillon, G.; Tourdes, F.; Rateau, S.; Le Gall, B.; Griffiths, N.

2007-01-01

Alveolar macrophages are a key element in the clearance of inhaled particles after phagocytosis, and thus participate actively in lung dose distribution and in the risk of tumour formation. We studied the influence of initial lung deposit (ILD) on lung clearance and distribution of activity from 3 d to 3 months after inhalation of two forms of PuO 2 (97% 239 Pu and 70% 239 Pu) in rats. ILDs ranging from 2.1 to 17 kBq were used. The total activity measured using X-ray spectrometry 3 months post-inhalation, relative to the ILD, showed a similar decrease in all groups, with the remaining activity representing ∼30% of the ILD. The total activity recovered in bronchoalveolar lavages represented ∼60% of the total lung activity. This ratio remained stable over time for the lowest ILD tested but decreased for higher ILD. In addition, the percentage of macrophages associated with particles decreased faster with time in rats with the highest ILD. Under our experimental conditions, there were no marked differences in lung clearance between groups. However, the distribution of the activity seems to vary with the time post-exposure between low and high ILD. (authors)

Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

Science.gov (United States)

Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

2016-01-01

This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects. © 2016 S. Karger AG, Basel.

Exposure of F344 rats to aerosols of 239PuO2 and chronically inhaled cigarette smoke

International Nuclear Information System (INIS)

Finch, G.L.; Nikula, K.J.; Barr, E.B.; Bechtold, W.E.; Chen, B.T.; Griffith, W.C.; Hobbs, C.H.; Hoover, M.D.; Mauderly, J.L.

1994-01-01

Nuclear workers may be accidently exposed to radioactive materials such as 239 PuO 2 by inhalation, and thus have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radionuclides and other carcinogens may increase the risk of cancer induction. An important and common lung carcinogen is cigarette smoke. This study is being conducted to better determine the combined effects of inhaled 239 PuO 2 and cigarette smoke on the induction of lung cancer in rats

COMPUTER RECONSTRUCTION OF A HUMAN LUNG MORPHOLOGY MODEL FROM MAGNETIC RESONANCE (MR) IMAGES

Science.gov (United States)

A mathematical description of the morphological structure of the lung is necessary for modeling and analysis of the deposition of inhaled aerosols. A morphological model of the lung boundary was generated from magnetic resonance (MR) images, with the goal of creating a frame...

Assessments of risk following the inhalation of plutonium oxide using observed lung clearance patterns

International Nuclear Information System (INIS)

Ramsden, D.

1977-10-01

Dose commitments and risk estimates for the inhalation of plutonium oxide are calculated using the lung clearance patterns observed at AEE Winfrith. These risks are compared with published data on risks arising from a lung clearance based on the ICRP Lung Model. (author)

Dosimetry of inhaled plutonium-239 dioxide in rodent lung: a morphometric study

International Nuclear Information System (INIS)

Rhoads, K.

1979-06-01

Morphometric analysis of rat and hamster lung did not demonstrate any extensive changes in lung composition or structure following inhalation exposure to 239 Pu0 2 at levels near that for maximum tumor yield in rats. The problem of dosimetry for this compound thus appears to be relatively uncomplicated by any major radiation-induced pathological alterations in the lung. Rat and hamster lung were found to be similar in structure and composition, with few significant differences which could be directly related to the different tumor responses. The distribution of 239 Pu0 2 particles was not uniform in all regions of the lung; thus estimation of the dose to specific tissues or regions within the lung requires a correction for this effect. Species differences were found for particle distribution in the subpleural region and major airways, and in the spatial association of particles, both of which may affect the tumor development process. These regions contain the principal target cells for tumor production and serve as foci for the origin of tumors. Different dose distributions within these regions may therefore explain, at least in part, the difference in tumor response to inhaled 239 Pu0 2 for rats and hamsters

Expert Nordic perspectives on the potential of novel inhalers to overcome unmet needs in the management of obstructive lung disease

DEFF Research Database (Denmark)

Løkke, Anders; Ahlbeck, Lars; Bjermer, Leif

2015-01-01

fails to achieve adequate lung deposition and therapeutic effect. In this report, the potential of novel inhaler devices to overcome unmet needs in the management of obstructive lung disease is considered by a panel of Nordic experts. The panel concludes that innovative inhalers can contribute to good......The effective self-management of obstructive lung disease is dependent upon the patient achieving good inhaler technique. However, many current inhalers are complicated to use, which may lead to handling difficulties. These difficulties can cause clinically relevant errors, whereby pharmacotherapy...... disease management and better use of healthcare resources....

Toxicity of inhaled alpha-emitting radionuclides - Status report

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Guilmette, R.A.; Gillett, N.A.; Diel, J.H.; Lundgren, D.L.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

1988-01-01

The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of 239 Pu, 238 Pu, 241 Am, or 244 Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

Research of transport and deposition of aerosol in human airway replica

Directory of Open Access Journals (Sweden)

Mravec Filip

2012-04-01

Full Text Available Growing concern about knowledge of aerosol transport in human lungs is caused by great potential of use of inhaled pharmaceuticals. Second substantial motive for the research is an effort to minimize adverse effects of particular matter emitted by traffic and industry on human health. We created model geometry of human lungs to 7th generation of branching. This model geometry was used for fabrication of two physical models. The first one is made from thin walled transparent silicone and it allows a measurement of velocity and size of aerosol particles by Phase Doppler Anemometry (PDA. The second one is fabricated by stereolithographic method and it is designed for aerosol deposition measurements. We provided a series of measurements of aerosol transport in the transparent model and we ascertained remarkable phenomena linked with lung flow. The results are presented in brief. To gather how this phenomena affects aerosol deposition in human lungs we used the second model and we developed a technique for deposition fraction and deposition efficiency assessment. The results confirmed that non-symmetric and complicated shape of human airways essentially affects transport and deposition of aerosol. The research will now focus on deeper insight in aerosol deposition.

Toxicity of 144Ce inhaled in a relatively insoluble form by beagle dogs

International Nuclear Information System (INIS)

Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1980-01-01

The metabolism, dosimetry and effects of 144 Ce inhaled in fused aluminosilicate particles are being investigated in the beagle dog to assess the long-term biological consequences of release of relatively insoluble aerosol forms of 144 Ce that could occur in nuclear accidents. The effects resulting from the relatively protracted radiation dose patterns to the lung from this form of 144 Ce are being compared with effects of other radiation dose patterns to the lung. One hundred eleven dogs were exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 0.0024 to 210 μCi/kg body weight and 15 control dogs were exposed to nonradioactive fused aluminosilicate particles. To date, 65 144 Ce-exposed and 2 control dogs have died or were euthanized at 143 to 4578 days after inhalation of 144 Ce. Prominent findings in the 144 Ce-exposed dogs were radiation pneumonitis in 17 dogs that died at early times and neoplastic disease in 39 of the 48 dogs that died 750 days or later. Observations are continuing on the 46 144 Ce-exposed and 13 control dogs remaining alive at this time, at least 3337 days after exposure

Relationships between Personal Measurements of 'Total' Dust, Respirable, Thoracic, and Inhalable Aerosol Fractions in the Cement Production Industry.

Science.gov (United States)

Notø, Hilde P; Nordby, Karl-Christian; Eduard, Wijnand

2016-05-01

The aims of this study were to examine the relationships and establish conversion factors between 'total' dust, respirable, thoracic, and inhalable aerosol fractions measured by parallel personal sampling on workers from the production departments of cement plants. 'Total' dust in this study refers to aerosol sampled by the closed face 37-mm Millipore filter cassette. Side-by-side personal measurements of 'total' dust and respirable, thoracic, and inhalable aerosol fractions were performed on workers in 17 European and Turkish cement plants. Simple linear and mixed model regressions were used to model the associations between the samplers. The total number of personal samples collected on 141 workers was 512. Of these 8.4% were excluded leaving 469 for statistical analysis. The different aerosol fractions contained from 90 to 130 measurements and-side-by side measurements of all four aerosol fractions were collected on 72 workers.The median ratios between observed results of the respirable, 'total' dust, and inhalable fractions relative to the thoracic aerosol fractions were 0.51, 2.4, and 5.9 respectively. The ratios between the samplers were not constant over the measured concentration range and were best described by regression models. Job type, position of samplers on left or right shoulder and plant had no substantial effect on the ratios. The ratios between aerosol fractions changed with different air concentrations. Conversion models for estimation of the fractions were established. These models explained a high proportion of the variance (74-91%) indicating that they are useful for the estimation of concentrations based on measurements of a different aerosol fraction. The calculated uncertainties at most observed concentrations were below 30% which is acceptable for comparison with limit values (EN 482, 2012). The cement industry will therefore be able to predict the health related aerosol fractions from their former or future measurements of one of the

Comparison of modeled estimates of inhalation exposure to aerosols during use of consumer spray products.

Science.gov (United States)

Park, Jihoon; Yoon, Chungsik; Lee, Kiyoung

2018-05-30

In the field of exposure science, various exposure assessment models have been developed to complement experimental measurements; however, few studies have been published on their validity. This study compares the estimated inhaled aerosol doses of several inhalation exposure models to experimental measurements of aerosols released from consumer spray products, and then compares deposited doses within different parts of the human respiratory tract according to deposition models. Exposure models, including the European Center for Ecotoxicology of Chemicals Targeted Risk Assessment (ECETOC TRA), the Consumer Exposure Model (CEM), SprayExpo, ConsExpo Web and ConsExpo Nano, were used to estimate the inhaled dose under various exposure scenarios, and modeled and experimental estimates were compared. The deposited dose in different respiratory regions was estimated using the International Commission on Radiological Protection model and multiple-path particle dosimetry models under the assumption of polydispersed particles. The modeled estimates of the inhaled doses were accurate in the short term, i.e., within 10 min of the initial spraying, with a differences from experimental estimates ranging from 0 to 73% among the models. However, the estimates for long-term exposure, i.e., exposure times of several hours, deviated significantly from the experimental estimates in the absence of ventilation. The differences between the experimental and modeled estimates of particle number and surface area were constant over time under ventilated conditions. ConsExpo Nano, as a nano-scale model, showed stable estimates of short-term exposure, with a difference from the experimental estimates of less than 60% for all metrics. The deposited particle estimates were similar among the deposition models, particularly in the nanoparticle range for the head airway and alveolar regions. In conclusion, the results showed that the inhalation exposure models tested in this study are suitable

Aerosol azacytidine inhibits orthotopic lung cancers in mice through Its DNA demethylation and gene reactivation effects.

Directory of Open Access Journals (Sweden)

Xuan Qiu

Full Text Available We devised an aerosol based demethylation therapy to achieve therapeutic efficacy in premalignant or in situ lesions of lung cancer, without systemic toxicity. Optimum regimens of aerosolized azacytidine (Aza were designed and used in orthotopic human non-small cell lung cancer xenograft models. The therapeutic efficacy and toxicity of aerosol Aza were compared with intravenously administered Aza. We observed that 80% of the droplets of the aerosol Aza measured ∼0.1-5 microns, which resulted in deposition in the lower bronchial airways. An animal model that phenocopies field carcinogeneisis in humans was developed by intratracheal inoculation of the human lung cancer cells in mice, thus resulting in their distribution throughout the entire airway space. Aerosolized Aza significantly prolonged the survival of mice bearing endo-bronchial lung tumors. The aerosol treatment did not cause any detectable lung toxicity or systemic toxicity. A pre-pharmacokinetic study in mice demonstrated that lung deposition of aerosolized Aza was significantly higher than the intravenous route. Lung tumors were resected after aerosol treatment and the methylation levels of 24 promoters of tumor-suppresser genes related to lung cancer were analyzed. Aerosol Aza significantly reduced the methylation level in 9 of these promoters and reexpressed several genes tested. In conclusion, aerosol Aza at non-cytotoxic doses appears to be effective and results in DNA demethylation and tumor suppressor gene re-expression. The therapeutic index of aerosol Aza is >100-fold higher than that of intravenous Aza. These results provide a preclinical rationale for a phase I clinical trial of aerosol Aza to be initiated at our Institution.

Deposition of plutonium in the lung of a worker following an accidental inhalation exposure

International Nuclear Information System (INIS)

Spitz, H.B.; Robinson, B.

The deposition of PuO 2 in the lungs of an occupationally exposed worker is characterized by assay for plutonium in excreta samples and from in vivo measurements of 241 Am in the thoracic region. Chelation therapy by intravenous injection of 1 gm Ca-DTPA was initially performed shortly after the incident and repeated using 0.5 gm of the chelate four additional times in subsequent days post intake. Analysis of the air sampler filter retrieved from the site of the exposure identified the isotopic composition and particle size of the plutonium material inhaled by the worker. Chelation with Ca-DTPA did not significantly reduce the magnitude of the lung or systemic deposition as determined from assay of plutonium in urine samples collected from the worker. In vivo measurements for 241 Am verify the retention of the inhaled material in the lung and also indicate the ingrowth of an amount of 241 Am as a daughter product of the 241 Pu initially inhaled

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury.

Science.gov (United States)

Lange, Matthias; Cox, Robert A; Enkhbaatar, Perenlei; Whorton, Elbert B; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Esechie, Aimalohi; von Borzyskowski, Sanna; Traber, Lillian D; Traber, Daniel L

2011-05-01

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Radiation dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1980-June 1981

International Nuclear Information System (INIS)

Mewhinney, J.A.

1982-04-01

The objective of this project is to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research being conducted. The first presents final results for several types of physical chemical characterization accomplished on samples of aerosols collected at an industrial facility during normal fabrication of mixed oxide fuel. Many of these characterizations were also done on aerosol samples collected during animal inhalation exposure procedures for biological studies using these aerosol materials. The second paper reports on the methods development process used for establishing a capability for measurement of the specific surface area of aerosols, an important determinant in the rate of dissolution of particulates deposited in lung. The third paper provides updated information on the retention, distribution and excretion of Pu after inhalation by Beagles of aerosols of either 750 0 C treated UO 2 + PuO 2 , 1750 0 C treated (U,Pu)O 2 or 850 0 C treated pure PuO 2 . This paper also reports the results of the formulation of a biomathematical model useful in describing the results of these three inhalation studies. The fourth paper describes the early results from two studies in which Fischer-344 rats received inhalation exposure to aerosols of (U,Pu)O 2 or pure PuO 2 to determine the relationship of radiation dose to biological response

Dry powder inhalation of hemin to induce heme oxygenase expression in the lung

NARCIS (Netherlands)

Zijlstra, G.S.; Brandsma, C.; Harpe, M.F.H.; Van Dam, G.M.; Slebos, D.J.; Kerstjens, H.A.M.; de Boer, Anne; Frijlink, H.W.

2007-01-01

The purpose of this study was to formulate hemin as a powder for inhalation and to show proof of concept of heme oxygenase 1 (HO-1) expression in the lungs of mice by inhalation of hemin. Hemin was spray dried from a neutralized sodium hydroxide solution. The particle size distribution of the powder

Lung dynamics of aerosol particles with special reference to deposition model

International Nuclear Information System (INIS)

Takahashi, Kanji

1977-01-01

A movement of aerosol particles in the lungs, which was inhaled into the respiratory organ was given an outline by means of technological deposition model. The respiratory organ was considered to be one airway system, and was divided into nasopharyngeal part, trachea-bronchial part, and pulmonary part. The transport of particles in the respiratory tract was explained by mentioning structual model of the airway system, standard respiratory flow, and distribution of flow speed in the respiratory tract. It was explained that particle deposition in the respiratory tract seemed to be caused by inertia impact at bifurcation, gravity deposition and scattering deposition at tubular wall, interruption effect in nasopharyngeal part, and scattering phoresis effect in the upper respiratory tract or gas exchange part. Furthermore, an outline of calculation of the deposition amount of particles was described from a standpoint of the above-mentioned structure, breathing air flow, and deposition structure of particles. (Kanao, N.)

Microprocessor-controlled inhalation system for repeated exposure of animals to aerosols

International Nuclear Information System (INIS)

Carpenter, R.L.; Barr, F.P.; Leydig, R.L.; Rajala, R.E.

1979-01-01

A microprocessor-controlled inhalation exposure system (MCIES) has been built to automate aerosol generation and sampling while controlling exposure time for animal toxicity studies. The system has a time resolution of 0.1 s and automatically sequences the exposure events from initiation to temination of the exposure. The operator is required to preset all airflows, read in a paper tape containing the time sequence of events, and initiate the automatic sequence by closing a switch

A study of the comparison between human and animal excretion data following inhalation exposure to plutonium 238 oxide aerosols

International Nuclear Information System (INIS)

Moss, W.D.; Martinez, G.; Gautier, M.A.

1985-01-01

Bioassay urine samples obtained since 1971 from eight Los Alamos employees, accidentally exposed by inhalation to high-fired plutonium-238 oxide aerosols, were studied and compared with excretion data obtained from Beagle dogs exposed to /sup 238/PuO/sub 2/ aerosols. The early period Pu human excretion data from the inhalation exposure were unexpected and were unlike previously studied occupational exposure urinary data obtained at Los Alamos. The initial urine samples collected on day one were below the detection limits of the analytical method (0.01 pCi). Within thirty days, however, detectible concentrations of Pu were measured in the urine for several of the exposed personnel. The amounts of Pu excreted continued to increase in each of the cases throughout the first year and the individual patterns of Pu excretion were similar. The human urinary excretion data was compared with similar excretion data obtained from an animal study conducted by the Inhalation Toxicology Research Institute (Me81). In the animal study, Beagle dogs received inhalation exposure to one of three sizes of monodisperse of polydisperse aerosol of /sup 238/PuO/sub 2/. Periodic sacrifice of pairs of dogs during the 4 years after the inhalation exposure provided data on the retention, translocation and mode of excretion of /sup 238/Pu. The comparison of human and animal /sup 238/Pu excretion data supported the observation that the excretion data were similar between the two species and that the animal excretion models can be applied to predict the human /sup 238/Pu excretion following inhalation exposure to high-fired oxides of /sup 238/Pu

Granulometric determinations and inhalation dose assessment for atmospheric aerosol contaminated by 137Cs

International Nuclear Information System (INIS)

Castellani, C.M.; Luciani, A.; Oliviero, L.; Donato, R.

1996-07-01

During the redevelopment of Brescia freight-yard a measurement campaign of atmospheric aerosol was carried out: in fact a 137 Cs ground contamination, caused by the permanence of wagons carrying iron materials contaminated by this radionuclide, had been found out. During the redevelopment phases of excavation and can filling the workers were exposed to the danger of radioactive aerosol inhalation. The aim of the measurement campaign was to test the aerosol sampling and granulometric analysis methodologies with their sensitivity related to the inhalation dose assessments. The results of both aerosuspended mass and activity, evaluated by means of a portable cascade impactor, are presented. The granulometries have been interpolated with a log normal distribution using an iterative routine minimizing the square deviation between the calculated and experimental data. The results related to the dose assessments are also presented. These evaluations have been carried out using both the granulometric information obtained and the more recent models (ICRP 66) both the total concentration data and the dose coefficients referring to the standard conditions of ICRP 68 and of the Italian law (D.Lgs. 230/95). Furthermore the significance and the reliability of the dose assessments referring to the different methodologies are discussed, also in relation to the possibility of using this sampling methodologies for other radionuclides and different exposure conditions

Quantitative analysis and design of a spray aerosol inhaler. Part 1: effects of dilution air inlets and flow paths.

Science.gov (United States)

Longest, P Worth; Hindle, Michael

2009-09-01

The objective of this study was to evaluate the effects of modifying inhaler design variables on aerosol drug deposition within the mouthpiece for a representative spray system using a quantitative analysis and design approach. Capillary aerosol generation (CAG) was selected as a model spray aerosol system in conjunction with four prototype inhaler body and mouthpiece combinations. In vitro experiments were used to determine drug deposition in the mouthpiece and induction port. Validated computational fluid dynamics (CFD) simulations were implemented to establish relationships between design variables, transport characteristics, and aerosol drug deposition. Results of this study indicated that both the size of the upstream dilution air inlets and the flow pathway configuration near the spray nozzle significantly influenced aerosol transport and deposition. CFD results showed that the primary transport characteristics associated with drug deposition were turbulence intensity and the effective diameter of the mouthpiece. Strong quantitative correlations were developed between the identified transport characteristics and mouthpiece drug deposition. Based on quantitative analysis and design, turbulence intensity and effective mouthpiece diameter were identified as key transport characteristics within the design space that directly influenced aerosol deposition and may be used to predict and optimize drug delivery to the patient.

Bronchial and pulmonary scintigraphy with radioactively marked aerosols

International Nuclear Information System (INIS)

Wuerstle, T.

1982-01-01

In 97 patients with bronchitis, bronchial asthma, tuberculosis, sarcoidosis, pneumoconiosis, or tumors the mucociliary clearance and/or deposit pattern after inhalation of radioactively marked aerosols (1 mCi 99m Tc sulfur colloid) was studied. Normal values of the mucociliary 30 min. clearance for the central bronchial/lung periphery are 21%/15%. There was a decreased clearance with bronchitis (11/8%), bronchial asthma, emphysema, tuberculosis, sarcoidosis, trachiobronchial amyloidosis, pleural scarring or interstitial pneumona. Increased clearance (29/19%) was shown with pneumoconiosis. The correlation of deposit pattern and disease, for example, bronchitis, bronchial asthma, bullous emphysema, pleural scarring, partial lung resection, bronchopneumonia, or bronchial restriction, is described. In comparison of aerosol scintigraphy to perfusion scintigraphy and ventilation with gaseous xenon, the aerosol scintigraphy is superior to xenon for certain indications. The aerosol particles, which are larger in comparison to xenon, settle easier by obstructions or flow variations and thereby give better clinical indications of regional differences. (orig.) [de

Toxicity of inhaled 144Ce fused clay particles in beagle dogs. VII

International Nuclear Information System (INIS)

Hahn, F.F.; Boecker, B.B.; Hobbs, C.H.; Jones, R.K.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1974-01-01

The metabolism, dosimetry, and effects of inhaled 144 Ce in fused clay particles are being investigated in the Beagle dog to aid in assessing the biological consequences of release of 144 Ce in a relatively insoluble form such as might occur in certain types of nuclear accidents. The toxicity of inhaled 144 Ce fused clay is also of general interest since it is representative of intermediate-lived beta-emitting radionuclides. Two major studies with young adult dogs (12 to 14 months of age at exposure) are involved: (1) a metabolism and dosimetry study in which 24 dogs were serially sacrificed over an extended period of time, and (2) a longevity study with 2 series of dogs; Series I with 15 dogs exposed to aerosols of 144 Ce in fused clay particles to yield initial lung burdens of 11 to 210 μCi/kg body weight and 3 control dogs exposed to nonradioactive fused clay particles and Series II with 96 dogs exposed to aerosols of 144 Ce in fused clay particles to yield initial lung burdens of 0.0024 to 66 μCi/kg body weight and 12 control dogs exposed to nonradioactive fused clay particles. Twenty-eight dogs died or were euthanized at 143 to 2396 days after inhalation of 144 Ce. The prominent findings were radiation pneumonitis in 17 dogs that died or were euthanized at early time periods and neoplastic disease in 10 of the 11 dogs that died or were euthanized at 750 days or later; 5 with hemangiosarcoma of the lung, 1 with both a hemangiosarcoma and a fibrosarcoma of the lung, 1 with both a bronchiolo-alveolar carcinoma and a hemangiosarcoma of lung, 1 with a hemangiosarcoma of lung, bronchiolo-alveolar carcinoma, and a bronchiogenic adenocarcinoma, and 1 each with a hemangiosarcoma of the mediastinum and of the spleen. The cumulative radiation dose to the lung at time of death has ranged from 22,000 to 140,000 rads. Serial observations are continuing on the 83 survivors and 15 controls. (U.S.)

Lung imaging in pulmonary disease

International Nuclear Information System (INIS)

Taplin, G.V.; Chopra, S.K.

1976-01-01

Although it has been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as a means of distinguishing pulmonary embolism (P.E.) from COPD is reported. Recent experience is reported with the use of both of these procedures in comparison with pulmonary function tests for the early detection of COPD in population studies and also in P.E. suspects. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imaging in the differential diagnosis of P.E. Finally, this paper is concerned with new developments in regional lung diffusion imaging following the inhalation of radioactive gases and rapidly absorbed radioaerosols. Their experimental basis is presented and their potential clinical applications in pulmonary embolism are discussed. As a result of these investigations, a functional (V/P) diagnosis of pulmonary embolism in patients may be possible in the near future with a sequential radioaerosol inhalation procedure alone

Uncertainties on lung doses from inhaled plutonium.

Science.gov (United States)

Puncher, Matthew; Birchall, Alan; Bull, Richard K

2011-10-01

In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

Aerosol deposition in the upper airways of a child

NARCIS (Netherlands)

de Jongh, Franciscus H.C.; Rinkel, M.J.G.; Hoeijmakers, Hendrik Willem Marie

2005-01-01

In a small child, normally only a small amount of inhaled aerosol particles reaches the lungs because the majority deposits in the upper airways. In this study, the upper airways of a 9- month-old child, based on computed tomography (CT) data, are modeled to serve as input for a computational fluid

An In Vitro Aerosolization Efficiency Comparison of Generic and Branded Salbutamol Metered Dose Inhalers

Directory of Open Access Journals (Sweden)

Sara Rahimkhani, Saeed Ghanbarzadeh, Ali Nokhodchi, Hamed Hamishehkar

2017-03-01

Full Text Available Background: Due to the high rate of pulmonary diseases, respiratory drug delivery systems have been attracted excessive attention for the past decades. Because of limitations and growing drug bill, physicians are encouraged to prescribe generically whenever possible. The purpose of this study was to evaluate whether there was any significant difference in aerosolization performance between a reference brand Salbutamol (A Metered Dose Inhalers (MDIs and two generic products (B and C. Methods: The aerosolization performance of MDIs was evaluated by calculating aerosolization indexes including fine particle fraction (FPF, fine particle dose (FPD, geometric standard deviation (GSD and mass median aerodynamic diameters (MMAD by using the next generation impactor. Results: Although aerosolization indexes of MDI A were superior than the Iranian brands, but the differences were not statistically significant. Conclusion: These results verified that generic MDIs deliver similar quantities of Salbutamol to the reference brand and aerosolization performance parameters of generic Salbutamol MDIs did not differ significantly from the reference brand.

Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

Directory of Open Access Journals (Sweden)

Barfod Kenneth K

2010-09-01

Full Text Available Abstract Background The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF, clearance of bacteria from the lung lumen and histological alterations of the lungs. Hazard identifications of the biopesticides were carried out using intratracheal (i.t. instillation, followed by an inhalation study. The two commercial biopesticides used were based on the Bt. subspecies kurstaki and israelensis, respectively. Groups of BALB/c mice were i.t instilled with one bolus (3.5 × 105 or 3.4 × 106 colony forming units (CFU per mouse of either biopesticide. Control mice were instilled with sterile water. BALFs were collected and the inflammatory cells were counted and differentiated. The BALFs were also subjected to CFU counts. Results BALF cytology showed an acute inflammatory response dominated by neutrophils 24 hours after instillation of biopesticide. Four days after instillation, the neutrophil number was normalised and inflammation was dominated by lymphocytes and eosinophils, whereas 70 days after instillation, the inflammation was interstitially located with few inflammatory cells present in the lung lumen. Half of the instilled mice had remaining CFU recovered from BALF 70 days after exposure. To gain further knowledge with relevance for risk assessment, mice were exposed to aerosols of biopesticide one hour per day for 2 × 5 days. Each mouse received 1.9 × 104 CFU Bt israelensis or 2.3 × 103 CFU Bt kurstaki per exposure. Seventy days after end of the aerosol exposures, 3 out of 17 mice had interstitial lung inflammation. CFU could be recovered from 1 out of 10 mice 70 days after exposure to aerosolised Bt kurstaki. Plethysmography showed that inhalation of Bt aerosol did not induce airway irritation. Conclusions Repeated low dose aerosol

Deposition and clearance of inhaled 18FDG powder in patients with chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Yanai, M.; Sasaki, H.; Hatazawa, J.; Ojima, F.; Itoh, M.; Ido, T.

1998-01-01

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 μm in mean diameter, was water soluble and labelled with 2-deoxy-2[ 18 F]-fluoro-D-glucose ( 18 FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normal and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8±2.6, mean±SD) and normals (2.6±0.8, mean±SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18 FDG, defined as the retention ratio of 18 FDG activity to the initially deposited 18 FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients. (au)

Toxicity of inhaled alpha-emitting radionuclides - Status report

Energy Technology Data Exchange (ETDEWEB)

Muggenburg, B A; Mewhinney, J A; Guilmette, R A; Gillett, N A; Diel, J H; Lundgren, D L; Hahn, F F; Boecker, B B; McClellan, R O

1988-12-01

The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of {sup 239}Pu, {sup 238}Pu, {sup 241}Am, or {sup 244}Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

Energy Technology Data Exchange (ETDEWEB)

McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: conor_mcgrath@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

2009-02-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

International Nuclear Information System (INIS)

McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

2009-01-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

The deposition, distribution and retention of inhaled 239PuO2 in the lungs of rats with pulmonary emphysema

International Nuclear Information System (INIS)

Lundgren, D.L.; Damon, E.G.; Diel, J.H.; Hahn, F.F.

1981-01-01

Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled 239 PuO 2 in rats. (author)

Quantitative analysis and design of a spray aerosol inhaler. Part 2: improvements in mouthpiece performance.

Science.gov (United States)

Hindle, Michael; Longest, P Worth

2013-10-01

The objective of this study was to utilize previously identified critical design attributes for the capillary aerosol generator as a model spray inhaler in order to develop a second-generation device that minimized aerosol drug deposition in the mouthpiece. Computational fluid dynamics (CFD) predictive analysis of the critical design attributes indicated that turbulence intensity should be reduced and the effective mouthpiece diameter should be increased. Two second-generation inhaler mouthpieces meeting these specifications were manufactured and tested. The first device (Design 1) implemented a larger cross-sectional area in the mouthpiece and streamlined flow, whereas the second device (Design 2) used a perforated mouthpiece wall. An in vitro deposition study was performed to quantify the deposition of drug mass in the mouthpieces and connected induction ports, and the results were compared with the CFD predictions. The two second-generation mouthpieces reduced in vitro aerosol deposition from the original value of 7.8% to values of 2.1% (Device 1) and 4.3% (Device 2), without largely altering the induction port deposition. This was achieved by design alterations aimed at reducing turbulence intensity and increasing the effective mouthpiece diameter. CFD model predictions were in good agreement with the in vitro experimental data. A second-generation spray inhaler mouthpiece with low drug deposition was developed using a predictive CFD model and in vitro experiments. Applying this quantitative analysis and design methodology to medical devices, which is similar to the Quality by Design paradigm, could provide significant advantages compared with traditional approaches.

Clinical assessment of a commercial aerosol delivery system for ventilation scanning by comparison with KR-81m

International Nuclear Information System (INIS)

Wollmer, P.; Eriksson, L.; Andersson, A.C.

1984-01-01

Radioactive aerosols offer a means for steady state ventilation scanning in multiple views. The clinical use of radioaerosol techniques has been hampered by the lack of delivery systems producing sufficiently small particles. If the aerosol contains large particles, heavy deposition occurs in major airways, especially in patients with airways disease. The authors have assessed a new, commercial aerosol delivery system (Syntevent) by comparison with Kr-81m ventilation scanning in 23 patients with airways obstruction. An indirect comparison was also made with a settling bad technique. Ventilation scans in four projections were obtained during continuous inhalation of Kr-81m. Subsequently, the patient inhaled an aerosol labelled with In-113m from the Syntevent system, and aerosol ventilation scans were obtained in the same projections. Spirometry was performed to establish the degree of airways obstruction. The aerosol delineated the ventilated regions of the lungs adequately in all the patients. Deposition of aerosol in larger airways was seen in a few patients only, and this did not impede the interpretation of the scintigram. A quantitative analysis of the penetration of the aerosol to the periphery of the lung failed to demonstrate any significant correlation between particle penetration and airways obstruction. Aerosol penetration was significantly greater (p<0.001) with the Syntevent system than with a settling bag technique

Late effects of inhaled 253Es(NO3)3 in the rat

International Nuclear Information System (INIS)

Ballou, J.E.; Smith, L.G.; Dagle, G.E.; Gies, R.A.

1979-01-01

The lungs of rats exposed to 253 Es(NO 3 ) 3 aerosols sustained the greatest cumulative radiation dose, approximately 6-fold higher than the skeletal dose. Malignant lung tumors (incidence 8.5, 27.6%) were observed after a mean cumulative lung dose of 26 and 400 rad, respectively. Higher lung doses were associated with severe life shortening that precluded the expression of delayed effects. Osteosarcomas of the skeleton (incidence 6.9%) were found after a mean cumulative skeletal dose of 68 rad. Earlier studies, which showed a high incidence of bone tumors and relatively fewer lung tumors after intratracheal instillation of 253 EsCl 3 , were not confirmed in this study with inhaled 253 Es(NO 3 ) 3

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Park, J.F.

1982-01-01

This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for lifespan dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12μCi. Nineteen of the dogs exposed to 238 Pu haved died during the first 7-1/2 yr after exposure due to bone and/or lung tumors; their body burdens at death ranged from 0.7 to 10μCi. Chronic lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2

Toxicity of inhaled 238PuO2 I

International Nuclear Information System (INIS)

Diel, J.H.; Mewhinney, J.A.

1980-01-01

The deposition, retention, translocation and microscopic distribution of inhaled 238 PuO 2 particles were studied to better define the organs at risk and uniformity of dose and cell types or structures at risk in the lung. Beagle dogs were exposed once by inhalation to an aerosol of 238 PuO 2 with particle aerodynamic diameters of 0.7, 1.4, or 2.7 μm (+-10%). Initial burdens averaged about 700 nCi, a level not expected to induce life-shortening effects in Beagle dogs. Animals were sacrificed at times from 4 hours to 2 years after exposure. Whole body retention of plutonium and its distribution among organs in the sacrificed animals was determined by radiochemical analysis for plutonium content of excreta and tissue samples. The distribution of particles in lung was determined using autoradiographs of lung tissue sections and computer-assisted data collection and analysis. Soon after exposure, PuO 2 was relatively insoluble in lung with individual particles being randomly distributed throughout the lung. A distinct change in the rate of dissolution from lung occurred at about 100 days after exposure resulting in decreased pulmonary retention and increased uptake by liver and skeleton. Particle breakup was observed in autoradiographs for time periods in excess of 128 days after exposure. Broken up particles dissolved rapidly leaving little residue in the lung. The remaining particles were randomly distributed in the lung. These results are discussed in relation to current radiation protection guides for plutonium radionuclides. (author)

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Energy Technology Data Exchange (ETDEWEB)

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. �

Examination of post operative split lung function using quantitative xenon 133 (133Xe) inhalation scan

International Nuclear Information System (INIS)

Omote, Yoshiharu; Maeda, Tomio; Ikeda, Koichiro; Kubo, Yoshihiko

1992-01-01

133 Xe inhalation scan and ordinary lung function testing were performed three times in 34 patients undergoing pulmonary resection: before surgery, and one and six months postoperatively. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1.0 ) were used as spirometric parameters. From the 133 Xe inhalation scan, a split lung capacity (right to left, upper, middle and lower) and T1/2 (time required for half of the inhalation of 133 Xe gas to be expired) were calculated by computer and used as indices of split lung capacity and ventilation, respectively. The predicted postoperative lung functions were calculated using preoperative spirometric respiratory function and 133 Xe inhalation data according to the formula reported by Ali and associates. At sixth postoperative month, both predicted FVC (r=0.895, p 1.0 (r=0.897, p<0.001) correlated highly with those actually observed. These results appear to be very useful for preoperative evaluation of operative indications and the choice of surgical method. The ratios of observed to predicted lung capacity in the post operative state were examined by splitting the right and left lung and the means±S.D.(%) were 80.5±9.7% on the operated side and 119.2±11.7% on the opposite side one month after surgery. Six months after surgery, the corresponding figures were 111.0±5.6% and 96.7±16.4%. The post operative T1/2 values on the operated sides were about 2.4 times the preoperative values at one month after surgery but returned to the preoperative values by the six postoperative month. From these results, it can be said that respiratory functions after pulmonary resection are maintained primarily by compensatory lung function of opposite and operated sides at one and six months, respectively. These results also provide valuable information on postoperative respiratory care for patients who have undergone lung resection. (author)

Aerosolized gadolinium-DTPA for demonstration of pulmonary ventilation in MR imaging of the lung

International Nuclear Information System (INIS)

Haage, P.; Adam, G.; Karaagac, S.; Pfeffer, J.G.; Glowinski, A.; Doehmen, S.; Guenther, R.W.; Misselwitz, B.; Tacke, J.

2000-01-01

Purpose: Magnetic resonance assessment of lung ventilation with aerosolized Gd-DTPA. Methods: Eleven experimental procedures were carried out in a domestic pig model. The intubated pigs were aerosolized for 30 minutes with an aqueous formulation of Gd-DTPA. The contrast agent aerosol was generated by a small particle aerosol generator. Imaging was performed on a 1.5 T MR imager using a T 1 -weighted turbo spin echo sequence with respiratory gating (T R 141 ms, T E 8.5 ms, 6 averages, slice thickness 10 mm). Pulmonary signal intensities before and after ventilation were measured in peripheral portions of both lungs. Results: Immediately after ventilation with aerosolized Gd-DTPA, the signal intensity in both lungs increased significantly in all animals with values up to 237% above baseline (mean 139%±48%), but within some cases considerable regional intra- and interindividual intensity differences. Distinctive parenchymal enhancement was readily visualized in all eleven cases with good spatial resolution. Conclusion: The presented data indicate that Gd-DTPA in aerosolized form can be used to demonstrate pulmonary ventilation in large animals with lung volumes comparable to man. Further experimental trials are necessary to improve reproducibility and to define the scope of this method for depicting lung disease. (orig.) [de

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

Science.gov (United States)

Benzing, A; Loop, T; Mols, G; Geiger, K

1999-10-01

Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the

Protective effects of edaravone combined puerarin on inhalation lung injury induced by black gunpowder smog.

Science.gov (United States)

Wang, Zhengguan; Li, Ruibing; Liu, Yifan; Liu, Xiaoting; Chen, Wenyan; Xu, Shumin; Guo, Yuni; Duan, Jinyang; Chen, Yihong; Wang, Chengbin

2015-05-01

The present study aimed to investigate the combined effects of puerarin with edaravone on inhalation lung injury induced by black gunpowder smog. Male Wistar rats were divided into five groups (control group, edaravone group, puerarin group, edaravone combined with puerarin group and inhalation group). The severity of pulmonary injuries was evaluated after inducing acute lung injury. Arterial blood gas, inflammatory cytokines, biochemical, parameters, cell counting, W/D weight ratio and histopathology were analyzed. Results in lung tissues, either edaravone or puerarin treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis (all pedaravone and puerarin demonstrated additive protective effects on smog-induced lung injury, compared with single treatment. Combination of edaravone and puerarin shows promise as a new treatment option for acute lung injury/acute respiratory distress syndrome patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Computational Fluid Dynamics Simulations of Inhaled Nano-and Micro-Particle Deposition in the Rhesus Monkey Nasal Passages

Science.gov (United States)

2016-12-01

reconstruction of the adult model was originally developed by Kepler et al. (1998) from serial Magnetic Resonance Imaging ( MRI ) sections of the right...upper airways and MRI imaging of a lung cast to form a contiguous reconstruction from the nostrils through 19 airway generations of the lung. For this...and Musante, C. J. (2001). A nonhuman primate aerosol deposition model for toxicological and pharmaceutical studies. Inhal. Toxicol. 13:307-324

A Comparison of the Pharmacokinetics and Pulmonary Lymphatic Exposure of a Generation 4 PEGylated Dendrimer Following Intravenous and Aerosol Administration to Rats and Sheep.

Science.gov (United States)

Ryan, Gemma M; Bischof, Robert J; Enkhbaatar, Perenlei; McLeod, Victoria M; Chan, Linda J; Jones, Seth A; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

2016-02-01

Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep. Lung-derived lymph could not be sampled in rats and so lymphatic transport of the dendrimer from the lung was assessed in sheep. Higher plasma concentrations were achieved when dendrimer was administered to the lungs of rats as a liquid instillation when compared to an aerosol. Plasma pharmacokinetics were similar between sheep and rats, although some differences in disposition patterns were evident. Unexpectedly, less than 0.5% of the aerosol dose was recovered in pulmonary lymph. The data suggest that rats provide a relevant model for assessing the pharmacokinetics of inhaled macromolecules prior to evaluation in larger animals, but that the pulmonary lymphatics are unlikely to play a major role in the absorption of nanocarriers from the lungs.

Tumorigenic responses from single or repeated inhalation exposures to relatively insoluble aerosols of Ce-144

International Nuclear Information System (INIS)

Boecker, B.B.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

1980-01-01

Human occupational or environmental inhalation exposures may involve repeated or chronic exposures, but most laboratory studies of inhaled radionuclides have involved single exposures. This study was designed to compare the biological effects of repeated inhalation exposures of dogs to a relatively insoluble form of 144 Ce with existing data for singly-exposed dogs that had the same cumulative dose to the lungs two years after exposure. To date, the biological effects observed in these repeatedly-exposed dogs have been substantially different from those seen in singly-exposed dogs, particularly during the first 5 years after the initial exposure. Although pulmonary hemangiosarcoma was the prominent biological effect seen in singly-exposed dogs between 2 and 4 years after exposure, no lung tumors were seen during the 5 years after the first of the repeated exposures. This response plus other clinical observations are discussed in relation to the patterns of dose rate and cumulative dose for the different exposure conditions. (H.K.)

Organ burdens and elimination rates of inhaled thorium and plutonium

International Nuclear Information System (INIS)

Unnikrishnan, K.; Murthy, K.B.S.; Sunta, C.M.

1986-01-01

For the purpose of interpreting observations from internal monitoring programmes, organ burdens and excretion rates resulting from inhalation of long-lived isotopes of plutonium and thorium have been calculated, on the basis of the ICRP model. Two types of inhalation, instantaneous (acute) and at a steady rate (chronic) are considered. The expected buildups of the burden in lungs, lymph nodes, bone, liver and other tissues, as well as the excretion rates, have been calculated for aerosol classes W and Y, and particle sizes of AMAD 1 μm and 6 μm. Further, in view of their use in selecting the periodicity of routine monitoring, theoretical results are also presented for the case of a total inhalation of 1 ALI in one year, instantaneously or at a constant rate. (author)

Toxicity studies of inhaled beta-emitting radionuclides - Status report

Energy Technology Data Exchange (ETDEWEB)

Hahn, F F; Boeker, B B; Gillett, N A; Griffith, W C; Lundgren, D L; McClellan, R O; Muggenburg, B A; Snipes, M B

1988-12-01

The effects of beta-emitting radionuclides inhaled in either a relatively soluble form ({sup 90}SrCl{sub 2}, {sup 144}CeCl{sub 3}, {sup 91}yl{sub 3}, or {sup 137}CsCl) or in a relatively insoluble form ({sup 90}Y, {sup 91}Y, {sup 144}Ce or {sup 90}Sr in fused aluminosilicate particles [FAP]) have been studied in laboratory animals. The results showed that the total beta dose and the dose-rate pattern can modify both the neoplastic and non-neoplastic effects of inhaled beta-emitting radionuclides. In addition, the solubility and chemical characteristics of the radionuclides influence which organs are affected. Effects are seen primarily in organs where the radionuclide is ultimately accumulated, e.g., lung, bone, liver, or tracheobronchial lymph nodes. In addition, effects may be seen in organs where there is little accumulation, but where the radiation dose may still be high, e.g., nasal epithelium and heart. Studies of inhaled {sup 144}Ce-FAP in four different species showed that, compared to mice and dogs, lung tumor risk factors are very low for Syrian hamsters and high for rats. Studies of mice, Syrian hamsters, rats, and dogs repeatedly exposed to aerosols of {sup 144}Ce-FAP showed that lung tumor incidence correlates better with cumulative dose to the lung than with dose rate. Most of the studies in this program are nearing completion and full analyses are in progress. (author)

Development and comparison of new high-efficiency dry powder inhalers for carrier-free formulations.

Science.gov (United States)

Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R; Hindle, Michael

2014-02-01

High-efficiency dry powder inhalers (DPIs) were developed and tested for use with carrier-free formulations across a range of different inhalation flow rates. Performance of a previously reported DPI was compared with two new designs in terms of emitted dose (ED) and aerosolization characteristics using in vitro experiments. The two new designs oriented the capsule chamber (CC) at different angles to the main flow passage, which contained a three-dimensional (3D) rod array for aerosol deaggregation. Computational fluid dynamics simulations of a previously developed deaggregation parameter, the nondimensional specific dissipation (NDSD), were used to explain device performance. Orienting the CC at 90° to the mouthpiece, the CC90 -3D inhaler provided the best performance with an ED = 73.4%, fine particle fractions (FPFs) less than 5 and 1 μm of 95.1% and 31.4%, respectively, and a mass median aerodynamic diameter (MMAD) = 1.5 μm. For the carrier-free formulation, deaggregation was primarily influenced by capsule aperture position and the NDSD parameter. The new CC-3D inhalers reduced the percent difference in FPF and MMAD between low and high flows by 1-2 orders of magnitude compared with current commercial devices. In conclusion, the new CC-3D inhalers produced extremely high-quality aerosols with little sensitivity to flow rate and are expected to deliver approximately 95% of the ED to the lungs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Regional deposition of inhaled fog droplets: preliminary observations

International Nuclear Information System (INIS)

Bowes, S.M. III; Laube, B.L.; Links, J.M.; Frank, R.

1989-01-01

The regional deposition of a monodisperse 10-micron mass median aerodynamic diameter fog was studied in four healthy adult male nonsmokers. The fog was radiolabeled with technetium-99m sulfur colloid to enable detection by an Anger camera of deposited activity in the following regions of the respiratory tract: oropharynx, larynx, trachea, and intrapulmonary airways. Intrapulmonary deposition was further analyzed by computer with inner, intermediate, and outer zones, and within apical, intermediate and basal zones of the right lung. The radiolabeled aerosol was inhaled by mouth through a face-mask with the nasal airway occluded. Respiratory frequency, tidal volume, and jaw position were controlled and were commensurate with the oral component of oronasal breathing during moderate exercise. Deposition in the larynx, trachea, and intrapulmonary airways was a function of the scrubbing efficiency of the oropharynx, which differed substantially among subjects, and ranged from 72 to 99%. The density of the aerosol deposit in the larynx probably exceeded that of any of the subdivisions of the tracheobronchial tree and lung. Within the lung, deposition favored the inner zone (assumed to contain the larger airways) over the outer zone (assumed to be dominated by smaller airways and alveoli). Intrapulmonary aerosol distribution in an elderly subject with borderline evidence of airway obstruction differed from that observed in younger subjects. The possible consequences of altered lung elastic recoil, as may occur with aging, for regional dosimetry is discussed

Deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in the lungs of rats with pulmonary emphysema

Energy Technology Data Exchange (ETDEWEB)

Lundgren, D L; Damon, E G; Diel, J H; Hahn, F F [Lovelace Foundation for Medical Education and Research, Albuquerque, NM (USA). Inhalation Toxicology Research Inst.

1981-02-01

Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in rats.

The relative effectiveness of inhaled alpha- and beta-emitting radionuclides in producing lung cancer

International Nuclear Information System (INIS)

Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Guilmetter, R.A.; Griffith, W.C.; McClellan, R.O.

1988-01-01

Proper assessment of a long-term human health risks associated with inhaled radionuclides requires knowledge of dose to critical cells and tissues and relationships between dose and effect for different biological end points. Results from epidemiological studies of exposed human populations provided important information for such assessments. However, because the types of exposures are limited, these results need to be supplemented with more detailed information on dosimetry and biological effects available through studies in laboratory animals and in vitro systems. To provide health risk information for inhaled fission product and actinide aerosols, life-span studies are being conducted using beagle dogs and other species at the Lovelace Inhalation Toxicology Research Institute (ITRI). Results of two life-span studies in dogs involving inhalation of the beta emitter 91 Y in fused aluminosilicate particles or the alpha emitter 239 PuO 2 are reported here

Classification of alpha-active workplace aerosols based on coefficient of transportability as measured by the dialysis method

International Nuclear Information System (INIS)

Khokhryakov, V.F.; Suslova, K.G.; Tseveloyova, I.A.; Aladova, E.E.; Filipy, R.E.

1998-01-01

This report describes a method by which potentially inhaled workplace aerosols containing plutonium compounds are classified on the basis of measured transportability in Ringer's solution. It is suggested that the criterion 'transportability' be used in the ICRP respiratory tract model. Transportability is measured as the fraction of plutonium alpha activity, deposited on a collecting filter, that passes through a semi-permeable membrane in Ringer's physiological solution during two days of dialysis. First order kinetic equations are used for explanation of dialysis results. The dissolution characteristics of alpha-active aerosols are important in interpretation of their passage from the lungs after inhalation. (author)

Real-world healthcare utilization in asthma patients using albuterol sulfate inhalation aerosol (ProAir® HFA with and without integrated dose counters

Directory of Open Access Journals (Sweden)

Kerwin EM

2017-05-01

Full Text Available Edward M Kerwin,1 Thomas J Ferro,2 Rinat Ariely,3 Debra E Irwin,4 Ruchir Parikh3 1Clinical Trials Division, Clinical Research Institute of Southern Oregon, PC, Medford, OR, 2Global Medical Affairs, 3Global Health Economics and Outcome Research, Teva Pharmaceuticals, Frazer, PA, 4Outcomes Research, Truven Health Analytics, Durham, NC, USA Background: Accurate tracking of the administered dose of asthma rescue inhalers is critical for optimal disease management and is related to reductions in rates of unscheduled health care utilization in asthma patients. There are few published data on the real-world impact of rescue inhalers with integrated dose counters (IDCs on health care resource utilization (HRU for asthma patients. This study evaluates HRU among users of ProAir® hydrofluoroalkane (HFA (albuterol sulfate inhalation aerosol, with IDC versus without IDC, in asthma patients.Methods: This was a retrospective administrative claims study of asthma patients receiving a new prescription for albuterol inhalation aerosol without IDC during 2 years (January 2011–December 2012 or with IDC during the first full year after IDC implementation in the USA (July 2013–July 2014. Six months of continuous enrollment with medical and prescription drug benefits were required before and after the first prescription during the study period. Data on respiratory-related hospitalizations and emergency department (ED visits were collected during the follow-up period.Results: A total of 135,305 (32% patients used albuterol inhalation aerosol with IDC, and 287,243 (68% patients received albuterol inhalation aerosol without IDC. After adjusting for baseline confounding factors, the odds ratio (OR for experiencing a respiratory-related hospitalization (OR=0.92; 95% confidence interval [CI] 0.88–0.96 or ED visit (OR=0.92; 95% CI 0.90–0.94 was significantly lower among patients using albuterol inhalation aerosol with IDC versus without IDC.Conclusion: In a real

Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

Energy Technology Data Exchange (ETDEWEB)

Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: colin_dickens@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

2009-02-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

International Nuclear Information System (INIS)

Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

2009-01-01

Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

Toxicity of 144Ce inhaled in a relatively insoluble form by Beagle dogs. XI

International Nuclear Information System (INIS)

Hahn, F.F.; Hanika-Rebar, C.; Boecker, B.B.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1978-01-01

The metabolism, dosimetry and effects of 144 Ce inhaled in fused aluminosilicate particles are being investigated in the Beagle dog to assess the biological consequences of release of 144 Ce in a relatively insoluble form such as might occur in certain types of nuclear accidents. The toxicity of inhaled 144 Ce is also of general interest since it is representative of intermediate-lived beta-emitting radionuclides. Two major studies with young adult dogs (12 to 14 months of age at exposure) are involved: (1) a metabolism and dosimetry study in which 24 dogs were serially sacrificed over an extended period of time, and (2) a longevity study with two series of dogs. Series I contains 15 dogs exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 11 to 210 μCi/kg body weight and three control dogs exposed to nonradioactive fused aluminosilicate particles. Series II contains 96 dogs exposed to aerosols of 144 Ce in fused aluminosilicate particles to yield initial lung burdens of 0.0024 to 66 μCi/kg body weight and 12 control dogs exposed to nonradioactive, fused aluminosilicate particles. To date, 51 dogs have died or were euthanized at 143 to 3280 days after inhalation of 144 Ce. The prominent findings were radiation pneumonitis in 17 dogs that died or were euthanized at 750 days or later. The cumulative radiation dose to the lung at time of death has ranged from 550 to 140,000 rads. Serial observations are continuing on the 60 survivors and 15 controls

Toxicity of inhaled 239PuO2 in immature Beagle dogs. VII

International Nuclear Information System (INIS)

Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; Boecker, B.B.; McClellan, R.O.

1985-01-01

Immature Beagle dogs have been exposed by inhalation to a monodisperse aerosol of 239 PuO 2 (1.5 μm AMAD) to compare the biological effects with those observed in dogs exposed to a similar aerosol as young or aged adults. The study includes 96 dogs exposed to 239 PuO 2 and 12 controls. The lung burdens of the plutonium-exposed dogs ranged from 0.00030 to 0.80 μCi/kg body weight (0.011-30 kBq/kg). No dogs died during this year. Seven dogs were diagnosed as having developing lung disease, mainly fibrosis, and one had a developing lung tumor. With 20 dogs having estimated cumulative radiation doses in excess of 1000 rad (10 Gy), the biological response of the dogs exposed as juveniles appears to be less than that seen in mature dogs. However, major uncertainties still exist in the current estimations of radiation dose, particularly regarding the local distribution of alpha radiation dose. 1 reference, 4 figures, 1 table

Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

Science.gov (United States)

Visser, R; Kelderman, S; de Jongh, F H C; van der Palen, J; Thio, B J

2015-10-01

Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 μg or 400 μg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 μg salbutamol compared to 200 μg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 μg compared to 200 μg salbutamol with a BAI does improve reversibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxicity of inhaled 239PuO2 in immature beagle dogs

International Nuclear Information System (INIS)

Guilmette, R.A.; Muggenburg, B.A.; Hahn, F.F.; Mauderly, J.L.; Boecker, B.B.; McClellan, R.O.

1980-01-01

Immature beagle dogs have been exposed by inhalation to a 1.5 μm aerodynamic diameter monodisperse aerosol of 239 PuO 2 to compare the biological effects with those seen in young adult and aged dogs exposed to a similar aerosol. To date, 18 dogs have been exposed to the aerosol, resulting in graded initial lung burdens ranging from 0.003 to 0.38 μCi/kg body weight. Two dogs have been exposed to the aerosol diluent and serve as controls. Two of the 18 exposed animals were sacrificed 8 days after exposure to provide information on initial deposition and distribution. All other exposed animals are alive 400 days after exposure. No dogs were exposed during the past year because of an outbreak of canine parvovirus enteritis which caused death in 8 to 10 week-old dogs

Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

Directory of Open Access Journals (Sweden)

Jill A. Poole

2012-07-01

Full Text Available Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE collected from a CAFO results in the activation of protein kinase C (PKC, elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6, and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF, tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability

TPP-dendrimer nanocarriers for siRNA delivery to the pulmonary epithelium and their dry powder and metered-dose inhaler formulations.

Science.gov (United States)

Bielski, Elizabeth; Zhong, Qian; Mirza, Hamad; Brown, Matthew; Molla, Ashura; Carvajal, Teresa; da Rocha, Sandro R P

2017-07-15

The regulation of genes utilizing the RNA interference (RNAi) mechanism via the delivery of synthetic siRNA has great potential in the treatment of a variety of lung diseases. However, the delivery of siRNA to the lungs is challenging due to the poor bioavailability of siRNA when delivered intraveneously, and difficulty in formulating and maintaining the activity of free siRNA when delivered directly to the lungs using inhalation devices. The use of non-viral vectors such as cationic dendrimers can help enhance the stability of siRNA and its delivery to the cell cytosol. Therefore, in this work, we investigate the ability of a triphenylphosphonium (TPP) modified generation 4 poly(amidoamine) (PAMAM) dendrimer (G4NH 2 -TPP) to enhance the in vitro transfection efficiency of siRNA in a model of the pulmonary epithelium and their aerosol formulations in pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). Complexes of siRNA and G4NH 2 -TPP were prepared with varying TPP densities and increasing N/P ratios. The complexation efficiency was modulated by the presence of the TPP on the dendrimer surface, allowing for a looser complexation compared to unmodified dendrimer as determined by gel electrophoresis and polyanion competition assay. An increase in TPP density and N/P ratio led to an increase in the in vitro gene knockdown of stably green fluorescent protein (eGFP) expressing lung alveolar epithelial (A549) cells. G4NH 2 -12TPP dendriplexes (G4NH 2 PAMAM dendrimers containing 12 TPP molecules on the surface complexed with siRNA) at N/P ratio 30 showed the highest in vitro gene knockdown efficiency. To assess the potential of TPP-dendriplexes for pulmonary use, we also developed micron particle technologies for both pMDIs and DPIs and determined their aerosol characteristics utilizing an Andersen Cascade Impactor (ACI). Mannitol microparticles encapsulating 12TPP-dendriplexes were shown to be effective in producing aerosols suitable for deep lung

Organ dose from inhaled radionuclides taking lull period into account

International Nuclear Information System (INIS)

Datta, S.

1982-01-01

The dosimetry of inhaled radionuclides is generally carried out in accordance with the lung model recommended by the ICRP Task Group on Lung Dynamics. The relevant expressions are integrated over a given period, assuming continuous inhalation in an atmosphere of constant aerosol concentration. Though for the same amount of intake the dose commitment is found to be independent of variations in the rate of intake, the dose determined over specific intervals of time, is influenced by it or by lull intervals therein. Formulae are developed to arrive at doses to different organs when the subject's intake is constant and continuous for 8 hours, followed by a lull period of 16 hours each day. Results are given for a number of radionuclides and are compared with values characteristic of continuous inhalation. It is observed that when exposure is assumed to be continuous the dose for the same intake of activity is underestimated as compared to the dose when lull period is taken into account. For working periods of 6 days and 30 days the underestimate ranges from 5%-20% and 0.6% to 4.5% respectively. (author)

Device for contaminating laboratory animals by inhalation of radioactive aerosols

International Nuclear Information System (INIS)

Lutz, M.; Rouvroy, H.

1966-01-01

The contamination enclosure is made up of a sphere to which are attached an aerosol generator, containers adapted to the animals to be used, and the atmospheric sampling system. The sphere is placed in a protective glove-box, the latter being itself protected by an introduction chamber fitted with locking access lids. A detailed description is given of the working principle. As an example, some results are given concerning the contamination of rats by a plutonium oxide aerosol: characteristics of the powder (mean diameter 0.50 μ - standard deviation: 1.4), examination and evolution of the atmospheric activity as a function of time, evaluation of the retention by the lungs by means of histological and autoradiographic examinations. (authors) [fr

Prevalidation of in vitro continuous flow exposure systems as alternatives to in vivo inhalation safety evaluation experimentations: outcome from MAAPHRI-PCRD5 research program.

Science.gov (United States)

Morin, Jean-Paul; Hasson, Virginie; Fall, Mamadou; Papaioanou, Eleni; Preterre, David; Gouriou, Frantz; Keravec, Veronika; Konstandopoulos, Athanasios; Dionnet, Frédéric

2008-06-01

Diesel engine emission aerosol-induced toxicity patterns were compared using both in vitro (organotypic cultures of lung tissue) and in vivo experimentations mimicking the inhalation situation with continuous aerosol flow exposure designs. Using liquid media resuspended diesel particles, we show that toxic response pattern is influenced by the presence of tensioactive agent in the medium which alter particle-borne pollutant bioavailability. Using continuous aerosol exposure in vitro, we show that with high sulfur fuel (300ppm) in the absence of oxidation catalysis, particulate matter was the main toxic component triggering DNA damage and systemic inflammation, while a very limited oxidant stress was evidenced. In contrast, with ultra-low sulfur fuel in the presence of strong diesel oxidation catalysis, the specific role of particulate matter is no longer evidenced and the gas phase then becomes the major component triggering strong oxidant stress, increased NO(2) being the most probable trigger. In vivo, plasma tumor necrosis factor alpha (TNFalpha), lung superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity levels varied in agreement with in vitro observations. Diesel emission treatment with oxycat provokes a marked systemic oxidant stress. Again NO(2) proved to account for a major part of these impacts. In conclusion, similar anti-oxidant responses were observed in in vitro and in vivo experiments after diesel emission aerosol continuous flow exposures. The lung slice organotypic culture model-exposed complex aerosol appears to be a very valuable alternative to in vivo inhalation toxicology experimentations in rodents.

NFAT5 participates in seawater inhalation-induced acute lung injury via modulation of NF-κB activity

Science.gov (United States)

Li, Congcong; Liu, Manling; Bo, Liyan; Liu, Wei; Liu, Qingqing; Chen, Xiangjun; Xu, Dunquan; Li, Zhichao; Jin, Faguang

2016-01-01

Nuclear factor of activated T cells 5 (NFAT5) is a transcription factor that can be activated by extracellular tonicity. It has been reported that NFAT5 may increase the transcription of certain osmoprotective genes in the renal system, and the aim of the current study was to explore the role of NFAT5 in seawater inhalation-induced acute lung injury. Though establishing the model of seawater inhalation-induced acute lung injury, it was demonstrated that seawater inhalation enhanced the transcription and protein expression of NFAT5 (evaluated by reverse transcription-polymerase chain reaction, immunohistochemistry stain and western blotting) and activation of nuclear factor (NF)-κB (evaluated by western blotting and mRNA expression levels of three NF-κB-dependent genes) both in lung tissue and rat alveolar macrophage cells (NR8383 cells). When expression of NFAT5 was reduced in NR8383 cells using an siRNA targeted to NFAT5, the phosphorylation of NF-κB and transcription of NF-κB-dependent genes were significantly reduced. In addition, the elevated content of certain inflammatory cytokines [tumor necrosis factor α, interleukin (IL)-1 and IL-8] were markedly reduced. In conclusion, NFAT5 serves an important pathophysiological role in seawater inhalation-induced acute lung injury by modulating NF-κB activity, and these data suggest that NFAT5 may be a promising therapeutic target. PMID:27779669

Applications of aerosol inhalation cine-scintigraphy for, clinical investigations of mucociliary transport

International Nuclear Information System (INIS)

Ito, Shinsaku; Mikami, Riichiro; Ryujin, Yoshitada; Imai, Teruhiko; Ohnuki, Masahiro; Narita, Nobuhiro

1984-01-01

Mucociliary transport and cough effect were studied in 10 healthy controls and 116 patients with respiratory diseases using aerosol inhalation cine-scintigraphy which permits visualization of the movement of inhaled aerosols. Additionally, the effectiveness of β-adrenergic stimulant on mucociliary transport was evaluated in 8 normal cases by this method. 1. In healthy controls, the aerosol-bolus moved to the cephalad side rapidly and smoothly in the main bronchus and the trachea, but in many cases of respiratory diseases, we recognized various abnormal patterns such as slow movement, spiral movement, regurgitation etc. We consider that the bolus movements can be used as an index of the mucociliary transport. 2. We found low grade abnormality of bolus movement in cases of atopic bronchial asthma, pulmonary emphysema, silicosis, interstitial pneumonia and asbestosis, but high grade abnormality in cases of bronchiectasis, pulmonary emphysema with chronic bronchitis, mixed or infectious bronchial asthma, chronic bronchitis and especially acute pulmonary infection and diffuse panbronchiolitis. Normal patterns were observed in atopic asthma patients in remission, but abnormal patterns in cases of attack. With larger daily volumes of sputum, the bolus movements showed higher greater abnormality. 3. Bolus movements by coughing were seen most frequently in patients who had produced moderate volumes of sputum and in whom the bolus had stopped at the first carina. Bolus movements by coughing were classified into three groups: expectoration, cephalad movement that stopped halfway, and regurgitation. When the bolus was in the trachea, especially located on the oral side, we observed that expectoration by coughing was more effective. Patients with obstructive pulmonary diseases had lower effciency of expectoration by coughing. 4. We confirmed that terbutaline (β-adrenergic stimulant) accelerated the mucociliary transport. (author)

Factors affecting the efficiency of aerosolized salbutamol delivery via a metered dose inhaler and equine spacer device.

Science.gov (United States)

Pirie, R S; McGorum, B C; Owen, C; Carr, O; Oakley, H; McLachlan, G

2017-06-01

Despite frequent use of metered dose inhalers (MDIs) and spacers in equine practice, limited information exists on the efficiency of aerosol delivery using such devices. We determined the particle size distribution within an MDI-generated salbutamol aerosol delivered via an equine spacer using 'best practice' delivery technique and assessed the effect of variations in MDI use technique (shaking prior to each actuation, rapid repetitive actuations, and MDI angulation) on aerosol delivery efficiency. Under optimal conditions, only 53(±18) μg salbutamol per 100 μg actuation was delivered beyond the spacer. Although this aerosol had a high [89.6% (±2.4)] fine particle (aerodynamic diameter [2.52 (±0.29) μm], and particle size variability [geometric SD - 1.66 (±0.16) μm], within all particle size fractions, there was a high coefficient of variance (31-79%) of the percentage salbutamol delivered between experimental runs, thus impeding any effort to predict drug delivery to the patient during equine inhalation therapy. Despite observable trends and with the exception of minor statistically significant changes in the least abundant particle sizes, none of the deviations from a 'best practice' delivery technique significantly altered the relative salbutamol delivery beyond the spacer, a finding which has potential relevance with regard to maintaining user compliance. © 2016 John Wiley & Sons Ltd.

Modifying effects of pre-existing fibrosis in rats exposed to aerosols of 239PuO2. II

International Nuclear Information System (INIS)

Lundgren, D.L.; Mauderly, J.L.; Gillett, N.A.; Hahn, F.F.

1988-01-01

We have initiated a study using rats to determine the modifying effects of pre-existing pulmonary fibrosis on the retention and biological effects of inhaled 239 PuO 2 . Pulmonary fibrosis was induced by intratracheal instillation of 8.5 IU/kg body weight of bleomycin at 45 to 49 days before inhalation exposure to an aerosol of 239 PuO 2 . The clearance of 239 Pu from the lungs of rats was decreased significantly (p 239 Pu, apparently by entrapping the particles in fibrotic areas of the lung. The life span of the rats with pulmonary fibrosis was decreased by up to 25% compared with control rats having similar initial lung burdens of 239 Pu. (author)

Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of plutonium from the rat

International Nuclear Information System (INIS)

Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

1976-01-01

After inhaling 1 to 4 HD (human dose equivalents, i.e. 1g of calcium trisodium N,N-bis(2-bis (carboxymethyl) amino ethyl)glycinate per 70kg of body weight) of Ca-DTPA, rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrified later than 3 weeks after the last exposure. Dogs were anesthetized and administered Ca-DTPA aerosols via an intratracheal catheter for 30min/day for 5 days. The average dose/exposure was 4 HD. One week after the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks post-exposure. Ephitheleal atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. In long-term studies, rats were administered a lung burden of about 78 nCi 239 Pu(NO 3 ) 4 by inhalation and 20 days later were given six inhalation treatments of about 1 HD Ca-DTPA. Over their lifetime these animals showed no difference in survival or bone or lung tumour incidence from rats receiving Pu alone. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months after the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed. (author)

Survey on the radiation exposure of the respiratory tract by inhalation of natural radionuclides

International Nuclear Information System (INIS)

Poretti, G.

1987-01-01

During the last twenty years, work carried out on radiation exposure of the respiratory tract due to the inhaled, naturally occurring nuclides radon, thoron and short-lived daughters has become increasingly important, because the doses received in the respiratory tract, due mainly to the effect of α rays, reach values among the general population which are comparable to or even higher than the average exposures per year of a population undergoing X-ray diagnostic examinations. A brief introduction to the physical characteristics of the natural radiation nuclides reaching the bronchi and lungs with the inhaled air (Rn-220 - thoron and short lived daughters), and the deposition and clearance of the nuclides (often linked to aerosols), is followed by a discussion of the anatomical/physiological characteristics of the ''lung models'', thanks to which it is possible to calculate the energy quantities (i.e. doses) deposited by the α rays in the epithelium of the lungs and bronchi. In addition the retention mechanisms of the radionuclides (as free ions or as aerosols) are briefly described, and finally the calculations to determine the quantity of radioactivity remaining on the walls of the respiratory tract are given. The construction of dosimetric models requires relatively precise knowledge of the thickness of the mucus layers and of the distribution of the nuclides in the mucus, the ciliary movement, the depth in the tissue of the radiation-sensitive cells etc. On the basis of local doses it is then possible to calculate approximately the regional doses for bronchi, lungs and other organs (via blood, accessible by the nuclides before excretion) for the short lived daughters of Rn-222 and Rn-220. Determination of the mean effective dose equivalent requires, amongst other things, knowledge of the concentration of the nuclides in the inhaled air and the mean respiratory frequency of the members of a population. (orig./HSI)

Biochemical effects of inhaled 239PuO2 on lung lipids

International Nuclear Information System (INIS)

Tombropoulos, E.G.; Hadley, J.G.; Thomas, J.M.; Craig, D.K.

1977-01-01

Results of experiments carried out to assess the effect of 239 Pu α irradiation on lung lipid biosynthesis and to determine the lungs ability to incorporate palmitate into lavage lecithin and its turnover are reported. The experiments were carried out on rats which had inhaled 239 PuO 2 particles. The study of palmitate incorporation into lipids shows conclusively that for medium (23 to 42 nCi) or high (more than 100 nCi) lung depositions the incorporation by isolated mitochondria is significantly (P 239 PuO 2 were positive, with respect to controls in 8 of 10 instances, when measured following the label of palmitate in lung lavage lecithin. The interpretation of the significant result (P < 0.05) is that: (1) initial and/or final lecithin pool sizes were different, (2) transfer rates were affected between blood and lung, or (3) rates of degradation of lung lavage lecithin were affected. (U.K.)

Deposition, translocation and effects of transuranic particles inhaled by experimental animals

International Nuclear Information System (INIS)

Craig, D.K.; Ballou, J.E.; Dagle, G.E.; Mahlum, D.D.; Park, J.F.; Sanders, C.L.; Sikov, M.R.; Stuart, B.O.

1977-01-01

Inhalation exposure constitutes the most likely route of entrance for transuranics into the body. Cancer is the most likely consequence of exposure, but several thousand workers have been exposed during the last 30 yrs without, so far, evidence of exposure-related effects. Several soluble and insoluble transuranic compounds have been studied in rodents and dogs, either alone or combined with exposure to other materials (e.g., PuO/sub 2/--UO/sub 2/ fuel and Na). These studies have provided a wide variety of spatial and temporal dose distribution patterns in the lung. The distribution and total initial deposition in the respiratory tract is a function of the physical characteristics of the inhaled aerosols (size distribution, shape, hygroscopicity) and of the morphology and physiology of the animal. Translocation rates, organ and tissue distribution and excretion in urine and feces, are a function of the physicochemical characteristics of the deposited material (solubility, specific activity, chemical compound, etc.). Differences in rate of translocation of the solubilized material, primarily to the liver and bone, determines the radiation dose to the various tissues involved. Insoluble particles of plutonium dioxide are transferred to the thoracic lymph nodes, which may be functionally destroyed as a consequence. Radiation pneumonitis and pulmonary fibrosis are the main causes of death in animals with cumulative radiation doses to the lung of a few thousand rads. The most significant long-term effect of inhaled transuranic compounds in animals is the development of lung and bone tumors. The main type of lung tumor in both dog and rat is the bronchioloalveolar carcinoma (adenocarcinoma). However, tumor type is a function of radiation dose and dose-distribution at high doses. Bone ranks next to lung as the tissue developing the most tumors following inhalation of transuranics

Deposition, translocation, and effects of transuranic particles inhaled by experimental animals

International Nuclear Information System (INIS)

Craig, D.K.; Ballou, J.E.; Dagle, G.E.; Mahlum, D.D.; Park, J.F.; Sanders, C.L.; Sikov, M.R.; Stuart, B.O.

1977-01-01

Inhalation exposure constitutes the most likely route of entrance for transuranics into the body. Cancer is the most likely consequence of exposure, but several thousand workers have been exposed during the last 30 yrs without, so far, evidence of exposure-related effects. Several soluble and insoluble transuranic compounds have been studied in rodents and dogs, either alone or combined with exposure to other materials (e.g., PuO 2 --UO 2 fuel and Na). These studies have provided a wide variety of spatial and temporal dose distribution patterns in the lung. The distribution and total initial deposition in the respiratory tract is a function of the physical characteristics of the inhaled aerosols (size distribution, shape, hygroscopicity) and of the morphology and physiology of the animal. Translocation rates, organ and tissue distribution and excretion in urine and feces, are a function of the physicochemical characteristics of the deposited material (solubility, specific activity, chemical compound, etc.). Differences in rate of translocation of the solubilized material, primarily to the liver and bone, determines the radiation dose to the various tissues involved. Insoluble particles of plutonium dioxide are transferred to the thoracic lymph nodes, which may be functionally destroyed as a consequence. Radiation pneumonitis and pulmonary fibrosis are the main causes of death in animals with cumulative radiation doses to the lung of a few thousand rads. The most significant long-term effect of inhaled transuranic compounds in animals is the development of lung and bone tumors. The main type of lung tumor in both dog and rat is the bronchioloalveolar carcinoma (adenocarcinoma). However, tumor type is a function of radiation dose and dose-distribution at high doses. Bone ranks next to lung as the tissue developing the most tumors following inhalation of transuranics

The lung cancer risk from inhalation of radon-222 decay products

International Nuclear Information System (INIS)

Jacobi, W.

1975-05-01

The results of surveys in the USA and the CSSR on the lung cancer mortality among uranium miners are compared. The relation between the observed excess lung cancer mortality and the cumulative exposure of these miners by inhaled Rn-daughters is discussed and the risk coefficients for radiation-induced lung cancer are estimated. The relative risk coefficients of both study groups of U-miners agree within the confidence limits and are in the range of 0.001 to 0.005 WLM -1 . The derived absolute risk coefficients of 20 +- 10 (USA group) and 150 +- 50 (CSSR group) additional lung cancer deaths per WLM and 10 6 miners are, however, significantly different. The influence of synergistic or cocancerogenic actions is discussed. The increase of lung cancer mortality with Rn-exposure is significantly correlated with an increase of the small-cell, undifferentiated type of carcinoma. (author)

Pulmonary and cardiovascular responses of rats to inhalation of silver nanoparticles.

Science.gov (United States)

Roberts, Jenny R; McKinney, Walter; Kan, Hong; Krajnak, Kristine; Frazer, David G; Thomas, Treye A; Waugh, Stacey; Kenyon, Allison; MacCuspie, Robert I; Hackley, Vincent A; Castranova, Vincent

2013-01-01

Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 μg/m(3) ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 μg/m(3)) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 μg Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.

Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model

Directory of Open Access Journals (Sweden)

O'Shaughnessy Patrick T

2011-01-01

Full Text Available Abstract Background There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure. Results In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m3, 4 hours/day, 10 days, 5 ± 2 nm primary size. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma - optical emission spectroscopy (ICP-OES was 31 μg/g lung (dry weight immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu. Conclusions Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

Dispersing the Mists: An Experimental History of Medicine Study into the Quality of Volatile Inhalations.

Science.gov (United States)

Murnane, Barry; Gallagher, Cathal T; Snell, Noel; Sanders, Mark; Moshksar, Ramin; Murnane, Darragh

2017-06-01

Dr. Nelson's Improved Inhaler was first marketed with an advertisement in The Lancet in 1865. Revolutionary at the time for its ease of use and patient-friendliness, the inhaler is still in use for self-treatment by many all over the world. On the occasion of its 150th anniversary, this study reports an experimental historical medicine approach to identify evidence for the quality of vapor inhalers. Through accessing reviews of the device's use by the contemporary medical establishment, it was established that Dr. Nelson's Inhaler enjoyed a reputation of quality and efficacy among reputable physicians generating empirical evidence of clinical performance. There was a general absence of product performance tests during this period. Therefore, modern inhalation performance testing was applied to test the aerosol delivery performance for Friars' Balsam, and its key chemical constituent, benzoic acid (BA). A respirable dose of 59.9 ± 9.0 μg of BA was aerosolized in a 10 minutes period from a dose of 3.3 mL Friars' Balsam (equivalent to 35.1 ± 0.2 mg of BA) in 375 mL of steaming water using the glass twin stage impinger at a flow rate of 60 L·min -1 . The respirable dose from a standardized aqueous BA inhalation formulation increased from 115.9 ± 10.6 to 200.2 ± 19.9 μg by increasing the simulated inhalation period from 5 to 10 minutes. When tested with a simulated inhalation maneuver (500 mL tidal volume, 13 minutes -1 respiration rate, 1:2 inspiratory:expiratory ratio) a respirable dose of 112.8 ± 40.3 μg was produced. This work has highlighted the potential for aerosol drug delivery using steam inhalers that are popular with patients. Physicians should therefore be aware of the potential for lung dosing with irritants when patients self-medicate using the Nelson Inhaler with vaporizing formulations such as Friars' Balsam.

Deposition of 0.1 μm chain aggregate aerosols in beagle dogs

International Nuclear Information System (INIS)

Wolff, R.K.; Kanapilly, G.M.; DeNee, P.B.; McClellan, R.O.

1981-01-01

Deposition and retention of ultrafine chain aggregate particles were studied in 20 beagle dogs. Aggregated particles of insoluble 67 Ga 2 O 3 in the 0.1 μm size range were generated by heat treatment of 67 Ga tetramethylheptanedione. Size characterization was done using electron microscopy, diffusion battery and electrical aerosol analyzer measurements. The average equivalent diffusion diameter of the aerosol was 0.07 μm and the volume median diameter (electrical mobility measurement) was 0.10 μm with a geometric standard deviation of 1.6. Primary particles from which the aggregates were formed were 0.01 to 0.02 μm in diameter. Whole-body counting and gamma camera imaging were used to measure deposition. Total deposition in the whole body was 33 +- 16 % (mean +-S.D.) of the inhaled particles; 82 +- 13 % of this material was deposited in the lung. Retention studies showed that 77 +- 3 % of the material deposited in the lung was in the pulmonary region. Thus, 21 % of the inhaled particles were deposited beyond ciliated airways in alveolar areas. (author)

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

DEFF Research Database (Denmark)

Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

2018-01-01

impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if they inhibited LS function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e. the in vitro method predicted...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...

Biokinetics and internal dosimetry of inhaled metal tritide particles

Science.gov (United States)

Wang, Yansheng

1998-12-01

Metal tritides (MT), stable chemical compounds of tritium, are widely used in nuclear engineering facilities. MT particles can be released as aerosols. Inhaling MT particles is a potential occupational radiation hazard. Little information is available on their dissolution behavior, biokinetics, and dosimetry. The objectives of present dissertation are to estimate dissolution rates, to develop biokinetic models, to improve internal dosimetric considerations, and to classify MT materials. This study consisted of three phases: In vitro dissolution in a simulated lung fluid, In vivo rat experiments on retention and clearance, and biokinetic modeling and dosimetric evaluation. There was a supporting study on self- absorption of tritium beta in MT particles. MT materials used in this study were titanium (Ti) and zirconium (Zr) tritides. Results shows considerable self-absorption of beta particles and their energy, even for respirable MT particles smaller than 5 μm. The self-absorption factors should be required for counting MT particle samples and for estimating absorbed dose to tissues. In vitro and in vivo dissolution data indicate that Ti and Zr tritides are poorly soluble materials. Ti tritide belongs to the W class or M type while Zr tritide can be classified as Y class or S type. Due to long retention time of the MT particles, tritium betas directly from the particles contribute over 90% of the absorbed dose to lung. The lung dose contributes most of the effective dose to the whole body. Dissolved tritium including tritiated water (HTO) and organically bound tritium (OBT) has less effect on the lung dose and effective dose. Results on the annual limit on intake (ALI) indicate that the current radiation protection guideline based on HTO is not adequate for inhalation exposure to MT particles and needs to be modified. The biokinetic models developed in this study have predictive powers to estimate the consequences of a human inhalation exposure to MT aerosols. The

Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats.

Science.gov (United States)

Pujalté, Igor; Dieme, Denis; Haddad, Sami; Serventi, Alessandra Maria; Bouchard, Michèle

2017-01-04

This study focused on the generation of aerosols of titanium dioxide (TiO 2 ) nanoparticles (NPs) and their disposition kinetics in rats. Male Sprague-Dawley rats were exposed by inhalation to 15mg/m 3 of anatase TiO 2 NPs (∼20nm) during 6h. Rats were sacrificed at different time points over 14days following the onset of inhalation. Ti levels were quantified by ICP-MS in blood, tissues, and excreta. Oxidative damages were also monitored (MDA). Highest tissue levels of Ti were found in lungs; peak values were reached only at 48h followed by a progressive decrease over 14days, suggesting a persistence of NPs at the site-of-entry. Levels reached in blood, lymph nodes and other internal organs (including liver, kidney, spleen) were circa one order of magnitude lower than in lungs, but the profiles were indicative of a certain translocation to the systemic circulation. Large amounts were recovered in feces compared to urine, suggesting that inhaled NPs were eliminated mainly by mucociliary clearance and ingested. TiO 2 NPs also appeared to be partly transferred to olfactory bulbs and brain. MDA levels indicative of oxidative damage were significantly increased in lungs and blood at 24h but this was not clearly reflected at later times. Translocation and clearance rates of inhaled NPs under different realistic exposure conditions should be further documented. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth

Science.gov (United States)

Walenga, Ross L.; Kaviratna, Anubhav; Hindle, Michael

2017-01-01

Abstract Background: Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. Materials and Methods: A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Results: Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%–134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%–17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%–90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. Conclusions: The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in

Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth.

Science.gov (United States)

Walenga, Ross L; Longest, P Worth; Kaviratna, Anubhav; Hindle, Michael

2017-06-01

Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%-134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%-17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%-90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a

Commentary on inhaled {sup 239}PuO{sub 2} in dogs - a prophylaxis against lung cancer?

Energy Technology Data Exchange (ETDEWEB)

Cuttler, J.M., E-mail: jerrycuttler@rogers.com [Cuttler and Associates, Vaughan, ON (Canada); Feinendegen, L. [Brookhaven National Laboratories, Upton, NY (United States)

2015-07-01

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the Linear No-Threshold (LNT) hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from {sup 239}PuO{sub 2} inhalation, as a prophylaxis against lung cancer. (author)

Commentary on inhaled {sup 239}PuO{sub 2} in dogs - a prophylaxis against lung cancer?

Energy Technology Data Exchange (ETDEWEB)

Cuttler, J.M. [Cuttler and Assoc., Vaughan, Ontario (Canada); Feinendegen, L. [Brookhaven National Laboratories, Upton, New York (United States)

2015-06-15

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the Linear No-Threshold (LNT) hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from {sup 239}PuO {sub 2} inhalation, as a prophylaxis against lung cancer. (author)

Toxicity of 90Sr inhaled in a relatively insoluble form by Beagle dogs. IX

International Nuclear Information System (INIS)

Snipes, M.B.; Hahn, F.F.; Muggenburg, B.A.; Mauderly, J.L.; McClellan, R.O.; Pickrell, J.A.

1978-01-01

Studies on the biological effects of 90 Sr inhaled in a relatively insoluble form by Beagle dogs are being conducted to define the biological consequences of inhaling this radionuclide in a form which has a long retention time in the lung. One hundred and six dogs were exposed to a polydisperse aerosol (AMAD 1.4 to 2.8 μm and sigma/sub g/ 1.4 to 2.7) of fused aluminosilicate particles labeled with 90 Sr. Initial lung burdens ranged from 0.21 to 94 μCi 90 Sr per kilogram of body weight (μCi/kg). Eighteen control dogs were exposed to an aerosol of stable strontium in fused aluminosilicate particles. To date, 34 dogs having initial lung burdens of 8.9 to 94 μCi 90 Sr/kg and cumulative doses to lung of 33,000 to 96,000 rads have died from radiation pneumonitis and/or pulmonary fibrosis between 159 and 2596 days after exposure. Twenty-nine dogs with initial lung burdens of 3.7 to 36 μCi 90 Sr/kg and cumulative doses to lung of 13,000 to 68,000 rads have died from hemangiosarcomas in the lung, heart or mediastinum between 644 and 2565 days after exposure. In addition, one dog developed a bronchioloalveolar carcinoma, another developed epidermoid carcinoma of the lung, another died of pneumonia while recovering from anesthesia, one dog died at 1821 days after exposure with an hemangiosarcoma of the spleen and two dogs developed squamous cell carcinomas in the nasal cavity. During the past year one dog was euthanized 2753 days after exposure (34,000 rads lung dose) as a result of an hemangiosarcoma which developed in a rib and spread widely. Another dog died 2830 days after exposure (35,000 rads lung dose) with a squamous cell carcinoma in the lung. An additional dog was euthanized 2636 days after exposure (12,000 rads lung dose) with widespread hemangiosarcoma of unknown origin. The remaining 36 exposed dogs and 18 controls are surviving at 1387 to 3168 days after exposure

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland.

NARCIS (Netherlands)

de Vocht, F.; Sobala, W.; Wilczynska, U.; Kromhout, H.; Szeszenia-Dabrowska, N.; Peplonska, B.

2009-01-01

AIM: Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or

Modeling lung cancer risks in laboratory dogs exposed to inhaled plutonium

International Nuclear Information System (INIS)

Gilbert, E.S.; Park, J.F.; Buschbom, R.L.

1990-06-01

These analyses are based on data from a lifespan study of beagle dogs exposed to inhaled plutonium being conducted at Pacific Northwest Laboratory. An important goal of this study is to increase understanding of health risk resulting from this exposure, with particular attention to lung cancer risks. Data on humans exposed to plutonium are inadequate for achieving this goal

Bronchopulmonary lavage and DTPA treatment for the removal of inhaled 239Pu of varied solubility in beagle dogs. II

International Nuclear Information System (INIS)

Muggenburg, B.A.; Mewhinney, J.A.; Miglio, J.J.; Slauson, D.O.; McClellan, R.O.

1974-01-01

The efficacy of bronchopulmonary lavage and chelation therapy was determined for removing 239 Pu from Beagle dogs after inhalation of 239 Pu aerosols of differing in vivo solubility. The four aerosols used were nebulized from a solution of 239 PuCl 4 and heat treated at temperatures of 325, 600, 900, and 1150 0 C, respectively. Six dogs were exposed to each of the four aerosols and three dogs in each group were treated subsequently by lavage and intravenous diethylenetriaminepentaacetic acid (DTPA); three dogs served as untreated controls. Tissue accumulation of 239 Pu in the untreated control dogs at sacrifice 56 days post-exposure, expressed as a percentage of the initial lung burden (ILB), was 6 percent in liver and 9 percent in skeleton for the 325 0 C aerosol group, 1 percent in liver and 2 percent in the skeleton for the 600 0 C group, and less than 0.6 percent in these tissues for the 900 0 and 1150 0 C aerosol groups. Tissue accumulation was 1.0 percent or less of the ILB for all organs in the treated groups of dogs. The urinary excretion of 239 Pu was increased in the treated dogs compared to the control dogs that inhaled the 325 0 C and 600 0 C aerosols and was low in all dogs exposed to the 900 0 and 1150 0 C treated aerosol particles. Ten bronchopulmonary lavage procedures removed a mean of 44 percent of the ILB of 239 Pu from the lungs. The aerosol temperature and resulting differences in solubility of the particles did not influence the efficacy of the lavage procedure. An in vitro solubility test predicted the relative in vivo solubility of the four aerosols. These results are discussed in relation to the choice of therapy and its timing. (U.S.)

Hot spots on Tc-99m MAA perfusion lung scan

International Nuclear Information System (INIS)

Lim, Seok Tae; Sohn, Myung Hee

2001-01-01

A 61 year-old woman underwent perfusion and inhalation lung scan for the evaluation of pulmonary thromboembolism. Tc-99m MAA perfusion lung scan showed multiple round hot spots in both lung fields. Tc-99m DTPA aerosol inhalation lung scan and chest radiography taken at the same time showed normal findings. A repeated perfusion lung scan taken 24 hours later demonstrated no abnormalities. Hot spots on perfusion lung scan can be caused by microsphere clumping due to faulty injection technique by radioactive embolization from upper extremity thrombophlebitis after injection. Focal hot spots can signify zones of atelectasis, where the hot spots probably represent a failure of hypoxic vasoconstriction. Artifactual hot spots due to microsphere clumping usually appear to be round and in peripheral location, and the lesions due to a loss of hypoxic vasoconstriction usually appear to be hot uptakes having linear borders. Although these artifactual hot spots have been well-known, we rarely encounter them. This report presents a case with artifactual hot spots due to microsphere clumping on Tc-99m MAA perfusion lung scan

Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group.

Science.gov (United States)

Murakami, S; Bacha, E A; Mazmanian, G M; Détruit, H; Chapelier, A; Dartevelle, P; Hervé, P

1997-08-01

Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.

Aerosolized prostacyclin for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)

DEFF Research Database (Denmark)

Afshari, Arash; Brok, Jesper; Møller, Ann

2010-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far.......Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far....

Clinical studies of alveolar-capillary permeability using technetium-99m DTPA aerosol

International Nuclear Information System (INIS)

Sundram, F.X.

1995-01-01

Soluble radioaerosols such as technetium-99m diethylene triamine pentacetate (DTPA) permit simple quantitative studies of alveolar-capillary permeability to be performed, since the submicronic aerosols are deposited mainly at the lung periphery and are cleared across the alveolar-capillary membrane. Regional alterations in permeability can also be noted using this radionuclide technique. We have measured the pulmonary epithelial permeability in normal subjects and the alteration in smokers, glue-sniffers, patients with inhalation burns, chronic obstructive pulmonary disease (COPD) and patients with lung metastases from thyroid cancer treated with radioiodine 131 I. In the normal volunteers, the time taken for 50% of inhaled 99m Tc DTPA to be cleared from the lungs (T1/2) was 66 minutes±1 sd of 12 mins. The smokers had a mean T1/2 of 20 mins±1 sd 4 min. In the hard-core glue-sniffing group, the majority were smokers who had stopped smoking and glue-sniffing for periods varying from 1 day to 42 days, and it was possible to note the changes in clearance times against period of abstinence. In the patients with inhalation burns, there was change in lung clearance arising from pulmonary epithelial damage; these patients showed increased rate of clearance (short T1/2) with mean T1/2 of 36 min±1 sd of 11 mins, while the retention images revealed regional lung damage in moderately severe inhalation burns. Twenty-four patients with COPD had inhalation scans done with Tc-99m tin colloid radioaerosol, and these images were compared with the perfusion lung scans done with 99m Tc macroaggregated albumin (MAA); in general the perfusion images matched the defects noted in the inhalation scans. The 99m Tc DTPA clearance rate in these patients was normal i.e. T1/2=78±14 mins. In the thyroid cancer patients with lung metastases, who had high doses of radioiodine treatment, the T1/2 values were normal or prolonged slightly, mean T1/2=76 min±23. (author)

The generation of diesel exhaust particle aerosols from a bulk source in an aerodynamic size range similar to atmospheric particles

Directory of Open Access Journals (Sweden)

Daniel J Cooney

2008-08-01

Full Text Available Daniel J Cooney1, Anthony J Hickey21Department of Biomedical Engineering; 2School of Pharmacy, University of North Carolina, Chapel Hill, NC, USAAbstract: The influence of diesel exhaust particles (DEP on the lungs and heart is currently a topic of great interest in inhalation toxicology. Epidemiological data and animal studies have implicated airborne particulate matter and DEP in increased morbidity and mortality due to a number of cardiopulmonary diseases including asthma, chronic obstructive pulmonary disorder, and lung cancer. The pathogeneses of these diseases are being studied using animal models and cell culture techniques. Real-time exposures to freshly combusted diesel fuel are complex and require significant infrastructure including engine operations, dilution air, and monitoring and control of gases. A method of generating DEP aerosols from a bulk source in an aerodynamic size range similar to atmospheric DEP would be a desirable and useful alternative. Metered dose inhaler technology was adopted to generate aerosols from suspensions of DEP in the propellant hydrofluoroalkane 134a. Inertial impaction data indicated that the particle size distributions of the generated aerosols were trimodal, with count median aerodynamic diameters less than 100 nm. Scanning electron microscopy of deposited particles showed tightly aggregated particles, as would be expected from an evaporative process. Chemical analysis indicated that there were no major changes in the mass proportion of 2 specific aromatic hydrocarbons (benzo[a]pyrene and benzo[k]fluoranthene in the particles resulting from the aerosolization process.Keywords: diesel exhaust particles, aerosol, inhalation toxicology

Lung lavage therapy to lessen the biological effects of inhaled 144Ce in dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Boecker, B.B.; Hahn, F.F.; McClellan, R.O.

1990-01-01

To evaluate the therapeutic effects of removal of an internally deposited radionuclide on long-term biological effects, lung lavage was used to treat dogs that had inhaled 144Ce in a relatively insoluble form, in fused aluminosilicate particles. Either 10 lung lavages were performed between Days 2 and 56 after exposure or 20 lung lavages were performed between Days 2 and 84 after exposure. Approximately one-half of the 144Ce was removed by the lavages, resulting in a corresponding reduction in the total absorbed beta dose to lung. The mean survival time of the treated dogs was 1270 days compared to 370 days for untreated dogs whose initial pulmonary burdens of 144Ce were similar. Treated dogs died late from cancers of the lung or liver, whereas the untreated dogs died at much earlier times from radiation pneumonitis. Dogs treated with lung lavage but not exposed to 144Ce had a mean survival of 4770 days. We concluded that removal of 144Ce from the lung by lavage resulted in increased survival time and in a change in the biological effects from inhaled 144Ce from early-occurring inflammatory disease to late-occurring effects, principally cancer. In addition, the biological effects occurring in the treated dogs could be better predicted from the total absorbed beta dose in the lung and the dose rate after treatment rather than from the original dose rate to the lung. Therefore, we concluded that prompt treatment to remove radioactive materials could be of significant benefit to persons accidentally exposed to high levels of airborne, relatively insoluble, radioactive particles

Size distribution of salbutamol/ipratropium aerosols produced by different nebulizers in the absence and presence of heat and humidification.

Science.gov (United States)

Yang, Ssu-Han; Yang, Tsung-Ming; Lin, Hui-Ling; Tsai, Ying-Huang; Fang, Tien-Pei; Wan, Gwo-Hwa

2018-02-01

Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0.2-μm polycarbonate filters. A greater inhaled drug mass was delivered using a vibrating mesh nebulizer (VMN) than by using a small volume nebulizer (SVN), when heated humidifiers were not employed. When heated and humidified medical gas was used, there was no significant difference between the inhaled drug mass delivered by the VMN and that delivered by the SVN. A significantly greater mass of inhaled 1.55-μm drug particles was produced by the VMN than with the SVN, under heated and humidified conditions. However, the mass median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN and VMN did not differ significantly under the same conditions. The VMN produced more fine particles of salbutamol/ipratropium, and the drug particle size clearly increased in the presence of heat and humidification. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathology associated with inhaled plutonium in beagles

International Nuclear Information System (INIS)

Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; Stevens, D.L.

1986-01-01

The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

Future options for aerosol delivery to children

DEFF Research Database (Denmark)

Bisgaard, H

1999-01-01

, 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......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...

The effect of actuator nozzle designs on the electrostatic charge generated in pressurised metered dose inhaler aerosols.

Science.gov (United States)

Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

2015-04-01

To investigate the influence of different actuator nozzle designs on aerosol electrostatic charges and aerosol performances for pressurised metered dose inhalers (pMDIs). Four actuator nozzle designs (flat, curved flat, cone and curved cone) were manufactured using insulating thermoplastics (PET and PTFE) and conducting metal (aluminium) materials. Aerosol electrostatic profiles of solution pMDI formulations containing propellant HFA 134a with different ethanol concentration and/or model drug beclomethasone dipropionate (BDP) were studied using a modified electrical low-pressure impactor (ELPI) for all actuator designs and materials. The mass of the deposited drug was analysed using high performance liquid chromatography (HPLC). Both curved nozzle designs for insulating PET and PTFE actuators significantly influenced aerosol electrostatics and aerosol performance compared with conducting aluminium actuator, where reversed charge polarity and higher throat deposition were observed with pMDI formulation containing BDP. Results are likely due to the changes in plume geometry caused by the curved edge nozzle designs and the bipolar charging nature of insulating materials. This study demonstrated that actuator nozzle designs could significantly influence the electrostatic charges profiles and aerosol drug deposition pattern of pMDI aerosols, especially when using insulating thermoplastic materials where bipolar charging is more dominant.

Frequency analysis of pulmonary tumors occurrence at the rat after exposure to actinide oxide aerosols. Risk factors identification by comparing NpO2 and PuO2

International Nuclear Information System (INIS)

Dudoignon, N.

2001-07-01

Inhalation of actinide oxide particles is potentially one route of contamination of workers, which might induce pulmonary tumours due to aerosol generation during nuclear fuel fabrication process. Dose-effect relationships for lung tumour induction have been well established from epidemiological and experimental studies. However, they do not take into account specific parameters of exposure. The aim of this study was to compare cancer incidence among groups of rats exposed either to NpO 2 or to PuO 2 , two actinide oxides with different specific activity, but with similar aerosol granulometry. During the rat life-span, lung tumour development could occur and the individual follow-up allowed the determination of lung dose at death. Although aerosol particle sizes were similar, the mean number of particles per unit of activity was 2400 times higher for NpO 2 as compared to PuO 2 . This range of variation appeared higher than the variation of specific activity (450). Initial distribution of aerosol was then much more homogeneous for neptunium. In the range of initial lung deposits studied, the only physiological changes observed concerned lung clearance and rat life- span after exposure to the highest levels of Np activity. Pathological examination performed at death showed that carcinogenic power of neptunium was 2 to 3 times higher than that of plutonium. Dose-effect relationships appeared linear and when compared to previous studies, showed an increase of lung cancer risk as the specific activity of the inhaled actinide oxide decreases. The range of risk variation can reach a factor of 10, revealing that the consideration of lung dose at death solely might not be sufficient for an accurate estimate of risk and that specific parameters of exposure, such as nature and granulometry of aerosols, should also be taken into account. (author)

Lung deposition of sub-micron aerosols calculated as a function of age and breathing rate

International Nuclear Information System (INIS)

James, A.C.

1978-01-01

Experimental measurements of lung deposition and especially of regional deposition, of aerosols in the sub-micron size range have been so few that it is worthwhile establishing a method of calculation. A computer routine has therefore been developed to calculate aerosol deposition in successive bronchial and bronchiolar generations of the Weibel 'A' model of human lung for the sub-micron size range where deposition occurs solely by diffusion. This model can be scaled to represent lungs at various ages and vital capacities. Some calculated results are presented here and compared with measurements of lung deposition made under carefully controlled conditions in humans. (author)

In vitro evaluation of radio-labeled aerosol delivery via a variable-flow infant CPAP system.

Science.gov (United States)

Farney, Kimberly D; Kuehne, Brandon T; Gibson, Laurie A; Nelin, Leif D; Shepherd, Edward G

2014-03-01

Nasal CPAP is widely used in neonatal ICUs. Aerosolized medications such as inhaled steroids and β agonists are commonly administered in-line through nasal CPAP, especially to infants with bronchopulmonary dysplasia. We hypothesized that aerosol delivery to the lungs via variable-flow nasal CPAP in an in vitro model would be unreliable, and that the delivery would depend on the position of the aerosol generator within the nasal CPAP circuit. We used a system that employed a test lung placed in a plastic jar and subjected to negative pressure. Simulated inspiration effort was measured with a heated-wire anemometer. We used technetium-99m-labeled diethylene triamine penta-acetic acid as our aerosol. The nebulizer was placed either close to the humidifier or close to the nasal prongs in the circuit, and patient effort was simulated with a minute ventilation of 0.4 L/min. Relative aerosol delivery to the infant test lung with the nebulizer close to the humidifier was extremely low (0.3 ± 0.4%), whereas placing the nebulizer close to the nasal prongs resulted in significantly (P CPAP was negligible in this in vitro setup; however, such delivery was significantly improved by locating the aerosol generator closer to the nasal CPAP interface.

In vitro evaluation of aerosol delivery by different nebulization modes in pediatric and adult mechanical ventilators.

Science.gov (United States)

Wan, Gwo-Hwa; Lin, Hui-Ling; Fink, James B; Chen, Yen-Hey; Wang, Wei-Jhen; Chiu, Yu-Chun; Kao, Yu-Yao; Liu, Chia-Jung

2014-10-01

Aerosol delivery through mechanical ventilation is influenced by the type of aerosol generator, pattern of nebulization, and a patient's breathing pattern. This study compares the efficiency of pneumatic nebulization modes provided by a ventilator with adult and pediatric in vitro lung models. Three pneumatic nebulization modes (inspiratory intermittent [IIM], continuous [CM], and expiratory intermittent [EIM]) provided by the Galileo Gold ventilator delivered medical aerosol to collection filters distal to an endotracheal tube with adult and pediatric test lungs. A unit dose of 5 mg/2.5 mL albuterol was diluted into 4 mL with distilled water and added to a jet nebulizer. The nebulizer was placed proximal to the ventilator, 15 cm from the inlet of the heated humidifier chamber with a T-piece and corrugated aerosol tubing and powered by gas from the ventilator in each of the 3 modes. Time for nebulization was recorded in minutes. Albuterol samples collected in the inhalation filter, nebulizer, T-piece, and corrugated tubing were eluted with distilled water and analyzed with a spectrophotometer. The inhaled drug, as a percentage of total dose in both lung models, was 5.1-7.5%, without statistical significance among the 3 modes. Median nebulization times for IIM, CM, and EIM were 38.9, 14.3, and 17.7 min, respectively, and nebulization time for the 3 modes significantly differed (P ventilator was not dependent on nebulization mode during simulated pediatric and adult conventional mechanical ventilation. Use of expiratory intermittent mode and continuous nebulization should be considered to reduce treatment time. Copyright © 2014 by Daedalus Enterprises.

Effect of InspirEase on the deposition of metered-dose aerosols in the human respiratory tract

International Nuclear Information System (INIS)

Newman, S.P.; Woodman, G.; Clarke, S.W.; Sackner, M.A.

1986-01-01

A radiotracer technique has been used to assess the effects of a 700-ml collapsible holding chamber (InspirEase, Key Pharmaceuticals Inc.) on the deposition of metered-dose aerosols in ten patients with obstructive airways disease (mean forced expiratory volume in one second [FEV1], 64.5 percent of predicted). Patterns of deposition obtained by patients' usual techniques with the metered-dose inhaler (MDI) were compared with those by correct MDI technique (actuation coordinated with slow deep inhalation and followed by ten seconds of breath-holding) and with those by InspirEase. Deposition of aerosol was assessed by placing Teflon particles labelled with 99mTc inside placebo canisters, and inhaling maneuvers were monitored by respiratory inductive plethysmography (Respitrace). Nine of the ten patients had imperfect technique with the MDI, the most prevalent errors being rapid inhalation and failure to hold their breath adequately. With patients' usual MDI techniques, 6.5 +/- 1.2 percent (mean +/- SE) of the dose reached the lungs. This was increased to 11.2 +/- 1.3 percent (p less than 0.02) with correct technique and increased further to 14.8 +/- 1.4 percent (p less than 0.05) with InspirEase. Oropharyngeal deposition exceeded 80 percent of the dose for the MDI alone but was only 9.5 +/- 0.9 percent with InspirEase (p less than 0.01); 59.2 +/- 2.1 percent of the dose was retained within InspirEase itself. It is concluded that InspirEase gives whole lung deposition of metered-dose aerosols greater than that from a correctly used MDI, while oropharyngeal deposition is reduced approximately nine times

An aerosole generator for production of radioactive aerosoles by evaporating uranium dioxide

International Nuclear Information System (INIS)

Pusch, W.M.

1975-01-01

In the Institut for Biology of the Austrian Research Center at Seibersdorf an experiment is running to study the behaviour of radioactive aerosoles in the organism of miniature swines after inhalation. In the work under discussion the aerosole generator of the equipment used for this inhalation experiments is described by means of which the aerosole-air mixtures are produced. The main part of this generator is a gas burner for evaporating irradiated UO 2 -pellets. (orig.) [de

Enhancements of a mechanical lung simulator for ex vivo measuring of aerosol deposition in lungs

Czech Academy of Sciences Publication Activity Database

Steiner, T.; Forjan, M.; Kopp, T.; Bureš, Zbyněk; Drauschke, A.

2012-01-01

Roč. 57, Suppl.1 (2012), s. 799-802 ISSN 0013-5585 Institutional research plan: CEZ:AV0Z50390512 Keywords : aerosol measurement * lung simulator Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 1.157, year: 2012

Low-level inhaled-239PuO2 life-span studies in rats

International Nuclear Information System (INIS)

Sanders, C.L.; McDonald, K.E.; Killand, B.W.; Mahaffey, J.A.; Cannon, W.C.

1986-01-01

This study determined the dose-response curve for lung tumor incidence in rats after inhalation of high-fired 239 PuO 2 , which gave radiation doses to the lung of from ∼5 to >1000 rads. Exposed rats were given a single, nose-only, inhalation exposure to 169 Yb- 239 PuO 2 aerosol (AMAD, 1.6 +- 0.11 μm). The effective half-time for 169 Yb in the lung was 14 days, whereas ∼76% of 239 Pu was cleared with a half-time of 20 days and 24%, with a half-time of 180 days. Whole-body counting for 169 Yb at 14 days after exposure was an accurate method for determining 239 Pu IAD in individual rats, even at IAD's as low as 0.60 nCi of 239 Pu. The 239 Pu lung-clearance curve and an equation describing changes in lung weight with body weight and age were used to determine lung radiation doses. The IAD's of exposure groups were 0.60 +- 0.15 nCi of 239 Pu (1000 rats), 0.98 +- 0.25 (531 rats), 2.4 +- 0.69 (209 rats), 5.7 +- 1.2 (98 rats), and 7.5 +- 2.0 to 150 +- 37 nCi (300 rats); corresponding radiation doses to the lung estimated at 3 years after exposure were 8.3, 14, 33, 79, and 100 to 2100 rads, respectively. 71 refs., 5 figs., 4 tabs

Protection of air in premises and environment against beryllium aerosols

Energy Technology Data Exchange (ETDEWEB)

Bitkolov, N.Z.; Vishnevsky, E.P.; Krupkin, A.V. [Research Inst. of Industrial and Marine Medicine, St. Petersburg (Russian Federation)

1998-01-01

First and foremost, the danger of beryllium aerosols concerns a possibility of their inhalation. The situation is aggravated with high biological activity of the beryllium in a human lung. The small allowable beryllium aerosols` concentration in air poses a rather complex and expensive problem of the pollution prevention and clearing up of air. The delivery and transportation of beryllium aerosols from sites of their formation are defined by the circuit of ventilation, that forms aerodynamics of air flows in premises, and aerodynamic links between premises. The causes of aerosols release in air of premises from hoods, isolated and hermetically sealed vessels can be vibrations, as well as pulses of temperature and pressure. Furthermore, it is possible the redispersion of aerosols from dirty surfaces. The effective protection of air against beryllium aerosols at industrial plants is provided by a complex of hygienic measures: from individual means of breath protection up to collective means of the prevention of air pollution. (J.P.N.)

Development of a Zealand white rabbit deposition model to study inhalation anthrax

Energy Technology Data Exchange (ETDEWEB)

Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

2016-01-28

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

Solubility of plutonium dioxide aerosols, in vitro

International Nuclear Information System (INIS)

Newton, G.J.; Kanapilly, G.M.

1976-01-01

Solubility of plutonium aerosols is an important parameter in establishing risk estimates for industrial workers who might accidentally inhale these materials and in evaluating environmental health impacts associated with Pu. In vitro solubility of industrial plutonium aerosols in a simulated lung fluid is compared to similar studies with ultrafine aerosols from laser ignition of delta phase plutonium metal and laboratory-produced spherical particles of 238 PuO 2 and 239 PuO 2 . Although relatively insoluble, industrial plutonium-mixed oxide aerosols were much more soluble than laboratory-produced plutonium dioxide particles. Chain agglomerate aerosols from laser ignition of metallic Pu indicated in vitro dissolution half-times of 10 and 50 days for activity median aerodynamic diameter (AMAD) of 0.7 and 2.3 μm, respectively. Plutonium-containing mixed oxide aerosols indicated dissolution half-times of 40 to 500 days for particles formed by industrial powder comminution and blending. Centerless grinding of fuel pellets yielded plutonium-containing aerosols with dissolution half-times of 1200 to 8000 days. All mixed oxide particles were in the size range 1.0 μm to 2.5 μm AMAD

Future options for aerosol delivery to children

DEFF Research Database (Denmark)

Bisgaard, H

1999-01-01

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......, 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...

Estimation of inhaled airborne particle number concentration by subway users in Seoul, Korea

International Nuclear Information System (INIS)

Kim, Minhae; Park, Sechan; Namgung, Hyeong-Gyu; Kwon, Soon-Bark

2017-01-01

Exposure to airborne particulate matter (PM) causes several diseases in the human body. The smaller particles, which have relatively large surface areas, are actually more harmful to the human body since they can penetrate deeper parts of the lungs or become secondary pollutants by bonding with other atmospheric pollutants, such as nitrogen oxides. The purpose of this study is to present the number of PM inhaled by subway users as a possible reference material for any analysis of the hazards to the human body arising from the inhalation of such PM. Two transfer stations in Seoul, Korea, which have the greatest number of users, were selected for this study. For 0.3–0.422 μm PM, particle number concentration (PNC) was highest outdoors but decreased as the tester moved deeper underground. On the other hand, the PNC between 1 and 10 μm increased as the tester moved deeper underground and showed a high number concentration inside the subway train as well. An analysis of the particles to which subway users are actually exposed to (inhaled particle number), using particle concentration at each measurement location, the average inhalation rate of an adult, and the average stay time at each location, all showed that particles sized 0.01–0.422 μm are mostly inhaled from the outdoor air whereas particles sized 1–10 μm are inhaled as the passengers move deeper underground. Based on these findings, we expect that the inhaled particle number of subway users can be used as reference data for an evaluation of the hazards to health caused by PM inhalation. - Highlights: • Size-dependent aerosol number was measured along the path of subway user. • Particles less than 0.4 μm were inhaled in outdoor but less so as deeper underground. • Coarse particles were inhaled significantly as users moved deeper underground. - We estimated the inhaled aerosol number concentration depending on particle size along the path of subway users.

Hematologic effects of inhaled plutonium in beagles

International Nuclear Information System (INIS)

Ragan, H.A.; Buschbom, R.L.; Park, J.F.; Dagle, G.E.; Weller, R.E.

1986-01-01

Beagle dogs were exposed, by inhalation, 5 to 11 years ago, to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 , at six dose levels resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Translocation of the plutonium to extrapulmonary sites was related to the physical-chemical characteristics of the plutonium compound. The highly insoluble 239 PuO 2 was retained primarily in the lung and associated lymph nodes, whereas 239 Pu(NO 3 ) 4 was much more soluble and translocated relatively rapidly to the skeleton and other extrapulmonary tissues. The 238 PuO 2 was intermediate in solubility and translocation characteristics. The hematologic effects of plutonium inhalation were most pronounced on lymphocyte populations. Evidence suggests that these effects result from irradiation of lymphocytes via the pulmonary lymph nodes with insoluble 239 PuO 2 , and via these same lymph nodes, extrapulmonary lymph nodes, and bone marrow lymphocytes with the more soluble forms, i.e., 238 PuO 2 and 239 Pu(NO 3 ) 4 . There is no evidence suggesting that these exposures increase the risk of developing myeloid or lymphoid neoplasia. 8 refs., 4 figs., 3 tabs

Inhalation drug delivery devices: technology update

Directory of Open Access Journals (Sweden)

Ibrahim M

2015-02-01

Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

Development of a High Efficiency Dry Powder Inhaler: Effects of Capsule Chamber Design and Inhaler Surface Modifications

Science.gov (United States)

Behara, Srinivas R.B.; Farkas, Dale R.; Hindle, Michael; Longest, P. Worth

2013-01-01

Purpose The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. Methods DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. Results The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. Conclusions High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD 90%, and ED > 80%. PMID:23949304

Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications.

Science.gov (United States)

Behara, Srinivas R B; Farkas, Dale R; Hindle, Michael; Longest, P Worth

2014-02-01

The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD  90%, and ED > 80%.

Lung physiology and how aerosol deposits in the lungs

International Nuclear Information System (INIS)

Isawa, Toyoharu

1994-01-01

Weibel's morphologic data has been referred to not only for predicting aerosol deposition in the lungs but also lung physiology. During breathing the volume of air passes all through the mouth, the larynx, the trachea and the conductive airways into the alveolar space. When the airflow is not laminar and disturbed at the bifurcation or the irregular airway surface, eddies and turbulence occur there to result in deposition of aerosol by impaction or sedimentation. At high flow rates, there are more chances for turbulence to occur at these sites. Because the cross-section and volume of the subsequent airways increase, the flow rate decreases. It is worthwhile to remember that the pressure drop and resistance do not necessarily follow Poiseuille's law even in the large airways, and that with the turbulent flow the density of a gas plays an important role. If Poiseuille's law is applied, the resistance becomes sixteenfold when the radius of the airway segment is halved. When we breathe quietly, the flow in the trachea and the intermediate conductive airways is laminar and in very small conductive airways including the terminal bronchioles the airflow becomes so slow in velocity that the axial diffusion becomes more prominent, especially distal to the terminal bronchioles the cross-sectional area increases so much that molecular diffusion becomes more important. For gas transfer to occur, molecules of oxygen should pass through the surfactant layer, the alveolar epithelium, the basement membrane, the endothelium of the capillaries, and the plasma to get to the red blood cell to combine with hemoglobin

Annual limits on intake for aerosols in the working environment on Magnox power stations

International Nuclear Information System (INIS)

Bosch, F.G.C.; Harte, G.A.

1983-09-01

Annual Limits on Intake (ALIs) for inhaled radionuclides given by the International Commission on Radiological Protection are derived for single isotopes and for an aerosol size (AMAD) of 1 micron. A recent investigation into aerosols in the pond hall of a Magnox Power Station has demonstrated that the aerosol in the pond hall consists of particles of corroded fuel and that the size distribution has an AMAD nearer 6 microns than 1 micron. Experiments in rodents with a simulated pond hall aerosol indicate that clearance characteristics of these particles in the lung are closer to ICRP's class W classification than to any other. Accordingly ALIs were calculated as a function of particle size and for various cooling times for Magnox-fuel of burnup 3500 MWd/t and 7000 MWd/t. Separate values for alpha and beta activity were derived, based on stochastic and non-stochastic dose limits. For a 6 micron aerosol the ALI (α-activity) based on limiting the committed dose to bone surfaces lies between 120 and 320 Bq, depending on fuel burnup and cooling time. The ALI (β-activity) in the same circumstances lies between 10 4 and 8 x 10 4 Bq. Beta activity in the aerosol is dominated by the fission products but dose is overwhelmingly due to the actinides in the fuel. In addition an attempt was made to construct or to find a lung model which more closely represented the observed clearance to blood in the animal experiments. A recent model for large inhaled particles derived at the NRPB was found to give the best fit to the experimental data. ALIs derived on the basis of this model, for a 6 micron aerosol, are roughly 2 times higher than those based completely on the ICRP recommendations. (author)

Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.

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Fechter, Laurence D; Nelson-Miller, Alisa; Gearhart, Caroline

2008-07-01

Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

Changes of indoor aerosol characteristics and their associated variation on the dose conversion factor due to radon progeny inhalation

International Nuclear Information System (INIS)

Tokonami, Shinji; Ishikawa, Tetsuo; Yonehara, Hidenori; Yamada, Yuji; Matsuzawa, Takao; Iimoto, Takeshi

2003-01-01

Since the dose conversion factor (hereafter called DCF) due to radon progeny inhalation is strongly dominated by aerosol characteristics in the environment, it is important to understand the air quality for accurate dose assessment. Thus temporal variations on aerosol concentration, its particle size and its related airborne radioactivities were continuously measured in an actual indoor environment with a relatively high radon concentration. The following human activities were added during the observation period: air-conditioning, removal of aerosol with an air cleaner and ventilation. DCFs based on these activities were evaluated with the latest International Commission of Radiological Protection (ICRP) respiratory tract model and were compared among them. Consequently, the present study has shown that operation of air cleaner enhanced the DCF critically because the unattached fraction increased significantly due to removal of aerosols. (author)

Risk analysis of fatal and incidental lung tumors in wister rats after inhalation of plutonium dioxide

International Nuclear Information System (INIS)

Kai, M.; Akahane, K.; Ogiso, Y.

2000-01-01

Cancer risk analysis was done in animal studies for inhalation of plutonium dioxide. Female Wister rats were exposed to an aerosol of plutonium with AMAD of 0.4-0.5 μm and followed up until they died. We made some model analyses using their likelihood function. This approach enables us to consider temporal variation in dose-response analysis. Each rat contributes to the total likelihood depending on fatal or incidental tumors. In Weibul model analysis, the logarithm of the hazard function can be linearly modeled with the term of log (dose), log-L model, and additional term of the square of log (dose), log-LQ model. The likelihood ratio statistics gave a significantly better fit of the log-LQ model. However, if data more than 4 Gy were excluded, there was no significant difference between both models. The ratio of hazard function at 1 Gy and 0 Gy, the excess relative risk, showed 30 for total tumors. This result was much different from those in PNL data (Sanders et al.). The difference of pulmonary deposition depending upon particle size would cause different tumor incidence. Our studies indicated significant increase of occurrence of fatal lung cancer at an average dose of 0.5 Gy and thus did not suggest that a life-span effective threshold for death was about 1 Gy to the lung, which is shown in some papers. In contrast PNL, the incidence of adenoma showing the maximum at 0.5 Gy decreased with increasing lung dose from 1.5 Gy or higher, where malignant tumors such as adenocarcinomas increased. This phenomenon was analyzed with carcinogenesis models. (author)

Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

Science.gov (United States)

Shim, Ilseob; Seo, Gyun-Baek; Oh, Eunha; Lee, Mimi; Kwon, Jung-Taek; Sul, Donggeun; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee; Kim, Hyun-Mi

2013-01-01

Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

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Weissmann Norbert

2005-11-01

Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

Inhaled antibiotics for lower airway infections.

Science.gov (United States)

Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

2014-03-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung

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Masanori Horie

2016-01-01

Full Text Available NiO nanoparticles were administered to rat lungs via intratracheal instillation or inhalation. During pulmonary toxicity caused by NiO nanoparticles, the induction of oxidative stress is a major factor. Both intratracheal instillation and inhalation of NiO nanoparticles induced pulmonary oxidative stress. The oxidative stress response protein, heme oxygenase-1 (HO-1, was induced by the administration of NiO nanoparticles at both the protein and gene expression level. Additionally, certain oxidative-stress markers in the lung, such as 8-iso-prostaglandin F2α, thioredoxin, and inducible nitric oxide synthase were increased. Furthermore, the concentration of myeloperoxidase (MPO in the lung was also increased by the administration of NiO nanoparticles. When the amount of NiO in the lung is similar, the responses against pulmonary oxidative stress of intratracheal instillation and inhalation are also similar. However, the state of pulmonary oxidative stress in the early phase was different between intratracheal instillation and inhalation, even if the amount of NiO in the lung was similar. Inhalation causes milder oxidative stress than that caused by intratracheal instillation. On evaluation of the nanoparticle-induced pulmonary oxidative stress in the early phase, we should understand the different states of oxidative stress induced by intratracheal instillation and inhalation.

Radiation dose estimates and hazard evaluations for inhaled airborne radionuclides: Final report

International Nuclear Information System (INIS)

Mewhinney, J.A.

1987-09-01

The project objective was to conduct confirmatory research on physical chemical characteristics of aerosols produced during manufacture of mixed plutonium and uranium oxide nuclear fuel, to determine the radiation dose distribution in tissues of animals after inhalation exposure to representative aerosols of these materials, and to provide estimates of the relationship of radiation dose and biological response in animals after such inhalation exposure. The first chapter summarizes the physical chemical characterization of samples of aerosols collected from gloveboxes at industrial facilities during normal operations. This chapter provides insights into key aerosol characteristics which are of potential importance in determining the biological fate of specific radionuclides contained in the particulates that would be inhaled by humans following accidental release. The second chapter describes the spatial and temporal distribution of radiation dose in tissues of three species of animals exposed to representative aerosols collected from the industrial facilities. These inhalation studies provide a basis for comparison of the influence of physical chemical form of the inhaled particulates and the variability among species of animal in the radiation dose to tissue. The third chapter details to relationship between radiation dose and biological response in rats exposed to two aerosol forms each at three levels of initial pulmonary burden. This study, conducted over the lifespan of the rats and assuming results to be applicable to humans, indicates that the hazard to health due to inhalation of these industrial aerosols is not different than previously determined for laboratory produced aerosol of PuO 2 . Each chapter is processed separately for the data base

Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects

International Nuclear Information System (INIS)

Phipps, P.R.; Gonda, I.; Anderson, S.D.; Bailey, D.; Bautovich, G.

1994-01-01

Nonisotonic aerosols are frequently used in the diagnosis and therapy of lung disease. The purpose of this work was to study the difference in the pattern of deposition of aerosols containing aqueous solutions of different tonicities. 99m Technetium-diethyltriaminepentaacetic acid ( 99m Tc-DTPA)-labelled saline aerosols, with mass median aerodynamic diameter 3.7-3.8 μm and geometric standard deviation 1.4, were inhaled under reproducible breathing conditions on two occasions. Hypotonic and hypertonic solutions were used in 11 normals subjects, isotonic and hypertonic solutions in 9 asthmatics. The regional deposition was quantified by a penetration index measured with the help of a tomographic technique. There was a small but significant increase (6.7%) in the penetration index of the hypotonic as compared to the hypertonic aerosols in the normal subjects. The region that was markedly affected was the trachea. The differences in the penetration of the isotonic and hypertonic aerosols in the asthmatics appeared to be strongly dependent on the state of the airways at the time of the study. These findings can be interpreted in terms of effects of growth or shrinkage of nonisotonic aerosols, as well as of airway narrowing, on regional deposition of aerosols. Tonicity of aerosols appears to affect their deposition both through physical and physiological mechanisms. This should be taken into account when interpreting the effects of inhaled aqueous solutions of various tonicities in patients in vivo. (au) (44 refs.)

Doses from potential inhalation by people living near plutonium contaminated areas

International Nuclear Information System (INIS)

Iranzo Gonzales, E.; Salvador Ruiz, S.

1983-09-01

An aviation accident above the town of Palomares, Spain resulted in four thermonuclear bombs carried by one of the planes falling. The nuclear fuel in two of them ignited and formed an aerosol which contaminated a 226-hectare area of underbrush, farmland and an urban center. The magnitude of risk to people living in the area who may have inhaled the plutonium aerosol or dusts during the fifteen-year period since the time the accident is addressed in this report. In addition the internal radiation doses that people may have received during this period and during a fifty-year period commencing with the accident is estimated. In brief summary, the lungs received the greatest dose equivalent (1966 to 1980). Over the fifty year period (to 2015) the bones are projected to receive the greatest dose. For the remaining organs - liver-intestines-kidneys, - the relationships or between the doses that will be accumulated up to the year 2015 and the corresponding annual dose equivalent limits are less than those for the bones and lungs

Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

International Nuclear Information System (INIS)

Nambiar, Madhusoodana P.; Gordon, Richard K.; Rezk, Peter E.; Katos, Alexander M.; Wajda, Nikolai A.; Moran, Theodore S.; Steele, Keith E.; Doctor, Bhupendra P.; Sciuto, Alfred M.

2007-01-01

To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m 3 of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure

Hypoadrenocorticism in beagles exposed to aerosols of plutonium-238 dioxide by inhalation

International Nuclear Information System (INIS)

Weller, R.E.; Buschbom, R.L.; Dagle, G.E.

1996-01-01

Hypoadrenocorticism, known as Addison's disease in humans, was diagnosed in six beagles after inhalation of at least 1.7 kBq/g lung of 238 PuO 2 . Histological examination of adrenal gland specimens obtained at necropsy revealed marked adrenal cortical atrophy in all cases. Autoadiographs showed only slight α-particle activity. Although the pathogenesis of adrenal cortical atrophy in these dogs is unclear, there is evidence to suggest an automimmune disorder linked to damage resulting from α-particle irradiation to the lymphatic system

Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

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David Gur

2018-04-01

Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

Mutual information based CT registration of the lung at exhale and inhale breathing states using thin-plate splines

International Nuclear Information System (INIS)

Coselmon, Martha M.; Balter, James M.; McShan, Daniel L.; Kessler, Marc L.

2004-01-01

The advent of dynamic radiotherapy modeling and treatment techniques requires an infrastructure to weigh the merits of various interventions (breath holding, gating, tracking). The creation of treatment planning models that account for motion and deformation can allow the relative worth of such techniques to be evaluated. In order to develop a treatment planning model of a moving and deforming organ such as the lung, registration tools that account for deformation are required. We tested the accuracy of a mutual information based image registration tool using thin-plate splines driven by the selection of control points and iterative alignment according to a simplex algorithm. Eleven patients each had sequential CT scans at breath-held normal inhale and exhale states. The exhale right lung was segmented from CT and served as the reference model. For each patient, thirty control points were used to align the inhale CT right lung to the exhale CT right lung. Alignment accuracy (the standard deviation of the difference in the actual and predicted inhale position) was determined from locations of vascular and bronchial bifurcations, and found to be 1.7, 3.1, and 3.6 mm about the RL, AP, and IS directions. The alignment accuracy was significantly different from the amount of measured movement during breathing only in the AP and IS directions. The accuracy of alignment including thin-plate splines was more accurate than using affine transformations and the same iteration and scoring methodology. This technique shows promise for the future development of dynamic models of the lung for use in four-dimensional (4-D) treatment planning

Development of a Zealand White Rabbit Deposition Model to Study Inhalation Anthrax

Science.gov (United States)

Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, A.P.; Corley, Richard A.

2016-01-01

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

Influence of radiation-dose pattern from inhaled beta--gamma-emitting radionuclides on canine peripheral lymphocytes

International Nuclear Information System (INIS)

Jones, R.K.; Boecker, B.B.; Pickrell, J.A.; Hobbs, C.H.; McClellan, R.O.

1976-01-01

As part of studies assess the biological hazards associated with inhaled radionuclides, periodic hematologic evaluations were performed on beagle dogs given a single nose-only exposure to aerosols of beta--gamma-emitting isotopes. The physical form and specific radionuclides selected produced radiation-dose patterns representative of those which might be encountered in the event of human accidental exposures. Dogs received graded lung burdens of either 90 Y, 91 Y, 144 Ce, or 90 Sr, each in fused clay. Differences in the effective half-lives of these radionuclides resulted in a spectrum of cumulative radiation doses to lung delivered at a variety of dose rates. Since the form in which the radionuclides were inhaled was relatively insoluble, the lung and intrathoracic tissues represented the primary recipient of the dose. Regardless of the effective half-life of radionuclide retention, a dose-related depression of peripheral lymphocytes was observed at various times after inhalation exposure. The time at which maximum depression and subsequent recovery occurred, however, was most directly related to the effective half-life of the radionuclide. Of special interest was the persistence of lymphopenia through 2 1 / 2 years after exposure to 144 Ce and 90 Sr in fused clay where, other than tracheobronchial lymph nodes, the lymphoid tissue received very little radiation dose. The possible mechanisms responsible for lymphocyte depression from these various radiation-dose patterns are discussed

Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study

Science.gov (United States)

Mainz, Jochen G; Schädlich, Katja; Schien, Claudia; Michl, Ruth; Schelhorn-Neise, Petra; Koitschev, Assen; Koitschev, Christiane; Keller, Peter M; Riethmüller, Joachim; Wiedemann, Baerbel; Beck, James F

2014-01-01

Rationale In cystic fibrosis (CF), the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa. Pathogens subsequently descend to the lower airways, with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease. Unlike conventional aerosols, vibrating aerosols applied with the PARI Sinus™ nebulizer deposit drugs into the paranasal sinuses. This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage. Objectives To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability. Methods Patients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days, with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline. Results Nine patients participated, six initially receiving tobramycin and three placebo. Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine. P. aeruginosa quantity decreased in four of six (67%) patients given tobramycin, compared with zero of three given placebo (non-significant). SNOT-20 scores were significantly lower in the tobramycin than in the placebo group (P=0.033). Conclusion Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF. PMID:24596456

Radioaerosol imaging of the lung. An IAEA [CRP] group study

International Nuclear Information System (INIS)

Yong Whee Bahk; Isawa, Toyoharu

1994-01-01

Nuclear scans, radiography and computed tomography (CT) of the lung make up three pantheonic pillars of the modem imaging diagnosis of pulmonary disorders and the contribution of these modalities to the progress of pulmonology has been immense. However the experiences accumulated during the past decades indicate that, with well-known advantages and drawbacks, not one of these imaging modalities can be perfect by itself alone, and it has become obvious that the individual tests are as much complementary to one another as unique. As a matter of fact, the nuclear lung imagings, that include inhalation scan, perfusion scan, ventilation scan and the most recently developed mucociliary transport and alveolar permeability tests, are very sensitive and efficient in respectively providing graphic information about airway patency and alveolar penetration, vascular patency and distribution pattern, alveolar gas exchange and bronchial epithelial integrity in both normal and pathological conditions. But these tests lack fine morphological information. In contrast, radiography with its extremely high level of resolution that is in the order of 30-100 line pairs/mm compared to 3-5 line/cm of nuclear scan resolution power, suffers from the lack of information about the alveolar gas exchange, pulmonary perfusion and respiratory function. Although incomparable to radiography, the resolution power of CT scan is also much greater than that of nuclear scan, but again this test cannot provide the information regarding function and physiology. The aerosol scan findings in each of these diseases are assessed in the i ht of and validated against chest radiography, conventional X-ray tomography and high resolution CT scan. The chapters in this monograph describe a history of radioaerosol lung imaging, radiopharmaceuticals, generation of aerosols by the BARC and other nebulizers, and pertinent lung physiology and the way how aerosol deposits in lung. The technical and constructional aspects

Radioaerosol imaging of the lung. An IAEA [CRP] group study

Energy Technology Data Exchange (ETDEWEB)

Bahk, Yong Whee [Departments of Radiology and Nuclear Medicine, Kangnam St. Mary' s Hospital, Catholic University Medical College, Seoul (Korea, Republic of); Isawa, Toyoharu [Tohoku University Research Institute for Chest Disease and Cancer, Sendai (Japan); eds.

1994-07-01

Nuclear scans, radiography and computed tomography (CT) of the lung make up three pantheonic pillars of the modem imaging diagnosis of pulmonary disorders and the contribution of these modalities to the progress of pulmonology has been immense. However the experiences accumulated during the past decades indicate that, with well-known advantages and drawbacks, not one of these imaging modalities can be perfect by itself alone, and it has become obvious that the individual tests are as much complementary to one another as unique. As a matter of fact, the nuclear lung imagings, that include inhalation scan, perfusion scan, ventilation scan and the most recently developed mucociliary transport and alveolar permeability tests, are very sensitive and efficient in respectively providing graphic information about airway patency and alveolar penetration, vascular patency and distribution pattern, alveolar gas exchange and bronchial epithelial integrity in both normal and pathological conditions. But these tests lack fine morphological information. In contrast, radiography with its extremely high level of resolution that is in the order of 30-100 line pairs/mm compared to 3-5 line/cm of nuclear scan resolution power, suffers from the lack of information about the alveolar gas exchange, pulmonary perfusion and respiratory function. Although incomparable to radiography, the resolution power of CT scan is also much greater than that of nuclear scan, but again this test cannot provide the information regarding function and physiology. The aerosol scan findings in each of these diseases are assessed in the i ht of and validated against chest radiography, conventional X-ray tomography and high resolution CT scan. The chapters in this monograph describe a history of radioaerosol lung imaging, radiopharmaceuticals, generation of aerosols by the BARC and other nebulizers, and pertinent lung physiology and the way how aerosol deposits in lung. The technical and constructional aspects

Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung.

Directory of Open Access Journals (Sweden)

Chad A Lerner

Full Text Available Oxidative stress and inflammatory response are the key events in the pathogenesis of chronic airway diseases. The consumption of electronic cigarettes (e-cigs with a variety of e-liquids/e-juices is alarmingly increasing without the unrealized potential harmful health effects. We hypothesized that electronic nicotine delivery systems (ENDS/e-cigs pose health concerns due to oxidative toxicity and inflammatory response in lung cells exposed to their aerosols. The aerosols produced by vaporizing ENDS e-liquids exhibit oxidant reactivity suggesting oxidants or reactive oxygen species (OX/ROS may be inhaled directly into the lung during a "vaping" session. These OX/ROS are generated through activation of the heating element which is affected by heating element status (new versus used, and occurs during the process of e-liquid vaporization. Unvaporized e-liquids were oxidative in a manner dependent on flavor additives, while flavors containing sweet or fruit flavors were stronger oxidizers than tobacco flavors. In light of OX/ROS generated in ENDS e-liquids and aerosols, the effects of ENDS aerosols on tissues and cells of the lung were measured. Exposure of human airway epithelial cells (H292 in an air-liquid interface to ENDS aerosols from a popular device resulted in increased secretion of inflammatory cytokines, such as IL-6 and IL-8. Furthermore, human lung fibroblasts exhibited stress and morphological change in response to treatment with ENDS/e-liquids. These cells also secrete increased IL-8 in response to a cinnamon flavored e-liquid and are susceptible to loss of cell viability by ENDS e-liquids. Finally, exposure of wild type C57BL/6J mice to aerosols produced from a popular e-cig increase pro-inflammatory cytokines and diminished lung glutathione levels which are critical in maintaining cellular redox balance. Thus, exposure to e-cig aerosols/juices incurs measurable oxidative and inflammatory responses in lung cells and tissues that

Measurement of specific parameters for dose calculation after inhalation of aerols containing transuranium elements

International Nuclear Information System (INIS)

Ramounet-le Gall, B.; Fritsch, P.; Abram, M.C.; Rateau, G.; Grillon, G.; Guillet, K.; Baude, S.; Berard, P.; Ansoborlo, E.; Delforge, J.

2002-01-01

A review on specific parameter measurements to calculate doses per unit of incorporation according to recommendations of the International Commission of Radiological Protection has been performed for inhaled actinide oxides. Alpha activity distribution of the particles can be obtained by autoradiography analysis using aerosol sampling filters at the work places. This allows us to characterize granulometric parameters of 'pure' actinide oxides, but complementary analysis by scanning electron microscopy is needed for complex aerosols. Dissolution parameters with their standard deviation are obtained after rat inhalation exposure, taking into account both mechanical lung clearance and actinide transfer to the blood estimated from bone retention. In vitro experiments suggest that the slow dissolution rate might decrease as a function of time following exposure. Dose calculation software packages have been developed to take into account granulometry and dissolution parameters as well as specific physiological parameters of exposed individuals. In the case of poorly soluble actinide oxides, granulometry and physiology appear as the main parameters controlling dose value, whereas dissolution only alters dose distribution. Validation of these software packages are in progress. (author)

Lung diffusion of soluble radioaerosols in scleroderma

International Nuclear Information System (INIS)

Chopra, S.K.; Taplin, G.V.; Tashkin, D.P.; Elam, D.

1978-01-01

Diffusion rates of soluble radioaerosols of sodium pertechnetate (/sup 99m/TcO 4 ; mol. wt. 163) and diethylentriaminepentaacetate (/sup 99m/Tc-DTPA; mol. wt. 492) were determined in ten normal subjects and ten patients with scleroderma having lung involvement. Twenty millicuries (mCi) each of /sup 99m/TcO 4 and /sup 99m/Tc-DTPA in 5 ml saline were aerosolized and inhaled on two different days. Initial lung retention after three minutes of administration was approximately 2 mCi. Two regions of interest over each posterior lung field were monitored with a scintillation camera and data were stored on magnetic tape. Decreasing levels of radioactivity were plotted semilogarithmically and half time (T 1 / 2 ) removal rates were calculated

Inhalation exposures during operations in spent fuel bays

International Nuclear Information System (INIS)

Dua, S.K.; Maniyan, C.G.; Kotrappa, P.

1987-01-01

Radioactive aerosols are generated during operations (transfer, cutting, storage and shipment of fuel) in spent fuel bays. A study has been carried out on the airborne concentration, size distribution and solubility of the aerosol, to evaluate the inhalation exposure of the workers. Personal air samplers were used for the measurement of concentration of airborne radioactivity and Andersen impactor for particle size distribution. Some of the collected sampels were followed for their solubility in lung serum simulant for a period of about 200 days. The observed concentrations of the aerosols and their activity median aerodynamic diameters (AMAD) were 418 ± 443 Bq m -3 (βγ), 1.28 ± 1.478 Bq m -3 (∞) and 6.79 ± 0.4μm respectively. Analysis of the samples revealed the presence of 239 Pu, U, 90 Sr and 137 Cs. The clearance half-life of the aerosols was the same (155 days) for all the isotopes (U, 239 Pu, 90 Sr; 137 Cs). Calculation of effective dose equivalent for the clearance half-life and for 6.79 μm AMAD aerosols was carried out using the method recommended in ICRP-30. Annual effective dose equivalent of the workers, if no respirators were worn, worked out to be 3.2 mSv (320 mrem), the contribution from alpha emitters being about 63 per cent of the total. (author). 5 refs., 2 tables

Bronchography by tantalum aerosols, an experimental investigation of lung clearance and retention

International Nuclear Information System (INIS)

Causse, Andre.

1974-01-01

Lung clearance of tantalum used as contrast medium has been studied in three animal species: rat, monkey and cat. In rats and monkeys, 80 to 90 percent of the inhaled tantalum was removed with a half life of 10 to 30 hr, but the residual fraction was removed with a half life longer than 100 days; consequently persistent roentgenographic pictures could be observed. These results were in accordance with those obtained by other authors studying dogs and men (accidental inhalation of radioactive tantalum). In cats, about 98 percent was removed with a half life of 15 hr and the remaining fraction with a half life of 18 days. In the three species, the physiological lung clearance mechanisms did not seem disturbed. Microscopic examination showed the peribronchiolar localisation of remaining tantalum in rats and monkeys, with proliferation of granulomes and fibrotic reaction. These results must induce to the greatest care when using tantalum in man in order to outline peripheral airways [fr

Pulmonary aerosol delivery and the importance of growth dynamics.

Science.gov (United States)

Haddrell, Allen E; Lewis, David; Church, Tanya; Vehring, Reinhard; Murnane, Darragh; Reid, Jonathan P

2017-12-01

Aerosols are dynamic systems, responding to variations in the surrounding environmental conditions by changing in size, composition and phase. Although, widely used in inhalation therapies, details of the processes occurring on aerosol generation and during inhalation have received little attention. Instead, research has focused on improvements to the formulation of the drug prior to aerosolization and the resulting clinical efficacy of the treatment. Here, we highlight the processes that occur during aerosol generation and inhalation, affecting aerosol disposition when deposited and, potentially, impacting total and regional doses. In particular, we examine the response of aerosol particles to the humid environment of the respiratory tract, considering both the capacity of particles to grow by absorbing moisture and the timescale for condensation to occur. [Formula: see text].

Toxicity of 144Ce inhaled in a relatively insoluble form by aged beagle dogs. VI

International Nuclear Information System (INIS)

Hahn, F.F.; Hanika-Rebar, C.; Boecker, B.B.; Hobbs, C.H.; McClellan, R.O.; Pickrell, J.A.

1977-01-01

The toxicity of 144 Ce inhaled in fused aluminosilicate particles by 8 to 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28 and 57 μCi 144 Ce/kg body weight. Six blocks of four male dogs each have been divided into three exposure levels with mean initial lung burdens of 7.2, 14 and 28 μCi 144 Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Eighteen dogs with initial lung burdens ranging from 14 to 75 μCi 144 Ce/kg body weight and cumulative doses to lung of from 22,000 to 74,000 rads have died or were euthanized 197 to 1207 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis

Toxicity of 144Ce fused clay particles inhaled by aged dogs. III

International Nuclear Information System (INIS)

Hahn, F.F.; Boecker, B.B.; Hobbs, C.H.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

1974-01-01

The toxicity of 144 Ce fused clay particles inhaled by 8- to 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies using dogs exposed at approximately 3 months or 12 to 14 months of age. To date, 7 blocks of 5 dogs each, divided into 4 exposure levels with mean initial lung burdens of 7.5, 14, 24, and 57 μCi/kg body weight and control dogs exposed to non-labeled fused clay particles have been entered into a longevity study. Twelve dogs with initial lung burdens ranging from 20 to 75 μCi 144 Ce/kg body weight and cumulative doses to lung of from 22,000 to 74,000 rads have died at 197 to 943 days post-inhalation with clinico-pathologic findings of radiation pneumonitis and pulmonary fibrosis. Two of these also had congestive heart failure. In addition, 4 dogs with ILBs of 8 to 14 μCi 144 Ce/kg body weight have died of mammary neoplasms or congestive heart failure but without radiation pneumonitis. One dog with an ILB of 9 μCi 144 Ce/kg body weight died with a chronic interstitial foreign body pneumonia. Two control dogs have died, one with a mammary carcinoma and one with pyometra. Pulmonary retention of the inhaled 144 Ce was similar to that observed previously in dogs exposed at 18 to 22 months of age in a radiation dose pattern study. Serial observations are continuing on the 11 surviving 144 Ce-exposed dogs and 5 controls. (U.S.)

A biokinetic model of inhaled Cm compounds in dogs: Application to human exposure data

International Nuclear Information System (INIS)

Guilmette, R.A.; Mewhinney, J.A.

1989-01-01

Curium isotopes are major by-products in irradiated nuclear reactor fuel and comprise a significant fraction of the alpha-emitting radionuclide inventory. Although little use is currently being made of purified Cm sources, such usage is possible if reprocessing of spent fuel becomes feasible. Because little information is available on the biokinetics and dosimetry of inhaled Cm compounds, a study was conducted in which adult beagle dogs received a single inhalation exposure to either a monodisperse aerosol of 244Cm2O3 (1.4 micron activity median aerodynamic diameter [AMAD]; sigma g = 1.16) or a polydisperse aerosol of 244Cm (NO3)3 (1.1 micron AMAD; sigma g = 1.74). At times ranging from 4 h to 2 y after exposure, animals were sacrificed and their tissues analyzed for Cm content. The data describing the uptake and retention of 244Cm in the different organs and tissues and the measured rates of excretion of these dogs formed the basis on which a biokinetic model of Cm metabolism was constructed. This Cm model was based on a previously published model of the biokinetics of 241Am that was shown to be applicable to data from human cases of inhalation exposure to 241Am aerosols. This Cm model was found to be adequate to describe the biological distribution of Cm in dogs and was also applied to the sparse data from humans. Reasonable agreement was found between the model predictions for lung retention of Cm and for urinary excretion patterns in humans

Superparamagnetic iron oxide nanoparticles (SPIONs)-loaded Trojan microparticles for targeted aerosol delivery to the lung.

Science.gov (United States)

Tewes, Frederic; Ehrhardt, Carsten; Healy, Anne Marie

2014-01-01

Targeted aerosol delivery to specific regions of the lung may improve therapeutic efficiency and minimise unwanted side effects. Targeted delivery could potentially be achieved with porous microparticles loaded with superparamagnetic iron oxide nanoparticles (SPIONs)-in combination with a target-directed magnetic gradient field. The aim of this study was to formulate and evaluate the aerodynamic properties of SPIONs-loaded Trojan microparticles after delivery from a dry powder inhaler. Microparticles made of SPIONs, PEG and hydroxypropyl-β-cyclodextrin (HPβCD) were formulated by spray drying and characterised by various physicochemical methods. Aerodynamic properties were evaluated using a next generation cascade impactor (NGI), with or without a magnet positioned at stage 2. Mixing appropriate proportions of SPIONs, PEG and HPβCD allowed Trojan microparticle to be formulated. These particles had a median geometric diameter of 2.8±0.3μm and were shown to be sensitive to the magnetic field induced by a magnet having a maximum energy product of 413.8kJ/m(3). However, these particles, characterised by a mass median aerodynamic diameter (MMAD) of 10.2±2.0μm, were considered to be not inhalable. The poor aerodynamic properties resulted from aggregation of the particles. The addition of (NH4)2CO3 and magnesium stearate (MgST) to the formulation improved the aerodynamic properties of the Trojan particles and resulted in a MMAD of 2.2±0.8μm. In the presence of a magnetic field on stage 2 of the NGI, the amount of particles deposited at this stage increased 4-fold from 4.8±0.7% to 19.5±3.3%. These Trojan particles appeared highly sensitive to the magnetic field and their deposition on most of the stages of the NGI was changed in the presence compared to the absence of the magnet. If loaded with a pharmaceutical active ingredient, these particles may be useful for treating localised lung disease such as cancer nodules or bacterial infectious foci. Copyright �

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation.

Science.gov (United States)

Kolanjiyil, Arun V; Kleinstreuer, Clement

2016-12-01

Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical

The influence of plutonium exposure and lung cancer on the frequency of x-ray-induced micronuclei in dog blood lymphocytes

International Nuclear Information System (INIS)

Brooks, A.L.; Rithidech, K.; Muggenburg, B.A.; Lozano, D.; Lundgren, D.L.

1988-01-01

This study determined if lung cancer or exposure to an inhaled alpha emitter, plutonium-239, increased the frequency of micronuclei in blood lymphocytes or altered the responsiveness of lymphocytes to induction of micronuclei by subsequent doses of X rays in vitro. Beagle dogs inhaled 1.5 mm ABAD monodisperse 239 PuO 2 aerosols. The exposure resulted in initial lung burdens of 1.8 KBq to 48 KBq and produced cumulative alpha radiation lung doses of 1.4 to 10.4 Gy at the time of this study. Blood lymphocytes were sampled and irradiated with either 0.0 or 2.0 Gy of X rays. The lymphocytes were stimulated to divide by phytohemagglutinin, cytokinesis was blocked with cytochalasin B, and the frequency of micronuclei was determined in binucleated cells. Plutonium inhalation alone produced no significant increase in the frequency of micronuclei in blood lymphocytes. When 2 Gy of X rays ws given to blood lymphocytes of dogs that had inhaled 239 PuO 2 , there was a linear increase in micronuclei frequency as a function of alpha dose to the lungs; micronuclei/binucleated cell = 0.15 +0.2 D, where D is the cumulative alpha-radiation dose to the lung in Gy. Dogs with 239 PuO 2 - induced lung cancer did not have a significant increase in the frequency of X- ray-induced micronuclei relative to dogs exposed to plutonium that did not have lung cancer. These data suggest that inhaled 239 PuO 2 alters the responsiveness of blood lymphocytes to subsequent X-ray exposure. (author)

Toxicity of 144Ce inhaled in a relatively insoluble form by aged Beagle dogs. VII

International Nuclear Information System (INIS)

Hahn, F.F.; Hanika-Rebar, C.; Boecker, B.B.; McClellan, R.O.; Pickrell, J.A.

1978-01-01

The toxicity of 144 Ce inhaled in fused aluminosilicate particles by 8- 10.5-year-old dogs is being investigated to provide information on age-related differences in the response of older members of the human population to accidental inhalation of radioactive aerosols. These data on aged dogs will be compared to the results of similar studies of dogs exposed at approximately 3 months or 12 to 14 months of age. Six blocks of five female dogs each have been divided into four exposure levels with mean initial lung burdens of 7.2, 14, 28, and 57 μCi 144 Ce/kg body weight. Six blocks of four male dogs each have been divided into three exposure levels with mean initial lung burdens of 7.2, 14, and 28 μCi 144 Ce/kg body weight. Controls in each block were exposed to fused aluminosilicate particles containing stable cerium. Nineteen dogs with initial lung burdens ranging from 14 to 75 μCi 144 Ce/kg body weight and cumulative doses to lung of from 20,000 to 74,000 rads have died or were euthanized 197 to 1849 days after exposure with clinicopathologic findings of radiation pneumonitis and pulmonary fibrosis. Eight control dogs have died. Pulmonary retention of the inhaled 144 Ce was similar to that observed previously in dogs exposed at 18 to 22 months of age in a radiation dose pattern study. Serial observations are continuing on the nine surviving 144 Ce-exposed and four control dogs

Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study.

Science.gov (United States)

Bernstein, D M; Toth, B; Rogers, R A; Sepulveda, R; Kunzendorf, P; Phillips, J I; Ernst, H

2018-04-26

This study provides an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake-dust (brakes manufactured with chrysotile). The design included a 28-day repeated multi-dose inhalation exposure (6 h/d, 5 d/wk, 4 wks) followed by 28-days without exposure. Fiber control groups included a similar grade chrysotile as used in the brakes and a commercial crocidolite asbestos. Aerosol fiber distributions of the chrysotile and crocidolite were similar (fiber-length > 20 μm/cm 3 : Chrysotile-low/high 42/62; Crocidolite-low/high 36/55; WHO-fibers/cm 3 : Chrysotile-low/high 192/219; Crocidolite-low/high 211/255). The total number of aerosol particles/cm 3 in the brake-dust was similar to that in the chrysotile (Brake-dust 710-1065; Chrysotile 532-1442). Brake-dust at particle exposure levels equal to or greater than chrysotile or crocidolite caused no indication of microgranulomas, epithelial hyperplasia, or fibrosis (Wagner score brake-dust and chrysotile-HD groups or in thickness of visceral or parietal pleural. The crocidolite exposure resulted in extensive inflammatory response, collagen development and adhesions between the visceral and parietal surfaces with double the surface thickness. These results provide essential information for the design of a subsequent subchronic study. Copyright © 2018. Published by Elsevier Inc.

Saharan dust levels in Greece and received inhalation doses

Directory of Open Access Journals (Sweden)

C. Mitsakou

2008-12-01

Full Text Available The desert of Sahara is one of the major sources of mineral dust on Earth, producing around 2×10⁸ tons/yr. Under certain weather conditions, dust particles from Saharan desert get transported over the Mediterranean Sea and most of Europe. The limiting values set by the directive EC/30/1999 of European Union can easily be exceeded by the transport of desert dust particles in the south European Region and especially in urban areas, where there is also significant contribution from anthropogenic sources. In this study, the effects of dust transport on air quality in several Greek urban areas are quantified. PM₁₀ concentration values from stationary monitoring stations are compared to dust concentrations for the 4-year period 2003–2006. The dust concentration values in the Greek areas were estimated by the SKIRON modelling system coupled with embedded algorithms describing the dust cycle. The mean annual dust contribution to daily-averaged PM₁₀ concentration values was found to be around or even greater than 10% in the urban areas throughout the years examined. Natural dust transport may contribute by more than 20% to the annual number of exceedances – PM₁₀ values greater than EU limits – depending on the specific monitoring location. In a second stage of the study, the inhaled lung dose received by the residents in various Greek locations is calculated. The particle deposition efficiency of mineral dust at the different parts of the human respiratory tract is determined by applying a lung dosimetry numerical model, which incorporates inhalation dynamics and aerosol physical processes. The inhalation dose from mineral dust particles was greater in the upper respiratory system (extrathoracic region and less significant in the lungs, especially in the sensitive alveolar region. However, in cases of dust episodes, the amounts of mineral dust deposited along the human lung are comparable to those

Lung inhalation scintigraphy with radioactive aerosols in several pulmonary diseases. Cintigrafia de ventialacao pulmonar por aerosol em diversas patologias pulmonares

Energy Technology Data Exchange (ETDEWEB)

Martins, L R; Marioni Filho, H [Instituto Dante Pazzanese de Cardiologia, Sao Paulo, SP (Brazil); Romaldini, H; Uehara, C; Alonso, G [Escola Paulista de Medicina, Sao Paulo, SP (Brazil)

1983-01-01

The pulmonary ventilation scintigraphy with 99m Tc diethylene-triamine-pentaacetate (99mTc-DTPA) delivered through a new nebulizer system when analyzed together with the classic lung perfusion scintigraphy with 99mTc-labeled albumin macroaggregates (99mTcMAA) is a very important diagnostic tool in several pulmonary diseases. Several aspects of the lung ventilation-perfusion scintigraphy are studied in 15 people with no lung disease, smokers and nonsmokers. The findings with the lung ventilation-perfusion scintigraphy are also discussed in 34 patients with several pulmonary diseases: lung cancer, chronic obstructive lung disease, policystic pulmonary disease, and pulmonary embolims. The authors concluded that the procedure is a valuable diagnostic tool in several pulmonary diseases, especially because good lung images are obtained, no side effects were detected, the technique is ease and low cost, and it brings new informations, not available with other diagnostic methods. (author).

Toxicity of inhaled 239PuO2 in Fischer 344 rats

International Nuclear Information System (INIS)

Redman, H.C.; Boecker, B.B.; Muggenburg, B.A.; Griffith, W.C.; Guilmette, R.A.; Mewhinney, J.A.; Scott, B.R.

1979-01-01

Studies on the biological effects of inhaled particles of 239 PuO 2 have been initiated in the Fischer 344 rat. To obtain information on the importance of homogeneity or nonhomogeneity of radiation dose to the lung, young adult (84 +- 7 days) animals have been exposed to monodisperse aerosols (sigma/sub g/ 239 PuO 2 of 1.0 and 2.8 μm aerodynamic diameter (AD). To determine the effects of age at exposure, aged rats (600 to 660 days) have been exposed to monodisperse aerosols of 239 PuO 2 of 1.0 μm aerodynamic diameter. To date, 480 young adult rats have been exposed to 239 PuO 2 : 240 rats to 1.0 μm AD particles and 240 rats to 2.85 μm AD particles. The projected exposure level ranged from 0.012 to 0.115 μCi/kg body weight. One hundred sixty rats were sham-exposed and maintained as controls. Also, 240 aged rats have been exposed to date to 1.0 μm AD particles of 239 PuO 2 . The projected activity level ranged from 0.012 to 0.115 μCi/kg body weight. Eighty rats were sham-exposed and maintained as controls. In addition, a serial sacrifice study to determine radiation-dose pattern in rats resulting from the inhalation of these monodisperse aerosols of 239 PuO 2 has been initiated in the young adult rat

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Anon.

1981-01-01

This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

Effect of aerosol inhalation of ipratropium bromide combined with budesonide and terbutaline on cytokines in children with bronchopneumonia

Directory of Open Access Journals (Sweden)

Xiang-Yu Che

2016-09-01

Full Text Available Objective: To explore the clinical efficacy of aerosol inhalation of ipratropium bromide combined with budesonide and terbutaline in the treatment of bronchopneumonia in children and the effect on cytokines. Methods: A total of 70 children with bronchopneumonia who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and randomized into the study group and the control group. The patients in the control group were given anti-infection, oxygen inhalation, cough and asthma relieving, acidosis correcting, mask+oxygen driven aerosol inhalation of budesonide (0.5 mg/time and terbutaline (1.0 mg/time, with an oxygen flow rate of 5-7 L/min, 5-10 min every time, twice a day. On the above basis, the patients in the study group were given additional ipratropium bromide (1.0 mg/time. After 7-day treatment, the efficacy was evaluated. The levels of IL-6, TNF-毩, CRP, and WBC before and after treatment were detected. PEF, FVC, and FEV1 before and after treatment were detected. The improvement of clinical symptoms and signs, and the occurrence of adverse reactions were observed. Results: The levels of IL-6, TNF-毩, CRP, and WBC counting after treatment in the two groups were significantly reduced when compared with before treatment (P0.05. Conclusions: Ipratropium bromide combined with budesonide and terbutaline in the treatment of bronchopneumonia in children can rapidly relieve the symptoms, and improve the cytokine level, without obvious adverse reactions; therefore, it deserves to be widely recommended in the clinic.

Microbial aerosol generation during laboratory accidents and subsequent risk assessment.

Science.gov (United States)

Bennett, A; Parks, S

2006-04-01

To quantify microbial aerosols generated by a series of laboratory accidents and to use these data in risk assessment. A series of laboratory accident scenarios have been devised and the microbial aerosol generated by them has been measured using a range of microbial air samplers. The accident scenarios generating the highest aerosol concentrations were, dropping a fungal plate, dropping a large bottle, centrifuge rotor leaks and a blocked syringe filter. Many of these accidents generated low particle size aerosols, which would be inhaled into the lungs of any exposed laboratory staff. Spray factors (SFs) have been calculated using the results of these experiments as an indicator of the potential for accidents to generate microbial aerosols. Model risk assessments have been described using the SF data. Quantitative risk assessment of laboratory accidents can provide data that can aid the design of containment laboratories and the response to laboratory accidents. A methodology has been described and supporting data provided to allow microbiological safety officers to carry out quantitative risk assessment of laboratory accidents.

Modifying effects of pre-existing fibrosis in rats exposed to aerosols of {sup 239}PuO{sub 2}. II

Energy Technology Data Exchange (ETDEWEB)

Lundgren, D L; Mauderly, J L; Gillett, N A; Hahn, F F

1988-12-01

We have initiated a study using rats to determine the modifying effects of pre-existing pulmonary fibrosis on the retention and biological effects of inhaled {sup 239}PuO{sub 2}. Pulmonary fibrosis was induced by intratracheal instillation of 8.5 IU/kg body weight of bleomycin at 45 to 49 days before inhalation exposure to an aerosol of {sup 239}PuO{sub 2}. The clearance of {sup 239}Pu from the lungs of rats was decreased significantly (p < 0.01) in rats with pre-existing pulmonary fibrosis compared with controls. Respiratory function, lung morphometric measurements and histological evaluations were all consistent with the presence of mild pulmonary fibrosis in the rats treated with bleomycin. Pre-existing pulmonary fibrosis resulted in an increased retention of the initial lung burdens of {sup 239}Pu, apparently by entrapping the particles in fibrotic areas of the lung. The life span of the rats with pulmonary fibrosis was decreased by up to 25% compared with control rats having similar initial lung burdens of {sup 239}Pu. (author)

Deposition of inhaled radionuclides in bronchial airways: Implications for extrapolation modeling

International Nuclear Information System (INIS)

Balashazy, I.; Hofmann, W.; Heistracher, T.

1996-01-01

The laboratory rat has frequently been used as a human surrogate to estimate potential health effects following the inhalation of radioactive aerosol particles. Interspecies differences in biological response are commonly related to interspecies differences in particle deposition efficiencies. In addition, the documented site selectivity of bronchial carcinomas suggests that localized particle deposition patterns within bronchial airway bifurcations may have important implications for inhalation risk assessments. Interspecies differences in particle deposition patterns may be related primarily to differences in airway morphometries. Thus the validity of extrapolating rat deposition data to human inhalation conditions depends on their morphometric similarities and differences. It is well known that there are significant structural differences between the human - rather symmetric - and the rat - monopodial - airway systems. In the present approach, we focus on localized deposition patterns and deposition efficiencies in selected asymmetric bronchial airway bifurcations, whose diameters, lengths and branching angles were derived from the stochastic airway models of human and rat lungs (Koblinger and Hofmann, 1985;1988), which are based on the morphometric data of Raabe et al. (1976). The effects of interspecies differences in particle deposition patterns are explored in this study for two asymmetric bifurcation geometries in segmental bronchi and terminal bronchioles of both the human and rat lungs at different particle sizes. In order to examine the effect of flow rate on particle deposition in the human lung, we selected two different minute volumes, i.e., 10 and 60 1 min -1 , which are representative of low and heavy physical activity breathing conditions. In the case of the rat we used a minute volume of 0.234 1 min -1 (Hofmann et al., 1993)

Microscopic dose distribution around PuO2 particles in lungs of hamsters, rats and dogs

International Nuclear Information System (INIS)

Diel, J.H.; Mewhinney, J.A.; Guilmette, R.A.

1982-01-01

Syrian hamsters, Fischer-344 rats and Beagle dogs inhaled monodisperse aerosols of PuO 2 and were sacrificed 1 to 16 days after exposure. The microscopic distribution of dose and tissue-at-risk around individual particles in lung was studied using autoradiographs of the lungs. The dose pattern in dogs and rats was more diffuse than in hamsters, resulting in a calculation of about twice the tumor incidence in rats and dogs as in hamsters on the basis of dose pattern using the same dose-effect model for all three species. The tumorigenic effect of inhaled insoluble PuO 2 particles depends on the species inhaling the material; Syrian hamsters are much less susceptible than are rats or dogs. It has been suggested that a difference in dose distribution resulting from differences in particle distributions in the two species may contribute to the differences in susceptibility in Syrian hamsters and rats. The role of dose distribution in lung cancer production is explored in this study by measuring microscopic dose patterns in regions surrounding single PuO 2 particles in lung. The alveolar structures of the dog and rat are different than those of the hamster. Based on these measurements, particles of PuO 2 in lung are more likely to cause lung cancer in dogs and rats than in hamsters

Inhalation Toxicology Research Institute. Annual report, October 1, 1981-September 30, 1982

International Nuclear Information System (INIS)

Snipes, M.B.; Marshall, T.C.; Martinez, B.S.

1982-12-01

Studies are presented of the effect on man of airborne particulates and gaseous emissions associated with the production of energy. Included in the report from the Inhalation Toxicology Research Institute are papers on: (1) the physical and chemical characterization of energy technology aerosols; (2) laboratory studies of aerosol generation and characterization; (3) in vitro predictors of toxicity; (4) disposition and fate of inhaled materials; (5) dose-response relationships for inhaled radionuclides; (6) dose-response relationships for inhaled chemical toxicants; (7) biological factors which influence dose-response relationships; and (8) risk assessment

Lung Deposition And Biological Effects Of Inhaled Radon Progenies

International Nuclear Information System (INIS)

Balashazy, I.; Farkas, A.; Szoke, I.; Moustafa, M.; Kudela, G.

2010-01-01

Inhaled radon progenies provide more than the half of natural radiation exposure. There is increasing evidence that the cellular distribution of radiation burden is an important factor regarding the biological response to ionisation radiation, thus, one of our tasks was the characterisation of the distribution of cellular exposure. Histological studies of former uranium miners presented strong correlation between primer deposition hot spots and neoplastic lesions. Most of these lesions were located along the carinal regions of the large bronchial airways. In the present work, computational fluid dynamics (CFD) approaches have been applied to simulate the deposition distribution of inhaled radon progenies along central human airways. The geometry and the cellular structure of epithelial lung tissue were numerically reconstructed based on anatomical and histological data. Single and multiple ha-hit and cellular dose distributions have been computed applying Monte Carlo modelling techniques at different breathing conditions. Figure 1. Deposition enhancement factor (EF) of inhaled radon progenies on a central airway bifurcation in airway generations 4-5 during light physical activity breathing condition. Size of scanning surface element is a 45μm side triangle. Left panel: EF max=1400,Dp=200 nm (attached). Right panel: EF max1290, Dp= 1 nm (unattached). Values of local per average deposition densities, that is, enhancement factors (Figure 1), hit probabilities and doses may be up to two-three orders of magnitude higher in the deposition hot spots than the average values. Dose calculations revealed that some cell clusters may receive high doses even at low exposure conditions. Applying the model to different radiation exposure conditions useful relations can be received regarding the linear-non threshold hypothesis

Interlaboratory comparison of techniques for measuring lung burdens of low-energy X-ray emitters. Part of a coordinated programme on the calibration of burdens of inhaled plutonium by external counting

International Nuclear Information System (INIS)

Newton, D.; Fry, F.A.; Taylor, B.T.; Eagle, M.C.; Sharma, R.C.

1978-02-01

An interlaboratory exercise has been conducted to assess techniques of detection and calibration in the direct measurement of lung contamination with plutonium and other nuclides emitting only low-energy X-rays. Three volunteers, of small, intermediate and large physique, inhaled an aerosol incorporating Pd-103, a 20-keV X-ray emitter, and visited 13 other laboratories in the UK, Europe and North America. Participants in the exercise were asked to estimate each subject's lung content, using their procedures for assessing burdens of plutonium, and their estimates were compared with values derived independently from measurements of Cr-51, also incorporated in the inhaled particles, by gamma-ray spectrometry. Laboratories' calibration procedures were in most cases based on elaborate thorax phantoms, and these generally led to underestimates of the subjects' contents, in some instances by a factor of three or more; only one such laboratory produced estimates in satisfactory agreement with the independently-known values. The ''phoswich'' detectors, employed by most participants, appeared to be more sensitive than gas counters. If a standard configuration were required, offering the highest sensitivity in most situations, the choice would be a pair of 12-cm diameter phoswich detectors viewing the left and right anterior surfaces of the upper thorax. No improvement in sensitivity would result from increasing the size, although larger units may offer other advantages

Influence of Natural Lung Surfactant Inhalations on Clinical Symptoms and Pulmonary Function Parameters in Patients with Bronchial Asthma. Communication 1

Directory of Open Access Journals (Sweden)

O.V. Stepanova

2016-12-01

Full Text Available Background: Damage to lung surfactant (LS enabling the lung local immunity may contribute to the development of bronchial inflammation in patients with bronchial asthma. Methods and Results: A 40-day course of 16 LS (Surfactant-BL inhalations at the dose of 25mg was added to inhaled corticosteroids (ICS and short/long-acting bronchodilators or combined inhalers in 14 patients with bronchial asthma. After 7 inhalations, patients demonstrated a significant decrease in shortness of breath and bronchospasm attacks, double reduction of ICS dose (p=0.01, and improvement of pulmonary function. Forced vital capacity (FVC increases during treatment in a linear fashion (y=62.9+5.60•x; p<0.05, reaching the normal level (80% after 9 inhalations (Day 15. Forced expiratory volume (FEV1 increases in a linear fashion (y=50.7+4.15•x; p<0.05 without reaching the normal level (80% after 16 inhalations (Day 41. The FEV1/FVC ratio does not change significantly in the time period between Day 1 to Day 15. By Day 41 the value decreases significantly to 67.4±4.66% (p<0.05. The peak expiratory flow (PEF parameter increases in a linear fashion (y=53.9+5.00•x; p<0.01 from 57.7±6.33% to 76.2±9.33% of the predicted value. Conclusion: LS inhalations improve the condition of patients with BA, allow ICS dose reduction by 2 times, and improve pulmonary function parameters.

Granulometric determinations and inhalation dose assessment for atmospheric aerosol contaminated by {sup 137}Cs; Determinazioni granulometriche e valutazioni di dose da inalazione per aerosol atmosferico contaminato da {sup 137}CS

Energy Technology Data Exchange (ETDEWEB)

Castellani, C.M.; Luciani, A. [ENEA, Centro Ricerche `E. Clementel`, Bologna (Italy). Dip. Ambiente; Oliviero, L.; Donato, R. [ENEA, Centro Ricerche Saluggia, Vercelli (Italy). Dip. Ambiente

1996-07-01

During the redevelopment of Brescia freight-yard a measurement campaign of atmospheric aerosol was carried out: in fact a {sup 137}Cs ground contamination, caused by the permanence of wagons carrying iron materials contaminated by this radionuclide, had been found out. During the redevelopment phases of excavation and can filling the workers were exposed to the danger of radioactive aerosol inhalation. The aim of the measurement campaign was to test the aerosol sampling and granulometric analysis methodologies with their sensitivity related to the inhalation dose assessments. The results of both aerosuspended mass and activity, evaluated by means of a portable cascade impactor, are presented. The granulometries have been interpolated with a log normal distribution using an iterative routine minimizing the square deviation between the calculated and experimental data. The results related to the dose assessments are also presented. These evaluations have been carried out using both the granulometric information obtained and the more recent models (ICRP 66) both the total concentration data and the dose coefficients referring to the standard conditions of ICRP 68 and of the Italian law (D.Lgs. 230/95). Furthermore the significance and the reliability of the dose assessments referring to the different methodologies are discussed, also in relation to the possibility of using this sampling methodologies for other radionuclides and different exposure conditions.

Effects of puerarin combined with edaravone on inhalation lung injury induced by black gunpowder smog in rats

Directory of Open Access Journals (Sweden)

Zheng-guan WANG

2015-04-01

Full Text Available Objective　To explore the protective effects of puerarin combined with edaravone on inhalation lung injury induced by black gunpowder smog in rats. Methods　Forty healthy male Wistar rats were randomly divided into normal control group (group N, inhalation group (group X, puerarin group (group P, edaravone group (group E and edaravone combined with puerarin group (group L, with 8 rats in each group. Rat model of inhalation lung injury was reproduced by a self-made smoke generator. Rats in group E were given intraperitoneal injections of edaravone (9 mg/kg at 30 minutes and 1 day after modeling (twice totally. Rats in group P were given intraperitoneal injections of puerarin (100 mg/kg at 30 minutes and 1, 2, 3, 4, 5 days after modeling (6 times totally. Rats in group L were treated the way of both group E and P. The rats in group N and group X were given intraperitoneal injections of normal saline (12 ml/kg at the time-points above. The animals were sacrificed 6 days after modeling, and the blood samples were collected from abdominal aorta to assess arterial blood gas values, meanwhile the serum levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, interleukin-10 (IL-10 were determined by ELISA. Lung tissue homogenates were prepared to determine the protein content and myeloperoxidase (MPO activity. The pathological changes in the lung tissue with HE staining were observed under light microscope. Results　Arterial blood gas analysis revealed that the PaO2 levels in groups P, E and L were higher than that in group X (P<0.05, and the PaO2 levels in groups E and L were higher than that in group P (P<0.05, while the PaCO2 level in group L was lower than that in groups X and E (P<0.05. The TNF-α, IL-6 and IL-10 levels in serum, the protein content and MPO activity in lung tissue homogenate in groups P, E and L were lower than those of group X (P<0.05. The TNF-α and IL-6 levels in serum and protein content and MPO activity in lung

Fate of inhaled azodicarbonamide in rats

International Nuclear Information System (INIS)

Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.; Dutcher, J.S.; Cheng, Y.S.; Bond, J.A.; Medinsky, M.A.; Henderson, R.F.; Birnbaum, L.S.

1987-01-01

Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [ 14 C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14 C-labeled compound present in excreta. [ 14 C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [ 14 C]ADA equivalents were not observed. The rate of buildup of [ 14 C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [ 14 C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine

Inhaled budesonide for treatment of recurrent wheezing in early childhood

DEFF Research Database (Denmark)

Bisgaard, H; Munck, Susanne; Nielsen, J P

1990-01-01

77 children, aged 11 to 36 months (mean 24) with moderately severe recurrent wheezing, were treated with budesonide pressurised aerosol 400 micrograms twice daily or placebo for 12 weeks in a double-blind, parallel-group trial. Aerosols were inhaled from a spacer with a facemask. Budesonide...... be ascribed to the active treatment. The findings indicate that young children below 3 years of age can inhale a pressurised aerosol from a spacer with a facemask. Use of topically active glucocorticosteroids with this simple device may reduce symptoms and distress in young children with moderately severe...

In vivo deposition of ultrafine aerosols in human nasal and oral airways

Energy Technology Data Exchange (ETDEWEB)

Yeh, Hsu-Chi; Swift, D.L. [John Hopkins Univ., Baltimore, MD (United States); Simpson, S.Q. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

1995-12-01

The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

In vivo deposition of ultrafine aerosols in human nasal and oral airways

International Nuclear Information System (INIS)

Yeh, Hsu-Chi; Swift, D.L.; Simpson, S.Q.

1995-01-01

The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 μm particles in 10 human subjects and in our preliminary studies using 0.004-0.15 μm particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 μm with the nasal dimensions of each subject

/sup 239/PuO/sub 2/ aerosol inhalation with emphasis on pulmonary connective tissue modifications

Energy Technology Data Exchange (ETDEWEB)

Metivier, H; Masse, R; Nobil' e, D; Lafuma, J

1975-09-01

Inhalation studies were undertaken in which plutonium dioxide (/sup 239/PuO/sub 2/) was administered to either unanesthetized Wistar rats or anaesthetized baboons. In both groups of animals some deaths occurred from acute lung damage resulting from cell necrosis particularly to vascular tissue followed by alveolar oedema. At later stages, marked interstitial pneumonitis and interstitial fibrosis occurred and deaths resulted from respiratory insufficiency preceded by high arterial blood pCO/sub 2/ and low pO/sub 2/. In rats as many as 50% of the animals finally developed lung neoplasms but only two such tumors were found in baboons. Attempts were made to correlate biochemical parameters with observed tissue damage and animal mortality.

Inhalation of uranium ores

International Nuclear Information System (INIS)

Stuart, B.O.; Jackson, P.O.

1975-01-01

In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

Evaluation of pN factors in patients with primary lung cancer by using perfusion, inhalation and ventilation studies

International Nuclear Information System (INIS)

Tamai, Toyosato; Tanabe, Masatada; Satoh, Katashi

1987-01-01

The interpretation of scintigraphic patterns and the role of pathophysiological mechanisms in patients with primary lung cancer were investigated. To determine the relative roles of perfusion, inhalation and ventilation scintigraphy, the relationship between the count ratio of the affected side to the healthy side and the post-surgical histological lymph nodes factors were observed in this study. These scintigraphic count ratio's in patients with primary lung cancer did not reflect the pN factors except in the perfusion study in patients with hilar primary lung cancer. (author)

Cancer hazard from inhaled plutonium

International Nuclear Information System (INIS)

Gofman, J.W.

1975-01-01

The best estimate of the lung cancer potential in humans for inhaled insoluble compounds of plutonium (such as PuO 2 particles) has been grossly underestimated by such authoritative bodies as the International Commission on Radiological Protection and the British Medical Research Council. Calculations are presented of lung cancer induction by 239 Pu as insoluble particles and for deposited reactor-grade Pu. The reason for the gross underestimate of the carcinogenic effects of Pu by ICRP or the British Medical Research Council (BMRC) is their use of a totally unrealistic idealized model for the clearance of deposited Pu from the lungs and bronchi plus their non-recognition of the bronchi as the true site for most human lung cancers. The erroneous model used by such organizations also fails totally to take into account the effect of cigarette-smoking upon the physiological function of human lungs. Plutonium nuclides, such as 239 Pu, or other alpha particle-emitting nuclides, in an insoluble form represent an inhalation cancer hazard in a class some 100,000 times more potent than the potent chemical carcinogens, weight for weight. The already-existing lung cancer data for beagle dogs inhaling insoluble PuO 2 particles is clearly in order of magnitude agreement with calculations for humans

Toxicity of inhaled 238PuO2 in beagle dogs. A. Monodisperse 1.5 μm 238PuO2. B. Monodisperse 3.0 μm 238PuO2 particles. III

International Nuclear Information System (INIS)

Lustgarten, C.S.; Mewhinney, J.A.; Hobbs, C.H.; Halliwell, W.H.; Jones, R.K.; Mauderly, J.L.; McClellan, R.O.; Mo, T.; Pickrell, J.A.

1976-01-01

To obtain essential information on the importance of the homogeneity or non-homogeneity of the radiation dose to lung (the hot particle question), Beagle dogs have been exposed to monodisperse aerosols (sigma/sub g/ 238 PuO 2 of either 1.5 μm or 3.0 μm aerodynamic diameter (AD). By using monodisperse particles of these two sizes, the average dose to lung is held constant for a given initial lung burden, but the local alpha dose around the two sizes of particles varies by a factor of about ten. All exposures have been completed with 72 days exposed to each of the two particle sizes of 238 PuO 2 (total of 144 dogs) resulting in graded initial lung burdens which range from .005 to 2.2 μCi/kg of body weight. Twenty-four dogs exposed to the diluent aerosol are serving as controls. The animals will be studied over their total life span. Two exposed dogs have died from pulmonary injury: Dog 710C (with an initial lung burden of 2.0 μCi/kg) died at 631 days after inhalation of 3.0 μm AD aerosol. The cause of death was radiation pneumonitis and pulmonary fibrosis, Dog 746B (with an initial lung burden of 1.3 μCi/kg) died at 791 days after inhalation of 1.5 μm AD aerosol. Death was attributed to intrapulmonic hemorrhage resulting from a degenerative vasculitis. One control dog (721A) was euthanized at 820 days after exposure due to a meningitis and encephalomalacia that caused a severe central nervous system disorder that made the dog difficult to handle.A leukopenia in exposed dogs to date has occurred earlier and to a greater degree in dogs exposed to 3.0 μm AD particles than in dogs that recevied 1.5 μm AD particles. One hundred forty-two exposed and 23 control dogs are surviving at 175 to 1024 days after exposure

Neuronal modulation of lung injury induced by polymeric hexamethylene diisocyanate in mice

International Nuclear Information System (INIS)

Lee, C.-T.; Poovey, Halet G.; Rando, Roy J.; Hoyle, Gary W.

2007-01-01

1,6-Hexamethylene diisocyanate biuret trimer (HDI-BT) is a nonvolatile isocyanate that is a component of polyurethane spray paints. HDI-BT is a potent irritant that when inhaled stimulates sensory nerves of the respiratory tract. The role of sensory nerves in modulating lung injury following inhalation of HDI-BT was assessed in genetically manipulated mice with altered innervation of the lung. Knockout mice with a mutation in the low-affinity nerve growth factor receptor (NGFR), which have decreased innervation by nociceptive nerve fibers, and transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secretory protein (CCSP) promoter, which have increased innervation of the airways, were exposed to HDI-BT aerosol and evaluated at various times after exposure. NGFR knockout mice exhibited significantly more, and CCSP-NGF transgenic mice exhibited significantly less injury and inflammation compared with wild-type mice, indicative of a protective effect of nociceptive nerves on the lung following HDI-BT inhalation. Transgenic mice overexpressing the tachykinin 1 receptor (Tacr1) in lung epithelial cells also showed less severe injury and inflammation compared with wild-type mice after HDI-BT exposure, establishing a role for released tachykinins acting through Tacr1 in mediating at least part of the protective effect. Treatment of lung fragments from Tacr1 transgenic mice with the Tacr1 ligand substance P resulted in increased cAMP accumulation, suggesting this compound as a possible signaling mediator of protective effects on the lung following nociceptive nerve stimulation. The results indicate that sensory nerves acting through Tacr1 can exert protective or anti-inflammatory effects in the lung following isocyanate exposure

Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

Science.gov (United States)

Bellmann, B.; Creutzenberg, O.; Ernst, H.; Muhle, H.

2009-02-01

The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m3. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

International Nuclear Information System (INIS)

Bellmann, B; Creutzenberg, O; Ernst, H; Muhle, H

2009-01-01

The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m 3 . The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.