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Sample records for 133xe inhalation method

  1. Cerebral hemodynamics in normal-pressure hydrocephalus. Evaluation by 133Xe inhalation method and dynamic CT study

    SciTech Connect

    Tamaki, N.; Kusunoki, T.; Wakabayashi, T.; Matsumoto, S.

    1984-09-01

    Cerebral hemodynamics in 31 patients with suspected normal-pressure hydrocephalus were studied by means of the xenon-133 (133Xe) inhalation method and on dynamic computerized tomography (CT) scanning. Cerebral blood flow (CBF) is reduced in all patients with dementia. Hypoperfusion was noted in a frontal distribution in these patients compared with normal individuals. There was no difference in CBF patterns between patients with good and those with poor outcome. The CBF was increased following cerebrospinal fluid (CSF) shunting in patients who responded to that procedure: increase in flow correlated with clinical improvement, frontal and temporal lobe CBF was most markedly increased, and the CBF pattern became normal. In contrast, CBF was decreased after shunt placement in patients who were considered to have suffered from degenerative dementia, as evidenced by non-response to shunting. Dynamic computerized tomography studies demonstrated that patients with a good outcome showed a postoperative reduction in mean transit time of contrast material, most prominent in the frontal and temporal gray matter, and slight in the deep frontal structures, but not in the major cerebral vessels. Patients with poor outcome after shunting, however, had an increase in transit time in all regions. This corresponded well with the results as determined by the 133Xe inhalation method.

  2. Penile xenon (/sup 133/Xe) washout: a rapid method of screening for vasculogenic impotence

    SciTech Connect

    Nseyo, U.O.; Wilbur, H.J.; Kang, S.A.; Flesh, L.; Bennett, A.H.

    1984-01-01

    The radioactive inert gas xenon (/sup 133/Xe) is a well-established isotopic indicator used to assess vascular status in many organ systems. Xenon-133 was used to evaluate male impotence. Xenon-133 was injected subcutaneously at the level of the coronal sulcus in the detumescent state. Using the gamma camera, sequential images were obtained and computer-generated curves calculated. The clearance time for 50 per cent washout of the injected /sup 133/Xe (T1/2) was then calculated for each patient, as well as a control group. Preliminary findings indicate a correlation with such established techniques of evaluating erectile impotence as history, physical examination, penile pulse Doppler tracings, and brachial-penile blood pressure index. The xenon-133 washout study was a rapid, minimally invasive, reproducible, and cost-effective method of screening those impotent patients for vasculogenic etiology of their erectile impotence. We recommend the addition of this method to the surgeon engaged in the care of impotent males.

  3. Crossed cerebellar diaschisis in ischemic stroke: a study of regional cerebral blood flow by /sup 133/Xe inhalation and single photon emission computerized tomography

    SciTech Connect

    Meneghetti, G.; Vorstrup, S.; Mickey, B.; Lindewald, H.; Lassen, N.A.

    1984-06-01

    Seventy measurements of CBF were performed in 12 stroke patients by /sup 133/Xe inhalation and a rapidly rotating single photon emission computerized tomograph. CBF was measured every other day during the acute phase and at 2- and 6-month follow-up visits. A persistent contralateral cerebellar blood flow depression was evident in five patients with severe hemispheric low flow areas, which correlated with large, hypodense lesions on the computerized tomographic scan. In a sixth patient with a small, deep infarct, a transient crossed cerebellar low flow was observed, while the clinical symptoms persisted. It is concluded from this serial study that crossed cerebellar diaschisis is a common finding in completed stroke. It is probably caused by disconnection of the corticopontine pathways, a disconnection that tends to persist. The phenomenon is in fact less variable than the stroke-related CBF changes in the infarcted hemisphere, in which a period of relative hyperemia is frequently seen.

  4. Reproducibility of the /sup 133/Xe inhalation technique in resting studies: task order and sex related effects in healthy young adults

    SciTech Connect

    Warach, S.; Gur, R.C.; Gur, R.E.; Skolnick, B.E.; Obrist, W.D.; Reivich, M.

    1987-12-01

    Repeated applications of the /sup 133/Xe inhalation technique for measuring regional CBF (rCBF) were made during consecutive resting conditions in a sample of young healthy subjects. Subjects were grouped by order and by sex (nine had resting studies as the initial two measurements in a series of four measurement (six men, three women) and six had these measurements later (two men, four women)). Three flow parameters were examined: f1 (fast flow) and IS (initial slope) for gray matter CBF, and CBF-15 for mean CBF (gray and white matter over 15-min integration), as well as w1, the percentage of tissue with fast clearing characteristics. With all groups combined, there were no significant differences between the two resting measurements, and high test-retest correlations were obtained for the flow parameters and w1. Analyses by order and sex grouping revealed, for the flow parameters, significant interactions of test-retest difference with order. Repeated initial studies showed reduced CBF from the first to second measurement, whereas resting studies performed later in the series showed no reduction. Interactions for test-retest difference with sex indicated that reduced CBF in serial measures was more pronounced for women. No hemispheric or regional specificity to account for these effects was found. Correction for PaCO/sub 2/ differences did not alter these results. The results resemble data regarding habituation effects measured for other psychophysiologic measures, and suggest that reduction in CBF for consecutive measurements made on the same day may reflect habituation. This underscores the importance of controlling for effects of habituation on serial measurements of CBF and metabolism.

  5. Effects of prolonged bedrest in antiorthostatic position on rCBF measured by /sup 133/Xe inhalation technique - effects of clonidine

    SciTech Connect

    Guell, A.; Victor, G.; Bru, A.; Montastruc, P.; Bes, A.

    1981-12-01

    Experiments involving prolonged bedrest in antiorthostatic position were performed in order to simulate cardiovascular changes observed in weightlessness. Six young healthy subjects were placed in strict bedrest in a -4-deg antiorthostatic position for seven days. The rCBF (regional cerebral blood flow) measurements were made by an Xe-133 inhalation method. Three of the subjects received 0.450 mg of clonidine during the experiment. A constant increase in rCBF was observed during the first 12 hours in subjects who did not receive clonidine at the 72nd hour, all values returned to the basal state. These findings agree with the rapid correction of hemodynamic disturbances observed in the first days of weightlessness. In subjects treated with clonidine, the increase in rCBF did not occur.

  6. Prospective use of xenon /sup 133/Xe clearance for amputation level selection

    SciTech Connect

    Moore, W.S.; Henry, R.E.; Malone, J.M.; Daly, M.J.; Patton, D.; Childers, S.J.

    1981-01-01

    Xenon /sup 133/Xe clearance was used to select the most distal amputation level that would allow sufficient blood flow for healing. Capillary blood flow was first measured at the most distal potential amputation level, then at successive proximal levels until an amputation site was found that had a capillary skin blood flow rate greater than or equal to 2.6 mL/min/100 g of tissue. Xenon /sup 133/Xe in saline was injected intracutaneously at each level, and flow rates were determined using a gamma camera interfaced with a computer system programmed for the Ketty-Schmidt formula modified for capillary blood flow. There were 45 cases, including one toes, six transmetatarsal, five Syme's, 25 below-knee, four knee disarticulation, three above-knee, and one hip disarticulation amputation. All amputations in patients with flow rates exceeding 2.4 mL/min/100 g of tissue healed, with two exceptions.

  7. Detection of (133)Xe from the Fukushima nuclear power plant in the upper troposphere above Germany.

    PubMed

    Simgen, Hardy; Arnold, Frank; Aufmhoff, Heinfried; Baumann, Robert; Kaether, Florian; Lindemann, Sebastian; Rauch, Ludwig; Schlager, Hans; Schlosser, Clemens; Schumann, Ulrich

    2014-06-01

    After the accident in the Japanese Fukushima Dai-ichi nuclear power plant in March 2011 large amounts of radioactivity were released and distributed in the atmosphere. Among them were also radioactive noble gas isotopes which can be used as tracers to test global atmospheric circulation models. This work presents unique measurements of the radionuclide (133)Xe from Fukushima in the upper troposphere above Germany. The measurements involve air sampling in a research jet aircraft followed by chromatographic xenon extraction and ultra-low background gas counting with miniaturized proportional counters. With this technique a detection limit of the order of 100 (133)Xe atoms in liter-scale air samples (corresponding to about 100 mBq/m(3)) is achievable. Our results provide proof that the (133)Xe-rich ground level air layer from Fukushima was lifted up to the tropopause and distributed hemispherically. Moreover, comparisons with ground level air measurements indicate that the arrival of the radioactive plume at high altitude over Germany occurred several days before the ground level plume.

  8. Cerebral blood flow studied by Xenon-133 inhalation technique in parkinsonism: loss of hyperfrontal pattern

    SciTech Connect

    Bes, A.; Gueell, A.; Fabre, N.; Dupui, P.; Victor, G.; Geraud, G.

    1983-03-01

    Cerebral blood flow (grey matter flow) in parkinsonism requires further investigation. The noninvasive method of /sup 133/Xe inhalation permits study of larger numbers of subjects than previously used invasive techniques such as the intracarotid /sup 133/Xe injection method. Measurements were made in this laboratory in 30 subjects having Parkinson's disease. Mean hemispheric blood flow (F1) values were 70.4 +/- 9.3 ml/100 g/min, compared to 76.3 for a group of age-matched normal subjects, which is a decrease of -7.8%. The most striking difference was the loss of the hyperfrontal distribution in parkinsonism. The prefrontal F1 values were only 1.8% greater than the hemisphere grey matter flow, compared with 8.5% in controls of a similar age group.

  9. Atmospheric transport modelling of time resolved 133Xe emissions from the isotope production facility ANSTO, Australia.

    PubMed

    Schöppner, M; Plastino, W; Hermanspahn, N; Hoffmann, E; Kalinowski, M; Orr, B; Tinker, R

    2013-12-01

    The verification of the Comprehensive Nuclear-Test Ban Treaty (CTBT) relies amongst other things on the continuous and worldwide monitoring of radioxenon. The characterization of the existing and legitimate background, which is produced mainly by nuclear power plants and isotope production facilities, is of high interest to improve the capabilities of the monitoring network. However, the emissions from legitimate sources can usually only be estimated. For this paper historic source terms of (133)Xe emissions from the isotope production facility at ANSTO, Sydney, Australia, have been made available in a daily resolution. Based on these high resolution data, different source term sets with weekly, monthly and yearly time resolution have been compiled. These different sets are then applied together with atmospheric transport modelling (ATM) to predict the concentration time series at two radioxenon monitoring stations. The results are compared with each other in order to examine the improvement of the prediction capability depending on the used time resolution of the most dominant source term in the region.

  10. Cerebral effects of scalp cooling and extracerebral contribution to calculated blood flow values using the intravenous 133Xe technique.

    PubMed

    Friberg, L; Kastrup, J; Hansen, M; Bülow, J

    1986-06-01

    With the intravenous 133Xe technique we measured cerebral blood flow (CBF) in eight healthy subjects during normal subcutaneous temperatures and during extracranial cooling. This gave rise to the possibility of evaluating the contribution of the extracerebral blood flow to the calculation of CBF values. With a two-compartmental analysis of the wash-out curves during cooling there was a significant reduction of the CBF indices f1, representing mainly fast blood flow in the grey matter and f2, representing blood flow in the slowly perfused white matter and extracerebral structures. The reduction of f1 was due to the 'slippage' phenomenon:calculation of f1 was affected by a reduction in f2 due to a considerably reduced extracerebral blood flow. The initial slope index (ISI) calculated from 30 to 90 s of the first part of the presumed mono-exponential 133Xe wash-out curve was not affected by slippage as the ISI remained unchanged in spite of reduced extracerebral blood flow. It is concluded that CBF was unaffected by extracranial cooling. Extracranial cooling can be used to reduce the extracerebral blood flow contribution to the calculated CBF values.

  11. Noninvasive method of estimating human newborn regional cerebral blood flow

    SciTech Connect

    Younkin, D.P.; Reivich, M.; Jaggi, J.; Obrist, W.; Delivoria-Papadopoulos, M.

    1982-12-01

    A noninvasive method of estimating regional cerebral blood flow (rCBF) in premature and full-term babies has been developed. Based on a modification of the /sup 133/Xe inhalation rCBF technique, this method uses eight extracranial NaI scintillation detectors and an i.v. bolus injection of /sup 133/Xe (approximately 0.5 mCi/kg). Arterial xenon concentration was estimated with an external chest detector. Cerebral blood flow was measured in 15 healthy, neurologically normal premature infants. Using Obrist's method of two-compartment analysis, normal values were calculated for flow in both compartments, relative weight and fractional flow in the first compartment (gray matter), initial slope of gray matter blood flow, mean cerebral blood flow, and initial slope index of mean cerebral blood flow. The application of this technique to newborns, its relative advantages, and its potential uses are discussed.

  12. Relationship of 133Xe cerebral blood flow to middle cerebral arterial flow velocity in men at rest

    NASA Technical Reports Server (NTRS)

    Clark, J. M.; Skolnick, B. E.; Gelfand, R.; Farber, R. E.; Stierheim, M.; Stevens, W. C.; Beck, G. Jr; Lambertsen, C. J.

    1996-01-01

    Cerebral blood flow (CBF) was measured by 133Xe clearance simultaneously with the velocity of blood flow through the left middle cerebral artery (MCA) over a wide range of arterial PCO2 in eight normal men. Average arterial PCO2, which was varied by giving 4% and 6% CO2 in O2 and by controlled hyperventilation on O2, ranged from 25.3 to 49.9 mm Hg. Corresponding average values of global CBF15 were 27.2 and 65.0 ml 100 g min-1, respectively, whereas MCA blood-flow velocity ranged from 42.8 to 94.2 cm/s. The relationship of CBF to MCA blood-flow velocity over the imposed range of arterial PCO2 was described analytically by a parabola with the equation: CBF = 22.8 - 0.17 x velocity + 0.006 x velocity2 The observed data indicate that MCA blood-flow velocity is a useful index of CBF response to change in arterial PCO2 during O2 breathing at rest. With respect to baseline values measured while breathing 100% O2 spontaneously, percent changes in velocity were significantly smaller than corresponding percent changes in CBF at increased levels of arterial PCO2 and larger than CBF changes at the lower arterial PCO2. These observed relative changes are consistent with MCA vasodilation at the site of measurement during exposure to progressive hypercapnia and also during extreme hyperventilation hypocapnia.

  13. Measurement of blood flow by the 133Xe clearance technique to grafts of amnion used in vestibuloplasty.

    PubMed

    Güler, R; Ercan, M T; Ulutunçel, N; Devrim, H; Uran, N

    1997-08-01

    The purpose of this study was to determine the blood supply to lyophilized amniotic membranes when used as graft material in vestibuloplasties. 133Xe clearance technique was used to measure the blood flow to the grafts. A total of 20 patients had either Clark (10) or Kazanjian (10) vestibuloplasties. The blood flow was determined at 2-3 days preoperatively and at 10 and 30 days postoperatively. The preoperative mandibular anterior alveolar mucosal blood flow was 34.4 +/- 10.7 and 23.1 +/- 13.1 ml/100 g/min for the Clark and Kazanjian groups, respectively. Ten days after vestibuloplasty operation with lyophilized amniotic membrane graft application the blood flow to the graft increased to 56.8 +/- 45.4 and 62.6 +/- 30.4 ml/100 g/min for the Clark and Kazanjian groups, respectively. The corresponding values at 30 days postoperatively were 24.6 +/- 10.2 and 22.2 +/- 9.2 ml/100 g/min, indicating the return to normal levels. The changes in blood flow as a function of time were statistically significant in each group (P<0.05). Our results demonstrated the angiogenic effect of lyophilized amniotic membranes until mucoid degeneration after 10-15 days.

  14. Effects of selected materials and geometries on the beta dose equivalent rate in a tissue equivalent phantom immersed in infinite clouds of 133Xe.

    PubMed

    Piltingsrud, H V; Gels, G L

    1986-06-01

    Most calculations of dose equivalent (D.E.) rates at 70-micron tissue depths in tissue equivalent (T.E.) phantoms from infinite clouds (radius exceeds maximum beta range in air) of 133Xe do not consider the possible effects of clothing overlays. Consequently, a series of measurements were made using a 1-mm-thick plastic scintillation detector assembly mounted in a tissue equivalent (T.E.) phantom with an overlay of 70 micron of T.E. material. This assembly was placed in an infinite cloud containing a known concentration of 133Xe. Material samples were placed at selected distances from the detector phantom, both individually and in various combinations. Pulse-height spectra resulting from beta radiations were converted to relative D.E. rates at a 70-micron tissue depth. The relative D.E. rates were reduced from values with no clothing cover by as little as 45% when placing a single thin nylon cloth 1 cm from the phantom, to 94% for a T-shirt material plus wool material plus denim placed 1/2, 1 and 3 cm, respectively, from the phantom. The results indicate that even loosely fitting clothing can have an important effect on reducing the D.E. rate. Close-fitting clothing appears to provide better protection.

  15. Inhalants

    MedlinePlus

    ... place a chemical- soaked rag in their mouth. Abusers may also inhale fumes from a balloon or ... by inhalants usually lasts just a few minutes, abusers often try to prolong it by continuing to ...

  16. Inhalants

    MedlinePlus

    ... Drug Facts Chat Day: Inhalants Drug Facts Chat Day: Inhalants Print Can you get high off of ... Cool Order Free Materials National Drugs & Alcohol Chat Day Newsletter Sign up to receive National Drug & Alcohol ...

  17. Computation and Analysis of the Global Distribution of the Radioxenon Isotope 133Xe based on Emissions from Nuclear Power Plants and Radioisotope Production Facilities and its Relevance for the Verification of the Nuclear-Test-Ban Treaty

    NASA Astrophysics Data System (ADS)

    Wotawa, Gerhard; Becker, Andreas; Kalinowski, Martin; Saey, Paul; Tuma, Matthias; Zähringer, Matthias

    2010-05-01

    Monitoring of radioactive noble gases, in particular xenon isotopes, is a crucial element of the verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The capability of the noble gas network, which is currently under construction, to detect signals from a nuclear explosion critically depends on the background created by other sources. Therefore, the global distribution of these isotopes based on emissions and transport patterns needs to be understood. A significant xenon background exists in the reactor regions of North America, Europe and Asia. An emission inventory of the four relevant xenon isotopes has recently been created, which specifies source terms for each power plant. As the major emitters of xenon isotopes worldwide, a few medical radioisotope production facilities have been recently identified, in particular the facilities in Chalk River (Canada), Fleurus (Belgium), Pelindaba (South Africa) and Petten (Netherlands). Emissions from these sites are expected to exceed those of the other sources by orders of magnitude. In this study, emphasis is put on 133Xe, which is the most prevalent xenon isotope. First, based on the emissions known, the resulting 133Xe concentration levels at all noble gas stations of the final CTBT verification network were calculated and found to be consistent with observations. Second, it turned out that emissions from the radioisotope facilities can explain a number of observed peaks, meaning that atmospheric transport modelling is an important tool for the categorization of measurements. Third, it became evident that Nuclear Power Plant emissions are more difficult to treat in the models, since their temporal variation is high and not generally reported. Fourth, there are indications that the assumed annual emissions may be underestimated by factors of two to ten, while the general emission patterns seem to be well understood. Finally, it became evident that 133Xe sources mainly influence the sensitivity of the

  18. Inhalants

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

  19. An evaluation of the external radiation exposure dosimetry and calculation of maximum permissible concentration values for airborne materials containing 18F, 15O, 13N, 11C and 133Xe.

    PubMed

    Piltingsrud, H V; Gels, G L

    1985-11-01

    To better understand the dose equivalent (D.E.) rates produced by airborne releases of gaseous positron-emitting radionuclides under various conditions of cloud size, a study of the external radiation exposure dosimetry of these radionuclides, as well as negatron, gamma and x-ray emitting 133Xe, was undertaken. This included a calculation of the contributions to D.E. as a function of cloud radii, at tissue depths of 0.07 mm (skin), 3 mm (lens of eye) and 10 mm (whole body) from both the particulate and photon radiations emitted by these radionuclides. Estimates of maximum permissible concentration (MPC) values were also calculated based on the calculated D.E. rates and current regulations for personnel radiation protection (CFR84). Three continuous air monitors, designed for use with 133Xe, were evaluated for applications in monitoring air concentrations of the selected positron emitters. The results indicate that for a given radionuclide and for a cloud greater than a certain radius, personnel radiation dosimeters must respond acceptably to only the photon radiations emitted by the radionuclide to provide acceptable personnel dosimetry. For clouds under that radius, personnel radiation dosimeters must also respond acceptably to the positron or negatron radiations to provide acceptable personnel dosimetry. It was found that two out of the three air concentration monitors may be useful for monitoring air concentrations of the selected positron emitters.

  20. Methods to Develop Inhalation Cancer Risk Estimates for ...

    EPA Pesticide Factsheets

    This document summarizes the approaches and rationale for the technical and scientific considerations used to derive inhalation cancer risks for emissions of chromium and nickel compounds from electric utility steam generating units. The purpose of this document is to discuss the methods used to develop inhalation cancer risk estimates associated with emissions of chromium and nickel compounds from coal- and oil-fired electric utility steam generating units (EGUs) in support of EPA's recently proposed Air Toxics Rule.

  1. An acoustic method of automatically evaluating patient inhaler technique.

    PubMed

    Holmes, Martin S; D'Arcy, Shona; Costello, Richard W; Reilly, Richard B

    2013-01-01

    Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) affect millions of people worldwide. Inhalers are devices utilized to deliver medication in small doses directly to the airways in the treatment of asthma and COPD. Despite the proven effectiveness of inhaler medication in controlling symptoms, many patients suffer from technique errors leading to decreased levels of medication efficacy. This study employs a recording device attached to a commonly used dry powder inhaler (DPI) to obtain the acoustic signals of patients taking their inhaler medication. The audio files provide information on how a patient uses their inhaler over a period of one month. Manually listening to such a large quantity of audio files would be a time consuming and monotonous process and therefore an algorithm that could automatically carry out this task would be of great benefit. An algorithm was thus designed and developed to detect inhalation, exhalation and blister events in the audio signals, analyze the quantity of each event, the order in which the events took place and finally provide a score on the overall performance. The algorithm was tested on a dataset of 185 audio files obtained from five community dwelling asthmatic patients in real world environments. Evaluation of the algorithm on this dataset revealed that it had an accuracy of 92.8% in deciding the correct technique score compared to manual detection methods.

  2. Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry

    EPA Pesticide Factsheets

    EPA's methodology for estimation of inhalation reference concentrations (RfCs) as benchmark estimates of the quantitative dose-response assessment of chronic noncancer toxicity for individual inhaled chemicals.

  3. Size analysis of suspension inhalation aerosols by inertial separation methods.

    PubMed

    Hallworth, G W; Andrews, U G

    1976-12-01

    The particle size distribution of beclomethasone dipropionate (BDP) aerosols delivered from pressurized metered dose suspension inhalers has been measured with three cascaded inertial separation instruments, the Casella Cascade Impactor, Multistage Liquid Impinger and Cascade Centripeter. Various methods for collecting the emitted aerosol before measurement have been examined. A bent glass tubular 'throat', used as a simulated oro-pharynx, collects 35-60% of the emitted dose by impingement of the wet spray cone in the throat. The aerosol passing through the throat has a similar but somewhat finer size distribution to that collected by firing directly into a large flask. The three cascaded instruments give similar results which in the Multistage Liquid Impinger also resemble those given by a salbutamol inhaler. The mass fraction (35-60%) emitted from the oral adaptor which is of a size capable of deep lung penetration ( less than 4 mum) is much higher than the fraction (10-16%) found in the lungs of dogs after inhalation of aerosol. The size distributions resemble those determined by microscopy and are expressed as aerodynamic sizes, thus showing that the particles approximate to unit density spheres. The performance of two simpler devices, Kirk's apparatus and the Harwell size selective air sampler are also assessed, the latter shows some promise for the simple evaluation of the respirable fraction of inhalation aerosols.

  4. INHALATION TOXICOLOGY METHODS: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

    PubMed Central

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology. PMID:25645246

  5. Simple and scalable method for peptide inhalable powder production.

    PubMed

    Schoubben, Aurélie; Blasi, Paolo; Giovagnoli, Stefano; Ricci, Maurizio; Rossi, Carlo

    2010-01-31

    The aim of this work was to produce capreomycin dry powder and capreomycin loaded PLGA microparticles intended for tuberculosis inhalation therapy, using simple and scalable methods. Capreomycin physico-chemical characteristics have been modified by hydrophobic ion pairing with oleate. The powder suspension was processed by high pressure homogenization and spray-dried. Spray-drying was also used to prepare capreomycin oleate (CO) loaded PLGA microparticles. CO powder was suspended in the organic phase containing PLGA and the suspension was spray-dried. Particle dimensions were determined using photon correlation spectroscopy and Accusizer C770. Morphology was investigated by scanning electron microscopy (SEM) and capreomycin content by spectrophotometry. Capreomycin properties were modified to increase polymeric microparticle content and obtain respirable CO powder. High pressure homogenization allowed to reduce CO particle dimensions obtaining a population in the micrometric (6.18 microm) and one in the nanometric (approximately 317 nm) range. SEM pictures showed not perfectly spherical particles with a wrinkled surface, generally suitable for inhalation. PLGA particles were characterized by a high encapsulation efficiency (about 90%) and dimensions (approximately 6.69 microm) suitable for inhalation. Concluding, two different formulations were successfully developed for capreomycin pulmonary delivery. The hydrophobic ion pair strategy led to a noticeable drug content increase.

  6. Atomization method for verifying size effects of inhalable particles on lung damage of mice.

    PubMed

    Tao, Chen; Tang, Yue; Zhang, Lan; Tian, Yonggang; Zhang, Yingmei

    2017-02-01

    To explore the size effects of inhalable particles on lung damage, aqueous aerosol containing cadmium was studied as a model to design a new type of two-stage atomization device that was composed of two adjustable parts with electronic ultrasonic atomization and pneumatic atomization. The working parameters and effectiveness of this device were tested with H2O atomization and CdCl2 inhalation, respectively. By gravimetrically detecting the mass concentrations of PM2.5 and PM10 and analysing the particle size with a laser sensor, we confirmed the particle size distribution of the aqueous aerosol produced by the new device under different working conditions. Then, we conducted experiments in male Kunming mice that inhaled CdCl2 to determine the size effects of inhalable particles on lung damage and to confirm the effectiveness of the device. The new device could effectively control the particle size in the aqueous aerosol. The inhaled CdCl2 entered and injured the lungs of the mice by causing tissue damage, oxidative stress, increasing endoplasmic reticulum stress and triggering an inflammatory response, which might be related to where the particles deposited. The smaller particles in the aqueous aerosol atomized by the new two-stage atomization device deposited deeper into lung causing more damage. This device could provide a new method for animal experiments involving inhalation with water-soluble toxins.

  7. Applicability of a modified MCE filter method with Button Inhalable Sampler for monitoring personal bioaerosol inhalation exposure.

    PubMed

    Xu, Zhenqiang; Xu, Hong; Yao, Maosheng

    2013-05-01

    In this study, a "modified" mixed cellulose ester (MCE) filter culturing method (directly placing filter on agar plate for culturing without extraction) was investigated in enumerating airborne culturable bacterial and fungal aerosol concentration and diversity both in different environments. A Button Inhalable Sampler loaded with a MCE filter was operated at a flow rate of 5 L/min to collect indoor and outdoor air samples using different sampling times: 10, 20, and 30 min in three different time periods of the day. As a comparison, a BioStage impactor, regarded as the gold standard, was operated in parallel at a flow rate of 28.3 L/min for all tests. The air samples collected by the Button Inhalable Sampler were directly placed on agar plates for culturing, and those collected by the BioStage impactor were incubated directly at 26 °C. The colony forming units (CFUs) were manually counted and the culturable concentrations were calculated both for bacterial and fungal aerosols. The bacterial CFUs developed were further washed off and subjected to polymerase chain reaction-denaturing gradient gel electrophoresis (DGGE) for diversity analysis. For fungal CFUs, microscopy method was applied to studying the culturable fungal diversity obtained using different methods. Experimental results showed that the performance of two investigated methods varied with sampling environments and microbial types (culturable bacterial and fungal aerosols). For bacterial aerosol sampling, both methods were shown to perform equally well, and in contrast the "modified" MCE filter method was demonstrated to enumerate more culturable fungal aerosols than the BioStage impactor. In general, the microbial species richness (number of gel bands) was observed to increase with increasing collection time. For both methods, the DGGE gel patterns were observed to vary with sampling time and environment despite of similar number of gel bands. In addition, an increase in sampling time from 20 to 30 min

  8. A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers.

    PubMed

    Gabrio, B J; Stein, S W; Velasquez, D J

    1999-09-10

    Two concerns raised when comparing metered dose inhalers (MDIs) to other inhalation devices are their relatively high throat deposition and the 'cold-Freon' effect seen in a small number of patients. The cold-Freon effect is presumed to be a result of the cold, forceful MDI plume impacting on the back of a patient's throat. This in vitro study uses a new plume characterization method to determine the spray force and plume temperature of various MDIs. Spray force measurements were made for 28 marketed products consisting of bronchodilators, steroids, press-and-breathe, breath-actuated and nasal inhalers. Results show that chlorofluorocarbon (CFC)-containing MDIs produce extremely forceful and cold plumes. Several hydrofluoralkane (HFA)-containing MDIs produced much softer and warmer plumes, but two HFA products had spray forces similar to the CFC products. Although the type of propellant used can affect spray force, actuator orifice diameter is the most important factor. Data obtained from marketed products and experimental inhalers show that MDIs that have a low spray force also have low throat deposition.

  9. Hypercapnic ventilation during exercise: effects of exercise methods and inhalation techniques.

    PubMed

    Kelley, M A; Owens, G R; Fishman, A P

    1982-10-01

    The effect of exercise on the ventilatory response to inhaled CO2 is uncertain because previous studies using different techniques have come to different conclusions. We undertook to resolve this problem by using multiple techniques and confining our study to a uniform level of mild exercise (VO2 = 10 ml/kg min). One group of subjects exercised on a treadmill and was tested with both rebreathing and steady-state CO2 methods. A second group exercised on a bicycle while using the rebreathing method. We found that the ventilatory response to CO2 was unchanged by mild exercise, regardless of the method used for CO2 inhalation or the technique used for exercise. These results indicate that under controlled conditions mild exercise does not produce any change in ventilatory sensitivity to CO2.

  10. Inhaled Steroids

    MedlinePlus

    ... Medications Long-Term Control Medications Inhaled Steroids Inhaled Steroids Make an Appointment Ask a Question Refer Patient ... more about steroids? What are some common inhaled steroids? Common inhaled steroids include: Asmanex ® (mometasone) Alvesco ® (ciclesonide) ...

  11. A simple pharmacokinetic method to evaluate the pulmonary dose in clinical practice--analyses of inhaled sodium cromoglycate.

    PubMed

    Lindström, Maria; Svensson, Jan Olof; Meurling, Lennart; Svartengren, Katharina; Anderson, Martin; Svartengren, Magnus

    2004-01-01

    When the expected effect of an inhaled drug is not achieved, the cause could be poor inhalation technique and consequently a low pulmonary dose. A simple in vivo test to evaluate the pulmonary dose would be a benefit. This study evaluates the relative and systemic bioavailability following inhalation of nebulized sodium cromoglycate (SCG) in healthy subjects. Blood samples were collected during 240 min and urine was collected in two portions, up to 6 h post-inhalation. Two exposures were performed and comparisons based on the quantification of drug in plasma and urine by a high-performance liquid chromatography (HPLC) procedure were done. In one of the exposures, a pulmonary function test was performed to study if an expected effect of increased absorption could be detected. There was a good correlation between the two exposures shown in the plasma concentrations, but not in the urine analyses. The forced exhaled volume manoeuvres were associated with a higher Cmax and plasma concentrations up to 60 min post-inhalation (P<0.01). This effect was not detected in the urine analyses. We conclude that this pharmacokinetic method with inhaled SCG and plasma analyses could be used to evaluate individual inhalation technique. The HPLC method used was rapid and had adequate sensitivity.

  12. New visible endotracheal intubation method using the endoscope system for mice inhalational anesthesia.

    PubMed

    Konno, Kenjiro; Itano, Naoki; Ogawa, Teppei; Hatakeyama, Mika; Shioya, Kyoko; Kasai, Noriyuki

    2014-06-01

    Appropriate and effective anesthesia is critical, because it has a strong influence on laboratory animals, and its affect greatly impacts the experimental data. Inhalational anesthesia by endotracheal intubation is currently prevailing in general anesthesia and is prefered over injection anesthesia, especially for large laboratory animals, because it is a safe and easy control agent. However, it is not common for small laboratory animals, because of the high degree of technical skills required. We assessed the capability of use for mice of the endotracheal intubation by using the endoscope system "TESALA AE-C1" and inhalational anesthesia using a ventilator. Endotracheal intubation was successfully performed on all 10 C57BL/6 mice injected with M/M/B: 0.3/4/5 comprised of medetomidine, midazoram and butorphanol, at a dose of 0.3 mg/kg + 4.0 mg/kg + 5.0 mg/kg body weight/mouse, respectively. After the intubated mice were connected with the inhalational anesthesia circuit and the ventilator, vital signs were measured until 15 min after the connection. The data with M/M/B: 0.3/4/5 showed stable and normal values, which indicated that this new endotracheal intubation method was simple, reliable and safe, which mean that this anesthesia is favorable in regard to the animal's welfare.

  13. Smoke inhalation injury

    NASA Astrophysics Data System (ADS)

    Birky, M.

    The cause of death by fires was studied. The present results and information are, however, not enough to reduce loss of life or inhalation injury. The magnitude and type of inhalation injury for civilians and firefighters represents the most inadequately defined human element of accidental fires. Little information is available on compounds other than carbon monoxide, which are responsible for respiration injury or toxicological syndrome. Effective treatment methods for inhalation victims and studies on fatalities, inhalation injury and animals are suggested.

  14. Improved dispersion method of multi-wall carbon nanotube for inhalation toxicity studies of experimental animals.

    PubMed

    Taquahashi, Yuhji; Ogawa, Yukio; Takagi, Atsuya; Tsuji, Masaki; Morita, Koichi; Kanno, Jun

    2013-01-01

    A multi-wall carbon nanotube (MWCNT) product Mitsui MWNT-7 is a mixture of dispersed single fibers and their agglomerates/aggregates. In rodents, installation of such mixture induces inflammatory lesions triggered predominantly by the aggregates/agglomerates at the level of terminal bronchiole of the lungs. In human, however, pulmonary toxicity induced by dispersed single fibers that reached the lung alveoli is most important to assess. Therefore, a method to generate aerosol predominantly consisting of dispersed single fibers without changing their length and width is needed for inhalation studies. Here, we report a method (designated as Taquann method) to effectively remove the aggregate/agglomerates and enrich the well-dispersed singler fibers in dry state without dispersant and without changing the length and width distribution of the single fibers. This method is base on two major concept; liquid-phase fine filtration and critical point drying to avoid re-aggregation by surface tension. MWNT-7 was suspended in Tert-butyl alcohol, freeze-and-thawed, filtered by a vibrating 25 µm mesh Metallic Sieve, snap-frozen by liquid nitrogen, and vacuum-sublimated (an alternative method to carbon dioxide critical point drying). A newly designed direct injection system generated well-dispersed aerosol in an inhalation chamber. The lung of mice exposed to the aerosol contained single fibers with a length distribution similar to the original and the Taquann-treated sample. Taquann method utilizes inexpensive materials and equipments mostly found in common biological laboratories, and prepares dry powder ready to make well-dispersed aerosol. This method and the chamber with direct injection system would facilitate the inhalation toxicity studies more relevant to human exposure.

  15. Brief inhalation method to measure cerebral oxygen extraction fraction with PET: Accuracy determination under pathologic conditions

    SciTech Connect

    Altman, D.I.; Lich, L.L.; Powers, W.J. )

    1991-09-01

    The initial validation of the brief inhalation method to measure cerebral oxygen extraction fraction (OEF) with positron emission tomography (PET) was performed in non-human primates with predominantly normal cerebral oxygen metabolism (CMRO2). Sensitivity analysis by computer simulation, however, indicated that this method may be subject to increasing error as CMRO2 decreases. Accuracy of the method under pathologic conditions of reduced CMRO2 has not been determined. Since reduced CMRO2 values are observed frequently in newborn infants and in regions of ischemia and infarction in adults, we determined the accuracy of the brief inhalation method in non-human primates by comparing OEF measured with PET to OEF measured by arteriovenous oxygen difference (A-VO2) under pathologic conditions of reduced CMRO2 (0.27-2.68 ml 100g-1 min-1). A regression equation of OEF (PET) = 1.07 {times} OEF (A-VO2) + 0.017 (r = 0.99, n = 12) was obtained. The absolute error in oxygen extraction measured with PET was small (mean 0.03 {plus minus} 0.04, range -0.03 to 0.12) and was independent of cerebral blood flow, cerebral blood volume, CMRO2, or OEF. The percent error was higher (19 {plus minus} 37), particularly when OEF is below 0.15. These data indicate that the brief inhalation method can be used for measurement of cerebral oxygen extraction and cerebral oxygen metabolism under pathologic conditions of reduced cerebral oxygen metabolism, with these limitations borne in mind.

  16. Rapid air titration method for determining SO/sub 2/ concentration in inhalation chambers

    SciTech Connect

    Snyder, E.A.; Palmes, E.D.

    1985-06-01

    A rapid air titration method for determining SO/sub 2/ concentration in inhalation chambers has been validated using the pararosaniline-formaldehyde (PRA) method of West and Gaeke. This air-titration (iodate) method is an adaptation of iodometric methods using a starch indicator. Potassium iodate and an excess of potassium iodide are used in the reaction. Sampling is completed in ten minutes or less and concentration is calculated by use of a simple formula. Linear equations were derived over the range of concentrations from 0.5 to 100 ppm SO/sub 2/ for uncorrected iodate bubbler results, data corrected for tandem bubbler concentrations and data corrected for mean iodate bubbler efficiency. Linear correlation with the PRA method over this range was 0.999 for all three sets of data.

  17. Development and application of an inhalation bioaccessibility method (IBM) for lead in the PM10 size fraction of soil.

    PubMed

    Boisa, Ndokiari; Elom, Nwabueze; Dean, John R; Deary, Michael E; Bird, Graham; Entwistle, Jane A

    2014-09-01

    An approach for assessing the inhalation bioaccessibility of Pb in the PM10 size fraction is presented, using an in vitro simulated epithelial lung fluid to represent the extracellular environment of the lung. The developed inhalation bioaccessibility method (IBM) is applied to a range of urban surface soils and mining wastes obtained from Mitrovica, Kosovo, a site where impacts upon human health following exposure to Pb have been internationally publicised. All Pb determinations were undertaken by inductively coupled plasma mass spectrometry (ICP-MS). The pseudo-total concentration of Pb (microwave acid digestion using aqua-regia) varied between matrices: smelter (20,900-72,800mgkg(-1)), topsoil (274-13,700mgkg(-1)), and tailings (2990mgkg(-1)-25,300mgkg(-1)). The in vitro inhalation bioaccessibility was typically several orders of magnitude lower: smelter (7.0-965mgkg(-1)), topsoil (9.8-1060mgkg(-1)), and tailings (0.7mgkg(-1)-49.2mgkg(-1)). The % inhalation bioaccessibility ranged from 0.02 to 11.0%, with the higher inhalation bioaccessible Pb concentrations being observed for samples from the Bosniak Mahalla area of Mitrovica (an area proposed for the relocation of internally displaced peoples). The estimated inhalation dose (for adults) calculated from the PM10 pseudo-total Pb concentration ranged from 0.369 to 1.284μgkg(-1)BWday(-1) (smelter), 0.005-0.242μgkg(-1)BWday(-1) (topsoil), and 0.053-0.446μgkg(-1)BWday(-1) (tailings). When daily inhalation doses were calculated using the bioaccessible Pb concentration the modelled exposure doses were much lower: smelter (0.0001-0.0170μgkg(-1)BWday(-1)), topsoil (0.0002-0.0187μgkg(-1)BWday(-1)) and tailings (0.0001-0.0009μgkg(-1)BWday(-1)). Modelled for the neutral pH conditions of the interstitial lung environment, the results indicate a low potential inhalation bioaccessibility for Pb in these samples. Given the already elevated environmental Pb burden experienced by the local population, where significant

  18. Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate “normative adherence”

    PubMed Central

    Hoo, Zhe Hui; Curley, Rachael; Campbell, Michael J; Walters, Stephen J; Hind, Daniel; Wildman, Martin J

    2016-01-01

    Background Preventative inhaled treatments in cystic fibrosis will only be effective in maintaining lung health if used appropriately. An accurate adherence index should therefore reflect treatment effectiveness, but the standard method of reporting adherence, that is, as a percentage of the agreed regimen between clinicians and people with cystic fibrosis, does not account for the appropriateness of the treatment regimen. We describe two different indices of inhaled therapy adherence for adults with cystic fibrosis which take into account effectiveness, that is, “simple” and “sophisticated” normative adherence. Methods to calculate normative adherence Denominator adjustment involves fixing a minimum appropriate value based on the recommended therapy given a person’s characteristics. For simple normative adherence, the denominator is determined by the person’s Pseudomonas status. For sophisticated normative adherence, the denominator is determined by the person’s Pseudomonas status and history of pulmonary exacerbations over the previous year. Numerator adjustment involves capping the daily maximum inhaled therapy use at 100% so that medication overuse does not artificially inflate the adherence level. Three illustrative cases Case A is an example of inhaled therapy under prescription based on Pseudomonas status resulting in lower simple normative adherence compared to unadjusted adherence. Case B is an example of inhaled therapy under-prescription based on previous exacerbation history resulting in lower sophisticated normative adherence compared to unadjusted adherence and simple normative adherence. Case C is an example of nebulizer overuse exaggerating the magnitude of unadjusted adherence. Conclusion Different methods of reporting adherence can result in different magnitudes of adherence. We have proposed two methods of standardizing the calculation of adherence which should better reflect treatment effectiveness. The value of these indices can

  19. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  20. Asthma Inhalers

    MedlinePlus

    ... an inhaler into the lungs. But CFCs are ozone-depleting substances (ODSs) that hurt the environment. Manufacturers ... inhalers, that do not rob the atmosphere of ozone. “The FDA [Food and Drug Administration] and various ...

  1. Inhalant Abuse

    MedlinePlus

    ... Who may be abusing inhalants?The most common abusers of inhalants are teenagers, especially those who are ... to your child about the dangers of trying drugs can help him or her make the right ...

  2. Methods to Develop Inhalation Cancer Risk Estimates for Chromium and Nickel Compounds

    EPA Science Inventory

    This document summarizes the approaches and rationale for the technical and scientific considerations used to derive inhalation cancer risks for emissions of chromium and nickel compounds from electric utility steam generating units.

  3. [Introduction of dinitrosyl iron complexes with thiol-containing ligands into animal organism by inhalation method].

    PubMed

    Vanin, A F; Mozhokina, G N; Tkachev, N A; Mikoian, V D; Borodulin, R R; Elistratova, N A

    2013-01-01

    The possibility of water-soluble dinitrosyl iron complexes (DNIC) with thiol-containing ligands introduction into lungs and other tissues of mice by free inhalation of little drops (2-3 microns diameter) of the solutions of these complexes was investigated. Little drops of 2-20 mM solutions of the complexes were obtained by using an inhalation apparatus (compressor nebulizer). A cloud of these little drops was then inhaled by animals in a closed chamber. A maximal amount of protein-bound DNICs formed in mouse lungs was 0.6 micromoles per kilogram of tissue weight. The amount of DNIC in lungs, liver and blood decreased to the undetected level within 2-3 hours after inhalation. No cytotoxic effect of DNIC formed in lungs on Mycobacterium tuberculosis was found in mice infected with these mycobacteria.

  4. Mass spectrometry method to monitor the sevoflurane concentration in an apparatus for inhalational anesthesia

    NASA Astrophysics Data System (ADS)

    Elokhin, V. A.; Ershov, T. D.; Levshankov, A. I.; Nikolaev, V. I.; Saifullin, M. F.; Elizarov, A. Yu.

    2010-08-01

    The feasibility of real-time monitoring of the inhalational anesthetic (sevoflurane) concentration in the respiratory circuit of an apparatus for inhalational anesthesia using mass spectrometry is considered. It is shown that the absolute anesthetic concentration can be monitored in real time if low-flow ventilation is provided during general anesthesia. The time dependences of the anesthetic concentration are taken at different stages of anesthesia in the inspiration-expiration regime.

  5. Overview of testing methods used in inhalation toxicity: from facts to artifacts.

    PubMed

    Pauluhn, Jürgen

    2003-04-11

    For smaller rodent species, homogenous in size and growth, small head or nose-only chambers are commonly used up to subchronic exposure durations, whereas larger whole-body exposure chambers are used for long-term exposures or exposure paradigms exceeding the normal working day. The advantages and disadvantages of each different technique have already been identified and published in detail. It is often believed best that whole-body inhalation chambers simulate potential human exposure to environmental chemicals or pesticides and this serves as a justification for preferring this mode of exposure. However, real-life exposure conditions of humans cannot be readily duplicated. A comparable mode of exposure may be employed rather than duplicating both the exposure regimens and atmospheres similar to those present in real-world settings. Especially in inhalation studies with complex mixtures, in which atmosphere generation is difficult to control, non-homogenous exposure atmospheres and artifacts are more likely to occur in larger whole-body chambers than in the smaller nose-only inhalation chambers. Inhalation studies with complex mixtures not only face all the challenges of traditional inhalation toxicity testing, but also they are frequently subject to artifacts not readily detected. Thus, a disproportionation of volatile and particulate constituents might occur in inhalation chambers depend on selected technical features, i.e., whether a dynamic or (quasi)static mode of exposure is chosen. Inappropriate timing of the sampling of biological specimens may lead to the underestimation of effects, especially in whole-body exposed animals.

  6. Development of a novel method to detect a potential inhalation of nanoaerosols

    NASA Astrophysics Data System (ADS)

    Marie-Desvergne, C.; Tardif, F.; Motellier, S.; Mossuz, V.

    2011-07-01

    In the context of the precautionary principle for engineered nanoparticles, a test able to verify the non exposure of individuals to nanoaerosols seems to be of great interest, especially for workers involved with nanomaterials. A novel method is proposed to detect the presence of nanoparticles in the nose. Different materials, including paper and polycarbonate, have been tested for their sampling efficiency towards ZnO nanoparticles. The detection of nanoparticles is performed by elemental analysis using Total Reflection X-Ray Fluorescence (TXRF). For an optimal sensitivity of the TXRF signal, samples have to be deposited on a smooth surface. Therefore, different materials have been compared as sample carrier. The results indicate that pure paper is the most efficient material for sampling nanoparticles (ZnO), while the use of polycarbonate, and even more flexible polyester, as sample carrier allows a better sensitivity for TXRF analysis. Therefore, the sampling device made of paper is digested under slightly acidic conditions in a microwave oven after collection, and the resulting solution is deposited on polyester for TXRF analysis. Internal calibration is performed thanks to an addition of Rb to the samples. The proposed method allows the chemical identification of nanoparticles deposited in the nose: a qualitative signature of a potential nanoaerosol inhalation.

  7. Substance use - inhalants

    MedlinePlus

    Substance abuse - inhalants; Drug abuse - inhalants; Drug use - inhalants; Glue - inhalants ... symptoms and may include: Strong cravings for the drug Having mood swings from feeling depressed to agitated ...

  8. Mass transport analysis: inhalation rfc methods framework for interspecies dosimetric adjustment.

    PubMed

    Hanna, L M; Lou, S R; Su, S; Jarabek, A M

    2001-05-01

    In 1994, the U.S. Environmental Protection Agency introduced dosimetry modeling into the methods used to derive an inhalation reference concentration (RfC). The type of dosimetric adjustment factor (DAF) applied had to span the range of physicochemical characteristics of the gases listed on the Clean Air Act Amendments in 1991 as hazardous air pollutants (HAPs) and accommodate differences in available data with respect to their toxicokinetic properties. A framework was proposed that allowed for a hierarchy of dosimetry model structures, from optimal to rudimentary, and a category scheme that provided for limiting model structures based on physicochemical and toxicokinetic properties. These limiting cases were developed from restricting consideration to specific properties relying on an understanding of the generalized system based on mass transport theory. Physiochemical characteristics included the solubility and reactivity (e.g., propensity to dissociate, oxidize, or serve as a metabolic substrate) of the gas and were used as major determinants of absorption. Dosimetric adjustments were developed to evaluate portal of entry (POE) effects as well as remote (systemic) effects relevant to the toxicokinetic properties of the gas of interest. The gas categorization scheme consisted of defining three gas categories: (1) gases that are highly soluble and/or reactive, absorbing primarily in the extrathoracic airways; (2) gases that are moderately soluble and/or reactive, absorbing throughout the airways, as well as accumulating in the bloodstream; and (3) gases that have a low water solubility and are lipid soluble such that they are primarily absorbed in the pulmonary region and likely to act systemically. This article presents the framework and the mass transport theory behind the RfC method. Comparison to compartmental approaches and considerations for future development are also discussed.

  9. Inhaler Technique in Asthma: How Does It Relate to Patients' Preferences and Attitudes Toward Their Inhalers?

    PubMed Central

    Jahedi, Lia; Downie, Sue R.; Saini, Bandana; Chan, Hak-Kim

    2017-01-01

    Abstract Background: Correct inhaler technique can increase medication efficacy, reducing both dose and side effects. Patient preference for inhaler device has not been fully explored, and we hypothesized that if patients have a preference and can choose their inhaler, they might be more likely to use it correctly. Our aim was to determine the preferences, attitudes, and perceptions of patients with asthma toward their inhalers, and to evaluate whether any of these factors were related to inhalation technique. Methods: Twenty-five patients with asthma (mean age 43.1 years) participated. Qualitative semi-structured interviews and quantitative patient satisfaction and preference questionnaires (PASAPQ) were used to explore patients' preferences, attitudes, and perceptions about their inhalers. Objective inhalation technique assessment was performed. Data were triangulated to identify characteristics that could indicate a relationship between inhaler technique, satisfaction, preference, and decision making. Results: Themes from qualitative interviews were as follows: asthma inhalers and expectations; inhaler preference; characteristics of an ideal inhaler; perceived effectiveness of inhalers; and inhalers and patient decision making. PASAPQ scores indicated that all patients were at least “somewhat satisfied” with their inhalers, regardless of technique. Only 12% of inhalers were used correctly, despite pilot PASAPQ data suggesting that most patients were confident with their technique. The inhaler technique was unlikely to be related to satisfaction, perception of inhaler devices, or choice in device selection. Patients with correct inhaler technique were more aware of their asthma and expressed motivation to achieve optimal asthma control. Conclusions: The majority of the asthmatic patients did not use their inhaler(s) correctly, despite most having confidence in their technique. Patients attributed confidence in their inhaler technique to their belief that

  10. Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

    PubMed Central

    Kuempel, Eileen D.; Sweeney, Lisa M.; Morris, John B.; Jarabek, Annie M.

    2015-01-01

    The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. PMID:26551218

  11. Determination of potential dermal and inhalation operator exposure to malathion in greenhouses with the whole body dosimetry method.

    PubMed

    Machera, K; Goumenou, M; Kapetanakis, E; Kalamarakis, A; Glass, C R

    2003-01-01

    One of the steps during the authorization process of plant protection products (PPP) in the European Union is to evaluate the safety of the operator. For this purpose, information on the probable levels of operator exposure during the proposed uses of the PPP is required. These levels can be estimated by using existing mathematical models or from field study data. However, the existing models have several shortcomings, including the lack of data for operator exposure levels during spray applications by hand lance, especially in greenhouses. The present study monitored the potential dermal and inhalation operator exposure from hand-held lance applications of malathion on greenhouse tomatoes at low and high spraying pressures. The methodology for monitoring potential exposure was based on the whole body dosimetry method. Inhalation exposure was monitored using personal air pumps and XAD-2 sampling tubes. For the monitoring of hand exposure, cotton gloves were used in two trials and rubber gloves in another three. The total volumes of spray solution contaminating the body of the operator were 25.37 and 35.83 ml/h, corresponding to 0.05 and 0.07% of the applied spray solution, respectively, in the case of low pressure knapsack applications and from 160.76 to 283.45 ml/h, corresponding to 0.09-0.19% of the spray solution applied, in the case of hand lance applications with tractor-generated high pressure. Counts on gloves depended on the absorbance/repellency of the glove material. The potential inhalation exposures were estimated at 0.07 and 0.09 ml/h in the case of low pressure knapsack applications, based on a ventilation rate of 25 l/min. Both potential dermal operator exposure (excluding hands) and potential inhalation exposure were increased by a factor of approximately 7 when the application pressure was increased from 3 to 18 bar in greenhouse trials with a tractor-assisted hand lance, the rest of the application conditions being very similar.

  12. Comparative study of various methods used for determining health effects of inhaled sulfates

    SciTech Connect

    Drummond, J.G.; Aranyi, C.; Schiff, L.J.; Fenters, J.D.; Graham, J.A.

    1986-01-01

    Various health-effect parameters were compared to determine which tests were the most-sensitive indicators of toxic effects of exposure to metallic sulfate aerosols. Inhalation studies were conducted involving either single 3-hr exposure to various concentrations of cupric sulfate (o.43-2.64 mg/m/sup 3/ SO/sub 4/), and aluminum ammonium sulfate (1.47-3.81 mg/m/sup 3/ SO/sub 4/) or multiple (five and ten) daily 3-hr exposures to cupric sulfate (0.1 mg/m/sup 3/ SO/sub 4/). Cupric sulfate was the most toxic of the three sulfates, but the differences between the toxicity of the aluminum sulfate and aluminum ammonium sulfate were less clear.

  13. The effects of continuous phonation on 133xenon-inhalation air curves (of the kind used in deriving regional cerebral blood flow).

    PubMed

    Formby, C; Thomas, R G; Brown, W S; Halsey, J H

    1987-07-01

    Regional cerebral blood flow (rCBF) may be measured with inhalation techniques that use end-expired values of radioactivity to estimate the isotope concentration in arterial blood. These end-expired data are used as an input function in a mathematical equation to derive rCBF. End-expired air is assumed normally to be in equilibrium with the arterial blood at the alveolar surface of the lung during regular (passive) breathing; this assumption may not be valid during continuous phonation. We therefore have analyzed breathing (inhalation/exhalation) patterns and end-expired radioactivity (133Xe) during (1) speaking, (2) singing, and (3) humming of the national anthem, and also during (4) passive breathing. Statistically significant differences in breathing patterns were measured between a group of nonmusicians and two groups of musicians (singers) during the phonation tasks: The nonmusicians breathed more often (and more rapidly) and exhibited less variability in their breathing patterns than did the musicians. Notwithstanding these differences, the shapes of smoothed functions derived from the end-expired values were not influenced appreciably during phonation (except possibly during talking). The latter finding suggests that estimates of rCBF derived with these data should not be confounded seriously because of the continuous phonation.

  14. Ciclesonide Oral Inhalation

    MedlinePlus

    ... ciclesonide inhaler while you are near an open flame or a heat source. The inhaler may explode ... inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct sunlight. ...

  15. Fluticasone Oral Inhalation

    MedlinePlus

    ... aerosol inhaler while you are near an open flame or a heat source. The inhaler may explode ... inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct sunlight. ...

  16. Flunisolide Oral Inhalation

    MedlinePlus

    ... flunisolide inhaler while you are near an open flame or a heat source. The inhaler may explode ... inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct sunlight. ...

  17. Wearable Sensors for Personal Monitoring and Estimation of Inhaled Traffic-Related Air Pollution: Evaluation of Methods.

    PubMed

    Dons, Evi; Laeremans, Michelle; Orjuela, Juan Pablo; Avila-Palencia, Ione; Carrasco-Turigas, Glòria; Cole-Hunter, Tom; Anaya-Boig, Esther; Standaert, Arnout; De Boever, Patrick; Nawrot, Tim; Götschi, Thomas; de Nazelle, Audrey; Nieuwenhuijsen, Mark; Int Panis, Luc

    2017-02-07

    Physical activity and ventilation rates have an effect on an individual's dose and may be important to consider in exposure-response relationships; however, these factors are often ignored in environmental epidemiology studies. The aim of this study was to evaluate methods of estimating the inhaled dose of air pollution and understand variability in the absence of a true gold standard metric. Five types of methods were identified: (1) methods using (physical) activity types, (2) methods based on energy expenditure, METs (metabolic equivalents of task), and oxygen consumption, (3) methods based on heart rate or (4) breathing rate, and (5) methods that combine heart and breathing rate. Methods were compared using a real-life data set of 122 adults who wore devices to track movement, black carbon air pollution, and physiological health markers for 3 weeks in three European cities. Different methods for estimating minute ventilation performed well in relative terms with high correlations among different methods, but in absolute terms, ignoring increased ventilation during day-to-day activities could lead to an underestimation of the daily dose by a factor of 0.08-1.78. There is no single best method, and a multitude of methods are currently being used to approximate the dose. The choice of a suitable method for determining the dose in future studies will depend on both the size and the objectives of the study.

  18. Comparative study of various methods used for determining health effects of inhaled sulfates

    SciTech Connect

    Drummond, J.G.; Aranyi, C.; Schiff, L.J.; Fenters, J.D.; Graham, J.A.

    1986-12-01

    Various health effect parameters were compared to determine which tests were the most sensitive indicators of toxic effects of exposure to metallic sulfate aerosols. Inhalation studies were conducted involving either single 3-hr exposure to various concentrations of cupric sulfate (0.43-2.64 mg/m3 SO/sub 4/), aluminum sulfate (1.65-2.75 mg/m3 SO/sub 4/), and aluminum ammonium sulfate (1.47-3.81 mg/m3 SO/sub 4/) or multiple (five and ten) daily 3-hr exposures to cupric sulfate (0.1 mg/m3 SO/sub 4/). The test parameters studied in male and female CD1 mice were changes in mortality after respiratory infection with Group C Streptococcus zooepidemicus; pulmonary bactericidal activity; pulmonary cell number, type, viability, and ATP content; and pulmonary morphology by scanning electron microscopy. Tracheal ciliary beating frequency and morphology were also studied in both CD1 mice and Syrian golden hamsters. Differences in bacteria-induced mortality rate appeared to be the most sensitive and consistent indicators of pollutant damage. The other parameters produced evidence of damage but generally only at the higher pollutant concentrations. Cupric sulfate was the most toxic of the three sulfates, but the differences between the toxicity of the aluminum sulfate and aluminum ammonium sulfate were less clear.

  19. Comparative study of various methods used for determined health effects of inhaled sulfates

    SciTech Connect

    Drummond, J.G.; Aranyi, C.; Schiff, L.J.; Fenters, J.D.; Graham, J.A.

    1985-12-01

    Various health effect parameters were compared to determine which tests were the most sensitive indicators of toxic effects of exposure to metallic sulfate aerosols. Inhalation studies were conducted involving either single 3-hr exposure to various concentrations of cupric sulfate (0.43-2.64 mg/m/sup 3/ SO/sub 4/), aluminum sulfate (1.65-2.75 mg/m/sup 3/ SO/sub 4/), and aluminum ammonium sulfate (1.47-3.81 mg/m/sup 3/ SO/sub 4/) or multiple (five and ten) daily 3-hr exposures to cupric sulfate (0.1 mg/m/sup 3/ SO/sub 4/). The test parameters studied in male and female CD/sub 1/ mice were changes in mortality after respiratory infection with Group C Streptococcus zooepidemicus; pulmonary bactericidal activity; pulmonary cell number, type, viability, and ATP content; and pulmonary morphology by scanning electron microscopy. Tracheal ciliary beating frequency and morphology were also studied in both CD/sup 1/ mice and Syrian golden hamsters. Differences in bacteria-induced mortality rate appeared to be the most sensitive and consistent indicators of pollutant damage. The other parameters produced evidence of damage but generally only at the higher pollutant concentrations. Cupric sulfate was the most toxic of the three sulfates, but the differences between the toxicity of the aluminum sulfate and aluminum ammonium sulfate were less clear.

  20. Inhalation Injury.

    DTIC Science & Technology

    1994-01-01

    alpha,-antitrypsin resulting cur most often as the result of tracheal in prolonged action of proteases such as or laryngeal damage from the endotra... curs is determined by physicochemical Turbulent airflow, such as at bifurca- properties of the inhaled substance, its tions of the airway, separates

  1. [Effects of Instruction on Inhalation Techniques Using iPads - Web Application "Inhalation Lessons"].

    PubMed

    Kogawa, Noriko; Ito, Reiko; Gon, Yasuhiro; Maruoka, Shuichiro; Hashimoto, Shu

    2015-12-01

    Instruction on inhalation techniques for chronic obstructive pulmonary disease(COPD)and asthma patients being treated with inhalants have sufficient therapeutic effects and are important to maintain adherence. However, problems continue to exist, including time constraints of medical staff that have a large number of patients and a lack of knowledge on inhalation instruction methods. A web application,"Inhalation Lessons,'for the iPad has been developed. It explains inhalation methods, and consists of videos and review tests. Instruction on inhalation techniques was performed using this application for patients that use Diskus, and the effects were examined. As a result, there are significant improvements in the inhalation techniques of patients after viewing the"Inhalation Lessons'application. Uniform instruction on inhalation techniques can be performed even in the field of homecare.

  2. Formulation pre-screening of inhalation powders using computational atom-atom systematic search method.

    PubMed

    Ramachandran, Vasuki; Murnane, Darragh; Hammond, Robert B; Pickering, Jonathan; Roberts, Kevin J; Soufian, Majeed; Forbes, Ben; Jaffari, Sara; Martin, Gary P; Collins, Elizabeth; Pencheva, Klimentina

    2015-01-05

    The synthonic modeling approach provides a molecule-centered understanding of the surface properties of crystals. It has been applied extensively to understand crystallization processes. This study aimed to investigate the functional relevance of synthonic modeling to the formulation of inhalation powders by assessing cohesivity of three active pharmaceutical ingredients (APIs, fluticasone propionate (FP), budesonide (Bud), and salbutamol base (SB)) and the commonly used excipient, α-lactose monohydrate (LMH). It is found that FP (-11.5 kcal/mol) has a higher cohesive strength than Bud (-9.9 kcal/mol) or SB (-7.8 kcal/mol). The prediction correlated directly to cohesive strength measurements using laser diffraction, where the airflow pressure required for complete dispersion (CPP) was 3.5, 2.0, and 1.0 bar for FP, Bud, and SB, respectively. The highest cohesive strength was predicted for LMH (-15.9 kcal/mol), which did not correlate with the CPP value of 2.0 bar (i.e., ranking lower than FP). High FP-LMH adhesive forces (-11.7 kcal/mol) were predicted. However, aerosolization studies revealed that the FP-LMH blends consisted of agglomerated FP particles with a large median diameter (∼4-5 μm) that were not disrupted by LMH. Modeling of the crystal and surface chemistry of LMH identified high electrostatic and H-bond components of its cohesive energy due to the presence of water and hydroxyl groups in lactose, unlike the APIs. A direct comparison of the predicted and measured cohesive balance of LMH with APIs will require a more in-depth understanding of highly hydrogen-bonded systems with respect to the synthonic engineering modeling tool, as well as the influence of agglomerate structure on surface-surface contact geometry. Overall, this research has demonstrated the possible application and relevance of synthonic engineering tools for rapid pre-screening in drug formulation and design.

  3. Single step spray drying method to develop proliposomes for inhalation: a systematic study based on quality by design approach.

    PubMed

    Patil-Gadhe, Arpana; Pokharkar, Varsha

    2014-04-01

    Quality by Design (QbD) is a systematic approach to develop drug products which includes evaluation of formulation parameters to achieve defined final product quality. In the present study principles of QbD were extended to the preparation, in-vitro and in-vivo performance of rifapentine-loaded proliposomes for pulmonary inhalation where final product needs to comply with specific properties. The rifapentine-loaded proliposomes for the treatment of tuberculosis were prepared in single step by spray drying method and independent variables were optimized using factorial design approach. Contour plots and multiple regression analysis were used to study the effect of selected independent variables on dependent variables. The effect of presence of drug: hydrogenated soya phosphatidylcholine (HSPC) and type of charged lipid in the formulation at three levels were studied on mass median diameter (MMD), liposomal vesicle size, % encapsulation efficiency (% EE), mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) as critical quality attributes. Optimized formulation (R-LDPI-7) with drug: HSPC ratio of 1:2 and stearyl amine as charged lipid were found to give respirable proliposomes with MMAD of 1.56 ± 0.16 μm and FPF of 92.5 ± 1.5%. Sustained drug release with Higuchi diffusion kinetics was achieved from liposomally encapsulated rifapentine. Pulmonary pharmacokinetics of optimized batch R-LDPI-7 revealed longer retention of drug in lungs with 7 fold increase in both, the mean residence time and t1/2 as compared to R-DPI-0. The study results demonstrated the application of QbD principles and design of experiment (DOE) approach to develop drug encapsulated proliposomes for inhalation by spray drying in single step.

  4. Development and validation of an ion-pair liquid chromatographic method for the quantitation of sodium cromoglycate in urine following inhalation.

    PubMed

    Aswania, O A; Corlett, S A; Chrystyn, H

    1997-03-07

    An ion-pair liquid high-performance chromatography method with solid-phase extraction for measuring urinary concentrations of sodium cromoglycate following inhalation has been developed and validated. Sodium cromoglycate was extracted from urine on a 100-mg phenyl cartridge (Isolute, Jones Chromatography) and then quantified on a 25-cm C8 Spherisorb 5 microns stationary phase with a mobile phase of methanol-0.045 M phosphate buffer-0.05 M dodecyl triethyl ammonium phosphate (550:447.6:2.4, v/v) pH 2.3, at 0.85 ml min-1 using nedocromil sodium as an internal standard and UV detection at 238 nm. The inter- and intra-day reproducibilities were 8.33 and 13.63%, respectively, at 0.25 mg l-1. The limit of determination for sodium cromoglycate was 0.25 mg l-1 (with a signal-to-noise ratio of greater than 10:1). Following oral and inhaled administration of 20 mg of sodium cromoglycate to eight healthy volunteers, the mean and S.D. of sodium cromoglycate excreted in the urine at 0.5, 1 and 24 h post-dose were 0.02, 0.05 and 0.33%, and 0.16, 0.30 and 1.55% of the dose, respectively. The urinary recovery of sodium cromoglycate at 0.5 and 1 h following inhalation can therefore be used to compare the amount of drug reaching the respiratory tract using different sodium cromoglycate inhaled products or inhalation methods.

  5. Levalbuterol Oral Inhalation

    MedlinePlus

    Levalbuterol comes as a solution (liquid) to inhale by mouth using a nebulizer (machine that turns medication into a mist that can be inhaled), a concentrated solution to be mixed with normal saline and inhaled ...

  6. Diagnostic efficacy of in vitro methods vs. skin testing in patients with inhalant allergies

    SciTech Connect

    Corey, J.P.; Liudahl, J.J.; Young, S.A.; Rodman, S.M. )

    1991-03-01

    The purpose of our study was to investigate the diagnostic efficacy of two selected methods of in vitro allergy testing. Specifically, the PRIST/modified RAST I125 isotope systems and the Quantizyme/modified EAST alkaline phosphatase method were compared. The time, expense, convenience, and diagnostic efficacy of the two procedures are discussed. Special attention is given to the practicality of each method for the practicing physician.

  7. Assessment of demented patients by dynamic SPECT of inhaled xenon-133

    SciTech Connect

    Komatani, A.; Yamaguchi, K.; Sugai, Y.; Takanashi, T.; Kera, M.; Shinohara, M.; Kawakatsu, S.

    1988-10-01

    We studied the potential for using dynamic single photon emission computed tomography of inhaled xenon-133 (/sup 133/Xe) gas in the assessment of demented patients. An advanced ring-type single photon emission computed tomography (SPECT) HEADTOME with improved spatial resolution (15 mm in full width at half maximum (FWHM)) was used for tomographic measurement of regional cerebral blood flow (rCBF). All 34 patients underwent a detailed psychiatric examination and x-ray computed tomography scan, and matched research criteria for Alzheimer's disease (n = 13), senile dementia of the Alzheimer type (n = 9), or multi-infarct dementia (n = 12). In comparison with a senile control group (n = 7), mean CBF of both the whole brain and the temporo-parietal region was significantly less in the Alzheimer's disease and senile dementia Alzheimer type groups, but no significant difference was seen between the senile control group and multi-infarct dementia group. The correlation was 0.72 (p less than 0.004) between the mean CBF of the whole brain and the score of Hasegawa's Dementia Scale, and 0.94 (p less than 0.0001) between rCBF of the temporo-parietal region and the scale in Alzheimer's disease. In the senile dementia Alzheimer type group, the correlations were 0.77 (p less than 0.01) and 0.83 (p less than 0.004) respectively. No significant correlations were found in the multi-infarct dementia group. A temporo-parietal reduction in the distribution of the rCBF characteristic in the Alzheimer's disease group and a patchy whole brain reduction characteristic in the multi-infarct dementia group was detected. The ability of our improved SPECT to provide both quantitative measurement of rCBF and characteristic rCBF distribution patterns, makes it a promising tool for research or routine examination of demented patients.

  8. Methods used to calculate doses resulting from inhalation of Capstone depleted uranium aerosols.

    PubMed

    Miller, Guthrie; Cheng, Yung Sung; Traub, Richard J; Little, Tom T; Guilmette, Raymond A

    2009-03-01

    The methods used to calculate radiological and toxicological doses to hypothetical persons inside either a U.S. Army Abrams tank or Bradley Fighting Vehicle that has been perforated by depleted uranium munitions are described. Data from time- and particle-size-resolved measurements of depleted uranium aerosol as well as particle-size-resolved measurements of aerosol solubility in lung fluids for aerosol produced in the breathing zones of the hypothetical occupants were used. The aerosol was approximated as a mixture of nine monodisperse (single particle size) components corresponding to particle size increments measured by the eight stages plus the backup filter of the cascade impactors used. A Markov Chain Monte Carlo Bayesian analysis technique was employed, which straightforwardly calculates the uncertainties in doses. Extensive quality control checking of the various computer codes used is described.

  9. Inhalation exposure of animals.

    PubMed Central

    Phalen, R F

    1976-01-01

    Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed. PMID:1017420

  10. Inhalation Therapy in Horses.

    PubMed

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials.

  11. Checklists for the Assessment of Correct Inhalation Therapy.

    PubMed

    Knipel, V; Schwarz, S; Magnet, F S; Storre, J H; Criée, C P; Windisch, W

    2017-02-01

    Introduction For the long-term treatment of obstructive lung diseases inhalation therapy with drugs being delivered directly to the lungs as an aerosol has become the method of choice. However, patient-related mistakes in inhalation techniques are frequent and recognized to be associated with reduced disease control. Since the assessment of patient-mistakes in inhalation has yet not been standardized, the present study was aimed at developing checklists for the assessment of correct inhalation. Methods Checklists were developed in German by an expert panel of pneumologists and professionally translated into English following back-translation procedures. The checklists comparably assessed three major steps of inhalation: 1) inhalation preparation, 2) inhalation routine, and 3) closure of inhalation. Results Checklists for eight frequently used inhalers were developed: Aerolizer, Breezhaler, Diskus (Accuhaler), metered-dose inhaler, Handihaler, Novolizer, Respimat, Turbohaler. Each checklist consists of ten items: three for inhalation preparation, six for inhalation routine, and one for closure of inhalation. Discussion Standardized checklists for frequently used inhalers are available in German and English. These checklists can be used for clinical routines or for clinical trials. All checklists can be downloaded free of charge for non-profit application from the homepage of the German Airway League (Deutsche Atemwegsliga e. V.): www.atemwegsliga.de.

  12. Formoterol Oral Inhalation

    MedlinePlus

    ... until you are ready to inhale your dose. Pull off the inhaler cover and twist the mouthpiece open in the direction shown by the arrow on the mouthpiece. Push the buttons on each side to be sure ...

  13. Albuterol Oral Inhalation

    MedlinePlus

    Albuterol is used to prevent and treat difficulty breathing, wheezing, shortness of breath, coughing, and chest tightness ... for oral inhalation is also used to prevent breathing difficulties during exercise. Albuterol inhalation aerosol (Proair HFA, ...

  14. Focus on Inhalants.

    ERIC Educational Resources Information Center

    Challenge: Safe, Disciplines, and Drug-Free Schools, 1994

    1994-01-01

    The use of inhalants is a major health concern among the school-age population. Information presented in this publication dispels the myths about inhalant use and presents common warning signs that alert teachers to a student's use. The short- and long-term effects of inhalant use are described to shed light on the health risks involved. Lesson…

  15. Experimental methods to determine inhalability and personal sampler performance for aerosols in ultra-low windspeed environments.

    PubMed

    Schmees, Darrah K; Wu, Yi-Hsuan; Vincent, James H

    2008-12-01

    Most previous experiments of aerosol inhalability as it relates to particle aerodynamic diameter were conducted in wind tunnels for windspeeds greater than 0.5 m s(-1). While that body of work was used to establish an inhalable aerosol convention, results from studies in calm air chambers (for essentially zero windspeed) are being discussed as the basis of a modified criterion. Meanwhile, however, information is lacking for windspeeds in the intermediate range, which--it so happens--pertain to most actual workplaces. With this in mind, we have developed a new experimental system to assess inhalability and personal sampler performance for aerosols with particle aerodynamic diameter within the range from 6 to 90 microm for ultra-low windspeed environments from about 0.1 to 0.5 m s(-1). In this range of conditions for particle size and windspeed, controlled aerosol experiments are very difficult to perform, most notably with respect to the problem of achieving uniform spatial distributions of both test aerosols and air velocity. In the work reported in this paper, we have addressed these difficulties in a new, custom-designed experimental facility. It is a novel wind tunnel design that provides stable and controllable low-turbulence air movement, and allows for the delivery of test aerosol to the working section both from upstream (as in conventional wind tunnel experiments) and from above (as in calm air studies). In this system, losses by elutriation of particles that are being convected in the horizontal aerosol flow are compensated by particles entering from above by gravitational settling. An important feature of the new facility is the life-size, breathing mannequin that contains physical means to achieve any combination of mouth and nasal inspiration and expiration, and allows any desired relevant breathing flowrate and pattern by means of an external computer-controlled breathing simulator. Special steps were taken in the detailed design to ensure that

  16. Inhalant Use in Florida Youth

    ERIC Educational Resources Information Center

    Siqueira, Lorena; Crandall, Lee A.

    2006-01-01

    Purpose: To determine (1) the prevalence of use, (2) risk and protective factors for use of inhalants in Florida youth. Methods: The Florida Youth Substance Abuse Survey 2004 is a comprehensive assessment of youth substance abuse attitudes and practices obtained by sampling youth from sixty-five counties. Results: The sample consisted of 60,345…

  17. Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA® Dry Powder Inhaler

    PubMed Central

    de Backer, Wilfried; Hamilton, Melanie; Cahn, Anthony; Preece, Andrew; Kelleher, Dennis; Baines, Amanda; Moore, Alison; Brealey, Noushin; Moynihan, Jackie

    2015-01-01

    Abstract Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion. Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8–110.6 L/min (range: 41.6–142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker. Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma

  18. [Inhaled therapy in asthma].

    PubMed

    Plaza Moral, Vicente; Giner Donaire, Jordi

    2016-04-01

    Because of its advantages, inhaled administration of aerosolized drugs is the administration route of choice for the treatment of asthma and COPD. Numerous technological advances in the devices used in inhaled therapy in recent decades have boosted the appearance of multiple inhalers and aerosolized drugs. However, this variety also requires that the prescribing physician is aware of their characteristics. The main objective of the present review is to summarize the current state of knowledge on inhalers and inhaled drugs commonly used in the treatment of asthma. The review ranges from theoretical aspects (fundamentals and available devices and drugs) to practical and relevant aspects for asthma care in the clinical setting (therapeutic strategies, education, and adherence to inhalers).

  19. Inhalant allergies in children.

    PubMed

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted.

  20. Inhalant Abuse and Dextromethorphan.

    PubMed

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan.

  1. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique.

    PubMed Central

    Newman, S P; Weisz, A W; Talaee, N; Clarke, S W

    1991-01-01

    BACKGROUND The metered dose inhaler is difficult to use correctly, synchronising actuation with inhalation being the most important problem. A breath actuated pressurised inhaler, designed to help patients with poor inhaler technique, was compared with a conventional metered dose inhaler in terms of aerosol deposition and bronchodilator response. METHODS Radioaerosol deposition and bronchodilator response to 100 micrograms salbutamol were measured in 18 asthmatic patients, who inhaled from a conventional metered dose inhaler by their own chosen metered dose inhaler technique, from a conventional metered dose inhaler by a taught metered dose inhaler technique, and from a breath actuated pressured inhaler (Autohaler). RESULTS In the 10 patients who could coordinate actuation and inhalation of the inhaler on their own deposition of aerosol in the lungs and bronchodilator response were equivalent on the three study days. By contrast, in the eight patients who could not coordinate the mean (SEM) percentage of the dose deposited in the lungs with their own inhaler technique (7.2% (3.4%] was substantial lower than those attained by the taught metered dose inhaler technique (22.8% (2.5%] and by Autohaler (20.8% (1.7%]. CONCLUSION Although of little additional benefit to asthmatic patients with good coordination, the Autohaler is potentially a valuable aid to those with poor coordination, and should be considered in preference to a conventional metered dose inhaler in any patient whose inhaler technique is not known to be satisfactory. Images PMID:1750017

  2. Modeling Deposition of Inhaled Particles

    EPA Science Inventory

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeutic dose delivered by inhaled pharmacological drugs. Howeve...

  3. Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation.

    PubMed

    Williams, R O; Brown, J; Liu, J

    1999-05-01

    The purpose of this study was to investigate the influence of micronization technique on performance and stability of the model drug formulated in a suspension-based pressurized metered-dose inhaler (pMDI). The model drug, triamcinolone acetonide (TAA), was subjected to ball milling or air-jet milling prior to formulation of the pMDI. The dose delivery characteristics of the emitted aerosol cloud were monitored for the ball-milled, air-jet-milled, and unmicronized TAA pMDI formulations prior to and after storage at 25 and 40 degrees C. Cascade impaction was used to determine the aerodynamic particle size distribution of the emitted dose. Both micronization techniques reduced the drug particle size distribution and the polydispersity of the drug particles to a similar extent, but the ball-milling technique reduced the crystallinity of the drug to a greater degree compared to the air-jet-milling technique. The air-jet-milled and unmicronized TAA pMDI displayed similar aerodynamic particle size distributions of the emitted aerosol and respirable fractions over the storage period. The ball-milled TAA resulted in a pMDI formulation with the smallest aerodynamically sized particles and the highest respirable fraction compared to the air-jet-milled or unmicronized TAA pMDI formulations. The micronization techniques significantly influenced the dose delivery characteristics as a result of different initial particle size distributions, amorphous contents, and surface energies.

  4. The efficacy and safety of triple inhaled treatment in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis using Bayesian methods

    PubMed Central

    Kwak, Min-Sun; Kim, Eunyoung; Jang, Eun Jin; Kim, Hyun Jung; Lee, Chang-Hoon

    2015-01-01

    Purpose Although tiotropium (TIO) and inhaled corticosteroid (ICS)/long-acting β-agonists are frequently prescribed together, the efficacy of “triple therapy” has not been scientifically demonstrated. We conducted a systematic review and meta-analysis using Bayesian methods to compare triple therapy and TIO monotherapy. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for randomized controlled trials comparing the efficacy and safety of triple therapy and TIO monotherapy in patients with chronic obstructive pulmonary disease (COPD). We conducted a meta-analysis to compare the effectiveness and safety of triple therapy and TIO monotherapy using Bayesian random effects models. Results Seven trials were included, and the risk of bias in the majority of the studies was acceptable. There were no statistically significant differences in the incidence of death and acute exacerbation of disease in the triple therapy and TIO monotherapy groups. Triple therapy improved the prebronchodilator forced expiratory volume in 1 second (mean difference [MD], 63.68 mL; 95% credible interval [CrI], 45.29–82.73), and patients receiving triple therapy showed more improvement in St George Respiratory Questionnaire scores (MD, −3.11 points; 95% CrI, −6.00 to −0.80) than patients receiving TIO monotherapy. However, both of these differences were lower than the minimal clinically important difference (MCID). No excessive adverse effects were reported in triple therapy group. Conclusion Triple therapy with TIO and ICSs/long-acting β-agonists was only slightly more efficacious than TIO monotherapy in treating patients with COPD. Further investigations into the efficacy of new inhaled drugs are needed. PMID:26604734

  5. Nonthermal Inhalation Injury.

    DTIC Science & Technology

    1992-01-01

    understand the effects of the various byproducts of combustion on the human body. A thorough knowledge of the physiological mechanisms , relevant...as soon as possible. Overview of Smoke Inhalation Physiology The physiologic mechanisms of injury from smoke inhalation are multiple and complex...to breathe Lower airway obstruction Dyspnea, tachypnea, wheezing, rhonchi, carbonaceous sputum Parenchymal injury Dyspnea, tachypnea, rales Table 1

  6. Inhalants in Peru.

    PubMed

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  7. Cerebral blood flow in sickle cell cerebrovascular disease

    SciTech Connect

    Huttenlocher, P.R.; Moohr, J.W.; Johns, L.; Brown, F.D.

    1984-05-01

    Cerebral blood flow (CBF) has been studied by the xenon-133 (/sup 133/Xe) inhalation method in 16 children with suspected sickle cell cerebrovascular disease. Abnormalities consisting of decreases in total, hemispheral, or regional CBF were found in 17 of 26 studies. Eleven studies performed immediately after stroke, transient ischemic attack, or depression of state of alertness showed abnormalities. In addition to confirming regional cerebrovascular insufficiency in children with stroke due to major cerebral artery occlusion, the method detected diffuse decrease in CBF in children with stupor, coma, and seizures who had normal angiographic findings. In contrast, six of seven studies obtained after exchange transfusion or during maintenance on hypertransfusion therapy showed normal findings. The difference between results in patients with acute neurologic disturbances and those receiving transfusion therapy was statistically significant (P less than .005). The data indicate that the /sup 133/Xe method reliably demonstrates cerebrovascular impairment in sickle cell disease. They also suggest that CBF changes in patients with sickle cell disease can be reversed by exchange transfusion and by hypertransfusion therapy. The /sup 133/Xe CBF method may be useful for following up children with sickle cell disease who are at high risk for recurrent stroke.

  8. An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma

    PubMed Central

    Burden, Anne; Roche, Nicolas; Miglio, Cristiana; Hillyer, Elizabeth V; Postma, Dirkje S; Herings, Ron MC; Overbeek, Jetty A; Khalid, Javaria Mona; van Eickels, Daniela; Price, David B

    2017-01-01

    Background Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre–post historical database study to investigate asthma-related outcomes by treatment. Methods We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Results Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%–100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. Conclusion We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require

  9. Evaluating the sensitivity, reproducibility and flexibility of a method to test hard shell capsules intended for use in dry powder inhalers.

    PubMed

    Chong, Rosalind H E; Jones, Brian E; Díez, Fernando; Birchall, James C; Coulman, Sion A

    2016-03-16

    Pharmaceutical tests for hard shell capsules are designed for orally administered capsules. The use of capsules in dry powder inhalers is widespread and increasing and therefore more appropriate tests are required to ensure quality and determine if these capsules are fit for purpose. This study aims to determine the flexibility, reproducibility and sensitivity of a quantitative method that is designed to evaluate the puncture characteristics of different capsule shell formulations under different climatic conditions. A puncture testing method was used to generate force displacement curves for five capsule formulations that were stored and tested at two different temperatures (5°C and 19°C). Force-displacement puncture profiles were reproducible for individual capsule shell formulations. The methodology was able to discriminate between capsules produced using different primary materials i.e. gelatin versus hypromellose, as well as more minor changes to capsule formulation i.e. different material grades and excipients. Reduced temperature increased the forces required for capsule puncture however further work is required to confirm its significance. Results indicate the method provides a reproducible and sensitive means of evaluating capsule puncture. Future studies should validate the methodology at different test sites, using different operators and with different capsule shell formulations.

  10. Budesonide Oral Inhalation

    MedlinePlus

    Budesonide is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma. Budesonide powder for oral inhalation (Pulmicort Flexhaler) is used in adults and children 6 ...

  11. Acetylcysteine Oral Inhalation

    MedlinePlus

    Acetylcysteine inhalation is used along with other treatments to relieve chest congestion due to thick or abnormal ... that causes problems with breathing, digestion, and reproduction). Acetylcysteine is in a class of medications called mucolytic ...

  12. Zanamivir Oral Inhalation

    MedlinePlus

    ... you use an inhaled medication to treat asthma, emphysema, or other breathing problems and you are scheduled ... the air passages that lead to the lungs); emphysema (damage to air sacs in the lungs); or ...

  13. Ipratropium Oral Inhalation

    MedlinePlus

    Ipratropium oral inhalation is used to prevent wheezing, shortness of breath, coughing, and chest tightness in people ... damage to the air sacs in the lungs). Ipratropium is in a class of medications called bronchodilators. ...

  14. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... mouth or throat irritation, rinse your mouth with water, chew gum, or suck sugarless hard candy after using pirbuterol.Inhalation devices require regular cleaning. Once a week, remove the mouthpiece cover, turn ...

  15. Umeclidinium Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... Do not use umeclidinium inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  16. Olodaterol Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... Do not use olodaterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  17. Inhaled human insulin.

    PubMed

    Strack, Thomas R

    2006-04-01

    The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human

  18. A novel sulfur mustard (HD) vapor inhalation exposure system for accurate inhaled dose delivery

    PubMed Central

    Perry, Mark R.; Benson, Eric M.; Kohne, Jonathon W.; Plahovinsak, Jennifer L.; Babin, Michael C.; Platoff, Gennady E.; Yeung, David T.

    2014-01-01

    Introduction A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube. Methods Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Animal breathing parameters were monitored real-time by an in-line pneumotach, pressure transducer, and Buxco pulmonary analysis computer/software. For each exposure, the challenge atmosphere was allowed to stabilize at the desired concentration while the anesthetized animal was provided humidity controlled clean air. Once the target concentration was achieved and stable, a portion of the challenge atmosphere was drawn past the endotracheal tube, where the animal inhaled the exposure ad libitum. During the exposure, HD vapor concentration and animal weight were used to calculate the needed inhaled volume to achieve the target inhaled dose (μg/kg). The exposures were halted when the inhaled volume was achieved. Results The exposure system successfully controlled HD concentrations from 22.2 to 278 mg/m3 and accurately delivered inhaled doses between 49.3 and 1120 μg/kg with actual administered doses being within 4% of the target level. Discussion This exposure system administers specific HD inhaled doses to evaluate physiological effects and for evaluation of potential medical countermeasure treatments. PMID:25291290

  19. Measurement of human CYP1A2 induction by inhalation exposure to benzo(a)pyrene based on in vivo isotope breath method.

    PubMed

    Duan, Xiaoli; Shen, Guofeng; Yang, Hongbiao; Lambert, George; Wei, Fusheng; Zhang, Junfeng Jim

    2016-01-01

    Cytochrome P450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of certain carcinogens, and inducible by toxic substrates. To date, few studies have investigated in vivo CYP1A2 induction in humans and its relationship to polycylic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). Non-smoking healthy male coke-oven workers (n = 30) were recruited as 'exposure' group, and non-smoking healthy office workers in the same city (n = 10) were selected as 'control' group, to test whether high inhalation exposure to PAHs can induce CYP1A2 activity in human livers. Significantly higher inhalation exposure of PAHs were found among the exposure group compared to the control. Inhalation BaP exposure concentration in the exposure group was more than 30 times higher than the control group (p < 0.001). However, the exposure group did not exhale significant higher levels of (13)CO2/(12)CO2 in breath samples (p = 0.81), and no significant relationship was found between the inhaled BaP concentration and the (13)CO2/(12)CO2 ratio (p = 0.91). A significant association was found between the (13)CO2/(12)CO2 exhalation and dietary BaP intake level. Hepatic CYP1A2 activity/induction level was not effected by inhaled BaP but was altered by ingestion of BaP.

  20. Olfactory deposition of inhaled nanoparticles in humans

    PubMed Central

    Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

    2016-01-01

    Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

  1. ASSOCIATION BETWEEN THE INTRODUCTION OF A NEW CYSTIC FIBROSIS INHALED ANTIBIOTIC CLASS AND CHANGE IN PREVALENCE OF PATIENTS RECEIVING MULTIPLE INHALED ANTIBIOTIC CLASSES

    PubMed Central

    Dasenbrook, Elliott C.; Konstan, Michael W.; VanDevanter, Donald R.

    2014-01-01

    Background In 2010, aztreonam for inhalation solution joined aminoglycosides and colistimethate as a new cystic fibrosis (CF) chronic inhaled antimicrobial therapy. We studied how introduction of this new inhaled antibiotic class changed management of US CF patients. Methods Use of inhaled aminoglycosides, colistimethate, and aztreonam among patients followed in the CF Foundation Patient Registry was analyzed by age group, lung disease stage, and microbiologic status both annually, and at individual visits between 2009 and 2012. Results The overall prevalence of inhaled antibiotic use did not change during the period, but the prevalence of annual and any visit treatment with >1 inhaled antibiotic class more than doubled. Adults, those with advanced lung disease, and those with >1 Pseudomonas aeruginosa respiratory culture were more likely to receive >1 antibiotic class. Conclusions Inhaled antibiotic management of US CF patients has dramatically changed in association with the introduction of a third inhaled antibiotic class. PMID:25496726

  2. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  3. Inhalation exposure methodology.

    PubMed Central

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.). PMID:6383799

  4. Extracellular killing of inhaled pneumococci in rats

    SciTech Connect

    Coonrod, J.D.; Marple, S.; Holmes, G.P.; Rehm, S.R.

    1987-12-01

    Early clearance of inhaled Staphylococcus aureus is believed to be caused by phagocytosis by alveolar macrophages. In murine models inhaled pneumococci are cleared even more rapidly than S. aureus. Conventional opsonins appear to play no role in this clearance, and recently it has been shown that murine alveolar lining material contains free fatty acids and other soluble factors that are directly bactericidal for pneumococci. To determine whether non-phagocytic factors are involved in pneumococcal clearance, we compared the site of killing of inhaled pneumococci and S. aureus in rats using histologic methods and bronchoalveolar lavage. Spontaneous lysis of pneumococci was prevented by use of autolysin-defective pneumococci or by substitution of ethanolamine for choline in the cell wall. Histologic studies showed that the percent of inhaled staphylococci associated with alveolar macrophages always exceeded the percent of staphylococci cleared, whereas there was little association of pneumococci with macrophages during clearance. Analysis of the intracellular or extracellular location of iron 59 in bronchoalveolar lavage fluid of rats that had inhaled aerosols of /sup 59/Fe-labeled bacteria suggested that staphylococci were killed predominantly in macrophages and pneumococci in the extracellular space. When /sup 59/Fe-labeled pneumococci or staphylococci were ingested and killed by macrophages in vitro, the /sup 59/Fe remained with the macrophages, suggesting that the extracellular location of /sup 59/Fe during pneumococcal killing in vivo was not caused by rapid turnover of /sup 59/Fe in macrophages. Studies of the site of killing of inhaled type 25 pneumococci labeled exclusively in the cell wall with carbon 14-ethanolamine confirmed the results obtained with /sup 59/Fe-labeled pneumococci. Thus, early killing of inhaled pneumococci, unlike staphylococci, appears to take place outside of macrophages.

  5. MODELING DEPOSITION OF INHALED PARTICLES

    EPA Science Inventory

    Modeling Deposition of Inhaled Particles: ABSTRACT

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeut...

  6. Pneumoconiosis after sericite inhalation

    PubMed Central

    Algranti, E; Handar, A; Dumortier, P; Mendonca, E; Rodrigues, G; Santos, A; Mauad, T; Dolhnikoff, M; De Vuyst, P; Saldiva, P; Bussacos, M

    2005-01-01

    Aims: To investigate and describe the radiological, clinical, and pathological changes in miners and millers exposed to sericite dust with mineralogical characteristics of inhaled dust. Methods: The working premises were visited to examine the sericite processing and to classify the jobs according to make qualitative evaluation. Respirable dust was collected and the amount of crystalline silica and particle size distribution were measured. Forty four workers were examined by a standard questionnaire for respiratory symptoms, spirometry, and chest x ray. Material from an open lung biopsy was reviewed for histopathological and mineralogical analysis, together with sericite samples from the work site to compare the mineral characteristics in lung lesions and work area. Results: Respirable dust contained 4.5–10.0% crystalline silica. Particle size distribution showed a heavy burden of very fine particles (23–55%) with a mean diameter of <0.5 µm. Mean age of sericite miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In 52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or above, and 18.2% (8/44) had a reduced FEV1. There was a significant association between exposure indices and x ray category. Histological studies of the lung biopsy showed lesions compatible with mixed dust fibrosis with no silicotic nodules. x Ray diffraction analysis of the lung dust residue and the bulk samples collected from work area showed similar mineralogical characteristics. Muscovite and kaolinite were the major mineral particle inclusions in the lung. Conclusion: Exposure to fine sericite particles is associated with the development of functional and radiological changes in workers inducing mixed dust lesions, which are distinct histologically from silicosis. PMID:15723874

  7. Inhalants. Specialized Information Service.

    ERIC Educational Resources Information Center

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about inhalant abuse. Article 1 presents findings on the psychophysiological effects related to the use of amyl or butyl nitrate as a "recreational drug." Article 2 suggests a strong association between chronic sniffing of the solvent toulene and irreversible brain damage. Article 3 warns…

  8. Antitubercular inhaled therapy: opportunities, progress and challenges.

    PubMed

    Pandey, Rajesh; Khuller, G K

    2005-04-01

    Pulmonary tuberculosis remains the commonest form of this disease and the development of methods for delivering antitubercular drugs directly to the lungs via the respiratory route is a rational therapeutic goal. The obvious advantages of inhaled therapy include direct drug delivery to the diseased organ, targeting to alveolar macrophages harbouring the mycobacteria, reduced risk of systemic toxicity and improved patient compliance. Research efforts have demonstrated the feasibility of various drug delivery systems employing liposomes, polymeric microparticles and nanoparticles to serve as inhalable antitubercular drug carriers. In particular, nanoparticles have emerged as a remarkably useful tool for this purpose. While some researchers have preferred dry powder inhalers, others have emphasized nebulization. Beginning with the respiratory delivery of a single antitubercular drug, it is now possible to deliver multiple drugs simultaneously with a greater therapeutic efficacy. More experience and expertise have been observed with synthetic polymers, nevertheless, the possibility of using natural polymers for inhaled therapy has yet to be explored. Several key issues such as patient education, cost of treatment, stability and large scale production of drug formulations, etc. need to be addressed before antitubercular inhaled therapy finds its way from theory to clinical reality.

  9. Deposition and biokinetics of inhaled nanoparticles

    PubMed Central

    2010-01-01

    Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones. The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles. We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures. PMID:20205860

  10. Vapor inhalation of alcohol in rats.

    PubMed

    Gilpin, Nicholas W; Richardson, Heather N; Cole, Maury; Koob, George F

    2008-07-01

    Alcohol dependence constitutes a neuroadaptive state critical for understanding alcoholism, and various methods have been utilized to induce alcohol dependence in animals, one of which is alcohol vapor exposure. Alcohol vapor inhalation provides certain advantages over other chronic alcohol exposure procedures that share the ultimate goal of producing alcohol dependence in rats. Chronic alcohol vapor inhalation allows the experimenter to control the dose, duration, and pattern of alcohol exposure. Also, this procedure facilitates testing of somatic and motivational aspects of alcohol dependence. Chronic exposure to alcohol vapor produces increases in alcohol-drinking behavior, increases in anxiety-like behavior, and reward deficits in rats. Alcohol vapor inhalation as a laboratory protocol is flexible, and the parameters of this procedure can be adjusted to accommodate the specific aims of different experiments. This unit describes the options available to investigators using this procedure for dependence induction, when different options are more or less appropriate, and the implications of each.

  11. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  12. Treatment of Inhalation Injury

    DTIC Science & Technology

    1983-01-21

    injuries not visible with endoscopy. . Thermal and especially chemical inhalation injuries. Direct damage to the surfactant is probably implicated. o...exists a set of indirect alveolar lesions, subordinated to the skin burn itself, which is common in patients with extensive burns. This we call the...normo or hypocapnia. Very likely, a 5th lesional level exists which is the capillary itself(Venus et al). By primary or secondary damage , it affects the

  13. Regional cerebral blood flow for singers and nonsingers while speaking, singing, and humming a rote passage

    SciTech Connect

    Formby, C.; Thomas, R.G.; Halsey, J.H. Jr. )

    1989-05-01

    Two groups of singers (n = 12,13) and a group of nonsingers (n = 12) each produced the national anthem by (1) speaking and (2) singing the words and by (3) humming the melody. Regional cerebral blood flow (rCBF) was measured at rest and during each phonation task from seven areas in each hemisphere by the {sup 133}Xe-inhalation method. Intrahemisphere, interhemisphere, and global rCBF were generally similar across phonation tasks and did not yield appreciable differences among the nonsingers and the singers.

  14. Regional cerebral blood flow in essential hypertension: data evaluation by a mapping system

    SciTech Connect

    Rodriguez, G.; Arvigo, F.; Marenco, S.; Nobili, F.; Romano, P.; Sandini, G.; Rosadini, G.

    1987-01-01

    Regional cerebral blood flow was studied by means of the 133Xe inhalation method in 26 untreated and 10 treated patients with essential hypertension. The untreated subjects were divided into newly and previously diagnosed groups to assess the relation between regional cerebral blood flow and the duration of hypertension. The overall flow reduction was more marked in the frontal and temporal regions in the previously diagnosed group, and this was attributed to pathological changes in the district served by the middle cerebral artery. Regional temporal lobe impairment was also noted in the newly diagnosed and treated subjects. A significant correlation was found between regional cerebral blood flow and mean arterial blood pressure.

  15. How to Use Metered-Dose Inhalers

    MedlinePlus

    ... inhaler the right way so that the full dose of medication reaches your lungs. You can use ... inhaler.These directions explain how to use metered-dose inhalers. If you are using a different type ...

  16. Inhalation delivery of protein therapeutics.

    PubMed

    Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

    2013-04-01

    Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

  17. Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalation.

    PubMed

    Aswania, Osama; Chrystyn, Henry

    2002-05-01

    The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4x5 mg from an Intal metered dose inhaler (MDI), (ii) 4x5 mg from an MDI attached to a large volume spacer (MDI+SP) and (iii) 20 mg from an Intal Spinhaler (DPI). Urine samples were provided at 0, 0.5, 1, 2, 5 and 24 h post dose. The mean (S.D.) amount of sodium cromoglycate excreted in the urine during the first 30 min post inhalation was 38.1 (27.5), 222.3 (120.3) and 133.1 (92.2) microg following MDI, MDI+SP and DPI, respectively. The mean ratio (90% confidence interval) of these amounts excreted in the urine over the first 30 min for MDI+SP vs. MDI, DPI vs. MDI and MDI+SP vs. DPI was 801.0 (358.0, 1244; p<0.002)%, 457.0 (244.0, 670.0; p<0.02)% and 262.4 (110.2, 414.5)%, respectively. Similarly for the 24 h cumulative amount of sodium cromoglycate excreted over the 24 h post inhalation the ratios were 375.4 (232.9, 517.9; p<0.005)%, 287.5 (183.4, 391.6; p<0.02)% and 211.4 (88.3, 334.5)%, respectively. The results highlight better lung deposition of sodium cromoglycate from a metered dose inhaler attached to a large volume spacer.

  18. Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers.

    PubMed

    Hochrainer, Dieter; Hölz, Hubert; Kreher, Christoph; Scaffidi, Luigi; Spallek, Michael; Wachtel, Herbert

    2005-01-01

    Apart from particle size distribution, spray velocity is one of the most important aerosol characteristics that influence lung deposition of inhaled drugs. The time period over which the aerosol is released (spray duration) is also important for coordination of inhalation. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that delivers drug to the lung much more efficiently than pressurised metered dose inhalers (pMDIs). The objective of this study was to compare the velocity and spray duration of aerosol clouds produced by Respimat SMI with those from a variety of chlorofluorocarbon (CFC) and hydrofluoroalkane (HFA) pMDIs. All inhalers contained solutions or suspensions of bronchodilators. A videorecording method was used to determine the aerosol velocity. For spray duration, the time for generation of the Soft Mist by Respimat SMI was initially determined using three different methods (videorecording [techniques A and B], laser light diffraction and rotating disc). Videorecording was then used to compare the spray duration of Respimat SMI with those from the other inhalers. The Soft Mist produced by Respimat SMI moved much more slowly and had a more prolonged duration than aerosol clouds from pMDIs (mean velocity at a 10-cm distance from the nozzle: Respimat SMI, 0.8 m/sec; pMDIs, 2.0-8.4 m/sec; mean duration: Respimat SMI, 1.5 sec; pMDIs, 0.15-0.36 sec). These characteristics should result in improved lung and reduced oropharyngeal deposition, and are likely to simplify coordination of inhaler actuation and inhalation compared with pMDIs.

  19. Evaluation of the effectiveness of four different inhalers in patients with chronic obstructive pulmonary disease.

    PubMed Central

    van der Palen, J.; Klein, J. J.; Kerkhoff, A. H.; van Herwaarden, C. L.

    1995-01-01

    BACKGROUND--The percentage of patients inhaling their medication effectively varies widely, according to methods of assessment and inhalers used. This study was carried out to assess differences among four types of inhalers using inhaler-specific checklists. METHODS--Inhalation technique was evaluated in adult patients with chronic obstructive pulmonary disease (COPD). Inhalers investigated were either metered dose inhalers (MDIs) or the dry powder inhalers Turbohaler (Turbuhaler), Diskhaler, and Rotahaler. Errors were recorded against inhaler-specific checklists. From these, scores were derived by dividing the number of items correctly completed by the total number of items on the checklist and the result was expressed as a percentage. For every inhaler "essential actions" were identified and scores on these key manoeuvres were calculated. The percentage of patients performing all these essential actions correctly was also calculated. Scores were also compared with adjustment for differences in relevant patient characteristics. RESULTS--Important differences among inhalers were found. Of 152 patients with COPD (mean (SD) age 55.1 (8.7) years), those with MDIs performed worst, especially when only essential items were considered. Patients with a Diskhaler did best, although after correction for patient characteristics the differences tended to diminish. Only 60% of patients were able to perform all essential inhaler actions satisfactorily. Of those using the Diskhaler, 96% did so correctly, while the corresponding figure for those using the MDI was only 24%. CONCLUSIONS--Many patients with COPD use their inhaler ineffectively. After adjusting for patient characteristics, differences among inhalers, although less pronounced, persist. Patients using a Diskhaler made fewest errors, while most patients using MDIs made crucial mistakes. Images PMID:8553275

  20. Exubera. Inhale therapeutic systems.

    PubMed

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  1. Investigation of Appropriate Inhalation Technique for Mometasone Furoate Dry Powder Inhaler.

    PubMed

    Yokoyama, Haruko; Ito, Kanako; Mihashi, Hirokazu; Shiraishi, Yasuyuki; Takayanagi, Risa; Yamada, Yasuhiko

    2016-01-01

    The aim of this study was to establish an appropriate inhalation method with a mometasone furoate dry powder inhaler (MF-DPI). Utilizing a tone-based inhalation training device, we investigated the maximum peak inspiratory flow rate time (Tmax PIFR) and peak inspiratory flow rate (PIFR) to determine whether either had an influence on lung deposition with use of an MF-DPI. A low tone indicated a PIFR of 28 L/min and a high tone that of 40 L/min, while 60 L/min was considered to be the standard. We established an inhalation profile in consideration of a human inhalation pattern, in which Tmax PIFR was set at 0.5 s (Tmax PIFR 0.5 s) and 2.5 s (Tmax PIFR 2.5 s). The reference cut-off value derived with a cascade impactor test was used for evaluation of the rate of delivered dose in the lung, which was the amount of drug from stage 3 to 7 at all PIFRs. We then investigated the relationship of the fine particle fraction (FPF) with the claimed dose at Tmax PIFR of 0.5 s and PIFR. There were no differences among the Tmax PIFR values for the doses emitted from the device or for the rate of delivered doses in stages 3-7. However, FPF for the claimed dose at 40 L/min was significantly lower than that at 60 L/min, which was dependent on PIFR. Our results showed that PIFR but not Tmax PIFR has an effect on lung deposition after inhalation with an MF-DPI.

  2. The rapid and effective administration of a beta 2-agonist to horses with heaves using a compact inhalation device and metered-dose inhalers.

    PubMed Central

    Tesarowski, D B; Viel, L; McDonell, W N; Newhouse, M T

    1994-01-01

    The purpose of the study was to administer therapeutic aerosol generated by metered-dose inhalers to horses exhibiting clinical signs of heaves using a compact inhalation device developed for human medicine. It was fitted to a custom face mask in order to study the effect of an inhaled beta 2-agonist, fenoterol. Pulmonary function testing was performed on six horses following an acute exacerbation of heaves, characterized by tachypnea, wheezes, crackles, and spasmodic cough. Horses inhaled fenoterol in 1 mg increments administered as one 200 microgram puff every 5-10 s with the recording of data 5 min after the cessation of drug inhalation. A significant effect of fenoterol was shown for maximum change in transpulmonary pressure, dynamic compliance, lung resistance, and work of breathing, and the wheezes and crackles disappeared when auscultation was performed at the end of the test. This study demonstrates a novel, highly effective method for the rapid administration of inhaled medication in horses. PMID:8055432

  3. Inhaled matters of the heart

    PubMed Central

    Zaky, Ahmed; Ahmad, Aftab; Dell’Italia, Louis J; Jahromi, Leila; Reisenberg, Lee Ann; Matalon, Sadis; Ahmad, Shama

    2015-01-01

    Inhalations of atmospheric pollutants, especially particulate matters, are known to cause severe cardiac effects and to exacerbate preexisting heart disease. Heart failure is an important sequellae of gaseous inhalation such as that of carbon monoxide. Similarly, other gases such as sulphur dioxide are known to cause detrimental cardiovascular events. However, mechanisms of these cardiac toxicities are so far unknown. Increased susceptibility of the heart to oxidative stress may play a role. Low levels of antioxidants in the heart as compared to other organs and high levels of reactive oxygen species produced due to the high energetic demand and metabolic rate in cardiac muscle are important in rendering this susceptibility. Acute inhalation of high concentrations of halogen gases is often fatal. Severe respiratory injury and distress occurs upon inhalation of halogens gases, such as chlorine and bromine; however, studies on their cardiac effects are scant. We have demonstrated that inhalation of high concentrations of halogen gases cause significant cardiac injury, dysfunction, and failure that can be critical in causing mortalities following exposures. Our studies also demonstrated that cardiac dysfunction occurs as a result of a direct insult independent of coexisting hypoxia, since it is not fully reversed by oxygen supplementation. Therefore, studies on offsite organ effects of inhaled toxic gases can impact development of treatment strategies upon accidental or deliberate exposures to these agents. Here we summarize the knowledge of cardiovascular effects of common inhaled toxic gases with the intent to highlight the importance of consideration of cardiac symptoms while treating the victims. PMID:26665179

  4. Inhaled insulin--does it become reality?

    PubMed

    Siekmeier, R; Scheuch, G

    2008-12-01

    After more than 80 years of history the American and European Drug Agencies (FDA and EMEA) approved the first pulmonary delivered version of insulin (Exubera) from Pfizer/Nektar early 2006. However, in October 2007, Pfizer announced it would be taking Exubera off the market, citing that the drug had failed to gain market acceptance. Since 1924 various attempts have been made to get away from injectable insulin. Three alternative delivery methods where always discussed: Delivery to the upper nasal airways or the deep lungs, and through the stomach. From these, the delivery through the deep lungs is the most promising, because the physiological barriers for the uptake are the smallest, the inspired aerosol is deposited on a large area and the absorption into the blood happens through the extremely thin alveolar membrane. However, there is concern about the long-term effects of inhaling a growth protein into the lungs. It was assumed that the large surface area over which the insulin is spread out would minimize negative effects. But recent news indicates that, at least in smokers, the bronchial tumour rate under inhaled insulin seems to be increased. These findings, despite the fact that they are not yet statistical significant and in no case found in a non-smoker, give additional arguments to stop marketing this approach. Several companies worked on providing inhalable insulin and the insulin powder inhalation system Exubera was the most advanced technology. Treatment has been approved for adults only and patients with pulmonary diseases (e.g., asthma, emphysema, COPD) and smokers (current smokers and individuals who recently quitted smoking) were excluded from this therapy. Pharmacokinetics and pharmacodynamics of Exubera are similar to those found with short-acting subcutaneous human insulin or insulin analogs. It is thus possible to use Exubera as a substitute for short-acting human insulin or insulin analogs. Typical side effects of inhaled insulin were coughing

  5. Laboratory study of selected personal inhalable aerosol samplers.

    PubMed

    Görner, Peter; Simon, Xavier; Wrobel, Richard; Kauffer, Edmond; Witschger, Olivier

    2010-03-01

    Assessment of inhalable dust exposure requires reliable sampling methods in order to measure airborne inhalable particles' concentrations. Many inhalable aerosol samplers can be used but their performances widely vary and remain unknown in some cases. The sampling performance of inhalable samplers is strongly dependent on particle size and ambient air velocity. Five inhalable aerosol samplers have been studied in two laboratory wind tunnels using polydisperse glass-beads' test aerosol. Samplers tested were IOM sampler (UK), two versions of CIP 10-I sampler, v1 and v2 (F), 37-mm closed face cassette sampler (USA), 37-mm cassette fitted up with an ACCU-CAP insert (USA), and Button sampler (USA). Particle size-dependent sampling efficiencies were measured in a horizontal wind tunnel under a 1 m s(-1) wind velocity and in a vertical tunnel under calm air, using a specific method with Coulter(R) counter particle size number distribution determinations. Compared with CEN-ISO-ACGIH sampling criteria for inhalable dust, the experimental results show fairly high sampling efficiency for the IOM and CIP 10-I v2 samplers and slightly lower efficiencies for the Button and CIP 10-I v1 samplers. The closed face cassette (4-mm orifice) produced the poorest performances of all the tested samplers. This can be improved by using the ACCU-CAP internal capsule, which prevents inner wall losses inside the cassette. Significant differences between moving air and calm air sampling efficiency were observed for all the studied samplers.

  6. Floating patterns of metered dose inhalers.

    PubMed

    Wolf, B L; Cochran, K R

    1997-01-01

    As long as metered dose inhalers have existed, patients have sought a reliable method to determine if a given canister was still potent. Concerning beta agonists, the answer to this question may be lifesaving. Issues of compliance have made dating canisters or counting doses impractical. Likewise, previous claims of floating characteristics are unreliable. In tap water, we float-tested 13 commonly used inhalers three times each, observing variations as they were incrementally actuated, emptying their contents. One essential pattern was observed. Almost all prescription-size canisters sink when full; all float by the time one-third of their contents is gone. Orientation of prescription-size canisters changes in a distinct pattern especially near 90% depletion. Sample-size canisters showed some variance. Results suggest that the pharmaceutical industry should include individual floating characteristics as part of the package insert as they provide a reproducible means of gauging contents.

  7. Assessing inhalation exposure from airborne soil contaminants

    SciTech Connect

    Shinn, J.H.

    1998-04-01

    A method of estimation of inhalation exposure to airborne soil contaminants is presented. this method is derived from studies of airborne soil particles with radioactive tags. The concentration of contaminants in air (g/m{sup 3}) can be derived from the product of M, the suspended respirable dust mass concentration (g/m{sup 3}), S, the concentration of contaminant in the soil (g/g), and E{sub f}, an enhancement factor. Typical measurement methods and values of M, and E{sub f} are given along with highlights of experiences with this method.

  8. Umeclidinium and Vilanterol Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... use umeclidinium and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  9. Fluticasone and Vilanterol Oral Inhalation

    MedlinePlus

    ... and chest tightness caused by chronic obstructive pulmonary (COPD; a group of diseases that affect the lungs ... use fluticasone and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short acting ( ...

  10. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... caused by asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic ... and salmeterol during an attack of asthma or COPD. Your doctor will prescribe a short-acting inhaler ...

  11. Potent Inhalational Anesthetics for Dentistry

    PubMed Central

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID:26866411

  12. Generation and characterization of aerosols and vapors for inhalation experiments.

    PubMed Central

    Tillery, M I; Wood, G O; Ettinger, H J

    1976-01-01

    Control of aerosol and vapor characteristics that affect the toxicity of inhaled contaminants often determines the methods of generating exposure atmospheres. Generation methods for aerosols and vapors are presented. The characteristics of the resulting exposure atmosphere and the limitations of the various generation methods are discussed. Methods and instruments for measuring the airborne contaminant with respect to various charcteristics are also described. PMID:797565

  13. [New inhalation anesthetics].

    PubMed

    Conzen, P; Nuscheler, M

    1996-08-01

    Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease.

  14. Smoke Inhalation Lung Injury: An Update

    PubMed Central

    Demling, Robert H.

    2008-01-01

    Objectives: The purpose of this study is to present a multifaceted, definitive review of the past and current status of smoke inhalation injury. History along with current understanding of anatomical, physiology, and biologic components will be discussed. Methods: The literature has been reviewed from the early onset of the concept of smoke inhalation in the 1920s to our current understanding as of 2007. Results: The results indicate that the current pathophysiologic concept is of a disease process that leads to immediate and delayed pulmonary injury best managed by aggressive physiologic support. Management approaches for the biochemical changes have not kept up with current knowledge. The lung injury process is activated by toxins in the smoke's gas and particle components and perpetuated by a resulting lung inflammation. This inflammatory process becomes self-perpetuating through the activation of a large number of inflammatory cascades. In addition, smoke injury leads to significant systemic abnormalities injuring other organs and accentuating the burn injury process and subsequently leading to mediator-induced cellular injury leading potentially to multisystem organ failure. Conclusions: Smoke inhalation injury results in the anatomic finding of denuded and sometimes sloughed airways mucosa. Physiologic findings include small airways containing fibrin casts of mucosa and neutrophils. Airway hyper-reactivity results as well, leading to further decreased collapse, causing obstruction. PMID:18552974

  15. Therapy and prophylaxis of inhaled biological toxins.

    PubMed

    Paddle, Brian M

    2003-01-01

    This review highlights the current lack of therapeutic and prophylactic treatments for use against inhaled biological toxins, especially those considered as potential biological warfare (BW) or terrorist threats. Although vaccine development remains a priority, the use of rapidly deployable adjunctive therapeutic or prophylactic drugs could be life-saving in severe cases of intoxication or where vaccination has not been possible or immunity not established. The current lack of such drugs is due to many factors. Thus, methods involving molecular modelling are limited by the extent to which the cellular receptor sites and mode of action and structure of a toxin need to be known. There is also our general lack of knowledge of what effect individual toxins will have when inhaled into the lungs - whether and to what extent the action will be cell specific and cytotoxic or rather an acute inflammatory response requiring the use of immunomodulators. Possible sources of specific high-affinity toxin antagonists being investigated include monoclonal antibodies, selected oligonucleotides (aptamers) and derivatized dendritic polymers (dendrimers). The initial selection of suitable agents of these kinds can be made using cytotoxicity assays involving cultured normal human lung cells and a range of suitable indicators. The possibility that a mixture of selected antibody, aptamer or dendrimer-based materials for one or more toxins could be delivered simultaneously as injections or as inhaled aerosol sprays should be investigated.

  16. Inhaler Costs and Medication Nonadherence Among Seniors With Chronic Pulmonary Disease

    PubMed Central

    Rogers, William H.; Safran, Dana Gelb; Wilson, Ira B.

    2010-01-01

    Background: Chronic pulmonary diseases (CPDs) such as asthma and COPD are associated with particularly high rates of cost-related medication nonadherence (CRN), but the degree to which inhaler costs contribute to this is not known. Here, we examine the relationship between inhaler-specific out-of-pocket costs and CRN in CPD. Methods: Using data obtained in 2006 in a national stratified random sample (N = 16,072) of community-dwelling Medicare beneficiaries aged ≥ 65 years, we used logistic regression to examine the relationship between inhaled medications, various types of out-of-pocket costs, and CRN in persons with CPD. Results: The prevalence of CRN in Medicare recipients with CPD using inhalers was 31%. In multivariate models, the odds that respondents with CPD using inhalers would report CRN was 1.43 (95% CI, 1.21-1.69) compared with respondents without CPD who were not using inhalers. Adjustment for out-of-pocket inhaler costs—but not adjustment for total medication costs or non-inhaler costs—eliminated this excess risk of CRN (OR, 0.95; 95% CI, 0.71-1.28). Patients paying > $20 per month for inhalers were at significantly higher risk for CRN compared with those who had no out-of-pocket inhaler costs. Conclusions: Individuals with CPD and high out-of-pocket inhaler costs are at increased risk for CRN relative to individuals on other medications. Physicians should be aware that inhalers can pose a particularly high risk of medication nonadherence for some patients. PMID:20418367

  17. Towards the optimisation and adaptation of dry powder inhalers.

    PubMed

    Cui, Y; Schmalfuß, S; Zellnitz, S; Sommerfeld, M; Urbanetz, N

    2014-08-15

    Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model.

  18. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  19. Inhaled chemotherapy in lung cancer: future concept of nanomedicine.

    PubMed

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

  20. The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes

    PubMed Central

    Bosnic-Anticevich, Sinthia; Chrystyn, Henry; Costello, Richard W; Dolovich, Myrna B; Fletcher, Monica J; Lavorini, Federico; Rodríguez-Roisin, Roberto; Ryan, Dermot; Wan Yau Ming, Simon; Price, David B

    2017-01-01

    Background Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known. Aims To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques. Methods A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an incidence rate ratio (IRR) comparing the rate of exacerbations between study cohorts. A secondary outcome compared average daily use of short-acting beta agonist (SABA). Results The final study sample contained 8,225 patients in each cohort (mean age 67 [SD, 10], 57% males, 37% current smokers). Patients in the similar-devices cohort had a lower rate of exacerbations compared with those in the mixed-devices cohort (adjusted IRR 0.82, 95% confidence interval [CI] 0.80–0.84) and were less likely to be in a higher-dose SABA group (adjusted proportional odds ratio 0.54, 95% CI 0.51–0.57). Conclusion COPD patients who were prescribed one or more additional inhaler devices requiring similar inhalation techniques to their previous device(s) showed better outcomes than those who were prescribed devices requiring different techniques. PMID:28053517

  1. Cerebral blood flow during paroxysmal EEG activation induced by sleep in patients with complex partial seizures

    SciTech Connect

    Gozukirmizi, E.; Meyer, J.S.; Okabe, T.; Amano, T.; Mortel, K.; Karacan, I.

    1982-01-01

    Cerebral blood flow (CBF) measurements were combined with sleep polysomnography in nine patients with complex partial seizures. Two methods were used: the 133Xe method for measuring regional (rCBF) and the stable xenon CT method for local (LCBF). Compared to nonepileptic subjects, who show diffuse CBF decreases during stages I-II, non-REM sleep onset, patients with complex partial seizures show statistically significant increases in CBF which are maximal in regions where the EEG focus is localized and are predominantly seen in one temporal region but are also propagated to other cerebral areas. Both CBF methods gave comparable results, but greater statistical significance was achieved by stable xenon CT methodology. CBF increases are more diffuse than predicted by EEG paroxysmal activity recorded from scalp electrodes. An advantage of the 133Xe inhalation method was achievement of reliable data despite movement of the head. This was attributed to the use of a helmet which maintained the probes approximated to the scalp. Disadvantages were poor resolution (7 cm3) and two-dimensional information. The advantage of stable xenon CT method is excellent resolution (80 mm3) in three dimensions, but a disadvantage is that movement of the head in patients with seizure disorders may limit satisfactory measurements.

  2. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  3. Parental Influence on Inhalant Use

    ERIC Educational Resources Information Center

    Baltazar, Alina; Hopkins, Gary; McBride, Duane; Vanderwaal, Curt; Pepper, Sara; Mackey, Sarah

    2013-01-01

    The purpose of this article is to examine the dynamics of the relationship between parents and their adolescent children and their association with lifetime and past-month inhalant usage. The population studied was seventh- through ninth-grade students in rural Idaho (N = 570). The authors found a small, but consistent, significant inverse…

  4. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  5. Dry powder inhalable formulations for anti-tubercular therapy.

    PubMed

    Parumasivam, Thaigarajan; Chang, Rachel Yoon Kyung; Abdelghany, Sharif; Ye, Tian Tian; Britton, Warwick John; Chan, Hak-Kim

    2016-07-01

    Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery.

  6. STATUS REPORT: EVIDENCE BASED ADVANCES IN INHALATION DOSIMETRY FOR GASES WITH EFFECTS IN THE LOWER RESPIRATORY TRACT AND IN THE BODY

    EPA Science Inventory

    This report summarizes the status of specific inhalation dosimetry procedures for gases as outlined in U.S. EPA’s 1994 Methods for Derivation of Inhalation Reference Concentrations and Applications of Inhalation Dosimetry (U.S. EPA 1994) and reviews recent scientific advances in...

  7. Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older

    PubMed Central

    Komase, Yuko; Asako, Akimoto; Kobayashi, Akihiro; Sharma, Raj

    2014-01-01

    Background In patients receiving inhaled medication, dissatisfaction with and difficulty in using the inhaler can affect treatment adherence. The incidence of handling errors is typically higher in the elderly than in younger people. The aim of the study was to assess inhaler preference for and handling errors with the ELLIPTA® dry powder inhaler (DPI), (GSK), compared with the established BREEZHALER™, a single-dose capsule DPI (Novartis), in inhalation device-naïve Japanese volunteers aged ≥40 years. Methods In this open-label, nondrug interventional, crossover DPI preference study comparing the ELLIPTA DPI and BREEZHALER, 150 subjects were randomized to handle the ELLIPTA or BREEZHALER DPIs until the point of inhalation, without receiving verbal or demonstrative instruction (first attempt). Subjects then crossed over to the other inhaler. Preference was assessed using a self-completed questionnaire. Inhaler handling was assessed by a trained assessor using a checklist. Subjects did not inhale any medication in the study, so efficacy and safety were not measured. Results The ELLIPTA DPI was preferred to the BREEZHALER by 89% of subjects (odds ratio [OR] 70.14, 95% confidence interval [CI] 33.69–146.01; P-value not applicable for this inhaler) for ease of use, by 63% of subjects (OR 2.98, CI 1.87–4.77; P<0.0001) for ease of determining the number of doses remaining in the inhaler, by 91% for number of steps required, and by 93% for time needed for handling the inhaler. The BREEZHALER was preferred to the ELLIPTA DPI for comfort of the mouthpiece by 64% of subjects (OR 3.16, CI 1.97–5.06; P<0.0001). The incidence of handling errors (first attempt) was 11% with ELLIPTA and 68% with BREEZHALER; differences in incidence were generally similar when analyzed by age (< or ≥65 years) or sex. Conclusion These data, obtained in an inhalation device-naïve population, suggest that the ELLIPTA DPI is preferred to an established alternative based on its ease

  8. [Inhalant abusers and psychiatric symptoms].

    PubMed

    Okudaira, K; Yabana, T; Takahashi, H; Iizuka, H; Nakajima, K; Saito, A

    1996-01-01

    There are different opinions about the cause of chronic psychiatric symptoms observed in drug abusers between Japanese and foreign psychiatrists. The Japanese seem to recognize the chronic psychosis as the result of drug abuse. In the other hand, foreigners diagnose these cases as dual diagnosis of drug abuse and psychosis. Authors studied the problem in this research. One of the authors has examined 120 inhalant abusers of all, in- and out-patients in Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital from 1991 to 1995. These patients were classified into three groups: psychosis group (23 patients), dependence group (51 patients) and abuse group (46 patients) according to their clinical courses and psychiatric symptoms. The psychosis group consists of patients who showed psychiatric symptoms such as hallucination, delusion and thought disturbance for long time after detoxification. The dependence group contains patients whose inhalant dependence was severe and met DSM-4 Diagnostic Criteria for Substance Dependence, but manifested no chronic psychiatric symptoms after detoxification. The patients belonging to abuse group were at the earlier stages of inhalant abuse and had no chronic psychiatric symptoms. The average age of the first inhalant abuse was 14.7 years old in the psychosis group, 14.8 years in the dependence group and 14.7 years in the abuse group. The average years of abuse was 9.0 years in the psychosis group, and 8.5 years in the dependence group. There was little difference between these two groups. The psychosis patients manifested chronic symptoms 5.7 years on average after the first abuse of inhalants. About one forth (26.1%) of the psychosis patients and only 5.9% of the dependence patients had family history of schizophrenia. The difference was statistically significant. These results suggest that chronic psychiatric symptoms are caused not only by inhalant abuse, but also by the genetic factors of psychosis of each patient. There have

  9. Inhalant Use among Indiana School Children, 1991-2004

    ERIC Educational Resources Information Center

    Ding, Kele; Torabi, Mohammad R.; Perera, Bilesha; Jun, Mi Kyung; Jones-McKyer, E. Lisako

    2007-01-01

    Objective: To examine the prevalence and trend of inhalant use among Indiana public school students. Methods: The Alcohol, Tobacco, and Other Drug Use among Indiana Children and Adolescents surveys conducted annually between 1991 and 2004 were reanalyzed using 2-way moving average, Poisson regression, and ANOVA tests. Results: The prevalence had…

  10. Study of inhaler technique in asthma patients: differences between pediatric and adult patients

    PubMed Central

    Manríquez, Pablo; Acuña, Ana María; Muñoz, Luis; Reyes, Alvaro

    2015-01-01

    Objective: Inhaler technique comprises a set of procedures for drug delivery to the respiratory system. The oral inhalation of medications is the first-line treatment for lung diseases. Using the proper inhaler technique ensures sufficient drug deposition in the distal airways, optimizing therapeutic effects and reducing side effects. The purposes of this study were to assess inhaler technique in pediatric and adult patients with asthma; to determine the most common errors in each group of patients; and to compare the results between the two groups. Methods: This was a descriptive cross-sectional study. Using a ten-step protocol, we assessed inhaler technique in 135 pediatric asthma patients and 128 adult asthma patients. Results: The most common error among the pediatric patients was failing to execute a 10-s breath-hold after inhalation, whereas the most common error among the adult patients was failing to exhale fully before using the inhaler. Conclusions: Pediatric asthma patients appear to perform most of the inhaler technique steps correctly. However, the same does not seem to be true for adult patients. PMID:26578130

  11. Inhalation therapy in mechanical ventilation

    PubMed Central

    Maccari, Juçara Gasparetto; Teixeira, Cassiano; Gazzana, Marcelo Basso; Savi, Augusto; Dexheimer-Neto, Felippe Leopoldo; Knorst, Marli Maria

    2015-01-01

    Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients. PMID:26578139

  12. Neptunium-237 inhalation in rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Buschbom, R L

    1986-12-01

    Groups of rats were exposed to aerosols of 237Np nitrate to determine clearance rates, retention and distribution at various intervals after inhalation. Initial lung burdens (ILB) after 237Np inhalation by three treatment groups were 0.12, 0.19 and 0.37 mu Ci/kg, respectively. Radiochemical analyses of animals killed at 4, 8, 14, 28 and 90 d, as well as data for others maintained until they became moribund, showed that their lung clearance followed a three-compartment model, clearance half-times for which were 1, 35, and 10,000 d, respectively. Only 3% of the ILB was retained after 90 d; 12% of that burden had translocated to the skeleton at 750 d; the half-time for skeletal retention was 2500 d. A single tumor was the only malignancy detected in the lungs of the 35 animals allowed to survive the early phase of the study.

  13. Inhaled anesthetics: an historical overview.

    PubMed

    Whalen, Francis X; Bacon, Douglas R; Smith, Hugh M

    2005-09-01

    Inhalational agents have played a pivotal role in anesthesia history. The first publicly demonstrated anesthetic of the modern era, diethyl ether, was an inhalational anesthetic. The attributes of a good agent, ability to rapidly induce anesthesia, with limited side effects has led research efforts for over a hundred and fifty years. The explosion hazard was largely conquered with the development of the halogenated agents in the 1950s. Rapid emergence, with limited nausea and vomiting continue to drive discovery efforts, yet the 'modern' agents continue to improve upon those in the past. The future holds promise, but perhaps the most interesting contrast over time is the ability to rapidly introduce new agents into practice. From James Young Simpson's dinner table one evening to the operating suite the next day, modern agents take decades from first synthesis to clinical introduction.

  14. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

    Hill, Nicholas S; Preston, Ioana R; Roberts, Kari E

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies.

  15. Brain permeability of inhaled corticosteroids.

    PubMed

    Arya, Vikram; Issar, Manish; Wang, Yaning; Talton, James D; Hochhaus, Guenther

    2005-09-01

    The aim of this study was to evaluate if the permeability of inhaled corticosteroids entering the brain is reduced and if P-glycoprotein (P-gp) transporters are involved. Currently employed inhaled corticosteroids were given intravenously and intratracheally to rats at a dose of 100 microg kg-1. An ex-vivo receptor binding assay was used to monitor over 12 h the glucocorticoid receptor occupancy in the brain and a systemic reference organ (kidney). The involvement of P-gp in the brain permeability of triamcinolone acetonide was assessed in wild-type mice and mdr1a(-/-) knockout mice (mice lacking the gene for expressing P-gp). After both forms of administration, the average brain receptor occupancies were 20-56% of those of the reference organ, with the more lipophilic drugs showing a more pronounced receptor occupation. While the receptor occupancies in the liver of wild-type and mdr1a(-/-) mice were similar after administration of triamcinolone acetonide, brain receptor occupancies in mdr1a(-/-) mice were significantly greater (mdr1a(-/-): 47.6%, 40.2-55.0%, n=14; 2; wild-type: 11.5+/-33.0%, n=14; 3). Penetration into the brain for inhaled corticosteroids (especially those of lower lipophilicity) is reduced. Experiments in mdr1a(-/-) mice confirmed the involvement of P-gp transporters. Further studies are needed to assess whether potential drug interactions at the transporter level are of pharmacological significance.

  16. Forced degradation study to develop and validate stability-indicating RP-LC method for the determination of ciclesonide in bulk drug and metered dose inhalers.

    PubMed

    Elkady, Ehab F; Fouad, Marwa A

    2011-12-15

    A simple, selective and precise stability-indicating reversed-phase liquid chromatographic method was developed and validated for the determination of ciclesonide. Ciclesonide was subjected to acid and alkali hydrolysis, oxidation, thermal and photo-degradation. The degradation products were well separated from the pure drug. The method was based on isocratic elution of ciclesonide and its degradation products on reversed phase C18 column (250 mm × 4.6 mm, 10 μm) - Phenomenex using a mobile phase consisting of ethanol-water (70:30, v/v) at a flow rate of 1 mL min(-1). Quantitation was achieved with UV detection at 242 nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 5-200 μg mL(-1). Desisobutyryl-ciclesonide was prepared by selective alkaline hydrolysis of the ester and proved to be the main degradation product. The proposed method was successfully applied to the determination of ciclesonide in bulk and in its pharmaceutical preparation.

  17. A Standard Reference Material for Calibration of the Cup Furnace Smoke Toxicity Method for Assessing the Acute Inhalation Toxicity of Combustion Products.

    PubMed

    Levin, Barbara C; Paabo, Maya; Schiller, Susannah B

    1991-01-01

    A standard reference material (SRM 1048) has been developed for use with the cup furnace smoke toxicity method. This SRM is to be used to calibrate the apparatus and to enable the user to have confidence that the method is being conducted in a correct manner and that the equipment is functioning properly. The toxicological results from this SRM should not be used to compare with those of other materials (i.e., to determine if the combustion products of a test material are more or less toxic than those from this SRM). SRM 1048 is an acrylonitrile-butadiene-styrene (ABS) and is the same as SRM 1007B which is used for calibrating the flaming mode of the Smoke Density Chamber test method (ASTM E-662 and NFPA 258). For the purposes of calibrating the cup furnace smoke toxicity method, LC50 and N-Gas values plus their respective 95% confidence limits have been determined and certified for two combustion modes (flaming and nonflaming) and two observation periods (for the 30 min exposure only and for the 30 min exposure plus a 14 d post-exposure period). The certified LC50 values plus 95% confidence intervals (in g/m(3)) are 27 ± 3 (30 min, flaming); 25 ± 3 (30 min+ 14 d, flaming); 58 ± 15 (30 min, nonflaming); and 53 + 12 (30 min+ 14 d, nonflaming). The certified N-Gas values plus 95% confidence intervals are 1.4 ± 0.2 (30 min, flaming); 1.5 ± 0.2 (30 min+ 14 d, flaming); 1.2 ± 0.2 (30 min, nonflaming); and 1.4 ± 0.2 (30 min+ 14 d, nonflaming). It is recommended that this SRM be used with the N-Gas approach to calibrate the cup furnace smoke toxicity method rather than to determine the complete LC50 values. The N-Gas approach has the advantage of providing information on the gases responsible for the lethalities as well as the toxic potency of the smoke. In addition, the N-Gas approach reduces the number of experimental animals, the time necessary to complete the calibration, and the expense.

  18. [Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti-infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris 2012].

    PubMed

    Peron, N; Le Guen, P; Andrieu, V; Bardot, S; Ravilly, S; Oudyi, M; Dubus, J-C

    2013-12-01

    The working group on aerosol therapy (GAT) of the Société de pneumologie de langue française (SPLF) organized its third "Aerosolstorming" in 2012. During the course of one day, different aspects of inhaled therapy were discussed, and these will be treated separately in two articles, this one being the first. Inhaled products represent a large volume of prescriptions both in the community and in hospital settings and they involve various specialties particularly ENT and respiratory care. Technical aspects of the development of these products, their mode of administration and compliance with their indications are key elements for the effective therapeutic use of inhaled treatments. In this first article, we will review issues concerning generic inhaled products, the existence of inhaled antidotes, new anti-infective agents and indications for inhaled pentamidine.

  19. Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

    PubMed Central

    Westerik, Janine A. M.; Carter, Victoria; Chrystyn, Henry; Burden, Anne; Thompson, Samantha L.; Ryan, Dermot; Gruffydd-Jones, Kevin; Haughney, John; Roche, Nicolas; Lavorini, Federico; Papi, Alberto; Infantino, Antonio; Roman-Rodriguez, Miguel; Bosnic-Anticevich, Sinthia; Lisspers, Karin; Ställberg, Björn; Henrichsen, Svein Høegh; van der Molen, Thys; Hutton, Catherine; Price, David B.

    2016-01-01

    Abstract Objective: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). Methods: This was a historical, multinational, cross-sectional study (2011–2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. Results: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26–3.40); obesity (OR 1.75; 1.17–2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04–2.36); female sex (OR 1.51; 1.08–2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04–2.02). Conclusions: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID:26810934

  20. A Novel Method for Quantifying the Inhaled Dose of Air Pollutants Based on Heart Rate, Breathing Rate and Forced Vital Capacity

    PubMed Central

    Greenwald, Roby; Hayat, Matthew J.; Barton, Jerusha; Lopukhin, Anastasia

    2016-01-01

    To better understand the interaction of physical activity and air pollution exposure, it is important to quantify the change in ventilation rate incurred by activity. In this paper, we describe a method for estimating ventilation using easily-measured variables such as heart rate (HR), breathing rate (fB), and forced vital capacity (FVC). We recruited healthy adolescents to use a treadmill while we continuously measured HR, fB, and the tidal volume (VT) of each breath. Participants began at rest then walked and ran at increasing speed until HR was 160–180 beats per minute followed by a cool down period. The novel feature of this method is that minute ventilation (V˙E) was normalized by FVC. We used general linear mixed models with a random effect for subject and identified nine potential predictor variables that influence either V˙E or FVC. We assessed predictive performance with a five-fold cross-validation procedure. We used a brute force selection process to identify the best performing models based on cross-validation percent error, the Akaike Information Criterion and the p-value of parameter estimates. We found a two-predictor model including HR and fB to have the best predictive performance (V˙E/FVC = -4.247+0.0595HR+0.226fB, mean percent error = 8.1±29%); however, given the ubiquity of HR measurements, a one-predictor model including HR may also be useful (V˙E/FVC = -3.859+0.101HR, mean percent error = 11.3±36%). PMID:26809066

  1. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-03-01

    acetyl -L- cysteine (Mucomyst™; NAC ), in ameliorating inhaled HD-induced lung injury was then assessed in the established model. This work was conducted...J and Sciuto AM. N- acetyl -L- cysteine ( NAC ) Protects Against Inhaled Sulfur Mustard (HD) Poisoning in the Large Swine. Clinical Toxicology, 2012...2012. N- acetyl -L- cysteine ( NAC ) Protects against inhaled sulfur mustard (HD) poisoning in the large swine. Clinical Toxicology; in preparation

  2. Disinfection of nitrous oxide inhalation equipment.

    PubMed

    Yagiela, J A; Hunt, L M; Hunt, D E

    1979-02-01

    Cross-infection by contaminated equipment is a potential hazard associated with conscious sedation with nitrous oxide and oxygen . Nosocomial infections have occasionally been linked wih the use of unsterile inhalation devices; microbial contamination of sterile nasal hoods routinely occurs during administration of nitrous oxide; and in vitro experiments indicate that subsequent use of contaminated nasal masks may lead to aspiration of microorganisms. Although the incidence of respiratory disease after such contamination is unknown, it is clear that disinfection of the nitrous oxide apparatus between patients is desirable. A simple cleaning method involving alkaline glutaraldehyde is described that provides adequate disinfection of the rubber goods used in the administration of gas. Superiority of this technique over previously recommended cleaning methods is shown.

  3. STIR Version 1.0 User's Guide for Pesticide Inhalation Risk

    EPA Pesticide Factsheets

    STIR estimates inhalation-type exposure based on pesticide-specific information. It also estimates spray droplet exposure using the application method and rate and then compares these exposure estimates to avian and mammalian toxicity data.

  4. Introduction of Inhaled Nitrous Oxide and Oxygen for Pain Management during Labour - Evaluation of Patients' and Midwives' Satisfaction.

    PubMed

    Dammer, U; Weiss, C; Raabe, E; Heimrich, J; Koch, M C; Winkler, M; Faschingbauer, F; Beckmann, M W; Kehl, S

    2014-07-01

    Aim: Effective pain management during labour is important because pain affects the birth experience. Epidural analgesia is effective but often it may not be possible; however, inhaled analgesia offers another option. Use of inhaled nitrous oxide and oxygen for pain management in labour is well established in obstetrics but is still not used much in Germany. This study aimed to investigate the acceptance of the inhaled analgesia of inhaled nitrous oxide and oxygen by midwives and pregnant women during labour. Material and Methods: In this observational study carried out between April and September 2013, a total of 66 pregnant women received inhaled nitrous oxide and oxygen during labour on request and after prior assessment of suitability. After the birth, all of the women and the responsible midwives were interviewed about their experience and satisfaction with the inhaled analgesia. Results: A statistically significant reduction of pain was achieved with nitrous oxide and oxygen. The inhaled analgesia was mostly used by women who refused epidural analgesia. The likelihood of using inhaled nitrous oxide and oxygen again was reported as higher for patients who tolerated it well (p = 0.0129) and used it in the second stage of labour (p = 0.0003) and when bearing down (p = 0.0008). Conclusion: Inhaled nitrous oxide and oxygen is an effective method for pain management during labour and is accepted well by women in labour and by midwives.

  5. Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion

    PubMed Central

    Aswania, O A; Corlett, S A; Chrystyn, H

    1999-01-01

    Aims To determine if a urinary excretion method, previously described for salbutamol, could also indicate the relative bioavailability of sodium cromoglycate to the lung following inhalation from a metered dose inhaler. Method Inhaled (INH), inhaled+oral charcoal (INHC), oral (ORAL) and oral+oral charcoal (ORALC) 20 mg doses of sodium cromoglycate were given via a randomised cross-over design to 11 healthy volunteers trained on how to use a metered dose inhaler. Urine samples were collected at 0.0, 0.5, 1.0 and up to 24 h post dosing and the sodium cromoglycate urinary concentration was measured using a high performance liquid chromatographic method. Results No sodium cromoglycate was detected in the urine up to 24 h following ORALC dosing. A mean (s.d.) of 3.6 (4.3) μg, 10.4 (10.9) μg and 83.7 (71.1) μg of the ORAL dose was excreted, in the urine, during the 0.5, 1.0 and 24 h post dose collection periods, respectively. Following INH dosing, the renal excretion was significantly higher (P < 0.01) with 32.9 (14.5) μg, 61.2 (28.3) μg and 305.6 (82.3) μg excreted, respectively. The SCG excreted at 0.5, 1.0 and 24 h collection periods following INHC dosing were 26.3 (8.4) μg, 49.3 (18.1) μg and 184.9 (98.4) μg, respectively. There was no significant difference between the excretion rate of sodium cromoglycate following INHC when compared with INH dosing in the first 0.5 and 1.0 h. Conclusions The urinary excretion of sodium cromoglycate in the first 0.5 h post inhalation can be used to compare the relative lung deposition of two inhaled products or of the same product using different inhalation techniques. This represents the relative bioavailability of sodium cromoglycate to the lung following inhalation. Similar 24 h urinary excretion of sodium cromoglycate can be use to compare the total dose delivered to the body from two different inhalation products/inhalation methods. This represents the relative bioavailability of sodium cromoglycate to the body

  6. Compliance with inhaled asthma medication in preschool children.

    PubMed Central

    Gibson, N. A.; Ferguson, A. E.; Aitchison, T. C.; Paton, J. Y.

    1995-01-01

    BACKGROUND--Previous studies have shown poor compliance with regular drug therapy in children and adults with asthma. In preschool children the parents supervise and are responsible for drug administration, but little is known of compliance in this group. In addition, there are few data on the patterns of drug use of inhaled prophylactic asthma therapy or of the relation between compliance and symptom control. A study was undertaken to address these issues with the hypothesis that parental supervision would result in good compliance. METHODS--The subjects were 29 asthmatic children aged 15 months to five years already established on inhaled prophylactic medication delivered through a large volume spacer. The prescribed drug regimens varied between subjects. This was an observational study using an electronic inhaler timer device to record the date and time of each actuation of the aerosol canister. Diary cards were used for parallel recording of symptoms and parentally reported compliance with a drug regimen. RESULTS--Variable and generally poor compliance was demonstrated with a median of 50% of study days with full compliance (subject range 0-94%) and an overall median of 77% of prescribed doses of therapy taken during the study period. No relation was found between frequency of prescribed regimen and good compliance. Day care was associated with poorer compliance. No relation between good compliance and low symptom scores was found. CONCLUSION--Compliance with inhaled prophylactic therapy is poor in preschool children with asthma whose medication is administered under parental supervision. Images PMID:8553301

  7. Wildlife ecological screening levels for inhalation of volatile organic chemicals.

    PubMed

    Gallegos, Patricia; Lutz, Jill; Markwiese, James; Ryti, Randall; Mirenda, Rich

    2007-06-01

    For most chemicals, evaluation of ecological risk typically does not address inhalation because ingestion dominates exposure. However, burrowing ecological receptors have an increased exposure potential from inhalation at sites contaminated with volatile chemicals in the subsurface. Evaluation of ecological risk from contaminants like volatile organic chemicals (VOCs) is constrained by a lack of relevant ecological screening levels (ESLs). To address this need, inhalation ESLs were developed for 16 VOCs: Acetone, benzene, carbon tetrachloride, chloroform, chloromethane, dichlorodifluoromethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,1-dichloroethene, methylene chloride, tetrachloroethene, toluene, 1,1,1-trichloroethane, trichloroethene, trichlorofluoromethane, and total xylene. These ESLs are based on Botta's pocket gopher (Thomomys bottae) as a representative fossorial receptor. The ESLs are presented with an emphasis on the process for developing inhalation toxicity reference values to illustrate the selection of suitable toxicity data and effect levels from the literature. The resulting ESLs provide a quantitative method for evaluating ecological risk of VOCs through comparison to relevant exposure data such as direct burrow-air measurements. The toxicity reference value development and ESL calculation processes and assumptions detailed here are provided as bases from which risk assessors can use or refine to suit site-specific needs with respect to toxicity and exposure inputs.

  8. Energy Efficient Monitoring of Metered Dose Inhaler Usage.

    PubMed

    Lalos, Aris S; Lakoumentas, John; Dimas, Anastasios; Moustakas, Konstantinos

    2016-12-01

    Life-long chronic inflammatory diseases of the airways, such as asthma and Chronic Obstructive Pulmonary Disease, are very common worldwide, affecting people of all ages, race and gender. One of the most important aspects for the effective management of asthma is medication adherence which is defined as the extent to which patients follow their prescribed action plan and use their inhaler correctly. Wireless telemonitoring of the medication adherence can facilitate early diagnosis and management of these diseases through the use of an accurate and energy efficient mHealth system. Therefore, low complexity audio compression schemes need to be integrated with high accuracy classification approaches for the assessment of adherence of patients that use of pressurized Metered Dose Inhalers (pMDIs). To this end, we propose a novel solution that enables the energy efficient monitoring of metered dose inhaler usage, by exploiting the specific characteristics of the reconstructed audio features at the receiver. Simulation studies, carried out with a large dataset of indoor & outdoor measurements have led to high levels of accuracy (98 %) utilizing only 2 % of the recorded audio samples at the receiver, demonstrating the potential of this method for the development of novel energy efficient inhalers and medical devices in the area of respiratory medicine.

  9. Inhaled corticosteroids: potency, dose equivalence and therapeutic index

    PubMed Central

    Daley-Yates, Peter T

    2015-01-01

    Glucocorticosteroids are a group of structurally related molecules that includes natural hormones and synthetic drugs with a wide range of anti-inflammatory potencies. For synthetic corticosteroid analogues it is commonly assumed that the therapeutic index cannot be improved by increasing their glucocorticoid receptor binding affinity. The validity of this assumption, particularly for inhaled corticosteroids, has not been fully explored. Inhaled corticosteroids exert their anti-inflammatory activity locally in the airways, and hence this can be dissociated from their potential to cause systemic adverse effects. The molecular structural features that increase glucocorticoid receptor binding affinity and selectivity drive topical anti-inflammatory activity. However, in addition, these structural modifications also result in physicochemical and pharmacokinetic changes that can enhance targeting to the airways and reduce systemic exposure. As a consequence, potency and therapeutic index can be correlated. However, this consideration is not reflected in asthma treatment guidelines that classify inhaled corticosteroid formulations as low-, mid- and high dose, and imbed a simple dose equivalence approach where potency is not considered to affect the therapeutic index. This article describes the relationship between potency and therapeutic index, and concludes that higher potency can potentially improve the therapeutic index. Therefore, both efficacy and safety should be considered when classifying inhaled corticosteroid regimens in terms of dose equivalence. The historical approach to dose equivalence in asthma treatment guidelines is not appropriate for the wider range of molecules, potencies and device/formulations now available. A more robust method is needed that incorporates pharmacological principles. PMID:25808113

  10. Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

    PubMed Central

    Albert, Martin; Corsilli, Daniel; Williamson, David R; Brosseau, Marc; Bellemare, Patrick; Delisle, Stéphane; Nguyen, Anne QN; Varin, France

    2017-01-01

    AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome (ARDS). METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of iNO (20 ppm) or nebulized epoprostenol (10 μg/mL) was done in all patients. Thereafter, inhaled milrinone (1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide (iNO) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen (PaO2) were recorded before and after each inhaled therapy administration. RESULTS The majority of ARDS were of pulmonary cause (n = 13) and pneumonia (n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass (n = 2), smoke inhalation injury (n = 1), thoracic trauma and pulmonary contusions (n = 2) and aspiration (n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and iNO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO2 from baseline was 8.8 mmHg [interquartile range (IQR) = 16.3], 6.0 mmHg (IQR = 18.4), 6 mmHg (IQR = 15.8) and 9.2 mmHg (IQR = 20.2) respectively with iNO, epoprostenol, inhaled milrinone, and iNO added to milrinone. Only iNO and the combination of inhaled milrinone and iNO had a statistically significant effect on PaO2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation

  11. Quality assurance test of delivered dose uniformity of multiple-dose inhaler and dry powder inhaler drug products.

    PubMed

    Tsong, Yi; Dong, Xiaoyu; Shen, Meiyu; Lostritto, Richard T

    2015-01-01

    The delivered dose uniformity is one of the most critical requirements for dry powder inhaler (DPI) and metered dose inhaler products. In 1999, the Food and Drug Administration (FDA) issued a Draft Guidance entitled Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products-Chemistry, Manufacturing and Controls Documentation and recommended a two-tier acceptance sampling plan that is a modification of the United States Pharmacopeia (USP) sampling plan of dose content uniformity (USP34<601>). This sampling acceptance plan is also applied to metered dose inhaler (MDI) and DPI drug products in general. The FDA Draft Guidance method is shown to have a near-zero probability of acceptance at the second tier. In 2000, under the request of The International Pharmaceutical Aerosol Consortium, the FDA developed a two-tier sampling acceptance plan based on two one-sided tolerance intervals (TOSTIs) for a small sample. The procedure was presented in the 2005 Advisory Committee Meeting of Pharmaceutical Science and later published in the Journal of Biopharmaceutical Statistics (Tsong et al., 2008). This proposed procedure controls the probability of the product delivering below a pre-specified effective dose and the probability of the product delivering over a pre-specified safety dose. In this article, we further propose an extension of the TOSTI procedure to single-tier procedure with any number of canisters.

  12. Effect of Menthol on Nicotine Pharmacokinetics in Rats After Cigarette Smoke Inhalation

    PubMed Central

    2012-01-01

    Introduction: The effect of menthol on nicotine disposition is important in understanding smoking behaviors among different racial groups. The present study was to evaluate whether menthol affects the pharmacokinetics of nicotine after cigarette smoke inhalation. Methods: Rats were exposed to mainstream smoke from either a nonmentholated or mentholated cigarette (1 puff/min for 10 min) using a smoke inhalation apparatus. For the multiple-cigarette smoke inhalation, rats received the smoke from either nonmentholated or mentholated cigarette (10 puffs) every 12 hr for a total of 17 cigarettes. Serial blood samples were collected during the 10-min inhalation phase for the single-cigarette smoke or the 17th cigarette inhalation and for 30 hr thereafter. Nicotine and its major metabolite cotinine were assayed by radioimmunoassay methods. Results: Following single-cigarette smoke inhalation, mentholated cigarettes significantly decreased the mean peak concentrations of nicotine in plasma (Cmax) from 27.1 to 9.61 ng/ml and the total area under the plasma concentration–time curves (AUC) from 977 to 391 ng min/ml as compared with those after nonmentholated cigarette smoke inhalation. Cmax and AUC values for cotinine were also significantly reduced by menthol. Similarly after multiple smoke inhalation, Cmax, AUC, and the mean average steady-state plasma concentration of nicotine as well as cotinine were significantly lower in mentholated cigarette inhalation. Interestingly, there was a significant increase in the cotinine to nicotine AUC ratio from 13.8 for the nonmentholated to 21.1 for the mentholated cigarette. Conclusions: These results suggest that menthol in mentholated cigarettes can substantially decrease the absorption and/or increase the clearance of nicotine. PMID:22311961

  13. Inhalant initiation and the relationship of inhalant use to the use of other substances.

    PubMed

    Shamblen, Stephen R; Miller, Ted

    2012-01-01

    Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study examined the sequencing of substances relative to inhalants and the post-initiation correlates of inhalant use between youth and young adulthood in nationally representative Add Health data. Analyses examined the relationship of substance of initiation to use of other substances, as well as an examination of the relationship between substance use and consequences. The analyses suggest that (a) those initiating their substance use careers with inhalants often go on to use hard drugs, (b) inhalant use likely occurs after alcohol and marijuana use, and (c) inhalant use during adolescence was associated with health and criminal consequences in both adolescence and young adulthood.

  14. How to use an inhaler - with spacer

    MedlinePlus

    ... After using your inhaler, rinse your mouth with water, gargle, and spit. This helps reduce side effects from your medicine. ... If you see powder in or around the hole, clean your inhaler. ... cap in warm water. Let them air dry overnight. In the morning, ...

  15. How to use an inhaler - no spacer

    MedlinePlus

    ... After using your inhaler, rinse your mouth with water, gargle, and spit. This helps reduce side effects from your medicine. ... If you see powder in or around the hole, clean your inhaler. ... cap in warm water. Let them air dry overnight. In the morning, ...

  16. Investigation of Inhalation Anthrax Case, United States

    PubMed Central

    Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-01-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States. PMID:24447835

  17. Investigation of inhalation anthrax case, United States.

    PubMed

    Griffith, Jayne; Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-02-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

  18. Parent's Guide to Preventing Inhalant Abuse

    MedlinePlus

    ... child or someone you know is an inhalant abuser, what can you do to help? Be alert for symptoms of inhalant abuse. If you suspect there's a problem, you should consider seeking professional help. Contact a local drug rehabilitation center or other services available in your ...

  19. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies.

    PubMed

    Klein, Christoph L; Wiench, Karin; Wiemann, Martin; Ma-Hock, Lan; van Ravenzwaay, Ben; Landsiedel, Robert

    2012-07-01

    A major health concern for nanomaterials is their potential toxic effect after inhalation of dusts. Correspondingly, the core element of tier 1 in the currently proposed integrated testing strategy (ITS) is a short-term rat inhalation study (STIS) for this route of exposure. STIS comprises a comprehensive scheme of biological effects and marker determination in order to generate appropriate information on early key elements of pathogenesis, such as inflammatory reactions in the lung and indications of effects in other organs. Within the STIS information on the persistence, progression and/or regression of effects is obtained. The STIS also addresses organ burden in the lung and potential translocation to other tissues. Up to now, STIS was performed in research projects and routine testing of nanomaterials. Meanwhile, rat STIS results for more than 20 nanomaterials are available including the representative nanomaterials listed by the Organization for Economic Cooperation and Development (OECD) working party on manufactured nanomaterials (WPMN), which has endorsed a list of representative manufactured nanomaterials (MN) as well as a set of relevant endpoints to be addressed. Here, results of STIS carried out with different nanomaterials are discussed as case studies. The ranking of different nanomaterials potential to induce adverse effects and the ranking of the respective NOAEC are the same among the STIS and the corresponding subchronic and chronic studies. In another case study, a translocation of a coated silica nanomaterial was judged critical for its safety assessment. Thus, STIS enables application of the proposed ITS, as long as reliable and relevant in vitro methods for the tier 1 testing are still missing. Compared to traditional subacute and subchronic inhalation testing (according to OECD test guidelines 412 and 413), STIS uses less animals and resources and offers additional information on organ burden and progression or regression of potential effects.

  20. A portable inhalational induction device provides co-operative induction of anaesthesia in preanaesthetic area for children

    PubMed Central

    Yun, Mi-Ja; Na, Hyo-Seok; Shin, Young Duck; Han, Jun-Sung; Hwang, Jung-Won; Kim, Chong Soo

    2010-01-01

    Background We introduce a new, simple portable inhalational induction device (PD) that provides co-operative inhalational induction of anaesthesia using N2O and subsequent sevoflurane in the preanaesthetic induction area in children. Methods Forty-five children (30 to 94 months old age, <35 kg) who were scheduled to undergo simple operations were assigned randomly to one of three regimens. Patients were encouraged by their parents to inhale N2O followed by sevoflurane (PD N2O-sevo group) or sevoflurane (PD sevo group) using a portable inhalational induction device in the preanaesthetic induction area until they were unable to respond to their names. They were then transferred to the operating room while maintaining inhalation of sevoflurane via the device. The control group underwent conventional inhalational induction in the operating room with the parents in attendance. Results Patients in the PD N2O-sevo group had a higher co-operative inhalation frequency than the patients in the PD sevo or the control group. Anaesthesia induction in the PD N2O-sevo and the PD sevo groups were faster than in the control group. Parent satisfaction score (0-100) was higher for the PD N2O-sevo group than for the control group. Conclusions A new portable inhalational induction device allows faster induction in co-operation with parents present in the preanaesthetic induction area compared to conventional inhalational induction in the unfamiliar operating room with the parents in attendance. PMID:20589175

  1. Relative lung bioavailability of generic sodium cromoglycate inhalers used with and without a spacer device.

    PubMed

    Aswania, O; Chrystyn, H

    2001-01-01

    The relative lung bioavailability of sodium cromoglycate following inhalation has been evaluated using urinary drug excretion in nine healthly volunteers. Each inhaled four 5 mg sodium cromoglycate doses from a generic metered dose inhaler (MDI) and when it was attached to large volume spacer (MDI + VOL). A breath-actuated MDI was also evaluated either used on its own (EB) or attached to a small volume spacer tube (EBO). The mean (SD) urinary excretion of sodium cromoglycate in the first 30 min post-inhalation was 34.1 (20.2), 211.7 (123.5), 29.3 (19.5) and 52.8 (36.0) microg following MDI, MDI+VOL, EB and EBO, respectively. The cumulative mean (SD) urinary excretion of sodium cromoglycate over the 24 h post-inhalation was 364.7 (266.2), 1227.1 (459.0), 280.2 (155.4) and 429.5 (176.7) microg. A metered dose inhaler attached to a large volume spacer delivers more sodium cromoglycate to the lungs than any other inhalation method.

  2. A review of the value of innovation in inhalers for COPD and asthma

    PubMed Central

    Virchow, Johann Christian; Akdis, Cezmi A.; Darba, Josep; Dekhuijzen, Richard; Hartl, Sylvia; Kobelt, Gisela; Roger, Albert; Simoens, Steven; Toumi, Mondher; Woodhouse, Ben; Plich, Adam; Torvinen, Saku

    2015-01-01

    Background Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. Methods In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. Conclusions The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms. PMID:27123170

  3. Experimental inhalation injury in the goat.

    PubMed

    Walker, H L; McLeod, C G; McManus, W F

    1981-11-01

    Inhalation injuries are usually produced by inhalation of gaseous or particulate products of incomplete combustion and are rarely due to heat per se unless steam is inhaled. The clinical and anatomic characteristics of an appropriate animal model should mimic the disease encountered clinically. A model of inhalation injury has been produced in anesthetized goats through the use of a modified bee smoker. The smoke is delivered at a low temperature and contains byproducts of incomplete combustion. This reproducible injury produces necrotic tracheobronchitis and bronchiolitis with pseudomembrane and cast formation in association with mild multifocal atelectasis and bronchopneumonia. These lesions spontaneously resolve within 3 weeks without supportive therapy. The upper trachea, protected from smoke injury by the inflated cuff of the endotracheal tube, showed no evidence of injury. This nonlethal injury is proposed as an appropriate model for evaluation of the pathophysiology and treatment of inhalation injury.

  4. Inhalants

    MedlinePlus

    ... area of the brain that gets damaged. The hippocampus, for example, is responsible for memory, so someone ... stimulants like cocaine and narcotics like heroin or morphine can kill you immediately. The old standbys like ...

  5. Inhalants

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  6. Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype

    EPA Science Inventory

    To determine if the GSTM1 null genotype is a risk factor for increased inflammatory response to inhaled endotoxin. Methods 35 volunteers who had undergone inhalation challenge with a 20 000 endotoxin unit dose of Clinical Center Reference Endotoxin (CCRE) were genotyped for the G...

  7. In Vitro Dosing Performance of the ELLIPTA® Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™)

    PubMed Central

    Leggett, Richard; Pang, Cheng; Charles, Stephen; Gillett, Ben; Prime, David

    2015-01-01

    Abstract Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA® dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo. Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast. A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler. Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only). Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6–136.9 L/min), pressure drops (1.2–13.8 kPa), and inhaled volumes through the inhaler (0.7–4.2L). DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed. Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy. Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy. Across a range of inspiratory profiles, DD was consistent, while ETD

  8. Factors related to the incorrect use of inhalers by asthma patients*

    PubMed Central

    Dalcin, Paulo de Tarso Roth; Grutcki, Denis Maltz; Laporte, Paola Paganella; de Lima, Paula Borges; Menegotto, Samuel Millán; Pereira, Rosemary Petrik

    2014-01-01

    OBJECTIVE: To evaluate inhaler technique in outpatients with asthma and to determine associations between the correctness of that technique and the level of asthma control. METHODS: This was a cross-sectional study involving patients > 14 years of age with physician-diagnosed asthma. The patients were recruited from the Asthma Outpatient Clinic of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, Brazil. The patients completed two questionnaires (a general questionnaire and an asthma control questionnaire based on the 2011 Global Initiative for Asthma guidelines), demonstrated their inhaler technique, and performed pulmonary function tests. Incorrect inhaler technique was defined as the incorrect execution of at least two of the predefined steps. RESULTS: We included 268 patients. Of those, 81 (30.2%) showed incorrect inhaler technique, which was associated with poor asthma control (p = 0.002). Logistic regression analysis identified the following factors associated with incorrect inhaler technique: being widowed (OR = 5.01; 95% CI, 1.74-14.41; p = 0.003); using metered dose inhalers (OR = 1.58; 95% CI, 1.35-1.85; p < 0.001); having a monthly family income < 3 times the minimum wage (OR = 2.67; 95% CI, 1.35-1.85; p = 0.008), and having > 2 comorbidities (OR = 3.80; 95% CI, 1.03-14.02; p = 0.045). CONCLUSIONS: In the sample studied, incorrect inhaler technique was associated with poor asthma control. Widowhood, use of metered dose inhalers, low socioeconomic level, and the presence of > 2 comorbidities were associated with incorrect inhaler technique. PMID:24626265

  9. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma

    PubMed Central

    Price, D; Hernandez, D; Magyar, P; Fiterman, J; Beeh, K; James, I; Konstantopoulos, S; Rojas, R; van Noord, J A; Pons, M; Gilles, L; Leff, J

    2003-01-01

    Background: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma. Methods: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 µg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 µg/day (n=448) or budesonide 1600 µg/day (n=441) for 12 weeks. Results: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1–3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" ß agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated. Conclusion: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone. PMID:12612295

  10. The importance of inhaler devices: the choice of inhaler device may lead to suboptimal adherence in COPD patients

    PubMed Central

    Darbà, Josep; Ramírez, Gabriela; Sicras, Antoni; Francoli, Pablo; Torvinen, Saku; Sánchez-de la Rosa, Rainel

    2015-01-01

    Objective This study aims to identify factors associated with poor adherence to COPD treatment in patients receiving a fixed-dose combination (FDC) of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), focusing on the importance of inhaler devices. Methods We conducted a retrospective and multicenter study based on a review of medical registries between 2007 and 2012 of COPD patients (n=1,263) treated with ICS/LABA FDC, whose medical devices were either dry powder inhalers (DPIs) or pressurized metered-dose inhalers (pMDI). Medication adherence included persistence outcomes through 18 months and medication possession ratios. Data on exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also included as confounders of adherence. Results The analyses revealed that COPD patients whose medication was delivered through a DPI were less likely to have medication adherence compared to patients with pMDI, after adjusting for confounding factors, especially active ingredients. Younger groups of patients were less likely to be adherent compared to the oldest group. Smoker men were less likely to be adherent compared to women and non-smokers. Comorbidities decreased the probability of treatment adherence. Those patients that visited their doctor once a month were more likely to adhere to their medication regimen; however, suboptimal adherence was more likely to occur among those patients who visited more than three times per month their doctor. We also found that worsening of COPD is negatively associated with adherence. Conclusion According to this study, inhaler devices influence patients’ adherence to long-term COPD medication. We also found that DPIs delivering ICS/LABA FDC had a negative impact on adherence. Patients’ clinic and socioeconomic characteristics were associated with adherence. PMID:26604733

  11. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

    Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation. Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data

  12. Particle inhalability at low wind speeds.

    PubMed

    Brown, James S

    2005-12-15

    Accurate quantification of the dose delivered by aerosol exposures is essential for estimating the risk of potential adverse health effects. The fraction of airborne particles that can enter the nose or mouth during inhalation is referred to as the inspirable particulate mass fraction. This inhalable fraction is equivalent to delivered dose for particles greater than approximately 25 microm (aerodynamic particle diameter, d(ae)), which deposit completely and almost exclusively in the extrathoracic airways. Particle inhalability at high wind speeds (1-9 m/s) has been well characterized. However, there is a paucity of data describing the inhalability of particles at low wind speeds (< or =0.3 m/s), which are typical of indoor environments. High-wind-speed criteria poorly describe inhalability at low wind speeds. Based on the aspiration efficiencies of blunt and sharp-edged inlets, a function was developed for oral inhalability, P(I(O)), of particles at low wind speeds. This function predicts a slow decline in P(I(O)) from 0.95 at d(ae)= 8 microm, to 0.5 at d(ae) = 74 microm, and 0.1 at d(ae)= 175 microm. Data available from the literature for inhalability at relatively low wind speeds during oral breathing are well described by this logistic function (r(2)= 0.69).

  13. Dynamics of airflow in a short inhalation

    PubMed Central

    Bates, A. J.; Doorly, D. J.; Cetto, R.; Calmet, H.; Gambaruto, A. M.; Tolley, N. S.; Houzeaux, G.; Schroter, R. C.

    2015-01-01

    During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective transport of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 l s−1 peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20 ms, resulting in large-amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions. PMID:25551147

  14. Inhalation challenge in humidifier fever.

    PubMed

    Edwards, J H; Cockcroft, A

    1981-05-01

    When exposed to an amount of contaminated humidifier water roughly equivalent to that inhaled over an 8-hour period at their work place, four out of six subjects developed symptoms of humidifier fever. Two non-exposed subjects failed to react to the same challenge. Characteristic lung function, temperature and leucocyte changes were recorded; however, a fall in gas transfer previously reported was not seen. That the reaction was immunologically mediated and not due to endotoxin activity was shown by a negative pyrogen response in rabbits inoculated intravenously with concentrated humidifier water. The nature of the immune response has not as yet been evaluated but it does not reside with the ability of humidifier fever antigens to activate complement. Skin testing produced an immediate weal and flare in the four subjects with precipitins and may reflect the presence of short-term anaphylactic IgG antibody.

  15. Inhaled Corticosteroids and Bone Health

    PubMed Central

    Chee, Carolyn; Sellahewa, Luckni; Pappachan, Joseph M

    2014-01-01

    Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease. PMID:25674178

  16. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  17. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  18. Animal model of sensitization by inhalation.

    PubMed Central

    Barboriak, J J; Knoblock, H W; Hensley, G T; Gombas, O F; Fink, J N

    1976-01-01

    Groups of rats exposed to daily inhalation challenge with aerosolized pigeon serum developed precipitating antibody within 2 weeks and definitive granulomatous inflammatory changes in the lung after 7 weeks of exposure. The dissociation of the two responses to an inhalation challenge indicate that the rat model may serve for screening of the various inhalant antigens for their sensitizing potential, and for investigation of the contributory role of some of the factors involved in the pathogenesis of hypersensitivity pneumonitis. Images FIG. 1 FIG. 2 PMID:939055

  19. Introduction: Aerosol Delivery of Orally Inhaled Agents

    PubMed Central

    Devadason, Sunalene G.; Kuehl, Philip J.

    2012-01-01

    Abstract Deposition scintigraphy methods have been used extensively to provide qualitative and quantitative data on aerosol drug deposition in the lungs. However, differences in methodology among the different centers performing these studies have limited the application of these techniques, especially in regulatory roles. As an introduction to the standardized techniques developed by the International Society for Aerosols in Medicine (ISAM) Regulatory Affairs Networking Group, we present potential advantages of the use of standard techniques for deposition scintigraphy. Specifically, we propose that standardized techniques would allow for better comparisons between labs and would facilitate multicenter studies. They would allow for improved methods of establishing equivalence and could be better utilized to establish dosing for new medications. They would allow for the performance of more accurate dose ranging or multidose studies and complement pharmacokinetic studies of new inhaled medications. Standardized techniques could help to establish the relationship between the deposition of drug in the lungs and clinical effect, and may also facilitate clinical measurements of deposited dose for medications with narrow therapeutic indices. In the sections that follow, we discuss the best techniques used to perform deposition scintigraphy through planar, single-photon emission computed tomography, and positron emission tomography modalities and propose a detailed set of standardized methods for each. These include methods for radiolabel validation, radiolabel accountability and mass balance, and imaging acquisition and analysis. PMID:23215846

  20. New noninvasive quantitative assessment of cerebral blood flow using N-isopropyl-(iodine 123)p-iodoamphetamine

    SciTech Connect

    Matsuda, H.; Higashi, S.; Tsuji, S.; Seki, H.; Sumiya, H.; Fujii, H.; Oba, H.; Terada, H.; Imai, K.; Tonami, N.

    1987-01-01

    The use of a nomogram is described as a new noninvasive quantitative assessment of cerebral blood flow using N-isopropyl-(/sup 123/I)p-iodoamphetamine (IMP) and single-photon emission computed tomography. The nomogram was constructed from a computer analysis of the flow value relative to varying washout rate of brain activities between early and late tomographic images, and partition coefficient between brain tissue and blood. The validity of this method was evaluated in normal volunteers and in patients with cerebrovascular disorders by comparing the cortical flow values (Y) estimated from the IMP-nomogram with initial slope indices (X) by the /sup 133/Xe inhalation method. A significant correlation (N = 42, r = 0.88, P less than .001) was demonstrated between them, and the regression line was Y = 1.6X-7. A development and confirmation of this method made it possible to measure flow values noninvasively with the use of IMP.

  1. A new noninvasive quantitative assessment of cerebral blood flow using N-isopropyl-(iodine 123)p-iodoamphetamine.

    PubMed

    Matsuda, H; Higashi, S; Tsuji, S; Seki, H; Sumiya, H; Fujii, H; Oba, H; Terada, H; Imai, K; Tonami, N

    1987-01-01

    The use of a nomogram is described as a new noninvasive quantitative assessment of cerebral blood flow using N-isopropyl-(123I)p-iodoamphetamine (IMP) and single-photon emission computed tomography. The nomogram was constructed from a computer analysis of the flow value relative to varying washout rate of brain activities between early and late tomographic images, and partition coefficient between brain tissue and blood. The validity of this method was evaluated in normal volunteers and in patients with cerebrovascular disorders by comparing the cortical flow values (Y) estimated from the IMP-nomogram with initial slope indices (X) by the 133Xe inhalation method. A significant correlation (N = 42, r = 0.88, P less than .001) was demonstrated between them, and the regression line was Y = 1.6X-7. A development and confirmation of this method made it possible to measure flow values noninvasively with the use of IMP.

  2. Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats.

    PubMed

    Zhou, Y; Zhu, W P; Cai, X J; Chen, M

    2016-04-07

    We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.

  3. Myocardial damage after inhalation of chloramines.

    PubMed

    Gonzalez-Castro, Alejandro; Holanda, Maria Soledad; Canas, Borja S; Morlote, Jesús G; Minambres, Eduardo; Prieto Solis, José A

    2006-04-01

    The objective of this case report was to document a rare case of myocardial damage, in the context of an accidental inhalation of chloramines, demonstrated by electrocardiogram and myocardium-specific enzymes.

  4. Asthma Inhalers: Which One's Right for You?

    MedlinePlus

    ... the medication is released by breathing in a deep, fast breath. Available types include a dry powder ... and convenient to carry. Doesn't require a deep, fast inhaled breath. Doesn't require a deep, ...

  5. ARDS following inhalation of hydrochloric acid.

    PubMed

    Bansal, D P; Ambegaonkar, Rahul; Radhika, P; Sharma, Manish

    2011-02-01

    The clinical spectrum of Inhalation injury can range from mild cough to a devastating ARDS. We herewith present a patient who is a goldsmith by occupation and his work consists of dissolving gold in Hydrochloric acid. He had accidentally inhaled fumes of Hydrochloric acid and presented with cough and breathlessness, later on required mechanical ventilation for ARDS and improved. This highlights the importance of not to neglect mild symptoms like cough and dyspnea in such a scenario which may have some hidden catastrophe.

  6. Conspicuous effect on treatment of mild-to-moderate COPD by combining deep-breathing exercise with oxygen inhalation.

    PubMed

    Liu, Yong-Qiang; Yan, Ling-Xian; Zhang, Li-Yan; Song, Qing-Hua; Xu, Rong-Mei

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) can lead to respiratory failure, but current pharmacological treatments focus on symptom relief or slowing disease progression. Here, the effectiveness of an alternative therapy combining deep-breathing exercises and oxygen inhalation therapy was assessed in mild-to-moderate COPD patients. Forty-two male mild-to-moderate COPD patients were randomly divided into a deep-breathing training group, an oxygen inhalation group, and a combination group (n=14 in each). In the deep-breathing training group, the patients were treated only by the deep-breathing exercise; in the oxygen inhalation group, the patients were treated only by oxygen inhalation; in the combination group, the patients were treated by combining the deep-breathing exercises with oxygen inhalation. Before treatment, there were no statistical differences in the general characteristics or lung function indexes between the three groups of patients (P > 0.05). However, after treatment, patients in the combination group had significantly better lung function indexes than they did before treatment, and their improvement was also superior to that of patients from the deep-breathing training group and the oxygen inhalation group (P < 0.01 and P < 0.05, respectively). Thus, a treatment method combining deep-breathing exercise with oxygen inhalation offers more significant lung function improvement in COPD patients than either the deep-breathing exercise or oxygen inhalation alone. This approach should be further explored for use in the clinic.

  7. Assessing inhalation injury in the emergency room

    PubMed Central

    Tanizaki, Shinsuke

    2015-01-01

    Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. PMID:27147888

  8. Home remedy or hazard? management and costs of paediatric steam inhalation therapy burn injuries

    PubMed Central

    Himdani, Sarah Al; Javed, Muhammad Umair; Hughes, Juliana; Falconer, Olivia; Bidder, Christopher; Hemington-Gorse, Sarah; Nguyen, Dai

    2016-01-01

    Background Steam inhalation has long been considered a beneficial home remedy to treat children with viral respiratory tract infections, but there is no evidence to suggest a benefit and children are at risk of serious burn injuries. Aim To determine the demographics, mechanism, management, and costs of steam inhalation therapy scalds to a regional burns centre in the UK, and to ascertain whether this practice is recommended by primary care providers. Design and setting A retrospective study of all patients admitted to a regional burns centre in Swansea, Wales, with steam inhalation therapy scalds. Method Patients who attended the burns centre for steam inhalation therapy scalds between January 2010 and February 2015 were identified using the burns database and data on patient demographics, treatment, and costs incurred were recorded. In addition, an electronic survey was e-mailed to 150 local GPs to determine whether they recommended steam inhalation therapy to patients. Results Sixteen children attended the burns centre with steam inhalation scalds. The average age attending was 7.4 years (range 1–15 years) and, on average, three children per year were admitted. The most common indication was for the common cold (n = 9). The average size of the burns was 3.1% (range: 0.25–17.0%) of total body area. One child was managed surgically; the remainder were treated with dressings, although one patient required a stay in a high-dependency unit. The total cost of treatment for all patients was £37 133. All in all, 17 out of 21 GPs surveyed recommended steam inhalation to their patients; eight out of 19 GPs recommended it for children aged <5 years. Conclusion Steam inhalation incurs a significant cost to patients and the healthcare system. Its practice continues to be recommended by GPs but children, due to their limited motor skills, curiosity, and poor awareness of danger, are at significant risk of burn injuries and this dangerous practice should no longer be

  9. Real-world asthma management with inhaler devices in Switzerland—results of the asthma survey

    PubMed Central

    Nicod, Laurent P.; Kohler, Malcolm

    2016-01-01

    Background The aim of the Asthma Survey was to generate insights about the daily practice of physicians with regard to inhaler devices used for treating asthma under real-world conditions in Switzerland. Methods A questionnaire was administered to 605 participating hospital- and practice-based Swiss physicians. Areas of interest were practical aspects of patient education, typical difficulties encountered when prescribing pressurized metered-dose inhalers (pMDI) and dry-powder inhalers (DPI), and reasons for physician preferences. Differences between the German-speaking part of Switzerland (D-CH) and French- and Italian-speaking parts of Switzerland (W-CH) linguistic regions were explored. Results Datasets from 529 physicians (291 D-CH and 238 W-CH) were suitable for analysis, 342 internists/general practitioners, 177 pulmonologists/allergologists, and 10 other. Approximately 90% of all participants declared being personally involved in providing inhaler device education to their patients. Practice assistants (33.0% vs. 9.2%, P<0.001) and pharmacists (6.9% vs. 19.7%, P<0.001) were more frequently involved in D-CH compared to W-CH. Patient skills with regard to inhalation technique were generally not monitored on a regular basis with only 34.0% of participants ensuring such checks at the scheduled visits. DPIs were overwhelmingly preferred over pMDI. Although the prevalence of typical handling errors was similar with both inhalers in the two regions, pMDIs were used more frequently in W-CH (P<0.001). Conclusions Real-world asthma management and inhaler preferences differ between D-CH and W-CH. While the importance of patient education is widely acknowledged, inhalation skills monitoring remains suboptimal. The reasons for higher pMDI preference in W-CH compared to D-CH deserve further research. PMID:28066588

  10. Inhaled delivery of Δ(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

    PubMed

    Nguyen, Jacques D; Aarde, Shawn M; Vandewater, Sophia A; Grant, Yanabel; Stouffer, David G; Parsons, Loren H; Cole, Maury; Taffe, Michael A

    2016-10-01

    Most human Δ(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano(®), e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ∼40 min of exposure, was of comparable magnitude (∼3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis.

  11. Inhaled nitric oxide and arterial oxygen tension in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension

    PubMed Central

    Katayama, Y.; Higenbottam, T. W.; d Diaz; Cremona, G.; Akamine, S.; Barbera, J. A.; Rodriguez-Roisin, R.

    1997-01-01

    BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which can improve gas exchange in acute lung injury. However, it is uncertain that this effect on arterial oxygenation can be generalised to all lung diseases. METHODS: The effects of inhaled NO on gas exchange were studied in nine patients with chronic obstructive pulmonary disease (COPD), 11 patients with severe pulmonary hypertension, and 14 healthy volunteers. A randomized sequence of 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask. RESULTS: Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension (TcPO2) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to 7.0 (0.5) kPa in patients with COPD. There was no change in TcPO2 in patients with severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon dioxide tension (TcPCO2), arterial oxygen saturation (SaO2) measured by pulse oximeter, or cardiac output determined by the transthoracic impedance method. CONCLUSIONS: Inhaled NO does not improve TcPO2 nor increase cardiac output in normal subjects and patients with COPD, suggesting that inhaled NO worsens gas exchange. This could represent inhaled NO overriding hypoxic pulmonary vasoconstriction in COPD. The finding that TcPO2 also fell when normal subjects inhaled NO suggests that a similar mechanism normally contributes to optimal gas exchange. Whilst inhaled NO can improve oxygenation, this effect should not be considered to be a general response but is dependent on the type of lung disease. 


 PMID:9059470

  12. Profile of inhalant users seeking treatment at a de-addiction centre in north India

    PubMed Central

    Gupta, Sunil; Nebhinani, Naresh; Basu, Debasish; Mattoo, Surendra Kumar

    2014-01-01

    Background & objectives: Inhalants are substances whose chemical vapors are inhaled to produce euphoric, disinhibiting, and exciting effects. Data on inhalant abuse in India are relatively scarce. We report the demographic and clinical profile of inhalant users among the treatment seekers at a Drug De-addiction and Treatment Centre in north India. Methods: The records of treatment seekers at the Drug De-addiction and Treatment Centre, over 10 years (2002-2011) were scanned to identify 92 cases reporting inhalant use. Of these 92 cases, the complete record files were available for 87 (94.6%) cases. These case files were reviewed and the relevant data were collected and analyzed. Results: Over the study period of 10 years, the number of cases with inhalant abuse per year rose steadily to peak at 20 cases (4.08% of new cases) in 2006 and then stabilized at 1-3 per cent of new cases annually. Of the 87 cases studied, all were males with a mean age of 18.9±4.12 yr, mean education of 9.8±3.42 yr and mean family income of 7676±7343.15 (median: 5000). Majority of subjects were unmarried (89.7%), urban resident (79.3%), and from a nuclear family (78.2%). About half of the subjects were students (50.6%). The most common inhalant used was typewriter correction fluid (73.6%) followed by typewriter diluent fluid (19.5%) and glue (6.9%). The most common reason for initiation was curiosity. The mean age of onset of inhalant use was 16.3±4.22 yr. Most subjects fulfilled the criteria for inhalant dependence (85.1%). Psychiatric co-morbidity and the family history of substance dependence were present in 26.4 and 32.9 per cent subjects, respectively. Majority of the subjects reported drug related problems, occupation and finance being the worst affected. Interpretations & conclusions: Our results showed that the inhalant users were mostly urban youth belonging to middle socio-economic class families. The principal sources of inhalant abuse were the commonly available substances

  13. Acute effect of inhaled bradykinin on tracheobronchial clearance in normal humans.

    PubMed Central

    Polosa, R; Hasani, A; Pavia, D; Agnew, J E; Lai, C K; Clarke, S W; Holgate, S T

    1992-01-01

    BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways. PMID:1465754

  14. Inhaled antibiotics in Cystic Fibrosis (CF) and non-CF bronchiectasis.

    PubMed

    Tay, George T P; Reid, David W; Bell, Scott C

    2015-04-01

    Bronchiectasis is a pathological diagnosis describing dilatation of the airways and is characterized by chronic lung sepsis. Bronchiectasis has multiple etiologies, but is usually considered in terms of whether it is due to the genetic disorder cystic fibrosis (CF) or secondary to other causes (non-CF bronchiectasis, NCFB). Inhaled antibiotics are used in bronchiectasis to suppress bacterial pathogens and reduce long-term lung function decline. The majority of the literature on inhaled antibiotics comes from studies on CF where the dominant bacterial pathogen in the airway is usually Pseudomonas aeruginosa. Thus, most aerosolized antibiotic regimens target this bacterium, but the emergence of molecular diagnostic methods has questioned this approach and more tailored strategies may need to be considered in CF based on the community composition of the lung microbiome. Similarly, the lung microbiome in NCFB has been found to be a complex polymicrobial one and the current practice of employing the same inhaled antibiotic regimes as are used in CF may no longer be appropriate in many patients. In this article, the use of inhaled antibiotics in CF and NCFB is considered in the light of improved understanding of the lung microbiome and why more tailored therapy may be needed based on molecular identification of the microbial pathogens present. The evidence for the use of currently available inhaled antibiotics and advances in inhaled drug packaging and delivery devices are discussed. Finally, the urgent need for prospective randomized clinical trials in CF and NCFB is highlighted and areas for future research identified.

  15. Validation of scores of use of inhalation devices: valoration of errors *

    PubMed Central

    Zambelli-Simões, Letícia; Martins, Maria Cleusa; Possari, Juliana Carneiro da Cunha; Carvalho, Greice Borges; Coelho, Ana Carla Carvalho; Cipriano, Sonia Lucena; de Carvalho-Pinto, Regina Maria; Cukier, Alberto; Stelmach, Rafael

    2015-01-01

    Abstract Objective: To validate two scores quantifying the ability of patients to use metered dose inhalers (MDIs) or dry powder inhalers (DPIs); to identify the most common errors made during their use; and to identify the patients in need of an educational program for the use of these devices. Methods: This study was conducted in three phases: validation of the reliability of the inhaler technique scores; validation of the contents of the two scores using a convenience sample; and testing for criterion validation and discriminant validation of these instruments in patients who met the inclusion criteria. Results: The convenience sample comprised 16 patients. Interobserver disagreement was found in 19% and 25% of the DPI and MDI scores, respectively. After expert analysis on the subject, the scores were modified and were applied in 72 patients. The most relevant difficulty encountered during the use of both types of devices was the maintenance of total lung capacity after a deep inhalation. The degree of correlation of the scores by observer was 0.97 (p < 0.0001). There was good interobserver agreement in the classification of patients as able/not able to use a DPI (50%/50% and 52%/58%; p < 0.01) and an MDI (49%/51% and 54%/46%; p < 0.05). Conclusions: The validated scores allow the identification and correction of inhaler technique errors during consultations and, as a result, improvement in the management of inhalation devices. PMID:26398751

  16. Intestinal circulation during inhalation anesthesia

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  17. Regional cerebral blood flow and anxiety: a correlation study in neurologically normal patients

    SciTech Connect

    Rodriguez, G.; Cogorno, P.; Gris, A.; Marenco, S.; Mesiti, C.; Nobili, F.; Rosadini, G.

    1989-06-01

    Regional CBF (rCBF) was evaluated by the /sup 133/Xe inhalation method in 60 neurologically normal patients (30 men and 30 women) and hemispheric and regional values were correlated with anxiety measurements collected by a self-rating questionnaire before and after the examination. Statistically significant negative correlations between rCBF and anxiety measures were found. rCBF reduction for high anxiety levels is in line with results previously reported by others and could be related to lower performance levels for moderately high anxiety scores as those reported in the present population. This could perhaps be explained by rearrangement of flow from cortical zones to deeper areas of the brain, classically known to be implicated in the control of emotions. However, these results should be interpreted cautiously, since they were obtained in patients and not in normal subjects.

  18. Safety of inhaled corticosteroids in the treatment of persistent asthma.

    PubMed Central

    Peters, Stephen P.

    2006-01-01

    OBJECTIVE: Inhaled corticosteroids (ICSs) are the most effective medications available for patients with persistent asthma of all severities and currently are recommended as the preferred asthma controller therapy by the National Heart, Lung and Blood Institute. Nevertheless, lingering concerns about potential adverse systemic effects of ICSs contribute to their underuse. This review discusses the safety of ICSs with respect to potential systemic effects of most concern to physicians and patients. METHODS: Articles reporting on the safety of ICSs in children and adults with persistent asthma were identified from the Medline database from January 1966 through December 2003, reference lists of review articles and international respiratory meetings. RESULTS: Ocular effects of ICSs and ICS effects on bone mineral density and adrenal function are minimal in patients maintained on recommended ICS doses. One-year growth studies in children have shown decreased growth velocity with ICSs, but long-term studies with inhaled budesonide and beclomethasone show no effect on final adult height, suggesting that these effects are transient. In addition, extensive data from the Swedish Medical Birth Registry show no increased risk of adverse perinatal outcomes when inhaled budesonide is administered to pregnant women with asthma. CONCLUSIONS: ICSs have minimal systemic effects in most patients when taken at recommended doses. The benefits of ICS therapy clearly outweigh the risks of uncontrolled asthma, and ICSs should be prescribed routinely as first-line therapy for children and adults with persistent disease. PMID:16775906

  19. [Inhalation therapy by dose-inhalers: analysis of patients performance and possibilities for improvement].

    PubMed

    Petro, W; Schuppenies, A

    2005-05-01

    Inhalation therapy in chronic obstructive airways disease requires an efficient inhalation technique. This study analyses step by step the mistakes made in the usage of different MDIs, relates these to patient information prior to the testing and examines several teaching procedures for improvement of knowledge and performance of the inhalation technique. 125 patients suffering from COPD were assigned to six different groups according to their background knowledge in the inhalation technique. The performance was assessed in standardized single steps and as overall performance. Furthermore the efficacy of an interactive pc-based-training program was evaluated. The worst performance was seen in patients who only used the suppliers medication leaflet as a guide. Patients trained in outpatient clinics as well as patients trained in small groups during an inpatient stay showed a better performance. A high improvement rate was seen in prior MDI naive patients after they had undergone the interactive pc-based training program. Most problems were detected in the application step "exhalation before inhalation" and in the actuation-inhalation step. Besides the classical and the pc-based training the use of MDI phantoms showed very good results. The practical conclusion of this study is that the ability of patients to use inhalation pharmacotherapy efficiently needs improvement. Training programs of different intensity lead to a different outcome in performance and knowledge depending on prior knowledge. Inhalation pharmacotherapy without adequate training is insufficient.

  20. Automatic identification and accurate temporal detection of inhalations in asthma inhaler recordings.

    PubMed

    Holmes, Martin S; Le Menn, Marine; D'Arcy, Shona; Rapcan, Viliam; MacHale, Elaine; Costello, Richard W; Reilly, Richard B

    2012-01-01

    Asthma is chronic airways disease characterized by recurrent attacks of breathlessness and wheezing. Adherence to medication regimes is a common failing for asthmatic patients and there exists a requirement to monitor such patients' adherence. The detection of inhalations from recordings of inhaler use can provide empirical evidence about patients' adherence to their asthma medication regime. Manually listening to recordings of inhaler use is a tedious and time consuming process and thus an algorithm which can automatically and accurately carry out this task would be of great value. This study employs a recording device attached to a commonly used dry powder inhaler to record the acoustic signals of patients taking their prescribed medication. An algorithm was developed to automatically detect and accurately demarcate inhalations from the acoustic signals. This algorithm was tested on a dataset of 255 separate recordings of inhaler use in real world environments. The dataset was obtained from 12 asthma outpatients who attended a respiratory clinic over a three month period. Evaluation of the algorithm on this dataset achieved sensitivity of 95%, specificity of 94% and an accuracy of 89% in detecting inhalations compared to manual inhalation detection.

  1. Inhalant Initiation and the Relationship of Inhalant Use to the Use of Other Substances

    ERIC Educational Resources Information Center

    Shamblen, Stephen R.; Miller, Ted

    2012-01-01

    Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study…

  2. Assessment of inhaler techniques employed by patients with respiratory diseases in southern Brazil: a population-based study*

    PubMed Central

    de Oliveira, Paula Duarte; Menezes, Ana Maria Baptista; Bertoldi, Andréa Dâmaso; Wehrmeister, Fernando César; Macedo, Silvia Elaine Cardozo

    2014-01-01

    OBJECTIVE: To identify incorrect inhaler techniques employed by patients with respiratory diseases in southern Brazil and to profile the individuals who make such errors. METHODS: This was a population-based, cross-sectional study involving subjects ≥ 10 years of age using metered dose inhalers (MDIs) or dry powder inhalers (DPIs) in 1,722 households in the city of Pelotas, Brazil. RESULTS: We included 110 subjects, who collectively used 94 MDIs and 49 DPIs. The most common errors in the use of MDIs and DPIs were not exhaling prior to inhalation (66% and 47%, respectively), not performing a breath-hold after inhalation (29% and 25%), and not shaking the MDI prior to use (21%). Individuals ≥ 60 years of age more often made such errors. Among the demonstrations of the use of MDIs and DPIs, at least one error was made in 72% and 51%, respectively. Overall, there were errors made in all steps in 11% of the demonstrations, whereas there were no errors made in 13%.Among the individuals who made at least one error, the proportion of those with a low level of education was significantly greater than was that of those with a higher level of education, for MDIs (85% vs. 60%; p = 0.018) and for DPIs (81% vs. 35%; p = 0.010). CONCLUSIONS: In this sample, the most common errors in the use of inhalers were not exhaling prior to inhalation, not performing a breath-hold after inhalation, and not shaking the MDI prior to use. Special attention should be given to education regarding inhaler techniques for patients of lower socioeconomic status and with less formal education, as well as for those of advanced age, because those populations are at a greater risk of committing errors in their use of inhalers. PMID:25410839

  3. [Health significance of inhaled particles].

    PubMed

    Gillissen, A; Gessner, C; Hammerschmidt, S; Hoheisel, G; Wirtz, H

    2006-03-24

    Particulates refer to particles, dust, dirt, soot and aerosol mists that has suspended in the surrounding air. They may consist of solids of various forms including fibres or liquids. Long term exposure to silicon dioxide containing dusts (crystalline silica: quartz, tridymite, cristobalite, coesite, stishovite) may cause pneumoconiosis in the form of acute or/either chronic silicosis. Asbestos refers to a divers family of crystalline hydrated fibrous siliates typically exhibiting a greater tha 3:1 length ot diameter ratio. It is subdivided into serpentine (Chrysotile) and amphibole (crocidolite, amosite, anthophyllite, tremolite, actinolite). Exposure to asbestos fibres may cause lung fibrosis and promote cancer of the lung or the pleura. Besides the induction of malignant diseases dust exposure may result in obstructive as well as restrictive lung diseases which may be compensate in case of the recognition as a occupational diseases. Other occupational exposures leading to pneumoconiosis are caused be talc, or metals including aluminium containing dusts. Also the group of man-made mineral (MMMFs) or vitreous fibres (MMVFs), including glass wool, rock wool, slag wool, glass filaments, microfibres, refractory ceramic fibres are bioactive under certain experimental conditions. Although it has been shown that MMMFs may cause malignancies when injected intraperitoneally in high quantities in rodents, inhalation trials and human studies could not reproduce these results in the same precision. Fine particles (particulate matter = PM) comprise one of the most widespread and harmful air pollutants in the industrialized world. PM may cause worsening of asthma and other respiratory diseases, reduce lung function development in children, potentially increased the risk of premature death in the elderly and enhance mortality from cardiac diseases. Because of the small size PM2.5 is seen to be even more hazardous than PM10.

  4. Inhaled linalool-induced sedation in mice.

    PubMed

    Linck, Viviane Moura; da Silva, Adriana Lourenço; Figueiró, Micheli; Piato, Angelo Luis; Herrmann, Ana Paula; Dupont Birck, Franciele; Caramão, Elina Bastos; Nunes, Domingos Sávio; Moreno, Paulo Roberto H; Elisabetsky, Elaine

    2009-04-01

    Linalool is a monoterpene often found as a major component of essential oils obtained from aromatic plant species, many of which are used in traditional medical systems as hypno-sedatives. Psychopharmacological evaluations of linalool (i.p. and i.c.v.) revealed marked sedative and anticonvulsant central effects in various mouse models. Considering this profile and alleged effects of inhaled lavender essential oil, the purpose of this study was to examine the sedative effects of inhaled linalool in mice. Mice were placed in an inhalation chamber during 60 min, in an atmosphere saturated with 1% or 3% linalool. Immediately after inhalation, animals were evaluated regarding locomotion, barbiturate-induced sleeping time, body temperature and motor coordination (rota-rod test). The 1% and 3% linalool increased (p<0.01) pentobarbital sleeping time and reduced (p<0.01) body temperature. The 3% linalool decreased (p<0.01) locomotion. Motor coordination was not affected. Hence, linalool inhaled for 1h seems to induce sedation without significant impairment in motor abilities, a side effect shared by most psycholeptic drugs.

  5. IRIS Toxicological Review of Formaldehyde (Inhalation) ...

    EPA Pesticide Factsheets

    UPDATE EPA is currently revising its Integrated Risk Information System (IRIS) assessment of formaldehyde to address the 2011 NAS peer review recommendations. This assessment addresses both noncancer and cancer human health effects that are relevant to assessing the risks from chronic inhalation exposure to formaldehyde. To facilitate discussion of several scientific issues pertinent to the assessment, EPA convened a state-of-the-science workshop on April 30 and May 1, 2014. This workshop focused on the following three themes: Evidence pertaining to the influence of formaldehyde that is produced endogenously (by the body during normal biological processes) on the toxicity of inhaled formaldehyde, and implications for the health assessment; Mechanistic evidence relevant to formaldehyde inhalation exposure and lymphohematopoietic cancers (leukemia and lymphomas); and Epidemiological research examining the potential association between formaldehyde exposure and lymphohematopoietic cancers (leukemia and lymphomas). June 2010: EPA is conducting an independent expert peer review by the National Academy of Sciences and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Formaldehyde-Inhalation that when finalized will appear on the Integrated Risk Information System (IRIS) database. This draft IRIS health assessment addresses both noncancer and cancer human health effects that may result from chronic inhal

  6. Method for detection of nuclear-plasma interactions in a 134Xe-doped exploding pusher at the National Ignition Facility

    DOE PAGES

    Bleuel, Daniel L.; Bernstein, Lee A.; Brand, Christopher A.; ...

    2016-06-10

    Angular momentum changes due to nuclear-plasma interactions on highly-excited nuclei in high energy density plasmas created at the National Ignition Facility can be measured through a change in isomer feeding following gamma emission. Here, we propose an experiment to detect these effects in 133Xe* in exploding pusher capsules.

  7. Mass spectrometer with a membrane interface for intraoperative monitoring the elimination of inhalation anesthetic and CO2 through the skin

    NASA Astrophysics Data System (ADS)

    Elizarov, A. Yu.; Ershov, T. D.; Levshankov, A. I.; Cherebillo, V. Yu.

    2016-11-01

    A new method is implemented in order to measure the concentration of CO2 and inhalation anesthetic sevoflurane eliminated through the skin during surgery. The concentration of inhalation anesthetic has been measured during general combined anesthesia (sevoflurane, fentanyl) and total intravenous anesthesia (propofol, fentanyl). The dependence of the concentration of CO2 and the inhalation anesthetic from the relaxation of smooth muscles in the walls of blood vessels under the effect of sevoflurane and propofol and on the stress response to surgical injury has been revealed for the first time.

  8. Inhaled Antibiotics for Lower Airway Infections

    PubMed Central

    Quon, Bradley S.; Goss, Christopher H.

    2014-01-01

    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. PMID:24673698

  9. Cow Dung Ingestion and Inhalation Dependence: A Case Report

    ERIC Educational Resources Information Center

    Khairkar, Praveen; Tiple, Prashant; Bang, Govind

    2009-01-01

    Although abuse of several unusual inhalants had been documented, addiction to cow dung fumes or their ashes has not been reported in medical literature as yet. We are reporting a case of cow dung dependence in ingestion and inhalational form.

  10. INHALATION EXPOSURE-RESPONSE ASSESSMENTS FOR FIVE CHEMICALS

    EPA Science Inventory

    Inhalation exposure-response assessments for five chemicals (acrolein, ethylene oxide, hexachlorocyclopentadiene, hydrogen sulfide, and phosgene) for less-than-lifetime durations are being developed to inform the development of the Inhalation Exposure-Response Analysis Methodolog...

  11. A cross-sectional observational study to assess inhaler technique in Saudi hospitalized patients with asthma and chronic obstructive pulmonary disease

    PubMed Central

    Ammari, Maha Al; Sultana, Khizra; Yunus, Faisal; Ghobain, Mohammed Al; Halwan, Shatha M. Al

    2016-01-01

    Objectives: To assess the proportion of critical errors committed while demonstrating the inhaler technique in hospitalized patients diagnosed with asthma and chronic obstructive pulmonary disease (COPD). Methods: This cross-sectional observational study was conducted in 47 asthmatic and COPD patients using inhaler devices. The study took place at King Abdulaziz Medical City, Riyadh, Saudi Arabia between September and December 2013. Two pharmacists independently assessed inhaler technique with a validated checklist. Results: Seventy percent of patients made at least one critical error while demonstrating their inhaler technique, and the mean number of critical errors per patient was 1.6. Most patients used metered dose inhaler (MDI), and 73% of MDI users and 92% of dry powder inhaler users committed at least one critical error. Conclusion: Inhaler technique in hospitalized Saudi patients was inadequate. Health care professionals should understand the importance of reassessing and educating patients on a regular basis for inhaler technique, recommend the use of a spacer when needed, and regularly assess and update their own inhaler technique skills. PMID:27146622

  12. Dry Powder Formulation of Plasmid DNA and siRNA for Inhalation.

    PubMed

    Chow, Michael Y T; Lam, Jenny K W

    2015-01-01

    Nucleic acid therapeutics has huge potential for the treatment of a wide range of diseases including respiratory diseases. Plasmid DNA (pDNA) and small interfering RNA (siRNA) are the two most widely investigated nucleic acids for therapeutic development. However, efficient and safe delivery of nucleic acids is still a major hurdle in translating nucleic acid therapy into clinical practice. For the treatment of respiratory diseases, administration via inhalation is the most direct and effective way to deliver therapeutic nucleic acids to the lungs. Although liquid aerosol formulation is investigated in most of the studies, it is not desirable in terms of maintaining the stability of nucleic acid especially during long-term storage. This problem could be circumvented by formulating the therapeutic nucleic acids into dry powder for inhalation, and should be considered as the future direction of developing inhalable nucleic acids. In this review, the three major particle engineering methods investigated for the preparation of inhalable pDNA and siRNA formulations, including spray drying (SD), spray freeze drying (SFD) and supercritical fluid (SFC) drying, are discussed and compared. Moreover, common assessment methods and the challenges of evaluating the biological activities of inhalable nucleic acid powders are also reviewed.

  13. Modification of sleep-waking and electroencephalogram induced by vetiver essential oil inhalation

    PubMed Central

    Cheaha, Dania; Issuriya, Acharaporn; Manor, Rodiya; Kwangjai, Jackapun; Rujiralai, Thitima; Kumarnsit, Ekkasit

    2016-01-01

    Background: Essential oils (EOs) have been claimed to modulate mental functions though the most of data were obtained from subjective methods of assessment. Direct effects of EO on brain function remained largely to be confirmed with scientific proof. This study aimed to demonstrate quantifiable and reproducible effects of commercial vetiver (Vetiveria zizanioides) EO inhalation on sleep-waking and electroencephalogram (EEG) patterns in adult male Wistar rats. The experiments were conducted during November 2013 - February 2014. Materials and Methods: The following electrode implantation on the skull, control, and treated animals were subjected for EEG recording while inhaling water and vetiver EO (20 and 200 µl), respectively. Fast Fourier transform was used for analysis of EEG power spectrum. Results: One-way ANOVA analysis confirmed that vetiver EO inhalation significantly increased total waking and reduced slow-wave sleep time. Moreover, EO inhalation decreased alpha and beta1 activity in both frontal and parietal cortices and increased gamma activity in the frontal cortex. Changes in these frequencies began almost from the start of the inhalation. Conclusion: These data suggest refreshing properties of vetiver EO on electrical brain activity and alertness. PMID:27069728

  14. Diagnostic Utility of Total IgE in Foods, Inhalant, and Multiple Allergies in Saudi Arabia.

    PubMed

    Al-Mughales, Jamil A

    2016-01-01

    Objective. To assess the diagnostic significance of total IgE in foods, inhalant, and multiple allergies. Methods. Retrospective review of the laboratory records of patients who presented with clinical suspicion of food or inhalant allergy between January 2013 and December 2014. Total IgE level was defined as positive for a value >195 kU/L; and diagnosis was confirmed by the detection of specific IgE (golden standard) for at least one food or inhalant allergen and at least two allergens in multiple allergies. Results. A total of 1893 (male ratio = 0.68, mean age = 39.0 ± 19.2 years) patients were included. Total IgE had comparable sensitivity (55.8% versus 59.6%) and specificity (83.9% versus 84.4%) in food versus inhalant allergy, respectively, but a superior PPV in inhalant allergy (79.1% versus 54.4%). ROC curve analysis showed a better diagnostic value in inhalant allergies (AUC = 0.817 (95% CI = 0.796-0.837) versus 0.770 (95% CI = 0.707-0.833)). In multiple allergies, total IgE had a relatively good sensitivity (78.6%), while negative IgE testing (<195 kU/L) predicted the absence of multiple allergies with 91.5% certitude. Conclusion. Total IgE assay is not efficient as a diagnostic test for foods, inhalant, or multiple allergies. The best strategy should refer to specific IgE testing guided by a comprehensive atopic history.

  15. [Xenon CT CBF mapping derived from two minutes inhalation].

    PubMed

    Toshima, R; Toyohara, K; Ebisawa, T; Ishikawa, K; Karashima, H; Shimojo, S; Miyahara, T

    1988-04-01

    Although xenon enhanced CT method for local cerebral blood flow measurement has been brought into a clinical practice, the technique has inherent limitations including anesthetic effects and expensive cost of xenon by a large consumption. To overcome these problems a modified method with a short-duration inhalation was developed and its validity was attested. Siemens Somatom SF with a resolution of 256 X 256 pixels and a scan time of 10 seconds was used. The subjects inhaled 50% Xe/O2 gas mixture from an apparatus consisted of Douglas bag and an open circuit. Xenon concentration in the expired gas was continuously monitored and estimated for arterial blood concentration by using a hematocrit correction. PaCO2 was monitored throughout the study. At the starting point and the endpoint of the inhalation two scans were performed respectively. Thus obtained four images were processed for CT noise cancellation, summation and subtraction to produce an in vivo autoradiography image. Local CBF was calculated from equations derived from the autoradiographic technique with a fixed partition coefficient of lambda = 1. Computer simulation studies were performed to find the optimal scan point to obtain an autoradiographic image and to estimate the calculation errors of this method. One minute and forty-five seconds was found to be the optimal scan point to gain an autoradiographic image in view of a balance between linearity of CBF/enhancement curve and total amount of tissue enhancement. The theoretical errors due to the assumption for a fixed partition coefficient were calculated to be 8% underestimation for gray matter and 5% overestimation for white matter.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to...

  17. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition...

  18. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition...

  19. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to...

  20. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition...

  1. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition...

  2. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to...

  3. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to...

  4. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition...

  5. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to...

  6. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation airflow will be measured in the facepiece or mouthpiece while the apparatus is operated by a...

  7. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation airflow will be measured in the facepiece or mouthpiece while the apparatus is operated by a...

  8. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation airflow will be measured in the facepiece or mouthpiece while the apparatus is operated by a...

  9. 40 CFR 79.61 - Vehicle emissions inhalation exposure guideline.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., densities and shapes, and to predict where in the respiratory tract such particles may be deposited. It... to particles which are capable of being inhaled and may be deposited anywhere within the respiratory...) Principles and design criteria of inhalation exposure systems. Proper conduct of inhalation toxicity...

  10. Physical Symptoms and Psychological Distress among Inhalant Users.

    ERIC Educational Resources Information Center

    Joe, George W.; And Others

    1991-01-01

    Among 110 Mexican-American adolescents with varying drug use histories, self-reported physical health problems were not related to inhalant use history, but blood analyses indicated a relationship between extensive inhalant use and liver problems. Psychological distress symptoms were related to inhalant use and physical symptoms. Contains 23…

  11. Trends in suicide by carbon monoxide inhalation in King County, Washington: 1996-2009.

    PubMed

    Schmitt, Michael W; Williams, Timothy L; Woodard, Kristinza R; Harruff, Richard C

    2011-05-01

    Carbon monoxide (CO) inhalation is one of the leading methods of suicide in the United States. A sharp increase in suicide by inhaling the CO produced from burning charcoal has been reported in parts of Asia; however, the incidence of this method has not been determined in a U.S. population. Thus, we determined trends of CO suicide in the ethnically diverse population of King County, Washington, U.S.A. During the period 1996-2009, we identified 158 cases of suicide by CO poisoning, with 125 because of automotive exhaust, 26 because of charcoal burning, and seven from other CO sources. While historical U.S. data indicate >99% of CO suicides in the United States occurring by automobile exhaust inhalation, in the most recent years analyzed, c. 40% of CO-related suicides in King County, Washington, were because of charcoal burning, indicating a possible shift in suicide trends that warrants further scrutiny in additional populations.

  12. Sudden death caused by 1,1-difluoroethane inhalation.

    PubMed

    Xiong, Zhenggang; Avella, Joseph; Wetli, Charles V

    2004-05-01

    A 20-year-old man was found dead on the floor next to a computer, with a nearly full can of "CRC Duster" dust remover located next to the deceased on the floor, and an empty can of the same product on the computer desk. Toxicologic evaluation using either gas chromatography/mass spectrometry (GC/MS) or gas chromatography/flame ionization detector (GC/FID) method identified the active ingredient 1,1-difluoroethane (Freon 152a) in all tissues analyzed. Tissue distribution studies revealed highest concentration in central blood, lung, and liver. It is believed that the 1,1-difluoroethane inhalation was the cause of death.

  13. Suicidal carbon monoxide inhalation of exhaust fumes. Investigation of cases

    SciTech Connect

    Tsunenari, S.; Yonemitsu, K.; Kanda, M.; Yoshida, S.

    1985-09-01

    The inhalation of automobile exhaust gases is a relatively frequent suicidal method. Two such cases of special interest to forensic pathology and toxicology have been introduced. In case 1, a suicide note disclosed the victim's mental state, the inside conditions of the car, and toxic effects of automobile exhaust. In case 2, a reconstruction experiment has revealed important factors for the investigation of the scene, such as the size of a vinyl hose, the conditions of connecting site of the hose with the exhaust pipe, etc.

  14. Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo

    PubMed Central

    2012-01-01

    Background Helium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific “conditioning” protocols. Before widespread use of this “conditioning” agent in clinical practice, negative side effects have to be ruled out. We investigated the effect of prolonged helium inhalation on the responsiveness of the human immune response in whole blood ex vivo. Methods Male healthy volunteers inhaled 30 minutes heliox (79%He/21%O2) or air in a cross over design, with two weeks between measurements. Blood was withdrawn at T0 (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not incubated (0 h). An additional group of six volunteers inhaled 60 minutes of heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ) and interleukin-2 (IL-2) was analyzed by cytometric bead array. Statistical analysis was performed by the Wilcoxon test for matched samples. Results Incubation with LPS, LTA or TCS significantly increased TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone. Thirty min of helium inhalation did not influence the amounts of TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to air. Sixty min of helium inhalation did not affect cytokine production after LPS stimulation. Conclusions We conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers. Trial registration Dutch Trial Register: http://www.trialregister.nl/ NTR2152 PMID:23006534

  15. AB036. Real-life experience of COPD patients on ease and accuracy of inhaler use: the REAL survey

    PubMed Central

    Keininger, Dorothy L.; Price, David; Viswanad, Boomi; Gasser, Matthias; Walda, Susann

    2016-01-01

    Background Many patients with chronic obstructive pulmonary disease (COPD) achieve incomplete benefit from their treatment, due to reasons including inadequate device training or incorrect inhaler technique. Dosing frequency has also been shown to impact COPD treatment compliance with inhaler overuse and underuse being the most common form of noncompliance. Between 28–68% of patients do not use their inhalers correctly, and 39–67% of health care professionals (HCPs) do not effectively train patients to correctly use their inhalers. This makes patients prone to committing inhaler use errors and may negatively impact treatment compliance. We conducted a computer-assisted telephonic survey in patients with COPD to evaluate patient-reported insights on real life aspects of inhaler use, training and check for correct use by HCP, device attributes and patient-reported compliance of inhaler or medication use. Methods Patients from 9 countries, diagnosed with mild to very severe COPD and using maintenance inhaled treatment (via Breezhaler®, Ellipta®, Genuair®, Respimat®) were included in this survey. Patient-reported data on correct inhaler use (training and check), inhalation pattern, and device attributes (ease of use and confidence of inhaling full dose), compliance and potential underuse or overuse was collected. Chi-square test was performed for testing significance and z-test was used for comparisons of proportions (significance level: alpha<0.05). Results A total of 764 patients (Breezhaler® =186; Ellipta® =191; Genuair® = 194; Respimat® =201) with mild to very severe COPD with a mean (±SD) age 56±9.8 years, completed the survey. Approximately, 30% of all patients reported not receiving any inhaler use training. Of the 70%, who received training on inhaler use, 83% felt that the demonstration of inhaler use was very helpful, followed by videos (58%), instructions for use (51%) and leaflets (34%), irrespective of the device used. About 29% of all

  16. Transrepression and transactivation potencies of inhaled glucocorticoids.

    PubMed

    Dirks, N L; Li, S; Huth, B; Hochhaus, G; Yates, C R; Meibohm, B

    2008-12-01

    The anti-inflammatory activity of inhaled glucocorticoids is primarily mediated through transrepression of pro-inflammatory transcription factors such as AP-1 and NF-kappaB, while systemic side effects are largely attributed to transactivation via glucocorticoid response elements (GRE) in the promoter region of responsive genes. The objective of this study is to investigate whether inhaled corticosteroids exhibit differences in their transactivation and transrepression potencies. A549 human alveolar epithelial type II like cells, stably transfected with a reporter plasmid containing an AP-1, NF-kappaB or GRE induced secreted alkaline phosphatase reporter gene (SEAP), were exposed to a panel of concentrations of the six inhaled and three systemic glucocorticoids. Glucocorticoid-induced changes in SEAP expression were quantified by chemiluminescence. For eight glucocorticoids (budesonide, desisobutyryl-cicle-sonide, dexamethasone, flunisolide, fluocortolone, fluticasone propionate, mometasone furoate, prednisolone) the EC50 for NF-kappaB mediated transrepression was significantly larger than that for both transactivation and transrepression via AP-1. For the remaining glucocorticoid (triamcinolone acetonide), it was greater than that for transactivation. It is concluded that, within the studied cell system, inhaled corticosteroids did not exhibit preferential transrepression, but had higher potencies for transactivation than for transrepression via NF-kappaB and had differential potencies for the two transrepression pathways.

  17. Patterns of Inhalant Use among Incarcerated Youth

    PubMed Central

    Snyder, Susan M.; Howard, Matthew O.

    2015-01-01

    Inhalant use is especially prevalent among antisocial youth and can have serious health consequences. However, the extant literature has not investigated how use of various inhalants may co-occur among incarcerated youth. This study begins to address this gap in the literature by using latent class analyses to form distinct typologies of inhalant use. Study participants were residents (N = 723) of 27 Missouri Division of Youth Services facilities. Interviews assessed psychiatric symptoms, antisocial traits, delinquency, trauma, suicidality, and substance use behaviors. The mean age of the mostly male, ethnically diverse sample was 15.5 (S.D. = 1.2) years old. The study revealed the following classes of inhalant use: (1) severe polyinhalant use; (2) moderate polyinhalant use; (3) gas and permanent marker use; and (4) low-use. Compared to the low-use class, members of the severe polyinhalant use class had experienced more than double the rate of head injuries, the highest rates of traumatic experiences, and the highest rates of mental illness diagnoses. The gas and markers class had the highest rate of reporting hearing voices, followed by the severe polyinhalant use class, and the moderate polyinhalant use class. Results of this study underscore the need to address the high rate of head injuries and mental health diagnoses that contribute to severe polyinhalant use. PMID:26333159

  18. Inhalant Use in Latina Early Adolescent Girls

    ERIC Educational Resources Information Center

    Guzmán, Bianca L.; Kouyoumdjian, Claudia

    2016-01-01

    The purpose of the current study was to examine how lifetime use and extent of use of inhalants by Latina girls is impacted by age, acculturation, grades, ditching, sexual behaviors (light petting, heavy petting, and going all the way) and sexual agency. A total of 273 females who self-identified as being Latina whose mean age was 13.94 completed…

  19. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... respiratory tract such particles may be deposited. This term is used in contrast to measured or geometric... within the respiratory tract. (3) The geometric mean diameter or the median diameter is the calculated... respiratory tract from the trachea to the alveoli. For man, inhalable diameter is considered as 15...

  20. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... respiratory tract such particles may be deposited. This term is used in contrast to measured or geometric... within the respiratory tract. (3) The geometric mean diameter or the median diameter is the calculated... respiratory tract from the trachea to the alveoli. For man, inhalable diameter is considered as 15...

  1. Manganese Inhalation as a Parkinson Disease Model

    PubMed Central

    Ordoñez-Librado, José Luis; Anaya-Martínez, Verónica; Gutierrez-Valdez, Ana Luisa; Colín-Barenque, Laura; Montiel-Flores, Enrique; Avila-Costa, Maria Rosa

    2011-01-01

    The present study examines the effects of divalent and trivalent Manganese (Mn2+/Mn3+) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive dopaminergic cell death, correlate those alterations with motor disturbances, and determine whether L-DOPA treatment improves the behavior, to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of Manganese chloride and Manganese acetate, one hour twice a week for five months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By the end of Mn exposure, 10 mice were orally treated with 7.5 mg/kg L-DOPA. After 5 months of Mn mixture inhalation, striatal dopamine content decreased 71%, the SNc showed important reduction in the number of TH-immunopositive neurons, mice developed akinesia, postural instability, and action tremor; these motor alterations were reverted with L-DOPA treatment. Our data provide evidence that Mn2+/Mn3+ mixture inhalation produces similar morphological, neurochemical, and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease. PMID:21209715

  2. Systemic Effects of Inhaled Corticosteroids: An Overview

    PubMed Central

    Pandya, Dhruti; Puttanna, Amar; Balagopal, Viswanatha

    2014-01-01

    Inhaled corticosteroids (ICS) are common medications, used in respiratory medicine for controlling conditions such as asthma and other obstructive airway diseases. The systemic effects of oral corticosteroids are well known and established; inhaled steroids have been known to cause relatively minor and localized adverse effects such as oral candidiasis. However, less attention has been paid to their systemic effects. Although currently there is a paucity of prospective studies demonstrating the systemic effects of inhaled corticosteroids, there are numerous retrospective studies adding evidence to this link. Inhaled corticosteroids can affect the hypothalamo-pituitary-adrenal axis, bone density and growth, eyes, skin and immunity including an increased risk of pneumonia. Clinicians are recommended to aim for the lowest possible dose to avoid these systemic side effects. Fluticasone is more likely to cause systemic effects compared to budesonide. Newer ICS molecules such as ciclesonide may be more beneficial in reducing such systemic complications on prolonged use. This paper provides an updated overview of the common systemic effects encountered with ICS treatment. PMID:25674175

  3. Subacute Inhalation Toxicity of 3-Methylpentane

    PubMed Central

    Chung, Yong Hyun; Shin, Seo-Ho; Han, Jeong Hee; Lee, Yong-Hoon

    2016-01-01

    3-Methylpentane (C6H14, CAS No. 96-14-0), isomer of hexane, is a colorless liquid originating naturally from petroleum or natural gas liquids. 3-Methylpentane has been used as a solvent in organic synthesis, as a lubricant, and as a raw material for producing carbon black. There is limited information available on the inhalation toxicity of 3-methylpentane, and the aim of this study was to determine its subacute inhalation toxicity. According to OECD Test Guideline 412 (subacute inhalation toxicity: 28-day study), Sprague Dawley rats were exposed to 0, 284, 1,135, and 4,540 ppm of 3-methylpentane for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, organ weights, and gross and histopathological findings were compared between control and all exposure groups. No mortality or remarkable clinical signs were observed during the study. No gross or histopathological lesions, or adverse effects on body weight, food consumption, hematology, serum chemistry, and organ weights were observed in any male or female rats in all exposure groups, although some statistically significant changes were observed in food consumption, serum chemistry, and organ weights. In conclusion, the results of this study indicate that no observable adverse effect level (NOAEL) for 3-methylpentane above 4,540 ppm/6 hr/day, 5 days/week for rats. PMID:27437092

  4. Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhaler.

    PubMed

    Hodder, Richard; Price, David

    2009-01-01

    Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations. A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients' adherence to treatment, and thus potentially affect the long-term outcome. The Respimat((R)) Soft Mist Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs). We review clinical studies of inhaler satisfaction and preference comparing Respimat((R)) SMI against other inhalers in COPD patients. Using objective and validated patient satisfaction instruments, Respimat((R)) SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics. In comparative studies with pMDIs, the patient total satisfaction score with Respimat((R)) SMI was statistically and clinically significantly higher than with the pMDI. In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler((R)) DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat((R)) SMI. Whether the observed higher levels of patient satisfaction reported with Respimat((R)) SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven.

  5. [Inhalation therapy with Respimat soft inhaler in patients with COPD and asthma].

    PubMed

    Voshaar, T; Hausen, T; Kardos, P; Köhler, D; Schultze-Werninghaus, G; Schürmann, W; Vogelmeier, C

    2005-01-01

    Developing more effective and convenient inhalation devices for the treatment of obstructive pulmonary diseases is at least as important as designing new drugs. In recent years, existing inhalation systems have undergone many technical modifications and there have also been many new developments. All of these systems have their own particular attributes and characteristics. Two fundamentally different modes of operation are represented by propellant-driven metered-dose inhalers (pMDI) on the one hand and dry powder inhalers (DPI) on the other. However, none of the systems developed so far can be considered ideal. The Respimat Soft Inhaler (Respimat SI) was developed in the light of experience with previous systems and was launched in Germany at the beginning of 2004. The aim in developing this new type of inhaler was to avoid the well-known drawbacks typically associated with pMDI and DPI. The Respimat SI requires neither a chemical propellant nor batteries. The active ingredients are dissolved in water and the solution is atomised using mechanical energy only imparted by a spring which, when released, provides the power to force the solution through an extremely fine nozzle system. Two fine jets of liquid are produced. They converge at an optimised angle and the resulting impact generates a fine mist which is slow-moving and lasts for about 1.5 seconds; moreover, a high proportion of the droplets fall into the fine particle fraction. All of these features allow excellent lung deposition and reduced oropharyngeal deposition. Coordination between actuation and inhalation is less critical as compared with pMDI due to the fact that the mist is both slow-moving and long-lasting. A further advantage is that the mist is generated independently of the patient's inspiratory flow. The Respimat SI meets the requirements for an ideal inhaler better than any other previous device and must therefore be regarded as a significant new development.

  6. Assessment of increased sampling pump flow rates in a disposable, inhalable aerosol sampler.

    PubMed

    Stewart, Justin; Sleeth, Darrah K; Handy, Rod G; Pahler, Leon F; Anthony, T Renee; Volckens, John

    2017-03-01

    A newly designed, low-cost, disposable inhalable aerosol sampler was developed to assess workers personal exposure to inhalable particles. This sampler was originally designed to operate at 10 L/min to increase sample mass and, therefore, improve analytical detection limits for filter-based methods. Computational fluid dynamics modeling revealed that sampler performance (relative to aerosol inhalability criteria) would not differ substantially at sampler flows of 2 and 10 L/min. With this in mind, the newly designed inhalable aerosol sampler was tested in a wind tunnel, simultaneously, at flows of 2 and 10 L/min flow. A mannequin was equipped with 6 sampler/pump assemblies (three pumps operated at 2 L/min and three pumps at 10 L/min) inside a wind tunnel, operated at 0.2 m/s, which has been shown to be a typical indoor workplace wind speed. In separate tests, four different particle sizes were injected to determine if the sampler's performance with the new 10 L/min flow rate significantly differed to that at 2 L/min. A comparison between inhalable mass concentrations using a Wilcoxon signed rank test found no significant difference in the concentration of particles sampled at 10 and 2 L/min for all particle sizes tested. Our results suggest that this new aerosol sampler is a versatile tool that can improve exposure assessment capabilities for the practicing industrial hygienist by improving the limit of detection and allowing for shorting sampling times.

  7. Sex differences in use of inhalants by elderly patients with asthma

    PubMed Central

    Hirose, Masahiro; Kondo, Rieko; Ban, Naoaki; Kuwabara, Kazunobu; Shiga, Mamoru; Horiguchi, Takahiko

    2015-01-01

    Background The number of elderly patients with asthma has been increasing in Japan. Treatment for these patients should be provided based on the condition of individual patients. This study was performed to clarify the relationship between inhalation procedure and sex difference in elderly patients with asthma. Methods The inhalation procedure was examined in 155 elderly patients with asthma (male: n=66, average age ± standard deviation: 75.5±5.65 years old; female: n=89, average age ± standard deviation: 78.7±6.87 years old) during a medical examination. Results For the three items that were common to all devices, the percentages of the 155 patients who could/could not perform the actions were examined by separate Fisher’s exact tests for males and females. A statistically significant difference (P=0.007) was observed for “breath holding”, and more females than males were not able to hold their breath. Although no significant difference was seen in the “accurate number of times of inhalation”, females tended to not be able to inhale accurately compared to males (P=0.072). Conclusion Our results suggest that elderly female patients with asthma have less understanding of inhaled steroid therapy, compared to elderly male patients. Therefore, it is particularly important to confirm that the correct inhalation procedure is used by elderly female patients with asthma. PMID:26300635

  8. Protective Effects of Hydrogen-Rich Saline on Rats with Smoke Inhalation Injury

    PubMed Central

    Chen, Xing; Liu, Qi; Wang, Dawei; Feng, Shihai; Zhao, Yongjian; Shi, Yun; Liu, Qun

    2015-01-01

    Objective. To explore the protective effects of hydrogen-rich saline on rats with smoke inhalation injury. Methods. 36 healthy male Sprague-Dawley rats were randomly divided into 3 groups (n = 12 per group): sham group (S), inhalation injury plus normal saline treatment group (I+NS), and inhalation injury plus hydrogen-rich saline treatment group (I+HS). 30 min after injury, normal saline and hydrogen-rich saline were injected intraperitoneally (5 mL/kg) in I+NS group and I+HS group, respectively. All rats were euthanized and blood and organ specimens were collected for determination 24 h after inhalation injury. Results. Tumor necrosis factor-alpha (TNF-α) levels, malondialdehyde (MDA) concentrations, nuclear factor kappa B (NF-κB) p65 expression, and apoptosis index (AI) in I+HS group were significantly decreased (P < 0.05), while superoxide dismutase (SOD) activities were increased compared with those in I+NS group; and a marked improvement in alveolar structure was also found after hydrogen-rich saline treatment. Conclusions. Hydrogen-rich saline treatment exerts protective effects in acute lung injury induced by inhalation injury, at least in part through the activation of anti-inflammatory and antioxidant pathways and inhibition of apoptosis. PMID:26090070

  9. Assessment of smoke inhalation injury using volumetric optical frequency domain imaging in sheep models

    NASA Astrophysics Data System (ADS)

    Applegate, Matthew B.; Hariri, Lida P.; Beagle, John; Tan, Khay Ming; Chee, Chunmin; Hales, Charles A.; Suter, Melissa J.

    2012-02-01

    Smoke inhalation injury is a serious threat to victims of fires and explosions, however accurate diagnosis of patients remains problematic. Current evaluation techniques are highly subjective, often involving the integration of clinical findings with bronchoscopic assessment. It is apparent that new quantitative methods for evaluating the airways of patients at risk of inhalation injury are needed. Optical frequency domain imaging (OFDI) is a high resolution optical imaging modality that enables volumetric microscopy of the trachea and upper airways in vivo. We anticipate that OFDI may be a useful tool in accurately assessing the airways of patients at risk of smoke inhalation injury by detecting injury prior to the onset of symptoms, and therefore guiding patient management. To demonstrate the potential of OFDI for evaluating smoke inhalation injury, we conducted a preclinical study in which we imaged the trachea/upper airways of 4 sheep prior to, and up to 60 minutes post exposure to cooled cotton smoke. OFDI enabled the visualization of increased mucus accumulation, mucosal thickening, epithelial disruption and sloughing, and increased submucosal signal intensity attributed to polymorphonuclear infiltrates. These results were consistent with histopathology findings. Bronchoscopic inspection of the upper airways appeared relatively normal with only mild accumulation of mucus visible within the airway lumen. The ability of OFDI to not only accurately detect smoke inhalation injury, but to quantitatively assess and monitor the progression or healing of the injury over time may provide new insights into the management of patients such as guiding clinical decisions regarding the need for intubation and ventilator support.

  10. Demographic and contextual factors associated with inhalant use among youth in rural Alaska

    PubMed Central

    Driscoll, David L.; Dotterrer, Bruce; Collins, David; Ogilvie, Kristen; Grube, Joel; Johnson, Knowlton

    2012-01-01

    Background Abuse of harmful legal products that can be inhaled or ingested is a serious and growing problem in many rural Alaskan communities, and particularly so among preteens. Methods This study analyses data collected during baseline measurements of a 5-year NIH/NIDA-funded study entitled A Community Trial to Prevent Youth's Abuse of Harmful Legal Products in Alaska. Youth in 8 communities located throughout the state participated in a survey during the fall of 2009 to measure the prevalence and availability of harmful legal products (n=697). The goal of the analysis presented here is to compare the contextual factors of inhalant users and non-users in rural Alaskan communities. Results As reported in national surveys of substance use among youth, participants in this study indicated using alcohol more than any other substance. Inhalants were the second-most common substance abused, higher than either cigarettes or marijuana. Lifetime use varied among demographic factors such as age, gender and ethnicity as well as contextual factors including academic performance, parent employment, household living situation and income. When compared to non-users, significantly larger proportions of participants reporting lifetime inhalant use indicated easy availability of inhalants in their home, school and retail outlets. Users were also significantly more likely than non-users to have consumed alcohol. Conclusion Results of this study may inform the development of effective interventions in other rural communities. PMID:22564464

  11. Effect of compression pressure on inhalation grade lactose as carrier for dry powder inhalations

    PubMed Central

    Raut, Neha Sureshrao; Jamaiwar, Swapnil; Umekar, Milind Janrao; Kotagale, Nandkishor Ramdas

    2016-01-01

    Introduction: This study focused on the potential effects of compression forces experienced during lactose (InhaLac 70, 120, and 230) storage and transport on the flowability and aerosol performance in dry powder inhaler formulation. Materials and Methods: Lactose was subjected to typical compression forces 4, 10, and 20 N/cm2. Powder flowability and particle size distribution analysis of un-compressed and compressed lactose was evaluated by Carr's index, Hausner's ratio, the angle of repose and by laser diffraction method. Aerosol performance of un-compressed and compressed lactose was assessed in dispersion studies using glass twin-stage-liquid-impenger at flow rate 40-80 L/min. Results: At compression forces, the flowability of compressed lactose was observed same or slightly improved. Furthermore, compression of lactose caused a decrease in in vitro aerosol dispersion performance. Conclusion: The present study illustrates that, as carrier size increases, a concurrent decrease in drug aerosolization performance was observed. Thus, the compression of the lactose fines onto the surfaces of the larger lactose particles due to compression pressures was hypothesized to be the cause of these observed performance variations. The simulations of storage and transport in an industrial scale can induce significant variations in formulation performance, and it could be a source of batch-to-batch variations. PMID:27014618

  12. Pharmacokinetics of Oral and Inhaled Terbutaline after Exercise in Trained Men

    PubMed Central

    Dyreborg, Anders; Krogh, Nanna; Backer, Vibeke; Rzeppa, Sebastian; Hemmersbach, Peter; Hostrup, Morten

    2016-01-01

    Aim: The aim of the study was to investigate pharmacokinetics of terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control. Methods: Twelve healthy well-trained young men (27 ±2 years; mean ± SE) underwent two pharmacokinetic trials that compared 10 mg oral terbutaline with 4 mg inhaled dry powder terbutaline. During each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0–4 h) and urine (0–24 h) samples were collected before and after administration of terbutaline. Samples were analyzed for concentrations of terbutaline by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Results: Pharmacokinetics differed between the two routes of administration. Serum Cmax and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (Cmax: 4.2 ± 0.3 vs. 8.5 ± 0.7 ng/ml, P ≤ 0.001; AUC: 422 ± 22 vs. 1308 ± 119 ng/ml × min). Urine concentrations (sum of the free drug and the glucuronide) were lower after oral administration compared to inhalation 2 h (1100 ± 204 vs. 61 ± 10 ng/ml, P ≤ 0.05) and 4 h (734 ± 110 vs. 340 ± 48 ng/ml, P ≤ 0.001) following administration, whereas concentrations were higher for oral administration than inhalation 12 h following administration (190 ± 41 vs. 399 ± 108 ng/ml, P ≤ 0.05). Urine excretion rate was lower after oral administration than inhalation the first 2 h following administration (P ≤ 0.001). Systemic bioavailability ratio between the two routes of administration was 3.8:1 (inhaled: oral; P ≤ 0.001). Conclusion: Given the higher systemic bioavailability of inhaled terbutaline compared to oral, our results indicate that it is difficult to differentiate allowed inhaled use of terbutaline from prohibited oral ingestion based on urine concentrations in doping control analysis. However given the potential performance

  13. Characterization of exogeous particale content: Of canine tissue urban vs. rural inhalation exposures

    NASA Astrophysics Data System (ADS)

    Kennedy, Jamell

    Exogenous zinc (Zn) is emerging as a serious contaminant in the environment. Yearly deposition of zinc particles line heavily traveled inner city roadways and less traveled rural roadways. Particle size for zinc ranges from approximately PM10 to PM 2.5 microm or less. These fine particles contain microscopic solids or liquids that can cause serious health problems. PM10 are considered to be "thoracic" sized particles, with the mass fraction of inhaled particles penetrating beyond the larynx. Whereas, PM2.5 are considered to be "respirable" sized particles, with the mass fraction of inhaled particles penetrating to the unciliated airways. Exogenous zinc can be used as a quantifiable marker to contrast the differences in exposures in canines originating from urban and rural environments. These exposures are analyzed using a scanning electron microscope with energy dispersive X-ray spectrometry, and usage of a morphometric point counting method for a physical count and categorization of composition of inhaled retained particle content.

  14. Inhalation exposure and risk from mobile source air toxics in future years.

    PubMed

    Cook, Richard; Strum, Madeleine; Touma, Jawad S; Palma, Ted; Thurman, James; Ensley, Darrell; Smith, Roy

    2007-01-01

    Modeling of inhalation exposure and risks resulting from exposure to mobile source air toxics can be used to evaluate impacts of reductions from control programs on overall risk, as well as changes in relative contributions of different source sectors to risk, changes in contributions of different pollutants to overall risk, and changes in geographic distributions of risk. Such analysis is useful in setting regulatory priorities, and informing the decision-making process. In this paper, we have conducted national-scale air quality, exposure, and risk modeling for the US in the years 2015, 2020, and 2030, using similar tools and methods as the 1999 National-Scale Air Toxics Assessment. Our results suggest that US Environmental Protection Agency emission control programs will substantially reduce average inhalation cancer risks and potential noncancer health risks from exposure to mobile source air toxics. However, cancer risk and noncancer hazard due to inhalation of air toxics will continue to be a public health concern.

  15. The Effects of Inhaled Steroids on Recurrent Wheeze After Acute Bronchiolitis

    PubMed Central

    Green, Patricia; Aronoff, Stephen C.

    2015-01-01

    Background. Acute bronchiolitis infection during infancy is associated with an increased risk of asthma later in life. The objective of this study was to determine if inhaled steroids are effective in preventing the development of recurrent wheeze or asthma following acute bronchiolitis. Methods. Multiple databases and bibliographies of selected references were searched. Inclusion required (a) a randomized controlled trial of inhaled steroids and control group, (b) at least 2 weeks duration of therapy started during the acute phase of disease, and (c) identification of the rate of recurrent wheeze or asthma at least 6 months after therapy. Results. Of 1410 studies reviewed, 8 reports were included in this meta-analysis (748 patients). The overall odds ratio for developing recurrent wheeze or asthma with treatment versus without treatment was 1.02 (95% confidence interval = 0.58-1.81). Conclusions. A course of inhaled steroids after acute bronchiolitis is not effective in preventing recurrent wheeze or asthma. PMID:27335972

  16. Cold blast furnace syndrome: a new source of toxic inhalation by nitrogen oxides

    PubMed Central

    Tague, I; Llewellin, P; Burton, K; Buchan, R; Yates, D

    2004-01-01

    Methods: Fourteen workers developed acute respiratory symptoms shortly after exposure to "air blast" from blast furnace tuyeres. These included chest tightness, dyspnoea, rigors, and diaphoresis. Chest radiographs showed pulmonary infiltrates, and lung function a restrictive abnormality. This report includes a description of clinical features of the affected workers and elucidation of the probable cause of the outbreak. Results: Clinical features and occupational hygiene measurements suggested the most likely cause was inhalation of nitrogen oxides at high pressure and temperature. While the task could not be eliminated, engineering controls were implemented to control the hazard. No further cases have occurred. Conclusions: "Cold blast furnace syndrome" represents a previously undescribed hazard of blast furnace work, probably due to inhalation of nitrogen oxides. It should be considered in the differential diagnosis of acute toxic inhalational injuries in blast furnace workers. PMID:15090669

  17. Tablet and inhaled controller medication refill frequencies in children with asthma.

    PubMed

    Fitzpatrick, Anne M; Kir, Tayfun; Naeher, Luke P; Fuhrman, Stephanie C; Hahn, Kimberly; Teague, W Gerald

    2009-04-01

    Poor medication adherence is an important problem in children with asthma. This study compared prescription refill frequencies between tablet and inhaled medications in children aged 3 to 18 years with mild (n = 45) and moderate (n = 52) persistent asthma over 4 months. Refill frequencies were higher for tablet versus inhaled medications in both groups (mild: 69% vs. 31%, p = .02; moderate: 55% vs. 41%, p = .03). Refills peaked at the first month and incrementally declined (p < .05). Expanded asthma education did not increase refill frequency. Other methods of improving medication adherence may be warranted in this population.

  18. [Inhalation therapy: inhaled corticosteroids in ENT, development and technical challenges of powder inhalers, nebulisers synchronized with breathing and aerosol size distribution. GAT aerosolstorming, Paris 2012].

    PubMed

    Le Guen, P; Peron, N; Durand, M; Pourchez, J; Cavaillon, P; Reychler, G; Vecellio, L; Dubus, J-C

    2013-10-01

    The working group on aerosol therapy (GAT) of the Société de Pneumologie de Langue Française (SPLF) has organized its third Aerosolstorming in 2012. During one single day, different aspects of inhaled therapies have been treated and are detailed in two articles, this one being the second. This text deals with the indications of inhaled corticosteroids in ENT, the development and technical challenges of powder inhalers, the advantages and disadvantages of each type of technologies to measure the particle sizes of inhaled treatments.

  19. Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler.

    PubMed

    Pitcairn, Gary; Reader, Sandie; Pavia, Demetri; Newman, Steve

    2005-01-01

    Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.

  20. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials

    PubMed Central

    2014-01-01

    Background A standard short-term inhalation study (STIS) was applied for hazard assessment of 13 metal oxide nanomaterials and micron-scale zinc oxide. Methods Rats were exposed to test material aerosols (ranging from 0.5 to 50 mg/m3) for five consecutive days with 14- or 21-day post-exposure observation. Bronchoalveolar lavage fluid (BALF) and histopathological sections of the entire respiratory tract were examined. Pulmonary deposition and clearance and test material translocation into extra-pulmonary organs were assessed. Results Inhaled nanomaterials were found in the lung, in alveolar macrophages, and in the draining lymph nodes. Polyacrylate-coated silica was also found in the spleen, and both zinc oxides elicited olfactory epithelium necrosis. None of the other nanomaterials was recorded in extra-pulmonary organs. Eight nanomaterials did not elicit pulmonary effects, and their no observed adverse effect concentrations (NOAECs) were at least 10 mg/m3. Five materials (coated nano-TiO2, both ZnO, both CeO2) evoked concentration-dependent transient pulmonary inflammation. Most effects were at least partially reversible during the post-exposure period. Based on the NOAECs that were derived from quantitative parameters, with BALF polymorphonuclear (PMN) neutrophil counts and total protein concentration being most sensitive, or from the severity of histopathological findings, the materials were ranked by increasing toxic potency into 3 grades: lower toxic potency: BaSO4; SiO2.acrylate (by local NOAEC); SiO2.PEG; SiO2.phosphate; SiO2.amino; nano-ZrO2; ZrO2.TODA; ZrO2.acrylate; medium toxic potency: SiO2.naked; higher toxic potency: coated nano-TiO2; nano-CeO2; Al-doped nano-CeO2; micron-scale ZnO; coated nano-ZnO (and SiO2.acrylate by systemic no observed effect concentration (NOEC)). Conclusion The STIS revealed the type of effects of 13 nanomaterials, and micron-scale ZnO, information on their toxic potency, and the location and reversibility of effects

  1. The ADMIT series - Issues in inhalation therapy. 4) How to choose inhaler devices for the treatment of COPD.

    PubMed

    Vincken, Walter; Dekhuijzen, Pn Richard; Barnes, Peter

    2010-03-01

    For patients with COPD, inhalation is the preferred route of administration of respiratory drugs for both maintenance and acute treatment. Numerous inhaler types and devices have been developed, each with their own particularities, advantages and disadvantages. Nevertheless, published COPD management guidelines pay little attention to the optimal choice of inhaler devices for COPD patients. Although efficacy and safety are the primary factors determining the choice of an inhaler device, randomised controlled trials (RCTs) directly comparing the efficacy and safety of different inhalers in COPD patients are scarce. Systematic reviews on this subject failed to find significant differences between devices for any of the clinical outcomes studied. When selecting a device for the delivery of inhaled drugs in 'real life' patients with COPD, other factors should be considered. These include availability and affordability of the inhaled drugs and inhaler devices, the uniformity of inhaler devices when several drugs are to be inhaled, the ability of patients to handle correctly the selected device - in particular taking into account the advanced age of the average COPD patient, and finally the patient's preference. The prescribing clinician's task is to provide comprehensive instructions for correct handling of the device and to review regularly the patient's inhalation technique.

  2. Rapid Transition from Inhaled Iloprost to Inhaled Treprostinil in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Bourge, Robert C; Tapson, Victor F; Safdar, Zeenat; Benza, Raymond L; Channick, Richard N; Rosenzweig, Erika B; Shapiro, Shelley; White, Richard James; McSwain, Christopher Shane; Gotzkowsky, Stephen Karl; Nelsen, Andrew C; Rubin, Lewis J

    2013-01-01

    Background Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy. Aims In this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6–9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed. Results Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (−74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001). Conclusions Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status. PMID:22970909

  3. Effect of inhaler design variables on paediatric use of dry powder inhalers.

    PubMed

    Lexmond, Anne J; Kruizinga, Tonnis J; Hagedoorn, Paul; Rottier, Bart L; Frijlink, Henderik W; de Boer, Anne H

    2014-01-01

    Age appropriateness is a major concern of pulmonary delivery devices, in particular of dry powder inhalers (DPIs), since their performance strongly depends on the inspiratory flow manoeuvre of the patient. Previous research on the use of DPIs by children focused mostly on specific DPIs or single inspiratory parameters. In this study, we investigated the requirements for a paediatric DPI more broadly using an instrumented test inhaler. Our primary aim was to assess the impact of airflow resistance on children's inspiratory flow profiles. Additionally, we investigated children's preferences for airflow resistance and mouthpiece design and how these relate to what may be most suitable for them. We tested 98 children (aged 4.7-12.6 years), of whom 91 were able to perform one or more correct inhalations through the test inhaler. We recorded flow profiles at five airflow resistances ranging from 0.025 to 0.055 kPa0.5.min.L-1 and computed various inspiratory flow parameters from these recordings. A sinuscope was used to observe any obstructions in the oral cavity during inhalation. 256 flow profiles were included for analysis. We found that both airflow resistance and the children's characteristics affect the inspiratory parameters. Our data suggest that a medium-high resistance is both suitable for and well appreciated by children aged 5-12 years. High incidences (up to 90%) of obstructions were found, which may restrict the use of DPIs by children. However, an oblong mouthpiece that was preferred the most appeared to positively affect the passageway through the oral cavity. To accommodate children from the age of 5 years onwards, a DPI should deliver a sufficiently high fine particle dose within an inhaled volume of 0.5 L and at a peak inspiratory flow rate of 25-40 L.min-1. We recommend taking these requirements into account for future paediatric inhaler development.

  4. Assessment of Airborne Particles. Fundamentals, Applications, and Implications to Inhalation Toxicity.

    ERIC Educational Resources Information Center

    Mercer, Thomas T., Ed.; And Others

    Concern over chemical and radioactive particulate matter in industry and over rapidly increasing air pollution has stimulated research both on the properties of airborne particles and methods for assessing them and on their biological effects following inhalation. The Third Rochester International Conference on Environmental Toxicity was,…

  5. Simulating the venting of radioactivity from a soviet nuclear test

    NASA Astrophysics Data System (ADS)

    Rodriguez, Daniel J.; Peterson, Kendall R.

    Fresh fission products were found in several routine air samples in Europe during the second and third weeks of March 1987. Initially, it was suspected that the radionuclides, principally 133Xe and 131I, had been accidentally released from a European facility handling nuclear materials. However, the announcement of an underground nuclear test at Semipalatinsk, U.S.S.R. on 26 February 1987 suggested that the elevated amounts of radioactivity may, instead, have been caused by a venting episode. Upon learning of these events, we simulated the transport and diffusion of 133Xe with our Hemispheric MEDIC and ADPIC models, assuming Semipalatinsk to be the source of the radioactive emissions. The correspondence between the calculated concentrations and the daily average 133Xe measurements made by the Federal Office for Civil Protection in F.R.G. was excellent. While this agreement does not, in itself, prove that an atmospheric venting of radioactive material occurred at Semipalatinsk, a body of circumstantial evidence exists which, when added together, strongly supports this conclusion. Our calculations suggested a total fission yield of about 40 kt, which is within the 20-150 kt range of tests acknowledged by the U.S.S.R. Finally, dose calculations indicated that no health or environmental impact occurred outside of the U.S.S.R. due to the suspected venting of 133Xe. However, the inhalation dose resulting from 133I, an unmodeled component of the radioactive cloud, represented a greater potential risk to public health.

  6. Fiber inhalability and head deposition in rats and humans. ...

    EPA Pesticide Factsheets

    Due to their dimensions and long durability, inhaled asbestos fibers clear slowly from lung airways. Retained fibers may injure the epithelium, interact with macrophages, or translocate to the interstitium to result in various respiratory diseases. Therefore, calculations of fiber inhalability, deposition, and retention in respiratory tract regions of both rats and humans are crucial, both to assess the health risk of fiber exposures and to facilitate inferences from rat inhalation studies. Rat inhalation experiments are underway at the EPA and NIEHS. A model of fiber inhalability and initial deposition in the human and rat nasal cavity was developed. Existing models for particles were extended to fibers by replacing particle diameter with an equivalent fiber diameter. Since fiber inhalability into the respiratory tract and deposition in the extra thoracic airways depended mainly on its inertia, equivalent impaction diameters were derived and substituted in expressions for spherical particle diameter to determine fiber inhalability and nasal losses. Fiber impaction diameter depended strongly on its orientation in the air. Highest inhalability was obtained when fibers were aligned perpendicular to the flow streamlines in the inhaled air. However, detailed calculations of fiber transport in slow moving air such as that in the atmosphere and in lung airways showed that fibers stayed primarily aligned (parallel) to the flow. Therefore, for inhalability calculations,

  7. Inhalation risk in low-gravity spacecraft.

    PubMed

    Todd, P; Sklar, V; Ramirez, W F; Smith, G J; Morgenthaler, G W; McKinnon, J T; Oberdorster, G; Schulz, J

    1994-07-01

    Inhalation risks on long-duration manned spaced flight include gasses chronically released by outgassing of materials, gasses released during spills, thermodegradation events (including fires) with their attendant particulates, and fire extinguishment. As an example, an event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom was modeled experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity environment was found to impact various stages of event simulation. Critical unknowns were identified, and these include the extent of production of ultrafine particles and polymeric products at the source in low gravity, the transport of ultrafine particles in the spacecraft air quality control system, and the biological response of the lung, including alveolar macrophages, to this inhalation risk in low gravity.

  8. ASSESSMENT OF DIOXIN INHALATION EXPOSURES AND ...

    EPA Pesticide Factsheets

    In the days following the September 11, 2001, terrorist attack on New York City's World Trade Center (WTC) towers, EPA, other federal agencies, and New York City and New York State public health and environmental authorities initiated numerous air monitoring activities to better understand the ongoing impact of emissions from that disaster. Using these data, EPA conducted an inhalation exposure and human health risk assessment. The overall evaluation focused on particulate matter, metals, polychlorinated biphenyls, dioxin-like compounds, asbestos, and volatile organic compounds. This paper reports on the analysis of dioxin-like compounds only.Lorber, M. 2003. Assessment of Dioxin Inhalation Exposures and Potential Health Impacts Following the Collapse of the World Trade Center Towers. Organohalogen Compounds 63 (no page numbers). journal article

  9. IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

    EPA Pesticide Factsheets

    EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the current toxicological information on ammonia posted in 1991. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA completed the Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

  10. Inhalation drug delivery devices: technology update

    PubMed Central

    Ibrahim, Mariam; Verma, Rahul; Garcia-Contreras, Lucila

    2015-01-01

    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. PMID:25709510

  11. Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes

    PubMed Central

    Belfort-DeAguiar, Renata D.; Naik, Sarita; Hwang, Janice; Szepietowska, Barbara

    2015-01-01

    OBJECTIVE Hypoglycemia is one of the major factors limiting implementation of tight glycemic control in patients with type 1 diabetes and is associated with increased morbidity and mortality during intensive insulin treatment. β-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled β-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established. RESEARCH DESIGN AND METHODS Seven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 μg), a highly specific β-2 AR agonist, or a placebo during a hyperinsulinemic-hypoglycemic clamp study to evaluate its capacity to antagonize the effect of insulin. In a second set of studies, five subjects with type 1 diabetes received inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia. RESULTS During a hyperinsulinemic-hypoglycemic clamp, compared with placebo, inhaled formoterol decreased the glucose infusion rate required to maintain plasma glucose at a target level by 45–50% (P < 0.05). There was no significant effect on glucagon, epinephrine, cortisol, or growth hormone release (P = NS). Furthermore, in volunteers with type 1 diabetes 1 h after increasing basal insulin delivery twofold, glucose levels dropped to 58 ± 5 mg/dL, whereas hypoglycemia was prevented by inhaled formoterol (P < 0.001). CONCLUSIONS Inhalation of the β-2 AR–specific agonist formoterol may be useful in the prevention or treatment of acute hypoglycemia and thus may help patients with type 1 diabetes achieve optimal glucose control more safely. PMID:26153273

  12. [Ventricular fibrillation following deodorant spray inhalation].

    PubMed

    Girard, F; Le Tacon, S; Maria, M; Pierrard, O; Monin, P

    2008-01-01

    We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

  13. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1976-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as determined principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of convenient approximations of the respiratory tract to predict tractional deposition according to fundamental physical processes of impaction, sedimentation, and diffusion. These theoretical models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with experimental studies of inhaled dusts in humans or experimental animals that have been performed in many laboratories over several decades. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior of very fine (less than 0.01 mum) particles requires further refinement.Properties of particle shape, charge, and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns and further experimental work is urgently needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of such techniques with selected inhaled particle size holds promise in possible diagnostic aid in diagnosis of normal versus disease conditions. Mechanisms of conducting airway and alveolar clearance processes involving mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic clearance are discussed. The roles of the pulmonary macrophage in airway and alveolar clearance are described, and the applicability of recent solubility models for translocation or deposited materials to liver, skeleton, or other systemic organs is discussed. PMID:797567

  14. Iodine Inhalation Study for Project Sedan

    DTIC Science & Technology

    1964-05-20

    was essential to prevent inhalation of resuspended material and in- gestion of material deposited on the nose and fur. Therefore, four animals at each...one dog from the 31 -mile station. -Z8- I 1 P J 7 ř-- COUNTED 1235 PDT JULY 8 w 1 w87 4_ COUTE 13235PTJL COUE.. 00187+ 1PJ2 I I z 132 II\\"\\/ I, w1. 7

  15. Inhaled histamine increases human lung mucociliary transport

    SciTech Connect

    Mussatto, D.J.; Garrard, C.S.; Trumbull, J.J.; Bowers, M.W.; Sanders, C.J.; Yeates, D.B.; Lourenco, R.V.

    1986-03-01

    Histamine, a mediator of airways constriction, alters ciliary beat frequency, bronchial mucus production, and epithelial ion transport; and in dogs, increases mucociliary transport. To evaluate the effect of inhaled histamine on human tracheobronchial mucociliary clearance, the authors measured lung mucociliary clearance (LMC) and tracheal mucociliary transport rate (TMTR) in 5 healthy, nonsmoking subjects in a randomized, double-blind, cross-over study. The concentration of inhaled histamine which produced a 20% fall in FEV/sub 1/ was established for each subject. On a separate day the subjects inhaled a 9 ..mu..m MMAD /sup 99m/Tc-Fe/sub 2/O/sub 3/ aerosol. LMC and TMTR were then measured for 2.5h using a gamma camera and a tracheal multidetector probe. Simultaneously, the subjects were challenged every 26 +/- 4 min with either PBS or histamine in PBS. The Fe/sub 2/O/sub 3/ retained after 24h for histamine (14.4 +/- 7.6%) and PBS studies (13.1 +/- 8.6%) indicated no difference in deposition of Fe/sub 2/O/sub 3/ (ANOVA). Fe/sub 2/O/sub 3/ clearance at 30 min was increased in the histamine studies (61 +/- 21% compared to the PBS studies (44 +/- 29%; p < 0.02, ANOVA)). TMTR was also increased with histamine (7.6 +/- 3.4 mm/min) compared to PBS (4.6 +/- 1.7 mm/min; p < 0.001, ANOVA). Results indicate an acute stimulatory effect of inhaled histamine on mucous transport in humans.

  16. Inhaled Nitric Oxide in Acute Lung Disease.

    DTIC Science & Technology

    1995-01-01

    seems likely ECMO extracorporeal membrane oxygenation EDRF endothelial-derived relaxing factor that the potent dose-related selective pulmonary GBS... ECMO ). To evaluate the dose response and time inhaled NO. (Fig. 7). The significant decrease in oxy- course of the pulmonary effects of NO., inspiratory...effects (39, 40). In many of these chil- dren, ECMO has been avoided. Similar improvement _0 has been noted in adult patients undergoing cardio- LPS NO

  17. Radioxenon standards used in laboratory inter-comparisons.

    PubMed

    Gohla, H; Auer, M; Cassette, Ph; Hague, R K; Lechermann, M; Nadalut, B

    2016-03-01

    Preparation methods for (133)Xe standards of activity concentration and the results of the 2014 (133)Xe laboratory inter-comparison exercise are described. One element of the quality assurance/quality control (QA/QC) program for laboratories of the International Monitoring System (IMS) will be regular inter-comparison exercises. However, until recently, no activity concentration standards for benchmarking were available. Therefore, two (133)Xe activity concentration reference standards were produced independently by Idaho National Laboratory and Seibersdorf Laboratories and used for the 2014 laboratory inter-comparison exercise. The preparation of a complementary (127)Xe activity concentration standard as well as a (127)Xe laboratory inter-comparison exercise suggests (127)Xe as a suitable isotope for QA/QC of remote IMS noble gas stations.

  18. Inhalation cancer risk assessment of cobalt metal.

    PubMed

    Suh, Mina; Thompson, Chad M; Brorby, Gregory P; Mittal, Liz; Proctor, Deborah M

    2016-08-01

    Cobalt compounds (metal, salts, hard metals, oxides, and alloys) are used widely in various industrial, medical and military applications. Chronic inhalation exposure to cobalt metal and cobalt sulfate has caused lung cancer in rats and mice, as well as systemic tumors in rats. Cobalt compounds are listed as probable or possible human carcinogens by some agencies, and there is a need for quantitative cancer toxicity criteria. The U.S. Environmental Protection Agency has derived a provisional inhalation unit risk (IUR) of 0.009 per μg/m(3) based on a chronic inhalation study of soluble cobalt sulfate heptahydrate; however, a recent 2-year cancer bioassay affords the opportunity to derive IURs specifically for cobalt metal. The mechanistic data support that the carcinogenic mode of action (MOA) is likely to involve oxidative stress, and thus, non-linear/threshold mechanisms. However, the lack of a detailed MOA and use of high, toxic exposure concentrations in the bioassay (≥1.25 mg/m(3)) preclude derivation of a reference concentration (RfC) protective of cancer. Several analyses resulted in an IUR of 0.003 per μg/m(3) for cobalt metal, which is ∼3-fold less potent than the provisional IUR. Future research should focus on establishing the exposure-response for key precursor events to improve cobalt metal risk assessment.

  19. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1984-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as governed principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of approximations of the respiratory tract to predict fractional deposition caused by fundamental physical processes of particle impaction, sedimentation, and diffusion. These models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with early and recent experimental studies. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior in the respiratory tract of very fine (less than 0.1 micron) particles requires further investigation. Properties of particle shape, charge and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns; definitive experimental work is needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of differing ventilation techniques with selected inhaled particle sizes holds promise in diagnosis of respiratory tract diseases. Mechanisms of conducting airway and alveolar clearance processes involving the pulmonary macrophage, mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic vessels are discussed. PMID:6376108

  20. A novel inhalable form of rifapentine.

    PubMed

    Chan, John G Y; Duke, Colin C; Ong, Hui Xin; Chan, Joseph C Y; Tyne, Anneliese S; Chan, Hak-Kim; Britton, Warwick J; Young, Paul M; Traini, Daniela

    2014-05-01

    Recent murine studies found that rifapentine, dosed daily, at least halved tuberculosis treatment times compared with standard rifampicin and isoniazid-containing regimens. However, in humans, an inhalable form of rifapentine may be necessary to considerably shorten treatment duration because of the physiological barriers associated with oral therapy. The current study compares two inhalable rifapentine dry powders-a novel pure crystalline form and an amorphous form-by a series of in vitro tests. The crystalline and amorphous powders had a mass median aerodynamic size of 1.68 ± 0.03 and 1.92 ± 0.01 μm, respectively, associated with a fine particle fraction of 83.2 ± 1.2% and 68.8 ± 2.1%, respectively. A quinone degradation product was identified in the amorphous powder stored for 1 month, whereas the crystalline form remained chemically stable after storage at both 0% and 60% relative humidity, 25°C, for at least 3 months. Solubilized rifapentine was well tolerated by pulmonary tissue and macrophage cells up to approximately 50 μM. The accumulation of rifapentine within alveolar macrophage cells was significantly higher than for rifampicin, indicating enhanced delivery to infected macrophages. The novel inhalable crystalline form of rifapentine is suitable for targeted treatment of tuberculosis infection and may radically shorten treatment duration.

  1. The pharmacology of chymotrypsin administered by inhalation

    PubMed Central

    Golberg, L.; Martin, L. E.; Sheard, P.; Harrison, C.

    1960-01-01

    The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [131I]. Quantitative measurements of the absorption and distribution of inhaled chymotrypsin- [131I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [131I] subsequently detached from it. The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm. ImagesFIG. 2FIG. 3 PMID:13850540

  2. Inhalant abuse among adolescents: neurobiological considerations

    PubMed Central

    Lubman, D I; Yücel, M; Lawrence, A J

    2008-01-01

    Experimentation with volatile substances (inhalants) is common during early adolescence, yet limited work has been conducted examining the neurobiological impact of regular binge use during this key stage of development. Human studies consistently demonstrate that chronic use is associated with significant toxic effects, including neurological and neuropsychological impairment, as well as diffuse and subtle changes in white matter. However, most preclinical research has tended to focus on acute exposure, with limited work examining the neuropharmacological or toxicological mechanisms underpinning these changes or their potential reversibility with abstinence. Nevertheless, there is growing evidence that commonly abused inhalants share common cellular mechanisms, and have similar actions to other drugs of abuse. Indeed, the majority of acute behavioural effects appear to be underpinned by changes in receptor and/or ion channel activity (for example, GABAA, glycine and 5HT3 receptor activation, NMDA receptor inhibition), although nonspecific interactions can also arise at high concentrations. Recent studies examining the effects of toluene exposure during the early postnatal period are suggestive of long-term alterations in the function of NMDA and GABAA receptors, although limited work has been conducted investigating exposure during adolescence. Given the critical role of neurotransmitter systems in cognitive, emotional and brain development, future studies will need to take account of the substantial neuromaturational changes that are known to occur in the brain during childhood and adolescence, and to specifically investigate the neuropharmacological and toxicological profile of inhalant exposure during this period of development. PMID:18332858

  3. Efficacy of two educational interventions about inhalation techniques in patients with chronic obstructive pulmonary disease (COPD). TECEPOC: study protocol for a partially randomized controlled trial (preference trial)

    PubMed Central

    2012-01-01

    Background Drugs for inhalation are the cornerstone of therapy in obstructive lung disease. We have observed that up to 75 % of patients do not perform a correct inhalation technique. The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction. The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD). Methods This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers. The participants will be divided into two groups and five arms. The two groups are: 1) the patients´ preference group with two arms and 2) the randomized group with three arms. In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B) designed for this study. In the randomized group the three arms comprise: intervention A, intervention B and a control arm. Intervention A is written information (a leaflet describing the correct inhalation techniques). Intervention B is written information about inhalation techniques plus training by an instructor. Every patient in each group will be visited six times during the year of the study at health care center. Discussion Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25 %. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice. Trial registration Current Controlled Trials ISRTCTN15106246 PMID:22613015

  4. Promising ternary dry powder inhaler formulations of cromolyn sodium: formulation and in vitro-in vivo evaluation.

    PubMed

    Elbary, Ahmed Abd; El-laithy, Hanan M; Tadros, Mina I

    2007-06-01

    Glucose monohydrate and sorbitol were evaluated as alternative carriers to á-lactose monohydrate in dry powder inhalations. Cromolyn sodium (CS) - carrier binary formulae were prepared and tested in vitro by aerosolization via a twin stage impinger using three types of inhaler devices; Spinhaler, Aerolizer and Handihaler. Glucose monohydrate and sorbitol-containing formulae that were inhaled via a Handihaler showed significantly higher drug fine particle fractions (P<0.001) than that of the same formulae aerosolized via other devices. Upon storage of the prepared formulae under uncontrolled humidity, that may be encountered during storage and use, marked reductions in these fractions were observed. Incorporation of an optimum Aerosil 200 concentration, as a ternary component, minimized this effect. A urinary excretion pharmacokinetic method was used to evaluate the bioavailability of the selected ternary formulae, inhaled via a Handihaler, relative to the marketed Intal Spincaps, inhaled via a Spinhaler. It was found that the relative bioavailability percentages of the developed formulae were more than twice that of the marketed one suggesting possible future utilization of these more effective ternrry formulae using the more efficient Handihaler inhaler device.

  5. Influence of Binasal and Uninasal Inhalations of Essential Oil of Abies koreana Twigs on Electroencephalographic Activity of Human

    PubMed Central

    Seo, Min; Sowndhararajan, Kandhasamy

    2016-01-01

    Objectives. The present work investigates the effect of essential oil from the twigs of Abies koreana on electroencephalographic (EEG) activity of human brain in order to understand the influence of binasal and uninasal inhalations. Methods. To accomplish this study, the essential oil from the twigs of A. koreana (AEO) was isolated by steam distillation and the EEG readings were recorded using QEEG-8 system from 8 grounding electrodes according to the International 10-20 System. Results. D-Limonene (25.29%), bornyl acetate (19.31%), camphene (12.48%), α-pinene (11.88%), β-pinene (6.45%), and eudesm-7(11)-en-ol (5.38%) were the major components in the essential oil. In the EEG study, the absolute alpha (left frontal and right parietal) and absolute fast alpha (right parietal) values significantly increased during the binasal inhalation of AEO. In the uninasal inhalation, absolute beta and theta values decreased significantly, especially in the right frontal and left and right parietal regions. The results revealed that the AEO produced different EEG power spectrum changes according to the nostril difference. Conclusion. The changes in EEG values due to the inhalation of AEO may contribute to the enhancement of relaxation (binasal inhalation) and alertness/attention (right uninasal inhalation) states of brain which could be used in aromatherapy treatments. PMID:28042202

  6. Induction of Food Allergy in Mice by Allergen Inhalation

    DTIC Science & Technology

    2014-10-01

    14. ABSTRACT The purpose of this project is to test the hypothesis that food allergy may develop in response to antigen inhalation. Studies in a...relative timing of antigen ingestion vs. antigen inhalation to lead to food allergy development. We are also testing whether exposure to aerosolized...antigen will reverse or exacerbate established food allergy to that antigen. Studies in year 1 of this project demonstrate that: 1) initial inhalation

  7. Budesonide inhalation suspension: a nebulized corticosteroid for persistent asthma.

    PubMed

    Szefler, Stanley J; Eigen, Howard

    2002-04-01

    Guidelines for managing asthma in pediatric patients published by the American Academy of Allergy, Asthma, and Immunology and the American Academy of Pediatrics recommend the use of inhaled corticosteroids for the management of persistent asthma in infants and young children. When these guidelines were published, pressurized metered-dose inhalers and dry-powder inhalers were the only delivery devices available for inhaled corticosteroids in the United States. These devices can be difficult for young children to use correctly. Furthermore, no inhaled corticosteroid was approved in the United States for the treatment of children younger than 4 years. Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, Del) was developed to meet the medication delivery needs of infants and young children with persistent asthma. Pulmicort Respules is the first inhaled corticosteroid approved for administration by means of a nebulizer and the only inhaled corticosteroid approved in the United States for infants as young as 12 months. Budesonide has been studied extensively worldwide. In the United States the tolerability and efficacy of budesonide inhalation suspension were confirmed in 3 placebo-controlled multicenter trials. These studies demonstrated that both once- and twice-daily dosing of budesonide inhalation suspension (0.25-1 mg) improved pulmonary function and ameliorated asthma symptoms in infants and young children with persistent asthma. Budesonide inhalation suspension was well tolerated, and the incidences of reported adverse events were similar among patients in the budesonide, placebo, and conventional asthma therapy groups. This article reviews the results of these studies, as well as the pharmacokinetics, pharmacodynamics, and clinical use of budesonide inhalation suspension.

  8. A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials

    PubMed Central

    SOTIRIOU, GEORGIOS A.; DIAZ, EDGAR; LONG, MARK S.; GODLESKI, JOHN; BRAIN, JOSEPH; PRATSINIS, SOTIRIS E.; DEMOKRITOU, PHILIP

    2013-01-01

    A novel method is presented which is suitable for assessing in-vivo the link between the physico-chemical properties of engineered nanomaterials (ENMs) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe2O3, SiO2, Ag and Ag/SiO2 was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in-vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe2O3 can cause both pulmonary and cardiovascular effects. PMID:21809902

  9. Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

    PubMed

    Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben

    2017-01-01

    Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r(2) values ranged between 0.46 and 0.90 and the secondary OA increased the r(2) values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r(2) 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs.

  10. Analysis of diacetylmorphine, caffeine, and degradation products after volatilization of pharmaceutical heroin for inhalation.

    PubMed

    Klous, Marjolein G; Lee, WeiChing; Hillebrand, Michel J X; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

    2006-01-01

    Pharmaceutical smokable heroin was developed for a clinical trial on medical co-prescription of heroin and methadone. This product, consisting of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate, was intended for use via "chasing the dragon", that is, inhalation after volatilization. This procedure involves heating the powder mixture, which may lead to formation of degradation products that could subsequently be inhaled. We developed a method that used a high-performance liquid chromatography system that was compatible with photodiode-array detection and mass spectrometric detection to separate diacetylmorphine- and caffeine-related compounds in a wide polarity range for analysis of the vapor. This method was used to analyze the contents of the plastic drinking straws that were used by patients to inhale the vapors from pharmaceutical heroin used via chasing the dragon, which were considered to be representative of the vapors the patients inhaled. They contained primarily unchanged diacetylmorphine, its main metabolite 6-acetylmorphine, caffeine, and some morphine. Several unidentified peaks were observed in the straw chromatograms. Chemical structures were proposed for nine degradation products: morphine derivatives with different substitution patterns of the C(3), C(6), and/or N(17) positions, which comprised 0.4-9.7% of the straw sample residue weight. Activity and toxicity of most of these compounds are unknown and require further investigation.

  11. Application and mechanism of inhalation profile improvement of DPI formulations by mechanofusion with magnesium stearate.

    PubMed

    Kumon, Michiko; Machida, Satoshi; Suzuki, Masahiko; Kusai, Akira; Yonemochi, Etsuo; Terada, Katsuhide

    2008-05-01

    In our previous paper, we reported the inhalation properties of dry powder inhaler (DPI) formulations containing Compound A and mechanofusion-processed lactose carriers. The mechanofusion process with magnesium stearate (Mg-St) on the lactose carrier enhanced the fine particle fraction (FPF) value of the Andersen cascade impactor (ACI) study. The increase of FPF seemed to be associated with the increase of the dispersibility of drug particles. The objectives of this study were (1) to evaluate the applicability of lactose carrier mechanofusion-processed with Mg-St and (2) to examine the mechanism of FPF alteration by the mechanofusion process applied on the lactose carrier with or without additive. The inhalation profiles of DPI formulations containing four different pharmaceutical compounds were evaluated with an ACI. The dispersibility of the formulations was observed by particle size distribution measurement in the air stream and the adhesive force was measured bydirect separation method. It was found that higher FPF was obtained with lactose mechanofusion-processed with Mg-St as compared to control lactose carriers for all four compounds. This suggested that mechanofusion process with Mg-St is widely applicable in DPI formulations. The homogenization of surface adhesiveness was attributed to the increased FPF of the DPI including lactose mechanofusion-processed with Mg-St, as suggested by the combination of several physicochemical characteristics. Combination of different characterization methods would be of help to clarify the whole mechanism which defines the inhalation properties of DPI formulations.

  12. Differences between inhaled and intravenous bronchial challenge to detect O(3)-induced hyperresponsiveness.

    PubMed

    Sommer, B; Vargas, M H; Chavez, J; Carbajal, V; Segura, P; Montaño, L M

    2001-12-01

    Ozone (O(3))-induced airway hyperresponsiveness in laboratory animals is usually demonstrated through dose-response curves with inhaled or intravenous bronchoconstrictor agonists. However, comparability of these two routes has not been well documented. Thus guinea pig airway responsiveness to ACh and histamine was evaluated 16-18 h after O(3) (3 parts/million, 1 h) or air exposure by two plethysmographic methods (spontaneously breathing and mechanically ventilated) and by two administration routes (inhalatory or intravenous). We found that O(3) caused airway hyperresponsiveness to intravenous, but not to inhaled, agonists, independent of the plethysmographic method used. Suitability of the inhalatory route to detect airway hyperresponsiveness was corroborated with inhaled ACh after an antigen challenge or extending O(3) exposure to 3 h. Acetylcholinesterase activity was not modified after O(3) exposure in lung homogenates and blood samples. Thus inhaled agonists were less effective to reveal the airway hyperresponsiveness after an acute O(3) exposure than intravenous ones, at least for the 1-h exposure to 3 parts/million, and this difference seems not to be related to an O(3)-induced inhibition of the acetylcholinesterase activity.

  13. Asphyxial suicide by inhalation of chloroform inside a plastic bag.

    PubMed

    Zorro, Andres Rodriguez

    2014-01-01

    Asphyxia suicide by placing a plastic bag over the head in addition with inhalation of gases or use of sedative substances is an unusual method of committing suicide, but frequently referenced by right to die groups in the Internet. This article reports 2 suicides in which chloroform was used to induce unconsciousness and subsequent asphyxia by placing the head in a plastic bag. Case histories of 2 males, ages 23 and 28, are described with special emphasis on characteristics death related to suffocation using plastic bags and chloroform. The final remarkable point in both cases is that the victims previously searched the WEB for instructions of suicide methods. The importance of the phenomenon of misuse of Internet by young people who commit suicide is stressed.

  14. Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug.

    PubMed Central

    O'Callaghan, C; Lynch, J; Cant, M; Robertson, C

    1993-01-01

    BACKGROUND--Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS--The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS--Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS--Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost. Images PMID:8346488

  15. Use of Respimat Soft Mist inhaler in COPD patients.

    PubMed

    Anderson, Paula

    2006-01-01

    Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy. Respimat Soft Mist Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices. The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs. This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy. In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI. In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases. Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD.

  16. Inhalation dosimetry modeling provides insights into regional respiratory tract toxicity of inhaled diacetyl.

    PubMed

    Cichocki, Joseph A; Morris, John B

    2016-11-13

    Vapor dosimetry models provide a means of assessing the role of delivered dose in determining the regional airway response to inspired vapors. A validated hybrid computational fluid dynamics physiologically based pharmacokinetic model for inhaled diacetyl has been developed to describe inhaled diacetyl dosimetry in both the rat and human respiratory tracts. Comparison of the distribution of respiratory tract injury with dosimetry estimates provides strong evidence that regional delivered dose rather than regional airway tissue sensitivity to diacetyl-induced injury is the critical determinant of the regional respiratory tract response to this water soluble reactive vapor. In the rat, inhalation exposure to diacetyl causes much lesser injury in the distal bronchiolar airways compared to nose and large tracheobronchial airways. The degree of injury correlates very strongly to model based estimates of local airway diacetyl concentrations. According to the model, regional dosimetry patterns of diacetyl in the human differ greatly from those in the rat with much greater penetration of diacetyl to the bronchiolar airways in the lightly exercising mouth breathing human compared to the rat, providing evidence that rat inhalation toxicity studies underpredict the risk of bronchiolar injury in the human. For example, repeated exposure of the rat to 200ppm diacetyl results in bronchiolar injury; the estimated bronchiolar tissue concentration in rats exposed to 200ppm diacetyl would occur in lightly exercising mouth breathing humans exposed to 12ppm. Consideration of airway dosimetry patterns of inspired diacetyl is critical to the proper evaluation of rodent toxicity data and its relevance for predicting human risk.

  17. Health effects of inhaled gasoline engine emissions.

    PubMed

    McDonald, Jacob D; Reed, Matthew D; Campen, Matthew J; Barrett, Edward G; Seagrave, JeanClare; Mauderly, Joe L

    2007-01-01

    Despite their prevalence in the environment, and the myriad studies that have shown associations between morbidity or mortality with proximity to roadways (proxy for motor vehicle exposures), relatively little is known about the toxicity of gasoline engine emissions (GEE). We review the studies conducted on GEE to date, and summarize the findings from each of these studies. While there have been several studies, most of the studies were conducted prior to 1980 and thus were not conducted with contemporary engines, fuels, and driving cycles. In addition, many of the biological assays conducted during those studies did not include many of the assays that are conducted on contemporary inhalation exposures to air pollutants, including cardiovascular responses and others. None of the exposures from these earlier studies were characterized at the level of detail that would be considered adequate today. A recent GEE study was conducted as part of the National Environmental Respiratory Center (www.nercenter.org). In this study several in-use mid-mileage General Motors (Chevrolet S-10) vehicles were purchased and utilized for inhalation exposures. An exposure protocol was developed where engines were operated with a repeating California Unified Driving Cycle with one cold start per day. Two separate engines were used to provide two cold starts over a 6-h inhalation period. The exposure atmospheres were characterized in detail, including detailed chemical and physical analysis of the gas, vapor, and particle phase. Multiple rodent biological models were studied, including general toxicity and inflammation (e.g., serum chemistry, lung lavage cell counts/differentials, cytokine/chemokine analysis, histopathology), asthma (adult and in utero exposures with pulmonary function and biochemical analysis), cardiovascular effects (biochemical and electrocardiograph changes in susceptible rodent models), and susceptibility to infection (Pseudomonas bacteria challenge). GEE resulted in

  18. Outcome of Inhaler Withdrawal in Patients Receiving Triple Therapy for COPD

    PubMed Central

    Kim, Sae Ahm; Lee, Ji-Hyun; Kim, Eun-Kyung; Kim, Tae-Hyung; Kim, Woo Jin; Lee, Jin Hwa; Yoon, Ho Il; Baek, Seunghee; Lee, Jae Seung; Oh, Yeon-Mok

    2016-01-01

    Background The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting β2-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice. Methods Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared with those who had undergone triple therapy for at least 1 year and subsequently, over 9 months, initiated inhaler withdrawal (step-down group, n=39). The index time was defined as the time of withdrawal in the stepdown group and as 1 year after the start of triple therapy in the triple group. Results Lung function at the index time was superior and the previous exacerbation frequency was lower in the stepdown group than in the triple group. Step-down resulted in aggravating disease symptoms, a reduced overall quality of life, decreasing exercise performance, and accelerated forced expiratory volume in 1 second (FEV1) decline (54.7±15.7 mL/yr vs. 10.7±7.1 mL/yr, p=0.007), but there was no observed increase in the frequency of exacerbations. Conclusion Withdrawal of a single inhaler during triple therapy in COPD patients should be conducted with caution as it may impair the exercise capacity and quality of life while accelerating FEV1 decline. PMID:26770231

  19. The enigma of inhaled salbutamol and sport: Unresolved after 45 years.

    PubMed

    Fitch, K D

    2017-03-11

    During the past 45 years, there have been more changes on the World Anti-Doping Agency's (WADA) Prohibited List (the List) to the status of inhaled salbutamol than any other substance. With 658 athletes, 6.1% of all participating athletes approved to inhale salbutamol at the 2008 Beijing Games, it is one of the medications used most frequently by Olympic athletes. Nevertheless, since the 2008 Games, WADA has made numerous changes to inhaled salbutamol on the List including prohibiting its use, then a year later permitting it without prior notification and recommending a pharmacokinetic study if an athlete exceeds the urinary threshold of 1000 ng/mL. Recently, an elite athlete undertook two pharmacokinetic studies and the results have raised several questions. These include whether WADA should continue to permit nebulized salbutamol as an acceptable method of inhalation and there is some justification for nebulized salbutamol to be prohibited in sport. Another question is whether the modified advisory on salbutamol in the 2017 List appropriately informs athletes of the risks of exceeding the urinary threshold and the recent changes may not inform athletes optimally. Finally, concern is expressed at the persistent failure of WADA to apply a correction down to a specific gravity of 1.020 when an exogenous substance is identified in the urine of a dehydrated athlete. It is recommended that this should be implemented.

  20. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  1. The effect of inhalation aromatherapy on anxiety level of the patients in preoperative period

    PubMed Central

    Fayazi, Sadigheh; Babashahi, Monireh; Rezaei, Mehdi

    2011-01-01

    BACKGROUND: Anxiety is the one of the most common problems before the surgery. Its prevalence rate ranged from 11 to 80 percent in all the adult patients. Delay in wound healing and increasing use of narcotics and anesthetics are some of the other accompanying problems. Aromatherapy is one of the complementary medicine components. It is applied by special type of oil extracted from aromatic plants for medical objectives. This study aimed to investigate the effects of inhalation aromatherapy on anxiety level in preoperative patients. METHODS: This was a clinical study done on 72 patients candidate for heart and abdominal surgery admitted in Golestan and Imam Khomeini hospitals. The patients were selected according to our study objectives and inclusion criteria. Then, they were divided in two case and control groups. The Spielberger scale was used for evaluating the anxiety level. Twenty minute of inhalation with handkerchief containing lavandula was used in the case group and placebo also (water) in the control group. RESULTS: The average of anxiety level in inhalation aromatherapy group decreased from 51.00 to 38.61 from before to after the intervention. This average in the inhalation group with placebo was 50.67 before the intervention and decreased to 49.53 after the intervention. The results of independent t-test statistically showed a significant difference between the two groups after the intervention. CONCLUSIONS: The findings showed that inhalation aromatherapy was effective on reduction of anxiety level and this method can be applied as a complementary medicine on the clinic. PMID:23449862

  2. Inhalational Anesthetics as Preconditioning Agents in Ischemic Brain

    PubMed Central

    Wang, Lan; Traystman, Richard J.; Murphy, Stephanie J.

    2008-01-01

    SUMMARY While many pharmacological agents have been shown to protect the brain from cerebral ischemia in animal models, none have translated successfully to human patients. One potential clinical neuroprotective strategy in humans may involve increasing the brain’s tolerance to ischemia by pre-ischemic conditioning (preconditioning). There are many methods to induce tolerance via preconditioning such as: ischemia itself, pharmacological, hypoxia, endotoxin, and others. Inhalational anesthetic agents have also been shown to result in brain preconditioning. Mechanisms responsible for brain preconditioning are many, complex, and unclear and may involve Akt activation, ATP-sensitive potassium channels, and nitric oxide, amongst many others. Anesthetics, however, may play an important and unique role as preconditioning agents, particularly during the perioperative period. PMID:17962069

  3. Inhalation toxicity of methyl difluoromalonyl fluoride in rats

    SciTech Connect

    Kennedy, G.L. Jr.; Burgess, B.A.; Chen, H.C.

    1988-06-01

    Methyl 2,2-difluoromalonyl fluoride (MMF) is highly toxic by inhalation producing mortality in rats exposed for 4 hours to 0.55 mg/L. Repeated inhalation exposures of rats to 0.009 mg/L produced irritation but no other signs of a toxic response. Mortality was encountered following repeated exposures to 0.066 mg/L.

  4. 49 CFR 179.102-3 - Materials poisonous by inhalation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Materials poisonous by inhalation. 179.102-3... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK... Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of...

  5. Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (Final Report)

    EPA Science Inventory

    EPA has finalized its Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide. This assessment addresses the potential carcinogenicity from long-term inhalation exposure to ethylene oxide. Now final, this assessment updates the carcinogenicity information in EPA’s 1985 Hea...

  6. [The choice of inhalation device: A medical act].

    PubMed

    Devillier, P; Salvator, H; Roche, N

    2015-06-01

    Inhaled treatments are essential for respiratory diseases management, including COPD and asthma. Optimal control of the disease largely depends on patient's compliance and proper use of these treatments. Different types of ready-to-use inhaler devices are available: metered dose inhaler, dry powder inhaler or soft mist inhaler. Each of these devices presents specific characteristics and constraints that have to be evaluated and taken into account before prescription. In order to optimize adherence and treatment efficacy, the choice of inhaler device should depend on the specific needs, abilities and preferences of each patient and a specific education to treatment should be provided. Inhaled treatments, even containing the same drug, have different technical constraints and are thus not easily interchangeable. Their substitution without prior medical consent and without proper training can lead to errors in taking treatment, treatment failures and increased health care consumption. In France, substitution by the pharmacist is not authorized. While patient education must be carried out in collaboration with all health professionals, it is preferable that the choice of inhaler device remains the responsibility of the physician.

  7. 49 CFR 179.102-3 - Materials poisonous by inhalation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a... 49 Transportation 3 2012-10-01 2012-10-01 false Materials poisonous by inhalation. 179.102-3 Section 179.102-3 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE...

  8. 49 CFR 179.102-3 - Materials poisonous by inhalation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a... 49 Transportation 3 2011-10-01 2011-10-01 false Materials poisonous by inhalation. 179.102-3 Section 179.102-3 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE...

  9. 49 CFR 179.102-3 - Materials poisonous by inhalation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a... 49 Transportation 3 2014-10-01 2014-10-01 false Materials poisonous by inhalation. 179.102-3 Section 179.102-3 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE...

  10. Purpura and dermal thinning associated with high dose inhaled corticosteroids.

    PubMed Central

    Capewell, S; Reynolds, S; Shuttleworth, D; Edwards, C; Finlay, A Y

    1990-01-01

    OBJECTIVE--To assess the effect of high dose inhaled corticosteroids on skin. DESIGN--Cross sectional study of patients receiving treatment for chest diseases. SETTING--Outpatient chest clinic in a teaching hospital. PATIENTS--68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES--Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS--Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION--Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids. PMID:2372620

  11. IRIS Toxicological Review of Ammonia Noncancer Inhalation (Final Report)

    EPA Science Inventory

    EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the ...

  12. The Deliberate Inhalation of Volatile Substances. Series 30, No. 1.

    ERIC Educational Resources Information Center

    Gamage, James R.; Zerkin, E. Lief

    This report, prepared by the National Clearinghouse for Drug Abuse Information, presents information on the deliberate inhalation of volatile substances--the treatment modalities, the pharmacology and chemistry of this drug abuse, and the opinions and practices of recognized authorities in the field. Substances which are currently being inhaled to…

  13. Use of nitric oxide inhalation in chronic obstructive pulmonary disease

    PubMed Central

    Ashutosh, K.; Phadke, K.; Jackson, J. F.; Steele, D.

    2000-01-01

    BACKGROUND—Inhalation of nitric oxide with oxygen could be a promising treatment in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension. However, the current methods of delivery of NO are cumbersome and unsuitable for long term use. The present study was undertaken to investigate the safety and efficacy of a mixture of nitric oxide (NO) and oxygen administered via a nasal cannula for 24 hours in patients with oxygen dependent COPD.
METHODS—Twenty five parts per million (ppm) of NO was administered by inhalation combined with supplemental oxygen at a flow rate of 2 l/min via a nasal cannula for 24 hours to 11 ambulatory men with stable, oxygen dependent COPD. Room air with supplemental oxygen at 2 l/min was administered in an identical manner for another 24 hours as control therapy in a randomised, double blind, crossover fashion to all patients. Pulmonary function tests, exercise tolerance, dyspnoea grade, and lung volumes were measured at baseline, 24, and 48 hours. Pulmonary artery pressure (PAP), cardiac output (CO), pulmonary vascular resistance (PVR), arterial blood gas tensions, and minute ventilation were measured at baseline, after 30 minutes and 24 hours of breathing NO and oxygen. Venous admixture ratio (Qs/Qt) and dead space ratio (Vd/Vt) were also calculated. Concentrations of nitrogen dioxide (NO2) and NO in the inhaled and ambient air were monitored continuously. Differences in pulmonary function, arterial blood gas tensions, pulmonary haemodynamics, exercise tolerance, and dyspnoea between oxygen and NO breathing periods were analysed for significance using paired t tests.
RESULTS—A significant (p<0.05) fall was observed in PVR (183.1 (116.05) and 137.2 (108.4) dynes.s.cm-3 before and after breathing NO for 24 hours, respectively) with NO administration without significant changes in symptoms, pulmonary function, arterial oxygen tension, or exercise tolerance.
CONCLUSIONS—NO at a concentration of 25 ppm

  14. The validity of the EASE expert system for inhalation exposures.

    PubMed

    Cherrie, John W; Hughson, Graeme W

    2005-03-01

    Estimation and Assessment of Substance Exposure (EASE) is a computerized expert system developed by the UK Health and Safety Executive to facilitate exposure assessments in the absence of exposure measurements. The system uses a number of rules to predict a range of likely exposures or an 'end-point' for a given work situation. The purpose of this study was to identify a number of inhalation exposure measurements covering a wide range of end-points in the EASE system to compare with the predicted exposures. Occupational exposure data sets were identified from previous research projects or from consultancy work. Available information for each set of measurements was retrieved from archive storage and reviewed to ensure that it was adequate to enable EASE (version 2) predictions to be obtained. Exposure measurements and other relevant contextual data were abstracted and entered into a computer spreadsheet. EASE predictions were then obtained for each task or job and entered into the spreadsheet. In addition, we generated a random exposure range for each data set for comparison with the EASE predictions. Finally, we produced exposure assessments for a subset of the data using a structured subjective assessment method. We were able to identify approximately 4000 inhalation exposure measurements covering 52 different scenarios and 28 EASE end-points. The data included measurements of solvent vapours, non-fibrous dusts and fibres. In 62% of the end-points the EASE predictions were generally greater than the exposure measurements and in 30% of the end-points the EASE estimates were comparable with the measurements. The random allocation of exposure ranges was, as expected, less reliable than EASE, although there were still about one-third of the cases where the randomly generated exposure ranges generally agreed with the measurements. The structured subjective assessments undertaken by a human expert produced exposure estimates in better agreement with the measurements

  15. Pulmonary and Systemic Immune Response to Chronic Lunar Dust Inhalation

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Quiriarte, Heather; Nelman, Mayra; Lam, Chiu-wing; James, John T.; Sams, Clarence

    2014-01-01

    Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra-fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non-exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post-exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL-1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL-1b and IL-6, and decreased IL-2

  16. Respiratory disorders associated with heavy inhalation exposure to dolomite dust

    PubMed Central

    Neghab, M; Abedini, R; Soltanzadeh, A; Iloon Kashkooli, A; Ghayoomi, S M A

    2012-01-01

    Background Although dolomite is classified as a relatively non-toxic, nuisance dust, little information exists as to its potential to produce respiratory disorders following occupational exposure. The purpose of this study was, therefore, to evaluate the possible effects, if any, of heavy inhalation exposure to this chemical on the prevalence of respiratory symptoms, functional impairments and radiographic abnormalities of the lungs. Methods The study population consisted of a group of 39 exposed subjects engaged in digging and excavating activities that were in operation for building a local dam, as well as 40 healthy non-exposed employees that served as the referent group. Subjects were interviewed and respiratory symptoms questionnaires, as suggested by the American Thoracic Society (ATS), were completed for them. Thereafter, they underwent chest X-ray and lung function tests. Additionally, using routine gravimetric techniques, personal dust monitoring for airborne inhalable and respirable dust was carried out at different dusty work sites. Finally to determine the chemical composition of the dust, it was analyzed by X-ray fluorescence (XRF) technique. Results XRF revealed that the major component (50.52%) of the dust was calcium magnesium carbonate, dolomite. Additionally, levels of exposure to inhalable and respirable dust were estimated to be 51.7±24.31 and 23.0±18.11mg/m3, respectively. Statistical analysis of the data showed that symptoms such as regular cough, phlegm, wheezing, productive cough and shortness of breath were significantly (p<0.05) more prevalent among exposed workers. Similarly, the ratio of FEV1/FVC in exposed subjects was significantly different from that of non-exposed individuals. In contrast, no significant abnormalities were observed in the chest radiographs of both groups. Conclusions In conclusion, while these data cast doubt on the notion that dolomite is a harmless chemical, they provide evidence in favour of the proposition that

  17. Inhaled corticosteroids in COPD: a controversy.

    PubMed

    Barnes, Peter J

    2010-01-01

    Inhaled corticosteroids (ICS) are now very widely used in high doses in the management of COPD patients. In sharp contrast to the situation in asthma, ICS provide little or no benefit in COPD patients and may have long-term detrimental effects. High doses of ICS fail to reduce disease progression or mortality, even when combined with a long-acting beta(2)-agonist (LABA). Several trials have demonstrated that ICS reduce exacerbations by 20-25%, particularly in patients with more severe disease, but these studies are confounded by poor trial design and more appropriate analysis shows no benefit. Indeed, the benefit of combination inhalers seems to be largely due to the effect of the LABA, and long-acting bronchodilators--including tiotropium--provide similar benefits in reducing exacerbations. However, there may be some COPD patients, for example those with concomitant asthma, who benefit from ICS. Yet it has not been possible to identify any clinical factors that predict corticosteroid responsiveness in COPD patients in the large clinical trials. There is increasing evidence that high doses of ICS may have detrimental effects on bones and may increase the risk of pneumonia. ICS fail to suppress inflammation in COPD patients because there is a marked reduction in histone deacetylase-2, the nuclear enzyme that corticosteroids require to switch off activated inflammatory genes. In the future, alternative anti-inflammatory treatments will be needed for COPD or therapeutic strategies which reverse the molecular pathways that causes corticosteroid resistance.

  18. IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

    EPA Pesticide Factsheets

    In September 2016, EPA finalized the IRIS assessment of Ammonia (Noncancer Inhalation). The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release in June 2016. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ammonia (Noncancer Inhalation) are posted on this site. Note: No major science comments were received on the Interagency Science Discussion Draft. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

  19. [Inhaled antibiotic therapy in cystic fibrosis].

    PubMed

    Girón Moreno, Rosa M; Salcedo Posadas, Antonio; Mar Gómez-Punter, Rosa

    2011-06-01

    Cystic fibrosis is the most frequent fatal genetically-transmitted disease among Caucasians. Chronic bronchial infection, especially by Pseudomonas aeruginosa, is the main cause of morbidity and mortality in this disease. Aerosolized antibiotic therapy achieves high drug concentrations in the airway with low toxicity, allowing chronic use. Currently, two antibiotics have been approved for inhalation therapy, tobramycin inhalation solution and colistimethate sodium aerosol. There is less evidence from clinical trials for the latter. The main indication for these drugs is chronic bronchial colonization by P. aeruginosa, although there is increasing evidence of the importance of the primary infection by this bacterium, whether treated by oral or intravenous antibiotics or not. More controversial is the use of aerosolized antibiotic therapy in bacterial prophylaxis or respiratory exacerbations. For many years, intravenous formulations of distinct antibiotics for aerosolized use have been employed, which are in distinct phases of research for use in nebulizer therapy. In addition to being used to treat P. aeruginosa infection, aerosolized antibiotics have been used to treat other pathogens such as methicillin-resistant Staphylococus aureus, Mycobacterium abscessus and Aspergillus fumigatus.

  20. Lethal methemoglobinemia and automobile exhaust inhalation.

    PubMed

    Vevelstad, Merete; Morild, Inge

    2009-05-30

    Inhalation of automobile exhaust gas often leads to death by CO intoxication. In some cases the measured carbon monoxide hemoglobin saturation level (COHb) is considerably below what is considered to be lethal. The death in such cases has been attributed to a combination of a high CO2 and a low O2 tension. In a recent case the deceased was found dead in a car equipped with a catalytic converter, with a hose leading exhaust from the engine to the interior of the car. Analysis revealed a moderately elevated COHb and a high methemoglobin saturation level (MetHb) in peripheral blood. No ethanol, narcotics or drugs were detected. Reports mentioning MetHb or methemoglobinemia in post-mortem cases are surprisingly scarce, and very few have related exhaust gas deaths to methemoglobinemia. High-degree methemoglobinemia causes serious tissue hypoxia leading to unconsciousness, arrhythmia and death. The existing literature in this field and the knowledge that exhaust fumes contain nitrogen oxide gases (NOx) that by inhalation and absorption can result in severe methemoglobinemia, led us to postulate that this death could possibly be attributed to a combination of methemoglobinemia and a moderately high COHb concentration.

  1. Reducing Agents Decrease the Oxidative Burst and Improve Clinical Outcomes in COPD Patients: A Randomised Controlled Trial on the Effects of Sulphurous Thermal Water Inhalation

    PubMed Central

    Gnesini, Giulia; Forini, Giacomo; Marku, Brunilda; Pauletti, Alessia; Padovani, Anna; Casolari, Paolo; Taurino, Liliana; Ferraro, Andrea; Chicca, Milva; Ciaccia, Adalberto; Papi, Alberto; Pinamonti, Silvano

    2013-01-01

    Background. Inhalation of thermal water with antioxidant properties is empirically used for COPD. Aims. To evaluate the effects of sulphurous thermal water (reducing agents) on airway oxidant stress and clinical outcomes in COPD. Methods. Forty moderate-to-severe COPD patients were randomly assigned to receive 12-day inhalation with sulphurous thermal water or isotonic saline. Patients were assessed for superoxide anion (O2−) production in the exhaled breath condensate and clinical outcomes at recruitment, the day after the conclusion of the 12-day inhalation treatment, and one month after the end of the inhalation treatment. Results. Inhalation of reducing agents resulted in a significant reduction of O2− production in exhaled breath condensate of COPD patients at the end of the inhalatory treatment and at followup compared to baseline. A significant improvement in the COPD assessment test (CAT) questionnaire was shown one month after the end of the inhalatory treatment only in patients receiving sulphurous water. Conclusion. Thermal water inhalation produced an in vivo antioxidant effect and improvement in health status in COPD patients. Larger studies are required in order to evaluate whether inhalation of thermal water is able to modify relevant clinical outcomes of the disease (the study was registered at clinicaltrial.gov—identifier: NCT01664767). PMID:24453924

  2. Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals

    PubMed Central

    Unfried, Klaus; Krämer, Ursula; Sydlik, Ulrich; Autengruber, Andrea; Bilstein, Andreas; Stolz, Sabine; Marini, Alessandra; Schikowski, Tamara; Keymel, Stefanie; Krutmann, Jean

    2016-01-01

    Background Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial. Objective The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin® inhalation solution) leads to a reduction of neutrophilic cells and interleukin-8 (IL-8) levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution. Methods A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined. Results While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite) were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence interval 0.45–0.93). Extended analyses considering period effects revealed that the percentage of neutrophils in sputum was significantly lower after ectoine inhalation than in the placebo group (P=0.035) even after the washout phase. Conclusion The current study is the first human trial in which the effects of inhaled ectoine on neutrophilic lung inflammation were investigated. Besides demonstrating beneficial effects on inflammatory sputum

  3. Relationship between the Use of Inhaled Steroids for Chronic Respiratory Diseases and Early Outcomes in Community-Acquired Pneumonia

    PubMed Central

    Almirall, Jordi; Bolíbar, Ignasi; Serra-Prat, Mateu; Palomera, Elisabet; Roig, Jordi; Hospital, Imma; Carandell, Eugenia; Agustí, Mercè; Ayuso, Pilar; Estela, Andreu; Torres, Antoni

    2013-01-01

    Background The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP). We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. Methods Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality). Results Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%). In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542), with COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. Conclusions Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis. PMID:24039899

  4. Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

    PubMed Central

    Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

    2012-01-01

    Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

  5. Decreased response to inhaled steroids in overweight and obese asthmatic children

    PubMed Central

    Forno, Erick; Lescher, Rachel; Strunk, Robert; Weiss, Scott; Fuhlbrigge, Anne; Celedón, Juan C.

    2011-01-01

    Background The mechanisms and consequences of the observed association between obesity and childhood asthma are unclear. Objectives To determine the effect of obesity on treatment responses to inhaled corticosteroids in asthmatic children. Methods We performed a post hoc analysis to evaluate the interaction between body mass index (BMI) and treatment with inhaled budesonide on lung function in the Childhood Asthma Management Program (CAMP) trial. Participants were then stratified into overweight/obese and non-overweight, and their response to inhaled budesonide was analyzed longitudinally over the 4 years of the trial. Results There was a significant interaction between BMI and budesonide for pre-BD FEV1/FVC (P=0.0007) and bronchodilator response (BDR) (P=0.049), and a non-significant trend for an interaction between BMI and budesonide on pre-BD FEV1 (P=0.15). Non-overweight children showed significant improvement with inhaled budesonide in lung function (FEV1, FEV1/FVC, and BDR) during the early (years 1–2) and late stages (years 3–4) of the trial. Overweight/obese children had improved FEV1 and BDR during the early but not the late stage of the trial, and showed no improvement in FEV1/FVC. When comparing time points where both groups showed significant response, the degree of improvement among non-overweight children was significantly greater than in overweight/obese children at most visits. Non-overweight children had a 44% reduction in the risk of ER visits or hospitalizations throughout the trial (P=0.001); there was no reduction in risk among overweight/obese (P=0.97). Conclusions Compared to children of normal weight, overweight/obese children in CAMP showed a decreased response to inhaled budesonide on measures of lung function and ER visits/hospitalizations for asthma. PMID:21377042

  6. Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

    PubMed Central

    Raphael, Gordon; Taveras, Herminia; Iverson, Harald; O’Brien, Christopher; Miller, David

    2016-01-01

    Abstract Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN). Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. Conclusions: The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma. PMID:26369589

  7. Pediatric in vitro and in silico models of deposition via oral and nasal inhalation.

    PubMed

    Carrigy, Nicholas B; Ruzycki, Conor A; Golshahi, Laleh; Finlay, Warren H

    2014-06-01

    Respiratory tract deposition models provide a useful method for optimizing the design and administration of inhaled pharmaceutical aerosols, and can be useful for estimating exposure risks to inhaled particulate matter. As aerosol must first pass through the extrathoracic region prior to reaching the lungs, deposition in this region plays an important role in both cases. Compared to adults, much less extrathoracic deposition data are available with pediatric subjects. Recently, progress in magnetic resonance imaging and computed tomography scans to develop pediatric extrathoracic airway replicas has facilitated addressing this issue. Indeed, the use of realistic replicas for benchtop inhaler testing is now relatively common during the development and in vitro evaluation of pediatric respiratory drug delivery devices. Recently, in vitro empirical modeling studies using a moderate number of these realistic replicas have related airway geometry, particle size, fluid properties, and flow rate to extrathoracic deposition. Idealized geometries provide a standardized platform for inhaler testing and exposure risk assessment and have been designed to mimic average in vitro deposition in infants and children by replicating representative average geometrical dimensions. In silico mathematical models have used morphometric data and aerosol physics to illustrate the relative importance of different deposition mechanisms on respiratory tract deposition. Computational fluid dynamics simulations allow for the quantification of local deposition patterns and an in-depth examination of aerosol behavior in the respiratory tract. Recent studies have used both in vitro and in silico deposition measurements in realistic pediatric airway geometries to some success. This article reviews the current understanding of pediatric in vitro and in silico deposition modeling via oral and nasal inhalation.

  8. 5% CO2 is a potent, fast acting inhalation anticonvulsant

    PubMed Central

    Tolner, Else A.; Hochman, Daryl W.; Hassinen, Pekka; Otáhal, Jakub; Gaily, Eija; Haglund, Michael M.; Kubová, Hana; Schuchmann, Sebastian; Vanhatalo, Sampsa; Kaila, Kai

    2010-01-01

    Purpose CO2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO2 can be used to suppress seizures in epilepsy patients. The effect of CO2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and a non-human primate and based on these data, preliminary tests were carried out in humans. Methods In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. 5% CO2 was applied for 5 minutes, 3 minutes before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG and received 5% CO2 in medical carbogen shortly after electrographic seizure onset. Results In rats, 5% CO2 strongly suppressed cortical afterdischarges, by ca. 75%, while responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO2 from 37 to 44-45 mmHg (corresponding to inhalation of 5% CO2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by ca. 25%. In a pilot trial carried out in 7 patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO2 was started after seizure generalization. Conclusions 5% CO2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO2 can be used for acute treatment to suppress seizures in epilepsy patients. PMID:20887367

  9. Reporting a sudden death due to accidental gasoline inhalation.

    PubMed

    Martínez, María Antonia; Ballesteros, Salomé; Alcaraz, Rafael

    2012-02-10

    The investigation of uncertain fatalities requires accurate determination of the cause of death, with assessment of all factors that may have contributed to it. Gasoline is a complex and highly variable mixture of aliphatic and aromatic hydrocarbons that can lead to cardiac arrhythmias due to sensitization of the myocardium to catecholamines or acts as a simple asphyxiant if the vapors displace sufficient oxygen from the breathing atmosphere. This work describes a sudden occupational fatality involving gasoline. The importance of this petroleum distillate detection and its quantitative toxicological significance is discussed using a validated analytical method. A 51 year-old Caucasian healthy man without significant medical history was supervising the repairs of the telephone lines in a manhole near to a gas station. He died suddenly after inhaling gasoline vapors from an accidental leak. Extensive blistering and peeling of skin were observed on the skin of the face, neck, anterior chest, upper and lower extremities, and back. The internal examination showed a strong odor of gasoline, specially detected in the respiratory tract. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography with flame ionization detector and confirmation was performed using gas chromatography-mass spectrometry. Disposition of gasoline in different tissues was as follows: heart blood, 35.7 mg/L; urine, not detected; vitreous humor, 1.9 mg/L; liver, 194.7 mg/kg; lung, 147.6 mg/kg; and gastric content, 116,6 mg/L (2.7 mg total). Based upon the toxicological data along with the autopsy findings, the cause of death was determined to be gasoline poisoning and the manner of death was accidental. We would like to alert on the importance of testing for gasoline, and in general for volatile hydrocarbons, in work-related sudden deaths involving inhalation of hydrocarbon vapors and/or exhaust fumes.

  10. Nicotine and Carbon Monoxide Exposure from Inhalation of Cigarillo Smoke

    PubMed Central

    Koszowski, Bartosz; Rosenberry, Zachary R.; Kanu, Alieu; Viray, Lauren C.; Potts, Jennifer L.; Pickworth, Wallace B.

    2015-01-01

    Background There has been an increase in the use of cigarillos in the US. People who smoke cigarillos typically also regularly smoke cigarettes (dual users). Methods We compared puffing topography, biomarkers of acute exposure [exhaled carbon monoxide (COex) and plasma nicotine] and physiologic effects from usual brand cigarette and Black & Mild cigarillo smoking in dual users (N=23) in two laboratory sessions. Results Participants (21 men) smoked an average of 17.5 cigarettes/day. Cigarillo consumption varied widely from as few as 1/week to daily. Participants were highly nicotine dependent (average FTND score: 6.3). There were statistically significant differences in smoking behavior between cigarette and cigarillo smoking in time to smoke, number of puffs, and total puff volume (all P<0.001). Average puff duration, interpuff interval average puff volume, and puff velocity did not differ between cigarettes and cigarillos. Nicotine boost was similar after both cigarettes and cigarillos. COex boost was significantly greater after cigarillo smoking compared to cigarette smoking (P<0.001). Conclusions The smoking pattern and exposure profile indicate that dual users inhale cigarillo smoke just as they inhale cigarette smoke thereby exposing themselves to considerable amounts of nicotine and other components of tobacco smoke. COex exposure results imply that cigarillo smoking may be associated with higher exposure to smoke-delivered volatile components of mainstream cigarillo smoke including carcinogens when compared to cigarettes. Impact The findings that cigarillos and cigarettes are smoked similarly in dual users are relevant to health and regulatory considerations on cigar products. PMID:26459155

  11. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients.

    PubMed

    Rook, Elisabeth J; van Ree, Jan M; van den Brink, Wim; Hillebrand, Michel J X; Huitema, Alwin D R; Hendriks, Vincent M; Beijnen, Jos H

    2006-01-01

    A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to

  12. Current Scientific and Regulatory Approaches for Development of Orally Inhaled and Nasal Drug Products: Overview of the IPAC-RS/University of Florida Orlando Inhalation Conference.

    PubMed

    Hochhaus, Guenther; Davis-Cutting, Craig; Oliver, Martin; Lee, Sau L; Lyapustina, Svetlana

    2015-09-01

    This article summarizes discussions at the March 2014 conference organized by the University of Florida (UF) and International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS), entitled "Orlando Inhalation Conference: Approaches in International Regulation." The special focus of the conference was on global scientific and regulatory issues associated with the testing and demonstration of equivalence for the registration of orally inhaled drug products (OIDPs) in the United States, Europe, Brazil, China, and India. The scope included all types of OIDPs throughout their lifecycle, e.g., innovator/brand-name products, generics, modifications due to lifecycle management, device changes, etc. Details were presented for the U.S. "weight of evidence approach" for registration of generic products (which includes demonstration of in vitro and in vivo equivalence, as well as quantitative and qualitative sameness, and device similarity). The European "stepwise" approach was elucidated, and the thinking of regulatory agencies in the major emerging markets was clarified. The conference also highlighted a number of areas that would benefit from further research and discussion, especially around patient/device interface and human factor studies, statistical methods and criteria for demonstrating equivalence, the relative roles of in vivo and in vitro tests, and appropriate designs and metrics for in vivo studies of inhaled drugs.

  13. Deposition, retention, and clearance of inhaled particles.

    PubMed Central

    Lippmann, M; Yeates, D B; Albert, R E

    1980-01-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  14. Performance of combination drug and hygroscopic excipient submicrometer particles from a softmist inhaler in a characteristic model of the airways.

    PubMed

    Longest, P Worth; Tian, Geng; Li, Xiang; Son, Yoen-Ju; Hindle, Michael

    2012-12-01

    Excipient enhanced growth (EEG) of inhaled submicrometer pharmaceutical aerosols is a recently proposed method intended to significantly reduce extrathoracic deposition and improve lung delivery. The objective of this study was to evaluate the size increase of combination drug and hygroscopic excipient particles in a characteristic model of the airways during inhalation using both in vitro experiments and computational fluid dynamic (CFD) simulations. The airway model included a characteristic mouth-throat (MT) and upper tracheobronchial (TB) region through the third bifurcation and was enclosed in a chamber geometry used to simulate the thermodynamic conditions of the lungs. Both in vitro results and CFD simulations were in close agreement and indicated that EEG delivery of combination submicrometer particles could nearly eliminate MT deposition for inhaled pharmaceutical aerosols. Compared with current inhalers, the proposed delivery approach represents a 1-2 order of magnitude reduction in MT deposition. Transient inhalation was found to influence the final size of the aerosol based on changes in residence times and relative humidity values. Aerosol sizes following EEG when exiting the chamber (2.75-4.61 μm) for all cases of initial submicrometer combination particles were equivalent to or larger than many conventional pharmaceutical aerosols that frequently have MMADs in the range of 2-3 μm.

  15. The Respimat Soft Mist Inhaler, a Novel Inhaled Drug Delivery Device.

    PubMed

    Perriello, Emily A; Sobieraj, Diana M

    2016-01-01

    Summary The Respimat SMI offers a novel delivery mechanism for the management of primarily COPD, but asthma as well. Presently, four different medications, as monotherapy or a combination of two active ingredients, are available using the Respimat SMI technology. Multiple studies have demonstrated safety and efficacy of these drugs when delivered via Respimat SMI. Patients tend to prefer the Respimat SMI over traditional inhaler devices, as it overcomes some of the disadvantages posed by traditional delivery devices.

  16. Nitrous Oxide Inhalation Among Adolescents: Prevalence, Correlates, and Co-Occurrence with Volatile Solvent Inhalation

    PubMed Central

    Garland, Eric L.; Howard, Matthew O.; Perron, Brian E.

    2010-01-01

    Few studies have examined the prevalence of nitrous oxide (NO) inhalation or co-occurrence of NO and volatile solvent (VS) use in adolescents. Study aims were to (1) describe the independent and conjoint prevalence of NO and VS use in incarcerated youth, (2) compare adolescent users of both NO and VS inhalants (NO+VS) to users of NO-only, VS-only, and nonusers of NO and VS (NO/VS nonusers) with regard to demographic, psychological, and behavioral characteristics, and (3) conduct logistic regression analyses identifying correlates of NO use. Residents (N = 723) of Missouri Division of Youth Services were assessed with standardized psychosocial measures. Participants averaged 15.5 (SD = 1.2) years of age, were ethnically diverse and predominantly male. Lifetime prevalence of NO use was 15.8%. NO+VS users evidenced greater impairments compared to NO+VS nonusers. VS-only users evidenced impairments that were similar in kind but at lower prevalences compared to those displayed by NO+VS users, whereas NO-only youth had profiles that were similar to those of NO/VS nonusers. Psychiatric disorders, polydrug use, and temperamental fearlessness were correlates of NO use. NO+VS users were at high risk for behavioral and emotional problems. Screening and interventions for NO and VS inhalant use should be implemented in juvenile justice facilities. PMID:20235440

  17. Cost Reduction of Inhaled Tobramycin by Use of Preservative-Free Intravenous Tobramycin Given via Inhalation

    PubMed Central

    Gauthier, Timothy P.; Wasko, Justin; Unger, Nathan R.; Abbo, Lilian M.; Fernandez, Margaret; Aragon, Laura

    2015-01-01

    This study evaluates drug cost outcomes related to automatic therapeutic substitution of branded tobramycin solution for inhalation (TOBI®) with inhaled generic preservative-free intravenous tobramycin (PFIT). A retrospective single-center evaluation of inhaled tobramycin use from 2008 through 2012 was performed. Number of doses dispensed and acquisition costs were obtained. Hourly wage data was acquired, pharmacy production costs were estimated and total cost-savings calculated. Days of therapy (DOTs) were determined for each year. Quality assurance and safety data was collected. In 2008, TOBI® drug costs and doses dispensed were $118,665 and 1769, respectively. Following implementation of the interchange in May 2009, TOBI® utilization ceased. PFIT costs in 2010 through 2012 averaged $34,775 annually and TOBI® cost-avoidance exceeded $94,000 annually when accounting for pharmacy production costs, which were determined to be at most $5.28 per dose. The maximum estimated pharmacy production cost ranged from $8812 to $11,299 annually. PFIT doses dispensed exceeded 1650 each year and annual DOTs ranged from 815 to 1069. The 40-month savings were calculated to be $374,706. Quality assurance and safety data identified one patient who refused PFIT due to odor complaints and one patient who was inappropriately administered a dose orally. Therapeutic substitution of TOBI® with PFIT can produce immediate and sustained savings with an acceptable safety profile. PMID:27025517

  18. Inhaled Formulation Design for the Treatment of Lung Infections.

    PubMed

    Garcia-Contreras, Lucila; Yadav, Khushwant S

    2015-01-01

    Lung infections may be bacterial, viral or fungal and they are typically treated with oral or parenteral antibiotics. Inhaled dry powder formulations offer unique opportunities for treating lung infections with enhanced effectiveness and stability. Since drug delivery to the lungs requires chronic and repeated administration of larger amounts of therapeutics, dry powder formulations are attractive alternatives to deliver drugs directly to the lungs as they are not limited by solubility issues and they are regarded as being more stable than liquid dosage forms. This state-of-the-art review presents the use of inhaled formulations for tuberculosis as a main focus, but also for other diseases such as bronchiectasis, chronic obstructive pulmonary disease (COPD), pneumonia and respiratory infections occurring as complications during lung transplants. Opportunities for the use of inhaled therapies and other respiratory diseases or as prevention or antidotes against warfare agents are offered. Typical and novel inhaled formulations that have been used as well as preclinical and clinical studies and evaluation of these inhaled therapies are discussed for each disease state. Lastly, the use of inhaled therapies as an alternative to end the emergence of drug resistant strains is discussed along with the risks of increasing these resistant strains if the inhaled therapy is not designed based on dosing regimens established by wellplanned pharmacokinetic and pharmacodynamic studies.

  19. [Wood dust as inhalative noxious agent].

    PubMed

    Kirsten, D; Liebetrau, G; Meister, W

    1985-01-01

    Wood dust is known as a cause of asthma and chronic bronchitis. From 1979 to 1983 we observed 115 patients with chronic lung diseases, who were exposed to wood dust during many years. We found an irritative pathogenesis in 101 patients with asthma or bronchitis. Twenty nine patients had got a positive skin test, especially with makoré, beech, koto, ash, pine. The inhalation test was positive in 7 of them. The occupational etiology was verified in 5 patients. Besides wood dust itself chemicals for wood protection or wood adhesives can have importance in the pathogenesis of these diseases. Fourteen patients had got alveolitis or lung fibrosis after wood-dust exposition. In each case we found precipitating antibodies against moulds, which could be cultivated from wood dust to which the patients were exposed.

  20. Combined inhaled corticosteroid and long-acting β2-adrenergic agonist therapy for noncystic fibrosis bronchiectasis with airflow limitation

    PubMed Central

    Wei, Ping; Yang, Jia-Wei; Lu, Hai-Wen; Mao, Bei; Yang, Wen-Lan; Xu, Jin-Fu

    2016-01-01

    Abstract Background and objective: There is presently no clear evidence on the effect of combined treatment for non-cystic fibrosis (non-CF) bronchiectasis with inhaled corticosteroid (ICS) and long-acting β2-adrenergic agonist (LABA). The objective of this study is to assess the efficacy and safety of salmeterol-fluticasone combined inhaled therapy for non-CF bronchiectasis with airflow limitation. Methods: An observational study was performed in 120 non-CF bronchiectasis patients diagnosed by high-resolution computed tomography (HRCT) scanning of the chest. Patients received either routine therapy or salmeterol-fluticasone (100/500 μg daily) combined inhaled therapy on the basis of routine therapy. Clinical symptoms, health-related quality of life (HRQL), lung function, short-acting β2-adrenergic agonist (SABA) use, and safety were monitored throughout the study. Results: OF the 120 subjects, 60 received combined inhaled therapy and 60 received routine therapy. Compared to the control group, the combined inhaled therapy group showed significant improvement in their clinical symptom scores (−2.21 vs. −0.31, P = 0.002) and a reduction in number of weekly SABA usage (−4.2 vs. 0.1, P < 0.01). In addition, patients in the inhaled therapy group achieved a significant improvement in HRQL based on mMRC (−1.51 vs. −0.31, P < 0.005) and SGRQ (−7.83 vs. −2.16, P < 0.01) scoring accompanied with no severe adverse events. There were fewer exacerbation frequencies in the combined inhaled therapy group over the 12 months of treatment compared to the control group (1 [0–2] vs. 2 [1–4], P = 0.017). Furthermore, stratified analysis indicated that combined inhaled therapy partially improve lung function for patients for whom it is severely impaired and those with pseudomonas aeruginosa isolated. Conclusion: Our results show that salmeterol-fluticasone combined inhaled therapy should be effective and safe for non-CF bronchiectasis patients

  1. Synthetic vitreous fibers--inhalation studies.

    PubMed

    McConnell, E E

    1994-12-01

    Synthetic vitreous fibers (SVFs), often referred to as "man-made vitreous fibers," are a class of materials that have their major uses for insulation against heat and sound. The original fibers are produced by melting various types of rock, clay, etc. and then blowing or extruding them into fibers of particular properties. During production and use small fractions of airborne fibers can be generated. Because of this a series of state-of-the-art inhalation studies was initiated to study the possible health hazards presented by the four major types of vitreous materials [two types of insulation glass wool, rock wool, slag wool, and four types of refractory ceramic fibers (RCF)] found in the workplace or to which the general public may be exposed. Rats and hamsters (30 mg/m3 kaolin-based RCF only) were exposed by nose-only inhalation to 3, 16, or 30 mg/m3 for 6 hr/day, 5 days/week, for 18 (hamsters) or 24 (rats) months and were held for lifetime observation (until approximately 20% survival) to study the chronic toxicity and potential carcinogenic activity of these classes of SVFs. Chrysotile or crocidolite asbestos served as positive controls. All of the fibers stimulated an inflammatory response characterized by an increase in the number of pulmonary macrophages at the level of the terminal bronchioles and proximal alveoli. RCF produced interstitial fibrosis in the walls of the proximal alveoli as early as 3 months and rock wool by 12 months. The only fiber which showed carcinogenic activity was RCF which produced a dose-related increase in both primary lung neoplasms (rats only) and mesotheliomas (rats and hamsters).

  2. Rapid transepithelial transport of prions following inhalation.

    PubMed

    Kincaid, Anthony E; Hudson, Kathryn F; Richey, Matthew W; Bartz, Jason C

    2012-12-01

    Prion infection and pathogenesis are dependent on the agent crossing an epithelial barrier to gain access to the recipient nervous system. Several routes of infection have been identified, but the mechanism(s) and timing of in vivo prion transport across an epithelium have not been determined. The hamster model of nasal cavity infection was used to determine the temporal and spatial parameters of prion-infected brain homogenate uptake following inhalation and to test the hypothesis that prions cross the nasal mucosa via M cells. A small drop of infected or uninfected brain homogenate was placed below each nostril, where it was immediately inhaled into the nasal cavity. Regularly spaced tissue sections through the entire extent of the nasal cavity were processed immunohistochemically to identify brain homogenate and the disease-associated isoform of the prion protein (PrP(d)). Infected or uninfected brain homogenate was identified adhering to M cells, passing between cells of the nasal mucosa, and within lymphatic vessels of the nasal cavity at all time points examined. PrP(d) was identified within a limited number of M cells 15 to 180 min following inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue (NALT). While these results support M cell transport of prions, larger amounts of infected brain homogenate were transported paracellularly across the respiratory, olfactory, and follicle-associated epithelia of the nasal cavity. These results indicate that prions can immediately cross the nasal mucosa via multiple routes and quickly enter lymphatics, where they can spread systemically via lymph draining the nasal cavity.

  3. [New technical developments for inhaled sedation].

    PubMed

    Meiser, A; Bomberg, H; Volk, T; Groesdonk, H V

    2017-01-31

    The circle system has been in use for more than 100 years, whereas the first clinical application of an anaesthetic reflector was reported just 15 years ago. In the circle system, all breathing gas is rebreathed after carbon dioxide absorption. A reflector, on the other hand, with the breathing gas flowing to and fro, specifically retains the anaesthetic during expiration and resupplies it during the next inspiration. A high reflection efficiency (number of molecules resupplied/number of molecules exhaled, RE 80-90%) decreases consumption. In analogy to the fresh gas flow of a circle system, pulmonary clearance ((1-RE) × minute ventilation) defines the opposition between consumption and control of the concentration.It was not until reflection systems became available that volatile anaesthetics were used routinely in some intensive care units. Their advantages, such as easy handling, and better ventilatory capabilities of intensive care versus anaesthesia ventilators, were basic preconditions for this. Apart from AnaConDa™ (Sedana Medical, Uppsala, Sweden), the new MIRUS™ system (Pall Medical, Dreieich, Germany) represents a second, more sophisticated commercially available system.Organ protective effects, excellent control of sedation, and dose-dependent deep sedation while preserving spontaneous breathing with hardly any accumulation or induction of tolerance, make volatile anaesthetics an interesting alternative, especially for patients needing deep sedation or when intravenous drugs are no longer efficacious.But obviously, the outcome is most important. We know that deep intravenous sedation increases mortality, whereas inhalational sedation could prove beneficial. We now need prospective clinical trials examining mortality, but also the psychological outcome of those most critically ill patients sedated by inhalation or intravenously.

  4. Qualitative assessment of attributes and ease of use of the ELLIPTA™ dry powder inhaler for delivery of maintenance therapy for asthma and COPD

    PubMed Central

    2013-01-01

    Background Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler. Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes. In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated. The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter. Methods Semi-structured, in-depth, qualitative interviews were carried out 2–4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI. Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach. Participants also rated the performance of the inhaler on several criteria, using a subjective 1–10 scale. Results Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI. It was frequently described as straightforward to operate and easy to use by interview participants. Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler. Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers. Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers. Overall average performance scores were >9 (out of 10) in participants with asthma and COPD

  5. Trends in Adolescent Inhalant Use: 2002 to 2007. The NSDUH Report

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration, 2009

    2009-01-01

    Preventing and treating inhalant use problems, as well as raising awareness about the dangers of inhalant use, are important ongoing goals of the Substance Abuse and Mental Health Services Administration (SAMHSA). Monitoring trends in inhalant use is vital to assessing policies intended to reduce inhalant use. This issue of "The NSDUH Report"…

  6. Understanding Inhalant Users: An Overview for Parents, Educators, and Clinicians. Revised.

    ERIC Educational Resources Information Center

    Texas State Commission on Alcohol and Drug Abuse, Austin.

    Various areas of research related to inhalants are summarized and general guidance in dealing with this complex and urgent problem is provided. Topics include (1) "Characteristics of Inhalants," which reviews chemicals found in inhalants and common modes of administration; (2) "Defining Inhalant Use and Abuse," which includes…

  7. Inhalant Use, Abuse, and Dependence among Adolescent Patients: Commonly Comorbid Problems.

    ERIC Educational Resources Information Center

    Sakai, Joseph T.; Hall, Shannon K.; Mikulich-Gilbertson, Susan K.; Crowley, Thomas J.

    2004-01-01

    Objective: Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol…

  8. Age of Inhalant First Time Use and Its Association to the Use of Other Drugs

    ERIC Educational Resources Information Center

    Ding, Kele; Chang, G. Andy; Southerland, Ron

    2009-01-01

    Inhalants are the 4th most commonly abused drugs after alcohol, tobacco, and marijuana. Although inhalants are often referred as Gateway Drugs this hypothesis is less examined. Using the 2003 National Survey on Drug Use and Health data, age of first time inhalant use was compared with the age of onset of other drugs among 6466 inhalant users who…

  9. Nitrite inhalants: history, epidemiology, and possible links to AIDS.

    PubMed Central

    Haverkos, H W; Kopstein, A N; Wilson, H; Drotman, P

    1994-01-01

    Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. PMID:9644194

  10. INHALATION EXPOSURE TO CARBON NANOTUBES (CNT) AND CARBON NANOFIBERS (CNF): METHODOLOGY AND DOSIMETRY

    PubMed Central

    Oberdörster, Günter; Castranova, Vincent; Asgharian, Bahman; Sayre, Phil

    2015-01-01

    Carbon nanotubes (CNT) and nanofibers (CNF) are used increasingly in a broad array of commercial products. Given current understandings, the most significant life-cycle exposures to CNT/CNF occur from inhalation when they become airborne at different stages of their life cycle, including workplace, use, and disposal. Increasing awareness of the importance of physicochemical properties as determinants of toxicity of CNT/CNF and existing difficulties in interpreting results of mostly acute rodent inhalation studies to date necessitate a reexamination of standardized inhalation testing guidelines. The current literature on pulmonary exposure to CNT/CNF and associated effects is summarized; recommendations and conclusions are provided that address test guideline modifications for rodent inhalation studies that will improve dosimetric extrapolation modeling for hazard and risk characterization based on the analysis of exposure-dose-response relationships. Several physicochemical parameters for CNT/CNF, including shape, state of agglomeration/aggregation, surface properties, impurities, and density, influence toxicity. This requires an evaluation of the correlation between structure and pulmonary responses. Inhalation, using whole-body exposures of rodents, is recommended for acute to chronic pulmonary exposure studies. Dry powder generator methods for producing CNT/CNF aerosols are preferred, and specific instrumentation to measure mass, particle size and number distribution, and morphology in the exposure chambers are identified. Methods are discussed for establishing experimental exposure concentrations that correlate with realistic human exposures, such that unrealistically high experimental concentrations need to be identified that induce effects under mechanisms that are not relevant for workplace exposures. Recommendations for anchoring data to results seen for positive and negative benchmark materials are included, as well as periods for postexposure observation

  11. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  12. Accuracy of inhaler use in patients with chronic obstructive pulmonary disease.

    PubMed

    Lee, Haejung; Boo, Sunjoo; Lim, Yeonjung; Kim, Sungmin; Kim, In-Ah

    2014-10-01

    Inaccurate use of medication inhalers can reduce effectiveness, patient adherence, and disease stability. Therefore, the accurate use of inhalers in patients with chronic obstructive pulmonary disease (COPD) is crucial. This cross-sectional study evaluated 196 Korean patients with COPD for step-by-step accuracy of inhaler use with four different types of inhalers (metered-dose inhaler [MDI], Turbuhaler, Diskus, and HandiHaler); differences in accuracy levels by sociodemographic or clinical characteristics were evaluated. Descriptive statistics and t tests were used for data analysis. The proportion of patients with completely accurate inhaler use was low, ranging from 21.9% (Turbuhaler) to 46.2% (MDI). Errors with all types of inhalers were most commonly seen in the "breathing out" steps, before and after medication inhalation. Personalized nursing educational programs, correcting errors individually for each patient, could dramatically increase the accuracy of inhaler use and the effectiveness of the inhaled medications in patients with COPD.

  13. Study protocol for a randomized, controlled trial comparing the efficacy of two educational interventions to improve inhalation techniques in patients with chronic obstructive pulmonary disease (COPD): TIEPOC Study

    PubMed Central

    Leiva-Fernández, José; Leiva-Fernández, Francisca; Vázquez-Alarcón, Rubén L; García-Ruiz, Antonio; Prados-Torres, Daniel; Barnestein-Fonseca, Pilar

    2014-01-01

    Background: An appropriate inhalation technique and adherence to treatment are both critical determinants of the success of chronic obstructive pulmonary disease (COPD) management. We have observed that up to 75% of patients do not use a successful inhalation technique. Knowledge evaluation and frequent reassessment of inhaler use, together with education of patients and healthcare professionals, can significantly improve the benefits that patients with COPD will derive from inhaler therapy. The objective of this study is to test the efficacy of two educational interventions to improve inhalation techniques in patients with COPD. Methods: Multicenter randomized controlled trial with 296 patients diagnosed with COPD selected by a non-probabilistic method of sampling from seven Spanish Primary Care Centers. The patients will be divided into three groups by block randomization. The three groups are: 1) control; 2) Intervention A; and 3) Intervention B. The control group will comprise patients with no explanations or written information; the Intervention A group will comprise patients to whom we give written information only; and the Intervention B group will comprise patients to whom we give written information plus instructor training. Every patient in each group will be visited four times during the year of the study at the health centers. Discussion: Our hypothesis is that the application of educational interventions (A or B) in patients with COPD who use inhaler therapy will increase the number of patients who perform a correct inhalation technique by at least 25%. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, where feasible within the context of clinical practice. PMID:24991223

  14. Effect of inhalation profile and throat geometry on predicted lung deposition of budesonide and formoterol (BF) in COPD: An in-vitro comparison of Spiromax with Turbuhaler.

    PubMed

    Chrystyn, Henry; Safioti, Guilherme; Keegstra, Johan René; Gopalan, Gokul

    2015-08-01

    Successful delivery of inhalation medication to the lungs can be affected by the inhalation manoeuvre used. Conventional in-vitro testing of the emitted dose from a dry powder inhaler (DPI) uses a vacuum pump to simulate an inhalation. We have adapted this method by replacing the pump with patient inhalation profiles and an anatomical throat. Three anatomical throat sizes and three inhalation profiles were used. The profiles represented the 10th, 50th and 90th percentiles of peak inhalation flow and acceleration of flow from a population of 50 COPD patients inhaling through empty Spiromax and Turbuhaler devices. Combining the dose emission results for the three throat sizes, the mean (SD) budesonide fine-particle dose (FPD) from budesonide-formoterol Spiromax 320/9 μg was 78.91 (20.18), 79.91 (15.36) and 75.10 (19.91)μg and the total emitted dose (TED) of budesonide was 263.69 (40.74), 261.20 (21.65) and 261.61 (45.65)μg. Similarly, the FPD from 320/9 μg Turbuhaler was 22.45 (3.24), 52.20 (12.57) and 69.11 (75.10)μg with a TED of 143.80 (14.90), 149.50 (26.61) and 158.61 (43.04)μg. Spiromax showed greater consistency than Turbuhaler over a range of inspiratory flow profiles. The results demonstrate the value of this new method to assess the doses that patients receive during real-life use of their DPI.

  15. New Developments in the Pathogenesis of Smoke Inhalation-Induced Pulmonary Edema

    PubMed Central

    Witten, Mark L.; Quan, Stuart F.; Sobonya, Richard E.; Lemen, Richard J.

    1988-01-01

    Smoke inhalation causes most of the deaths in fire-related injuries, with pulmonary edema as a major determinant in the outcome of smoke-inhalation injury. The pathophysiology of pulmonary edema is thought to be related to the products of incomplete combustion. Damage to the integrity of the alveolar epithelium is one of the determinants of the development of smoke-induced pulmonary edema. In recent studies using lung clearance of aerosolized pentetic acid (DTPA [diethylenetriaminepentaacetic acid]) labeled with technetium Tc 99m to assess the permeability of the alveolar epithelium, several factors were identified that may increase a person's susceptibility to smoke-induced acute lung injury. These are increased initial alveolar permeability and alterations in the number and activity of alveolar macrophages. Clinical measurement of 99mTcDTPA clearance may provide a sensitive and convenient method for the early detection and serial assessment of smoke-induced alveolar epithelial permeability changes. Images PMID:3277334

  16. Novel budesonide particles for dry powder inhalation (DPI) prepared using a microfluidic reactor coupled with ultrasonic spray freeze drying.

    PubMed

    Saboti, Denis; Maver, Uroš; Chan, Hak-Kim; Planinšek, Odon

    2017-03-09

    Budesonide is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers (MDI), nebulizers and dry powder inhalers (DPI). Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of this study was therefore to develop a novel method for preparation of fine budesonide particles using a microfluidic reactor coupled with ultrasonic spray freeze drying, and hence avoiding the need of additional homogenization or stabilizer use. A T-junction microfluidic reactor was employed to produce particle suspension (using an ethanol-water, methanol-water and an acetone-water system), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final preparation step. The result were fine crystalline budesonide powders which, when blended with lactose and dispersed in an Aerolizer at 100 L/min, generated fine particle fraction in the range 47.6±2.8% to 54.9±1.8%, thus exhibiting a good aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a viable solution for particle isolation in microfluidics in general.

  17. Fiber inhalability and head deposition in rats and humans.

    EPA Science Inventory

    Due to their dimensions and long durability, inhaled asbestos fibers clear slowly from lung airways. Retained fibers may injure the epithelium, interact with macrophages, or translocate to the interstitium to result in various respiratory diseases. Therefore, calculations of fibe...

  18. Photochemical Reaction Altered Cardiac Toxicity of Diesel Exhaust Inhalation

    EPA Science Inventory

    Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled diesel exhaust and compared with photochemically altered d...

  19. Inhalation of Simulated Smog Affects Cardiac Function in Mice

    EPA Science Inventory

    Rationale: The health effects of individual criteria air pollutants have been well investigated. Little is known about health effects of inhaled multi-pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the card...

  20. Interactions between diltiazem and inhalation anaesthetics in the isolated heart.

    PubMed

    Carceles, M D; Miralles, F S; Laorden, M L; Hernandez, J

    1989-09-01

    It has been postulated that inhalation anaesthetics may interfere with calcium movement across cell membranes. We have evaluated the interaction between diltiazem and the inhalation anaesthetics halothane and isoflurane on sinus automaticity in the isolated right atrium (SAIRA). Isoflurane significantly reduced atrial rate at all concentrations tested. However, halothane produced only a small but significant decrease at the higher concentrations used (1-2 v/v%). Diltiazem modified the maximal negative chronotropic response to inhalation anaesthetics. Maximum depression of SAIRA was significantly greater in the presence of two different doses of diltiazem compared with exposure to halothane and isoflurane alone. These results suggest that inhalation anaesthetics may block the influx of extracellular calcium through voltage-dependent calcium channels inhibited by diltiazem.

  1. Inhaled therapy for the management of perioperative pulmonary hypertension

    PubMed Central

    Thunberg, C. A.; Morozowich, S. T.; Ramakrishna, Harish

    2015-01-01

    Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators. PMID:26139748

  2. Pathophysiology, management and treatment of smoke inhalation injury

    PubMed Central

    Rehberg, Sebastian; Maybauer, Marc O; Enkhbaatar, Perenlei; Maybauer, Dirk M; Yamamoto, Yusuke; Traber, Daniel L

    2009-01-01

    Smoke inhalation injury continues to increase morbidity and mortality in burn patients in both the third world and industrialized countries. The lack of uniform criteria for the diagnosis and definition of smoke inhalation injury contributes to the fact that, despite extensive research, mortality rates have changed little in recent decades. The formation of reactive oxygen and nitrogen species, as well as the procoagulant and antifibrinolytic imbalance of alveolar homeostasis, all play a central role in the pathogenesis of smoke inhalation injury. Further hallmarks include massive airway obstruction owing to cast formation, bronchospasm, the increase in bronchial circulation and transvascular fluid flux. Therefore, anticoagulants, antioxidants and bronchodilators, especially when administered as an aerosol, represent the most promising treatment strategies. The purpose of this review article is to provide an overview of the pathophysiological changes, management and treatment options of smoke inhalation injury based on the current literature. PMID:20161170

  3. FACTORS AFFECTING THE DEPOSITION OF INHALED POROUS DRUG PARTICLES

    EPA Science Inventory

    Abstract
    Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol ...

  4. Behavorial effects of subchronic inhalation of toluene in adult rats

    EPA Science Inventory

    Whereas the acute neurobehavioral effects oftoluene are robust and well characterized, evidence for persistent effects ofrepeated exposure to this industrial solvent is less compelling. The present studies sought to determine whether repeated inhalation oftoluene caused persist...

  5. Mexican-American Adolescent Inhalant Abuse: A Proposed Model.

    ERIC Educational Resources Information Center

    Dworkin, A. Gary; Stephens, Richard C.

    1980-01-01

    Drawing from literature on differences between the Mexican American experience and that of other groups, offers a model to explain the higher rates of inhalant abuse among Mexican American youth. Considers cultural, ecological, structural, and economic factors. (Author/GC)

  6. Typewriter correction fluid inhalation: a new substance of abuse.

    PubMed

    Pointer, J

    1982-07-01

    The first known case of inhalation of liquid typewriter correction fluid (TCF) is reported. Respiratory exposure to TCF can produce coma and death. Treatment is mainly supportive. Clinicians should be alerted to this new form of substance abuse.

  7. Triple inhaled therapy for chronic obstructive pulmonary disease.

    PubMed

    Montuschi, Paolo; Malerba, Mario; Macis, Giuseppe; Mores, Nadia; Santini, Giuseppe

    2016-11-01

    Combining individual drugs in a single inhaler is the most convenient way to deliver triple therapy. A long-acting muscarinic receptor antagonist (LAMA) added to an inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) fixed-dose combination (FDC) can improve efficacy of pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD). New inhaled ICS/LABA/LAMA FDCs, including fluticasone furoate/vilanterol/umeclidinium, budesonide/formoterol/glycopyrronium and beclometasone/formoterol/glycopyrronium, are in Phase III of clinical development for COPD. Triple inhaled therapy might be particularly useful in patients with severe to very severe COPD, above all in those with peripheral blood or sputum eosinophilia, asthma-COPD overlap syndrome (ACOS) or frequent exacerbators. Future prospective studies should assess efficacy and safety of triple ICS/LABA/LAMA therapy in selected COPD phenotypes.

  8. Inhaler Reminders Significantly Improve Asthma Patients' Use of Controller Medications

    MedlinePlus

    ... of controller medications Share | Inhaler reminders significantly improve asthma patients’ use of controller medications Published Online: July ... effective in reducing the burden and risk of asthma, but many patients do not use them regularly. ...

  9. A novel inhalation challenge set to study animal model of allergic alveolitis.

    PubMed

    Golec, Marcin; Skórska, Czesława; Lemieszek, Marta; Dutkiewicz, Jacek

    2009-01-01

    A novel inhalation challenge set for the study of experimental allergic alveolitis (hypersensitivity pneumonitis) in mice was designed. A finely dispersed aerosol of allergenic extract generated by the commercial ultrasonic nebulizer "TAJFUN MU1" (produced by Medbryt, Warsaw, Poland) was transported to the airtight inhalation chamber. In the chamber were placed 15 perforated containers made of transparent plastic, each containing one mouse. They were coupled in 3 units, each consisted of 5 containers. The constant flow of aerosol through the chamber was assured by commercial vacuum pump "PL 2/3" (AGA LABOR S.C., Warsaw, Poland). The applied set enabled the natural exposure of mice via the inhalation route to known quantities of allergen (usually microbial) suspended in saline, and then dispersed in form of fine aerosol by ultrasonic nebulizer. This method assures the penetration of allergen into the deep parts of lungs, alveoli and bronchioli. The detailed study of histopathological and biochemical changes in the lungs of exposed animals will be the subject of further publications. So far, the retention of endotoxin in the lungs of mice exposed to the extract of a Gram-negative bacterium Pantoea agglomerans and appearance of positive serologic reactions to this extract indicate the effectiveness of the method.

  10. Heroin self-administration by means of 'chasing the dragon': pharmacodynamics and bioavailability of inhaled heroin.

    PubMed

    Hendriks, V M; van den Brink, W; Blanken, P; Bosman, I J; van Ree, J M

    2001-06-01

    In this controlled clinical study, the bioavailability and pharmacodynamics of inhaled heroin are evaluated and compared between 'chasing the dragon' and inhalation from a heating device, and at three dose levels, 25, 50 and 100 mg heroin, in two separate study phases. In study phase 1, no differences between the inhalation methods were detected on any of the physiological or behavioral measures, nor in bioavailability. Subjectively, the participants had a strong preference for the method of chasing, which was therefore used in study phase 2. In phase 2, heroin produced a dose-related increase in subjective drug-liking, body temperature and heart rate, and a clear, dose-related decline in reaction time. Linearly dose-related differences were found in the amount of total morphine in urine, amounting to an average of 45% of the parent heroin base received. Based on these findings, it is concluded that chasing is quite an effective route of heroin administration, producing rapid, dose-related subjective and objective effects and a sufficiently high and reproducible bioavailability.

  11. Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking

    PubMed Central

    Carroll, Mary V.; Weiss, Patricia M.; Shihadeh, Alan L.; Shensa, Ariel; Farley, Steven T.; Fine, Michael J.; Eissenberg, Thomas; Nayak, Smita

    2016-01-01

    Objective Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. Methods We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between-study heterogeneity using chi-squared and I-squared statistics. Results Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta-analyses matched precisely between the two researchers (100% agreement, Cohen's k=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. Conclusions One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming. PMID:26843673

  12. Myocardial injury following the intentional inhalation of typewriter correction fluid.

    PubMed

    Wodka, R M; Jeong, E W

    1991-04-01

    The first known case of myocardial injury, as documented by evolutionary electrocardiographic changes and echocardiographic septal wall motion abnormality associated with the voluntary inhalation of typewriter correction fluid, is reported. Typewriter correction fluid, which contains a combination of chlorinated hydrocarbons, is rapidly becoming a substance of abuse. Therefore, primary care practitioners should be alerted to specific organ system damages that may arise from the voluntary inhalation of this substance.

  13. Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology.

    PubMed

    Nguyen, Jacques D; Aarde, Shawn M; Cole, Maury; Vandewater, Sophia A; Grant, Yanabel; Taffe, Michael A

    2016-10-01

    Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.

  14. Psychomotor and cognitive effects of 15-minute inhalation of methoxyflurane in healthy volunteers: implication for post-colonoscopy care

    PubMed Central

    Nguyen, Nam Q.; Burgess, Jenna; Debreceni, Tamara L.; Toscano, Leanne

    2016-01-01

    Background and study aims: Colonoscopy with portal inhaled methoxyflurane (Penthrox) is highly feasible with low sedation risk and allows earlier discharge. It is unclear if subjects can return to highly skilled psychomotor skill task shortly after Penthrox assisted colonoscopy. We evaluated the psychomotor and cognitive effects of 15-minute inhalation of Penthrox in adults. Patients and methods: Sixty healthy volunteers (18 to 80 years) were studied on 2 occasions with either Penthrox or placebo in a randomized, double-blind fashion. On each occasion, the subject’s psychomotor function was examined before, immediately, 30, 60, 120, 180 and 240 min after a 15-minute inhalation of studied drug, using validated psychomotor tests (Digit Symbol Substitution Test (DSST), auditory reaction time (ART), eye-hand coordination (EHC) test, trail making test (TMT) and logical reasoning test (LRT). Results: Compared to placebo, a 15-minute Penthrox inhalation led to an immediate but small impairment of DSST (P < 0.001), ART (P < 0.001), EHC (P < 0.01), TMT (P = 0.02) and LRT (P = 0.04). In all subjects, the performance of all 5 tests normalized by 30 minutes after inhalation, and was comparable to that with placebo. Although increasing age was associated with a small deterioration in psychomotor testing performance, the magnitude of Penthrox effects remained comparable among all age groups. Conclusions: In all age groups, a 15-minute Penthrox inhalation induces acute but short-lasting impairment of psychomotor and cognitive performance, which returns to normal within 30 minutes , indicating that subjects who have colonoscopy with Penthrox can return to highly skilled psychomotor skills tasks such as driving and daily work the same day. PMID:27853742

  15. Experimental investigation of design parameters on dry powder inhaler performance.

    PubMed

    Ngoc, Nguyen Thi Quynh; Chang, Lusi; Jia, Xinli; Lau, Raymond

    2013-11-30

    The study aims to investigate the impact of various design parameters of a dry powder inhaler on the turbulence intensities generated and the performance of the dry powder inhaler. The flow fields and turbulence intensities in the dry powder inhaler are measured using particle image velocimetry (PIV) techniques. In vitro aerosolization and deposition a blend of budesonide and lactose are measured using an Andersen Cascade Impactor. Design parameters such as inhaler grid hole diameter, grid voidage and chamber length are considered. The experimental results reveal that the hole diameter on the grid has negligible impact on the turbulence intensity generated in the chamber. On the other hand, hole diameters smaller than a critical size can lead to performance degradation due to excessive particle-grid collisions. An increase in grid voidage can improve the inhaler performance but the effect diminishes at high grid voidage. An increase in the chamber length can enhance the turbulence intensity generated but also increases the powder adhesion on the inhaler wall.

  16. Intrapulmonary distribution of inhaled chrysotile and crocidolite asbestos: ultrastructural features.

    PubMed Central

    Oghiso, Y.; Kagan, E.; Brody, A. R.

    1984-01-01

    Although all commercial types of asbestos can cause pulmonary fibrosis, little is known about ultrastructural differences in the evolution of pulmonary lesions induced by amphiboles and serpentines. The present study was designed to compare the histological and ultrastructural effects produced by chronic inhalation of either crocidolite (amphibole) or chrysotile (serpentine) asbestos in the rat. Animals, exposed by intermittent inhalation for 3 months, were killed after 2 to 16 months. When inhaled, both types of asbestos caused thickened alveolar duct bifurcations associated with macrophage aggregates. Crocidolite inhalation also produced subpleural collections of alveolar macrophages and lymphocytes. Electron microscopy revealed some similarities, but also distinct differences, in the pulmonary distribution of inhaled chrysotile and crocidolite. Whereas both asbestos varieties were identified within the pulmonary interstitium, only crocidolite was detected inside alveolar macrophages. Chrysotile fibres were seen infrequently within the vascular compartment. Microcalcifications were noted after chrysotile inhalation, but were never observed following crocidolite exposure. Both asbestos types induced slight pulmonary fibrosis. These findings indicate that crocidolite and chrysotile produce different pathogenetic features, although both are fibrogenic. Images Fig. 4 Fig. 7 Fig. 8 Fig. 5 Fig. 1 Fig. 2 Fig. 3 Fig. 6 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:6087872

  17. Inhalation of two putative Gulf War toxins by mice.

    PubMed

    Repine, John E; Wilson, Paul; Elkins, Nancy; Klawitter, Jelena; Christians, Uwe; Peters, Ben; Smith, Dwight M

    2016-01-01

    We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB4) (a biomarker of inflammation) and PGF2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB4 and PGF2α levels but no increase in lung lavage LTB4, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals.

  18. Protocols of radiocontaminant air monitoring for inhalation exposure estimates

    SciTech Connect

    Shinn, J.H.

    1995-09-01

    Monitoring the plutonium and americium particle emissions from soils contaminated during atmospheric nuclear testing or due to accidental releases is important for several reasons. First, it is important to quantify the extent of potential human exposure from inhalation of alpha-emitting particles, which is the major exposure pathway from transuranic radionuclides. Second, the information provided by resuspension monitoring is the basis of criteria that determine the target soil concentrations for management and cleanup of contaminated soil sites. There are other radioactive aerosols, such as the fission products (cesium and strontium) and neutron-activation products (europium isotopes), which may be resuspended and therefore necessary to monitor as well. This Standard Protocol (SP) provides the method used for radiocontaminant air monitoring by the Health and Ecological Assessment Division (formerly Environmental Sciences Division), Lawrence Livermore National Laboratory, as developed and tested at Nevada Test Site (NTS) and in the Marshall Islands. The objective of this SP is to document the applications and methods of monitoring of all the relevant variables. This protocol deals only with measuring air concentrations of radionuclides and total suspended particulates (TSP, or {open_quotes}dust{close_quotes}). A separate protocol presents the more difficult measurements required to determine transuranic aerosol emission rates, or {open_quotes}resuspension rate{close_quotes}.

  19. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice

    PubMed Central

    Lim, S.; Jatakanon, A.; Gordon, D.; Macdonald, C.; Chung, K. F.; Barnes, P.

    2000-01-01

    BACKGROUND—Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.
METHODS—In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 µg beclomethasone dipropionate (BDP) daily and inhaled β2 agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 µg BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 µg BDP) over a six month period was examined.
RESULTS—One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.
CONCLUSION—There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

 PMID:10992535

  20. Feasibility of Deploying Inhaler Sensors to Identify the Impacts of Environmental Triggers and Built Environment Factors on Asthma Short-Acting Bronchodilator Use

    PubMed Central

    Su, Jason G.; Barrett, Meredith A.; Henderson, Kelly; Humblet, Olivier; Smith, Ted; Sublett, James W.; Nesbitt, LaQuandra; Hogg, Chris; Van Sickle, David; Sublett, James L.

    2016-01-01

    Background: Epidemiological asthma research has relied upon self-reported symptoms or healthcare utilization data, and used the residential address as the primary location for exposure. These data sources can be temporally limited, spatially aggregated, subjective, and burdensome for the patient to collect. Objectives: First, we aimed to test the feasibility of collecting rescue inhaler use data in space–time using electronic sensors. Second, we aimed to evaluate whether these data have the potential to identify environmental triggers and built environment factors associated with rescue inhaler use and to determine whether these findings would be consistent with the existing literature. Methods: We utilized zero-truncated negative binomial models to identify triggers associated with inhaler use, and implemented three sensitivity analyses to validate our findings. Results: Electronic sensors fitted on metered dose inhalers tracked 5,660 rescue inhaler use events in space and time for 140 participants from 13 June 2012 to 28 February 2014. We found that the inhaler sensors were feasible in passively collecting objective rescue inhaler use data. We identified several environmental triggers with a positive and significant association with inhaler use, including: AQI, PM10, weed pollen, and mold. Conversely, the spatial distribution of tree cover demonstrated a negative and significant association with inhaler use. Conclusions: Utilizing a sensor to capture the signal of rescue inhaler use in space–time offered a passive and objective signal of asthma activity. This approach enabled detailed analyses to identify environmental triggers and built environment factors that are associated with asthma symptoms beyond the residential address. The application of these new technologies has the potential to improve our surveillance and understanding of asthma. Citation: Su JG, Barrett MA, Henderson K, Humblet O, Smith T, Sublett JW, Nesbitt L, Hogg C, Van Sickle D, Sublett JL

  1. Evaluation of dry powder inhalers with a focus on ease of use and user preference in inhaler-naïve individuals.

    PubMed

    von Schantz, Sofia; Katajavuori, Nina; Antikainen, Osmo; Juppo, Anne

    2016-07-25

    Inhaler errors are common amongst inhaler users. Therefore, in the development work of new inhalation devices, it is important to characterize the ease of use of the inhalers. In this study four dry powder inhalers, Diskus, Easyhaler, Ellipta and Turbuhaler, were evaluated, focusing on ease of use and patient preference. The study used a triangular methodology. The sample consisted of 31 inhaler naïve individuals. Educational videos for all inhalers were watched, and afterwards, the use of all four inhalers was demonstrated in a random order. The demonstrations were videotaped. Thereafter they were checked against a predefined checklist and all mistakes were recorded. Only 33% of inhaler demonstrations were completed without the participants making any mistakes. The proportions of subjects who used the devices correctly were as follows: Diskus 48%, Easyhaler 19%, Ellipta 55% and Turbuhaler 16%. When comparing correct and incorrect inhaler technique for each inhaler pair the following differences were statistically significant: Diskus vs. Easyhaler (p<0.05), Ellipta vs. Easyhaler (p<0.01), Diskus vs. Turbuhaler (p<0.01), Ellipta vs. Turbuhaler (p<0.01). In the participants' ranking, the inhalers Ellipta, followed by Turbuhaler, were most often ranked as most preferred. Participants' preference of Ellipta over Easyhaler (p<0.01) and over Diskus (p<0.001) were statistically significant.

  2. Protective effects of hydrogen sulfide inhalation on oxidative stress in rats with cotton smoke inhalation-induced lung injury

    PubMed Central

    HAN, ZHI-HAI; JIANG, YI; DUAN, YUN-YOU; WANG, XIAO-YANG; HUANG, YAN; FANG, TING-ZHENG

    2015-01-01

    The aim of the present study was to investigate the mechanism by which hydrogen sulfide (H2S) inhalation protects against oxidative stress in rats with cotton smoke inhalation-induced lung injury. A total of 24 male Sprague-Dawley rats were separated randomly into four groups, which included the control, H2S, smoke and smoke + H2S groups. A rat model of cotton smoke inhalation-induced lung injury was established following inhalation of 30% oxygen for 6 h. In addition, H2S (80 ppm) was inhaled by the rats in the H2S and smoke + H2S groups for 6 h following smoke or sham-smoke inhalation. Enzyme-linked immunosorbent assays were performed to measure various indices in the rat lung homogenate, while the levels of nuclear factor (NF)-κBp65 in the lung tissue of the rats were determined and semiquantitatively analyzed using immunohistochemistry. In addition, quantitative fluorescence polymerase chain reaction was employed to detect the mRNA expression of inducible nitric oxide synthase (iNOS) in the rat lung tissue. The concentrations of malondialdehyde (MDA), nitric oxide (NO), inducible iNOS and NF-κBp65, as well as the sum-integrated optical density of NF-κBp65 and the relative mRNA expression of iNOS, in the rat lung tissue from the smoke + H2S group were significantly lower when compared with the smoke group. The concentrations of MDA, NO, iNOS and NF-κBp65 in the H2S group were comparable to that of the control group. Therefore, inhalation of 80 ppm H2S may reduce iNOS mRNA transcription and the production of iNOS and NO in rats by inhibiting NF-κBp65 activation, subsequently decreasing oxidative stress and cotton smoke inhalation-induced lung injury. PMID:26170929

  3. Traumatic Inhalation due to Merapi Volcanic Ash.

    PubMed

    Trisnawati, Ika; Budiono, Eko; Sumardi; Setiadi, Andang

    2015-07-01

    Pneumonoultramicroscopicsilicovolcanoconiosis is fibrotic lung diseases of the pulmonary parenchyma following chronic inhalation of inorganic dusts containing crystalline silicon dioxide. The acute manifestations observed after heavy ashfalls include attacks of asthma and bronchitis, with an increased reporting of cough, breathlessness, chest tightness, and wheezing due to irritation of the lining of the airways. The chronic health condition of most concern is silicosis, a diffuse nodular fibrosis of the lungs, develops slowly, usually appearing 10 to 30 years after first exposure. A 35 years old male was admitted to Sardjito Hospital, Yogyakarta with complaints of progressive dyspnoea, right side chest pain since last 3 month and periodic episodes of dry cough. He had history of exposure to volcanic ash at the location around volcano eruption for about 10 month. Examination revealed hyperresonant note, diminished vesicular breath sounds in lower right side of the chest. The chest X-ray presence leads to bleb. Based on the clinical and radiological suspicion of pneumoconiosis the patient was submitted to computed tomography of the chest and revealed bilateral multiple bullae mainly at the right lung field. The biopsy specimen verified the diagnosis of anthrocosilicosis. There is no proven specific therapy for any form of silicosis. Symptomatic therapy should include treatment of airflow limitation with bronchodilators, aggressive management of respiratory tract infection with antibiotics, and use of supplemental oxygen (if indicated) to prevent complications of chronic hypoxemia.

  4. Inhaled treprostinil and pulmonary arterial hypertension

    PubMed Central

    Nadler, Samuel T; Edelman, Jeffrey D

    2010-01-01

    Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432

  5. Incinerator air emissions: Inhalation exposure perspectives

    SciTech Connect

    Rogers, H.W.

    1995-12-01

    Incineration is often proposed as the treatment of choice for processing diverse wastes, particularly hazardous wastes. Where such treatment is proposed, people are often fearful that it will adversely affect their health. Unfortunately, information presented to the public about incinerators often does not include any criteria or benchmarks for evaluating such facilities. This article describes a review of air emission data from regulatory trial burns in a large prototype incinerator, operated at design capacity by the US Army to destroy chemical warfare materials. It uses several sets of criteria to gauge the threat that these emissions pose to public health. Incinerator air emission levels are evaluated with respect to various toxicity screening levels and ambient air levels of the same pollutants. Also, emission levels of chlorinated dioxins and furans are compared with emission levels of two common combustion sources. Such comparisons can add to a community`s understanding of health risks associated with an incinerator. This article focuses only on the air exposure/inhalation pathway as related to human health. It does not address other potential human exposure pathways or the possible effects of emissions on the local ecology, both of which should also be examined during a complete analysis of any major new facility.

  6. Biliary Cast Syndrome in an Opium Inhaler

    PubMed Central

    Dabiri, Reza; Aghdae, Hamid Asadzadeh; Rajabalinia, Hasan; Mohammad Alizadeh, Amir Houshang

    2013-01-01

    Biliary cast syndrome (BCS) is an uncommon complication which is mostly described in orthotopic liver transplantation. However, BCS has also been reported rarely in non-liver transplant patients. We describe a male long-term opium inhaler with BCS who underwent successful endoscopic cast removal by balloon enteroscopy-guided endoscopic retrograde cholangiopancreatography. A 52-year-old man, who was a known case of opium addiction, presented with the chief complaint of epigastric pain for 1 week prior to admission. Routine laboratory evaluation revealed cholestatic liver enzyme elevation. A cholestatic pattern was seen in radiographic modalities. Endoscopic retrograde cholangiopancreatography showed a linear filling defect in the intra- and extrahepatic duct. A long biliary cast was successfully removed using an extractor balloon. After removal of the biliary cast the patient is receiving ursodeoxycholic acid and does not report any problem 4 months after treatment. It seems that biliary dyskinesia due to long-term opium use can be a predisposing factor for biliary cast formation. PMID:24163648

  7. [A case of subacute stroke with high uptake of 99mTc-HMPAO in the reperfused infarct corresponding to low perfusion area].

    PubMed

    Sugawara, Y; Tanada, S; Murase, K; Inoue, T; Miki, H; Okumura, A; Hamamoto, K; Ueda, T; Ohta, S; Sakaki, S

    1994-06-01

    We reported a case of subacute stroke which showed high uptake of 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) in the reperfused infarct corresponding to slightly decreased perfusion by 133Xe inhalation CBF measurement. In the chronic stage, both SPECT images of 99mTc-HMPAO and 133Xe showed low perfusion in the affected lesion. It was, therefore, considered that the high uptake of 99mTc-HMPAO had represented luxury perfusion. In the subacute stage of stroke, high uptake of 99mTc-HMPAO may imply luxury perfusion but not always hyperperfusion. It is suggested that the fractional fixation of 99mTc-HMPAO temporarily change in the affected lesion and it is essential to take into consideration the clinical stage for the interpretation of SPECT images.

  8. Safety assessment for hair-spray resins: risk assessment based on rodent inhalation studies.

    PubMed

    Carthew, Philip; Griffiths, Heather; Keech, Stephen; Hartop, Peter

    2002-04-01

    The methods involved in the safety assessment of resins used in hair-spray products have received little peer review, or debate in the published literature, despite their widespread use, in both hairdressing salons and the home. The safety assessment for these resins currently involves determining the type of lung pathology that can be caused in animal inhalation exposure studies, and establishing the no-observable-effect level (NOEL) for these pathologies. The likely human consumer exposure is determined by techniques that model the simulated exposure under "in use" conditions. From these values it is then possible to derive the likely safety factors for human exposure. An important part of this process would be to recognize the intrinsic differences between rodents and humans in terms of the respiratory doses that each species experiences during inhalation exposures, for the purpose of the safety assessment. Interspecies scaling factors become necessary when comparing the exposure doses experienced by rats, compared to humans, because of basic differences between species in lung clearance rates and the alveolar area in the lungs. The rodent inhalation data and modeled human exposure to Resin 6965, a resin polymer that is based on vinyl acetate, has been used to calculate the safety factor for human consumer exposure to this resin, under a range of "in use" exposure conditions. The use of this safety assessment process clearly demonstrates that Resin 6965 is acceptable for human consumer exposure under the conditions considered in this risk assessment.

  9. Comparative inhalation toxicology of selected materials. Final report on Phase 1

    SciTech Connect

    Snipes, M.B.; Burt, D.G.; Eidson, A.F.; Hahn, F.F.; Harmsen, A.G.

    1986-09-01

    Studies are being conducted with Fischer-344 rats to determine the inhalation toxicology of a respirable power of copper-zinc alloy. Phase I involved standardization of methods, characterization of aerosols, and exposures of rats in whole-body of nose-only systems to air concentrations of 100 mg Cu-Zn/m/sup 3/, or 100 mg titanium dioxide/m/sup 3/. The titanium dioxide was included to determine if effects observed in exposed animals resulted from inhaling the Cu-Zn powder or inhaling a comparable amount of nuisance dust. Sham-exposed and shelf control rats were included. Rats were exposed 2.5 hr/day for 2 or 5 consecutive days, then killed for evaluations. Results include body weights, core temperatures, selected organ weights, hematology, clinical chemistry, and histopathology. Significant findings were 1) all rats were stressed when exposed in whole-body or nose-only exposure systems, 2) except for a greater body weight loss for rats exposed nose-only, indicators of stress were similar for the two types of exposure systems, 3) no consistent differences were seen between sham-exposed and TiO/sub 2/-exposed rats, and 4)adverse effects from exposure to Cu-Zn alloy powder included body weight loss, decreased ability to maintain body temperature (measured in rats exposed nose-only), rhinitis, and an inflammatory response in the lung.

  10. The Effects of Inhaled β-Adrenergic Agonists in Transient Tachypnea of the Newborn

    PubMed Central

    Keleş, Esengul; Gebeşçe, Arzu; Demirdöven, Mehmet; Yazgan, Hamza; Baştürk, Bülent; Tonbul, Alparslan

    2016-01-01

    Aim. To investigate the efficacy of an inhaled β-adrenergic agonists in transient tachypnea of the newborn (TTN). Method. We retrospectively analyzed a cohort of 51 term infants (Group 1) and 37 term infants (Group 2) monitored in the newborn intensive care unit diagnosed with TTN. Infants in Group 1 received humidified oxygen alone, and infants in Group 2 were administered the inhaled β-2 agonist plus humidified oxygen. Results. TTN clinical respiratory assessment, respiratory rate, oxygen saturation values, need for supplemental oxygen therapy, blood gas PH, PO2, and duration of hospitalization were significantly improved in infants in Group 2 as compared with infants in Group 1 (P < .05). No statistically significant difference was observed with regard to blood glucose, potassium, heart rate, and PCO2 (P > .05). Conclusion. Inhaled β-adrenergic agonist added to humidified oxygen was found to improve clinical and laboratory parameters. We believe that further studies should be conducted with larger groups to demonstrate the efficacy of β-2 agonists in TTN patients. PMID:27336017

  11. Impact of bronchial circulation on bronchial exudation following combined burn and smoke inhalation injury in sheep

    PubMed Central

    Morita, Naoki; Enkhbaatar, Perenlei; Maybauer, Dirk M.; Maybauer, Marc O.; Westphal, Martin; Murakami, Kazunori; Hawkins, Hal K.; Cox, Robert A.; Traber, Lillian. D.; Traber, Daniel L.

    2011-01-01

    We previously reported bronchial circulation contributes to pulmonary edema and increases shunt fraction following smoke inhalation, and bronchial blood flow significantly increases in inhalation injury. We hypothesized reduction of bronchial blood flow reduces exudation to the airway and ameliorates lung injury from combined burn and smoke insults (B & S injury). Method Merino ewes (n=28) randomly divided into three groups (1: bronchial artery ligated and injured (Injury + ligation group); 2: bronchial artery left intact and injured (Injury + no ligation group); 3: bronchial artery ligated but not injured (No injury + ligation group) were subjected to a flame burn and inhalation injury under halothane anesthesia. Parameters were analyzed using Scheffe’s post hoc test (P<0.05). All Groups were resuscitated with Ringer lactate solution and placed on a ventilator for 48 hours. Results Pulmonary gas exchange (PaO2/FiO2) improved in injury + ligation group. Further, obstruction score, an index of airway cast formation, significantly changed between injury + no ligation group compared to both ligation groups. Conclusion Bronchial circulation plays a significant role in lung injury after B & S injury, and reduction of bronchial blood flow by bronchial artery ligation reduces bronchial exudation, resulting in improved gas exchange. PMID:21195551

  12. An experimental study quantifying pulmonary ventilation on inhalation of aerosol under steady and episodic emission.

    PubMed

    Poon, Carmen K M; Lai, Alvin C K

    2011-09-15

    Estimating inhalation dose accurately under realistic conditions can enhance the accuracy of risk assessment. Conventional methods to quantify aerosol concentration that susceptible victims in contaminated environments are exposed to use real time particle counters to measure concentrations in environments without occupancy. Breathing-induced airflow interacts and influences concentration around nostrils or mouth and alter the ultimate exposure. This subject has not yet been systematically studied, particularly under transient emission. In this work, an experimental facility comprising two manikins was designed and fabricated. One of them mimicked realistic breathing, acting as a susceptible victim. Both steady and episodic emissions were generated in an air-conditioned environmental chamber in which two different ventilation schemes were tested. The scaled-dose of the victim under different expiratory velocities and pulmonary ventilation was measured. Inferring from results obtained from comprehensive tests, it can be concluded that breathing has very significant influence on the ultimate dose compared with that without breathing. Majority of results show that breathing reduces inhalation quantity and the reduction magnitude increases with breathing rate. This is attributed to the fact that the exhalation process plays a more significant role in reducing the dose level than the enhanced effect during inhalation period. The higher the breathing rate, the sharper the decline of the resultant concentration would be leading to lower dose. Nevertheless, under low pulmonary ventilation, results show that breathing increases dose marginally. Results also reveals that ventilation scheme also affects the exposure.

  13. The Effects of Inhalation Aromatherapy on Anxiety in Patients With Myocardial Infarction: A Randomized Clinical Trial

    PubMed Central

    Najafi, Zahra; Taghadosi, Mohsen; Sharifi, Khadijeh; Farrokhian, Alireza; Tagharrobi, Zahra

    2014-01-01

    Background: Anxiety is an important mental health problem in patients with cardiac disease. Anxiety reduces patients’ quality of life and increases the risk of different cardiac complications. Objectives: The aim of this study was to investigate the effects of inhalation aromatherapy on anxiety in patients with myocardial infarction. Patients and Methods: This was a randomized clinical trial conduced on 68 patients with myocardial infarction hospitalized in coronary care units of a large-scale teaching hospital affiliated to Kashan University of Medical Sciences, Kashan, Iran in 2013. By using the block randomization technique, patients were randomly assigned to experimental (33 patients receiving inhalation aromatherapy with lavender aroma twice a day for two subsequent days) and control (35 patients receiving routine care of study setting including no aromatherapy) groups. At the beginning of study and twenty minutes after each aromatherapy session, anxiety state of patients was assessed using the Spielberger’s State Anxiety Inventory. Data was analyzed using SPSS v. 16.0. We used Chi-square, Fisher’s exact, independent-samples T-test and repeated measures analysis of variance to analyze the study data. Results: The study groups did not differ significantly regarding baseline anxiety mean and demographic characteristics. However, after the administration of aromatherapy, anxiety mean in the experimental group was significantly lower than the control group. Conclusions: Inhalation aromatherapy with lavender aroma can reduce anxiety in patients with myocardial infarction. Consequently, healthcare providers, particularly nurses, can use this strategy to improve postmyocardial infarction anxiety management. PMID:25389481

  14. Inhalation of Shin-I essential oil enhances lactate clearance in treadmill exercise

    PubMed Central

    Chen, Hsuan-Ying; Wang, Ming-Fu; Lin, Jun-Ying; Tsai, Ying-Chieh; Cheng, Fu-Chou

    2014-01-01

    Objective To evaluate the effect of Shin-I essential oil inhalation on blood lactate changes in rats subjected to treadmill exercise. Methods : Adult male Sprague Dawley rats (n=12) were randomly divided into the control or the Shin-I group. Rats were subjected to a treadmill exercise program (15 m/min for 30 min). After exercise, rats were exposed to 200 µL of water or Shin-I essential oil, respectively, using a nebulizer for 180 min during the recovery period. Blood samples were collected every 15 min. Blood glucose and lactate concentrations were determined in a CMA 600 analyzer. Results : The basal glucose and lactate levels were no significantly different between two groups. After exercise, glucose levels were slightly increased to about 110%-120% of the basal level in both groups. Lactate levels of both groups reached to 110%-140% of basal levels during exercise. In the recovery period, lactate levels further increased to 180% of the basal level and were maintained at a plateau in the control group. However, lactate levels gradually decreased to 60%-65% of the basal level in the Shin-I group. Lactate clearance was significantly enhanced after Shin-I essential oil inhalation. Conclusions : Our results provide evidence that Shin-I essential oil inhalation may accelerate recovery after exercise in rats. PMID:25182288

  15. Validation of specific inhalation challenge for the diagnosis of occupational asthma due to persulphate salts

    PubMed Central

    Munoz, X; Cruz, M; Orriols, R; Torres, F; Espuga, M; Morell, F

    2004-01-01

    Background: The significant value of tests used to certify the diagnosis of occupational asthma due to persulphate salts remains uncertain. Aims: To validate the specific inhalation challenge (SIC) test for the diagnosis of occupational asthma. Methods: Eight patients with occupational asthma due to persulphate salts, eight patients with bronchial asthma who were never exposed to persulphate salts, and ten healthy subjects were studied. Clinical history taking, spirometry, bronchial challenge with methacholine, skin prick testing to common inhalant allergens and persulphate salts, total IgE levels, and SIC to potassium persulphate were carried out in all subjects. The SIC used increasing concentrations of potassium persulphate (5, 10, 15, and 30 g) mixed with 150 g of lactose. Patients tipped the mixture from one tray to another at a distance of 30 cm from the face for 10 minutes in a challenge booth. Results: The SIC was positive in all subjects with persulphate induced asthma and in one patient with bronchial asthma who had never been exposed to persulphate salts. Sensitivity was 100% (95% CI 67.6 to 100) and specificity was 87.5% (95% CI 52.9–97.8) when patients with occupational asthma due to persulphate salts were compared with those with bronchial asthma never exposed to persulphate salts. Conclusions: SIC to persulphate salts performed according to the protocol described appears to be useful for the diagnosis of occupational asthma secondary to inhalation of this substance. PMID:15377773

  16. Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

    PubMed Central

    Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

    2016-01-01

    Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

  17. Effect of Vitamin D and Inhaled Corticosteroid Treatment on Lung Function in Children

    PubMed Central

    Tantisira, Kelan; Fuhlbrigge, Anne L.; Weiss, Scott T.; Litonjua, Augusto

    2012-01-01

    Rationale: Low vitamin D levels are associated with asthma and decreased airway responsiveness. Treatment with inhaled corticosteroids improves airway responsiveness and asthma control. Objectives: To assess the effect of vitamin D levels on prebronchodilator FEV1, bronchodilator response, and responsiveness to methacholine (PC20, provocative concentration of methacholine producing a 20% decline in FEV1) in patients with asthma treated with inhaled corticosteroids. Methods: We measured 25-hydroxyvitamin D levels in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program. We divided subjects into the vitamin D sufficiency (>30 ng/ml), insufficiency (20–30 ng/ml), and deficiency (<20 ng/ml) groups. Covariates included age, treatment, sex, body mass index, race, history of emergency department visits, hospitalizations, and season that vitamin D specimen was drawn. Our main outcome measures were change in prebronchodilator FEV1, bronchodilator response, and PC20 from enrollment to 8–12 months. Measurements and Main Results: Of the 1,024 subjects, 663 (65%) were vitamin D sufficient, 260 (25%) were insufficient, and 101 (10%) were deficient. Vitamin D–deficient subjects were more likely to be older, African American, and have a higher body mass index compared with the vitamin D–sufficient and insufficient subjects. In the inhaled corticosteroid treatment group, prebronchodilator FEV1 increased from randomization to 12 months by 140 ml in the vitamin D–deficient group and prebronchodilator FEV1 increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group (P = 0.0072), in adjusted models. Conclusions: In children with asthma treated with inhaled corticosteroids, vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency. PMID:22798322

  18. Inhaled Nitric Oxide Improves Outcomes After Successful Cardiopulmonary Resuscitation in Mice

    PubMed Central

    Minamishima, Shizuka; Kida, Kotaro; Tokuda, Kentaro; Wang, Huifang; Sips, Patrick Y.; Kosugi, Shizuko; Mandeville, Joseph B.; Buys, Emmanuel S.; Brouckaert, Peter; Liu, Philip K.; Liu, Christina H.; Bloch, Kenneth D.; Ichinose, Fumito

    2011-01-01

    Introduction Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia-reperfusion (IR) injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR). Methods and Results Adult male mice were subjected to potassium-induced CA for 7.5 min whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 parts per million (ppm) NO for 23h. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4/13), depressed neurological and left ventricular (LV) function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24h after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23h starting 1h after CPR attenuated neurological and LV dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11/13, P=0.003 vs Air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum NOx levels. Deficiency of the α1 subunit of soluble guanylate cyclase (sGC), a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR. Conclusions These results suggest that NO inhalation after CA and successful CPR improves outcome via sGC-dependent mechanisms. PMID:21931083

  19. SAW atomization application on inhaled pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Qi, Aisha; Friend, James; Yeo, Leslie

    2008-12-01

    Pulmonary drug delivery transports the drug formulations directly to the respiratory tract in the form of inhaled particles or droplets. Because of the direct target treatment, it has significant advantages in the treatment of respiratory diseases, for example asthma. However, it is difficult to produce monodispersed particles/droplets in the 1-10 micron range, which is necessary for deposition in the targeted lung area or lower respiratory airways, in a controllable fashion. We demonstrate the use of surface acoustic waves (SAWs) as an efficient method for the generation of monodispersed micron dimension aerosols for the treatment of asthma. SAWs are ten nanometer order amplitude electroacoustic waves generated by applying an oscillating electric field to an interdigital transducer patterned on a piezoelectric substrate. The acoustic energy in the waves induces atomization of the working fluid, which contains a model drug, albuterol. Laser diffraction techniques employed to characterize the aerosols revealed mean diameter of the aerosol was around 3-4 μm. Parallel experiments employing a one-stage (glass) twin impinger as a lung model demonstrated a nearly 80% of atomized drug aerosol was deposited in the lung. The aerosol size distribution is relatively independent of the SAW frequency, which is consistent with our predictive scaling theory which accounts for the dominant balance between viscous and capillary stresses. Moreover, only 1-3 W powers consumption of SAW atomization suggests that the SAW atomizer can be miniaturized into dimensions commensurate with portable consumer devices.

  20. Washout kinetics of inhaled hydrogen cyanide in breath.

    PubMed

    Stamyr, Kristin; Nord, Pierre; Johanson, Gunnar

    2008-06-10

    Hydrogen cyanide (HCN) intoxication causes or contributes significantly to many of the fatalities among fire victims. To enable fast treatment of HCN poisoning, a more rapid diagnostic method than currently available is required. One possibility would be measurement in exhaled air. However, as HCN is highly water soluble, it may be absorbed during inhalation and reabsorbed during exhalation. If this, so-called, washin-washout effect is substantial it may interfere with the diagnosis, as a major part of breath HCN may originate from the respiratory tract, due to recent exposure, and not from systemic exposure. The aim of this study was to estimate the importance of the washin-washout effect of HCN. The time-course of cyanide in exhaled air was measured with an electrochemical detector in 10 volunteers during and after a 1 min x 10 ppm exposure to HCN. The experiment revealed an average half-life of 16s (range 10-24s) in breath. Extrapolating the results to higher exposures suggests that the contribution from washin-washout from the airways will be negligible even at fatal exposures. The results support the use of breath HCN as a potential indicator of systemic intoxication.

  1. A Comparison of "Total Dust" and Inhalable Personal Sampling for Beryllium Exposure

    SciTech Connect

    Carter, Colleen M.

    2012-05-09

    In 2009, the American Conference of Governmental Industrial Hygienists (ACGIH) reduced the Beryllium (Be) 8-hr Time Weighted Average Threshold Limit Value (TLV-TWA) from 2.0 μg/m3 to 0.05 μg/m3 with an inhalable 'I' designation in accordance with ACGIH's particle size-selective criterion for inhalable mass. Currently, per the Department of Energy (DOE) requirements, the Lawrence Livermore National Laboratory (LLNL) is following the Occupational Health and Safety Administration (OSHA) Permissible Exposure Limit (PEL) of 2.0 μg/m3 as an 8-hr TWA, which is also the 2005 ACGIH TLV-TWA, and an Action Level (AL) of 0.2 μg/m3 and sampling is performed using the 37mm (total dust) sampling method. Since DOE is considering adopting the newer 2009 TLV guidelines, the goal of this study was to determine if the current method of sampling using the 37mm (total dust) sampler would produce results that are comparable to what would be measured using the IOM (inhalable) sampler specific to the application of high energy explosive work at LLNL's remote experimental test facility at Site 300. Side-by-side personal sampling using the two samplers was performed over an approximately two-week period during chamber re-entry and cleanup procedures following detonation of an explosive assembly containing Beryllium (Be). The average ratio of personal sampling results for the IOM (inhalable) vs. 37-mm (total dust) sampler was 1.1:1 with a P-value of 0.62, indicating that there was no statistically significant difference in the performance of the two samplers. Therefore, for the type of activity monitored during this study, the 37-mm sampling cassette would be considered a suitable alternative to the IOM sampler for collecting inhalable particulate matter, which is important given the many practical and economic advantages that it presents. However, similar comparison studies would be necessary for this conclusion to be applied to other types of

  2. Uncertainties on lung doses from inhaled plutonium.

    PubMed

    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.

  3. [Physio-pathological impacts of inhaled nanoparticles].

    PubMed

    Baeza-Squiban, Armelle

    2014-01-01

    Nanomaterials are defined as materials with any external dimension in the nanoscale or having an internal structure or surface structure in the nanoscale, approximately 1 nm to 100 nm. They exhibit new or reinforced properties as compared to the same material at the micrometric scale, providing a benefit in numerous technological applications. However, their specific surface properties in addition to their shape, composition, size are suspected to elicit adverse responses from biological systems, underlining the need for a thorough hazard assessment. Increasing use of nanomaterials in industrial as well as consumer products extends the possibilities of environmental and occupational human exposures. During all their life cycle, from their production to their destruction through their use, engineered nanoparticles can be released and the respiratory route is one of the main unintentional routes of exposure. Although the respiratory tract is equipped with efficient clearance mechanisms, there is increasing evidence that nanoparticles exhibit an ability to cross biological barriers, getting access to the bloodstream and secondary target organs. Different features of nanomaterials (size, form, surface reactivity...) contribute to their internalization and translocation through the respiratory barrier. Short term inhalation exposure to nanoparticles induces pulmonary inflammation the extent of which is dependent on the type of nanoparticles according to shape, size, solubility...Oxidative stress is considered as a major toxicity pathway triggered by nanomaterials as they can intrinsically produce reactive oxygen species or induced the intracellular production of reactive oxygen species or anti-oxidant depletion upon interaction with cells. Alternative mechanisms are suspected, related to the ability of nanoparticles to interact with proteins. As they get in contact with biological fluids, nanoparticles are covered by a protein corona that modifies their interactions

  4. Plume temperature emitted from metered dose inhalers.

    PubMed

    Brambilla, G; Church, T; Lewis, D; Meakin, B

    2011-02-28

    The temperature of the drug cloud emitted from a pressurised metered dose inhaler (pMDI) may result in patient discomfort and inconsistent or non-existent dose delivery to the lungs. The effects of variations in formulation (drug, propellant, co-solvent content) and device hardware (metering volume, actuator orifice diameter, add-on devices) upon the temperature of pMDI plumes, expressed as replicate mean minimum values (MMPT), collected into a pharmacopoeial dose unit sampling apparatus (DUSA), have been investigated. Ten commercially available and two development products, including chlorofluorocarbon (CFC) suspensions and hydrofluoroalkane (HFA) solutions or suspensions, were examined together with a number of drug products in late stage development and a variety of HFA 134a placebo pMDIs. Plume temperatures were observed to be lowest in the proximity of the product's actuator mouthpiece where rapid flashing and evaporation of the formulation's propellant and volatile excipients cause cooling. The ability to control plume temperature by judicious choice of formulation co-solvent content, metering volume and the actuator orifice diameter is identified. An ethanol based HFA 134a formulation delivered through a fine orifice is inherently warmer than one with 100% HFA 134a vehicle delivered through a coarse actuator orifice. Of the 10 commercial products evaluated, MMPTs ranged from -54 to +4°C and followed the formulation class rank order, HFA suspensions

  5. Stop inhaling smoke: prevent coronary heart disease.

    PubMed

    Kilburn, Kaye H

    2003-02-01

    Acute myocardial infarction (AMI) was rare a century ago and was diagnosed in few living patients prior to 1925. By 1950, it was the most common heart problem seen by clinicians. Thought at first to have been overlooked, there were many explanations offered for its neglect. Smoking, hypertension, and elevated cholesterol are associated with AMI, but of these only smoking should be considered a cause. Hypertension and hypercholesterolemia may be co-effects, perhaps of inflammation stimulated in the lung and blood vessels by smoking and air pollution, thus affecting vessels and arteries subjected to systemic blood pressure. Air pollution--the 20th century's other "big smoke"--deserves consideration as a 2nd cause. Auto exhaust blankets the world's cities. It consists of smoke and other effluents of petroleum vaporization and combustion that emanate from the crankcases and exhaust pipes of trucks and automobiles. The major living spaces (conurbations) of the world now imitate and exceed Los Angeles in their levels of air pollution. Auto exhaust gases fit the timeline, and their increasing amounts parallel the worldwide rise in coronary heart disease. Increasing doses of these chemicals imitate cigarette smoke and stimulate inflammation in the lungs. They appear to be absorbed into the blood, where they cause inflammation in blood vessels, increased blood pressure, and clogged coronary arteries. Avoidance is the obvious solution. Quit inhaling cigarette smoke and motor vehicle exhaust. The benefits have been shown and can be proved by intervention. The quest for clean air is hygienic-like avoiding water contaminated with feces was 150 yr ago. Clear air must be made a moral right. Its attainment requires a major revolution in priorities for energy use and lifestyle. Two types of smoke must be avoided. The world's most lethal disease.

  6. Systematic Review of Inhaled Bronchodilator and Corticosteroid Therapies in Infants with Bronchopulmonary Dysplasia: Implications and Future Directions

    PubMed Central

    Clouse, Brian J.; Jadcherla, Sudarshan R.; Slaughter, Jonathan L.

    2016-01-01

    Background There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD). Objective The objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-termoutcomes. Methods The databases of Academic Search Complete, CINAHL, PUBMED/MEDLINE, and Scopus were searched for studies that evaluated both acute and long-term clinical outcomes related to the delivery and therapeutic efficacy of inhaled beta-agonists, anticholinergics and corticosteroids in infants with developing and/or established BPD. Results Of 181 articles, 22 met inclusion criteria for review. Five evaluated beta-agonist therapies (n = 84, weighted gestational age (GA) of 27.1(26–30) weeks, weighted birth weight (BW) of 974(843–1310) grams, weighted post menstrual age (PMA) of 34.8(28–39) weeks, and weighted age of 53(15–86) days old at the time of evaluation). Fourteen evaluated inhaled corticosteroids (n = 2383, GA 26.2(26–29) weeks, weighted BW of 853(760–1114) grams, weighted PMA of 27.0(26–31) weeks, and weighted age of 6(0–45) days old at time of evaluation). Three evaluated combination therapies (n = 198, weighted GA of 27.8(27–29) weeks, weighted BW of 1057(898–1247) grams, weighted PMA of 30.7(29–45) weeks, and age 20(10–111) days old at time of evaluation). Conclusion Whether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear. Literature regarding these therapies mostly addresses evolving BPD. There appears to be heterogeneity in treatment responses, and may be related to varying modes of administration. Further research is needed to evaluate inhaled therapies in infants with severe BPD. Such investigations should focus on appropriate definitions of disease and subject selection, timing of therapies, and new drugs, devices and delivery

  7. Cognitive performance correlates with cerebrovascular impairments in multi-infarct dementia

    SciTech Connect

    Judd, B.W.; Meyer, J.S.; Rogers, R.L.; Gandhi, S.; Tanahashi, N.; Mortel, K.F.; Tawaklna, T.

    1986-05-01

    Cerebral blood flow (CBF) was measured by the /sup 133/Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses to situational demands and predisposes to cerebral ischemia. Loss of cerebral vasomotor responsiveness among MID patients, which is a biologic marker of cerebrovascular disease, provides confirmatory evidence of the vascular etiology of MID and assists in separating MID from AD patients.

  8. A Curious Case of Inhalation Fever Caused by Synthetic Cannabinoid

    PubMed Central

    Chinnadurai, Thiru; Shrestha, Srijan; Ayinla, Raji

    2016-01-01

    Patient: Male, 29 Final Diagnosis: Inhalation fever induced by synthetic cannabinoid Symptoms: Agitation • smoked synthetic cannabinoid Medication: Ringer’s lactate solution • Ceftriaxone • Azithromycin• Magnesium sulfate • Potassium Phosphate • Levofloxacin • Risperidone Clinical Procedure: Chest radiograph • CBC • urine toxicology Specialty: Pulmonology Objective: Unusual clinical course Background: This case report describes inhalation fever as an uncommon pulmonary adverse effect of synthetic cannabinoids. Case Report: A 29-year-old man was brought in for severe agitation after smoking K2, a synthetic cannabinoid. He required multiple doses of lorazepam and haloperidol for sedation. His vital signs were notable for a mild fever and tachycardia. Otherwise, the rest of his exam was unremarkable. The laboratory test was significant for leucocytosis and diffuse reticular-nodular and interstitial infiltrates on chest radiograph. Urine drug toxicology was negative. Interestingly, his symptoms and pulmonary infiltrates on the chest radiograph resolved spontaneously after 24 hours of observation. Conclusions: This patient developed transient pulmonary infiltrates and fever following the synthetic cannabinoid inhalation, as seen in self-limiting inhalation fever. Inhalation fever as a consequence of synthetic cannabinoid has not been described previously and there is a need for further research in this field. PMID:27262587

  9. Rethinking the paradigm for the development of inhaled drugs.

    PubMed

    Pritchard, John N

    2015-12-30

    Nebulized treatment is an important delivery option for the young, elderly, and those with severe chronic respiratory disease, but there is a lack of new nebulized drug products being produced for these patients, leading to the potential for under-treatment. This communication describes a new drug development paradigm as a timely solution to this issue. Often, drug development is initiated with nebulizers in the early stages, to provide cheaper and faster drug development, and then switched to inhaler devices in later clinical trials to address the majority of patients. However, the waste of resource on parallel development of the inhaler can be large due to the high early attrition rate of new drug development. The new paradigm uses the nebulizer to continue drug development through to market, and initiates inhaler development after completion of the riskier early phase studies. New drug safety and efficacy can be assessed faster and more efficiently by using a nebulized formulation rather than developing an inhaler. The results of calculations of expected net present value showed that the new paradigm produced higher expected net present values than the conventional model over a range of economic scenarios. This new paradigm could therefore provide improved returns on investments, as well as more modern drugs in nebulized form for those patients unable to use inhalers.

  10. Influences of gender and anthropometric features on inspiratory inhaler acoustics and peak inspiratory flow rate.

    PubMed

    Taylor, Terence E; Holmes, Martin S; Sulaiman, Imran; Costello, Richard W; Reilly, Richard B

    2015-01-01

    Inhalers are hand-held devices used to treat chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Medication is delivered from an inhaler to the user through an inhalation maneuver. It is unclear whether gender and anthropometric features such as age, height, weight and body mass index (BMI) influence the acoustic properties of inspiratory inhaler sounds and peak inspiratory flow rate (PIFR) in inhalers. In this study, healthy male (n=9) and female (n=7) participants were asked to inhale at an inspiratory flow rate (IFR) of 60 L/min in four commonly used inhalers (Turbuhaler(™), Diskus(™), Ellipta(™) and Evohaler(™)). Ambient inspiratory sounds were recorded from the mouthpiece of each inhaler and over the trachea of each participant. Each participant's PIFR was also recorded for each of the four inhalers. Results showed that gender and anthropometric features have the potential to influence the spectral properties of ambient and tracheal inspiratory inhaler sounds. It was also observed that males achieved statistically significantly higher PIFRs in each inhaler in comparison to females (p<;0.05). Acoustic features were found to be significantly different across inhalers suggesting that acoustic features are modulated by the inhaler design and its internal resistance to airflow.

  11. The Combined Use of Inhaled and Intravenous Steroids for Children With Chemical Pneumonitis After Ingestion of Paint Thinner

    PubMed Central

    Konca, Capan; Tekin, Mehmet; Turgut, Mehmet

    2016-01-01

    Background Some studies in the literature support the use of either inhaled or systemic steroids for the treatment of chemical pneumonitis; however, no data have been published on the combined use of inhaled and intravenous (IV) steroids. Objectives This brief report describes the effective use of inhaled plus systemic steroids in managing six critical pediatric patients. Patients and Methods Medical records of patients were analyzed retrospectively. Results Of the six patients, 83.3% (n = 5) were male and 16.7% (n = 1) were female, with a mean age of 2.1 ± 0.49 years. The most common clinical signs were dyspnea (83.3%), fever (66.6%), and vomiting (66.6%). Owing to supportive treatments and the combined steroid treatment, respiratory distress diminished and there was no need for oxygen in any of the patients after 5 days. All patients were discharged without any sequelae. Conclusions The use of steroids in treating hydrocarbon pneumonias is still controversial. However, we suggest that the combined use of inhaled and intravenous steroids had positive effects on the clinical and radiological recovery of our patients. PMID:27651946

  12. Analytical findings of an acute intoxication after inhalation of methoxetamine.

    PubMed

    Imbert, Laurent; Boucher, Alexandra; Delhome, Gilles; Cueto, Thierry; Boudinaud, Michel; Maublanc, Julie; Dulaurent, Sylvain; Descotes, Jacques; Lachâtre, Gérard; Gaulier, Jean-Michel

    2014-09-01

    Methoxetamine (MXE) is increasingly used and abused, as it is frequently presented as being safer than ketamine, and legal. Cases of only MXE consumption being associated with the occurrence of seizures are rarely reported. A single MXE intoxication case by inhalation is described concerning a 21-year-old man, not known to be epileptic, who was found collapsed in his bedroom, supposedly after an epileptic seizure. He was transferred to the Emergency Department of the Henri Mondor Hospital, Aurillac, France. He was conscious, but with a sinus bradycardia (48/min) and an ST-segment elevation on the electrocardiogram, and a slightly increased creatine kinase level (270 U/L) and hyponatremia (127 mmol/L). New seizure activity occurred during hospitalization, but the clinical course in the intensive care unit was favorable. Quantitation of MXE in serum and urine using gas chromatography coupled to mass spectrometry (GC-MS) was developed, as well as a liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) method for the determination of MXE in hair. Limits of detection and quantification were, respectively, 2 and 10 µg/L for the GC-MS method and both 0.5 pg/mg for the LC-MS-MS method. Concentrations of 30 and 408 µg/L were, respectively, measured in serum and urine. Concentrations of 135 and 145 pg/mg were detected in two 2.5 cm hair strands, consistent with one or several consumptions during the 2 ½ months prior to sampling. A sample of the powder consumed was available and also analyzed. This case illustrates the dangers of this drug, which justify its classification as a narcotic in France since August 2013.

  13. Pharmacokinetics of inhaled monodisperse beclomethasone as a function of particle size

    PubMed Central

    Esposito-Festen, J E; Zanen, P; Tiddens, H A W M; Lammers, J-W J

    2007-01-01

    What is already known about this subject For asthmatic adults, bronchodilators with a MMAD between 3 and 6 µm were shown to give the best improvement in lung function and the least systemic side-effects. It is not known, however, what is the most efficacious particle size for inhaled steroids in asthmatic adults. Clinical efficacy and systemic side-effects of inhaled steroids should be measured to define the optimal particle size. What this study adds Our study investigated the systemic absorption of inhaled steroids. We found that a particle size of 2.5 µm and 4.5 µm gave a higher pulmonary bioavailability compared with the 1.5 µm monodisperse aerosols in adults with mild asthma and therefore were more likely to elicit systemic adverse effects. Aims For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes. Methods In a randomized single-blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 µm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17-beclomethasone monopropionate (17-BMP) were measured by liquid chromatography plus mass spectrometry. Results Aerosols with MMADs of 1.5 µm, 2.5 µm, and 4.5 µm gave mean maximum concentrations (Cmax) of 17-BMP of 475 pg ml−1, 1300 pg ml−1, and 1161 pg ml−1, respectively. The area under the curve (AUC) values of 17-BMP for MMADs of 1.5 µm, 2.5 µm, and 4.5 µm were 825 pg ml−1 h, 2629 pg ml−1 h, and 2276 pg ml−1 h, respectively. The mean terminal half-time of 17-BMP for all three aerosol sizes was around 1.5 h. Conclusions Monodisperse BDP aerosols with a MMAD of 1.5 µm gave two-three fold lower values for Cmax

  14. Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis

    PubMed Central

    2011-01-01

    Background Little is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children. Methods We compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90). Results Median [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045). Conclusions These data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC

  15. [Inhaled in chronic obstructive pulmonary disease therapy update].

    PubMed

    Viejo-Casas, A; Bonnardeaux-Chadburn, C; Ginel-Mendoza, L; Quintano-Jimenez, J A

    2016-10-01

    Knowledge of chronic obstructive pulmonary disease has increased significantly in recent years, and today we have a more comprehensive concept of the disease. Additionally, drug development allows having a wide range of therapeutic options. The inhaled route is the choice, as it allows drugs to act directly on the bronchial tree. In the past few months, new molecules and devices have been developed that increases our options when treating, but also our doubts when choosing one or the other, so an update of inhaled medications for chronic obstructive pulmonary disease is necessary. The different types of inhalers currently available are reviewed in this article, as well as the advantages and disadvantages of each of them, in order to determine how to choose the right device.

  16. Inhaled formulations and pulmonary drug delivery systems for respiratory infections.

    PubMed

    Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim

    2015-05-01

    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'.

  17. Inhalation Lung Injury Associated with Humidifier Disinfectants in Adults

    PubMed Central

    2016-01-01

    We recently established a novel disease entity presented as progressive respiratory failure associated with the inhalation of humidifier disinfectants. In April 2011, we encountered a series of peripartum patients with complaints of respiratory distress of unknown etiology, which was an uncommon phenomenon. Accordingly, we created a multidisciplinary team comprising intensivists, radiologists, pathologists, epidemiologists, and the Korea Centers for Disease Control and Prevention (KCDC). Further, we defined the disease entity and performed a case-control study, epidemiologic investigation, and animal study to determine the etiology. The study findings indicated that the lung injury outbreak was related to the inhalation of humidifier disinfectants and showed that household chemical inhalation can cause severe respiratory failure. Following the withdrawal of humidifier disinfectants from the Korean market in 2012, no such cases were reported. This tragic event is a warning that appropriate safety regulations and monitoring for potential toxic household chemicals are critical to protect public health. PMID:27822921

  18. The role of inhalant food allergens in occupational asthma.

    PubMed

    Cartier, André

    2010-09-01

    Workers handling food products and derivatives are at increased risk of developing occupational asthma. Exposure to food allergens occurs primarily through inhalation of dust, steam, vapors, and aerosolized proteins generated during cutting, scrubbing or cleaning, cooking or boiling, and drying activities. Suspicion of the diagnosis of occupational asthma should lead to proper investigation to confirm the diagnosis objectively. Most inhaled food allergy is IgE mediated, and skin prick tests or specific IgE tests are useful tools to support the diagnosis, but objective evidence of asthma by monitoring of peak expiratory flows at and off work or specific inhalation challenges offers a better diagnostic value. This article provides a list of the various foods, food additives, and contaminants that have been associated with occupational asthma.

  19. Particulate oil shale inhalation and pulmonary inflammatory response in rats

    SciTech Connect

    Wilson, J.S.; Holland, L.M.; Halleck, M.S.; Martinez, E.; Saunders, G.

    1983-01-01

    This experiment detrimetal that long-term inhalation of shale dusts by rats elicits a limited inflammatory response in the lung less profound than that observed in animals exposed to equivalent levels of quartz alone. This observation suggests that organic and inorganic constituents of shale may provide a protective effect. The implications for fibrogenic disease are two-fold: (1) inhalation of oil shale dusts appeared to be less detriemtal than the inhalation of quartz along, and (2) there was no apparent synergistic action of quartz and the complex of organic materials present in shale. Animals exposed to shale dusts failed to develop any significant lung lesions, while all of the animals exposed to quartz developed granulomas and some frank fibrosis.

  20. Toxic alveolitis after inhalation of a water repellent.

    PubMed

    Epping, Guido; Van Baarlen, Joop; Van Der Valk, Paul D L P M

    2011-12-01

    Inhalation of fluorocarbon polymers can cause pulmonary toxicity. Although multiple cases of lung injury have been reported, cellular characterization of the associated alveolitis occurring acutely after inhalation is limited. We report the case of a previously healthy woman who presented at our Emergency Department with an acute pneumonitis following inhalation of a fluorocarbon polymer-based rain-proofing spray. Bronchoalveolar lavage (BAL) performed shortly after the presentation showed an elevated total cell count, with a high proportion of neutrophils (58%) and eosinophils (9%). In addition, a lipid stain (Oil-Red-O-stain) showed a high level of lipid laden macrophages, a marker that could reflect a direct toxic effect of the spray on alveolar cells. The patient made a full recovery after four days of in-hospital observation with supportive care.

  1. Optimization of a DPI Inhaler: A Computational Approach.

    PubMed

    Milenkovic, Jovana; Alexopoulos, Aleck H; Kiparissides, Costas

    2017-03-01

    Alternate geometries of a commercial dry powder inhaler (DPI, i.e., Turbuhaler; AstraZeneca, London, UK) are proposed based on the simulation results obtained from a fluid and particle dynamic computational model, previously developed by Milenkovic et al. The alternate DPI geometries are constructed by simple alterations to components of the commercial inhaler device leading to smoother flow patterns in regions where significant particle-wall collisions occur. The modified DPIs are investigated under the same conditions of the original studies of Milenkovic et al. for a wide range of inhalation flow rates (i.e., 30-70 L/min). Based on the computational results in terms of total particle deposition and fine particle fraction, the modified DPIs were improved over the original design of the commercial device.

  2. Inhaled Bordetella pertussis vaccine decreases airway responsiveness in guinea pigs.

    PubMed

    Vargas, M H; Bazán-Perkins, B; Segura, P; Campos, M G; Selman, M; Montaño, L M

    1995-01-01

    Bordetella pertussis (BP) has been used as adjuvant for experimental animal immunization, but its effects on airway responsiveness are uncertain. Three groups of guinea pigs were used: animals with a single exposure to inhaled BP vaccine (strain 134, total dose 1.24 x 10(12) germs), animals submitted to a sensitization procedure through inhalation of ovalbumin plus BP, and healthy control animals. Four weeks after inhalation of BP or after the beginning of sensitization, dose- or concentration-response curves to histamine were constructed in vivo and in vitro (tracheal and parenchymal preparations). We found that BP alone produced lower responses to histamine than control guinea pigs in vivo (insufflation pressure, p = 0.0003) and in tracheal tissues (p = 0.04), but not in parenchymal preparations. Sensitization did not modify the responsiveness compared with their respective controls. These results suggest that some BP component(s), probably pertussis toxin, causes a long lasting airway hyporesponsiveness in guinea pigs.

  3. Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

    PubMed

    Dykes, John C; Torres, Marilyn; Alexander, Plato J

    2016-03-01

    This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.

  4. Inhalation a significant exposure route for chlorinated organophosphate flame retardants.

    PubMed

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J

    2016-05-01

    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds.

  5. Challenges in inhaled product development and opportunities for open innovation.

    PubMed

    Forbes, Ben; Asgharian, Bahman; Dailey, Lea Ann; Ferguson, Douglas; Gerde, Per; Gumbleton, Mark; Gustavsson, Lena; Hardy, Colin; Hassall, David; Jones, Rhys; Lock, Ruth; Maas, Janet; McGovern, Tim; Pitcairn, Gary R; Somers, Graham; Wolff, Ron K

    2011-01-01

    Dosimetry, safety and the efficacy of drugs in the lungs are critical factors in the development of inhaled medicines. This article considers the challenges in each of these areas with reference to current industry practices for developing inhaled products, and suggests collaborative scientific approaches to address these challenges. The portfolio of molecules requiring delivery by inhalation has expanded rapidly to include novel drugs for lung disease, combination therapies, biopharmaceuticals and candidates for systemic delivery via the lung. For these drugs to be developed as inhaled medicines, a better understanding of their fate in the lungs and how this might be modified is required. Harmonized approaches based on 'best practice' are advocated for dosimetry and safety studies; this would provide coherent data to help product developers and regulatory agencies differentiate new inhaled drug products. To date, there are limited reports describing full temporal relationships between pharmacokinetic (PK) and pharmacodynamic (PD) measurements. A better understanding of pulmonary PK and PK/PD relationships would help mitigate the risk of not engaging successfully or persistently with the drug target as well as identifying the potential for drug accumulation in the lung or excessive systemic exposure. Recommendations are made for (i) better industry-academia-regulatory co-operation, (ii) sharing of pre-competitive data, and (iii) open innovation through collaborative research in key topics such as lung deposition, drug solubility and dissolution in lung fluid, adaptive responses in safety studies, biomarker development and validation, the role of transporters in pulmonary drug disposition, target localisation within the lung and the determinants of local efficacy following inhaled drug administration.

  6. Inhaled cellulosic and plastic fibers found in human lung tissue.

    PubMed

    Pauly, J L; Stegmeier, S J; Allaart, H A; Cheney, R T; Zhang, P J; Mayer, A G; Streck, R J

    1998-05-01

    We report the results of studies undertaken to determine whether inhaled plant (i.e., cellulosic; e.g., cotton) and plastic (e.g., polyester) fibers are present in human lungs and, if so, whether inhaled fibers are also present in human lung cancers. Specimens of lung cancer of different histological types and adjacent nonneoplastic lung tissue were obtained from patients undergoing a lung resection for removal of a tumor. With the protection of a laminar flow hood and safeguards to prevent contamination by extraneous fibers, fresh, nonfixed, and nonstained samples of lung tissue were compressed between two glass microscope slides. Specimens in these dual slide chambers were examined with a microscope configured to permit viewing with white light, fluorescent light, polarizing light, and phase-contrast illumination. Near-term fetal bovine lungs and nonlung human tumors were used as controls. In contrast to the observations of these control tissues, morphologically heterogeneous fibers were seen repetitively in freshly excised human lung tissue using polarized light. Inhaled fibers were present in 83% of nonneoplastic lung specimens (n = 67/81) and in 97% of malignant lung specimens (n = 32/33). Thus, of the 114 human lung specimens examined, fibers were observed in 99 (87%). Examination of histopathology slides of lung tissue with polarized light confirmed the presence of inhaled cellulosic and plastic fibers. Of 160 surgical histopathology lung tissue slides, 17 were selected for critical examination; of these, fibers were identified in 13 slides. The inhalation of mineral (e.g., asbestos) fibers has been described by many investigators; we believe, however, that this is the first report of inhaled nonmineral (e.g., plant and plastic) fibers. These bioresistant and biopersistent cellulosic and plastic fibers are candidate agents contributing to the risk of lung cancer.

  7. Preclinical safety evaluation of inhaled cyclosporine in propylene glycol.

    PubMed

    Wang, Tao; Noonberg, Sarah; Steigerwalt, Ronald; Lynch, Maryellen; Kovelesky, Rosemary A; Rodríguez, Carlos A; Sprugel, Katherine; Turner, Nancy

    2007-01-01

    Cyclosporine inhalation solution has the potential to improve outcomes following lung transplantation by delivering high concentrations of an immunosuppressant directly to the allograft while minimizing systemic drug exposure and associated toxicity. The objective of these studies was to evaluate the potential toxicity of aerosolized cyclosporine formulated in propylene glycol when given by inhalation route to rats and dogs for 28 days. Sprague-Dawley rats received total inhaled doses of 0 (air), 0 (vehicle, propylene glycol), 7.4, 24.3, and 53.9 mg cyclosporine/kg/day. In a separate study, beagle dogs were exposed to 0, 4.4, 7.7, and 9.7 mg cyclosporine/kg/day. Endpoints used to evaluate potential toxicity of inhaled cyclosporine were clinical observations, body weight, food consumption, respiratory functions, toxicokinetics, and clinical/anatomic pathology. Daily administration of aerosolized cyclosporine did not result in observable accumulation of cyclosporine in blood or lung tissue. Toxicokinetic analysis from the rat study showed that the exposure of cyclosporine was approximately 18 times higher in the lung tissue compared to the blood. Systemic effects were consistent with those known for cyclosporine. There was no unexpected systemic toxicity or clinically limiting local respiratory toxicity associated with inhalation exposure to cyclosporine inhalation solution at exposures up to 2.7 times the maximum human exposure in either rats or dogs. There were no respiratory or systemic effects of high doses of propylene glycol relative to air controls. These preclinical studies demonstrate the safety of aerosolized cyclosporine in propylene glycol and support its continued clinical investigation in patients undergoing allogeneic lung transplantation.

  8. The electrospray and its application to targeted drug inhalation.

    PubMed

    Gomez, Alessandro

    2002-12-01

    This review explains the fundamentals of electrostatic spray (electrospray) atomization, with emphasis on operation in the so called cone-jet mode, which produces droplets with a very narrow size distribution. Since the control of droplet size is key to maximizing distal lung deposition, the electrospray should be well-suited to targeted drug inhalation. Electrospray droplets are a few micrometers in diameter, but they originate from a much larger nozzle, which allows nebulization of suspensions without clogging. Also discussed are: the physical principles of the break-up of the liquid ligament; droplet dispersion by Coulombic forces; and the most important scaling law linking the droplet size to liquid flow rate and liquid physical properties. The effects of the most critical of those properties may result in some restrictions on drug formulation. Droplets produced by electrospray are electrically charged, so to prevent electrostatic image forces from causing upper respiratory tract deposition. The charge is neutralized by generating a corona discharge of opposite polarity. Briefly discussed are the main differences between the laboratory systems (with which the electrospray has been quantitatively characterized during research in the past 10 years) and commercial electrospray inhalers under development at BattellePharma. Some remarkable miniaturization has incorporated liquid pump, power supply, breath activation, and dose counter into a palm-size portable device. The maximum flow rates dispersed from these devices are in the range of 8-16 microL/s, which makes them suitable for practical drug inhalation therapy. Fabrication is economically competitive with inexpensive nebulizers. Dramatic improvements in respirable dose efficiency (up to 78% by comparison with commercial metered-dose inhalers and dry powder inhalers) should ensure the commercialization of this promising technology for targeted drug inhalation.

  9. A review of the development of Respimat Soft Mist Inhaler.

    PubMed

    Dalby, R; Spallek, M; Voshaar, T

    2004-09-28

    Respimat Soft Mist Inhaler (SMI) is a new generation inhaler from Boehringer Ingelheim developed for use with respiratory drugs. The device functions by forcing a metered dose of drug solution through a unique and precisely engineered nozzle (the uniblock), producing two fine jets of liquid that converge at a pre-set angle. The collision of these two jets generates the soft mist. The soft mist contains a high fine particle fraction of approximately 65 to 80%. This is higher than aerosol clouds from conventional portable inhaler devices, such as pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). In addition, the relatively long generation time of the aerosol cloud (approximately 1.5s) facilitates co-ordination of inhalation and actuation--a major problem with pMDIs. These features, together with the slow velocity of the soft mist, result in larger amounts of the drug reaching the lungs and less being deposited in the oropharynx compared with either pMDIs or DPIs. Generation of the soft mist from Respimat SMI is purely mechanical, so propellants are not necessary. The innovative design of Respimat SMI, using water-based drug formulations, ensures patients receive consistent and reliable doses of the drug with each actuation. The device was initially tested in scintigraphic lung deposition studies and produced encouraging results when compared with the chlorofluorocarbon-based pMDI (CFC-MDI). Subsequent clinical studies have confirmed that Respimat SMI is effective and safe in delivering bronchodilators to patients with asthma or chronic obstructive pulmonary disease.

  10. A Simple and Disposable Sampler for Inhalable Aerosol

    PubMed Central

    L’Orange, Christian; Anderson, Kimberly; Sleeth, Darrah; Anthony, T. Renée; Volckens, John

    2016-01-01

    The state-of-the-art for personal sampling for inhalable aerosol hazards is constrained by issues of sampler cost and complexity; these issues have limited the adoption and use of some samplers by practicing hygienists. Thus, despite the known health effects of inhalable aerosol hazards, personal exposures are routinely assessed for only a small fraction of the at-risk workforce. To address the limitations of current technologies for inhalable aerosol sampling, a disposable inhalable aerosol sampler was developed and evaluated in the laboratory. The new sampler is designed to be less expensive and simpler to use than existing technologies. The sampler incorporates a lightweight internal capsule fused to the sampling filter. This capsule-filter assembly allows for the inclusion of particles deposited on the internal walls and inlet, thus minimizing the need to wash or wipe the interior sampling cassette when conducting gravimetric analyses. Sampling efficiency and wall losses were tested in a low-velocity wind tunnel with particles ranging from 9.5 to 89.5 μm. The results were compared to the proposed low-velocity inhalability criterion as well as published data on the IOM sampler. Filter weight stability and time-to-equilibrium were evaluated as these factors affect the practicality of a design. Preliminary testing of the new sampler showed good agreement with both the IOM and the proposed low-velocity inhalability curve. The capsule and filter assemblies reached equilibrium within 25h of manufacturing when conditioned at elevated temperatures. After reaching equilibrium, the capsule-filter assemblies were stable within 0.01mg. PMID:26467335

  11. Bronchoscopy-Derived Correlates of Lung Injury Following Inhalational Injuries: A Prospective Obervational Study

    EPA Science Inventory

    Acute lung injury (ALI) is a major factor determining morbidity following burns and inhalational injury. In experimental models, factors potentially contributing to ALI risk include inhalation of toxins directly causing cell damage; inflammation; and infection. However, few studi...

  12. Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: experience from bulk maritime transport.

    PubMed

    Höfer, Thomas; James, Derek; Syversen, Tore; Bowmer, Tim

    2011-12-01

    Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory requirement for the carriage of bulk liquid chemicals transported by sea in tank ships, thereby creating the need for inhalation data on many hundreds of chemicals in bulk maritime transport. Taking note of previously published proposals for estimating acute inhalation toxicity hazards for chemicals, and the paucity of measured experimental data, an extrapolation method has been developed by the Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) to partly fulfil this need. This method should be seen as a pragmatic approach to the challenge of missing measured experimental test data, with the added benefit of reducing tests in experimental animals. The method is based on a route-to-route (i.e. between-route) extrapolation of information on acute oral and/or dermal toxicity, in combination with data on the potential for irritation and/or corrosion to skin and eyes. The validation of this method was based on the individual evaluation of inhalation toxicity studies for 330 chemicals, including mixtures and many important chemical groups, for which the IMO holds public and industry-confidential data. The authors contend that this extrapolation method offers a reliable basis for hazard evaluation in the context of bulk maritime transport, and the 'GESAMP inhalation toxicity extrapolation method' has become part of the IMO regulatory system for the carriage of bulk liquids (i.e. noxious liquid substances) on board tank ships.

  13. [Fatal acute silicosis caused by voluntary inhalation of scouring powder].

    PubMed

    Vincent, M; Arthaud, Y; Crettet, G; Gerard, F; Laennec, E; Peyrol, S; Pouchelle, C; Loire, R

    1995-01-01

    We report a case of acute fatal fibrosing silico-proteinosis occurring in nine months in a young woman who had voluntarily inhaled scouring powder. We recall the reports in the literature of the subacute or chronic forms associated with systemic diseases occurring after such inhalational practices. We recall the need for specific questioning and to complete the study, the need for microscopy and electron-microscopy associated with X-ray defraction, either on the alveolar lavage fluid or on a lung biopsy.

  14. Post-accident inhalation exposure and experience with plutonium

    SciTech Connect

    Shinn, J

    1998-06-01

    This paper addresses the issue of inhalation exposure immediately afterward and for a long time following a nuclear accident. For the cases where either a nuclear weapon burns or explodes prior to nuclear fission, or at locations close to a nuclear reactor accident containing fission products, a major concern is the inhalation of aerosolized plutonium (Pu) particles producing alpha-radiation. We have conducted field studies of Pu- contaminated real and simulated accident sites at Bikini, Johnston Atoll, Tonopah (Nevada), Palomares (Spain), Chernobyl, and Maralinga (Australia).

  15. An interesting case of characteristic methanol toxicity through inhalational exposure

    PubMed Central

    Kumar, Pratyush; Gogia, Atul; Kakar, Atul; Miglani, Pratyush

    2015-01-01

    Methanol poisoning is rare but carries high risk of morbidity and mortality. Most of the cases witnessed in emergency are due to consumption of adulterated alcohol. Here we are reporting a very rare case of methanol poisoning through inhalational exposure leading to putamen necrosis and decreased visual acuity. He had dyselectrolytemia and metabolic acidosis which was successfully managed with early intervention. Its importance lies in the fact that inhalational methanol poisoning is an entity which if picked up early can prevent long-term neurological sequelae. PMID:26285665

  16. Inhaled iloprost for therapy in pulmonary arterial hypertension.

    PubMed

    Ewert, Ralf; Gläser, Sven; Bollmann, Tom; Schäper, Christoph

    2011-04-01

    Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.

  17. The subacute inhalation toxicity of 109 industrial chemicals

    PubMed Central

    Gage, J. C.

    1970-01-01

    Gage, J. C. (1970).Brit. J. industr. Med.,27, 1-18. The subacute inhalation toxicity of 109 industrial chemicals. The inhalation toxicity of 109 substances has been studied by exposing experimental animals to known concentrations in air for periods of about three weeks. The toxic properties of these substances are reviewed in relation to the effects of similar compounds on animals and on man. Provisional operational limits are suggested to assist in the design of new plant and in the establishment of codes for safe manufacturing practice. PMID:5418916

  18. Partition of xenon and iodoantipyrine among erythrocytes, plasma, and myocardium.

    PubMed

    Carlin, R; Chien, S

    1977-05-01

    A new method was developed for determining directly the distribution of 133Xe between red cells and plasma in vitro without an air-fluid interface; the partitioning of 133Xe and 133-i-iodantipyrine between blood and myocardium was investigated in the dog in situ. The red cell-plasma partition coefficient for 133Xe (lambdacpX, unit: ml/ml) at 37 degrees C was 2.27 +/- 0.07 (mean +/- SD) for human blood and 3.31 +/- 0.06 for dog blood. The red cell-plasma partition coefficient for 131I-iodantipyrine (lambdacpI, ml/ml) was 0.75 +/- 0.04 for human blood and 0.97 +/- 0.03 for dog blood. lambdacpX and lambdacpI did not change significantly after the intravenous administration of sodium pentobarbital (30 mg/kg) into the dog. lambdacpX of dog blood varied inversely with temperature, whereas lambdacpI showed very little change with temperature. The blood-left ventricle partition coefficient for 133Xe (lambda'btX, corrected for trapped blood) varied directly with directly with red cell volume fraction (H): lambda'btX = 1.32 + 2.00 H. Blood-left ventricle partition coefficient for 131I-iodoanitpyrine did not vary significantly with H. The results support the concept of a three-compartment partition of the indicator among erythrocytes, plasma, and myocardium. The mean values (+/- SD) of the hematocrit-independent plasma-tissue partition coefficient in the left ventricle for 133Xe and 131I-iodoantipyrine were 1.08 +/- 0.16 and 1.54 +/- 0.20 g/ml, respectively.

  19. Laboratory approach for diagnosis of toluene-based inhalant abuse in a clinical setting

    PubMed Central

    Jain, Raka; Verma, Arpita

    2016-01-01

    The steady increase of inhalant abuse is a great challenge for analytical toxicologists. This review describes an overview of inhalant abuse including the extent of the problem, types of products abused, modes of administration, pharmacology and effects of inhalants, the role of laboratory, interpretation of laboratory results and clinical considerations. Regular laboratory screening for inhalant abuse as well as other substance abuse and health risk behaviors must be a part of standard clinical care. PMID:26957863

  20. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma

    PubMed Central

    Ducharme, Francine M; Ni Chroinin, Muireann; Greenstone, Ilana; Lasserson, Toby J

    2014-01-01

    Background In asthmatic patients inadequately controlled on inhaled corticosteroids and/or those with moderate persistent asthma, two main options are recommended: the combination of a long-acting inhaled ß2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids. Objectives To determine the effect of the combination of long-acting ß2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the risk of asthma exacerbations, pulmonary function and on other measures of asthma control, and to look for characteristics associated with greater benefit for either treatment option. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (MEDLINE, EMBASE and CINAHL), bibliographies of RCTs, clinical trial registries and correspondence with manufacturers until May 2008. Selection criteria RCTs that compared the combination of inhaled LABA and ICS to a higher dose of inhaled corticosteroids, in children and adults with asthma. Data collection and analysis Two authors independently assessed methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the number of patients experiencing one or more asthma exacerbations requiring oral corticosteroids. Main results This review included 48 studies (15,155 participants including 1155 children and 14,000 adults). Participants were inadequately controlled on their current ICS regimen, experiencing ongoing symptoms and with generally moderate (FEV1 60% to 79% of predicted) airway obstruction. The studies tested the combination of salmeterol or formoterol with a median dose of 400 mcg/day of beclomethasone or equivalent (BDP-eq) compared to a median of 1000 mcg/day of BDP-eq, usually for 24 weeks or less. There was a statistically significantly lower risk of exacerbations requiring systemic corticosteroids in patients treated with LABA and ICS

  1. Validation of radiolabeling of drug formulations for aerosol deposition assessment of orally inhaled products.

    PubMed

    Devadason, Sunalene G; Chan, Hak-Kim; Haeussermann, Sabine; Kietzig, Claudius; Kuehl, Philip J; Newman, Stephen; Sommerer, Knut; Taylor, Glyn

    2012-12-01

    Radiolabeling of inhaler formulations for imaging studies is an indirect method of determining lung deposition and regional distribution of drug in human subjects. Hence, ensuring that the radiotracer and drug exhibit similar aerodynamic characteristics when aerosolized, and that addition of the radiotracer has not significantly altered the characteristics of the formulation, are critical steps in the development of a radiolabeling method. The validation phase should occur during development of the radiolabeling method, prior to commencement of in vivo studies. The validation process involves characterization of the aerodynamic particle size distribution (APSD) of drug in the reference formulation, and of both drug and radiotracer in the radiolabeled formulation, using multistage cascade impaction. We propose the adoption of acceptance criteria similar to those recommended by the EMA and ISAM/IPAC-RS for determination of therapeutic equivalence of orally inhaled products: (a) if only total lung deposition is being quantified, the fine particle fraction ratio of both radiolabeled drug and radiotracer to that of the reference drug should fall between 0.85 and 1.18, and (b) if regional lung deposition (e.g., outer and inner lung regions) is to be quantified, the ratio of both radiolabeled drug and radiotracer to reference drug on each impactor stage or group of stages should fall between 0.85 and 1.18. If impactor stages are grouped together, at least four separate groups should be provided. In addition, while conducting in vivo studies, measurement of the APSD of the inhaler used on each study day is recommended to check its suitability for use in man.

  2. Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

    PubMed Central

    Simon, Marc A.; Vanderpool, Rebecca R.; Nouraie, Mehdi; Bachman, Timothy N.; White, Pamela M.; Sugahara, Masataka; Gorcsan, John; Parsley, Ed L.; Gladwin, Mark T.

    2016-01-01

    BACKGROUND. Pulmonary hypertension (PH) is associated with poor outcomes, yet specific treatments only exist for a small subset of patients. The most common form of PH is that associated with left heart disease (Group 2), for which there is no approved therapy. Nitrite has shown efficacy in preclinical animal models of Group 1 and 2 PH, as well as in patients with left heart failure with preserved ejection fraction (HFpEF). We evaluated the safety and efficacy of a potentially novel inhaled formulation of nitrite in PH-HFpEF patients as compared with Group 1 and 3 PH. METHODS. Cardiopulmonary hemodynamics were recorded after acute administration of inhaled nitrite at 2 doses, 45 and 90 mg. Safety endpoints included change in systemic blood pressure and methemoglobin levels. Responses were also compared with those administered inhaled nitric oxide. RESULTS. Thirty-six patients were enrolled (10 PH-HFpEF, 20 Group 1 pulmonary arterial hypertension patients on background PH-specific therapy, and 6 Group 3 PH). Drug administration was well tolerated. Nitrite inhalation significantly lowered pulmonary, right atrial, and pulmonary capillary wedge pressures, most pronounced in patients with PH-HFpEF. There was a modest decrease in cardiac output and systemic blood pressure. Pulmonary vascular resistance decreased only in Group 3 PH patients. There was substantial increase in pulmonary artery compliance, most pronounced in patients with PH-HFpEF. CONCLUSIONS. Inhaled nitrite is safe in PH patients and may be efficacious in PH-HFpEF and Group 3 PH primarily via improvements in left and right ventricular filling pressures and pulmonary artery compliance. The lack of change in pulmonary vascular resistance likely may limit efficacy for Group 1 patients. TRIAL REGISTRATION. ClinicalTrials.gov NCT01431313 FUNDING. This work was supported in part by the NIH grants P01HL103455 (to MAS and MTG), R01HL098032 (to MTG), and R01HL096973 (to MTG), and Mast Therapeutics, Inc. PMID

  3. A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers

    PubMed Central

    Cassella, James V.; Spyker, Daniel A.; Yeung, Paul P.

    2015-01-01

    Objective: This randomized, double-blind, active- and placebo-controlled, crossover, thorough QT study assessed the effect of two inhaled loxapine doses on cardiac repolarization as measured by corrected QT (QTc) interval in healthy subjects (ClinicalTrials.gov NCT01854710). Methods: Subjects received two doses of inhaled loxapine (10 mg) 2 hours apart + oral placebo, two doses of inhaled placebo + oral placebo, or two doses of inhaled placebo + oral moxifloxacin (400 mg; positive control), with ≥ 3 days washout between treatments. Two-sided 90% confidence intervals (CIs) were calculated around least-squares mean predose placebo-subtracted individually corrected QT durations (ΔΔQTcIs) at 12 time points throughout 24 hours after dosing. A ΔΔQTcI 95% upper CI exceeding 10 msec was the threshold indicating QTc prolongation (primary endpoint). Secondary endpoints included Fridericia- and Bazett-corrected QT duration and QTcI outliers. Pharmacokinetics and adverse events (AEs) were also assessed. Results: Of 60 subjects enrolled (mean age, 33.8 years; 52% male), 44 completed the study. Post loxapine dosing, no ΔΔQTcI 95% upper CI exceeded 10 msec; the largest was 6.31 msec 5 minutes post dose 2. Methodology was validated by ΔΔQTcI 95% lower CIs exceeding 5 msec at 9 of 12 time points after moxifloxacin dosing. Loxapine plasma concentrations increased rapidly (mean Cmax, 177 ng/mL; median tmax 2 minutes after dose 2, 2.03 hours after dose 1). There were no deaths, serious AEs, or AEs leading to discontinuation, and one severe AE. Conclusions: Primary and secondary endpoints indicated two therapeutic doses of inhaled loxapine did not cause threshold QTc prolongation in this study. PMID:26501204

  4. Lung [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation

    PubMed Central

    Musch, Guido; Winkler, Tilo; Harris, R. Scott; Vidal Melo, Marcos F.; Wellman, Tyler J.; de Prost, Nicolas; Kradin, Richard L.; Venegas, Jose G.

    2014-01-01

    Background Acute lung injury (ALI) occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48 to 72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced ALI. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, we hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of ALI are not yet expected. Methods In five sheep we induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. We used positron emission tomography with: 1) [18F]fluorodeoxyglucose to measure pulmonary inflammatory cell metabolic activity; and 2) [13N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. Results The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1, P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02, P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01, P < 0.05). Conclusion Using noninvasive imaging we demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation. PMID:24051392

  5. The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder.

    PubMed

    Yang, Michael Y; Verschuer, Jordan; Shi, Yuyu; Song, Yang; Katsifis, Andrew; Eberl, Stefan; Wong, Keith; Brannan, John D; Cai, Weidong; Finlay, Warren H; Chan, Hak-Kim

    2016-11-20

    The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with (99m)Tc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50-70L/min to 110-130L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R(2)=1.0). On the other hand, the PI had a stronger association with the MMAD (R(2)=1.0) than the FPF (R(2)=0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution.

  6. Inhalant Use and Delinquent Behaviors among Young Adolescents. The NSDUH Report

    ERIC Educational Resources Information Center

    US Department of Health and Human Services, 2005

    2005-01-01

    This report presents the prevalence of inhalant use among young adolescents aged 12 or 13, the association between inhalant use and delinquent behaviors within this age group, and the association between early onset of inhalant use and problems later in life. Early onset of substance use has been linked to substance use disorders, delinquent…

  7. 78 FR 63227 - Determination That INTAL (cromolyn sodium) Inhalation Capsule, 20 Milligrams, Was Not Withdrawn...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Determination That INTAL (cromolyn sodium) Inhalation... determined that INTAL (cromolyn sodium) Inhalation Capsule, 20 milligrams (mg), was not withdrawn from sale... drug applications (ANDAs) for cromolyn sodium inhalation capsule, 20 mg, if all other legal...

  8. Inhalant Use and Risky Behavior Correlates in a Sample of Rural Middle School Students

    ERIC Educational Resources Information Center

    Muilenburg, Jessica Legge; Johnson, William D.

    2006-01-01

    This study found 20.4% of children attending a middle school located in rural Mississippi had used inhalants to "get high," a figure that is much larger than the national average. Many (3.4%) students reported they had used inhalants on 10 or more occasions. Inhalant use was most associated with being younger, ever smoking, riding with a…

  9. Cyanide Antidotes for Mass Casualties: Comparison of Intramuscular Injector by Autoinjector, Intraosseous Injection, and Inhalational Delivery

    DTIC Science & Technology

    2013-10-01

    held high- throughput ultrasonic monodisperse aerosol inhalers for detoxification of massive CN poisoning. IV. CONCLUSIONS Significant effect of...Comparison of Intramuscular Injector by Autoinjector, Intraosseous Injection, and Inhalational Delivery PRINCIPAL INVESTIGATOR: Gerry R...Antidotes for Mass Casualties: Comparison of Intramuscular Injector by Autoinjector, Intraosseous Injection, and Inhalational Delivery 5a. CONTRACT

  10. 21 CFR 250.100 - Amyl nitrite inhalant as a prescription drug for human use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Amyl nitrite inhalant as a prescription drug for... Prescription Status of Specific Drugs § 250.100 Amyl nitrite inhalant as a prescription drug for human use. (a) Amyl nitrite inhalant has been available over-the-counter for emergency use by the patient in...

  11. 21 CFR 250.100 - Amyl nitrite inhalant as a prescription drug for human use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Amyl nitrite inhalant as a prescription drug for... Prescription Status of Specific Drugs § 250.100 Amyl nitrite inhalant as a prescription drug for human use. (a) Amyl nitrite inhalant has been available over-the-counter for emergency use by the patient in...

  12. TARGETED DELIVERY OF INHALED PHARMACEUTICALS USING AN IN SILICO DOSIMETRY MODEL

    EPA Science Inventory

    We present an in silico dosimetry model which can be used for inhalation toxicology (risk assessment of inhaled air pollutants) and aerosol therapy ( targeted delivery of inhaled drugs). This work presents scientific and clinical advances beyond the development of the original in...

  13. [Inhaled treatments: Choice of devices, systemic absorption of inhaled drugs and bitter taste receptors in the respiratory tract].

    PubMed

    Benattia, A; Cavaillon, P; Gachelin, E; Devillier, P; Vecellio, L; Williams, G; Dubus, J-C

    2015-10-01

    Inhaled drugs are now routinely prescribed in daily medical practice. Recent topics about these treatments have been developed during the fourth annual meeting of the Groupe de travail aérosolthérapie (GAT) of the French-speaking respiratory society (Société de pneumologie de langue française). This article focuses mainly upon the choice of devices, systemic absorption of inhaled drugs and bitter taste receptors in the respiratory tract, a potential new target for drug development.

  14. Detection of acute inhalation injury in fire victims by means of technetium-99m DTPA radioaerosol inhalation lung scintigraphy.

    PubMed

    Lin, W Y; Kao, C H; Wang, S J

    1997-02-01

    Mortality and morbidity in fire victims are largely a function of injury due to heat and smoke. While the degree and area of burn together constitute a reliable numerical measure of cutaneous injury due to heat, as yet no satisfactory measure of inhalation injury has been developed. In this study, we employed technetium-99m diethylene triamine penta-acetic acid (DTPA) radioaerosol lung scintigraphy (inhalation scan) to evaluate acute inhalation injury in fire victims. Ten normal controls and 17 survivors from a fire accident were enrolled in the study. All patients suffered from respiratory symptoms (dyspnoea and/or cough with sputum). 99mTc-DTPA aerosol inhalation lung scintigraphy was performed in all subjects, using a commercial lung aerosol delivery unit. The degree of lung damage was presented as the clearance rate (k; %/min) calculated from the time-activity curve over the right lungs. In addition, the distribution pattern of the radioactivity in the lungs was evaluated and classified into two groups: homogeneous distribution and inhomogeneous distribution. A plain chest radiograph (CxR) and pulmonary function test (PFT) were performed in the same group of patients. The results showed that 6/17 (35.3%) patients had inhomogeneous distribution of radioactivity in their inhalation scans, and 11/17 (64.7%) had homogeneous scans. Five of the six patients with inhomogeneous scans were admitted for further management, and all patients with homogeneous scans were discharged from the emergency department and needed no further intensive care. The clearance rates of the right lung were 0.73%+/-0.13%/min for normal controls and 1.54%+/-0.58%/min for fire victims. The difference was significant, with a P value of less than 0.01. Using a cut-off value of 0.9%/min (all normal subjects were below 0. 9%/min), 14 (82.4%) patients had abnormal clearance rates of 99mTc-DTPA from the lung. In contrast, only three (17.6%) patients had abnormal CxR and three (17.6%) had abnormal

  15. A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration.

    PubMed

    Argenti, D; Shah, B; Heald, D

    2000-05-01

    The impending phaseout of chlorofluorocarbons as propellants in pressurized metered-dose inhalers used in the treatment of asthma has resulted in the development of alternative devices to deliver drug to the pulmonary airways. These alternative devices include metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated dry-powder inhalers. The purpose of this study was to compare the single- and multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide (Azmacort HFA 225 mcg Inhalation Aerosol) to that of the dry-powder formulation of budesonide (Pulmicort Turbuhaler 200 mcg). This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide, 600 mcg dose of budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum cortisol, 24-hour overnight serum cortisol AUC(0-24), and 24-hour urinary-free cortisol after the last evening dose of test drug. Tolerability was assessed through physical examinations, vital signs, 12-lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24-hour serum cortisol AUC(0-24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.

  16. Inhaled fluticasone in bronchiectasis: a 12 month study

    PubMed Central

    Tsang, K; Tan, K; Ho, P; Ooi, G; Ho, J; Mak, J; Tipoe, G; Ko, C; Yan, C; Lam, W; Chan-Yeung, M

    2005-01-01

    Background: The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation. Methods: After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 µg twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion. Results: 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency ⩽2/year (p = 0.04), and sputum purulence score >5 (p = 0.03). Conclusions: ICS treatment is beneficial to patients with bronchiectasis, particularly those with P aerurginosa infection. PMID:15741443

  17. Characterization of inhaled asbestos fibers in the lung of baboons

    SciTech Connect

    Murai, Y.; Hiroshima, K.; Suzuki, Y.; Goldstein, B.; Webster, I. National Center for Occupational Health, Johannesburg )

    1991-03-15

    The histopathological changes of the lungs of 7 baboons after exposure to asbestos fibers were studied, and the size distribution of the fibers was determined by electron microscopy using 25 {mu} paraffin sections and low temperature-ashing method. The size distribution of the fibers in four locations in the lung, peribronchiolar area, alveolar area, subpleural area, and interlobular connective tissue was studied. Both amosite and chrysotile induced pulmonary asbestosis and pleural thickening. Asbestosis occurred more severely in amosite-exposed animals than in chrysotile-exposed ones, and one pleural mesothelioma was found 49 months after exposure to amosite and after another 59 months of recovery in non-dusting conditions. The length, width and aspect ratios of the UICC standard sample fibers used had geometric means (G.M.) of 3.3 {mu} 0.28 {mu}, 11.8 for amosite and 1.1 {mu}, 0.12{mu}, 9.8 for chrysotile. As a whole, intrapulmonary amosite fibers were shorter than the UICC standard samples in the four baboons dusted. After 48 months exposure with or without recovery, amosite fibers found in the lungs were thinner when compared to the standard samples. For chrysotile, the length of fibers after 13 months and 26 months exposure was longer than those of standard samples of 8.5 months exposure. After inhalation, the width of the chrysotile fibers were thinner than the standard sample fibers. The size distribution of amosite fibers found in the lung and in the mesotheliomatous tissue was not significantly different.

  18. Inhaled treatment of COPD: a Delphi consensus statement

    PubMed Central

    Ninane, Vincent; Corhay, Jean-Louis; Germonpré, Paul; Janssens, Wim; Joos, Guy F; Liistro, Giuseppe; Vincken, Walter; Gurdain, Sandra; Vanvlasselaer, Evelyne; Lehouck, An

    2017-01-01

    Background Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy (2015) provides guidance for the treatment of chronic obstructive pulmonary disease (COPD) with different first-choice options per GOLD category without specification. Objectives To evaluate the level of medical experts’ consensus on their preferred first-choice treatment within different COPD categories. Methods A two-round Delphi Panel consisting of 15 questions was completed by Belgian pulmonologists (n=31) and European (n=10) COPD experts. Results Good consensus was reached by both expert groups for long-acting bronchodilators instead of short-acting bronchodilators as first-choice treatment in GOLD A. Single bronchodilation with long-acting muscarinic antagonist (LAMA) was preferred over long-acting β2-agonist (LABA) and LABA/LAMA as first-choice treatment in GOLD B and GOLD C. For GOLD D patients based on the forced expiratory volume in 1 second (FEV1)<50%, a very good consensus was reached for LAMA/LABA as first-choice treatment. For GOLD D patients based on frequent or severe exacerbations, there was a good consensus for LABA/LAMA/inhaled corticosteroids (ICS) as first choice in the Belgian group. According to the European experts, both LABA/LAMA and LABA/LAMA/ICS could be the first choice for these patients. Conclusion Belgian and European experts recommend long-acting bronchodilators as first-choice treatment. Treatment containing ICS was found only appropriate in patients with FEV1<50% and ≥2 moderate exacerbations or 1 severe exacerbation/year. PMID:28293106

  19. Endothelial Inflammatory Transcriptional Responses Induced by Plasma Following Inhalation of Diesel Emissions

    PubMed Central

    Schisler, Jonathan C.; Ronnebaum, Sarah M.; Madden, Michael; Channell, Meghan M.; Campen, Matthew J.; Willis, Monte S.

    2016-01-01

    Background Air pollution, especially emissions derived from traffic sources, is associated with adverse cardiovascular outcomes. However, it remains unclear how inhaled factors drive extrapulmonary pathology. Objectives Previously, we found that canonical inflammatory response transcripts were elevated in cultured endothelial cells treated with plasma obtained after exposure compared with pre-exposure samples or filtered air (sham) exposures. While the findings confirmed the presence of bioactive factor(s) in the plasma after diesel inhalation, we wanted to better examine the complete genomic response to investigate 1) major responsive transcripts and 2) collected response pathways and ontogeny that may help to refine this method and inform the pathogenesis. Methods We assayed endothelial RNA with gene expression microarrays, examining the responses of cultured endothelial cells to plasma obtained from 6 healthy human subjects exposed to 100 μg/m3 diesel exhaust or filtered air for 2 h on separate occasions. In addition to pre-exposure baseline samples, we investigated samples obtained immediately-post and 24h-post exposure. Results Microarray analysis of the coronary artery endothelial cells challenged with plasma identified 855 probes that changed over time following diesel exhaust exposure. Over-representation analysis identified inflammatory cytokine pathways were upregulated both at the 2 and 24 h condition. Novel pathways related to FOX transcription factors and secreted extracellular factors were also identified in the microarray analysis. Conclusions These outcomes are consistent with our recent findings that plasma contains bioactive and inflammatory factors following pollutant inhalation. The specific study design implicates a novel pathway related to inflammatory blood borne components that may drive the extrapulmonary toxicity of ambient air pollutants. PMID:25942053

  20. [Clinical utility of inhaled iloprost in pulmonary arterial hypertension].

    PubMed

    Santos-Martínez, Luis Efren; Moreno-Ruiz, Luis Antonio; Jiménez-Santos, Moisés; Olmos-Temois, Sergio Gabriel; Bojorquez-Guerrero, Luis Armando; Baranda-Tovar, Francisco Martín

    2014-01-01

    Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

  1. The happy land homicides: 87 deaths due to smoke inhalation.

    PubMed

    Gill, James R; Goldfeder, Lara B; Stajic, Marina

    2003-01-01

    We reviewed all 87 deaths from the Happy Land Social Club fire. All deaths were due to smoke inhalation. The carboxyhemoglobin (COHb) concentrations ranged from 37 to 93% with a mean of 76.5%. The vast majority (97%) of the decedents had a COHb concentration over 50%. Cyanide blood concentrations ranged from 0 to 5.5 mg/L with a mean of 2.2 mg/L. Nine decedents had no cyanide detected, and seven had cyanide concentrations of less than 1 mg/L. Fewer than one third of the decedents had thermal injuries, and most were partial thickness burns involving less than 20% body surface area. Ethanol was detected in 72% of decedents with a range of 0.01 to 0.29 g% and a mean blood concentration of 0.11 g%. Cocaine or cannabinoid use was identified in 9% of the decedents. All decedents were visually identified, and all had soot in the airway extending to the major bronchi. Carboxyhemoglobin concentrations corresponded well with deaths from smoke inhalation. Cyanide concentrations did not correspond with the extent of smoke inhalation, and the role of cyanide in contributing to these deaths is doubtful. Hydrogen chloride inhalation, as evidenced by comparison of the pH of tracheal mucosa to controls, was not a factor.

  2. Pathways of inhalation exposure to manganese in children ...

    EPA Pesticide Factsheets

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source. The purpose of this study was to use a structural equations modeling approach combined with exposure estimates derived from air-dispersion modeling to assess potential inhalation exposure pathways for children to a

  3. Inhaled Antibiotics for Gram-Negative Respiratory Infections.

    PubMed

    Wenzler, Eric; Fraidenburg, Dustin R; Scardina, Tonya; Danziger, Larry H

    2016-07-01

    Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

  4. Inhaled therapeutics for prevention and treatment of pneumonia.

    PubMed

    Safdar, Amar; Shelburne, Samuel A; Evans, Scott E; Dickey, Burton F

    2009-07-01

    The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise.

  5. Evidence for Adverse Phonatory Change Following an Inhaled Combination Treatment

    ERIC Educational Resources Information Center

    Erickson, Elizabeth; Sivasankar, Mahalakshmi

    2010-01-01

    Purpose: Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE),…

  6. Infant with Altered Consciousness after Cannabis Passive Inhalation

    ERIC Educational Resources Information Center

    Zarfin, Yehoshua; Yefet, Enav; Abozaid, Said; Nasser, Wael; Mor, Tamer; Finkelstein, Yoram

    2012-01-01

    We report on an infant who was admitted to hospital with severe neurological symptoms following passive inhalation of cannabis. To date, cannabis abuse has been described almost entirely in adolescents and adults. In early childhood, however, cannabis effects were almost exclusively discussed in the context of maternal prenatal exposure, and the…

  7. The Influence of Inhalation Injury and Pneumonia on Burn Mortality

    DTIC Science & Technology

    1987-01-01

    were treated with appli- cations of silver sulfadiazine ’ and mafenide acetate cream Tl,, olo)’o, t,- ’.sertions contained herein are the private views...Trauma 1981; 21:690-692. inhalation: cellular responses and scanning electron microscopy. 4. Fox CL Jr. Silver sulfadiazine , a new topical therapy for

  8. Inhalation of Carbon Black Nanoparticles Aggravates Pulmonary Inflammation in Mice

    PubMed Central

    Saputra, Devina; Yoon, Jin-ha; Park, Hyunju; Heo, Yongju; Yang, Hyoseon; Lee, Eun Ji; Lee, Sangjin; Song, Chang-Woo; Lee, Kyuhong

    2014-01-01

    An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-γ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be 12.5 μg/m3) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions. PMID:25071917

  9. [Acute respiratory insufficiency in burn patients from smoke inhalation].

    PubMed

    Gartner, R; Griffe, O; Captier, G; Selloumi, D; Otman, S; Brabet, M; Baro, B

    2002-03-01

    Respiratory injuries by smoke inhalation are one of the most frequent reasons for acute respiratory failure in burn victims. They are most often of chemical origin and are responsible of a 20 to 70% increase of the mortality compared to the mortality of patients with similar burn injuries, but without inhalation lesions. They are often associated to a certain degree to other factors of acute respiratory failure: superior air way obstruction by oedema in face and neck burns, thoracic expansion hindrance due to thoracic burns, lung trauma lesions by blast injury. The generalized inflammatory reaction due to the extent of burns and an initial inadequate resuscitation are worsening factors. The inflammatory process may be responsible of lung injuries similar to those induced by smoke inhalation, even when there is no inhalation. The treatment remains symptomatic and based on the oxygen therapy, mechanical ventilation, prevention of infections and maintain of homeostasis by hydroelectrolytic adequate resuscitation. The nitric oxyde associated to the almitrin allows in a certain number of cases to minimize intra pulmonary shunting and to normalize the VA/O ratio. The development of treatments allowing to modulate inflammatory mediators may lead to news therapies in the future.

  10. Essentials of an Acceptable School for Inhalation Therapy Technicians.

    ERIC Educational Resources Information Center

    American Medical Association, Chicago, IL. Council on Medical Education.

    Prepared by the Council with the cooperation of the Society of Anesthesiologists, the Society of Chest Physicians, and the American Association for Inhalation Therapy, the standards are intended for informing of physicians, hospitals, and prospective students and for the protecting of the public. Twenty-two standards are organized under the…

  11. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... where in the respiratory tract such particles may be deposited. Concentration is expressed as weight of... of being inhaled and deposited anywhere within the respiratory tract . LC 50 (median lethal... to initiating the study, animals must be monitored for known viral and bacterial...

  12. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... where in the respiratory tract such particles may be deposited. Concentration is expressed as weight of... of being inhaled and deposited anywhere within the respiratory tract . LC 50 (median lethal... to initiating the study, animals must be monitored for known viral and bacterial...

  13. INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

    EPA Science Inventory

    A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

  14. Nonrespirability of Carbon Fibers in Rats from Repeated Inhalation Exposure

    DTIC Science & Technology

    1990-09-01

    They thank Erica R. Riley, Physics Division, CRDEC, for her SEM analysis of the generated material and Dr. Lucas Brennecke, Pathology Associates, for... Ballantyne , B., and Clary, J.J., "Subchronic Inhalation Toxicology of Carbon Fibers," J., Vol. 28, pp 373-376 (1986). 15. Guide for th,’ Care and Use

  15. COMPARTMENTALIZATION OF THE INFLAMMATORY RESPONSE TO INHALED GRAIN DUST

    EPA Science Inventory


    Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

  16. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS...

  17. Inhaled corticosteroids and Aspergillus fumigatus isolation in cystic fibrosis.

    PubMed

    Noni, Maria; Katelari, Anna; Dimopoulos, George; Kourlaba, Georgia; Spoulou, Vana; Alexandrou-Athanassoulis, Helen; Doudounakis, Stavros-Eleftherios; Tzoumaka-Bakoula, Chryssa

    2014-10-01

    Aspergillus fumigatus isolation in cultures from respiratory specimens of patients with cystic fibrosis (CF) is quite common; however, the role of A. fumigatus as a pathogen and whether its presence is associated with progression of pulmonary disease remain unclear. We investigated the association between inhaled corticosteroids and the recovery of A. fumigatus by performing a retrospective cohort study of CF patients born between 1988 and 1996. The patients' medical records from their first visit to the CF Center until December 2010 were reviewed. Outcomes were the occurrence of A. fumigatus first isolation, chronic colonization, or the last visit at the CF Center. A number of possible confounders were included in the multivariate logistic regression analysis in order to identify an independent association between inhaled corticosteroids and colonization status. A total of 121 patients were included in the study. Thirty-nine patients (32.2%) had at least one positive culture and 14 (11.6%) developed chronic colonization. Multivariate logistic regression analysis was used to determine the independent effect of inhaled corticosteroids on the odds of first isolation (odds ratio [OR], 1.165; 95% confidence interval [CI], 1.015-1.337; P = 0.029) and chronic colonization (OR, 1.180; 95% CI, 1.029-1.353; P = 0.018). In conclusion, A. fumigatus first isolation and chronic colonization are associated with the duration of inhaled corticosteroid treatment.

  18. Exposure to inhalable, respirable, and ultrafine particles in welding fume.

    PubMed

    Lehnert, Martin; Pesch, Beate; Lotz, Anne; Pelzer, Johannes; Kendzia, Benjamin; Gawrych, Katarzyna; Heinze, Evelyn; Van Gelder, Rainer; Punkenburg, Ewald; Weiss, Tobias; Mattenklott, Markus; Hahn, Jens-Uwe; Möhlmann, Carsten; Berges, Markus; Hartwig, Andrea; Brüning, Thomas

    2012-07-01

    This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements inhalable fraction of the welding fume (expressed as their mass) remains challenging.

  19. Inhaled therapeutics for prevention and treatment of pneumonia

    PubMed Central

    Safdar, Amar; Shelburne, Samuel A.; Evans, Scott E.; Dickey, Burton F.

    2015-01-01

    The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise. PMID:19538104

  20. CONTROLLED, SHORT-TERM DERMAL AND INHALATION EXPOSURE TO CHLOROFORM

    EPA Science Inventory

    Studies were conducted to determine the uptake by humans of chloroform as a result of controlled short-term dermal and inhalation exposures. The approach used continuous real-time breath analysis to determine exhaled-breath profiles and evaluate chloroform kinetics in the huma...