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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. Cerebral hemodynamics in patients with moyamoya disease. A study of regional cerebral blood flow by the /sup 133/Xe inhalation method

    SciTech Connect

    Takeuchi, S.; Tanaka, R.; Ishii, R.; Tsuchida, T.; Kobayashi, K.; Arai, H.

    1985-05-01

    Regional cerebral blood flow was measured by the /sup 133/Xe inhalation method in 20 young patients with moyamoya disease and five young healthy volunteers. Most patients showed low values of mean hemispheric blood flow in both hemispheres. Regional cerebral blood flow was at a low value in the upper frontal region and at an almost average value in the posterotemporal and occipital regions, which was different from the ''hyperfrontal'' pattern in healthy volunteers. Regional cerebral blood flow was reduced evenly by hyperventilation. By 5% CO/sub 2/ inhalation, regional cerebral blood flow was increased in the temporooccipital regions and was nearly unchanged or decreased in the frontal region.

  3. [Evaluation of gamma camera collimator for regional cerebral blood flow measurements using a 133Xe inhalation method].

    PubMed

    Saegusa, K; Arimizu, N; Uematsu, S

    1984-09-01

    In the measurements of regional cerebral blood flow (rCBF) using inhalation of 133Xe gas, the activity present is generally limited in lower levels than those of usual brain scintigraphy. Measurements with low count-rate are usually resulted in diminishing the accuracies of results obtained. Therefore, it is necessary to make measurements using a high sensitive collimator for getting as much count-rate as possible when a gamma camera is used. The relationships among sensitivity and structures of multi-parallel collimator were mathematically analyzed. The results of analysis suggested that sensitivity usually increased by using a collimator with holes of reduced height and diameter. A prototype multi-parallel collimator with holes of low height and small diameter was made in our laboratory for testing sensitivity and resolution. The collimator possessing 1141 holes of 6 mm phi in hole diameter, 1.5 cm is hole height and septal thickness of 1 mm lead showed 24 times more sensitive than those of a general all purpose collimator supplied by the manufacturer. However, resolution measured in FWHM was of 9 to 14 mm at the collimator face and of 29 to 38 mm at 5 cm from the face. The results indicated that this collimator was useful enough in rCBF measurements with 133Xe inhalation using a gamma camera. The mathematical analysis however, suggested that optimum collimator for rCBF measurements was approximate 4.5 mm phi in hole diameter and 1.0 cm in hole height. PMID:6515050

  4. Cerebral blood flow studied by /sup 133/Xe 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.

  5. Intraoperative sup 133 Xe cerebral blood flow measurements by intravenous versus intracarotid methods

    SciTech Connect

    Young, W.L.; Prohovnik, I.; Schroeder, T.; Correll, J.W.; Ostapkovich, N. )

    1990-10-01

    To document the comparability of cerebral blood flow (CBF) values determined by quantification of 133Xe washout after either intravenous or intracarotid administration, 12 patients undergoing elective carotid endarterectomy anesthetized with N2O/O2 and either isoflurane or halothane were studied. Scintillation counters were placed over the middle cerebral artery territory ipsilateral to the operated carotid artery. CBF was measured by the intravenous method during dissection of the carotid sheath and was calculated as the initial slope index from head washout curves collected for 11 min after injection of 10-20 mCi 133Xe in saline into a large vein. Immediately prior to carotid occlusion, CBF was determined by direct injection of 1 mCi 133Xe in saline into either the internal carotid artery or the common carotid artery with the external carotid artery occluded. For the intracarotid injections, the initial slope was calculated from the 1st min of washout. Data were analyzed by linear regression and analysis of variance. Values are expressed as mean +/- SD. The mean CBF for intravenous and intracarotid methods were both 29 +/- 10 ml.100 g-1.min-1. The correlation between CBF measured by intravenous and intracarotid methods was excellent and was described by the line y = x + 0.6, r = 0.92. We conclude that in the flow range studied, the intravenous technique may be applied to measure CBF in physiologically stable situations in which direct intracarotid injection is not feasible.

  6. 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.

  7. 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.

  8. A method for estimating (41)Ar, (85)(,88)Kr and (131m,133)Xe doses to non-human biota.

    PubMed

    Vives I Batlle, J; Jones, S R; Copplestone, D

    2015-06-01

    A method is presented for estimating (41)Ar, (85,88)Kr and (131m,133)Xe dose rates to terrestrial wildlife without having to resort to comparisons with analogue radionuclides. The approach can be used to calculate the dose rates arising from external exposures to given ambient air concentrations of these isotopes. Dose conversion coefficient (DCC) values for a range of representative organisms are calculated, using a Monte Carlo approach to generate absorbed fractions based on representing animals as reference ellipsoid geometries. Plume immersion is the main component of the total DCC. DCC values calculated for a human-sized organism are compared with human dose conversion factors from ICRP Publication 119, demonstrating the consistency of the biota approach with that for humans. An example of application is provided for hypothetical nuclear power plant atmospheric discharges with associated exposures to birds and insects. In this example, the dose rates appear to be dominated by (133)Xe and (88)Kr, respectively. The biota considered would be protected from the effects of noble gas radiation from a population protection perspective.

  9. A method for estimating (41)Ar, (85)(,88)Kr and (131m,133)Xe doses to non-human biota.

    PubMed

    Vives I Batlle, J; Jones, S R; Copplestone, D

    2015-06-01

    A method is presented for estimating (41)Ar, (85,88)Kr and (131m,133)Xe dose rates to terrestrial wildlife without having to resort to comparisons with analogue radionuclides. The approach can be used to calculate the dose rates arising from external exposures to given ambient air concentrations of these isotopes. Dose conversion coefficient (DCC) values for a range of representative organisms are calculated, using a Monte Carlo approach to generate absorbed fractions based on representing animals as reference ellipsoid geometries. Plume immersion is the main component of the total DCC. DCC values calculated for a human-sized organism are compared with human dose conversion factors from ICRP Publication 119, demonstrating the consistency of the biota approach with that for humans. An example of application is provided for hypothetical nuclear power plant atmospheric discharges with associated exposures to birds and insects. In this example, the dose rates appear to be dominated by (133)Xe and (88)Kr, respectively. The biota considered would be protected from the effects of noble gas radiation from a population protection perspective. PMID:25863225

  10. Evaluation of 133Xe radiation exposure dosimetry for workers in nuclear medicine laboratories.

    PubMed

    Piltingsrud, H V; Gels, G L

    1982-06-01

    Evaluation of past studies of 133Xe dosimetry and nuclear medicine laboratory air concentrations of 133Xe indicates that significant levels of 133Xe may exist in routine operational environments of a nuclear medicine laboratory. This leads to the question of whether present health physics radiation control methods are adequate to keep occupational personnel exposures within acceptable levels. It would appear that if personnel dosimeters (film and TLD badges) respond properly to the radiation of 133Xe, normal health physics control procedures are probably adequate. If they do not respond adequately, personnel exposures may exceed recommended levels and special instrumentation or administrative procedures are called for. Therefore, the first step in studying potential problems in the subject area is to evaluate the response of a variety of personnel radiation dosimeters to 133Xe. This paper describes the methods and materials used to expose personnel dosimeters to known amounts of 133Xe radiations in an exposure chamber constructed at the BRH Nuclear Medicine Laboratory. Also presented are calculated values for Dose Equivalents (D.E.) in a phantom from external radiation resulting from immersion in clouds having a constant concentration of 133Xe but varying cloud radii. This implies the relative importance of the beta and the X + gamma radiation responses of the personnel dosimeters under various exposure conditions. Results of this study indicate that none of the dosimeter systems evaluated provide adequate performance for use as a primary indicator of the D.E. resulting from 133Xe radiations for a worker in a nuclear medicine laboratory, and that personnel dosimetry considerations in 133Xe-containing atmospheres are very dependent on the radii of the 133Xe clouds.

  11. Response of Panasonic dosimeters to submersion exposure by 133Xe.

    PubMed

    Hoffman, J M; Catchen, G L

    1990-01-01

    The dose response to 133Xe radiation of several types of Panasonic 800 series thermoluminescent dosimeters (TLD) were evaluated. The dosimeters were exposed by submersion in 133Xe gas. The relative sensitivities of the lithium borate and the calcium sulfate phosphors were determined for several configurations. The TLDs were exposed in the holders (as the devices came from the vendor) with various shields covering the elements, and they were exposed with the TLDs removed from the holders. Some dosimeters were exposed, both in holders and out of holders (TL insert only configuration), both in plastic bags and free in air. For the in-holder configuration, the responses of the heavily shielded (greater than 170 mg cm-2) elements were used to obtain the photon dose-rate component, and the responses of the lightly shielded (less than 13 mg cm-2) element were used to obtain the beta component. Similarly, for the insert-only configurations, the observed over-response of the calcium sulfate phosphors to low-energy photons could be used to separate the beta dose rate component. By using the calculated beta doses, correction factors were determined for the apparent under-responses of the elements to beta radiation. The results of both methods are consistent. These results also suggest that the beta component could be used in environmental monitoring as a more sensitive means to determine 133Xe activities in clouds and to separate some of the effects of submersion exposure from those of distant exposure.

  12. Evaluation of 133Xe and 133Xe(m) decay data.

    PubMed

    Galán, M

    2009-01-01

    This paper presents the decay data evaluation of (133)Xe and (133)Xe(m), which includes the most recent available data, such as half-life results and gamma-ray intensities that have not been considered in previous evaluations. The adopted internal conversion coefficients (ICC) have been calculated using the 'Frozen Orbital' approximation and are compared here to recent measured values. Recent Q-value tabulations, recommended gamma-ray energies for calibrations, as well as new evaluated gamma-ray intensities for the 81- and 233-keV lines (37.0 (3)% and 10.16 (13)%, respectively) are also presented in this evaluation. Atomic radiation emission probabilities (X-ray and Auger electron) associated with nuclear radiations have been deduced and also included in this work. PMID:18805017

  13. Response of Panasonic dosimeters to submersion exposure by sup 133 Xe

    SciTech Connect

    Hoffman, J.M.; Catchen, G.L. )

    1990-01-01

    The dose response to {sup 133}Xe radiation of several types of Panasonic 800 series thermoluminescent dosimeters (TLD) were evaluated. The dosimeters were exposed by submersion in {sup 133}Xe gas. The relative sensitivities of the lithium borate and the calcium sulfate phosphors were determined for several configurations. The TLDs were exposed in the holders (as the devices came from the vendor) with various shields covering the elements, and they were exposed with the TLDs removed from the holders. Some dosimeters were exposed, both in holders and out of holders (TL insert only configuration), both in plastic bags and free in air. For the in-holder configuration, the responses of the heavily shielded (greater than 170 mg cm-2) elements were used to obtain the photon dose-rate component, and the responses of the lightly shielded (less than 13 mg cm-2) element were used to obtain the beta component. Similarly, for the insert-only configurations, the observed over-response of the calcium sulfate phosphors to low-energy photons could be used to separate the beta dose rate component. By using the calculated beta doses, correction factors were determined for the apparent under-responses of the elements to beta radiation. The results of both methods are consistent. These results also suggest that the beta component could be used in environmental monitoring as a more sensitive means to determine {sup 133}Xe activities in clouds and to separate some of the effects of submersion exposure from those of distant exposure.

  14. Dose dependence of the production yield of endohedral 133Xe-fullerene by ion implantation

    NASA Astrophysics Data System (ADS)

    Watanabe, S.; Ishioka, N. S.; Shimomura, H.; Muramatsu, H.; Sekine, T.

    2003-05-01

    The production yield of endohedral 133Xe-fullerene by ion implantation has been studied by taking advantage of the radioactivity of 133Xe. Fullerene targets, which were produced by vacuum evaporation of C 60 or C 70 on a Ni backing, were bombarded with 30-38 keV 133Xe ions by using an isotope separator at doses ranging from 1 × 10 12 to 1 × 10 14 cm -2. The production yield of endohedral 133Xe-fullerene was determined by an high performance liquid chromatography analysis following the dissolution of the targets in o-dichlorobenzene. It was found that the production yield decreased with increasing dose and incident energy, and the production yield of 133Xe@C 70 was higher than that of 133Xe@C 60 for the same dose and incident energy. Those production yields are discussed in connection with amorphization of fullerene molecules in collisions with 133Xe ions.

  15. A semiconductor silicon PIN diode matrix detector for measurement of 133Xe washout in small regional skin areas.

    PubMed

    Jensen, J H; Sørensen, J L; Hauge, E N; Sejrsen, P; Bojsen, J

    1993-05-01

    Local variations in microvascularization are expected in lesions and lesion-free skin of patients with pressure sores. To investigate these variations, methods for studies of the regional blood flow rate within small skin areas are needed. Regional blood flow can be estimated by measuring the washout of 133Xe from the tissue. This study describes a 2 x 12 Si PIN diode matrix detector capable of 133Xe detection, and equipped with a collimator to improve the spatial resolution. Thus the regional blood flow in subcutaneous skin areas down to about 2 cm2 can be investigated when the atraumatic epicutaneous labelling technique is used. The capability of the matrix detector and its collimator is described by laboratory investigations. In pilot investigations three normal subjects and three paraplegics with pressure sores were studied. In each individual study the detector matrix was divided into six square areas containing four diode detectors each. Thus six 133Xe disappearance rate constants from adjacent subcutaneous tissue could be determined simultaneously. PMID:8334415

  16. 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.

  17. 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. PMID:24607612

  18. 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.

  19. Vertebrobasilar insufficiency revealed by xenon-133 inhalation SPECT

    SciTech Connect

    Delecluse, F.; Voordecker, P.; Raftopoulos, C.

    1989-07-01

    A study of cerebral and cerebellar blood flow reactivity to acetazolamide by xenon-133-inhalation single photon emission computed tomography (/sup 133/Xe SPECT) was carried out in a patient with bouts of transient basilar ischemia, whose neurological examination, computed tomographic scan, and auditory evoked potentials were normal. Though the patient was symptom-free at the time of the study, /sup 133/Xe SPECT demonstrated vertebrobasilar insufficiency by showing an impaired vasodilatory response in both the occipital lobes and the right cerebellar hemisphere. Three weeks later, the patient suffered an extensive stroke in these same areas. We therefore suggest that this method could be of great value in the assessment of vertebrobasilar insufficiency.

  20. Studies on 133Xe wash-out from human skin: quantitative measurements of blood flow in normal and corticosteroid-treated skin.

    PubMed

    Kristensen, J K; Wadskov, S

    1977-04-01

    Blood flow was measured by the 133Xe technique in normal and corticosteroid-treated skin. Epicutaneous and intracutaneous methods of tracer application were compared in normal skin. The two labeling methods were equally suitable for measuring cutaneous blood flow provided calculations in both cases were based on a biexponential resolution of the wash-out curve in its cutaneous and subcutaneous components and provided the traumatic hyperemia phase was considered, when intracutaneous application of the tracer was used. Results were invalidated if calculations were based on initial slope of the wash-out curves.Topical application of beta-methasone valerate in a reduction in cutaneous blood flow as measured by the intracutaneous technique with curve resolution, whereas no effect could be demonstrated when calculations were based on the initial slopes of the curves. The 133Xe technique is a simple and reliable method for measuring cutaneous blood flow, which might prove useful in estimations of penetration ability and potency of topical corticosteroids.

  1. 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.

  2. Measured absorbed dose rates from semi-infinite hemispherical volumes of 133Xe.

    PubMed

    Munyon, W J; Barber, D E; Howley, J R

    1986-07-01

    Surface absorbed dose rates from different hemispheric volumes of 133Xe have been measured directly with an extrapolation chamber. The results indicate that a linear relationship exists between the radius of the cloud volume and the surface absorbed dose rate for radii between 0 and 23 cm. If cloud volumes with radii larger than 23 cm are taken to be infinite with respect to the range of the charged particles emitted, the absorbed dose rate calculated based on that assumption will be within the uncertainty of any measurement of absorbed dose rate that might be made. For hemispheric volumes having radii less than or equal to 23 cm, the surface absorbed dose rate in tissue-equivalent material, in mGy h-1, is approximated (+/- 20%) by the product of [1.30 mGy h-1 cm-1 kBq-1 cm3] X [cloud radius, cm] X [cloud activity concentration, kBq cm-3].

  3. 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.

  4. 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.

  5. 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.

  6. Concentration Independent Calibration of β-γ Coincidence Detector Using 131mXe and 133Xe

    SciTech Connect

    McIntyre, Justin I.; Cooper, Matthew W.; Carman, April J.; Bowyer, Ted W.; Day, Anthony R.; Haas, Derek A.; Hayes, James C.; Heimbigner, Tom R.; Hubbard, Charles W.; Litke, Kevin E.; Ripplinger, Michael D.; Schrom, Brian T.; Suarez, Reynold

    2009-12-01

    Absolute efficiency calibration of radiometric detectors is frequently difficult and requires careful detector modeling and accurate knowledge of the radioactive source used. In the past we have calibrated the b-g coincidence detector of the Automated Radioxenon Sampler/Analyzer (ARSA) using a variety of sources and techniques which have proven to be less than desirable.[1] A superior technique has been developed that uses the conversion-electron (CE) and x-ray coincidence of 131mXe to provide a more accurate absolute gamma efficiency of the detector. The 131mXe is injected directly into the beta cell of the coincident counting system and no knowledge of absolute source strength is required. In addition, 133Xe is used to provide a second independent means to obtain the absolute efficiency calibration. These two data points provide the necessary information for calculating the detector efficiency and can be used in conjunction with other noble gas isotopes to completely characterize and calibrate the ARSA nuclear detector. In this paper we discuss the techniques and results that we have obtained.

  7. Sources of variability of resting cerebral blood flow in healthy subjects: a study using 133Xe SPECT measurements

    PubMed Central

    Henriksen, Otto M; Kruuse, Christina; Olesen, Jes; Jensen, Lars T; Larsson, Henrik B W; Birk, Steffen; Hansen, Jakob M; Wienecke, Troels; Rostrup, Egill

    2013-01-01

    Measurements of cerebral blood flow (CBF) show large variability among healthy subjects. The aim of the present study was to investigate the relative effect of established factors influencing CBF on the variability of resting CBF. We retrospectively analyzed spontaneous variability in 430 CBF measurements acquired in 152 healthy, young subjects using 133Xe single-photon emission computed tomography. Cerebral blood flow was correlated positively with both end-tidal expiratory PCO2 (PETCO2) and female gender and inversely with hematocrit (Hct). Between- and within-subject CO2 reactivity was not significantly different. Including PETCO2, Hct and gender in the model reduced between-subject and within-subject variance by 14% and 13.5%, respectively. Within-subject variability was mainly influenced by PETCO2 and between-subject variability mostly by Hct, whereas gender appeared to be of little added value when Hct was also accounted for. The present study confirms large between-subject variability in CBF measurements and that gender, Hct, and PETCO2 explain only a small part of this variability. This implies that a large fraction of CBF variability may be due to unknown factors such as differences in neuron density or metabolism that could be subject for further studies. PMID:23403374

  8. Adsorption and desorption of noble gases on activated charcoal: I. 133Xe studies in a monolayer and packed bed.

    PubMed

    Scarpitta, S C; Harley, N H

    1990-10-01

    Detailed desorption studies using petroleum-based activated charcoals were conducted in monolayers and packed beds. Less extensive studies were conducted on several other types of charcoal. Kinetic studies, using 133Xe, demonstrated the existence of a micropore volume with entrance capillaries that together determined the response characteristics of charcoal to external concentration gradients of tracer gases. This new two-phase model, composed of micropores and entrance capillaries, describes the desorption dynamics of an adsorbed gas in the presence of water vapor. Condensed water vapor in the entrance capillaries of the charcoal reduced the effective pore radius and increased the diffusion half-time. Water could also adversely affect the integrating capability of the charcoal dramatically if the adsorbed water completely blocked the entrance capillaries. The amount of adsorbed water required to block the capillaries varied with the charcoal type and was termed here as the "break-point." The desorption parameters measured in this work can be used to design an improved passive Rn monitor to effectively integrate during a 3-7 d exposure period by eliminating the adverse effects of water vapor. The improved canister design would provide more accurate and reproducible measurements of indoor Rn concentrations than are currently available. PMID:2398007

  9. /sup 133/Xe blood flow monitoring during arteriovenous malformation resection: a case of intraoperative hyperperfusion with subsequent brain swelling

    SciTech Connect

    Young, W.L.; Solomon, R.A.; Prohovnik, I.; Ornstein, E.; Weinstein, J.; Stein, B.M.

    1988-04-01

    Measurement of regional cerebral blood flow (rCBF) using the i.v. 133Xe technique was carried out during resection of a right temporooccipital arteriovenous malformation (AVM) with ipsilateral middle and posterior cerebral arterial supply. Intraoperatively, a rCBF detector was in place over the right frontotemporal area, about 5 to 6 cm from the border of the AVM. Anesthesia was 0.75% isoflurane in oxygen and nitrous oxide. After dural exposure, the rCBF was 27 ml/100 g/min at a pCO2 of 29 mm Hg and a mean arterial pressure (MAP) of 90 mm Hg. The pCO2 was then elevated to 40 mm Hg, and the rCBF was increased to 55 ml/100 g/min at a MAP of 83 mm Hg. After AVM removal, the rCBF rose to 50 ml/100 g/min at a pCO2 of 27 mm Hg and a MAP of 75 mm Hg. The pCO2 was elevated to 33 mm Hg and the rCBF increased to 86 ml/100 g/min at a MAP of 97 mm Hg. During skin closure, the rCBF was 94 ml/100 g/min at a pCO2 of 26 mm Hg and a MAP of 97 mm Hg. The patient was neurologically normal postoperatively except for a mild, new visual field defect. After 2 to 3 days, the patient gradually developed lethargy, confusion, and nausea with relatively normal blood pressure. An angiogram revealed residual enlargement of the posterior cerebral artery feeding vessel. Computed tomography showed edema extending from the area of AVM resection as far as the frontal region, producing a significant midline shift anteriorly. Intraoperative rCBF monitoring revealed significant hyperperfusion after AVM resection, which was associated with signs and symptoms of the normal perfusion pressure breakthrough syndrome.

  10. 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.

  11. 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. PMID:3710789

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

    SciTech Connect

    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 /sup 133/Xe 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 /sup 133/Xe. 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.

  13. Inhalation exposure systems: design, methods and operation.

    PubMed

    Wong, Brian A

    2007-01-01

    The respiratory system, the major route for entry of oxygen into the body, provides entry for external compounds, including pharmaceutic and toxic materials. These compounds (that might be inhaled under environmental, occupational, medical, or other situations) can be administered under controlled conditions during laboratory inhalation studies. Inhalation study results may be controlled or adversely affected by variability in four key factors: animal environment; exposure atmosphere; inhaled dose; and individual animal biological response. Three of these four factors can be managed through engineering processes. Variability in the animal environment is reduced by engineering control of temperature, humidity, oxygen content, waste gas content, and noise in the exposure facility. Exposure atmospheres are monitored and adjusted to assure a consistent and known exposure for each animal dose group. The inhaled dose, affected by changes in respiration physiology, may be controlled by exposure-specific monitoring of respiration. Selection of techniques and methods for the three factors affected by engineering allows the toxicologic pathologist to study the reproducibility of the fourth factor, the biological response of the animal. PMID:17325967

  14. 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 ...

  15. 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 ...

  16. 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

  17. Inhalants

    MedlinePlus

    ... or LSD. But you may not realize the dangers of substances in your own home. Household products such as glues, hair sprays, paints and lighter fluid can be drugs for kids in search of a quick high. Many young people ... need to know the dangers. Even inhaling once can disrupt heart rhythms and ...

  18. 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.

  19. Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.

    PubMed Central

    Hindle, M.; Chrystyn, H.

    1994-01-01

    BACKGROUND--Inhalation aids do not require coordination between actuation of a metered dose inhaler (MDI) with inspiration and reduce oropharyngeal impaction. The delivery of salbutamol to the lung and systemic availability following inhalation with three commonly used spacers and an open mouth technique have been evaluated using a simple noninvasive technique based on urinary excretion 30 minutes and 24 hours after the dose. METHODS--Ten healthy subjects inhaled, on randomised study days, 4 x 100 micrograms from a Ventolin MDI and, subsequently, with the aid of a Volumatic, Bricanyl Spacer, and Nebuhaler spacer device. In addition, an open mouth inhaler technique was evaluated. Urine samples were collected 0-30 minutes and 0.5-24 hours after inhalation. From these samples the relative bioavailability to the lung (urinary salbutamol excretion 30 minutes after dosing) and the systemic bioavailability of the dose (24 hour urinary excretion of salbutamol and its metabolite) for each inhalation method was obtained. RESULTS--The mean (SD) urinary excretion of salbutamol 30 minutes after inhalation using the MDI alone and with the Volumatic, Bricanyl Spacer, Nebuhaler, and open mouth technique was 2.83 (0.78)%, 3.37 (0.69)%, 4.09 (0.91)%, 4.34 (1.60)%, and 3.49 (0.98)%, respectively, expressed as a percentage of the nominal dose. The nebuhaler and Bricanyl Spacer spacer devices were found to increase the relative bioavailability of salbutamol to the lung compared with the MDI alone. Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of the urinary excretion method. In 11 individuals who each repeated the same inhalation procedure on four separate occasions, the mean (SD) coefficient of variation was 8.24 (2.36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26.6 (6.79), 27.0 (7.95), and 55.6 (9.74)% of the salbutamol dose for the Volumatic, Nebuhaler, and MDI, respectively. Similar

  20. Inhalation toxicology methods: the generation and characterization of exposure atmospheres and inhalational exposures.

    PubMed

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this unit, 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 are outlined. The following methods are described: (1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; (2) the 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, a description beyond exposures to single agents and simple mixtures is presented, and included are methods for evaluating biological responses to complex environmental mixtures. It is also emphasized 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

  1. 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

  2. Two administration methods for inhaled salbutamol in intubated patients

    PubMed Central

    Garner, S; Wiest, D; Bradley, J; Habib, D

    2002-01-01

    Aims: To compare serum concentrations and effects on respiratory mechanics and haemodynamics of salbutamol administered by small volume nebuliser (SVN) and metered dose inhaler (MDI) plus spacer. Methods: Blinded, randomised, crossover study in 12 intubated infants and children (mean age 17.8 months) receiving inhaled salbutamol therapy. Subjects received salbutamol as 0.15 mg/kg by SVN and four puffs (400 µg) by MDI plus spacer at a four hour interval in random order. Passive respiratory mechanics were measured by a single breath/single occlusion technique, and serum salbutamol concentrations by liquid chromatography–mass spectrometry at 30 minutes, 1, 2, and 4 hours after each dose. Haemodynamics (heart rate and blood pressure) were recorded at each measurement time. Results: There was no difference in percentage change in respiratory mechanics or haemodynamics between the two methods of administration. Mean area under the curve (AUC0–4) was 5.86 for MDI plus spacer versus 4.93 ng/ml x h for SVN. Conclusions: Serum concentrations and effects on respiratory mechanics and haemodynamics of salbutamol were comparable with the two administration methods under the conditions studied. Future studies are needed to determine the most effective and safe combination of dose and administration method of inhaled salbutamol in mechanically ventilated infants and children. PMID:12089124

  3. An Analysis of Inhalation Injury Diagnostic Methods and Patient Outcomes.

    PubMed

    Ching, Jessica A; Ching, Yiu-Hei; Shivers, Steven C; Karlnoski, Rachel A; Payne, Wyatt G; Smith, David J

    2016-01-01

    The purpose of this study was to compare patient outcomes according to the method of diagnosing burn inhalation injury. After approval from the American Burn Association, the National Burn Repository Dataset Version 8.0 was queried for patients with a diagnosis of burn inhalation injury. Subgroups were analyzed by diagnostic method as defined by the National Burn Repository. All diagnostic methods listed for each patient were included, comparing mortality, hospital days, intensive care unit (ICU) days, and ventilator days (VDs). Z-tests, t-tests, and linear regression were used with a statistical significance of P value of less than .05. The database query yielded 9775 patients diagnosed with inhalation injury. The greatest increase in mortality was associated with diagnosis by bronchoscopy or carbon monoxide poisoning. A relative increase in hospital days was noted with diagnosis by bronchoscopy (9 days) or history (2 days). A relative increase in ICU days was associated with diagnosis according to bronchoscopy (8 days), clinical findings (2 days), or history (2 days). A relative increase in VDs was associated with diagnosis by bronchoscopy (6 days) or carbon monoxide poisoning (3 days). The combination of diagnosis by bronchoscopy and clinical findings increased the relative difference across all comparison measures. The combination of diagnosis by bronchoscopy and carbon monoxide poisoning exhibited decreased relative differences when compared with bronchoscopy alone. Diagnosis by laryngoscopy showed no mortality or association with poor outcomes. Bronchoscopic evidence of inhalation injury proved most useful, predicting increased mortality, hospital, ICU, and VDs. A combined diagnosis determined by clinical findings and bronchoscopy should be considered for clinical practice. PMID:26594867

  4. Adhesion forces in interactive mixtures for dry powder inhalers--evaluation of a new measuring method.

    PubMed

    Lohrmann, Maike; Kappl, Michael; Butt, Hans-Juergen; Urbanetz, Nora Anne; Lippold, Bernhard Christian

    2007-09-01

    Dry powder inhalers mostly contain carrier based formulations where micronized drug particles are adhered to coarse carrier particles. The performance of the dry powder inhaler depends on the inhaler device, the inhalation manoeuvre and the formulation. The most important factor influencing the behaviour of the formulation is the adhesion force acting between the active ingredient and the carrier particles, which can be measured using different methods, for example the centrifuge technique or atomic force microscopy. In this study the tensile strength method, usually applied to determine cohesion forces between powder particles of one material, is optimized for adhesion force measurements between powder particles of unlike materials. Adhesion force measurements between the carrier materials lactose or mannitol and the drug substance salbutamol sulphate using the tensile strength method and the atomic force microscopy show higher values with increasing relative humidity. Consequently, the fine particle fraction determined using the Next Generation Impactor decreases with increasing relative humidity as a result of the enhanced interparticle interactions.

  5. A Kr-81m inhalation method for detection of absence of uniform ventilation in asthma

    SciTech Connect

    Kawakami, K.; Katsuyama, N.; Fukuda, Y.; Mori, Y.; Shimada, T.; Iikura, Y.

    1981-10-01

    In an attempt to compare inhalation methods in detecting abnormal patterns of ventilation, the following four techniques were applied in 12 asthmatic patients: spontaneous respiration with a Kr-81m gas-air mixture (SP technique); serial inhalation of a Kr-81m gas-air mixture from the level of residual volume to total lung capacity (VC technique); bolus inhalation of 10 ml or Kr-81m gas from the level of residual volume, followed by air, to total lung capacity (RV technique); bolus inhalation of 10 ml of Kr-81m gas from the level of functional residual capacity, followed by air, to total lung capacity (FRC technique). Before exercise, abnormalities were detected by the RV and FRC techniques, but no abnormalities were detected by SP and VC techniques. On studies done after exercise, the abnormalities were detected by all the described techniques. However, they were best demonstrated by the RV technique and shown least well by the VC method.

  6. 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

  7. 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.

  8. Development and application of quantitative methods for monitoring dermal and inhalation exposure to propiconazole.

    PubMed

    Flack, Sheila; Goktepe, Ipek; Ball, Louise M; Nylander-French, Leena A

    2008-03-01

    Quantitative methods to measure dermal and inhalation exposure to the fungicide propiconazole were developed in the laboratory and applied in the occupational exposure setting for monitoring five farm workers' exposure during pesticide preparation and application to peach crops. Dermal exposure was measured with tape-strips applied to the skin, and the amount of propiconazole was normalized to keratin content in the tape-strip. Inhalation exposure was measured with an OVS tube placed in the worker's breathing-zone during pesticide handling. Samples were analyzed by GC-MS in EI+ mode (limit of detection 6 pg microl(-1)). Dermal exposure ranged from non-detectable to 32.1 +/- 22.6 ng per microg keratin while breathing-zone concentrations varied from 0.2 to 2.2 microg m(-3). A positive correlation was observed between breathing-zone concentrations and ambient air temperature (r2 = 0.87, p < 0.01). Breathing-zone concentrations did not correlate with dermal exposure levels (r2 = 0.11, p = 0.52). Propiconazole levels were below limit of detection when rubber gloves, coveralls, and full-face mask were used. The total-body propiconazole dose, determined for each worker by summing the estimated dermal dose and inhalation dose, ranged from 0.01 to 12 microg per kg body weight per day. Our results show that tape-stripping of the skin and the OVS can be effectively utilized to measure dermal and inhalation exposure to propiconazole, respectively, and that the dermal route of exposure contributed substantially more to the total dose than the inhalation route.

  9. A Review of Methods for Evaluating Particle Stability in Suspension Based Pressurized Metered Dose Inhalers.

    PubMed

    D'Sa, Dexter; Chan, Hak-Kim

    2015-01-01

    Advances in particle engineering techniques, such as spray drying, freeze drying and supercritical fluid precipitation, have greatly enhanced the ability to control the structure, morphology, and solid state phase of inhalable sized particles (1 - 5 µm) for formulation in pressurized metered dose inhalers (pMDI). To optimize the properties of these engineered particles for formulation in hydrofluoroalkane propellants (HFA 134a / 227) it is necessary to measure both bulk and individual particle properties before, after, and during formulation. This review examines established and recently developed methods for evaluating a variety of particle properties including but not limited to size, surface and internal morphology, chemical composition, and solid state phase. Novel methods for evaluating particle physical and chemical stability directly in propellant or similar environments are also discussed.

  10. 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.

  11. Correlation of clinical and angiographic findings in brain ischemia with regional cerebral blood flow measured by the xenon inhalation technique

    SciTech Connect

    Awad, I.; Little, J.R.; Furlan, A.J.; Weinstein, M.

    1982-07-01

    Eighty-eight patients with brain ischemia underwent cerebral angiography and measurement of regional cerebral blood flow (rCBF) after /sup 133/Xe inhalation. A fast compartment flow rate and an initial slope index were computed for each detector and for each hemisphere. The clinical presentation, angiographic findings, and rCBF results were then examined for significant correlations. Patients with hemispheric infarction most frequently showed bilateral diffusely decreased rCBF. In patients with transient ischemic attacks, no specific pattern emerged. Patients with unilateral internal carotid artery occlusion frequently hd bilateral diffusely decreased rCBF. Patients with severe internal carotid artery stenosis were more likely to show decreased rCBF than were patients with mild or moderate stenosis. The initial slope index seemed to be a more sensitive indicator of brain ischemia than the fast compartment flow rate. The possible pathophysiological significance and relationship to patient management of the various rCBF patterns are discussed.

  12. 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.

  13. An in vitro method for predicting inhalation toxicity of impregnation spray products.

    PubMed

    Sørli, Jorid B; Hansen, Jitka S; Nørgaard, Asger W; Levin, Marcus; Larsen, Søren T

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases are reported frequently. The toxicity appears to be driven by a disruption of the pulmonary surfactant film, which coats the inside of the lungs. Due to the complex chemistry of impregnation spray products, it is impossible to predict if inhalation of an aerosolized product is toxic in vivo. The aim of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film-forming compounds, were identified by mass spectrometry. We used a capillary surfactometry method to assess disruption of pulmonary surfactant function in vitro and a mouse model to evaluate acute respiratory toxicity during inhalation. Concentration-response relationships were successfully determined both in vitro and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing.

  14. An in vitro method for predicting inhalation toxicity of impregnation spray products.

    PubMed

    Sørli, Jorid B; Hansen, Jitka S; Nørgaard, Asger W; Levin, Marcus; Larsen, Søren T

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases are reported frequently. The toxicity appears to be driven by a disruption of the pulmonary surfactant film, which coats the inside of the lungs. Due to the complex chemistry of impregnation spray products, it is impossible to predict if inhalation of an aerosolized product is toxic in vivo. The aim of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film-forming compounds, were identified by mass spectrometry. We used a capillary surfactometry method to assess disruption of pulmonary surfactant function in vitro and a mouse model to evaluate acute respiratory toxicity during inhalation. Concentration-response relationships were successfully determined both in vitro and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing. PMID:25651757

  15. The hydrogen gas clearance method for liver blood flow examination: inhalation or local application of hydrogen?

    PubMed

    Metzger, H P

    1989-01-01

    The combined method of hydrogen inhalation and local hydrogen production enable the determination of hepatic blood flow (HBF) and local hepatic blood flow (LHBF). LHBF was registered within a small superficial tissue volume of 0.5 mm in diameter by means of a multi-wire electrode having 200 microns producing and 100 microns measuring wires arranged within less than 300 microns distance between the measuring wires. The feeding current for hydrogen production was 1 microA, the potential less than 10 V. The clearance in response to inhalation was registered by means of the same measuring electrodes within the same tissue volume. Spontaneously breathing rats (Wistar-Frömter strain, 180-230 g bw, N = 19, ketamin-xylazine anesthesia, artificial respiration) showed the following flow values: HBF +/- SD = 0.50 +/- 0.26 ml/g.min, n = 48 registrations; LHBF +/- SD = 4.66 +/- 2.13 ml/g.min, n = 43. The validity of the combined method is demonstrated in the LHBF/HBF graph which summarizes the data of hemorrhagic and control animals, m = 0.1 and yo = 0.001. The correlation coefficient of r = 0.685 shows a reasonable correlation of the combined data despite the wide scattering of the individual values.

  16. Method for chronic nose-only exposures of laboratory animals to inhaled fibrous aerosols

    SciTech Connect

    Smith, D.M.; Ortiz, L.W.; Archuleta, R.F.; Spalding, J.F.; Ettinger, H.J.; Thomas, R.G.

    1980-01-01

    A study is currently being conducted to determine any biological effects when rats and hamsters inhale man-made mineral fibers (MMMFs). The MMMF's to be tested include glass fibers, mineral wool, and ceramic fibers, with crocidolite asbestos serving as a positive control aerosol material. A prime objective of this study is to expose animals to high airborne concentrations of long thin fibers. Animal exposures are currently being conducted with a 0.45 ..mu..m mean diameter glass microfiber material and the standard UICC crocidolite. A specialized method of restraining rats and hamsters for inhalation exposure was developed providing for aerosol exposure only to the nose and a small fraction of the animal's head. This method eliminates external contamination and prevents animals from burying their noses in their fur to filter out aerosolized particles. Stainless steel chambers have been modified by placing two metal insert panels in place of doors, each containing 45 insert ports for Syrian hamsters or 32 for rats. Animals are loaded into tapered polycarbonate holding tubes and the tubes placed in the panel inserts for exposure. Body weights, rectal temperatures, clinical chemistry profiles, complete blood counts, and plasma corticosterone levels clearly indicate that this technique does not produce measurable stress in the animals.

  17. How to Use Metered-Dose Inhalers

    MedlinePlus

    ... methods really work, and people who use these methods may continue to use their inhalers after the inhalers are empty.Some inhalers come with a counter that shows the number of sprays that remain in the inhaler. If your inhaler ...

  18. 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

  19. Regional cerebral blood flow in schizophrenics. Tests using the xenon Xe 133 inhalation method

    SciTech Connect

    Ariel, R.N.; Golden, C.J.; Berg, R.A.; Quaife, M.A.; Dirksen, J.W.; Forsell, T.; Wilson, J.; Graber, B.

    1983-03-01

    Measurements of intrahemispheric and bilateral regional cerebral blood flow (CBF) for gray and white matter were compared in 29 schizophrenic patients and 22 normal controls, using the xenon Xe 133 inhalation method. Results showed significantly lower CBF values for all brain regions in the schizophrenic group, and post hoc comparisons showed relatively greater reduced gray-matter CBF values in the anterior areas of the brain. There was also a left-hemisphere frontal loss similar to that reported previously, although it was in the context of a generalized loss in anterior functioning. Interhemispheric comparison within both groups showed no differences between homologous regions for gray matter, and greater white-matter CBF values in the right hemisphere than in the left hemisphere. The findings support a hypothesis of a bilateral anterior deficit in schizophrenia.

  20. 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

  1. 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 ...

  2. [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.

  3. 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.

  4. [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. PMID:23755557

  5. Inhalational anthrax.

    PubMed

    Cuneo, Brian M

    2004-03-01

    Anthrax remains a real threat. In a spore form, it is highly infectious and dispersible. The initial symptoms are similar to those of influenza, and the early stage of inhalational anthrax may not be recognized. Early antibiotic treatment is important to achieving a good outcome. Contrary to historical experience. many patients with even advanced anthrax can be saved with aggressive medical care. Prevention of anthrax infections requires vigilant infection control methods as well as a rational prophylactic plan. All health care providers should be familiar with the symptoms and treatment of this disease. It is hoped that future research will clarify tests for early diagnosis, the best methods of prophylaxis, and the most effective treatments. Unfortunately the threat of bioterrorism, and anthrax in particular, is unlikely to go away. PMID:15062228

  6. Inhalant Abuse

    MedlinePlus

    ... risk of being hurt in a fall, a fire or a car crash (for example, if your child tries to drive while he or she is high on an inhalant). Inhalants block oxygen flow to the brain and every other organ ...

  7. 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

  8. Treatment effect of the method of Tai Chi exercise in combination with inhalation of air negative oxygen ions on hyperlipidemia

    PubMed Central

    Ma, Ming; Song, Qing-Hua; Xu, Rong-Mei; Zhang, Quan-Hai; Shen, Guo-Qing; Guo, Yan-Hua; Wang, Yi

    2014-01-01

    Objective: To observe the improvement effect of the treatment method of Tai Chi exercise in combination with inhalation of the air negative oxygen ions on the blood lipid indicator of the patient suffering from the hyperlipidemia. Methods: 56 patients, who are diagnosed with hyperlipidemia, are the study objects and divided into an observation group and a control group by the random number method. Each group consists of 28 patients. The patients in the control group do Tai Chi exercise for about 60 min once a day; the patients in the observation group, in addition to Tai Chi exercise, are treated by inhalation of the air negative oxygen ions. Before the treatment and after 6 months’ treatment, respectively test and compare body fat content, blood lipid, blood rheology and psychological adaptation as well as other indicators for these two groups of patients. Results: In comparison with the ordinary materials of the patients in two groups before the treatment, it shows no significant difference, P>0.05; after they are respectively treated for 6 months, it is found that the testing indicators of the patients in two groups are improved to some extent, but those of the observation group are better. Compared with the improvement effect of the control group, the difference has statistical significance, P<0.05. Conclusion: Tai Chi Exercise can improve the blood lipid indicator of the patient suffering from hyperlipidemia to some extent, however, the treatment method, in combination with inhalation of air negative oxygen ion, can obtain better effect than that of single Tai Chi exercise. Tip: the environment of the exercise plays an important intervention role in the treatment effect. PMID:25232426

  9. [Oxidative stress in pathogenesis of bronchial asthma: a method of correction by inhalation of phospholipid nanoparticles].

    PubMed

    Lisitsa, A V; Soodaeva, S K; Klimanov, I A; Aver'ianov, A V

    2014-01-01

    The authors present the results of a prospective simple blind randomized placebo-controlled study for the evaluation of dynamics of biomarkers of oxidative stress (total concentration of nitrate- and nitrite-anions in condensed exhaled breath and plasma, pH of exhaled breath, total antioxidative activity of plasma in patients with bronchial asthma inhaling phospholipid nanoparticles. The results suggest significant positive effect of proposed therapy on dynamics of the main parameters of oxidative stress including reduced concentration of nitric oxide metabolites and increased total antioxidative activity of plasma. No clinically significant reactions were documented.

  10. Convenient methods for ingestion of molecular hydrogen: drinking, injection, and inhalation.

    PubMed

    Kurokawa, Ryosuke; Seo, Tomoki; Sato, Bunpei; Hirano, Shin-Ichi; Sato, Fumitake

    2015-01-01

    Molecular hydrogen (H2) is clinically administered; however, in some hospitals, H2 is given to patients without consideration of its safe use. In the present study, we prepared convenient and safe devices for the drinking of super-saturated H2 water, for intravenous drip infusion of H2-rich saline, and for the inhalation of H2 gas. In order to provide useful information for researchers using these devices, the changes in H2 concentration were studied. Our experimental results should contribute to the advance of non-clinical and clinical research in H2 medicine. PMID:26504515

  11. Asthma Inhalers

    MedlinePlus

    ... reduce the release of chlorofluorocarbons (CFCs) into the atmosphere when taking certain asthma medications. Until recently, most ... hydrofluoroalkane (HFA) inhalers, that do not rob the atmosphere of ozone. “The FDA [Food and Drug Administration] ...

  12. Indacaterol Oral Inhalation

    MedlinePlus

    ... as a powder-filled capsule to inhale by mouth using a special inhaler. It is usually inhaled ... stop the pieces of capsule from reaching your mouth as you inhale the medication. Very tiny pieces ...

  13. Inhaled Asthma Medications

    MedlinePlus

    ... metered – dose inhaler (MDI), which uses a chemical propellant to push the medication out of the inhaler. ... powder inhalers (DPIs) deliver medication without using chemical propellants, but they require a strong and fast inhalation. ...

  14. 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.

  15. 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.

  16. 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

    2015-01-01

    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.

  17. Inhaled Corticosteroids

    PubMed Central

    Barnes, Peter J.

    2010-01-01

    Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness and control asthma symptoms. ICS are now first-line therapy for all patients with persistent asthma, controlling asthma symptoms and preventing exacerbations. Inhaled long-acting β2-agonists added to ICS further improve asthma control and are commonly given as combination inhalers, which improve compliance and control asthma at lower doses of corticosteroids. By contrast, ICS provide much less clinical benefit in COPD and the inflammation is resistant to the action of corticosteroids. This appears to be due to a reduction in HDAC2 activity and expression as a result of oxidative stress. ICS are added to bronchodilators in patients with severe COPD to reduce exacerbations. ICS, which are absorbed from the lungs into the systemic circulation, have negligible systemic side effects at the doses most patients require, although the high doses used in COPD has some systemic side effects and increases the risk of developing pneumonia.

  18. Stability indicating HPTLC method for determination of terbutaline sulfate in bulk and from submicronized dry powder inhalers.

    PubMed

    Faiyazuddin, Md; Ahmad, Sayeed; Iqbal, Zeenat; Talegaonkar, Sushma; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Khar, Roop Krishen

    2010-01-01

    A stability-indicating high-performance thin-layer chromatographic (HPTLC) method has been developed for the determination of terbutaline sulfate (TBS) as a bulk drug and in pharmaceutical formulations (submicronized dry powder inhalers). The separation was achieved on TLC aluminum plates precoated with silica gel 60F-254 using chloroform-methanol (9.0:1.0 v/v) as mobile phase. The densitometric analysis was carried out at 366 nm wavelength. Compact spots appeared at R(f) = 0.34 +/- 0.02. For the proposed procedure, linearity (r(2) = 0.9956 +/- 0.0015), limit of quantification (28.35 ng spot(-1)), limit of detection (9.41 ng spot(-1)), recovery (97.06-99.56%), and precision (< or = 1.86) were found to be satisfactory. TBS was subjected to acid and alkali hydrolyses, oxidation and photodegradation treatments. The degraded products were well separated from the pure drug. Statistical analysis reveals that the developed method has potential for routine analysis and stability testing of terbutaline sulfate in pharmaceutical drug delivery systems.

  19. 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.

  20. 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.

  1. Methods Used to Calculate Doses Resulting from Inhalation of Capstone Depleted Uranium Aerosols

    SciTech Connect

    Miller, Guthrie; Cheng, Yung-Sung; Traub, Richard J.; Little, Thomas T.; Guilmette, Ray A.

    2009-02-26

    The methods used to calculate radiological and toxicological doses to hypothetical persons inside either a United States Army Abrams tank or Bradley Fighting Vehicle that has been perforated by depleted uranium munitions is 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 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.

  2. The head dome: A simplified method for human exposures to inhaled air pollutants

    SciTech Connect

    Bowes, S.M. III; Frank, R.; Swift, D.L. )

    1990-05-01

    Acute controlled exposures of human subjects to air pollutants are customarily carried out with whole-body chambers, masks, or mouthpieces. The use of these methods may be limited by cost or technical considerations. To permit a study involving a highly unstable pollutant, artificial acid fog, administered to subjects during natural breathing, a head-only exposure chamber, called a head dome, was developed. It consists of a transparent cylinder with a neck seal which fits over the subject's head and rests lightly on his shoulders. The head dome does not constrain the upper airways or impede exercise on a bicycle ergometer. Ventilation can be monitored accurately and unobtrusively with a pneumotachograph at the exhaust port of the dome. A thermocouple may be used to monitor the onset and persistence of oronasal breathing. For short-term exposures to unstable or reactive pollutants lasting up to several hours, the head dome is an effective alternative to a whole-body chamber and probably superior to a face mask or mouthpiece.

  3. Clinically relevant test methods to establish in vitro equivalence for spacers and valved holding chambers used with pressurized metered dose inhalers (pMDIs).

    PubMed

    Mitchell, Jolyon; Dolovich, Myrna B

    2012-08-01

    Regulatory guidance in Canada and Europe recommends that the manufacturer of an inhaled drug product delivered by pressurized metered-dose inhaler (pMDI) identify a spacer (S) or valved holding chamber (VHC) to be used with their designated product. It therefore becomes necessary to include the S/VHC in the process of establishing bioequivalence (BE) to the reference pMDI product for both new-entry generic and subsequent market entry products (SMEPs). S/VHCs substantially modify the aerodynamic particle size distribution (APSD) of the inhaled medication, and potentially the spatial distribution of the mass of active pharmaceutical ingredient(s) [API(s)] depositing in the respiratory tract. The processes whereby S/VHCs can influence BE outcomes are examined, and the inadequacy of compendial in vitro methods to provide pertinent information to assess BE for the pMDI+VHC combination is highlighted. A three-part strategy is proposed whereby in vitro testing for BE can simulate more clinically-relevant conditions than in the current compendial procedures: 1. The inclusion of a short delay between inhaler actuation and sampling onset is appropriate when determining APSD at flow rate(s) suitable for the intended patient population; 2. Assessment of total emitted mass ex S/VHC by simulating tidal breathing pattern(s) appropriate for intended use; 3. Incorporation of appropriate face model(s), representative of the intended patient age range(s), into test procedures for S/VHCs with facemask, enabling clinically-appropriate dead space and fit-to-face to be simulated. Although the compendial authorities have been slow to recognize the need for such in vitro testing, a Canadian standard provides direction for implementing most proposals, which should result in better performance predictions and more appropriate clinical outcomes, highlighting similarities and differences between reference and test products.

  4. Recognition and prevention of inhalant abuse.

    PubMed

    Anderson, Carrie E; Loomis, Glenn A

    2003-09-01

    Inhalant abuse is a prevalent and often overlooked form of substance abuse in adolescents. Survey results consistently show that nearly 20 percent of children in middle school and high school have experimented with inhaled substances. The method of delivery is inhalation of a solvent from its container, a soaked rag, or a bag. Solvents include almost any household cleaning agent or propellant, paint thinner, glue, and lighter fluid. Inhalant abuse typically can cause a euphoric feeling and can become addictive. Acute effects include sudden sniffing death syndrome, asphyxia, and serious injuries (e.g., falls, burns, frostbite). Chronic inhalant abuse can damage cardiac, renal, hepatic, and neurologic systems. Inhalant abuse during pregnancy can cause fetal abnormalities. Diagnosis of inhalant abuse is difficult and relies almost entirely on a thorough history and a high index of suspicion. No specific laboratory tests confirm solvent inhalation. Treatment is generally supportive, because there are no reversal agents for inhalant intoxication. Education of young persons and their parents is essential to decrease experimentation with inhalants. PMID:13678134

  5. 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

  6. A method for repeated evaluation of benzene uptake in rats and mice during a six hour inhalation period.

    PubMed

    Eutermoser, M; Rusch, G M; Kuna, R A; O'Grodnick, J; Rinehart, W E

    1986-01-01

    Benzene uptake measurements and respiratory minute volume (RMV) were assessed in rats and mice during a 6-hour inhalation exposure to 300 ppm (v/v) of benzene vapor. The values for benzene uptake and RMV were used to compare predictions of inhaled dose in both species. The theoretical prediction assumed an unchanging RMV. The next prediction allowed adjustments for changes in RMV during exposure. The final prediction addressed benzene uptake directly. The uptake characteristics of benzene in both species were different from the theoretical prediction, from the prediction adjusted for changing RMV and from each other. The greatest difference was seen in rats where the observed benzene dose was only 28% of the theoretical value. The experiment was not designed to elucidate the causes for the difference between the predictions, nor was the data sufficient to suggest whether the rat or the mouse was a suitable model of benzene uptake in humans.

  7. Mometasone Oral Inhalation

    MedlinePlus

    ... or she watches.The dose counter on the base of your mometasone inhaler tells you how many ... Hold the inhaler straight up with the colored base on the bottom. Twist the white cap counterclockwise ...

  8. Budesonide Oral Inhalation

    MedlinePlus

    ... 6 years of age and older. Budesonide suspension (liquid) for oral inhalation (Pulmicort Respules) is used in ... of inhalations even if it still contains some liquid and continues to release a spray when it ...

  9. 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

  10. Beclomethasone Oral Inhalation

    MedlinePlus

    ... with water and spit. Do not swallow the water. Keep the inhaler clean and dry with the cover tightly in place ... all times. To clean your inhaler, use a clean, dry tissue or cloth. Do not wash or put any part of your inhaler in water.

  11. Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol--I. Introduction, experimental design, and aerosol generation methods.

    PubMed

    Ulrich, C E; Rinehart, W; Busey, W

    1979-03-01

    A brief literature review on manganese toxicity is presented; as related to designing a chronic inhalation study for evaluating methylcyclopentadienyl manganese tricarbonyl when utilized as a motor fuel additive. The experimental design of this study is described. The generation system utilized to simulate the manganese aerosol produced by an internal combustion engine is described in detail. This generation system operated twenty-four hours per day, seven days per week producing aerosols at 11.6, 112.5, and 1152 micrograms Mn/m3 with an aerodynamic diameter of approximately 0.11 micron.

  12. Urine excretion of inhaled technetium-99m-DTPA: an alternative method to assess lung epithelial transport.

    PubMed

    Köhn, H; König, B; Klech, H; Pohl, W; Mostbeck, A

    1990-04-01

    Technetium-99m DTPA clearance (99mTc-DTPA) clearance measured by a gamma camera or a scintillation probe not only reflects epithelial transport, but is also influenced by an unknown amount of mucociliary clearance depending on particle size and aerosol deposition. This is confirmed by factor analysis of dynamic inhalation studies. Assessment of epithelial absorption by urinary excretion of inhaled 99mTc-DTPA is largely independent of aerosol lung deposition. Twenty-four-hour excretion reflects the amount of aerosol cleared by absorption, while two-hour excretion is a quantitative measure of the aerosol absorption rate from the epithelium into blood. Urinary 99mTc-DTPA excretion of two aerosols with different particle size correlated significantly (p less than 0.001) with analysis of lung clearance curves. A very similar regression in the form of a cumulative exponential function was found with both aerosols. Two-hour urine values of nonsmokers differed significantly from those of smokers or patients with active interstitial or infectious lung disease. This alternative procedure is suited as a bedside test and holds promise for patient monitoring and follow-up.

  13. 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…

  14. 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

  15. Emitted dose and lung deposition of inhaled terbutaline from Turbuhaler at different conditions.

    PubMed

    Abdelrahim, Mohamed E

    2010-05-01

    Turbuhaler has a very high resistance hence patient inhalation flow when using it would be low. The total emitted dose (TED) of 500microg terbutaline sulphate from a Bricanyl Turbuhaler was determined using a range of inhalation flows (10-60L min(-1)) with inhalation volume of 2 and 4L using a DPI sampling apparatus after one and two inhalations. The relative lung and systemic bioavailability of terbutaline from Bricanyl Turbuhaler when used by healthy subjects and COPD patients were determined after one and two inhalations at slow and fast inhalation flows using a novel urinary terbutaline pharmacokinetic method. The TED resulted from the one and two inhalations increased significantly (p<0.05) with the increase of the inhalation flow at both 2 and 4L inhalation volumes. The relative lung and systemic bioavailability after one inhalation at fast inhalation flow were significantly higher (p<0.01) than at slow inhalation flow in both healthy subjects and patients. Also the healthy subjects results were significantly higher (p<0.05) than the COPD patients after one inhalation. However after two inhalations there was no significant difference between slow and fast inhalation flow or healthy subjects and COPD patients. Hence it is essential to inhale twice and as deep and hard as possible from each dose of Turbuhaler for patients with low inspiratory flow and limited inhalation volume as they may not receive much benefit from one inhalation. PMID:20004090

  16. [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). PMID:26683076

  17. 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. PMID:27338970

  18. Insulin inhalation: NN 1998.

    PubMed

    2004-01-01

    insulin administered once or twice daily. In 2003, the US FDA adopted new GMP guidelines requiring sterile production of inhalation products and their devices. Novo Nordisk, therefore, will need to repeat phase III studies following device optimisation. These studies may begin at the end of 2004 and will include efficacy studies for 6-12 months and safety studies for up to 2 years (Lehman Brothers, Equity research, 7 August 2003). A phase IIb, 12-week clinical trial in 107 patients with type 2 diabetes was completed in the US. This trial was designed to compare the safety and efficacy of pulmonary insulin delivered via AERx iDMS, with intensified treatment with subcutaneous insulin administered at mealtimes. The results of the study positively compared pulmonary insulin with intensified subcutaneous insulin. Aradigm Corporation has a total of 85 patents pertaining to its proprietary AERx drug delivery system. Among those granted patents, 18 patents cover pulmonary insulin formulation including the method of patient breathing technique during pulmonary delivery of insulin. This patent guides patients on how to breathe in certain defined ways to achieve an effective amount and reproducibility of blood levels of insulin.

  19. 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...

  20. SDAT – Analysis of 131mXe with 133Xe Interference

    SciTech Connect

    Biegalski, Steven R.; Foltz Biegalski, Kendra M.; Haas, Derek A.

    2009-12-01

    The Spectral Deconvolution Analysis Tool (SDAT) software was developed at The University of Texas at Austin. SDAT utilizes a standard spectrum technique for the analysis of beta-gamma coincidence spectra. Testing was performed on the software to compare the standard spectrum analysis technique with a region of interest (ROI) analysis technique. Experimentally produced standard spectra and sample data were produced at the Nuclear Engineering Teaching Laboratory (NETL) TRIGA reactor. The results of the testing showed that the standard spectrum technique had lower errors than the ROI analysis technique for samples with low counting statistics. In contrast, the ROI analysis technique outperformed the standard spectrum technique in high counting statistics samples. It was also shown that the standard spectrum technique benefitted from a compression of the number of channels within the spectra.

  1. 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

  2. Inhalant Abuse and Dependence Among Adolescents in the United States

    PubMed Central

    WU, LI-TZY; PILOWSKY, DANIEL J.; SCHLENGER, WILLIAM E.

    2005-01-01

    Objective To examine the patterns of inhalant use and correlates of the progression from inhalant use to abuse and dependence among adolescents aged 12 to 17. Method Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Multinominal logistic regression was used to identify the characteristics associated with progression to inhalant abuse and dependence. Results Inhalant use was common among the studied adolescents. Among adolescents aged 12 to 17, 0.4% met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors. Conclusions Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youths with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school–age children. PMID:15381887

  3. Inhaled drug delivery in the hands of the patient.

    PubMed

    Lavorini, Federico

    2014-12-01

    Asthma and chronic obstructive pulmonary disease (COPD) are both diseases with an increasing prevalence worldwide. Inhaled therapy for these conditions has a number of advantages over systemic therapy, but requires the patients to use, and to master the use of, an inhaler device. However, many patients cannot use inhalers correctly, and over 50% of patients struggle to use a metered-dose inhaler properly. Poor inhaler technique is associated with a reduced asthma control, worst COPD outcomes, and wastage of economic resources. Of perhaps more concern is the fact that many health professionals also do not know how to use inhalers correctly and are therefore not in a position to coach patients effectively. Training patients and caregivers in the correct inhaler preparation and use is an essential component in the process toward achieving reliable and repeatable medication delivery. Instructions should be inhaler-specific, and they include instruction on how to load or prime the device. Providing only the leaflet that comes with the medicines does not lead to adequate inhalation technique, not even immediately after the patient has read the instructions and practiced with the inhaler. One-on-one sessions with health-care professionals probably represent the most effective educational method. However, it appears that, by itself, even repeated instruction could be insufficient to achieve improved adherence in the long term, as there is a tendency for patients or caregivers to forget what they have learned as time elapses since the training event. Thus, despite the development of several new and improved types of inhaler device, the evidence currently available points to little or no progress having been made with patients' ability to use their inhalers. As the range of drugs delivered by inhalation increases, inhaler technique checks and training need to be an integral part of the routine management of any patient with either asthma or COPD. PMID:25238005

  4. 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.

  5. Levalbuterol Oral Inhalation

    MedlinePlus

    ... inhaler or nebulizer. Ask your doctor, pharmacist, or respiratory therapist to show you how to use it. ... propranolol (Inderal); digoxin (Digitek, Lanoxin); diuretics ('water pills'); epinephrine (Epipen, Primatene Mist); medications for colds; and other ...

  6. Albuterol Oral Inhalation

    MedlinePlus

    ... on the bottom and the inhaler pointing upwards, load the dose by opening the protective dust cap ... or face mask. Connect the nebulizer to the compressor. Place the mouthpiece in your mouth or put ...

  7. Substance use - inhalants

    MedlinePlus

    ... it has been sprayed or put into a paper or plastic bag Ballooning. Inhaling a gas from ... empty soda cans, empty perfume bottles, and toilet paper tubes stuffed with rags or toilet paper soaked ...

  8. Formoterol Oral Inhalation

    MedlinePlus

    ... shortness of breath, and breathing difficulties caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema) in adults. Formoterol inhalation powder ...

  9. Olodaterol Oral Inhalation

    MedlinePlus

    ... of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, which includes chronic bronchitis and emphysema). Olodaterol oral inhalation is in ...

  10. Umeclidinium Oral Inhalation

    MedlinePlus

    ... of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, that includes chronic bronchitis and emphysema). Umeclidinium inhalation is in a ...

  11. Cromolyn Oral Inhalation

    MedlinePlus

    ... difficulties (bronchospasm) caused by exercise, cold and dry air, or by inhaling substances such as pet dander, ... of substances that cause inflammation (swelling) in the air passages of the lungs.

  12. Fluticasone Oral Inhalation

    MedlinePlus

    ... you are near an open flame or a heat source. The inhaler may explode if it is ... Nizoral); clarithromycin (Biaxin); HIV protease inhibitors such as atazanavir (Reyataz, in Evotaz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir ( ...

  13. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

  14. Overview of inhalation toxicology.

    PubMed Central

    Dorato, M A

    1990-01-01

    The development of inhalation toxicology as a distinct discipline can be traced back well over one hundred years. The technology has advanced in terms of materials and designs used to construct inhalation chambers and the equipment used to generate controlled test atmospheres of a wide variety of gases, vapors, dusts, and droplets. Consideration of metered dose inhalers, a relatively recent concern, has led to the design of new equipment for administering this unique dosage form. The parameters used to evaluate inhalation toxicity are similar to those used for any other route of administration. In addition, there are some unique procedures for early screening of pulmonary toxicity, especially within a series of related chemicals. Images FIGURE 1. FIGURE 3. FIGURE 7. FIGURE 8. PMID:2200660

  15. Correlations between regional cerebral blood flow and age-related brain atrophy: a quantitative study with computed tomography and the xenon-133 inhalation method

    SciTech Connect

    Yamaguchi, T.; Hatazawa, J.; Kubota, K.; Abe, Y.; Fujiwara, T.; Matsuzawa, T.

    1983-07-01

    One hundred and two subjects (40 men and 62 women) neither having a history of neurologic deficits nor showing organic lesions on computed tomographic examination of the brain were studied. Ages of the subjects ranged from 26 to 81 years. Regional cerebral blood flow was measured by the xenon-133 inhalation method, and the volume percentage of brain with respect to the cranial cavity (craniocerebral index) was calculated by means of computer programs. Regional cerebral blood flow was computed as the fast component of two-compartmental analysis and as the initial slope index value. The percentage of each subject's craniocerebral index in relation to the standard for subjects with non-atrophied brains (brain volume index) was calculated as the indicator of brain atrophy. Both the mean brain fast component values and the mean brain initial slope index values correlated closely with the brain volume index in the elderly. Low cerebral blood flow values coincided with loss of brain substance in the final stage of age-related brain atrophy, but not in the intermediate stage.

  16. 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.

  17. 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. PMID:26552516

  18. [Prognosis of inhalation-related injuries in accidental release of ammonium and chlorine by the method of dynamic concentration].

    PubMed

    Litvinov, N N; Kazachkov, V I; Grigorevskaia, Z P; Tsygankov, S S; Iagund, G K; Bodanskiĭ, M D; Ivanov, A Iu; Shmelev, K V

    2000-01-01

    The article deals with new approaches to evaluate casualty effect of accidental chemical release exemplified by common and dangerous industrial chemicals ammonium and chlorine. Dynamic concentration method considers effects of high concentrations inducing instant reflex cardiac and respiratory arrest as well as lesions caused by variable toxic doses. PMID:11019541

  19. Development of a Microemulsion High Performance Liquid Chromatography (MELC) Method for Determination of Salbutamol in Metered-Dose Inhalers (MDIS)

    PubMed Central

    Althanyan, MS; Clark, BJ; Hanaee, J; Assi, KH

    2013-01-01

    Introduction A sensitive and rapid oil-in-water (O/W) microemulsion high performance liquid chromatography (MELC) method has been developed. The water-in-oil (w/o) microemulsion was used as a mobile phase in the determination of salbutamol in aqueous solutions. In addition, the influence of operating parameters on the separation performance was examined. Methods The samples were injected into C18, (250mm×4.6mm) analytical columns maintained at 25oC with a flow rate 1 ml/min. The mobile phase was 95.5% v/v aqueous orthophosphate buffer 20 mM (adjusted to pH 3 with orthophosphoric acid), 0.5% ethyl acetate, 1.5% Brij35, and 2.5% 1-butanol, all w/w. The salbutamol and internal standard peaks were detected by fluorescence detection at the excitation and emission wavelengths of 267 and 313 nm respectively. Results The method had an accuracy of > 97.78% and the calibration curve was linear (r2 = 0.99) over salbutamol concentrations ranging from 25 to 500 ng/mL. The intra-day and inter-day precisions (CV %) were <1.6 and <1.8, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) were 9.61ng/ml and 29.13ng/ml, respectively. Conclusion The method reported is simple, precise and accurate, and has the capacity to be used for determination of salbutamol in the pharmaceutical preparation. PMID:23678468

  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. 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

  2. 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

  3. 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

  4. [Inhalational or intravenous anesthesia?].

    PubMed

    Dahan, A; Aarts, L P H J

    2016-01-01

    The debate continues whether there is a difference in patient outcome following inhalational versus intravenous anesthesia. A recent meta-analysis showed improved outcome following inhalational anesthesia in patients undergoing cardiac surgery but not in patients undergoing non-cardiac procedures. In this article we discuss the meta-analysis and its caveats, taking into account additional comparative studies. Our overall conclusion is that it is too early to definitively claim that one anesthesia technique results in a better outcome than the other. PMID:27650024

  5. 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.

  6. 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...

  7. 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

  8. Liposomal formulations for inhalation.

    PubMed

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478

  9. 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 about the…

  10. 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

  11. Vapor Inhalation of Alcohol in Rats

    PubMed Central

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

    2008-01-01

    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. PMID:18634001

  12. Toxicological Assessment of Noxious Inhalants

    PubMed Central

    Kleinsasser, N. H.; Sassen, A. W.; Wallner, B. W.; Staudenmaier, R.; Harréus, U. A.; Richter, E.

    2004-01-01

    In the past centuries mankind has been exposed to various forms of air pollution not only at his occupational but also in his social environment. He mainly gets exposed with these pollutants through the respiratory organs and partially absorbs them into the body. Many of these airborne substances can be harmful for humans and some of them may account for tumorigenic effects. The following essay describes the main features of toxicological assessment of inhalative environmental and workplace xenobiotics. The essay also explains relevant characteristics and limit values of noxious compounds and gases and depicts modern testing methods. To this end, emphasis is given on methods characterizing the different stages of tumorigenic processes. Various test systems have been developed which can be used in vivo, ex vivo or in vitro. They are to a great part based on the evidence of changes in DNA or particular genes of cells. Among others they have highlighted the impact of interindividual variability on enzymatic activation of xenobiotics and on susceptibility of the host to tumor diseases. Unfortunately, for many inhalative environmental noxious agents no sufficient risk profiles have been developed. The completion of these profiles should be the goal of toxicological assessment in order to allow reasonable socioeconomic or individual-based risk reduction. PMID:22073045

  13. Delivery of beclomethasone dipropionate from a spacer device: what dose is available for inhalation?

    PubMed Central

    O'Callaghan, C.; Cant, M.; Robertson, C.

    1994-01-01

    BACKGROUND--It is common for inhaled steroids to be delivered through a large volume spacer device. Comparatively little is known about how this practice affects the dose of drug received by patients compared with drug delivered directly from a metered dose inhaler. METHODS--The amount of beclomethasone dipropionate, contained in particles of various size, available for inhalation from a 750 ml polycarbonate spacer (Volumatic) was determined by impinger measurement and high performance liquid chromatography. Three strengths of metered dose inhalers were studied (50 micrograms, 100 micrograms, and 250 micrograms/actuation). The effect of multiple actuations of beclomethasone dipropionate into a Volumatic spacer, and increasing residence times of drug within the spacer before inhalation, on the amount of drug available to the patient for inhalation was determined. RESULTS--The amount of beclomethasone dipropionate in particles < 5 microns when delivered by a spacer device or directly from a metered dose inhaler was similar. The total amount of beclomethasone dipropionate available for inhalation per actuation decreased by 20 micrograms with the 50 micrograms inhaler, 48 micrograms with the 100 micrograms inhaler, and 161 micrograms with the 250 micrograms inhaler, when given via the spacer compared with delivery directly from a metered dose inhaler. There was a progressive decrease in drug available for inhalation per actuation as the number of actuations into the spacer increased, for all strengths of beclomethasone dipropionate tested. A progressive decrease in drug recovered per actuation was also seen with increasing residence times of drug within the spacer before inhalation. CONCLUSIONS--Use of the spacer device significantly reduced the amount of nonrespirable beclomethasone dipropionate available for inhalation. The amount of beclomethasone dipropionate within respirable particles decreased considerably following multiple actuations into the spacer and with

  14. 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.

  15. 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.

  16. Insulin inhalation--Pfizer/Nektar Therapeutics: HMR 4006, inhaled PEG-insulin--Nektar, PEGylated insulin--Nektar.

    PubMed

    2004-01-01

    type 1 and type 2 diabetes mellitus in 120 centres worldwide, and will use a fourth prototype inhaler device that is half the size of the first prototype, and has reduced manufacturing costs. Pfizer and its partner, Aventis Pharma, are conducting additional long-term pulmonary safety data studies in patients with type 1 and type 2 diabetes. Pfizer is also conducting phase III clinical trials with inhaled insulin in paediatric patients aged 6-17 years. Nektar Therapeutics is using its Advanced PEGylation technology to develop a dry powder-inhaled polyethylene glycol (PEG) formulation for delivering peptides efficiently across the lungs and to promote prolonged serum concentration of the peptide. PEG is a neutral, water-soluble, nontoxic polymer comprising any number of repeating units of ethylene oxide. PEGylation is designed to increase the size of the active molecule and ultimately improve drug performance by optimising pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. The investigation has begun with inhaled, long-acting (PEGylated) insulin [inhaled PEG-insulin, PEGylated insulin--Nektar], and is funded by Pfizer. Preclinical results of a dry powder formulation of inhaled PEG-insulin presented at the 63rd Scientific Sessions of the American Diabetes Association (ADA-2003) [June 2003, New Orleans, LA, USA] demonstrated prolonged systemic activity of insulin in dogs. Nektar Therapeutics was granted US patent 5,997,848 on a method for delivering inhalable insulin. The patent covers a method for delivering of 0.5-15 mg of aerosol dry powder insulin per dosing session in 1-4 individual dosages into the deep lung for systemic absorption. The patent does not specify the formulation of insulin or aerosol delivery device. Nektar Therapeutics estimated in June 2002 that Exubera could earn the company potential revenues of >200 million US dollars. PMID:15139780

  17. About Steroids (Inhaled and Oral Corticosteroids)

    MedlinePlus

    ... dose-inhalers ( inhaled steroids ), oral forms (pills or syrups) , injections (shots) and intravenous (IV) solutions. Healthcare providers ... slowly decreased. Inhaled steroids and steroid pills and syrups are often prescribed for people with a chronic ...

  18. Parent's Guide to Preventing Inhalant Abuse

    MedlinePlus

    ... conditioning coolants. How can you tell if a young person is an inhalant abuser? If someone is ... youths involved with inhalant abuse. How does a young person who abuses inhalants die? There are many ...

  19. Asymptomatic inhaled foreign body

    PubMed Central

    Salim, Muhammad U.; Asghar, Asif; Tareen, Irum; Azhar, Muhammad

    2016-01-01

    It is very rare to have a big foreign body in the lungs without any complications or symptoms for 2 years. A 14-year-old male with episodes of minor hemoptysis for 4 weeks had a history of inhalation of a bullet 2 years earlier. He had asymptomatic for lung complications for 2 years. The bullet was removed by right thoracotomy and non-anatomical wedge stapled resection, and he followed an uneventful recovery. An aspirated foreign body although big can remain asymptomatic for a long time, especially if it has migrated to the periphery. PMID:27652366

  20. Posterior subcapsular cataract and inhaled corticosteroid therapy.

    PubMed Central

    Abuekteish, F.; Kirkpatrick, J. N.; Russell, G.

    1995-01-01

    BACKGROUND--Although posterior subcapsular cataract complicates both systemic and topical corticosteroid therapy, the literature on the effects of inhaled corticosteroids is conflicting. METHODS--One hundred and forty children and young adults on inhaled corticosteroids were examined by slit lamp ophthalmoscopy after pupillary dilatation; 103 had received one or more short courses (< or = 7 days) of oral corticosteroids in the management of acute asthmatic attacks and four had also received one or more prolonged courses (> or = 4 weeks) of alternate day oral corticosteroid therapy. RESULTS--Bilateral posterior subcapsular cataract was identified in one girl who had received several prolonged courses of oral corticosteroids, but was not identified in any other patient. CONCLUSIONS--There is no evidence to support the contention that inhaled corticosteroid therapy on its own, or in association with short courses of oral corticosteroid therapy, might cause cataracts. Although children receiving long term systemic corticosteroid therapy should be screened for cataracts, this is unnecessary in children on inhaled corticosteroids alone. PMID:7638813

  1. Behavioral changes in mice following benzene inhalation.

    PubMed

    Evans, H L; Dempster, A M; Snyder, C A

    1981-01-01

    Although benzene is an important occupational health hazard and a carcinogen, the possibility that behavioral changes may forewarn of the later-occurring hematological changes has not been investigated. A time-sampling protocol was used to quantify the occurrence of 7 categories of behavior in the homecage following daily 6-hr exposures to two strains of adult mice (CD1 and C57BL/6J). The behavioral categories were stereotypic behavior, sleeping, resting, eating, grooming, locomotion, and fighting. The inhalation exposures were designed to reflect occupational exposure. Dynamic vapor exposure techniques in standard inhalation chambers were employed. Exposure to 300 or 900 ppm benzene increased the occurrence of eating and grooming and reduced the number of mice that were sleeping or resting. The responses to benzene of both the CD1 and the C57 strains were similar. The positive findings with benzene inhalation indicate the utility of behavioral investigations into the toxicology of inhaled organic solvents. The methods described herein illustrate an objective observation of animal behavior that is capable of documenting toxicity and of guiding detailed follow-up studies aimed at mechanism of action.

  2. 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.

  3. Inter-professional education unveiling significant association between asthma knowledge and inhaler technique

    PubMed Central

    Basheti, Iman A.; Hamadi, Salim A.; Reddel, Helen K.

    2015-01-01

    Objectives: To explore whether an association exists between health care professionals’ (HCPs) asthma knowledge and inhaler technique demonstration skills. Methods: HCPs’ asthma knowledge and inhaler technique demonstration skills were assessed at baseline at an inter-professional educational workshop focusing on asthma medication use. Asthma knowledge was assessed via a published questionnaire. Correct inhaler technique for the three inhalers, the Accuhaler, Turbuhaler and pressurized Metered Dose Inhaler (pMDI) was assessed using published checklists. Results: Two hundred HCPs agreed to participate: 10 specialists (medical doctors specialized in respiratory diseases) (5%), 46 general practitioners (23%), 79 pharmacists (39%), 15 pharmacists’ assistants (8%), 40 nurses (20%) and 10 respiratory therapists (5%). Backwards stepwise multiple regression conducted to determine predictors of HCPs’ inhaler technique, showed that out of many independent variables (asthma knowledge score, profession, age, gender, place of work, years in practice and previous personal use of the study inhaler/s), asthma knowledge score was the only variable showing significant association with inhaler technique (R2=0.162, p<0.001). Conclusion: This study revealed significant associations between asthma knowledge and inhaler technique scores for all HCPs. Providing inter-professional workshops for all HCPs involved integrating education on asthma knowledge and practice of inhaler technique skills are looked-for. PMID:27011779

  4. Inhaled medicinal cannabis and the immunocompromised patient.

    PubMed

    Ruchlemer, Rosa; Amit-Kohn, Michal; Raveh, David; Hanuš, Lumír

    2015-03-01

    Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk. PMID:25216851

  5. Inhaled medicinal cannabis and the immunocompromised patient.

    PubMed

    Ruchlemer, Rosa; Amit-Kohn, Michal; Raveh, David; Hanuš, Lumír

    2015-03-01

    Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk.

  6. Toxicity of inhaled methyl isocyanate vapor

    SciTech Connect

    Ferguson, J.S.

    1988-01-01

    The toxicity of inhaled isocyanate (MIC) vapor was evaluated using several bioassays designed to investigate the toxicity of airborne chemicals. Two methods which measure changes in respiratory rate and identify characteristic breathing patterns in mice were used to evaluate the potency of MIC as a sensory and pulmonary irritant. Using the CO{sub 2} challenge method in conjunction with the measurement of airflow (V) and tidal volume (VT), the pulmonary effects and subsequent recovery process following a single exposure to MIC were studied in guinea pigs for a period of one year. Flow-volume loops were also obtained by plotting V vs. VT. Measurement of O{sub 2} uptake and CO{sub 2} output were also performed to determine the acute and chronic effects of MIC exposure on gas exchange. Lastly, guinea pigs and mice were exposed to {sup 14}C-MIC in an effort to determine uptake and fate of inhaled MIC.

  7. 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

  8. Inhalation delivery of asthma drugs.

    PubMed

    Matthys, H

    1990-01-01

    In the immediate future, metered-dose inhalers (MDIs) with spacers remain the aerosol application of choice for topical steroids, mainly to reduce side effects. For beta 2-agonist, anticholinergics and prophylactic drugs, MDI (with or without demand valve), dry powder inhalers (multidose inhalers), ultrasonic or jet aerosol generators (with or without mechanical breathing assistance [IPPB]) are chosen according to the preference or the ability of the patients to perform the necessary breathing maneuvers as well as the availability of different products in different countries.

  9. 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.

  10. 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.

  11. Potent Inhalational Anesthetics for Dentistry.

    PubMed

    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. Potent Inhalational Anesthetics for Dentistry.

    PubMed

    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.

  13. 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

  14. 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

  15. 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

  16. General practitioners’ prescribing behaviour as a determinant of poor persistence with inhaled corticosteroids in children with respiratory symptoms: mixed methods study

    PubMed Central

    Klok, Ted; Kaptein, Ad A; Duiverman, Eric; Oldenhof, Frank S; Brand, Paul L P

    2013-01-01

    Objectives To evaluate general practitioners’ (GPs’) prescribing behaviour as a determinant of persistence with and adherence to inhaled corticosteroids (ICS) in children. Design Prospective observational study of persistence with and adherence to ICS followed by a focus group study of the GPs prescribing this treatment. Setting 7 primary care practices in the area of Zwolle, the Netherlands. Participants 134 children aged 2–12 years had been prescribed ICS in the year before the study started by their 19 GPs. Main outcome measures Patterns and motives of GPs’ prescribing behaviour and the relationship with persistence with and adherence to ICS. Results GPs’ prescribing behaviour was characterised by prescribing short courses of ICS to children with various respiratory symptoms without follow-up for making a diagnosis of asthma. This was driven by the GPs’ pragmatic approach to deal with the large number of children with respiratory symptoms, and by beliefs about ICS which differed from currently available evidence. This prescribing behaviour was the main reason why 68 (51%) children did not persist with the use of ICS. In children with persistent use of ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was 70% (41–84%), and was similar for patients with persistent asthma and children lacking a diagnosis or symptoms of asthma. Conclusions Inappropriate prescription of ICS to children by GPs is common and drives the lack of persistence with ICS therapy in primary care. This finding should be taken into account when interpreting data from large prescription database studies. Improving primary healthcare providers’ knowledge and competence in diagnosing and managing asthma in children is needed. PMID:23558733

  17. Zinc toxicology following particulate inhalation.

    PubMed

    Cooper, Ross G

    2008-04-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl(2) inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection.

  18. Zinc toxicology following particulate inhalation

    PubMed Central

    Cooper, Ross G.

    2008-01-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl2 inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection. PMID:20040991

  19. Anaphylaxis induced by lentil inhalation.

    PubMed

    Ayşenur, Kaya; Akan, Ayşegül; Mustafa, Erkoçoğlu; Müge, Toyran; Kocabaş, Can Naci

    2012-06-01

    Anaphylaxis is a rapid onset serious allergic reaction which may be fatal. Foods are the most common allergens leading to anaphylaxis especially for childhood. Most of the food-induced anaphylactic reactions take place after ingestion of the allergic food and only a few cases exist with anaphylactic reactions induced by inhalation of foods such as peanut, soybean and lupine. The case we present is unusual in that an 8 1/2-year-old boy developed anaphylaxis with the inhalation of steam from boiling lentils.

  20. Empowering family physicians to impart proper inhaler teaching to patients with chronic obstructive pulmonary disease and asthma

    PubMed Central

    Leung, Janice M; Bhutani, Mohit; Leigh, Richard; Pelletier, Dan; Good, Cathy; Sin, Don D

    2015-01-01

    BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and asthma depend on inhalers for management, but critical errors committed during inhaler use can limit drug effectiveness. Outpatient education in inhaler technique remains inconsistent due to limited resources and inadequate provider knowledge. OBJECTIVE: To determine whether a simple, two-session inhaler education program can improve physician attitudes toward inhaler teaching in primary care practice. METHODS: An inhaler education program with small-group hands-on device training was instituted for family physicians (FP) in British Columbia and Alberta. Sessions were spaced one to three months apart. All critical errors were corrected in the first session. Questionnaires surveying current inhaler teaching practices and attitudes toward inhaler teaching were distributed to physicians before and after the program. RESULTS: Forty-one (60%) of a total 68 participating FPs completed both before and after program questionnaires. Before the program, only 20 (49%) reported providing some form of inhaler teaching in their practices, and only four (10%) felt fully competent to teach patients inhaler technique. After the program, 40 (98%) rated their inhaler teaching as good to excellent. Thirty-four (83%) reported providing inhaler teaching in their practices, either by themselves or by an allied health care professional they had personally trained. All stated they could teach inhaler technique within 5 min. Observation of FPs during the second session by certified respiratory educators found that none made critical errors and all had excellent technique. CONCLUSION: A physician inhaler education program can improve attitudes toward inhaler teaching and facilitate implementation in clinical practices. PMID:26436910

  1. 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

  2. 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. PMID:24792975

  3. 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.

  4. Self-reported osteoporosis prevention in inhaled corticosteroid users in community pharmacy setting

    PubMed Central

    Chan, Valerie; Cave, Andrew J

    2015-01-01

    Objectives: The use of inhaled corticosteroids is the standard maintenance therapy in asthma therapy and as adjunct therapy in moderate to severe chronic obstructive pulmonary disease. A dose-related increase in fracture risk is associated with inhaled corticosteroid use; there is an inverse relationship between bone mineral density and duration and cumulative dose of inhaled corticosteroid. Adequate intake of calcium and vitamin D are cornerstones of osteoporosis prevention. The objectives are to assess whether the proportion of patients receiving inhaled corticosteroids are taking calcium and vitamin D; the association between long-term inhaled corticosteroid use and abnormal bone mineral density or fractures; and how many qualified patients received bone mineral density scans. Methods: Patients who filled a prescription for inhaled corticosteroids at selected community pharmacies across Alberta were recruited for a survey of their osteoporosis prevention activities. Results: A total of 256 patients from 12 community pharmacies were included. The average age was 60 ± 17.4 years with 65% female. There were 21%, 51%, and 28% of patients on high, medium, and low dose inhaled corticosteroids, respectively. Only 17% of patients >50 years old received recommended calcium and vitamin D supplementation and 87 (73%) of the qualified patients received bone mineral density scan. Conclusion: Osteoporosis prevention in inhaled corticosteroid users is currently poorly addressed. More promotion is needed to raise pharmacist awareness of the risks of inhaled corticosteroids. PMID:26770786

  5. 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

  6. The toxicology of inhaled woodsmoke.

    PubMed

    Zelikoff, Judith T; Chen, Lung Chi; Cohen, Mitchell D; Schlesinger, Richard B

    2002-01-01

    In addition to developing nations relying almost exclusively upon biomass fuels, such as wood for cooking and home heating, North Americans, particularly in Canada and the northwestern and northeastern sections of the United States, have increasingly turned to woodburning as an alternate method for domestic heating because of increasing energy costs. As a result, the number of households using woodburning devices has increased dramatically. This has resulted in an increase in public exposure to indoor and outdoor woodsmoke-associated pollutants, which has prompted widespread concern about the adverse human health consequences that may be associated with prolonged woodsmoke exposure. This mini-review article brings together many of the human and animal studies performed over the last three decades in an attempt to better define the toxicological impact of inhaled woodsmoke on exposed children and adults; particular attention is given to effects upon the immune system. General information regarding occurrence and woodsmoke chemistry is provided so as to set the stage for a better understanding of the toxicological impact. It can be concluded from this review that exposure to woodsmoke, particularly for children, represents a potential health hazard. However, despite its widespread occurrence and apparent human health risks, relatively few studies have focused upon this particular area of research. More laboratory studies aimed at understanding the effects and underlying mechanisms of woodsmoke exposure, particularly on those individuals deemed to be at greatest risk, are badly needed, so that precise human health risks can be defined, appropriate regulatory standards can be set, and accurate decisions can be made concerning the use of current and new woodburning devices.

  7. 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...

  8. 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…

  9. 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 ...

  10. 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. PMID:27212477

  11. Pressurised aerosol inhalers: the cost of misuse.

    PubMed

    King, D; Earnshaw, S M; Delaney, J C

    1991-01-01

    Bronchodilator aerosols, if used correctly, have many advantages over other therapies in patients with chronic airflow limitation caused by asthma or chronic bronchitis. The use of pressurized aerosol inhalers was examined in a district general hospital: of 57 patients on these inhalers, 39 were unable to use the inhaler effectively, and 23 had never received any advice on inhaler technique. A single demonstration of correct technique decreased the failures to 21 patients and, after two demonstrations, to ten. The cost of the misused inhalers in this relatively small population was 450 pounds, and obviously this figure escalates when the prescription for these inhalers is repeated monthly. It is also increased when the total numbers of misused inhalers in the country are accounted for. The cost in terms of finance, in these days of medical audit and drug budgets, and, more importantly, in terms of patient health, is unacceptable and can be avoided by repeated tuition of technique.

  12. 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...

  13. 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

  14. 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.

  15. The Moderating Effects of Perceived Emotional Benefits on Inhalant Initiation Among American Indian and White Youth

    PubMed Central

    Swaim, Randall C.

    2015-01-01

    Background Inhalant use co-occurs with emotional distress. Inhalant use may be a means of self-medicating distress, but more recent study focuses on the cognitive appraisal of personal benefits of using substances. Objectives Objectives were to determine whether emotional distress variables predict early versus later initiation of inhalant use, whether such relationships differ between American Indian and white youth, and whether perceived emotional benefits of inhalant use moderates the relationship between emotional distress and stage of inhalant initiation. Methods Data were from a study of 7–12th grade American Indian youth who live on or near reservations. A total of 856 students from 32 schools surveyed from 2009 to 2012, who reported having used inhalants (American Indian = 683; white = 173), were surveyed about age first use of inhalants, levels of emotional distress, and perceived benefits of inhalant use. SEM models were used to assess study objectives. Results Depression and anger did not discriminate between early and later initiation. Lower self-esteem related to earlier initiation, but only among American Indian students. Perceived emotional benefits of inhalant use did not moderate the relationship between self-esteem and stage of initiation. Discussion and Conclusions Among middle school and high school American Indian and white youth living on or near American Indian reservations, emotional distress is not strongly related to stage of inhalant initiation. Scientific Significance These findings raise questions about the timing and strength of relationship between emotional distress and early inhalant initiation. Prospective studies are need to assess this relationship more fully. PMID:26246198

  16. 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

  17. [Inhaled insulin, new perspective for insulin therapy].

    PubMed

    Radermecker, R P; Sélam, J L

    2005-01-01

    Since the discovery of insulin and its use in diabetes care, patients, physicians and nurses dream of another way of insulin administration than the subcutaneous injections actually used. Different types of insulin administration have been evaluated and, particularly, that using the pulmonary route. The use of this alternative method to deliver insulin may result in improved patient compliance, facilitate intensified therapies and avoid the delay of initiating insulin administration because patient's reluctance. The different insulin pulmonary delivering devices actually studied will be presented. Preliminary data comparing this way of administration and the subcutaneous injection of human regular insulin are good, but sufficient data comparing inhaled insulin with the new short-acting insulin analogues are not yet available. Among various difficulties of the pulmonary insulin delivery, the finding of an effective promoter, capable of increasing the bioavailability of insulin, is a crucial issue. The cost of such insulin administration might also be a problem. Finally, careful studies concerning the safety of this kind of administration, particularly potential long-term pulmonary toxicity, are mandatory. Nevertheless, inhaled insulin is an attractive topic in which most important pharmaceutical companies are currently involved.

  18. 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

  19. Volumatic usage: some generic salbutamol metered dose inhalers can be used.

    PubMed Central

    Chege, J. K.; Chrystyn, H.

    1994-01-01

    BACKGROUND--The 30 minute and 24 hour post-inhalation urinary excretion of salbutamol represents the relative amount of drug deposited in the lungs and total systemic absorption, respectively. Using this method two metered dose inhalers used with a Volumatic (Allen and Hanburys Ltd, UK) large volume spacer have been compared. METHOD--Eleven healthy volunteers inhaled 4 x 100 micrograms salbutamol from either a generic salbutamol (Baker Norton, UK) or Ventolin (Allen and Hanburys Ltd, UK) metered dose inhaler with a Volumatic. The order of administration was randomised with a seven day washout period. Urine samples were collected for 0-30 minutes and then pooled up to 24 hours after inhalation. RESULTS--The mean (SD) urinary salbutamol excretion 30 minutes after inhalation with the metered dose inhalers used with the Volumatic was 22.22 (4.63) and 21.30 (5.91) micrograms for the Baker Norton and Ventolin respectively, with a mean difference (95% confidence interval (CI)) of 0.92 (-0.65 to 2.49) micrograms. Similar amounts were excreted up to 24 hours after the dose with a mean (SD) urinary excretion of 116.1 (24.3) micrograms and 114.8 (22.3) micrograms, respectively, and a mean difference (95% CI) of 1.22 (-20.39 to 22.84) micrograms. CONCLUSION--Inhalations from generic salbutamol (Baker Norton) and Ventolin metered dose inhalers with a Volumatic inhalation aid deliver similar amounts of drug to the lungs and the total systemic absorption from the two products is the same. PMID:7831635

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

    PubMed

    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 ([Formula: see text]) 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 [Formula: see text] 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 ([Formula: see text]/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 ([Formula: see text]/FVC = -3.859+0.101HR, mean percent error = 11.3±36%). PMID:26809066

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

    PubMed

    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 ([Formula: see text]) 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 [Formula: see text] 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 ([Formula: see text]/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 ([Formula: see text]/FVC = -3.859+0.101HR, mean percent error = 11.3±36%).

  2. Inhalation therapy: technological milestones in asthma treatment.

    PubMed

    Dalby, Richard; Suman, Julie

    2003-07-18

    The humble origins of the propellant driven metered dose inhaler, as a response to a child's enquiry, initiated an industry which supplies approximately a half billion inhalers globally for the treatment of asthma. These inhalers fall into three major groups: nebulizers; propellant driven metered dose inhalers and dry powder inhalers. Each requires drug formulation, metering and device technology to be successful. In recent years there have been several new developments in the field including auxiliary systems to improve drug delivery from the device to the patient and new categories of device, notably single breath aqueous systems. As device technology improves and our understanding of the disease leads to new drugs the only barrier to therapy is the patient. Patient training and compliance will continue to be important factors in the success, or failure, of inhaled therapy and the role of health care professionals will depend on who sponsors their intervention.

  3. 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

  4. Misuse of xylometazoline nasal drops by inhalation.

    PubMed

    Anand, Jacek Sein; Salamon, Marek; Habrat, Boguslaw; Scinska, Anna; Bienkowski, Przemyslaw

    2008-12-01

    Six male prisoners who misused xylometazoline nasal drops by inhalation were interviewed by a prison physician in 2006. The prisoners received xylometazoline drops during regular visits in the prison ambulatory service. In order to get the medication, the subjects reported false symptoms of rhinosinusitis and allergic reactions. Psychoactive effects of inhaled xylometazoline were described as "stimulation," "excitation," and "feeling of strength." Although preliminary, our findings suggest that topical adrenergic decongestants can produce rewarding effects when administered by inhalation. PMID:19085441

  5. AB034. Comparative effectiveness of prescribing similarversusdissimilar inhalers for COPD therapy

    PubMed Central

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

    2016-01-01

    Background Prescription of different inhaler types for patients with chronic obstructive pulmonary disease (COPD) may lead to poorer outcomes through increased demands on patients to master dissimilar inhalation and dose preparation manoeuvres. To describe the demographic, co-morbidity, and clinical characteristics of patients with COPD prescribed ‘dissimilar’versus‘similar’ inhalers. Methods The study was a historical cohort observational design assessing a 1-year baseline period for patient characterization and categorisation of inhalers, and an index date to signal the last date of data extraction from the UK Optimum Patient Care Research Database (OPCRD). Patients had 1-year of continuous data between February 2008 and February 2015, a Quality and Outcomes Framework (QOF) coded diagnosis for COPD, were aged 40 and over, and had evidence of two or more inhaled respiratory treatments. Descriptive statistics included demographic, co-morbidity and clinical characteristics of patients, and comparison of patients prescribed similarversusdissimilar inhalers by GOLD group, FEV1, and number of exacerbations. Based on inhalation technique and dose preparation data in the OPCRD, two different categorisations were used to describe prescribed inhaler type: ‘similar inhalers’ included those patients prescribed either aerosols or similar dry-powder inhalers (DPIs), while ‘dissimilar inhalers’ included those prescribed both aerosols and DPIs. Results A total of 53,817 patients were selected [mean age of 71 years (SD 10.6); males: 51% in total population]. 13% were non-smokers, 30% current smokers, 52% ex-smokers and 5% with missing smoking status. In the baseline year, 39% received a QOF coded diagnosis for asthma, 36% for diabetes, 26% for ischaemic heart disease, 6% for actively treated rhinitis, and 1.3% for diagnosis for pneumonia. Patients prescribed dissimilar inhalers were of similar age to those prescribed similar inhalers (mean age of 71 in each cohort

  6. Allergic reactions to foods by inhalation.

    PubMed

    James, John M; Crespo, Jesús Fernández

    2007-06-01

    Although allergic reactions to foods occur most commonly after ingestion, inhalation of foods can also be an underlying cause of these reactions. For example, published reports have highlighted the inhalation of allergens from fish, shellfish, seeds, soybeans, cereal grains, hen's egg, cow's milk, and many other foods in allergic reactions. Symptoms have typically included respiratory manifestations such as rhinoconjunctivitis, coughing, wheezing, dyspnea, and asthma. In some cases, anaphylaxis has been observed. In addition, there have been many investigations of occupational asthma following the inhalation of relevant food allergens. This report reviews the current literature focusing on allergic reactions to foods by inhalation.

  7. Treatment Seeking Behavior of Inhalant Using Street Children: Are We Prepared to Meet Their Treatment Needs

    PubMed Central

    Dhawan, Anju; Chopra, Anita; Ambekar, Atul; Ray, Rajat

    2015-01-01

    Context: There is a lack of evidence for help and treatment seeking behavior of street children using inhalants. Aims: The present study was planned to provide a comprehensive understanding on the patterns, correlates of inhalant use and treatment seeking behavior of street children from Delhi, India. Material and Methods: Participants were a purposive sample of 100 inhalant using street children below 18 years identified with the assistance of five community service organizations/nongovernmental organization working with street children in the city of Delhi. Information on a semi-structured questionnaire with items pertaining to the demographic and drug use parameters was collected by trained research staff in a one-to-one in field setting. Statistical Analysis: All data were entered into SPSS 12.0, data quality checks performed and examined. Results: The sample had an average age of 12.8 ± 2.4 years (range 4-17 years), 96.5% reported regular past month and 87.0% past 24 h use of inhalants. The mean age of onset of inhalant use was 9.3 ± 2.8 years The substances most commonly reported were toluene from eraser fluid (by 83.0%), glues (34.0%) and petroleum products (3.0%); mean frequency of use was 9.8 times in a day. Of the sample, 18% used inhalants when they were alone, and the rest reported using with drug using network friends; 76% reported tolerance and mild withdrawal symptoms such as restlessness, anxiety, craving, irritability and lethargy. A variety of problems and perceived benefits due to inhalant use were reported; 46% inhalant users had never abstained from its use, and 77% reported never having sought any medical help. Conclusions: Study findings provide a better contemporary understanding of inhalant abuse among Delhi street children. This information can assist in the formulation of a needs-based intervention for the inhalant using street children. PMID:26664076

  8. Symposium Summary: "Breathe In, Breathe Out, Its Easy: What You Need to Know About Developing Inhaled Drugs".

    PubMed

    Tepper, Jeffrey S; Kuehl, Philip J; Cracknell, Stuart; Nikula, Kristen J; Pei, Luqi; Blanchard, James D

    2016-07-01

    Developing inhaled drugs requires knowledge of lung anatomy, cell biology, respiratory physiology, particle physics, and some plumbing. Although dose makes the poison, in the context of an inhaled drug, the "dose" is not easily defined. This lack of clarity around dose poses issues and challenges in the design of inhalation toxicology programs. To better understand dose, the influence of ventilation is discussed as are the perturbations in pulmonary function observed with inhalation exposure that can affect dose. Methods for determining inhaled drug deposition to arrive at an estimate of lung dose are examined. Equally important to understanding dose are the techniques used to deliver aerosols to animals. With a better understanding of dose and inhalation exposure, species-specific histopathologic lesions, both common background and toxicologically significant lesions, are reviewed. Finally, insight into how regulators synthesize and evaluate these complex findings to assess clinical safety risks is presented.

  9. Inhaled magnesium fluoride reverse bronchospasma.

    PubMed

    Gandia, Fedoua; Rouatbi, Sonia; Latiri, Imed; Guénard, Hervé; Tabka, Zouhair

    2010-01-01

    Asthma is a global health problem. Asthma attacks are becoming more severe and more resistant to usual treatment by beta(2) agonists nebulisation. The search for a new product that could reduce the morbidity of asthmatic disease seems necessary. The objective of this study was to compare the effectiveness of inhaled magnesium fluoride (MgF(2)) with that of magnesium sulphate (MgSO(4)) 15% alone and sodium fluoride (NaF) 0.5 M alone in rats pre-contracted by methacholine (MeCh). Fifty six adult male Wistar rats of medium weight 259 +/- 15 g were divided randomly into five groups. They inhaled respectively: MeCh, MgF(2) + NaCl 0.9%, MgF(2) + acetic acid, MgSO(4) 15% single and NaF (0.5 M) single. Airway resistances were measured after each dose of MeCh by pneumomultitest equipment. Results indicated that (1) MgF(2) + NaCl 0.9%, MgF(2) + acetic acid and MgSO(4) reversed significantly the methacholine-induced bronchial constriction in rats and had a bronchodilating effect at the moment of its administration (2) MgF(2) + acetic acid led to a greater decrease (P<0.05) of bronchial resistances when compared to that obtained from MgF(2) + NaCl 0.9%, NaF exclusively and MgSO(4) alone (3) inhaled NaF alone led to a significant bronchorelaxing effect (P<0.05) that starts at the sixth dose of MeCh (17 mg/L). As a matter of fact, MgF(2) dissolved in acetic acid and delivered in aerosol form reduces significantly bronchial spasm. In conclusion, MgF(2) can be used as a bronchodilator for diseases with bronchospasma such as asthma and chronic obstructive pulmonary disease (COPD).

  10. Inhalant abuse: youth at risk.

    PubMed

    Ahern, Nancy R; Falsafi, Nasrin

    2013-08-01

    Inhalant abuse is a significant problem affecting many people, particularly youth. The easy availability of products containing volatile substances (e.g., aerosol sprays, cleaning products, paint) provides opportunity for mind-altering experiences. Unfortunately, serious complications such as brain, cardiovascular, liver, and renal damage or even death may ensue. Adolescents perceive the risk as low, and parents may be unaware of the risks. Health care providers, particularly psychiatric nurses, should undertake strategies of prevention, assessment, and treatment of this challenging problem. PMID:23786241

  11. 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.

  12. 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

  13. [Recent progress of dry powder inhalation of proteins and peptides].

    PubMed

    Zhou, Jie-yu; Zhang, Lan; Mao, Shi-rui

    2015-07-01

    To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder. PMID:26552141

  14. Using artificial burrows to evaluate inhalation risks to burrowing mammals.

    PubMed

    Markwiese, James T; Tiller, Brett; Ryti, Randall T; Bauer, Roy

    2008-10-01

    Since the onset of plutonium production at the U.S. Department of Energy's Hanford Site, several hundred cubic meters of carbon tetrachloride (CCl4) has been discharged to the soil column, resulting in a dispersed CCI4 vapor plume in the subsurface. Inhalation of volatile organic chemicals could be an important exposure pathway for burrowing animals there. Historical levels of CCl4 in soil pore gas exceeded the inhalation ecological screening level for CCl4. Thus, the inhalation exposure pathway was evaluated with the use of artificial burrows deployed at locations that had elevated levels of CCl4 in soil gas. Artificial burrows were designed on the basis of information available for Hanford Site fossorial wildlife. After installation, the artificial burrow atmosphere was sampled and analyzed for CCl4 and its degradation products: chloroform, methylene chloride, and chloromethane. Sampling was repeated on 3 occasions to capture varying atmospheric conditions affecting exposure concentrations. CCl4 was detected in the artificial burrows, and maximum exposures were observed during relatively low barometric conditions. The highest CCl4 detections were still well below the inhalation-based ecological screening level and CCl4 degradation products were never detected. This study shows that artificial burrows are an efficient method for obtaining relevant exposure data and illustrates the utility of directly measuring the medium for exposure under ecologically realistic conditions.

  15. Inhalation challenge with ragweed pollen in ragweed-sensitive asthmatics.

    PubMed

    Rosenberg, G L; Rosenthal, R R; Norman, P S

    1983-03-01

    We reexamined the ability of inhaled ragweed pollen to induce bronchoconstriction in ragweed-sensitive asthmatic patients using a turbo-inhaler to administer pollen quantitatively. Adult subjects were selected for study on the basis of fall season asthmatic attacks, positive skin test, histamine release, RAST, and bronchial challenge responses to ragweed extract. Not one of 12 such subjects had any bronchial response to oral inhalation of whole pollen grains even when the dose was increased to 7640 pollen grains (more than the estimated maximum daily exposure in season), whereas nasal challenge by the same method produced brisk hay fever responses without bronchospasm. On the other hand, when the pollen was ground to fragments with a size range of 1 to 8 micrometers, oral inhalation produced a 35% fall in airways conductance in six of seven subjects in doses ranging from 59 to 20,000 pollen grain equivalents. Atropine pretreatment did not modify the response to pollen fragments, making an irritant response unlikely. These data, coupled with earlier observations that no more than a few pollen grains penetrate further than the larynx, raise further questions about the role of whole ragweed pollen in fall asthma in allergic patients. In addition, ragweed-allergic asthmatics appear not to have their symptoms at the time of maximum pollen load in the air. We believe that small-particle allergens other than ragweed pollen should be considered in most cases of fall seasonal asthma.

  16. Inhalants

    MedlinePlus

    ... for the wide variety of substances—including solvents, aerosols, gases, and nitrites—that are rarely, if ever, ... a glue bottle or a marking pen), spray aerosols (such as computer cleaning dusters) directly into their ...

  17. Inhalants

    MedlinePlus

    ... electronic contact cleaner Aerosols are sprays that contain propellants and solvents. They include: Spray paint, hair spray, ... burn injuries Freon (difluoroethane substitutes) Refrigerant and aerosol propellant Sudden sniffing death Breathing problems and death (from ...

  18. Tips for Teens: The Truth about Inhalants

    MedlinePlus

    ... site at www. whitehousedrugpolicy. gov. No.Even though household products like glue and air freshener have legal,useful ... A. A. Q.Since inhalants are found in household products,aren’t they safe? Q.Can inhalants make ...

  19. 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.

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

    PubMed Central

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

    2013-01-01

    Purpose The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. Methods DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. Results The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. Conclusions High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD < 1.5 µm, FPF<5µm/ED > 90%, and ED > 80%. PMID:23949304

  1. [Dry powder inhalers in cystic fibrosis].

    PubMed

    Steinkamp, G

    2014-06-01

    Inhaled medications play an important role in the daily treatment of patients with cystic fibrosis (CF). The classic route of administration was nebulisation via jet nebulisers. Respiratory delivery of fluid particles should loosen the viscid respiratory secretions, making airway clearance via cough or physiotherapy more efficient. Until recently, only jet nebulisers allowed to administer high doses of aerosolised antipseudomonal antibiotics. Powder inhalers for the treatment of cystic fibrosis have recently been made available. The newly developed powders and inhalers differ considerably from conventional dry powder inhalers used for the treatment of chronic obstructive airway disease. The present article will review two inhaled antibiotics, i. e. tobramycin and colistin, and the hyperosmotic agent mannitol, which increases the hydration of the airways. Topics are particle engineering, efficacy and tolerability results from clinical trials, as well as functional and practical aspects related to these new drugs. PMID:24664997

  2. The ozone layer and metered dose inhalers.

    PubMed

    Boulet, L P

    1998-01-01

    The stratospheric ozone layer plays a crucial role in protecting living organisms against ultraviolet radiation. Chlorofluorocarbons (CFC) contained in metered-dose inhalers (MDIs) contribute to ozone depletion and in accordance with the Montreal Protocol on Substances That Deplete the Ozone Layer established 10 years ago, phase-out strageies have been developed worldwide for this category of agents. Alternatives to CFC-containing inhalers have been developed, such as powder inhalers and those using hydrofluoroalkanes (HFAs) as propellants, which have been shown to be as safe and effective as CFC-containing inhalers and even offer interesting advantages over older inhalers. The transition to non-CFC MDIs requires a major effort to make the new products available and to ensure adequate comparision with the previous ones. It also requires a harmonization of actions taken by industry, government, licencing bodies and patients or health professional associations to ensure adequate information and education to the public and respiratory care providers.

  3. 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

  4. Inhalation Incidents and Respiratory Health: Results From the European Community Respiratory Health Survey

    PubMed Central

    Mirabelli, Maria C.; Olivieri, Mario; Kromhout, Hans; Norbäck, Dan; Radon, Katja; Torén, Kjell; van Sprundel, Marc; Villani, Simona; Zock, Jan-Paul

    2009-01-01

    Background Inhalation incidents are an important cause of acute respiratory symptoms, but little is known about how these incidents affect chronic respiratory health. Methods We assessed reported inhalation incidents among 3,763 European Community Respiratory Health Survey (ECRHS) participants with and without cough, phlegm, asthma, wheezing or bronchial hyperresponsiveness. We then examined whether inhalation incidents during the 9-year ECRHS follow-up period were associated with a new onset of any of these respiratory outcomes among 2,809 participants who were free of all five outcomes at the time of the baseline ECRHS survey. Results Inhalation incidents were reported by 5% of participants, with higher percentages reported among individuals with asthma-related outcomes at the time of the baseline survey. Among participants without symptoms at baseline, our analyses generated non-statistically significant elevated estimates of the risk of cough, phlegm, asthma and wheezing and a non-statistically significant inverse estimate of the risk of bronchial hyperresponsiveness among participants who reported an inhalation incident compared to those without such an event reported. Discussion Our findings provide limited evidence of an association between inhalation incidents and asthma-related symptoms. These data could be affected by differences in the reporting of inhalation incidents according to symptom status at the time of the baseline survey; they should thus be interpreted with caution. PMID:18942122

  5. 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

  6. Inhaled Amikacin for Treatment of Refractory Pulmonary Nontuberculous Mycobacterial Disease

    PubMed Central

    Shaw, Pamela A.; Glaser, Tanya S.; Bhattacharyya, Darshana; Fleshner, Michelle; Brewer, Carmen C.; Zalewski, Christopher K.; Folio, Les R.; Siegelman, Jenifer R.; Shallom, Shamira; Park, In Kwon; Sampaio, Elizabeth P.; Zelazny, Adrian M.; Holland, Steven M.; Prevots, D. Rebecca

    2014-01-01

    Rationale: Treatment of pulmonary nontuberculous mycobacteria, especially Mycobacterium abscessus, requires prolonged, multidrug regimens with high toxicity and suboptimal efficacy. Options for refractory disease are limited. Objectives: We reviewed the efficacy and toxicity of inhaled amikacin in patients with treatment-refractory nontuberculous mycobacterial lung disease. Methods: Records were queried to identify patients who had inhaled amikacin added to failing regimens. Lower airway microbiology, symptoms, and computed tomography scan changes were assessed together with reported toxicity. Measurements and Main Results: The majority (80%) of the 20 patients who met entry criteria were women; all had bronchiectasis, two had cystic fibrosis and one had primary ciliary dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M. abscessus and 5 for Mycobacterium avium complex and had received a median (range) of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a median of 19 (1, 50) months. Eight (40%) patients had at least one negative culture and 5 (25%) had persistently negative cultures. A decrease in smear quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of 19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%), and worsened in four (20%). Improvement on computed tomography scans was noted in 6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and nephrotoxicity, persistent dysphonia, and vertigo in one each. Conclusions: In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted. PMID:24460437

  7. 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...

  8. 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

  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. Single and 14-day repeated dose inhalation toxicity studies of hexabromocyclododecane in rats.

    PubMed

    Song, Naining; Li, Lei; Li, Haishan; Ai, Wenchao; Xie, Wenping; Yu, Wenlian; Liu, Wei; Wang, Cheng; Shen, Guolin; Zhou, Lili; Wei, Changlei; Li, Dong; Chen, Huiming

    2016-05-01

    Limited toxicological information is available for hexabromocyclododecane (HBCD),a widely used additive brominated flame retardant. Inhalation is a major route of human exposure to HBCD. The aim of this study was to determine the acute inhalation toxicity and potential subchronic inhalation toxicity of HBCD in Sprague-Dawley rats exposed to HBCD only through inhalation. The acute inhalation toxicity of HBCD was determined using the limit test method on five male and five female Sprague-Dawley rats at a HBCD concentration of 5000 mg/m(3). Repeated-dose toxicity tests were also performed, with 20 males and 20 females randomly assigned to four experimental groups (five rats of each sex in each group). There were three treatment groups (exposed to HBCD concentrations of 125,500, and 2000 mg/m(3)) and a blank control group (exposed to fresh air). In the acute inhalation toxicity study, no significant clinical signs were observed either immediately after exposure or during the recovery period. Gross pathology examination revealed no evidence of organ-specific toxicity in any rat. The inhalation LC50(4 h) for HBCD was higher than 5312 ± 278 mg/m3 for both males and females. In the repeated dose inhalation study, daily head/nose-only exposure to HBCD at 132 ± 8.8, 545.8 ± 35.3, and 2166.0 ± 235.9 mg/m(3) for 14 days caused no adverse effects. No treatment-related clinical signs were observed at any of the test doses. The NOAEL for 14-day repeated dose inhalation toxicity study of HBCD is 2000 mg/m(3). PMID:26929994

  11. 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

  12. Emerging inhaled bronchodilators: an update.

    PubMed

    Cazzola, M; Matera, M G

    2009-09-01

    Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field. The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients. A variety of beta(2)-agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development. The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.

  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 exposure technology, dosimetry, and regulatory issues.

    PubMed

    Dorato, M A; Wolff, R K

    1991-01-01

    Inhalation toxicology technology has provided the scientific community with important advances in studies of inhaled toxicants. These advances include new and more efficient exposure systems (e.g., flow-past nose-only exposure systems), and improved approaches to inhalation chamber environmental control (e.g., temperature, humidity, air quality). Practical problems and approaches to testing and operating inhalation exposure systems and the advantages and disadvantages of the major inhalation exposure types (e.g., whole-body, nose-only) are discussed. Important aspects of study design, such as high level particulate exposures resulting in large lung burdens (e.g., greater than or equal to 2 mg/g of lung), slowed pulmonary clearance rates, and nonspecific toxicity are considered, along with practical issues of comparative dosimetry. Regulatory guidelines have continued to present challenges in designing and conducting acute, subchronic, and chronic inhalation studies. The important regulatory issue of performing acute inhalation toxicity studies at high aerosol concentrations and "respirable" particle size distribution is discussed. PMID:1813983

  15. 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...

  16. 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...

  17. 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... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  18. 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... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  19. 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... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  20. Inhalation errors due to device switch in patients with chronic obstructive pulmonary disease and asthma: critical health and economic issues

    PubMed Central

    Roggeri, Alessandro; Micheletto, Claudio; Roggeri, Daniela Paola

    2016-01-01

    Background Different inhalation devices are characterized by different techniques of use. The untrained switching of device in chronic obstructive pulmonary disease (COPD) and asthma patients may be associated with inadequate inhalation technique and, consequently, could lead to a reduction in adherence to treatment and limit control of the disease. The aim of this analysis was to estimate the potential economic impact related to errors in inhalation in patients switching device without adequate training. Methods An Italian real-practice study conducted in patients affected by COPD and asthma has shown an increase in health care resource consumption associated with misuse of inhalers. Particularly, significantly higher rates of hospitalizations, emergency room visits (ER), and pharmacological treatments (steroids and antimicrobials) were observed. In this analysis, those differences in resource consumption were monetized considering the Italian National Health Service (INHS) perspective. Results Comparing a hypothetical cohort of 100 COPD patients with at least a critical error in inhalation vs 100 COPD patients without errors in inhalation, a yearly excess of 11.5 hospitalizations, 13 ER visits, 19.5 antimicrobial courses, and 47 corticosteroid courses for the first population were revealed. In the same way, considering 100 asthma patients with at least a critical error in inhalation vs 100 asthma patients without errors in inhalation, the first population is associated with a yearly excess of 19 hospitalizations, 26.5 ER visits, 4.5 antimicrobial courses, and 21.5 corticosteroid courses. These differences in resource consumption could be associated with an increase in health care expenditure for INHS, due to inhalation errors, of €23,444/yr in COPD and €44,104/yr in asthma for the considered cohorts of 100 patients. Conclusion This evaluation highlights that misuse of inhaler devices, due to inadequate training or nonconsented switch of inhaled medications

  1. Pharmacokinetics and pharmacodynamics of intravenous and inhaled fluticasone furoate in healthy Caucasian and East Asian subjects

    PubMed Central

    Allen, Ann; Bal, Joanne; Cheesbrough, Anne; Hamilton, Melanie; Kempsford, Rodger

    2014-01-01

    AIM The aim of the study was to evaluate the pharmacokinetics (PK) of inhaled and intravenous (i.v.) fluticasone furoate (FF) in healthy Caucasian, Chinese, Japanese and Korean subjects. METHOD This was an open label, randomized, two way crossover study in healthy Caucasian, Chinese, Japanese and Korean subjects (n = 20 per group). Inhaled FF (200 μg for 7 days, then 800 μg for 7 days from a dry powder inhaler [DPI]) was administered in one treatment period and i.v.FF (250 μg infusion) in the other. FF PK and serum cortisol (inhaled 200 μg only) were compared between the ethnic groups using analysis of variance. P450 CYP3A4 activity and safety were also assessed. RESULTS Ethnic differences in i.v. FF PK were accounted for by body weight differences. CYP3A4 activity was similar across the groups. Higher FF systemic exposure was seen following inhaled dosing in Chinese, Japanese and Korean subjects compared with Caucasian subjects. Absolute bioavailability was greater (36%–55%) in all East Asian groups than for Caucasian subjects following inhaled FF 800 μg. Deconvolution analysis suggested inhaled FF resided in the lung of East Asian subjects longer than for Caucasians (time for 90% to be absorbed [t90]: 29.1–30.8 h vs. 21.4 h). In vitro simulation method predicted comparable delivered lung dose across ethnic groups. Serum cortisol weighted mean was similar between Caucasians and Chinese or Koreans, while in Japanese was on average 22% lower than in Caucasians. All FF treatments were safe and well tolerated. CONCLUSION Modestly higher (<50%) FF systemic exposure seen in East Asian subjects following inhaled dosing was not associated with a clinically significant effect on serum cortisol, suggesting that a clinical dose adjustment in East Asian subjects is not required. PMID:24152086

  2. Improvement of inhaler efficacy by home-made spacer.

    PubMed

    Sritara, P; Janvitayanuchit, S

    1993-12-01

    The delivery of aerosol from a metered dose inhaler (MDI) was reported to be more efficient with a spacer. Hence, a home-made spacer modified from a 950 ml low cost plastic bottle, was compared with a MDI and with a 750 ml imported spacer (Nebuhaler). On three consecutive days, at the same time of day, 20 adult patients with chronic asthma inhaled two puffs of terbutaline sulphate (0.5 mg), delivered from MDI alone, MDI with a 750 ml Nebuhlaer and MDI with a home-made spacer. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate. These measurements were carried out immediately before and at 5, 20, 60 min after inhalation of terbutaline. FEV1 was significantly increased (P < 0.05) at 5, 20 and 60 min after administration of terbutaline with MDI via either spacers than with MDI alone but no significant difference was observed between Nebuhaler and the home-made spacer. FVC and pulse rate showed no significant change with each method of administration. In conclusion, terbutaline delivered by MDI and home-made spacer was more effective in bronchodilatation than by MDI alone and was just as effective as MDI and Nebuhaler. The home-made spacer therefore offers a simple, inexpensive and more effective method for delivering aerosol drug. PMID:7798822

  3. Hematotoxicity and carcinogenicity of inhaled benzene.

    PubMed

    Cronkite, E P; Drew, R T; Inoue, T; Hirabayashi, Y; Bullis, J E

    1989-07-01

    CBA/Ca male mice have been exposed to benzene in air at 10, 25, 100, 300, 400, and 3000 ppm for variable intervals 6 hr/day, 5 days/week for up to 16 weeks. Two weeks of inhaling 10 ppm produced no hematologic effects; 25 ppm induced a significant lymphopenia. Inhalation of 100, 300, and 400 ppm produced dose-dependent decreases in blood lymphocytes, bone marrow cellularity, marrow content of spleen colony-forming units (CFU-S) and an increased fraction of CFU-S in DNA synthesis. Exposure of mice to 300 ppm for 2, 4, 8, and 16 weeks produced severe lymphopenia and decrease in marrow CFU-S. Recovery was rapid and complete after 2 and 4 weeks of exposure. After 8 and 16 weeks of exposure, recovery of lymphocytes was complete within 8 weeks. It took 16 weeks for the CFU-S to recover to that of the age-matched controls after 8 weeks of exposure and 25 weeks to recover to age-matched after 16 weeks of exposure. Inhalation of 3000 ppm for 8 days was less damaging than inhalation of 300 ppm for 80 days (same integral amount of benzene inhaled). The inhalation of 3000 ppm has not increased the incidence of leukemia or shortened its latency for development. Inhalation of 300 ppm 6 hr/day for 16 weeks significantly increases the incidence of myelogenous neoplasms in male CBA/Ca mice. Inhalation of 100 ppm for same interval does not influence incidence of myelogenous neoplasms but does increase incidence of solid neoplasms particularly in female CBA/Ca mice. Benzene is a potent carcinogen in CBA/Ca mice.

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

    PubMed Central

    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. PMID:26309676

  5. Inhaling to mitigate exhaled bioaerosols.

    PubMed

    Edwards, David A; Man, Jonathan C; Brand, Peter; Katstra, Jeffrey P; Sommerer, K; Stone, Howard A; Nardell, Edward; Scheuch, Gerhard

    2004-12-14

    Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These "exhaled bioaerosols" may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these "high-producer" individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 +/- 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension.

  6. [Evoked potentials and inhalation anesthetics].

    PubMed

    Thiel, A; Russ, W; Hempelmann, G

    1988-01-01

    Intraoperative monitoring of evoked potentials can be affected by various factors including volatile anaesthetics. These effects have to be considered in order to give correct interpretations of the obtained data. Visual evoked potentials (VEP) and auditory evoked potentials (AEP) will show strong alterations under general anaesthesia whereas brainstem auditory evoked potentials (BAEP) are slightly affected. The effects of nitrous oxide, halothane, enflurane, and isoflurane on somatosensory evoked potentials (SEP) after median nerve stimulation were studied in 35 healthy adult patients. pCO2 and tympanic membrane temperature were held constant. Simultaneous cervical and cortical SEP recording was performed using surface electrodes. After induction of anaesthesia SEP were recorded during normoventilation with 100% oxygen and after inhalation of 66.6% nitrous oxide. 10 patients received halothane at inspired concentrations of 0.5, 1.0, 1.5, and 2.0%. After nitrous oxide had been replaced by oxygen, halothane was reduced in steps of 0.5%. SEP were recorded at the end of each period (15 min). Equipotent doses of enflurane or isoflurane were administered to 15 and 10 patients, respectively. Nitrous oxide depressed early cortical SEP amplitude. Halothane, enflurane, and isoflurane caused dose dependent increases of latencies. Reduction of amplitude was most pronounced with isoflurane. Using high doses of enflurane in oxygen cortical SEP showed unusual high amplitudes associated with marked increases of latencies. Even under high concentrations of volatile anaesthetics cervical SEP were minimally affected. The effects of anaesthetic gases have to be considered when SEP are recorded intraoperatively.

  7. 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.

  8. Inhaling to mitigate exhaled bioaerosols

    PubMed Central

    Edwards, David A.; Man, Jonathan C.; Brand, Peter; Katstra, Jeffrey P.; Sommerer, K.; Stone, Howard A.; Nardell, Edward; Scheuch, Gerhard

    2004-01-01

    Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These “exhaled bioaerosols” may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these “high-producer” individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 ± 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension. PMID:15583121

  9. Inhaled Corticosteroids in Lung Diseases

    PubMed Central

    Raissy, Hengameh H.; Kelly, H. William; Harkins, Michelle

    2013-01-01

    Inhaled corticosteroids (ICSs) are used extensively in the treatment of asthma and chronic obstructive pulmonary disease (COPD) due to their broad antiinflammatory effects. They improve lung function, symptoms, and quality of life and reduce exacerbations in both conditions but do not alter the progression of disease. They decrease mortality in asthma but not COPD. The available ICSs vary in their therapeutic index and potency. Although ICSs are used in all age groups, younger and smaller children may be at a greater risk for adverse systemic effects because they can receive higher mg/kg doses of ICSs compared with older children. Most of the benefit from ICSs occurs in the low to medium dose range. Minimal additional improvement is seen with higher doses, although some patients may benefit from higher doses. Although ICSs are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is more controversial. When used appropriately, ICSs have few adverse events at low to medium doses, but risk increases with high-dose ICSs. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICSs as the preferred initial long-term controller therapy for asthma, but more effective initial controller therapy could be developed for COPD. PMID:23370915

  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. PMID:27256501

  11. Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics

    PubMed Central

    Wu, Ann C.; Himes, Blanca E.; Lasky-Su, Jessica; Litonjua, Augusto; Peters, Stephen P.; Lima, John; Kubo, Michiaki; Tamari, Mayumi; Nakamura, Yusuke; Qiu, Weiliang; Weiss, Scott T.; Tantisira, Kelan

    2013-01-01

    Background Single nucleotide polymorphisms (SNPs) influence a patient's response to inhaled corticosteroids and β2-agonists, and the effect of treatment with inhaled corticosteroids is synergistic with the effect of β2-agonists. We hypothesized that use of inhaled corticosteroids could influence the effect of SNPs associated with bronchodilator response. Objective To assess whether, among asthma subjects, the association of SNPs with bronchodilator response is different between those treated with inhaled corticosteroids vs. those on placebo. Methods A genome-wide association analysis was conducted using 581 white subjects from the Childhood Asthma Management Program (CAMP). Using data for 449,540 SNPs, we conducted a gene by environment analysis in PLINK with inhaled corticosteroid treatment as the environmental exposure and bronchodilator response as the outcome measure. We attempted to replicate the top 12 SNPs in the Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol (LOCCS) Trial. Results The combined P-value for the CAMP and LOCCS populations was 4.81E-08 for rs3752120, which is located in the zinc finger protein gene ZNF432, and has unknown function. Conclusions Inhaled corticosteroids appear to modulate the association of bronchodilator response with variant(s) in the ZNF432 gene among adults and children with asthma. Clinical Implications Clinicians who treat asthma patients with inhaled corticosteroids should be aware that the patient's genetic makeup likely influences response as measured in lung function. Capsule Summary Our study suggests that inhaled corticosteroids could influence the effect of multiple SNPs associated with bronchodilator response across the genome. PMID:24280104

  12. 1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.

    PubMed Central

    Penn, A; Nath, R; Pan, J; Chen, L; Widmer, K; Henk, W; Chung, F L

    2001-01-01

    Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group) for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. In the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm groups than in HEPA-filtered air controls. However, in the day 10 group, adduct levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalation, acrolein inhalation did not accelerate plaque development. Thus, even though repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposure to acrolein elicits repairable DNA damage to the artery wall. These results suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants can act. PMID:11333181

  13. Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler

    PubMed Central

    Esterlis, Irina; Mitsis, Effie M.; Batis, Jeffery C.; Bois, Frederic; Picciotto, Marina R.; Stiklus, Stephanie M.; Kloczynski, Tracy; Perry, Edward; Seibyl, John P.; McKee, Sherry; Staley, Julie K.; Cosgrove, Kelly P.

    2012-01-01

    The Nicotrol® (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of β2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9±6.4% occupancy of β2*-nAChRs 2–5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6±14.1% occupancy 1.5–5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of β2*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms. PMID:21029513

  14. Bronchoscopy-Derived Correlates of Lung Injury following Inhalational Injuries: A Prospective Observational Study

    PubMed Central

    Jones, Samuel W.; Zhou, Haibo; Ortiz-Pujols, Shiara M.; Maile, Robert; Herbst, Margaret; Joyner Jr, Benny L.; Zhang, Hongtao; Kesic, Matthew; Jaspers, Ilona; Short, Kathleen A.; Meyer, Anthony A.

    2013-01-01

    Background 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 studies have been done in humans. Methods We carried out a prospective observational study of patients admitted to the NC Jaycees Burn Center who were intubated and on mechanical ventilation for burns and suspected inhalational injury. Subjects were enrolled over an 8-month period and followed till discharge or death. Serial bronchial washings from clinically-indicated bronchoscopies were collected and analyzed for markers of cell injury and inflammation. These markers were compared with clinical markers of ALI. Results Forty-three consecutive patients were studied, with a spectrum of burn and inhalation injury severity. Visible soot at initial bronchoscopy and gram negative bacteria in the lower respiratory tract were associated with ALI in univariate analyses. Subsequent multivariate analysis also controlled for % body surface area burns, infection, and inhalation severity. Elevated IL-10 and reduced IL-12p70 in bronchial washings were statistically significantly associated with ALI. Conclusions Independently of several factors including initial inhalational injury severity, infection, and extent of surface burns, high early levels of IL-10 and low levels of IL-12p70 in the central airways are associated with ALI in patients intubated after acute burn/inhalation injury. Lower airway secretions can be collected serially in critically ill burn/inhalation injury patients and may yield important clues to specific pathophysiologic pathways. PMID:23691180

  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. Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine.

    PubMed Central

    Michel, O; Ginanni, R; Sergysels, R

    1992-01-01

    BACKGROUND: Bronchoconstriction has developed after inhalation of lipopolysaccharide in a dose of 20 micrograms in asthmatic patients and of 200 micrograms in normal subjects. This study set out to determine whether the bronchial response to lipopolysaccharide was related to non-specific bronchial responsiveness and atopy. METHODS: Sixteen subjects with a fall in specific airway conductance of 40% (PD40sGaw) after inhaling up to 900 micrograms histamine inhaled 20 micrograms lipopolysaccharide (from Escherichia coli type 026:B6) a week after bronchial challenge with a control solution of saline. The bronchial response over five hours was measured as change in FEV1 and area under the FEV1-time curve. RESULTS: FEV1 fell significantly more after lipopolysaccharide than after diluent inhalation, the difference in mean (SE) FEV1 being 4.6% (5.4%); response was maximal 60 minutes after lipopolysaccharide inhalation and lasted more than five hours. Histamine PD20FEV1 and PD40sGaw correlated with the fall in FEV1 after lipopolysaccharide inhalation. There was no difference in the proportions of responders and non-responders to lipopolysaccharide who were atopic. CONCLUSION: Lipopolysaccharide induced bronchial obstruction is associated with non-specific responsiveness but not with atopy. PMID:1585294

  17. Influence of inhaler technique on asthma and COPD control: a multicenter experience

    PubMed Central

    Dudvarski Ilic, Aleksandra; Zugic, Vladimir; Zvezdin, Biljana; Kopitovic, Ivan; Cekerevac, Ivan; Cupurdija, Vojislav; Perhoc, Nela; Veljkovic, Vesna; Barac, Aleksandra

    2016-01-01

    Background The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life. Improvement of patients’ adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD. Objective The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up. Methods A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients’ usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients’ subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires. Results Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P<0.001). Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P<0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively; P<0.001). Patients’ subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (P<0.001). Conclusion Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients’ inhalation technique with different

  18. Extrapulmonary transport of MWCNT following inhalation exposure

    PubMed Central

    2013-01-01

    Background Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the tracheobronchial lymphatics, parietal pleura, respiratory musculature and/or extrapulmonary organs. Male C57BL/6 J mice were exposed in a whole-body inhalation system to a 5 mg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks, lung burden 28.1 ug/lung). At 1 day and 336 days after the 12 day exposure period, mice were anesthetized and lungs, lymph nodes and extrapulmonary tissues were preserved by whole body vascular perfusion of paraformaldehyde while the lungs were inflated with air. Separate, clean-air control groups were studied at 1 day and 336 days post-exposure. Sirius Red stained sections from lung, tracheobronchial lymph nodes, diaphragm, chest wall, heart, brain, kidney and liver were analyzed. Enhanced darkfield microscopy and morphometric methods were used to detect and count MWCNT in tissue sections. Counts in tissue sections were expressed as number of MWCNT per g of tissue and as a percentage of total lung burden (Mean ± S.E., N = 8 mice per group). MWCNT burden in tracheobronchial lymph nodes was determined separately based on the volume density in the lymph nodes relative to the volume density in the lungs. Field emission scanning electron microscopy (FESEM) was used to examine MWCNT structure in the various tissues. Results Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively. Although agglomerates account for approximately 54% of lung burden, only singlet MWCNT were observed in the diaphragm, chest wall, liver, kidney, heart and brain. At one day post exposure, the average length of singlet MWCNT in liver and kidney, was comparable to that of singlet MWCNT in the lungs 8.2 ± 0.3 versus 7.5 ± 0.4 um, respectively. On average, there were 15,371 and 109,885 fibers per gram in

  19. White phosphorus burns and arsenic inhalation: a toxic combination.

    PubMed

    Berndtson, Allison E; Fagin, Alice; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

    2014-01-01

    White phosphorus is a common industrial and military compound, which can cause severe thermal and chemical burns beyond what would be predicted from body surface area alone. The authors present a rare case of a 45-year-old male patient who suffered white phosphorus burns combined with arsenic inhalation because of an industrial accident. The presented case is used to review the history and the toxicities of these chemicals as well as current methods of treatment. A literature review was performed to summarize the current knowledge of white phosphorus burns, as well as arsenic poisoning, and no similar case reports of the two combined were found. The patient ultimately recovered and was discharged, though with significant chronic complications. This case highlights the risk of burns and inhalation injury present in industrial manufacturing jobs, as well as the potential severity of these conditions. The systemic effects of chemicals absorbed across burned skin and via inhalation were the main contributors to our patient's severe illness, and required more intensive treatment than the burns themselves. Arsenic toxicity is rare and could easily have been missed without the appropriate patient history.

  20. 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

  1. Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

    PubMed

    Bonam, Matthew; Christopher, David; Cipolla, David; Donovan, Brent; Goodwin, David; Holmes, Susan; Lyapustina, Svetlana; Mitchell, Jolyon; Nichols, Steve; Pettersson, Gunilla; Quale, Chris; Rao, Nagaraja; Singh, Dilraj; Tougas, Terrence; Van Oort, Mike; Walther, Bernd; Wyka, Bruce

    2008-01-01

    The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

  2. Inhalational drug delivery from seven different spacer devices.

    PubMed Central

    Barry, P. W.; O'Callaghan, C.

    1996-01-01

    BACKGROUND: A study was performed to determine in vitro the difference in drug output of seven currently available spacer devices when used with different inhaled medications. METHODS: A glass multistage liquid impinger (MSLI) was used to determine the amount of disodium cromoglycate (DSCG, 5 mg), salbutamol (100 micrograms), or budesonide (200 micrograms) obtained in various particle size ranges from metered dose inhalers (MDIs) actuated directly into the MSLI or via one of seven different spacer devices; the Fisonair, Nebuhaler, Volumatic, Inspirease, Aerochamber, Aerosol Cloud Enhancer, and Dynahaler. RESULTS: In particles smaller than 5 microns in diameter the dose of DSCG recovered from the Fisonair and Nebuhaler was 118% and 124%, respectively, of that recovered using the MDI alone. The dose recovered from the smaller volume spacers was 90% (Inspirease), 36% (Aerochamber), 33% (Aerosol Cloud Enhancer), and 21% (Dynahaler) of that from the MDI alone. The Volumatic increased the amount of salbutamol in particles smaller than 5 microns to 117% of that from the MDI, and the Inspirease and Aerochamber spacers decreased it by nearly 50%. The amount of budesonide in small particles recovered after use of the Nebuhaler, Inspirease, and the Aerochamber was 92%, 101%, and 78%, respectively, of that from the MDI alone. CONCLUSIONS: Under the test conditions used, large volume spacers such as the Fisonair, Nebuhaler, and Volumatic delivered significantly more DSCG and salbutamol than the smaller spacers tested. The differences between spacers were less for budesonide than the other medications studied. This study shows that there are significant differences in the amount of drug available for inhalation when different spacers are used as inhalational aids with different drugs. Spacer devices need to be fully evaluated for each drug prescribed for them. Images PMID:8795674

  3. 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…

  4. Influence of peak inspiratory flow rates and pressure drops on inhalation performance of dry powder inhalers.

    PubMed

    Hira, Daiki; Okuda, Tomoyuki; Ichihashi, Mika; Mizutani, Ayano; Ishizeki, Kazunori; Okada, Toyoko; Okamoto, Hirokazu

    2012-01-01

    The aim of this study was to reveal the relationship between human inspiratory flow patterns and the concomitant drops in pressure in different inhalation devices, and the influence of the devices on inhalation performance. As a model formulation for inhalers, a physically mixed dry powder composed of salbutamol sulfate and coarse lactose monohydrate was selected. The drops in pressure at 28.3 L/min of three inhalation devices, Single-type, Dual-type, and Reverse-type, was 1.0, 5.1, and 8.7 kPa, respectively. Measurements of human inspiratory patterns revealed that although the least resistant device (Single) had large inter- and intra-individual variation of peak flow rate (PFR), the coefficients of variation of PFR of the three devices were almost the same. In tests with a human inspiratory flow simulator in vitro, inhalation performance was higher, but the variation in inhalation performance in the range of human flow patterns was wider, for the more resistant device. To minimize the intra- and inter-individual variation in inhalation performance for the model formulation in this study, a formulation design that allows active pharmaceutical ingredient to detach from the carrier with a lower inhalation flow rate is needed.

  5. Metered-dose inhalers and dry powder inhalers in aerosol therapy.

    PubMed

    Hess, Dean R

    2005-10-01

    Inhaled drug delivery is an important part of the armamentarium of clinicians caring for patients with pulmonary disease. An increasing variety of metered-dose inhalers and dry powder inhalers are becoming available. This has been driven by the development of new formulations and the impending ban on chlorofluorocarbon propellants. The result is a proliferation of devices, resulting in a confusing number of choices for the clinician, as well as confusion for patients trying to use these devices correctly. The presenters at this conference included many of the world's authorities on metered-dose inhalers and dry powder inhalers, and were an appropriate mix of academic aerosol scientists, clinician researchers with an interest in aerosol therapy, and aerosol scientists working for industry. Improper inhaler technique is common among patients. One of the important take-home messages of this conference is the importance of clinicians knowledgeable in the use of aerosol delivery devices and clinicians' ability to teach patients how to use these devices correctly. Respiratory therapists are uniquely positioned to provide this service, and there is evidence that respiratory therapists may do this better than others. The proceedings of this conference provide the current state of the art of metered-dose inhalers and dry powder inhalers.

  6. Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma

    PubMed Central

    Lee, Daniel K C; Jackson, Catherine M; Currie, Graeme P; Cockburn, Wendy J; Lipworth, Brian J

    2003-01-01

    Aims Inhalers combining long acting β2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma. Methods Twenty-nine patients with mean FEV1 (± SEM) of 78 ± 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 µg + formoterol 12 µg (BUD + FM) combination twice daily followed by 1 week of BUD 400 µg alone twice daily, or 4 weeks of fluticasone propionate 250 µg + salmeterol 50 µg (FP + SM) combination twice daily followed by 1 week of FP 250 µg alone twice daily. Measurements were made at baseline and following each randomized treatment. Results FEV1 increase from pretreatment baseline as mean (± SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 ± 1%) vs BUD (2 ± 1%), and for FP + SM (8 ± 1%) vs FP (2 ± 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 ± 1%), BUD (24 ± 1%), FP + SM (23 ± 1%) and FP (23 ± 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 ± 35.5) vs BUD (281.1 ± 52.8), and with FP + SM (553.1 ± 34.1) vs FP (368.3 ± 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments. Conclusions Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on

  7. Conference report: 2nd Medicon Valley Inhalation Symposium.

    PubMed

    Lastow, Orest

    2014-02-01

    2nd Medicon Valley Inhalation Symposium 16 October 2013, Lund, Sweden The 2nd Medicon Valley Inhalation Symposium was arranged by the Medicon Valley Inhalation Consortium. It was held at the Medicon Village, which is the former AstraZeneca site in Lund, Sweden. It was a 1 day symposium focused on inhaled drug delivery and inhalation product development. 120 delegates listened to 11 speakers. The program was organized to follow the value chain of an inhalation product development. This year there was a focus on inhaled biomolecules. The inhaled delivery of insulin was covered by two presentations and a panel discussion. The future of inhaled drug delivery was discussed together with an overview of the current market situation. Two of the inhalation platforms, capsule inhalers and metered-dose inhalers, were discussed in terms of the present situation and the future opportunities. Much focus was on the regulatory and intellectual aspects of developing inhalation products. The manufacturing of a dry powder inhaler requires precision filling of powder, and the various techniques were presented. The benefits of nebulization and nasal delivery were illustrated with some case studies and examples. The eternal challenge of poor compliance was addressed from an industrial design perspective and some new approaches were introduced.

  8. Dose to lung from inhaled tritiated particles.

    PubMed

    Richardson, R B; Hong, A

    2001-09-01

    Tritiated particulate materials are of potential hazard in fission, fusion, and other tritium handling facilities. The absorbed fractions (fraction of energy emitted that is absorbed by the target region) are calculated for tritiated particles deposited in the alveolar-interstitial (AI) region of the respiratory tract. The energy absorbed by radiologically sensitive tissue irradiated by tritiated particles, in regions of the lung other than in the AI region, is negligible. The ICRP Publication 71 assumes the absorbed fraction is unity for tritium deposited in the AI region. We employed Monte Carlo methods in a model to evaluate the energy deposition in the wall of the alveolar sac from particles of tritiated beryllium, tritiated graphite, titanium tritide, tritiated iron hydroxide and zirconium tritide. For the five materials examined, the absorbed fraction in alveolar tissue ranged from 0.31 to 0.61 for particles of 1 microm physical diameter and 0.07 to 0.21 for 5 microm diameter particles. The dose to alveolar tissue, for an acute inhalation of tritiated particles by an adult male worker, was calculated based on the ICRP 66 lung model and the particle dissolution model of Mercer (1967). For particles of 5 microm activity median aerodynamic diameter (AMAD), the committed equivalent dose to alveolar tissue, calculated for the five materials, ranged from 32-42%, respectively, of the committed equivalent dose derived assuming the absorbed fractions were unity. PMID:11513464

  9. 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

  10. 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.

  11. Inhaler devices: what remains to be done?

    PubMed

    Smith, Ian J; Bell, John; Bowman, Nic; Everard, Mark; Stein, Stephen; Weers, Jeffry G

    2010-12-01

    The 1000 Years of Pharmaceutical Aerosols Conference convened posing the question; "what remains to be done?" When applying this question to the topic of inhaler devices, two hugely different perspectives could be taken. On the one hand, it could be argued that because there is an array of delivery systems available and the industry, prescribing physicians and patients alike have considerable choice, why would we believe it necessary to do anything further? On the other hand, as an industry, we are constantly reminded by our "customers" that the inhaler devices available are less than adequate, and in some cases woefully inadequate, that they are not "patient" friendly, not intuitive to use and importantly do nothing to encourage the patient to take the medication as intended and as prescribed. So, taking the second point of view as more reflective of reality--the Voice of the Customer--our starting point must be that there is still much to do in the field of inhaler devices. The purpose of this article is to outline some key basic requirements for inhaler design and perhaps to question some of the entrenched thinking that has pervaded inhaler product design for too many years.

  12. The dispersion behaviour of dry powder inhalation formulations cannot be assessed at a single inhalation flow rate.

    PubMed

    Grasmeijer, Floris; de Boer, Anne H

    2014-04-25

    The dispersion performances of inhalation powders are often tested at only one inhalation flow rate in mechanistic formulation studies. This limited approach is challenged by studies showing that interactions exist between inhalation flow rate and the effects on dispersion performance of several formulation variables. In this note we explain that such interactions with inhalation flow rate are, in fact, always to be expected. Because these interactions may greatly affect conclusions concerning the effects of formulation variables and their underlying mechanisms, the utility of future dry powder inhalation formulation studies may benefit from an approach in which dispersion performance is by default tested over a range of inhalation flow rates.

  13. Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate

    PubMed Central

    Said, Amira S A; Harding, Lindsay P; Chrystyn, Henry

    2012-01-01

    AIM Urinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP). METHOD Ethics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 µg BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10 100 µg inhalations from a Qvar® Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 µg inhalations from a Clenil® pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone-17-monopropionate (17-BMP) and beclometasone (BOH) were measured. RESULTS No BDP, 17-BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17-BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17-BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %. CONCLUSION The urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies. PMID:22299644

  14. 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

  15. The pathophysiology of smoke inhalation injury.

    PubMed Central

    Stephenson, S F; Esrig, B C; Polk, H C; Fulton, R L

    1975-01-01

    The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiecy was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant. Images Fig. 8. Fig. 10. PMID:242281

  16. 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.

  17. 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...

  18. 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

  19. 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. PMID:27314052

  20. Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

    PubMed Central

    Reissig, Chad J.; Harrison, Joseph A.; Carter, Lawrence P.; Griffiths, Roland R.

    2014-01-01

    Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low. PMID:25199955

  1. Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin Free Base in Non-Cystic Fibrosis Bronchiectasis Patients

    PubMed Central

    Hagedoorn, Paul; Alffenaar, Jan-Willem C.; van der Werf, Tjip S.; Kerstjens, Huib A. M.; Frijlink, Henderik W.; de Boer, Anne H.

    2016-01-01

    Rationale Bronchiectasis is a condition characterised by dilated and thick-walled bronchi. The presence of Pseudomonas aeruginosa in bronchiectasis is associated with a higher hospitalisation frequency and a reduced quality of life, requiring frequent and adequate treatment with antibiotics. Objectives To assess local tolerability and the pharmacokinetic parameters of inhaled excipient free dry powder tobramycin as free base administered with the Cyclops dry powder inhaler to participants with non-cystic fibrosis bronchiectasis. The free base and absence of excipients reduces the inhaled powder dose. Methods Eight participants in the study were trained in handling the device and inhaling correctly. During drug administration the inspiratory flow curve was recorded. Local tolerability was assessed by spirometry and recording adverse events. Serum samples were collected before, and 15, 30, 45, 60, 75, 90, 105, 120 min; 4, 8 and 12 h after inhalation. Results and Discussion Dry powder tobramycin base was well tolerated and mild tobramycin-related cough was reported only once. A good drug dose-serum concentration correlation was obtained. Relatively small inhaled volumes were computed from the recorded flow curves, resulting in presumably substantial deposition in the central airways—i.e., at the site of infection. Conclusions In this first study of inhaled dry powder tobramycin free base in non-cystic fibrosis bronchiectasis patients, the free base of tobramycin and the administration with the Cyclops dry powder device were well tolerated. Our data support further clinical studies to evaluate safety and efficacy of this compound in this population. PMID:26959239

  2. 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…

  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 172.429 - 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. Mathematics Achievement and Inhalant Allergy in Middle School Children.

    ERIC Educational Resources Information Center

    Burchfield, Patricia Crosby; Easterday, Kenneth E.

    1991-01-01

    This study of 137 students in grades 6 through 8 found no significant differences between the mean scores of sixth and seventh grade students with and without inhalant allergies on a mathematics concepts subtest, but found that eighth grade students with inhalant allergies performed better than eighth grade students without inhalant allergies.…

  14. 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.

  15. 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

  16. Inhaled antibiotics in mechanically ventilated patients.

    PubMed

    Michalopoulos, A S; Falagas, M E

    2014-02-01

    During the last decade, inhaled antibiotics, especially colistin, has been widely used worldwide as a therapeutic option, supplementary to conventional intravenous antibiotics, for the treatment of multidrug-resistant (MDR) Gram-negative nosocomial and ventilator-associated pneumonia (VAP). Antimicrobial aerosols are commonly used in mechanically ventilated patients with VAP, although information regarding their efficacy and optimal technique of administration has been limited. Recent studies showed that the administration of inhaled antibiotics in addition to systemic antibiotics provided encouraging results associated with low toxicity for the management of VAP mainly due to MDR Gram negative bacteria. Although the theory behind aerosolized administration of antibiotics seems to be sound, there are limited data available to support the routine use of this modality since very few randomized controlled trials (RCTs) have still examined the efficacy of this approach in patients with VAP. Additionally, this route of antibiotic delivery has not been approved until now neither by the FDA nor by the European Medicines Agency (EMEA) in patients with VAP. However, since the problem of VAP due to MDR bacteria has been increased worldwide RCTs are urgently needed in order to prove the safety, efficiency and efficacy of inhaled antimicrobial agents administered alone or in conjunction with parenteral antibiotics for the management of VAP in critically ill patients. Indeed, more data are needed to establish the appropriate role of inhaled antibiotics for the treatment of VAP.

  17. Collagen breakdown and nitrogen dioxide inhalation.

    PubMed

    Hatton, D V; Leach, C S; Nicogossian, A E

    1977-01-01

    Measurements of urinary hydroxylysine glycosides indicate that considerable collagen degradation occurred during the reentry into the earth's atmosphere of the American astronauts of the Apollo-Soyuz mission. Since the crew accidentally inhaled nitrogen dioxide, a recognized pulmonary irritant, and showed clinical and roentgenographic signs of diffuse chemical pneumonitis, it is likely that collagen degradation occurred in the pulmonary parenchyma.

  18. Parental Influences on Inhalant Use by Children.

    ERIC Educational Resources Information Center

    Smith, Stephanie S.; And Others

    1991-01-01

    Among 78 mothers of Mexican-American adolescent inhalant users, many did not adhere to traditional marital and maternal roles, but this was not related to child's drug use. Child's drug use was related to indicators of household stability, including parents' marital status, father's employment status, and maternal emotional adjustment. (Author/SV)

  19. 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…

  20. 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

  1. Subacute Inhalation Toxicity of 3-Methylpentane.

    PubMed

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

    2016-07-01

    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

  2. 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

  3. Influence of Delivery Devices on Efficacy of Inhaled Fluticasone Propionate: A Comparative Study in Stable Asthma Patients

    PubMed Central

    Kolasani, Bhanu Prakash; Lanke, Venu Madhavi; Diyya, Sudheer

    2013-01-01

    Background: Inhaled corticosteroids are the preferred treatment for long-term control of all grades of persistent asthma. These are administered by various delivery devices with very little information whether these devices can affect the efficacy of inhaled corticosteroids. Fluticasone propionate is a relatively new inhalational corticosteroid compared to older ones like beclomethasone and budesonide. Aims & Objective: To assess the relative efficacy of fluticasone propionate administered from different delivery devices to adult patients of chronic stable bronchial asthma as measured by pulmonary function test parameters. Material and Methods: This prospective study was undertaken to assess the relative efficacy of fluticasone propionate administered from different delivery devices to adult patients of chronic stable bronchial asthma as measured by pulmonary function test parameters. Fourty eight subjects were administered, fluticasone propionate (250 μg) by dry powder inhaler, metered dose inhaler, metered dose inhaler with spacer and fluticasone (1mg) via nebulizer consecutively each week for four weeks under direct supervision. Pulmonary function test was done before and one hour after administration of the drug on each visit. Results: After excluding nine patients who were lost to follow up, data was analysed for the remaining thirty nine patients and no significant difference in peak expiratory flow rate (p=0.77), forced expiratory volume in one second (p=0.95), forced vital capacity (p=0.24) and forced expiratory volume in one second and forced vital capacity ratio (p=0.22) was seen after giving fluticasone by different devices. Conclusion: Fluticasone propionate delivered by different devices like dry powder inhaler, metered dose inhaler, metered dose inhaler with spacer and nebulizer have similar effect on lung function in patients of chronic stable bronchial asthma and may be used interchangeably. PMID:24179895

  4. Risk for Inhalant Initiation Among Middle School Students: Understanding Individual, Family, and Peer Risk and Protective Factors

    PubMed Central

    Ober, Allison J.; Miles, Jeremy N. V.; Ewing, Brett; Tucker, Joan S.; D’Amico, Elizabeth J.

    2013-01-01

    Objective: Because initiation of inhalants at an early age is associated with a range of health and behavioral problems, including an increased likelihood of inhalant dependence (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), we conducted discrete time survival analyses to determine the role of time-invariant and time-variant (over five waves) risk and protective factors as well as grade in inhalant initiation among middle school students. Method: The current study uses data from 3,215 students who were initially surveyed as sixth graders in 2008–2009 and were resurveyed in seventh and eighth grades. Students were part of a larger substance use prevention trial conducted in greater Los Angeles. The sample is racially/ethnically diverse (54% Hispanic/Latino, 16% Asian, 14% White, 3% African American) and 51% male. Results: Seventeen percent of youths initiated inhalants during middle school. Higher drug refusal self-efficacy, familism (i.e., values related to family), and parental respect were associated with decreased odds of inhalant initiation. Having a significant adult or older sibling who used substances was associated with increased risk of initiation, but adult influence declined linearly and by the end of seventh grade was no longer a risk factor. Self-rated popularity was associated with inhalant initiation in seventh grade only, and perceived substance use by peers was associated with inhalant initiation in sixth grade only. Conclusions: The influence of adults, siblings, and peers on inhalant use may be strongest in sixth and seventh grade. Interventions to prevent inhalant initiation should target sixth and seventh graders, address influence by family and peers, and provide skills training to improve drug refusal self-efficacy. PMID:24172109

  5. The ADMIT series--issues in inhalation therapy. 5) Inhaler selection in children with asthma.

    PubMed

    Pedersen, Søren; Dubus, Jean Christophe; Crompton, Graham K

    2010-09-01

    Many children with asthma do not use their inhalers correctly and consequently gain little or no therapeutic benefit from the treatment. The focus of inhalation therapy should be on those inhalers which are easiest to use correctly by various groups of children and the amount of tuition and training required to obtain a correct technique. It is recommended that clinicians focus on a limited number of inhalers. Most children can be taught effective inhalation therapy by using a pMDI, a pMDI with a spacer ,or a DPI. Most preschool children can be taught effective use of a pMDI and spacer with a valve system and a face mask. Therefore, this is the preferred mode of delivery in these age groups. When the child is capable of using the spacer without a face mask this administration technique should be adopted. In older children pMDIs are more difficult to use correctly than a pMDI with a spacer, a DPI ,or a breath-actuated pMDI. Because DPIs and breath-actuated pMDIs are more convenient to use these devices are normally considered the preferred inhalation devices in these age groups except for administration of beclometasone dipropionate, which for safety reasons should be delivered by a spacer.

  6. Clinical expert panel on monitoring potential lung toxicity of inhaled oligonucleotides: consensus points and recommendations.

    PubMed

    Alton, Eric W; Boushey, Homer A; Garn, Holger; Green, Francis H; Hodges, Michael; Martin, Richard J; Murdoch, Robert D; Renz, Harald; Shrewsbury, Stephen B; Seguin, Rosanne; Johnson, Graham; Parry, Joel D; Tepper, Jeff; Renzi, Paolo; Cavagnaro, Joy; Ferrari, Nicolay

    2012-08-01

    Oligonucleotides (ONs) are an emerging class of drugs being developed for the treatment of a wide variety of diseases including the treatment of respiratory diseases by the inhalation route. As a class, their toxicity on human lungs has not been fully characterized, and predictive toxicity biomarkers have not been identified. To that end, identification of sensitive methods and biomarkers that can detect toxicity in humans before any long term and/or irreversible side effects occur would be helpful. In light of the public's greater interests, the Inhalation Subcommittee of the Oligonucleotide Safety Working Group (OSWG) held expert panel discussions focusing on the potential toxicity of inhaled ONs and assessing the strengths and weaknesses of different monitoring techniques for use during the clinical evaluation of inhaled ON candidates. This white paper summarizes the key discussions and captures the panelists' perspectives and recommendations which, we propose, could be used as a framework to guide both industry and regulatory scientists in future clinical research to characterize and monitor the short and long term lung response to inhaled ONs.

  7. Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate

    PubMed Central

    Mahachoklertwatta..., P; Sudkronrayudh, K; Direkwattanachai, C; Choubtum, L; Okascharoen, C

    2004-01-01

    Aims: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. Methods: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250–750 µg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. Results: Eighteen asthmatic patients (10 boys, 8 girls), aged 7–17 years received inhaled fluticasone therapy at a median dose of 477 µg/m2 per day for 5–16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2–3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. Conclusion: After therapy for asthma with inhaled fluticasone at approximately 500 µg daily for up to 16 weeks, half the children had evidence of adrenal suppression. PMID:15499064

  8. 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.

  9. Validation of a metered dose inhaler electronic monitoring device: implications for asthma clinical trial use

    PubMed Central

    Pilcher, Janine; Holliday, Mark; Ebmeier, Stefan; McKinstry, Steve; Messaoudi, Fatiha; Weatherall, Mark; Beasley, Richard

    2016-01-01

    Background The SmartTouch Ventolin monitor (Adherium, Auckland, New Zealand) is an electronic monitor for use with a Ventolin metered dose inhaler, which records the date and time of inhaler actuations. This technology has the potential to allow in-depth analysis of patterns of inhaler use in clinical trial settings. The aim of this study was to determine the accuracy of the SmartTouch Ventolin monitor in recording Ventolin actuations. Methods 20 SmartTouch Ventolin monitors were attached to Ventolin metered dose inhalers. Bench testing was performed over a 10-week period, to reflect the potential time frame between visits in a clinical trial. Inhaler actuations were recorded in a paper diary, which was compared with data uploaded from the monitors. Results 2560 actuations were performed during the 10-week study period. Monitor sensitivity for diary-recorded actuations was 99.9% with a lower 97.5% confidence bound of 99.7%. The positive predictive value for diary-recorded actuations was 100% with a 97.5% lower confidence bound of 99.9%. Conclusions The SmartTouch Ventolin monitor is highly accurate in recording and retaining electronic data. It can be recommended for use in clinical trial settings in which training and quality control systems are incorporated into study protocols to ensure accurate data acquisition. PMID:27026805

  10. Inhalation studies for the safety assessment of nanomaterials: status quo and the way forward.

    PubMed

    Landsiedel, Robert; Ma-Hock, Lan; Haussmann, Hans-Juergen; van Ravenzwaay, Ben; Kayser, Martin; Wiench, Karin

    2012-01-01

    While technical and medical potential offered by nanotechnologies increase, the safety assessment of engineered nanomaterials (NMs) needs to follow this pace. Inhalation is a major route of occupational and environmental exposure, and is most relevant for most of the respective safety assessment studies. Control and generation of aerosol from the test materials for this route of administration are technically demanding, and not surprisingly, there are relatively few NMs tested in toxicokinetic, short-term, and subchronic inhalation studies. These studies were in part adapted to the peculiarities of inhaled NMs, but few were also conducted according to organization for economic co-operation and development (OECD) test guidelines. Inhalation studies on the potential to develop chronic diseases, or studies to check the potential analogy to cardiovascular diseases associated with adverse health effects from ambient air pollution, are largely missing. On the way forward, appropriate inhalation studies need to be performed on a number of NMs to assess their hazards and to provide a sound database for correlation and validation of alternative in vitro methods. Moreover, these studies can potentially aid in the grouping of different NMs based on their biokinetics or biological effects. For carcinogenic and cardiovascular effects, research studies are needed to verify-or disprove-the relevance and the mechanisms by which NMs contribute to these effects.

  11. 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

  12. 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

  13. Agglomerate behaviour of fluticasone propionate within dry powder inhaler formulations.

    PubMed

    Le, V N P; Robins, E; Flament, M P

    2012-04-01

    Due to their small size, the respirable drug particles tend to form agglomerates which prevent flowing and aerosolisation. A carrier is used to be mixed with drug in one hand to facilitate the powder flow during manufacturing, in other hand to help the fluidisation upon patient inhalation. Depending on drug concentration, drug agglomerates can be formed in the mixture. The aim of this work was to study the agglomeration behaviour of fluticasone propionate (FP) within interactive mixtures for inhalation. The agglomerate phenomenon of fluticasone propionate after mixing with different fractions of lactose without fine particles of lactose (smaller than 32 μm) was demonstrated by the optical microscopy observation. A technique measuring the FP size in the mixture was developed, based on laser diffraction method. The FP agglomerate sizes were found to be in a linear correlation with the pore size of the carrier powder bed (R(2)=0.9382). The latter depends on the particle size distribution of carrier. This founding can explain the role of carrier size in de-agglomeration of drug particles in the mixture. Furthermore, it gives more structural information of interactive mixture for inhalation that can be used in the investigation of aerosolisation mechanism of powder. According to the manufacturing history, different batches of FP show different agglomeration intensities which can be detected by Spraytec, a new laser diffraction method for measuring aerodynamic size. After mixing with a carrier, Lactohale LH200, the most cohesive batch of FP, generates a lower fine particle fraction. It can be explained by the fact that agglomerates of fluticasone propionate with very large size was detected in the mixtures. By using silica-gel beads as ball-milling agent during the mixing process, the FP agglomerate size decreases accordingly to the quantity of mixing aid. The homogeneity and the aerodynamic performance of the mixtures are improved. The mixing aid based on ball

  14. 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

  15. Quantity and Quality of Inhaled Dose Predicts Immunopathology in Tuberculosis

    PubMed Central

    Fennelly, Kevin P.; Jones-López, Edward C.

    2015-01-01

    Experimental animal models of tuberculosis (TB) have convincingly demonstrated that inhaled dose predicts immunopathology and survival. In contrast, the importance of inhaled dose has generally not been appreciated in TB epidemiology, clinical science, or the practice of TB control. Infectiousness of TB patients has traditionally been assessed using microscopy for acid-fast bacilli in the sputum, which should be considered only a risk factor. We have recently demonstrated that cough aerosol cultures from index cases with pulmonary TB are the best predictors of new infection among household contacts. We suggest that cough aerosols of M. tuberculosis are the best surrogates of inhaled dose, and we hypothesize that the quantity of cough aerosols is associated with TB infection versus disease. Although several factors affect the quality of infectious aerosols, we propose that the particle size distribution of cough aerosols is an important predictor of primary upper airway disease and cervical lymphadenitis and of immune responses in exposed hosts. We hypothesize that large droplet aerosols (>5 μ) containing M. tuberculosis deposit in the upper airway and can induce immune responses without establishing infection. We suggest that this may partially explain the large proportion of humans who never develop TB disease in spite of having immunological evidence of M. tuberculosis infection (e.g., positive tuberculin skin test or interferon gamma release assay). If these hypotheses are proven true, they would alter the current paradigm of latent TB infection and reactivation, further demonstrating the need for better biomarkers or methods of assessing TB infection and the risk of developing disease. PMID:26175730

  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. 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.

  18. 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

  19. Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes.

    PubMed

    Engel, T; Scharling, B; Skovsted, B; Heinig, J H

    1992-04-01

    1. The efficacy of a metered dose inhaler (MDI) is highly dependent on the mode of inhalation. The relatively high built-in resistance in the Turbohaler (TBH), a new dry powder inhaler device for inhalation of terbutaline sulphate and budesonide, reduces the flow during inhalation. We compared five different modes of inhalation using the terbutaline TBH in 10 stable asthmatic subjects, who were tested on 5 consecutive days. 2. Measurement of 10 different parameters of pulmonary function indicated that the full bronchodilatory effect of an inhaled dose was already achieved at 5 min after the inhalation. Inspiratory flows through the TBH varying from 34 to 88 l min-1 resulted in comparable bronchodilation, and a previous exhalation to residual volume proved of no value. However, if, prior to inhalation, an exhalation through the device was performed, a substantially reduced effect was seen. 3. Reducing the inspiratory flow to approximately 34 l min-1 produced slightly reduced side effects and lower plasma terbutaline concentrations. PMID:1576070

  20. Relative bioavailability of terbutaline to the lung following inhalation, using urinary excretion

    PubMed Central

    Abdelrahim, Mohamed E; Assi, Khaled H; Chrystyn, Henry

    2011-01-01

    AIMS The aim of the study was to determine the relative lung and systemic bioavailability of terbutaline. METHODS On separate days healthy volunteers received 500 µg terbutaline study doses either inhaled from a metered dose inhaler or swallowed as a solution with and without oral charcoal. Urine samples were provided at timed intervals post dosing. RESULTS Mean (SD) urinary terbutaline 0.5 h post inhalation, in 12 volunteers, with (IC) and without (I) oral charcoal and oral (O) dosing was 7.4 (2.2), 6.5 (2.1) and 0.2 (0.2) µg. I and IC were similar and both significantly greater than O (P < 0.001). Urinary 24 h terbutaline post I was similar to IC + O. The method was linear and reproducible, similar to that of the urinary salbutamol method. CONCLUSIONS The urinary salbutamol pharmacokinetic method post inhalation applies to terbutaline. Terbutaline study doses can replace routine salbutamol during these studies when patients are studied. PMID:21395654

  1. 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,…

  2. Interspecies modeling of inhaled particle deposition patterns

    SciTech Connect

    Martonen, T.B.; Zhang, Z.; Yang, Y.

    1992-01-01

    To evaluate the potential toxic effects of ambient contaminants or therapeutic effects of airborne drugs, inhalation exposure experiments can be performed with surrogate laboratory animals. Herein, an interspecies particle deposition theory is presented for physiologically based pharmacokinetic modeling. It is derived to improve animal testing protocols. The computer code describes the behavior and fate of particles in the lungs of human subjects and a selected surrogate, the laboratory rat. In the simulations CO2 is integrated with exposure chamber atmospheres, and its concentrations regulated to produce rat breathing profiles corresponding to selected levels of human physical activity. The dosimetric model is used to calculate total, compartmental (i.e., tracheobronchial and pulmonary), and localized distribution patterns of inhaled particles in rats and humans for comparable ventilatory conditions. It is demonstrated that the model can be used to predetermine the exposure conditions necessary to produce deposition patterns in rats that are equivalent to those in humans at prescribed physical activities.

  3. Exogenous lipoid pneumonia caused by herbicide inhalation.

    PubMed

    Hotta, Takamasa; Tsubata, Yukari; Okimoto, Tamio; Hoshino, Teppei; Hamaguchi, Shun-Ichi; Isobe, Takeshi

    2016-09-01

    Exogenous lipoid pneumonia is caused by aspiration or inhalation of oily substances. Generally, lipoid pneumonia has non-specific clinical and radiological presentations and may be misdiagnosed as bacterial pneumonia. Our patient, a 68-year-old man who had been diagnosed with pneumonia on three previous occasions, was admitted to our hospital with a fourth similar episode. Computed tomography of the chest revealed extensive consolidations with air bronchograms in lung fields on the right side. The bronchoalveolar lavage fluid (BALF) increased ghost-like macrophages that stained positive for lipid. Our patient reported that he had sprayed herbicide in large quantities without wearing a mask. We analysed the BALF and herbicide by gas chromatography and diagnosed exogenous lipoid pneumonia caused by inhalation of herbicide. Clinicians should be aware of lipoid pneumonia, which may present as infectious pneumonia. PMID:27516888

  4. 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

  5. [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.

  6. Effects of inhaled acids on lung biochemistry

    SciTech Connect

    Last, J.A.

    1989-02-01

    Effects of respirable aerosols of sulfuric acid, ammonium sulfate, sodium sulfite, and ammonium persulfate on lungs of rats are reviewed. The literature regarding interactions between ozone or nitrogen dioxide and acidic aerosols (ammonium sulfate, sulfuric acid) is discussed. An unexpected interaction between nitrogen dioxide and sodium chloride aerosol is also discussed. An attempt is made to identify bases for prediction of how and when acid aerosols might potentiate effects of inhaled gases.

  7. Effects of inhaled acids on lung biochemistry.

    PubMed

    Last, J A

    1989-02-01

    Effects of respirable aerosols of sulfuric acid, ammonium sulfate, sodium sulfite, and ammonium persulfate on lungs of rats are reviewed. The literature regarding interactions between ozone or nitrogen dioxide and acidic aerosols (ammonium sulfate, sulfuric acid) is discussed. An unexpected interaction between nitrogen dioxide and sodium chloride aerosol is also discussed. An attempt is made to identify bases for prediction of how and when acid aerosols might potentiate effects of inhaled gases.

  8. 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

  9. 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

  10. Inhalant abuse among adolescents: neurobiological considerations.

    PubMed

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

    2008-05-01

    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, GABA(A), glycine and 5HT(3) 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 GABA(A) 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

  11. Enhanced interleukin activity following asbestos inhalation.

    PubMed Central

    Hartmann, D P; Georgian, M M; Oghiso, Y; Kagan, E

    1984-01-01

    Asbestos inhalation can cause pulmonary fibrosis and is associated with a variety of immunological abnormalities. The purpose of this study was to evaluate the effects of asbestos inhalation on interleukin-1 (IL-1) and interleukin-2 (IL-2) production in a rodent model. Two groups of rats were exposed, by intermittent inhalation, to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A third (control) group of rats was sham exposed to clean air. Animals from the three exposure groups were thereafter immunized (or not immunized) with fetal calf serum antigens. In order to assay interleukin activity, supernatants were generated from cultures containing alveolar macrophages and autologous splenic lymphocytes, and from cultures containing alveolar macrophages alone. Using assay systems designed to detect IL-1 and IL-2 functional activity, the supernatants were evaluated for their capacity to stimulate lymphoproliferation and fibroblast DNA synthesis. Macrophage-lymphocyte co-culture supernatants, when obtained from immunized, asbestos exposed rats, contained greater IL-1 and IL-2 activity than identical supernatants from immunized, sham exposed animals. These between group differences were not, however, observed in supernatants from unimmunized rats, or when supernatants were generated in the absence of immune lymphocytes. These observations suggest that asbestos exposure is associated with enhanced activation of lymphocytes by antigens. The possible relevance of these findings to asbestos related fibrogenesis and immunological stimulation is discussed. PMID:6608427

  12. The nasal distribution of metered dose inhalers.

    PubMed

    Newman, S P; Morén, P F; Clarke, S W

    1987-02-01

    The intranasal distribution of aerosol from a metered dose inhaler has been assessed using a radiotracer technique. Inhalers were prepared by adding 99Tcm-labelled Teflon particles (simulating the drug particles) to chlorofluorocarbon propellants, and scans of the head (and chest) taken with a gamma camera. Ten healthy subjects (age range 19-29 years) each performed two radioaerosol studies with the inhaler held in two different ways: either in a single position (vial pointing upwards) or in two positions (vial pointing upwards and then tilted by 30 degrees in the sagittal plane). The vast majority of the dose (82.5 +/- 2.8 (mean +/- SEM) per cent and 80.7 +/- 3.1 per cent respectively for one-position and two-position studies) was deposited on a single localized area in the anterior one-third of the nose, the initial distribution pattern being identical for each study. No significant radioaerosol was detected in the lungs. Only 18.0 +/- 4.7 per cent and 15.4 +/- 4.1 per cent of the dose had been removed by mucociliary action after 30 minutes, and it is probable that the remainder had not penetrated initially beyond the vestibule. Since the deposition pattern was highly localized and more than half the dose probably failed to reach the turbinates it is possible that the overall effect of nasal MDIs is suboptimal for the treatment of generalized nasal disorders.

  13. Fragrance sensitisers: Is inhalation an allergy risk?

    PubMed

    Basketter, David; Kimber, Ian

    2015-12-01

    It is well established that some fragrance substances have the potential to cause skin sensitisation associated with the development of allergic contact dermatitis (ACD). Fragrances are invariably relatively volatile leading to the consideration that inhalation of fragrances might be a relevant route for either the induction of allergic sensitisation or the elicitation of allergic reactions. Moreover, there has been increasing recognition that allergic sensitisation of the respiratory tract can be induced by topical exposure to certain chemical allergens. Here the central question addressed is whether inhalation exposure to fragrance allergens has the potential to cause skin and/or respiratory sensitisation via the respiratory tract, or elicit allergic symptoms in those already sensitised. In addressing those questions, the underlying immunobiology of skin and respiratory sensitisation to chemicals has been reviewed briefly, and the relevant experimental and clinical evidence considered. The essential mechanistic differences between skin and respiratory allergy appear consistent with other sources of information, including the phenomenon of ACD that can arise from topical exposure to airborne allergens, but in the absence of accompanying respiratory effects. The conclusion is that, in contrast to topical exposure (including topical exposure to airborne material), inhalation of fragrance sensitisers does not represent a health risk with respect to allergy.

  14. Inhaled nano- and microparticles for drug delivery

    PubMed Central

    El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

    2015-01-01

    The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

  15. PREFACE: Inhaled Particles X: 23-25 September 2008, Sheffield UK

    NASA Astrophysics Data System (ADS)

    Kenny, Lee; Hurley, Fintan

    2009-07-01

    Multi-disciplinary research is vital to the science of particle-mediated lung disease and a distinctive feature of the Inhaled Particles Conference series. Continuing this tradition, Inhaled Particles X brought together world-renowned and up-and-coming researchers from a wide range of specialist disciplines, but with a common interest and purpose: to understand better the nature of inhalable particles and their effects once inhaled, for the protection of workers' and public health. IPX was an integrative Conference, in three ways. First, as usual with Inhaled Particles, IPX welcomed the full range of disciplines and scientists concerned with protection of health from inhaled particles. This included engineers concerned with dust control; scientists characterising and modelling emissions; exposure measurement, in the field and in the laboratory; experts in particle deposition and clearance; toxicologists discovering mechanisms of damage; epidemiologists developing and applying methods to link exposure with risk; and those concerned with policy - with setting standards, with protection of individuals. Secondly, IPX was concerned with particles in the workplace, in outdoor air, and in the general indoor environment; and tried to find common threads and encourage cross-over of ideas between these three broad fields. And thirdly, IPX integrated experience and perspectives internationally, including issues such as silicosis and pneumoconiosis that are now unfashionable as research topics in the developed Western economies but still constitute a major public health risk internationally. Contributors to IPX were invited to submit extended abstracts for publication in these Proceedings; in addition, all authors were asked to prepare a short abstract. These short abstracts (including those attached to extended abstracts and papers) are collected and published together in this Conference Overview, to maintain the integrity of the Proceedings as a record of the Conference as a

  16. Airway epithelial NF-κB activation promotes the ability to overcome inhalational antigen tolerance

    PubMed Central

    Ather, Jennifer L.; Foley, Kathryn L.; Suratt, Benjamin T.; Boyson, Jonathan E.; Poynter, Matthew E.

    2015-01-01

    Background Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development of asthma. Objectives We examined in vivo whether pre-existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF-κB in conducting airway epithelial cells, and used a combination of in vivo and in vitro approaches to examine the mechanisms involved. Methods Wildtype and transgenic mice capable of expressing constitutively active IκB kinase β (CAIKKβ) in airway epithelium were tolerized to inhaled ovalbumin. Twenty-eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA on day 30 in an attempt to overcome inhalational tolerance. Results Following ovalbumin challenge on days 40-42, CAIKKβ mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyperresponsiveness. Increases in the CD103+ and CD11bHI lung dendritic cell populations were present in CAIKKβ mice on day 31. Bronchoalveolar lavage from mice expressing CAIKKβ mice induced CD4+ T cells to secrete TH2 and TH17 cytokines, an effect that required IL-4 and IL-1 signaling, respectively. CAIKKβ mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated mRNA expression of the TH2-polarizing cytokine IL-4. Finally, airway epithelial NF-kB activation induced allergic sensitization in CAIKKβ mice on Dox that required IL-4 and IL-1-signaling in vivo. Conclusions Our studies demonstrate that soluble mediators generated in response to airway epithelial NF-κB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL-1 and IL-4, on pulmonary dendritic cells as well as innate lymphoid and CD

  17. In vitro dry powder inhaler formulation performance considerations.

    PubMed

    Ziffels, Susanne; Bemelmans, Norman L; Durham, Phillip G; Hickey, Anthony J

    2015-02-10

    It has long been desired to match airflow conditions during formulation evaluation to those of relevance to lung deposition. In this context several strategies have been adopted involving sampling at different: flow rate (without consideration of flow conditions, e.g. shear, Reynolds number, work function); pressure drop (with and without consideration of flow conditions) and; flow rate and pressure drop. Performance testing has focused on the influence of these sampling conditions on delivered dose uniformity and aerodynamic particle size distribution. However, in order to be physiologically relevant it is also important to know when the drug was delivered with respect to initiation of airflow as variation in this parameter would influence lung deposition. A light obscuration method of detecting the dose delivered from a dry powder inhaler while sampling for aerodynamic particle size distributions (APSD) by inertial impaction has been developed. Four formulations of albuterol sulfate and budesonide in sieved and milled lactose, respectively, were dispersed and their rate of delivery monitored. The differences observed have the potential to impact the site of delivery in the lungs. The rate of delivery of drug is clearly an important companion measurement to delivered dose and APSD if the intent is to predict the similarity of in vivo performance of dry powder inhaler products.

  18. Checklists for powder inhaler technique: a review and recommendations.

    PubMed

    Basheti, Iman A; Bosnic-Anticevich, Sinthia Z; Armour, Carol L; Reddel, Helen K

    2014-07-01

    Turbuhaler and Diskus are commonly used powder inhaler devices for patients with respiratory disease. Their effectiveness is limited in part by a patient's ability to use them correctly. This has led to numerous studies being conducted over the last decade to assess the correct use of these devices by patients and health care professionals. These studies have generally used device-specific checklists to assess technique, this being the most feasible and accessible method for assessment. However, divergence between the checklists and scoring systems for the same device in different studies makes direct comparison of results difficult and at times inappropriate. Little evidence is available to assess the relative importance of different criteria; however, brief patient training based on specific inhaler technique checklists leads to significant improvement in asthma outcomes. This paper reviews common checklists and scoring systems used for Turbuhaler and Diskus, discusses the problem of heterogeneity between different checklists, and finally recommends suitable checklists and scoring systems for these devices based on the literature and previous findings. Only when similar checklists are used across different research studies will accurate comparisons and meta-analysis be possible.

  19. N-nitrosamines as "special case" leachables in a metered dose inhaler drug product.

    PubMed

    Norwood, Daniel L; Mullis, James O; Feinberg, Thomas N; Davis, Letha K

    2009-01-01

    N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.

  20. 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

  1. Nitrite inhalant use among young gay and bisexual men in Vancouver during a period of increasing HIV incidence

    PubMed Central

    Lampinen, Thomas M; Mattheis, Kelly; Chan, Keith; Hogg, Robert S

    2007-01-01

    Background Nitrite inhalants ("poppers") are peripheral vasodilators which, since the beginning of the epidemic, have been known to increase risk for acquiring HIV infection among men who have sex with men (MSM). However, few studies in recent years have characterized use. From 1999 to 2004, new HIV diagnoses among MSM in British Columbia increased 78%, prompting us to examine the prevalence and correlates of this modifiable HIV risk factor. Methods Self-administered questionnaires were completed between October 2002 and May 2004 as part of an open cohort study of HIV-seronegative young MSM. We measured nitrite inhalant use during the previous year and use during sexual encounters with casual partners specifically. Correlates of use were identified using odds ratios. Results Among 354 MSM surveyed, 31.6% reported any use during the previous year. Nitrite inhalant use during sexual encounters was reported by 22.9% of men and was strongly associated with having casual partners, with greater numbers of casual partners (including those with positive or unknown serostatus) and with anal intercourse with casual partners. Nitrite inhalant use was not associated with non-use of condoms with casual sexual partners per se. Conclusion Contemporary use of nitrite inhalants amongst young MSM is common and a strong indicator of anal intercourse with casual sexual partners. Since use appears to increase the probability of infection following exposure to HIV, efforts to reduce the use of nitrite inhalants among MSM should be a very high priority among HIV prevention strategies. PMID:17362516

  2. 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.

  3. 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

  4. 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.

  5. Adolescent inhalant use prevention, assessment, and treatment: A literature synthesis.

    PubMed

    Nguyen, Jacqueline; O'Brien, Casey; Schapp, Salena

    2016-05-01

    Inhalant use refers to the use of substances such as gases, glues, and aerosols in order to achieve intoxication, while inhalant use disorder (IUD) encompasses both DSM-IV-TR criteria for inhalant abuse and dependence. Inhalant use among adolescents is an international public health concern considering the severe medical and cognitive consequences and biopsychosocial correlates. In this paper, we summarize the current state of the literature on inhalant use among adolescents focusing on social context, prevention, assessment, and treatment strategies. Psychoeducation, skills training, and environmental supply reduction are helpful strategies for preventing adolescent inhalant use, while parent and adolescent self-report as well as physician report of medical signs and symptoms can aid in assessment and diagnosis. Although research has only begun to explore the treatment of inhalant use, preliminary findings suggest that a multimodal approach involving individual counselling (i.e., CBT brief intervention), family therapy, and activity and engagement programs is the first-line treatment, with residential treatment programs indicated for more severe presentations. The limited nature of treatments developed specifically for inhalant use combined with high prevalence rates and potential for significant impairment within the adolescent population indicate the need for further research. Research should focus on understanding the social context of use, establishing the efficacy of current adolescent substance use treatments adapted for inhalant use, and exploring long-term outcomes. PMID:26969125

  6. Positron emission tomography (PET) for assessing aerosol deposition of orally inhaled drug products.

    PubMed

    Dolovich, Myrna B; Bailey, Dale L

    2012-12-01

    The topical distribution of inhaled therapies in the lung can be viewed using radionuclides and imaging. Positron emission tomography (PET) is a three-dimensional functional imaging technique providing quantitatively accurate localization of the quantity and distribution of an inhaled or injected PET radiotracer in the lung. A series of transaxial slices through the lungs are obtained, comparable to an X-ray computed tomography (CT) scan. Subsequent reformatting allows coronal and sagittal images of the distribution of radioactivity to be viewed. This article describes procedures for administering [(18)F]-fluorodeoxyglucose aerosol to human subjects for the purpose of determining dose and distribution following inhalation from an aerosol drug delivery device (ADDD). The advantages of using direct-labeled PET drugs in the ADDD are discussed with reference to the literature. The methods for designing the inhalation system, determining proper radiation shielding, calibration, and validation of administered radioactivity, scanner setup, and data handling procedures are described. Obtaining an X-ray CT or radionuclide transmission scan to provide accurate geometry of the lung and also correct for tissue attenuation of the PET radiotracer is discussed. Protocols for producing accurate images, including factors that need to be incorporated into the data calibration, are described, as well as a proposed standard method for partitioning the lung into regions of interest. Alternate methods are described for more detailed assessments. Radiation dosimetry/risk calculations for the procedures are appended, as well as a sample data collection form and spreadsheet for calculations. This article should provide guidance for those interested in using PET to determine quantity and distribution of inhaled therapeutics. PMID:23215847

  7. A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics.

    PubMed

    Persson, G; Gruvstad, E; Ståhl, E

    1988-08-01

    Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma. PMID:3234516

  8. 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.

  9. 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. PMID:26613951

  10. Inhaled therapy in cystic fibrosis: agents, devices and regimens

    PubMed Central

    Parrott, Helen

    2015-01-01

    Key points There have been significant advances in both inhalation medicines and delivery devices with “intelligent nebulisers” and “dry-powder inhalers” becoming commonplace in CF care. Inhaled medicines generate high levels of a drug within the airways with limited systemic effects, offering safe and convenient antibiotic and mucolytic therapy for individuals with CF. Variations in adherence are not unique to CF; however, treatment burden is high and therefore fast inhaled drug delivery devices may assist individuals in completing the prescribed treatment regimes. Prescribers of inhaled medicines have a responsibility to consider, in addition to efficacy, the appropriated drug/device combination for each individual in order to promote adherence and achieve the desired clinical benefit. Summary The recognised mainstay daily treatments for cystic fibrosis (CF) focus on inhaled and oral medications, airway clearance and optimised nutrition. This review discusses recent advances in inhaled therapies for the management of CF, including devices such as intelligent nebulisers, drug formulations and supporting evidence for inhaled antibiotics (for the management of chronic Pseudomonas aeruginosa) and muco-active drugs. We include practical advice for clinicians regarding the optimisation of inhalation technique and education. The influence of adherence on the use of inhaled therapies in CF is also reviewed. Educational aims To inform readers about the history and progression of inhaled therapies for people with CF with reference to the literature supporting current practice. To highlight the factors that may impact the success of inhaled therapies, including those which are device specific such as drug deposition and those which influence adherence. PMID:26306111

  11. Inhaled drugs as risk factors for community-acquired pneumonia.

    PubMed

    Almirall, J; Bolíbar, I; Serra-Prat, M; Palomera, E; Roig, J; Hospital, I; Carandell, E; Agustí, M; Ayuso, P; Estela, A; Torres, A

    2010-11-01

    The effect of inhaled drugs in community-acquired pneumonia (CAP) is unclear. This case-control study was designed to determine whether inhaled drugs were risk factors for CAP. All incident cases of confirmed CAP that occurred over 1 yr in patients with chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD) or asthma were included, as well as CB, COPD and asthma controls. Risk factors for CAP and inhaled treatment were recorded during a personal interview. An effect of inhaled drugs on the risk of CAP was observed in COPD and asthma patients after adjusting for the effect of other respiratory diseases and their concomitant treatments. In COPD patients, inhaled steroids had a risk OR of 3.26 (95% CI 1.07-9.98) and in asthma patients inhaled anticholinergics had a risk OR of 8.80 (95% CI 1.02-75.7). In CB patients, no association with CAP was observed for any inhaler. These effects were independent of adjusting variables related to severity and other respiratory and non-respiratory risk factors for CAP, including vaccines. Inhaled β(2)-adrenergic agonists did not show a significant effect on the risk of CAP in any of the respiratory diseases. Inhaled steroids may favour CAP in COPD patients, whereas anticholinergics may favour CAP in asthma patients. It is difficult to differentiate the effect of inhaled therapy from the effect of COPD or asthma severity on the risk of CAP, and these relationships may not be causal, but could call attention to inhaled therapy in COPD and asthma patients.

  12. High-flow oxygen therapy and other inhaled therapies in intensive care units.

    PubMed

    Levy, Sean D; Alladina, Jehan W; Hibbert, Kathryn A; Harris, R Scott; Bajwa, Ednan K; Hess, Dean R

    2016-04-30

    In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method.

  13. High-flow oxygen therapy and other inhaled therapies in intensive care units.

    PubMed

    Levy, Sean D; Alladina, Jehan W; Hibbert, Kathryn A; Harris, R Scott; Bajwa, Ednan K; Hess, Dean R

    2016-04-30

    In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method. PMID:27203510

  14. INHALED ALPHA1-PROTEINASE INHIBITOR THERAPY IN PATIENTS WITH CYSTIC FIBROSIS

    PubMed Central

    Gaggar, Amit; Chen, Junliang; Chmiel, James F; Dorkin, Henry L; Flume, Patrick A; Griffin, Rhonda; Nichols, David; Donaldson, Scott H

    2016-01-01

    Background Inhaled alpha1-proteinase inhibitor (PI) is known to reduce neutrophil elastase burden in some patients with CF. This phase 2a study was designed to test inhaled Alpha-1 HC, a new aerosolized alpha1-PI formulation, in CF patients. Methods We performed a randomized, double-blind, placebo-controlled study and evaluated the safety of 100 or 200 mg of inhaled Alpha-1 HC once daily for 3 weeks in subjects with CF. Thirty adult subjects were randomized in a 2:1 ratio to receive Alpha-1 HC or placebo. Results Drug delivery was confirmed by a dose-dependent increase in the sputum alpha1-PI. Seven (20.0%) of the 35 adverse events in the 100-mg dose group, 3 (13.0%) of 23 in the 200-mg dose group, and 4 (14.3%) of 28 in the placebo group were drug-related in these subjects. One serious adverse event occurred in 1 subject within each group. Conclusions Alpha-1 HC inhalation was safe and well tolerated. PMID:26321218

  15. Treatment of acute severe asthma with inhaled albuterol delivered via jet nebulizer, metered dose inhaler with spacer, or dry powder.

    PubMed

    Raimondi, A C; Schottlender, J; Lombardi, D; Molfino, N A

    1997-07-01

    Despite the increasing use of dry powder formulations in the ambulatory setting, there is a paucity of information on the efficacy of this therapeutic modality to treat acute severe asthma. In addition, studies that compared wet nebulization vs metered dose inhalers formulated with chlorofluorocarbon (CFCMDI) attached to holding chambers have yielded discrepant results. Thus, it is unclear which of the three delivery systems would elicit a superior bronchodilator response, particularly in patients with life-threatening asthma. In a prospective, randomized open design, we studied the response to inhaled albuterol (salbutamol) in 27 adult asthmatics presenting to the emergency department (ED) with an FEV1 <30% predicted. Subjects were treated with one of the following regimens (nine subjects in each group): group A, mean (SD) baseline FEV1 of 0.7 (0.2) L, received albuterol solution, 5 mg, via a nebulizer (Puritan-Bennett Raindrop; Lawrenceville, Ga) impelled with oxygen (O2) at 8 L/min; group B, baseline FEV1 of 0.6 (0.15) L, received albuterol, 400 microg, via a CFCMDI attached to a 145-mL valved aerosol holding chamber (Aerochamber; Trudell Medical; London, ON); and group C, baseline FEV1 of 0.6 (0.17) L, received albuterol powder, 400 microg, by another means (Rotahaler; Glaxo; Research Triangle Park, NC). All groups received the respective treatments on arrival in the ED, every 30 min during the first 2 h, and then hourly until the sixth hour. Clinical parameters and FEV1 were recorded on ED admission and 15 min after each dose of albuterol. At the time of ED admission, all patients also received continuous O2 and one dose of I.V. steroids (dexamethasone, 8 mg). The total dose of inhaled albuterol administered during the 6-h treatment was 45 mg of nebulized solution in group A and 3,600 microg of albuterol aerosol and dry powder in groups B and C, respectively. No significant differences were found in the population demographics, baseline FEV1, and arterial

  16. Estimation of the radioactive source dispersion from Fukushima nuclear power plant accident.

    PubMed

    Schöppner, Michael; Plastino, Wolfango; Povinec, Pavel; Nikkinen, Mika; Ruggieri, Federico; Bella, Francesco

    2013-11-01

    Following the Fukushima nuclear power plant accident detections of (133)Xe have been made in various locations. Using results of these remote measurements the Fukushima (133)Xe source term has been reconstructed and compared with previously reconstructed (137)Cs and (131)I source terms. The reconstruction is accomplished by applying atmospheric transport modeling and an adapted least square error method. The obtained results are in agreement with previous estimations of the Fukushima radionuclide source, and also serve as a proof of principle for source term reconstruction based on atmospheric transport modeling.

  17. Inhalational anaesthesia with low fresh gas flow

    PubMed Central

    Hönemann, Christian; Hagemann, Olaf; Doll, Dietrich

    2013-01-01

    During the inhalation of anaesthesia use of low fresh gas flow (0.35-1 L/min) has some important advantages. There are three areas of benefit: pulmonary - anaesthesia with low fresh gas flow improves the dynamics of inhaled anaesthesia gas, increases mucociliary clearance, maintains body temperature and reduces water loss. Economic - reduction of anaesthesia gas consumption resulting in significant savings of > 75% and Ecological - reduction in nitrous oxide consumption, which is an important ozone-depleting and heat-trapping greenhouse gas that is emitted. Nevertheless, anaesthesia with high fresh gas flows of 2-6 L/min is still performed, a technique in which rebreathing is practically negligible. This special article describes the clinical use of conventional plenum vaporizers, connected to the fresh gas supply to easily perform low (1 L/min), minimal (0.5 L/min) or metabolic flow anaesthesia (0.35 L/min) with conventional Primus Draeger® anaesthesia machines in routine clinical practice. PMID:24163447

  18. Diabetes therapy trials with inhaled insulin.

    PubMed

    Fineberg, Samuel Edwin

    2006-07-01

    Administration of insulin by inhalation was first attempted > 50 years ago. At that time, little was known concerning effective delivery systems and insulin formulations. The recent development of pulmonary delivery systems for the administration of insulin is driven by the reluctance of patients and their providers to initiate insulin earlier in the course of Type 2 diabetes, the desire to reduce the number of daily insulin injections for both Type 1 and 2 patients, and the recent emphasis on intensified glycaemic control including postprandial glycaemic control. The deep lung is a unique mucosal tissue having a surface area of > 100 m2 and is readily accessible both to the external environment and to drug delivery, provided that appropriate conditions are met. There have been four mid- to late-phase pulmonary insulin programmes using modern inhalation devices that will be reported in this paper. The programmes differ in the choice of delivery systems, the formulations of insulin and reported bioavailability, pharmacokinetic and glucodynamic profiles and adverse events. However, all systems successfully deliver insulin to the deep lung and biological effectiveness compares favourably with injected subcutaneous insulins.

  19. Chronic inhalation exposure of rats to nitromethane.

    PubMed

    Griffin, T B; Coulston, F; Stein, A A

    1996-07-01

    Male and female Long-Evans rats were housed in inhalation chambers and exposed to vapors of nitromethane (NM) at either 100 or 200 ppm. The animals were exposed 7 hr per day, 5 days per week for 2 years. Control groups of rats were also housed in a similar inhalation chamber, but NM was not introduced into the chamber. The animals were observed daily for signs of pharmacologic or toxicologic effect and body weights were recorded periodically. At the 2-year termination of the exposure period, clinical laboratory examinations (serum chemistry and hematology) were performed on selected animals and all surviving animals were sacrificed. All animals were necropsied and subjected to a thorough histopathologic examination. During the study there were no pharmacologic effects from exposure to NM at either 100 or 200 ppm. There was no effect on mortality on either sex at either exposure level. Body weights of male rats exposed to NM were not significantly different from those of control rats, but the body weights of female rats of both exposure groups were slightly less than their controls. There was no effect of exposure of rats of either sex to either level of NM on hematology. There were no clinically significant effects on serum chemistry. There were no effects of exposure to NM on organ weights. There were no significant differences in the nonneoplastic or neoplastic pathology related to exposure to NM. PMID:8812175

  20. Alveolar proteinosis associated with aluminium dust inhalation.

    PubMed

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. PMID:27099254

  1. Active and intelligent inhaler device development.

    PubMed

    Tobyn, Mike; Staniforth, John N; Morton, David; Harmer, Quentin; Newton, Mike E

    2004-06-11

    The dry powder inhaler, which has traditionally relied on the patient's inspiratory force to deaggregate and deliver the active agent to the target region of the lung, has been a successful delivery device for the provision of locally active agents for the treatment of conditions such as asthma and chronic obstructive pulmonary disease (COPD). However, such devices can suffer from poor delivery characteristics and/or poor reproducibility. More recently, drugs for systemic delivery and more high value compounds have been put into DPI devices. Regulatory, dosing, manufacturing and economic concerns have demanded that a more efficient and reproducible performance is achieved by these devices. Recently strategies have been put in place to produce a more efficient DPI device/formulation combination. Using one novel device as an example the paper will examine which features are important in such a device and some of the strategies required to implement these features. All of these technological advances are invisible, and may be irrelevant, to the patient. However, their inability to use an inhaler device properly has significant implications for their therapy. Use of active device mechanisms, which reduce the dependence on patient inspiratory flow, and sensible industrial design, which give the patient the right clues to use, are important determinants of performance here.

  2. [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. PMID:21703474

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

    EPA Science Inventory

    The U.S. Environmental Protection Agency's (USEPA) 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 ammon...

  4. 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…

  5. 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

  6. 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

  7. Whole-body nanoparticle aerosol inhalation exposures.

    PubMed

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

    2013-01-01

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σg < 2.5 (5). The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M

  8. Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges.

    PubMed

    Haque, Shadabul; Whittaker, Michael R; McIntosh, Michelle P; Pouton, Colin W; Kaminskas, Lisa M

    2016-08-01

    The inhaled delivery of nanomedicines can provide a novel, non-invasive therapeutic strategy for the more localised treatment of lung-resident diseases and potentially also enable the systemic delivery of therapeutics that are otherwise administered via injection alone. However, the clinical translation of inhalable nanomedicine is being hampered by our lack of understanding about their disposition and clearance from the lungs. This review provides a comprehensive overview of the biodegradable nanomaterials that are currently being explored as inhalable drug delivery systems and our current understanding of their disposition within, and clearance from the lungs. The safety of biodegradable nanomaterials in the lungs is discussed and latest updates are provided on the impact of inflammation on the pulmonary pharmacokinetics of inhaled nanomaterials. Overall, the review provides an in-depth and critical assessment of the lung clearance mechanisms for inhaled biodegradable nanomedicines and highlights the opportunities and challenges for their translation into the clinic.

  9. Observation of two suicides by helium inhalation in a prefilled environment.

    PubMed

    Ogden, Russel D

    2010-06-01

    In recent years information about suicide with helium has spread rapidly on the Internet, in print, and even on video. Increased awareness of this suicide method means that instead of turning to a physician for aid in dying, some people will terminate their lives with this nonpharmaceutical method. Although there are many case reports of hypoxic suicide by helium inhalation, little is known about the pathophysiology of this type of death. Pathologists should know what hypoxic suicide looks like. Carefully planned, autonomous suicides present possibilities for passive, naturalistic observation of the phenomenon. This article describes a method for direct observation of suicide and reports on 2 hypoxic suicides from inhalation of helium inside a prefilled environment.

  10. Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

    PubMed Central

    Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

    2013-01-01

    Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

  11. Inhaled Steroids Modulate Extracellular Matrix Composition in Bronchial Biopsies of COPD Patients: A Randomized, Controlled Trial

    PubMed Central

    Kunz, Lisette I. Z.; Strebus, Jolanda; Budulac, Simona E.; Lapperre, Therese S.; Sterk, Peter J.; Postma, Dirkje S.; Mauad, Thais; Timens, Wim; Hiemstra, Pieter S.

    2013-01-01

    Rationale Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix. This is thought to contribute to airway remodeling and airflow obstruction. We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD. We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD. Objective To compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD. Methods We included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31–54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively. Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content. Percentage and density of stained area were calculated by digital image analysis. Results 30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo. Increased collagen I staining density correlated with increased post-bronchodilator FEV1 after inhaled steroids treatment (Rs = 0.45, p = 0.04). There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins. Conclusions These data show that long-term inhaled corticosteroids treatment partially changes the

  12. 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

  13. 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

  14. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial

    PubMed Central

    2014-01-01

    Background Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. Methods The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. Discussion As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. Trial registration NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013. Recruiting. Randomisation commenced on 1 January 2014. PMID:24661817

  15. Evaluation of a Novel Nicotine Inhaler Device: Part 1—Arterial and Venous Pharmacokinetics

    PubMed Central

    Hearn, Alex; Redfern, Andrew

    2015-01-01

    Introduction: In the United Kingdom, licensed nicotine-containing products can be recommended to reduce the harm associated with smoking. Many smokers find currently available nicotine replacement products unsatisfactory. The arterial and venous pharmacokinetics (PK) of nicotine delivered via a novel inhaler device were determined. Methods: Results are reported for Parts A (N = 18) and C (N = 18) of a 4-part (A–D) Phase I study. Participants (18–55 years, ≥10 cigarettes/day, smoking within 1hr of waking, expired carbon monoxide >10 ppm on screening) orally inhaled 2 single doses of nicotine (2 of 3 dose levels [0.22, 0.45, and 0.67 mg]) (Part A) and repeated hourly doses of 0.67mg nicotine for 12hr (Part C), via the novel device. Arterial and venous PK and tolerability were assessed. Results: In Part A, mean arterial plasma nicotine concentrations at 2min after the start of inhalation were 1.10, 2.06, and 2.59ng/mL for the 0.22, 0.45, and 0.67mg doses, respectively. Mean maximum arterial plasma nicotine concentrations (C max) were 2.11, 3.73, and 4.38ng/mL and mean times to C max were 10.2, 7.3, and 6.5min after the start of inhalation for the 0.22, 0.45, and 0.67mg doses, respectively. In Part C, the mean pre- and postdose venous plasma nicotine concentration increased steadily and fluctuated in the range 8–10mg/mL after 9hr. The novel device was well tolerated; most adverse events were mild. Conclusion: The novel inhaler device delivers nicotine rapidly into the systemic circulation and offers a viable alternative to cigarettes for those finding it difficult to quit the behavioral and sensorial aspects of smoking. PMID:25385878

  16. Characterization of inhalation aerosols: a critical evaluation of cascade impactor analysis and laser diffraction technique.

    PubMed

    de Boer, A H; Gjaltema, D; Hagedoorn, P; Frijlink, H W

    2002-12-01

    Cascade impactor analysis is the standard technique for in vitro characterization of aerosol clouds generated by medical aerosol generators. One important reason for using this inertial separation principle is that drug fractions are classified into aerodynamic size ranges that are relevant to the deposition in the respiratory tract. Measurement of these fractions with chemical detection methods enables establishment of the particle size distribution of the drug in the presence of excipients. However, the technique is laborious and time consuming and most of the devices used for inhaler evaluation lack sufficient possibilities for automation. In addition to that, impactors often have to be operated under conditions for which they were not designed and calibrated. Particularly, flow rates through impactors are increased to values at which the flow through the nozzles is highly turbulent. This has an uncontrolled influence on the collection efficiencies and cut-off curves of these nozzles. Moreover, the cut-off value varies with the flow rate through an impactor nozzle. On the other hand, the high air flow resistances of most impactors are rather restricting to the attainable (fixed) inspiratory flow curves through these devices. Especially for breath actuated dry powder inhalers, higher flow rates and flow increase rates may be desirable than can be achieved in combination with a particular type of impactor. In this paper, the applicability of laser diffraction technology is evaluated as a very fast and highly reliable alternative for cascade impactor analysis. With this technique, aerodynamic diameters cannot be measured, but for comparative evaluation and development, comprising most in vitro applications, this is not necessary. Laser diffraction has excellent possibilities for automated recording of data and testing conditions, and the size classes are independent of the flow rate. Practical limitations can be overcome by using a special inhaler adapter which

  17. 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

  18. 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

  19. Computed tomography--a possible aid in the diagnosis of smoke inhalation injury?

    PubMed

    Reske, A; Bak, Z; Samuelsson, A; Morales, O; Seiwerts, M; Sjöberg, F

    2005-02-01

    Inhalation injury is an important contributor to morbidity and mortality in burn victims and can trigger acute lung injury and acute respiratory distress syndrome (ARDS) (1-3). Early diagnosis and treatment of inhalation injury are important, but a major problem in planning treatment and evaluating the prognosis has been the lack of consensus about diagnostic criteria (4). Chest radiographs on admission are often non-specific (5, 6), but indicators include indoor fires, facial burns, bronchoscopic findings of soot in the airways, and detection of carbon monoxide or cyanide in the blood (7). Changes in the lungs may be detected by bronchoscopy with biopsy, xenon imaging, or measurement of pulmonary extracellular fluid (4, 5, 8). These methods have, however, been associated with low sensitivity and specificity, as exemplified by the 50% predictive value in the study of Masanes et al. (8). Computed tomographs (CTs) are better than normal chest radiographs in the detection of other pulmonary lesions such as pulmonary contusion (9, 10). The importance of CT scans in patients with ARDS has been reviewed recently (9), but unfortunately there has been no experience of CT in patients with smoke inhalation injury. To our knowledge, there are only two animal studies reporting that smoke inhalation injury can be detected by CT (4, 11); specific changes in human CT scans have not yet been described. Therefore, confronted with a patient with severe respiratory failure after a burn who from the history and physical examination showed the classic risk factors for inhalation injury, we decided to request a CT. PMID:15715631

  20. 99mTc-labeled Therapeutic Inhaled Amikacin Loaded Liposomes

    PubMed Central

    Lee, Jae-Ho; Cheng, Kenneth T.; Malinin, Vladimir; Li, Zhili; Yao, Zhengsheng; Lee, Sung-Jin; Gould, Christine M.; Olivier, Kenneth N.; Chen, Clara; Perkins, Walter R.; Paik, Chang H.

    2014-01-01

    The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e., an antibiotic, amikacin) loaded liposomes with 99mTc, nebulization properties of 99mTc-labeled liposomal amikacin for inhalation (99mTc-LAI), and its stability by size exclusion low pressure liquid chromatography (LPLC). LAI was reacted with 99mTc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified 99mTc-LAI in 1.5% NaCl solution was incubated at 4oC to assess its stability by LPLC. The purified 99mTc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of 99mTc-LAI, indicating that 99mTc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl2 in 0.91mM ascorbic acid produced 99mTc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy. PMID:23879241

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

    PubMed

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

    1980-11-01

    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

  2. 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

  3. Evaluation of inhaler handling-errors, inhaler perception and preference with Spiromax, Easyhaler and Turbuhaler devices among healthy Finnish volunteers: a single site, single visit crossover study (Finhaler)

    PubMed Central

    Sandler, Niklas; Holländer, Jenny; Långström, Disa; Santtila, Pekka; Saukkonen, Anni; Torvinen, Saku

    2016-01-01

    Introduction Correct inhaler technique and device preference are positively correlated with improved adherence and clinical outcomes. This study was designed to investigate inhaler technique mastery and device preference for three different dry powder inhalers, Spiromax, Easyhaler and Turbuhaler. Methods This was a single site, single visit, crossover study assessing device mastery, handling errors and preference using empty Spiromax, Easyhaler and Turbuhaler devices in healthy adult Finnish volunteers. Inhaler naïve adult participants were observed by healthcare professionals (HCPs) to evaluate the proportion of participants achieving device mastery (defined as an absence of HCP observed errors) using a three-step approach: (1) intuitive use (with no instructions), (2) after reading the patient information leaflet and (3) after HCP instruction. HCPs monitored and recorded errors based on device-specific handling error checklists. At the end of the study, participants completed a device preference questionnaire and rated their satisfaction with the three devices. Results Spiromax was correctly used by 37.5% and 93.3% of participants in steps 1 and 2, respectively, compared with 0% and 58.3% with Easyhaler, and 9.2% and 76.7% with Turbuhaler. All three devices showed high mastery (>95%) in step 3. The most common error reported with Spiromax was related to the orientation of the device. Not shaking the device was the most common error with Easyhaler. Errors in priming the device were the most common with Turbuhaler. Spiromax, Easyhaler and Turbuhaler were rated as the ‘easiest device to use’ by 73.1%, 12.6% and 14.3% of participants, respectively. The HCP instructions clearly improved the use of all devices. Conclusion Higher levels of device mastery, including intuitive/ease of use, were reported by naïve users when using Spiromax compared with Easyhaler and Turbuhaler. PMID:27026804

  4. Preference, satisfaction and critical errors with Genuair and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study

    PubMed Central

    Pascual, Sergi; Feimer, Jan; De Soyza, Anthony; Sauleda Roig, Jaume; Haughney, John; Padullés, Laura; Seoane, Beatriz; Rekeda, Ludmyla; Ribera, Anna; Chrystyn, Henry

    2015-01-01

    Background: The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). Aims: To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use. Methods: Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device. Results: Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively). Conclusions: Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. PMID:25927321

  5. 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. PMID:27509644

  6. 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

  7. 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

  8. Human inhalation pharmacokinetics of chlorodifluoromethane (HCFC22).

    PubMed

    Woollen, B H; Marsh, J R; Mahler, J D; Auton, T R; Makepeace, D; Cocker, J; Blain, P G

    1992-01-01

    Two groups of three male volunteers were exposed to atmospheric concentrations of either 327 or 1833 mg m-3 chlorodifluoromethane (HCFC22) for 4 h. Blood, urine and expired air samples were taken during and after the exposure period and analysed for HCFC22. Urine samples were also analysed for fluoride ion. During the exposure period, blood concentrations of HCFC22 approached a plateau, and the average peak blood concentrations of 0.25 and 1.36 micrograms cm-3 were proportional to dose. HCFC22 concentrations in expired air were similar to the exposure concentration during the exposure period. The ratio between venous blood and breath concentrations of HCFC22 towards the end of the exposure period was on average 0.77, which is consistent with in vitro estimates of the partition coefficient. In the post-exposure period, three phases for the elimination of HCFC22 were identified, with estimated half-lives of 0.005, 0.2 and 2.6h. HCFC22 was detected in urine samples taken in the post-exposure period, and the rate of decline was consistent with the terminal rate of elimination estimated from blood and breath measurements. On average 2.1% of the inhaled HCFC22 was recovered in breath within 26 h of exposure. This is consistent with the low solubility in blood and fat. Minimal changes in fluoride ion concentrations in urine following exposure indicate that HCFC22 is unlikely to be metabolised to a significant extent. Following inhalational exposure HCFC22 is poorly absorbed and is rapidly eliminated from the body. Possible biological monitoring strategies could be based on measurements of HCFC22 in urine or breath samples collected after the end of an exposure period.

  9. 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). PMID:7724853

  10. Specific Inhalation Challenge in Persulfate Asthma.

    PubMed

    Hagemeyer, O; Marek, E; van Kampen, V; Sander, I; Raulf, M; Merget, R; Brüning, T

    2015-01-01

    Specific inhalation challenge (SIC) may be considered the 'gold standard' for the diagnosis of occupational asthma due to persulfate salts. The aim of the study was to develop a safe SIC protocol. Between 2003 and 2014, eight patients with suspected occupational asthma due to persulfate salts were examined (7 females, all hair-dressers). SIC was done with a dosimeter and a nebulizer using ammonium persulfate dissolved in phosphate buffer. Until 2009, a four-step-protocol (doses: 0.0004, 0.0045, 0.045, 0.45 mg; cumulative: 0.5 mg) was used, afterwards a six-step-protocol (doses: 0.0004, 0.0018, 0.007, 0.028, 0.113, 0.45 mg; cumulative: 0.6 mg). With each SIC protocol, four subjects were tested. Skin prick tests with ammonium persulfate (20 mg/mL) were performed in all and patch tests in four subjects. In total, four subjects showed a positive SIC, two with each protocol. All subjects showed an isolated late reaction. The greatest decrease of volume in 1 s was 35 % about 3.5 h after the last inhalation (four-step-protocol). Skin prick test with ammonium persulfate was positive in one SIC positive (2 mm wheal) and in two SIC negative patients (3 and 4 mm wheal). All four subjects tested with patch tests showed a positive reaction; three of them were SICpos. We recommend to include patch-testing in the diagnosis of suspected occupational asthma due to persulfate salts. Isolated late asthmatic reactions may occur after SIC. The proposed six-step SIC protocol was safe in this limited number of subjects. PMID:26022895

  11. Effect of 4% lidocaine inhalation in bronchial asthma.

    PubMed

    Prakash, G S; Sharma, S K; Pande, J N

    1990-01-01

    The effect of 4% lidocaine inhalation was studied in a single-blind fashion in 18 patients with chronic stable asthma. Inhalation of normal saline solution was used as placebo. None of the parameters except flow rate at 50% of vital capacity (V50) showed any statistically significant change from baseline values. V50 at 15 min was significantly lower (p less than 0.05) after 4% lidocaine inhalation. Considering more than 10% change from the baseline value as significant, 8 of 15 patients showed decrease in airway resistance (Raw) and 7 of the 15 patients showed an increase in specific airway conductance (SGaw) after 15 min of inhalation. However, V50 (8/18 patients), flow rate at 25% vital capacity [V25 (6/15 patients], and forced expiratory flow rate at 25-75% of the vital capacity (FEF25-75) (5/15 patients) showed a decrease after 15 min of 4% lidocaine inhalation. No change in pulmonary function was noted after 30 min of lidocaine inhalation. It is concluded from this study that lidocaine produces a small bronchodilatory effect on the large airways and a bronchoconstrictor effect on the small airways after 15 min of inhalation, but this effect is not statistically significant. It can be safely used as topical agent for bronchoscopy in patients with bronchial asthma.

  12. Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.

    PubMed

    Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kloft, Charlotte

    2015-07-01

    During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes, has strongly increased. However, this increase could not equally be observed for orally inhaled drugs. The objectives of this review are to understand the reasons for this gap and to demonstrate the opportunities that mathematical modeling of pharmacokinetics of orally inhaled drugs offers. To achieve these objectives, this review (i) discusses pulmonary physiological processes and their impact on the pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of published pharmacokinetic models, (iii) categorizes these models into physiologically based pharmacokinetic (PBPK) and (clinical data-derived) empirical models, (iv) explores both their (mechanistic) plausibility, and (v) addresses critical aspects of different pharmacometric approaches pertinent for drug inhalation. In summary, pulmonary deposition, dissolution, and absorption are highly complex processes and may represent the major challenge for modeling and simulation of PK after oral drug inhalation. Challenges in relating systemic pharmacokinetics with pulmonary efficacy may be another factor contributing to the limited number of existing pharmacokinetic models for orally inhaled drugs. Investigations comprising in vitro experiments, clinical studies, and more sophisticated mathematical approaches are considered to be necessary for elucidating these highly complex pulmonary processes. With this additional knowledge, the PBPK approach might gain additional attractiveness. Currently, (semi-)mechanistic modeling offers an alternative to generate and investigate hypotheses and to more mechanistically understand the pulmonary and systemic pharmacokinetics after oral drug inhalation including the impact of pulmonary diseases.

  13. 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

  14. 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

  15. Orofacial and digital frostbite caused by inhalant abuse.

    PubMed

    Koehler, Matthew M; Henninger, Camille A

    2014-05-01

    Inhalation of volatile substances is a cheap and accessible way for individuals, most commonly teenagers, to ingest mind-altering substances. The adverse effects of using inhalants, including cardiac dysrhythmia, respiratory tract injury, and asphyxiation, can be devastating. Detection often is difficult, but a high degree of suspicion with patterns of perioral, perinasal, and/or digital lesions can help identify use. We report an uncommon case of severe orofacial and digital frostbite initially mistaken for an allergic reaction in a 20-year-old man following intentional inhalation of a commercial air-dusting agent containing 1,1,1,2-tetrafluoroethane (HFC-134a).

  16. Pharmacogenomic test that predicts response to inhaled corticosteroids in adults with asthma likely to be cost-saving

    PubMed Central

    Wu, Ann Chen; Gay, Charlene; Rett, Melisa D; Stout, Natasha; Weiss, Scott T; Fuhlbrigge, Anne L

    2015-01-01

    Aim To identify the clinical and economic circumstances under which a pharmacogenomic test that predicts response to inhaled corticosteroids might be a cost-effective option for individuals with asthma. Materials & methods We synthesized published data on clinical and economic outcomes to project 10-year costs, quality-adjusted life-years and cost–effectiveness of pharmacogenomic testing for inhaled corticosteroid response. We assumed the pharmacogenomic test cost was $500 with a sensitivity and specificity of 84 and 98%, respectively. These were varied in sensitivity analyses. Results Both strategies, pharmacogenomic testing for inhaled corticosteroid response and no testing conferred 7.1 quality-adjusted life-years. Compared with no testing, pharmacogenomic testing costs less. Conclusion Pharmacogenomic testing for asthma is cost-saving and noninferior in improving health. PMID:25880024

  17. 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…

  18. 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"…

  19. 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…

  20. The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Liberda, Eric N.

    Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

  1. 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

  2. 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

  3. Orally inhaled drug performance testing for product development, registration, and quality control.

    PubMed

    Lastow, Orest; Svensson, Mårten

    2014-12-01

    A DPI can be split into three different modules; device, formulation, process. These are developed in parallel, and together with the user they provide the performance of an inhalation product. During product development, these modules are evolving and changing, whereas the requirements on an inhalation product are always expressed in terms of the performance of the final commercial product. To do performance testing during development when the product is not finished presents many challenges and can be confusing and misleading. During development, the performance of the final product is typically being predicted by testing ever changing prototypes. This article describes methods and approaches to manage such development and to, during development, provide relevant predictions of the in vitro and in vivo performances of the final product.

  4. Decorporation of inhaled americium-241 dioxide and nitrate from hamsters using ZnDTPA and Puchel.

    PubMed

    Stradling, G N; Stather, J W; Sumner, S A; Moody, J C; Strong, J C

    1984-06-01

    Accidental intakes of 241AmO2 and 241Am(NO3)3 can be treated with some success by inhalation of ZnDTPA . The main advantage of this method of treatment is that it can be self-administered very soon after an accidental intake, and it is effective for reducing the lung content of Am at doses about 10 times less than those usually used intravenously. Otherwise the efficacy of injected ZnDTPA is superior since in addition to removing 241Am from the lungs it can deplete appreciably the systemic deposit of the nuclide. There appears to be no advantage in using the lipophilic form of DTPA code-named Puchel , since following the inhalation or injection of the compound decorporation is not significantly increased relative to ZnDTPA . PMID:6724941

  5. 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...

  6. The use of inhaled corticosteroids in pediatric asthma: update.

    PubMed

    Hossny, Elham; Rosario, Nelson; Lee, Bee Wah; Singh, Meenu; El-Ghoneimy, Dalia; Soh, Jian Yi; Le Souef, Peter

    2016-01-01

    Despite the availability of several formulations of inhaled corticosteroids (ICS) and delivery devices for treatment of childhood asthma and despite the development of evidence-based guidelines, childhood asthma control remains suboptimal. Improving uptake of asthma management plans, both by families and practitioners, is needed. Adherence to daily ICS therapy is a key determinant of asthma control and this mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices. The potential adverse effects of ICS need to be weighed against the benefit of these drugs to control persistent asthma especially that its safety profile is markedly better than oral glucocorticoids. This article reviews the key mechanisms of inhaled corticosteroid action; recommendations on dosage and therapeutic regimens; potential optimization of effectiveness by addressing inhaler technique and adherence to therapy; and updated knowledge on the real magnitude of adverse events. PMID:27551328

  7. 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...

  8. 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...

  9. 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

  10. 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...

  11. 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 ...

  12. Drug delivery to the lungs from dry powder inhalers.

    PubMed

    Newman, Stephen P

    2003-04-01

    When asthma is being treated, it is essential that sufficient drug is deposited at the site(s) where it is needed. In recent years, many dry powder inhalers have been developed by the pharmaceutical industry. Drug delivery to the lung from dry powder inhalers is dependent upon the patient's peak inhaled flow rate, and so it is very important to be able to assess the amount and location of drug delivered from different devices. Lung deposition has recently been assessed from a new dry powder inhaler, the Novolizer (ASTA Medica, now VIATRIS GmbH & Co. KG, subsidiary Sofotec GmbH & Co. KG, Frankfurt, Germany), using gamma scintigraphy. It was shown that the Novolizer deposited significantly more budesonide in the lungs than a Turbuhaler used either at similar inspiratory flow rates or with similar inspiratory effort. Equivalent clinical efficacy and safety profiles have also been shown in asthmatic patients treated with budesonide from each device.

  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. A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level

    PubMed Central

    2012-01-01

    Background In animal experiments, use of molecular hydrogen ( H2) has been regarded as quite safe and effective, showing benefits in multiple pathological conditions such as ischemia-reperfusion injury of the brain, heart, kidney and transplanted tissues, traumatic and surgical injury of the brain and spinal cord, inflammation of intestine and lung , degenerative striatonigral tissue and also in many other situations. However, since cerebral ischemia patients are in old age group, the safety information needs to be confirmed. For the feasibility of H2 treatment in these patients, delivery of H2 by inhalation method needs to be checked for consistency. Methods Hydrogen concentration (HC) in the arterial and venous blood was measured by gas chromatography on 3 patients, before, during and after 4% (case 1) and 3% (case2,3) H2 gas inhalation with simultaneous monitoring of physiological parameters. For a consistency study, HC in the venous blood of 10 patients were obtained on multiple occasions at the end of 30-min H2 inhalation treatment. Results The HC gradually reached a plateau level in 20 min after H2 inhalation in the blood, which was equivalent to the level reported by animal experiments. The HC rapidly decreased to 10% of the plateau level in about 6 min and 18 min in arterial and venous blood, respectively after H2 inhalation was discontinued. Physiological parameters on these 3 patients were essentially unchanged by use of hydrogen. The consistency study of 10 patients showed the HC at the end of 30-min inhalation treatment was quite variable but the inconsistency improved with more attention and encouragement. Conclusion H2 inhalation of at least 3% concentration for 30 min delivered enough HC, equivalent to the animal experiment levels, in the blood without compromising the safety. However, the consistency of H2 delivery by inhalation needs to be improved. PMID:22916706

  15. 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.

  16. Regular inhaled beta agonist in asthma: effects on exacerbations and lung function.

    PubMed Central

    Taylor, D R; Sears, M R; Herbison, G P; Flannery, E M; Print, C G; Lake, D C; Yates, D M; Lucas, M K; Li, Q

    1993-01-01

    BACKGROUND: A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported. This paper presents additional information on exacerbations of asthma and trends in lung function, airways hyperresponsiveness to methacholine, and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment. METHODS: Subjects undertook a year long randomised, double blind crossover study of regular upsilon as needed inhaled beta agonist treatment. Fenoterol (400 micrograms) or matching placebo was inhaled as a dry powder four times daily for 24 weeks, then subjects crossed over to the alternative regimen. Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study. Symptoms, peak expiratory flow rates, and drug use were recorded daily, spirometry was performed every four weeks, and methacholine and bronchodilator responsiveness were measured every eight weeks. RESULTS: Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment. Prebronchodilator forced expiratory volume in one second (FEV1) was on average 0.15 litres lower (95% confidence interval (95% CI) 0.11-0.19) and vital capacity (VC) 0.12 litres lower (95% CI 0.08-0.16) than during the placebo period. Morning peak flow rates were significantly lower and evening peak flow rates significantly higher, with an increase in diurnal variation from 9.8% (95% CI 6.9-12.8) to 17.5% (95% CI 13.8-21.3) during regular treatment. Geometric mean concentration of methacholine causing a 20% fall in FEV1 from the value after saline (PC20) decreased significantly from 1.63 to 1.15 mg/ml, indicating increased bronchial hyperresponsiveness during regular treatment

  17. Inhaled Hydrogen Sulfide Improves Graft Function in an Experimental Model of Lung Transplantation

    PubMed Central

    George, Timothy J.; Arnaoutakis, George J.; Beaty, Claude A.; Jandu, Simran K.; Santhanam, Lakshmi; Berkowitz, Dan E.; Shah, Ashish S.

    2014-01-01

    Objectives: Ischemia-reperfusion(IRI) is a common complication of lung transplantation(LTx). Hydrogen sulfide(H2S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pre-treatment with inhaled H2S would improve graft function in an ex vivo model of LTx. Methods: Rabbits(n=10) were ventilated for 2 hours prior to heart-lung bloc procurement. The treatment group(n=5) inhaled room air(21% O2) supplemented with 150 ppm H2S while the control group(n=5) inhaled room air alone. Both groups were gradually cooled to 34 C. All heart-lung blocs were then recovered and cold-stored in low potassium dextran solution for 18 hours. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. Results: Prior to heart-lung bloc procurement, rabbits pre-treated with H2S exhibited similar oxygenation(p=0.1), ventilation(p=0.7), and heart rate(p=0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures(p=0.01). During reperfusion, lungs pre-treated with H2S had better oxygenation(p<0.01) and ventilation(p=0.02) as well as lower pulmonary artery pressures(p<0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion(p=0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity(p=0.01). Conclusions: To our knowledge, this study represents the first reported therapeutic use of inhaled H2S in an experimental model of LTx. After prolonged ischemia, lungs pre-treated with inhaled H2S exhibited improved graft function during reperfusion. Donor pre-treatment with inhaled H2S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration. PMID:22771242

  18. [Food hypersensibility: inhalation reactions are different from ingestion reactions].

    PubMed

    Baranes, T; Bidat, E

    2008-06-01

    Eight children, aged from 3 to 9 years, presented to inhaled peanut an immediate allergic reaction. All were sensitized to peanut but none had already ingested it overtly. A strict avoidance diet was prescribed concerning this food allergen. An oral provocation challenge was realized to determine the eliciting dose (ED) to ingestion. The ED was high enough to allow all the children a less restrictive diet. Inhaled allergic reaction to peanut does not always justify a strict avoidance diet.

  19. Optimising inhaled mannitol for cystic fibrosis in an adult population

    PubMed Central

    Flume, Patrick A.; Aitken, Moira L.; Agent, Penny; Charlton, Brett; Forster, Emma; Fox, Howard G.; Hebestreit, Helge; Kolbe, John; Zuckerman, Jonathan B; Button, Brenda M.

    2015-01-01

    Abstract There has been remarkable progress in the treatment of cystic fibrosis (CF) patients over the past 20 years. However, limitations of standard therapies have highlighted the need for a convenient alternative treatment to effectively target the pathophysiologic basis of CF-related disease by improving mucociliary clearance of airway secretions and consequently improve lung function and reduce respiratory exacerbations. Mannitol is an osmotic agent available as a dry powder, dispensed in a convenient disposable inhaler device for the treatment of adult patients with CF. Inhalation of mannitol as a dry powder is thought to change the viscoelastic properties of airway secretions, increase the hydration of the airway surface liquid and contribute to increased mucociliary and cough clearance of retained secretions. In two large phase 3 studies [1, 2], long-term use of inhaled mannitol resulted in a significant and clinically meaningful improvement in lung function relative to control in adult CF subjects and had an acceptable safety profile. Clinical experience with inhaled mannitol confirms that it is safe and effective. A minority of patients are unable to tolerate the medication. However, through training in proper inhaler technique and setting clear expectations regarding therapeutic effects, both the tolerance and adherence necessary for long term efficacy can be positively influenced. Educational aims To discuss the importance of airway clearance treatments in the management of cystic fibrosis. To describe the clinical data that supports the use of mannitol in adult patients with cystic fibrosis. To highlight the role of mannitol tolerance testing in screening for hyperresponsiveness. To provide practical considerations for patient education in use of mannitol inhaler. Key points Inhaled mannitol is a safe and effective option in adult patients with cystic fibrosis. Mannitol tolerance testing effectively screens for hyperresponsiveness prior to initiation

  20. [Food hypersensibility: inhalation reactions are different from ingestion reactions].

    PubMed

    Baranes, T; Bidat, E

    2008-06-01

    Eight children, aged from 3 to 9 years, presented to inhaled peanut an immediate allergic reaction. All were sensitized to peanut but none had already ingested it overtly. A strict avoidance diet was prescribed concerning this food allergen. An oral provocation challenge was realized to determine the eliciting dose (ED) to ingestion. The ED was high enough to allow all the children a less restrictive diet. Inhaled allergic reaction to peanut does not always justify a strict avoidance diet. PMID:18456474

  1. Risk of Adverse Gastrointestinal Events from Inhaled Corticosteroids

    PubMed Central

    Hansen, Richard A.; Tu, Wanzhu; Wang, Jane; Ambuehl, Roberta; McDonald, Clement J.; Murray, Michael D.

    2009-01-01

    Study Objective Previous studies suggest a risk of gastrointestinal events in patients prescribed oral corticosteroids, but gastrointestinal events have not commonly been documented in patients prescribed inhaled corticosteroids. We explored whether patients prescribed inhaled corticosteroids are at risk of adverse gastrointestinal effects. Design A retrospective cohort study was conducted using 25 years of electronic medical record data. Setting An urban health center with an academic affiliation. Patients The incidence of adverse gastrointestinal events in patients prescribed inhaled corticosteroids and albuterol (n = 7,156) was compared to those prescribed albuterol alone (n = 12,287). Measurements and Main Results Adverse gastrointestinal outcomes included events such as gastritis, ulcers, and bleeding. Cox proportional hazards models were used to determine the risk of adverse events controlling for possible confounders such as alcohol use or non-steroidal anti-inflammatory drug use. Adverse gastrointestinal events were observed in 461 (6.4%) patients prescribed inhaled corticosteroids and albuterol and in 302 (2.5%) patients prescribed only albuterol. Patients prescribed inhaled albuterol and inhaled corticosteroids had an increased risk of adverse gastrointestinal events compared to patients prescribed only albuterol [hazard ratio 1.26 (95% confidence interval 1.02 to 1.56)] after controlling for potential confounders. A prescription for a spacer device reduced this risk among patients prescribed inhaled steroid [hazard ratio 0.26 (95% confidence interval 0.20 to 0.34)]. Conclusions Patients prescribed inhaled corticosteroids appear to have a slight risk of adverse gastrointestinal events that is mitigated in patients prescribed a spacer device. PMID:18956992

  2. Breath-synchronized plume-control inhaler for pulmonary delivery of fluticasone propionate.

    PubMed

    Shrewsbury, Stephen B; Armer, Thomas A; Newman, Stephen P; Pitcairn, Gary

    2008-05-22

    A novel breath-synchronized, plume-control inhaler (Tempo inhaler) was developed to overcome limitations of a pressurized metered-dose inhaler. This report compared the Tempo inhaler and a commercial inhaler for fine particle distribution and lung deposition of fluticasone propionate. In vitro fine particle distribution was determined using the Andersen Cascade Impactor at inspiration rates of 28.3 and 45L/min. In vivo lung deposition was assessed in a randomized, two-arm, crossover study of (99m)Tc-radiolabeled fluticasone propionate in 12 healthy adult subjects, analyzed by gamma scintigraphy. In vitro: fine particle fractions at 28.3 and 45L/min were 88.6+/-3.6% and 89.2+/-3.0% (Tempo inhaler) versus 40.4+/-4.7% and 43.1+/-4.4% (commercial inhaler). In vivo: lung deposition was 41.5+/-9.8% (Tempo inhaler) versus 13.8+/-7.4% (commercial inhaler) and oropharyngeal deposition was 18.3+/-7.7% (Tempo inhaler) versus 76.8+/-7.1% (commercial inhaler). Variability of lung deposition was reduced from 55% (commercial inhaler) to 24% (Tempo inhaler) of the delivered dose. The Tempo inhaler produced significantly higher fine particle fraction values, reduced oropharyngeal deposition by 75%, and increased whole, central, intermediate, and peripheral lung delivery by more than 200%. Thus, the Tempo inhaler enhances efficient drug delivery to the lungs.

  3. 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

  4. Influencing Inhalant Intentions by Changing Socio-Personal Expectations

    PubMed Central

    Alvaro, Eusebio M.; Crano, William D.; Skenderian, Jessica; Lac, Andrew; Patel, Neil

    2008-01-01

    This study investigates an approach for reducing inhalant initiation among younger adolescents: altering Socio-Personal Expectations (SPEs), a term referring to perceived linkages between behavior and personally relevant social outcomes. The study focuses specifically on SPEs regarding outcomes associated with increased social status and popularity. An anti-inhalant message was embedded within a short anti-bullying education video. Young adolescents (N=893) were assigned randomly to receive a message focused on the physical or the social harms of inhalant use. The objectives of this study were to test: (1) the malleability of SPEs, (2) SPEs’ predictive validity for future inhalant use, and (3) whether being exposed to a socio-personal threat, rather than a physical threat, led to different variables affecting drug-relevant decision-making processes. Analysis of variance suggested the malleability of SPEs (p<.001). Multiple regression analysis revealed that SPEs were predictive of future inhalant use. SPEs accounted for a significant portion of variance in future intentions over and above demographic variables, prior use, psychosocial variables, and perceived physical harm (R2=.26, p<.01). Moreover, being exposed to a social, rather than a physical threat, message resulted in different variables being predictive of future intentions to use inhalants. PMID:18543103

  5. Inhalers and nebulizers: which to choose and why.

    PubMed

    Pedersen, S

    1996-02-01

    It is obvious that many factors should be considered when an inhaler is prescribed. Based upon the information discussed above, a rational inhaler strategy could be as follows: (1) Children < or = 5 years and elderly patients are prescribed a spacer with a valve system (and a face mask for the children) for the delivery of all drugs. When they are severely obstructed, some may need a nebulizer. If the patient cannot be taught the correct use of a spacer, a nebulizer should be prescribed. (2) Children > or = 5 years and adults are prescribed a spacer or a Turbuhaler for the administration of inhaled corticosteroids and a dry powder inhaler (preferably multiple dose) or a breath-actuated MDI for other drugs. If these alternatives are not available or the patient prefers, a conventional MDI can be used (preferably not for other corticosteroids than fluticasone propionate) provided that careful tuition is given. Fluticasone dipropionate may be given by DPI, Spacer or MDI. (3) Nebulizers are mainly reserved for severe acute attacks of bronchoconstriction. With this approach, most patients can be taught effective inhaler use with a minimum of instructional time. Finally, it must always be remembered to consider the patient's wish, since prescription of an inhaler which the physician likes but the patient does not is likely to reduce compliance.

  6. From inhaler to lung: clinical implications of the formulations of ciclesonide and other inhaled corticosteroids

    PubMed Central

    Nave, Ruediger; Mueller, Helgert

    2013-01-01

    Asthma continues to be a global health problem and currently available treatments such as corticosteroids can cause unwanted side effects. Inhaled corticosteroids (ICS) are recommended as first-line therapy for reducing airway inflammation and have a distinct advantage over oral preparations as they provide a direct route of delivery to the lungs. However, local deposition of ICS in the oropharynx can lead to oral candidiasis, dysphonia, and pharyngitis. The pharmaceutical quality is a primary concern of any ICS asthma treatment, with a higher quality product resulting in improved efficacy and safety profiles. The particle size distribution and the spray force velocity of an ICS may directly influence lung deposition, and the spray duration of a device is another important factor when coordinating inhalation. Recent advances in ICS device and formulation technology have resulted in significant improvements in the efficacy of available asthma treatments. In particular, hydrofluoroalkane (HFA) solution technology and the development of smaller particle sizes have resulted in the production of new ICS formulations that have the ability to directly target drug delivery to the site of airway inflammation. Both the ICS formulation and the pressurized metered-dose inhaler device used to administer ciclesonide (CIC) HFA have been developed to treat the underlying chronic inflammation associated with asthma. CIC is administered as a prodrug which is activated in the lungs, leading to minimal oropharyngeal deposition. The small particle size of CIC results in the delivery of a high fraction of respirable particles to the small airways of the lungs, resulting in high lung deposition and continual dose consistency. This review summarizes how CIC administered as an HFA formulation is an effective treatment for asthma. PMID:23516175

  7. Advances in metered dose inhaler technology: formulation development.

    PubMed

    Myrdal, Paul B; Sheth, Poonam; Stein, Stephen W

    2014-04-01

    Pressurized metered dose inhalers (MDIs) are a long-standing method to treat diseases of the lung, such as asthma and chronic obstructive pulmonary disease. MDIs rely on the driving force of the propellant, which comprises the bulk of the MDI formulation, to atomize droplets containing drug and excipients, which ideally should deposit in the lungs. During the phase out of chlorofluorocarbon propellants and the introduction of more environmentally friendly hydrofluoroalkane propellants, many improvements were made to the methods of formulating for MDI drug delivery along with a greater understanding of formulation variables on product performance. This review presents a survey of challenges associated with formulating MDIs as solution or suspension products with one or more drugs, while considering the physicochemical properties of various excipients and how the addition of these excipients may impact overall product performance of the MDI. Propellants, volatile and nonvolatile cosolvents, surfactants, polymers, suspension stabilizers, and bulking agents are among the variety of excipients discussed in this review article. Furthermore, other formulation approaches, such as engineered excipient and drug-excipient particles, to deliver multiple drugs from a single MDI are also evaluated. PMID:24452499

  8. Inhaled toxic agents: An evaluation of dose. Final report

    SciTech Connect

    Hanna, L.M.

    1993-01-01

    A mathematical model was developed for the absorption of gases or vapors in the respiratory tract for use in determining the dose of inhaled gases and vapors to the airways of an individual and to extrapolate doses from animals to human subjects. The physical and chemical properties of the gas or vapor determine its absorption and must be considered in extrapolation between species. The method developed depends on determining the dimensions of the airspace surrounding each turbinate and assumes the airspace is geometrically similar to an annulus or a duct. The method may be used to quantify regional variability in airway dimensions of a population. Casted models of air passages made from cadavers were also studied and found to differ significantly from those of living human subjects. The extrapolations made using these cadaver models may not accurately reveal the flow and deposition rates found in living persons. Measurements which were made from hand traced images of airway dimensions were significantly different from measurements made with an image analyzer in which the digital data containing the scanned images were downloaded to the analyzer.

  9. 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}.

  10. 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.

  11. 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. PMID:27277119

  12. Lupine inhalation induced asthma in a child.

    PubMed

    Moreno-Ancillo, Alvaro; Gil-Adrados, Ana C; Domínguez-Noche, Carmen; Cosmes, Pedro M

    2005-09-01

    The ingestion of lupine seed flour has been reported as a cause of allergic reactions. There is some evidence of its allergenic potential after inhalation. An 8-year-old asthmatic child, who was allergic to peanut, was studied in our clinic with the suspicion of an adverse drug reaction due to salbutamol. He suffered an asthma attack while playing with his brother, who had been eating lupine seed as snack; surprisingly, the asthma attack worsened with salbutamol. The skin tests showed a positive result with Lupinus albus extract, peanut, garbanzo bean, navy bean, pea, green bean, lentil, soy, Olea europea pollen, grass pollen and Plantago lanceolata pollen. The prick-by-prick tests both from dried seeds and those preserved in salt and water were strongly positive. Serum specific IgE antibodies were positive to Lupine albus (1.43 kU/l), peanut (4.32 kU/l), soy (2.15 kU/l), lentil (3.12 kU/l) and garbanzo (0.7 kU/l). After informed consent salbutamol was well tolerated but the patient had asthma in 5 min of manipulation of the lupine seeds. In our case, reactivity with other legumes was also demonstrated, but only peanut allergy was relevant because boiled legumes were tolerated. It is also notorious that anamnesis is so important to assess the true etiological agents of asthma.

  13. 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. PMID:26586390

  14. Early interventions in asthma with inhaled corticosteroids.

    PubMed

    Laitinen, L A; Altraja, A; Karjalainen, E M; Laitinen, A

    2000-02-01

    We have earlier shown epithelial damage in the airway mucosa in patients with asthma. Later other structural changes have been recognized in asthma, such as deposition of collagen and tenascin in the subepithelial basement membrane and changes in the laminin subchain composition. These processes are modified by an inflammatory process in the airways. Both the United States National Institutes of Health and the British Thoracic Society guidelines on the management of asthma emphasize the need for early use of anti-inflammatory drugs. Many clinical studies that used airway biopsy specimens have shown a decrease in airway inflammatory cell numbers after inhaled corticosteroid therapy. However, there is very little information on the effects of asthma medication on the structural components of the airways. Both the synthesis and degradation of many extracellular matrix components may be affected by the disease process and the drugs resulting in altered remodeling and gene expression in the airways. Because there are only a few studies that try to identify early changes in asthma, it is not known whether the anti-inflammatory treatment of asthma proposed by the guidelines is started early enough.

  15. 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.

  16. Novolizer: how does it fit into inhalation therapy?

    PubMed

    Magnussen, Helgo

    2005-01-01

    Inhalation therapy is the preferred route of administration of anti-asthmatic drugs to the lungs. However, the vast majority of patients cannot use their inhalers correctly, particularly pressurised metered dose inhalers (pMDIs). The actual proportion of patients who do not use their inhalers correctly may even be under-estimated as GPs tend to over-estimate correct inhalation technique. Dry powder inhalers (DPIs) have many advantages over pMDIs. Unlike pMDIs, they are environmentally-friendly, contain no propellant gases and, more importantly, they are breath-activated, so that the patient does not need to coordinate actuation of the inhaler with inspiration. Three key parameters for correct inhaler use should be considered when evaluating existing or future DPI devices and especially when choosing the appropriate device for the patient: (1) usability, (2) particle size distribution of the emitted drug and (3) intrinsic airflow resistance of the device. The Novolizer is a breath-activated, multidose, refillable DPI. It is easy to use correctly, has multiple feedback and control mechanisms which guide the patient through the correct inhalation manoeuvre. In addition, the Novolizer has an intelligent dose counter, which resets only after a correct inhalation and may help to monitor patient compliance. The Novolizer has a comparable or better lung deposition than the Turbuhaler at similar or higher peak inspiratory flow (PIF) rates. A flow trigger valve system ensures a clinically effective fine particle fraction (FPF) and sufficient drug delivery, which is important for a good lung deposition. The FPF produced through the Novolizer is also relatively independent of flow rate and the device shows better reproducibility of metering and delivery performance compared to the Turbuhaler. The low-to-medium airflow resistance means that the Novolizer is easy for patients to use correctly. Even children, patients with severe asthma and patients with moderate

  17. 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.

  18. Air permeability of powder: a potential tool for Dry Powder Inhaler formulation development.

    PubMed

    Le, V N P; Robins, E; Flament, M P

    2010-11-01

    Dry Powder Inhalers have drawn great attention from pharmaceutical scientists in recent years in particular those consisting of low-dose micronized drug particles associated with larger carrier particles and called interactive mixtures. However, there is little understanding of the relation between bulk powder properties such as powder structure and its aerodynamic dispersion performance. The aim of this work was to develop a simple method to measure the air permeability of interactive mixtures used in Dry Powder Inhalers by using Blaine's apparatus--a compendial permeameter and to relate it to the aerodynamic behaviour. The study was done with fluticasone propionate and terbutaline sulphate as drug models that were blended with several lactoses having different particle size distribution thus containing different percentages of fine particle lactose. The quality of the blends was examined by analysing the drug content uniformity. Aerodynamic evaluation of fine particle fraction was obtained using a Twin Stage Impinger. A linear correlation between a bulk property--air permeability of packed powder bed--and the fine particle fraction of drug was observed for the tested drugs. The air permeability reflects the quantity of the free particle fraction in the interparticulate spaces of powder bed that leads to fine particle fraction during fluidization in air flow. A theoretical approach was developed in order to link the air permeability of powder bed and drag force acting on powders during aerosolization process. The permeability technique developed in this study provides a potential tool for screening Dry Powder Inhaler formulations at the development stage.

  19. Air permeability of powder: a potential tool for Dry Powder Inhaler formulation development.

    PubMed

    Le, V N P; Robins, E; Flament, M P

    2010-11-01

    Dry Powder Inhalers have drawn great attention from pharmaceutical scientists in recent years in particular those consisting of low-dose micronized drug particles associated with larger carrier particles and called interactive mixtures. However, there is little understanding of the relation between bulk powder properties such as powder structure and its aerodynamic dispersion performance. The aim of this work was to develop a simple method to measure the air permeability of interactive mixtures used in Dry Powder Inhalers by using Blaine's apparatus--a compendial permeameter and to relate it to the aerodynamic behaviour. The study was done with fluticasone propionate and terbutaline sulphate as drug models that were blended with several lactoses having different particle size distribution thus containing different percentages of fine particle lactose. The quality of the blends was examined by analysing the drug content uniformity. Aerodynamic evaluation of fine particle fraction was obtained using a Twin Stage Impinger. A linear correlation between a bulk property--air permeability of packed powder bed--and the fine particle fraction of drug was observed for the tested drugs. The air permeability reflects the quantity of the free particle fraction in the interparticulate spaces of powder bed that leads to fine particle fraction during fluidization in air flow. A theoretical approach was developed in order to link the air permeability of powder bed and drag force acting on powders during aerosolization process. The permeability technique developed in this study provides a potential tool for screening Dry Powder Inhaler formulations at the development stage. PMID:20854906

  20. 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

  1. 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

  2. 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

  3. 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

  4. Comparison of speed of inhalational induction in children with and without congenital heart disease

    PubMed Central

    Hasija, Suruchi; Chauhan, Sandeep; Jain, Pawan; Choudhury, Arin; Aggarwal, Neelam; Pandey, Ravinder Kumar

    2016-01-01

    Background: Conduct of stable inhalational anesthetic induction in children with congenital heart disease (CHD) presents special challenges. It requires in-depth understanding of the effect of congenital shunt lesions on the uptake, delivery, and equilibration of anesthetic drugs. Intracardiac shunts can alter the induction time and if delivery of anesthetic agent is not carefully titrated, can lead to overdosing and undesirable myocardial depression. Aims: To study the effect of congenital shunt lesions on the speed of inhalational induction and also the impact of inhalational induction on hemodynamics in the presence of congenital shunt lesions. Setting: Tertiary care hospital. Design: A prospective, single-center clinical study. Materials and Methods: Ninety-three pediatric patients undergoing elective surgery were segregated into three equal groups, namely, Group 1: no CHD, Group 2: acyanotic CHD, and Group 3: cyanotic CHD. General anesthesia was induced with 8% sevoflurane in 6 L/min air-oxygen. The time to induction was noted at loss of eyelash reflex and decrease in bispectral index (BIS) value below 60. End-tidal sevoflurane concentration, minimum alveolar concentration, and BIS were recorded at 15 s intervals for the 1st min followed by 30 s interval for another 1 min during induction. Hemodynamic data were recorded before and after induction. Results: Patients in Group 3 had significantly prolonged induction time (99 ± 12.3 s; P < 0.001), almost twice that of the patients in other two groups (51 ± 11.3 s in Group 1 and 53 ± 12.0 s in Group 2). Hypotension occurred after induction in Group 1. No other adverse hemodynamic perturbations were observed. Conclusion: The time to inhalational induction of anesthesia is significantly prolonged in patients with right-to-left shunt, compared to patients without CHD or those with left-to-right shunt, in whom it is similar. Sevoflurane is safe and maintains stable hemodynamics in the presence of CHD. PMID:27397451

  5. Modification of the methacholine inhalation test and its epidemiologic use in polyurethane workers

    SciTech Connect

    Hendrick, D.J.; Fabbri, L.M.; Hughes, J.M.; Banks, D.E.; Barkman, H.W. Jr.; Connolly, M.J.; Jones, R.N.; Weill, H.

    1986-04-01

    The dosimeter method of administering doubling cumulative doses of methacholine to measure bronchial responsiveness was standardized to control for the effects of a number of potential influencing variables. The aerodynamic mass median diameter of the challenge aerosol produced from a DeVilbiss 646 nebulizer proved to be 1.2 mu, and the mean output per inhalation 8.9 microliters. Each challenge dose comprised 5 inhalations. Cumulative doses ranged from 0.3 methacholine inhalation units (1 unit = 1 inhalation of aerosol from a 1-mg/ml solution of methacholine, i.e., 8.9 micrograms methacholine) to a possible 640 units, the maximum that was considered reasonable to avoid the risk of unacceptable systemic effects. Responsiveness was expressed as the dose provoking a 20% decline (PD20) in FEV1. Modifications in this full protocol were introduced to facilitate epidemiologic investigations. Physician assessments coupled with baseline measurements of ventilatory function allowed starting at higher dosages for persons with low probability of hyperresponsiveness, thereby shortening the time required for testing to an average of 38 min. In a validation study of 20 persons using both the full and modified protocols, no significant differences were detected between measured PD20 values (geometric means Full versus Modified, 14.83 versus 14.88; r = 0.99). The modified protocol was used to measure bronchial responsiveness in 254 workers exposed to toluene diisocyanate. It proved to be safe and acceptable. Sixty-four workers (25.2%) were found to be reactors. The frequency distribution of the PD20 values exhibited a steadily increasing trend, consistent with a unimodal distribution.

  6. 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

  7. Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children.

    PubMed Central

    Clark, D. J.; Clark, R. A.; Lipworth, B. J.

    1996-01-01

    BACKGROUND: The aim of this study was to compare the systemic bioactivity of inhaled budesonide (B) and fluticasone propionate (F), each given by large volume spacer, on a microgram equivalent basis in asthmatic children. METHODS: Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second (FEV1) 81.6% predicted, who were receiving treatment with < or = 400 micrograms/day of inhaled corticosteroid, were studied in a placebo controlled single blind (investigator blind) randomised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800 micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion. RESULTS: The results of overnight 12 hour urinary cortisol output (nmol/12 hours) showed suppression with all doses of fluticasone propionate (as geometric means): F400 micrograms (11.99), F800 micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas budesonide caused no suppression at any dose. A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26 to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to 5.15). The results for the cortisol/creatinine ratio were similar to that of urinary cortisol, with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms. CONCLUSIONS: Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is due mainly to lung bioavailability. PMID:8984708

  8. Researches regarding the Morton ether inhaler at Massachusetts General Hospital, Boston.

    PubMed

    Haridas, Rajesh P; Mifflin, Jeffrey A

    2013-11-01

    The Morton ether inhaler in the possession of Massachusetts General Hospital, Boston, MA, was traced back to 1906 when the earliest known photograph of it was published. The authors believe that the inhaler was given by William T. G. Morton, MD, to J. Mason Warren, MD, in January 1847. The inhaler was acquired by the Warren Anatomical Museum at an unknown date, loaned to Massachusetts General Hospital in October 1946, and placed on permanent loan to Massachusetts General Hospital in April 1948. Many documents relating to the inhaler have disappeared, and it was only identified in 2009 as the inhaler that probably belonged to J. Mason Warren, MD. The inhaler is not believed to be the one that Morton used on October 16, 1846, at Massachusetts General Hospital. It is the only known example of a Morton ether inhaler with valves (excluding replicas or reproduction inhalers) and is probably of similar design to the inhaler that Morton used on October 16, 1846.

  9. An optimization strategy for a biokinetic model of inhaled radionuclides

    SciTech Connect

    Shyr, L.J.; Griffith, W.C.; Boecker, B.B. )

    1991-04-01

    Models for material disposition and dosimetry involve predictions of the biokinetics of the material among compartments representing organs and tissues in the body. Because of a lack of human data for most toxicants, many of the basic data are derived by modeling the results obtained from studies using laboratory animals. Such a biomathematical model is usually developed by adjusting the model parameters to make the model predictions match the measured retention and excretion data visually. The fitting process can be very time-consuming for a complicated model, and visual model selections may be subjective and easily biased by the scale or the data used. Due to the development of computerized optimization methods, manual fitting could benefit from an automated process. However, for a complicated model, an automated process without an optimization strategy will not be efficient, and may not produce fruitful results. In this paper, procedures for, and implementation of, an optimization strategy for a complicated mathematical model is demonstrated by optimizing a biokinetic model for 144Ce in fused aluminosilicate particles inhaled by beagle dogs. The optimized results using SimuSolv were compared to manual fitting results obtained previously using the model simulation software GASP. Also, statistical criteria provided by SimuSolv, such as likelihood function values, were used to help or verify visual model selections.

  10. 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.

  11. Translocation pathways for inhaled asbestos fibers.

    PubMed

    Miserocchi, G; Sancini, G; Mantegazza, F; Chiappino, Gerolamo

    2008-01-01

    We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation) wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation). Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots) reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow) and in the liver (reflecting high microvascular permeability) while it is relatively low in the brain (due to low permeability of blood-brain barrier). Ultrafine fibers (length < 5 mum, diameter < 0.25 mum) can travel larger distances due to low steric hindrance (in mesothelioma about 90% of fibers are ultrafine). Fibers translocation is a slow process developing over decades of life: it is aided by high biopersistence, by inflammation-induced increase in permeability, by low steric

  12. 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

  13. 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.

  14. 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

  15. Inhalability for aerosols at ultra-low windspeeds

    NASA Astrophysics Data System (ADS)

    Sleeth, Darrah K.; Vincent, James H.

    2009-02-01

    Most previous experimental studies of aerosol inhalability were conducted in wind tunnels for windspeeds greater than 0.5 ms-1. While that body of work was used to establish a convention for the inhalable fraction, results from studies in calm air chambers (for essentially zero windspeed) are being discussed as the basis of a modified criterion. 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, ultimately, personal sampler performance - for aerosols with particle aerodynamic diameter within the range from about 9 to 90 μm for ultra-low windspeed environments from about 0.1 to 0.5 ms1. This new system contains an aerosol test facility, fully described elsewhere, that combines the physical attributes and performance characteristics of moving air wind tunnels and calm air chambers, both of which have featured individually in previous research. It also contains a specially-designed breathing, heated, life-sized mannequin that allows for accurate recovery of test particulate material that has been inhaled. Procedures have been developed that employ test aerosols of well-defined particle size distribution generated mechanically from narrowly-graded powders of fused alumina. Using this new system, we have conducted an extensive set of new experiments to measure the inhalability of a human subject (as represented by the mannequin), aimed at filling the current knowledge gap for conditions that are more realistic than those embodied in most previous research. These data reveal that inhalability throughout the range of interest is significantly different based on windspeed, indicating a rise in aspiration efficiency as windspeed decreases. Breathing flowrate and mode of breathing (i.e. nose versus mouth breathing) did not show significant differences for the inhalability of aerosols. On the whole

  16. 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

  17. 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

  18. Nicotine nasal spray and vapor inhaler: abuse liability assessment.

    PubMed

    Schuh, K J; Schuh, L M; Henningfield, J E; Stitzer, M L

    1997-04-01

    Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products. PMID:9160851

  19. Effects of CO2 inhalation exposure on mice vomeronasal epithelium.

    PubMed

    Hacquemand, Romain; Buron, Gaelle; Pourié, Gregory; Karrer, Melanie; Jacquot, Laurence; Brand, Gerard

    2010-08-01

    Nasal epitheliums are the first sites of the respiratory tract in contact with the external environment and may therefore be susceptible to damage from exposure to many toxic volatile substances (i.e., volatile organic components, vapors, and gases). In the field of inhalation toxicology, a number of studies have considered the main olfactory epithelium, but few have dealt with the epithelium of the vomeronasal organ (VNO). However, in several species such as in rodents, the VNO (an organ of pheromone detection) plays an important role in social interactions, and alterations of this organ are known to induce adaptative behavioral disturbances. Among volatile toxicants, health effects of inhaled gases have been thoroughly investigated, especially during CO(2) inhalation because of its increasing atmospheric concentration. Therefore, this work was designed to examine the effects of 3% CO(2) inhalation on VNO in two different exposure conditions (5 h/day and 12 h/day) in mice. Behavioral sensitivity tests to urine of congener and histological measurements of VNO were conducted before, during (weeks 1-4), and after (weeks 5-8) CO(2) inhalation exposures. Results showed no significant modifications of behavioral responses to urine, but there were significant changes of both cell number and thickness of the VNO epithelium. Moreover, the findings indicated a selectively dose-dependent effect of CO(2), and further research could use other gases in the same manner for comparison.

  20. 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. PMID:26475968

  1. Raxibacumab: potential role in the treatment of inhalational anthrax

    PubMed Central

    Kummerfeldt, Carlos E

    2014-01-01

    Anthrax is a highly contagious and potentially fatal human disease caused by Bacillus anthracis, an aerobic, Gram-positive, spore-forming rod-shaped bacterium with worldwide distribution as a zoonotic infection in herbivore animals. Bioterrorist attacks with inhalational anthrax have prompted the development of more effective treatments. Antibodies against anthrax toxin have been shown to decrease mortality in animal studies. Raxibacumab is a recombinant human monoclonal antibody developed against inhalational anthrax. The drug received approval after human studies showed its safety and animal studies demonstrated its efficacy for treatment as well as prophylaxis against inhalational anthrax. It works by preventing binding of the protective antigen component of the anthrax toxin to its receptors in host cells, thereby blocking the toxin’s deleterious effects. Recently updated therapy guidelines for Bacillus anthracis recommend the use of antitoxin treatment. Raxibacumab is the first monoclonal antitoxin antibody made available that can be used with the antibiotics recommended for treatment of the disease. When exposure is suspected, raxibacumab should be given with anthrax vaccination to augment immunity. Raxibacumab provides additional protection against inhalational anthrax via a mechanism different from that of either antibiotics or active immunization. In combination with currently available and recommended therapies, raxibacumab should reduce the morbidity and mortality of inhalational anthrax. PMID:24812521

  2. Effects of CO2 inhalation exposure on mice vomeronasal epithelium.

    PubMed

    Hacquemand, Romain; Buron, Gaelle; Pourié, Gregory; Karrer, Melanie; Jacquot, Laurence; Brand, Gerard

    2010-08-01

    Nasal epitheliums are the first sites of the respiratory tract in contact with the external environment and may therefore be susceptible to damage from exposure to many toxic volatile substances (i.e., volatile organic components, vapors, and gases). In the field of inhalation toxicology, a number of studies have considered the main olfactory epithelium, but few have dealt with the epithelium of the vomeronasal organ (VNO). However, in several species such as in rodents, the VNO (an organ of pheromone detection) plays an important role in social interactions, and alterations of this organ are known to induce adaptative behavioral disturbances. Among volatile toxicants, health effects of inhaled gases have been thoroughly investigated, especially during CO(2) inhalation because of its increasing atmospheric concentration. Therefore, this work was designed to examine the effects of 3% CO(2) inhalation on VNO in two different exposure conditions (5 h/day and 12 h/day) in mice. Behavioral sensitivity tests to urine of congener and histological measurements of VNO were conducted before, during (weeks 1-4), and after (weeks 5-8) CO(2) inhalation exposures. Results showed no significant modifications of behavioral responses to urine, but there were significant changes of both cell number and thickness of the VNO epithelium. Moreover, the findings indicated a selectively dose-dependent effect of CO(2), and further research could use other gases in the same manner for comparison. PMID:19924548

  3. 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

  4. 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.

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

    PubMed

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

    2002-12-01

    An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles (i.e. carrier crystals) from the aerosol cloud before it is exposed to the laser beam. It also has a fine particle collector for measuring the emitted mass fraction of fines by chemical detection methods after laser diffraction sizing. The closed system enables flow control through the aerosol generators and all test conditions, including ambient temperature and relative humidity, are automatically recorded. Counter flows minimize particle deposition onto the two windows for the laser beam, which make successive measurements without cleaning of these windows possible. The adapter has successfully been tested for nebulizers, mdis and dpis. In a comparative study with ten nebulizers it was found that these devices differ considerably in droplet size (distribution) of the aerosol cloud for the same 10% aqueous tobramycin solution (volume median diameters ranging from 1.25 to 3.25 microm) when they are used under the conditions recommended by the manufacturers. The droplet size distribution generated by the Sidestream (with PortaNeb compressor) is very constant during nebulization until dry running of the device. Comparative testing of dpis containing spherical pellet type of formulations for the drug (e.g. the AstraZeneca Turbuhaler) with the adapter is fast and simple. But also formulations containing larger carrier material could successfully be measured. Disintegration efficiency of a test inhaler with carrier retainment (acting as a pre-separator) could be measured quite accurately both for a colistin sulfate formulation with 16.7% of a lactose fraction 106-150 microm and for a budesonide formulation with a carrier mixture of Pharmatose 325 and 150 M. Therefore, it is

  6. 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.

  7. 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'.

  8. 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.

  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. 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. PMID:26775187

  11. 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.

  12. 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

  13. Use of inhaled anticholinergic agents in obstructive airway disease.

    PubMed

    Restrepo, Ruben D

    2007-07-01

    In the last 2 decades, anticholinergic agents have been generally regarded as the first-choice bronchodilator therapy in the routine management of stable chronic obstructive pulmonary disease (COPD) and, to a lesser extent, asthma. Anticholinergics are particularly important bronchodilators in COPD, because the vagal tone appears to be the only reversible component of airflow limitation in COPD. The inhaled anticholinergics approved for clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide. This article reviews the most current evidence for inhaled anticholinergics in obstructive airway disease and summarizes outcomes reported in randomized controlled trials.

  14. Non-CFC metered dose inhalers: the patent landscape.

    PubMed

    Bowman, P A; Greenleaf, D

    1999-09-10

    There have been many patent applications to the European Patent Office over the past decade involving the transition of pressurised metered dose inhalers from the CFCs to non-CFC propellants. In addition to those where formulations are changed, there are those relating to specific drugs or drug classes, processes of manufacture and modifications to the container/closure system. Many of these have been opposed, usually on the grounds of obviousness. However, due to the length of time for the opposition process and the fact that there are few non-CFC pressurised inhalers on the market yet, the complete picture of which patents are valid has yet to unfold.

  15. 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).

  16. Inhalational and dermal exposures during spray application of biocides.

    PubMed

    Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

    2005-01-01

    Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

  17. 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...

  18. A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma.

    PubMed

    Hultquist, C; Ahlström, H; Kjellman, N I; Malmqvist, L A; Svenonius, E; Melin, S

    1989-09-01

    Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use. PMID:2683835

  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. Inhaled Lavender Effect on Anxiety and Pain Caused From Intrauterine Device Insertion

    PubMed Central

    Shahnazi, Mahnaz; Nikjoo, Roya; Yavarikia, Parisa; Mohammad-Alizadeh-Charandabi, Sakineh

    2012-01-01

    Introduction: Intrauterine device (IUD) is the most common reliable, effective and reversible contraceptive method used worldwide and in areas with high growth rate is of particular importance. IUD insertion is associated with high anxiety in most people that causes pain and discomfort. The aim of this study was to determine the effects of aromatherapy on anxiety and pain caused by IUD insertion. Methods: This study was conducted on 106 women in a health care center located in Ardebil, Iran. Participants were divided into two groups by randomized blocks of 4 and 6. In the experimental group lavender scent was inhaled and in the control group the placebo was inhaled 30 minutes before IUD insertion. The anxiety of the participants was measured by Spielberger questionnaire, and the pain of IUD insertion was measured immediately after the insertion using visual analog scale (range 0-10). Results: The mean score (standard deviation) of anxiety before intervention was 43.2 (9.2) in the experimental group that decreased after intervention to 39.0 (10.5) (p < 0.001), while this score was 42.2 (9.0) and 41.5 (8.4) before and after the intervention in the control group (p = 0.21). Mean differences of anxiety in both groups was statistically significant (p < 0.001). The pain score after intervention did not show significant difference between two groups (p = 0.51). Conclusion: Aromatherapy with lavender inhalation was effective in decreasing anxiety in IUD procedure, and this method can be used in health care centers as complementary treatments. PMID:25276703

  1. 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

  2. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Aqueous-based drug products for oral inhalation. 200.51 Section 200.51 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must...

  3. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Aqueous-based drug products for oral inhalation. 200.51 Section 200.51 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must...

  4. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Aqueous-based drug products for oral inhalation. 200.51 Section 200.51 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must...

  5. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Aqueous-based drug products for oral inhalation. 200.51 Section 200.51 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must...

  6. 42 CFR 84.137 - Inhalation and exhalation valves; check valves; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Inhalation and exhalation valves; check valves... PROTECTIVE DEVICES Supplied-Air Respirators § 84.137 Inhalation and exhalation valves; check valves; minimum requirements. (a) Inhalation and exhalation valves shall be provided where necessary and protected...

  7. 42 CFR 84.137 - Inhalation and exhalation valves; check valves; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Inhalation and exhalation valves; check valves... PROTECTIVE DEVICES Supplied-Air Respirators § 84.137 Inhalation and exhalation valves; check valves; minimum requirements. (a) Inhalation and exhalation valves shall be provided where necessary and protected...

  8. [Dermal and inhalation poisoning. Rare guests in our intensive care units?].

    PubMed

    Sagoschen, I

    2013-09-01

    Patients with dermal and inhalation poisoning are uncommon in intensive care treatment. We describe the diagnostics and specific toxicological treatment of patients with hydrofluoric acid burns. For inhalation poisoning, we focus on smoke inhalation, especially the management of cyanide and carbon monoxide poisoning. Special attention is given to the use of hyperbaric oxygenation for the treatment of carbon monoxide poisoning.

  9. 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...

  10. 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

  11. Lung burden of a glass fiber by inhalation.

    PubMed

    Tanaka, I; Akiyama, T; Kido, M

    1991-01-01

    Pulmonary deposition and clearance of deposited particles from lungs are very important factors in order to induce pneumoconioses. In this paper, five Wistar male rats were exposed to glass fiber particles (mass median aerodynamic diameter (MMAD), 2.8 microns) for 6 hrs/day, 5 days/week for 4 weeks. The average exposure concentration was controlled by a continuous fluidized bed with a screw feeder and an overflow pipe at 0.79 mg/m3 during the exposure period. The fibrous particles concentrations in the exposure chamber were monitored by a light scattering method and showed to be constant during the exposure. The rats were sacrificed at 24 hours after the termination of the exposure and then the wet lung weight and the silica concentration in the lungs were measured. The lungs were treated for low temperature ashing (ca. 150 degrees C) by a plasma asher. After ashing, these samples were melted with sodium carbonate in platinum pot for the measurement of the silica content by the absorption spectrophotometry. The maximum content of SiO2 was 45 micrograms in the exposed rats and 20 micrograms in the control. The deposited amount of SiO2 by the exposure to glass fiber was 25 micrograms. The apparent deposition fraction defined as the deposited amount in the lungs to the amount of the inhaled glass fiber during the exposure was 6.8%. There was no significant difference of the apparent deposition fraction at same MMAD between glass fiber in this study and non-fibrous particles.

  12. 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.

  13. 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...

  14. 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…

  15. 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...

  16. [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.

  17. Inhalation trauma due to overheating in a microwave oven.

    PubMed Central

    Zanen, A L; Rietveld, A P

    1993-01-01

    The microwave oven is a kitchen appliance that has become increasingly popular in recent years. In some instances the temperature in the microwave oven can become exceedingly high. A case is discussed of a patient with respiratory distress after inhalation of gas from an overheated microwave oven. Images PMID:8497834

  18. 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),…

  19. 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…

  20. 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...

  1. Exposure to Inhalable, Respirable, and Ultrafine Particles in Welding Fume

    PubMed Central

    Pesch, Beate

    2012-01-01

    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. PMID:22539559

  2. Stepping down inhaled corticosteroids in asthma: randomised controlled trial

    PubMed Central

    Hawkins, Gillian; McMahon, Alex D; Twaddle, Sara; Wood, Stuart F; Ford, Ian; Thomson, Neil C

    2003-01-01

    Objectives To determine whether the dose of inhaled corticosteroids can be stepped down in patients with chronic stable asthma while maintaining control. Design One year, randomised controlled, double blind, parallel group trial. Setting General practices throughout western and central Scotland. Participants 259 adult patients with asthma receiving regular treatment with inhaled corticosteroids at high dose (mean dose 1430 μg beclomethasone dipropionate). Interventions Participants were allocated to receive either no alteration to their dose of inhaled corticosteroid (control) or a 50% reduction in their dose if they met criteria for stable asthma (stepdown). Main outcome measures Comparison of asthma exacerbation rates, asthma related visits to general practice and hospital, health status measures, and corticosteroid dosage between the two groups. Results The proportions of subjects with asthma exacerbations were not significantly different (stepdown 31%, control 26%, P=0.354). Similarly, the numbers of visits to general practice or hospital and the disease specific and generic measures of health status over the one year period were not significantly different. On average the stepdown group received 348 μg (95% confidence interval 202 μgto494 μg) of beclomethasone dipropionate less per day than the controls (a difference of 25%), with no difference in the annual dose of oral corticosteroids between the two treatment regimens. Conclusions By adopting a stepdown approach to the use of inhaled steroids at high doses in asthma a reduction in the dose can be achieved without compromising asthma control. PMID:12763981

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.102-3 Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a...), enclose the service equipment within a protective housing and cover. (1) Tank cars must be equipped with...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.102-3 Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a...), enclose the service equipment within a protective housing and cover. (1) Tank cars must be equipped with...

  5. 49 CFR 179.102-3 - Materials poisonous by inhalation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.102-3 Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a...), enclose the service equipment within a protective housing and cover. (1) Tank cars must be equipped with...

  6. 49 CFR 179.102-3 - Materials poisonous by inhalation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CARS Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.102-3 Materials poisonous by inhalation. (a) Each tank car built after March 16, 2009 for the transportation of a...), enclose the service equipment within a protective housing and cover. (1) Tank cars must be equipped with...

  7. 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. PMID:22539559

  8. Short-term cardiovascular and autonomic effects of inhaled salbutamol.

    PubMed

    Edgell, Heather; Moore, Linn E; Chung, Carol; Byers, Bradley W; Stickland, Michael K

    2016-09-01

    Asthma independently increases the risk of developing cardiovascular disease. As inhaled β-agonists have systemic cardiovascular effects, and elevations in arterial stiffness and sympathetic nerve activity are associated with increased cardiovascular morbidity/mortality, this study examines the effect of salbutamol use on pulse wave velocity (PWV) and muscle sympathetic nervous activity (MSNA). Healthy men and women (26.2±1.5years) were recruited for: Day 1: 4 inhalations of placebo followed by 4 inhalations of salbutamol (4×100μg); Day 2: placebo only; Day 3: carotid-femoral PWV measurements before/after placebo/salbutamol. Heart rate (HR), mean arterial pressure (MAP), and carotid-radial PWV were obtained on Day 1 and 2. MSNA was obtained on Day 1. Salbutamol increased HR and total MSNA (Baseline1: 2.8±2.8au; Placebo: 2.4±2.1au; Baseline2: 2.7±3.0au; Salbutamol: 3.3±2.9au; p=0.05), with no changes in MAP or PWV. There were no effects of placebo on HR, MSNA, or PWV. Acute salbutamol use increases sympathetic activity suggesting that salbutamol could contribute to cardiovascular morbidity/mortality in individuals using inhaled β-agonists. PMID:27236040

  9. 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

  10. Risk from inhaled mycotoxins in indoor office and residential environments.

    PubMed

    Kelman, Bruce J; Robbins, Coreen A; Swenson, Lonie J; Hardin, Bryan D

    2004-01-01

    Mycotoxins are known to produce veterinary and human diseases when consumed with contaminated foods. Mycotoxins have also been proposed to cause adverse human health effects after inhalation exposure to mold in indoor residential, school, and office environments. Epidemiologic evidence has been inadequate to establish a causal relationship between indoor mold and nonallergic, toxigenic health effects. In this article, the authors model a maximum possible dose of mycotoxins that could be inhaled in 24 h of continuous exposure to a high concentration of mold spores containing the maximum reported concentration of aflatoxins B1 and B2, satratoxins G and H, fumitremorgens B and C, verruculogen, and trichoverrols A and B. These calculated doses are compared to effects data for the same mycotoxins. None of the maximum doses modeled were sufficiently high to cause any adverse effect. The model illustrates the inefficiency of delivery of mycotoxins via inhalation of mold spores, and suggests that the lack of association between mold exposure and mycotoxicoses in indoor environments is due to a requirement for extremely high airborne spore levels and extended periods of exposure to elicit a response. This model is further evidence that human mycotoxicoses are implausible following inhalation exposure to mycotoxins in mold-contaminated home, school, or office environments. PMID:15162841

  11. 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.

  12. 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...

  13. Dermal & inhalation exposure of operators during fungicide application in vineyards. Evaluation of coverall performance.

    PubMed

    Tsakirakis, Angelos N; Kasiotis, Konstantinos M; Charistou, Agathi N; Arapaki, Niki; Tsatsakis, Aristidis; Tsakalof, Andreas; Machera, Kyriaki

    2014-02-01

    In the present study the dermal and the inhalation exposure of five operators during fungicide applications in vineyards were determined. The produced exposure datasets can be used as surrogate for the estimation of the actual and the potential dermal as well as inhalation operator exposure levels for this application scenario. The dermal exposure was measured using the whole body dosimetry method while the inhalation exposure with the use of personal air sampling devices with XAD tubes located on the operator's breathing zone. Ten field trials were carried out by 5 different operators using a tractor assisted hand-held lance with spray gun at the Tanagra region of Viotia, Greece. An in-house GC-ECD analytical method was developed and validated for the determination of penconazole, which was the active substance (a.s.) of the fungicide formulation used in field trials. The mean recovery of field-fortified samples was 81%. The operator exposure results showed expected variability and were compared to those derived from the German model for prediction of operator exposure. The comparison of the 75th percentile values for an operator wearing personal protection equipment has shown that the measured levels were 2.2 times lower than those estimated by the German model. The levels of actual dermal exposure ranged from 2 to 19 mg/kg a.s. applied. The protection provided by the two types of coveralls was evaluated and in comparison to the existing reduction factors used for other types of PPE (coveralls) was found satisfactory for the operator under the conditions of the specific applications. PMID:24140699

  14. 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

  15. Dermal & inhalation exposure of operators during fungicide application in vineyards. Evaluation of coverall performance.

    PubMed

    Tsakirakis, Angelos N; Kasiotis, Konstantinos M; Charistou, Agathi N; Arapaki, Niki; Tsatsakis, Aristidis; Tsakalof, Andreas; Machera, Kyriaki

    2014-02-01

    In the present study the dermal and the inhalation exposure of five operators during fungicide applications in vineyards were determined. The produced exposure datasets can be used as surrogate for the estimation of the actual and the potential dermal as well as inhalation operator exposure levels for this application scenario. The dermal exposure was measured using the whole body dosimetry method while the inhalation exposure with the use of personal air sampling devices with XAD tubes located on the operator's breathing zone. Ten field trials were carried out by 5 different operators using a tractor assisted hand-held lance with spray gun at the Tanagra region of Viotia, Greece. An in-house GC-ECD analytical method was developed and validated for the determination of penconazole, which was the active substance (a.s.) of the fungicide formulation used in field trials. The mean recovery of field-fortified samples was 81%. The operator exposure results showed expected variability and were compared to those derived from the German model for prediction of operator exposure. The comparison of the 75th percentile values for an operator wearing personal protection equipment has shown that the measured levels were 2.2 times lower than those estimated by the German model. The levels of actual dermal exposure ranged from 2 to 19 mg/kg a.s. applied. The protection provided by the two types of coveralls was evaluated and in comparison to the existing reduction factors used for other types of PPE (coveralls) was found satisfactory for the operator under the conditions of the specific applications.

  16. Evidence of validity of an inhalant-craving questionnaire.

    PubMed

    Alonso-Matías, Lizeth; Páez-Martínez, Nayeli; Reyes-Zamorano, Ernesto; González-Olvera, Jorge J

    2015-12-15

    Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach's Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users.

  17. Evidence of validity of an inhalant-craving questionnaire.

    PubMed

    Alonso-Matías, Lizeth; Páez-Martínez, Nayeli; Reyes-Zamorano, Ernesto; González-Olvera, Jorge J

    2015-01-01

    Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach's Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users. PMID:26706810

  18. Evaluation of cerebral ischemia using near-infrared spectroscopy with oxygen inhalation

    NASA Astrophysics Data System (ADS)

    Ebihara, Akira; Tanaka, Yuichi; Konno, Takehiko; Kawasaki, Shingo; Fujiwara, Michiyuki; Watanabe, Eiju

    2012-09-01

    Conventional methods presently used to evaluate cerebral hemodynamics are invasive, require physical restraint, and employ equipment that is not easily transportable. Therefore, it is difficult to take repeated measurements at the patient's bedside. An alternative method to evaluate cerebral hemodynamics was developed using near-infrared spectroscopy (NIRS) with oxygen inhalation. The bilateral fronto-temporal areas of 30 normal volunteers and 33 patients with cerebral ischemia were evaluated with the NIRS system. The subjects inhaled oxygen through a mask for 2 min at a flow rate of 8 L/min. Principal component analysis (PCA) was applied to the data, and a topogram was drawn using the calculated weights. NIRS findings were compared with those of single-photon-emission computed tomography (SPECT). In normal volunteers, no laterality of the PCA weights was observed in 25 of 30 cases (83%). In patients with cerebral ischemia, PCA weights in ischemic regions were lower than in normal regions. In 28 of 33 patients (85%) with cerebral ischemia, NIRS findings agreed with those of SPECT. The results suggest that transmission of the changes in systemic SpO2 were attenuated in ischemic regions. The method discussed here should be clinically useful because it can be used to measure cerebral ischemia easily, repeatedly, and noninvasively.

  19. Prolonged asthma after smoke inhalation: A report of three cases and a review of previous reports

    SciTech Connect

    Moisan, T.C. )

    1991-04-01

    The development of prolonged obstructive airways disease after smoke inhalation is of concern to fire victims and fire fighters. Three cases of asthma that developed following the inhalation of pyrolysis products are presented along with a review of previous reports of airway injury from smoke inhalation. Polyvinyl chloride pyrolysis products seem to pose a high risk, but other toxic inhalants are also implicated. There is substantial evidence that prolonged airway hyper-responsiveness and asthma may follow numerous inflammatory insults including smoke inhalation. Studies to identify specific individual risk factors and asthmagenic pyrolysis products are needed. Early, postexposure anti-inflammatory treatment may modify the outcome. 42 refs.

  20. Childhood histories of attention-deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: preliminary report.

    PubMed

    Matsumoto, Toshihiko; Kamijo, Atsushi; Yamaguchi, Akiko; Iseki, Eizo; Hirayasu, Yoshio

    2005-02-01

    The present study examined childhood histories of attention-deficit hyperactivity disorder (ADHD) in 54 methamphetamine and 12 inhalant abusers using the Wender Utah Rating Scale. The inhalant abusers experienced initial drinking at a younger age than methamphetamine abusers (P=0.038). The Wender Utah Rating Scale score was significantly higher in the inhalant abusers than in the methamphetamine abusers (P=0.013) although 83.3% of inhalant and 55.6% of methamphetamine abusers had higher scores than the cut-off for ADHD. These findings suggest that drug abuse is associated with childhood ADHD, and that inhalant abusers have a higher incidence of childhood ADHD than methamphetamine abusers.