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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. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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. PMID:7107291

  8. Monoexponential analysis of /sup 133/Xe clearance curves for regional cerebral blood flow measurements

    SciTech Connect

    Ryding, E.

    1984-06-01

    The theoretical properties of a monoexponential flow index, analogous to the one used earlier by other investigators for regional CBF (rCBF) measured after intraarterial injection, were investigated after the administration of /sup 133/Xe intraarterially, intravenously, and by inhalation under high and low flow conditions. The sensitivity of the flow index to changes in fast flow components or changes in the weight ratio between the fast and the slow flow compartments was found to be dependent on whichever part of the /sup 133/Xe clearance curve was used for the flow calculation and on the shape of the input function for /sup 133/Xe. Since biexponential analysis of the clearance curves includes a monoexponential approximation for each of the two components of the clearance curve corresponding to the high and the low flow ''families'' in the brain, the limitations of the monoexponential flow index observed are in principle also valid for the results of biexponential analysis of the clearance curves.

  9. Measurement of both left ventricular function and regional myocardial perfusion with 133Xe in dogs.

    PubMed

    Ruddy, T D; Yasuda, T; Barlai-Kovach, M; Nedelman, M A; Moore, R H; Alpert, N M; Correia, J A; Newell, J B; Okada, R D; Boucher, C A

    1987-01-01

    A technique to measure left ventricular (LV) function and myocardial perfusion was validated in 12 dogs. 133Xe in saline was injected into the left atrium (LA) or LV and two data sets were obtained using gamma camera imaging: 1) A first pass gated scan for LV function; followed by 2) Sequential images for regional myocardial perfusion. LV ejection fraction and wall motion measurements from the 133Xe blood pool images were compared to ejection fraction (r = 0.88, P less than 0.01) and wall motion (r = 0.83, P less than 0.01) data from 99mTc labeled blood pool scans. The perfusion measurements obtained with the 133Xe method were compared to microsphere data (r = 0.79, P less than 0.01). Measurements after LV 133Xe injection were similar to data following LA injection. Thus, quantitative assessment of global LV function, regional wall motion and myocardial perfusion is possible with LA or LV 133Xe injection and gamma camera imaging. PMID:3569342

  10. Comparison of external lung monitoring with end-tidal air detection using the xenon-133 inhalation method

    SciTech Connect

    Hazelrig, J.B.; Halsey, J.H. Jr.; Wilson, E.M.; Wills, E.L.

    1985-11-01

    When the 133Xe inhalation method is employed for measuring regional cerebral blood flow, the arterial 133Xe concentration is usually approximated by the end-tidal air concentration. However, this approximation may be invalid in the presence of certain lung pathologies or when the breathing pattern is irregular. Jaggi and Obrist, using an intravenous injection of 133Xe, suggested that the counts detected by an external lung probe could provide an alternative estimate for arterial blood concentration once the noise produced by 133Xe in superficial tissues is removed from the signal. A mathematical model, based on hypotheses similar to theirs is presented here together with a new computational procedure for removing the noise. Results from normal rest studies on ten healthy young males indicate that the approximations for arterial blood concentration obtained from end-tidal air and from corrected lung counts are not equivalent when 133Xe is administered by inhalation. The concentration-time curves have different shapes, and these differences are reflected in blood flow values computed by head channel. However, there is no effect on comparisons between homologous regions of the left and right hemispheres.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Effect of Anti-inflammatory Drug Therapy on Clearance of 133Xe from Knee Joints of Patients with Rheumatoid Arthritis

    PubMed Central

    Dick, C.; Dick, P. H.; Nuki, G.; Whaley, K.; Boyle, J. A.; Shenkin, A.; Downie, W. W.; Buchanan, W. W.

    1969-01-01

    The degree of joint inflammation in 13 patients with rheumatoid arthritis, as measured by clinical indices, was reduced by both sodium salicylate and indomethacin. The clearance rate of 133Xe was reduced by indomethacin alone, and showed no correlation with the clinical features. PMID:4895341

  16. Some experimental errors in calculating regional cerebral blood flow from the intracarotid 133Xe clearance curve. A quantitative evaluation employing a digital model.

    PubMed

    Kanno, I; Uemura, K

    1975-01-01

    A digital model study has been developed for quantitative assessment of experimental errors in the analysis of 133Xe clearance curve from the brain. A small computer synthesized a model of the clearance curve, varying combinations of fast and slow components. The curves were convoluted with Poisson random digits to simulate statistical fluctuations. Identical curves were overlapped with varying intervals to study the influence of remaining activity. The height over area method to ten minutes was confirmed to overestimate CBF by 10% to 15% with a slow component of 20 ml/100 gm per minute, and the overstimation was increased with a lower slow flow component. The initial slope value was shown to have a close relationship with the fast flow component when the latter was less than 100 ml/100 gm per minute. Errors due to statistical fluctuations were determined only by the initial height (Ho cps), as the percent standard deviation was deltaHo/Ho in the height over area method and 2 deltaHo/HologHo in the initial slope method, where deltaHo equals square rootHo. Remaining activity caused errors of 1% to 3% in the initial slope method with an injection interval of 15 minutes. The influence of remaining activity can be eliminated with an injection interval of more than 25 to 30 minutes in the initial slope method and more than 40 minutes in the height over area method. PMID:1154473

  17. 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.

  18. 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.

  19. Inhalants

    MedlinePlus

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  20. Inhalants

    MedlinePlus

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  1. 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 ...

  2. SAMPLING AND DATA HANDLING METHODS FOR INHALABLE PARTICULATE SAMPLING

    EPA Science Inventory

    The report reviews the objectives of a research program on sampling and measuring particles in the inhalable particulate (IP) size range in emissions from stationary sources, and describes methods and equipment required. A computer technique was developed to analyze data on parti...

  3. 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

  4. 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

  5. Abnormal cerebral vasodilation in aneurysmal subarachnoid hemorrhage: use of serial 133Xe cerebral blood flow measurement plus acetazolamide to assess cerebral vasospasm.

    PubMed

    Tran Dinh, Y R; Lot, G; Benrabah, R; Baroudy, O; Cophignon, J; Seylaz, J

    1993-10-01

    A patient with cerebral vasospasm following subarachnoid hemorrhage (SAH) was investigated by serial measurement of cerebral blood flow (CBF) using the xenon-133 emission tomography method. The CBF was measured before and after acetazolamide injection. On Day 2 after SAH, there was early local hyperperfusion in the middle cerebral artery (MCA) territory, ipsilateral to the left posterior communicating artery aneurysm. The regional CBF of this arterial territory decreased slightly after acetazolamide injection, probably because of vasoplegia and the "steal" phenomenon, and thus surgery was delayed. A right hemiplegia with aphasia and disturbed consciousness occurred 4 days later (on Day 6 after SAH) due to arterial vasospasm, despite treatment with a calcium-channel blocker. The initial hyperemia of the left MCA territory was followed by ischemia. The vasodilation induced by acetazolamide administration was significantly subnormal until Day 13, at which time CBF and vasoreactivity amplitude returned to normal and the patient's clinical condition improved. Surgery on Day 14 and outcome were without complication. It is concluded that serial CBF measurements plus acetazolamide injection are useful for monitoring the development of cerebral vasospasm to determine the most appropriate time for aneurysm surgery. PMID:8410215

  6. 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.

  7. A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

    PubMed

    Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

    2016-03-01

    The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function. PMID:26524226

  8. Interim methods for development of inhalation reference concentrations. Draft report

    SciTech Connect

    Blackburn, K.; Dourson, M.; Erdreich, L.; DeRose, C.; Graham, J.A.

    1990-08-01

    An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)). The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.

  9. Direct-reading inhalable dust monitoring--an assessment of current measurement methods.

    PubMed

    Thorpe, Andrew; Walsh, Peter T

    2013-08-01

    Direct-reading dust monitors designed specifically to measure the inhalable fraction of airborne dust are not widely available. Current practice therefore often involves comparing the response of photometer-type dust monitors with the concentration measured with a reference gravimetric inhalable sampler, which is used to adjust the dust monitor measurement. However, changes in airborne particle size can result in significant errors in the estimation of inhalable concentration by this method. The main aim of this study was to assess how these dust monitors behave when challenged with airborne dust containing particles in the inhalable size range and also to investigate alternative dust monitors whose response might not be as prone to variations in particle size or that could be adapted to measure inhalable dust concentration. Several photometer-type dust monitors and a Respicon TM, tapered element oscillating microbalance (TEOM) personal dust monitor (PDM) 3600, TEOM 1400, and Dustrak DRX were assessed for the measurement of airborne inhalable dust during laboratory and field trials. The PDM was modified to allow it to sample and measure larger particles in the inhalable size range. During the laboratory tests, the dust monitors and reference gravimetric samplers were challenged inside a large dust tunnel with aerosols of industrial dusts known to present an inhalable hazard and aluminium oxide powders with a range of discrete particle sizes. A constant concentration of each dust type was generated and peak concentrations of larger particles were periodically introduced to investigate the effects of sudden changes in particle size on monitor calibration. The PDM, Respicon, and DataRam photometer were also assessed during field trials at a bakery, joinery, and a grain mill. Laboratory results showed that the Respicon, modified PDM, and TEOM 1400 observed good linearity for all types of dust when compared with measurements made with a reference IOM sampler; the

  10. COMPARISONS OF ACUTE REFERENCE VALUES IN DEVELOPING AN ACUTE INHALATION ASSESSMENT METHOD

    EPA Science Inventory

    A method is being developed for performing assessments of human health risk from acute (less than 24 hour) inhalation exposures. The methodology will be flexible in its ability to utilize variously robust data sets of dose-response information. A supporting task is a comparati...

  11. Plasma concentrations of disodium cromoglycate after various inhalation methods in healthy subjects

    PubMed Central

    Kato, Y; Muraki, K; Fujitaka, M; Sakura, N; Ueda, K

    1999-01-01

    Aims To compare the plasma concentrations of disodium cromoglycate (DSCG) following various inhalation procedures in healthy volunteers. Methods Nine healthy subjects inhaled 2 mg of aerosol, 20 mg of nebuliser solution only, 20 mg of nebuliser solution mixed with isotonic saline, or 20 mg of nebuliser solution mixed with saline and procaterol, a β2-adenoceptor agonist, on separate occasions 2–3 weeks apart. Plasma concentrations of DSCG were determined by high-performance liquid chromatography (h.p.l.c.). Results The peak plasma concentrations of DSCG were 1.5±0.7 (range 0.4–2.4) ng ml−1 in the aerosol group, 8.8±6.2 (range 5.3–19.9) ng ml−1 in the nebuliser solution only group, 17.2±16.3 (range 5.0–38.6) ng ml−1 in the nebuliser solution plus isotonic saline group, and 24.5±11.9 (range 10.2–44.9) ng ml−1 in the nebuliser solution plus saline and procaterol group. Thus subjects who used the nebuliser had markedly higher plasma concentrations of DSCG than subjects who used the aerosol inhaler. Conclusions These findings may have important implications for the evaluation of inhalation treatment with DSCG for bronchial asthma. PMID:10417491

  12. 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. PMID:18392276

  13. 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. PMID:26290200

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

    PubMed

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

    2013-01-01

    A multi-wall carbon nanotube (MWCNT) product Mitsui MWNT-7 is a mixture of dispersed single fibers and their agglomerates/aggregates. In rodents, installation of such mixture induces inflammatory lesions triggered predominantly by the aggregates/agglomerates at the level of terminal bronchiole of the lungs. In human, however, pulmonary toxicity induced by dispersed single fibers that reached the lung alveoli is most important to assess. Therefore, a method to generate aerosol predominantly consisting of dispersed single fibers without changing their length and width is needed for inhalation studies. Here, we report a method (designated as Taquann method) to effectively remove the aggregate/agglomerates and enrich the well-dispersed singler fibers in dry state without dispersant and without changing the length and width distribution of the single fibers. This method is base on two major concept; liquid-phase fine filtration and critical point drying to avoid re-aggregation by surface tension. MWNT-7 was suspended in Tert-butyl alcohol, freeze-and-thawed, filtered by a vibrating 25 µm mesh Metallic Sieve, snap-frozen by liquid nitrogen, and vacuum-sublimated (an alternative method to carbon dioxide critical point drying). A newly designed direct injection system generated well-dispersed aerosol in an inhalation chamber. The lung of mice exposed to the aerosol contained single fibers with a length distribution similar to the original and the Taquann-treated sample. Taquann method utilizes inexpensive materials and equipments mostly found in common biological laboratories, and prepares dry powder ready to make well-dispersed aerosol. This method and the chamber with direct injection system would facilitate the inhalation toxicity studies more relevant to human exposure. PMID:23824017

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

    SciTech Connect

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

    1991-09-01

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

  16. 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

  17. 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.

  18. 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 ...

  19. 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

  20. 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.

  1. 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

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

    EPA Science Inventory

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

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

    PubMed

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

    2013-01-01

    The possibility of water-soluble dinitrosyl iron complexes (DNIC) with thiol-containing ligands introduction into lungs and other tissues of mice by free inhalation of little drops (2-3 microns diameter) of the solutions of these complexes was investigated. Little drops of 2-20 mM solutions of the complexes were obtained by using an inhalation apparatus (compressor nebulizer). A cloud of these little drops was then inhaled by animals in a closed chamber. A maximal amount of protein-bound DNICs formed in mouse lungs was 0.6 micromoles per kilogram of tissue weight. The amount of DNIC in lungs, liver and blood decreased to the undetected level within 2-3 hours after inhalation. No cytotoxic effect of DNIC formed in lungs on Mycobacterium tuberculosis was found in mice infected with these mycobacteria. PMID:23755557

  4. REVIEW AND ANALYSIS OF INHALATION DOSIMETRY METHODS FOR APPLICATION TO CHILDREN'S RISK ASSESSMENT

    EPA Science Inventory

    A manuscript has been prepared that reviews and compares inhalation dosimetry available to address childrens unique sensitivities. The manuscript has beenpublished in the April, 2005 issue of the Journal of Toxicology and Environmental Health. A supporting workshop to engage e...

  5. 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 ...

  6. Azodicarbonamide: methods for the analysis in tissues of rats and inhalation disposition.

    PubMed

    Bechtold, W E; Medinsky, M A; Cheng, Y S; Hobbs, C H

    1989-09-01

    1. A method has been developed for measuring azodicarbonamide (ADA) and its metabolite biurea in tissues of rat. The method is based on the reaction of ADA with triphenylphosphine; the derivative so formed was isolated and quantified using reversed-phase h.p.l.c. Quantification was by u.v. detection with 14C-ADA as internal standard. Biurea was measured by oxidation to ADA, followed by treatment as described above. 2. When biurea was added to tissues at 100-400 micrograms, recoveries of 92-125% were observed. In contrast, recoveries of ADA added to tissues were generally much less than 100% and could not be reliably determined. The inability to quantify ADA added to tissues was ascribed to its rapid and facile reduction by tissue sulphydryl groups. 3. When rats were exposed to ADA aerosol concentrations of 200, 100, 50 and 0 mg/m3 for 13 weeks by inhalation, a non-linear dose-dependent accumulation of biurea was observed in lungs. No ADA was detected in lungs. Neither biurea nor ADA could be detected in kidneys. PMID:2815834

  7. Fluticasone Oral Inhalation

    MedlinePlus

    ... by mouth using an inhaler and as a powder to inhale by mouth using an inhaler. Fluticasone ... Flovent® HFA) is usually inhaled twice daily. Fluticasone powder for oral inhalation (Flovent® Diskus) is usually inhaled ...

  8. [Inhalable particulate matter and fine particulate matter: their basic characteristics, monitoring methods, and forest regulation functions].

    PubMed

    Wang, Hua; Lu, Shao-Wei; Li, Shao-Ning; Pan, Qing-Hua; Zhang, Yu-ping

    2013-03-01

    Both inhalable particulate matter (PM10) and fine particulate matter (PM2.5) are not only one of the main causes of air pollution, but also the primary pollutants in most cities. Based on the analysis of the impacts of PM10 and PM2.5 on the environment and human health, this paper summarized the components, sources, and mass concentration variations of PM10 and PM2.5 and related affecting factors, and introduced the network layout of PM10 and PM2.5 monitoring and its principles and features. The research methods on the removal of PM10 and PM2.5 by forests, the removal rates of PM10 and PM2.5 by different forests, and the related affecting mechanisms were summed up at regional and individual scales, and the existed problems in this research field were discussed. Due to the lack of the comparable observation studies on the atmospheric PM10 and PM2.5 along different gradients and in background areas, the joint effects of multiple factors on the PM10 and PM2.5 concentrations are not revealed. It was suggested that to make a rational network layout of PM10 and PM2.5 monitoring, to correctly select proper monitoring methods, and to compare and calibrate the observed results from classical manual methods would be the bases to guarantee the validity of PM10 and PM2.5 monitoring data. At present, there are few reports about the PM2.5 removal by forests, and it's not clear about the physiological processes and ecological mechanisms of PM10 and PM2.5 removal at cell, tissue, organ, and individual level. PMID:23755507

  9. 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 ...

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

    PubMed Central

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

    2015-01-01

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

  11. Mometasone Oral Inhalation

    MedlinePlus

    ... powder to inhale by mouth and as an aerosol to inhale by mouth using an inhaler. Mometasone ... inhaler is not working properly.To use the aerosol inhaler, follow these steps: Remove the cap from ...

  12. Tiotropium Oral Inhalation

    MedlinePlus

    ... use the inhaler to breathe in the dry powder contained in the capsules. Tiotropium is usually inhaled ... the inhaler it comes with to inhale the powder in the capsules. Never try to inhale them ...

  13. 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] ...

  14. Mometasone Oral Inhalation

    MedlinePlus

    ... children 12 years of age and older. Mometasone powder for oral inhalation (Asmanex® Twisthaler) is used in ... Mometasone inhalation comes as a powder to inhale by mouth and as an aerosol to inhale by mouth using an inhaler. Mometasone oral inhalation is usually inhaled ...

  15. Insulin Human Inhalation

    MedlinePlus

    ... inhalation comes as a powder to inhale by mouth using a special inhaler. It is usually used ... to your doctor.Before you use your insulin oral inhaler the first time, read the written instructions ...

  16. 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. ...

  17. 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.

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

    SciTech Connect

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

    1986-12-01

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

  19. Inhalation Injuries

    MedlinePlus

    ... increase mortality 30% to 40% when patients with cutaneous burns and inhalation injury are compared with patients ... nasal hairs • Facial burns • Burns around the mouth • Mineral spirits – 104º F – paint thinner, brush cleaner. • Redness, ...

  20. 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. PMID:25380027

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

    PubMed

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

    2015-12-01

    Instruction on inhalation techniques for chronic obstructive pulmonary disease(COPD)and asthma patients being treated with inhalants have sufficient therapeutic effects and are important to maintain adherence. However, problems continue to exist, including time constraints of medical staff that have a large number of patients and a lack of knowledge on inhalation instruction methods. A web application,"Inhalation Lessons,'for the iPad has been developed. It explains inhalation methods, and consists of videos and review tests. Instruction on inhalation techniques was performed using this application for patients that use Diskus, and the effects were examined. As a result, there are significant improvements in the inhalation techniques of patients after viewing the"Inhalation Lessons'application. Uniform instruction on inhalation techniques can be performed even in the field of homecare. PMID:26809400

  2. Effects of continuous phonation on /sup 133/xenon-inhalation air curves (of the kind used in deriving regional cerebral blood flow)

    SciTech Connect

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

    1987-07-01

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

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

    PubMed

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

    1987-07-01

    Regional cerebral blood flow (rCBF) may be measured with inhalation techniques that use end-expired values of radioactivity to estimate the isotope concentration in arterial blood. These end-expired data are used as an input function in a mathematical equation to derive rCBF. End-expired air is assumed normally to be in equilibrium with the arterial blood at the alveolar surface of the lung during regular (passive) breathing; this assumption may not be valid during continuous phonation. We therefore have analyzed breathing (inhalation/exhalation) patterns and end-expired radioactivity (133Xe) during (1) speaking, (2) singing, and (3) humming of the national anthem, and also during (4) passive breathing. Statistically significant differences in breathing patterns were measured between a group of nonmusicians and two groups of musicians (singers) during the phonation tasks: The nonmusicians breathed more often (and more rapidly) and exhibited less variability in their breathing patterns than did the musicians. Notwithstanding these differences, the shapes of smoothed functions derived from the end-expired values were not influenced appreciably during phonation (except possibly during talking). The latter finding suggests that estimates of rCBF derived with these data should not be confounded seriously because of the continuous phonation. PMID:3620907

  4. On-line high-performance liquid chromatography method for analyte quantitation from pressurized metered dose inhalers.

    PubMed

    Gupta, Abhishek; Myrdal, Paul B

    2004-04-01

    A sensitive and rapid, on-line reversed-phase high-performance liquid chromatographic method for quantitation of compounds at low concentrations in pressurized metered dose inhaler (MDI) systems was developed. Traditional methods for the quantitation of compounds in MDI formulations involve the opening of the MDI vial along with sample dilution prior to quantitation. The new method, reported in this study, involves a direct injection from the MDI vial into the needle injector port of a manual injector. Since there is no dilution step involved, this method can be used to quantitate low concentrations of compounds in MDIs with excellent precision. In addition, since the method requires a small injection volume of 5 microl, repeated analyses can be performed in order to generate multiple data points using the same MDI vial. Validation of the method was performed using ethanol-1,1,1,2-tetrafluoroethane (134a)-based MDIs. Beclomethasone dipropionate (BDP), a corticosteroid used for the treatment of asthma, was used as a model compound. Phase separation studies were conducted to investigate the miscibility of the ethanol-134a mixtures with different mobile phase solvent compositions. For the MDI systems in this study, an acetonitrile-water (90:10, v/v) mobile phase at a flow rate of 0.9 ml/min was found to give acceptable chromatography for BDP on a Apollo C18 5 microm, 150 mm x 4.6 mm column (Alltech Associates, Deerfield, IL, USA). Ultraviolet detection was done at 240 nm and the retention time of BDP was 2.7 min. The on-line HPLC method was characterized to be accurate, precise, sensitive, and specific. PMID:15072294

  5. 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.

  6. Levalbuterol Oral Inhalation

    MedlinePlus

    ... by mouth using a nebulizer, and as an aerosol to inhale by mouth using an inhaler. The ... will come in canisters. Each canister of levalbuterol aerosol is designed to provide 200 inhalations. After the ...

  7. Albuterol Oral Inhalation

    MedlinePlus

    ... that affect the lungs and airways). Albuterol inhalation aerosol and powder for oral inhalation is also used to prevent breathing difficulties during exercise. Albuterol inhalation aerosol (Proair HFA, Proventil HFA, Ventolin HFA) is used ...

  8. Substance use - inhalants

    MedlinePlus

    ... in (inhaled). Common types of abused inhalants are: Aerosols, such as air freshener, deodorant, fabric protector, hair ... a gas from a balloon Dusting: Spraying an aerosol into the nose or mouth Glading: Inhaling air- ...

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

    PubMed

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

    2009-03-01

    The methods used to calculate radiological and toxicological doses to hypothetical persons inside either a U.S. Army Abrams tank or Bradley Fighting Vehicle that has been perforated by depleted uranium munitions are described. Data from time- and particle-size-resolved measurements of depleted uranium aerosol as well as particle-size-resolved measurements of aerosol solubility in lung fluids for aerosol produced in the breathing zones of the hypothetical occupants were used. The aerosol was approximated as a mixture of nine monodisperse (single particle size) components corresponding to particle size increments measured by the eight stages plus the backup filter of the cascade impactors used. A Markov Chain Monte Carlo Bayesian analysis technique was employed, which straightforwardly calculates the uncertainties in doses. Extensive quality control checking of the various computer codes used is described. PMID:19204488

  10. Development of recommended test method for toxicological assessment of inhaled combustion products. Final report

    SciTech Connect

    Birky, M.M.; Paabo, M.; Levin, B.C.; Womble, S.E.; Malek, D.

    1980-09-01

    The objective of the project supported by PRC was to develop a test method for measuring the toxicity of combustion products from polymeric materials including cellular plastics. The development of such a test procedure was considered an essential first step to determine the hazard to life when cellular plastics are involved in fire. As result of this work, a test procedure was developed. It consists of 3 major elements; (1) combustion system, (2) chemical analysis system and (3) animal exposure system. Two biological endpoints obtained from the exposure are: (1) incapacitation in 30 minute exposure period, and (2) lethality in 30 minutes plus 14 days post exposure. The test apparatus has been evaluated to determine mixing rates and loss of reactive chemicals in the exposure chamber. In addition, a statistical evaluation of the experimental results demonstrated that order of incapacitation was independent of animal location. Evaluation of a limited number of different materials that produce different toxicological syndromes has demonstrated the utility of all 3 endpoints. Two natural polymers (wood and wool) and 2 synthetic materials (modacrylic and PTFE) have been studied in detail. In addition, preliminary data have been obtained on a flexible polyurethane foam (CM-21).

  11. The head dome: a simplified method for human exposures to inhaled air pollutants.

    PubMed

    Bowes, S M; 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. PMID:2346113

  12. 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.

  13. Fluticasone Oral Inhalation

    MedlinePlus

    ... fluticasone aerosol inhaler while you are near an open flame or a heat source. The inhaler may explode if it is exposed ... Do not store the inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct ...

  14. Flunisolide Oral Inhalation

    MedlinePlus

    ... your flunisolide inhaler while you are near an open flame or a heat source. The inhaler may explode if it is exposed ... Do not store the inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct ...

  15. Ciclesonide Oral Inhalation

    MedlinePlus

    ... your ciclesonide inhaler while you are near an open flame or a heat source. The inhaler may explode if it is exposed ... Do not store the inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct ...

  16. Zanamivir Oral Inhalation

    MedlinePlus

    Zanamivir comes as a powder to inhale (breathe in) by mouth. To treat influenza, it is usually inhaled twice daily for 5 days. You should ... plastic inhaler called a Diskhaler (device for inhaling powder) and five Rotadisks (circular foil blister packs each ...

  17. Budesonide Oral Inhalation

    MedlinePlus

    ... tightness, wheezing, and coughing caused by asthma. Budesonide powder for oral inhalation (Pulmicort Flexhaler) is used in ... Budesonide comes as a powder to inhale by mouth using an inhaler and as a suspension to inhale by mouth using a special jet nebulizer ( ...

  18. Ciclesonide Oral Inhalation

    MedlinePlus

    Ciclesonide comes as an aerosol to inhale by mouth using an inhaler. Ciclesonide is usually inhaled twice a day. Try to use ciclesonide at around ... than usual.The inhaler that comes with ciclesonide aerosol is designed for use only with a canister ...

  19. 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. PMID:22857273

  20. 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

  1. 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.

  2. Indacaterol Oral Inhalation

    MedlinePlus

    ... a short-acting beta agonist inhaler such as albuterol (Proventil, Ventolin) to use during attacks. If you ... stop the pieces of capsule from reaching your mouth as you inhale the medication. Very tiny pieces ...

  3. 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

  4. [Inhalation of nitric oxide - dependence: case report

    PubMed

    Carvalho, W B; Matsumoto, T; Horita, S M; Almeida, N M; Martins, F R

    2000-01-01

    OBJECTIVE: Describe the hemodynamic response with rebound of pulmonary hypertension after withdrawal of inhaled nitric oxide (NO) in a pediatric patient with acute respiratory distress syndrome (ARDS). METHODS: Case report of a child with ARDS and pulmonary hypertension evaluated through ecocardiografic with dopller, receiving inhaled NO for a period of 21 days. RESULTS: There was a decrease of the pulmonary artery pressure (PAP) from 52 mmHg to 44 mmHg after the initial titulation of NO inhalation dose. After the withdrawal of inhaled NO an elevation of PAP was observed (55 mmHg). It was necessary to reinstall the inhaled NO to obtain a more appropriate value (34 mmHg). A new attempt of interruption of the inhaled NO after prolonged inhalation (20 days) resulted in a new clinic worsening and increase of PAP, with the indication to reinstall the inhaled NO. In the 24th day of permanence in the intensive care unit the patient died due to multiple organ dysfunction. CONCLUSIONS: The possibility of pulmonary hypertension rebound after withdrawal of inhaled NO is a complication that may have important clinical implications for patients who need a prolonged treatment with NO. This case report emphasizes these implications. PMID:14647690

  5. Hydrazine inhalation hepatotoxicity.

    PubMed

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management. PMID:17761725

  6. Flunisolide Oral Inhalation

    MedlinePlus

    Flunisolide comes as an aerosol to inhale by mouth. It usually is inhaled twice daily. Try to use flunisolide at around the same times every ... acting medication than usual.Each canister of flunisolide aerosol is designed to provide 60 or 120 inhalations, ...

  7. Carcinogenicity of inhaled nanoparticles.

    PubMed

    Roller, Markus

    2009-07-01

    Large epidemiological studies in the United States have shown a statistical association between air concentration of the fine dust fraction PM(2.5) in the general environment and increased risk of lung cancer. A quantitative risk assessment for lung cancer based on these studies corresponds to risk estimates based on studies at workplaces with exposure to diesel engine emissions; its magnitude cannot be explained by the known carcinogenicity of organic substances or metals adsorbed to the insoluble particle core. Carcinogenic effects of diesel particles were observed after inhalation in rats independently in several studies. The surprisingly strong effect of diesel particles was partially attributed to their small size. This hypothesis was corroborated by inhalation studies with synthetic nanoparticles virtually free of organic compounds. IARC found sufficient evidence for the carcinogenicity of carbon black and of titanium dioxide in experimental animals. Long-term studies by the method of intratracheal instillation confirmed the carcinogenic effects in rats for an even broader spectrum of synthetic nanoparticles. Non-positive studies with hamsters are not valid because hamsters did not develop lung tumors after inhalation of some known human carcinogens. In recent years, the number of publications reporting in vitro genotoxicity of TiO(2) and of carbon black nanomaterials has increased. Overall, there is clear positive evidence for carcinogenicity in rats, together with supporting evidence from human data of structurally related substances. Therefore, the European Union (EU) criteria for category 2 of carcinogenic substances appear to be fulfilled for bio-durable nanoparticles consisting of matter without known significant specific toxicity. PMID:19558247

  8. 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…

  9. 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

  10. 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

  11. [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

  12. 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

  13. 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...

  14. Inhalation of chlorine gas.

    PubMed

    Williams, J G

    1997-11-01

    The clinical features of acute chlorine gas inhalation, and its management are reviewed. Current medical views on the chronic effects of an acute overwhelming exposure on lung function (reactive airways dysfunction syndrome), and the more controversial field of lung disease secondary to repeated inhalations of lower concentrations of chlorine gas are discussed. PMID:9519180

  15. Inhaled Hydrogen Sulfide

    PubMed Central

    Volpato, Gian Paolo; Searles, Robert; Yu, Binglan; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.; Ichinose, Fumito; Zapol, Warren M.

    2010-01-01

    Background Breathing hydrogen sulfide (H2S) has been reported to induce a suspended animation–like state with hypothermia and a concomitant metabolic reduction in rodents. However, the impact of H2S breathing on cardiovascular function remains incompletely understood. In this study, the authors investigated the cardiovascular and metabolic effects of inhaled H2S in a murine model. Methods The impact of breathing H2S on cardiovascular function was examined using telemetry and echocardiography in awake mice. The effects of breathing H2S on carbon dioxide production and oxygen consumption were measured at room temperature and in a warmed environment. Results Breathing H2S at 80 parts per million by volume at 27°C ambient temperature for 6 h markedly reduced heart rate, core body temperature, respiratory rate, and physical activity, whereas blood pressure remained unchanged. Echocardiography demonstrated that H2S exposure decreased both heart rate and cardiac output but preserved stroke volume. Breathing H2S for 6 h at 35°C ambient temperature (to prevent hypothermia) decreased heart rate, physical activity, respiratory rate, and cardiac output without altering stroke volume or body temperature. H2S breathing seems to induce bradycardia by depressing sinus node activity. Breathing H2S for 30 min decreased whole body oxygen consumption and carbon dioxide production at either 27° or 35°C ambient temperature. Both parameters returned to baseline levels within 10 min after the cessation of H2S breathing. Conclusions Inhalation of H2S at either 27° or 35°C reversibly depresses cardiovascular function without changing blood pressure in mice. Breathing H2S also induces a rapidly reversible reduction of metabolic rate at either body temperature. PMID:18362598

  16. Animal models of smoke inhalation induced injuries.

    PubMed

    David, Poon; Dunsford, Denny; Lu, Jia; Moochhala, Shabbir

    2009-01-01

    Smoke inhalation injury is the leading cause of mortality from structural fires, as a result of complications such as systemic inflammatory response syndrome and chronic obstructive pulmonary disease, which can be caused by a localized or systemic response. In this review, the pathophysiology of smoke inhalation injury, along with the characteristics found in clinical settings, common animal models, current treatment methods and future potential therapeutics are discussed. PMID:19273376

  17. Amorphous powders for inhalation drug delivery.

    PubMed

    Chen, Lan; Okuda, Tomoyuki; Lu, Xiang-Yun; Chan, Hak-Kim

    2016-05-01

    For inhalation drug delivery, amorphous powder formulations offer the benefits of increased bioavailability for poorly soluble drugs, improved biochemical stability for biologics, and expanded options of using various drugs and their combinations. However, amorphous formulations usually have poor physicochemical stability. This review focuses on inhalable amorphous powders, including the production methods, the active pharmaceutical ingredients and the excipients with a highlight on stabilization of the particles. PMID:26780404

  18. 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.

  19. KINETICS OF INGESTED (222)RN IN HUMANS DETERMINED FROM MEASUREMENTS WITH (133)XE

    EPA Science Inventory

    The problem of naturally occurring 222-radon contamination has received a great deal of public and scientific attention over the past several years, and has become a major public health issue worldwide. The purpose of the work reported in the document was to provide information a...

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

    PubMed

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

    2016-03-16

    Pharmaceutical tests for hard shell capsules are designed for orally administered capsules. The use of capsules in dry powder inhalers is widespread and increasing and therefore more appropriate tests are required to ensure quality and determine if these capsules are fit for purpose. This study aims to determine the flexibility, reproducibility and sensitivity of a quantitative method that is designed to evaluate the puncture characteristics of different capsule shell formulations under different climatic conditions. A puncture testing method was used to generate force displacement curves for five capsule formulations that were stored and tested at two different temperatures (5°C and 19°C). Force-displacement puncture profiles were reproducible for individual capsule shell formulations. The methodology was able to discriminate between capsules produced using different primary materials i.e. gelatin versus hypromellose, as well as more minor changes to capsule formulation i.e. different material grades and excipients. Reduced temperature increased the forces required for capsule puncture however further work is required to confirm its significance. Results indicate the method provides a reproducible and sensitive means of evaluating capsule puncture. Future studies should validate the methodology at different test sites, using different operators and with different capsule shell formulations. PMID:26806464

  1. Inhalation treatment for asthma.

    PubMed Central

    Reiser, J; Warner, J O

    1986-01-01

    Inhaled medication has revolutionised the lives of many children with asthma. Despite this we see many children for whom appropriate inhaled medication has been prescribed but whose symptoms continue to be poorly controlled. In our experience this is often due to poor technique or inappropriately prescribed devices and an inadequate understanding of when and how to use the treatment. The prescribing physician must have a clear idea of the optimal inhalation technique. We have reviewed the standard devices available and our use of them in the treatment of childhood asthma. PMID:3082295

  2. 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

  3. Inhaled insulin: too soon to be forgotten?

    PubMed

    Zarogoulidis, Paul; Papanas, Nikolaos; Kouliatsis, Georgios; Spyratos, Dionysis; Zarogoulidis, Kostas; Maltezos, Efstratios

    2011-10-01

    Inhalation is a potentially viable route of administration for numerous agents. In diabetes mellitus, the need for frequent injections to achieve ideal glycemic control remains a significant limitation for initiating and complying with insulin therapy in a large number of patients. To overcome this barrier, inhaled insulin was developed. The inhalation form of regular human insulin has been tested and administered in a large number of trials. Respiratory capacity was evaluated in patients with normal lung parenchyma in whom inhaled insulin was administered without complications. However, issues like cost, bulky device, fear for lung safety, and the small number of studies in subjects with underlying respiratory disease prevented widespread use of this new mode of delivery. In the present review, we will suggest a number of methods that could be applied in this form of administration to maximize drug absorption and fully exploit the advantages of this route of administration. PMID:21689020

  4. Insulin Human Inhalation

    MedlinePlus

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  5. 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 ... Do not use olodaterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  6. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... used to prevent and treat wheezing, shortness of breath, coughing, and chest tightness caused by asthma, chronic ... the puff; continue to take a full, deep breath. Take the inhaler away from you mouth, hold ...

  7. Albuterol Oral Inhalation

    MedlinePlus

    ... in the dose counter go down. Do not waste doses by opening the inhaler unless you are ... refrigerator or at room temperature away from excess heat and moisture (not in the bathroom). Store the ...

  8. Umeclidinium Oral Inhalation

    MedlinePlus

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  9. 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.

  10. Arformoterol Oral Inhalation

    MedlinePlus

    ... a short acting beta agonist inhaler such as albuterol (Proventil, Ventolin) to use during attacks. If you ... Sit upright and place the mouthpiece in your mouth or put on the facemask. Turn on the ...

  11. 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 ...

  12. 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

  13. Clinical efficacy and safety of beclomethasone dipropionate inhalation capsules inhaled by Cyclohaler compared with Becotide Rotacaps inhaled by Rotahaler.

    PubMed

    Vink-van Wijngaarden, T; Blom-Ross, M E; Lansdorp, D; Goedhart, D M; Eelhart, J; Guelen, P J; de Vos, D

    1998-09-01

    The study was undertaken to compare the efficacy and safety of beclomethasone dipropionate inhalation powder inhaled by Rotahaler (Becotide Rotacaps, Glaxo Wellcome) and by Cyclohaler (Beclomethasone Cyclocaps, Pharmachemie). Both the Cyclohaler and the Rotahaler are single-dose dry powder inhalation devices for inhalation capsules. 182 asthma patients stabilized on inhaled beclomethasone dipropionate 800 micrograms daily, were randomly assigned to treatment with 800 micrograms beclomethasone dipropionate inhaled by Rotahaler (91 patients) or Cyclohaler (91 patients) in a double-blind manner, using the double-dummy method. It was shown that the asthma remained stable during the 16-week study period with both preparations. There were no statistically significant differences in the pulmonary parameters (morning PEF, evening PEF, FEV1). The test/reference ratio of the morning PEF (99.5%, CI 93.0% - 106.5%) was well within the equivalence interval, which had been set a priori from 85% to 117.6%. There were no marked differences between the Cyclocaps and Rotacaps group in symptom scores and adverse events. A total of 12 patients had an asthma exacerbation: 8 exacerbations occurred in the Rotahaler group and 4 in the Cyclohaler group. The difference was not statistically significant. The use of rescue medication was somewhat higher in the Rotahaler group, but the difference did not reach statistical significance. Significantly more patients (17 patients) withdrew from the study in the Rotahaler group than in the Cyclohaler group (5 patients). In conclusion, there was no difference in asthma control of patients treated with Beclomethasone Cyclocaps inhaled by Cyclohaler and Becotide Rotacaps inhaled by Rotahaler. Both preparations are therapeutically equivalent. PMID:9760014

  14. 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

  15. [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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... doctor about how you should take your other oral or inhaled medications for asthma during your treatment with salmeterol and fluticasone inhalation. If you were using a short-acting beta agonist inhaler such as albuterol (Proventil, Ventolin) on a regular basis, your doctor ...

  2. 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...

  3. Inhalant Abuse and Dependence among Adolescents in the United States

    ERIC Educational Resources Information Center

    Wu, Li-Tzy; Pilowsky, Daniel J.; Schlenger, William E.

    2004-01-01

    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…

  4. 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

  5. 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

  6. 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…

  7. Isoetharine Oral Inhalation

    MedlinePlus

    Isoetharine comes as an aerosol and a solution to inhale by mouth. It is used as needed to relieve symptoms but usually should not be ... proper disposal of your medication. Avoid puncturing the aerosol container, and do not discard it in an ...

  8. 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.

  9. Deposition and biokinetics of inhaled nanoparticles

    PubMed Central

    2010-01-01

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

  10. Vapor Inhalation of Alcohol in Rats

    PubMed 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

  11. 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

  12. VALIDATION OF SAMPLERS FOR INHALED PARTICULATE MATTER

    EPA Science Inventory

    Methods for the testing of new samplers for inhalable particles have been developed and applied to the dichotomous sampler and the size-selective hi-vol. The sampling effectiveness of the inlet to the dichotomous sampler was measured and found to be excessively dependent on wind ...

  13. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

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

  14. Technosphere inhaled insulin (Afrezza).

    PubMed

    Rendell, M

    2014-12-01

    Technosphere® insulin uses a unique carrier -fumaryl diketopiperazine (FDKP)- which adsorbs insulin to form microparticles to permit delivery to the alveoli by inhalation. Toxicity studies have been entirely negative. The pulmonary absorption of insulin is very rapid, and the disappearance time is shorter than for subcutaneously delivered rapid-acting insulins. As a result, after inhalation, there is a rapid drop in glucose levels which subsequently return to normal in a shorter time than after subcutaneous insulin administration. Consequently, there is a lower incidence of hypoglycemic reactions. Pulmonary function studies have shown a small, reversible decrease in FEV1, and pulmonary imaging studies have shown no adverse effect. The inhalation of Technosphere insulin can produce a cough in up to 27% of patients. The cough has resulted in discontinuance in as many as 9% of users. Technosphere insulin has been approved for use in type 1 and type 2 diabetes. Long-term studies of pulmonary safety and surveillance for malignancy will be performed in the future. Studies to assess the optimal time dosing regimen are needed. PMID:25588086

  15. Personal exposure to inhalable cement dust among construction workers.

    PubMed

    Peters, Susan; Thomassen, Yngvar; Fechter-Rink, Edeltraud; Kromhout, Hans

    2009-01-01

    Objective- A case study was carried out to assess cement dust exposure and its determinants among construction workers and for comparison among workers in cement and concrete production.Methods- Full-shift personal exposure measurements were performed and samples were analysed for inhalable dust and its cement content. Exposure variability was modelled with linear mixed models.Results- Inhalable dust concentrations at the construction site ranged from 0.05 to 34 mg/m(3), with a mean of 1.0 mg/m(3). Average concentration for inhalable cement dust was 0.3 mg/m(3) (GM; range 0.02-17 mg/m(3)). Levels in the ready-mix and pre-cast concrete plants were on average 0.5 mg/m(3) (GM) for inhalable dust and 0.2 mg/m(3) (GM) for inhalable cement dust. Highest concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM = 55 mg/m(3); inhalable cement dust GM = 33 mg/m(3)) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages during reinforcement work and pouring. Most likely other sources were contributing to dust concentrations, particularly at the construction site. Within job groups, temporal variability in exposure concentrations generally outweighed differences in average concentrations between workers. 'Using a broom', 'outdoor wind speed' and 'presence of rain' were overall the most influential factors affecting inhalable (cement) dust exposure.Conclusion- Job type appeared to be the main predictor of exposure to inhalable (cement) dust at the construction site. Inhalable dust concentrations in cement production plants, especially during cleaning tasks, are usually considerably higher than at the construction site. PMID:19137154

  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. 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 ...

  18. 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 ...

  19. Accidental condom inhalation.

    PubMed

    Arya, C L; Gupta, Rajnish; Arora, V K

    2004-01-01

    A 27-year-old lady presented with persistent cough, sputum and fever for the preceding six months. Inspite of trials with antibiotics and anti-tuberculosis treatment for the preceeding four months, her symptoms did not improve. A subsequent chest radiograph showed non-homogeneous collapse-consolidation of right upper lobe. Videobronchoscopy revealed an inverted bag like structure in right upper lobe bronchus and rigid bronchoscopic removal with biopsy forceps confirmed the presence of a condom. Detailed retrospective history also confirmed accidental inhalation of the condom during fellatio. PMID:14870871

  20. Metallic hairpin inhalation: a healthcare problem facing young Muslim females

    PubMed Central

    2014-01-01

    Objectives To perform an epidemiological assessment of metallic hairpin inhalation in young Muslim females and highlight the need for a health education program in this population. Methods We performed a retrospective analysis of females with a history of metallic hairpin inhalation presenting to the Otolaryngology and Cardiothoracic Surgery Departments at Mansoura University Hospitals from January 2000 to October 2006. Results A total of 83 patients were identified with metallic hairpin inhalation, of which 2 were excluded as they were coughed and expelled by the patient. Ages ranged from 7 to 19 years. A history of inhaled foreign body (FB) was found in all cases but the majority of patients were asymptomatic, with only 6 patients (7%) presenting with cough. Chest x-rays confirmed the presence of metallic hairpin inhalation in all cases. The metallic hairpins were present in the trachea in 7 patients (9%), in the left bronchial tree in 43 patients (53%) and in the right bronchial tree in 31 patients (38%). Rigid bronchoscopy was performed in all patients with a retrieval rate of 80%. Repeat bronchoscopy was performed in 16 patients (20%), which was successful in 11 patients (14%). The remaining 5 patients required thoracotomy for removal of the metallic hairpin (6%). Conclusion The significant number of inhaled metallic hairpins in young Muslim females highlights the need for a health education program in this population. Rigid bronchoscopy remains the primary tool for retrieval of these inhaled foreign bodies. However, when repeat broncoscopy is necessitated, a thoracotomy may be required. PMID:25085592

  1. 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

  2. Inhalation injury in severely burned children does not augment the systemic inflammatory response

    PubMed Central

    Finnerty, Celeste C; Herndon, David N; Jeschke, Marc G

    2007-01-01

    Introduction Inhalation injury in combination with a severe thermal injury increases mortality. Alterations in inflammatory mediators, such as cytokines, contribute to the incidence of multi-organ failure and mortality. The aim of the present study was to determine the effect of inhalation injury on cytokine expression in severely burned children. Methods Thirty severely burned pediatric patients with inhalation injury and 42 severely burned children without inhalation injury were enrolled in the study. Inhalation injury was diagnosed by bronchoscopy during the first operation. Blood was collected within 24 hours of admission and again at five to seven days following admission. Cytokine expression was profiled using multi-plex antibody-coated beads. Significance was accepted at a p value of less than 0.05. Results The mean percentages of total body surface area burned were 67% ± 4% (56% ± 6%, third-degree burns) in the inhalation injury group and 60% ± 3% (45% ± 3%, third-degree burns) in the non-inhalation injury group (p value not significant [NS]). Mean age was 9 ± 1 years in the inhalation injury group and 8 ± 1 years in the non-inhalation injury group (p value NS). Time from burn to admission in the inhalation injury group was 2 ± 1 days compared to 3 ± 1 days in the non-inhalation injury group (p value NS). Mortalities were 40% in the inhalation injury group and 12% in the non-inhalation injury group (p < 0.05). At the time of admission, serum interleukin (IL)-7 was significantly increased in the non-inhalation injury group, whereas IL-12p70 was significantly increased in the inhalation injury group compared to the non-inhalation injury group (p < 0.05). There were no other significant differences between groups. Five to seven days following admission, all cytokines decreased with no differences between the inhalation injury and non-inhalation injury cohorts. Conclusion In the present study, we show that an inhalation injury causes alterations in IL-7

  3. 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

  4. 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.

  5. Mephedrone inhalation causes pneumomediastinum

    PubMed Central

    Graham, Ruth; Bowen, Nia; Singh, Joy

    2014-01-01

    A 17-year-old male patient presented to A&E with swelling on the right side of his neck, extending to below the clavicle, associated with neck pain and dysphonia. On examination, subcutaneous supraclavicular and chest wall emphysema was noted. Clinical observations and bloods were normal. A chest X-ray and subsequent CT of the thorax showed evidence of pneumomediastinum and subcutaneous emphysema. The patient denied any history of trauma but admitted to inhalation of mephedrone 3 days previously. The patient was discussed with the regional cardiothoracic unit who advised conservative management. He was treated prophylactically with antibiotics and was initially kept nil by mouth, but diet was introduced 24 h later. He remained well, his dysphonia resolved and his subcutaneous emphysema improved. He was discharged after 3 days. He has not attended any formal follow-up but was well when contacted by phone. PMID:24614784

  6. Toxic inhalational exposures.

    PubMed

    Chen, Tze-Ming Benson; Malli, Harjoth; Maslove, David M; Wang, Helena; Kuschner, Ware G

    2013-01-01

    Respirable toxicants are a spectrum of irritant and nonirritant gases, vapors, fumes, and airborne particles that can be entrained into the body through the respiratory tract, resulting in exposures that cause pulmonary injury and/or systemic disease. Sources of respirable toxicants include structural fires, industrial accidents, domestic mishaps, and intentional releases of injurious agents on the battleground (warfare) or in civilian settings (acts of terrorism). Acute toxic inhalational exposures may result in respiratory failure, multisystem organ dysfunction, and death. Management of victims includes assessment and protection of the airway, monitoring and treatment of systemic toxicity, and delivery of exposure-specific and nonspecific therapies that improve outcomes. Treatments may include antidotes, hyperbaric oxygen, and other nonspecific life-supporting interventions. PMID:22232204

  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. Inhaled antibiotics: dry or wet?

    PubMed

    Tiddens, Harm A W M; Bos, Aukje C; Mouton, Johan W; Devadason, Sunalene; Janssens, Hettie M

    2014-11-01

    Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching. In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed. PMID:25323242

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

    PubMed Central

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

    1994-01-01

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

  10. Inhaled insulin--does it become reality?

    PubMed

    Siekmeier, R; Scheuch, G

    2008-12-01

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

  11. 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.

  12. 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.

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

    PubMed

    Formby, C; Thomas, R G; Halsey, J H

    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 133Xe-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. PMID:2720376

  14. Fluticasone and Vilanterol Oral Inhalation

    MedlinePlus

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  15. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... in the dose counter go down. Do not waste doses by closing or tilting the inhaler, playing ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  16. Umeclidinium and Vilanterol Oral Inhalation

    MedlinePlus

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  17. Foreign object - inhaled or swallowed

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000036.htm Foreign object - inhaled or swallowed To use the sharing features ... please enable JavaScript. If you breathe a foreign object into your nose, mouth, or respiratory tract, it ...

  18. 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

  19. Switching from branded to generic inhaled medications: potential impact on asthma and COPD.

    PubMed

    Lavorini, Federico; Ninane, Vincent; Haughney, John; Bjermer, Leif; Molimard, Mathieu; Dekhuijzen, Richard Pn

    2013-12-01

    Pressure on healthcare budgets is increasing, while at the same time patent protection for many branded inhaled medications has expired, leading to the development and growing availability of generic inhaled medicines. Generic inhaled drugs are therapeutically equivalent to original branded options but may differ in their formulation and inhalation device. This new situation raises questions about the potential impact of switching from branded to generic drug/inhaler combination products in patients with asthma or COPD, with or without their consent, in countries where this is permitted. Inhalation devices, particularly dry powder inhalers, vary markedly in their design, method of operation and drug delivery to the lungs. Current guidelines stress the importance of training patients how to use their inhalers but offer little or no guidance on how this should be achieved. Non-adherence to therapy and incorrect inhaler usage are recognised as major factors in poorly or uncontrolled asthma and COPD and switching patients to a different inhaler device may exacerbate these problems, particularly in patients who disagree to switch. Where switching is permitted or mandatory, adequate patient instruction and follow-up monitoring should be provided routinely. PMID:24224777

  20. Acoustic Analysis of Inhaler Sounds From Community-Dwelling Asthmatic Patients for Automatic Assessment of Adherence

    PubMed Central

    D'arcy, Shona; Costello, Richard W.

    2014-01-01

    Inhalers are devices which deliver medication to the airways in the treatment of chronic respiratory diseases. When used correctly inhalers relieve and improve patients' symptoms. However, adherence to inhaler medication has been demonstrated to be poor, leading to reduced clinical outcomes, wasted medication, and higher healthcare costs. There is a clinical need for a system that can accurately monitor inhaler adherence as currently no method exists to evaluate how patients use their inhalers between clinic visits. This paper presents a method of automatically evaluating inhaler adherence through acoustic analysis of inhaler sounds. An acoustic monitoring device was employed to record the sounds patients produce while using a Diskus dry powder inhaler, in addition to the time and date patients use the inhaler. An algorithm was designed and developed to automatically detect inhaler events from the audio signals and provide feedback regarding patient adherence. The algorithm was evaluated on 407 audio files obtained from 12 community dwelling asthmatic patients. Results of the automatic classification were compared against two expert human raters. For patient data for whom the human raters Cohen's kappa agreement score was \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${>}{0.81}$\\end{document}, results indicated that the algorithm's accuracy was 83% in determining the correct inhaler technique score compared with the raters. This paper has several clinical implications as it demonstrates the feasibility of using acoustics to objectively monitor patient inhaler adherence and provide real-time personalized medical care for a chronic respiratory illness. PMID:27170883

  1. 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. PMID:20040991

  2. 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. PMID:22830298

  3. 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

  4. 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

  5. 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

  6. ISOTOPIC STUDY OF THE INHALATION TOXICOLOGY OF OXIDANTS

    EPA Science Inventory

    The purpose of these studies was to develop novel methods to investigate the biological fate of inhaled ozone and other oxygen-containing pollutants in animal and human tissues using the heavy isotope of oxygen, oxygen-18 (18O). Methods were developed which facilitated the conver...

  7. 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

  8. Linearization correction of /sup 99m/Tc-labeled hexamethyl-propylene amine oxime (HM-PAO) image in terms of regional CBF distribution: comparison to C VO2 inhalation steady-state method measured by positron emission tomography

    SciTech Connect

    Inugami, A.; Kanno, I.; Uemura, K.; Shishido, F.; Murakami, M.; Tomura, N.; Fujita, H.; Higano, S.

    1988-12-01

    The radioisotope distribution following intravenous injection of 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) in the brain was measured by single photon emission computed tomography (SPECT) and corrected for the nonlinearity caused by differences in net extraction. The linearization correction was based on a three compartment model, and it required a region of reference to normalize the SPECT image in terms of regional cerebral blood flow distribution. Two different regions of reference, the cerebellum and the whole brain, were tested. The uncorrected and corrected HM-PAO images were compared with cerebral blood flow (CBF) image measured by the C VO2 inhalation steady state method and positron emission tomography (PET). The relationship between uncorrected HM-PAO and PET-CBF showed a correlation coefficient of 0.85 but tended to saturate at high CBF values, whereas it was improved to 0.93 after the linearization correction. The whole-brain normalization worked just as well as normalization using the cerebellum. This study constitutes a validation of the linearization correction and it suggests that after linearization the HM-PAO image may be scaled to absolute CBF by employing a global hemispheric CBF value as measured by the nontomographic TTXe clearance method.

  9. William TG Morton's early ether inhalers: a tale of three inhalers and their inscriptions.

    PubMed

    Haridas, R P

    2009-07-01

    Three ether inhalers with inscriptions stating that they had been used in early ether anaesthesia were found. All three inhalers were initially linked to WTG Morton. Two of the inhalers were probably among several types of inhalers used by Morton. The third inhaler was found to have been incorrectly attributed to Morton. It was first used by John Foster Brewster Flagg, a dentist in Philadelphia. PMID:19705631

  10. 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…

  11. 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...

  12. 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 ...

  13. 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

  14. 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...

  15. Impact of inhalation therapy on oral health

    PubMed Central

    Godara, Navneet; Godara, Ramya; Khullar, Megha

    2011-01-01

    Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Beta-2 agonists, anticholinergic bronchodilators, inhaled corticosteroids, and sodium cromoglycate are often used alone or in combination in an inhaled form. Studies have shown that inhaled drugs used in the treatment have some adverse effects on the oral health based on their dosage, frequency, and duration of use. Several oral conditions such as xerostomia, dental caries, candidiasis, ulceration, gingivitis, periodontitis, and taste changes have been associated with inhalation therapy. Since the prevalence of chronic respiratory diseases is rising, it is important to provide optimal oral care to the individuals receiving inhalation therapy. This article will review the influence of inhaled drugs on the oral health of individuals and adequate management and prevention of the same. PMID:22084541

  16. Inhaled crocidolite mutagenicity in lung DNA.

    PubMed Central

    Rihn, B; Coulais, C; Kauffer, E; Bottin, M C; Martin, P; Yvon, F; Vigneron, J C; Binet, S; Monhoven, N; Steiblen, G; Keith, G

    2000-01-01

    We used transgenic mice carrying the lacI reporter gene to study the mutagenesis potential of asbestos crocidolite. The animals were exposed by nose-only inhalation to an aerosol containing 5.75 mg/m(3) crocidolite dust for 6 hr/day and 5 consecutive days. After 1, 4, and 12 weeks, we examined four end points: the cytology of bronchoalveolar lavage, the lung load of crocidolite, the hydrophobic DNA adducts, and the mutations in the lacI reporter gene. Twelve weeks after exposure, nearly 10% of the inhaled fibers remained in the lung (227 +/- 103 ng/mg lung). There was evidence of a typical inflammatory response consisting of multinucleate macrophages at weeks 4 and 12, whereas immediately after the exposure, we observed numerous polymorphonuclear neutrophils. The mutant frequency significatively increased during the fourth week after the exposure: 13.5 [time] 10(-5) in the exposed group versus 6. 9 10(-5) in the control group. The induction factor, defined by the ratio of checked mutants of exposed mice to checked mutants of control mice, was 1.96. The mutation spectrum of control lung DNA and exposed lung DNA was similar, suggesting the possible involvement of a DNA repair decrease in crocidolite-treated animals. We used the (32)P-postlabeling method and did not detect any increase of either 5 mC or bulky adduct in treated mice. This is the first study that demonstrates asbestos mutagenicity in vivo after a nose-only inhalation. Images Figure 1 Figure 2 PMID:10753093

  17. [Evaluations of a specified number of inhalations and how to assess the contents in metered-dose inhalers].

    PubMed

    Obata, T; Fujikawa, M; Obata, Y; Obata, J

    1996-10-01

    Many kinds of Metered-Dose Inhalers (MDI) have been clinically available for bronchial asthma. Although manufacturers demonstrate the specified number of inhalations per canister on an attached document or on a plastic bag, the information provided are usually inadequate and inconsistent. They provide no information on the problems of the Metered-Dose Inhalers beyond the maximum specified number of actuations and the time when to exchange for a new one. We examined the technique how to evaluate the contents of MDI and their accuracy. Patients and their parents depended on inaccurate methods, such as shaking the inhalers to listen to the sound of contents, estimating the weight of the canisters and the size of emissions, and only a half of them were able to distinguish between 1/3 and 2/ 3 of remaining doses. Three Metered-Dose Inhalers with anti-inflammatory drugs and one MDI with beta-stimulant supplied consistent doses until they reached the maximum specified number. The 4 MDIs floated in the water in different ways and provided information when to replace for new ones in some MDIs. PMID:8958655

  18. Effect of inhaled steroids on laryngeal microflora.

    PubMed

    Turan, Mahfuz; Ekin, Selami; Ucler, Rıfkı; Arısoy, Ahmet; Bayram, Yasemin; Yalınkılıç, Abdulaziz; Bozan, Nazım; Garca, Mehmet Fatih; Çankaya, Hakan

    2016-07-01

    Conclusions As is known, this study is the first study to evaluate the effect of inhaled steroids on laryngeal microflora. The data support that ICS usage causes changes in the larynx microflora. Purpose The aim of this study was to determine the alteration in larynx microbial flora of the patients treated with ICS comparing the culture results of a control group. In addition, laryngeal microflora was compared to the smears obtained from the vallecula and pharynx. Materials and methods The study included 39 patients (mean age = 45.56 ± 12.76 years) who had been using a corticosteroid inhaler and control group consisting of 27 persons (mean age = 43.07 ± 13.23 years). Culture samples were obtained from the pharynx, larynx, and vallecula in the patient and control groups, and they were evaluated in the microbiology laboratory. Obtained culture results were named by the same microbiologist according to the basic microorganism classification method. Results Coagulase-negative staphylococci (CNS), Streptococcus viridians (VGS) and candida albicans were detected to grow significantly more in the patient group in all three anatomic localizations compared to the control group. Neisseria spp, basillus spp, and Non-viridans alpha-hemolytic streptococcus were detected to grow significantly more in the control group in all three anatomic localizations compared to the patient group. PMID:26901427

  19. 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

  20. ALTERATIONS IN LUNG STRUCTURE CAUSED BY INHALATION OF OXIDANTS

    EPA Science Inventory

    Morphometric and morphologic methods have been used to evaluate changes in rat lungs caused by the inhalation of a variety of oxidants. Exposure to 100% oxygen causes diffuse pulmonary injury and leads to death after 66-72 h of exposure. The primary insult leading to death in rat...

  1. 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

  2. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

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

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies. PMID:26070575

  3. [Significance of inhaled environmental allergens].

    PubMed

    Zochert, J

    1983-01-01

    Whereas the importance of pollen as inhalative allergens has been largely investigated and is generally known, the experience in the frequency and the role of the sensibilization with air-borne fungi is relatively limited. In 720 patients with Asthma bronchiale the degree of sensitization has been tested with various extracts of air-borne fungi of SSW Dresden (mould mixture, aspergillin, mucor, cladosporium and penicillium and alternaria). The most frequent and also the strongest reactions were found with alternaria and the smallest part of positive skin reactions with penicillium. An isolated sensitization with mould has been demonstrated in 20 per cent of the cases. In 60 per cent of the tested patients a manifest mould allergy was shown by means of the Inhalative Allergen Test, the most favourable correlation between Intracutaneous Test (ICT) and Inhalative Test (IAT) was found with alternaria (76%). A conformance between ICT and basophils degranulation test (BDT) was stated in 69% of the cases. The aim should be comparable tests with allergen extracts without irritative effects and qualitative measurements of air-borne fungi. PMID:6649704

  4. 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

  5. Inhalation with Fucose and Galactose for Treatment of Pseudomonas Aeruginosa in Cystic Fibrosis Patients

    PubMed Central

    Hauber, Hans-Peter; Schulz, Maria; Pforte, Almuth; Mack, Dietrich; Zabel, Peter; Schumacher, Udo

    2008-01-01

    Background: Colonisation of cystic fibrosis (CF) lungs with Pseudomonas aeruginosa is facilitated by two lectins, which bind to the sugar coat of the surface lining epithelia and stop the cilia beating. Objectives: We hypothesized that P. aeruginosa lung infection should be cleared by inhalation of fucose and galactose, which compete for the sugar binding site of the two lectins and thus inhibit the binding of P. aeruginosa. Methods: 11 adult CF patients with chronic infection with P. aeruginosa were treated twice daily with inhalation of a fucose/galactose solution for 21 days (4 patients only received inhalation, 7 patients received inhalation and intravenous antibiotics). Microbial counts of P. aeruginosa, lung function measurements, and inflammatory markers were determined before and after treatment. Results: The sugar inhalation was well tolerated and no adverse side effects were observed. Inhalation alone as well as combined therapy (inhalation and antibiotics) significantly decreased P. aeruginosa in sputum (P < 0.05). Both therapies also significantly reduced TNFα expression in sputum and peripheral blood cells (P < 0.05). No change in lung function measurements was observed. Conclusions: Inhalation of simple sugars is a safe and effective measure to reduce the P. aeruginosa counts in CF patients. This may provide an alternative therapeutical approach to treat infection with P. aeruginosa. PMID:19043609

  6. Nitrite Inhalants Use and HIV Infection among Men Who Have Sex with Men in China

    PubMed Central

    Li, Dongliang; Yang, Xueying; Zhang, Zheng; Qi, Xiao; Ruan, Yuhua; Jia, Yujiang; Pan, Stephen W.; Xiao, Dong; Jennifer Huang, Z.; Luo, Fengji; Hu, Yifei

    2014-01-01

    Objective. This is the first study in China to examine the use of nitrite inhalants and its correlates among men who have sex with men (MSM) in Beijing, China. Methods. A cross-sectional survey was conducted in 2012. Structured interviews collected data on demographics, sexual and drug use behaviors, and the use of HIV services. Blood specimens were collected and tested for HIV and syphilis. Results. A total of 400 MSM eligible for the study were between 19 and 63 years of age and overall HIV prevalence was 6.0% (9.0% among nitrite inhalant users and 3.3% among nonusers). Nearly half (47.3%) of them reported ever using nitrite inhalants and 42.3% admitted using nitrite inhalants in the past year. Multivariable logistic analysis revealed that ever using nitrite inhalants in the past was independently associated with being aged ≤25 years, having higher education attainment, seeking sex via Internet, having casual partners in the past three months, and being HIV positive. Conclusion. The use of nitrite inhalants was alarmingly prevalent among MSM in Beijing. The independent association of the nitrite inhalant use with more casual sex partners and HIV infection underscored the need for intervention and prevention of nitrite inhalant use. PMID:24800219

  7. Inhaled Anesthetic Potency in Aged Alzheimer Mice

    PubMed Central

    Bianchi, Shannon L.; Caltagarone, Breanna M.; LaFerla, Frank M.; Eckenhoff, Roderic G.; Kelz, Max B.

    2016-01-01

    BACKGROUND The number of elderly patients with frank or incipient Alzheimer’s disease (AD) requiring surgery is growing as the population ages. General anesthesia may exacerbate symptoms of and the pathology underlying AD, so minimizing anesthetic exposure may be important. This requires knowledge of whether the continuing AD pathogenesis alters anesthetic potency. METHODS We determined the induction potency and emergence time for isoflurane, halothane, and sevoflurane using the minimum alveolar anesthetic concentration for loss of righting reflex as an end point in 12- to 14-mo-old triple transgenic Alzheimer (3xTgAD) mice and wild type C57BL6 controls. 3xTgAD mice model AD by harboring three distinct mutations: the APPSwe, Tau, and PS1 human transgenes, each of which has been associated with familial forms of human AD. RESULTS The 3xTgAD mice exhibited mild resistance (from 8% to 30%) to volatile anesthetics but displayed indistinguishable emergence patterns from all three inhaled anesthetics. CONCLUSIONS These results show that the genetic vulnerabilities and neuropathology associated with AD produce a small but significant decrease in sensitivity to the hypnotic actions of three inhaled anesthetics. Emergence times were not altered. PMID:19820240

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

    PubMed Central

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

    2016-01-01

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

  9. The Skeletal Effects of Inhaled Glucocorticoids.

    PubMed

    Sutter, Stephanie A; Stein, Emily M

    2016-06-01

    The skeletal effects of inhaled glucocorticoids are poorly understood. Children with asthma treated with inhaled glucocorticoids have lower growth velocity, bone density, and adult height. Studies of adults with asthma have reported variable effects on BMD, although prospective studies have demonstrated bone loss after initiation of inhaled glucocorticoids in premenopausal women. There is a dose-response relationship between inhaled glucocorticoids and fracture risk in asthmatics; the risk of vertebral and non-vertebral fractures is greater in subjects treated with the highest doses in the majority of studies. Patients with COPD have lower BMD and higher fracture rates compared to controls, however, the majority of studies have not found an additional detrimental effect of inhaled glucocorticoids on bone. While the evidence is not conclusive, it supports using the lowest possible dose of inhaled glucocorticoids to treat patients with asthma and COPD and highlights the need for further research on this topic. PMID:27091558

  10. 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

  11. 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

  12. 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

  13. 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. PMID:26857693

  14. 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

  15. Azithromycin May Antagonize Inhaled Tobramycin When Targeting Pseudomonas aeruginosa in Cystic Fibrosis

    PubMed Central

    Nick, Jerry A.; Moskowitz, Samuel M.; Chmiel, James F.; Forssén, Anna V.; Kim, Sun Ho; Saavedra, Milene T.; Saiman, Lisa; Taylor-Cousar, Jennifer L.

    2014-01-01

    Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting azithromycin use (28 d: −0.51 vs. 3.43%, P < 0.01; 140 d: −1.87 vs. 6.07%, P < 0.01). Combined azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant azithromycin use. Outcomes in those not using azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection. PMID:24476418

  16. Inhaled allergen bronchoprovocation tests.

    PubMed

    Diamant, Zuzana; Gauvreau, Gail M; Cockcroft, Don W; Boulet, Louis-Philippe; Sterk, Peter J; de Jongh, Frans H C; Dahlén, Barbro; O'Byrne, Paul M

    2013-11-01

    The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and experienced investigators, it is safe and highly reproducible. In combination with validated airway sampling and sensitive detection techniques, allergen challenge allows the study of several features of the physiology of mainly TH2 cell-driven asthma in relation to the kinetics of the underlying airway pathology occurring during the allergen-induced late response. Furthermore, given the small within-subject variability in allergen-induced airway responses, allergen challenge offers an adequate disease model for the evaluation of new (targeted) controller therapies for asthma in a limited number of subjects. In proof-of-efficacy studies thus far, allergen challenge showed a fair positive predicted value and an excellent negative predictive value for the actual clinical efficacy of new antiasthma therapies, underscoring its important role in early drug development. In this review we provide recommendations on challenge methods, response measurements, sample size, safety, and harmonization for future applications. PMID:24119772

  17. Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children

    PubMed Central

    Cates, Christopher J; Lasserson, Toby J

    2014-01-01

    Background Traditionally inhaled treatment for asthma has been considered as preventer and reliever therapy. The combination of formoterol and budesonide in a single inhaler introduces the possibility of using a single inhaler for both prevention and relief of symptoms (single inhaler therapy). Objectives The aim of this review is to compare formoterol and corticosteroid in single inhaler for maintenance and relief of symptoms with inhaled corticosteroids for maintenance and a separate reliever inhaler. Search methods We last searched the Cochrane Airways Group trials register in September 2008. Selection criteria Randomised controlled trials in adults and children with chronic asthma. Data collection and analysis Two review authors independently assessed studies for inclusion and extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes. Main results Five studies on 5,378 adults compared single inhaler therapy with current best practice, and did not show a significant reduction in participants with exacerbations causing hospitalisation (Peto OR 0.59; 95% CI 0.24 to 1.45) or treated with oral steroids (OR 0.83; 95% CI 0.66 to 1.03). Three of these studies on 4281 adults did not show a significant reduction in time to first severe exacerbation needing medical intervention (HR 0.96; 95% CI 0.85 to 1.07). These trials demonstrated a reduction in the mean total daily dose of inhaled corticosteroids with single inhaler therapy (mean reduction ranged from 107 to 267 micrograms/day, but the trial results were not combined due to heterogeneity). The full results from four further studies on 4,600 adults comparing single inhaler therapy with current best practice are awaited. Three studies including 4,209 adults compared single inhaler therapy with higher dose budesonide maintenance and terbutaline for symptom relief. No significant reduction was found with single inhaler therapy

  18. 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

  19. 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

  20. [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

  1. A collaborative European study of personal inhalable aerosol sampler performance.

    PubMed

    Kenny, L C; Aitken, R; Chalmers, C; Fabriès, J F; Gonzalez-Fernandez, E; Kromhout, H; Lidén, G; Mark, D; Riediger, G; Prodi, V

    1997-04-01

    Following the adoption of new international sampling conventions for inhalable, thoracic and respirable aerosol fractions, a working group of Comité Européen de Normalisation (CEN) drafted a standard for the performance of workplace aerosol sampling instruments. The present study was set up to verify the experimental, statistical and mathematical procedures recommended in the draft performance standard and to check that they could be applied to inhalable aerosol samplers. This was achieved by applying the tests to eight types of personal inhalable aerosol sampler commonly used for workplace monitoring throughout Europe. The study led to recommendations for revising the CEN draft standard, in order to simplify the tests and reduce their cost. However, some further work will be needed to develop simpler test facilities and methods. Several of the samplers tested were found to perform adequately with respect to the inhalable sampling convention, at least over a limited range of typical workplace conditions. In general the samplers were found to perform best in low external wind speeds, which are the test conditions thought to be closest to those normally found in indoor workplaces. The practical implementation of the CEN aerosol sampling conventions requires decisions on which sampling instruments to use, estimation of the likely impact that changing sampling methods could have on apparent exposures, and adjustment where necessary of exposure limit values. The sampler performance data obtained in this project were affected by large experimental errors, but are nevertheless a useful input to decisions on how to incorporate the CEN inhalable sampling convention into regulation, guidance and occupational hygiene practice. PMID:9155236

  2. 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.

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

    PubMed

    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. PMID:7163722

  4. 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

  5. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Inhalation toxicity. 798.2450 Section 798.2450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2450 Inhalation toxicity. (a) Purpose. In the assessment...

  6. How to use an inhaler - with spacer

    MedlinePlus

    ... out through your mouth. After using your inhaler, rinse your mouth with water, gargle, and spit. This helps reduce side effects from your medicine. Keep your inhaler clean Look at the ... mouthpiece. Rinse only the mouthpiece and cap in warm water. ...

  7. 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 ...

  8. Inhaled antimicrobial therapy - barriers to effective treatment.

    PubMed

    Weers, Jeffry

    2015-05-01

    Inhaled antibiotics dramatically improve targeting of drug to the site of respiratory infections, while simultaneously minimizing systemic exposure and associated toxicity. The high local concentrations of antibiotic may enable more effective treatment of multi-drug resistant pathogens. This review explores barriers to effective treatment with inhaled antibiotics. In addition, potential opportunities for improvements in treatment are reviewed. PMID:25193067

  9. Nanotechnology and pharmaceutical inhalation aerosols.

    PubMed

    Patel, A R; Vavia, P R

    2007-02-01

    Pharmaceutical inhalation aerosols have been playing a crucial role in the health and well being of millions of people throughout the world for many years. The technology's continual advancement, the ease of use and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years. But administration of drugs by the pulmonary route is technically challenging because oral deposition can be high, and variations in inhalation technique can affect the quantity of drug delivered to the lungs. Recent advances in nanotechnology, particularly drug delivery field have encouraged formulation scientists to expand their reach in solving tricky problems related to drug delivery. Moreover, application of nanotechnology to aerosol science has opened up a new category of pharmaceutical aerosols (collectively known as nanoenabled-aerosols) with added advantages and effectiveness. In this review, some of the latest approaches of nano-enabled aerosol drug delivery system (including nano-suspension, trojan particles, bioadhesive nanoparticles and smart particle aerosols) that can be employed successfully to overcome problems of conventional aerosol systems have been introduced. PMID:17375556

  10. Inhalants

    MedlinePlus

    ... that your kids will use drugs such as marijuana 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 ...

  11. 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 ...

  12. 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 ...

  13. 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

  14. 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

  15. 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...

  16. AB027. Long-acting beta-agonist in combination or separate inhaler as step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids

    PubMed Central

    Turner, Steve; Richardson, Kathryn; Murray, Clare; Thomas, Mike; Hillyer, Elizabeth V.; Burden, Anne; Price, David B.

    2016-01-01

    Background Adding a long-acting β2-agonist (LABA) to inhaled corticosteroids (ICS) using a fixed-dose combination (FDC) inhaler containing ICS and LABA is the UK guideline-recommended step-up option for children aged >4 years with uncontrolled asthma on ICS monotherapy. The evidence of benefit of FDC inhalers over adding a separate LABA inhaler to ICS therapy is limited. Our aim was to compare outcomes for FDCversusseparate LABA + ICS inhalers for children by analyzing routinely-acquired clinical and prescribing data. Methods This matched cohort study used large UK primary care databases to study children prescribed their first step-up from ICS monotherapy at 5–12 years of age as add-on LABA, either via separate LABA inhaler or FDC inhaler. A baseline year was examined to characterize patients and identify potential confounders; outcomes were examined during the subsequent year. The primary outcome was overall asthma control. Results After matching, there were 1,330 children in each cohort [mean age (SD) 9 (2) years; 59% male]. All measures of asthma exacerbations and control improved during the outcome year in both cohorts. In the separate ICS + LABA cohort, the odds of failing to achieve overall asthma control were higher [adjusted odds ratio 1.30, (95% CI, 1.10–1.52) P=0.002] compared with the FDC cohort. Acute respiratory events were more frequent [adjusted rate ratio 1.21, (1.04–1.39) P=0.012] in the ICS + LABA compared to the FDC cohort. Conclusions These results support current recommendations that add-on LABA therapy for children should be administered as an FDC and not as separate inhaler.

  17. 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

  18. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. 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

  1. [Influence of inhaler and fine particle on efficacy of inhalation therapy in COPD].

    PubMed

    Sliwiński, Paweł; Chazan, Ryszarda; Dąbrowiecki, Piotr; Jahnz-Różyk, Karina; Mróz, Robert; Pirożyński, Michał

    2014-01-01

    Orally inhaled products delivered via inhalation exert their effect directly to the target organ. This allows to administer a very low dose of a drug compared with an oral route with similar clinical effect and significantly reduced toxicity. However inhalation therapy is also limited by several factors. Delivery of the desired dose of the drug to the airways depends on a type of the inhaler - pressurised metered-dose inhaler (pMDI) or dry powder inhaler (DPI), inhaler characteristics (low or high internal resistance, diameter of particles and distribution of the generated aerosol fine particles), thermal conditions of air, and ability of patient to generate sufficient inspiratory flow (for DPI) or to coordinate actuation with inhalation (for pMDI). Unlike pMDIs, DPIs are breath- -actuated, hence avoiding the need for the patient to coordinate actuation with inspiration. Furthermore, DPIs are propellant-free and do not produce the cold sensation on inhalation. Currently available DPIs vary widely in design, operating characteristics and performance. And poor inhalation technique may compromise treatment efficacy. Hence, there is a clear need for a careful selection of DPIs for different patient groups, including children, elderly patients and those with severe airway obstruction. PMID:24793155

  2. 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

  3. Introduction: Aerosol delivery of orally inhaled agents.

    PubMed

    Corcoran, Timothy E; Devadason, Sunalene G; Kuehl, Philip J

    2012-12-01

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

  4. 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

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

    PubMed

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

    2016-01-01

    We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection. PMID:27173212

  6. Endotoxin Inhalation Alters Lung Development in Neonatal Mice

    PubMed Central

    Kulhankova, Katarina; George, Caroline L.S.; Kline, Joel N.; Darling, Melissa; Thorne, Peter S.

    2012-01-01

    Background Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life. Methods We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses. Results Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization. Conclusions Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children. PMID:22576659

  7. INTERSPECIES MODELING OF INHALED PARTICLE DEPOSITION

    EPA Science Inventory

    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. erein, an interspecies particle deposition theory is presented for physiologically based p...

  8. Nitrous Oxide and the Inhalation Anesthetics

    PubMed Central

    Becker, Daniel E; Rosenberg, Morton

    2008-01-01

    Nitrous oxide is the most commonly used inhalation anesthetic in dentistry and is commonly used in emergency centers and ambulatory surgery centers as well. When used alone, it is incapable of producing general anesthesia reliably, but it may be combined with other inhalation and/or intravenous agents in deep sedative/general anesthestic techniques. However, as a single agent, it has impressive safety and is excellent for providing minimal and moderate sedation for apprehensive dental patients. To gain a full appreciation of the pharmacology, physiologic influences, and proper use of nitrous oxide, one must compare it with other inhalation anesthetics. The purpose of this CE article is to provide an overview of inhalation anesthetics in general and to address nitrous oxide more specifically in comparison. PMID:19108597

  9. REGIONAL DEPOSITION OF INHALED REACTIVE GASES

    EPA Science Inventory

    A critical concept in inhalation toxicology involves the determination of dose as the first component for providing a perspective to judge the applicability of various toxicological results to human exposure conditions. Available experimental data for reactive gases were reviewed...

  10. 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

  11. Assessing inhalation injury in the emergency room

    PubMed Central

    Tanizaki, Shinsuke

    2015-01-01

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

  12. Comparing Usability of NEXThaler® with Other Inhaled Corticosteroid/Long-Acting β2-Agonist Fixed Combination Dry Powder Inhalers in Asthma Patients

    PubMed Central

    Voshaar, Thomas; Linnane, Patrick; Campanini, Alice; Lock, Daniel; Lafratta, Anthony; Scuri, Mario; Ronca, Barbara; Melani, Andrea S.

    2014-01-01

    Abstract Background: Inhaler mishandling is a common issue among patients suffering from asthma and is associated with poor clinical outcomes and greater consumption of health-care resources. Ease of use can improve inhaler technique and, possibly, patients' preference for their inhaler device, which in turn may lead to better adherence to therapy. Methods: This study investigated usability characteristics of NEXThaler® versus two other dry powder inhalers (DPIs; Diskus® and Turbuhaler®). Sixty-six adult patients with asthma (mean age 42.9±17.7 years) and with no previous experience of using a DPI were included in a randomized crossover comparison of the three devices. The main measures of usability were the number of steps failed for each device and the number of people who were able to use the device successfully (effectiveness), the time it took patients to set up the device and the time to read the instructions for use (IFU; efficiency), and patient preferences (satisfaction). Inhaler technique was evaluated after the IFU leaflet was read. Results: NEXThaler was found to be superior to the other two DPIs in terms of the number of device use failures (p<0.001), time to set up (p<0.001), and time to read IFU (p<0.001). Additionally, the proportion of participants who completed a successful inhalation without any errors at all was significantly higher for NEXThaler than for Diskus and Turbuhaler (p<0.001). Patients rated NEXThaler as the easiest to use and most preferred inhaler to own (p<0.001). Conclusions: NEXThaler displayed better usability compared with Diskus and Turbuhaler. The improved usability and higher satisfaction with the device may contribute to increased patient adherence to asthma treatment. PMID:24299501

  13. 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. PMID:15583121

  14. 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.

  15. 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

  16. 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

  17. Inhaler Use in Hospitalized Patients with Chronic Obstructive Pulmonary Disease or Asthma: Assessment of Wasted Doses

    PubMed Central

    Sakaan, Sami; Ulrich, Dagny; Luo, Jenny; Finch, Christopher K.; Self, Timothy H.

    2015-01-01

    Background: Hospitalized patients with chronic obstructive pulmonary disease (COPD) or asthma routinely have inhaled medications ordered for acute and maintenance therapy. Treatment may be administered via metered-dose inhaler (MDI) or dry-powder inhaler (DPI). These products must be appropriately labeled to be released home with the patient or discarded before discharge. Objective: To assess the amount and estimated cost of wasted doses of medications via MDI or DPI for hospitalized patients with COPD/asthma. Methods: A retrospective study was conducted at a university-affiliated hospital. Patients admitted between January 2011 and June 2012 with a primary diagnosis of COPD or COPD with asthma and who were ≥40 years of age were included. Information collected included use of albuterol, ipratropium, inhaled corticosteroids, long-acting beta agonist, or tiotropium and whether treatments were given by nebulizer, MDI, MDI plus valved holding chamber (VHC), or DPI. The number of doses dispensed, as well as doses not used, via MDI, MDI + VHC, or DPI were collected from electronic medical records. Costs associated with wasted medications were evaluated. Results: Of 555 patient admissions screened, 478 (mean age, 66 years; 58% women; 74% African American) met study criteria. Of the total MDI or DPI doses dispensed, 87% were wasted, and associated hospital cost was approximately $86,973. Conclusions: Substantial waste of inhaled medications was found in our study. Practical strategies are needed to reduce wasted inhalers. Further assessment of this problem is needed in other US hospitals. PMID:26405325

  18. 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

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

    PubMed Central

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

    2014-01-01

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

  20. Pharmacoscintigraphic evaluation of lipid dry powder budesonide formulations for inhalation.

    PubMed

    Sebti, Thami; Pilcer, Gabrielle; Van Gansbeke, Bernard; Goldman, Serge; Michils, Alain; Vanderbist, Francis; Amighi, Karim

    2006-08-01

    Lung deposition of new formulations of budesonide, using solid lipid microparticles (SLmP) as a pharmaceutically acceptable filler and carrier for inhalation aerosols, and administered from a dry powder inhaler (Cyclohaler), were compared with that from Pulmicort Turbuhaler. Six healthy volunteers took part in a three-way randomized cross-over study, and inhaled a nominal dose of 400 microg budesonide, labelled with 99mTc, on each study day. Lung deposition was determined by gamma scintigraphy and by a pharmacokinetic method. The percentage of dose (SD) in the whole lung was 49.9 (3.7)% for the lipidic matricial form (M) and 62.8 (4.9)% for the lipidic physical blend formulation (PB). These results corresponded well with the in vitro fine particle assessment. In comparison with data recorded in literature for in vivo deposition obtained with Pulmicort Turbuhaler, it was estimated that lung deposition was 1.5 and 2.0 times higher for the M and PB formulations, respectively. Furthermore, the relative drug availability obtained from the pharmacokinetic evaluation, expressed as the percentage of pulmonary absorption of the comparator product, was 154% and 220% for M and PB, respectively. The results of the present study indicate that pulmonary administration using SLmP gives a prominent and significant increase in budesonide lung deposition. PMID:16697169

  1. 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

  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. 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

  4. 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…

  5. 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

  6. Cariogenic Potential of Inhaled Antiasthmatic Drugs

    PubMed Central

    Brigic, Amela; Kobaslija, Sedin; Zukanovic, Amila

    2015-01-01

    Introduction: The organism of children with asthma is exposed to the effects of the disease but also the drugs for its treatment. Antiasthmatic drugs have different modes that promote the caries formation which varies according to their basic pharmacological composition. Namely, these drugs have a relatively low pH (5.5), can contain sweeteners such as lactose monohydrate in order to improve the drug taste or both. Frequent consumption of these inhalers in combination with reduced secretion of saliva increases the risk of caries. Material and methods: The study sample consisted of 200 patients, age from 7-14 years, divided into two groups: control group (n1 = 100) consisted of healthy children and the experimental group consisted of children suffering from asthma (n2 = 100). In both groups of respondents are determined the DMFT index, plaque index value and hygienic-dietary habits using the questionnaire. The subjects in the control group had significantly higher DMFT index than subjects in the experimental group (p = 0.004). It is determined that there are no significant differences in the values of plaque index (p>0.05). Conclusion: The effect of different diseases or medications from their treatment, diet and fermentable carbohydrates in the etiology of dental caries cannot be observed outside the living conditions of subjects, their social epidemiologic status, age, habits, oral hygiene, fluoride use, etc. PMID:26543312

  7. 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

  8. Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation

    PubMed Central

    2011-01-01

    Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS) and long acting beta-agonists (LABA). Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7%) received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F) pressurized metered dose inhaler (pMDI), 25 (22.5%) fluticasone-salmeterol (FP/S) dry powder inhaler (DPI), and 33 (29.7%) budesonide-formoterol (BUD/F) DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively) and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both. PMID:21762500

  9. 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

  10. Inhalation injury: a decade without progress.

    PubMed

    Sobel, J B; Goldfarb, I W; Slater, H; Hammell, E J

    1992-01-01

    Despite major advances in the management of patients with critical burn injuries, inhalation injury continues to be a major determinant of death resulting from burn injuries. Two cohort groups of victims with burn and inhalation injuries, separated by a decade, were retrospectively reviewed in an effort to determine the impact of newer treatment modalities. Patients were categorized as being at "high" or "low" risk on the basis of primary and secondary diagnostic criteria. Despite a statistically significant decrease in the percent of total body surface injury, no change in mortality rate was noted between the two groups. The advent of sophisticated diagnostic and management techniques does not appear to have decreased the mortality rate associated with inhalation injury. PMID:1452592

  11. 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

  12. 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...

  13. 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.

  14. Fewer Inhaled Steroids May Be OK for Asthmatic Children

    MedlinePlus

    ... gov/medlineplus/news/fullstory_159083.html Fewer Inhaled Steroids May Be OK for Asthmatic Children Study suggests ... 2016 FRIDAY, May 27, 2016 (HealthDay News) -- Inhaled steroid therapy is commonly used to treat asthmatic children ...

  15. [Inhaled corticosteroids: Which regimens are appropriate?].

    PubMed

    Giovannini-Chami, L; Piccini-Bailly, C; Albertini, M

    2016-06-01

    Inhaled corticosteroids are the cornerstone of asthma management. Inhaled corticosteroid regimens differ slightly in various international guidelines on asthma management but are based on the principles of continuous treatment and titration to the lowest effective dose. Several recent studies, nevertheless, appear to demonstrate the potential value of preemptive or "pro re nata" regimens in infants and children. These studies were included in GINA 2015 for children 5 years of age and younger in whom discontinuous treatment is proposed as a second-line option. Should we change our practices after a critical reading of these studies? PMID:27133372

  16. 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

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

    PubMed

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

    1988-04-01

    Although xenon enhanced CT method for local cerebral blood flow measurement has been brought into a clinical practice, the technique has inherent limitations including anesthetic effects and expensive cost of xenon by a large consumption. To overcome these problems a modified method with a short-duration inhalation was developed and its validity was attested. Siemens Somatom SF with a resolution of 256 X 256 pixels and a scan time of 10 seconds was used. The subjects inhaled 50% Xe/O2 gas mixture from an apparatus consisted of Douglas bag and an open circuit. Xenon concentration in the expired gas was continuously monitored and estimated for arterial blood concentration by using a hematocrit correction. PaCO2 was monitored throughout the study. At the starting point and the endpoint of the inhalation two scans were performed respectively. Thus obtained four images were processed for CT noise cancellation, summation and subtraction to produce an in vivo autoradiography image. Local CBF was calculated from equations derived from the autoradiographic technique with a fixed partition coefficient of lambda = 1. Computer simulation studies were performed to find the optimal scan point to obtain an autoradiographic image and to estimate the calculation errors of this method. One minute and forty-five seconds was found to be the optimal scan point to gain an autoradiographic image in view of a balance between linearity of CBF/enhancement curve and total amount of tissue enhancement. The theoretical errors due to the assumption for a fixed partition coefficient were calculated to be 8% underestimation for gray matter and 5% overestimation for white matter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3401410

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

    PubMed

    Chow, Michael Y T; Lam, Jenny K W

    2015-01-01

    Nucleic acid therapeutics has huge potential for the treatment of a wide range of diseases including respiratory diseases. Plasmid DNA (pDNA) and small interfering RNA (siRNA) are the two most widely investigated nucleic acids for therapeutic development. However, efficient and safe delivery of nucleic acids is still a major hurdle in translating nucleic acid therapy into clinical practice. For the treatment of respiratory diseases, administration via inhalation is the most direct and effective way to deliver therapeutic nucleic acids to the lungs. Although liquid aerosol formulation is investigated in most of the studies, it is not desirable in terms of maintaining the stability of nucleic acid especially during long-term storage. This problem could be circumvented by formulating the therapeutic nucleic acids into dry powder for inhalation, and should be considered as the future direction of developing inhalable nucleic acids. In this review, the three major particle engineering methods investigated for the preparation of inhalable pDNA and siRNA formulations, including spray drying (SD), spray freeze drying (SFD) and supercritical fluid (SFC) drying, are discussed and compared. Moreover, common assessment methods and the challenges of evaluating the biological activities of inhalable nucleic acid powders are also reviewed. PMID:26290202

  19. 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

  20. Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions

    PubMed Central

    Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René

    2015-01-01

    Abstract Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide–formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Results: Mean values for both budesonide and formoterol were within 85%–115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective

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

    PubMed Central

    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

  2. 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

  3. The Treatment of Pulmonary Diseases and Respiratory-Related Conditions with Inhaled (Nebulized or Aerosolized) Glutathione

    PubMed Central

    2008-01-01

    Reduced glutathione or simply glutathione (γ-glutamylcysteinylglycine; GSH) is found in the cytosol of most cells of the body. GSH in the epithelial lining fluid (ELF) of the lower respiratory tract is thought to be the first line of defense against oxidative stress. Inhalation (nebulized or aerosolized) is the only known method that increases GSH's levels in the ELF. A review of the literature was conducted to examine the clinical effectiveness of inhaled GSH as a treatment for various pulmonary diseases and respiratory-related conditions. This report also discusses clinical and theoretical indications for GSH inhalation, potential concerns with this treatment, its presumed mechanisms of action, optimal doses to be administered and other important details. Reasons for inhaled GSH's effectiveness include its role as a potent antioxidant, and possibly improved oxygenation and host defenses. Theoretical uses of this treatment include Farmer's lung, pre- and postexercise, multiple chemical sensitivity disorder and cigarette smoking. GSH inhalation should not be used as a treatment for primary lung cancer. Testing for sulfites in the urine is recommended prior to GSH inhalation. Minor side effects such as transient coughing and an unpleasant odor are common with this treatment. Major side effects such as bronchoconstriction have only occurred among asthma patients presumed to be sulfite-sensitive. The potential applications of inhaled GSH are numerous when one considers just how many pulmonary diseases and respiratory-related conditions are affected by deficient antioxidant status or an over production of oxidants, poor oxygenation and/or impaired host defenses. More studies are clearly warranted. PMID:18317545

  4. Beneficial effects of inhaled NO on apoptotic pneumocytes in pulmonary thromboembolism model

    PubMed Central

    2014-01-01

    Background Lung ischemia–reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. Inhaled NO may be useful in treating acute and chronic pulmonary thromboembolism (PTE) due to the biological effect property of NO. Methods A PTE canine model was established through selectively embolizing blood clots to an intended right lower lobar pulmonary artery. PaO2/FiO2, the mPAP and PVR were investigated at the time points of 2, 4, 6 hours after inhaled NO. Masson’s trichrome stain, apoptotic pneumocytes and lung sample ultrastructure were also investigated among different groups. Results The PaO2/FiO2 in the Inhaled NO group increased significantly when compared with the Reperfusion group at time points of 4 and 6 hours after reperfusion, mPAP decreased significantly at point of 2 hours and the PVR decreased significantly at point of 6 hours after reperfusion. The amounts of apoptotic type II pneumocytes in the lower lobar lung have negative correlation trend with the arterial blood PaO2/FiO2 in Reperfusion group and Inhaled NO group. Inhaled nitric oxide given at 20 ppm for 6 hours can significantly alleviate the LIRI in the model. Conclusions Dramatic physiological improvements are seen during the therapeutic use of inhaled NO in pulmonary thromboembolism canine model. Inhaled NO may be useful in treating LIRI in acute or chronic PTE by alleviating apoptotic type II pneumocytes. This potential application warrants further investigation. PMID:25109474

  5. Development of a murine nose-only inhalation model of influenza: comparison of disease caused by instilled and inhaled A/PR/8/34

    PubMed Central

    Bowen, Larry E.; Rivers, Katie; Trombley, John E.; Bohannon, J. Kyle; Li, Shixiong X.; Boydston, Jeremy A.; Eichelberger, Maryna C.

    2012-01-01

    Influenza continues to cause widespread disease and death during winter months. In preclinical studies to evaluate the potential efficacy of drugs and vaccines, influenza challenge virus is usually instilled into the noses of animals in the form of large liquid drops. Since inhalation of aerosolized influenza is commonly associated with human transmission, instillation of challenge virus raises uncertainty about the applicability of results. In order to compare the challenge methods, we established conditions to generate influenza aerosols with a mass median aerodynamic diameter (MMAD) of 1 μm that were delivered to mice in a nose-only inhalation system. In this report, we describe the system and compare the 50% lethal dose (LD50) of instilled and inhaled A/PR/8/34 (PR8) in BALB/c mice. The estimated LD50 for inhaled virus was 8.7 plaque forming units (PFU) and the mean time to death was 7.7 days, whereas the estimated LD50 for instilled virus was 51.6 PFU and the mean time to death was 8.2 days. Our results show that mice are more sensitive to inhaled virus than virus delivered by intranasal instillation. The murine nose-only inhalation model of influenza infection can be used to infect large numbers of animals simultaneously with well-characterized, homogenous PR8 bioaerosol in a controlled and reproducible manner. This model provides the means to evaluate the efficacy of drug and vaccine candidates against the relevant route of challenge, thereby providing data that may better predict clinical outcome. PMID:22919665

  6. 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

  7. 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.

  8. 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.…

  9. 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…

  10. 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...

  11. 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...

  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. 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...

  14. 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...

  15. 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...

  16. THE METABOLISM OF NALED INHALED BY RATS

    EPA Science Inventory

    Naled (Dibrom) was prepared with a (14)carbon label in the 1-ethyl position. The labeled compound was administered in appropriate formulation vehicles to female rats by the inhalation, oral or intraperitoneal routes. Treated animals were either placed in metabolism cages and thei...

  17. A murine model of smoke inhalation.

    PubMed

    Matthew, E; Warden, G; Dedman, J

    2001-04-01

    The United States has one of the world's largest per capita fire death rates. House fires alone kill >9,000 Americans annually, and smoke inhalation is the leading cause of mortality from structural fires. Animal models are needed to develop therapies to combat this problem. We have developed a murine model of smoke inhalation through the design, construction, and use of a controlled-environment smoke chamber. There is a direct relationship between the quantity of wood combusted and mortality in mice. As with human victims, the primary cause of death from smoke inhalation is an elevated blood carboxyhemoglobin level. Lethal (78%) and sublethal (50%) carboxyhemoglobin levels were obtained in mice subjected to varying amounts of smoke. Mice exposed to wood smoke demonstrated more dramatic pathology than mice exposed to cotton or polyurethane smoke. A CD-1 model of wood smoke exposure was developed, demonstrating type II cell hypertrophy, cytoplasmic blebbing, cytoplasmic vacuolization, sloughing, hemorrhage, edema, macrophage infiltration, and lymphocyte infiltration. The bronchoalveolar lavage fluid of smoke-exposed mice demonstrated a significant increase in total cell counts compared with those in control mice. These findings are comparable to the lung tissue response observed in human victims of smoke inhalation. PMID:11238012

  18. Inhalation exposure in secondary aluminium smelting.

    PubMed

    Healy, J; Bradley, S D; Northage, C; Scobbie, E

    2001-04-01

    Inhalation exposure at seven UK secondary aluminium smelters was investigated to quantify the main exposures and identify their sources. The substances monitored were gases (carbon monoxide, hydrogen sulphide and nitrogen dioxide), total inhalable dust, metals, ammonia, polycyclic aromatic hydrocarbons (PAHs), particulate fluoride salts and acids. The results showed that people were exposed to a range of workplace air pollutants. Personal exposure results for total inhalable dust were between 700 and 5600 microg x m(-3) and the maximum personal exposure result for particulate fluoride salts was 690 microg x m(-3) (as F). The maximum aluminium, total PAH and lead personal exposure results were 900, 19 and 18 microg x m(-3) respectively. The average proportion of aluminium in total inhalable dust samples was 13% and rotary furnace processes generated the most dust. Particulate fluoride salt exposure was more widespread than hydrofluoric acid exposure. The source of the salt exposure was fluoride containing fluxes. The lead exposure source was lead solder contamination in the furnace charge. PMID:11295145

  19. CYTOGENETIC EFFECTS OF PHOSPHINE INHALATION BY RODENTS

    EPA Science Inventory

    Phosphine (PH3) is a highly toxic grain fumigant that can be produced from the reaction of metal phosphides with water. o determine the in vivo cytogenetic effects of inhalation of PH3, male CD-1 mice were exposed to either 0, 5, 10, or 15 ppm target concentrations of PH3 for 6 h...

  20. DEVELOPMENTAL NEUROTOXICITY OF INHALED METHANOL IN RATS

    EPA Science Inventory

    Dr. Weiss and his colleagues conducted a controlled series of experiments in which they exposed pregnant rats and their newborn offspring to 4,500 parts per million (ppm) methanol by inhalation, and then submitted them to tests of behavioral function.

    Exposure to 4,500...

  1. 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)

  2. Ozone inhalation modifies the rat liver proteome☆

    PubMed Central

    Theis, Whitney S.; Andringa, Kelly K.; Millender-Swain, Telisha; Dickinson, Dale A.; Postlethwait, Edward M.; Bailey, Shannon M.

    2013-01-01

    Ozone (O3) is a serious public health concern. Recent findings indicate that the damaging health effects of O3 extend to multiple systemic organ systems. Herein, we hypothesize that O3 inhalation will cause downstream alterations to the liver. To test this, male Sprague-Dawley rats were exposed to 0.5 ppm O3 for 8 h/day for 5 days. Plasma liver enzyme measurements showed that 5 day O3 exposure did not cause liver cell death. Proteomic and mass spectrometry analysis identified 10 proteins in the liver that were significantly altered in abundance following short-term O3 exposure and these included several stress responsive proteins. Glucose-regulated protein 78 and protein disulfide isomerase increased, whereas glutathione S-transferase M1 was significantly decreased by O3 inhalation. In contrast, no significant changes were detected for the stress response protein heme oxygenase-1 or cytochrome P450 2E1 and 2B in liver of O3 exposed rats compared to controls. In summary, these results show that an environmentally-relevant exposure to inhaled O3 can alter the expression of select proteins in the liver. We propose that O3 inhalation may represent an important unrecognized factor that can modulate hepatic metabolic functions. PMID:25544660

  3. A pharmacokinetic simulation tool for inhaled corticosteroids.

    PubMed

    Weber, Benjamin; Hochhaus, Guenther

    2013-01-01

    The pharmacokinetic (PK) behavior of inhaled drugs is more complicated than that of other forms of administration. In particular, the effects of certain physiological (mucociliary clearance and differences in membrane properties in central and peripheral (C/P) areas of the lung), formulation (as it relates to drug deposition and particle dissolution rate), and patient-related factors (lung function; effects on C/P deposition ratio) affect the systemic PKs of inhaled drugs. The objectives of this project were (1) to describe a compartmental model that adequately describes the fate of inhaled corticosteroids (ICS) after administration while incorporating variability between and within subjects and (2) based upon the model, to provide a freely available tool for simulation of PK trials after ICS administration. This compartment model allows for mucociliary removal of undissolved particles from the lung, distinguishes between central and peripheral regions of the lung, and models drug entering the systemic circulation via the lung and the gastrointestinal tract. The PK simulation tool is provided as an extension package to the statistical software R ('ICSpkTS'). It allows simulation of PK trials for hypothetical ICS and of four commercially available ICS (budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide) in a parallel study design. Simulated PK data and parameters agreed well with literature data for all four ICS. The ICSpkTS package is especially suitable to explore the effect of changes in model parameters on PK behavior and can be easily adjusted for other inhaled drugs. PMID:23139018

  4. 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

  5. FATE OF INHALED FLY ASH IN HAMSTERS

    EPA Science Inventory

    To determine pulmonary deposition, translocation, and clearance of inhaled fly ash, hamsters received a single 95-min nose-only exposure to neutron-activated fly ash. Over a period of 99 days postexposure, the hamsters were sacrificed in groups of six animals. Lungs, liver, kidne...

  6. 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…

  7. 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

  8. Patterns of Inhalant Use among Incarcerated Youth.

    PubMed

    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

  9. Inhalation delivery of proteins from ethanol suspensions.

    PubMed

    Choi, W S; Murthy, G G; Edwards, D A; Langer, R; Klibanov, A M

    2001-09-25

    To circumvent inherent problems associated with pulmonary administration of aqueous-solution and dry-powder protein drugs, inhalation delivery of proteins from their suspensions in absolute ethanol was explored both in vitro and in vivo. Protein suspensions in ethanol of up to 9% (wt/vol) were readily aerosolized with a commercial compressor nebulizer. Experiments with enzymic proteins revealed that nebulization caused no detectable loss of catalytic activity; furthermore, enzyme suspensions in anhydrous ethanol retained their full catalytic activity for at least 3 weeks at room temperature. With the use of Zn(2+)-insulin, conditions were elaborated that produced submicron protein particles in ethanol suspensions. The latter (insulin/EtOH) afforded respirable-size aerosol particles after nebulization. A 40-min exposure of laboratory rats to 10 mg/ml insulin/EtOH aerosols resulted in a 2-fold drop in the blood glucose level and a marked rise in the serum insulin level. The bioavailability based on estimated deposited lung dose of insulin delivered by inhalation of ethanol suspension aerosols was 33% (relative to an equivalent s.c. injection), i.e., comparable to those observed in rats after inhalation administration of dry powder and aqueous solutions of insulin. Inhalation of ethanol in a relevant amount/time frame resulted in no detectable acute toxic effects on rat lungs or airways, as reflected by the absence of statistically significant inflammatory or allergic responses, damage to the alveolar/capillary barrier, and lysed and/or damaged cells. PMID:11562495

  10. 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

  11. Are Sudanese community pharmacists capable to prescribe and demonstrate asthma inhaler devices to patrons? A mystery patient study

    PubMed Central

    Osman, Abuzar; Ahmed Hassan, Imad S.; Ibrahim, Mohamed Izham M.

    Although community pharmacists have become more involved in the care of asthma patients, several studies have assessed pharmacists’'ability to illustrate appropriately inhalation technique of different asthma devices. Many studies addressed inappropriate use of asthma devices by patients and pharmacists, in addition to its clinical, humanistic and economic burden. Objective To evaluate community pharmacists' practical knowledge and skills of demonstrating proper inhalation technique of asthma inhaler devices available in Sudan. Methods Three hundred community pharmacies located around the three major hospitals in the capital city (Khartoum) and four other provinces were approached, and four asthma devices were assessed: Metered-dose inhaler (MDI) (n=105), MDI with Spacer (n=83), Turbuhaler (n=61), and Diskus (n=51). Investigator (a pharmacist) acted as a mystery patient. He selected one device and asked the serving pharmacist to demonstrate how to use the device. Investigator completed a checklist of 9 steps of inhaler device use immediately after leaving the pharmacy. Essential steps derived from published literature were pre-specified for each device. Five evaluation categories were accordingly formulated as follows: optimal technique, adequate technique, poor technique, totally unfamiliar with the device, and does not know. Results More than half of the pharmacists approached with metered dose inhaler did not know how to use optimal technique (ie all steps correct) all through. A third poorly demonstrated the technique, and only one pharmacist was categorized as being able to demonstrate an "optimal technique". The majority of pharmacists approached with spacing chamber and dry powder inhalers (Turbuhaler and Diskus) either did not know proper technique or were totally unfamiliar with the devices. Conclusions The majority of community pharmacists, who were expected to educate asthma patients on their dispensed inhalers, lack the basic knowledge of proper use

  12. Comparison of long-term quality of life of pediatric burn survivors with and without inhalation injury⋆

    PubMed Central

    Rosenberg, Marta; Ramirez, Maribel; Epperson, Kathy; Richardson, Lisa; Holzer, Charles; Andersen, Clark R.; Herndon, David N.; Meyer, Walter; Suman, Oscar E.; Mlcak, Ronald

    2015-01-01

    Objective To examine the long-term quality of life of pediatric burn survivors with and without inhalation injuries. We hypothesized that patients with inhalation injury would report more disability and lower quality of life. Methods We examined 51 patients with inhalation injury and 72 without inhalation injury who had burns of ≥10% total body surface area, were age ≥16 years at time of the interview, and were greater than 5 years from injury. Subjects completed the World Health Organization Disability Assessment Scale II (WHODAS II) and the Burn Specific Health Scale-Brief (BSHS-B). Multiple regression analyses were used to measure the effects of inhalation injury while controlling for age at burn and TBSA. Results The mean age of burn of participants with inhalation injury was 11.7 ± 3.6 years, mean TBSA 55% ± 18, and mean ventilator days 8.4 ± 9. The mean age of burn of participants without inhalation injury was 10.3 ± 34.1 years, mean TBSA 45% ± 20, and mean ventilator days 1.3 ± 5.2. Inhalation injury did not appear to significantly impact participants' scores on the majority of the domains. The WHODAS II domain of household activities showed a significant relation with TBSA (p = 0.01). Increased size of burn was associated with difficulty completing tasks for both groups. The BSHS-B domain of treatment regimen showed a relation with age at burn (p = 0.02). Increased age was associated difficulty in this area for both groups. Conclusions Overall the groups were comparable in their reports of disability and quality of life. Inhalation injury did not affect long-term quality of life. PMID:25670250

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

    PubMed Central

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

    2016-01-01

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

  14. Patterns of substance use, delinquency, and risk factors among adolescent inhalant users

    PubMed Central

    Nakawaki, Brandon; Crano, William

    2015-01-01

    Background Despite insidious effects, use of inhalant substances by adolescents remains an understudied phenomenon. Objective This research was designed to identify patterns of past year substance use and delinquency among adolescent inhalant users. Method The study used a sample of adolescent inhalant users (ages ranged from 12-17 years, n = 7,476) taken from a pooled sample of the 2002 through 2012 National Survey of Drug Use and Health (NSDUH). Three-step latent class analyses were conducted with past year substance use and delinquency behaviors as class indicators. Demographic and social covariates were included in the analyses. Results Analyses yielded a six-class solution comprised of classes of users characterized by low substance use/low delinquency, high substance use/low delinquency, low substance use/fighting, cigarettes/alcohol/marijuana, high substance use/high delinquency, and cigarettes/alcohol/marijuana/opioids/moderate delinquency. Conclusions Findings provide insight into the taxonomy of adolescent inhalant user heterogeneity, and may inform future efforts at detection and prevention of inhalant use by suggesting warning signs of co-occurring externalizing behaviors and possible indications of underlying internalized issues. PMID:25290663

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

    PubMed Central

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

    2012-01-01

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

  16. 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.

  17. Public crack cocaine smoking and willingness to use a supervised inhalation facility: implications for street disorder

    PubMed Central

    2011-01-01

    Background The health risks of crack cocaine smoking in public settings have not been well described. We sought to identify factors associated with public crack smoking, and assess the potential for a supervised inhalation facility to reduce engagement in this behavior, in a setting planning to evaluate a medically supervised crack cocaine smoking facility. Methods Data for this study were derived from a Canadian prospective cohort of injection drug users. Using multivariate logistic regression we identified factors associated with smoking crack cocaine in public areas. Among public crack smokers we then identified factors associated with willingness to use a supervised inhalation facility. Results Among our sample of 623 people who reported crack smoking, 61% reported recently using in public locations. In multivariate analysis, factors independently associated with public crack smoking included: daily crack cocaine smoking; daily heroin injection; having encounters with police; and engaging in drug dealing. In sub analysis, 71% of public crack smokers reported willingness to use a supervised inhalation facility. Factors independently associated with willingness include: female gender, engaging in risky pipe sharing; and having encounters with police. Conclusion We found a high prevalence of public crack smoking locally, and this behavior was independently associated with encounters with police. However, a majority of public crack smokers reported being willing to use a supervised inhalation facility, and individuals who had recent encounters with police were more likely to report willingness. These findings suggest that supervised inhalation facilities offer potential to reduce street-disorder and reduce encounters with police. PMID:21345231

  18. Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation.

    PubMed

    Chao, Yen-Chin; Chang, Shwu-Fen; Lu, Shao-Chun; Hwang, Tzyh-Chang; Hsieh, Wei-Hsien; Liaw, Jiahorng

    2007-03-12

    Modifications of both carriers and host barriers have been investigated for efficient inhalation gene delivery to lung. Here we used a biocompatible, non-ionic poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) polymeric micelles (PM) as a carrier and combined it with ethanol to enhance membrane penetration of delivered DNA. The inhalation delivery with six 100 microg doses of pCMV-Lac Z with PM co-formulated with 10%-40% ethanol to nude mice in 2 days at 8 h interval was performed. The beta-galatosidase (beta-Gal) activity was assessed using chlorophenol red-beta-d galactopyranoside (CPRG) and X-gal staining for quantitative and qualitative analysis in tissues. The results showed that beta-Gal activity was significantly increased by 38% in lung around bronchioles when inhalation with PM and 10% ethanol was given. The 10% ethanol also increased the intracellular apparent permeability by 42% in stomach and by 141% in intestine at 48 h after the first dosage of delivery. Also delivery of DNA encoding a functional human cystic fibrosis transmembrane protein (CFTR) using the same inhalation delivery method co-formulated with 10% ethanol, an increased expression of CFTR in lung was detected by immunostaining. We concluded that 10% ethanol co-formulated with the PM system could enhance inhaled gene delivery to airway and gastrointestinal (GI) tract. PMID:17258837

  19. 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

  20. 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

  1. 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

  2. Fate of inhaled azodicarbonamide in rats

    SciTech Connect

    Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.; Dutcher, J.S.; Cheng, Y.S.; Bond, J.A.; Medinsky, M.A.; Henderson, R.F.; Birnbaum, L.S.

    1987-04-01

    Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of (/sup 14/C)ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only /sup 14/C-labeled compound present in excreta. (/sup 14/C)ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for (/sup 14/C)ADA equivalents were not observed. The rate of buildup of (/sup 14/C)ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of (/sup 14/C)ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine.

  3. 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

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

    PubMed Central

    Green, Patricia; Aronoff, Stephen C.

    2015-01-01

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

  5. Petrol-inhalation in aboriginal towns. Its remedy: the homelands movement.

    PubMed

    Eastwell, H D

    1979-09-01

    Regular petrol-inhaling involves 50 children ("sniffers"), aged nine to 14 years, at the Aboriginal town of Maningrida--over one-third of resident children of this age. Children of two closely related clan-language groups comprise the majority of inhalers. Similarly, at the town of Galiwinku the children of two deprived clans are involved almost exclusively. These are the only clans in eastern Arnhem Land without outstations on their homelands. Revitalization of these clans appears the only effective method of containing the practice. Petrol-inhaling is associated with delinquency, low body weight, venereal disease, and elevated levels of blood lead. The effectiveness of past remedial action is in doubt. PMID:514145

  6. 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.

  7. 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

  8. Changes in atherosclerotic plaques induced by inhalation of diesel exhaust

    PubMed Central

    Bai, Ni; Kido, Takashi; Suzuki, Hisashi; Yang, Grace; Kavanagh, Terrance J.; Kaufman, Joel D.; Rosenfeld, Michael E.; van Breemen, Cornelis; van Eeden, Stephan F.

    2015-01-01

    Objective Exposure to particulate matter air pollution may be an independent risk factor for cardiovascular morbidity and mortality; however, the biological mechanisms are unclear. We hypothesize that exposure to diesel exhaust (DE), an important source of traffic-related particulate air pollution, promotes changes of atherosclerotic plaque component that may lead to plaque vulnerability. Methods and results 30-week old ApoE knockout mice fed with regular chow inhaled DE (at 200 μg/m3 of particulate) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week) (12 mice/group). Total number of alveolar macrophages (p < 0.01) and alveolar macrophages positive for particles (p < 0.0001) were more than 8-fold higher after DE inhalation than the control. DE inhalation caused 1.5 to 3-fold increases in plaque lipid content (p<0.02), cellularity (p<0.02), foam cell formation (p<0.04), and smooth muscle cell content (p<0.05). The expression of oxidative stress markers, iNOS, CD36, and nitrotyrosine was significantly increased by 1.5 to 2-fold in plaques, with enhanced systemic lipid and DNA oxidation (p<0.02). Increased foam cells and the expression of iNOS (R2 = 0.72, p = 0.0081) and CD36 (R2 = 0.49, p = 0.015) in plaques were positively correlated with the magnitude of DE exposure. Conclusions Exposure to DE promotes changes in atherosclerotic plaques characteristic of unstable vulnerable plaques. Increased systemic and plaque oxidative stress markers suggest that these changes in plaques could be due to DE-induced oxidative stress. PMID:21435644

  9. 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

  10. 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

  11. 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.

  12. Effect of flunarizine on regional cerebral blood flow in common and complicated migraine. Pilot study.

    PubMed

    Lagrèze, H L; Tsuda, Y; Hartmann, A; Bülau, P

    1986-01-01

    Alterations of regional cerebral blood flow (rCBF) are at least epiphenomena of common and complicated migraine, but may lead to serious clinical complications. Since flunarizine seems to be effective in migraine prevention it may exert a beneficial influence on rCBF in migraine as well. rCBF was assessed using the 133Xe inhalation method in 5 patients with common and 8 patients with complicated migraine. Measurements were done interictally prior and after therapy with 15 mg flunarizine p.o. daily over a period of 4 weeks. Major abnormalities of grey matter flow were observed even interictally. Significant improvement of rCBF in initially hypoemic regions may be attributed to flunarizine therapy. These preliminary data suggest that calcium entry blockers may prevent the ischemic complications of migraine. PMID:3093236

  13. Effect of Inhaler Design Variables on Paediatric Use of Dry Powder Inhalers

    PubMed Central

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

    2014-01-01

    Age appropriateness is a major concern of pulmonary delivery devices, in particular of dry powder inhalers (DPIs), since their performance strongly depends on the inspiratory flow manoeuvre of the patient. Previous research on the use of DPIs by children focused mostly on specific DPIs or single inspiratory parameters. In this study, we investigated the requirements for a paediatric DPI more broadly using an instrumented test inhaler. Our primary aim was to assess the impact of airflow resistance on children’s inspiratory flow profiles. Additionally, we investigated children’s preferences for airflow resistance and mouthpiece design and how these relate to what may be most suitable for them. We tested 98 children (aged 4.7–12.6 years), of whom 91 were able to perform one or more correct inhalations through the test inhaler. We recorded flow profiles at five airflow resistances ranging from 0.025 to 0.055 kPa0.5.min.L−1 and computed various inspiratory flow parameters from these recordings. A sinuscope was used to observe any obstructions in the oral cavity during inhalation. 256 flow profiles were included for analysis. We found that both airflow resistance and the children’s characteristics affect the inspiratory parameters. Our data suggest that a medium-high resistance is both suitable for and well appreciated by children aged 5–12 years. High incidences (up to 90%) of obstructions were found, which may restrict the use of DPIs by children. However, an oblong mouthpiece that was preferred the most appeared to positively affect the passageway through the oral cavity. To accommodate children from the age of 5 years onwards, a DPI should deliver a sufficiently high fine particle dose within an inhaled volume of 0.5 L and at a peak inspiratory flow rate of 25–40 L.min−1. We recommend taking these requirements into account for future paediatric inhaler development. PMID:24901338

  14. Safety assessment of inhaled xylitol in mice and healthy volunteers

    PubMed Central

    Durairaj, Lakshmi; Launspach, Janice; Watt, Janet L; Businga, Thomas R; Kline, Joel N; Thorne, Peter S; Zabner, Joseph

    2004-01-01

    Background Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. Methods This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. Results In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were

  15. 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

  16. 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,…

  17. 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

  18. 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.

  19. Inhalation risk in low-gravity spacecraft

    NASA Astrophysics Data System (ADS)

    Todd, Paul; Sklar, Michael V.; Ramirez, W. Fred; Smith, Gerald J.; Morgenthaler, George W.; McKinnon, J. T.; Oberdörster, Günter; Schulz, Jon

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

  20. 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

  1. Regional deposition of inhaled reactive gases

    SciTech Connect

    Miller, F.J.; Overton, J.H.; Graham, R.C.

    1987-03-01

    A critical concept in inhalation toxicology involves the determination of dose as the first component for providing a perspective to judge the applicability of various toxicological results to human-exposure conditions. Available experimental data for reactive gases were reviewed, and basic concepts in the formulation of mathematical dosimetry models were discussed. The complexity of factors influencing dose was illustrated as related to rate-constant sensitivity, thickness of the protective layer of the lungs, the choice of anatomical model, ventilatory parameters, and path distance. Results obtained thus far illustrate the feasibility of making interspecies dosimetric comparisons as an integral step in evaluating the toxicity of inhaled reactive gases, assisting in experimental design, and providing sensitivity studies to determine parameters and processes needing additional research.

  2. 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.

  3. 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

  4. 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

  5. Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

    PubMed Central

    Gorgun, Falih Murat; Zhuo, Ming; Singh, Shilpee; Englander, Ella W.

    2014-01-01

    Context Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (neuron specific globin protein) attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by neuroglobin in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults. Objective To determine to what extent elevated neuroglobin ameliorates post smoke-inhalation brain bioenergetics and homeostasis in neuroglobin overexpressing transgenic mouse. Methods Smoke inhalation induced changes in bioenergetics were measured in the wild type and neuroglobin transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery. Results Cortical mitochondria from neuroglobin transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in neuroglobin transgene compared to wild type brain after smoke. Conclusion Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the neuroglobin overexpressing mouse, suggesting that neuroglobin mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury. PMID:24730682

  6. Inhaler Devices for Chronic Obstructive Pulmonary Disease: Insights from Patients and Healthcare Practitioners

    PubMed Central

    Colthorpe, Paul

    2015-01-01

    Abstract Background: The choice of inhaler device for patients with chronic obstructive pulmonary disease (COPD) depends upon multiple attributes. An online survey was devised to assess COPD patients' and healthcare practitioners' (HCPs; physicians and nurses) opinions and preferences for inhaler devices. Methods: Patients diagnosed with COPD ≥6 months from United States (US), United Kingdom (UK), France, and Germany, and HCPs from the US, UK, France, Italy, and Japan were enrolled to participate in an online quantitative 35 minutes survey. A proprietary analytical tool from Sawtooth Software was used to collect, randomize, and analyze participant opinions and preferences of device attributes, including functionality. Results: A total of 245 patients (mean age, 60.7 years) completed the survey. Of these, 124 and 121 patients were taking fluticasone/salmeterol, and tiotropium, respectively. Patients cited ease of use, dose recording, and dose capacity (single or multi-dose) as important attributes for the device. Key factors that patients considered would make the device easier to use were fewer steps to operate the inhaler, confirmation that the dose has been taken correctly, easier coordination of breathing manoeuver, and least resistance while inhaling. A total of 504 HCPs (380 physicians and 124 nurses) completed the survey, and cited patient satisfaction and ease of use as the most important attributes when selecting an inhaler device for patients. Dose recording and multi-dose versus single-dose designs were given less importance than other attributes such as patient satisfaction and cost by HCPs. Conclusion: The survey provides important insights into what patients and HCPs consider to be key attributes of an ideal inhaler device for COPD management. Given that patients with COPD self-administer their COPD chronic medication and need to deliver the correct dose, it is important to consider these insights for the appropriate management of COPD. PMID:25265316

  7. TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

    PubMed Central

    2014-01-01

    Background Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B). Methods Following animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring. Results The repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring. Conclusions In comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics. PMID:24904234

  8. Inhalation cancer risk assessment of cobalt metal.

    PubMed

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

    2016-08-01

    Cobalt compounds (metal, salts, hard metals, oxides, and alloys) are used widely in various industrial, medical and military applications. Chronic inhalation exposure to cobalt metal and cobalt sulfate has caused lung cancer in rats and mice, as well as systemic tumors in rats. Cobalt compounds are listed as probable or possible human carcinogens by some agencies, and there is a need for quantitative cancer toxicity criteria. The U.S. Environmental Protection Agency has derived a provisional inhalation unit risk (IUR) of 0.009 per μg/m(3) based on a chronic inhalation study of soluble cobalt sulfate heptahydrate; however, a recent 2-year cancer bioassay affords the opportunity to derive IURs specifically for cobalt metal. The mechanistic data support that the carcinogenic mode of action (MOA) is likely to involve oxidative stress, and thus, non-linear/threshold mechanisms. However, the lack of a detailed MOA and use of high, toxic exposure concentrations in the bioassay (≥1.25 mg/m(3)) preclude derivation of a reference concentration (RfC) protective of cancer. Several analyses resulted in an IUR of 0.003 per μg/m(3) for cobalt metal, which is ∼3-fold less potent than the provisional IUR. Future research should focus on establishing the exposure-response for key precursor events to improve cobalt metal risk assessment. PMID:27177823

  9. 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

  10. 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

  11. 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

  12. 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

  13. Potassium Channel Complex Autoimmunity Induced by Inhaled Brain Tissue Aerosol

    PubMed Central

    Meeusen, Jeffrey W.; Klein, Christopher J.; Pirko, Istvan; Haselkorn, Keegan E.; Kryzer, Thomas J.; Pittock, Sean J.; Lachance, Daniel H.; Dyck, P. James; Lennon, Vanda A.

    2011-01-01

    Objective Test the hypothesis that autoimmunity induced by inhalation of aerosolized brain tissue caused outbreaks of sensory-predominant polyradiculoneuropathy among swine abattoir employees in Midwestern USA Methods Mice were exposed intranasally, 5 days weekly, to liquefied brain tissue. Serum from exposed mice, patients and unaffected abattoir employees were analyzed for clinically pertinent neural autoantibodies. Results Patients, coworkers and mice exposed to liquefied brain tissue had an autoantibody profile dominated by neural cation channel IgGs. The most compelling link between patients and exposed mice was MRI evidence of grossly swollen spinal nerve roots. Autoantibody responses in patients and mice were dose-dependent and declined after antigen exposure ceased. Autoantibodies detected most frequently, and at high levels, bound to detergent-solubilized macromolecular complexes containing neuronal voltage-gated potassium channels ligated with a high affinity Kv1 channel antagonist, 125I-α-dendrotoxin. Exposed mice exhibited a behavioral phenotype consistent with potassium channel dysfunction recognized in drosophila with mutant (“shaker”) channels: reduced sensitivity to isoflurane-induced anesthesia. Pathological and electrophysiological findings in patients supported peripheral nerve hyperexcitability over destructive axonal loss. The pain-predominant symptoms were consistent with sensory nerve hyperexcitability Interpretation Our observations establish that inhaled neural antigens readily induce neurological autoimmunity and identify voltage-gated potassium channel complexes as a major immunogen. PMID:22451206

  14. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    PubMed Central

    Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun

    2012-01-01

    Objectives This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. Results During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. Conclusion The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS). PMID:23019535

  15. Effect of Formaldehyde on Asthmatic Response to Inhaled Allergen Challenge

    PubMed Central

    Ezratty, Véronique; Bonay, Marcel; Neukirch, Catherine; Orset-Guillossou, Gaëlle; Dehoux, Monique; Koscielny, Serge; Cabanes, Pierre-André; Lambrozo, Jacques; Aubier, Michel

    2007-01-01

    Background Exposure to formaldehyde may lead to exacerbation of asthma. Objectives Our aim in this study was to investigate whether exposure to a low level (500 μg/m3) of formaldehyde enhances inhaled allergen responses. Methods Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge. Results The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD15FEV1) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before. Conclusion In this study, exposure to 500 μg/m3 formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect. PMID:17384766

  16. 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. PMID:25497311

  17. 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. PMID:20088245

  18. Occupational exposure to inhalable and total aerosol in the primary nickel production industry.

    PubMed Central

    Tsai, P J; Vincent, J H; Wahl, G; Maldonado, G

    1995-01-01

    OBJECTIVES--This paper describes a study that was carried out in the primary nickel production industry to investigate the levels of personal exposure to aerosols containing nickel and the impact on exposure assessment of introducing new personal sampling techniques with performance consistent with the latest particle size-selective criteria. METHODS--Experiments were carried out at workplaces in mining, milling, smelting, and refining works to investigate the effect of changing from the current method of total aerosol (with the widely used 37 mm filter holder) to the new method of measuring inhalable aerosol (with the Institute of Occupational Medicine (IOM) inhalable aerosol sampler). RESULTS--The results show that inhalable aerosol exposure concentrations--for both overall aerosol and for total nickel--were consistently and significantly higher than the corresponding total aerosol concentrations. Weighted least squares linear regression yielded IOM/37 mm factors ranging from about 1.2 to 4.0. The exposure data for each company process were found to be log-normally distributed. CONCLUSIONS--The results suggest the possibility of generating a single pragmatic factor for each company process for converting current total aerosol exposures to new exposures based on the inhalability concept contained in the latest particle size-selective criteria for aerosol exposure assessment. Such data may be important in determining new occupational exposure limits for nickel. PMID:8563841

  19. 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

  20. Diagnosis and management of inhalation injury: an updated review.

    PubMed

    Walker, Patrick F; Buehner, Michelle F; Wood, Leslie A; Boyer, Nathan L; Driscoll, Ian R; Lundy, Jonathan B; Cancio, Leopoldo C; Chung, Kevin K

    2015-01-01

    In this article we review recent advances made in the pathophysiology, diagnosis, and treatment of inhalation injury. Historically, the diagnosis of inhalation injury has relied on nonspecific clinical exam findings and bronchoscopic evidence. The development of a grading system and the use of modalities such as chest computed tomography may allow for a more nuanced evaluation of inhalation injury and enhanced ability to prognosticate. Supportive respiratory care remains essential in managing inhalation injury. Adjuncts still lacking definitive evidence of efficacy include bronchodilators, mucolytic agents, inhaled anticoagulants, nonconventional ventilator modes, prone positioning, and extracorporeal membrane oxygenation. Recent research focusing on molecular mechanisms involved in inhalation injury has increased the number of potential therapies. PMID:26507130

  1. Corpus callosum size and shape alterations in adolescent inhalant users.

    PubMed

    Takagi, Michael; Lubman, Dan I; Walterfang, Mark; Barton, Sarah; Reutens, David; Wood, Amanda; Yücel, Murat

    2013-09-01

    Inhalants, frequently abused during adolescence, are neurotoxic to white matter. We investigated the impact of inhalant misuse on the morphology of the corpus callosum (CC), the largest white matter bundle in the brain, in an adolescent sample of inhalant users [n = 14; mean age = 17.3; standard deviation (SD) = 1.7], cannabis users (n = 11; mean age = 19.7; SD = 1.7) and community controls (n = 9; mean age = 19.5; SD = 2.6). We identified significant morphological differences in the CC among inhalant users compared with community controls. There were no morphological differences between inhalant and cannabis users. Our findings may represent the early stages of neurobiological damage associated with chronic inhalant misuse. PMID:21955104

  2. 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

  3. 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

  4. Corticosteroid inhalation in the treatment of childhood asthma.

    PubMed

    Munasir, Z; Knol, K

    1990-01-01

    Inhaled corticosteroids are a dramatic advance in the therapy of chronic asthma. Corticosteroid inhalation therapy in children offers the same advantages over oral medication as in adults. Inhaled corticosteroids have better effects compared with other prophylactic antiasthma therapy such as theophylline, sodium cromoglycate and ketotifen. However, it is obvious that inhaled corticosteroids are not completely free of side effects, both topical and systemic such as suppression of HPA, growth retardation, osteoporosis, cataract formation, blood count and immunoglobulin changes, oropharyngeal candidiasis and dysphonia. Recently, many clinicians have been using this effective and save treatment more freely and for longterm administration. PMID:2077473

  5. Effect of Nano-sized Carbon Black Particles on Lung and Circulatory System by Inhalation Exposure in Rats

    PubMed Central

    Kang, Min-Gu; Cho, Hae-Won; Han, Jeong-Hee; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun; Kim, Hwa; Lee, Moo-Yeol

    2011-01-01

    Objectives We sought to establish a novel method to generate nano-sized carbon black particles (nano-CBPs) with an average size smaller than 100 nm for examining the inhalation exposure risks of experimental rats. We also tested the effect of nano-CBPs on the pulmonary and circulatory systems. Methods We used chemical vapor deposition (CVD) without the addition of any additives to generate nano-CBPs with a particle size (electrical mobility diameter) of less than 100nm to examine the effects of inhalation exposure. Nano-CBPs were applied to a nose-only inhalation chamber system for studying the inhalation toxicity in rats. The effect on the lungs and circulatory system was determined according to the degree of inflammation as quantified by bronchoalveolar lavage fluid (BALF). The functional alteration of the hemostatic and vasomotor activities was measured by plasma coagulation, platelet activity, contraction and relaxation of blood vessels. Results Nano-CBPs were generated in the range of 83.3-87.9 nm. Rats were exposed for 4 hour/day, 5 days/week for 4 weeks to 4.2 × 106, 6.2 × 105, and 1.3 × 105 particles/cm3. Exposure of nano-CBPs by inhalation resulted in minimal pulmonary inflammation and did not appear to damage the lung tissue. In addition, there was no significant effect on blood functions, such as plasma coagulation and platelet aggregation, or on vasomotor function. Conclusion We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of 4.2 × 106 particles/cm3 in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats. PMID:22953212

  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. Health effects of inhaled gasoline engine emissions.

    PubMed

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

    2007-01-01

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

  9. Zinc chloride (smoke bomb) inhalational lung injury

    SciTech Connect

    Matarese, S.L.; Matthews, J.I.

    1986-02-01

    Physicians, military and civilian alike, may be called upon to recognize, treat, and provide long-term care to patients who have suffered a zinc chloride (smoke bomb) inhalational injury. Pathologic changes described in the literature include laryngeal, tracheal, and bronchial mucosal edema and ulceration; interstitial edema; interstitial fibrosis; alveolar obliteration; and bronchiolitis obliterans. Acute injury is associated with a high mortality. Following is a report of a patient with a zinc chloride smoke injury which resulted in subpleural emphysematous blebs complicated by pneumothorax and abnormal exercise physiology. Gradual recovery occurred over several months. However, the chest roentgenogram remains abnormal with emphysematous blebs.

  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. PMID:20525710

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

    PubMed Central

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

    2016-01-01

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

  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. The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma

    PubMed Central

    2010-01-01

    GSK256066 is a selective phosphodiesterase 4 inhibitor that can be given by inhalation, minimising the potential for side effects. We evaluated the effects of GSK256066 on airway responses to allergen challenge in mild asthmatics. Methods In a randomised, double blind, cross-over study, 24 steroid naive atopic asthmatics with both early (EAR) and late (LAR) responses to inhaled allergen received inhaled GSK256066 87.5 mcg once per day and placebo for 7 days, followed by allergen challenge. Methacholine reactivity was measured 24 h post-allergen. Plasma pharmacokinetics were measured. The primary endpoint was the effect on LAR. Results GSK256066 significantly reduced the LAR, attenuating the fall in minimum and weighted mean FEV1 by 26.2% (p = 0.007) and 34.3% (p = 0.005) respectively compared to placebo. GSK256066 significantly reduced the EAR, inhibiting the fall in minimum and weighted mean FEV1 by 40.9% (p = 0.014) and 57.2% (p = 0.014) respectively compared to placebo. There was no effect on pre-allergen FEV1 or methacholine reactivity post allergen. GSK256066 was well tolerated, with low systemic exposure; plasma levels were not measurable after 4 hours in the majority of subjects. Conclusions GSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma. Trial Registration This study is registered on clinicaltrials.gov NCT00380354 PMID:20193079

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

    PubMed Central

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

    2014-01-01

    Objective Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs. Methods The following nanocarriers were studied: micelles, liposomes, mesoporous silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All particles were characterized using the following methods: dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Results Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation of liposomes and micelles in lungs remained relatively high even 24 h after inhalation when compared with MSNs, QDs, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer. Conclusion The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer. PMID:24738038

  17. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

    PubMed Central

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-01-01

    Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h

  18. 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

  19. 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

  20. IMPROVED STREET SWEEPERS FOR CONTROLLING URBAN INHALABLE PARTICULATE MATTER

    EPA Science Inventory

    The report gives results of an experimental program to develop design modifications that can be used to improve the ability of municipal street sweepers to remove inhalable dust particles from streets. (Dust emissions from paved roads are a major source of urban inhalable particu...

  1. Laryngeal aspergilloma: a complication of inhaled fluticasone therapy for asthma

    PubMed Central

    Darley, David; Lowinger, David; Plit, Marshall

    2014-01-01

    Primary laryngeal aspergillosis in immunocompetent patients is rare. We describe a case of a 59-year-old woman with laryngeal aspergillosis thought to be secondary to long-term inhaled fluticasone therapy. Laryngeal aspergillosis may be an underrecognized complication of inhaled corticosteroid therapy. PMID:25530858

  2. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying with § 172.407, the background on the POISON INHALATION HAZARD label and the symbol must be white. The background of the upper diamond must be black and the lower point of the upper diamond must be 14 mm...

  3. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying with § 172.407, the background on the POISON INHALATION HAZARD label and the symbol must be white. The background of the upper diamond must be black and the lower point of the upper diamond must be 14 mm...

  4. IS INHALED ARSENIC CARCINOGENIC FOR SITES OTHER THAN THE LUNG?

    EPA Science Inventory

    The carcinogenic risk from inhaled arsenic for sites other an the lung is discussed. Data from persons ingesting arsenic as well as from persons inhaling arsenic are considered in arriving at the conclusions. n the past, lung cancer has generally been assumed to be the only cance...

  5. Inhalant Abuse: Your Child at Risk! Asian Language Initiative.

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, Washington, DC.

    This brochure is aimed at helping Asian American and Pacific Islander adults communicate with young people about the consequences of inhalant abuse. The booklet addresses the issue of preventing youth substance abuse as part of balancing traditional values with American culture. Also explained are symptoms of inhalant use, common names and, most…

  6. Personal exposure to inhalable cement dust among construction workers

    NASA Astrophysics Data System (ADS)

    Peters, Susan; Thomassen, Yngvar; Fechter-Rink, Edeltraud; Kromhout, Hans

    2009-02-01

    A case study was carried out in 2006-2007 to assess the actual cement dust exposure among construction workers involved in a full-scale construction project and as a comparison among workers involved in various stages of cement and concrete production. Full-shift personal exposure measurements were performed for several job types. Inhalable dust and cement dust (based on analysis of elemental calcium) concentrations were determined. Inhalable dust exposures at the construction site ranged from 0.05 to 34 mg/m3, with a mean concentration of 1.0 mg/m3. For inhalable cement dust mean exposure was 0.3 mg/m3 (range 0.02-17 mg/m3). Reinforcement and pouring workers had the lowest average concentrations. Inhalable dust levels in the ready-mix and pre-cast concrete plants were, on average, below 0.5 mg/m3 for inhalable dust and below 0.2 mg/m3 for inhalable cement dust. Highest dust concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM=55 mg/m3; inhalable cement dust GM=33 mg/m3) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages of cement during reinforcement work and pouring.

  7. Inhalant use among antisocial youth: prevalence and correlates.

    PubMed

    Howard, M O; Jenson, J M

    1999-01-01

    The current (2.9%), annual (19.6%), and lifetime (34.3%) prevalence of inhalant use among 475 youth (M age = 15.5; SD = 1.5; 87.4% male) on probation in a western state of the United States was assessed. Inhalant users reported significantly less family support and cohesiveness and lower self-esteem, and significantly more lifetime thoughts of suicide and suicide attempts, neighborhood gang activity, peer and parental substance abuse, intentions to engage in illegal behavior, substance-related criminality, and substance abuse than did nonusers. Ethnicity, self-esteem, suicidality, number of substance-using peers, and extent of substance-related criminality significantly discriminated inhalant users from nonusers in a logistic regression analysis. Multiple linear regression analyses indicated that age, perceived school ability, age at initiation of alcohol use, self-esteem, and substance-related criminality significantly predicted age at onset of inhalant use (R2 = .30). Age at initiation of inhalant use, gang membership, truancy, and substance-related criminality significantly predicted lifetime frequency of inhalant use (R2 = .20). Study findings indicate that inhalant-using delinquents evidence significantly greater antisocial attitudes, personal and familial dysfunction, and substance abuse, than do their non-inhalant-using counterparts. PMID:10189973

  8. 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 material poisonous by inhalation must, in addition to the requirements prescribed in §...

  9. 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 material poisonous by inhalation must, in addition to the requirements prescribed in §...

  10. 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 material poisonous by inhalation must, in addition to the requirements prescribed in §...

  11. 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…

  12. Epidemiology of Inhalant Abuse: An Update. NIDA Research Monograph 85.

    ERIC Educational Resources Information Center

    Crider, Raquel A., Ed.; Rouse, Beatrice A., Ed.

    This publication consists of papers and discussion from a comprehensive RAUS (Research Analysis and Utilization System) review focusing on factors relating to a multi-year increase in inhalant abuse among high school seniors. The document contains the following articles: (1) "Inhalant Overview" (Raquel A. Crider and Beatrice A. Rouse); (2)…

  13. INHALATION TERATOLOGY STUDIES OF CAPTAN AND FOLPET IN MICE

    EPA Science Inventory

    Timed pregnant CD-1 mice were exposed to captan or folpet by the intragastric, subcutaneous or inhalation route. A dose of 100 mg/kg/day of captan or folpet was administered subcutaneously or intragastrically from day 6-15 of gestation. The dose levels for the inhalation route we...

  14. SPECIES COMPARISON OF ACUTE INHALATION TOXICITY OF OZONE AND PHOSGENE

    EPA Science Inventory

    A comparison of the concentration-response effects of inhaled ozone (O3) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation studies of this gas. The effect of 4 hour exposure to ozone (O3) at conc...

  15. Characterization of a new inhalable thymopentin formulation.

    PubMed

    Wang, Lei; Zhang, Yu; Tang, Xing

    2009-06-22

    The present work describes a new dry powder containing thymopentin (TP5) suitable for inhalation. A total of 21 dry powders were produced by co-spray drying TP5 with lactose or mannitol as a bulking agent, leucine as a dispersibility enhancer and poloxamer 188 as a drug stabilizer. Analyses by scanning electron microscopy, laser diffractometry, thermogravimetry, Twin Stage Impactor and HPLC were performed to characterize the manufactured powders. The results revealed that formulation compositions greatly influenced the physical characteristics of the powders, such as the angle of repose, tapped density, particle size and aerodynamic diameter which, in turn, affected their aerodynamic behavior. A higher loading of leucine in the formulations (>63% by dry weight) improved the aerosolization properties of the powders by producing aerodynamically lighter particles. The optimum formulation, which had a tapped density of 0.31 g/cm(3), an aerodynamic diameter of 1.9 microm and an in vitro deposition of 45%, was obtained by combining TP5/mannitol/leucine in the ratio of 10/18/72. In addition, it was interesting to find that poloxamer 188 had a significant impact on improving the powder flowability rather than stabilizing TP5. In conclusion, the chosen composition promises an enhanced aerosol performance for the new TP5 inhalation formulation, suitable for deep lung deposition. PMID:19443146

  16. Formulation Design of Dry Powders for Inhalation.

    PubMed

    Weers, Jeffry G; Miller, Danforth P

    2015-10-01

    Drugs for inhalation are no longer exclusively highly crystalline small molecules. They may also be amorphous small molecules, peptides, antibodies, and myriad types of engineered proteins. The evolution of respiratory therapeutics has created a need for flexible formulation technologies to engineer respirable particles. These technologies have enabled medicinal chemists to focus on molecular design without concern regarding compatibility of physicochemical properties with traditional, blend-based technologies. Therapeutics with diverse physicochemical properties can now be formulated as stable and respirable dry powders. Particle engineering technologies have also driven the deployment of new excipients, giving formulators greater control over particle and powder properties. This plays a key role in enabling efficient delivery of drugs to the lungs. Engineered powder and device combinations enable aerosols that largely bypass the mouth and throat, minimizing the inherent variability among patients that arises from differences in oropharyngeal and airway anatomies and in breathing profiles. This review explores how advances among molecules, particles, and powders have transformed inhaled drug product development. Ultimately, this scientific progress will benefit patients, enabling new classes of therapeutics to be formulated as dry powder aerosols with improved efficacy, reduced variability and side effects, and improved patient adherence. PMID:26296055

  17. Technosphere insulin: an inhaled prandial insulin product.

    PubMed

    Neumiller, Joshua J; Campbell, R Keith

    2010-06-01

    Given the important role of insulin in the treatment of diabetes mellitus and in light of common barriers to insulin use, new strategies for insulin delivery by routes other than intravenous and subcutaneous injection have been investigated since the discovery of insulin in the 1920s. Most companies researching and developing pulmonary administration systems for the use of insulin announced the termination of product development following the failure of the first US FDA-approved inhaled insulin product, Exubera. One company in particular continued their pursuit of a useful inhaled insulin product. MannKind Corporation has developed a powder formulation of insulin that allows for a high percentage of the administered insulin to be absorbed via the lung. Their product, AFREZZA (Technosphere insulin), is currently under review by the FDA for use in patients with diabetes. Technosphere insulin appears to overcome some of the barriers that contributed to the market withdrawal of Exubera by the manufacturer. Studies with Technosphere insulin have shown it to be a unique insulin formulation in that it is very rapid acting, has a relatively short duration of action, and is efficacious in terms of improved glycemic control without contributing to increased weight gain or the incidence of hypoglycemia when compared with other prandial insulin products. Additionally, Technosphere insulin has demonstrated a favorable safety and tolerability profile in clinical studies to date. PMID:20462282

  18. Lethal methemoglobinemia and automobile exhaust inhalation.

    PubMed

    Vevelstad, Merete; Morild, Inge

    2009-05-30

    Inhalation of automobile exhaust gas often leads to death by CO intoxication. In some cases the measured carbon monoxide hemoglobin saturation level (COHb) is considerably below what is considered to be lethal. The death in such cases has been attributed to a combination of a high CO2 and a low O2 tension. In a recent case the deceased was found dead in a car equipped with a catalytic converter, with a hose leading exhaust from the engine to the interior of the car. Analysis revealed a moderately elevated COHb and a high methemoglobin saturation level (MetHb) in peripheral blood. No ethanol, narcotics or drugs were detected. Reports mentioning MetHb or methemoglobinemia in post-mortem cases are surprisingly scarce, and very few have related exhaust gas deaths to methemoglobinemia. High-degree methemoglobinemia causes serious tissue hypoxia leading to unconsciousness, arrhythmia and death. The existing literature in this field and the knowledge that exhaust fumes contain nitrogen oxide gases (NOx) that by inhalation and absorption can result in severe methemoglobinemia, led us to postulate that this death could possibly be attributed to a combination of methemoglobinemia and a moderately high COHb concentration. PMID:19261402

  19. 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

  20. 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

  1. Whole-Body Nanoparticle Aerosol Inhalation Exposures

    PubMed Central

    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 m3 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/cm3) 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/m3). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpreand Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is

  2. 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. PMID:27033834

  3. Inhaled carbon nanotubes reach the subpleural tissue in mice

    NASA Astrophysics Data System (ADS)

    Ryman-Rasmussen, Jessica P.; Cesta, Mark F.; Brody, Arnold R.; Shipley-Phillips, Jeanette K.; Everitt, Jeffrey I.; Tewksbury, Earl W.; Moss, Owen R.; Wong, Brian A.; Dodd, Darol E.; Andersen, Melvin E.; Bonner, James C.

    2009-11-01

    Carbon nanotubes are shaped like fibres and can stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice, raising concerns that inhaled nanotubes may cause pleural fibrosis and/or mesothelioma. Here, we show that multiwalled carbon nanotubes reach the subpleura in mice after a single inhalation exposure of 30 mg m-3 for 6 h. Nanotubes were embedded in the subpleural wall and within subpleural macrophages. Mononuclear cell aggregates on the pleural surface increased in number and size after 1 day and nanotube-containing macrophages were observed within these foci. Subpleural fibrosis unique to this form of nanotubes increased after 2 and 6 weeks following inhalation. None of these effects was seen in mice that inhaled carbon black nanoparticles or a lower dose of nanotubes (1 mg m-3). This work suggests that minimizing inhalation of nanotubes during handling is prudent until further long-term assessments are conducted.

  4. 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

  5. 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

  6. Similar Results in Children with Asthma for Steady State Pharmacokinetic Parameters of Ciclesonide Inhaled with or without Spacer

    PubMed Central

    Boss, H.; Minic, P.; Nave, R.

    2010-01-01

    Background: Ciclesonide is an inhaled corticosteroid administered by a metered dose inhaler (MDI) to treat bronchial asthma. After inhalation, the inactive ciclesonide is converted by esterases in the airways to active metabolite desisobutyryl-ciclesonide (des-CIC). Aim: To compare the pharmacokinetic (PK) parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus™). Methods: Open-label, 3 period, cross over, repeated dose, PK study in 37 children with mild to moderate stable asthma (age: 6–11 y; body weight: 20–53 kg). During each 7-day treatment period, ciclesonide was inhaled once in the morning: A) 160 μg MDI with spacer, B) 80 μg MDI with spacer, and C) 160 μg MDI without spacer. Serum PK parameters of ciclesonide and des-CIC were determined on Day 7 of each period. The primary PK parameters were the AUCτ and Cmax for des-CIC. Results: Inhaling ciclesonide with spacer led to a dose proportional systemic exposure (AUCτ) of des-CIC (0.316 μg*h/L for 80 μg and 0.663 μg*h/L for 160 μg). The dose-normalized systemic exposure for des-CIC (based on AUCτ) was 27% higher after inhalation of ciclesonide 80 μg or 160 μg with spacer than without spacer; the corresponding Cmax values for des-CIC were, respectively, 63% and 55% higher with spacer. No clinically relevant abnormalities or adverse drug reactions were observed. Conclusions: Inhalation of therapeutic ciclesonide dose with spacer led to a slight increase in the systemic exposure of des-CIC, which does not warrant dose adjustment. PMID:23761990

  7. 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

  8. 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

  9. 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

  10. Inhaled Aztreonam Lysine for Chronic Airway Pseudomonas aeruginosa in Cystic Fibrosis

    PubMed Central

    McCoy, Karen S.; Quittner, Alexandra L.; Oermann, Christopher M.; Gibson, Ronald L.; Retsch-Bogart, George Z.; Montgomery, A. Bruce

    2008-01-01

    Rationale: The effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study. Objectives: To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF. Methods: After randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; ⩾6 yr; ⩾3 TIS courses within previous year; FEV1 ⩾ 25% and ⩽75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV1), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored. Measurements and Main Results: AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV1 (6.3%, P = 0.001), and sputum PA density (−0.66 log10 cfu/g, P = 0.006) compared with placebo; no AZLI dose–response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar. Conclusions: AZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520

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

    PubMed Central

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

    2012-01-01

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

  12. 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

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

    PubMed

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

    2014-06-01

    Respiratory tract deposition models provide a useful method for optimizing the design and administration of inhaled pharmaceutical aerosols, and can be useful for estimating exposure risks to inhaled particulate matter. As aerosol must first pass through the extrathoracic region prior to reaching the lungs, deposition in this region plays an important role in both cases. Compared to adults, much less extrathoracic deposition data are available with pediatric subjects. Recently, progress in magnetic resonance imaging and computed tomography scans to develop pediatric extrathoracic airway replicas has facilitated addressing this issue. Indeed, the use of realistic replicas for benchtop inhaler testing is now relatively common during the development and in vitro evaluation of pediatric respiratory drug delivery devices. Recently, in vitro empirical modeling studies using a moderate number of these realistic replicas have related airway geometry, particle size, fluid properties, and flow rate to extrathoracic deposition. Idealized geometries provide a standardized platform for inhaler testing and exposure risk assessment and have been designed to mimic average in vitro deposition in infants and children by replicating representative average geometrical dimensions. In silico mathematical models have used morphometric data and aerosol physics to illustrate the relative importance of different deposition mechanisms on respiratory tract deposition. Computational fluid dynamics simulations allow for the quantification of local deposition patterns and an in-depth examination of aerosol behavior in the respiratory tract. Recent studies have used both in vitro and in silico deposition measurements in realistic pediatric airway geometries to some success. This article reviews the current understanding of pediatric in vitro and in silico deposition modeling via oral and nasal inhalation. PMID:24870701

  14. 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

  15. Inhalant Use Among Schoolchildren in Northeast India: A Preliminary Study

    PubMed Central

    Akoijam, Brogen Singh; Jamir, M. Nukshisangla; Phesao, Ebenezer; Senjam, Gojendra Singh

    2013-01-01

    Inhalant use by children leads to poor performance in school and has been observed to precede substance use later in life. There is paucity of data on inhalant use among school children in India, particularly in the Northeast region of the country. We determined the prevalence and documented inhalant use characteristics among schoolchildren in the Northeast region of India. This cross sectional study was conducted in six states in the Northeast region of India. Schoolchildren between eighth and eleventh standards from the capital areas of the states were included in the study. Data were collected using a questionnaire. Analysis was done using descriptive statistics and Chi-square test. Of the 4074 enrolled students, data from 3943 students who responded to the inhalant use question were analyzed. Mean age was 14.8 ± 1.2 years and 51.2% of participants were male. The proportion of students who had ever used inhalants (ever user) was 18.8% and adhesive/glue was the inhalant misused by most of the students. A higher proportion of males than females were ever users (P ≤ 0.001) and the most common place of use was at home (33.1%). Being in the presence of an older person using an inhalant or tobacco was found to be associated with use of inhalants among students. Nearly one-fifth of the students had used inhalants and nearly half used inhalants in the past month. Sensitization of the parents and school authorities to the problem, as well as preventive and curative services, should be considered. PMID:24250225

  16. (99m)Tc-labeled therapeutic inhaled amikacin loaded liposomes.

    PubMed

    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

    2013-12-01

    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 (99m)Tc, nebulization properties of (99m)Tc-labeled liposomal amikacin for inhalation ((99m)Tc-LAI), and its stability by size exclusion low-pressure liquid chromatography (LPLC). LAI was reacted with (99m)Tc 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 (99m)Tc-LAI in 1.5% NaCl solution was incubated at 4 °C to assess its stability by LPLC. The purified (99m)Tc-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 (99m)Tc-LAI, indicating that (99m)Tc-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 0.91 mM ascorbic acid produced (99m)Tc-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

  17. Euthanasia by CO₂ inhalation affects potassium levels in mice.

    PubMed

    Traslavina, Ryan P; King, Edward J; Loar, Andrew S; Riedel, Elyn R; Garvey, Michael S; Ricart-Arbona, Rodolfo; Wolf, Felix R; Couto, Suzana S

    2010-05-01

    We and others frequently have noted serum potassium levels of 8.0 +/- 0.85 mEq/L or greater in laboratory mice; this concentration has even been published as the upper limit of a 'normal' reference range. However, if bone fide, this potassium concentration would be incompatible with life in all species. We investigated conditions frequently encountered in the research setting to distinguish artifactual from true hyperkalemia. Variables evaluated included site of collection, time allowed for clot formation before serum separation, time elapsed between collection and analysis of samples collected in a serum separator tube, precollection method of anesthesia, and euthanasia technique. Serum potassium was measured from 75 C57BL/6NTac 10-wk-old female mice and divided into at least 5 mice per variable. Animals were euthanized by exsanguination immediately after terminal CO₂ or ketamine-xylazine (KX) administration. Mice euthanized with CO₂ had higher mean serum potassium (7.0 +/- 0.5 mEq/L) and range serum potassium (6.0 to 8.1 mEq/L) than did KX-treated mice. CO₂ inhalation resulted in significantly lower blood pH (6.9 +/- 0.1), higher pCO₂ (153.3 +/- 38.8 mm Hg), and higher lactate levels (3.9 +/- 0.9 mmol/L) than did KX anesthesia followed by exsanguination. These results suggest that antemortem respiratory acidosis from CO₂ administration causes artifactual hyperkalemia in mice. Therefore, blood collection under KX anesthesia is preferable over CO₂ inhalation to obtain accurate potassium values from mice. PMID:20587163

  18. 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

  19. 5% CO2 is a potent, fast acting inhalation anticonvulsant

    PubMed Central

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

    2010-01-01

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

  20. 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

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

    PubMed

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

    2015-09-01

    This article summarizes discussions at the March 2014 conference organized by the University of Florida (UF) and International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS), entitled "Orlando Inhalation Conference: Approaches in International Regulation." The special focus of the conference was on global scientific and regulatory issues associated with the testing and demonstration of equivalence for the registration of orally inhaled drug products (OIDPs) in the United States, Europe, Brazil, China, and India. The scope included all types of OIDPs throughout their lifecycle, e.g., innovator/brand-name products, generics, modifications due to lifecycle management, device changes, etc. Details were presented for the U.S. "weight of evidence approach" for registration of generic products (which includes demonstration of in vitro and in vivo equivalence, as well as quantitative and qualitative sameness, and device similarity). The European "stepwise" approach was elucidated, and the thinking of regulatory agencies in the major emerging markets was clarified. The conference also highlighted a number of areas that would benefit from further research and discussion, especially around patient/device interface and human factor studies, statistical methods and criteria for demonstrating equivalence, the relative roles of in vivo and in vitro tests, and appropriate designs and metrics for in vivo studies of inhaled drugs. PMID:26033698

  2. 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

  3. 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

  4. 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

  5. Performance of Combination Drug and Hygroscopic Excipient Submicrometer Particles from a Softmist Inhaler in a Characteristic Model of the Airways

    PubMed Central

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

    2012-01-01

    Excipient enhanced growth (EEG) of inhaled submicrometer pharmaceutical aerosols is a recently proposed method intended to significantly reduce extrathoracic deposition and improve lung delivery. The objective of this study was to evaluate the size increase of combination drug and hygroscopic excipient particles in a characteristic model of the airways during inhalation using both in vitro experiments and CFD simulations. The airway model included a characteristic mouth-throat (MT) and upper tracheobronchial (TB) region through the third bifurcation (B3) and was enclosed in a chamber geometry used to simulate the thermodynamic conditions of the lungs. Both in vitro results and CFD simulations were in close agreement and indicated that EEG delivery of combination submicrometer particles could nearly eliminate MT deposition for inhaled pharmaceutical aerosols. Compared with current inhalers, the proposed delivery approach represents a 1–2 order of magnitude reduction in MT deposition. Transient inhalation was found to influence the final size of the aerosol based on changes in residence times and relative humidity values. Aerosol sizes following EEG when exiting the chamber (2.75–4.61 μm) for all cases of initial submicrometer combination particles were equivalent to or larger than many conventional pharmaceutical aerosols that frequently have MMADs in the range of 2–3 μm. PMID:22820981

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

    PubMed

    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. 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

  8. 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

  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. Acute inhalation toxicity of silver nanoparticles.

    PubMed

    Sung, Jae Hyuck; Ji, Jun Ho; Song, Kyung Seuk; Lee, Ji Hyun; Choi, Kyung Hee; Lee, Sang Hee; Yu, Il Je

    2011-03-01

    The acute inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Seven-week-old rats, weighing approximately 218 g (males) and 153 g (females), were divided into four groups (five rats in each group): fresh-air control, low-dose (0.94 × 10(6) particle/cm(3), 76 µg/m(3)), middle-dose (1.64 × 10(6) particle/ cm(3), 135 µg/m( 3)), and high-dose (3.08 × 10(6) particle/cm(3), 750 µg/m(3)). The animals were then exposed to silver nanoparticles (average diameter 18-20 nm) for 4 hours in a whole-body inhalation chamber. The experiment was conducted following Organization Economic Cooperation and Development (OECD) test guideline 403 with the application of good laboratory practice (GLP). In addition to mortality and clinical observations, the body weights, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, and the organ weights measured. The lung function was also measured twice per week after the initial 4-hour exposure. No significant body weight changes or clinical changes were found during the 2-week observation period. The lung function tests also indicated no significant difference between the fresh air control and the exposed groups. Thus, LC50 silver nanoparticles are suggested for higher than 3.1 × 10(6) particles/cm(3) (750 µg/m(3)). PMID:20870693

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

    NASA Astrophysics Data System (ADS)

    Rodriguez, Daniel J.; Peterson, Kendall R.

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

  12. Are serum cytokines early predictors for the outcome of burn patients with inhalation injuries who do not survive?

    PubMed Central

    Gauglitz, Gerd G; Finnerty, Celeste C; Herndon, David N; Mlcak, Ronald P; Jeschke, Marc G

    2008-01-01

    Introduction Severely burned patients suffering from inhalation injury have a significantly increased risk for mortality compared with burned patients without inhalation injury. Severe burn is associated with a distinct serum cytokine profile and alterations in cytokines that contribute to morbidity and mortality. The aim of the present study was therefore to determine whether severely burned pediatric patients with concomitant inhalation injury who had a fatal outcome exhibited a different serum cytokine profile compared with burn patients with inhalation injury who survived. Early identification followed by appropriate management of these high-risk patients may lead to improved clinical outcome. Methods Thirteen severely burned children with inhalation injury who did not survive and 15 severely burned pediatric patients with inhalation injury who survived were enrolled in the study. Blood was collected within 24 hours of admission and 5 to 7 days later. Cytokine levels were profiled using multiplex antibody coated beads. Inhalation injury was diagnosed by bronchoscopy during the initial surgery. The number of days on the ventilator, peak inspiratory pressure rates, arterial oxygen tension (PaO2)/fraction of inspired oxygen (FiO2) ratio and incidence of acute respiratory distress syndrome were recorded for those patients. Results Significantly altered levels of IL-4, IL-6, IL-7, IL-10, and IL-13 were detected within the first 7 days after admission in serum from burn pediatric patients with concomitant inhalation injury who did not survive when compared with similar patients who did (P < 0.05). Alterations in these cytokines were associated with increased incidence of acute respiratory distress syndrome, number of days under ventilation, increased peak inspiratory pressure, and lower PaO2/FiO2 ratio in this patient population. Multiple logistic regression analysis revealed that patients with increased IL-6 and IL-10 as well as decreased IL-7 serum levels had a

  13. A Descriptive Study of Clinical, Hematological, and Biochemical Parameters of Inhalant Users Seeking Treatment at a Tertiary Care Center in India

    PubMed Central

    Quraishi, Rizwana; Pattanayak, Raman Deep; Jain, Raka; Dhawan, Anju

    2013-01-01

    Background: Inhalant (or solvent) abuse is the purposeful inhalation of vapors or gases, intended to produce pleasurable psychoactive effects. There is a dearth of Indian studies on inhalant users. Aim: The present study aimed to describe the socio-demographic, clinical, and psychosocial characteristics of inhalant users visiting a Tertiary Care Center in North India. Materials and Methods: The study was a retrospective chart review for 50 inhalant users who sought treatment for the first time from the center over a period of 2 years. All patients seeking treatment for inhalant use at the center were evaluated by a psychiatrist. Results: Mean age of the sample was 17.16±4.09 years and majority comprised of children and adolescents (72.2%). There were only three girls (6%). Majority comprised of school drop-outs (82%), from lower socio-economic status (80%). Mean age of initiation of first substance was 14.13±4.27 years and inhalants were first drugs for 38%. Duration of inhalant use ranged between 1 month and 7.5 years. Use was mostly uninterrupted, and 88% were dependent users. Correction fluid was the commonest product, used by huffing or sniffing. A large majority (86%) had used at least one other substance besides inhalants, and 8% reported involvement in high-risk sexual behaviors. Comorbid psychiatric disorder was seen in 8% of sample. Positive family history was observed in 30% of the sample. The mean hemoglobin of the sample was 11.88±0.60, with low hemoglobin in 25% of users. Neutrophils, lymphocytes, eosinophils, and monocytes were elevated beyond normal in 10.8%, 6.5%, 15.2%, and 7.5%, respectively. There was no evidence of leucopenia. Bilirubin and serum glutamic pyruvic transaminase was elevated in 6.6% and 13% of inhalant users, respectively. Conclusion: The study adds to the limited date available on the treatment-seeking inhalant users from Indian settings. There is a need to examine the pattern of inhalant use in larger samples, across multiple

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

    PubMed Central

    2013-01-01

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

  15. 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

  16. Effects of inhalation of beta 2-sympathicomimetic and anticholinergic agents on the impedance of the respiratory system in normal subjects.

    PubMed

    Wesseling, G; Vonk, H M; Wouters, E F

    1990-05-01

    Impedance measurement of the respiratory system by forced oscillations is a sensitive and accurate method to detect mechanical parameters, especially in normal subjects. The effects of inhalation of 0.2 mg of fenoterol and 0.02 mg of ipratropium bromide on the impedance of the respiratory system was studied in 20 healthy subjects in a frequency spectrum between 4 and 52 Hz. Both agents caused a statistically significant decrease in resistance (Rrs). Inhalation of fenoterol and ipratropium bromide caused a significant increase in reactance (Xrs). The decrease in Rrs was greater after inhalation of fenoterol than after ipratropium bromide. Fenoterol and ipratropium bromide caused qualitatively similar changes in Rrs and Xrs of the respiratory system. The changes in Rrs can be explained by dilation of the central airways. The changes in Xrs are supposed to be the result of an increase in the capacitance of the lungs. PMID:2139600

  17. Orally inhaled fixed-dose combination products for the treatment of asthma and chronic obstructive pulmonary disease: not simple math.

    PubMed

    Ehrick, Jason D; Wylie, Jennifer; Goodey, Adrian P; Li, Ying; Liu, Oscar; Donovan, Brent

    2014-03-01

    Over the past decade, orally inhaled fixed-dose combination products (FDCs) have emerged as an important therapeutic class for the treatment of asthma and chronic obstructive pulmonary disease. However, the conceptual simplicity of inhaled FDCs belies both the complexity of their development, and the profound advantages they offer patients. The benefits of combining agents are not merely additive, and range from increased compliance via simple convenience to complex receptor-level synergies. Similarly, though, the development challenges often exceed the sum of their parts. FDC formulation and analytical method development is generally more complex than for two monotherapy products. Likewise, FDC clinical programs can easily eclipse those of their monotherapy peers and their inherent complexity is often furthered by the diverse regulatory requirements for worldwide approval. As such, the proposition of developing an orally inhaled FDC for global registration often represents a significant increase in both the potential rewards and assumed risks of drug development. PMID:24592955

  18. 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). PMID:24897139

  19. Pulmonary oedema due to inhalation of detergent aerosol.

    PubMed

    Rao, J; Das, P K

    1994-12-01

    Healthy adult male albino rats were subjected to inhalation of increasing doses of detergent (dioctyl sodium sulfo-succinate) aerosol ranging from 100 mg to 500 mg. Administration of 500 mg of detergent aerosol resulted in peribronchial and focal alveolar oedema in 3 out of 5 animals. The lungs of control animals which were subjected to inhalation of vehicle aerosol (ethanol and saline) did not show any abnormality. It is possible that pulmonary oedema observed in detergent aerosol inhalation may be due to the action of detergents on the surfactant system of the lung. PMID:9053567

  20. 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

  1. Inhalation Exposure to Carbon Nanotubes (CNT) and Carbon Nanofibers (CNF): Methodology and Dosimetry.

    PubMed

    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. 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

  3. 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

  4. 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"…

  5. 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…

  6. 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…

  7. 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. PMID:26682890

  8. Short-term effects of inhaled salbutamol on autonomic cardiovascular control in healthy subjects: a placebo-controlled study

    PubMed Central

    Cekici, Leyla; Valipour, Arschang; Kohansal, Robab; Burghuber, Otto Chris

    2009-01-01

    AIMS To investigate short-term effects of inhaled salbutamol on haemodynamic changes and cardiovascular autonomic control. METHODS A randomized, single-blinded, placebo-controlled study of 0.2 mg of inhaled salbutamol was conducted on 12 healthy nonsmoking volunteers with a mean age of 24 ± 2 years at two different testing sessions. Non-invasively obtained continuous haemodynamic measurements of cardiac output, beat-to-beat arterial blood pressure, and total peripheral resistance were recorded prior to and for a total of 120 min after inhalation of the respective study drug. Continuous cardiovascular autonomic tone was recorded using power spectral analysis of heart rate and blood pressure variability. Spontaneous baroreceptor activity was assessed by the sequence method. RESULTS There were no significant changes in any of the baseline parameters between the different testing sessions. Inhalation of salbutamol caused a significant increase in cardiac output from 6.7 ± 1.3 to 7.7 ± 1.4 l min−1 (P < 0.05), and a decrease in total peripheral resistance from 1076 ± 192 to 905 ± 172 dyne s−1 cm−5 (P < 0.05) within 15 min after inhalation. Moreover, salbutamol significantly increased sympathetically mediated low-frequency heart rate variability (P < 0.01), whereas parasympathetically mediated high-frequency heart rate variability decreased (P < 0.01). All changes persisted for approximately 30 min and were fully reversible at 120 min. There were no significant changes in systolic blood pressure variability or spontaneous baroreceptor activity. CONCLUSIONS Inhalation of therapeutic doses of salbutamol in healthy subjects resulted in significant haemodynamic changes and a shift of sympathovagal balance towards increased sympathetic tone in the absence of baroreceptor activation. PMID:19371312

  9. Near infrared transillumination imaging of breast cancer with vasoactive inhalation contrast

    PubMed Central

    Dixit, Sanhita S.; Kim, Hanyoup; Comstock, Christopher; Faris, Gregory W.

    2010-01-01

    Inhalation of vasoactive gases such as carbon dioxide and oxygen can provide strong changes in tissue hemodynamics. In this report, we present a preliminary clinical study aimed at assessing the feasibility of inhalation-based contrast with near infrared continuous wave transillumination for breast imaging. We describe a method for fitting the transient absorbance that provides the wavelength dependence of the optical pathlength as parametrized by tissue oxygenation and scatter power as well as the differential changes in oxy- and deoxy-hemoglobin. We also present a principal component analysis data reduction technique to assess the dynamic response from the tissue that uses coercion to provide single temporal eigenvalues associated with both oxy- and deoxy-hemoglobin changes. PMID:21258467

  10. 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

  11. 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

  12. 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. PMID:26043823

  13. 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

  14. 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...

  15. 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

  16. 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...

  17. MATHEMATICAL MODEL FOR THE SELECTIVE DEPOSITION OF INHALED PHARMACEUTICALS

    EPA Science Inventory

    To accurately assess the potential therapeutic effects of airborne drugs, the deposition sites of inhaled particles must be known. erein, an original theory is presented for physiologically based pharmacokinetic modeling and related prophylaxis of airway diseases. he mathematical...

  18. Mexican-American Adolescent Inhalant Abuse: A Proposed Model.

    ERIC Educational Resources Information Center

    Dworkin, A. Gary; Stephens, Richard C.

    1980-01-01

    Drawing from literature on differences between the Mexican American experience and that of other groups, offers a model to explain the higher rates of inhalant abuse among Mexican American youth. Considers cultural, ecological, structural, and economic factors. (Author/GC)

  19. Inhaled medical gases: more to breathe than oxygen.

    PubMed

    Gentile, Michael A

    2011-09-01

    The mixture of oxygen and nitrogen is usually sufficient to achieve the therapeutic objective of supporting adequate gas exchange. Pediatric and neonatal patients have an assortment of physiologic conditions that may require adjunctive inhaled gases to treat the wide variety of diseases seen in this heterogeneous population. Inhaled nitric oxide, helium oxygen mixtures, inhaled anesthetics, hypercarbic mixtures, hypoxic mixtures, inhaled carbon monoxide, and hydrogen sulfide have been used to alter physiology in an attempt to improve patient outcomes. Balancing the therapeutic potential, possible adverse effects, and the complexity of the technical aspects of gas delivery, it is essential that clinicians thoroughly understand the application of medical gas therapy beyond the traditional nitrogen/oxygen mixture. PMID:21944684

  20. 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...

  1. Inhaled therapy for the management of perioperative pulmonary hypertension

    PubMed Central

    Thunberg, C. A.; Morozowich, S. T.; Ramakrishna, Harish

    2015-01-01

    Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators. PMID:26139748

  2. 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 ...

  3. Bioavailability of therapeutic proteins by inhalation--worker safety aspects.

    PubMed

    Pfister, Thomas; Dolan, David; Bercu, Joel; Gould, Janet; Wang, Bonnie; Bechter, Rudolf; Barle, Ester Lovsin; Pfannkuch, Friedlieb; Flueckiger, Andreas

    2014-08-01

    A literature review and analysis of inhalation bioavailability data for large therapeutic proteins was conducted in order to develop a practical estimate of the inhalation bioavailability of these drugs. This value is incorporated into equations used to derive occupational exposure limits(OELs) to protect biopharmaceutical manufacturing workers from systemic effects. Descriptive statistics implies that a value of 0.05, or 5% is an accurate estimate for large therapeutic proteins (molecular weight ≥ 40kDa). This estimate is confirmed by pharmacokinetic modeling of data from a human daily repeat-dose inhalation study of immunoglobulin G. In conclusion, we recommend using 5% bioavailability by inhalation when developing OELs for large therapeutic proteins. PMID:24958792

  4. USER'S GUIDE FOR THE AUTOMATED INHALATION EXPOSURE METHODOLOGY (IEM)

    EPA Science Inventory

    The Inhalation Exposure Methodology(IEM) is a system of computer programs that estimates atmospheric transport of and population exposure to airborne pollutants. This paper discusses the capabilities of IEM and gives detailed instructions for executing the automated, interactive ...

  5. 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

  6. Effectiveness of inhaler types for real-world asthma management: retrospective observational study using the GPRD

    PubMed Central

    Price, David; Haughney, John; Sims, Erika; Ali, Muzammil; von Ziegenweidt, Julie; Hillyer, Elizabeth V; Lee, Amanda J; Chisholm, Alison; Barnes, Neil

    2011-01-01

    Purpose: Results of randomized controlled trials may not predict effectiveness of inhaled corticosteroids (ICS) in real-world clinical practice, where inhaler technique and device characteristics can influence effectiveness. We compared asthma outcomes for ICS delivered via three different inhaler devices: pressurized metered-dose inhaler (pMDI), breath-actuated MDI (BAI), and dry powder inhaler (DPI). Patients and methods: This retrospective database study evaluated 1-year outcomes for primary care patients with asthma aged 5–60 years prescribed their first ICS (initiation population) by pMDI (n = 39,746), BAI (n = 9809), or DPI (n = 6792), or their first ICS dose increase (step-up population) by pMDI (n = 6245), BAI (n = 1388), or DPI (n = 1536). Co-primary outcome measures were composite proxy measures of asthma control (no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory infection) and severe exacerbations (unscheduled hospital admission, emergency room attendance, or oral corticosteroids). Outcomes were adjusted for potential confounding factors identified during a baseline year. Results: In the initiation population, adjusted odds ratios (95% confidence intervals [CI]) for asthma control, as compared with pMDIs, were significantly better for BAIs (1.08 [1.02–1.14]) and DPIs (1.13 [1.06–1.21]), while adjusted exacerbation rate ratios (95% CI) were 1.00 (0.93–1.08) and 0.88 (0.81–0.95), respectively. In the step-up population, adjusted odds of asthma control were 1.21 (1.05–1.39) for BAIs and 1.13 (0.99–1.29) for DPIs; adjusted exacerbation rate ratios were 0.83 (0.71–0.98) for BAIs and 0.85 (0.74–0.98) for DPIs, compared with pMDIs. Conclusion: Inhaler device selection may have a bearing on clinical outcomes. Differences in real-world effectiveness among these devices require closer evaluation in well-designed prospective trials. PMID:21698214

  7. The Acute Exposure Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    PubMed Central

    Liberda, Eric N; Cuevas, Azita K; Qu, Qingshan; Chen, Lung Chi

    2014-01-01

    Introduction The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures such as increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiated atherosclerosis in murine species. Methods Following an acute whole body inhalation exposure to 500μg/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 (CEPCs), circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure. Results and Conclusions Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating 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. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. This data provides new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration permissible exposure limit may adversely affect EPCs. PMID:25144474

  8. Effects of inhaled acids on respiratory tract defense mechanisms.

    PubMed Central

    Schlesinger, R B

    1985-01-01

    The respiratory tract is endowed with an interlocking array of nonspecific and specific defense mechanisms which protect it from the effects of inhaled microbes and toxicants, and reduce the risk of absorption of materials into the bloodstream, with subsequent systemic translocation. Ambient acids may compromise these defenses, perhaps providing a link between exposure and development of chronic and acute pulmonary disease. This paper reviews the effects of inhaled acids upon the nonspecific clearance system of the lungs. PMID:3908089

  9. Comparison of absorption after inhalation and instillation of uranium octoxide.

    PubMed

    Pellow, P G D; Hodgson, S A; Hodgson, A; Rance, E; Ellender, M; Guilmette, R A; Stradling, G N

    2003-01-01

    Values for the absorption parameters were compared after inhalation or intratracheal instillation of 1.5 microm mass median aerodynamic diameter (MMAD) 233U3O8 particles into the lungs of HMT strain rats. The two sets of parameter values were similar, as were the calculated dose coefficients and predicted biokinetics for workers. Hence the inhalation and instillation techniques can probably both be used to generate values of the absorption parameters for U3O8. PMID:14526937

  10. [Inhaled nitric oxide: one modality in the treatment of ARDS].

    PubMed

    Carrillo-Esper, R; Ramírez-Hernández, J M; Gargallo-Hernández, J J; Hernández-Vásquez, R; Domínguez-Rodríguez, M I; Alemán-Alarcón, C E; Gallegos-Rodríguez, G

    1999-01-01

    We describe a patient with acute respiratory distress syndrome (ARDS), refractory to treatment with conventional mechanical ventilation. The hemodynamic parameters showed severe pulmonary hypertension with increased intrapulmonary shunt. Inhaled nitric oxide was administered and we observed a diminishing in pulmonary hypertension and intrapulmonary shunt with an important increase of oxygen exchange. We reviewed the literature and make a suggestion concerning use of inhaled nitric oxide in patients with ARDS. PMID:10491897

  11. 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

  12. Exposures to inhalable and "total" oil mist aerosol by metal machining shop workers.

    PubMed

    Wilsey, P W; Vincent, J H; Bishop, M J; Brosseau, L M; Greaves, I A

    1996-12-01

    Several recent studies have compared worker personal aerosol exposures as measured by the current method with those obtained by a new approach based on collecting the inhalable fraction, intended to represent all the particles that are capable of entering through the nose and/or mouth during breathing. The present study investigated this relationship for a metal machining facility where aerosols were generated from severely refined, nonaqueous ("straight") cutting oils used during the lathe working of metal rod stock. Workers (n = 23) wore two personal aerosol samplers simulataneously, one of the 37-mm type (for "total" aerosol exposure, E37) and the other of the Institute of Occupational Medicine (IOM) type (for inhalable aerosol exposure, EIOM). The data were analyzed by weighted least squares linear regression to determine the coefficient S in the relation EIOM = S.E37. It was found that S = 2.96 +/- 0.60. This ratio-in which exposure to inhalable aerosol was greater than to "total" aerosol-is consistent with previous observations in other industries. The relative coarsenss of the oil mist aerosol, as estimated by cascade impactor measurements, probably explains the difference between the sampling methods. The collection of large "splash" droplets, may also contribute. Future occupational aerosol standards for metalworking fluids will be based on the new, health-related criteria, and exposures will be assessed on the basis of the inhalable fraction. Results of studies like that described here will enable assessment of the impact on future workplace aerosol exposure assessments of introducing new standards. PMID:8976589

  13. Human inhalation exposure to ethylene glycol.

    PubMed

    Carstens, Jörn; Csanády, György A; Faller, Thomas H; Filser, Johannes G

    2003-08-01

    Two male volunteers (A and B) inhaled 1.43 and 1.34 mmol, respectively, of vaporous (13)C-labeled ethylene glycol ((13)C(2)-EG) over 4 h. In plasma, (13)C(2)-EG and its metabolite (13)C(2)-glycolic acid ((13)C(2)-GA) were determined together with the natural burden from background GA using a gas chromatograph equipped with a mass selective detector. Maximum plasma concentrations of (13)C(2)-EG were 11.0 and 15.8 micromol/l, and of (13)C(2)-GA were 0.9 and 1.8 micromol/l, for volunteers A and B, respectively. Corresponding plasma half-lives were 2.1 and 2.6 h for (13)C(2)-EG, and 2.9 and 2.6 h for (13)C(2)-GA. Background GA concentrations were 25.8 and 28.3 micro mol/l plasma. Unlabeled background EG, GA and oxalic acid (OA) were detected in urine in which the corresponding (13)C-labeled compounds were also quantified. Within 28 h after the start of the exposures, 6.4% and 9.3% (13)C(2)-EG, 0.70% and 0.92% (13)C(2)-GA, as well as 0.08% and 0.28% (13)C(2)-OA of the inhaled amounts of (13)C(2)-EG, were excreted in urine by volunteers A and B, respectively. The amounts of (13)C(2)-GA represented 3.7% and 14.2% of background urinary GA excreted over 24 h (274 and 88 micromol). The amounts of (13)C(2)-OA were 0.5% and 2.1% of background urinary OA excreted over 24 h (215 and 177 micromol). From the findings obtained in plasma and urine and from a toxicokinetic analysis of these data, it is highly unlikely that workplace EG exposure according to the German exposure limit (MAK-value 10 ppm EG, 8 h) could lead to adverse effects from the metabolically formed GA and OA. PMID:12856104

  14. Subchronic inhalation toxicity of gold nanoparticles

    PubMed Central

    2011-01-01

    Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold

  15. Experimental investigation of design parameters on dry powder inhaler performance.

    PubMed

    Ngoc, Nguyen Thi Quynh; Chang, Lusi; Jia, Xinli; Lau, Raymond

    2013-11-30

    The study aims to investigate the impact of various design parameters of a dry powder inhaler on the turbulence intensities generated and the performance of the dry powder inhaler. The flow fields and turbulence intensities in the dry powder inhaler are measured using particle image velocimetry (PIV) techniques. In vitro aerosolization and deposition a blend of budesonide and lactose are measured using an Andersen Cascade Impactor. Design parameters such as inhaler grid hole diameter, grid voidage and chamber length are considered. The experimental results reveal that the hole diameter on the grid has negligible impact on the turbulence intensity generated in the chamber. On the other hand, hole diameters smaller than a critical size can lead to performance degradation due to excessive particle-grid collisions. An increase in grid voidage can improve the inhaler performance but the effect diminishes at high grid voidage. An increase in the chamber length can enhance the turbulence intensity generated but also increases the powder adhesion on the inhaler wall. PMID:24055597

  16. Off-label use of inhaled tobramycin in Ontario, Canada.

    PubMed

    Tadrous, Mina; Khuu, Wayne; Paterson, J Michael; Mamdani, Muhammad M; Juurlink, David N; Gomes, Tara

    2016-09-01

    Inhaled tobramycin solution is indicated for use in the management of Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Concerns have been raised regarding increasing off-label use of inhaled tobramycin, particularly for the management of COPD. We conducted an 8-year repeated cross-sectional study examining the indication for prescription claims for inhaled tobramycin in Ontario paid for by the Public Drug Benefit Program, which covers all Ontario residents with financial needs or aged 65 and older. Inhaled tobramycin prescription claims increased approximately 3 times greater from 86 prescriptions in the second quarter of 2007 to 261 prescriptions in the first quarter of 2015. Approximately half of all prescriptions (range: 46-65%) per quarter were dispensed to patients with CF. A large proportion of prescriptions (range: 31-36%) were dispensed to individuals who did not have a diagnosis of CF but had a diagnosis of COPD. In 2014, there were 324 unique users of inhaled tobramycin solution in the Ontario Public Drug Program (OPDP). Only half of users (54%; n=163) had a diagnosis of CF. Our study found increasing prescriptions of inhaled tobramycin from 2007 to 2015 in the OPDP with approximately half of these claims being for off-label use, mostly among patients with COPD. PMID:27165985

  17. 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

  18. Inhalation of two putative Gulf War toxins by mice.

    PubMed

    Repine, John E; Wilson, Paul; Elkins, Nancy; Klawitter, Jelena; Christians, Uwe; Peters, Ben; Smith, Dwight M

    2016-06-01

    We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB4) (a biomarker of inflammation) and PGF2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB4 and PGF2α levels but no increase in lung lavage LTB4, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals. PMID:26950528

  19. Cigarette smoke inhalation and the acute airway response.

    PubMed Central

    Higenbottam, T; Feyeraband, C; Clark, T J

    1980-01-01

    The acute airway response to smoking varying numbers (one to four) of identical cigarettes in rapid succession and smoking single cigarettes of differing tar/nicotine yields was assessed repeatedly in 13 healthy smokers. The airway response was variable, indicating airway narrowing consistently in only three subjects. There appeared no difference between forced spirometry and measurement of airway resistance in detecting the airway response. No relationship was observed between the airway response and amount of smoke inhaled into the lungs as measured either by changes in venous blood nicotine or percentage carboxyhaemoglobin. When five smokers inhaled smoke directly from a cigarette acute airway narrowing was consistently observed. A normal smoking pattern consisting of an initial drag of smoke into the mouth, followed after a pause by inhalation of smoke diluted with air, did not consistently cause airway narrowing although similar amounts of smoke as the direct drag were inhaled as assessed by changes in venous blood nicotine. The manner of smoke inhalation affects the relative concentrations of the different constituents of smoke reaching the lungs and also appears to be the main determinant of the acute airway response to smoking, which was unrelated to the number of cigarettes smoked or the tar content of the smoke. This suggests that patterns of smoke inhalation may influence the pathogenesis of bronchial disease associated with smoking. PMID:7434266

  20. 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

  1. 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

  2. Homicide facilitated by inhalation of chloroform.

    PubMed

    Nashelsky, M B; Dix, J D; Adelstein, E H

    1995-01-01

    Three related homicides in which each decedent had significant concentrations of chloroform in blood, fat, brain and/or liver are described. The tissue concentrations of chloroform in one of three decedents were within reported lethal ranges. The concentrations in the remaining two decedents were less than lethal but were well above blood levels in nonoccupationally exposed, healthy subjects. The cause of death in one decedent with sublethal chloroform concentrations was suffocation; the cause of death in the other decedent could not be determined with certainty. The manner of death in each case was homicide. Through a review of the literature the authors discuss the history of chloroform as an inhalation anesthetic and the history of chloroform as an agent of abuse, suicide, assault, and homicide. Blood and/or tissue concentrations of chloroform in nonoccupationally exposed, healthy subjects and victims of suicide or homicide from previous reports are compared and contrasted with the amounts in blood and/or tissue in the three subjects described in this study. The authors conclude that, in addition to a direct lethal effect, chloroform may be used to incapacitate a victim of assault who then dies by another cause. PMID:7876797

  3. 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. PMID:16176404

  4. 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

  5. Inhaled Corticosteroids and Secondary Adrenal Insufficiency

    PubMed Central

    Sannarangappa, Vishnu; Jalleh, Ryan

    2014-01-01

    Inhaled corticosteroids (ICS) have been used as first line treatment of asthma for many decades. ICS are a form of exogenous glucocorticosteroids that can suppress the endogenous production of glucocorticosteroids, a condition known as adrenal suppression (AS). As a result, cessation, decreasing the dose or changing the type of ICS may trigger features of adrenal insufficiency (AI). AI may cause a spectrum of presentations varying from vague symptoms of fatigue to potentially life threatening acute adrenal crises. This article reviews the current literature on ICS and AI particularly in adults (although majority of data available is from the paediatric population). It aims to increase awareness of the potential risk of AI associated with ICS use, delineate the pathogenesis of AI and to provide recommendations on screening and management. From our literature review, we have found numerous case reports that have shown an association between ICS and AI particularly in children and patients using high doses. However, there have also been reports of AI in adults as well as in patients using low to moderate doses of ICS. To conclude, we recommend screening for AI in select patient groups with an initial early morning serum cortisol. If results are abnormal, more definitive testing such as the low dose corticotropin stimulation test may be done to confirm the diagnosis. PMID:25674179

  6. 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.

  7. Inhaled corticosteroids in COPD: the clinical evidence.

    PubMed

    Ernst, Pierre; Saad, Nathalie; Suissa, Samy

    2015-02-01

    In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), including treatment with combinations of long-acting β-agonist (LABA) bronchodilators and ICS. Our emphasis is on the methodological strengths and limitations that guide the conclusions that may be drawn. The evidence of benefit of ICS and, therefore, of the LABA/ICS combinations in COPD is limited by major methodological problems. From the data reviewed herein, we conclude that there is no survival benefit independent of the effect of long-acting bronchodilation and no effect on FEV1 decline, and that the possible benefit on reducing severe exacerbations is unclear. Our interpretation of the data is that there are substantial adverse effects from the use of ICS in patients with COPD, most notably severe pneumonia resulting in excess deaths. Currently, the most reliable predictor of response to ICS in COPD is the presence of eosinophilic inflammation in the sputum. There is an urgent need for better markers of benefit and risk that can be tested in randomised trials for use in routine specialist practice. Given the overall safety and effectiveness of long-acting bronchodilators in subjects without an asthma component to their COPD, we believe use of such agents without an associated ICS should be favoured. PMID:25537556

  8. Schedules of Controlled Substances: Table of Excluded Nonnarcotic Products: Nasal Decongestant Inhaler/Vapor Inhaler. Final rule.

    PubMed

    2016-02-01

    This final rule adopts, without change, the interim final rule that was published in the Federal Register on October 27, 2015. The Drug Enforcement Administration is amending the table of Excluded Nonnarcotic Products to update the company name for the drug product Nasal Decongestant Inhaler/Vapor Inhaler (containing 50 milligrams levmetamfetamine) to Aphena Pharma Solutions--New York, LLC. This over-the-counter, nonnarcotic drug product is excluded from the provisions of the Controlled Substances Act. PMID:26859907

  9. Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes

    PubMed Central

    Bodnár, Réka; Mészáros, Ágnes; Oláh, Máté; Ágh, Tamás

    2016-01-01

    Background Inhaled antibiotics (ABs) are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF. Methods A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality. Results The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3), proportion of adherent patients (>75%–80% of required doses taken) ranged from 86% to 97%; in prospective cohort studies (n=3), adherence rates ranged between 36% and 92%, and in retrospective studies (n=4) it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste), and patient satisfaction. Conclusion The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies) and the lack of a commonly accepted consensus on the definition of adherence in the reviewed articles. Routine adherence monitoring during CF care, discussing the possible reasons of suboptimal adherence with the patient, and changing treatment regimens on the basis of patient burden can individualize CF therapy for patients and

  10. Evaluation of dry powder inhalers with a focus on ease of use and user preference in inhaler-naïve individuals.

    PubMed

    von Schantz, Sofia; Katajavuori, Nina; Antikainen, Osmo; Juppo, Anne

    2016-07-25

    Inhaler errors are common amongst inhaler users. Therefore, in the development work of new inhalation devices, it is important to characterize the ease of use of the inhalers. In this study four dry powder inhalers, Diskus, Easyhaler, Ellipta and Turbuhaler, were evaluated, focusing on ease of use and patient preference. The study used a triangular methodology. The sample consisted of 31 inhaler naïve individuals. Educational videos for all inhalers were watched, and afterwards, the use of all four inhalers was demonstrated in a random order. The demonstrations were videotaped. Thereafter they were checked against a predefined checklist and all mistakes were recorded. Only 33% of inhaler demonstrations were completed without the participants making any mistakes. The proportions of subjects who used the devices correctly were as follows: Diskus 48%, Easyhaler 19%, Ellipta 55% and Turbuhaler 16%. When comparing correct and incorrect inhaler technique for each inhaler pair the following differences were statistically significant: Diskus vs. Easyhaler (p<0.05), Ellipta vs. Easyhaler (p<0.01), Diskus vs. Turbuhaler (p<0.01), Ellipta vs. Turbuhaler (p<0.01). In the participants' ranking, the inhalers Ellipta, followed by Turbuhaler, were most often ranked as most preferred. Participants' preference of Ellipta over Easyhaler (p<0.01) and over Diskus (p<0.001) were statistically significant. PMID:27208655

  11. Inhalational anesthesia for organ procurement: potential indications for administering inhalational anesthesia in the brain-dead organ donor.

    PubMed

    Elkins, Laurie J

    2010-08-01

    Organs needed for transplantation far outweigh their availability. There is minimal research regarding perioperative care of the brain-dead organ donor during the procurement procedure. Current research attributes a great deal of organ damage to autonomic or sympathetic storm that occurs during brain death. Literature searches were performed with the terms brain death, organ donor, organ procurement, anesthesia and organ donor, anesthesia and brain death, anesthesia and organ procurement, inhalational anesthetics and organ procurement, and inhalational anesthetics and brain dead. Additional resources were obtained from reference lists of published articles. The literature review showed there is a lack of published studies researching the use of inhalational anesthetics in organ procurement. No studies have been published evaluating the effect of preconditioning with inhalational agents (administering 1.3 minimal alveolar concentration of an inhalational agent for the 20 minutes before periods of ischemia) in the brain-dead organ donor population. Further studies are required to determine if administration of inhalational anesthetics reduces catecholamine release occurring with surgical stimulation during the organ procurement procedure and whether this technique increases viability of transplanted organs. Anesthetic preconditioning before the ischemic period may reduce ischemia-reperfusion injury in transplanted organs, further increasing viability of transplanted organs. PMID:20879630

  12. 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

  13. Inhaled house dust mite induces pulmonary T helper 2 cytokine production

    PubMed Central

    Gregory, L. G.; Causton, B.; Murdoch, J. R.; Mathie, S. A.; O’Donnell, V.; Thomas, C. P.; Priest, F. M.; Quint, D. J.; Lloyd, C. M.

    2012-01-01

    Background Inhaled house dust mite (HDM) results in T-helper (TH) 2 type pathology in unsensitized mice, in conjunction with airway hyperreactivity and airway remodelling. However, the pulmonary cytokine and chemokine profile has not been reported. Methods We have performed a time course analysis of the characteristic molecular mediators and cellular influx in the bronchoalveolar lavage (BAL) and lung in order to define the pulmonary inflammatory response to inhaled HDM extract. Mice were exposed five times a week to soluble HDM extract for 3 weeks. Lung function was measured in groups of mice at intervals following the final HDM challenge. Recruitment of inflammatory cells and inflammatory mediator production was then assessed in BAL and lungs of individual mice. Results We found that Th2 cytokines were significantly increased in BAL and lung after HDM challenge from as early as 2 h post-final challenge. The levels of cytokines and chemokines correlated with the influx of eosinophils and Th2 cells to the different compartments of the lung. However, the production of key cytokines such as IL-4, IL-5 and IL-13 preceded the increase in airways resistance. Conclusion Inhaled HDM challenge induces a classical Th2 inflammatory mediator profile in the BAL and lung. These data are important for studies determining the efficacy of novel treatment strategies for allergic airways disease. PMID:19545261

  14. 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

  15. A short-term inhalation study protocol: designed for testing of toxicity and fate of nanomaterials.

    PubMed

    Ma-Hock, Lan; Hofmann, Thomas; Landsiedel, Robert; van Ravenzwaay, Bennard

    2014-01-01

    The Short-Term Inhalation Toxicity Study Design described here was specifically developed for the testing of nanoparticles. It consists of a 5-day inhalation exposure with a subsequent 3-week exposure-free period. The protocol has been optimized for the detection of toxic effects in the respiratory tract by incorporation of additional endpoints like collection of bronchoalveolar lavage and measurement of biomarkers indicative for pro-inflammatory and inflammatory changes. Analytical determination of the test compound concentrations in the lung and other organs can be included in the study design for the determination of organ burden and fate of the tested nanomaterial. Over 20 nanomaterials have been tested with this method. In case of those compounds, where data of 90-day inhalation studies were available, the qualitative effects were comparable in both study types. Likewise, the No Observed Adverse Effect Levels were similar between the two study types, showing that the short-term design is suitable for a first risk assessment. PMID:25103811

  16. 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

  17. 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

  18. Time course of bronchodilating effect of inhaled formoterol, a potent and long acting sympathomimetic.

    PubMed Central

    Derom, E Y; Pauwels, R A

    1992-01-01

    BACKGROUND: Most of the currently available inhaled beta 2 agonists are short acting bronchodilators. The aim of this study was to compare the rate of onset and duration of the bronchodilating activity of formoterol and salbutamol. METHODS: Fourteen patients with reversible airways obstruction received placebo, 200 micrograms salbutamol, and 12, 24, and 48 micrograms formoterol from a metered dose inhaler, according to a double blind, randomised crossover design. Forced expiratory volume in one second (FEV1) and specific airways conductance (sGaw) were measured over 12 hours. RESULTS: Salbutamol and all doses of formoterol caused a significant and substantial increase in sGaw one minute after inhalation. The mean maximum increase in FEV1 was 58% (8%) after 200 micrograms salbutamol compared with 63% (11%), 62% (10%), and 74% (10%) after 12, 24, and 48 micrograms formoterol, respectively. The mean maximum increase in FEV1 occurred 57 (12) minutes after administration of salbutamol compared with 137 (16), 141 (21), and 161 (33) minutes after 12, 24, and 48 micrograms formoterol respectively. The bronchodilating effect of salbutamol did not differ from placebo after six hours. In contrast, the mean increase in FEV1 12 hours after 12 micrograms formoterol (26% (8%) of baseline) significantly exceeded the change after placebo. Tremor was recorded in four patients after 48 micrograms formoterol. CONCLUSION: Formoterol is a potent, fast acting bronchodilator with a long duration of action. PMID:1539141

  19. Sulfur mustard inhalation induced respiratory lesions in guinea pigs: Physiological, biochemical, and histological study

    SciTech Connect

    Allon, N.; Gilat, E.; Amir, A.; Fishbine, E.; Liani, H.

    1993-05-13

    Inhalation exposure to sulfur mustard (SM) vapor causes long term damage to the respiratory system. The lesions were characterized by specific physiological, biochemical and histopathological methods. Awake 128 guinea-pigs (GP) were exposed for 10 min to SM (1200-1700 microns x min/1). Respiratory parameters were monitored per animal before, during and after the exposure using plethysmography. Biochemical and histological evaluations were performed at different time intervals for up to 7 days post exposure. SM inhalation resulted in a decrease in both respiratory rate and minute volume, and in an increase in tidal volume. These changes occurred immediately after the onset of exposure and lasted for up to 7 days. The changes in the respiratory parameters were accompanied by a massive reduction in O2 diffusion capacity. Evaluation of bronchoalveolar lavage (BAL) fluid indicated neutrophil infiltration, an increase in the protein content, and in the activity of both lysosomal enzymes and lactic dehydrogenase (LDH) in the alveolar space. In addition, a decrease in glutathione content was observed one day post exposure in the BAL fluid and the lung whereas an increase in lung glutathione content was observed 6 days later. Histological evaluation of the lungs and trachea revealed severe lesions in both tissues. Recovery was incomplete 7 days post exposure. The detailed characterization of the effect of SM inhalation offers a reliable model for the evaluation of potential therapies against SM exposure.

  20. Impact of bronchial circulation on bronchial exudation following combined burn and smoke inhalation injury in sheep

    PubMed Central

    Morita, Naoki; Enkhbaatar, Perenlei; Maybauer, Dirk M.; Maybauer, Marc O.; Westphal, Martin; Murakami, Kazunori; Hawkins, Hal K.; Cox, Robert A.; Traber, Lillian. D.; Traber, Daniel L.

    2011-01-01

    We previously reported bronchial circulation contributes to pulmonary edema and increases shunt fraction following smoke inhalation, and bronchial blood flow significantly increases in inhalation injury. We hypothesized reduction of bronchial blood flow reduces exudation to the airway and ameliorates lung injury from combined burn and smoke insults (B & S injury). Method Merino ewes (n=28) randomly divided into three groups (1: bronchial artery ligated and injured (Injury + ligation group); 2: bronchial artery left intact and injured (Injury + no ligation group); 3: bronchial artery ligated but not injured (No injury + ligation group) were subjected to a flame burn and inhalation injury under halothane anesthesia. Parameters were analyzed using Scheffe’s post hoc test (P<0.05). All Groups were resuscitated with Ringer lactate solution and placed on a ventilator for 48 hours. Results Pulmonary gas exchange (PaO2/FiO2) improved in injury + ligation group. Further, obstruction score, an index of airway cast formation, significantly changed between injury + no ligation group compared to both ligation groups. Conclusion Bronchial circulation plays a significant role in lung injury after B & S injury, and reduction of bronchial blood flow by bronchial artery ligation reduces bronchial exudation, resulting in improved gas exchange. PMID:21195551

  1. 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

  2. Inhaled corticosteroids for asthma: impact of practice level device switching on asthma control

    PubMed Central

    Thomas, Mike; Price, David; Chrystyn, Henry; Lloyd, Andrew; Williams, Angela E; von Ziegenweidt, Julie

    2009-01-01

    Background As more inhaled corticosteroid (ICS) devices become available, there may be pressure for health-care providers to switch patients with asthma to cheaper inhaler devices. Our objective was to evaluate impact on asthma control of inhaler device switching without an accompanying consultation in general practice. Methods This 2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation for ≥5 patients within 3 months. Patients 6–65 years of age from these practices whose ICS device was switched were individually matched with patients using the same ICS device who were not switched. Asthma control over 12 months after the switch was assessed using a composite measure including short-acting β-agonist and oral corticosteroid use, hospitalizations, and subsequent changes to therapy. Results A total of 824 patients from 55 practices had a device switch and could be matched. Over half (53%) of device switches were from dry powder to metered-dose inhalers. Fewer patients in switched than matched cohort experienced successful treatment based on the composite measure (20% vs. 34%) and more experienced unsuccessful treatment (51% vs. 38%). After adjusting for possible baseline confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29 (95% confidence interval [CI], 0.19 to 0.44; p < 0.001) and for unsuccessful treatment was 1.92 (95% CI, 1.47 to 2.56; p < 0.001). Conclusion Switching ICS devices without a consultation was associated with worsened asthma control and is therefore inadvisable. PMID:19121204

  3. 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

  4. Particle engineering of materials for oral inhalation by dry powder inhalers. II-Sodium cromoglicate.

    PubMed

    Nolan, Lorraine M; Li, Jianhe; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

    2011-02-28

    Sodium cromoglicate is an antiasthmatic and antiallergenic drug used in inhalation therapy and commonly administered by a dry powder inhaler. In the present study we sought to examine the feasibility of producing nanoporous microparticles (NPMPs) of this hydrophilic material by adaptation of a spray drying process previously applied to hydrophobic drugs, and to examine the physicochemical and in vitro deposition properties of the spray dried particles in comparison to a commercial product. The storage stability of successfully prepared NPMPs was assessed under a number of conditions (4°C with dessicant, 25°C at 60% relative humidity and 25°C with dessicant). Spray dried sodium cromoglicate was amorphous in nature. NPMPs of sodium cromoglicate displayed superior aerodynamic properties resulting in improved in vitro drug deposition, as assessed by Andersen Cascade Impactor and twin impinger studies, in comparison to the commercial product, Intal. Deposition studies indicated that porosity and sphericity were important factors in improving deposition properties. The optimum solvent system for NPMP production was water:methanol:n-butyl acetate, as spherical NPMPs spray dried from this solvent system had a higher respirable fraction than non-spherical NPMPs of sodium cromoglicate (spray dried from methanol:n-butyl acetate), non-porous sodium cromoglicate (spray dried from water) and micronised sodium cromoglicate (Intal). While particle morphology was altered by storage at high humidity (60% RH) and in vitro deposition performance deteriorated, it was possible to maintain NPMP morphology and aerosolisation performance by storing the powder with dessicant. PMID:21129460

  5. Comparison of the effectiveness of antibody and cell-mediated immunity against inhaled and instilled influenza virus challenge

    PubMed Central

    2013-01-01

    Background To evaluate immunity against influenza, mouse challenge studies are typically performed by intranasal instillation of a virus suspension to anesthetized animals. This results in an unnatural environment in the lower respiratory tract during infection, and therefore there is some concern that immune mechanisms identified in this model may not reflect those that protect against infectious virus particles delivered directly to the lower respiratory tract as an aerosol. Method To evaluate differences in protection against instilled and inhaled virus, mice were immunized with influenza antigens known to induce antibody or cell-mediated responses and then challenged with 100 LD50 A/PR/8/34 (PR8) in the form of aerosol (inhaled) or liquid suspension (instilled). Results Mice immunized with recombinant adenovirus (Ad) expressing hemagglutinin were protected against weight loss and death in both challenge models, however immunization with Ad expressing nucleoprotein of influenza A (NPA) or M2 resulted in greater protection against inhaled aerosolized virus than virus instilled in liquid suspension. Ad-M2, but not Ad-NPA-immunized mice were protected against a lower instillation challenge dose. Conclusions These results demonstrate differences in protection that are dependent on challenge method, and suggest that cell-mediated immunity may be more accurately demonstrated in mouse inhalation studies. Furthermore, the data suggest immune mechanisms generally characterized as incomplete or weak in mouse models using liquid intranasal challenge may offer greater immunity against influenza infection than previously thought. PMID:23777453

  6. Washout kinetics of inhaled hydrogen cyanide in breath.

    PubMed

    Stamyr, Kristin; Nord, Pierre; Johanson, Gunnar

    2008-06-10

    Hydrogen cyanide (HCN) intoxication causes or contributes significantly to many of the fatalities among fire victims. To enable fast treatment of HCN poisoning, a more rapid diagnostic method than currently available is required. One possibility would be measurement in exhaled air. However, as HCN is highly water soluble, it may be absorbed during inhalation and reabsorbed during exhalation. If this, so-called, washin-washout effect is substantial it may interfere with the diagnosis, as a major part of breath HCN may originate from the respiratory tract, due to recent exposure, and not from systemic exposure. The aim of this study was to estimate the importance of the washin-washout effect of HCN. The time-course of cyanide in exhaled air was measured with an electrochemical detector in 10 volunteers during and after a 1 min x 10 ppm exposure to HCN. The experiment revealed an average half-life of 16s (range 10-24s) in breath. Extrapolating the results to higher exposures suggests that the contribution from washin-washout from the airways will be negligible even at fatal exposures. The results support the use of breath HCN as a potential indicator of systemic intoxication. PMID:18490114

  7. Preparation and evaluation of inhalable itraconazole chitosan based polymeric micelles

    PubMed Central

    2012-01-01

    Background This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA). Methods Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering and transmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger. Results The polymeric micelles prepared in this study could entrap up to 43.2±2.27 μg of ITRA per milliliter. All micelles showed mean diameter between 120–200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF) varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process. Conclusions In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation. PMID:23351398

  8. 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.

  9. 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

  10. Inhaled innate immune ligands to prevent pneumonia

    PubMed Central

    Evans, Scott E; Tuvim, Michael J; Fox, Cory J; Sachdev, Nidhi; Gibiansky, Leonid; Dickey, Burton F

    2011-01-01

    Epithelial surfaces throughout the body continuously sample and respond to environmental stimuli. The accessibility of lung epithelium to inhaled therapies makes it possible to stimulate local antimicrobial defences with aerosolized innate immune ligands. This strategy has been shown to be effective in preclinical models, as delivery of innate immune ligands to the lungs of laboratory animals results in protection from subsequent challenge with microbial pathogens. Survival of the animal host in this setting correlates directly with killing of pathogens within the lungs, indicating the induction of a resistance mechanism. Resistance appears to be mediated primarily by activated epithelial cells rather than recruited leucocytes. Resistance reaches a peak within hours and persists for several days. Innate immune ligands can interact synergistically under some circumstances, and synergistic combinations of innate ligands delivered by aerosol are capable of inducing a high level of broad host resistance to bacteria, fungi and viruses. The induction of innate antimicrobial resistance within the lungs could have clinical applications in the prevention of lower respiratory tract infection in subjects transiently at high risk. These include cancer patients undergoing myeloablative chemotherapy, intubated patients being mechanically ventilated, vulnerable individuals during seasonal influenza epidemics, asthmatic subjects experiencing a respiratory viral infection, and healthy subjects exposed to virulent pathogens from a bioterror attack or emergent pandemic. In summary, stimulation of the lung epithelium to induce localized resistance to infection is a novel strategy whose clinical utility will be assessed in the near future. LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1 PMID:21250981

  11. 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

  12. 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

  13. 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

  14. Presumed Pseudotumor Cerebri Syndrome After Withdrawal of Inhaled Glucocorticoids.

    PubMed

    Kwon, Young Joon; Allen, Julian L; Liu, Grant T; McCormack, Shana E

    2016-06-01

    Pseudotumor cerebri syndrome (PTCS) is characterized by increased intracranial pressure with normal brain parenchyma and cerebrospinal fluid constituents. PTCS after withdrawal of systemic corticosteroids also has been described in children. In contrast, to our knowledge, PTCS after withdrawal of inhaled glucocorticoids has not previously been described. Here we report the case of an 8-year and 6-month-old girl who developed signs and symptoms consistent with PTCS after withdrawal of inhaled glucocorticoids. The patient had excellent adherence to inhaled glucocorticoid therapy for ∼1 year before presentation, after which the therapy was stopped for concern related to poor growth. The withdrawal of inhaled glucocorticoids was associated with the development of severe headaches and diplopia, and further clinical examination led to the patient's diagnosis of likely PTCS. Although its occurrence is likely rare, clinicians caring for the many children receiving inhaled glucocorticoid therapy should be aware of the potential for PTCS after abrupt withdrawal of such treatment, and consider ophthalmology evaluation if patients report suggestive symptoms, such as headaches or vision changes in this context. PMID:27244842

  15. Pulmonary vasodilation by inhaled nitric oxide after endothelial injury

    SciTech Connect

    Rimar, S.; Gillis, C.N. )

    1992-11-01

    Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation the authors studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 [+-] 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 [+-] 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 [+-] 1 and 9 [+-] 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa ([minus]9 [+-] 3 and [minus]4 [+-] 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation. 21 refs., 4 figs.

  16. 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

  17. Asthma control: the right inhaler for the right patient.

    PubMed

    Scichilone, Nicola

    2015-04-01

    Inhaled therapy is the cornerstone of asthma management in that it optimizes the delivery of the medication to the site of action. The effectiveness of inhaled therapy is affected by the correct choice of the device and proper inhalation technique. In fact, this influences the drug delivery and distribution along the bronchial tree, including the most peripheral airways. In this context, accumulating evidence supports the contribution of small airways in asthma, and these have become an important target of treatment. In reality, the "ideal inhaler" does not exist, and not all inhalers are the same. Advances in technology has highlighted these differences, and have led to the design of new devices and the development of formulations characterized by extrafine particles that facilitate the distribution and deposition of the drug particles along the respiratory tract. In addition, efforts have been made to implement adherence to chronic treatment, which translates into clinical benefit. Taken together, the optimal control of asthma depends on the drug that is selected, the device that is employed and the removal of factors that reduce patient's adherence to therapy. PMID:25845769

  18. 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

  19. 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

  20. Inhaled corticosteroids: hazardous effects on voice-an update.

    PubMed

    Gallivan, Gregory J; Gallivan, K Holly; Gallivan, Helen K

    2007-01-01

    Inhaled corticosteroids (ICS) have become the prevalent treatment in asthmatics. Hazards to voice are under-recognized. A total of 38 patients with voice complaints associated with the use of ICS were assessed by 79 strobovideolaryngoscopy (SVL) examinations, 24 single and 14 multiple SVL. Hoarseness and dysphonia were the primary reasons for referral. The ICS initially used most frequently was Advair Diskus (fluticasone propionate and salmeterol-inhalation powder-[IP]) in 22 patients, followed by Flovent (fluticasone propionate inhalation aerosol-pressurized metered-dose inhaler-[PMDI]) in 11. Duration of ICS usage varied from 2 weeks to 4-5 years. Higher dosage and frequency of use exacerbated problems. Hazards to voice previously unrecognized by real-time indirect mirror or fiberoptic laryngoscopy were identified by meticulous attention to SVL abnormalities. There was essentially no difference in occurrence of abnormalities whether analyzed from the perspective of the initial 38 or all 79 examinations. These included abnormal mucosal wave symmetry/periodicity (76-63%), phase closure (74-63%), glottic closure (63-59%), mucosal wave amplitude/magnitude (50-35%), supraglottic hyperactivity (39-25%), mucosal quality (34-34%), and glottic plane (10-5%). Candidiasis of the larynx was infrequently observed. Fluticasone ICS were a cause of steroid inhaler laryngitis, and the best treatment was their avoidance or cessation. Further prospective studies ideally might include SVL documented as a pretherapy baseline and then repeated in each ICS patient who developed hoarseness/dysphonia. PMID:16442776